Therapeutic Goods Administration

As per the TGAct, the TGR, and the G-CTHandbook, the Therapeutic Goods Administration (TGA) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections in Australia at the national level. The TGA allows for the supply of unapproved therapeutic goods to be used in clinical trials for experimental purposes in humans in accordance with the provisions in the TGAct and the TGR. There are two (2) regulatory schemes for supplying unapproved therapeutic goods in clinical investigations, which are more fully examined in the Scope of Assessment section.

As per AUS-28, the TGA is part of the Health Products Regulation Group (HPRG) within the Australian Department of Health and Aged Care. The TGA’s Pharmacovigilance Branch is responsible for evaluating and authorizing certain clinical trials for all types of therapeutic products. According to the G-TrialsSOP and AUS-32, the TGA also regulates the supply, import, export, manufacturing, and advertising of therapeutic goods. Per AUS-31, therapeutic goods include prescription medicines, vaccines, sunscreens, vitamins and minerals, medical devices, blood, and blood products.

The TGA manages the Australian Register of Therapeutic Goods (ARTG) (AUS-22), a public database of therapeutic goods that can be legally supplied in Australia. According to the TGAct, the TGA grants exemptions from inclusion in the ARTG for unapproved therapeutic goods to be supplied in clinical trials.

Other Considerations

According to AUS-74, the TGA closely aligns its regulatory approaches to therapeutic products with those of comparable international regulatory counterparts, including the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the European Medicines Agency (EMA), and the United States Food & Drug Administration (FDA), wherever possible. For more information on the international scientific guidelines adopted in Australia, see AUS-74.

Contact Information

Per AUS-23 and AUS-47, the contact information for the TGA is as follows:

Postal Address:
P.O. Box 100
Woden ACT 2606
Australia

For general questions:

Phone: 1 800 020 653 (free call within Australia) or +61 2 6289 4124 (international calls)
Fax: 02 6203 1605
E-mail: use online form (see AUS-11)

For clinical trial questions:

Phone: Same as the general questions numbers
E-mail: clinical.trials@health.gov.au

Pharmacy Board of Sierra Leone

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

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

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

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

Other Considerations

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

Contact Information

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

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

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

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

Overview

In accordance with the G-CTHandbook, the G-TrialsSOP, and AUS-47, the Therapeutic Goods Administration (TGA) allows for the supply of unapproved therapeutic goods to be used in clinical trials under two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme and the Clinical Trial Approval (CTA) scheme. The G-CTHandbook specifies that the scope of the TGA’s assessment includes all clinical trials (Phases I-IV).

Under either regulatory scheme, per the TGR, the G-CTHandbook, the G-TrialsSOP, and AUS-47, an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) must approve the research protocol. The G-NatlStmt further specifies that any research that involves greater than low risk must be reviewed by an EC.

According to AUS-40, all public and private health organizations must also undertake a site-specific assessment (SSA) of each research project. This allows the institution to consider whether the project is suitable for the site and whether it has the capacity to conduct the research at that site. Per the G-TrialsSOP, the SSA and ethics review may occur in parallel. However, EC approval must be obtained and submitted to the research governance officer (RGO) of each participating institution before institutional authorization is granted.

For summaries of the clinical trials regulatory environment, legislation, and guidance, see AUS-40.

Clinical Trial Review Process

Per the G-CTHandbook, the sponsor is responsible for the overall decision as to whether the CTN or CTA scheme should be used. Consulting the EC responsible for protocol approval may assist the sponsor in making the decision. The main difference between the CTN and CTA schemes is the TGA’s level of involvement in reviewing data about the therapeutic goods before the clinical trial commences.

See AUS-27 for more information on choosing a clinical trial scheme.

CTN Scheme

As per the G-CTHandbook, the G-TrialsSOP, and AUS-47, under the CTN scheme, the sponsor must notify the TGA of its intention to sponsor a clinical trial involving an unapproved therapeutic good. The TGA does not assess any data relating to the proposed trial at the time of submission. As further indicated in AUS-47, sponsors may submit the CTN to the TGA concurrently with the EC’s and institution’s review and approval/authorization. However, it is the sponsor’s responsibility to ensure that all relevant approvals and authorizations are in place before commencement of the trial.

The G-CTHandbook indicates that a clinical trial is deemed to be notified as soon as the online CTN form (via the TGA Business Services (TBS) webpage (AUS-36)) has been submitted and the relevant fee has been paid. If there are any changes to the trial details notified to the TGA (such as a change in the details of the principal investigator (PI), the address of the site, or the therapeutic good), the sponsor must update the relevant fields on the online CTN form.

The G-CTHandbook further states that the TGA may request additional information if the trial raises any concern, or ask specific questions to address any deficiencies. Specifically, the TGA can request certain information or documents from the sponsor relating to the supply and handling of the goods, as well as the monitoring and results of the supply of the goods. If the TGA directs a trial notified under the CTN scheme not to be conducted or becomes aware that conducting or continuing the trial would be contrary to the public interest, then the goods used in the trial would no longer be exempt from inclusion in the Australian Register of Therapeutic Goods (ARTG) (AUS-22) and cannot be lawfully supplied. This may occur if the TGA becomes aware that allowing the trial to proceed or continue carries an unacceptable risk of death, serious illness, or serious injury.

CTA Scheme

According to AUS-47, parties that are considering submitting a CTA application are strongly encouraged to contact the TGA at clinical.trials@health.gov.au for advice regarding the application process (some class IV biologicals must be submitted under the CTA scheme). Pre-submission meetings with the TGA may be requested through the forms found on AUS-17.

AUS-47 indicates that the CTA scheme consists of a two (2)-part process. Part 1 constitutes the formal CTA application, which the sponsor completes and submits directly to the TGA. Part 2 requires the sponsor to notify the TGA when a trial commences and alert the TGA to new sites in ongoing CTA trials.

As per the G-CTHandbook, the TGA reviews relevant, but limited, scientific data, and its primary responsibility is to review the safety of the product. In addition, the TGA can request certain information or documents from the sponsor about therapeutic goods approved under the CTA scheme relating to the supply and handling of the goods, as well as the monitoring and results of the supply of the goods.

AUS-47 further specifies that the evaluation of a CTA application includes consideration of the manufacturing and quality and safety data in conjunction with the trial's usage guidelines, to inform a risk-benefit decision by the TGA on whether or not to approve the clinical trial. Any significant changes to the information provided in support of the trial are considered a variation and need to be approved, since they have the potential to affect the initial decision to approve a trial. The TGA advises clinical trial sponsors to contact them via clinical.trials@health.gov.au if they intend to change a previously approved CTA application.

The G-CTHandbook further states that the TGA can revoke an approval of a clinical trial under the CTA scheme where the conditions of approval are not met.

Inspection

According to the G-GCP-Inspect, clinical trials of medicines and biologicals regulated under the CTN or CTA schemes are subject to the TGA’s Good Clinical Practice (GCP) inspection program. The TGA can conduct a GCP inspection at any stage of the clinical trial lifecycle from the early phase of participant recruitment to completed trials. Additionally, the TGA can request certain information or documents about therapeutic goods exempt under the CTN scheme or approved under the CTA scheme. This can include the investigator’s brochure and protocol, further information about safety reports, clarification about the safety profile of a specific therapeutic good, and/or details of problems or complaints. The TGA will normally give advance notice of its intention to conduct a GCP inspection but has the right to perform an inspection at any time. In exceptional circumstances, the TGA can perform an inspection without notice.

See the G-GCP-Inspect for more details on how the TGA prioritizes and schedules GCP inspections, the kinds of inspections the TGA might conduct, the inspection process, and how the TGA reports and follows up on inspections.

Overview

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

Clinical Trial Review Process

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

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

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

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

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

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

Expedited Review During a Public Health Emergency

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

Other Considerations

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

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

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

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

Therapeutic Goods Administration

As per the TGR, the sponsor is responsible for paying a fee to the Therapeutic Goods Administration (TGA) to submit an application under the Clinical Trial Notification (CTN) or Clinical Trial Approval (CTA) scheme for evaluation. Per the G-FeesCharges, the fees are as follows:

• $429 Australian dollars for unapproved medicines CTN, and for each notification of one (1) or more additional trial sites
• $2,046 Australia dollars for unapproved medicines CTA (30-day evaluation)
• $562 Australian dollars for unapproved medicines CTA – variation (30-day evaluation)
• $25,426 Australian dollars for unapproved medicines CTA (50-day evaluation)
• $6,940 Australian dollars for unapproved medicines CTA – variation (50-day evaluation)
• $429 Australian dollars for unapproved biologicals CTN, and for each notification of one (1) or more additional trial sites
• $30,964 Australian dollars for unapproved biologicals CTA
• $8,448 Australian dollars for unapproved biologicals CTA – variation

According to AUS-47, a higher fee is applicable to clinical trial applications under the CTA scheme due to the more complex nature of the evaluation process. Certain variations to an existing CTN may incur a fee, such as the addition of a new site, change to a previously notified therapeutic good that creates separate and distinct goods, or the addition of a new therapeutic good to a previously notified trial. For additional fee information, refer to Schedules 9 and 9A of the TGR and the G-FeesCharges.

Payment Instructions

AUS-66 indicates that regulatory fees and charges may be paid online or by bank transfer (electronic funds transfer (EFT)). Online payment by credit card is the preferred payment option, and all payments must be in Australian dollars.

As stated in AUS-25, online payment is made via the TGA Online Payment Portal (AUS-16). Once the payment has been finalized, the Portal will confirm that the payment has been successful. The user may request an email confirmation. Certain payments, including a CTN fee and a variation to a medicine (e.g., a therapeutic good), may be made online without an invoice. See AUS-25 for more information on TGA fees and payments. Also see AUS-49 for additional guidance and system screenshots related to paying CTN fees.

AUS-66 further indicates that to ensure all payments made by EFT are correctly allocated, the organization’s Identification Number (e.g., TGA00xxxxx) should be included in the payment ‘Reference’ field. Bank transfer fees are the payer’s responsibility. Additionally, bank transfers must be accompanied by a remittance advice, which must be issued within 24 hours for all bank transfers. Remittance advices must be emailed to TGARemittanceAdvices@health.gov.au and contain the organization’s Identification Number in the subject field. The TGA’s bank account details are as follows:

Bank: Commonwealth Bank of Australia
BSB: 062-909
Account Number: 10215498

Per AUS-66, payments from overseas can only be accepted in Australian denominations. Payers must ensure that their payment covers any international banking fees. The TGA’s international banking details are as follows:

IBAN: 06290910215498
Swift Code: CTBAAU2S

Pharmacy Board of Sierra Leone

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

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

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

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

Payment Instructions

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

Overview

As indicated in the TGAct, the TGR, the G-CTHandbook, the G-NatlStmt, and AUS-47, Australia has a decentralized process for the ethics review and approval of clinical trial research. According to the TGR, the G-CTHandbook, the G-TrialsSOP, and AUS-47, Australia requires human research protocols to be reviewed by an institutional-level ethics committee (EC). The G-NatlStmt further specifies that any research that involves greater than low risk must be reviewed by an EC. (Note: Institutional ECs are referred to as Human Research Ethics Committees (HRECs) in Australia.)

The G-NatlStmt indicates that one (1) or more institutions can individually or jointly establish an EC or any other ethics review body. Institutions that establish an EC are responsible for adequately resourcing and maintaining it, including providing sufficient administrative support. Per the TGAct and AUS-20, ECs are required to be constituted and operate in accordance with the guidelines issued by the National Health and Medical Research Council (NHMRC), and to have notified the NHMRC of their existence. According to the TGR, the G-NatlStmt, the G-TrialsSOP, and AUS-20, institutional ECs ensure that clinical trial research complies with the NHMRC’s ethical standards published in the G-NatlStmt. See the Oversight of Ethics Committees section for more information on notification.

For summaries of the clinical trials regulatory environment, legislation, and guidance, see AUS-40.

Ethics Committee Composition

As stated in the G-NatlStmt, an EC must be composed of at least eight (8) members in the following categories:

• A chairperson with suitable experience
• Two (2) people who bring a broader community or consumer perspective and have no paid affiliation with the institution
• One (1) person with knowledge of and current experience in the professional care, counseling, and/or treatment of people
• One (1) person who performs a pastoral care role in the community
• One (1) qualified lawyer, who may or may not be currently practicing and, where possible, is not engaged to advise the institution on research-related or any other matters
• Two (2) people with current research experience relevant to the research proposals to be considered at the meetings they attend

The G-NatlStmt further states that wherever possible, one (1) or more of the members listed above should be experienced in reflecting on and analyzing ethical decision-making. As far as is practicable, institutions should ensure that their EC’s membership at each meeting has diversity, including gender diversity, and at least one third of those participating in each meeting are from outside of the institution. ECs that review research about Aboriginal and Torres Strait Islander people or communities should appoint one (1) or more members who have knowledge of research with Aboriginal and Torres Strait Islander peoples or are familiar with relevant cultural knowledge, if such a person has not already been appointed.

Per the G-NatlStmt, ECs may also include other members with the above areas of expertise or with additional areas of expertise. Institutions are encouraged to establish a pool of appointed EC members to draw on as needed to help meet minimum membership requirements and/or provide additional experience or expertise. The institution should ensure that its EC has access to the expertise necessary to properly review research, which may necessitate going outside of the EC’s membership.

Terms of Reference, Review Procedures, and Meeting Schedule

As delineated in the G-NatlStmt, institutional ECs must ensure that it documents, implements, and publicizes standard operating procedures (SOPs) that promote good ethics review, including:

• Meeting frequency, attendance, and conduct
• Minutes and agenda preparation
• Timely distribution of materials to members before meetings
• Timely consideration of applications
• Methods of deliberation and decision-making
• Processes, if any, for reviewing applications from unaffiliated or international researchers
• Disclosure of interests and management of conflicts of interest
• Appropriate confidentiality of the content of applications and the deliberations of review bodies
• Prompt notification of decisions to researchers
• Communicating with researchers, including face to face, by telephone and in writing, (including available forms of electronic communication)
• Record keeping
• Monitoring of approved research
• Reporting and handling of adverse events
• Receiving and handling of complaints
• Advising the institution(s) of decisions to suspend or withdraw ethics approval of research projects
• Attendance of people other than members at meetings

Pursuant to the G-NatlStmt, EC members should be familiar with the G-NatlStmt and other relevant guidelines; prepare for and attend EC meetings or, if unavailable, provide opinions before the meetings; and attend research ethics training programs or continuing education at least every three (3) years. Members should be appointed to an EC using open and transparent processes, and institutions should consider reviewing appointments to the EC at least every three (3) years.

The G-NatlStmt states that as far as possible, each EC meeting should be arranged to enable attendance of all members of the minimum membership categories listed above and other relevant appointed members, either in person or via available technology. Meeting papers should be provided enough in advance to enable members to be fully informed. An EC’s decision about whether a research proposal meets the requirements of the G-NatlStmt must be informed by an exchange of opinions from all members of the EC participating in the meeting. The exchange should, ideally, take place at a meeting with all those members present. Where there is less than full attendance of the minimum membership categories at a meeting, the chairperson must be satisfied, before a decision is reached, that the views of those absent who belong to the minimum membership have been received and considered. The EC should attempt to reach decisions by general agreement or consensus. Voting is neither required nor prohibited. Some decisions may not be unanimous, and a dissent should be recorded in the minutes of the meeting. Where requested by a dissenting member, the reasons for the dissent should also be recorded in the minutes of the meeting.

