Liberia Medicines and Health Products Regulatory Authority

As per the LMHRA-Act 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 the following:

• 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 the 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 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

According to LBR-29, the LMHRA has also established a Scientific Advisory Committee (SAC), that is responsible for providing technical support for the review of clinical trial applications and for post-approval safety and compliance issues.

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
West Africa

Phone: (+231) 777-140-555 or (+231) 888-140-555
Email: info@lmhra.gov.lr

Overview

In accordance with the LMHRA-Act 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 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. Per LBR-29, the LMHRA has established a Scientific Advisory Committee (SAC) that is responsible for providing technical support for the review of clinical trial applications and for post-approval safety and compliance issues.

Per the G-LibClinTrial, the LMHRA will only process an application upon receipt of a completed application and the prescribed fees. The G-LibClinTrial indicates that 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, 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. 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. During this 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, the applicant must modify the application within an established timeline, or it 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. 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.

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). 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.

In addition, as delineated in the G-LibClinTrial, the LMHRA may inspect clinical trial sites and/or the sponsor's or the contract research organization (CRO)’s premises and/or the manufacturer to ensure that clinical trials comply with the good clinical practice (GCP) provisions before, during, or after a trial is conducted. NREB representatives may accompany the LMHRA during clinical trial site inspections as well as other relevant regulatory authorities. If the LMHRA has reasonable cause to believe that the approved protocol is being violated, 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 principal investigator (PI) and/or sponsor while safeguarding confidential aspects. The report may also be made available to the NREB and other regulatory authorities upon their request.

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

Liberia Medicines and Health Products Regulatory Authority

The G-LibClinTrial requires proof of payment of the clinical trial application fee in the application dossier. Per 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 for the LMHRA clinical trial application fee.

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 and LBR-13 state 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)), and with Liberia’s applicable regulations and guidelines. In addition, per the G-NREB and LBR-13, the NREB is responsible for reviewing all clinical research protocols involving human participants submitted by individual investigators affiliated with nationally and internationally recognized institutions.

Per the NatResHlthPlcy, the G-NREB, and LBR-13, the NREB is also responsible for the following (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• Establishing guidelines for the review of research for health protocols for use by other review boards
• Reviewing and approving protocols in line with established ethics guidelines
• Giving advice on ethical research issues to the MoH and related government ministries and agencies
• Monitoring the conduct of research for health to ensure compliance with approved protocols
• Establishing and maintaining a repository of all protocols reviewed in the country along with finished research/study reports
• Supporting research ethics capacity building

The G-NREB and LBR-13, further identify the following NREB duties (Note: The sources provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• Setting norms and standards for conducting research on humans and animals, including clinical trials
• Informing professional bodies of any breaches of professional ethical standards
• Recommending disciplinary action(s), where appropriate

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. ACRE IRB does not review and approve clinical trial protocols.

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. LBR-38 also specifies 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.

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 and LBR-15, 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. Per the G-NREB and LBR-14, 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. The G-NREB and LBR-16 explain that all complete applications submitted by the deadline must be reviewed at the next regularly scheduled meeting if the number of applications meet the threshold. The G-NREB and LBR-14 further specify that 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, LBR-13, LBR-15, LBR-14, and LBR-16 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.

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 member(s) who is/are unavailable during a meeting), 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

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 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 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 G-LibClinTrial, any substantial amendment to the clinical trial research protocol must be approved by the LMHRA and the NREB before such amendments are carried out.

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. Per the G-NREB and LBR-16, 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 and LBR-16 explain 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 the G-NREB, 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. Refer to the G-NREB for detailed continuing review submission requirements and the Timeline of Review section for detailed timeline information.

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. 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.

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, ACRE IRB does not review and approve clinical trial protocols.

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. Please 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.

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.

Overview

There are no applicable regulations or guidance regarding the authorization of ethics committees (ECs) in Liberia. However, per G-NREB and LBR-13, 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

In accordance with the LMHRA-Act and the G-LibClinTrial, the sponsor or the representative is responsible for submitting a clinical trial application to the Liberia Medicines and Health Products Regulatory Authority (LMHRA). The G-LibClinTrial, in turn, states 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). However, per the G-ACRE-IRB and the G-NREB, the PI must obtain ethics committee (EC) approval. The G-LibClinTrial states that the NREB and LMHRA reviews may be conducted in parallel. Therefore, 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 G-LibClinTrial, the sponsor or the representative should submit the application form and associated documents both electronically and as printed copies (four (4) sets) 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.

