Liberia Medicines and Health Products Regulatory Authority

As per the LMHRA-Act, the LibCTReg, and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections. According to the LMHRA-Act, the LMHRA operates as an autonomous government agency that reports to the President of the Republic of Liberia. In addition to its role in authorizing clinical trials, the LMHRA-Act indicates that the LMHRA’s responsibilities also include drug and health care product registration, inspections, import/export control, licensing, quality control, advertising and promotion, and pharmacovigilance and post-marketing surveillance.

Per LBR-30, the Clinical Trials Unit within LMHRA’s Pharmacovigilance & Clinical Trials Department is responsible for coordinating all aspects of clinical trials in Liberia including:

• Receiving and assessing all clinical trial applications submitted to the LMHRA
• Conducting good clinical practice (GCP) inspections of trial sites and GCP training for inspectors and the study team to ensure compliance that is in line with LMHRA regulatory requirements and international best practices
• Reviewing all reports from clinical trial sites and advising management on appropriate regulatory actions
• Investigating the conduct of clinical trials
• Suspending or stopping clinical trials (depending on the magnitude of the offense)
• Serving as secretariat for the Scientific Advisory Committee (SAC) on clinical trials
• Reviewing importation permits for investigational products (IPs) that are required for the conduct of clinical trials
• Conducting pre-submission meetings to discuss issues related to application processes
• Reviewing all reports (safety reports, quarterly reports, Serious Adverse Events (SAE) reports and final or close-out reports) from clinical trial studies conducted

Per the LibCTReg, the LMHRA can establish advisory committees for the review of clinical trial applications and for post-approval safety and compliance issues, if needed, and especially in the event of new/emerging technologies. According to LBR-29, the LMHRA has established an SAC to provide technical support to review clinical trial applications.

Other Considerations

Please note: Liberia is party to the Nagoya Protocol on Access and Benefit-sharing (LBR-3), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see LBR-17.

Contact Information

Per LBR-19, the LMHRA contact information is as follows:

Liberia Medicines and Health Products Regulatory Authority (LMHRA)
2^nd & 3^rd Floors Clay Building
Sekou Toure Avenue
Mamba Point
Monrovia, Liberia
Phone: (+231) 777-140-555 or (+231) 888-140-555
Email: info@lmhra.gov.lr

Pharmacy Board of Sierra Leone

As per the G-SLAppClinTrial and the SL-GCPs, the Pharmacy Board of Sierra Leone (PBSL) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections in the country. SLE-22 states that the PBSL was originally established through an Act of Parliament in 1988, and re-established in 2001 by the PDA2001, to regulate pharmaceutical products, medical devices, cosmetic chemical substances, food and dietary supplement and herbal products, the practice of pharmacy, and any other related matters. The PBSL operates within the Ministry of Health and Sanitation (MoHS). Per SLE-13, the PBSL is responsible for the safety, efficacy, and quality of all locally manufactured, imported, exported, distributed, sold or used drugs, medical devices, cosmetics, and nutritional agents.

Per the G-SLAppClinTrial, the PBSL monitors a clinical trial from beginning to end in order to ensure adequate protection of the general public against the risk of adverse events from authorized clinical trials. The PBSL also conducts on-site inspections of the clinical trial site, sponsor, or manufacturing facilities to ensure the safety of clinical trial participants, the quality and reliability of data obtained in a trial, and that the facilities used continue to be acceptable throughout the clinical investigation.

The G-SLAppClinTrial requires that the PBSL establish an Expert Committee on Pharmacovigilance and Clinical Trials to provide support in reviewing and authorizing clinical trial applications, and to give medical and scientific opinions on issues related to clinical trials and medicines safety. The PBSL acts as the Secretariat for the committee. For more information, see the G-SLAppClinTrial.

SLE-15 indicates that the PBSL’s Pharmacovigilance and Clinical Trials department is responsible for ensuring that the PBSL’s legal obligations in relation to drug safety are fulfilled in accordance with PDA2001.

Other Considerations

Please note: Sierra Leone is party to the Nagoya Protocol on Access and Benefit-sharing (SLE-2), which may have implications for studies of investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see SLE-18.

Contact Information

According to the PBSL website, the contact information for the PBSL is as follows:

Pharmacy Board of Sierra Leone
Central Medical Stores Compound
New England Ville, Freetown
P.M.B. 322
Sierra Leone
Phone: +232 73994830 and +232 99117117
Email: info@pharmacyboard.gov.sl; registrar@pharmacyboard.gov.sl

SLE-4 provides the following details for the Pharmacovigilance and Clinical Trials Department:

Head of Department: Pharm. Onome Abiri Thomas
Phone: +232 78534757

Overview

In accordance with the LMHRA-Act, the LibCTReg, and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) is responsible for reviewing, evaluating, and approving applications for clinical trials using registered or unregistered investigational products (IPs). According to the G-LibClinTrial, proposed clinical trials of registered medicines may include changes to indications, new methods of administration, or new combinations, etc. The G-LibClinTrial specifies that the scope of the LMHRA’s assessment includes all clinical trials (Phases I-IV). In addition, per the LibCTReg and the G-LibClinTrial, the National Research Ethics Board of Liberia (NREB) and LMHRA reviews may be conducted in parallel. However, the G-LibClinTrial and the G-NREB specify that the LMHRA will only issue final approval once NREB (ethics committee (EC)) approval is obtained.

Clinical Trial Review Process

According to LBR-30, the LMHRA’s Clinical Trials Unit within the Pharmacovigilance & Clinical Trials Department is responsible for coordinating all clinical trial activities. According to LBR-29, the LMHRA has established a Scientific Advisory Committee (SAC) to review clinical trial applications.

Per the G-LibClinTrial, the LMHRA will only process an application upon receipt of a completed application and the prescribed fees. Upon receipt, the LMHRA screens the clinical trial application package for completeness and must inform the applicant in writing about the validity of the application or the formal grounds for non-acceptance of the application. After validating the application package is complete, the LMHRA conducts a scientific assessment of the application.

During the clinical trial scientific assessment process, the LibCTReg and G-LibClinTrial also explain that relevant clinical trial decisions, reports, or information from other national regulatory authorities or regional and international bodies can be recognized or used by the LMHRA. The LibCTReg further specifies that the scope/extent of utilization of relevant clinical trial decisions, reports, or information from other national regulatory authorities or regional and international bodies will be at the sole discretion of the LMHRA. In such instances, business and company secrets must remain confidential.

The LibCTReg also states that the LMHRA must inform the NREB if it is in possession of information bearing on other clinical trials which is of significance to the board's assessment of the clinical trial on which it is to issue an expert opinion; this applies especially to information on aborted or otherwise prematurely discontinued investigations. In such instances, business and company secrets must remain confidential. Also, the LMHRA must ensure that the list of approved and rejected clinical trial applications as well as summary of evaluation reports and status of approved clinical trials are publicly available and periodically updated.

Per G-LibClinTrial, all applications must be evaluated with the same set of criteria based on up-to-date scientific knowledge and ethics standards, regardless of the applicant. The LMHRA may also request additional documents or changes through a query letter. Once a query has been raised and issued to the applicant, the process stops when the LMHRA receives a written response to the query. If the LMHRA requires changes to the application, the applicant must modify the application within an established timeline, or it will be rejected.

As indicated in the G-LibClinTrial, the LMHRA must issue a clinical trial certificate indicating the LMHRA clinical trial number to the applicant upon application approval. The clinical trial certificate may contain conditions required by the LMHRA with respect to the conduct or reporting of the trial. If the application is rejected, the applicant can submit a written appeal to the LMHRA’s Managing Director. Moreover, the information provided in a clinical trial application must not be disclosed by the LMHRA to a third party except with the written consent of the applicant or in accordance with the directive of the LMHRA Board of Directors.

Per the LibCTReg and the G-LibClinTrial, under certain circumstances, the LMHRA may accept an expedited application and review process for clinical trials (e.g., epidemics or other urgent public health interests requiring fast use of new medicines or health products and/or fast gathering of health product information). The LibCTReg also notes that in the case of emergency situations, the LMHRA may also make exemptions to the documentation requirements for the submission of clinical trial applications. Refer to 2.3 of the G-LibClinTrial for additional information on how to submit an expedited clinical trial application package. In the case of trials involving human participants, per the G-LibClinTrial, the applicant must provide proof of current, relevant, and appropriate study insurance for all participants or professional indemnity insurance for investigators as part of the application submission package to be sent to the LMHRA.

As delineated in the LibCTReg, any amendments to approved clinical trial documentation, trial arrangements, and the IPs referenced in the application must be classified and processed as determined by the LMHRA in the corresponding guidelines. The G-LibClinTrial explains that depending on the nature of the change, trial amendments are regarded as substantial or non-substantial/minor amendments. Amendments to a clinical trial are regarded as “substantial” when they are likely to have significant impact on the safety or physical or mental integrity of the trial participants and/or the scientific value of the trial. Any substantial amendments to the clinical trial protocol, clinical trial arrangements, or the IP or related product deemed to be an amendment must be approved by the LMHRA and the NREB before such amendments are carried out. Written NREB approval is also required before the LMHRA can reach a decision on an amendment. The LMHRA should respond within 20 calendar days upon receipt of the NREB’s written decision. The LMRHA may reject or accept the changes, or recommend a revision of the sponsor’s classification.

Per the G-LibClinTrial, non-substantial/minor amendments, by comparison, can be implemented immediately by the sponsor and should always be documented and notified to the LMHRA and the NREB. However, in order to allow the LMHRA to exercise its clinical trial oversight function, the sponsor should ensure that the LMRHA is aware of a non-substantial amendment(s) as soon as possible. For example, progress reports including safety data as well as annual updates of the investigator's brochure (IB) are not considered amendments per se, and therefore, do not have to be notified as substantial amendments to the LMHRA. However, the sponsor has to verify whether the data presented requires a change to the documentation submitted with the request for clinical trial authorization. If this amendment is substantial, the rules for notification of substantial amendments apply to these changes. See the G-LibClinTrial for additional amendment requirements. See the Submission Process section for amendment submission requirements.

Per the LibCTReg, the LMHRA’s written approval of a clinical trial with IPs involving human participants is based on the conclusion that the anticipated therapeutic and public benefits justify the risk and may be continued only if compliance with this requirement is permanently monitored. An LMHRA authorization may only be refused if:

• The documents submitted are incomplete up to the expiration of an appropriate deadline given to the applicant for their supplementation
• The documents submitted, especially the data on the IP(s) and the trial protocol including the investigator's brochure (IB), do not comply with the current state of scientific knowledge, and especially, the clinical trial is unsuitable for providing proof of IP(s) safety or efficacy, or
• In the case of trials involving human participants, the documentation requirements (see Section 1 (4) of LibCTReg), particularly insurance coverage for trial participants, are not fulfilled
• The LMHRA is in possession of findings which indicate that the testing facility is not suitable to conduct the clinical trial
• The LMHRA is of the opinion that the number of clinical trial participants to be recruited in the trial is not scientifically justified, or
• The requirements provided for in the general conditions and special preconditions for conducting a clinical trial (see Chapter II (Sections 1-2) of LibCTReg) are no longer fulfilled

The LibCTReg indicates that in a clinical trial of an IP consisting of a genetically modified organism, consisting of a combination of genetically modified organisms, or containing such organisms, unjustifiable harmful effects on the health of third persons and the environment are not to be expected when the trial is conducted according to the state of scientific knowledge in relation to the trial’s purpose.

(See the Submission Process and Submission Content sections for detailed submission requirements and the Timeline of Review section for additional LMHRA timeline information.)

The LibCTReg further explains that a clinical trial authorization must be suspended by the LMHRA for a limited period of time if at least one (1) of the following is true:

• It becomes known that one (1) of the grounds for refusal previously indicated existed at the time the trial authorization was issued (see also Chapter II (Section 5 (3)) of LibCTReg)
• The conditions surrounding the clinical trial do not correspond to the information contained in the authorization application
• The facts presented give reason to doubt the safety or the scientific basis of the clinical trial

Per the LibCTReg, the LMHRA must withdraw a clinical trial authorization when scientific justification for resuming the trial is not provided to address the reasons previously indicated for suspension. The LMHRA must also immediately inform the NREB through a written communication stating the grounds for its action. Before a decision is taken, the applicant must be allowed a deadline of 10 working days to submit a statement, unless the LMHRA orders the immediate interruption of the clinical trial. The lodging of an objection and an action to rescind the withdrawal or the order to suspend the authorization should not have a suspensive effect. If the authorization to conduct a clinical trial is withdrawn or suspended, the clinical trial may not be continued. Also, if the LMHRA, in the context of its activities, becomes aware of facts which justify the assumption that one (1) or more of the investigators or the sponsor or the sponsor’s representative no longer fulfills their obligations with regard to the proper conduct of the clinical trial, the LMHRA must immediately inform this individual(s) and must order remedial measures to be taken by the individual(s).

Pursuant to Part VIII of the LMHRA-Act, the LibCTReg states that any person(s), institution(s), corporate entity(ies), their designees, or legal representatives who violates the clinical trial authorization procedures, the serious adverse event notification requirements, and/or the suspension/withdrawal provisions delineated in the LibCTReg will be liable to pay administrative fines. See the LibCTReg for details.

Inspection

As stated in the LibCTReg, the LMHRA should inspect a clinical trial to ensure that the general public is adequately protected against the adverse event risks related to a clinical trial with IP(s); and, to confirm that the PI and the sponsor, including the sponsor’s representatives, are strictly adhering to the specific and general conditions to which the trial was authorized. The G-LibClinTrial also indicates that the LMHRA may inspect clinical trial sites and/or the sponsor's/contract research organization (CRO)’s premises and/or the manufacturer’s premises to ensure that the clinical trials comply with good clinical practice (GCP) provisions before, during, or after the trial is conducted.

Per the LibCTReg and the G-LibClinTrial, NREB representatives may accompany the LMHRA during clinical trial site inspections, or, per the LibCTReg, they may choose to do the inspections independently. The G-LibClinTrial also notes that the LMHRA may include other relevant regulatory authorities in the inspection. The PI and/or the sponsor/CRO and/or the manufacturer must be notified in writing of the inspection unless the LMHRA has reasonable cause to believe that the approved protocol is being violated. In this case, an unannounced inspection may be conducted. Following these inspections, the LMHRA must prepare an inspection report, and the report will be made available to the PI and/or sponsor while safeguarding the confidential aspects. The report may also be made available to the NREB and other regulatory authorities upon their request.

Additionally, the LibCTReg specifies that the LMHRA may also:

• Request additional information
• Inspect any resources that are deemed by the LMHRA to be related to the clinical trial and that may be located at the trial site, the sponsor´s and/or CRO’s facilities, or other establishments deemed appropriate by the LMHRA
• Suspend or stop a clinical
• Withdraw the authorization to conduct a clinical trial, if the LMHRA is of the opinion that the safety of the trial participants may be compromised, that the scientific reasons for conducting the trial have changed, or if the integrity of the data is compromised

Overview

In accordance with the G-SLAppClinTrial and the SL-GCPs, the Pharmacy Board of Sierra Leone (PBSL) is the regulatory authority responsible for reviewing, evaluating, and approving applications for clinical trials using registered and unregistered investigational products (IPs). The scope of the PBSL’s assessment includes all clinical trials (Phases I-IV). As delineated in the G-SLAppClinTrial, clinical trial application submissions to the PBSL and the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), may be made in parallel in the case of a public health emergency or as deemed fit by the PBSL.

Clinical Trial Review Process

As set forth in the G-SLAppClinTrial and the SL-GCPs, the PBSL coordinates the clinical trial application process. The SL-GCPs states that the sponsor/principal investigator (PI) must apply to the PBSL for approval to conduct a trial for a non-registered drug or a registered drug for new indications. The PBSL is responsible for reviewing the study design, which involves reviewing all significant ethical questions. The PBSL does a thorough scientific review of all applications for clinical trials to be conducted in Sierra Leone. According to the G-SLAppClinTrial, the PBSL must issue a Clinical Trial Certificate to authorize the initiation and conduct of the clinical trial.

As delineated in the G-SLAppClinTrial, the PBSL will inform the applicant in writing about the receipt of a valid clinical trial application or the formal grounds for non-acceptance, and the applicant must address formal grounds for non-acceptance. If changes are required and the applicant fails to modify the application correspondingly within a maximum of 30 working days, following the reasoned objections, the application will be deemed rejected. During evaluation, additional documents or changes may be requested through a query letter. Once a query has been raised and issued to the applicant, the process stops until the PBSL receives a written response to the query. If the PBSL requires changes to the application and the applicant fails to modify the application correspondingly within a maximum of 90 days following the reasoned objections, the application will be deemed rejected. See Figure 1 in Section 5.17 of the G-SLAppClinTrial for more details on the PBSL’s clinical trial authorization process.

The G-SLAppClinTrial indicates that any proposed amendment to the trial application, trial arrangements, and IP must be submitted to the SLESRC and the PBSL for approval before such amendments are carried out. If the amendments are substantial and are likely to have an impact on the safety of the trial participants, or are likely to change the interpretation of the scientific documents in support of the conduct of the trial, the sponsor must notify PBSL of the reasons for, and the content of, the amendments. For more details on amendment requirements, see the G-SLAppClinTrial.

According to the G-SLAppClinTrial, the Clinical Trial Certificate must be renewed annually with an application for renewal to the PBSL. A Clinical Trial Certificate will be revoked if conditions for which the certificate was issued are violated.

The G-SLAppClinTrial further states that if a clinical trial application is rejected by the PBSL, any person or institution may appeal the decision in writing within 60 days after receipt of the decision, to request PBSL review or reconsideration of the initial decision. The applicant must give grounds for review for each reason given in the clinical trial rejection. The grounds for the request must be based on the information that was submitted in the application. Upon review of the appeal application, the PBSL must provide the appeal application decision in writing, including a statement of reasons (e.g., findings, references to evidence, and reasons for the decision). For more information on appeal contents and timelines, see the G-SLAppClinTrial.

The G-SLInspect indicates that clinical trial inspections through on-site visits form part of the PBSL’s monitoring activities. Periodic good clinical practice (GCP) inspections of trial sites are conducted to ensure that the facilities used continue to be acceptable throughout the clinical investigation. The inspections may be carried out randomly and/or for specific reasons and are either announced or unannounced. An inspection would consist of a comparison of the procedures and practices of the PI with the commitments set out in the protocol and reports submitted to the PBSL by the investigator or the sponsor. See the G-SLInspect for more information.

Expedited Review During a Public Health Emergency

According to the G-SLAppClinTrial, if expedited review of a clinical trial during a public health emergency is anticipated, the applicant should inform the PBSL in writing. This will allow for a review team to be assembled and plans to be made to manage the workload as well as interactions with other oversight bodies such as the SLESRC. To ensure a rapid start of the clinical study, the PBSL will conduct simultaneous review, rather than sequential review, of the application with the SLESRC. For more information on expedited review, see the G-SLAppClinTrial.

Other Considerations

The G-SLAppClinTrial indicates that the PBSL may accept the decisions or scientific opinions of other national regulatory authorities, regional bodies, and international bodies if the IP or trial has been authorized by:

• International Council for Harmonisation (ICH) founding regulatory members
• ICH standing regulatory members
• ICH regulatory members
• ICH legislative and administrative authorities
• The African Vaccine Regulatory Forum (AVAREF) at a joint review meeting facilitated by the World Health Organization (WHO) with the provision of a favorable scientific opinion
• Any other regulatory decision deemed appropriate by the PBSL

According to the G-SLAppClinTrial, the PBSL may also consider an application for joint or assisted review by multiple national regulatory authorities and ECs for certain medical products of high public health value to countries on the African continent. For more information, see the G-SLAppClinTrial.

For information on applications involving biosimilar products, see the G-SLBiosimilar.

Liberia Medicines and Health Products Regulatory Authority

The LibCTReg and the G-LibClinTrial require proof of payment of the clinical trial application fee in the application dossier. Per LibCTReg and LBR-39, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) charges a non-refundable fee to submit a clinical trial application for authorization. As delineated below, authorization fees vary depending on the phase and institution conducting the study:

• Industry Funded (Phase I): $25,000 USD
• Industry Funded (Phase II): $20,000 USD
• Industry Funded (Phase III): $15,000 USD
• Clinical Research Organization (CRO) Funded Phase I: $10,000 USD
• CRO Funded Phase II: $8,000 USD
• CRO Funded Phase III: $6,000 USD
• Investigator/Local Phases III & IV: $2,500 USD
• Academic Research Trial (Individual): $2,000 USD
• Amendment (Substantial) to Clinical Trial Protocol: $1,000 USD

Payment Instructions

No information is available regarding payment instructions.

Pharmacy Board of Sierra Leone

As per the G-SLAppClinTrial, the applicant is responsible for paying a non-refundable fee to the Pharmacy Board of Sierra Leone (PBSL) to submit a clinical trial application for authorization. As delineated below, the authorization fees for foreign sponsored clinical trials of therapeutics, vaccines, and other biological products are as follows:

• Industry Funded (Phase I): $6,500 USD
• Industry Funded (Phase II): $6,500 USD
• Industry Funded (Phase III): $7,000 USD
• Research Institution Funded: $5,000 USD
• Protocol Amendment: $1,000 USD
• Expedited Protocol Review: $1,200 USD
• Renewal of Clinical Trial Certificate (yearly): $100 USD

For locally sponsored clinical trials of therapeutics, vaccines, and other biological products the fees are as follows:

• Investigator/Local Phases: $2,000 USD
• Protocol Amendment: $750 USD
• Expedited Protocol Review: $900 USD
• Renewal of Clinical Trial Certificate (yearly): $50 USD

Payment Instructions

No information is currently available regarding payment instructions for the clinical trial application fee to the PBSL.

Overview

Per the G-ACRE-IRB and the G-NREB, all research involving human participants should be reviewed by an ethics committee (EC). According to the NatResHlthPlcy, Liberia has two (2) ethics committees (ECs): the National Research Ethics Board of Liberia (NREB) and the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) (formerly known as the University of Liberia-Pacific Institute for Research and Evaluation Institutional Review Board (UL-PIRE-IRB)).

National Research Ethics Board of Liberia

As explained in the G-NREB, the NREB is an advisory institution that reports to the Ministry of Health (MoH), and its members are appointed by the Minister of Health. According to LBR-38, only the NREB has the sole responsibility to review all clinical trial protocols. The G-NREB states that the board ensures all research related protocols within and outside of Liberia are in compliance with internationally recognized ethical standards (including the Belmont Report (LBR-11), the Declaration of Helsinki (LBR-27), the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (LBR-8), and the Council for International Organizations of Medical Sciences (CIOMS’) International Ethical Guidelines for Health-related Research Involving Humans (LBR-2)), as well as Liberia’s applicable regulations and guidelines. In addition, per the G-NREB and LBR-12, the NREB is responsible for reviewing research proposals involving human participants to assess their compliance with ethical principles, regulatory requirements, and international guidelines, and for approving research protocols that meet ethical standards and providing recommendations for addressing any ethical concerns.

Per the NatResHlthPlcy the G-NREB, and LBR-12, the NREB is also responsible for the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Ensuring that researchers obtain informed consent from participants and protect their rights, privacy, and confidentiality
• Evaluating the potential risks and benefits of research projects and ensure that they are justified and minimized
• Developing and disseminating policies, guidelines, and standards for ethical conduct in research
• Providing guidance and support to researchers, research institutions, and ECs on ethical issues related to research involving human participants
• Fostering awareness and understanding of ethical principles and regulatory requirements among stakeholders in the research community
• Conducting training programs, workshops, and seminars to educate researchers, EC members, and other stakeholders on ethical principles and best practices in research ethics
• Building the capacity of research institutions and ECs to effectively review and oversee research involving human participants
• Promoting a culture of ethical conduct and responsible research practices within the research community
• Monitoring compliance with approved research protocols and ethical standards throughout the duration of research projects
• Conducting periodic reviews or audits of research activities to ensure adherence to ethical principles and regulatory requirements
• Investigating and addressing any allegations of research misconduct or breaches of ethical standards
• Establishing guidelines for the review of research for health protocols for use by other review boards
• Giving advice on ethical research issues to the MoH and related government ministries and agencies
• Engaging with the public, policymakers, and other stakeholders to raise awareness of ethical issues in research and foster dialogue on ethical considerations
• Advocating for the protection of research participants’ rights and the promotion of ethical conduct in research at the national and international levels
• Collaborating with relevant government agencies, institutions, and organizations to advance the ethical governance of research
• Establishing and maintaining a repository of all protocols reviewed in the country along with finished research/study reports

Atlantic Center for Research and Evaluation Institutional Review Board

As noted in the G-ACRE-IRB, the ACRE IRB is mandated by the Board of Directors of the ACRE Africa Center. According to LBR-28, the ACRE IRB has the expertise to review clinical research, and some members of the ACRE IRB also serve on the NREB and provide expertise in the review of clinical trial protocols. However, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical research protocols submitted to the ACRE IRB are referred to the NREB.