According to the G-NatlStmt, ECs may invite researchers, and researchers may request, to be present for discussion of their proposed research. In addition, ECs may seek advice from external experts to help in considering a research proposal. Communication between the sponsor and the EC is not prohibited but should be restricted so that it does not inappropriately influence the review of any relevant research proposals.

As delineated in the G-NatlStmt, ECs must maintain a complete record of all research proposals received and reviewed. Approved project documentation and any relevant correspondence must also be retained. Records must be maintained in accordance with the requirements of relevant Commonwealth and state or territory legislation and guidelines. See G-NatlStmt for detailed records requirements.

For more details on the governance and responsibilities of Australian institutional ECs, see the G-NatlStmt.

Overview

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

Ethics Committee Composition

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

• At least five (5) members

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

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

Terms of Reference, Review Procedures, and Meeting Schedule

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

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

Overview

According to the G-NatlStmt, the institutional ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) is responsible for protecting the interests of research participants and for promoting good research by ensuring adherence to the values of research merit and integrity, beneficence, justice, and respect for persons throughout the conduct of the research project. The EC must review the recruitment and consent processes, weigh the benefits and risks of the research, and consider the impact of the research on certain groups of participants deemed to merit special consideration. Additionally, ECs may conduct both scientific and ethics review or may delegate scientific review to a sub-committee.

Pursuant to the G-NatlStmt, the establishment and maintenance of ethics review processes and processes for assessing the risk level of the research are part of an institution’s overall governance responsibility. In addition to ethics approval, research must also be authorized by each institution with responsibility for oversight of the research before it can proceed. See the Oversight of Ethics Committees, Submission Process, Submission Content, Timeline of Review, and Initiation, Agreements & Registration sections for more information on research governance requirements.

Role in Clinical Trial Approval Process

According to the G-CTHandbook, the G-TrialsSOP, and AUS-47, ECs are responsible for reviewing and approving protocols involving unapproved therapeutic goods under one (1) of two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme or the Clinical Trial Approval (CTA) scheme—prior to the sponsor initiating a trial. According to AUS-40, all public and private health organizations must also undertake a site-specific assessment (SSA) of each research project. This allows the institution to consider whether the project is suitable for the site, and whether it has the capacity to conduct the research at that site. Per the G-TrialsSOP, the SSA and ethics review may occur in parallel. However, EC approval must be obtained and submitted to the research governance officer (RGO) of each participating institution before institutional authorization is granted.

The G-CTHandbook states that a CTN scheme is a notification scheme under which the Therapeutic Goods Administration (TGA) does not review or evaluate any data relating to the clinical trial. The EC is responsible for assessing the scientific validity of the trial design, the balance of risk versus harm of the therapeutic good(s), and the overall ethical acceptability of the trial. Per AUS-47, EC and institutional review and approval/authorization may be conducted in parallel to the CTN form submission to the TGA; however, it is the sponsor’s responsibility to ensure that all relevant approvals and authorizations are in place before commencement of the trial.

Under the CTA scheme, as delineated in the G-CTHandbook, the TGA reviews relevant, but limited, scientific data, while the EC is responsible for considering the scientific and ethical issues of the proposed trial protocol.

Per the G-CTHandbook, the sponsor determines whether to conduct a clinical trial under the CTN or CTA scheme. Consulting the EC responsible for protocol approval may assist the sponsor in making the decision. One of the determining factors for an EC is whether the committee has access to appropriate scientific and technical expertise in order to assess the safety of the product. If an EC feels that it requires additional expertise to review a CTN, it may seek advice from external authorities or it may seek to collaborate with another EC that has the required expertise. An EC may also determine that it does not have access to the appropriate scientific and technical expertise to review the proposed trial under the CTN scheme and recommend review under the CTA scheme.

AUS-14 states that prior to approving a clinical trial, the EC must be satisfied that the trial protocol complies with the following requirements:

• G-NatlStmt
• Declaration of Helsinki (AUS-52)
• AU-ICH-GCPs
• TGA requirements, including the G-CTHandbook and the G-SafetyDataMgt
• Any relevant Australian Government and/or state/territory laws

The G-CTHandbook and the TGR state that during its review, the EC also needs to be aware of relevant state and territory laws pertaining to the supply of therapeutic goods or other clinical trial-related matters. The G-CTHandbook further indicates that ECs have a high level of independence and are responsible for establishing their own processes for reviewing research proposals. According to the G-CTHandbook and the AU-ICH-GCPs, if requirements specified in the G-NatlStmt appear to differ from those specified in the AU-ICH-GCPs, the TGA recommends compliance with the G-NatlStmt.

As stated in AUS-20, ECs also consider the protection of privacy for humans participating in research and their data. ECs do this by considering whether the research proposal conforms to relevant legislation, principles, and guidelines, including federal and/or state/territory legislation as well as the G-PrivacyAct95 and G-PrivacyAct95A guidelines. See the Personal Data Protection section for more information.

Per the G-NatlStmt, an EC may approve, request modification of, reject, or withdraw approval of a research proposal. The EC must clearly communicate its decision to the researcher(s):

• Where a proposal is approved or rejected, or where approval is withdrawn, communication must be in writing (which may include electronic formats) and should include an explicit statement that the proposal meets or did not meet the requirements of the G-NatlStmt. If rejecting or withdrawing approval of a research proposal, the EC should provide the rationale for its decision, including citing the provisions of the G-NatlStmt or relevant institutional policy that underpins its decision, if relevant.
• Where modifications are requested, communication may be written or, where appropriate, informal; however, a record should be kept of any informal communication, and guidance should be clearly communicated regarding to whom the researcher’s response should be directed .

According to the G-NatlStmt, varying processes may be used for the review and approval of project extensions, amendments to an approved project, progress reports, and renewal of project approval. Appropriate processes depend on the nature of the original project and any proposed changes, but any process authorized by an institution for these purposes must prioritize the safety and well-being of participants, researchers, and/or the community.

Pursuant to the G-CTHandbook and the TGR, when the EC approves a trial protocol, it takes responsibility for monitoring the progress and conduct of the trial. However, the G-NatlStmt indicates that each institution has ultimate responsibility for ensuring, via its research governance arrangements, that all its authorized research is monitored. Monitoring arrangements should be commensurate with the risk, size, and complexity of the research. Monitoring responsibilities that are performed by the institution’s EC should be based on the EC’s review of the project. However, where research that will take place at multiple sites has been reviewed by only one (1) EC, the ECs of the other institutions participating in the project do not have knowledge of the project. In such cases, only the reviewing EC can take on those elements of monitoring a research project that are commonly performed by ECs.

Per the G-NatlStmt, if the EC or institution has reason to believe that continuance of a research project would compromise participants' welfare, or if the conditions of ethics approval for the project are not being adhered to, it should immediately seek to establish whether ethical approval for the project should be suspended or withdrawn. If an institution or EC considers that suspension of research is necessary, the instruction to stop should come from the management of the institution. If ethics approval for a research project is suspended, the researcher, the institution(s), and, where possible, the participants should be informed of the suspension.

As indicated in the G-NatlStmt, ECs may require researchers to amend research procedures to protect participants. If an EC determines that such changes cannot achieve that end, the EC may decline to grant an extension to project approval or decide to withdraw approval for the research. Where ethics approval for a research project is withdrawn:

• The researcher, the institution(s), and, where possible, the participants should be informed of the withdrawal
• Continuation of the research project is subject to re-application and re-approval by the EC

See the G-NatlStmt for more details on institutional and EC responsibilities regarding research monitoring.

External Ethics Approval and the National Mutual Acceptance Scheme

The G-NatlStmt encourages the minimization of unnecessary duplication of ethics review, including for research conducted in multiple Australian jurisdictions or across international boundaries. Institutions may accept an ethics review conducted by an entity external to the institution (including overseas review bodies) and should determine their criteria for this acceptance.

Per the G-NatlStmt, researchers who wish to submit evidence of ethics approval by an external EC in support of single ethics review should be aware of existing national or international programs, protocols, policies, standards, and guidance that may be relevant to the institutional decision to accept the review. To facilitate the efficient ethics review of research, researchers must inform any EC of:

• All sites at which the research will be conducted
• Any information on local site circumstances that is relevant to the ethics review
• Any other body that will be considering ethical issues related to the research
• Any previous decisions to approve, re-consider, or deny approval of the research by another review body in Australia or elsewhere

See the G-NatlStmt for more information on external ethics approval.

As described in AUS-21 and AUS-41, the National Mutual Acceptance (NMA) scheme further supports the acceptance of a single scientific and ethical review of multicenter research conducted in publicly funded health services. All state and territory-certified public health organizations in Australia are part of the NMA scheme.

Per AUS-68, in order for ethics reviews of human research to be accepted under NMA, the EC conducting the review must be certified under the National Health and Medical Research Council (NHMRC) National Certification Scheme of Institutional Processes Related to the Ethical Review of Multi-centre Research (National Certification Scheme), and also be a “Certified Reviewing HREC” under the NMA scheme.

For more information on submissions to ECs under the NMA scheme and the National Certification Scheme, see the Submission Process and Oversight of Ethics Committees sections.

Exemption from Ethics Review

As stated in the G-NatlStmt, some research may be eligible for exemption from ethics review. Where appropriate, exemption is granted, or not, by the institution responsible for the research. Where there is no institution providing oversight of the research, researchers should request a grant of exemption from an EC. Research that may be eligible for exemption from ethics review includes research that carries a lower risk to participants or the community, and satisfies one (1) or more of the following conditions:

• The research involves the use of collections of information or data from which all personal identifiers have been removed prior to being received by the researchers, and where researchers explicitly agree: (i) not to attempt to re-identify those with whom the information or data is associated; (ii) to take all reasonable steps to prevent re-identification of the information or data for unauthorized purposes or access to the information or data by those who are not authorized; and (iii) that any sharing of any research data during or after the project will not create any additional risks of re-identification of the information or data
• The research is restricted to surveys and observation of public behavior using information that was or will be collected and recorded without personal identifiers and is highly unlikely to cause distress to anyone associated with the information or the outcomes of the research
• Is conducted as part of an educational training program in which the research activity is for training purposes only and where any outcomes or documentation are for program use only
• The research uses only information that is publicly available through a mechanism set out by legislation or regulation and that is protected by law, such as mandatory reporting information, information obtained from registries of births and deaths, coroner’s investigations, or reports of the Australian Bureau of Statistics

The G-NatlStmt indicates that institutions or other granting bodies must keep a record of any decision to grant exemption from ethics review. See the G-NatlStmt for more information on ethics review exemption.

Overview

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

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

Role in Clinical Trial Approval Process

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

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

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

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

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

The G-NatlStmt indicates that when establishing an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia), an institution must set out and publicize its terms of reference, including its schedule of fees charged, if any, for ethics review. The institution is responsible for ensuring that its EC operates in accordance with the G-NatlStmt, which includes being satisfied that any fees charged for EC review do not discourage research that the institution has an obligation to support.

Sierra Leone Ethics and Scientific Review Committee

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

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

Payment Instructions

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

Overview

As per the TGAct, the G-TrialsSOP, and the G-CTHandbook, the National Health and Medical Research Council (NHMRC) is responsible for receiving applications from ethics committees (ECs) (Human Research Ethics Committees (HRECs) in Australia) to be registered. The NHMRC was established by the NHMRCAct. Per the NHMRCAct, the NHMRC’s activities are designed to raise the standard of individual and public health throughout Australia; to foster the development of consistent health standards between the various states and territories; to foster medical and public health research and training throughout Australia; and to foster consideration of ethical issues relating to health.

Research Governance

Pursuant to the G-NatlStmt, institutions may fulfill their research governance responsibilities by establishing and overseeing different levels of ethics review. One (1) or more institutions can individually or jointly establish an EC or any other ethics review body. Institutions that establish an EC are responsible for adequately resourcing and maintaining it, including providing sufficient administrative support.

According to the G-NatlStmt, institutions should ensure that all ethics review processes and the criteria that are used for determining the appropriate process are clear, transparent, and published to enable researchers to submit their research proposals efficiently.

The G-NatlStmt further states that institutions should clearly publicize their policy for access to their EC or other ethics review processes by researchers who are not affiliated with the institution. Additionally, institutions should regularly assess all their ethics review processes, including the criteria for allocating research to different levels of review, to ensure that those processes continue to enable the institution to meet its responsibilities under the G-NatlStmt. Where possible this assessment should be informed by the documented experience of research participants and/or by involving participants or the wider community in the assessment.

Furthermore, as delineated in the G-NatlStmt, institutions should have in place an auditing process to confirm that research is being reviewed at the levels of review that their criteria require and research is being exempted from review only in accordance with the criteria set out in the G-NatlStmt. See the Scope of Review section for more information on exemption criteria.

Registration, Auditing, and Accreditation

According to the G-NatlStmt, institutions that have responsibility for oversight of research and maintain ECs must register their ECs with the NHMRC. ECs that are not associated with institutions must register themselves with the NHMRC.

Per AUS-20, registration means that the EC has notified the NHMRC of its existence and declared that it meets the requirements of the G-NatlStmt. In order to review and monitor clinical trials of unregistered therapeutic goods, an EC must be notified to the NHMRC, and constituted and operating in accordance with the G-NatlStmt. Forms for registering an EC, notifying the NHMRC of changes to the EC, or terminating an EC’s registration are available at AUS-20.

As per the G-NatlStmt, an institution and its EC must report annually, or upon request, to the NHMRC. The NHMRC, through the Australian Health Ethics Committee (AHEC), will review the activities of ECs to ensure conformance with the G-NatlStmt. Reportable information may include:

• Membership/membership changes
• Number of meetings
• Confirmation of participation in meetings by members in minimum membership categories
• The number of research proposals presented, the number approved, the number requiring modification prior to approval, and the number rejected
• Monitoring procedures that are in place and any problems encountered with monitoring of projects
• Complaints procedures and number of complaints handled
• Any other relevant policies, procedures, or processes as determined by the NHMRC

The G-NatlStmt further indicates that failure to comply with the requirements of the G-NatlStmt may result in the EC being removed from the list of ECs registered with NHMRC. See AUS-20 for more information and the list of registered ECs.

National Certification Scheme

According to AUS-21, the NHMRC developed the National Certification Scheme of Institutional Processes Related to the Ethical Review of Multi-centre Research (National Certification Scheme) to enable the single ethics and scientific review of human research occurring at multiple institutions in Australia. Under this scheme, certified institutions can have their ethics review accepted by other institutions participating in the research project. As part of the National Certification Scheme, certified institutions and their ECs are required to report to the NHMRC on their multicenter research activities.

As per AUS-21, the NHMRC assesses each institution’s interest in certification on a case-by-case basis. Certification respects institutional decisions about research governance matters, including whether research should be conducted at a given site. Before commencing steps to apply for certification, institutions should contact HREC.admin@nhmrc.gov.au.

For more information on the National Certification Scheme and the NHMRC’s continuous certification process, see AUS-21.