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)
VP Road, Tubman Boulevard
Old Road, Sinkor
1000 Monrovia, 10 Liberia
West Africa

Ethics Review Submission

National Research Ethics Board of Liberia

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

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). According to LBR-28, the ACRE IRB suspended the requirement during the pandemic for PIs to submit eight (8) hard copies of the protocol and they have not yet reinstated it. 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.

Regulatory Authority Requirements

As set forth in the G-LibClinTrial, Liberia requires the sponsor or the representative to obtain clinical trial authorization from the Liberia Medicines and Health Products Regulatory Authority (LMHRA). Per the G-ACRE-IRB and the G-NREB, the principal investigator (PI) must also obtain ethics committee (EC) approval.

As per the G-LibClinTrial, the following documentation must be submitted to the LMHRA:

• Cover letter (signed, witnessed, and notarized)
• Clinical trial application form
• 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) (also referred to as an investigational medicinal product (IMP)) 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)), assent form in case minors 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
• Content of the labelling of the IP(s)
• 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
• Signed declaration by the 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 clinical trial monitor(s)
• Signed declaration by the sponsor/sponsor-investigator
• Signed joint financial declaration by sponsor and/or PI
• 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)
• 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
• 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
• Investigational medicinal product dossier (IMPD), if applicable
• Proof of payment of the appropriate application fee

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

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:

• 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 the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (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

Atlantic Center for Research and Evaluation Institutional Review Board

According to the G-ACRE-IRB, the clinical 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).

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.

Overview

According to 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 G-LibClinTrial indicates 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 G-LibClinTrial further explains 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 indicated in G-LibClinTrial 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

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.

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.

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 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. 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 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 protocol amendments prior to those changes being implemented. The 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 protocol amendment documentation submission and procedural requirements.

Overview

In accordance with the LMHRA-Act 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 G-LibClinTrial, in turn, states 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.

The G-LibClinTrial further specifies 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. The G-NREB also indicates that research in Liberia should comply with LBR-8.

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 G-LibClinTrial, 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 World Health Organization (WHO) Primary Registry (LBR-35).

Safety Reporting Definitions

According to 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: the sources provide overlapping and unique elements, so each of the items listed below will not necessarily be in each.):

• 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 response in a participant to an investigational medicinal product 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, 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)
• Unexpected Adverse Drug Reaction – An adverse reaction where the nature or severity is inconsistent with the applicable product information

Safety Reporting Requirements

The G-LibClinTrial requires the principal investigator (PI) or the sponsor to report all SAEs/SADRs suspected of being related to the investigational products (IPs) (also known as investigational medicinal products (IMPs)) to the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and indicate the timelines allocated for related investigations.

Per the G-LibClinTrial, the PI or the sponsor should also report any SAEs/SADRs suspected to be related to the IP (which occurred in Liberia) immediately, and in any event, no later than three (3) calendar days after becoming aware of the event. In the case of multicenter trials involving clinical trial sites 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.

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. 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.

Investigator Responsibilities

The G-NREB indicates that investigators are required to submit a report to the National Research Ethics Board of Liberia (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:

• 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
• Provision of additional information 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 (Table 1 in the G-LibPV and downloadable via LBR-21).

LBR-21 also provides an online platform for submitting a completed Suspected Adverse Drug Reaction Reporting Form.

Atlantic Center for Research and Evaluation Institutional Review Board

Per LBR-28, AEs/ADRs and SAEs/SADRs should be sent to the following ACRE IRB mail or email addresses:

Prof. Edward G. Smith
Chairperson
ACRE IRB
Ground Floor, GD Bldg.
University of Liberia
Capitol Hill
Monrovia, Liberia
Phone: +(231) (0) 777-547-343 or +(231) (0) 777-583-774
E-mail: smithedwardg@yahoo.com and also copy ulpireirb@gmail.com

National Research Ethics Board of Liberia

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

Interim and Annual Progress Reports

Liberia Medicines and Health Products Regulatory Authority

As stated in the G-LibClinTrial, the applicant must provide a progress report at least annually on the clinical trial to the Liberia Medicines and Health Products Regulatory Authority (LMHRA), unless otherwise stipulated in the clinical trial certificate. The report should contain recruitment status, safety updates, and Data and Safety Monitoring Board (DSMB) reports, as well as update the use and results collected on biological samples exported out of Liberia, if applicable.

