Policy for research involving the recruitment of human participants

1. Purpose

This policy sets out Cancer Research UK’s (CRUK) position on all research involving recruitment of human participants (including interventional and observational studies) as referred to in Section 3.2 of the UK Policy Framework for Health and Social Care Research.

2. Scope

This policy applies to all research involving human participants, including clinical trials, and population and behavioural intervention studies; and includes such studies funded or endorsed by all CRUK Funding Committees and CRUK Scientific Executive Board, as well as any studies associated with a CRUK Accelerator Award. Trials sponsored and/or managed by CRUK’s Centre for Drug Development (CDD) are covered separately in CDD’s suite of policies. From here on in, clinical trials, behavioural intervention trials and clinical studies will collectively be referred to as research projects throughout this policy, with specific requirements for interventional clinical trials outlined in the appropriate sections.

This policy forms part of our grant conditions and sets out the requirements for our Grantholders before, during and after their CRUK supported research projects.

3. Key points

3.1 Pre-research project requirements

3.1.1 Approvals

Grantholders and Host Institutions must have the relevant regulatory and ethical approvals and appropriate governance mechanisms in place before participants can be recruited. CRUK reserves the right to view approvals documentation.

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

3.1.2 Declaration of Interests

Grantholders and Host Institutions should adhere to Section 8 of CRUK’s Grant Conditions and must avoid any conflicts of interest in relation to the project and notify CRUK if any conflict of interest arises.

Applicants may be required to complete a Disclosure of potential competing interests form at application stage as outlined in the application scheme guidelines.

3.1.3 Sponsorship & Insurance

All research projects must have a sponsor/co-sponsors who can accept the required responsibilities and accountabilities. If a sponsor(s) is not established in the UK or in an European Economic Area (EEA) country, Grantholders must appoint a legal representative based in the UK or an EEA country for the purposes of the research project. In addition, UK sponsors of research projects in the EU/EEA must now have legal representation in the EU.

Any changes in sponsorship during the course of the research project must be communicated to CRUK in writing as soon as possible.

The sponsor is responsible for ensuring adequate provision is made for insurance or indemnity to cover liabilities which may arise in relation to the design, management and conduct of the research project.

3.1.4 Registration

Grantholders must register any CRUK-funded or endorsed clinical trial on a recognised trials registry such as the ISRCTN registry or the ClinicalTrials.gov registry before the first participant receives the first medical intervention in the trial.

Grantholders must notify CRUK of the registration number no later than the time of the subsequent scientific milestone report. CRUK reserves the right to suspend awards that have not been appropriately registered but have recruited patients until the trial has been registered. Details included in the registry must be kept up-to-date throughout the lifetime of the trial. Clinical trial registry records should be updated as necessary to include final enrolment numbers achieved, and the date of primary study completion (defined as the last data collection timepoint for the last subject for the primary outcome measure). If clinical trials are terminated, their status should be updated to note the date of termination, and to report the numbers enrolled up to the date of termination.

Clinical trials of investigational medicinal products (CTIMPs) involving sites in a European Union country must be registered on the European Clinical Trials Database and obtain a EudraCT number as part of regulatory approval from the relevant competent authority/ies. All research projects must follow the required registration guidance and principles in all countries where the study is running.

3.1.5 CRUK Trials Database

Grantholders and Research Personnel conducting interventional trials will assist the CRUK Patient Involvement Team by:

including the URL for CRUK’s clinical trial database (cruk.org/trials) on the patient information sheet (including the CRUK logo is also strongly encouraged);
providing CRUK with the study protocol and patient information sheet to support the development of an accurate lay summary of the trial;
assisting CRUK to draft a lay summary of the trial and or study (and findings, as and when Results are available) for inclusion on CRUK’s online clinical trials database and subsequently provide regular updates to the information as requested, so that the database can be kept reasonably up to date.

3.2 Research project requirements

3.2.1 Conduct of Research Projects

All research projects must be conducted in accordance with the UK Policy Framework for Health and Social Care Research, and/or any relevant frameworks of local ethics committees, recognised good practice guidelines, and any applicable regulatory requirements.

