Science and Technology CommitteeWritten evidence submitted by AMRC

Key Points

Clinical trials are integral to the development of new treatments and provide clinicians and patients the information that they require to make informed healthcare decisions.

We welcome the EU Commission’s proposal to replace Directive 2011/20/EC, which has created barriers to the conduct of clinical trials in the UK and in Europe. We are pleased to see greater emphasis on the involvement of patients.

The HRA has a valuable role in streamlining regulation of clinical trials, helping important research to go ahead and make the UK an attractive place for investment. It also has an important role in maintaining public confidence in the regulation of clinical trials, including the promotion of transparency as part of ethical approval.

Medical research charities want to see the findings of research disseminated for the benefit of researchers, clinicians and patients. AMRC recommends that members that fund clinical trials stipulate in their grant terms and conditions that the results must be published.

Medical research charities are working with the wider medical research community to improve access to clinical trial data and findings.

1. We welcome the opportunity to respond to this consultation. Several of our members have also responded individually.

2. The Association of Medical Research Charities is a membership organisation of the leading medical and health charities funding research in the UK. Working with our members, we aim to support the sector’s effectiveness and advance medical research by developing best practice, improving public dialogue about research and science, and influencing government to ensure the best research can go ahead and be translated into new treatments.

3. Medical research charities exist because the public choose to donate their money to support research to develop new treatments and cures. In 2010–11, AMRC members invested over £1 billion into health research in the UK. Through charities, the public fund clinical research, but they also wish to become involved in research—72% of the public would like to be offered opportunities to be involved in trials of new medicines or treatments for conditions that affect their daily lives.1 They want to be involved both because they hope that new treatments will benefit them, and because they want to improve treatment for others in the future. Ensuring data and findings are made available for others to learn from is key to delivering this.

4. Many medical research charities have patient groups closely allied to them and as such are able to provide a unique perspective, representing the needs of both patients and researchers.

Do the European Commission’s proposed revisions to the Clinical Trials Directive address the main barriers to conducting clinical trials in the UK and EU?

5. The Directive 2011/20/EC governing clinical trials is widely considered to have placed barriers to the conduct of clinical trials in the UK and across Europe, including introducing delays in trial setup due to inconsistent implementation of the Directive by Member States, increased bureaucracy and inflexible regulation. AMRC supports a joint statement from non-commercial and commercial organisations welcoming the proposals for the introduction of a new Regulation to replace the 2001 Directive.2 The statement calls for further clarity on the scope of the new Regulation and states that any new regulatory framework should include steps to streamline authorisation processes; adoption of a risk-based approach to the regulation of clinical trials; and the provision of clearer guidance.

6. We believe EU institutions, national governments and national bodies need to work together to develop a supportive environment for conducting clinical trials. Revisions should focus on reducing bureaucracy, which acts as a disincentive to setting up clinical trials, while maintaining public safety and increasing confidence through transparency in the regulatory system and greater public involvement.

7. The proposed Regulation also provides a mechanism for involving patients and their representatives in the panel involved in the assessment of clinical trial applications. We welcome greater involvement of patients in all areas of clinical trials, from identifying need and research questions, trial design, authorisation and dissemination of outcomes.

8. There are also barriers within the UK that can be addressed outside of EU legislation. Researchers in the UK experience delays in obtaining NHS R&D permissions and find the process of gaining regulatory approval from multiple agencies (the MHRA, HTA and HRA for example) an overly-bureaucratic process.3 Multi-site trials confound these problems, requiring permissions to be sought at each site individually, leading to duplication of effort for the researcher. Time spent on these hurdles adds cost to the project and introduces delays. A “one-stop-shop” for researchers, whereby they would have one point of contact through which to negotiate all regulatory and governance approvals, would make it clearer and simpler for them to negotiate the processes to set up trials, so cutting the time and costs involved. As discussed further below, we welcome efforts by the National Institute for Health Research (NIHR) and the HRA to reduce complexity in the current system.

What is the role of the Health Research Authority (HRA) in relation to clinical trials and how effective has it been to date?

9. We welcome the work of the HRA since its creation as a Special Health Authority. We are also pleased to see proposals contained within the draft Care and Support Bill to establish the HRA as a non-departmental public body, which will provide important independence.4

10. To reduce the complexity of the regulatory and governance environment for health research in the UK, regulation must be proportionate, coordinated and standardised across the UK. We are pleased to see clarification of the HRA’s role in promoting this in the draft Bill. We also welcome the clarity provided in the Bill that the HRA will work closely with the health regulatory functions of the devolved administrations and is able to exercise some functions on their behalf where appropriate; the success of this relationship is vital to lead to well-integrated, proportionate regulation across the UK.