As stated in AUS-68, EC certification under the National Certification Scheme is required in order for ethics reviews of human research to be accepted under the National Mutual Acceptance (NMA) scheme. The NMA scheme facilitates single scientific and ethical review of clinical trials conducted in participating jurisdiction’s public health organizations. See the Scope of Review section for more information on NMA.

Overview

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

Registration, Auditing, and Accreditation

No applicable requirements.

Overview

In accordance with the G-CTHandbook, the G-TrialsSOP, and AUS-47, Australia requires the sponsor to obtain clinical trial authorization from the Therapeutic Goods Administration (TGA) for the supply of unapproved therapeutic goods for clinical trials for experimental purposes in humans. The sponsor can apply under two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme and the Clinical Trial Approval (CTA) scheme.

Under either regulatory scheme, per the TGR, the G-CTHandbook, the G-TrialsSOP, and AUS-47, an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) must approve the research protocol. The G-NatlStmt further specifies that any research that involves greater than low risk must be reviewed by an EC. AUS-47 indicates that the review and approval/authorization by an EC and institution may be conducted in parallel to the CTN form submission to the TGA, but it is the sponsor’s responsibility to ensure that all relevant approvals and authorizations are in place before commencement of the trial.

According to AUS-40, all public and private health organizations must also undertake a site-specific assessment (SSA) of each research project. This allows the institution to consider whether the project is suitable for the site, and whether it has the capacity to conduct the research at that site. Per the G-TrialsSOP, the SSA and ethics review may occur in parallel. However, EC approval must be obtained and submitted to the research governance officer (RGO) of each participating institution before institutional authorization is granted. While there is no submission language requirement stated in the requirements, the official language of Australia is English.

Regulatory Submission

Per AUS-17, sponsors may request pre-submission meetings with the TGA. See AUS-17 for the applicable forms.

CTN Scheme

According to AUS-47 and AUS-30, CTN forms are submitted online through the TGA Business Services (TBS) webpage (AUS-36). The sponsor must have or obtain a TGA Client Identification Number.

As per AUS-49, to submit the online CTN form successfully through AUS-36, the sponsor must accept a declaration to assume responsibility for the trial. After accepting the declaration, a webpage will advise the sponsor that the CTN submission has been successful. According to AUS-47, the TGA does not send an acknowledgement letter by email since this information is available for viewing and printing via the online portal. The TGA advises clinical trial sponsors to obtain and save a printout of notification at each stage of the submission process.

AUS-49 indicates that the sponsor may delegate duties and correspondence with the TGA to an authorized agent, which is able to create and submit a CTN on behalf of a sponsor. If an agent has submitted a CTN on the sponsor’s behalf, the sponsor will not have access to view or vary the CTN. Access is only granted to the agent.

See AUS-30 and AUS-49 for additional information on using and submitting the online form.

CTA Scheme

According to AUS-47, the sponsor must complete and submit two (2) forms (AUS-56 and AUS-57) to the TGA via email at clinical.trials@health.gov.au. Supporting data for the CTA application should be provided in electronic format, preferably on USB or CD-ROM via post. The trial commencement notification form (AUS-57) must be sent to the TGA within 28 days of commencing supply of the unapproved therapeutic goods.

Per AUS-47, those with queries regarding the CTA scheme are encouraged to contact the TGA directly at clinical.trials@health.gov.au.

Ethics Review Submission

AUS-46 indicates that the National Health and Medical Research Council (NHMRC) developed the Human Research Ethics Application (HREA) form (AUS-9) as a concise application to facilitate timely and efficient ethics review for research involving humans. The HREA assists researchers in considering the ethical principles of the G-NatlStmt in relation to their research and is accepted by institutions that participate in the National Mutual Acceptance (NMA) scheme, which facilitates single ethics review by multiple public health organizations for most human research.

According to the G-CTHandbook, trial sponsors and researchers should use the HREA unless advised otherwise. AUS-19 contains resources for using the HREA.

Per AUS-46, research proposals should be submitted to ECs associated with public health institutions in New South Wales, Queensland, South Australia, Australian Capital Territory, and Victoria, as well as Mater Research, via the Research GEMS system (AUS-55), the Ethical Review Manager (ERM) website (AUS-8), and/or the Research Ethics and Governance Information System (REGIS) (AUS-10), depending on which jurisdictions are involved. For research in the Northern Territory, Tasmania, or Western Australia, the EC should be contacted for their local submission requirements.

The G-CTHandbook further states that ECs have a high level of independence and are responsible for establishing their own processes for receiving research proposals.

Research Governance

According to the G-NatlStmt, institutions should publish (such as on their website) clear policies and procedures for institutional authorization of research. As noted in the G-CTHandbook, individual jurisdictions have specific requirements as a part of their SSA and authorization processes. South Australia sites use the online SSA form found in the Research GEMS system (AUS-55), while the ERM website (AUS-8) is used for SSA form submission for Mater Research, Queensland, and Victoria. New South Wales and the Australian Capital Territory use REGIS (AUS-10) for site governance applications.

Overview

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

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

Regulatory Submission

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

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

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

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

Ethics Review Submission

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

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

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

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

Regulatory Authority Requirements

Clinical Trial Notification (CTN) Scheme

As delineated in AUS-49, the following information must be submitted to the Therapeutic Goods Administration (TGA) through the online form on the TGA Business Services (TBS) webpage (AUS-36):

• Sponsor name and address
• Sponsor declaration
• Notification fee (See Regulatory Fees section)
• Organization-nominated contact’s name, phone number, and email
• An optional alternative contact, which may be chosen from the contacts for the agent or sponsor organization submitting the CTN. An Australian contact number is required to be listed with either the primary sponsor contact or the alternate sponsor contact
• Protocol number
• Expected trial start and completion dates
• Potential use of restricted goods
• Study title and description, which must be a minimum of 250 characters (spaces included) and up to a maximum of 2,500 characters
• “This Trial” check boxes indicating whether the trial involves the use of a medicine, a medical device, and/or a biological. For a medicine or biological, additional information must be provided, such as dosage form, route of administration, indication, and the good manufacturing practice (GMP) license/clearance number of a relevant exemption
• Trial type
• Whether the trial is a first in human trial
• Whether the trial, in part or as a whole, has been halted/stopped/withdrawn or rejected in another country due to safety concerns
• Total number of trial participants
• Therapeutic area
• Investigational product (IP) details
• Whether it is a multi-center trial
• Whether the trial is being conducted in other countries
• Preceding trial details
• Trial site details

See AUS-49 for detailed descriptions of each required item.

Clinical Trial Approval (CTA) Scheme

AUS-47 states that the CTA scheme application consists of two (2) forms – Part 1: the application (AUS-56), and Part 2: Notification of the conduct of a trial under the CTA scheme (AUS-57).

The Part 1 CTA application form (AUS-56) requires general information (sponsor name, data details, and sponsor declaration) and details on the medicine (active ingredient)/biological be submitted to the TGA.

The Part 2 CTA application form (AUS-57) requires trial sponsor information (name and client ID code), the IP or biological, and the notification type, as well as trial and trial site details (title of study and trial type). The form also requires signed certifications from the sponsor, the principal investigator (PI), the ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia), and the authority approving the conduct of the trial.

Ethics Committee Requirements

Per the G-CTHandbook, the EC and the institution are responsible for establishing what information should be provided in support of an application. The EC should request any additional information that it believes is necessary to undertake review of the proposed research. Unless advised otherwise, trial sponsors and researchers should use the Human Research Ethics Application (HREA) for submitting proposals for research involving humans to ECs.

AUS-46 indicates that the HREA assists researchers in considering the ethical principles of the G-NatlStmt in relation to their research. The G-NatlStmt requires that those who conduct and approve human research to consider:

• How the research question/theme is identified or developed
• The alignment between the research aims and methods
• How the researchers and the participants will engage with one another
• How the research data or information are to be collected, stored, and used
• How the results or outcomes will be communicated
• What will happen to the data and information after the project is completed

For more information on the HREA, see the Submission Process section.

The G-NatlStmt further specifies that in an application for review of their research, researchers should determine and state in plain language:

• The research question or questions that the project is intended to explore
• The potential benefit of exploring the question or questions including to whom that potential benefit is likely to flow, and whether that benefit is a contribution to knowledge or understanding, improved social or individual wellbeing, or the skill and expertise of researchers
• The basis for that potential benefit as described in either relevant literature or a review of prior research unless, due to the novelty of the question, there is scarce literature or prior research
• How the design and methods of the project will enable adequate exploration of the research questions and achieve the aims of the research
• How the design of the project will maintain respect for the participants
• Where relevant, that the research meets the requirements of any relevant regulations or guidelines authorized by law (such as those related to privacy and reporting requirements for disclosure of child abuse)
• Whether or not the project has been reviewed by a formally constituted academic, scientific, or professional review process, and, if so, the outcome of that review

Research Governance

According to the G-NatlStmt, institutions should publish (such as on their website) clear policies and procedures for institutional authorization of research. See the Research GEMS system (AUS-55), the Ethical Review Manager (ERM) (AUS-8), and the Research Ethics and Governance Information System (REGIS) (AUS-10) websites for public health organization site-specific assessment (SSA) forms, which may differ between institutions and states or territories.

Clinical Protocol

The G-TrialsSOP indicates that where the investigator is responsible for the protocol development, the investigator must ensure the protocol follows the outline in the AU-ICH-GCPs. Specific content of a protocol will vary depending on the research area, the level of risk to participants, the phase of the research and study design, and whether a medicinal product or a device or a therapeutic intervention is being researched. If satellite sites for a teletrial are involved in the study, no specific additional wording is required in the protocol, as relevant considerations will be addressed in other study-specific documents which may be annexed to the protocol.

The AU-ICH-GCPs provides the following outline of the protocol:

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

Regulatory Authority Requirements

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

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

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

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

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

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

Ethics Committee Requirements

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

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

Clinical Protocol

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

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

Overview

In accordance with the G-CTHandbook, the G-TrialsSOP, and AUS-47, the Therapeutic Goods Administration (TGA) is responsible for authorizing the supply of unapproved therapeutic goods for clinical trials under two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme and the Clinical Trial Approval (CTA) scheme. According to the TGR, the G-CTHandbook, the G-TrialsSOP, and AUS-47, under either regulatory scheme, an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) must approve research protocols. The G-NatlStmt further specifies that any research that involves greater than low risk must be reviewed by an EC. AUS-47 indicates that the review and approval/authorization by an EC and institution may be conducted in parallel to the CTN form submission to the TGA, but it is the sponsor’s responsibility to ensure that all relevant approvals and authorizations are in place before commencement of the trial.

According to AUS-40, all public and private health organizations must also undertake a site-specific assessment (SSA) of each research project. Per the G-TrialsSOP, the SSA and ethics review may occur in parallel.

Regulatory Authority Approval

AUS-47 states that the TGA’s target time to process online CTNs is five (5) to seven (7) working days, but the agency tries to process the notification as soon as possible. This timeframe does not include the time taken for TGA finance to match the payment (if required) to a submission. For information on how to check the status of a CTN, see AUS-49.

No timeline information is available for applications under the CTA scheme. Per AUS-47, parties that are considering submitting a CTA application are strongly encouraged to contact the TGA at clinical.trials@health.gov.au for advice regarding the application process.

Ethics Committee Approval

The EC review and approval process timeline varies by institution. However, according to the G-NatlStmt, the institutional EC must implement standard operating procedures that promote good ethics review, including timely consideration of applications.

Research Governance

The G-GovHndbk indicates that ethical review and site assessment, both components of research governance, are two (2) distinct processes relating to the ethical approval and institutional authorization of research involving humans. However, because evidence of EC approval is a component of the site assessment process, institutional authorization of a research project cannot be given until EC approval has been provided. The G-TrialsSOP further specifies that EC approval must be obtained and submitted to the research governance officer (RGO) of each participating institution before institutional authorization is granted.

While some parts of the research governance review must occur after the EC review, the G-GovHndbk recommends that as part of the national approach to single ethical review, institutions establish processes to facilitate parallel review. Project documentation processes related to site assessment may be considered as falling into these categories:

• That which can be assessed independent of ethical review, such as evidence of research qualifications, supporting department approval forms, contracts, budgets, and insurance and indemnity documents
• That which is subject to ethical review, but can be submitted prior to or in parallel with ethical review to enable independent assessment of other documentation, such as initial project application documents
• That which can only be assessed subsequent to ethical approval, such as approved project application documents, fully signed regulatory documents, and a certificate of ethical approval

See the G-GovHndbk for additional National Health and Medical Research Council (NHMRC) guidance on best practices in the governance of multicenter human research as part of the national approach to single ethical review.

The NHMRC also developed the GPP-SiteAssess to help institutions streamline the research governance process and shorten clinical trial start-up times. See the GPP-SiteAssess for more information.

Overview

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

Regulatory Authority Approval

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

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

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

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

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

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

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

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

Ethics Committee Approval

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

Overview

In accordance with the G-TrialsSOP, the G-CTHandbook, and AUS-47, clinical trials involving unapproved therapeutic goods can only commence under the Clinical Trial Notification (CTN) scheme or the Clinical Trial Approval (CTA) scheme. According to the G-GovHndbk and the G-TrialsSOP, under either scheme, both institutional ethics committee (EC) (Human Research Ethics Committees (HRECs) in Australia) approval and research governance authorization are required before a research project can commence at a site.

Research Governance

Per the G-GovHndbk, research must be governed by the institution at all stages of a project. Ethical review and site assessment, both components of research governance, are two (2) distinct processes relating to the ethical approval and institutional authorization of research involving humans. According to AUS-40, all public and private health organizations must undertake a site-specific assessment (SSA) of each research project. This allows the institution to consider whether the project is suitable for the site, and whether it has the capacity to conduct the research at that site. Pursuant to the G-NatlStmt, authorization of research by the institution should consider, but not re-review, any issues raised during the ethics review of the research proposal, and each institution should have a process or processes for assessing the risk level of the research. These processes may involve seeking advice from relevant clinical or administrative staff, members of an EC, or a full meeting of the EC. All research should be developed, reviewed, authorized, conducted, and monitored in accordance with a research governance framework as described in an institution’s policy. For more information on institutional responsibilities, see the Site/Investigator Selection section.

The G-TrialsSOP states that in the case of a teletrial, the principal investigator (PI) must ensure that a robust site assessment is undertaken that fully quantifies the capabilities of each satellite site to inform the extent to which trial related activities can be delegated to the site. This may include a pre-commencement assessment before a specific trial is proposed so that the process of trial start up is expedited when a suitable trial is identified.

Per the G-TrialsSOP, prior to a study’s commencement, the PI must:

• Submit the primary site's Clinical Trial Research Agreement (CTRA), EC approval, the SSA form, evidence of any relevant good clinical practice (GCP) training, and any other required documentation to the institution’s research governance officer (RGO)
• Ensure all documentation and correspondence pertaining to the submission and approval processes is filed in the study master file (SMF) (see Appendix 8 of the G-TrialsSOP)
• Ensure each satellite site completes and submits to their RGO a clinical trial sub-contract and a SSA form
• Await site specific RGO authorization before any study related activity can occur at that site
• Ensure the satellite site files all documentation in the satellite site study file (SSSF)

The G-TrialsSOP further states that prior to the initiation of a study, the investigator must also mutually agree with the sponsor on a scheduled date, time, and location for a study initiation visit at the participating site to ensure the site is prepared to commence the study. In the case of a teletrial, this may be at the primary site only, or could include (remotely) the satellite site(s) as determined by the study complexity by the sponsor/PI.