Ethics Committee Composition

National Research Ethics Board of Liberia

According to the G-NREB, the NREB is composed of 21 members who jointly represent a diverse community with a range of expertise. The G-NREB notes that the majority of the board members are clinicians, scientists, and national subject matter experts. Per LBR-18, the NREB board typically consists of experts in various fields related to research ethics, such as medicine, public health, social sciences, ethics, law, and community representatives. Board members may include researchers, ethicists, healthcare professionals, legal experts, and representatives from government agencies and civil society organizations. LBR-38 further specifies that the NREB membership includes, but is not limited to, a sociologist, an infectious disease scientist, a biologist, a lawyer, a pharmacist, an epidemiologist, a statistician, a bioethicist, a mental health specialist, a health system strengthening specialist, a religious elder, community elders, surgeons, clinicians, and public health specialists.

In addition, per LBR-18, although the NREB organization structure may vary based on its specific mandate, size, and operational requirements, the board typically consists of a chairperson/executive director, a secretariat or administrative staff, ethics review committees/panels, and advisory groups that may provide specialized expertise or support for specific activities or initiatives.

Atlantic Center for Research and Evaluation Institutional Review Board

As specified in the G-ACRE-IRB, the ACRE IRB members (full, regular, and ad-hoc) must be recommended by the ACRE IRB Chair and appointed by the ACRE Board of Directors. The ACRE IRB must be comprised of 12 members with the qualifications and experience, individually and collectively, to review and evaluate the scientific, medical, and ethical aspects of research protocol submissions. The membership must include both scientists and non-scientists from diverse backgrounds to undertake an impartial and adequate review of research proposals. The ACRE IRB membership must include the following:

• Scientists (including, but not limited to, professionals in natural science, social science, and behavioral science)
• Non-scientists (health practitioners, legal experts representing the community, and civil society)

In addition, the ACRE IRB must ensure social inclusivity and gender sensitivity in its membership and recruitment of ad-hoc reviewers. There must be adequate representation by age, gender, community, etc., on the board to safeguard the interests and welfare of all segments of society. ACRE IRB members must be drawn from both public and private institutions within the country.

Terms of Reference, Review Procedures, and Meeting Schedule

National Research Ethics Board of Liberia

Pursuant to the G-NREB, the NREB follows standard operating procedures (SOPs) as well as relevant ethical guidelines and regulations to ensure compliance with research ethics principles and to uphold societal interests. The NREB may seek subject matter expert opinions regarding specific research protocols and/or issues, as long as the experts have no conflict of interest, including participation in the research, financial interest in the outcome, and/or involvement in competing research, among other reasons. NREB members should meet bi-monthly for regular meetings and adhere to the board’s threshold requirement to review a minimum of three (3) complete applications at each meeting. When applicable, the NREB director may also convene ad-hoc meetings. All complete applications submitted by the deadline must be reviewed at the next regularly scheduled meeting if the number of applications meet the threshold. Members are encouraged to attend all meetings and the quorum required for voting is two-thirds of the NREB membership. Members who cannot attend a meeting due to unforeseen reasons must inform the NREB director two (2) weeks prior to the scheduled meeting. If unable to attend, members must also advise the NREB director regarding their views or concerns on specific agenda items one (1) week prior to a scheduled meeting. Meeting agendas and research protocols should be distributed to members no later than three (3) weeks before a regular meeting. Refer to the G-NREB and LBR-12 for detailed committee requirements.

Atlantic Center for Research and Evaluation Institutional Review Board

As delineated in the G-ACRE-IRB, the ACRE IRB Chair must be the head and chief spokesperson of the board and must conduct meetings in accordance with the policies, regulations, and timetable approved by the board. ACRE IRB members must be appointed initially for a term of three (3) years, which must be renewable and is subject to the ACRE IRB Board of Directors’ decision. To maintain continuity in ACRE IRB operations, at least one-third of the membership must be retained at any given time. The outgoing Chair must be an ex-officio member of the incoming ACRE IRB. ACRE IRB members and consultant reviewers must be provided with all relevant SOPs by the Secretariat to guide in the review process of all submitted protocols. ACRE IRB members are required to review, discuss, and consider protocols submitted to the board for evaluation to safeguard the rights, safety, and well-being of study participants; review progress reports and monitor ongoing research studies appropriately; evaluate final reports and outcomes; maintain absolute confidentiality in all document deliberations at board meetings; state conflicts of interest, where applicable; and participate during deliberations. Members with a conflict of interest will recuse themselves from the review of submissions with which they have a conflict, except to answer specific questions posed by the board. Additionally, per LBR-28, ACRE IRB reviews are conducted virtually via the Zoom platform.

The ACRE IRB must convene a meeting every month or when deemed necessary. The Chair, or a delegated board member, must call the meeting to order, provided there is a quorum. If there is no quorum, the meeting must be rescheduled. A quorum must be greater than 50% of the voting board members at any given event. A quorum must consist of regular and/or alternate board members (persons formally selected by the board to substitute for regular members who are unavailable ), and it must include at least one (1) member whose primary background is science related, and one (1) member whose primary background is not science related. Special/independent consultants cannot be used to establish a quorum. Members who are recused from the review of a protocol cannot be used to establish a quorum. A simple majority vote of ACRE IRB members in attendance is required for a protocol to be approved.

The ACRE IRB Chair may invite individuals with competence in special areas to assist in the review of issues that require expertise beyond or in addition to that available on the board. These individuals will be required to sign a confidentiality agreement before they review a protocol or attend a board protocol discussion, however, they are not permitted to vote. The consultant will provide the Chair with a written report to be shared with all reviewers summarizing relevant information.

Refer to the G-ACRE-IRB for detailed information on ACRE IRB administrative processes.

Overview

The G-SLAppClinTrial states that in Sierra Leone, the Sierra Leone Ethics and Scientific Review Committee (SLESRC) fulfills the functions of the ethics committee (EC) (known as an Independent Ethics Committee (IEC) in Sierra Leone). Ethical clearance for all phases of clinical trials involving humans must be sought from the SLESRC. The SLESRC is responsible for ensuring the protection of the rights, safety, and well-being of trial participants, and providing assurance of that protection by reviewing, approving, and providing comments on trial protocols and the suitability of the investigator(s), facilities, and the methods and materials to be used in obtaining and documenting informed consent of the trial participants.

Ethics Committee Composition

As per the SL-GCPs, the EC (i.e., the SLESRC) should consist of members who collectively have the qualifications and experience required to review and evaluate the scientific, medical, and ethical aspects of a proposed clinical trial. Specifically, it is recommended that the EC should include:

• At least five (5) members

• At least one (1) member whose primary area of interest is nonscientific

• At least one (1) member who is independent of the institution/trial site

Terms of Reference, Review Procedures, and Meeting Schedule

As set forth in the SL-GCPs, the EC (i.e., the SLESRC) must perform its functions according to written standard operating procedures (SOPs), maintain written records of its activities and meeting minutes, and comply with good clinical practice (GCP) and other applicable regulatory requirements. An EC must make its decisions at announced meetings where a quorum, as stipulated in the SOPs, is present. Only those EC members who are independent of the trial’s principal investigator (PI) and sponsor should vote or provide an opinion on any trial-related matters. In addition, only members who participate in the EC review process and discussion should vote and provide their opinion.

The SL-GCPs also states that the EC must retain all relevant records (e.g., written procedures, membership lists, lists of occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for at least three (3) years after the study’s conclusion, and make them available to the Pharmacy Board of Sierra Leone (PBSL) upon request. The EC may be asked by investigators, sponsors, or the PBSL to provide its written procedures and membership lists.

Overview

According to the G-ACRE-IRB and the G-NREB, the primary scope of information assessed by ethics committees (ECs) in Liberia relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. According to the NatResHlthPlcy, Liberia has two (2) ECs: the National Research Ethics Board of Liberia (NREB) and the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) (formerly the University of Liberia-Pacific Institute for Research and Evaluation Institutional Review Board (UL-PIRE-IRB)).

The G-ACRE-IRB and the G-NREB also state that the ECs are responsible for ensuring independent, timely, and competent reviews of all ethical aspects of the clinical trial protocol. The ECs must also act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants, and they must verify the adequacy of confidentiality and privacy safeguards. As per the G-ACRE-IRB, the ACRE IRB must pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed to be vulnerable, including children.

See the G-ACRE-IRB and the G-NREB for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

As per the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and the NREB must approve a clinical trial application prior to the sponsor or the representative initiating the clinical trial. Per the LibCTReg and the G-LibClinTrial, the NREB and LMHRA reviews may be conducted in parallel. However, the G-LibClinTrial and the G-NREB specify that the LMHRA will only issue final approval once NREB approval is obtained. In addition, per the LibCTReg and the G-LibClinTrial, any substantial amendment to the approved clinical trial research protocol must be approved by the LMHRA and the NREB before such amendments are carried out.

Additionally, per the LibCTReg, the LMHRA must inform the NREB if it is in possession of information bearing on other clinical trials which is of significance to the board's assessment of the clinical trial on which it is to issue an expert opinion; this applies especially to information on aborted or otherwise prematurely discontinued investigations. In such instances, business and company secrets must remain confidential.

National Research Ethics Board of Liberia

Per the G-LibClinTrial and the G-NREB, ethical clearance by the NREB is required as part of the LMHRA clinical trial approval process. As per the G-NREB, a protocol will be reviewed if the number of submitted protocols meets the board’s threshold requirement to review a minimum of three (3) complete applications at each meeting.

As delineated in the LibCTReg, the NREB provides its opinion on the application for a clinical trial in line with its written standard operating procedures (SOPs). According to LBR-20, upon receiving the research proposals, the NREB conducts a preliminary screening to ensure that all required documents and information are included and that the proposals meet the submission requirements. Incomplete or insufficient proposals may be returned to researchers with instructions for revisions or additional information. An ethics review committee/panel composed of experts in relevant fields, such as medicine, public health, ethics, law, and community representatives is then assigned by the NREB, and the committee members review the proposals independently or collectively, depending on the complexity of the research and the availability of resources. The ethics review committee/panel thoroughly evaluates each research proposal based on established ethical review criteria.

Per LBR-31, the NREB follows established ethical review criteria to evaluate research proposals to help ensure that research studies adhere to ethical principles and protect the rights, welfare, and dignity of research participants. The ethical criteria delineated in LBR-31 include informed consent, beneficence, justice, privacy and confidentiality, respect for participants’ rights and dignity, scientific validity and integrity, and compliance with regulatory requirements. See LBR-31 for details.

Per LBR-20, the committee members also assess the ethical implications of the proposed research, including the risks and benefits to participants, the adequacy of the informed consent process, the protection of vulnerable populations, and the equitable distribution of research burdens and benefits. The review process may involve discussions, debates, and deliberations among committee members to reach consensus on the ethical acceptability of the research proposals. See also LBR-23 for additional EC review guidelines.

LBR-20 further explains that the NREB communicates the outcomes of the ethical review process to researchers, including decisions on approval, conditional approval pending revisions, or rejection. Researchers receive feedback and recommendations from the EC to address any ethical concerns raised during the review process and may be required to make revisions to their proposals, provide additional information, or address specific ethical issues before final approval is granted. The LibCTReg also notes that a written permission from the NREB may only be refused if the documents submitted are incomplete up to the expiration of an appropriate deadline given to the applicant for their supplementation; the documents submitted, including the trial protocol, the investigator’s brochure, the modalities for selecting trial participants, and informed consent/assent, do not correspond to the current state of scientific knowledge, and especially, the clinical trial is unsuitable for providing IP(s) proof of safety or efficacy, or; the applicable requirements specified in the general conditions for conducting clinical trials (see Chapter II (Section 1) of LibCTReg) are not fulfilled.

Per the G-NREB, a principal investigator (PI) will be contacted by written communication (letter or email) if the NREB determines that additional materials are required to complete its review. PIs may also be asked to be available for presentations and/or contacted during the meetings. The G-NREB also explains that the NREB should notify PIs in writing of its decision within two (2) weeks following a board meeting, where applicable, following a complete review of the protocols. The NREB will also communicate its decisions to the NREB Secretariat. An approval expiration date is not specified. Pursuant to the G-NREB, PIs may also re-submit previously considered protocols, which will require a full NREB review. Per LBR-20, once all the ethical requirements have been met, the NREB grants final approval for the research proposals to proceed.

As indicated in the G-NREB, for continuing review submissions, PIs must submit review reports to the NREB Secretariat at least eight (8) weeks prior to the approved protocol’s expiration. If the NREB has not reviewed and approved a study’s request by the current expiration date, study activities should cease until the board determines whether continuing the research is in the best interest of all previously enrolled participants. The NREB will also review continuing review submissions prior to the expected expiration date of NREB approval for requests to extend the ethical approval to continue implementation of the research project. See LBR-6 for the NREB Continuing Review Form. See the Progress Reporting section for additional information on continuing review.

Additionally, per LibCTReg, the NREB’s written permission must be withdrawn if the NREB subsequently becomes aware that grounds for a refusal as referred to in the clinical trial authorization procedures (see Chapter II (Section 5 (1)) of LibCTReg) existed at the time the authorization was issued. The authorization must be withdrawn if the NREB becomes aware of the fact that subsequently at least one (1) of the following is true:

• Requirements regarding the suitability of the investigator, the investigator’s deputy, or the trial site are no longer fulfilled
• Trial participants are no longer properly insured or the prerequisites for an exception to the insurance obligation no longer exist
• Modalities for selecting trial participants no longer correspond to the current state of medical knowledge and, especially, the clinical trial is unsuitable for providing proof of the IP(s) safety or efficacy
• Prerequisites for the inclusion of persons pursuant to the general conditions and special preconditions for conducting a clinical trial (see Chapter II (Sections 1-2) of LibCTReg) are no longer fulfilled. The NREB shall inform the LMHRA through a written communication

For protocol amendments, per the G-NREB, the NREB must review and approve any protocol amendments prior to implementation. The NREB secretariat must first consult with the NREB Chair to determine the type of review required (full board review or expedited due to risk). Protocols that pose no or minimal risk to participants, have no formal informed consent process, or are subject to NREB continuing review, may be considered exempt and may qualify for expedited review. Refer to the G-NREB for detailed information on the decision types and various review processes the NREB uses to consider protocol submissions.

Additionally, the G-NREB explains that as a condition of research protocol approval, the NREB requires the PI to provide regular updates to the Secretariat from the date of approval. LBR-20 also notes that researchers are required to report any significant deviations from the approved protocols or ethical concerns that arise during the course of the research to the NREB for review and guidance. The NREB may also provide ongoing monitoring and oversight to ensure continued compliance with ethical standards and regulatory requirements. The G-NREB specifies that the NREB must conduct site visits at appropriate intervals. In certain cases, the site visits may be unannounced to ensure the integrity of the study.

Reviews During Public Health Emergencies

As delineated in the G-CTEmergncy, in the event a public health emergency is declared in Liberia or a neighboring country by the World Health Organization (WHO), the Ministry of Health (MoH), or the National Public Health Institute of Liberia (NPHIL), the NREB will expedite the initiation of research and many processes (i.e., drafting documents, translations, and obtaining approvals) will occur in parallel, rather than sequentially, as is typical during non-emergency situations.

Per the G-CTEmergncy, in addition to the NREB review form (if applicable), the following checklist will be included to streamline fast-tracking of epidemic-related research:

• Identify the research as epidemic or outbreak-related to facilitate fast-tracking
• Specify whether prior research data on the disease exists, referencing relevant local and international studies
• Ensure the inclusion of at least one (1) (preferably two (2)) PIs or co-PIs from the country where the research and review take place
• Provide qualifications of key investigators, including details of their previous experience with outbreak-relevant research
• Indicate if the protocol is part of a multicenter trial. If so, describe the status of ethics approval for the master protocol or the ethics approval from the sponsoring country

The G-CTEmergncy indicates that the NREB will also use the following guidelines to ensure compliance during health emergencies:

• Establish surge capacity for reviews and systems for virtual discussions (via platforms like Zoom)
• Identify core members who will handle the majority of the review burden, providing specialized training in outbreak-related research review to ensure high standards without compromising ethical considerations. Additional members can be called upon as demand increases
• The Director will alert members and determine whether they are available for emergency review
• Identify subject experts (technical and ethical) within the country and abroad who are willing to serve as ad hoc or co-opted members during outbreaks, anticipating the need to review multiple studies in a short time
• Establish a quorum consisting of one-third of NREB members, including pre-identified subject matter experts. If a pre-identified member submits their review but cannot attend the meeting, the member will still count towards the quorum

The G-CTEmergncy further states that revised SOPs will be circulated to all review committee members. Meetings may be virtual or electronic to reduce health risks during highly infectious outbreaks (e.g., COVID-19, Ebola). Protocols should be submitted electronically for efficiency, with hard copies to follow if mandatory. PIs must inform the NREB as early as possible about their intent to submit a high-level overview of their research (e.g., trial of a new medicine or vaccine, observational study, or survey) to prepare the committee for forthcoming protocols. Face-to-face meetings with PIs are not mandatory and may be conducted electronically or virtually if necessary. Also, protocols will be sent to reviewers within 48 hours of submission. Reviewers should complete their reviews within five (5) days during an outbreak. The PI should receive consolidated reviews with suggestions or approval within 10 working days, and should respond to the review within 48 hours. The director of the NREB secretariat will be the primary contact for communication with PIs, and all communications will be documented and archived for future reference.

Atlantic Center for Research and Evaluation Institutional Review Board

Per G-ACRE-IRB, the ACRE IRB’s purpose is to review and certify the ethical acceptability of all research involving human participants conducted in Liberia. However, per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.

Per G-ACRE-IRB, all studies submitted to the ACRE must be approved by the ACRE IRB. This includes all studies conducted by ACRE investigators as well as all research conducted by outside investigators or students and faculty of universities in Liberia. The G-ACRE-IRB is intended to ensure quality and consistency in the ACRE IRB’s review of social, behavioral, clinical, and biomedical research protocols that comply with the Council for International Organizations of Medical Sciences (CIOMS’) International Ethical Guidelines for Health-related Research Involving Humans (LBR-2) and the national ethical guidelines for research on human participants.

According to G-ACRE-IRB, on receipt of a proposal for review, the ACRE IRB Secretariat will preliminarily assess the completeness of the submission. If the submission is incomplete, the Secretariat will inform the PI accordingly and request the additional materials. Once the submission is deemed complete, the Secretariat will notify the PI and distribute the materials to the assigned ACRE IRB members. Exempt studies will be reviewed by all board members; expedited studies will be reviewed by all board members; full review studies will be sent to the entire ACRE IRB membership for review. An expedited study is defined as one which does not require review by a convened ACRE IRB quorum because it has been determined that participants are subject to low risk. Additional information about the various review types can be found in the G-ACRE-IRB. The PI must check the level at which the protocol will be reviewed and confirm the required documents before submitting it for review. Please refer to the G-ACRE-IRB for additional information on the administrative processes relating to proposal submission.

As specified in the G-ACRE-IRB, the ACRE IRB approval will commence on the day the study is approved and will expire within a defined time period based on the risk assessment and regulations. If specific conditions are stipulated in the approval letter, those conditions must be met by the designated date or approval may be withdrawn.

The G-ACRE-IRB also states that the ACRE IRB must review and approve any protocol amendments prior to those changes being implemented. The protocol submission is reviewed either via expedited procedures (for minor changes) or via full ACRE IRB review (for all other changes). The criteria for approval are the same as for initial review. In addition, the ACRE IRB has a continuing responsibility to monitor the approved trial(s) to ensure ethical compliance throughout the study duration. A continuing review is conducted to review progress of an ongoing study, and not just changes made in the study, in order to ensure continued protection of the rights and welfare of research participants. Refer to the G-ACRE-IRB for protocol amendment and continuing review documentation submission and procedural requirements.

Additionally, per the G-ACRE-IRB, a protocol may be selected to undergo post-approval monitoring due to reported complaints and/or requests by the convened EC. Other reasons for post-approval monitoring may include:

• From continuing review or reports from other sources, it is revealed that material changes may have occurred without ACRE IRB approval
• Where an investigator conducting a project has previous records of noncompliance
• Projects involving vulnerable populations that raise cause for concern
• Complex projects involving unusual levels or types of risks to participants
• Upon request by the investigator
• In response to inquiries from external regulatory agencies

The G-ACRE-IRB further notes that if the monitoring reveals serious or continuing noncompliance, the EC Secretariat or EC designee will compile the information regarding the allegation, complaint, or report and submit the information to the EC for further review and processing as needed. See the G-ACRE-IRB for additional information on monitoring procedures, reporting of monitoring results, and noncompliance.

As described in the G-ACRE-IRB, the ACRE IRB is also authorized to suspend or terminate an approved research study for a variety of reasons, including but not limited to:

• Failure to obtain appropriate consent or keep appropriate study-related paperwork
• Conduct of research activities without prior ACRE IRB approval
• Serious adverse event(s)
• Detrimental change in the risk-benefit ratio of the study
• Failure of investigators to complete required training

The convened board is specifically authorized to suspend or terminate approval of research protocols that are not being conducted in accordance with the ACRE IRB’s requirements or that has been associated with serious harm to the participants. The ACRE IRB Chair, or the designee, is authorized to suspend research protocols in emergency situations, such as when the rights, safety, or welfare of research participants are at immediate risk. Refer to the G-ACRE-IRB for detailed information on the board’s process for study suspension/termination, notification of the investigator, the consequences of study suspension/termination, and ACRE IRB requirements for permitting study reinstatement.

Overview

According to the G-SLAppClinTrial and the SL-GCPs, the primary scope of information assessed by the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), relates to protecting the well-being and rights of research participants and ensuring their safety throughout their participation in a clinical trial.

As per the SL-GCPs, the EC (i.e., the SLESRC) must also pay special attention to trials that may include vulnerable subjects.

Role in Clinical Trial Approval Process

As indicated in the G-SLAppClinTrial, clinical trial application submissions to the Pharmacy Board of Sierra Leone (PBSL) and the SLESRC may be made in parallel in the case of a public health emergency or as deemed fit by the PBSL. For parallel submissions, the PBSL requires proof of the application’s submission to the SLESRC, as well as any updated versions of documents or information as requested by the SLESRC.

The G-SLEthics further specifies that the principal investigator (PI) must obtain approval for a clinical trial from the SLESRC. The PI should submit a proposal along with other required documentation to the SLESRC Chair at least two (2) calendar months prior to the anticipated commencement of the proposed study.

The SL-GCPs requires that the EC review a proposed clinical trial within a reasonable time and document its views in writing, clearly identifying the trial, the documents reviewed, and the dates for the following: approval/favorable opinion; modifications required prior to its approval/favorable opinion; disapproval/negative opinion; and termination/suspension of any prior approval/favorable opinion. The EC must conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to human participants, but at least once per year.

There is no stated expiration date for EC approval in the G-SLAppClinTrial, the SL-GCPs, or the G-SLEthics.

(See the Submission Process and Timeline of Review sections for detailed submission process requirements.)

National Research Ethics Board of Liberia

As described in the G-NREB, the National Research Ethics Board of Liberia (NREB) must charge a minimal fee for the review of each submission type. Submissions include research protocols, re-submissions, amendments, and continuing reviews. The fee structure is based on the following application types: research protocol, behavioral research, investigational product (IP) (clinical trial), non-clinical trial, or waiver/exemption. Fees specifically associated with conducting a clinical trial involving IPs is based on a project’s scope, duration, sample size, and complexity as well as the types and quantities of IPs, among other criteria. The fees delineated in the G-NREB are as follows:

• Clinical trial: $7,000 USD
• Re-submission: $1,500 USD
• Continuing Review: $1,500 USD
• Amendment: $1,500 USD

Payment Instructions

No information is available regarding payment instructions for the NREB.

