In September the Commons Science and Technology Committee made recommendations to improve the conduct and transparency of clinical trials in the UK. The government, the Health Research Authority (HRA) and the Medical Research Council (MRC) have responded to explain how they are addressing these issues.
- Explain how the EU Clinical Trials Regulation will improve on the current Directive regulating clinical trials across Europe
- Outline the steps the HRA is taking to simplify and refine the process of setting up clinical trials
- Describe how the HRA is increasing its profile among the clinical research community and the public
- Outline how the government will increase participation in clinical trials including redeveloping the UK Clinical Trials Gateway and making lay summaries of clinical trials available to the public
- Describe initiatives aimed at improving trial transparency through increased registration of clinical trials and publication of results. The MRC’s response highlights the importance of clarifying the definition of clinical trials in order to improve registration rates.
- Support the idea of ‘safe havens’ for individual patient data from clinical trials and discuss which organisation(s) should take on this role (the committee had suggested that the HRA might do this but the HRA explains why this does not fit with their role).
Following the inquiry the Committee published a report which made a number of recommendations to improve the conduct of clinical trials in the UK. These included:
- Urging the government to engage with EU-level clinical trial policy development to represent UK researchers
- Welcoming steps taken by the Health Research Authority (HRA) to streamline UK regulation and governance of health research
- Calling for improved information resources for the public and giving them more opportunities to take part in research
- Calling for all future trials to be included in a publicly-accessible register
- Recommending steps to ensure results (including negative ones) of all trials should be published and funders should develop systems to monitor compliance.
- Calling on the government to give NICE the resources to ensure emerging evidence is incorporated into clinical practice so that increased transparency translates into improved patient care
- Recommending “safe havens” be created to allow safe and controlled access for researchers to the individual patient-level data collected through clinical trials.
We wrote a blog about the Committee’s report which discusses these recommendations in more detail.
So what are the government, HRA and MRC doing?
EU Clinical Trials Directive
The government’s response acknowledges that the European Clinical Trials Directive has acted as a barrier to research in the UK and failed in its aim to harmonise requirements across Europe. It suggests that this will not be the case with the new European Regulation which “will be directly binding and should therefore dramatically reduce the scope for Member States to introduce national requirements”.
The response also confirms that the government is working with other Member States to ensure the Regulation is “sufficiently clear without being overly restrictive”. The Commission’s proposal introduces the concepts of low-intervention trials and risk-adapted monitoring which the government believe will create a proportionate approach to clinical trial regulation throughout Europe. The Regulation is currently in trilogue negotiations between MEPs, Members States on the Council and the European Commission and we expect it to be passed before the European elections in May 2014.
Tackling complex regulation and governance
Both the government’s and the HRA’s responses agree with the Committee that the HRA can do more to simplify and refine the process of setting up clinical trials, outlining work already underway. The HRA have carried out a feasibility study to examine the possibility of integrating parts of the NHS R&D Assessment and the Research Ethics Committee (REC) review into a single HRA assessment. These pilots were successful and the HRA have produced plans for implementing this integrated assessment. These are with the Department of Health.
The Committee had raised concerns that the HRA were not engaged with the clinical research community, they have developed a Strategy for Public Involvement and recently published the findings of their Public Dialogue Project.
Increasing public awareness and recruitment
The Committee was concerned that the public are unaware of the value of clinical research or how to take part in clinical trials. The NHS Constitution includes a pledge to inform patients of research studies in which they may be eligible to participate and the government confirms that NHS England’s draft research strategy will address how the NHS are doing to do that. At our AGM last week, Steve Fairman, Director of Business, Improvement and Research for NHS England, confirmed that a public consultation on the strategy will be launched before Christmas.
The government response also outlines plans to redevelop the UK Clinical Trials Gateway which aims to provide a one-stop-shop for people to find out about clinical trials relevant to them. A review of the Gateway in July 2012 found that 67 per cent of survey respondents thought the information provided was "very clear" or "fairly clear", however some respondents wanted greater consistency in the quality of plain language summaries.
