Research integrity: clinical trials transparency Contents

Conclusions and recommendations

The current state of clinical trials transparency and related legislation

1.A range of UK and EU rules and guidelines are in force to improve clinical trials transparency, in terms of tackling non-registration, non-reporting and mis-reporting. Despite these rules, around half of clinical trials are left unreported, clinical trial registration is not yet universal in the UK and reported outcomes do not always align with the original study proposal. Further action is needed to improve reporting and registration of clinical trials, as we set out in this Report. The Government should not rely on the higher reporting rates for trials funded by the Medical Research Council to suggest that the problem is being addressed, as these represent a small proportion of the total number of clinical trials undertaken in the UK. (Paragraph 15)

2.The Government should explicitly commit to introducing the clinical trials transparency requirements in the EU Clinical Trials Regulation that are expected to be applied in the EU shortly after Brexit. (Paragraph 16)

3.Compliance with transparency rules varies by sponsor—while pharmaceutical companies have good rates of reporting within a reasonable timeframe, the picture is much more mixed for universities. We welcome the Science Minister and the Government Chief Scientist’s call for universities to deal with this problem and expect universities to take heed. Every university should aim for 100% compliance. We recommend that the updated and strengthened Concordat to Support Research Integrity being developed by Universities UK should include requirements on universities to ensure that all trials are reported, and that efforts are made to share best practice in achieving compliance with reporting rules within the university sector. (Paragraph 19)

4.It is particularly disappointing that trusted bodies such as Public Health England and a range of NHS Foundation Trusts are also failing to report results from clinical trials. Public trust in medicine could easily be eroded by failures in clinical trials transparency from such important parts of the health system. Public Health England should write to us with an explanation and the steps it will take to correct this. Public Health England should write to us with an explanation and the steps it will take to correct this (Paragraph 21)

Improving clinical trials transparency

5.Our predecessor Committee concluded in 2013 that it had “not been impressed” by the Government’s efforts to resolve the problem of un-registered, non-reported and mis-reported clinical trials. We believe that while there have been some improvements there is still much more to be done. (Paragraph 25)

6.We welcome the recent statements and recommendations from the WHO and the UN on clinical trials transparency aimed at improving registration and reporting rates. The Ebola epidemic prompted political attention in the UK to the risks to public health of non-publication of clinical trial results, with the then Prime Minister David Cameron making commitments to clinical trials transparency in 2015. Since then, progress has slowed in the UK at a political level. Clinical trials transparency is as much a question of political will as it is a technical issue. We recommend that the Government explicitly re-commit to tackling clinical trials transparency, perhaps through a focused ministerial speech on this issue. This should set a clear time limit for institutions to fully comply with clinical trials transparency requirements and make clear what the consequences will be of failing to meet that deadline. (Paragraph 26)

7.Non-compliance with reporting rules is not currently documented by public bodies on a trial-by-trial basis. Official publication of such information would expose where there are weaknesses in compliance and where best practice within the sector could be found and shared. We welcome recent efforts by Dr Goldacre and the AllTrials campaign to make information on reporting rates available online. However, it should not be left to researchers and campaigners to collate and publish this information themselves. We turn to the issue of who should produce this information later in this chapter. (Paragraph 31)

8.We recommend that the Health Research Authority (HRA) should be provided with funding to establish a national audit programme of clinical trials transparency, including the publication of a single official list of which UK trials have published results and those which are due to but have not. In the first instance this should focus on providing information on whether any results have been published in an academic journal following global best practice, building on the automated methods already developed by others. We recognise that there are other dissemination routes for clinical trials results beyond academic journals that automated methods might not capture. Where alternative means have been used to publish information the HRA can use this process to prompt lead investigators to provide details of where the results have been posted so that the entry for that trial can be corrected as necessary. (Paragraph 36)

9.We are disappointed that the HRA does not believe it can secure funding for a more comprehensive form of audit and does not see this as a priority. Even if the cost of fully assessing reported trial outcomes against the original specification in the application for ethical approval amounts to £2.4m per year, as the HRA suggested in evidence to us, this is a small price to pay compared with the sums of money involved in policy decisions that draw on clinical trials evidence, such as the £424m the Government spent on stockpiling Tamiflu without full access to evidence on its effectiveness. We recommend that the HRA undertake further work to determine an accurate figure for the cost of such an audit and prepare a funding proposal for the Government to consider. The cost should be weighed against the potential public savings made by tackling mis-reporting, in terms of reduced ‘research wastage’ and the scope for better procurement decisions. If this model is pursued, then the results should be published trial-by-trial rather than simply at the summary level. (Paragraph 37)

10.The Government should direct the HRA to publish information on trials that have received ethical approval but are not registered in a publicly-accessible register, on a trial-by-trial basis. (Paragraph 38)

11.The HRA appears to be reluctant to enforce its rules, or to make previous compliance with transparency legislation a pre-requisite for ethical approval of future trials. As a result, there are currently no sanctions imposed on sponsors or investigators who fail to comply with HRA rules, or even on those who fail to respond to the HRA when their non-compliance is queried. Echoing our predecessor Committee’s conclusions from 2013, we recommend that the HRA introduce a system of sanctions to drive improvements in clinical trials transparency, such as withdrawing favourable ethical opinion or preventing further trials from taking place. The Government should consult specifically on whether to provide the HRA with the statutory power to fine sponsors for non-compliance. (Paragraph 41)

12.The Health Research Authority has been explicitly responsible for “promoting research transparency” as part of its statutory objectives since 2014, but this does not appear to have brought about significant change in this area over the last four years. We recommend that the Government ask the HRA to publish, by December 2019, a detailed strategy for achieving full clinical trials transparency, with a clear deadline and milestones for achieving this. We also recommend that the Government write to the HRA to clarify that it should interpret the Care Act 2014 to mean that it is responsible for driving improvements in clinical trials transparency—as opposed to ‘promoting’ transparency as a virtue. The performance of the HRA should then be explicitly measured on this basis through its annual report, including through specific measurable performance indicators. If further financial resource for the HRA is required to tackle clinical trials transparency then the Government should consider favourably such requests. (Paragraph 45)

13.We recommend that the Government consult further with the HRA on whether it is capable of delivering the improvements to clinical trials transparency needed within its current remit. If necessary its remit should be extended through introducing legislation which amends the provisions of the Care Act 2014. (Paragraph 46)

Published: 30 October 2018