Atlantic Center for Research and Evaluation Institutional Review Board

As per the G-ACRE-IRB, the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) fees for protocol review other than clinical trials are as follows:

• Health, Behavioral and Education Research: $500 USD
• Re-Submission: $500 USD
• Continuing Review: $500 USD
• Amendment: $250 USD
• Foreign Student: $300 USD
• Liberian Student: $100 USD

The fee for non-sponsored research conducted by individual investigators is 50 percent of the sponsored research fee.

Payment Instructions

No information is available regarding payment instructions for the ACRE IRB.

Sierra Leone Ethics and Scientific Review Committee

The G-SLEthics indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), requires the principal investigator (PI) to pay a nonrefundable administrative fee to submit a protocol for ethical review and approval. The fees are as follows:

• For self-funded, individual Sierra Leonean researchers based in Sierra Leone: 300,000 Leones
• For graduate students studying in Sierra Leone: 200,000 Leones
• For Sierra Leonean students studying abroad: $100 United States Dollars (USD)
• For Sierra Leonean academics abroad: $150 USD
• For all foreign students studying abroad: $200 USD
• For self-funded, international researchers: $400 USD
• For national/local non-governmental organizations (NGOs)/community-based organizations (CBOs): 2,000,000 Leones
• For international NGOs based in Sierra Leone and international universities conducting non-clinical research: 4,000,000 Leones
• For multinational institutions, donor agencies, and institutions not ordinarily based in Sierra Leone: $1,500 USD
• For exclusively government funded studies: 500,000 Leones (must be submitted with a cover letter from the Permanent Secretary of the relevant Ministry or the Chief Medical Officer in the case of the Ministry of Health and Sanitation (MoHS))
• For any amendment made to a previously approved application: 25% of the current fee for the first request, 50% for the second, and 100% for subsequent ones. Sierra Leonean students are exempt from this charge.
• For an application extension: 25% of the original fee
• For exclusively electronic applications: additional $50 USD

Payment Instructions

No information is currently available regarding payment instructions for the SLESRC.

Overview

There are no applicable regulations or guidance regarding the authorization of ethics committees (ECs) in Liberia. However, per G-NREB, the National Research Ethics Board of Liberia (NREB) is responsible for maintaining a registry of health research ECs and mitigating conflicts among ECs, researchers, and research entities.

Registration, Auditing, and Accreditation

No information is available on registration, auditing, and accreditation requirements.

Overview

SLE-3 indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), does not have a supervisory or oversight mandate over institutional ECs for health research. Few institutions have their own institutional ECs.

Registration, Auditing, and Accreditation

No applicable requirements.

Overview

In accordance with the LibCTReg and the G-LibClinTrial, the sponsor, the legal representative, the principal investigator (PI), or the sponsor-investigator is responsible for submitting a clinical trial application to the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and obtain written permission from the National Research Ethics Board of Liberia (NREB). However, per the G-NREB, the PI must obtain ethics committee (EC) approval. The LibCTReg and the G-LibClinTrial state that the NREB and LMHRA reviews may be conducted in parallel. Per the G-LibClinTrial and the G-NREB, the LMHRA will only issue final approval once NREB approval is obtained.

Regulatory Submission

As indicated in the LibCTReg and the G-LibClinTrial, the sponsor or the representative should submit the application form and associated documents along with the prescribed fee. Also, per the G-LibClinTrial, four (4) sets of the application should be submitted both electronically and as printed copies to the LMHRA. The clinical trial application and any accompanying material must be submitted in English. If the documents are written in another language, a certified translation is required. Per LBR-29, the sponsor's representative must also submit a power of attorney attesting that the representative is a duly appointed agent.

Additionally, per the LibCTReg and the G-LibClinTrial, any substantial amendment to the approved clinical trial documentation, trial arrangements, and the investigational product must be submitted by the applicant to the LMHRA and the NREB together with the prescribed fee for the evaluation and authorization related to such amendment. Per the G-LibClinTrial, the submitted amendment(s) must be indicated in a signed cover letter identifying the clinical trial, the sponsor (applicant) and must include the possible consequences for the evaluation of the results. The amendment(s) must also be described in a completed Clinical Trial Amendment form (Annex 2 of the G-LibClinTrial), and the new version of the documents identified should include an updated version number and date. Also, the submitted document should clearly present scientific arguments justifying classification of an amendment to the LMHRA and the NREB, and, where applicable, supporting information must be included with the submission.

Per the G-LibClinTrial, the signed cover letter and clinical trial application dossier should be sent to the following:

The Managing Director
Liberia Medicine and Health products Regulatory Authority (LMHRA)
2^nd & 3^rd Floors Clay Building
Sekou Toure Avenue
Mamba Point
Monrovia, Liberia

Ethics Review Submission

National Research Ethics Board of Liberia

As delineated in the LibCTReg, application submissions to the NREB must include all of the information and documents as required for the board’s opinion. According to the G-NREB, PIs must submit typed, dated, and signed submissions electronically and by hard copy to the NREB. The documents should be formatted in standard font size 12, double-spaced, with the pages printed on one (1) side only. The NREB requires 15 comb-bound copies of the full research protocol along with the attachments listed in the G-NREB, and where applicable, an email version that includes the protocol title and the PI’s name. In addition, all protocols must be numbered appropriately and separately from all other supporting documentation (e.g., letters, participant information sheets and consent forms, questionnaires, curriculum vitae(s) (CVs), etc.). Supporting documents should also be numbered separately. Refer to LBR-32 for the NREB Research Protocol Template.

In addition to protocol submission requirements, the G-NREB also specifies that the complete application for ethical review and approval of a proposed health research study should be submitted by a PI to the NREB Secretariat. Applicants should submit the application three (3) weeks prior to the next NREB meeting. Applications submitted by a PI and researchers from foreign institutions must also include a local (resident) Liberian researcher on the research team as well as support letters and CV(s). See the G-NREB for detailed application submission requirements.

Per the G-NREB, NREB submissions should be submitted to the following address:

Director
National Research Ethics Board of Liberia (NREB)
First Floor West, John F. Kennedy Medical Center
Monrovia, Liberia
Email: nreb.liberia.gov@gmail.com

As delineated in the G-CTEmergncy, during a public health emergency in Liberia or in a neighboring country, the NREB requires protocols to be written in English and include, at a minimum, the proposed study, corresponding ethics approval, consent or assent forms, and data collection tools and forms. In addition, along with the usual documents for review (protocols, CVs, Human Subject Certificates, Good Clinical Practice, etc.), the following must be submitted:

• A collaboration letter (in the form of a memorandum of understanding) with sponsor institutions and research funders, including declarations of interest when possible
• A monitoring and safety management plan for the project provided by the PI and study sponsor
• Data-sharing and material transfer agreements for data and biological materials, especially if samples will be exported out of the country, ensuring compliance with the Laws of Liberia (a draft version may be submitted initially)
• Clear procedures for dissemination, publication, co-authorship, co-presentation, and intellectual property rights
• Plans to disseminate findings to the affected community, ensuring continued engagement and trust, especially among research participants
• Depending on the type of research, a local insurance policy for trials and interventions may be required

Atlantic Center for Research and Evaluation Institutional Review Board

As indicated in the G-ACRE-IRB, PIs are required to submit the research protocol as part of an application packet that includes the documentation specified by the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) submission form (see Article XXV in the G-ACRE-IRB). (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.) According to LBR-28, the ACRE IRB has not reinstated the requirement for PIs to submit eight (8) hard copies of the protocol. Applications should be submitted electronically. See the Submission Content section for additional documentation requirements.

Per the G-ACRE-IRB, all research proposals are to be submitted (either via electronic mail or in person) to:

The IRB Coordinator
Atlantic Center for Research and Evaluation (ACRE)
Ground Floor, Graduate School Building
University of Liberia
Capitol Hill
Monrovia, Liberia

Proposals submitted electronically should be sent to jktegli@yahoo.com and ulpireirb@gmail.com.

Overview

In accordance with the G-SLAppClinTrial and the SL-GCPs, Sierra Leone requires the sponsor and principal investigator (PI) to obtain clinical trial authorization from the Pharmacy Board of Sierra Leone (PBSL) before commencement of the clinical trial. Furthermore, per the G-SLEthics, the PI is required to obtain ethics approval from the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC).

As indicated in the G-SLAppClinTrial, a favorable opinion from the SLESRC is a required element of a clinical trial application to the PBSL. However, submissions to the PBSL and the SLESRC may be made in parallel in the case of a public health emergency or as deemed fit by the PBSL.

Regulatory Submission

The G-SLAppClinTrial indicates that applicants must submit 15 hard copies of all clinical trial application documents to the PBSL, as well as one (1) soft copy in Microsoft Word format (Acrobat PDF files are also acceptable).

As per the G-SLAppClinTrial, the delivery address for a clinical trial application is as follows:

The Registrar
Pharmacy Board of Sierra Leone
Central Medical Stores
New England Ville, Freetown
P.M.B. 322
Sierra Leone

As per SLE-23, the clinical trial application and accompanying material must be provided in English.

Ethics Review Submission

The G-SLEthics states that the PI should submit to the SLESRC five (5) hard copies of the full research proposal (and all supporting documents) detailing the ethical issues in the study and how they will be addressed (only three (3) copies for extensions), each in a separate envelope. In addition, an electronic copy of the application should be emailed to efoday@health.gov.sl. The G-SLEthics also indicates that the PI may submit an exclusively electronic application for an additional fee. See the Ethics Committee Fees section for more information.

The G-SLEthics states that PIs should submit their applications with a cover letter addressed to the Chair of the SLESRC at least two (2) calendar months before the anticipated commencement of the proposed study.

Per the G-SLEthics, the delivery information for the SLESRC is as follows:

Office of the Sierra Leone Ethics and Scientific Review Committee
Ministry of Health and Sanitation
Directorate of Policy, Planning & Information (DPPI)
Youyi Building, Fifth Floor, East Wing
Freetown
Sierra Leone
Phone: +23278 366493

Regulatory Authority Requirements

As set forth in the LibCTReg and the G-LibClinTrial, the sponsor, the legal representative, the principal investigator (PI), or the sponsor-investigator is required to obtain clinical trial authorization from the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and written permission from the National Research Ethics Board of Liberia (NREB). However, per the G-NREB, the PI must obtain ethics committee (EC) approval.

As per the LibCTReg and the G-LibClinTrial, the following documentation must be submitted to the LMHRA (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Cover letter (signed, witnessed, and notarized) including list of documents submitted and their version numbers and date
• Clinical trial application form including cover page
• Clinical trial protocol (see below for detailed protocol requirements)
• A list of the planned clinical trial sites and the planned number of study participants to be recruited at the sites located in Liberia
• Details of the site(s) where the trial is to be conducted and a duly justified written statement on the suitability of the clinical trial sites adapted to the nature and use of the investigational product (IP) and including a description of the suitability of facilities, equipment, human resources, and description of expertise, issued by the head of the clinic/institution at the trial site or by some other responsible person
• Participant information sheet, informed consent form(s) (ICF(s)) or video(s), or assent form(s) in case of minor(s) or persons under legal disability who are to participate in the trial, and informed consent procedure for clinical trials in humans
• Product information if the IP is registered (summary of product characteristics, patient information leaflet/package insert and labelling)
• Investigator’s Brochure (IB) containing relevant chemical, pharmaceutical, pre-clinical pharmacological and toxicological data, and where applicable, human or animal pharmacological and safety and efficacy clinical data about the IP
• If applicable, synopsis of previous trials with the IP(s)
• If applicable, electronic copies of key, peer-reviewed publications following the International Committee of Medical Journal Editors (ICMJE) recommendations to support the application
• Copy or copies of recruitment advertisement(s), if applicable, and questionnaires
• Investigational medicinal product (IMP) dossier, if applicable
• Product information and certificate of analysis (CoA) for the concomitant and rescue medications
• Good Manufacturing Practice (GMP) certificate issued from the national regulatory authority of the country where the IP is manufactured, translated into English language
• CoA of the IP(s)
• Certificate(s) of accreditation for the central laboratories
• Workload forms for investigators
• Signed declaration by the applicant (includes a commitment to adhere to the ethical principles outlined in the Declaration of Helsinki (LBR-27) and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (LBR-8)
• Signed declaration by the national PI
• Signed curriculum vitae (CV) for all key staff participating in the conduct of the clinical trial (e.g., PI and/or co-investigators, study coordinator, regional and local monitor, contract research affiliate, etc.)
• Signed declaration(s) by each investigator(s)
• Signed joint financial declaration between the sponsor and the PI
• Signed declaration by the sub-investigators and key staff participating in the trial
• Signed declaration by the regional clinical trial monitor(s)
• Signed declaration by the sponsor/sponsor-investigator
• Proof of registration with the Pan African Clinical Trials Registry (PACTR) (LBR-36) or another World Health Organization (WHO) Primary Registry (LBR-35)
• Active clinical trial insurance (Phase I, II, and III)
• Evidence of Insurance coverage for prospective participants
• Proof of sponsor indemnification for investigators and trial site
• Good Clinical Practice (GCP) certificates for the investigators
• Proof of registration of the key investigators with a professional statutory body, if applicable
• Proof of residence in Liberia for the PI
• Proof of professional indemnity (i.e., malpractice insurance)
• Study budget
• In case of parallel submission, proof of submission of the clinical trial application to the National Research Ethics Board of Liberia (NREB)
• The written permission of the NREB in case of sequential submission, and in case of parallel submission, the updated versions of documents or information as requested by the NREB, for the conduct of the clinical trial, if applicable
• Information on the composition of the Data and Safety Monitoring Board (DSMB)—including the list, terms of reference, and CVs for its members—justifying their expertise as members of the DSMB
• Summary of product characteristics or other professional information for all registered medicines used in the trial, or the international equivalent thereof if the medicines are not registered in Liberia
• Registered IPs should include registered indication or registered dosage regimen
• Recruitment arrangements
• Request for authorization of export of biological samples out of Liberia as well as the respective material transfer agreement, if applicable
• Summary of the clinical trial (100-150 words) to be made publicly available on the LMHRA website
• Proof of payment of the appropriate application fee

Refer to the LibCTReg and the G-LibClinTrial for detailed application requirements and expedited application documentation requirements.

The LibCTReg also notes that in the case of emergency situations, the LMHRA may also make exemptions to the documentation requirements for the submission of clinical trial applications. Refer to 2.3 of the G-LibClinTrial for additional information on how to submit an expedited clinical trial application package.

Ethics Committee Requirements

National Research Ethics Board of Liberia

As indicated in the G-NREB, for clinical trials and biomedical/epidemiological study submissions, the following documents may be included, but are not limited to:

• Full protocol and executive summary (refer to LBR-32 for research protocol template)
• Sponsor’s protocol, if applicable (per LBR-32)
• Signed agreement between sponsors and PI, where applicable
• A statement that the researcher(s) agree to comply with ethical principles set out in relevant guidelines
• IB
• Material Transfer Agreement (MTA) for shipment of specimen(s)/biological material(s) outside of Liberia, where applicable (See also Specimen Import & Export and Consent for Specimen sections)
• Data Sharing Agreement, where applicable
• Administrative information on sponsors of the study
• Signatory page of key persons from the collaborative institutions involved in the study (i.e., Sponsor Signatory Approval Page duly signed, with date, where applicable)
• Written ICF with dates and version number and translations into the local language, where necessary
• Written parental consent form for children under 17 years of age (if study involves minors)
• Written parental consent form and assent form for children under 18 years of age (15-17 years) (if study involves adolescents)
• All forms, documents, and community engagement advertisements to be used in the recruitment of potential participants
• All data collection forms to be used in the research including, but not limited to, case report forms, questionnaires, interview schedules, etc., clearly indicated and dated
• Referral forms for treatment, where applicable
• Study budget
• Study timeline
• Any other information deemed necessary to facilitate the review process
• Current CV(s) of PI and co-investigator(s) if not submitted to the NREB in the preceding 12 months
• Profile on previous study (i.e., Phase I & Phase II studies, where applicable)
• Investigator Agreement (PI’s responsibility), page duly signed with name and date, and current Certificate of Training in GCP for PI(s)
• DSMB membership and charter of work/current member CVs
• Insurance coverage for study participants
• Scientific review approval
• LMHRA approval letter for use of the IPs/devices and clinical trial approval (this should be submitted after the NREB approval)

Atlantic Center for Research and Evaluation Institutional Review Board

Per the G-ACRE-IRB, the following documentation must be submitted along with the application for an initial application review of a protocol for clinical research other than a clinical trial (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• Cover letter
• Protocol summary (Article XXV (Section 25.02) in the G-ACRE-IRB)
• Protocol and/or amendments (including data collection instruments, surveys, tests, questionnaires, debriefing information, etc.)
• IB, where applicable
• Evidence of submission and/or approval from other ECs, where applicable
• Proof of research ethics training (i.e., certificate in human subject protection) by research team members
• ICFs, where applicable
• Questionnaires and other study instruments, where applicable (including interview schedules, recruitment and interview scripts, and recruitment materials (Article XXV (Section 25.02) in the G-ACRE-IRB)
• DSMB and Institutional Biosafety Committee (IBC) records, if applicable
• MTA, if applicable (See also Specimen Import & Export and Consent for Specimen sections)
• Status report for ongoing study (applicable for continuing review)
• Letter of collaboration or support with collaborating entity/researcher(s), if applicable
• Capacity building plan for collaborating agency/researcher, if applicable
• Investigator(s) CVs
• Social corporate responsibility plan for communities, if applicable
• Letter from an appropriate official permitting research activities on their premises, if the research/recruitment will take place in or through schools, businesses, care facilities, or other organizations
• Budget

Clinical Protocol

Liberia Medicines and Health Products Regulatory Authority

Per the G-LibClinTrial, the contents and format of the clinical trial protocol should follow the requirements laid down in LBR-8. Accordingly, LBR-8 requires the following protocol contents:

• General information (protocol title, identifying number, and date; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study)
• Background information
• Objectives and purpose
• Trial design
• Selection, withdrawal, and treatment of participants
• Assessment of efficacy
• Assessment of safety
• A description of the statistical methods to be used in the trial
• Direct access to source data and documents
• Quality control and quality assurance
• Ethical considerations
• Data handling and recordkeeping
• Publication policy

In addition, as indicated in the G-LibClinTrial, the protocol should contain a statement that the trial will be conducted in compliance with the protocol, GCP, and the applicable regulatory requirements, and signed and dated by both the sponsor/sponsor’s representative and PI to document the investigator’s and sponsor’s agreement to the protocol. If the protocol is not signed and dated by both parties, a corresponding declaration that is signed and dated by both must be provided to the LMHRA with the application.

National Research Ethics Board of Liberia

The LBR-32 requires the following elements to be included in the research protocol template submission:

• Specific aims
• Background and significance of research
• Research locations and collaborating sites
• Study team
• Study design
• Recruitment methods
• Consent process
• HIPAA privacy protections
• Vulnerable populations
• Risks
• Benefits
• Participant privacy
• Data confidentiality
• Data/statistical analysis plan
• Costs and compensation
• Sharing study results
• Research related injuries
• Reportable events
• Regulatory compliance
• Data or specimen banking (repositories)
• Clinical trials
• Device, if applicable
• Drug/biologic

National Research Ethics Board of Liberia/Atlantic Center for Research and Evaluation Institutional Review Board

Per the NatResHlthPlcy, Liberian ECs including the NREB and the ACRE IRB, should structure the research protocol according to the follow format:

• Title
• Investigators’/Researchers’ information including contact addresses
• Abstract/Summary
• Background/Introduction
• Aims and objectives
• Study design and methods
• Data collection, management, and analysis
• Study administration and ethical issues
• Resource requirements
• Study plan
• Supervision
• Dissemination and outcome

For more details, see Annex 2 of the NatResHlthPlcy.

Atlantic Center for Research and Evaluation Institutional Review Board

According to the G-ACRE-IRB, the clinical research protocol should contain the elements included in the ACRE IRB submission form (see Article XXV in the G-ACRE-IRB). The initial protocol submission should also contain:

• Original protocol (including cover sheet, abstract, and research section including the Human Subjects Section)
• Application letter
• ICF and/or assent form
• Sample questions survey
• Investigator(s) CVs
• Qualification of study site(s)
• Protocol budget
• Copy of ACRE IRB approval, if available
• Study design
• Study participation, including informed consent procedures and content/language and participant information sheet content (See also the Documentation Requirements section)

Note: Per the G-ACRE-IRB, for regular renewal or interim modification reviews of a protocol, PIs should attach current consent document(s) and include instruments ONLY if changes are being proposed (Article XXV (Section 25.02) in the G-ACRE-IRB).

Regulatory Authority Requirements

As per the G-SLAppClinTrial and SLE-9, the following documentation must be submitted to the Pharmacy Board of Sierra Leone (PBSL) (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Cover letter, including the list of documents submitted and their version number and date
• Non-refundable application fee as specified in the PBSL’s Fee Schedule (see Appendix I of the G-SLAppClinTrial)
• Protocol with all the relevant sections including site-specific addendums (see below for detailed protocol requirements)
• Two (2) copies of the completed clinical trial application forms signed by authorized persons, including cover page (see Appendix II of the G-SLAppClinTrial)
• Proof of registration with the Pan African Clinical Trial Registry (PACTR) (SLE-19) or an internationally recognized PBSL-approved online registry
• Investigator’s Brochure (IB)
• Synopsis of previous trial(s) with the investigational product(s) (IP(s)), if applicable
• Summary of product characteristics or other professional information for all registered medicines used in the trial, or the international equivalent if the medicines are not registered in Sierra Leone
• A list of the planned clinical trial sites and the planned number of trial participants at the sites
• The name and position of the principal investigator(s) (PI(s)) who will be responsible for the sites where the trial is to be conducted, who must be registered with the relevant statutory health council, where applicable, and a resident in Sierra Leone
• Signed curriculum vitae(s) (CVs) for all key staff participating in the conduct of the clinical trial, as well as other relevant documents (see Annex 8 of SLE-6 for the recommended CV format for staff conducting clinical trials)
• Proof of current training in good clinical practice (GCP) for investigator(s), pharmacist(s), and monitor(s)
• Proof of registration of the key investigators with a professional statutory body, if applicable
• Any previous training in the principles of GCP or experience obtained from work with clinical trials and patient care
• Any conditions, such as economic interests and institutional affiliations, that might influence the impartiality of the investigator(s)
• Proof of current, relevant, and appropriate study insurance for all participants undertaken by the sponsor
• Proof of sponsor indemnification for investigator(s) and trial site(s) (see Annex 7 of SLE-6 for suggested wording of the sponsor indemnification)
• Professional indemnity insurance for investigator(s) and other trial staff
• Details of the site(s) where the trial is to be conducted and a duly justified written statement on the suitability of the clinical trial sites adapted to the nature and use of the IP. This should include a description of the suitability of facilities, equipment, and human resources, and a description of expertise, issued by the head of the clinic/institution at the clinical trial site or other responsible party
• A favorable opinion from the Sierra Leone Ethics and Scientific Review Committee (SLESRC). In the case of a parallel submission, proof of clinical trial application submission to the SLESRC and the updated versions of documents or information as requested by the SLESRC are required
• Recruitment arrangements
• Signed joint financial declaration between the sponsor and the PI (see Appendix IIIc of the G-SLAppClinTrial and Annex 4 of SLE-6)
• Data Safety Monitoring Board (DSMB) membership, CVs, and signed charter
• IP dossier and label
• Product information if the IP is registered: summary of product characteristics, patient information leaflet/package insert, and labelling
• Current good manufacturing practice (GMP) certificate issued from the national regulatory authority of the country where the IP is manufactured
• Product information and certificate of analysis for the concomitant and rescue medications
• Certificate(s) of analysis of the IP
• Certificate(s) of accreditation for the central laboratories
• Participant information sheet, informed consent form (ICF), and informed consent procedure
• Signed declaration by the applicant (see Annex 2 of SLE-6)
• Sponsor/PI contractual agreement, including the study budget
• Signed declaration by the PI and the sponsor of the trial that they are familiar with and understand the protocol, and will comply with GCP as determined by the PBSL in the conduct of the trial (see Appendix IIIa of the G-SLAppClinTrial and Annex 4 on page 12 of SLE-6)
• Workload forms for investigator(s)
• Signed declaration(s) by the local PI, as well as each investigator and key staff participating in the clinical trial (see Appendix IIIb of the G-SLAppClinTrial and Annex 5 of SLE-6)
• Signed declaration(s) by the sub-investigators and key staff participating in the clinical trial

• CVs and signed declaration by regional monitor(s) (see Annex 6 of SLE-6)

• Copies of recruitment advertisement(s) and questionnaires, if applicable
• Electronic copies of key peer reviewed publications following International Committee of Medical Journal Editors (ICMJE) recommendations to support the application, if applicable
• Labelled CD-ROM (list of files submitted on CD-ROM)

See the G-SLAppClinTrial for more details, including the application submission checklist (Appendix IIa) and the application form (Appendix IIb). The application checklist and form are also available at SLE-9 and SLE-6, respectively.