3.2.2 Chief Investigator Expectations

All research projects must be led by a Chief Investigator, who is responsible for the overall conduct of the research project. A Chief Investigator’s responsibilities are set out in more detail in the UK Policy Framework for Health and Social Care Research. CRUK expects all research projects in the UK to be a led by a Chief Investigator who is a scientist, statistician, epidemiologist, clinician or healthcare worker in a UK university, medical school, hospital, clinical trials unit or research institution. Any change to the Chief Investigator must be agreed with CRUK.

Grantholders are strongly encouraged to use any CRUK supported research project to facilitate the training and development of any junior investigators on the research project team.

3.2.3 Making the Protocol Public

For all research projects, CRUK expects a sufficiently detailed summary of the research project protocol, including the intended analysis plan, to be made publicly available prior to the start of recruitment.

For interventional clinical trials, details of where and how the trial protocol and analysis plan may be accessed must be provided on the registry and on the trial website, if one exists. Any approved changes to the protocol must be updated on the registry as soon as possible.

3.2.4 Governance

For early phase interventional trials, observational studies and other research projects:

Governance arrangements must be agreed with CRUK at the application stage. For all trials, a Trial Management Group should be established to monitor all aspects of the conduct and progress of the trial, ensure that the protocol is adhered to and take appropriate action to safeguard participants and the quality of the trial itself.

In addition, Trial Steering and Independent Data Monitoring Committees should be established if required.

For late phase clinical trials:

Trial Steering Committee (TSC)

In addition to a Trial Management Group, a Trial Steering Committee (TSC) should be set up. The membership should include an independent chair, a statistician, a clinician(s), and any others with expertise relevant to the project, with at least one individual who is able to contribute a patient and/or wider public perspective and any additional relevant observers. Please note that independent members (i.e. individuals not partly or fully employed by the Host Institution listed on the grant application, or anyone who would expect to be an author on the main trial publication or who is named on the grant application) must make up a minimum of two thirds of the TSC membership.

In some cases, an Umbrella Trial Steering Committee (UTSC) may be appropriate (e.g. for a group of trials within the same disease area), and in this case Grantholders must ensure the UTSC has the required expertise.

Responsibilities of the TSC/UTSC should be set out in a Terms of Reference or Charter, and should include:

approving the trial protocol and any significant amendments;
supervising the progress and conduct of the study, and;
where applicable, consider recommendations from the Independent Data Monitoring Committee.

CRUK reserves the right to attend TSC/UTSC meetings as an observer.

Copies of all UTSC/TSC minutes should be included in Scientific Milestone Reports.

Independent Data Monitoring Committee (IDMC)

The research project sponsor should determine whether an Independent Data Monitoring Committee (IDMC) is required. Members of the IDMC should be independent of the study team and the TSC.

Responsibilities of the IDMC should be set out in a Terms of Reference or Charter, and may include:

reviewing the conduct of the trial, and the safety and efficacy data;
advising whether the trial should continue, be amended or closed.

Copies of all open IDMC minutes should be included in Scientific Milestone Reports.

For research projects with an international sponsor:

There may be differing oversight committee arrangements, and these should be clearly presented to CRUK in the relevant application form. As a minimum, CRUK expects either a UK Trial Management Group to be established, or UK involvement in an international TMG with relevant minutes included in Scientific Milestone Reports. In addition, if an IDMC or TSC is in place then the relevant minutes should also be included in Scientific Milestone Reports.

3.2.5 Monitoring by CRUK

All supported research projects must be reviewed via independent peer review as per the relevant CRUK funding committee review processes. Grantholders must provide adequately completed milestone reports as requested by CRUK and in line with timelines set by the relevant CRUK panel or committee as required.

CRUK reserves the right to withdraw funding or endorsement if deemed appropriate following independent peer review. In these cases, CRUK will work with the Grantholder to develop an effective plan to withdraw support in the most appropriate way, without detrimental impact to patients receiving treatment through the trial. If CRUK deems it appropriate to withdraw funding or endorsement, CRUK will inform the NIHR Clinical Research Network about this change if appropriate.

