Clinical trials policy

Wellcome 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’.

It includes randomised controlled trials and clinical trials of investigational medicinal products.

We fund clinical trials through our health challenges: mental health, infectious disease and climate and health. Our discovery research schemes do not provide support for purely translational research aimed at developing, testing or implementing interventions or treatments.

Where we consider applications for clinical trials, we include, but are not limited to, trials:

• of non-pharmacological interventions, for example, behavioural or psychological studies
• designed to provide insights into disease pathogenesis, including pharmacological trials
• designed to understand and improve health service delivery
• designed to provide clinical proof of concept
• designed to evaluate safety and other aspects of a new technology requiring regulatory approval (this might be a small molecule/biologic therapeutic, vaccine, cell-based therapy, diagnostic test or medical device).

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.

Wellcome will fund clinical trials in any global region. If your trial is based in a low- or middle-income country, you should read our guidance about this.

Approvals and contracts

Grantholders and administering organisations must have the relevant regulatory and ethical approvals and appropriate governance mechanisms in place before a trial can begin. Wellcome reserves the right to view approvals documentation.

Approvals are not required when you submit your grant application, but you must get these if your funding application is successful.

If you plan to subcontract any part of the trial to a third party, you must have a formal contract in place before they start work.

Sponsorship and insurance

All trials must have a sponsor/sponsors who can accept the responsibilities and accountabilities that go with the role. Wellcome does not act as a clinical trials sponsor.

A sponsor can be:

• your employing organisation

or

• one of the employing organisations where the trial is located eg an NHS trust, pharmaceutical company or university.

We require information about the sponsor, or sponsors, in your grant application, and you must tell us about any subsequent changes to the sponsorship arrangements.

For all trials, the sponsor is responsible for ensuring there is appropriate indemnity insurance.

Registration

All clinical trials that fall within the scope of this policy must be 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).

You must register the clinical trial before the first subject receives the first medical intervention in the trial, in line with the Declaration of Helsinki 2013.

When you register you 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 summary of the trial
• state that the trial has been funded by Wellcome, and cite the relevant grant number.

We will meet the costs associated with registering the trial. You can ask for these as part of your grant application.

You must update the registry record, 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, you must update the registry record to include:

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

Plans and protocols

When you apply for Wellcome funding for a clinical trial, you must submit an outputs management plan with your grant application. This should describe how and when trial data will be made more widely available, while maintaining the confidentiality and privacy of trial participants.

You must make a sufficiently detailed clinical trial protocol and statistical analysis plan (SAP) publicly available. This is to ensure that researchers and other interested parties can interpret the results of your trial.

You must publish the trial protocols and SAPs before trial recruitment is complete. You can use Wellcome Open Research, along with other journals and platforms such as Trials and Protocols.io, to do so.

Standards of care for control groups

Where a healthcare intervention is being examined through a trial, the standard of healthcare provided to a control group subject must be at least equivalent to the best local, currently available and affordable standard of care.

Grantholders, in consultation with ethics committees, are responsible for determining these healthcare standards.

Conduct

All trials must be conducted in accordance with recognised good practice guidelines, for example the UK Policy Framework for Health and Social Care Research. Our guidelines on the responsible conduct of research provide more detailed advice on research design. You must also abide by Wellcome’s research involving human participants policy.

We expect grantholders to have an appropriate gender balance in their clinical and pre-clinical studies and be able to justify their study design.

We're establishing a Good Clinical Trials Collaborative to look at new clinical practice guidelines, where the current guidelines are not fit for purpose.

Including people from under-served groups

It’s important that the healthcare intervention is safe and effective for everyone. To ensure this you should:

• recruit a diverse group of participants that, at a minimum, represent the population needing the healthcare intervention
• consider recruiting more people from under-served groups than statistically necessary, to improve the quality of your results in relation to those groups.

There is no single definition that covers all under-served groups. 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.

Read the NIHR’s guidance for more information on defining and including under-served groups.

In your application

You 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.
   

Governance

Trial Steering Committee

If you receive a grant from Wellcome, you will usually need to set up a Trial Steering Committee (TSC) and tell us about its proposed members. The purpose of the TSC is to:

• approve the trial protocol before the trial starts
• monitor and supervise the trial’s progress.

We expect to have observer status and reserve the right to attend TSC meetings.

If you want to make material changes to the protocol during the trial, these must be approved by the TSC.

You must send us copies of all reports issued by the TSC. These should reflect on the key issues [DOC 73KB].

If a TSC is not necessary (eg if the trial is very small), you must still explain how you will monitor the trial.

Data Monitoring Committee

The TSC may need to set up a Data Monitoring Committee (DMC) to regularly assess and advise 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.

The trial sponsor should complete a risk assessment to determine if a DMC is needed and to form one, if necessary.

If a DMC isn't necessary, you must explain how you will monitor the trial.

Members of the DMC should be independent of both the study management and the TSC.

Monitoring

Your research protocol should include any necessary post-research health monitoring related to a volunteer's participation. This is the responsibility of the grantholder.

Wellcome may provide funds for post-research health monitoring where it is an integral part of your research proposal, for example certain long-term drug or vaccine trials.

Grantholders are responsible for complying with any requirements for monitoring of adverse events, at any stage of the research.

Publishing trial results

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

You must:

Post your summary trial results: These should be posted in the clinical trial registry where your trial was originally registered.

Publish your findings: Our preferred route is to publish in a peer-reviewed journal, but grantholders can also publish their findings via a publishing platform (such as Wellcome Open Research) or pre-print server (such as MedRxiv).

You must:

• include the trial registry ID
• list Wellcome as a funder, and
• ensure the publication is made freely available.

This is in line with our open access policy.

Any peer-reviewed publications that arise from Wellcome funding must be made freely available in line with our open access policy.

Clinical trial data must be managed and shared in accordance with our policy on data, software and materials management and sharing.

Data underlying your research publications must be made accessible to other researchers no later than the time of publication – either openly or via a managed access approach.

Wellcome supports researchers to meet our data sharing requirements by funding reasonable costs to prepare, store, and access clinical data in ways that are aligned to the FAIR principles. We encourage researchers to consider these costs in their outputs management plans at the application stage, but we may also be able to support unforeseen additional costs at a later stage if requested, for example the anonymisation of identifiable data, or repository fees. Please contact openresearch@wellcome.org with any questions.

If you fail to comply with this policy, we will consider appropriate sanctions. These may include suspending your grant or not accepting new grant applications from you.

• 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) Regulation 2004
• EU Clinical Trial Regulation (2019)
• ICMJE Data Sharing Statement for Clinical Trials

This policy was updated in August 2021.