11. The process of obtaining R&D permissions from NHS Trusts has been identified as a significant barrier to research projects in the UK, introducing delays and increasing costs.5 This process remains the responsibility of NHS providers and we welcome action taken by NIHR to streamline this process but believe there is a role for the HRA as well.6 There is mention in Factsheet 8 accompanying the draft Care and Support Bill that the HRA would “continue work that has already started, through cooperation with other bodies, to create a unified approval process for research”.7 The HRA’s recently launched feasibility study to provide a single, quality-assured HRA assessment to replace duplicated aspects of local research governance will hopefully show how this will work in practice and is welcome.8 Should this prove successful the HRA should take on this quality-assurance role. We would welcome further clarification on how it will work with local NHS providers and other bodies involved in NHS research governance to take further opportunities for streamlining.

12. It is also important for the HRA to assess and demonstrate its effectiveness. This will both enable it to identify areas where action can be taken to improve its processes and the regulatory system and through publicly setting objectives and measuring progress, it can demonstrate to an international stage of potential investors progress in streamlining the regulatory and governance pathways for clinical trials and other types of health research across the UK.

13. The HRA also has an important role to play in maintaining public confidence in the regulation and conduct of clinical trials. Transparency is key to this. As part of the research approval process, applications to the Research Ethics Committees (RECs), which are part of the HRA, must include how the researcher intends to register the trial, publish and disseminate the findings of the research, make data and tissue available, and how they will tell participants about the outcomes of the research. We welcome plans set out by Dr Janet Wisely in her evidence to the Joint Committee on the draft Care and Support Bill, that from April, the HRA will check the final trial report received by RECs to confirm that commitments made in the application have been met and is looking at other ways to promote transparency.9 Should compliance be found to be low, mechanisms must be found to increase compliance without being disproportionately burdensome to researchers. Charities also recognise the importance of transparency and many also ask for this information as part of the grant application process. Audit of compliance will increasingly be supported by research evaluation systems to monitor and record the outcomes and impact of research (discussed further below).

14. Through RECs and its other functions, the HRA can play an important role in promoting transparency, it should and has committed to this but cannot be seen as the sole guardian of this responsibility. We would support a duty to promote transparency being placed upon the HRA in the Care and Support Bill but believe that the HRA can only perform this duty in concert with other bodies, most notably the Medicines and Healthcare Products Regulatory Agency (MHRA), which may be better placed to take a leading role. To be effective, other regulators, research funders, the NHS, sponsors, publishers and researchers must play also their part and recognise this as an important issue.

15. We are pleased that the HRA will be working with Sciencewise to hold a series of events with people around the UK to talk about how they want to be involved in research and how the HRA should work so that they can be confident in the system. This is vital if members of the public are to feel confident about taking part in clinical research.

How could the occurrence and results of clinical trials be made more open to scrutiny? Who should be responsible?

16. Medical research charities fund clinical trials and are keen to ensure the whole system works to deliver the best healthcare for patients—this includes ensuring results and data are shared responsibly and effectively and clinicians have access to the best information to make decisions about how to treat their patients. This is true for all forms of research and consideration of transparency issues should not be limited to clinical trials of medicinal products—it is just as important for research involving devices and surgical techniques, for example.

17. It is also important to remember that research is an international pursuit and that action in the UK alone is not sufficient to increase transparency for the benefit of patients.

Registering clinical trials

18. Clinical trials of investigational medicinal products conducted within the EU are subject to the EU Clinical Trials Directive 2001, which is put into UK law by the Medicines for Human Use (Clinical Trials) Regulations 2004. Researchers in the EU have a legal responsibility to register their studies on the EudraCT clinical trials database.10 Registration is a pre-requisite for applying for authorisation from the MHRA and REC approval.

Publishing results of clinical trials

19. Under the Medicines for Human Use (Clinical Trials) Regulations 2004, trial sponsors (which in academia can be universities or NHS trusts) have a legal responsibility to provide an end-of-trial report to the MHRA and REC 12 months from the end of the trial. As outlined above, RECs can play an important role ensuring that results are reported for use by the medical research community. Research funders, including charities, also have an important role to play in this.

20. Charities have a responsibility to put useful research findings into the public domain and we advise all AMRC members to include a requirement to publish (within a reasonable time frame) in the terms and conditions of their awards.11 When charities work in collaboration with industry we recommend a clear agreement and terms and conditions outlining each partner’s expectations, particularly around intellectual property, publications and exploitation.12

21. We surveyed members of AMRC that are funding clinical research (41 charities in total), either individually or in collaboration with industry, other charities or public funders. 80% of respondents (17/21) include a requirement in their terms and conditions that the results of the research that they fund should be published. Many also request that published research be made “open access” (free to view) on sites such as Europe PubMed Central. This promotes the dissemination of results, ensuring researchers, clinicians and the public are not prevented from accessing them.