See the G-TrialsSOP for more information on site initiation requirements for primary and satellite sites.

The G-GovHndbk further indicates that in the national approach to single ethical review, site assessment and project authorization are the responsibility of each institution participating in a multicenter human research project while ethical review is provided by a single EC using certified ethical review processes. Each institution collaborating in a multicenter project utilizing the outcome of a single ethical review must individually authorize the commencement of research at their institution. To avoid unnecessary delays in research commencing at all collaborating centers and sites, each institution should consider relevant local matters prior to or in parallel with ethical review.

Clinical Trial Agreement

As delineated in the AU-ICH-GCPs, the sponsor must sign an agreement between all involved parties, including investigators, institutions, contract research organizations, and others for documentation purposes. Further, the sponsor should obtain the investigator’s/institution's agreement:

• To conduct the trial in compliance with good clinical practice, with the applicable regulatory requirement(s), and with the protocol agreed to by the sponsor and given approval/favorable opinion by the EC
• To comply with procedures for data recording and reporting
• To permit monitoring, auditing, and inspection
• To 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.

For the purposes of the G-TrialsSOP, the CTRA for the primary site and the sub-contract for each satellite site constitute part of a research governance application, which is submitted to the RGO. The CTRA covers matters such as confidentiality, intellectual property, ownership of data, insurance, and indemnity. The Medicines Australia CTRA (see AUS-38) is the recommended standard form.

Clinical Trial Registration

The G-NatlStmt requires that clinical trials be registered on a publicly accessible register complying with international standards before recruitment of the first participant. For information on these standards, see the World Health Organization (WHO)’s International Clinical Trials Registry Platform (ICTRP) (AUS-67). Per AUS-15, the Australian and New Zealand Clinical Trials Registry (ANZCTR) (AUS-12) recommends applying for registration at the same time as ethics submission.

Overview

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

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

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

Clinical Trial Agreement

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

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

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

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

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

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

Clinical Trial Registration

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

Safety Reporting Definitions

According to the G-SftyRpt, the following definitions provide a basis for a common understanding of Australia’s safety reporting requirements:

• Adverse Event (AE) – Any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product and that does not necessarily have to have a causal relationship with this treatment
• Adverse Reaction (AR) – Any untoward and unintended response to an investigational medicinal product related to any dose administered
• Unexpected Adverse Reaction (UAR) – An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., investigator's brochure (IB) for an unapproved investigational medicinal product)
• Serious Adverse Event (SAE) or Serious Adverse Reaction (SAR) – Any adverse event/adverse reaction that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect
• Suspected Unexpected Serious Adverse Reaction (SUSAR) – An adverse reaction that is both serious and unexpected
• Significant Safety Issue (SSI) – A safety issue that could adversely affect the safety of participants or materially impact the continued ethical acceptability or conduct of the trial
• Urgent Safety Measure (USM) – A measure required to be taken in order to eliminate an immediate hazard to a participant’s health or safety (Note: This type of SSI can be instigated by either the investigator or sponsor and can be implemented before seeking approval from ethics committees (ECs) or institutions)

Safety Reporting Requirements

Investigator Responsibilities

As specified in the G-SftyRpt, the investigator is responsible for recording and assessing all AEs that occur at the site. The investigator is also required to inform the sponsor of all SAEs, and all USMs instigated by the site, within 24 hours of becoming aware of the event. All safety critical events must be reported to the sponsor, and for reported deaths, the investigator should supply the sponsor with any additional requested information. Further, the investigator must report to the institution all SSIs and SUSARs arising from the local site within 72 hours of becoming aware of the event.

However, the G-TrialsSOP states that the investigator must also report any SUSARs to the sponsor within 24 hours of becoming aware of the event, and USMs instigated by the investigator or site must be reported to the sponsor within 72 hours. Furthermore, the investigator must report all other significant issues to the sponsor within 15 days of instigating or becoming aware of the event. The investigator must notify the sponsor promptly regarding any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants. The investigator must also be available to meet with the sponsor to discuss study progress, issues, and safety.

The G-TrialsSOP requires that within 72 hours of instigating or becoming aware of the event, the investigator must notify the institution of:

• USMs
• SUSARs arising from the local site
• Any information received from the sponsor that may be new and have an impact on the continued ethical acceptability of the trial or may indicate the need for amendments to the trial protocol, including monitoring of safety

The G-TrialsSOP indicates that for satellite site(s) in teletrials, staff must report safety issues directly to the sponsor as per the timelines specified in the clinical trial protocol and the safety monitoring plan or similar document, in the same way as the primary site. Certified copies of the relevant safety reports/documentation generated at the satellite site must be sent to the primary site for filing in a study master file.

According to the G-TrialsSOP, the principal investigator (PI) must ensure that study staff, including those at teletrial satellite sites, are trained in the protocol, investigator’s brochure (IB), study procedures, and AE/SAE reporting. The PI must also ensure that a system for safety reporting duties is in place for all study staff. For more information on investigator responsibilities related to standard operating procedures (SOPs), see the G-TrialsSOP.

Sponsor Responsibilities

As delineated in the G-SafetyDataMgt, the G-SftyRpt, and the G-CTHandbook, the sponsor is required to expedite reporting of SUSARs to the Therapeutic Goods Administration (TGA).

The G-SafetyDataMgt indicates that other situations requiring expedited reporting may include information that might materially influence the benefit-risk assessment of an investigational product, or that would be sufficient to consider changes in the administration or conduct of a clinical trial.

According to the G-SftyRpt and the G-TrialsSOP, expedited reporting requires the sponsor to file reports to the TGA in the following specified timelines:

• For an Australian SUSAR that is fatal or life-threatening, immediately, but no later than seven (7) calendar days, with any follow-up information within eight (8) calendar days
• For all other Australian SUSARs, no later than 15 calendar days after becoming aware of the case

The G-SftyRpt and the G-TrialsSOP further indicate that the TGA, the EC, and investigators must also be notified of all SSIs that adversely affect the safety of participants, or materially impact the continued ethical acceptability or conduct of the trial. SSIs that meet the definition of a USM should be reported within 72 hours, and all other SSIs should be reported within 15 calendar days of the sponsor being made aware of the issue. It is strongly recommended that the sponsor contact the TGA within 24 hours of a USM being taken, and if initial contact is by telephone, it should be followed up with a written notification provided by e-mail within 72 hours. See AUS-53 for additional information on SSIs and USMs.

Per the G-SftyRpt, submitting individual reports of AEs, SAEs, and SUSARs to ECs, institutions, and investigators are no longer required. However, according to the G-TrialsSOP, the sponsor must provide the EC with an updated IB at least annually that supports trial oversight, depicts a clear picture of the evolving trial safety profile, and provides evidence that the sponsor is conducting its safety monitoring appropriately.

The G-CTHandbook and the G-SftyRpt further require the sponsor to maintain records of all other single case AEs and submit them to the TGA upon request. The G-CTHandbook indicates that the TGA does not require sponsors to submit individual SUSARs from outside Australia. Sponsors should continually monitor the safety of their clinical program and advise the TGA of any SSIs that arise from their analysis of overseas reports, or of any action that has been taken by another country’s regulatory agency. Investigators and ECs should also be informed of this information, and sponsors must be able to provide the TGA with the clinical details of any individual overseas AE reports if requested.

According to the G-TrialsSOP, the sponsor’s plans for safety data monitoring should be documented in a safety monitoring plan or similar document and be given to the PI prior to commencement of the clinical trial. The plan must be continually reviewed and updated during the trial, as real-time assessments of safety data are performed, and outcomes are made available.

Other Safety Reports

The G-SftyRpt delineates that the sponsor must provide the EC with an annual safety report including a clear summary of the evolving trial safety profile. The annual safety report should generally include:

• A brief description and analysis of new and relevant findings
• For investigational products (IPs) not on the Australian Register of Therapeutic Goods (ARTG) (AUS-22), a brief analysis of the safety profile of the IP and its implications for participants
• A brief discussion of the implications of the safety data to the trial’s risk-benefit ratio
• A description of any measures taken or proposed to minimize risks

A Development Safety Update Report (DSUR) or other similar document may also serve as the annual safety report. See the G-SftyRpt for more information.

Form Completion & Delivery Requirements

As per the G-CTHandbook, all SUSARs from Australian sites must be reported to the TGA using one (1) of three (3) formats:

• The Electronic Data Interchange (EDI) functionality, which allows sponsors to submit AE reports directly from their system to the TGA (more information can be found at AUS-26)
• The online reporting form, which can be accessed from AUS-51
• The CIOMS Form I (AUS-4) or the TGA’s Blue Card Adverse Reaction Reporting Form (AUS-3)

Per AUS-3, the Blue Card form may be emailed to adr.reports@tga.gov.au or mailed to Pharmacovigilance and Special Access Branch, Reply Paid 100, Woden ACT 2606. More information about reporting to the TGA may be found at AUS-7.

See AUS-37 for the SSI/USM reporting form.

Safety Reporting Definitions

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

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

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

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

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

Safety Reporting Requirements

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

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

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

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

Investigator Responsibilities

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

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

Sponsor Responsibilities

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

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

Other Safety Reports

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

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

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

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

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

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

Form Completion & Delivery Requirements

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

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

Interim and Annual Progress Reports

As per the AU-ICH-GCPs, the G-NatlStmt, and the G-TrialsSOP, the investigator(s) is responsible for submitting progress reports to the ethics committee (EC) (known as Human Research Ethics Committee in Australia) annually, or more frequently if requested. The AU-ICH-GCPs and the G-TrialsSOP state that if there are significant changes in trial conduct or safety, the investigator should submit a written report to the sponsor, the EC, and where applicable, the institution. The G-NatlStmt indicates that at regular periods (reflecting the degree of risk, and at least annually), researchers should provide reports to the relevant EC(s) and institution(s), including information on:

• Progress to date
• The security of project-related data and information
• Compliance with the approved proposal
• Compliance with any conditions of approval

According to the G-NatlStmt, progress report forms should be designed to collect information that can provide meaningful assistance to reviewers in determining whether continuation of ethics approval is warranted. See the G-NatlStmt for more details.

Final Report

AUS-47 indicates that for trials conducted under the Clinical Trial Approval (CTA) scheme, the CTA clinical trial completion advice form (AUS-58) is used to notify the Therapeutic Goods Administration (TGA) of the trial completion. AUS-58 indicates that upon completion, the form may be emailed to the TGA at clinical.trials@tga.gov.au (preferred) or faxed to 02 6232 8112.

Per AUS-49, for trials conducted under the Clinical Trial Notification (CTN) scheme, a completion advice should be submitted through the TGA Business Services (TBS) webpage (AUS-36). The completion advice must include the date the trial was completed at all Australian sites, as well as the completion reason. See AUS-49 for additional information on the completion advice.

The AU-ICH-GCPs and the G-TrialsSOP indicate that the investigator should provide the EC with a final clinical study report. As per the G-TrialsSOP, the investigator must also notify the research governance officer that the trial has been terminated/closed. At the completion of the project, a report with the same information as described above for progress reports (per G-NatlStmt) must also be provided to the relevant EC(s) and institution(s), but it should include information on the outcome of the completed research.

Additionally, the TGA has adopted the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)’s Topic E 3: Structure and Content of Clinical Study Reports (AUS-81). For more information, see AUS-81.

Interim and Annual Progress Reports

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

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

Final Report

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

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

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

As per the AU-ICH-GCPs and the G-TrialsSOP, a sponsor is defined as an individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.

In accordance with the AU-ICH-GCPs, Australia permits a sponsor to transfer any or all of its trial-related duties and functions to a contract research organization (CRO). Any trial-related duties and functions transferred to a CRO should be specified in a written agreement, and the sponsor should ensure oversight of such transferred responsibilities. Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor. The sponsor retains overall responsibility for the trial data’s quality and integrity, as well as the conduct of the trial. As stated in the G-TrialsSOP, the sponsor is also responsible for ensuring that appropriate approvals are obtained prior to the commencement of the clinical trial, that conditions of any approvals are adhered to during the course of the clinical trial, and that the ethics principles of research merit and integrity, justice, beneficence, and respect are applied to the conduct of clinical trials.

According to the G-CTHandbook, if the investigator initiates and organizes the trial, the role of trial sponsor is assumed. If another party (such as a pharmaceutical company) provides the IP or other support for an investigator-led trial, that party is not required to assume the sponsor role.

As per the G-CTHandbook, the G-TrialsSOP, and AUS-47, a sponsor must be an Australian entity.

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

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

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

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

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

Overview

As set forth in the AU-ICH-GCPs, the sponsor should select the investigator(s) and the institution(s) for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. The sponsor must also ensure that the investigator(s) are qualified by training and experience. Prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure.

According to the G-TrialsSOP, the principal investigator (PI) must ensure that all required staff who assist with the clinical trial are informed about and trained on the protocol, any investigational product (IP), and their research-related duties and functions. This can be in the form of an initiation meeting held by any communication means, including face-to-face, videoconference, telehealth, etc. The PI must also have sufficient time to properly conduct and complete the research within the specified period, as well as an adequate number of qualified staff and adequate facilities for the foreseen duration of the research. When a teletrial is being conducted, the PI, who is always at the primary site and never at the satellite site, remains responsible for the trial across the cluster. For more information on PI site staff training and qualification requirements, see the G-TrialsSOP.

See AUS-64 for additional clinical trial and researcher resources.

Research Governance

The G-NatlStmt indicates that institutions must ensure that any human research for which they are responsible is designed, reviewed, approved, authorized, conducted, and monitored in accordance with the G-CodeConduct and the G-NatlStmt, along with any policies that they have developed that form part of their research governance framework. Each institution should be satisfied that the human research for which it is responsible meets both relevant ethical standards and scholarly or scientific standards, and ensure that those conducting the research (i) are either adequately experienced and qualified, or supervised; (ii) understand the need to assess risks to their own safety and that of participants; and (iii) are aware they are free to withdraw from research on conscientious grounds. Institutions should publish (such as on their website) clear policies and procedures for ethics review and approval and institutional authorization of research. They may establish their own processes for ethics review of research or use the review processes of another institution or external ethics review body.

Per AUS-63, the Australian Commission on Safety and Quality in Health Care developed the National Clinical Trials Governance Framework (AUS-63), which embeds clinical trials into routine health service provisions and strengthens the clinical and corporate governance arrangements for parties that deliver clinical trials. All jurisdictions have agreed to implement the framework in health service organizations, meaning the organizations will be assessed concurrently for clinical and corporate services and clinical trial service provisions. The framework describes the systems and processes that should be in place to implement an effective governance system considering local needs, values, and the context in which services are provided. For more information about implementation timing and assessments under the National Safety and Quality Health Service (NSQHS) standards, see AUS-63.

Foreign Sponsor Responsibilities

As per the G-CTHandbook, the G-TrialsSOP, and AUS-47, a sponsor must be an Australian entity.