National Research Ethics Board of Liberia

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 National Research Ethics Board of Liberia (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 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.

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

As per the G-LibClinTrial, the applicant must notify the LMHRA within 30 business days from the end of a clinical trial. The end of the trial definition should be documented in the clinical trial protocol. The applicant must also submit a closeout report with a disposal certificate to the LMHRA within 90 days from completion of the clinical trial. In addition, 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 end of the trial. The 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.

Atlantic Center for Research and Evaluation Institutional Review Board

According to LBR-28, for studies using the ACRE IRB, a final report must be submitted to the ACRE IRB within 30 days following completion of the trial. 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.

As stated in 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-NREB also indicates that research in Liberia should comply with LBR-8. Per LBR-8, 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 also defines 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, LBR-8 explains that a sponsor may transfer responsibility for any or all of the sponsor’s obligations to a contract research organization (CRO). However, 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.

Overview

According to 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, 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 (GCPs) 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.

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 (also known as an investigational medicinal product (IMP)) 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 GCPs, with the applicable regulatory requirement(s), and with 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.

Insurance

As set forth in the G-LibClinTrial, 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 and clinical trial protocol number and the countries to which the cover is extended. The insurance cover should be provided from an internationally recognized company. 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.

The G-LibClinTrial also specifies that 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 as well as proof of professional indemnity (malpractice insurance) has been obtained.

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 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. The G-NREB also indicates that research in Liberia should comply with LBR-8. 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.

Trial Participation

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

Quality Assurance/Quality Control

As specified in 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. The G-NREB also indicates that research in Liberia should comply with LBR-8. 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))

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

The G-LibClinTrial 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).

In addition, 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.

Per the G-ACRE-IRB, investigator(s) may close a research study under the following circumstances:

• When further interventions/interactions with participants, follow-ups, or access to personal identifiable information for research purposes are taking place
• When all data analysis of the study is complete, or data have been de-identified and no direct identifiers or code keys (if data are coded) exist that would allow for potential identification of participants, and
• Grant funds associated with the protocol are no longer being accessed; or an associated grant remains active, but the human participant research activities have ended

See the G-ACRE-IRB for additional investigator instructions on closing a research study per Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) guidelines.

Electronic Data Processing System

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

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.

Per the G-ACRE-IRB, for 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:

• 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

For detailed ACRE IRB recordkeeping requirements, refer to the G-ACRE-IRB.

In addition, per the G-ACRE-IRB, investigator(s) may close a protocol for board reviewed research by submitting study closure materials electronically before the expiration of board approval. According to LBR-28, an email should be sent to one (1) of the following addresses to close a study: jktegli@yahoo.com or ulpireirb@gmail.com. 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.

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.

The G-LibClinTrial also 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.

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

No information is available related to consent for processing personal data.

Obtaining Consent

In accordance with 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-NREB also indicates that research in Liberia should comply with LBR-8, the Belmont Report (LBR-11), the Declaration of Helsinki (LBR-27), and the Council for International Organizations of Medical Sciences (CIOMS)’ International Ethical Guidelines for Health-related Research Involving Humans (LBR-2).