Additionally, see Appendix V of the G-SLAppClinTrial for the Clinical Trial Amendment Form. See also SLE-8 for the amendment checklist.

Ethics Committee Requirements

As per the G-SLEthics, the SLESRC requires the PI to submit the following documentation for ethics approval:

• Cover letter to the Chair of the Committee
• ICF attached to each proposal (Committee does not accept verbal consent, except where it is supported by an independent witness)
• Completed checklist for the Essential Elements in the Application for Approval (see the G-SLEthics)
• Brief CV for the PI and associates clearly stating their roles (not more than four (4) pages each)
• Study proposals submitted for award of a degree must be accompanied by a letter of confirmation from the supervisor and approval by the institution’s review board
• Requests for amendment or extension of study should include a copy of the previous approval letter
• A non-refundable administrative fee for each proposal submitted (see the Ethics Committee Fees section for detailed fee information)

Clinical Protocol

The G-SLAppClinTrial indicates that the clinical trial protocol must comply with the International Council for Harmonisation's (ICH) Guideline for Good Clinical Practice E6(R2) (SLE-24) and the SL-GCPs. Accordingly, the protocol must include:

• General information (protocol title, identifying number, and date; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study)
• Background information
• Objectives and purpose
• Trial design
• Selection, withdrawal, and treatment of participants
• Assessment of efficacy
• Assessment of safety
• A description of the statistical methods to be used in the trial
• Direct access to source data and documents
• Quality control and quality assurance
• Ethical considerations
• Data handling and recordkeeping
• Financing and insurance
• Publication policy

Overview

According to the LibCTReg and the G-LibClinTrial, the National Research Ethics Board of Liberia (NREB) and the Liberia Medicines and Health Products Regulatory Authority (LMHRA) reviews may be conducted in parallel. However, per the G-LibClinTrial and the G-NREB, the LMHRA will only issue final approval once NREB approval is obtained.

Regulatory Authority Approval

The LibCTReg and the G-LibClinTrial indicate that upon receipt of a clinical trial application, the LMHRA screens the application package for completeness and must inform the applicant in writing about the validity of the application or the formal grounds for non-acceptance of the application within 10 working days of application receipt. If applicable, the applicant, in turn, must address formal grounds for non-acceptance within 10 working days.

The LibCTReg and the G-LibClinTrial further explain that after validation of a complete clinical trial application, the LMHRA must inform the applicant in writing about the outcome of the scientific assessment of the application within a maximum of 60 working days, or according to the following timeline for the different types of investigational products (IPs), unless otherwise specified by the LMHRA on a case-by-case basis:

• Pharmaceutical IPs: 45 working days
• Biological and biotechnology IPs: 60 working days
• Genetically modified organism IPs: 90 working days

As indicated in the LibCTReg and the G-LibClinTrial, these timelines exclude time taken for the applicant to respond to queries from the LMHRA during the review and decision process. If changes are required and the applicant fails to modify the application within a maximum of 30 working days, the application will be rejected. Per the G-LibClinTrial, during the clinical trial scientific assessment process, the LMHRA may request additional documents or changes through a query letter. Once a query has been raised and issued to the applicant, the process stops when the LMHRA receives a written response to the query. If the LMHRA requires changes to the application, and the applicant fails to modify the application within a maximum of 90 days, the application will be rejected.

As explained in the G-LibClinTrial, the LMHRA must issue a clinical trial certificate indicating the LMHRA clinical trial number to the applicant upon application approval. The clinical trial certificate may contain conditions required by the LMHRA with respect to the conduct or reporting of the trial. If the application is rejected, the applicant can submit a written appeal to the LMHRA’s Managing Director within 60 days of receipt of the rejection notice.

Per the G-LibClinTrial, in the case of expedited clinical trial application reviews, the LMHRA will review the application in no more than 14 working days for approved products and within 21 days for new products.

Additionally, per the G-LibClinTrial, the LMHRA must respond to any substantial clinical trial amendment within 20 calendar days upon receipt of the written decision from the NREB.

Ethics Committee Approval

National Research Ethics Board of Liberia

Pursuant to the G-NREB, principal investigators (PIs) are required to submit new research protocols no later than one (1) month prior to the next bi-monthly board meeting. The NREB should notify PIs in writing of its decision within two (2) weeks following a board meeting, where applicable, following a complete review of the protocols. The G-NREB does not specify an approval expiration date.

The G-NREB explains that for protocol amendments, the NREB Secretariat, in consultation with the Chair, will make a determination regarding the type of review (full board review or expedited given the risk) and will notify the investigator within three (3) weeks upon submission per the board’s decision. Expedited reviews must take no more than three (3) weeks, and if any committee member raises a concern about a protocol that was expedited, the protocol must undergo a full board review.

Refer to the G-NREB for additional information on the various submission types that may be submitted to the board and their corresponding review and approval processes.

Atlantic Center for Research and Evaluation Institutional Review Board

As specified in the G-ACRE-IRB, PIs are required to submit all application materials to the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) four (4) weeks in advance of the date that a decision is requested. (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.) In the case of full review studies, submission is required four (4) weeks prior to the next scheduled ACRE IRB meeting. The ACRE IRB will convene a special meeting, if necessary, to accommodate the PI’s compliance with an external funding deadline; however, submission is required four (4) weeks prior to the special meeting date.

As specified in the G-ACRE-IRB, the ACRE IRB approval will commence on the day the study is approved and will expire within a defined time period based on a risk assessment and regulations. If specific conditions are stipulated in the approval letter, those conditions must be met by the designated date or approval may be withdrawn. No timeline of review is specified for the ACRE IRB’s review. However, the G-ACRE-IRB states that the clinical research protocol and accompanying documents are approved as they are submitted.

The G-ACRE-IRB states that the ACRE IRB must also review and approve any clinical research protocol amendments prior to those changes being implemented. The clinical research protocol submission is reviewed either via expedited procedures (for minor changes) or via full board review (for all other changes). Refer to the G-ACRE-IRB for clinical research protocol amendment documentation submission and procedural requirements.

Overview

The G-SLAppClinTrial indicates that the Pharmacy Board of Sierra Leone (PBSL) and the Sierra Leone Ethics and Scientific Review Committee (SLESRC) reviews may be conducted in parallel in the case of a public health emergency or as deemed fit by the PBSL. For parallel submissions, the PBSL requires proof of the application’s submission to the SLESRC, as well as any updated versions of documents or information as requested by the SLESRC.

Regulatory Authority Approval

Per the G-SLAppClinTrial, the PBSL’s processing times of clinical trial applications for different investigational products (IPs) are as follows, unless otherwise specified by the PBSL on a case-by-case basis:

• Medical devices - 40 working days
• Pharmaceuticals - 50 working days
• Biological and biotechnology medical products - 60 working days
• Genetically modified organisms - 120 working days

As delineated in the G-SLAppClinTrial, the PBSL will inform the applicant in writing about the receipt of a valid clinical trial application or the formal grounds for non-acceptance within 10 working days from the receipt of the application. The applicant must address formal grounds for non-acceptance within 10 working days. If changes are required and the applicant fails to modify the application correspondingly within a maximum of 30 working days, following the reasoned objections, the application will be deemed rejected. If the PBSL requires changes to the application and the applicant fails to modify the application correspondingly within a maximum of 90 days following the reasoned objections, the application will be deemed rejected. See Figure 1 in Section 5.17 of the G-SLAppClinTrial for more details on the PBSL’s clinical trial authorization process.

According to the G-SLAppClinTrial, if expedited review of a clinical trial during a public health emergency is anticipated, the applicant should inform the PBSL in writing. The timeline for processing such applications is 10-20 working days. For more information on expedited review, see the Scope of Assessment section and the G-SLAppClinTrial.

The G-SLAppClinTrial further indicates that any proposed amendment to the trial application, trial arrangements, and IP must be submitted to the SLESRC and the PBSL for approval before such amendments are carried out. The PBSL’s processing time for protocol amendment applications is 30 working days. For more details on amendment requirements, see the G-SLAppClinTrial.

The G-SLAppClinTrial states that the PBSL must issue a Clinical Trial Certificate to authorize the trial to be conducted, which must be renewed annually. The PBSL’s processing time for a Clinical Trial Certificate renewal application is 15 working days.

The G-SLAppClinTrial further states that if a clinical trial application is rejected by the PBSL, any person or institution may appeal the decision in writing within 60 days after receipt of the decision, to request PBSL review or reconsideration of the initial decision. The PBSL’s response to the appeal application must be addressed to the affected person or institution within 90 days of the appeal’s submission. For more information on appeal contents and timelines, see the G-SLAppClinTrial.

According to the G-SLAppClinTrial, the PBSL’s processing time for IP import permits is 10 working days.

Ethics Committee Approval

No information is currently available on the SLESRC’s timeline of review.

Overview

In accordance with the LMHRA-Act, the LibCTReg, and the G-LibClinTrial, a clinical trial can only commence after the sponsor or the representative receives authorization from the Liberia Medicines and Health Products Regulatory Authority (LMHRA). The LibCTReg and the G-LibClinTrial, in turn, state that the sponsor, the legal representative, the principal investigator (PI), or the sponsor-investigator must obtain written permission from the National Research Ethics Board of Liberia (NREB). In addition, per the G-LibClinTrial, the appointed PI must provide proof of residency in Liberia in the clinical trial application submission package.

As per the G-LibClinTrial, the sponsor or the representative is required to obtain LMHRA approval for the clinical trial before the import of an investigational product (IP) to be used in the trial is authorized. However, parallel submission for approval of the clinical trial and the permit to import the IP is possible if the import permit application is included in the clinical trial application submission package.

In addition, per the LibCTReg, the applicant must inform the LMHRA in writing of the exact clinical trial commencement date (i.e., first patient first visit). If the trial does not begin within 90 calendar days from issuance of the clinical trial certificate, the applicant must show cause for the failure to commence as scheduled and solicit issuance of a new clinical trial certificate. Pursuant to Part VIII of the LMHRA-Act, the LibCTReg delineates that failure to inform the LMHRA of the commencement or not starting the clinical trial within this period will have regulatory implications including, but not limited to, the payment of administrative charges for the re-issuance of the clinical trial certificate on its expiration.

The LibCTReg also states that the sponsor, the investigator, and all of the persons involved in the clinical trial must fulfill the requirements of good clinical practice in accordance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (LBR-8) and the World Health Organization (WHO)'s Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (LBR-25) as determined by the LMHRA. The G-LibClinTrial further specifies that the LMHRA has adopted LBR-8 for use along with the LMHRA guidelines.

Clinical Trial Agreement

While a signed clinical trial agreement is not an official requirement, the G-LibClinTrial states that the protocol should contain a statement that the trial will be conducted in compliance with the protocol, LBR-8, and the applicable regulatory requirements. The protocol should also be signed and dated by both the sponsor or the representative and the PI to document the investigator’s and the sponsor’s agreement to the protocol. If the protocol is not signed and dated by both parties, a corresponding declaration signed and dated by both must be provided to the LMHRA with the application.

Clinical Trial Registration

As delineated in the LibCTReg, the sponsor or the sponsor-investigator must register all clinical trials with a public international database. The G-LibClinTrial further specifies that the LMHRA requires the sponsor or the representative to provide proof of registration with the Pan African Clinical Trials Registry (PACTR) (LBR-36) or another WHO Primary Registry (LBR-35).

Overview

In accordance with the G-SLAppClinTrial, a clinical trial can only commence after the sponsor and the principal investigator (PI) receive authorization from Sierra Leone’s Pharmacy Board of Sierra Leone (PBSL) via a Clinical Trial Certificate. Additionally, per the G-SLAppClinTrial, the Sierra Leone Ethics and Scientific Review Committee (SLESRC) fulfills the functions of the ethics committee (EC) (known as an Independent Ethics Committee (IEC) in Sierra Leone) in the country. Ethics approval must be obtained from the SLESRC prior to initiating a study. The G-SLEthics indicates that the PI must obtain the SLESRC approval.

In addition, as per SLE-23, no waiting period is required following the applicant’s receipt of PBSL and SLESRC approval. According to the G-SLAppClinTrial, the PBSL must be informed of the trial’s initiation in writing on the exact date the study commences. If the trial does not begin or is delayed, then the PBSL must be informed of the new commencement date within 90 days of the Clinical Trial Certificate’s issuance. SLE-23 further indicates that investigators are required to notify their local institution prior to initiating a trial.

As per the G-SLAppClinTrial, a permit from the PBSL is required for the import of an investigational product (IP) to be used in a trial. (See the Manufacturing & Import section for additional information.)

Clinical Trial Agreement

The G-SLAppClinTrial and the SL-GCPs state that the clinical protocol submitted to the PBSL must include a signed contractual agreement between the sponsor and the PI.

As required by the G-SLAppClinTrial, the sponsor/PI contractual agreement must have sections indicating:

• Study title
• Protocol version and date
• Trial site
• IP information
• Definitions of all terms
• Effective date of agreement
• Outline of the sponsor’s responsibilities, which must include general management of the trial; provision of adequate funding, resources/logistics and IPs for the study; and insurance for the study participants
• Outline of the PI’s responsibilities, which must include retaining all trial related essential documents until the sponsor informs the PI these documents are no longer needed
• Term (period of study duration) and termination of agreement (conditions for this)
• Confidentiality

Per the SL-GCPs, the sponsor should obtain the investigator’s/institution’s agreement to:

• Conduct the trial in compliance with good clinical practice (GCP), with the applicable regulatory requirement(s), and with the PBSL-approved protocol
• Comply with procedures for data recording/reporting
• Permit monitoring, auditing, and inspection

The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Clinical Trial Registration

The G-SLAppClinTrial states that proof of trial registration with the Pan African Clinical Trial Registry (PACTR) (SLE-19), or an internationally recognized PBSL-approved online registry, must be submitted as part of a clinical trial application to the PBSL.

Safety Reporting Definitions

According to the LibCTReg, the G-LibPV, and the G-ACRE-IRB, the following definitions provide a basis for a common understanding of Liberia’s safety reporting requirements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product, or any abnormal sign (e.g., any abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant’s involvement in the research; AEs encompass both physical and psychological harms
• Adverse Drug Reaction (ADR) – Any noxious and unintended responses in a participant to an investigational medicinal product which is related to any dose administered to that participant. A causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out
• Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or may jeopardize the participant’s health and may require medical or surgical intervention based upon appropriate medical judgment (e.g., the development of drug dependency or drug abuse). A causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out
• Unexpected Adverse Drug Reaction – An adverse reaction where the nature or severity is inconsistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational product (IP) or package insert/summary of product characteristics for an approved product)

Safety Reporting Requirements

Per the LibCTReg and the G-LibClinTrial, the principal investigator (PI) or the sponsor should report any SAEs/SADRs suspected to be related to the IP immediately, and in any event, no later than three (3) calendar days after becoming aware of the event to the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and the National Research Ethics Board of Liberia (NREB). Per the G-LibClinTrial, in the case of multicenter trials involving clinical trial sites (in and outside of Liberia), the PI or sponsor must submit all SAEs/SADRs deemed to be related to the IP within 15 calendar days to the LMHRA and the NREB. The PI or the sponsor is also required to indicate the timelines allocated for related investigations.

The G-LibPV provides the following scale by which to assess the severity of AEs/ADRs: Mild, Moderate, Severe, or Fatal. For more details, see Table 2 in G-LibPV. The G-LibPV also provides criteria for determining the link between the intervention and the AEs/ADRs as either certain, probably/likely, possible, unlikely, conditional/unclassified, or un-assessable/unclassified. For more details, see Table 3 in G-LibPV.

Investigator Responsibilities

The G-NREB indicates that investigators are required to submit a report to the NREB for all AEs except those resulting in death within seven (7) calendar days. Investigator(s) must report all deaths that are possibly, probably, or definitely related to the study within 24 hours to the NREB.

Other events that must be reported to the NREB include the following:

• Unanticipated problems involving risks to participants or others
• Non-compliance (including major protocol deviations and non-compliance unrelated to a protocol deviation)
• New information that might affect the willingness of participants to enroll or continue to participate in the study

As indicated in the G-ACRE-IRB, for studies using the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB), the investigator must promptly report any unanticipated problems to the ACRE IRB in accordance with the following guidelines (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• Unanticipated problems that are SAEs must be reported to the ACRE IRB within five (5) business days of the investigator becoming aware of the event. The board strongly recommends that a preliminary report be submitted by the investigator within 48 hours of learning of the SAE with a formal follow-up report submitted within the above timeline
• Any other unanticipated problem should be reported to the ACRE IRB within two (2) weeks of the investigator becoming aware of the problem. The board strongly recommends that a preliminary report be submitted by the investigator within five (5) business days of learning of the unanticipated problem with a formal follow-up report submitted within the above timeline

In addition, per the G-ACRE-IRB, when making a report to the ACRE IRB, the investigator should include the following information:

• The appropriate identifying information for the research protocol, such as the title, the investigator’s name, and the ethics committee (EC) project number
• A detailed description of the AE, incident, experience, or outcome; however, to maintain confidentiality, participants’ names and identifiable information should not be included in the report
• An explanation of the basis for determining that the AE, incident, experience, or outcome represents an unanticipated problem
• A description of any changes to the protocol or other corrective actions that have been taken or are proposed in response to the unanticipated problem

Other Safety Reports

As explained in the G-ACRE-IRB, for studies using the ACRE IRB, the ACRE IRB Executive Committee conducts the initial review of unanticipated problems. This committee is authorized to take the following actions in response to any incident report:

• Conduct an administrative review of the report, including assessing whether the incident constitutes an unanticipated problem
• If a convened ACRE IRB review is needed, the Chair assigns the incident report for review at the next available regularly scheduled ACRE IRB meeting
• Alternately, the ACRE IRB Executive Committee may convene an emergency meeting of the ACRE IRB to review the report
• If the ACRE IRB Executive Committee finds that the rights, safety, and welfare of the participants are jeopardized by the research, the Chair may suspend the research until such time when the full ACRE IRB can convene to review the report. When reviewing a particular incident, experience, or outcome reported as an unanticipated problem by the investigator, the board may determine that the incident, experience, or outcome does not meet the criteria for an unanticipated problem

Following a review of the unanticipated problem report, per the G-ACRE-IRB, the ACRE IRB may require the following actions, in order to protect the ongoing safety of the research participants:

• Modification of participant inclusion or exclusion criteria to mitigate the newly identified risks
• Implementation of additional procedures for monitoring participants
• Modification of informed consent documents to include a description of newly recognized risks
• Addition of provisions about newly recognized risks to previously enrolled participants
• Suspension of enrollment of new participants
• Suspension of research procedures in currently enrolled participants
• Suspension of the entire study
• Termination of approval for the entire study

Per the G-ACRE-IRB, if the solution to an unanticipated problem is to amend the research protocol and/or informed consent forms, then an amendment request must be made to the ACRE IRB. If the changes are minor, they may be reviewed by expedited review procedures. If the changes are major, they must be reviewed and approved by the convened board. Changes made in response to an unanticipated problem must be reviewed and approved by the ACRE IRB before being implemented, except where implementation is necessary to eliminate immediate hazards to research participants.

Form Completion & Delivery Requirements

Liberia Medicines and Health Products Regulatory Authority

As per the G-LibPV, all SAEs/SADRs and SUSARs must be reported on the LMHRA’s Suspected Adverse Drug Reaction Reporting Form (Annex 3 in the G-LibClinTrial).

Atlantic Center for Research and Evaluation Institutional Review Board

Per LBR-28, since all clinical trials protocols submitted to the ACRE IRB are referred to the NREB for review, all AEs/ADRs and SAEs/SADRs are only sent to the NREB.

National Research Ethics Board of Liberia

No information is available on NREB safety reporting forms and delivery requirements.

Safety Reporting Definitions

According to the G-SLAppClinTrial and the SL-GCPs, the following definitions provide a basis for a common understanding of Sierra Leone’s safety reporting requirements:

• Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant to whom an investigational product (IP) has been administered, including occurrences which are not necessarily caused by or related to that product

• Adverse Drug Reaction (ADR) – Any noxious and unintended response to an IP which is related to any dose administered to that participant

• Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect

• Unexpected Adverse Event/Adverse Drug Reaction – An adverse reaction where the nature or severity is inconsistent with the applicable product information

Safety Reporting Requirements

As stated in the G-SLAppClinTrial, the sponsor and the principal investigator(s) (PIs) are responsible for proper reporting of AEs and SAEs. The sponsor should expedite the reporting of all AEs that are both serious and unexpected. Any SAEs/SADRs must be reported to the Pharmacy Board of Sierra Leone (PBSL) immediately where possible. In any event, the SAEs/SADRs must be reported to the PBSL within 48 hours of site awareness, but no later than 15 calendar days.

The SL-GCPs indicates that all SAEs/SADRs should be reported immediately except for those incidents documented by the protocol or the investigator’s brochure that do not require immediate reporting. The immediate reports should be followed promptly by detailed, written reports. The reports should identify participants by unique code numbers. AEs and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the PBSL. Furthermore, per the G-SLAppClinTrial, any SAE/SADR related to the IP should receive immediate medical attention.

In addition, per the G-SLAppClinTrial, any frequent AEs/ADRs should be reported to the PBSL immediately where possible, and in any event, within seven (7) days of site awareness. Non-serious AEs must be reported to the PBSL on request and, where applicable, submitted as part of an application for registration.

The G-SLAppClinTrial indicates that non-serious AEs must be reported on request and where applicable, submitted as part of an application for registration.

Investigator Responsibilities

The G-SLAppClinTrial states that in the event of an SAE/SADR, the PI is required to submit follow-up information (e.g., copies of diagnostic test results, laboratory reports, medical record progress notes) as soon as it becomes available. This information should be clearly marked as updated information and include the protocol and participant numbers. Follow-up reports must be submitted immediately when there is a change in the severity of the SAE/SADR initially reported, whenever there is any new development on an initially reported SAE/SADR, and/or when the SAE/SADR is resolved. Follow-up reports must include an assessment of the importance and implication of any findings. All fatal cases must be accompanied by a formal autopsy report. In exceptional circumstances where a formal autopsy is not practicable, provision of a verbal autopsy report must be prior approved by the PBSL and be given with ample reasons. SLE-23 indicates that the investigator is responsible for submitting these follow-up reports, but the sponsor can also report through the contract research organization.

As per the SL-GCPs, the investigator should also comply with applicable regulatory requirements related to reporting unexpected SAEs/SADRs to the PBSL. For a reported death, the investigator should supply the PBSL with any additional requested information (e.g., autopsy reports and terminal medical reports).

Sponsor Responsibilities

According to the G-SLAppClinTrial and the SL-GCPs, the sponsor is required to expedite the reporting of all AEs/ADRs that are both serious and unexpected to the PBSL. The SL-GCPs further indicates that the sponsor must also expedite the reporting of all AEs/ADRs that are both serious and unexpected to all concerned investigator(s)/institutions(s) and the ethics committee(s).

Per the SL-GCPs, the sponsor is responsible for the ongoing safety evaluation of IPs, and should promptly notify the investigator(s)/institution(s) and the PBSL of findings that could adversely affect participant safety, impact the conduct of the trial, or alter the PBSL’s approval of the trial.

Other Safety Reports

The G-SLAppClinTrial indicates that notifications of changes in nature, severity, or frequency of risk factors must be submitted to the PBSL within 28 days, and new information that impacts the risk benefit profile of the product or conduct of the trial must be reported within seven (7) days.

Per the G-SLSftyMntrng and the G-SLAppClinTrial, a Development Safety Update Report (DSUR) must be submitted annually to the PBSL.

According to the G-SLSftyMntrng, the main objective of a DSUR is to present a comprehensive, thoughtful annual review and evaluation of pertinent safety information collected during the reporting period related to a drug under investigation, whether or not it is marketed, by:

• Examining whether the information obtained by the sponsor during the reporting period is in accord with previous knowledge of the IP’s safety
• Describing new safety issues that could have an impact on the protection of clinical trial participants
• Summarizing the current understanding and management of identified and potential risks, and
• Providing an update on the status of the clinical investigation/development program and study results

For more information on DSURs, see Section 12 of the G-SLSftyMntrng.

