Clinical Trials Policy

1. Purpose

Clinical trials are an essential step in translating research advances into health innovations and evaluating new interventions.

2. Definition

SEA DREAM uses the World Health Organization (WHO) definition of a clinical trial: ‘any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes.' Health outcomes can include both biomedical and behavioral outcomes.

Within this definition, SEA DREAM includes trials designed to:

• test investigational medicinal products
• evaluate safety and other aspects if a new technology requiring regulatory approval (this might be a small molecule/biologic therapeutic, vaccine, cell-based therapy, diagnostic test, digital health technology or medical device)
• test non-pharmacological interventions, for example, behavioural or psychological studies, and changes in the environment of an individual or group
• provide insights into disease pathogenesis, including pharmacological trials
• enhance mechanistic understanding of interventions
• understand and improve health service delivery

3. Funding for Clinical Trials

We recognise that research projects involving clinical trials may require some pre-trial work. We will consider funding for systematic reviews as part of a broader research project. SEA DREAM will fund clinical trials in any Southeast Asian country. In some exceptional cases, clinical trials to be done in outside of Southeast Asia can also be supported on a case-by-case basis at the discretion of SEA DREAM. 

4. Pre-trial Requirements

4.1. Trial design

Grantees must integrate sex and gender considerations in their clinical and pre-clinical studies and justify their study design in their application. Trials must recruit a diverse group of participants that, at a minimum, represent the population needing the intervention.  

Meaningful engagement with potential and enrolled participants and their communities should occur before, during, and following the clinical trial. Costs associated with undertaking engaged research activities can be requested in applications.

Trials should be designed and conducted to reduce the emissions and natural resources they use.

4.2. Sponsorship

All trials must have a sponsor(s) that accepts the overall responsibility for proportionate, effective arrangements being in place to set up, run and report a research project. SEA DREAM does not act as a clinical trials sponsor. 

A sponsor can be:

• the lead organisation (or consortium lead), or
• one of the employing organisations where the trial is located (for example: the Ministry of Health, pharmaceutical company, or university)

The grant application must say who the sponsor(s) will be. Grantees must tell us about any subsequent changes to the sponsorship arrangements. The sponsor has overall responsibility for the research, including:

• identifying and addressing quality issues with trial planning, proposals and protocols
• ensuring the trial is run by a suitable team, at suitable site(s)
• ensuring that roles and responsibilities of the parties involved in the research and any delegation by the sponsor of its tasks are agreed and documented
• ensuring adequate provision is made for insurance indemnity to cover liabilities which may arise in relation to the design, management and conduct of the research project
  • clinical trial insurance can be requested in applications where it is a direct cost of the research
• verifying that regulatory and practical arrangements are in place before permitting the research to begin
• putting and keeping in place arrangements for adequate finance and management of the trial including competent risk management and data management

4.3. Governance and approvals

Relevant regulatory and ethical approvals are not required when grant applications are submitted, but these must be obtained if the funding application is successful. Approvals must be in place before the first participant is recruited. The proofs of approval then need to be shared with SEA DREAM as a requirement of a due diligence process. 

If any part of the trial work is subcontracted to a third party, a formal contract must be in place before they start work. Governance mechanisms must be in place before the trial begins. Volunteer expenses for people involved in trial governance committees/boards can be requested in applications.  

4.3.1. Trial Steering Committee 

All trials funded by SEA DREAM should have a Trial Steering Committee (TSC) or an equivalent unless the trial is very small or short, in which case grantees must tell us how the trial will be monitored. The purpose of the TSC is to (i) approve the trial protocol before the trial starts, and (ii) monitor and supervise the trial’s progress. The TSC Chair and at least half of the committee must be independent of the trial management.  

Grantees must:

• obtain TSC approval to make material changes to the trial protocol, and tell SEA DREAM about any material changes
• give SEA DREAM observer status so a staff member may attend TSC meetings
• send us copies of all meeting papers and reports issued by the TSC (Annex II)

4.3.2. Data and Safety Monitoring Board/Data Monitoring Committee

The purpose of this group is to advise the TSC on: 

• the progress of the clinical trial
• the safety data
• the critical efficacy endpoints
• whether to recommend to the trial sponsor to continue, modify or stop a trial

4.4. Registration

Sponsors must ensure that all clinical trials are prospectively registered on at least one of the following:

• ClinicalTrials.gov
• ISRCTN registry
• Another registry listed on the WHO International Clinical Trials Registry Platform (ICTRP)

The registration entry must:

• include a data sharing plan as part of the trial registration, in line with the 2017 International Committee of Medical Journal Editors (ICMJE) requirements on data sharing statements for clinical trials
• provide a synopsis of the trial, that includes a brief summary, study design, sample size, inclusion and exclusion criteria and end points
• state that the trial has been funded by SEA DREAM, and cite the grant number [314988/Z/24/Z]

Costs associated with registering the trial can be requested as part of the grant application. The clinical trial must be registered before the first participant receives the first intervention/visit in the trial, in line with the Declaration of Helsinki 2024. 

