This year the Health Research Authority (HRA) started submitting to the ISRCTN registry all UK clinical trials entered for combined review by the HRA and the Medicines and Healthcare products Regulatory Agency (MHRA). It is one of a series of measures announced in the HRA’s widely welcomed transparency strategy Make It Public. Read on to find out more about the history behind the HRA’s partnership with ISRCTN and the worldwide movement to promote scientific transparency.
The ISRCTN registry is inviting feedback on the way it helps its users achieve complete and understandable registration and reporting of clinical trials. The rich information in the registry can be useful to anyone interested in evidence underpinning health care. It is not just for the nurses, doctors and scientists who run clinical trials and related health research.
Why ask for feedback now? Because the HRA and ISRCTN will progressively ensure all UK clinical trials are registered with ISRCTN, and hence in the World Health Organization System, at no cost to registrants. Drawing information from the UK’s combined review system will ensure registration is completed immediately on approval and before recruitment begins.
For years, too many trials have gone unreported. Since 2021, the HRA has begun requiring a summary report one year after a UK clinical trial ends. US and EU law require public registration and timely reporting of trials. The USA now enforces its law on reporting results. Registration with ISRCTN complies with one of the key transparency provisions of the EU’s law on clinical trials. Now that Regulation 536/2014 is coming into force, EU states will have to penalise non-compliance, and the EU will use a new Clinical Trials Information System.
The UK is consulting on changes in the law regulating clinical trials, now that it has left the EU. To embed research transparency in the regulation of clinical trials, it proposes legislating for several transparency provisions, policies and processes in the HRA’s strategy, including reporting. It also proposes to require the involvement of people with relevant lived experience in the design, management, conduct and dissemination of a trial. Let the MHRA know your views by 14 March.
Why does this matter? Because under-reporting does not just limit and distort the evidence available for decisions about new and existing treatments. Clinical research depends on the commitment of everyone who takes part. Completing clinical trials but not reporting them can undermine everyone’s willingness to support new research. It also wastes the time and skills of the many people who help to set up and run a trial, and all the supplies and other research resources the funding paid for. All are in short supply. My article on reproducibility and research integrity for Times Higher Education argued that one lesson from the pandemic might be to do less, but better-planned, research.
In the turmoil of the last few years you could be forgiven for missing previous milestones on the way to complete reporting of clinical research. In 2019, the British National Institute for Health Research (NIHR) launched its policy on registration and disclosure. This policy made good on a commitment that major funders of health research made at the World Health Organization in 2017. A joint statement promised that each of these funders would publish a policy to implement the transparent registration and reporting agreed in a WHO declaration reflecting the World Medical Association's Declaration of Helsinki.
The NIHR’s policy laid out the practicalities of prospective registration of UK clinical trials, data sharing, and the timely disclosure of results. The ISRCTN registry sends information about active trials to the NIHR’s website Be Part of Research, which helps people find studies they might want to take part in. As the UK’s primary registry in the WHO System, ISRCTN is the NIHR’s preferred registry. By publishing its transparency policy, the NIHR put its weight behind a growing international movement.
Of the other co-signatories in 2017, the Wellcome Trust has a similar policy, as does the Medical Research Council. The Bill and Melinda Gates Foundation was a pioneer in open access. What about Europe? For France, the Inserm was a co-signatory. It updated its transparency policy in 2021. The European and Developing Countries Clinical Trials Partnership published its policy in 2018, and the Coalition for Epidemic Preparedness Innovations has done so too. The German Federal Government too has terms of grant like the WHO declaration.
Is your favourite research funder keeping up? How about your favourite university or hospital? If you can’t easily find its registration, data or reporting policies, keep asking. They might be deep in an annex to the conditions of grant, or five clicks down in an unexpected part of its website. This won't do. Trialists, their sponsors, funders and the public all need to know from the outset what is expected of them. Then research institutions and funders can plan for resources to keep the public record accurate, and ensure they finish the job with competent reporting and feedback to participants. None of this should be an afterthought or a casualty of poor preparation.
The growing consensus on transparency builds on a 20-year collaboration, coordinated by the WHO, around an international network of clinical trial registries, with a single framework of standards, exchanging information through a portal. The WHO System shifts the focus towards keeping the public record complete and accurate and making reports of findings and publications readily accessible. There are seventeen primary registries. Between them and others contributing data, they give open access via the WHO portal to standard records describing well over 650,000 studies.
ISRCTN was one of the founders of the WHO System. It is an independent international research registry which has recorded over 11,600 studies in the UK since 2000, and some 10,000 studies in other countries. The world’s largest registry is the US government’s ClinicalTrials.gov. It contributes data to the portal but is not a WHO primary registry. It has registered 400,000 studies, over 60% them outside the USA. 21,000 of the studies on the US registry are from the UK. ClinicalTrials.gov operates under US laws which allow for a fine for breaking the rules on registering and reporting – but the penalties don’t apply to studies outside US jurisdiction. The UK does not fine institutions for failing to report their trials.
A report in 2018 from the British Parliament’s Science and Technology Committee criticised universities and NHS research centres – with some honourable exceptions – for their poor record in ensuring disclosure of findings and data from studies they had sponsored. The Committee recommended the HRA should take action against institutions which do not register studies or report findings promptly. For years, ethics committees have accepted assurances about registration, reporting and feedback to participants. But these commitments were widely ignored. In 2020, the HRA published its transparency strategy. Here is its first annual report.
How is the ISRCTN registry helping research teams, their sponsors and funders to meet their legal and ethical obligations? Since 2016, the registry has prompted research teams to do better by reminding them about milestones when they should update the record on the registry. ISRCTN sends reminders at various stages when the record suggests action has been missed.
|Reminders to keep ISRCTN up to date
The current ISRCTN reminders are:
The ISRCTN registry has aligned its approach to licensing with CC-BY. It encourages unrestricted use of metadata derived from study records. The team at the registry have been working to make the registration, updating and reporting processes easy to follow, and to improve the search facility so that it is easier to find out the status of studies and whether findings are available.
How can you help? The advanced search on ISRCTN helps you find which studies funded by your favourite charity have ended, and how many have reported a publication to ISRCTN. If there is no publication, you should expect to see a summary of basic results 12 months after completion.
Of course, you will find some trials reported “stopped” for valid reasons - because of recruitment, funding, or other problems. But what about complete but unreported studies? To keep faith with everyone who consented to take part in them, at least a summary of basic results should appear on a registry where anyone using the international network of clinical trial registries can find it.
Try searching for studies funded by your favourite research charity, or for studies sponsored by your favourite hospital or university. Do you think they can be happy with the reporting from the trials they were responsible for? Could you defend it to the people who took part? If not, please ask those responsible how they plan to improve.
Search for clinical trials that interest you:
We invite practical suggestions to make the ISRCTN registry easier to use – whether for research teams, for sponsors, for funders, or for anyone who cares about the public interest in transparent and productive science.
Please send your feedback to firstname.lastname@example.org.
- The ISRCTN registry of health research is managed and published by BMC on behalf of ISRCTN, a not-for-profit company registered in the United Kingdom.
- The registry is funded from income for registering studies, including a contract for the free registration of UK clinical trials.
- It is independent of government, industry, and research institutions.