22. It is in the best interests of researchers to publish so that they receive the recognition for the work that they have done and also to improve the science base that all scientists benefit from—including preventing duplication and verifying findings. All forms of research, including basic research, are of greatest benefit when made widely available. Likewise, negative findings are valuable and should also be made available.

23. We welcome proposals by the European Commission to expand the EudraCT database to collect results and make them publicly available.13 But research findings must be accessible and understandable to the public. Resources such as CancerHelp UK14 provide plain English explanations of trials and their findings so that the public can make use of them. This is important to maintain public trust in the system and support for clinical research. The UK Clinical Trials Gateway is another valuable resource for the public seeking information about clinical trials and we welcome recent recommendations to improve the service.15

Making data available

24. The detailed data from clinical trials is also valuable for conducting further analysis. Some funders ask that researchers provide data management and sharing plans as part of their research proposals (eg the Wellcome Trust policy on data management and sharing16) and these are also considered by RECs in the ethical approval process.

Additional issues to consider when making data available include ensuring that:

Patient confidentiality is protected and that data is published with their consent.

The data sets and methodology are accessible in a useable format for researchers.

The originating researchers have time to analyse the data before making it publicly available.

That data sets linked to negative results are also published.

That secondary analyses of data refer to the publication where the data were first analysed, and are linked to the original data.

25. The European Medicines Agency (EMA) has committed to making available clinical trials data for drugs that have been approved for license in the EU, and is currently working with a variety of stakeholders including research charities to develop plans on how best to achieve this.17

26. We are working with our members to review practices relating to trial registration, reporting of results and sharing of data. This includes considering what further steps charities funding clinical research can take to audit publication of results and ensure their terms and conditions are complied with. Many of our charities are developing research evaluation systems which will allow them to follow-up the impact of research they have funded. Researchfish18 is a prominent example of such a system and AMRC is facilitating the adoption of this system throughout the medical research community in collaboration with the Medical Research Council.19

February 2013

1 Ipsos MORI poll commissioned by AMRC, Breast Cancer Campaign and the British Heart Foundation, 2011—http://www.ipsos-mori.com/researchpublications/researcharchive/2811/Public-support-for-research-in-the-NHS.aspx

2 http://www.cancerresearchuk.org/prod_consump/groups/cr_common/@nre/@pol/documents/generalcontent/cr_077460.pdf

3 Academy of Medical Sciences, A new pathway for the regulation and governance of health research, 2011—http://www.acmedsci.ac.uk/p47prid88.html

4 Department of Health, Draft Care and Support Bill, 2013—http://www.official-documents.gov.uk/document/cm83/8386/8386.pdf

5 Academy of Medical Sciences, A new pathway for the regulation and governance of health research, 2011—http://www.acmedsci.ac.uk/p47prid88.html

6 HM Treasury and BIS, The Plan for Growth, 2011—http://cdn.hm-treasury.gov.uk/2011budget_growth.pdf

7 Department of Health, The draft Care and Support Bill—Health Research Authority (HRA), Factsheet 8 http://www.dh.gov.uk/health/files/2012/07/Care-and-Support-Bill-Factsheet-8-Health-Research-Authority.pdf

8 http://www.hra.nhs.uk/hra-news-and-announcements/hra-given-go-ahead-for-feasibility-study-hra-assessment-for-approval-of-research-in-the-nhs/

9 http://www.parliament.uk/documents/joint-committees/Draft%20Care%20and%20Support%20Bill/HC822-viii%20Thursday%2031%20January%202013%20Uncorrected%20Transcript.pdf

10 Available at https://eudract.ema.europa.eu/

11 AMRC, Charities and medical research, 1998—http://www.amrc.org.uk/research-resources_guidance

12 AMRC, An essential partnership: Principles & guidelines for working with industry, 2007. Available at http://www.amrc.org.uk/research-resources_guidance

13 http://ec.europa.eu/health/files/eudralex/vol-10/2012_302-03/2012_302-03_en.pdf

14 http://www.cancerresearchuk.org/cancer-help/trials/

15 NIHR, UK Clincal Trials Gateway: Public and Patient Survey 2012, 2012—http://www.nihr.ac.uk/files/Publications/UKCTG%20Report_Jan%202013.pdf

16 Wellcome Trust, 2010. Policy on data management and sharing. Available at http://www.wellcome.ac.uk/about-us/policy/policy-and-position-statements/wtx035043.htm

17 http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000556.jsp&mid

18 https://www.researchfish.com/

19 http://www.amrc.org.uk/research-resources_tracking-the-impact-of-charity-research-funding

Prepared 16th September 2013