The Commons Science and Technology Committee has published its report on clinical trials following the inquiry it held earlier this year. It has made a number of recommendations to improve the conduct of clinical trials in the UK and increase public trust and awareness, including:
- 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
- Improving information resources for the public and giving them more opportunities to take part in research
- Mandating trial registration
- Recommending steps to ensure results (including negative ones) of all trials – not just industry trials but those publicly funded by research councils and charities - should be published and funders should develop systems to monitor compliance. However, the committee did not think that highly detailed Clinical study Reports (CSRs) must be produced and published for non-commercial trials
- 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 to individual patient-level data for researchers.
Clinical trials are an essential step in turning a discovery in a lab into a treatment for patients. This POSTnote gives a great overview of clinical trials.
41 of our member charities are currently funding clinical trials either individually or in collaboration with industry, other charities or public funders. Patients want the opportunity to be involved in trials of new treatments - in the hope that the treatment will benefit them, but also altruistically to improve treatment for others in the future. Transparency about how these trials are conducted and the publication of the results is central to research, helping other researchers to learn from this information and make further advances. As well as the overall results of the trial, the detailed data gathered are very valuable for researchers.
The House of Commons Science and Technology Committee launched an inquiry into clinical trials in December 2012. AMRC responded and our chief executive, Shar, also gave evidence in front of the Committee.
What did the report say?
EU Clinical Trials Directive
The Committee – like everyone else – recognised the difficulties that the 2001 Directive has created, largely due to increased bureaucracy and inconsistent implementation by different countries. The Committee urged the government and MHRA to engage with the proposed new EU Regulation on clinical trials currently being discussed in Brussels and also with work being done by the European Medicines Agency (EMA) to ensure that future legislation was “pragmatic and proportionate”.
Regulation and governance complexity and the HRA
The report highlights the difficulty many researchers face setting up trials, quoting our survey which found that:
40% of polled hospital doctors cited difficulties navigating regulatory processes as a barrier to them taking part in medical research in the last two years.
The Committee commended the Health Research Authority (HRA) and its ambition to streamline the process of setting up trials, however they wanted to see more measurable targets to know whether improvements were being made and greater engagement with stakeholders. They suggested a triennial review to review progress and identify further improvements. The committee also called on the government to update them on progress towards reducing the time taken to set up trials:
The Government as failed to meet its own 2012 deadline for measuring NHS Trust performance against a 70-day benchmark for clinical trial initiation and we query whether this deadline is realistic in the short-term.
Increasing public awareness and recruitment
The Committee were concerned that the public are not aware of the value of clinical research to improve healthcare or how to take part and are wary of industry involvement. It asked the government to explain how it is communicating changes to the NHS Constitution and encouraging the public to take part in research, and follow up with a 12 month report of the effectiveness of their initiatives.
The Committee were very impressed with Cancer Research UK’s CancerHelpUK, which provides easy-to understand information on clinical trials and urged the government to improve the Clinical Trials Gateway in a similar vein.
The report outlines the benefits of greater transparency – improved patient outcomes based on more information being available to clinicians, enhanced scientific knowledge, increased public trust and “fulfilment of basic ethical standards”. But they also noted the need to protect personal privacy, intellectual property and the risk of data being misused.
Registration and publication of trials - Weighing up the costs and benefits, the Committee decided that summary-level information should be made available for all trials, published through peer-reviewed journals. They felt however that it would be too burdensome to require detailed Clinical Study Reports (CSRs) for non-commercial trials where they would not routinely be produced. They acknowledged the difficulties in releasing data and information from historical unpublished trials, saying that this should not be mandated. But they did say that retrospective registration of all trials is vital to allow others to assess which historical trials should be looked at more closely. The Committee also recommended that when trial data is released that it be “accessible, assessable, intelligible and usable.” They suggested levers that the government and research funders could use to encourage the registration and publishing of trials:
We recommend that registration in a WHO-listed registry and publication of summary-level results in a peer-reviewed journal be made contractual requirements for all publicly-funded trials, including research supported by the Charity Research Support Fund. The wording of these requirements should be standardised across all contracts to ensure consistency.