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). The NatResHlthPlcy states that 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). Per the G-ACRE-IRB, the 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:

• 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 and/or the legal representative(s) or guardian(s). Per G-ACRE-IRB, investigators must also honor any other commitments agreed to as part of the approved research, for example, providing information about the study results to research participants, commitment to research participants for use of their samples or data in future research, and commitments for compensation to research participants for their participation in the trial. 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, and/or the legal representative(s) or guardian(s), 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 and/or the legal representative(s) and/or guardian(s) 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 and/or the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s) 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

Per LBR-8, before participating in the study, the participant or the legal representative(s) and/or guardian(s) should receive a copy of the signed and dated ICF. The participant or the legal representative(s) or guardian(s) 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 the legal representative(s) and/or guardian(s)
• The participant and the legal representative(s) and/or guardian(s), 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 the legal representative(s) or guardian(s) 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 or by 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, or
• The participants or their legal representative(s) or guardian(s) 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

Liberia Medicines and Health Products Regulatory Authority

As specified in 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 and/or the legal representative(s) or guardian(s) 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

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:

• The study involves research and an explanation of its purpose
• The expected duration of a participant’s involvement in the trial
• 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 trial participants, and whom to contact in the event of trial-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 the legal representative(s) or guardian(s); 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 also the Consent for Specimen section for additional information on informed consent relating to specimens.

National Research Ethics Board of Liberia

The following elements are to be included in the National Research Ethics Board of Liberia (NREB) Exempt Human Research Consent Script Form (LBR-33) and the NREB Short Consent Form (LBR-34) respectively (Note: the forms provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• 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

Additionally, the G-NREB indicates that research in Liberia should comply with LBR-8.

Overview

As specified in 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-NREB also indicates that research in Liberia should comply with LBR-8, the Belmont Report (LBR-11), the Declaration of Helsinki (LBR-27), and the Council for International Organizations of Medical Sciences (CIOMS)’ International Ethical Guidelines for Health-related Research Involving Humans (LBR-2). The G-ACRE-IRB also complies with LBR-2 and the national ethical guidelines for research on human participants.

As per LBR-8 and LBR-27, Liberia’s ethical standards promote respect for all human beings and safeguard the rights of research participants. LBR-8, LBR-27, 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 and/or the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s) 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 and LBR-27 state that the research participant’s right to safety and the protection of the participant’s health 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.)

The G-LibClinTrial explains 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. The G-NREB also indicates that research in Liberia should comply with LBR-8. 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 when 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(s) or guardian(s) should be obtained. If the prior consent of the participant and/or the legal representative(s) or guardian(s) 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 and/or the participant’s legal representative(s) or guardian(s) should be informed about the trial and provide consent as soon as possible.

As indicated in the G-LibClinTrial, under certain circumstances, the LMHRA may accept an expedited application and review process for clinical trials. Examples of such 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.

Overview

According to LBR-27 and LBR-8, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Vulnerable populations include those participants who cannot give or refuse consent for themselves, those who may be giving consent under duress, those who will not benefit personally from the research, and those for whom the research is combined with medical care. This may include, but is 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.

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

According to 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.

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:

• 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 parents and/or the legal representative(s) or guardian(s). 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.

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, and a witness must also 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, he or she should sign and personally date the written informed consent.

Assent Requirements

As per the G-LibClinTrial and LBR-27, when the research participant is a minor, the investigator must obtain assent from the child/minor. LBR-27 further states that the consent of the legal representative(s) or guardian(s) must also be obtained. 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 and a witness must also 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 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 signature of the child (due to age or ability), the board requires that the document be signed by the investigator (or the designee) and the parent(s)/legal representative(s)

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.

As set forth in 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-NREB also indicates that research in Liberia should comply with LBR-8, which states that the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant.

As stated in the G-ACRE-IRB, for 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:

• 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, and
• Individuals engaged in the research will have no part in determining the viability of a fetus

Pursuant to the G-ACRE-IRB, for 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. 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, and
• 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

As set forth in 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-NREB also indicates that research in Liberia should comply with LBR-8, which states that when a clinical trial includes participants with mental impairment (e.g., those with severe dementia), the participant should be informed about the trial to the extent compatible with his or her understanding and, if capable, he or she should sign and personally date the written informed consent.

Additionally, as per the Declaration of Helsinki (LBR-27), the following conditions must be met for clinical trials involving participants who are mentally incapable of giving consent:

• Informed consent must be obtained from the legal representative(s) or guardian(s)
• This group should not be included in research unless the research is necessary to promote the health of the population represented, and this research cannot instead be performed on legally competent persons
• The specific reason for involving research study participants with a condition that renders them unable to give informed consent should be stated in the experimental protocol for consideration and approval of the ethics committee (EC)

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.