Data Safety Monitoring Boards

G-DSMB indicates that the sponsor may establish a Data Safety Monitoring Board (DSMB) (also referred to as Data Monitoring Committees (DMCs)) to review accumulating trial data in order to monitor the progress of a trial. The role of a DSMB is to provide advice on safety and/or trial conduct issues by making recommendations to the sponsor or trial steering committee on whether to continue, modify, or stop a trial. Per the AU-ICH-GCPs, the DSMB should have written standard operating procedures (SOPs) and maintain written records of all its meetings.

According to the G-TrialsSOP, the sponsor may utilize a DSMB or independent individuals (e.g., a medical monitor) to:

• Review accruing trial safety data in either an unblinded or blinded manner to assess treatment exposure
• Access, assess, and review emerging efficacy data for the trial
• Assess the balance of risks and benefits within the trial
• Document the outcome of these reviews

Additionally, the Therapeutic Goods Administration (TGA) has adopted the European Medicines Agency (EMA)’s Guideline on Data Monitoring Committees (AUS-78), which discusses the key issues involved when sponsors include DSMBs as part of their trial management. For more information, see AUS-78.

Multicenter Studies

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

• All investigators conduct the trial in strict compliance with the protocol that was agreed to by the sponsor and the TGA (if required), and that was approved by the ethics committee (EC)
• The case report forms (CRFs) capture the required data at all multicenter trial sites
• The responsibilities of coordinating investigator(s) and the other participating investigators are documented prior to the start of the trial
• All investigators are given instructions on following the protocol, on complying with a uniform set of standards to assess clinical and laboratory findings, and on completing the CRFs
• Communication among investigators is facilitated

As noted in the G-TeletrialPrncpls, Australian jurisdictions agree that “traditionally” multicenter clinical trials assume one (1) PI per geographic site, differing from teletrials. However, for the purposes of teletrials, multicenter trials may include some sites that have satellite sites supervised under teletrial guidance, including the Clinical Oncology Society of Australia (COSA)’s Australasian Tele-trial Model (AUS-2), the G-TeletrialPrncpls, and the G-TrialsSOP. Sponsor responsibilities in teletrials, as described in the G-TrialsSOP, are discussed throughout the Australia profile alongside other clinical trial regulations and guidance. See each section of the Sponsorship topic for additional applicable information.

Overview

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

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

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

Foreign Sponsor Responsibilities

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

Data and Safety Monitoring Board

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

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

Multicenter Studies

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

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

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

Insurance

The AU-ICH-GCPs and the G-NatlStmt state that the sponsor should provide insurance in accordance with applicable regulatory requirements. In addition, according to the G-NatlStmt, institutions must ensure that sponsors have insurance arrangements in accordance with applicable regulatory requirements. The federal documents cited here do not explicitly require insurance.

Per the G-GovHndbk, the institution and investigator are responsible for managing risks of any proposed research, including providing appropriate insurance coverage.

Compensation

Injury or Death

According to the G-NatlStmt, institutions must ensure that sponsors have indemnity and compensation arrangements in accordance with applicable regulatory requirements, and that arrangements are in place to compensate trial participants for harm resulting from negligence in research. The AU-ICH-GCPs further indicates that the sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries. The federal documents cited here do not explicitly require indemnity.

The G-TrialsSOP states that if the investigator is notified or becomes aware that a trial participant intends to make a claim against the institution or sponsor for injuries arising as a result of participating in a clinical trial undertaken at the institution (or any of the satellite sites under supervision by the institution in a teletrial), the investigator must promptly notify the following parties in writing that such an action is intended:

• The institution’s authority
• The coordinating principal investigator (CPI)/principal investigator (PI)/associate investigator, as relevant
• The sponsor

In addition, if the institution is notified or becomes aware that a trial participant intends to make a claim for compensation against the institution or sponsor for injuries arising as a result of participating in a clinical trial undertaken at the institution (or any of the satellite sites under supervision by the institution in a teletrial), the institution must promptly notify the institution’s insurer in writing that such an action is intended.

See AUS-39 for indemnity and injury compensation guidelines for commercially-sponsored trials.

Trial Participation

The G-NatlStmt states that it is generally appropriate to reimburse participants for the costs associated with taking part in research including travel, accommodations, and parking. Sometimes participants may also be paid for time involved. However, payment may not be disproportionate to the time involved, or include other incentives that encourage participants to take risks. Further, payment or reimbursement decisions should consider customs and practices of the community in which the trial will be conducted.

According to the G-ResearchPayment, any proposal for payment of participants should be considered by the ethics committee (EC) reviewing the research. The EC should be provided with a payment plan that includes:

• A rationale for the proposed payments
• The method and timing of any disbursements, including how they have been calculated, and
• Information about how prospective participants will be advised of the provision of payment

Payment of participants is ethically appropriate if it is equitable and proportionate to the burden of the research, and does not:

• Undermine a participant’s capacity to provide voluntary and informed consent
• Unduly influence a participant to accept a risk or burden that is greater than they would otherwise accept in everyday living or to compromise their fundamental values
• Unduly influence a participant to make false representations about or conceal information that is relevant to their eligibility for the research, their contribution to the research, or the risks related to participation

To minimize the likelihood of a payment acting as an undue influence, the G-ResearchPayment further indicates that payment of participants should generally be limited to reimbursement of documented expenses and remuneration for time and inconvenience. Payment may be offered as an incentive to participate in cases where the research offers little or no benefit to individuals or where the research requires the participation of target populations that are difficult to recruit. In these cases, adequate processes must be in place to promote valid consent. For more information and examples of payment models, see the G-ResearchPayment.

According to the AU-ICH-GCPs, payments to a participant should be prorated and not wholly contingent on completion of the trial by the participant.

Post-Trial Access

Per the G-NatlStmt, researchers must make clear to the participant if there are any intended therapeutic benefits from the trial, and if the treatment will be available only through participation in the trial. In addition, researchers must make it clear to the participant whether they will have access to the treatment or information they received after completion of the trial.

Insurance

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

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

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

Compensation

Injury or Death

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

Trial Participation

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

Quality Assurance/Quality Control

As per the TGR and the AU-ICH-GCPs, 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.

According to the AU-ICH-GCPs, the quality management system should use a risk-based approach that includes:

• Identifying processes and data that are critical to ensure participant protection and the reliability of trial results during protocol development
• Identifying risks to critical trial processes and data
• Evaluating the identified risks against existing risk controls
• Deciding which risks to reduce and/or 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
• Describing the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report

The G-RBMgmtMntring provides further guidance on the application of risk-based trial processes, particularly as a reference to sponsors of non-commercial trials.

The AU-ICH-GCPs further indicates that the sponsor is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data generated, recorded, and reported in compliance with the protocol, the AU-ICH-GCPs, and the applicable regulatory requirements. The sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial-related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. The sponsor should implement a system to manage quality throughout all stages of the trial process, and QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed. Any agreements between the sponsor and investigator, or with any other parties involved in the clinical trial, should be written, either within the protocol or in a separate agreement.

As per AUS-74, the Therapeutic Goods Administration (TGA) has adopted certain guidelines released by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the European Medicines Agency (EMA), and the United States Food & Drug Administration (FDA) regarding quality management and technical aspects of clinical trials. See each of these documents for additional details:

· ICH Guideline E8 (R1) on General Considerations for Clinical Studies (AUS-76)

· Guideline on Strategies to Identify and Mitigate Risks for First-in-Human Clinical Trials with Investigational Medicinal Products (AUS-77)

· Guideline on Clinical Trials in Small Populations (AUS-79)

· ICH E11(R1) Guideline on Clinical Investigation of Medicinal Products in the Pediatric Population (AUS-80)

· Use of Electronic Health Record Data in Clinical Investigations - Guidance for Industry (AUS-82)

· Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products - Guidance for Industry (AUS-83)

· ICH Topic E 10 Choice of Control Group in Clinical Trials (AUS-84)

· ICH Topic E 9 - Statistical Principles for Clinical Trials (AUS-85)

See AUS-74 for more information on, as well as a list of, the international scientific guidelines adopted by the TGA.

Responsible Research Conduct

The G-CodeConduct outlines principles, responsibilities, and expectations for institutions and researchers to facilitate responsible research practices. Australian institutions must establish and maintain good governance and management practices for responsible research conduct. In addition, researchers must comply with the relevant laws, regulations, disciplinary standards, ethics guidelines, and institutional policies related to responsible research conduct. Compliance with the G-CodeConduct is a requirement to receiving funding from the National Health and Medical Research Council (NHMRC) or the Australian Research Council (ARC).

The G-CodeBreaches describes the preferred model for institutions to use to investigate and manage potential code breaches, to determine any corrective actions, and when a finding of research misconduct may be made. The Australian Research Integrity Committee uses the G-CodeBreaches as a guide for reviewing how NHMRC- and ARC-funded institutions manage potential code breaches.

The G-RptBreachGCP requires the sponsor to notify the reviewing ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) within seven (7) days of confirming a serious breach of good clinical practice (GCP). A serious breach is defined as one that is likely to affect to a significant degree: the safety or rights of a trial participant or the reliability and robustness of the data generated in the trial. Sponsors should also develop documented processes for managing serious breaches. The G-TrialsSOP notes that although all deviations or breaches of the protocol must be reported by the investigator to the sponsor, only serious breaches must be reported to the EC. Serious breaches should also be reported by the principal investigator (PI) to their institution, as they may have an impact on medico-legal risk, the responsible conduct of research, or adherence to contractual obligations.

The supplementary guidance G-RptBreachGCP should be read alongside the G-CodeConduct and the G-CodeBreaches.

Monitoring Requirements

As part of its QA system, the AU-ICH-GCPs notes that the sponsor should ensure the trial is monitored and audited. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, the AU-ICH-GCPs, and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. The sponsor should ensure that the auditors are qualified by training and experience, and the auditor’s qualifications should be documented. The sponsor must also ensure that the audit is conducted in accordance with its own SOPs and that the auditor’s observations are documented.

Per the G-TrialsSOP, the PI must ensure audit/inspection readiness throughout the study, have oversight of any audit or inspection of the trial at both primary and satellite sites, and ensure any deficiencies identified through audit or inspection are actively managed to ensure continuous improvement.

The TGR further states that the sponsor must provide a written assurance to comply with any trial-related requests by an authorized TGA officer(s), which includes allowing inspection of clinical trial sites. The PI is required to comply with requests and answer any questions the authorized officer(s) may have. According to the G-GCP-Inspect, clinical trial sites that have been notified of a GCP inspection should prepare for the inspection by:

· Ensuring their authorizing institution, trial sponsor, and clinical team are advised of the inspection (the G-GCP-Inspect notes that although the TGA does not require that the sponsor be informed, there is generally a requirement in the contract between the site and the sponsor to share this type of information)

· Ensuring access for the inspectors to clinical trial records and source documents is arranged for the time of the inspection

· Ensuring their IT processes allow them to grant view-only access to the inspectors

The G-GCP-Inspect adds that ECs and trial sponsors are not included in the scope of the TGA’s GCP inspection program. The site PI can invite the sponsor representative(s) to attend the inspection opening and closing meeting. See the Scope of Assessment section and the G-GCP-Inspect for more information on TGA inspections.

Premature Study Termination/Suspension

As per the G-CTHandbook, procedures following the TGA’s revocation of approval under the Clinical Trial Approval (CTA) scheme or a breach of the conditions of the Clinical Trial Notification (CTN) scheme would be determined on a case-by-case basis based on the impact on participants and their ongoing safety. The AU-ICH-GCPs states that if a trial is prematurely terminated or suspended, the sponsor should promptly inform the investigator(s), institution(s), the EC, and the TGA. The sponsor should provide the reason(s) for the termination or suspension. Additionally, as indicated in the G-CTHandbook, the sponsor must notify all sites in the case of a multicenter trial. A lead EC in a multicenter study will need to liaise with the sites and sponsor when determining which, if any, are affected and the actions they need to apply.

According to the G-TrialsSOP, if a trial is prematurely terminated or suspended for any reason, the investigator must:

• Promptly inform the sponsor, EC, research governance officer, associate investigator, any satellite site, and the TGA by providing a detailed written explanation of the premature termination or suspension
• Promptly inform the trial participant and the participant’s primary care physician where the trial participant has consented, of the termination or suspension and, if applicable, of the investigational product (IP) and dose that was administered
• Assure appropriate therapy and follow up for the participant’s continued care

As per the G-NatlStmt, if an institution or EC considers that suspension of research is necessary, the instruction to stop should come from the management of the institution. Where ethics approval for a research project is suspended:

• The institution must ensure that the researcher promptly suspends the research and makes arrangements to meet the needs of participants, such as ensuring that appropriate counselling support or the provision of standard care continues
• The research may not be resumed unless: (i) the research is modified to provide sufficient protection or participants or address the concerns that led to the suspension; or (ii) the researcher establishes to the satisfaction of the EC that continuation of the research will not compromise participants’ welfare; and (iii) the institution authorizes the continuation of the research

The G-NatlStmt further indicates that if ethics approval for a research project is withdrawn, the researcher must promptly halt the research, make arrangements to meet the needs of participants, and notify the institution that these steps have been taken.

Quality Assurance/Quality Control

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

Monitoring Requirements

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

Premature Study Termination/Suspension

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

Electronic Data Processing System

When using electronic trial data handling systems, the sponsor must ensure and document that the electronic data processing system conforms to its established requirements for completeness, accuracy, reliability, and consistent intended performance, and that standard operating procedures (SOPs) are maintained for using these systems. Refer to the AU-ICH-GCPs for additional information.

The Therapeutic Goods Administration (TGA) has adopted the United States Food & Drug Administration (FDA)’s Use of Electronic Health Record Data in Clinical Investigations - Guidance for Industry (AUS-82). For more information, see AUS-82.

Records Management

According to the G-CodeConduct and the G-DataInfoMgt, institutions must provide access to facilities for the safe and secure storage and management of research data, records, and primary materials.

The G-DataInfoMgt requires that institutional policy include guidance for managing research data and primary materials that addresses the following:

• Ownership, stewardship, and control
• Storage, retention, and disposal
• Safety, security, and confidentiality
• Access by interested parties

Furthermore, institutional policies on ownership of, and access to, databases and archives must require that:

• Researchers are informed of relevant confidentiality agreements and restrictions on the use of research data
• Computing systems are secure
• Information technology personnel understand their responsibilities for network security and access control
• Those holding primary material, including electronic material, understand their responsibilities for security and access

The G-CodeConduct and the G-DataInfoMgt further state that researchers must retain clear, accurate, secure, and complete records of all research including research data and primary materials. Additionally, the G-NatlStmt indicates that when multiple researchers are collaborating on the collection, storage, and/or analysis of data or information, they should agree to the arrangements for custodianship, storage, retention, and destruction of those materials, as well as the rights of access, rights to analyze/use and re-use the data or information, and the right to produce research outputs based upon them.

According to the G-TrialsSOP, the investigator must maintain adequate source documents and trial records, including all key observations on each of the trial participants. The investigator must also store all trial related documents in a study master file (SMF) and take measures to prevent accidental or premature destruction of these documents. In the case of a teletrial, the SMF is stored at the primary site, and the principal investigator (PI) must have control of all essential documents and records generated by the investigator(s), institution, and satellite site(s) before, during, and after the trial. The PI must also establish the maintenance rules of the SMF and relationship between the primary site’s SMF and any satellite site study files. For more information on the SMF, see the G-TrialsSOP.