CRUK expects most awards to be completed within the agreed duration, but we accept there may be occasions where there are unforeseen delays and extensions, amendments or suspensions may need to be requested to ensure the research deliverables are met. All Grantholders must follow the relevant funding committee process for any costed/non-costed amendments or extensions.

CRUK will carry out ongoing monitoring to ensure research projects are registered and reported in line with the expectations outlined within this document.

3.2.6 Expectations of Patient and Public Involvement (PPI)

CRUK is committed to ensuring high quality patient and public involvement and engagement plays a critical role in all supported trials, and Grantholders must incorporate meaningful patient involvement throughout their study.

CRUK expects patient and public involvement to be meaningful, and not tokenistic, at every stage, including in the defining and developing of any research questions and study rationale, where possible. In addition, patient and public involvement should be included in, but not limited to, the following activities:

planning and design of the study
ongoing input into the governance, management and the monitoring of the study (including having an active role in Trial Management Groups and/or Steering Committees)
developing and maintaining patient facing materials
contributing to dissemination plans

Grantholders should ensure that the quality of PPI is continuously considered and evaluated for the duration of the trial to ensure ongoing relevant and maximum impact, and Grantholders should provide training and support to PPI representatives as required to ensure high quality input. CRUK encourages all Grantholders to consider how PPI can best represent diverse perspectives, to identify, reduce and remove any potential barriers to participation that may be faced by any potentially underserved groups within the trial population in question.

For further information, please refer to our PPI Statement of Intent.

3.2.7 Including People from Under-served Groups

CRUK is committed to equality, diversity and inclusion. Furthermore, it is essential that any intervention is safe and effective for the whole population.

In light of this, CRUK expects Grantholders for all research projects supported after March 2022 to:

endeavour to recruit a diverse group of participants that represent the population needing the healthcare intervention;
take steps to remove any potential barriers to people from under-served groups participating in research.

CRUK expects Grantholders to review their research project target population, intervention and research questions to identify what ‘under-served’ means for their project.

CRUK expects Grantholders to have developed recruitment strategies that aim to reach and engage any relevant under-served groups, and to be able to justify any inclusion and exclusion criteria that have been defined. Where appropriate equality, diversity and inclusion considerations should be accounted for in the statistical analysis plan.

3.2.8 Collection of NHS Numbers

The NHS number (or equivalent) should be recorded for all patients or participants entering clinical trials supported by CRUK. The collection of NHS numbers is strongly encouraged in other research projects involving healthy volunteers and any other CRUK-supported study where long-term follow-up is likely. The purpose of this is to enable linkage between routine and clinical data sets.

3.2.9 Trials Supported by Commercial Entities

Where a research project is supported in any way by a commercial entity, Grantholders should adhere to Section 11 of CRUK’s Grant Conditions.

3.3 Post-research project requirements

3.3.1 Reporting of Results

Summary results: Grantholders are required to make summary results (whether positive or negative) of their CRUK-funded or CRUK-endorsed research project publicly available, without unreasonable delay, and generally within 12 months of the end of the research project (unless there is a scientifically justified longer time period). The results must be posted on the same registry as the research project was listed

Publish findings: Every effort should be made to ensure results are published in a peer-reviewed journal. Grantholders are also strongly encouraged to post preprints of their work en route to publication in a peer-reviewed journal.

Grantholders must:

include the trial registry ID;
acknowledge CRUK’s support; and
ensure publications are in line with our Policy on Open Access. Our Policy requires immediate open access upon publication for CRUK-funded articles accepted for final publication on or after 1 January 2022.

For further information on expectations for publication, Grantholders should refer to Section 13 of CRUK Grant Conditions.

3.3.2 Making Datasets Accessible for Further Research

By publication of the primary analysis of the research project results, Grantholders are required to make their datasets available to other legitimate access requests for secondary academic research. They must ensure discoverability of the research project data set (for example through a suitable clinical trials data sharing repository) and have processes in place to manage data access requests and to achieve secure transfer of data where requests are granted.

Data must be managed in accordance with our Policy on Data Sharing and Preservation.