Per 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-NREB also indicates that research in Liberia should comply with LBR-8.

As delineated in LBR-8, an investigational product (IP) (also referred to as an investigational medicinal product (IMP)) 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.

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.

As set forth in the G-LibClinTrial, the 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 delineated in LBR-8, the sponsor should insure that an investigational product (IP) (also referred to as an investigational medicinal product (IMP)) including 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 good manufacturing practices (GMPs). 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.

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 G-LibClinTrial, the import permit application must include at least the following information:

• The clinical trial title and identification number for which the application is made
• The planned clinical trial sites and the planned number of participants at the sites
• The description of the IP(s) by name or code, strength, and dosage form
• The unit of issue, total quantity, batch number, and expiry dates of the product(s)
• Justification of the quantity of the IP(s), health products, or any auxiliary medicines to be imported relative to the clinical trial protocol timelines
• Letter of authorization of the clinical trial

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.

Investigator’s Brochure

Per 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. In accordance with LBR-8, the sponsor or the representative is responsible for providing the investigators with an Investigator’s Brochure (IB) and may follow the World Health Organization (WHO)'s Good Clinical Practice Guidelines (LBR-25) when compiling the IB information. Per the LBR-8, the sponsor should also update the IB as significant new information becomes available.

As specified in 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 also LBR-25 and LBR-8 for additional details regarding the IB.

Quality Documentation

Per the G-LibClinTrial, the Good Manufacturing Practice (GMP) certificate issued from the national regulatory authority of the country where the investigational product (IP) (also referred to as investigational medicinal product (IMP)) 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).

Investigational product (IP) labeling in Liberia must comply with the requirements set forth in 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).

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.

The G-LibClinTrial also indicates that in the clinical trial application submission package to the Liberia Medicines and Health Products Regulatory Authority (LMHRA), if the IP is registered, then product information is required including a summary of product characteristics, a patient information leaflet/package insert, and labeling. The content of the IP labeling should also be included in the submission package.

Per 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 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.

Supply, Storage, and Handling Requirements

Per 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.

According to LBR-8, the sponsor or the representative must also supply the investigator(s)/institution(s) with the IPs (also referred to as investigational medicinal products (IMPs)). 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 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)).

In addition, per LBR-8, the sponsor must also ensure the following:

• Timely delivery of the IP(s)
• 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 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 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.

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

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). According to LBR-25, the allocation of recordkeeping and data handling responsibilities should be specified in the protocol or other written agreement(s) between the sponsor and the investigator(s). For detailed recordkeeping and data handling information, please refer to section 8 of LBR-25. LBR-8 also explains that the sponsor should ensure the protocol or other written agreement specifies that the investigator(s)/institution(s) provide direct access to source data/documents for trial-related monitoring, audits, ethics committee review, and regulatory inspection.

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

The G-LibClinTrial states that, if applicable, request for authorization of export of biological samples out of Liberia as well as the respective material transfer agreement (MTA) should be included in the clinical trial application submission package. In addition, the applicant must provide a progress report on the clinical trial to the LMHRA that should contain recruitment status, safety updates, and data and safety monitoring board reports as well as an update on the use and results collected on biological samples exported out of Liberia, if applicable.

Material Transfer Agreement

According to the G-ACRE-IRB and the G-NREB, the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) and the National Research Ethics Board of Liberia (NREB) require 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.

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 law, regulations, and enactment in 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).

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 law, regulations, and enactment 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

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).

In addition, 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.

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

Per the G-ACRE-IRB, in the event of a request to amend the study, the following study procedures will not require review:

• Rescheduling of a data collection as a result of a research participant missing an appointment or incomplete data collection due to unforeseen circumstances that do not increase risk to the participants
• Rescheduling of specimen collections as a result of a research participant missing an appointment or incomplete specimen collection due to unforeseen circumstances that do not increase risks to the participant. The following specimen collections qualify for this category: collection of blood via finger, or ear stick; hair and nail clippings collected in a non-disfiguring manner; excreta and external secretions (including sweat); and sputum collected through expectoration, etc.

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 the legal representative(s) or guardian(s); 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.