As set forth in the annotated AU-ICH-GCPs, the TGA requires that the sponsor retain records for 15 years following the completion of a clinical trial. However, product liability is the overriding consideration, and the sponsor should be able to produce records at any time, including possibly beyond the life of a product, in the event of an adverse event claim. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

The TGA has adopted the European Medicines Agency (EMA)’s Guideline on the Content, Management and Archiving of the Clinical Master File (Paper and/or Electronic) (AUS-75). For more information on the clinical trial master file, see AUS-75.

Data Management Plan

According to the G-NatlStmt and the G-DataInfoMgt, researchers should create a data management plan, which should be developed as early as possible in the research process and should include details regarding:

• Physical, network, system security, and any other technological security measures
• Policies and procedures
• Contractual and licensing arrangements and confidentiality agreements
• Training for members of the project team and others, as appropriate
• The form in which the data or information will be stored
• The purposes for which the data or information will be used and/or disclosed
• The conditions under which access to the data or information may be granted to others
• What information from the data management plan, if any, needs to be communicated to potential participants

The G-NatlStmt states that in the data management plan, researchers should also clarify whether they will seek extended or unspecified consent for future research, or permission from a review body to waive the requirement for consent. In addition, the security arrangements specified in the plan should be proportional to the risks of the research project and the sensitivity of the information.

In accordance with the G-NatlStmt, researchers must comply with all relevant legal and regulatory requirements that pertain to the data or information collected, used, or disclosed as well as the conditions of the consent provided by participants. Data, information, and biospecimens used in research should be disposed of in a manner that is safe and secure, consistent with the consent obtained and any legal requirements, and appropriate to the research design.

The G-NatlStmt indicates that in the absence of justifiable ethical reasons and to promote access to the benefits of research, researchers should collect and store data, or information generated by research projects, in such a way that they can be used in future research projects. A justification must be provided when a researcher believes there are valid reasons for not making data or information accessible. More details are provided in the G-NatlStmt.

In addition, for details related to secondary use and sharing of data or information, see the G-NatlStmt.

Electronic Data Processing System

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

Records Management

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

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

Responsible Parties

Per AUS-70, the PrivacyAct regulates how certain health service providing organizations collect and handle personal information, including health information. It also includes provisions that generally allow an individual to access information held about them.

According to the PrivacyAct, agencies and organizations as defined in the PrivacyAct must comply with the Act and the Australian Privacy Principles (APP), found in Schedule 1, and are referred to as APP entities.

Data Protection

Per the PrivacyAct’s APP, an APP entity must have a clearly expressed and up-to-date policy about the management of personal information by the entity. Individuals must have the option of not identifying themselves or of using a pseudonym, and an APP entity must not collect sensitive information about an individual unless the individual consents to the collection of the information.

The APP outline further requirements for the consideration of personal information privacy; the collection of personal information; dealing with personal information; the integrity of personal information; and access to, and correction of, personal information. For the full list of APP, see Schedule 1 of the PrivacyAct.

Consent for Processing Personal Data

The PrivacyAct’s APP indicate that if an APP entity holds personal information about an individual that was collected for a particular purpose, the entity must not use or disclose the information for another purpose unless consent is obtained from the individual. There are limited exceptions to this requirement, which can be found in Schedule 1 of the PrivacyAct.

AUS-70 notes that in certain circumstances, the PrivacyAct permits the handling of health information and personal information for health and medical research purposes, where it is impracticable for researchers to obtain individuals' consent, recognizing: the need to protect health information from unexpected uses beyond individual healthcare, and the important role of health and medical research in advancing public health. To promote these ends, the Office of the Australian Information Commissioner (OAIC) approved the National Health and Medical Research Council (NHMRC)’s legally binding guidelines, G-PrivacyAct95 and G-PrivacyAct95A, which researchers must follow when handling health information for research purposes without individuals' consent. The guidelines also assist ethics committees (ECs) (known as the Human Research Ethics Committees in Australia) in deciding whether to approve research applications. The guidelines are:

• G-PrivacyAct95, which sets out procedures that ECs and researchers must follow when personal information is disclosed from a federal agency for medical research purposes
• G-PrivacyAct95A, which provides a framework for ECs to assess proposals to handle health information held by organizations for health research (without individuals' consent). It ensures that the public interest in the research activities substantially outweighs the public interest in the protection of privacy

See the PrivacyAct, the G-PrivacyAct95, and the G-PrivacyAct95A for more information.

No information is currently available regarding personal data protection requirements.

Obtaining Consent

In all Australian clinical trials, valid consent is required from each participant in accordance with the requirements set forth in the AU-ICH-GCPs and the G-NatlStmt. According to the AU-ICH-GCPs, if requirements specified in the G-NatlStmt appear to differ from those specified in the AU-ICH-GCPs, the Therapeutic Goods Administration (TGA) recommends compliance with the G-NatlStmt.

As per the AU-ICH-GCPs, the informed consent form (ICF) (also referred to as a participant information sheet and consent form (PICF) in Australia) is viewed as an essential document that must be reviewed and approved by an institutional ethics committee (EC) (known as a Human Research Ethics Committee in Australia) and kept on file before the trial commences. (See the Required Elements section for details on what should be included in the form.)

According to the G-TrialsSOP, the principal investigator (PI) for any research project retains overall responsibility for ensuring a participant’s consent has been obtained in the correct manner prior to the participant’s entry into the project. This includes where consent is obtained from participants at satellite sites in a teletrial. The PI can delegate the duty for obtaining consent to a suitably qualified associate investigator at the PI’s discretion, but the PI remains responsible for any delegated activity. Furthermore, the investigator must ensure that institutional authorization is obtained, inclusive of approval by an appropriate EC, for all written information and any other media used to provide information to potential participants prior to their usage to obtain consent from any participant.

The AU-ICH-GCPs states that the investigator must provide detailed research study information to the participant or legal representative/guardian. The ICF content should be as non-technical as practical and understandable to the participant or legal representative/guardian. The G-TrialsSOP further indicates that the ICF and relevant EC-approved participant information documents can be provided in person, by telehealth, or by telephone and email or weblink. If informed consent is obtained by telephone, this must be recorded on the ICF and in the participant’s health and medical record, and/or source document, stating (as an example): “The protocol was discussed with [participant’s name] via telephone on [DD/MM/YYYY].”

According to the G-TrialsSOP, e-consent may be the preferable option for teletrials, as consent signatures can be obtained contemporaneously at both primary and satellite sites. For more information on obtaining consent using telehealth, see the G-TrialsSOP.

As per the AU-ICH-GCPs, the ICF content should be clearly presented orally, or in a written language that is easy to understand, and commensurate with the age and comprehension level of the research participant. The participant and legal representative/guardian should also be given adequate time to consider whether to participate. According to the G-NatlStmt, information should also be presented to potential participants in ways that help them make informed choices. To this end, the researcher should take into account cultural and language barriers, the need for accurate and reliable translation, the participant’s educational background, the participant’s age and maturity level, and whether there is a visual, hearing, or communication impairment. See AUS-65 for researcher guidance on how to talk to potential participants.

Furthermore, as delineated in the G-TrialsSOP, the PI or delegate must assess the potential participant’s understanding of what they are agreeing to, that they are aware of the purpose of the study, what will be involved, and any risks that may exist. The participants must demonstrate that they fully understand the implications of decisions that may be made within the course of the research.

Per the G-NatlStmt, where a potential participant lacks the capacity to consent, a person or appropriate statutory body exercising lawful authority for the potential participant should be provided with relevant information and decide whether the individual will participate. That decision must not be contrary to the individual’s best interests. Researchers should bear in mind that the capacity to consent may fluctuate, and even without that capacity, people may have some understanding of the research and the benefits and burdens of their participation. Additionally, within some communities, decisions about participation in research may involve not only individuals but also properly interested parties such as formally constituted bodies, institutions, families, or community elders. See the Emergencies, Vulnerable Populations, Children/Minors, Prisoners, and Mentally Impaired sections for additional information about these populations.

As per the AU-ICH-GCPs, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or to appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representative(s) from liability for negligence. Per the G-NatlStmt, no person should be subject to coercion or pressure in deciding whether to participate in a trial.

The G-NatlStmt indicates that consent may be:

• Specific – limited to the specific project under consideration
• Extended – given for the use of data or tissue in future research projects that are: (i) an extension of, or closely related to, the original project; or (ii) in the same general area of research (for example, genealogical, ethnographical, epidemiological, or chronic illness research)
• Unspecified – given for the use of data or tissue in any future research

The G-NatlStmt further states that when unspecified consent is sought, its terms and wide-ranging implications should be clearly explained to potential participants. When such consent is given, its terms should be clearly recorded. Subsequent reliance, in a research proposal, on existing unspecified consent should describe the terms of that unspecified consent. See the G-NatlStmt for more information on consent to future use of data and tissue in research. Additionally, see the Consent for Specimen section for more information on consent related to use of tissue in research.

Re-Consent

According to the AU-ICH-GCPs and the G-TrialsSOP, any change in the ICF that is relevant to the participant’s consent should be approved by the EC prior to implementing any changes. The participant or legal representative/guardian should also be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented. The G-TrialsSOP further specifies that unless there is a significant safety concern, ECs will not usually require that participants be recontacted immediately since there are potential implications related to blinding. If approved by the EC, continued consent may be obtained verbally and recorded in the participant’s medical records and relevant documents. Re-consent may also be obtained by telephone if approved by an EC.

The G-NatlStmt notes that in some research, consent may occasionally need to be renegotiated or confirmed, especially where projects are complex or long-running, or participants are vulnerable. Research participants should be told if there are changes to the terms to which they originally agreed and given the opportunity to continue their participation or withdraw.

Language Requirements

Pursuant to the G-NatlStmt, methods for presenting research information to participants should take into account the need for accurate and reliable translation into the participant’s first language or dialect, as well as culture and its effects on the communication process. According to the G-TrialsSOP, in cases where translation is required, a professional interpreter should facilitate the process.

Documenting Consent

The AU-ICH-GCPs and the G-TrialsSOP state that the participant or legal representative(s)/guardian(s) and the investigator(s) must sign and date the ICF. Where the participant is unable to read or the legal representative/guardian is unable to read, an impartial witness should be present during the entire informed consent discussion. After the following steps have occurred, the witness should sign and date the ICF attesting that the information in the ICF was accurately explained to, and apparently understood by the participant or legal representative/guardian:

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

Before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF.

The G-TrialsSOP further indicates that where consent is obtained by telehealth or telephone, once the ICF is signed and dated by both the participant and the investigator (and any other person present, for example an interpreter), the participant must select the statement identifying that consent was obtained by telehealth or telephone with the name of the investigator. Similarly, the investigator must select the statement identifying that consent was obtained by telehealth or telephone with the name of the participant. For more information on informed consent documentation, see the G-TrialsSOP.

According to the G-NatlStmt, consent may be expressed orally, in writing, or by some other means (such as return of a survey or conduct implying consent), depending on the nature, complexity, and level of risk of the research, and the participant’s personal and cultural circumstances.

Waiver of Consent

The G-NatlStmt specifies that although voluntary consent is a requirement for every trial, the EC may approve an alteration to the consent requirements. Limited disclosure to participants of the aims and/or methods of research may be justifiable. However, only an EC can review and approve research that involves active concealment or planned deception or aims to expose illegal activity.

Per the G-NatlStmt, it may be appropriate to use an opt-out approach for participant recruitment when obtaining explicit consent is neither practical nor feasible. An opt-out approach is a method used in the recruitment of research participants where information is provided to the potential participant regarding the research and their involvement, and where their participation is presumed unless they take action to decline to participate. An EC may approve the use of an opt-out approach for research if the study satisfies all of the following conditions:

• It involves only low risk to participants
• The public interest in the proposed activity substantially outweighs the public interest in the protection of privacy
• The research activity is likely to be compromised if the participation rate is not near complete, and the requirement for explicit consent would compromise the necessary level of participation
• Reasonable attempts are made to provide participants with appropriate plain language information explaining the nature of the information to be collected, the purpose of collecting it, and procedure to decline participation or withdraw from the research
• A reasonable time period is allowed between the provision of information to prospective participants and the use of their data so that an opportunity for them to decline to participate is provided before the research begins
• A mechanism is provided for prospective participants to obtain further information and decline to participate
• The data collected will be managed and maintained in accordance with relevant security standards
• There is a governance process in place that delineates specific responsibility for the project and for the appropriate management of the data
• The opt-out approach is not prohibited by state, federal, or international law

According to the G-NatlStmt, only an EC may grant a waiver of consent for research using personal information in medical research, or personal health information. However, other review bodies may grant a waiver of consent for other research. In order to help maintain public confidence in the research process, each institution must make publicly accessible summary descriptions of all its research projects for which consent has been waived.

As stated in the G-NatlStmt, an EC may waive the requirement for consent if the study satisfies all of the following conditions:

• Involvement in the research carries no more than low risk to participants
• The benefits from the research justify any risks of harm associated with not seeking consent
• It is impracticable to obtain consent (for example, due to the quantity, age, or accessibility of records)
• There is no known or likely reason for thinking that participants would not have consented if they had been asked
• There is sufficient protection of their privacy
• There is an adequate plan to protect the confidentiality of data
• There is, where practicable, a plan for making information arising from the research available to participants in cases where the results have significance for their welfare
• The possibility of commercial exploitation of derivatives of the data or tissue will not deprive the participants of any financial benefits to which they would be entitled
• The waiver is not prohibited by state, federal, or international law

See the G-NatlStmt for more information on conditions for the opt-out approach or waiving consent.

Obtaining Consent

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

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

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

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

Re-Consent

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

Language Requirements

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

Documenting Consent

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

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

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

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

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

Waiver of Consent

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

Based on the AU-ICH-GCPs and the G-NatlStmt, both the informed consent discussion and the written informed consent form (ICF) (also referred to as a participant information sheet and consent form (PICF) in Australia) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• That the trial involves research
• The purpose of the trial
• The trial treatment(s) and the probability for random assignment to each treatment
• The trial procedures to be followed, including all invasive procedures
• The participant's responsibilities
• Those aspects of the trial that are experimental
• The reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant
• The reasonably expected benefits, including to the wider community. When there is no intended clinical benefit to the participant, the participant should be made aware of this
• The alternative procedure(s) or course(s) of treatment that may be available to the participant, and their important potential benefits and risks
• The compensation and/or treatment available to the participant in the event of trial-related injury, including provision of services to participants adversely affected by the research
• The amounts and sources of funding for the research, as well as financial or other relevant declarations of interests of researchers, sponsors, or institutions
• The anticipated prorated payment, if any, to the participant for participating in the trial
• The anticipated expenses, if any, to the subject for participating in the trial
• That participation in the trial is voluntary and that the participant may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled
• Any implications of withdrawal from the trial, and whether it will be possible to withdraw data
• How the research will be monitored
• That the monitor(s), the auditor(s), the ethics committee (EC), and the regulatory authority(ies) will be granted direct access to the participant's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the participant, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the participant or legal representative/guardian is authorizing such access
• That records identifying the participant will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, the participant’s identity will remain confidential
• That the participant or legal representative/guardian will be informed in a timely manner if information becomes available that may be relevant to the participant's willingness to continue participation in the trial
• 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
• Contact details of a person to receive complaints and of the researchers
• The foreseeable circumstances and/or reasons under which participation in the trial may be terminated
• The expected duration of participation in the trial
• The approximate number of participants involved in the trial
• The likelihood and form of dissemination of the research results, including publication
• Any other relevant information, including research-specific information required under other chapters of the G-NatlStmt

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

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

• Trial procedures to be followed, including all invasive procedures

• Expected duration of participation

• Participant’s responsibilities in the trial

• Experimental aspects of the study

• Approximate number of participants involved in the trial

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

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

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

• Alternative procedures or treatment that may be available

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

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

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

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

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

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

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

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

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

Overview

In accordance with the AU-ICH-GCPs and the G-NatlStmt, Australia’s ethical standards protect participants’ rights and promote respect for human beings, research merit and integrity, justice, and beneficence. The G-NatlStmt further recognizes that state or territory authorities may have additional statutes regarding the use of human tissues, guardianship, and illegal and unprofessional conduct. Furthermore, a participant’s rights must be clearly addressed in the informed consent form (ICF) (also referred to as a participant information sheet and consent form (PICF) in Australia).

