Research integrity: clinical trials transparency Contents

Summary

Selective non-publication of the results of research distorts the published evidence base and is a threat to research integrity. In the case of clinical trials, non-publication of results means that information on the efficacy of new drugs or other medical interventions cannot be used. Falling short on ‘clinical trials transparency’ in this way presents risks to human health, contributes to research wastage and means that clinical decisions are made without access to all the available evidence.

A range of UK and EU rules and guidelines are now in force to improve clinical trials transparency, in terms of tackling non-registration, non-reporting and mis-reporting. However, despite these rules, around half of clinical trials are currently left unreported, clinical trial registration is not yet universal in the UK, and reported outcomes do not always align with the original study proposal.

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. 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.

The Health Research Authority (HRA) 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. The Government should 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. The performance of the HRA should then be explicitly measured on this basis through its annual report.

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. The HRA should be provided with funding to establish a national programme to audit 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 are disappointed that the HRA does not believe it can secure funding for a more comprehensive form of audit focusing on mis-reporting of trials 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. 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.

Meanwhile, the HRA appears to be reluctant to enforce its transparency 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. The HRA should 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, and the Government should consult specifically on whether to provide the HRA with the statutory power to fine sponsors for non-compliance.

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. 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.





Published: 30 October 2018