A board has been set up to oversee the project which will include redesigning the presentation of information and functionality of the site to make it more accessible for patients. This will involve working with the HRA to make patient information sheets produced for patients taking part in clinical trials more user-friendly.
As part of the redevelopment process the government considered re-writing into plain language the description of all trials currently on the Gateway but decided this would not be a worthwhile investment. However, INVOLVE have produced recommendations on plain language summaries which NIHR will be implementing over the coming year. In addition, in their response the MRC committed to working with public funders of clinical trials to ensure appropriate information about the trials is available to the public.
The government, MRC and the HRA all state that they are committed to greater clinical trial transparency.
At Report Stage of the Care Bill, which includes clauses establishing the HRA as a non-departmental public body (it is operating as a special health authority at the moment), the government tabled an amendment which made it explicit that the HRA have a duty to promote transparency in research.
The government and the HRA outline steps they have taken to increase the registration and publication of trial information while emphasising the importance of protecting patient confidentiality.
Ensuring the registration and publication of trials
The Committee recommended that the government make the registration and publication of summary-level results in a peer-reviewed journal a contractual requirement for all publicly funded trials and suggested that the government consider ways in which clinical trial transparency could be further incentivised through value-based pricing (VBP).
- The HRA recently announced that the registration of clinical trials in a publicly accessible database should become a condition of a favourable ethics committee opinion, allowing a trial to go ahead
- They are also undertaking investigative work to better understand current publication rates in the UK and how these can be improved
- The MRC response places great emphasis on the need to clarify the definition of clinical trials for mandatory registration to be truly effective
- With regards to the publication of results it is a requirement of MRC funding that outcomes must be published. The MRC are currently investigating how Researchfish, grant-tracking software, which is also used by many AMRC members to follow what happens with the research they fund, could be used to monitor registration and publication of clinical trial information
- On VBP the government disagree with the Committee’s recommendation saying that the pharmaceutical industry should aspire to greater transparency as an end in itself and not in response to rewards or incentives.
The Committee also suggested that the government should support the retrospective registration of all trials conducted on treatments currently available through the NHS. The government response describes this task as unfeasible, however the MRC’s response is more positive referring to the registration of all trials providing evidence relating to current NHS treatments as “desirable” but “challenging.” The MRC will endeavour to support the Government in addressing this recommendation as far as is feasible.
Making patient-level data available
All three responses discuss the tricky issue of releasing individual patient data (IDP) from clinical trials without compromising patient confidentiality and support the idea of "safe havens". The government is considering how these should be accredited and the MRC are working with the Wellcome Trust and the Academy of Medical Sciences to refine current approaches and determine how ‘safe havens’ would work in practice.
The Committee suggested that the HRA act as an independent gatekeeper for access to IDP but the HRA suggest it would be more appropriate for the Health and Social Care Information Centre (HSCIC) to take on this role.
Putting research findings into practice
The Committee highlighted the importance of increased clinical trial transparency resulting in improved healthcare for patients. They asked the government to ensure NICE has the resources it needs to assimilate emerging evidence into its guidance. The MRC are working with NICE to ensure that innovative methods are available to deal with rapidly expanding availability of data—both from increased clinical trial transparency but also other approaches to research, such as medical bioinformatics and population-based research.
The Care Bill has been discussed by the House of Lords and is now in the Commons. There will be opportunities for more discussion and debate of the clauses establishing the HRA including new clause 108(7) which defines the HRA’s role in promoting transparency.
The European Clinical Trials Regulation is in trilogue in Europe at the moment but we expect final legislation to be agreed and passed before the European parliament disbands for the elections in May 2014.
We’re waiting to hear more on the roll-out of the HRA’s new integrated assessment process for clinical trial applications. Work is ongoing to continue refining and streamlining the process while maintaining high quality standards and patient safety.
And the All.Trials campaign is continuing to push for more action at an international scale to improve transparency worldwide – recognising that research is taking place, and results being shared, all round the world.
We will be keeping an eye on all of these developments and will keep you updated as they progress.