The Right to Participate, Abstain, or Withdraw

As stated in the AU-ICH-GCPs and the G-NatlStmt, the participant or the legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled. The G-TrialsSOP further specifies that participants may withdraw their consent at any time without giving a reason.

Per the G-NatlStmt, the participant should be informed of any implications of withdrawal and whether it is possible to withdraw data.

The Right to Information

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

The Right to Privacy and Confidentiality

According to the AU-ICH-GCPs and the G-NatlStmt, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. Privacy is also subject to national, state, and territory laws, including the PrivacyAct. As per the G-TrialsSOP, if telehealth is used, all measures must be taken to ensure privacy and confidentiality of the participant’s identity.

See the Personal Data Protection section for more details on personal information collection and handling requirements.

The Right of Inquiry/Appeal

The AU-ICH-GCPs and the G-NatlStmt state that the research participant or the legal representative/guardian should be provided with contact information for the individual responsible for addressing trial-related inquiries and/or rights.

AUS-45 provides information on who the participant or the legal representative/guardian may contact regarding a concern with the clinical trial. The options include contacting the researcher(s) directly, the ethics committee (EC) (known as Human Research Ethics Committee in Australia), the institution, the healthcare complaints entity in the state or territory, or the National Health and Medical Research Council (NHMRC). Concerns may also be reported to the Therapeutic Goods Administration (TGA). See AUS-45 for more information on the types of concerns that may be reported to each party.

See the G-NatlStmt for more information on institutional requirements for receipt of complaints.

The Right to Safety and Welfare

The AU-ICH-GCPs (which upholds the Declaration of Helsinki (AUS-52)) and the G-NatlStmt clearly state that a research participant’s right to safety and protection of 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.

Overview

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

The Right to Participate, Abstain, or Withdraw

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

The Right to Information

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

The Right to Privacy and Confidentiality

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

The Right of Inquiry/Appeal

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

The Right to Safety and Welfare

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

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

The AU-ICH-GCPs states that in emergency situations, when prior consent of the participant is not possible, the consent of the legal representative/guardian, if present, should be requested. When prior consent of the participant is not possible, and the legal representative/guardian is not available, enrollment of the participant should require measures described in the protocol and/or elsewhere, with documented approval/favorable opinion by the ethics committee (EC) (known as the Human Research Ethics Committee in Australia), to protect the rights, safety, and well-being of the participant and to ensure compliance with applicable regulatory requirements, including the G-NatlStmt. Per the AU-ICH-GCPs, the participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

The G-NatlStmt recognizes that in emergency care research, recruitment into a research project often must be achieved rapidly. Where the research involves emergency treatment and meets the G-NatlStmt’s requirements for research involving people highly dependent on medical care, consent for the research may be waived. See the Vulnerable Populations section for more information on people highly dependent on medical care, and the Documentation Requirements section for more details on waiver of consent.

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

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

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

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

Overview

The AU-ICH-GCPs characterizes vulnerable populations as those who may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation in a clinical trial, or of a retaliatory response for not participating. Examples are 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 subjects include patients with incurable diseases, residents of nursing homes, unemployed or impoverished persons, patients in emergency situations, homeless persons, nomads, refugees, minors, and those incapable of giving consent. Per the G-NatlStmt, people who may be involved in illegal activities, Aboriginal and Torres Strait Islander peoples, ethnic minority groups, and people in other countries are other groups for which specific ethical considerations are required.

People Highly Dependent on Medical Care

According to the G-NatlStmt, research involving people who are highly dependent on medical care may be approved where:

• It is likely that the research will lead to increased understanding about, or improvements in, the care of this population
• The requirements of relevant jurisdictional laws are taken into account
• Either: 1) any risk or burden of the proposed research to this particular participant is justified by the potential benefits, or 2) where participants have capacity to consent, any risk or burden is acceptable to them and justified by the potential benefits of the research

The G-NatlStmt indicates that when a researcher is also the treating health professional, it should be considered whether an independent person should seek the consent of potential participants who are highly dependent on medical care. In addition, the participant and/or the participant’s relatives and an authorized representative should be informed of the participant’s inclusion in the research and of the option to withdraw from it without any reduction in quality of care.

The G-NatlStmt states that when neither the potential participant nor the legal representative/guardian can consider the proposal and give consent, an ethics committee (EC) (known as the Human Research Ethics Committee in Australia) may, having taken account of relevant jurisdictional laws, approve a research project without prior consent if:

• There is no reason to believe that, were the participant or legal representative/guardian to be informed of the proposal, the participant would be unwilling to consent
• The risks of harm to individuals, families, or groups linked to the participant, or to their financial or social interests, are minimized
• The project is not controversial and does not involve significant moral or cultural sensitivities in the community

And, where the research is interventional, these additional conditions apply:

• The research supports a reasonable possibility of benefit over standard care
• Any risk or burden of the intervention to the participant is justified by its potential benefits
• Inclusion in the research project is not contrary to the interests of the participant

The G-NatlStmt further provides specific requirements related to conducting research on participants in terminal care, which is characterized by the short remaining life expectancy of the participants and their vulnerability to unrealistic expectations of benefits. Terminal care research should be designed so that the benefits of research justify any burden, discomfort, or inconvenience to the participants; the prospect of benefit from research participation is not exaggerated; the needs and wishes of participants to spend time as they choose are respected; and the entitlement of those receiving palliative care to participate is recognized.

Aboriginal and Torres Strait Islander Peoples

The G-NatlStmt states that research involving Aboriginal and Torres Strait Islander Peoples must be reviewed and approved by an EC and include assessment and advice from: people who have networks with and/or knowledge of Aboriginal and Torres Strait Islander Peoples; and people familiar with the culture and practices of the relevant Aboriginal and Torres Strait Islander community(ies). In addition, the researcher should ensure the following:

• Research methods are respectful and acknowledge the cultural distinctiveness of participating Aboriginal and Torres Strait Islander communities and groups
• There is evidence of support for the research project from relevant Aboriginal and Torres Strait Islander communities or groups and the research methodology engages with their social and cultural practices
• The research methods provide for mutually agreed mechanisms for recruitment, information provided about the research, notification of participants’ consent and of research progress, and final reporting
• Procedures and actions have been taken to monitor and, where appropriate, minimize any potential negative consequences of the proposed research

For more information on research involving Aboriginal and Torres Strait Islander Peoples, see the G-AboriginalEthic, the G-EthicsRsrchTrackII, and the G-AIATSISCode.

People in Dependent Groups

The G-NatlStmt cautions that dependent or unequal relationships that might compromise the voluntary character of a participant’s decision should be considered. Examples of such relationships include caregivers and people with chronic conditions/disabilities; health care professionals and their patients; teachers and their students; prison authorities and prisoners; governmental authorities and refugees; employers/supervisors and their employees (including members of police and Defense Forces); and service-providers and especially vulnerable communities to whom the services are provided. Where potential participants are especially vulnerable or powerless, consideration should be given to the appointment of a participant advocate.

Per the G-NatlStmt, when a researcher and potential participant have a pre-existing relationship, it should be considered whether an independent person should seek the consent of the participant.

People Who May Be Involved in Illegal Activities

The G-NatlStmt provides specific requirements related to conducting research on participants who may be involved in illegal activities. Research that is intended to study or expose, or likely to expose, illegal activity should be reviewed and approved by an EC. Researchers should be satisfied that participants who are subject to criminal justice processes are aware that the research may discover illegal activity and do not have unrealistic expectations of benefit from their participation. Finally, research designed to expose illegal activity should only be approved where the illegal activity bears on the discharge of a public responsibility or the fitness to hold public office, the risks are justified by the benefits, and the research meets the other requirements in the G-NatlStmt.

People in Other Countries

The G-NatlStmt states that research involving people in other countries must be reviewed and approved by an EC and comply with the G-NatlStmt. The research design, protocol, and consent process should take into consideration the local cultural values, yet still result in participants being treated with no less respect and protection than what is provided in the G-NatlStmt. Additional details are provided in the G-NatlStmt.

Overview

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

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

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

Persons Highly Dependent on Medical Care

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

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

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

Persons in Dependent Groups

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

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

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

The FamLawAct defines a child as a person who is under 18 years of age. Per AUS-71, different states or territories may have specific legislation about a parent/guardian providing consent to medical treatment for a minor; otherwise, the FamLawAct has provisions that may apply.

According to AUS-71, children under 16 cannot give legal consent, which must be given by a parent/guardian, but they can and should be involved in the decision. Young people over 16 can give legal consent to medical treatment; however, they usually cannot provide legal consent to participate in research until they are 18. Nonetheless, some ethics committees (ECs) (known as Human Research Ethics Committees in Australia) do allow mature young people under 18 to give their consent for some kinds of research.

The AU-ICH-GCPs states that minors should be informed to the extent compatible with their maturity and understanding, and if capable, they should sign and personally date the informed consent form (ICF) (also referred to as a participant information sheet and consent form (PICF) in Australia). In accordance with the G-NatlStmt, consent requirements for conducting clinical trials follow the general requirements listed in the Required Elements section.

The G-NatlStmt states before including a child or young person in research, researchers must establish that there is no reason to believe that such participation is contrary to that child's or young person's best interest. Furthermore, a child or young person's refusal to participate in research should be respected wherever the child or young person has the capacity to give consent to that same research. Where a child or young person lacks this capacity, the child or young person’s refusal may be overridden by the judgement of the parent/guardian as to what is in the child's best interest.

The G-NatlStmt indicates that an EC may approve research to which only the child or young person consents if it is satisfied that:

• The child or young person is mature enough to understand the relevant information and give consent
• The research involves low risk
• The research aims to benefit children or young people
• The child or young person is estranged or separated from the parent/guardian and the researcher ensures the child or young person’s safety, security, and well-being in the research conduct; or it would be contrary to the best interests of the child or young person to seek consent from the parent/guardian, and the researcher ensures the child or young person’s safety, security, and well-being in the research conduct

In addition, as stated in the G-NatlStmt, children and young people who are not of sufficient maturity to consent should only participate in clinical studies when: the research is likely to advance knowledge about the health or welfare of, other matters relevant to, children and young people; or their participation is indispensable to the conduct of the research. When considering the inclusion of children and young people in research, the researchers and EC must consider their level of maturity to ensure adequate protections for their welfare.

Assent Requirements

AUS-71 indicates that when a parent/guardian gives consent for their child to take part in a clinical trial, researchers may also ask the child for their permission or agreement, also referred to as assent. The researchers must do this in an age-appropriate manner. Both the parent/guardian and the child should have the chance to ask any questions before agreeing to participate and at any time during a trial. In order for a child to provide their consent or assent they must:

• Understand the research process
• Understand the purpose of the trial
• Be told what they are expected to do or what will happen to them during the trial

AUS-71 further states that children should be able to express their views and any worries they might have about participating in a trial, and have their questions answered. Children should always be given information in a form that they can understand. Additionally, AUS-80 indicates that refusal to assent or withdrawal of assent by a child should be respected. Over the course of a clinical study, it may be necessary to reassess the assent of a child in recognition of their advancing age, evolving maturity, and competency, especially for long-term studies or studies that may require sample retention. During clinical studies, it is required to obtain adequate informed consent for continued participation from pediatric participants once a child reaches the age of legal consent. Local regulations related to confidentiality and privacy of pediatric participants must be followed.

Furthermore, the G-NatlStmt states that except in cases involving standing parental consent, specific consent must be obtained from the child or young person whenever the child or young person has the capacity to make this decision, and either one (1) parent, except when the EC decides that the risks require the consent of both parents, or the child or young person’s parent/guardian.

Per the G-NatlStmt, researchers must respect the developing capacity of children and young people to be involved in decisions about participation in research. The child or young person's particular level of maturity has implications for whether consent is necessary and/or sufficient to authorize participation. However, it is not possible to attach fixed ages to each level of maturity, which may vary from child to child. The following guidelines on maturity and corresponding capacity to consent are provided:

• Infants, who are unable to take part in discussion about the research and its effects
• Young children, who are able to understand some relevant information and take part in limited discussion about the research, but whose consent is not required
• Young people of developing maturity, who are able to understand the relevant information but whose relative immaturity means that they remain vulnerable; the consent of these young people is required, in addition to consent from a parent or guardian
• Young people who are mature enough to understand and consent, and are not vulnerable through immaturity in ways that warrant additional consent from a parent or guardian

See the G-NatlStmt for more information on consent and assent involving children and young people.

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

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

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

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

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

Assent Requirements

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

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

As per the G-NatlStmt, studies involving pregnant women, fetuses, and neonates require additional safeguards to ensure that the research assesses the risks to the pregnant women, fetuses, and neonates. The wellbeing and care of the woman who is pregnant and of her fetus always takes precedence over research considerations, and research involving a fetus or fetal tissue should be conducted in a manner that maintains a clear separation between the woman’s clinical care and the research. Additionally, research should be designed to minimize pain or distress for the fetus, include steps for monitoring for signs of fetal pain or distress, and include steps for suspending or ceasing the research if necessary.

In accordance with the G-NatlStmt, consent requirements for conducting clinical trials follow the general requirements listed in the Required Elements section. However, except for therapeutic innovative therapy cases, the process of providing information and obtaining consent for participating in research should be clearly separate from clinical care if the woman is pregnant and the fetus is in utero. Further, per the G-NatlStmt, the woman should be informed of the following:

• That she should consider whether to seek consent to the proposed research from any other person (e.g., the other parent)
• Whether it is possible to store the fetus or fetal tissues for later use in research
• That she is free to withdraw her consent to the research at any time, whether before or after a termination or other loss of a fetus
• Whether there is potential for commercial application of outcomes of the research, including the development of cell lines
• That she will not be entitled to a share in the profits of any commercial applications
• Whether fetal organs or stem cell lines developed from them will be exported to another country

In addition, the G-NatlStmt states that if, for research purposes, fetal cells are to be derived from the fetal tissue and stored or propagated in tissue culture, or tissues or cells are to be used in human transplantation, the woman's consent is required. Others whom the woman identifies may also need to be involved in decisions about these matters.

For requirements related to assisted reproductive technology, including research involving the creation of human embryos using precursor cells from a human embryo or a human fetus, see the G-EthicsART.