For safety reporting from foreign sites and other reporting requirements, see Appendicies VIa – VIc of the G-SLAppClinTrial.

Form Completion & Delivery Requirements

According to the G-SLAppClinTrial, the SAE/SADR report form must include detailed information to enable a causality assessment report to be prepared by the PBSL’s Expert Committee on Drug Safety. The SAE/SADR form must conform to the format of the Council for International Organizations of Medical Sciences’ (CIOMS) Form I (SLE-7), or must be previously approved by the PBSL. Furthermore, all SAEs/suspected unexpected serious adverse reactions (SUSARs) and AEs/ADRs must be reported using the SLE-7 form format and also electronically through the PBSL’s online reporting platform (SLE-14). Frequent AEs/ADRs should be reported to the PBSL in a line listing and through the PBSL’s online reporting platform. Electronic submissions must be E2B compliant. See SLE-12 for the International Council for Harmonisation (ICH)’s E2B Guidelines.

For non-serious AEs, the G-SLAppClinTrial indicates that individual reporting must be formatted in accordance with the data elements specified in the ICH Harmonised Tripartite Efficacy Guideline on Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (see SLE-12).

Interim and Annual Progress Reports

Liberia Medicines and Health Products Regulatory Authority

Pursuant to the LibCTReg, the applicant must submit to the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and the National Research Ethics Board of Liberia (NREB) progress reports containing safety updates and duly signed and authenticated Data and Safety Monitoring Board (DSMB) reports, as specified in the corresponding clinical trial guidelines. As specified in the G-LibClinTrial, the applicant must provide a progress report at least annually on the clinical trial to the LMHRA, unless otherwise stipulated in the clinical trial certificate. The report should contain recruitment status, safety updates, and DSMB reports, as well as an update on the use and results collected on biological samples exported out of Liberia, if applicable.

National Research Ethics Board of Liberia

As indicated in the G-NREB, for continuing review submissions, PIs must submit review reports to the NREB Secretariat at least eight (8) weeks prior to the approved protocol’s expiration. See LBR-6 for the NREB Continuing Review Form. Additionally, according to LBR-38, the NREB is also using LBR-24 for continuing review, for annual reports, and as a final report to close a study.

Per the G-LibClinTrial and the G-NREB, research in Liberia should comply with the International Council for Harmonisation's (ICH)’s Guideline for Good Clinical Practice E6(R2) (LBR-8). As part of the country’s compliance with LBR-8, the investigator should submit written summaries of the trial status to the NREB annually, or more frequently, if requested by the board. The investigator should also promptly provide written reports to the sponsor, the NREB, and where applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

Atlantic Center for Research and Evaluation Institutional Review Board

For clinical research studies using the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB), the G-ACRE-IRB requires the principal investigator(s) (PIs) to submit progress reports (also referred to as continuing review submissions in Liberia) to the ACRE IRB. If no work was conducted on a study during the last approval period, the PIs should explain why (e.g., too busy with other projects; a delay in funding; or unable to hire a graduate student to work on the project). If the PI(s) are closing the study, a copy of any publications or manuscripts resulting from the study should be attached. (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.)

As indicated in the G-ACRE-IRB, the following list provides the required documentation to submit a continuing review to the ACRE IRB:

• A completed Continuing Review form
• A copy of the current informed consent document(s) or any newly proposed consent document(s) if enrollment is ongoing
• A copy of current recruitment material(s) or any newly proposed recruitment material(s) if enrollment is ongoing
• A summary of adverse events and any unanticipated problems involving risks to participants
• Numbers of and reason for withdrawal of participants from the research
• A summary of any relevant information about risks associated with the research
• Number and demographics of participants enrolled
• Changes in the principal and/or associate investigator(s)
• A summary description of participant experiences
• Research results obtained thus far
• A current risk-benefit assessment based on the study results
• Any new information since the ACRE IRB’s last review

After the Secretary and the Coordinator have determined that the continuing review submission is complete, the documentation must be submitted to the ACRE IRB and reviewed by the convened board, or by the expedited reviewer(s), if necessary, for an expedited review.

Final Report

Liberia Medicines and Health Products Regulatory Authority

The LibCTReg states that the applicant is required to submit a final clinical trial summary report to the LMHRA. As per the LibCTReg and the G-LibClinTrial, the applicant must notify the LMHRA within 30 business days from the end of a clinical trial. Per the G-LibClinTrial, the end of the trial definition should be documented in the clinical trial protocol.

The LibCTReg and the G-LibClinTrial also indicate that the applicant must submit a closeout report with a copy of the LMHRA-issued disposal certificate to the LMHRA. The G-LibClinTrial specifies this report should be submitted within 90 days from completion of the clinical trial. (See Annex 5 of the G-LibClinTrial for closeout report form).

In addition, per the LibCTReg and the G-LibClinTrial, the applicant must submit a comprehensive end of study report conforming to the ICH’s Structure and Content of Clinical Study Reports (E3) (LBR-37) guidelines, within one (1) year from the trial’s completion.

Per the LibCTReg and the G-LibClinTrial, the end of study report must also contain any adverse events reported by the PIs.

Per LBR-8, the investigator, where applicable, should inform the institution; the investigator/institution should provide the ethics committee with a summary of the trial’s outcome, and the regulatory authority (LMHRA) with any reports required.

National Research Ethics Board

The LibCTReg states that the applicant is required to submit a final clinical trial summary report to the NREB. The applicant must also notify the NREB within 30 business days from the end of a clinical trial.

Additionally, per the LibCTReg, the PI must also inform the NREB of any adverse events as part of the end of study report.

The LibCTReg further specifies that the applicant must submit a comprehensive end of study report to the NREB conforming to the LBR-37 guidelines, within one (1) year from the trial’s completion.

According to LBR-38, the NREB is using LBR-24 for continuing review, for annual reports, and as a final report to close a study.

Atlantic Center for Research and Evaluation Institutional Review Board

Per the G-ACRE-IRB, PI(s) should complete Section 12 (Disposition of Project) of the ACRE IRB Submission Form (Section 25.02 in Article XXV of the G-ACRE-IRB) for the final ACRE IRB review. For the board’s purposes, the project has ended when there is no further participant enrollment, intervention(s), or data collection, and the remaining data are either de-identified or maintained with safeguards. The PI(s) should use this section to describe the disposition of the project and its data and provide a brief summary of their findings.

Interim and Annual Progress Reports

Per the SL-GCPs, the investigator should submit written summaries of the trial status to the Pharmacy Board of Sierra Leone (PBSL) as required in the G-SLAppClinTrial, or more frequently, if requested by the PBSL. The investigator should also promptly provide written reports to the PBSL on any changes that significantly affect the conduct of the trial and/or increase the risk to participants.

As set forth in the G-SLAppClinTrial, quarterly reports must be submitted starting from the date the Clinical Trial Certificate is issued using the Quarterly Progress Report Form provided in Appendix VIIb. The reports must be submitted to the PBSL within 21 days following the end of the previous quarter, and an interim report must be submitted within 21 days after the end of the first half of the trial period, and as stipulated in the protocol. If the trial is interrupted, the reason must be communicated in writing to the PBSL within 10 working days. See the G-SLAppClinTrial for additional details on preparing progress reports.

Final Report

According to the G-SLAppClinTrial, the principal investigator (PI) or the sponsor must notify the PBSL no later than 30 days following the trial’s completion and submit a preliminary report on the trial. This report, referred to as a close-out report in the G-SLAppClinTrial, must be submitted to PBSL after study completion in the recommended format as per Appendix VIII.

The G-SLAppClinTrial delineates that in addition to the close-out report, the PI or the sponsor must compile and submit a comprehensive formal report to the PBSL no later than 90 days following the trial’s completion. The report should conform to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline - Structure and Content of Clinical Study Reports (E3) (SLE-11). The report must include a short but comprehensive summary of the essential findings of the trial, as well as its methodology and course, and be submitted in hard and soft copies. Publication(s) of the study in a scientific journal or other medium for the purpose of disseminating the information obtained to stakeholders may be done only after notification of the PBSL.

The SL-GCPs indicates that the investigator is responsible for submitting the final report summarizing the trial’s outcome to the PBSL.

As stated in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with LMHRA guidelines. Per LBR-8 and the LibCTReg, the sponsor is defined as an individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.

LBR-8 and the LibCTReg also define a sponsor-investigator as an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational product is administered or dispensed. The term does not include any person other than an individual. The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

In addition, per the LibCTReg, the sponsor may hire a contract research organization (CRO) (commercial, academic, or other) to perform one (1) or more of the sponsor’s trial-related duties and functions. LBR-8 further explains that although a sponsor may transfer responsibility for any or all of the sponsor’s obligations to a CRO, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. The sponsor should also ensure oversight of any trial-related duties and functions carried out on its behalf, including trial-related duties and functions that are subcontracted to another party by the sponsor’s CRO. Any trial-related responsibilities transferred to a CRO should be specified in writing. The CRO should implement quality assurance and quality control.

As per the G-SLAppClinTrial and the SL-GCPs, a sponsor is defined as an individual, company, institution, or organization that takes ultimate responsibility for the initiation, management, and financing of a trial.

In accordance with the G-SLAppClinTrial and the SL-GCPs, the sponsor may authorize a contract research organization (CRO) to perform one (1) or more of its trial-related duties and functions. However, the ultimate responsibility for the trial’s data quality and integrity always resides with the sponsor.

The SL-GCPs further requires that any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing. The sponsor should ensure oversight of any trial-related duties and functions carried out on its behalf, including trial-related duties and functions that are subcontracted to another party by the sponsor’s contracted CRO(s). Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor.

Additionally, as delineated in the SL-GCPs, a sponsor-investigator is defined as an individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a participant. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

Per SLE-23, a foreign individual/organization may be the sponsor of a clinical trial, but a local representative in Sierra Leone is required.

Overview

According to the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with LMHRA guidelines. Per LBR-8, the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial. Each investigator should be qualified by training and experience and should have adequate resources to properly conduct the trial for which the investigator is selected. LBR-8 also explains that the sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial, to handle the data, to verify the data, to conduct the statistical analyses, and to prepare the trial reports.

As indicated in LBR-8, the investigator(s) should be qualified by education, training, and experience to assume responsibility for the proper conduct of the trial, should meet all the qualifications specified by the applicable regulatory requirement(s), and should provide evidence of such qualifications through up-to-date curriculum vitae (CV) and/or other relevant documentation requested by the sponsor, the ethics committee (EC), and/or the regulatory authority(ies) (see section 4 in LBR-8 for detailed investigator requirements).

As stated in the G-LibClinTrial, all investigators must be trained in good clinical practices (GCP) documented by the provision of training certificates not older than three (3) years at the time of application. Any other training or experience from previous clinical trials and patient care as needed for the conduct of the trial must be provided for the investigators to prove their qualifications. The principal investigators (PIs) should have acted as PI or at least as an investigator in at least one (1) prior clinical trial and must provide proof of residency in Liberia in the clinical trial application submission package. The LibCTReg also states that the trial is to be conducted in an appropriate facility by a suitably qualified investigator in a responsible manner and managed by an investigator who can provide evidence of sufficient experience in the conduct of clinical trials as determined by the LMHRA.

Per the G-NREB, PIs are also required to be able to provide a current Certificate of Training in GCP for PIs, be qualified to undertake the particular study, and be knowledgeable in the values and tenets of ethical and regulatory principles and scientific method applications associated with conducting research in human participants.

In addition, the G-LibClinTrial requires the applicant to provide details of the site(s) where the clinical trial is to be conducted and a duly justified written statement on the suitability of the trial sites adapted to the nature and use of the investigational product in the clinical trial application submission package. The statement should include a description of the suitability of facilities, equipment, human resources, and description of expertise, issued by the head of the clinic/institution at the trial site or by some other responsible person.

Furthermore, per LBR-8, the sponsor should obtain the investigator's/institution's agreement to:

• Conduct the trial in compliance with GCP, the applicable regulatory requirement(s), and the approved protocol
• Comply with procedures for data recording/reporting
• Permit monitoring, auditing, and inspection
• Retain the trial related essential documents until the sponsor informs the investigator/institution these documents are no longer needed

The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Foreign Sponsor Responsibilities

No information is available on foreign sponsor requirements.

Data and Safety Monitoring Board

As per the G-LibClinTrial, the sponsor or the representative should provide information on the composition of the Data and Safety Monitoring Board (DSMB) in the clinical trial application submission package. This information should include the list of members, the terms of reference, and the CVs of its members to justify their expertise as members of the DSMB.

LBR-8 further indicates that the sponsor may consider establishing a DSMB (also known as an independent data monitoring committee (IDMC)) to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial. The DSMB should have written operating procedures and maintain written records of all its meetings.

Multicenter Studies

As delineated in LBR-8, in the event of a multicenter clinical trial, the sponsor must ensure that:

• All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor and are given EC approval
• The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
• Investigator responsibilities are documented prior to the start of the trial
• All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
• Communication among investigators is facilitated

Further, per LBR-8, if the organization of a coordinating committee and/or selection of coordinating investigator(s) are to be used in multicenter trials, their organization and/or selection are the sponsor's responsibility.

Overview

The SL-GCPs states that the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial and for ensuring that the investigator(s) are qualified by training and experience. Additionally, the sponsor must define and allocate all trial-related duties and responsibilities to the relevant parties. Prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure.

As stated in the G-SLAppClinTrial, the principal investigator (PI) directly in charge of a trial, and at each site in a multi-center trial, must possess appropriate qualifications, training, and experience. The PI must be a scientist and domicile in Sierra Leone.

The G-SLAppClinTrial and the SL-GCPs further indicate that the PI must be responsible for the proper conduct of the trial(s), have previous experience as a co-investigator in at least two (2) trials in the relevant professional area, and have proof of formal training in good clinical practice (GCP) for at least two (2) years. See the G-SLAppClinTrial and the SL-GCPs for additional requirements.

Foreign Sponsor Responsibilities

Per SLE-23, a foreign individual/organization may be the sponsor of a clinical trial, but a local representative in Sierra Leone is required.

Data and Safety Monitoring Board

As indicated in the G-SLAppClinTrial, the sponsor must establish an independent data-monitoring committee, such as a Data and Safety Monitoring Board (DSMB), to regularly assess the trial’s progress and analyze safety data. The applicant must provide a copy of the DSMB’s membership, curriculum vitaes, and signed charter in the clinical trial application package submitted to the Pharmacy Board of Sierra Leone (PBSL). However, the SL-GCPs indicates that establishing a DSMB is optional.

The G-SLAppClinTrial further indicates that a duly signed and authenticated DSMB report(s) and/or minutes must be forwarded to the PBSL upon request. For more information on DSMB requirements, see the G-SLAppClinTrial.

Multicenter Studies

As delineated in the SL-GCPs, in the event of a multicenter clinical trial, the sponsor must ensure that:

• All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and the approvals of the PBSL and the ethics committee
• The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
• Investigator responsibilities are documented prior to the start of the trial
• All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
• Communication between investigators is facilitated

In addition, the sponsor may organize a coordinating committee or select coordinating investigators.

Insurance

As set forth in the LibCTReg and the G-LibClinTrial, the applicant should include documentation in the clinical trial application submission package to verify active clinical trial insurance that covers phases I, II, and III, proof of professional indemnity (malpractice insurance), and proof of sponsor indemnification for investigators and the trial site. The LibCTReg also notes that an indemnity in the form determined by the Liberia Medicines and Health Products Regulatory Authority (LMHRA) is to be signed by the participant protecting the LMHRA from liability related to an injury or an adverse event which may be sustained by a person, directly or indirectly, as a result of the conduct of the trial and which occurs or reveals itself at the time of the trial or subsequently.

The G-LibClinTrial also specifies that a study insurance certificate and an indemnity provision should be current and valid for the full duration of the trial and follow-up period. If the validity is shorter, a written renewal commitment for the trial duration is required. The certificate should contain a reference to the clinical trial, the clinical trial protocol number, and the countries to which the insurance cover is extended. The insurance cover should be provided from an internationally recognized company. Additionally, the LibCTReg, requires an insurance policy to be in place to provide benefits in the event that a clinical trial participant suffers injury or death related to the study.

Per LBR-29, both clinical trial insurance and indemnification certificates must be included in the clinical trial application dossier in accordance with the African Vaccine Regulatory Forum (AVAREF)’s Clinical Trial Application Checklist (LBR-1). According to LBR-4, the AVAREF was established by the World Health Organization (WHO) in 2006 to promote the harmonization of ethics and regulatory processes in Africa.

In addition, per the G-LibClinTrial, under certain circumstances, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) may accept an expedited application and review process for clinical trials (e.g., epidemics or other urgent public health interests requiring fast use of new medicines or health products and/or fast gathering of health product information). In the case of trials involving human participants, the applicant must provide proof of current, relevant, and appropriate study insurance for all participants or professional indemnity insurance for investigators as part of the application submission package to be sent to the LMHRA. Furthermore, as specified in the LibCTReg and the G-LibClinTrial, the LMHRA has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. LBR-8 states that if required by the applicable regulatory requirement(s), the sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/the institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.

Compensation

Injury or Death

Per LBR-8, the sponsor or the representative is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death.

LBR-8 states that the sponsor's policies and procedures should address the treatment costs of trial participants in the event of trial-related injuries, and when trial participants receive compensation, the method and manner of compensation should comply with applicable regulatory requirement(s). According to LBR-29, the LMHRA does not have a compensation committee.

In addition, per the LibCTReg, any person(s), institution(s), corporate entity(ies), their designees, or legal representative(s) who does not provide insurance coverage for prospective participants as required, and in the course of the research bodily injury or substantial harm results, the person(s), institution(s), corporate entity(ies), their designees, or legal representative(s) commits a first degree misdemeanor consistent with the PenalLaw. The PenalLaw states a person commits a misdemeanor of the first degree if the person recklessly engages in conduct which creates a substantial risk of death or serious bodily injury to another.

Pursuant to Part VIII of the LMHRA-Act, the LibCTReg also specifies that the principal investigator or organization is subject to an action of damages for any Serious Adverse Event (SAE)/Serious Adverse Drug Reaction (SADR) that is life-threatening, or results in persistent or significant disability/incapacity or congenital anomaly/birth defect, during the conduct of a clinical trial. Additionally, any SAE that results in the death of a participant during the conduct of a clinical trial must constitute negligent homicide consistent with the PenalLaw which states that a person is guilty of negligent homicide if the person causes the death of another human being negligently; negligent homicide is a felony of the third degree.

Trial Participation

Per LBR-8, the participant should be provided with information regarding any anticipated prorated payment, if any, for participating in the trial.

Insurance

The G-SLAppClinTrial states that for all sponsor-initiated trials, a valid insurance certificate for the duration of the study must be provided before initiating the study, and a copy of this coverage must be included in the clinical trial application submission to the Pharmacy Board of Sierra Leone (PBSL). Sponsors and principal investigators (PIs) must ensure insurance cover for clinical trial participants and must submit a certificate of insurance cover for participants as evidence. The certificate must at least contain:

• Insurance company
• Policy number
• Initial date
• Expiry date
• Insured (Policy Holder/Sponsor)
• Description of activity (purpose of the policy)

The G-SLAppClinTrial and the SL-GCPs also state that the sponsor must provide insurance or indemnify the investigator(s)/institution(s) against claims arising from the trial, except for those claims arising from malpractice and/or negligence as stipulated in the G-SLAppClinTrial. See Annex 7 of SLE-6 for suggested wording of the sponsor indemnification.

Compensation

Injury or Death

The SL-GCPs indicate that the sponsor's policies and procedures should address the costs of treatment of trial subjects in the event of trial-related injuries in accordance with the applicable requirement(s). In addition, when trial participants receive compensation, the method and manner of compensation should comply with the PBSL's requirements.

Trial Participation

According to the SL-GCPs, the ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) should review both the amount and method of payment to participants to assure that neither presents problems of coercion or undue influence. Payments to a participant should be prorated and not wholly contingent on the participant’s completion of the trial. The EC should also ensure that information regarding payment to participants, including the methods, amounts, and schedule of payment, is set forth in the written informed consent form and any other written information to be provided to participants. The way payment will be prorated should be specified.

Quality Assurance/Quality Control

As specified in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation (ICH)'s Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. Per LBR-8, sponsors are responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol.

Per LBR-8, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

• During protocol development, identifying processes and data that are critical to ensure participant protection and the reliability of trial results
• Identifying risks to critical trial processes and data
• Evaluating the identified risks against existing risk controls
• Deciding which risks to reduce and/or which risks to accept
• Documenting quality management activities and communicate to those involved in or affected by these activities
• Periodically reviewing risk control measures to ascertain whether the implemented quality management activities are effective and relevant
• In the clinical study report, describing the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken (Refer to the ICH’s Structure and Content of Clinical Study Reports (E3) guidelines (LBR-37))

Pursuant to Part VIII of the LMHRA-Act, the LibCTReg states that any person(s), institution(s), corporate entity(ies), their designees, or legal representatives who violates the clinical trial authorization procedures, the serious adverse event notification requirements, and/or the suspension/withdrawal provisions delineated in the LibCTReg will be liable to pay administrative fines. See the LibCTReg for details.

Monitoring Requirements

Per LBR-8, if or when sponsors perform audits as part of implementing quality assurance, they should consider the following:

• The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, good clinical practice (GCP), and applicable regulatory requirements
• The selection and qualification of auditors who are independent of clinical trials/systems to conduct audits; the sponsors should ensure the auditors are qualified by training and experience to conduct audits properly and have appropriate qualifications that should be documented
• Auditing procedures that ensure the auditing of clinical trials/systems is conducted in accordance with the sponsor’s written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports

In addition, per LBR-8, the sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose on-site monitoring, a combination of on-site and centralized monitoring, or where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).

Refer to LBR-8 additional audit procedure details.

Premature Study Termination/Suspension

Pursuant to the LibCTReg, if the trial is suspended or terminated before its purpose is achieved, the applicant must convey the reason(s) in writing to the LMHRA and the National Research Ethics Board of Liberia (NREB) within 10 working days and all information must be provided as determined by the LMHRA. The G-LibClinTrial also states that the applicant must inform the LMHRA of a clinical trial suspension or premature termination of a clinical trial within 10 working days and clearly explain the reasons for this decision. LBR-8 further explains that if a trial is prematurely terminated or suspended, the sponsor should promptly inform the investigator(s)/institution(s) and the regulatory authority(ies) of the termination or suspension and the reason(s) for the termination or suspension. The ethics committee (EC) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution, as specified by the applicable regulatory requirement(s). Additionally, according to LBR-8, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the sponsor should promptly inform the EC and provide the reason(s) for the termination or suspension.

Quality Assurance/Quality Control

As stated in the SL-GCPs, the sponsor is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol, good clinical practice (GCP), and the Pharmacy Board of Sierra Leone (PBSL)’s regulatory requirement(s). The sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed.

Monitoring Requirements

As part of its QA system, the SL-GCPs notes that the sponsor may choose to perform a clinical trial audit. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, the PBSL, and other applicable regulatory requirements. The sponsor should ensure that the auditors are qualified by training and experience, and that their qualifications are documented. The sponsor must also ensure that the audit is conducted in accordance with the sponsor’s own written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports. The observations and findings of the auditor(s) should be documented. No specific timeframe is provided for the audit process. See the SL-GCPs for detailed audit requirements.

Premature Study Termination/Suspension

As per the SL-GCPs, if a trial is terminated or suspended prematurely, the sponsor should promptly inform the investigator(s)/institution(s) and the PBSL of the termination or suspension, and explain the reason(s) for the termination or suspension. The ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution.

Electronic Data Processing System

As specified in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation (ICH)'s Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines.

As per LBR-8, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. Sponsors should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, sponsors should maintain standard operation procedures (SOPs) for the systems that cover system setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training in their use. Refer to LBR-8 for additional information.

Records Management

The G-LibClinTrial specifies that the principal investigator (PI) must keep an Investigator Site File (ISF), and the sponsor must keep a Trial Master File (TMF) containing essential documents relating to the clinical trial, which provide verification for the trial conduct and the quality of the data generated, taking into account all trial characteristics. The files must be readily available and directly accessible upon request from the LMHRA. The sponsor and the investigator must archive the contents of the TMF and ISF, respectively, for at least 25 years after the end of the trial including the medical files of study participants.