They also wanted to see public funders of research rapidly put in place mechanisms to monitor compliance with transparency policies. Many AMRC members are now using ResearchFish - grant-tracking software that will allow them to follow what is done with the research that they fund, including of course any publications. And the Committee identified value-based pricing (VBP) – the proposed system for setting the costs of medicines – as another lever to encourage transparency from industry:
The Government should consider ways in which clinical trial transparency could be incentivised in the future through VBP and the current renegotiation of the Pharmaceutical Price Regulation Scheme (PPRS).
Adding that the HRA has an important role to play:
We agree with the Joint Committee that the Care and Support Bill should make the promotion of research transparency a statutory objective of the HRA and we recommend that the Government includes the necessary provision.
(The Care and Support Bill is currently being debated in the House of Lords before being discussed in the Commons and includes clauses formally establishing the HRA and outlining its functions). The Committee rejected the argument made to them that publishing negative results is not possible but did acknowledge that research funders should provide more resources to ensure that researchers have no excuse not to publish. They also said that journals must stop banning the republishing of trial data outside of their own publication – the so called “Ingelfinger” restriction.
We suggest that the AllTrials campaign clearly set out what it considers a full trial report to contain, particularly when prepared for non-commercial purposes, so that its supporters can work together to achieve a specific set of common goals.
Making patient data available - The Committee considered the issues surrounding the release of patient-level data from clinical trials:
We are not in favour of placing anonymised individual patient-level data (IPD) in the public domain in an unrestricted manner… We agree with the Caldicott 2 Review that providing specific individuals with controlled access to personal confidential data such as IPD through carefully managed and secure “safe havens”, together with contractual agreements about how that data can be used, is the best way forward. We also consider that access should be facilitated by an independent “gatekeeper”, responsible for evaluating research proposals and ensuring that data is handled responsibly and in a way that makes a useful contribution to scientific knowledge.
They went on to suggest that the UK could take an international lead in this approach, with the HRA taking responsibility for implementation.
Putting research findings into practice
The Committee acknowledged that transparency isn’t an end in itself and all these steps won’t improve healthcare for patients unless mechanisms are put in place to incorporate emerging evidence into clinical practice. They said that NICE is well placed to do this and recommended that it is given the resources to do this. You can read the full report here.
The government will respond to the report and its recommendations.
There is a lot going on across the medical research community looking to address many of the issues raised in the report. Just this week, the HRA published plans to ensure researchers register trials and publish the findings for others to learn from – more from Becky here. And earlier this year the Wellcome Trust convened a workshop to discuss steps to promote transparency in clinical research. A list of actions were drawn up from this. These are now being taken forward by different partners including professional bodies, journals, regulators, funders and registries.
As research is international and takes place all around the world, any solutions to improve transparency have to be global. Conversations are underway between international registries to explore how they can be made interoperable at an international level, including giving trials one single identifier, and allowing information about the trial to be uploaded. This might include a lay summary and details of the study protocol, and potentially the trial results when complete.
Work is also underway to explore how the underlying patient-level data from a trial on which the findings are based, can be made accessible for re-analysis by other researchers. GlaxoSmithKline has developed a model to do this and other companies funding research are exploring similar solutions. Public funders are also looking at a system to enable safe and secure access to these data; research is underway to better understand the value of accessing these data to inform the design of such a system.
The European Medicines Agency is currently consulting on its draft policy aiming to improve transparency; we will be responding.
The All.Trials campaign is continuing to maintain the momentum of these discussions and organising meetings to develop practical solutions, including a planned meeting of patient groups to discuss what information patients want when they are choosing whether to take part and taking part in research.
We are involved in these discussions and will keep you updated as they progress.