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

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

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

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

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

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

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

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

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

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

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

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

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

The G-NatlStmt refers to prisoners and prison authorities as an example of people who may be in dependent or unequal relationships.

Per the G-NatlStmt, a research study involving people in dependent or unequal relationships (such as prisoners) should, wherever possible, invite prospective participants to discuss their participation with someone who is able to support them in making their decision. If prospective participants are especially vulnerable, researchers should consider appointing a participant advocate.

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

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

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

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

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

Cognitive Impairment, Intellectual Disability, or Mental Illness

The G-NatlStmt discusses the requirements for research involving participants with cognitive impairment, intellectual disability, and mental illness together, noting that many of the ethical issues they raise about research participation are similar. An ethics committee (EC) (known as Human Research Ethics Committee in Australia) must review and approve research involving such participants, except where the research uses collections of non-identifiable data and involves negligible risk.

Per the G-NatlStmt, the research design should take into account factors that may affect the capacity to receive information, to consent to the research, or to participate in it. Additionally, care should be taken to determine whether the participant’s cognitive impairment, intellectual disability, or mental illness increases the susceptibility to some forms of discomfort or distress. Ways of minimizing effects of this susceptibility should be described in the research proposal.

As delineated in the G-NatlStmt, the participant must consent if the participant has the capacity, or the participant’s legal representative/guardian must consent on behalf of the participant. Where a legal representative/guardian has given consent, the researchers still must explain to the participant what the research is about and what participation involves. If the participant recovers the capacity to consent, the researcher should offer the opportunity to continue participation or withdraw. Refusal or reluctance to participate in a research project should be respected.

The G-NatlStmt states that if the participant’s impairment, disability, or illness is temporary or episodic, researchers should seek consent when the condition does not interfere with the capacity to give consent. This consent should occur in the presence of a witness who is familiar with the participant, is independent from the research, and understands the research’s merits, risks, and procedures.

Research Involving Unconscious Persons

The G-NatlStmt states when prior consent is not possible for research involving unconscious persons, consent should be provided by the participant’s legal representative/guardian. However, relevant jurisdictional laws must be taken into account. Because of their extreme vulnerability, unconscious persons should be excluded from all but minimally invasive research, or in research designed both to be therapeutic for them and to improve treatment for the condition from which they suffer.

The G-TrialsSOP notes that as per the Declaration of Helsinki (AUS-52), for research involving participants who are physically or mentally incapable of giving consent (e.g., unconscious patients/participants), the study must be relevant to the physical or mental condition of the participant(s) that prevents them from being able to consent to participate in the study.

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

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

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

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

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

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

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

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

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

In Australia, IPs are also referred to as unapproved therapeutic goods. As per the G-CTHandbook and AUS-47, an unapproved therapeutic good includes:

• Any medicine, biological, or medical device not entered on the Australian Register of Therapeutic Goods (ARTG) (AUS-22), including any new formulation, strength or size, dose, name, indications, directions for use or type of container of a medicine already in the ARTG
• Any therapeutic good already in the ARTG to be used in a manner not covered by the existing ARTG entry

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

Manufacturing

As specified in the TGAct, the TGR, and the G-CTHandbook, the Therapeutic Goods Administration (TGA) authorizes the manufacture of investigational products (IPs) in Australia. As per AUS-47 and AUS-49, the sponsor provides manufacturer and/or active ingredient information to the TGA in the clinical trial application under one (1) of the two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme or the Clinical Trial Approval (CTA) scheme. AUS-49 indicates that as part of a CTN scheme application involving a medicine or biological, the sponsor must provide either the TGA-issued good manufacturing practice (GMP) license, the GMP certification (for overseas manufacturers), or a relevant exemption.

Pursuant to TGManuf, Australia adopted the Pharmaceutical Inspection Co-operation Scheme (PIC/S) Guide to Good Manufacturing Practice for Medicinal Products, PE 009-16 (AU-PIC-S-GMP-Guide) regarding the manufacture of therapeutic goods. Per the AU-PIC-S-GMP-Guide, the holder of a manufacturing authorization must manufacture IPs to ensure that they are fit for their intended use, comply with the requirements of the clinical trial authorization, and do not place participants at risk due to inadequate safety, quality, or efficacy. The production of IPs involves added complexity in comparison to marketed products and therefore requires personnel with a thorough understanding of, and training in, the application of GMP to IPs. For manufacturers to be able to apply and comply with GMP for IPs, cooperation between manufacturers and sponsors of clinical trials is required.

Additionally, the principles of the AU-PIC-S-GMP-Guide on certification by an authorized person and batch release also apply to IPs for human use. Although the ultimate responsibility for the performance of a medicinal product over its lifetime, as well as its safety, quality, and efficacy, lies with the marketing authorization holder, the authorized person is responsible for ensuring that each individual batch has been manufactured and checked in compliance with national requirements in accordance with the requirements of the marketing authorization and with GMP.

See the AU-PIC-S-GMP-Guide for detailed manufacturing requirements. Additionally, see AUS-73 for the TGA’s summary of the changes in version 16 of the AU-PIC-S-GMP-Guide.

Import

The G-CTHandbook and AUS-47 indicate that IPs may be imported and held under the direct control of the sponsor (importer) until the IPs are the subject of a notification to the TGA under the CTN scheme or an approval under the CTA scheme. The IPs must be kept in a warehouse or other properly secured area. There is no requirement for the CTN or CTA process to have been completed prior to importation of the clinical trial goods.

Per AUS-47, importers are advised to contact other relevant agencies, as there may be further restrictions on importation imposed through other legislation.

Other Considerations

AUS-47 states that Australian clinical trial product importers/manufacturers are not required to provide the TGA with six (6) monthly reports under regulation 47B of the TGR. However, the TGA can require information or documents relating to the supply (including quantity) of therapeutic goods that are exempt under the CTN scheme or approved under the CTA scheme.

Manufacturing

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

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

Import

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

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

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

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

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

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

Investigator’s Brochure

According to the AU-ICH-GCPs, the sponsor is responsible for providing the investigators with an investigator’s brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs), including significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information. The sponsor must ensure that an up-to-date IB is made available to the investigator(s), and the investigator(s) must provide an up-to-date IB to the ethics committee.

According to the G-TrialsSOP, where the investigator contributes to the content and development of the IB, the investigator must ensure the IB follows the outline in the AU-ICH-GCPs. The AU-ICH-GCPs requires the IB to cover the following areas:

• Physical, chemical, and pharmaceutical properties and formulation parameters

• Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)

• Effects of IP in humans (pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)

• Summary of data and guidance for the investigator(s)

See Section 7 of the AU-ICH-GCPs for detailed content guidelines.

Quality Management

As specified in the AU-ICH-GCPs, the sponsor must ensure that the products are manufactured in accordance with Good Manufacturing Practice (GMP). Furthermore, 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.

Per the AU-PIC-S-GMP-Guide, GMP ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the clinical trial authorization. A pharmaceutical quality system designed, set up, and verified by the manufacturer or importer should be described in written procedures, taking into account the guidance in Chapter 1 or Part I of the AU-PIC-S-GMP-Guide. Manufacturers should maintain documentation including specifications and instructions; the IP order; manufacturing formulae and processing instructions; packaging instructions; and batch records. The product specifications and manufacturing instructions may be changed during development, but full control and traceability of the changes should also be maintained. The product specification file should be continually updated as development of the product proceeds, ensuring appropriate traceability to the previous versions.

See the AU-PIC-S-GMP-Guide for more details on quality system and documentation requirements.

Investigator’s Brochure

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

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

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

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

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

Quality Management

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

Investigational product (IP) labeling in Australia must comply with the requirements set forth in the G-CTHandbook, the AU-ICH-GCPs, and the AU-PIC-S-GMP-Guide. Per the AU-PIC-S-GMP-Guide, as annotated by the G-CTHandbook, the following information must be included on the IP label:

• Sponsor’s name, address, and phone number. The main contact details for information on the product, clinical trial, and emergency unblinding must be an Australian contact
• Pharmaceutical dosage form, route of administration, and quantity of dosage units. For closed blinded trials, the labeling should include a statement indicating “placebo or [name/identifier] + [strength/potency]”
• The batch and/or code number to identify the contents and packaging operation
• A trial reference code, which should identify the particular trial site, unless provided elsewhere or its absence can be justified. The trial reference code used should also identify the Australian trial sponsor, unless provided as the main contact or its absence can be justified
• The trial participant identification number/treatment number
• Investigator’s name. The name of the principal investigator should appear on the label unless already included in a trial reference code or unless its absence can be justified
• Directions for use
• “For clinical trial use only” or similar wording
• The storage conditions
• The period of use (use-by date, expiry date, or re-test date as applicable) in month/year format and in a manner that avoids any ambiguity
• “Keep out of reach of children” except when the product is not taken home by participants

The G-CTHandbook recognizes that in exceptional circumstances, it may not be possible to meet the requirements of Annex 13 of the AU-PIC-S-GMP-Guide for labeling IPs. In this case, the sponsor must contact the Therapeutic Goods Administration (TGA) (see AUS-23) if they wish to request a departure from the requirements of Annex 13.

In addition, the AU-ICH-GCPs states that the IP must be coded and labeled in a manner that protects the blinding, if applicable.

Per the G-CTHandbook, labeling is a manufacturing step under the TGAct. However, an exemption from the requirement to hold a manufacturing license may apply to certain persons identified within the TGR, to allow relabeling of the IP with name and address of the new sponsor. If there is a change of Australian trial sponsor, the clinical trial medication should be relabeled appropriately with the details of the new trial sponsor at the time of transfer. See the G-CTHandbook for more details on these manufacturing exemptions.

Additional details on IP labeling are provided in the G-CTHandbook and the AU-PIC-S-GMP-Guide.

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

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

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

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

Supply, Storage, and Handling Requirements

As stated in the AU-ICH-GCPs, the sponsor must supply the investigator(s) with the investigational product(s) (IPs)). The G-CTHandbook and AUS-47 indicate that Therapeutic Goods Administration (TGA) approval through the Clinical Trial Approval (CTA) scheme or notification through the Clinical Trial Notification (CTN) scheme must occur prior to supplying the IP(s) to the trial site(s).

The AU-ICH-GCPs specifies that the sponsor must ensure the following:

• Timely delivery of the IP(s)

• Records maintained for IP document shipment, receipt, disposition, return, and destruction

• A system for retrieving or disposing of IP(s) and documenting this retrieval or disposal

• Written procedures including instructions for IP handling and storage, adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor
• IP product quality and stability over the period of use
• IP manufactured according to any application of the Good Manufacturing Practice (GMP)
• Proper coding packaging, and labeling of the IP(s)
• Acceptable IP handling and storage conditions and shelf-life

In addition, the AU-ICH-GCPs states that the IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage. Refer to the AU-ICH-GCPs for detailed sponsor-related IP requirements.

As per the G-TrialsSOP, responsibility for IP management and accountability at the trial site rests with the principal investigator (PI). However, the PI may delegate responsibility for IP management to the site pharmacist or, where a pharmacist is not available or involved, to an appropriately qualified person. The site pharmacist or the appropriately qualified person will undertake IP management at the primary site and/or the satellite site in a teletrial. The investigator, pharmacist, or appropriately qualified non-pharmacist must ensure the IP is used only in accordance with the approved protocol and confirm IP certification and all relevant trial approvals/notifications are in place before releasing the IP for dispensing to participants. Refer to the G-TrialsSOP for detailed investigator-related IP requirements.

The AU-PIC-S-GMP-Guide indicates that the manufacturer or sponsor’s representative should destroy IPs only with prior written authorization by the sponsor. The arrangements for destruction of IPs must be described in the protocol. Any related arrangement between the sponsor and manufacturer should be defined in their technical agreement. Destruction of unused IPs should be carried out only after reconciliation of delivered, used, and recovered products and after investigation and satisfactory explanation of any discrepancies upon which the reconciliation has been accepted.

Record Requirements

According to the G-TrialsSOP, the investigator, pharmacist, or appropriately qualified non-pharmacist must maintain records of all IP management aspects. These records at a minimum should include: shipping documents; date of each transaction; quantities; batch/serial numbers; expiration dates/retest dates (if applicable); temperature logs showing the storage conditions of the IP throughout the trial period; the set of unique code numbers assigned to the IP and to the trial participant; and record of destruction/return.

As set forth in the AU-ICH-GCPs, the sponsor must retain essential documents for 15 years following completion of the trial. The sponsor should inform the investigator(s) and institution(s) in writing when record retention is needed and when the trial-related records are no longer needed. Per the AU-PIC-S-GMP-Guide, documents which are part of the product specification file must be retained for at least five (5) years. If the sponsor and the manufacturer are not the same entity, the sponsor must make appropriate arrangements with the manufacturer to fulfil the sponsor’s requirement to retain the clinical trial master file. Arrangement for retention of such documents and the type of documents to be retained should be defined in an agreement between the sponsor and manufacturer.

Supply, Storage, and Handling Requirements

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

The SL-GCPs specifies that the sponsor must:

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

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

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

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

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

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

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

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

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

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

Record Requirements

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

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

• Treat or prevent disease, ailment, defect, or injury
• Diagnose the condition of a person
• Alter the physiological processes of a person
• Test the susceptibility of a person to disease
• Replace or modify a person’s anatomy

The G-TrialsSOP indicates that to ensure the integrity of biological samples has been maintained, there should be evidence of the chain of custody from their point of collection through processing, storage, transport, through to disposal, with evidence of appropriate storage and transit conditions. Equipment used for processing and storage of samples (e.g., centrifuges, fridges, and freezers) should be maintained by suitably qualified persons and periodically inspected, cleaned, and calibrated to the relevant International Organization for Standardization (ISO) standard according to local policy and manufacturer’s manuals. Additionally, the investigator must ensure all study staff, who have cause to handle or ship biological substances, hold a current certificate in the International Air Transport Association (IATA) Approved, Civil Aviation Safety Authority (CASA) Certified Dangerous Goods Packaging Course. The investigator must also ensure that documentation (e.g., receipts, shipping records, order forms, and proformas) related to handling and shipment of biological specimens is maintained and filed in the respective site file.

Additional details on import and export requirements are provided in the G-CTHandbook, the G-TrialsSOP, the G-SpecExport, and AUS-24.

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

Export

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

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

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

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

• The research for which their biospecimens will be used and, where extended or unspecified consent is sought, and sufficient information is provided to meet the general requirements of consent
• How their biospecimens will be stored, used, and disposed of, including any processes to be adopted that respect their personal or cultural sensitivities
• The extent to which their biospecimens will be reasonably identifiable, and how their privacy and confidentiality will be protected
• Whether the biospecimen research is likely to provide information that may be important to their health or to the health of their blood relatives or their community; and, if such information is likely to be revealed, whether they have the choice to receive this information, whether they have the choice for it to be provided to their relatives or their community, and how these will be managed
• Whether their biospecimens and associated data may be distributed to other researchers, including those outside Australia
• Their right to withdraw consent for the continued use of their biospecimens or associated data in research, and any limitations that may be relevant to their withdrawal of consent
• Any relevant financial or personal interests that those engaged in the collection, processing, storage and distribution, and use of their biospecimens may have
• Any potential for commercial application of any outcomes of the research and how this will be managed and to whom the benefits, if any, will be distributed