As set forth in LBR-8, the sponsor should inform the investigator(s)/institution(s) in writing of the need for record retention and should notify the investigator(s)/institution(s) in writing when the trial related records are no longer needed. Sponsor-specific essential documents should be retained for at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the investigational product’s clinical development. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

In addition, LBR-8 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial. Per LBR-8, the sponsor should ensure the protocol or other written agreement specify that the investigator(s)/institution(s) provide direct access to source data/documents for trial related monitoring, audits, ethics committee review, and regulatory inspection.

As per the G-LibClinTrial, data handling and recordkeeping should be conducted in conformity with the World Health Organization's Good Clinical Practice Guidelines (LBR-25) (refer to Section 8 for details).

Per the G-ACRE-IRB, for clinical research studies using the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB), the ACRE IRB must retain all relevant records (e.g., study documents specific to board activities and administrative documents related to ACRE IRB internal operations) per the following timelines (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the National Research Ethics Board of Liberia (NREB) and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• All records regarding a research application (regardless of whether it is approved) must be retained for at least three (3) years
• All records regarding all applications that are approved, and the research initiated must be retained for at least three (3) years after completion of the research
• Denied applications will be treated as terminated files and records must be retained for three (3) years after the denial of the research

The G-ACRE-IRB further explains the research records from a study must be retained by the investigator(s) for a period of no more than five (5) years following the closure date. If other regulations and policies apply to a particular protocol, then the duration of protocol retention is in accordance with the applicable regulations/policies. For detailed ACRE IRB recordkeeping requirements, refer to the G-ACRE-IRB.

The G-ACRE-IRB also specifies that although a research protocol has been closed, the investigator(s) should keep the data they have collected, including identifiable private data, in a manner consistent with the board-approved protocol and participant consent requirements. The investigator(s) must continue to honor any confidentiality protections of the data. Refer to the Informed Consent topic for additional information on documentation requirements and research participant rights during the informed consent process.

Electronic Data Processing System

As delineated in the SL-GCPs, when using electronic trial data handling and/or remote electronic data systems, the sponsor must ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance, and that the sponsor maintains standard operating procedures (SOPs) for using these systems. The responsibilities of the sponsor, investigator, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use. Refer to the SL-GCPs for detailed information on electronic trial data systems.

Records Management

As set forth in the SL-GCPs, the sponsor, or other data owners, should retain all sponsor-specific essential documents pertaining to the trial for at least two (2) years after formal discontinuation of the trial or in conformance with the applicable regulatory requirement(s) of the country(ies) where the product is approved, and/or where the sponsor intends to apply for approval(s). In addition, all clinical and experimental data (electronic or paper) must be kept in a secure place for a period of five (5) years, or 20 years for a new drug application, after a trial’s completion. The data must also be readily available for review upon request by the Pharmacy Board of Sierra Leone (PBSL).

See the SL-GCPs for a list of essential documents for the conduct of a clinical trial.

Responsible Parties

No information is available related to responsible parties for personal data protection.

Data Protection

No information is available related to data protection.

Consent for Processing Personal Data

As stated in the LibCTReg, the clinical trial participant must be informed of the purpose and scope of the collection and use of personal data, especially medical data. The trial participant must be informed especially of the fact that where necessary, the collected data should be:

• Kept available for inspection by the Liberia Medicines and Health Products Regulatory Authority (LMHRA) or for monitoring or auditing by the sponsor in order to verify the proper conduct of the clinical trial
• Be passed on to the sponsor and the LMHRA without disclosing the identity of the trial participant

No information is currently available regarding personal data protection requirements.

Obtaining Consent

In accordance with the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. Per LBR-8, a freely given informed consent must be obtained from every study participant prior to clinical trial participation. According to the G-ACRE-IRB, the G-NREB, and LBR-8, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an ethics committee (EC).

As delineated in the LibCTReg, the trial participant should be informed of the nature, significance, and implications of the clinical trial and have given a voluntary written informed consent. The trial participant or witness, if applicable, must be informed by an investigator, who is a healthcare professional or a person designated by the investigator, and who is knowledgeable about the nature, significance, risks, and implications of the clinical trial as well as about the participant’s right to withdraw from the clinical trial at any time. A generally comprehensible information sheet is to be handed out to the participant. The trial participant is also to be given the opportunity to have a counseling session with an investigator or a person designated by the investigator about the other conditions surrounding the conduct of the clinical trial.

The LibCTReg further notes that a declaration of consent to participate in a clinical trial can be revoked at any time in the presence of the investigator or a member of the investigating team, orally or in writing, without disadvantage to the trial participant. In the case of a revocation of consent, the study participant must decide whether their stored data may continue to be used.

Per the G-ACRE-IRB, the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) must assess the study to ensure the voluntary, non-coercive recruitment of research participants. The board must ensure that they have adequately considered the following in the protocol (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the National Research Ethics Board of Liberia (NREB) and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• Procedures for obtaining informed consent
• Content of the participant information sheet
• Content and language of the informed consent document
• Translation of the informed consent document into the local language
• The language used in the documents should be simple relative to the general public’s level of understanding
• Contact persons with their addresses and telephone numbers (for both the study team and the EC)
• Privacy and confidentiality
• Risks (physical, mental, social)
• Benefits to participants and to others
• Compensation (reasonable/unreasonable)
• Involvement of vulnerable participants
• Provision for medical/psychosocial support
• Treatment for study-related injuries
• Use of biological materials

Per the G-ACRE-IRB, if the informed consent procedures and consent document(s) are reviewed by the ACRE IRB Secretariat and found to be complete, the documentation is then submitted to the board for review. If the documentation qualifies for expedited review, the chairperson or a designated expedited reviewer will evaluate the materials. After the investigator makes the required changes suggested by the ACRE IRB, the application may be approved by the chair.

(See the Required Elements section for details on what should be included in the ACRE IRB and NREB forms. Refer to LBR-33 for the NREB Exempt Human Research Consent Script Form and LBR-34 for the NREB Short Consent Form.)

LBR-8 states that the investigator or the designated representative must provide detailed research study information to the participant or legal representative/guardian. LBR-8 further specifies that the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant or legal representative/guardian, should also be given adequate time to consider whether to participate.

Further, per LBR-8, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or the legal representative/guardian to waive or to appear to waive the legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

Re-Consent

According to LBR-8, the LMHRA and an EC should approve any change in the ICF due to a protocol modification before such changes are implemented. The participant or legal representative/guardian should be informed in a timely manner if new information becomes available that might be relevant to the participant’s willingness to continue participation in the trial. The participant or legal representative/guardian will also be required to re-sign the revised ICF and receive a copy of any amended documentation.

In addition, per the G-ACRE-IRB, in the case that ACRE IRB approval is reinstated, the ACRE IRB may require previously enrolled participants to re-consent.

Language Requirements

As stated in the G-LibClinTrial, all clinical trial application documentation must be submitted in English. If documents are written in another language, a certified translation is required.

Documenting Consent

The LibCTReg states that if the trial participant is unable to read or write English, the informed consent should be obtained in the language the participant understands and in the presence of at least one (1) witness. The witness, who should be able to read and write English and understand the local language in which the trial participant is informed, should not be a member of the investigating team. The consent given by the trial participant must be documented in writing, dated, and signed by the witness and thumb printed by the trial participant.

Per LBR-8, before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF. The participant or legal representative/guardian should also receive a copy of the signed and dated consent form updates and a copy of any amendments to the written information provided to the participants.

LBR-34 also provides a sample NREB ICF for adults capable of consent. A witness must also be present during the consent process and the witness must sign and date the ICF. The number of copies to be signed and distributed is not specified.

Per LBR-8, if a participant is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

• The written ICF and any other written information provided to the participant is read and explained to the participant and legal representative/guardian
• The participant and legal representative/guardian, have orally consented to the participant’s involvement in the trial, and has personally signed and dated the ICF, if capable of doing so

Waiver of Consent

As specified in the G-ACRE-IRB, to obtain a waiver or alteration of informed consent, the investigator must include the request (and provide justification for the waiver or alteration) in the protocol submission to the ACRE IRB. The request for waiver or alteration will be reviewed by the convened board, the ACRE IRB Chair, or the designated expedited reviewer. The ACRE IRB reviewer (Chair or designee) may approve the waiver or alteration of informed consent, if the board reviewer can establish that the research is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine:

• Public benefit or service programs
• Procedures for obtaining benefits or services under those programs
• Possible changes in or alternatives to those programs or procedures, or
• Possible changes in methods or levels of payment for benefits or services under those programs

The ACRE IRB reviewer should also be able to ascertain that the research could not practicably be carried out without the waiver or alteration.

Additionally, per the G-ACRE-IRB, the ACRE IRB reviewer may approve the waiver or alteration of informed consent, if the reviewer determines the following:

• The research involves no more than minimal risk to the participants
• The research could not practicably be conducted without the requested waiver or alteration
• If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format
• The waiver or alteration will not adversely affect the rights and welfare of the participants, and
• Whenever appropriate, the participants or legal representative/guardian will be provided with additional pertinent information after participation. The ACRE IRB reviewer will document the findings for waiver or alteration of informed consent. An alteration to informed consent may apply when conducting a study where there is deception or an incomplete disclosure (for example, studies that require deception because the study would be compromised if participants were told the true purpose)

In addition, the G-ACRE-IRB explains that a waiver of a signed ICF may be appropriate for some research studies such as survey or interview studies containing highly sensitive questions (e.g., health status, sexual practices, criminal behavior, etc.), or surveys containing non-sensitive information. To obtain a waiver of documented (signed) informed consent, the investigator must include the request (and provide justification for the waiver or alteration) in the protocol submission process. The request for waiver or alteration will be reviewed by the convened ACRE IRB, the Chair, or the designated expedited reviewer. The ACRE IRB reviewer will consider the investigator’s request and review the request to determine if:

• The only record linking the participant and the research would be the consent document, and the principal risk would be potential harm resulting from a breach of confidentiality
• The research presents no more than minimal risk of harm to participants and involves no procedures for which written consent is normally required outside of the research context
• The participants or legal representative/guardian are members of a distinct cultural group or community in which signing forms is not the norm, that the research presents no more than minimal risk of harm to participants, and provided that there is an appropriate alternative mechanism for documenting that informed consent was obtained. In cases where the documentation requirement is waived, the ACRE IRB may require the investigator to provide participants with a written statement regarding the research, such as an information sheet, instead of an informed consent document

Obtaining Consent

In all Sierra Leone clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the SL-GCPs. In obtaining and documenting informed consent, the investigator should comply with Pharmacy Board of Sierra Leone (PBSL) requirements and should adhere to good clinical practice (GCP) and to the ethical principles that have their origin in the Declaration of Helsinki (SLE-5), which is available in Appendix 3 of the SL-GCPs.

As per the SL-GCPs and the G-SLAppClinTrial, the informed consent form (ICF) is viewed as an essential document. The sponsor and principal investigator (PI) must submit the ICF to the PBSL with the clinical trial application. The G-SLEthics further indicates that the PI must also submit the ICF to the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), for review. (See the Required Elements section for details on what should be included in the form.)

The SL-GCPs states that the investigator, or the investigator’s designated representative, must provide detailed research study information to the participant or legal representative/guardian. In addition, the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant or legal representative/guardian should also be given adequate time to consider whether to participate.

As per the SL-GCPs, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

Re-Consent

According to the SL-GCPs, the participant or legal representative/guardian should be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented, and the participant or legal representative/guardian should receive a copy of the signed and dated ICF updates, including a copy of any amendments to the written information provided to the participants.

Language Requirements

As per SLE-23, the clinical trial application and accompanying material must be provided to the PBSL in English.

Documenting Consent

The SL-GCPs states that the participant or legal representative/guardian, as well as the investigator(s), must sign and date the ICF.

Where the participant is illiterate or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after:

• The written ICF and any other written information is read and explained to the participant or legal representative/guardian;
• The participant or legal representative/guardian has orally consented to the participant’s involvement in the trial; and
• The participant or legal representative/guardian has signed and dated the ICF, if capable of doing so.

According to the G-SLEthics, the SLESRC does not accept verbal consent, except when supported by an independent witness.

Per the SL-GCPs, before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF.

Waiver of Consent

The SL-GCPs delineates that where the protocol indicates that prior consent of the participant or legal representative/guardian is not possible, the EC (i.e., the SLESRC) should determine whether the proposed protocol and/or other document(s) adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such trials. See the Emergencies and Mentally Impaired sections for more information.

Liberia Medicines and Health Products Regulatory Authority

As specified in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) to comply with informed consent requirements for use along with the LMHRA guidelines.

LBR-8 states that the informed consent form (ICF) should include the following statements or descriptions, as applicable:

• The study involves research and an explanation of its purpose
• Trial treatment(s) and the probability for random assignment to each treatment
• Trial procedures to be followed, including all invasive procedures
• The participant’s responsibilities in participating in the trial
• Experimental aspects of the study
• Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
• Alternative procedures or treatment that may be available to the participant, and if any, which might be advantageous to the participant
• Compensation and/or medical treatment available to the participant or the participant’s family or dependents in the event of a trial-related injury
• Any expected benefits or prorated payment to the participant for participating in the trial
• Any additional costs to the participant that may result from participation in the research
• Participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled
• The LMHRA, the monitor(s), the auditor(s), and the ethics committee (EC) will be granted direct access to the participant’s original medical records to verify clinical trial procedures and/or data without violating the participant’s confidentiality
• A statement describing the extent to which, if any, confidentiality of records identifying the participant will be maintained, and if the results of the trial are published, the participant’s identity will remain confidential
• The participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant's willingness to continue
• The person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury
• Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent
• The expected duration of the participant's participation
• Approximate number of participants involved in the trial

National Research Ethics Board of Liberia

The following elements are to be included in the National Research Ethics Board of Liberia (NREB)’s Exempt Human Research Consent Script Form (LBR-33) and the NREB Short Consent Form (LBR-34) respectively (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Indication that the person is being asked to take part in a research study
• Research study purpose and reason for participant’s eligibility to participate in study
• Duration of research study
• Participation is voluntary and participant may withdraw at any time
• Explanation of study-specific procedures and sample questions provided to participants
• Possible risks associated with participating in study
• Benefits to participant or to others from participating in study
• Appropriate alternative procedures, or courses of treatment, if any
• Explanation of what is experimental vs. routine standard of care
• Statement regarding who will have access to the participant’s personal information
• Participant’s right to decline participating in any part of study for any reason and right to end participation at any time, and refusal to participate will not be held against the participant
• Researcher’s contact information for any questions the participant may have prior to deciding to participate and throughout the participant’s involvement in the study

See LBR-33 and LBR-34 for additional details.

Per LBR-34, if applicable, the following information is also included in the NREB Short Consent Form:

• Whether the participant will get treated or paid if injured
• The possibility of unknown risks
• When the participant may be taken off the research study without the participant’s agreement
• Added costs from taking part in the study
• What will happen if the participant stops taking part
• Steps to safely stop taking part
• What new information will be shared with the participant
• The number of participants expected to take part in the study
• What happens to the participant’s collected data if the participant withdraws from the trial
• An explanation of the ClinicalTrials.gov (LBR-40) website

Atlantic Center for Research and Evaluation Institutional Review Board

The G-ACRE-IRB indicates that the principal investigator (PI) is responsible for preparing the ICF and that the ICF should include the following statements or descriptions (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• The study involves research and an explanation of its purpose
• The expected duration of a participant’s involvement in the research
• A description of the procedures to be followed
• Identification of any experimental study procedures
• Any foreseeable risks or discomforts to the participant
• Any benefits to the subject or to others that may reasonably be expected from the research
• Alternative procedures or treatment that may be available to the participant, and if any, which might be advantageous to the participant
• A statement describing the extent to which, if any, confidentiality of records identifying the participant will be maintained
• A statement noting the possibility that the EC (or its designees) and the study sponsor may inspect the study records, if the research is sponsored by a funding source
• For research involving more than minimal risk, an explanation of compensation and/or medical treatment available to the participant or the family or dependents in the event of a trial-related injury, and if injury occurs, what the medical treatments consist of, or where further information may be obtained
• The person(s) to contact for further information regarding the trial and the rights of research participants, and whom to contact in the event of research-related injury
• Participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled

In addition to the required elements listed above, per the G-ACRE-IRB, for research involving the collection of identifiable private information or identifiable biospecimens, one (1) of the following must be included in the informed consent:

• A statement that identifiers will be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies without additional informed consent from the participant or legal representative/guardian
• A statement that the participant's information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies

See also the Consent for Specimen section for additional information on informed consent relating to specimens.

Based on the SL-GCPs, the informed consent form (ICF) should include the following statements or descriptions, as applicable:

• The study involves research and an explanation of its nature and purpose

• Trial procedures to be followed, including all invasive procedures

• Expected duration of participation

• Participant’s responsibilities in the trial

• Experimental aspects of the study

• Approximate number of participants involved in the trial

• The trial treatment(s) and the probability for random assignment to each treatment

• Any foreseeable risks or discomforts, and when applicable, to an embryo, fetus, or nursing infant

• Any expected benefits or prorated payment; if no benefit is expected, the participant should also be made aware of this

• Alternative procedures or treatment that may be available

• Compensation and/or medical treatment available to the participant in the event of a trial-related injury

• Person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury

• Any additional costs that may result from participation in the research

• That the monitor(s), the auditor(s), the ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)), and the Pharmacy Board of Sierra Leone (PBSL) will be granted direct access to the participant’s original medical records to verify clinical trial procedures and/or data without violating the participant’s confidentiality

• That records identifying the participant will be kept confidential and, to the extent permitted by applicable laws and/or regulations, will not be made publicly available. If the results are published, the participant’s identity will remain confidential

• Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent

• That participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled

• The participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant's willingness to continue

Additionally, see Annex 1 of SLE-6 for standardized wording for the ICF.

Overview

As specified in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. The G-ACRE-IRB also complies with the Council for International Organizations of Medical Sciences (CIOMS)’ International Ethical Guidelines for Health-related Research Involving Humans (LBR-2) and the national ethical guidelines for research on human participants. (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the National Research Ethics Board of Liberia (NREB) and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.)

As per LBR-8, Liberia’s ethical standards promote respect for all human beings and safeguard the rights of research participants. LBR-8 and the G-ACRE-IRB state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process.

The Right to Participate, Abstain, or Withdraw

As set forth in the G-ACRE-IRB, LBR-8, LBR-33, and LBR-34, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As per the G-ACRE-IRB, LBR-8, LBR-33, and LBR-34, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study. (See the Required Elements section for a more detailed list.)

The Right to Privacy and Confidentiality

As per LBR-8 and the G-ACRE-IRB, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

The Right of Inquiry/Appeal

The G-ACRE-IRB, LBR-8, LBR-33, and LBR-34, state that the research participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries.

The Right to Safety and Welfare

LBR-8 states that the research participant’s rights, safety, and well-being must take precedence over the interests of science and society.

(See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

Overview

In accordance with the SL-GCPs, which is guided by the International Council for Harmonsation’s Guideline for Good Clinical Practice E6(R2) (SLE-24), the Declaration of Helsinki (SLE-5), and other international guidelines, Sierra Leone’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The SL-GCPs and the G-SLAppClinTrial state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process.

The Right to Participate, Abstain, or Withdraw

As stated in the SL-GCPs, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As per the SL-GCPs, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

According to the SL-GCPs and the G-SLAppClinTrial, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

The Right of Inquiry/Appeal

The SL-GCPs states that the research participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or the participant’s rights.

The Right to Safety and Welfare

As set forth in the SL-GCPs and the G-SLAppClinTrial, the research participant’s dignity, safety, and welfare must take precedence over the interests of science and society.

See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.

As set forth in the LibCTReg, in an emergency situation where consent cannot be obtained, treatment which is necessary without delay to save the life of the trial participant can be started immediately. Such situations must be defined by the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and consent for continued participation must be obtained as soon as possible and not later than as defined by the National Research Ethics Board of Liberia (NREB) for a given clinical trial.

The LibCTReg and the G-LibClinTrial further explain that the LMHRA has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. LBR-8 makes provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies in which prior consent from the participant is not possible.

As delineated in LBR-8, in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of the legal representative/guardian should be obtained. If the prior consent of the participant or legal representative/guardian cannot be obtained, the participant’s enrollment should follow measures specified in the protocol, and/or elsewhere, with documented LMHRA approval to protect the rights, safety, and well-being of the participant, and to ensure compliance with ethics committee (EC) and LMHRA requirements. The participant or the participant’s legal representative/guardian should be informed about the trial and provide consent as soon as possible.

Per the G-LibClinTrial, examples of emergency situations are epidemics or other urgent public health interests that require fast utilization of new medicines or health products and/or fast gathering of information on products. Information provided to clinical trial participants about the process of obtaining consent must be included in the documents submitted to the LMHRA. Refer to 2.3 of the G-LibClinTrial for additional information on how to submit an expedited clinical trial application package.

The SL-GCPs make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by emergency situations.

As delineated in the SL-GCPs, if the signed informed consent form (ICF) cannot be obtained from the research participant in an emergency, then the consent of the legal representative/guardian, if present, should be obtained. If prior consent of the participant or legal representative/guardian cannot be obtained, then the participant’s enrollment should follow measures specified in the protocol, and/or elsewhere, with documented approval/favorable opinion by the ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) and the Pharmacy Board of Sierra Leone (PBSL) to protect the rights, safety, and well-being of the participant and ensure compliance with EC and PBSL requirements. The participant or legal representative/guardian should be informed about the trial and provide consent as soon as possible.

In addition, per the SL-GCPs, because the participants who are experiencing medical emergencies are usually extremely vulnerable, these individuals should be excluded from all but minimally invasive observational research. ECs must also take great care when assessing emergency care research. Once the researcher has presented clear reasons to justify the initiation of emergency care research without consent to the EC, the EC may approve the research provided it is satisfied that:

• Reasonable steps are being taken to ascertain the religious and cultural sensitivities of participants experiencing medical emergencies
• The condition of the participant precludes the giving of consent
• Inclusion in the trial is not contrary to the interests of the participant
• The research is intended to be therapeutic and poses no more risk than is inherent to the patient’s condition or would be caused by alternative methods of treatment
• The participant and the legal representative/guardian will be informed as soon as is reasonably possible of the patient’s inclusion in the study and of the option to withdraw from the research project at any time
• The participant will be informed, and consent obtained, once the participant who has undergone the necessary emergency procedures has regained consciousness
• The research is based on valid scientific hypotheses and offers a realistic possibility of benefit over standard care

Overview

The LibCTReg and the G-LibClinTrial explain that the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. According to LBR-8, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process.

LBR-8 explains that vulnerable populations include those participants whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples may include, but are not limited to, members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students; subordinate hospital and laboratory personnel; employees of the pharmaceutical industry; members of the armed forces; and persons kept in detention. Other vulnerable study participants include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

Persons with Diseases

As indicated in the LibCTReg, in the case of a clinical trial on a person of legal age who is suffering from a disease for which the investigational product (IP) is to be used, one (1) of the following conditions should be applied along with the general clinical trial requirements delineated in the LibCTReg:

• The use of the IP is indicated according to the findings of medical science in order to save the person's life
• The IP must be of direct benefit to the group of patients who are suffering from the same disease as this person

Persons Under Legal Disability

As set forth in the LibCTReg, “persons under legal disability” are defined as being under the same category as a minor in terms of the individual’s ability to grant consent, except that the person under disability may be above the age of consent (18 years), but may be too ill to participate in decisions regarding their own health. In this case, priority is not given to parents or next of kin to petition the Probate Court for Guardianship, but priority is given to any natural person who demonstrates best interest in the welfare of the disabled.

The LibCTReg further explains that a person under legal disability may participate in a trial, if their parents/legal guardians have be informed of the nature, significance, and implications of the clinical trial and have given a written voluntary informed consent. If the informed implication is grave, it may be necessary for the guardian to secure the permission from the Probate Court before granting consent, due to the fact that the Decree of Guardianship has a clause that the Court appointed guardian should not release the disabled person to any other body in which case their welfare will be put at peril. Otherwise, it can be argued that the appointed guardian has breached their fiduciary duty to the Court by releasing the disabled person to peril.

See the Children/Minors and Mentally Impaired sections for additional information about these vulnerable populations.

Overview

As per the SL-GCPs, in all Sierra Leonean clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process.

According to the SL-GCPs and the G-SLAppClinTrial, vulnerable populations include individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with the participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. The SL-GCPs states that other participants representing vulnerable populations include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. Additionally, types of research that need additional attention include research involving collectivities, indigenous medical systems, innovative therapy or interventions, HIV and AIDS clinical and epidemiological research, and emergency care research.