Grantees must keep us updated on the progress of the clinical trials funded by SEA DREAM in the progress reports and end-of-grant report and provide the Trial Registry ID. 

The registry record must be updated in a timely manner to include:

• final enrolment numbers
• the date the primary study was completed (this is defined as the last data collection timepoint for the last subject for the primary outcome measure)

If a clinical trial is terminated, the registry record must be updated to include:

• enrolment numbers up to the termination date
• the termination date

4.5. Outputs Management Plans

An outputs management plan (OMP) must be submitted at the time of full application. This should describe how and when trial data will be made more widely available, while maintaining the confidentiality and privacy of trial participants.

See: 

• Annex I for the guidance on how to complete an OMP
• How to prepare the output management plan?

5. Trial requirements

5.1. Conduct

5.2. Publishing plans and protocols

Before trial recruitment is complete, researchers must publish:

• A sufficiently detailed clinical trial protocol using the Standard Protocol Items: Recommendations for Interventional Trial (SPIRIT) framework (or relevant extension), and
• A statistical analysis plan (SAP) to ensure that researchers and other interested parties can interpret the results of your trial.

5.3. Standards of care for control groups

The standard of healthcare provided to a control group participant must be at least equivalent to the best local, currently available and affordable standard of care. Grantees, in consultation with ethics committees, are responsible for determining these healthcare standards. Interventions that are found to be effective should be made available to the control group where this is feasible. Where treatment costs are not met by other sources, the costs for this can be met by direct cost in the grant and should be incurred before the grant end date.

5.4. Including people from under-served groups

There is no single definition that covers all under-served groups. Different groups may be under-served in different contexts and geographies. For example, it could depend on the:

• population
• condition being studied
• question being asked by the research teams
• intervention being tested

The National Institute for Health Research (NIHR) lists some key characteristics common to several under-served groups as follows:

• lower inclusion in research studies than one would expect from population estimates
• high healthcare burden that is not matched by the volume of research designed for the group
• important differences in how a group responds to, or engages with, healthcare interventions compared to other groups, with previous research neglecting to address these factors

To ensure health-related interventions are safe and effective for everyone, trials must consider recruiting more people from under-served groups than statistically necessary, to improve the quality of the results in relation to those groups. Applicants should demonstrate knowledge of the place and communities they plan to work with. Applications must:

• tell us how your recruitment and retention methods will engage with under-served groups .
• describe and justify your inclusion and exclusion criteria for study participants.

6. Post-trial requirements

6.1. Monitoring

Grantees must ensure the trial protocol includes any necessary post-research health monitoring related to a volunteer's participation.  Funds for post-research health monitoring can be requested in applications where it is an integral part of the research proposal, for example certain long-term drug or vaccine trials. 

Grantees are responsible for complying with any requirements for monitoring of adverse events, at any stage of the research. Grantees must notify SEA DREAM of trial-related serious adverse events as identified by the Trial Steering Committee (or other trial monitoring mechanism).

6.2. Publishing trial results

Grantees must maximise opportunities to make their research findings freely available. This includes null and negative results.

Trials must be reported following established guidelines where available, for example, the Consolidated Standards of Reporting Trials -CONSORT- guidelines for randomised trials.

Grantees must:

• offer to share a summary of results with participants (or their representatives) in a format they can easily understand
• post summary trial results in the registry where the trial was originally registered within 12 months of primary study completion
• publish their findings in accordance with our Open Access Policy. This can be in a peer reviewed journal and can also be via a publishing platform such as Wellcome Open Research or pre-print server (such as MedRxiv)

Publications must:

• include the trial registry ID, and;
• acknowledge SEA DREAM as a funder using a standard format mentioned in our Open Access Policy.

7. More information

The following resources might provide further information on good practices and ethical standards in relation to conducting clinical trials:

• Wellcome’s approach to engaged research
• WHO Joint statement on public disclosure of results from clinical trials
• Medicines and Healthcare Products Regulatory Agency (MHRA) guidance on clinical trials
• UK Policy Framework for Health and Social Care Research
• Medicines for Human Use (Clinical Trials) (Amendment) Regulation 2024
• ICMJE Data Sharing Statement for Clinical Trials
• World Medical Association Declaration of Helsinki
• WHO Guidance for best practice for clinical trials 2024
• International Council For Harmonisation Of Technical Requirements For Pharmaceuticals For Human Use – Guideline for Good Clinical Practice E6 (R3)
• Statement of intent: Integrating older age into health and care research
• NIHR’s guidance: Improving inclusion of under-served groups in clinical research
• Reporting guidelines for all study types are available from the EQUATOR network

8. Annexes

Annex I. Guidance on how to complete an outputs management plan

Annex II. Trial Steering Committee Report – Information to Be Included