The SL-GCPs indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to protecting the welfare of certain classes of participants, including minors, women, persons with mental disabilities or substance abuse related disorders, persons in dependent relationships or comparable situations, prisoners, and persons highly dependent on medical care.

Persons Highly Dependent on Medical Care

According to the SL-GCPs, participants who are highly dependent on medical care must be given special attention to protect the welfare of this vulnerable study population. Researchers need to acknowledge that the participant’s medical condition may compromise the participant’s informed consent and affect the participant’s ability to form an opinion or to communicate. There may also be a perception of coercion if a participant is reluctant to refuse consent for fear that it may compromise the participant’s medical treatment.

As delineated in the SL-GCPs, the following research areas require investigators to pay special attention to these participants to safeguard their welfare and ensure proper consent:

• Intensive care research – Characteristic features are the difficulties in communicating with participants receiving ventilatory assistance and the impairment of cognition in heavily sedated participants. Whenever possible, information should be obtained from potential participants prior to their admission to intensive care. These participants should be excluded from all but minimally invasive observational research due to their extreme vulnerability.
• Neonatal intensive care research – Research involving infants should be conducted in strict accordance with the principles discussed in the Children/Minors section. These principles do not permit research that is contrary to the child’s best interests.
• Terminal care research – Research in terminal care is distinguished by the short remaining life expectancy of participants and potential vulnerability to unrealistic expectations of benefits. Researchers must ensure that the prospect of benefit from research participation is neither exaggerated nor used to justify a higher risk than that involved in the participant’s current treatment.
• Research involving persons with impaired capacity to communicate or unconscious persons – Refer to the Mentally Impaired section.

Persons in Dependent Groups

As set forth in the SL-GCPs, for participants whose proposed involvement in research arises from dependent or comparable relationships, the EC must be satisfied that the participants’ consent is both adequately informed and voluntary. The following list provides some examples of hierarchically structured groups and the junior or subordinate relationships that may exist in these groups:

• Older persons and their caregivers
• Persons with chronic conditions or disabilities and their caregivers
• Wards of the state and guardians
• Patients and healthcare professionals
• Students and teachers
• Prisoners and prison authorities
• Persons with life-threatening illnesses
• Employees and employers (e.g., farm workers and their employers, members of the uniformed services and hospital staff and their employers)

See the Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations.

According to the LibCTReg and the G-NREB, Liberia defines children and minors as those persons under 18 years of age. The G-NREB also defines adolescents as those between the ages of 15 and 17.

The LibCTReg also states that the definition of legal guardian or the “legal representative of a minor” is based on the premise that a minor cannot grant consent or enter into an agreement. According to LibCTReg, the interest of a minor must be firstly protected by the parents (the father if the parents are married or the child is legitimized) or the mother of the child if the parents are not married. Where there is no parent alive, especially the mother if the child is not born out of wedlock or legitimized, any next of kin, preferably the grandparents first, the siblings second, or any person with interest in the welfare of the child, may petition the Probate Court for Decree of Guardianship. A guardian must be authorized to give consent for the minor child. No institution can serve as guardian and give consent for research on the child. A guardian must be a natural person, not an institution.

Additionally, per the LibCTReg, a minor may participate in a trial, if their parents/legal guardians have been informed of the nature, significance, and implications of the clinical trial and have given a written voluntary informed consent. If the informed implication is grave, it may be necessary for the guardian to secure the permission from the Probate Court before granting consent, due to the fact that the Decree of Guardianship has a clause that the Court appointed guardian should not release the minor to any other body in which case their welfare will be put at peril. Otherwise, it can be argued that the appointed guardian has breached their fiduciary duty to the Court by releasing the minor or disabled to peril.

Also, as indicated in LibCTReg, in the case of a clinical trial on a minor who suffers or may suffer from a disease for which the investigational product (IP) is to be used, the following conditions should be applied:

• The use of the IP must be indicated according to the findings of medical science in order to save the life of the trial participant, to restore the participant to health, to alleviate suffering, or to prevent a disease
• The clinical trial must be of direct benefit to the group of patients suffering from the same disease as the trial participant
• The research must be absolutely necessary in order to confirm data obtained in clinical trials on other persons or by means of other research methods
• The research must relate to a clinical condition from which the minor concerned is suffering or may suffer
• The research may cause only minimal risk and minimal burden to the trial participant

LBR-34 also provides a sample National Research Ethics Board of Liberia (NREB) informed consent form (ICF) for children that explains the parents’ or guardian’s signatures document their permission for the child to take part in a research study as well as their permission for the use and disclosure of the child’s protected health information. If a second parent’s signature is not obtained, the first parent or guardian needs to choose one (1) of the following options on the form to justify why this is not possible:

• The ethics committee (EC) has determined that the permission of one (1) parent is sufficient (this option is only listed on the form if it has been approved by the EC)
• Second parent is deceased
• Second parent is unknown
• Second parent is incompetent
• Second parent is not reasonably available
• Only one (1) parent has legal responsibility for the care and custody of the child

In addition, an individual may provide permission as a guardian for a child only if that individual can provide a written document indicating that the individual is legally authorized to consent to the child’s general medical care and this documentation must be attached to the signed ICF. LBR-34 indicates that the EC must approve the consent form, a witness must be present during the consent process, and the witness must sign and date the ICF.

LBR-8 further states that when a clinical trial includes minors, the minor should be informed about the trial to the extent compatible with his or her understanding and, if capable, the minor should sign and personally date the written informed consent.

As delineated in the G-ACRE-IRB, the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) must classify research involving children into one (1) of four (4) categories and document its discussion of the risks and benefits of the research study in order to approve such research. The risk/benefit categories are as follows (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• When the ACRE IRB determines that the risk is no more than minimal to children in a study, it may approve the research only if adequate provisions are made for soliciting the assent of the children and permission of their parents or legal guardians
• When the ACRE IRB determines that more than minimal risk to children is presented by a procedure that indicates the prospect of direct benefit to an individual child, or by a monitoring procedure that is likely to contribute to the child’s well-being, the ACRE IRB may approve the research if it is established that: the risk is justified by the anticipated benefit to the children; the relation of the anticipated benefit to the risk is at least as favorable to the children as that presented by available alternative approaches; and adequate provisions are made for soliciting the assent of the children and permission of their parents or legal guardians
• When the ACRE IRB determines that the study presents more than minimal risk to children and does not hold out the prospect of direct benefit for the individual child, but is likely to contribute generalizable knowledge about the child’s disorder or condition, the board may approve the research if it established that: the risk represents a minor increase over minimal risk; the study intervention or procedure presents experiences to participants that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations; the intervention or procedure is likely to yield generalizable knowledge about the participants’ disorder or condition which is of vital importance for the understanding or improvement of the participants’ disorder or condition; and adequate provisions are made for soliciting the assent of the children and permission of their parents or legal guardians
• When the ACRE IRB determines that the research does not meet the requirements in any of the above three (3) categories, the board may only approve the research if it finds that the study presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children

The G-ACRE-IRB further states that the ACRE IRB should ensure that adequate permissions are made for soliciting the permission of each child’s parent/legal guardian. The following provisions are used depending on the category of research:

• Research not involving greater than minimal risk to children: Where parental permission is to be obtained, the ACRE IRB may suggest that the permission of one (1) parent is sufficient for research not involving greater than minimal risk
• Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual child: Where parental permission is to be obtained, the board may suggest that the permission of one (1) parent is sufficient for research involving greater than minimal risk but presenting the prospect of direct benefit to the individual participants
• Research involving greater than minimal risk and no prospect of direct benefit to the individual child, but likely to yield generalizable knowledge about the child’s disorder or condition: When the research is approved under this category, both parents must give their permission unless one (1) parent is deceased, unknown, incompetent, not reasonably available, or when only one (1) parent has legal responsibility for the care and custody of the child

If the ACRE IRB determines that a research study is designed for a participant population for which approval from the parents and/or legal guardian(s) or representative(s) is not reasonably required to protect the participants (e.g., neglected or abused children), the G-ACRE-IRB indicates that the consent requirements may be waived. In order to protect the rights and welfare of children in a research study, the board should consider the involvement of a court appointed guardian.

Assent Requirements

Per the LibCTReg, an assent form must be signed, and, if possible, dated by the minor. Similarly, per the G-LibClinTrial, when the research participant is a minor, the investigator must obtain assent from the child/minor. The G-NREB also indicates that both written parental consent and assent forms should be completed for children less than 18 years of age. Per LBR-34, the child’s assent should also be attained unless this can be justified by one (1) of the following reasons:

• The EC determined that assent of the child was not a requirement
• The capability of the child is so limited that the child cannot reasonably be consulted

According to LBR-34, the EC must approve the assent form, a witness must be present during the consent process, and the witness must sign and date the ICF.

In addition, the G-ACRE-IRB explains that adequate provisions for the assent of children include the following:

• Children capable of assenting: After the ACRE IRB determines that a child is capable of assenting, the proposed research procedures should be explained to the child in a language that is appropriate to the age, experience, maturity, and condition of the child and should include any discomforts and inconveniences the child may experience if the child agrees to participate in the study
• The option to withdraw: As they are in the developmental stage, children should be asked if they do or do not wish to participate in the research, especially where the research does not involve interventions likely to be of benefit to the participants but that they will be volunteers for the benefit of others
• The signing of assent or consent: When an assent requirement is established, the investigator or the designee and the child (when appropriate) will sign the study consent form. When it is inappropriate for the child to sign the form (due to age or ability), the board requires that the document be signed by the investigator (or the designee) and the parent/legal guardian

Per the G-ACRE-IRB, the ACRE IRB may determine that assent may be waived if the capability of some or all of the children is so limited that they cannot reasonably be consulted; or the intervention or procedure involved in the research has a direct benefit to the health or well-being of the children and is available only in the context of the research. In such instances, a child’s dissent which should normally be respected, may be overruled by the child’s parents at the discretion of the board (for example, when a research study involves providing experimental therapies for life-threatening diseases such as Ebola Virus Disease, severe COVID-19, or cancer, parents may wish to try anything to help their children, even with the likelihood of success being uncertain). If the child is a matured adolescent, the child’s wishes should be respected.

According to the SL-GCPs, a minor is someone under 18 years of age.

As set forth in the SL-GCPs, when the participant is a minor, informed consent must be obtained from the participant’s parent/legal guardian. Assent from the minor must also be obtained where the minor is capable of understanding. A minor’s refusal to participate in research must be respected.

The SL-GCPs indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to protecting the welfare of certain classes of participants, including minors. Research involving minors should be approved only if:

• The research interventions, including those in observational research, presents the participant with no greater than minimal risk; or
• The research interventions present more than minimal risk but hold out the prospect of direct benefit for the participant; or
• The research interventions, including those in observational research, present more than minimal risk and do not hold out the prospect of direct benefit to the participant, but have a high probability of yielding generalizable knowledge.

In all cases, the protocol must provide sufficient information to justify clearly why minors should be included as participants.

Assent Requirements

The G-SLAppClinTrial also states that in trials involving minors, the parent/legal guardian of a minor is required to sign an informed consent form (ICF). In addition, an assent form similar to the ICF must also be signed and dated by a minor who is capable of understanding as a confirmation of the minor’s willingness to participate in a trial, after having been informed of all aspects of the trial that are relevant to the minor’s decision to participate.

As delineated in the SL-GCPs, assent refers to a minor’s affirmative agreement to participate in research. If a minor fails to object, this should not be construed as assent. The EC (i.e., the SLESRC) must ensure that adequate steps are specified in the protocol to obtain the minor’s assent when, in the EC’s judgment, the minor is capable of providing such assent. Additionally, when the EC determines that assent is required, it must also indicate whether and how such assent must be documented.

As set forth in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines.

As stated in the G-ACRE-IRB, for clinical research studies using the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB), pregnant women or fetuses may be involved in research if all the following conditions are met (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the National Research Ethics Board of Liberia (NREB) and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses
• The risk to the fetus is caused solely by the interventions or procedures considered directly beneficial for the woman or the fetus; or, if there is no such prospect of specific benefit, the risk to the fetus is not greater than minimal and the purpose of the research is for the development of important biomedical knowledge which cannot be obtained by any other means
• Any risk is the least possible for achieving the objectives of the research
• Consent is obtained in accordance with the informed consent provisions in the G-ACRE-IRB if the research holds out the prospect of direct benefit to a pregnant woman; the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman or the fetus when risk to the fetus is not greater than minimal; and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means
• If the research holds the prospect of direct benefit solely to the fetus, then the consent of the pregnant woman and the father is obtained in accordance with the informed consent provisions in the G-ACRE-IRB, except that the father’s consent need not be obtained if he is unable to consent due to unavailability, incompetence, or temporary incapacity, or, the pregnancy resulted from rape or incest (close relationship)
• Each person providing consent is fully informed regarding the foreseeable impact of the research on the fetus and/or resultant child
• For children who are pregnant, assent and permission are obtained in accordance with the provisions for children indicated in this guideline
• No inducements, monetary or otherwise, will be offered to terminate a pregnancy
• Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy
• Individuals engaged in the research will have no part in determining the viability of a fetus

The SL-GCPs requires that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), pay special attention to protecting the welfare of certain classes of participants, including women who are or may become pregnant.

The SL-GCPs states that the following conditions must be met for research conducted with pregnant women and fetuses:

• Applicable studies on animals and non-pregnant individuals have been completed
• The purpose of the study is to meet the health needs of the mother of the particular fetus, the risk to the fetus is minimal and, in all cases, presents the least possible risk for achieving the study’s objectives
• Individuals engaged in the study will have no part in any decision as to the timing, method, and procedures used to terminate the pregnancy, and determining the viability of the fetus at the termination of the pregnancy
• No procedural changes that could cause greater than minimal risk to the fetus or the pregnant woman will be introduced into the procedure for terminating the pregnancy solely in the interest of the activity

Per the SL-GCPs, for any study to be conducted that is associated with either the fetus in utero or ex utero, the parents should be legally competent and have given their informed consent.

The SL-GCPs also specifies that the father’s informed consent does not need to be obtained if any of the following applies:

• The study purpose is to meet the mother’s health needs
• The father’s identity or whereabouts cannot be reasonably established
• The father is not reasonably available
• The pregnancy is the result of rape

Further, per the SL-GCPs, no fetus in utero may be involved as a research participant unless:

• The purpose of the study is to meet the health needs of the particular fetus, and the fetus will be placed at risk only to the minimum extent necessary to meet these needs
• The risk to the fetus in the proposed study is minimal, and the study’s objective is to obtain biomedical knowledge that cannot be achieved by other means

According to the SL-GCPs, until it has been established whether a fetus ex utero is viable, a fetus ex utero may not be involved as a participant in any research study unless one (1) of the following conditions is met:

• The fetus faces no added risk from participation in the study, and the purpose of the study is to develop biomedical knowledge that cannot be obtained by other means
• The purpose of the study is to enhance the possibility of survival of the particular fetus to the point of viability

The SL-GCPs states that nonviable fetuses may not be involved as participants in any research activity unless both of these conditions are met:

• The vital functions of the fetus will not be artificially maintained; experimental activities that would terminate the heartbeat or respiration of the fetus will not be employed
• The purpose of the study is to acquire biomedical knowledge not otherwise obtainable

Participants engaged in the study will have no part in any decision as to timing, method, and procedures used to terminate the pregnancy, and/or determining the viability of the fetus at the pregnancy’s termination.

Pursuant to the G-ACRE-IRB, for clinical research studies using the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB), due to the vulnerability of prisoners, research involving prisoners should be reviewed by a fully convened ACRE IRB. (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the National Research Ethics Board of Liberia (NREB) and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.) Per the G-ACRE-IRB, the ACRE IRB may only approve research projects involving prisoners if the research falls under one (1) of the following categories:

• Study of possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk or inconvenience to the participant
• Study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the participants
• Research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on Ebola, COVID-19, hepatitis, as well as social and psychological research such as alcoholism, drug addiction, and sexual assaults)
• Research on practices that are intended and have the probability of improving the health or well-being of the participants

In addition, per the G-ACRE-IRB, the ACRE IRB must review research involving prisoners and approve such research only if it finds that:

• The risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers
• Procedures for the selection of participants within the prison are fair to all prisoners, and free of arbitrary interference by prison authorities or prisoners. Other than the investigator’s justification to the ACRE IRB, the use of other procedures, and the selection of control participants from the available prisoner population for a particular research study should be randomly done
• The information is presented in a language that is understandable to the participant population
• There is adequate assurance that parole boards will not take into account a prisoner’s participation, withdrawal, or lack of participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that their participation, withdrawal, or lack of participation in the research will have no effect on his or her parole
• The ACRE IRB should ensure that adequate provisions are made where there will be a follow-up examination or care of participants after the end of their participation, considering the variable lengths of individual prisoners’ sentences, and informing participants of this information

The SL-GCPs indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to protecting the welfare of certain classes of participants, including prisoners. Prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. A research study may only involve prisoners as participants when the EC (i.e., the SLESRC) has ensured that the clinical trial involves:

• The study of the possible causes, effects, and processes of incarceration and of criminal behavior with no more than minimal risk and inconvenience to the participants
• The study of prisons as institutional structures or of prisoners as incarcerated persons
• Research on conditions particularly affecting prisoners as a class (e.g., vaccine trials and other research on diseases that may be more prevalent in prisons, and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults) only after appropriate experts have been consulted
• Research on practices, both innovative and accepted, that have the intent and probability of improving the health or wellbeing of prisoners

In addition, per the SL-GCPs, in a study where some prisoners may be assigned to control groups that may not benefit from the research, the study may proceed only after appropriate experts have been consulted. Research that could be conducted on a population other than prisoners should not be permitted unless the EC is presented with a valid case and is convinced that the study does not represent exploitative research.

The SL-GCPs also states that when the EC reviews research involving prisoners, the following requirements must be met:

• The majority of the EC members, other than prison members, must have no association with the prison(s) involved
• At least one (1) member of the EC must be a prisoner, or a prisoners’ representative with appropriate background and experience to serve in that capacity. Where a research project is reviewed by more than one (1) EC, only one (1) EC need satisfy this requirement

As set forth in the LibCTReg, “persons under legal disability” is defined as being under the same category as a minor in terms of the individual’s ability to grant consent, except that the person under disability may be above the age of consent (18 years) even though the person may lack the mental capacity to reason properly and grant consent. In this case, priority is not given to parents or next of kin to petition the Probate Court for Guardianship, but priority is given to any natural person who demonstrates the best interest in the welfare of the disabled.

The LibCTReg further explains that a person under legal disability may participate in a trial, if their parents/legal guardians have be informed of the nature, significance, and implications of the clinical trial and have given a written voluntary informed consent. If the informed implication is grave, it may be necessary for the guardian to secure the permission from the Probate Court before granting consent, due to the fact that the Decree of Guardianship has a clause that the court-appointed guardian should not release the disabled person to any other body in which case their welfare will be put at peril. Otherwise, it can be argued that the appointed guardian has breached their fiduciary duty to the court by releasing the disabled person to peril.

Also, as indicated in LibCTReg, in the case of a clinical trial on a person of legal age who is incapable of comprehending the nature, significance, and implications of a clinical trial and of determining their will in the light of these facts, and who is also suffering from a disease which is to be treated by the investigational product (IP), the following conditions should be applied:

• The use of the IP must be indicated, according to the findings of medical science, in order to save the life of the trial participant, to restore the participant to health or to alleviate suffering
• The research must relate directly to a life-threatening or highly debilitating clinical condition suffered by the trial participant and the clinical trial may involve as little burden and other foreseeable risks as possible for the trial participant. Both the degree of burden and the risk threshold must be defined specifically in the trial protocol and monitored constantly by the investigator. The clinical trial may only be conducted if there is a justified expectation that the benefits of using the IP for the trial participant outweigh the risks
• Consent should be given by the legal representative/guardian after participant has been duly informed per the general clinical trial requirements in LibCTReg
• The research must be absolutely necessary for the confirmation of data obtained from clinical trials conducted on persons capable of granting informed consent or by means of other research methods
• With the exception of adequate compensation, no advantages may be granted

Additionally, as per the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines.

LBR-34 provides a sample National Research Ethics Board of Liberia (NREB) informed consent form (ICF) for adults unable to consent, which explains that the signature of the legally authorized representative documents their permission for the participant named in the ICF to take part in this research study, as well as their permission for the use and disclosure of the participant’s protected health information. The participant’s assent should also be attained unless this can be justified by one (1) of the following reasons:

• The EC determined that assent of the participant was not a requirement
• The capability of the participant is so limited that the participant cannot reasonably be consulted

The previously listed options are only available if they have been approved by the EC. A witness must also be present during the consent process and the witness must sign and date the ICF.

According to the SL-GCPs, the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to research participants with mental disabilities, including those with psychiatric, cognitive, or developmental disorders, or participants with substance abuse related disorders. Individuals who have been institutionalized may be further compromised in terms of their capacity to make a truly voluntary decision to participate in a study.

Per the SL-GCPs, research involving people with mental disabilities or with substance abuse related disorders must therefore:

• Be relevant to mental disabilities or substance abuse related disorders so that it is necessary to involve people who have a mental disability and/or a substance abuse related disorder(s)
• Justify the involvement, as the study population, of institutionalized people with mental disabilities
• Ensure appropriate evaluation procedures for ascertaining the participants’ ability to provide informed consent. If participants are deemed unable to understand and make a choice, then consent should be obtained from the participant’s legal representative/guardian
• Ensure that consent is free from coercion and risk to participants
• Ensure that only minimal risk is involved, and that the risk is outweighed by the anticipated benefits for the participants and by the importance of the knowledge that will be derived from the research

In addition, the SL-GCPs notes that persons with intellectual or mental impairment should not participate in research that might be conducted equally well with individuals without those impairments. Consent cannot be given that is contrary to the interests of a participant with mental or intellectual impairment, and the person's refusal to participate in research must always be respected. Accordingly, consent must be obtained from one (1) of the following:

• The participant to the extent that the participant is competent to give informed consent
• The participant’s legal representative/guardian when the participant is deemed not competent to do so
• An authority, organization, or individual legally authorized to do so

The SL-GCPs further states that research involving participants with impaired capacity to communicate also requires special attention. The distinguishing features of research involving participants with impaired capacity to communicate include acute impairment states requiring medical care, as well as non-acute states. In acute impairment states, the condition and medical care may mask the participant’s degree of cognition and require different means of expression. In non-acute impairment states, the condition may prevent the participant from expressing wishes at all.

As indicated in the SL-GCPs, research involving unconscious persons requires consent to be provided by the participant’s legal representative/guardian, including any relevant statutory authorities, on that person’s behalf. Because of their extreme vulnerability, unconscious persons should be excluded from all but minimally invasive observational research. When neither the prospective participant nor the legal representative/guardian is able to give consent in advance, the EC (i.e., the SLESRC) may approve a research project without prior consent if it is satisfied that:

• Inclusion in the trial is not contrary to the interests of the participant
• The research is intended to be therapeutic and poses no more risk than is inherent to the participant’s condition or would be caused by alternative methods of treatment
• The participant and the legal representative/guardian will be informed as soon as is reasonably possible of the participant’s inclusion in the study and of the option to withdraw from the research project at any time
• The research is based on valid scientific hypotheses and offers a realistic possibility of benefit over standard care

Per the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines.

As delineated in LibCTReg and LBR-8, an investigational product (IP) is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form, when used for an unapproved indication, or when used to gain further information about an approved use. In Liberia, IPs are referred to as investigational medicinal products (IMPs).

As delineated in the G-SLAppClinTrial and the SL-GCPs, an investigational product (IP) is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form, when used for an unapproved indication, or when used to gain further information about an approved use.

Manufacturing

As set forth in the LMHRA-Act, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) is responsible for issuing licenses or permits for premises and personnel to engage in the manufacture of medicinal products in Liberia. The LibCTReg also states that investigational products (IPs) for clinical trials must be manufactured according to internationally accepted good manufacturing practice (GMP) principles.

Per the LibCTReg and the G-LibClinTrial, the LMHRA has also adopted the International Council for Harmonisation (ICH)'s Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. LBR-8 notes that the sponsor should ensure an IP including the active comparator(s) and placebo, if applicable, is characterized as appropriate to the IP’s stage of development and is manufactured in accordance with applicable GMP. Per LBR-29, the World Health Organization’s (WHO) GMP Guidelines for IPs (LBR-26) and the International Council for Harmonisation (ICH) Harmonised Tripartite GMP Guide for Active Pharmaceutical Ingredients (LBR-9) must also be complied with during the IP manufacturing process.

As explained in G-Inspec-PMS, where pharmaceutical factories have not yet established validated manufacturing processes for pharmaceuticals for use in clinical trials, or have not yet established comprehensive manufacturing control standards, the factories must establish written operational procedures and keep detailed and accurate records for each batch of products manufactured, and each batch of raw material used. Batch manufacturing records must be kept until clinical trials are completed, or until at least two (2) years after the product is completed, whichever period is longer. Additionally, where pharmaceutical factories produce biopharmaceuticals or biotechnology products for use in clinical trials, impurities caused by virus inactivation/removal or other organisms may not exceed the limits imposed on other similar products on the market; where operational procedures for said products have not yet been validated, quality control tests must be performed.

Import

As set forth in the LMHRA-Act, the LMHRA is also responsible for issuing licenses or permits for the import/export of medicinal products in Liberia. Pursuant to the G-Inspec-PMS, authorization must be obtained from the LMHRA for the importation of medicines to be used in clinical trials. Per LBR-30, the Clinical Trials Unit within the LMHRA’s Pharmacovigilance & Clinical Trials Department is responsible for reviewing importation permits for IPs that are required for the conduct of clinical trials. Per LBR-5, the department is also responsible for receiving IP application submissions in Liberia and coordinating with the LMHRA’s Clinical Trial Team to ensure the safety and efficacy of the IPs to be used in clinical trials.

According to LBR-5, the IP dossier documentation requirements for the LMHRA’s approval are as follows:

• Submit typewritten application as per G-LibClinTrial
• Pay the required fee into the LMHRA bank account
• Submit payment slip to the Finance Department to obtain an official LMHRA receipt
• Present the IP dossier(s) along with the official receipt and product samples to the LMHRA

The G-LibClinTrial further explains that if the IP(s), health products, or any auxiliary medicinal product must be imported, the clinical trial must be approved by the LMHRA before the import can be authorized. IPs may only be imported if they are not locally available or if the need for importation is otherwise justified. The justification must be stated in the import permit application letter.

Per the LibCTReg and the G-LibClinTrial, the import permit application must contain the following information and documentation:

• Name and address of the sponsor, the sponsor’s legal representative, or the sponsor-investigator (both physical and postal)
• Principal investigator’s name, address (both physical and postal), and contact details (e.g., phone number and email)
• The clinical trial for which the application is made
• The planned clinical trial sites and the planned number of participants at the sites
• IP(s) description by name or code, strength, and dosage form
• IP(s) unit of issue, total quantity, batch number, manufacture, and expiry dates
• Sample labels of the primary and secondary containers
• Planned return of unused IP(s) to sponsor or destruction at the clinical trial site

The LibCTReg also notes that an application letter should be sent to the LMHRA Managing Director along with the required documentation.

In addition, per G-LibClinTrial, a parallel submission for approval of the clinical trial and the import permit application is possible. In this case, the import permit application can be included in the clinical trial application package.

Please note: Liberia is party to the Nagoya Protocol on Access and Benefit-sharing (LBR-3), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see LBR-17.

Manufacturing

As set forth in the PDA2001, the Pharmacy Board of Sierra Leone (PBSL) is responsible for authorizing the manufacture of all drug products in Sierra Leone. According to the SL-GCPs, the sponsor must ensure that the investigational product (IP) is manufactured in accordance with applicable good manufacturing practice (GMP).

The G-SLAppClinTrial states that a GMP certificate from the national competent authority of the country of origin is required when the IP has no marketing authorization in Sierra Leone, or has marketing authorization but its original indication is modified for the purpose of the trial. The GMP certificate should conform to the World Health Organization (WHO) format.

Import

The G-SLAppClinTrial states that the PBSL is responsible for authorizing the import of IPs. A request to import an IP may be submitted after the PBSL has approved the clinical trial application.

The G-SLAppClinTrial indicates that the import application submission must include the following documentation:

• Letter stating the name/description and quantities of each IP, placebo, and trial related product to be imported as well as the details of the location where the product is coming from and details of the recipient in Sierra Leone
• Certificate of analysis of IP and placebo for all batches to be imported
• Lot release certificate (where applicable) for all batches to be imported
• Investigator, sponsor, and recognized clinical research entity’s name and address

According to the G-SLAppClinTrial, the PBSL’s processing time for IP import permits is 10 working days. Imported IPs may be inspected by PBSL officials at the port of entry before they are released to the recognized clinical research entity. The PBSL may order for destruction or re-exportation of the IPs if it has any reason to believe that there is a protocol violation resulting in the termination of the study. See the G-SLAppClinTrial for detailed IP import requirements.

As per the G-FastReg, if a product being registered in Sierra Leone is going to be used in a clinical trial, the registration application may be expedited. If the conditions for expedited registration are fulfilled, the PBSL will process the application and communicate its decision within 21 calendar days.

Please note: Sierra Leone is party to the Nagoya Protocol on Access and Benefit-sharing (SLE-2), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see SLE-18.

Investigator’s Brochure

Per the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. Per the LBR-8, the sponsor should also update the investigator’s brochure (IB) as significant new information becomes available.

As specified in the LBR-8, the IB must provide coverage of the following areas:

• Physical, chemical, and pharmaceutical properties
• Pharmaceutical aspects
• Pharmacokinetics and metabolism
• Toxicological effects in any animal species tested under a single dose study, a repeated dose study, or a special study
• Results of clinical pharmacokinetic studies
• Information regarding safety, pharmacodynamics, efficacy, adverse events data, and dose responses obtained from prior clinical trials in humans

See the LBR-8 for additional details regarding the IB.

Quality Management

Per the G-LibClinTrial, the Good Manufacturing Practice (GMP) certificate issued from the national regulatory authority of the country where the investigational product (IP) is manufactured must be included in the clinical trial application submission package, if applicable. If necessary, the certificate must be translated to English.

According to LBR-29, the sponsor or the representative must also ensure that the products are manufactured in accordance with the WHO’s GMP Guidelines for Investigational Products (LBR-26) and the ICH Harmonised Tripartite Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (LBR-9).

Per LBR-8, the sponsor must maintain a Certificate of Analysis to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

(See Product Management section for additional information on sponsor requirements).

Investigator’s Brochure

In accordance with the G-SLAppClinTrial and the SL-GCPs, the Investigator’s Brochure (IB) is a compilation of the clinical and nonclinical data on the investigational product(s) (IP(s)) which is relevant to the study of the IP(s) in human participants.

As per the SL-GCPs, the sponsor is responsible for providing the investigators with an IB, and the sponsor should update the IB as significant new information becomes available. The G-SLAppClinTrial further specifies that an updated IB should be submitted at least once a year, or whenever it is updated within this period. Additional information and any changes that have been incorporated in the updated IB should be highlighted for ease of review and evaluation.

According to the G-SLAppClinTrial, the content and structure of the IB must comply with the SL-GCPs and the International Council for Harmonisation’s (ICH) Guideline for Good Clinical Practice E6(R2) (SLE-24). Accordingly, the IB must provide coverage of the following areas:

• Physical, chemical, and pharmaceutical properties and formulation parameters
• Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
• Effects of IP in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
• Summary of data and guidance for the investigator(s)
• Toxicological effects in any animal species tested under a single dose study, a repeated dose study, or a special study

See the SL-GCPs and SLE-24 for detailed content guidelines.

Quality Management

According to the G-SLAppClinTrial, a good manufacturing practice (GMP) certificate from the national competent authority of the country of origin is required when the IP has no marketing authorization in Sierra Leone, or has marketing authorization but its original indication is modified for the purpose of the trial. The GMP certificate should conform to the World Health Organization (WHO) format.

Investigational product (IP) labeling in Liberia must comply with the requirements set forth in the LibCTReg, the G-LibClinTrial, and the G-Inspec-PMS. While there is no specified language requirement for IP labeling, English appears to be the preferred language. (Note: IPs are also referred to as investigational medicinal products (IMPs)). Per the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines.

The LibCTReg specifies that IPs to be used in a clinical trial center must be properly labelled and the package must sufficiently identify the following:

• The clinical trial to be carried out
• The medicine(s) to be used
• The trial participant identification number to whom the medicine is to be administered
• The name and address of the site where the clinical trial is conducted
• The directions in regard to the manner in which such medicine should be used
• The date of dispensing, if applicable
• The storage conditions
• The use-by, expiry, or re-test date, as applicable
• The reference number, as applicable
• Any other information as may be required by the LMHRA

As delineated in the G-LibClinTrial, if the primary container takes the form of blister packs or small units such as ampoules, the secondary packaging should be provided bearing a label with the required particulars. However, the primary container should bear the following information:

• Name of the sponsor, contract research organization (CRO), or investigator
• Route of administration (may be excluded for oral solid dosage forms) and in the case of open trials, the name/identifier of the IP and strength/potency
• Batch and/or code number to identify the contents and packaging operation
• A trial reference code allowing identification of the trial, site, investigator, and sponsor if not given elsewhere
• The trial participant identification number/treatment number and where relevant, the visit number

In addition, the G-LibClinTrial explains that if it becomes necessary to change the expiry/use-by date, an additional label should be affixed to the IP which should state the new use-by date and repeat the batch number. It may be superimposed on the old date, but for quality control reasons, not on the original batch number. The operation should be performed at an appropriately authorized manufacturing site. However, when justified, the operation may be performed at the investigational site by or under the supervision of the clinical trial site pharmacist (if available), the principal investigator, or the clinical trial monitor(s), who should be appropriately trained. The provisions listed above may apply for auxiliary medicinal products. An auxiliary medicinal product is a medicinal product used for the needs of a clinical trial as described in the protocol, but not as an IP (e.g., medicinal products used as rescue medication, challenge agents, to assess endpoints in the clinical trial, or background treatment).

As explained in the G-Inspec-PMS, where pharmaceutical factories produce pharmaceuticals for use in clinical trials, the IPs must also be labeled “for use in clinical trials only” and marked with the name of the party that commissioned the clinical trial and a trial code sufficient to identify the trial location and the research personnel involved. However, where pharmaceuticals for use in clinical trials are tested in closed trials (double-blind trials), drug name, potency, and efficacy may be replaced by product codes, serial numbers, and packaging batch numbers.

LBR-8 states that the IP must be coded and labeled in a manner that protects the blinding, if applicable, and comply with applicable regulatory requirements. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

Investigational product (IP) labeling in Sierra Leone must comply with the requirements set forth in the G-SLAppClinTrial and the SL-GCPs. As stated in the G-SLAppClinTrial, all label information should be in English and the print should be clear, legible, and indelible.

As set forth in the G-SLAppClinTrial, the Pharmacy Board of Sierra Leone (PBSL) requires the following information be included on the labels:

• Sponsor details
• Pharmaceutical dosage form, route of administration, quantity of dosage units, and in the case of open trials, the name/identifier and strength/potency
• Batch number
• Trial reference number
• Trial subject identification number
• Name and address of the clinical trial site and the principal investigator
• Directions for use and any warnings or precautions that may be necessary
• Statement indicating “For clinical trial/research use only”
• Storage conditions
• Period of use (use-by date, expiry date, or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity as well as date of dispensing, if applicable
• Statement indicating “Keep out of reach of children” except when the product is for use in trials where the product is not taken home by participants

The SL-GCPs further states that in blinded trials, the coding system for the IP(s) should include a mechanism that permits rapid identification of the product(s) in case of a medical emergency, but does not permit undetectable breaks of the blinding.

Supply, Storage, and Handling Requirements

Per the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation (ICH)'s Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. According to LBR-29, the World Health Organization's (WHO) Good Manufacturing Practice (GMP) Guidelines for Investigational Products (IPs) (LBR-26) and the ICH Harmonised Tripartite Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (LBR-9) must also be complied with during IP product management. In addition, per the LMHRA-Act, the LMHRA is responsible for the supply and storage of medicinal products in Liberia. See LBR-26 and LBR-9 for details.

The LibCTReg specifies that it is the responsibility of the sponsor to supply IPs (also referred to as investigational medicinal products (IMPs)) produced in compliance with internationally accepted GMP principles. According to LBR-8, the sponsor or the representative must also supply the investigator(s)/institution(s) with the IPs. The sponsor or the representative should not supply either party with the IP(s) until all the required documentation is obtained. In this case, per the LMHRA-Act, the LMHRA approval license/permit is the required documentation. Per LBR-8, the IPs should be manufactured, handled, and stored in accordance with applicable GMP and the sponsor must ensure that the written procedures include instructions that the investigator/institution should follow for the handling and storage of IP(s) for the trial and documentation thereof. The procedures should address adequate and safe receipt, handling, storage, dispensing, retrieval of unused product from participants, and return of unused IP(s) to the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the applicable regulatory requirement(s)). The sponsor must also ensure the timely delivery of the IP(s).

LBR-8 specifies that the sponsor should determine acceptable storage temperatures, storage conditions (e.g., protection from light), storage times, reconstitution fluids and procedures, and devices for product infusion for the IPs, if any. The sponsor should inform all involved parties (e.g., monitors, investigators, pharmacists, storage managers) of these determinations. Further, the sponsor should also take steps to ensure that the IPs are stable for the period of use and maintain sufficient quantities of IPs to reconfirm specifications, and if necessary, maintain records of batch sample analyses and characteristics. To the extent stability permits, samples should be retained either until the trial data analyses are complete, or as required by the applicable regulatory requirements, whichever represents the longer retention period. Refer to LBR-8 for detailed, sponsor-related IP requirements.

The LibCTReg further specifies that destruction operations for IPs should be carried out in such a manner that all operations may be accounted for. Documentation should clearly identify, or allow traceability to, the batches and/or trial participant numbers involved and the actual quantities destroyed. The G-LibClinTrial also states that if the IP(s), health product(s), or auxiliary medicine(s) used in a clinical trial are to be destroyed at any point in time, a respective destruction procedure must be provided to the LMHRA as part of the clinical trial protocol. The sponsor or the contract research organization (CRO) must bear the cost of the disposal.

As per the LibCTReg, if the sponsor or sponsor-investigator would like to export the IP(s) remaining after the clinical trial has been stopped or completed, the sponsor, the legal representative, or the sponsor-investigator must obtain an export authorization from the LMHRA.

Per the G-Inspec-PMS, pharmaceutical factories must determine a suitable expiration date for pharmaceuticals for use in clinical trials based on the product properties, container characteristics, and storage conditions. See the G-Inspec-PMS for additional information.

Record Requirements

Per LBR-8, the sponsor must ensure the following:

• Maintain records that document IP(s) shipment, receipt, disposition, return, and destruction
• Maintain a system for retrieving IPs and documenting this retrieval
• Maintain a system for the disposition of unused IP(s) and for the documentation of this disposition

LBR-8 also specifies that the investigator/institution and/or a pharmacist, or other appropriate individual who is designated by the investigator/institution, should maintain records of the IP's delivery to the trial site, the inventory at the site, the use by each participant, and the return to the sponsor or alternative disposition of unused product(s). These records should include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the unique code numbers assigned to the IP(s) and trial participants. Investigators should maintain records that document adequately that the participants were provided the doses specified by the protocol and reconcile all IP(s) received from the sponsor.

In addition, per LBR-8, sponsor-specific essential documents should also be retained until at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the IP’s clinical development.

Supply, Storage, and Handling Requirements

As delineated in the SL-GCPs, the sponsor must supply the investigator(s)/institution(s) with the investigational product(s) (IP(s)). The sponsor should not supply either party with the IP(s) until obtaining approval from the Pharmacy Board of Sierra Leone (PBSL).

The SL-GCPs specifies that the sponsor must:

• Ensure timely delivery of the IP(s) to the investigator(s)

• Maintain records that document shipment, receipt, disposition, return, and destruction of the IP(s)

• Maintain a system for retrieving IPs and documenting this retrieval
• Maintain a system for the disposition of unused IP(s) and documenting this disposition

• Take steps to ensure IP stability over the period of use
• Maintain sufficient quantities of the IP(s) to reconfirm specifications, if needed, and maintain records of batch sample analyses and characteristics

• Ensure the IP is manufactured according to any applicable good manufacturing practice (GMP)

• Ensure proper coding, packaging, and labeling of the IP(s)

Refer to the SL-GCPs for detailed sponsor-related IP requirements.

Per the SL-GCPs, the IP(s) should be packaged to prevent contamination and unacceptable deterioration during transport and storage. Additionally, per the G-SLAppClinTrial, the PBSL requires the IP packaging to comply with the following requirements:

• The container in which the product is contained should be of good quality
• The container and closure should be properly sealed in order to protect the product from the impact of outside environmental factors
• Each sample should contain an insert

According to the G-SLAppClinTrial, the principal investigator (PI) must notify the PBSL of each consignment of IP batches received on site. The notification must include the product name(s), quantities received, and batches received. The PBSL must approve destruction of IPs, which should be carried out in such a manner that all operations may be accounted for. These documents should clearly identify, or allow traceability to, the batches and/or participant numbers involved, and the actual quantities destroyed. A destruction certificate will be issued by the PBSL.

Record Requirements

The G-SLAppClinTrial indicates that for IPs purchased locally, the PI must document the source, proof of purchase, quantities purchased, and the Certificate of Analysis for each batch of IPs. Copies of all documents on the IP(s), whether purchased locally or imported, must be kept on site for verification and accountability during good clinical practice (GCP) inspections.

As per the SL-GCPs, the sponsor should retain all sponsor-specific essential documents in conformance with the applicable regulatory requirement(s) of the country(ies) where the product is approved, and/or where the sponsor intends to apply for approval(s). All sponsor-specific essential documents should be retained for at least two (2) years after formal discontinuation of the trial or in conformance with applicable regulatory requirements. In addition, all clinical and experimental data (electronic or paper) should be kept in a secure place for a period of five (5) years, and 20 years for a new drug application after a trial’s completion, and be readily available for review upon request by the PBSL.

While the Liberia Medicines and Health Products Regulatory Authority (LMHRA) does not provide a formal definition for specimens, the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) describes examples of specimens in the G-ACRE-IRB. As per the G-ACRE-IRB, examples of biological specimens include:

• Collection of blood via finger or ear stick
• Hair and nail clippings collected in a non-disfiguring manner
• Excreta and external secretions (including sweat)
• Sputum collected through expectoration
• Bodily fluids
• Tissue biopsies

Import

Information is unavailable regarding the Liberia Medicines and Health Products Regulatory Authority (LMHRA)’s role in approving the import of biological specimens.

Export

As set forth in the LibCTReg and the G-LibClinTrial, the applicant must obtain an authorization from the LMHRA if biological samples are to be exported out of Liberia. Additionally, per the LibCTReg and G-LibClinTrial, the applicant must provide an annual progress report on the use and results obtained from the biological samples exported out of Liberia. Pursuant to Part VIII of the LMHRA-Act, the LibCTReg also states that any person(s), institution(s), corporate entity(ies), their designees or legal representatives who is found in violation of any provision of the biological sample export requirements delineated in LibCTReg will be liable to fines as prescribed by the LMHRA at the time of commission.

Material Transfer Agreement

Per the LibCTReg and the G-LibClinTrial, a material transfer agreement (MTA) must also be provided to the LMHRA. The G-LibClinTrial notes that the authorization request and the MTA should be included in the clinical trial application submission package.

The G-NREB indicates that the National Research Ethics Board of Liberia (NREB) requires the MTA process be used for the shipment of specimens/biological materials outside of Liberia. The G-NREB also specifies that when a protocol application is submitted for review by the NREB, the accompanying documentation should also include an MTA for the shipment of the specimen/biological materials outside of Liberia (where applicable).

According to the G-ACRE-IRB, the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) requires the MTA process be used for the shipment of specimens/biological materials outside of Liberia. The G-ACRE-IRB further explains that the purpose of an MTA is to protect the interests of local researchers and Liberia’s human and natural resources in all its biodiversity and how they can be legitimately used. It ensures that the interests of all relevant parties are protected from exploitation and egregious harm. (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.)

Per the G-ACRE-IRB, for studies using the ACRE IRB, the MTA must detail the type of materials, anticipated use, location of storage outside Liberia, duration of such storage, and limitations on use, transfer, and termination of use of such materials subject to any laws, regulations, and enactments in Liberia.

In addition, per the G-ACRE-IRB, the ACRE IRB requires an MTA be signed by all parties involved in the research including local and international principal investigators, heads of local institutions, research sponsors, and other relevant entities prior to the transfer or export of biological samples out of Liberia. The MTA must detail the type of materials, anticipated use, location of storage outside Liberia, duration of such storage, limitations on use, transfer, and termination of use of such materials, subject to any laws, regulations, and enactments in Liberia. The following requirements must also be met:

• The ACRE IRB (the provider institution) must review the MTA to ensure consistency with the stated objectives of the research, the contents of the informed consent documents, and the principles stated in the G-ACRE-IRB. The ACRE IRB must grant provisional approval pending the submission of the MTA to the ethics committee (EC) (the recipient institution) and the EC’s receipt of acknowledgement
• The applicant for research review (the scientist or sponsor at the provider institution) must file a copy of the MTA and provisional approval by the ACRE IRB (the provider institution) with the EC (the recipient institution) for record purposes only
• The EC (the recipient institution) must acknowledge receipt of the MTA to the applicant (the scientist or sponsor at the provider institution) who must inform the ACRE IRB (the provider institution)
• The ACRE IRB (the provider institution) is required to grant final approval to research involving international transfer of Liberian samples after all the other stated criteria have been met and upon acknowledgement of MTA receipt

According to the G-SLAppClinTrial and SLE-23, the Pharmacy Board of Sierra Leone (PBSL) is responsible for authorizing the import and export of all biological specimens in Sierra Leone. However, the G-SLAppClinTrial does not have any additional information regarding specimens import.

Export

As set forth in the G-SLAppClinTrial, all institutions or individuals that wish to export any clinical information, medical records, and/or biological samples from Sierra Leone to an institution outside of the country must complete the PBSL’s requirements for material transfer authorization. The sponsor must provide annual updates on the use of, and results obtained from, biological samples exported out of Sierra Leone.

Per the G-SLAppClinTrial and the G-MTA, the local principal investigator or study lead must submit an application for an export permit submitted through the Ministry of Health and Sanitation (MoHS) to the PBSL. All applications must be accompanied by the following documents:

• Evidence of informed consent for use of medical records, clinical information, and biological samples from living participants
• MoHS authorization for deceased patients
• Memorandum of understanding (MOU) between MoHS and the applicant
• Signed and dated Material Transfer Agreement (MTA)
• Payment of PBSL prescribed export permit fee

Please refer to SLE-1 for the materials transfer template.

Detailed information is unavailable regarding the Liberia Medicines and Health Products Regulatory Authority (LMHRA)’s requirements for obtaining informed consent from participants prior to collecting, storing, or using their biological sample(s). Additionally, no applicable requirements are available regarding the National Research Ethics Board of Liberia (NREB)’s requirements for obtaining participant informed consent prior to collecting, storing, or using their biological sample(s).

However, the G-ACRE-IRB notes that for studies using the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB), the Material Transfer Agreement (MTA) does not invalidate the right of research participants or communities to request that their samples be withdrawn from research according to the terms of the informed consent process. (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.)

As delineated in the G-ACRE-IRB, the following information must be provided for the ACRE IRB’s review of a research protocol involving specimens:

• A full description of any specimens that will be collected (blood, bodily fluids, tissue biopsies, etc.)
• Plans for obtaining consent and clearance from participants and the ACRE IRB, for long-term storage, export, and future research
• Arrangements for transfer and disposal
• Community considerations
• The impact and relevance of the research on the local community from where the research participants are recruited as well as the wider communities and the environment of concern
• The consultation procedures with the concerned communities at the time of the planning and designing of the research
• The influence of the community on the consent of the research participants/individuals
• Proposed community consultation during the course of the research
• The extent to which the research contributes to capacity-building, such as the improvement of local healthcare, research, and the ability to respond to public health needs
• Description of how the research results will be made available to the research participants and the concerned communities

Pursuant to the G-ACRE-IRB, for research that involves the collection of identifiable private information or identifiable biospecimens, one (1) of the following must be included in the informed consent:

• A statement that identifiers will be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies without additional informed consent from the participant or legal representative/guardian; or
• A statement that the participant's information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies

See the Required Elements and Participant Rights sections for additional information on informed consent.