UK shuts down all ‘unviable’ clinical trials
The UK is asking research funders and sponsors to wind down clinical trials that have little chance of being completed to free up resources for more promising research projects.
UPDATE 03 June: Information from NIHR website and additional links added, see further below.
UPDATE 17 June: The BMJ reports on mixed reactions from UK staekholders.
The uncoordinated proliferation internationally of clinical trials during the Covid pandemic has thrown a harsh spotlight on research waste in medicine. Most Covid drug trials conducted outside the UK were doomed to irrelevance before they even started because they were weakly designed, underpowered, and/or needlessly duplicated other research.
These flawed trials actively undermined the search for effective treatments because they siphoned off limited resources – including healthcare staff and potential trial participants – from more promising studies.
UK shuts down unviable trials
The UK’s Health Research Authority is now calling for the “closure of studies that are not viable”:
“The NHS [National Health Service] is still struggling for capacity. The research community has come together to review the full research portfolio to make sure that precious NHS resources are focussed on studies that can be completed.”
“Sponsors and funders have been asked to review their study portfolios and make changes to any which are struggling to deliver (for example, studies which are not meeting recruitment targets, or studies where the delivery plan is not practical due to the availability of staff).”
“Giving as many studies as possible the chance of completing and generating evidence will require closure of studies that are not viable.”
Trial portfolios under review
In late March, the UK Department of Health and Social Care had sent a letter to UK funders and trial sponsors asking them “to review their portfolios now to take firm action on studies that are struggling to deliver” due to recruitment challenges, resource constraints, or “the scientific question no longer being relevant”.
The letter states that:
“We have asked the NIHR Clinical Research Network (CRN) to identify studies that are behind their targets and potentially ‘at risk’ of closure to recruitment or set-up based on the principles outlined above.”
“NIHR CRN is currently reviewing the integrity of the data on study recruitment to ensure that it reflects the current position.”
“Funders and sponsors are asked to support this process by providing accurate, up-to-date data and to respond promptly to CRN requests on data integrity. This will enable lists of these studies to be shared with funders and sponsors in April.”
“[W]e also ask that NHS sites provide sponsors with realistic assessments of whether they can deliver a study to meet the recruitment targets and timelines indicated. NHS sites are asked not to accept new studies or continue set-up activities if they realistically do not have the capacity to deliver to time and target. We plan to incorporate a new ‘deliverability’ requirement as part of the eligibility criteria for NIHR CRN portfolio adoption.”
“[W]e shall seek to move to nationally mandated action if substantial improvements in study delivery cannot be achieved.”
NIHR explains rationale and process
The National Institute for Health Research has explained that:
“The capacity of the NHS to support research delivery remains under continued pressure from workload and workforce issues, as well as the need to reduce the elective backlog. Limited capacity and resource means that some studies have struggled in the current environment and have little chance of meeting their research endpoints and objectives. For others, the reduced resource and capacity means that study delivery within acceptable timescales is threatened.”
“It is essential that the research system focuses on the studies that can be delivered with the capacity and resource available, whilst recognising there are some studies (e.g. in rare diseases) for which recruitment is expected to be less regular.”
“The programme is led by DHSC, with input from an advisory group including representatives from industry, medical research charities, NHS Research and Development, research delivery workforce representatives across NHS settings, patient and public representatives, medical Royal Colleges, universities, the Medical Research Council and NHS regions across the UK.”
“NIHR is collating the data provided by funders and sponsors, to identify lists of studies that meet certain criteria indicating a study may be suitable for review and action.”
“This will be shared with funders and sponsors, who can then take appropriate steps. This could include closure in line with HRA guidance, or provision of more up-to-date data, should currently-listed data be inaccurate. Slow recruitment due to a study serving the needs of a rare disease will also be taken into consideration. Funders and sponsors are expected to work with and involve study participants, their patient communities and other stakeholders throughout the review process.”
The NIHR notes that these activities align with the NIHR document Saving and Improving Lives: the future of UK clinical research delivery and points to the website for the UK Clinical Research Recovery, Resilience and Growth programme for further information.
Mixed reactions from UK researchers
Simon Kolstoe, an academic who chairs a UK ethics committee and who has long studied research waste, told TranspariMED that:
“There is about to be a mass enforced culling of unviable studies just to prevent continuing waste.”
He added that trials not running to completion, and thus not having anything to publish, may be an even bigger source of research waste than clinical trials that complete but then fail to make their results public.
However, some experts have criticised the way the measure is being implemented. Nikola Sprigg, a professor of stroke medicine at the University of Nottingham, told the Guardian that:
“It is a good idea in principle, but the process is taking so long that it’s leaving people in limbo, and causing extra delays.”
“Often, some of the most important trials are the hardest ones to do. I think there needs to be some kind of process to make sure really important questions, or potentially beneficial treatments aren’t discarded inappropriately.”
UK cull has global implications
The UK’s move is likely to be watched closely by regulators and funders worldwide.
The UK was the driving force behind a recent World Health Assembly resolution that calls on research funders worldwide to “[prevent] underpowered, poorly-designed clinical trials.”
The country prevented Covid research chaos by carefully coordinating clinical research and focusing all resources on a small number of clinical trials, including the widely lauded RECOVERY trial. As a result, the UK – with just one percent of the world’s population – arguably produced more clinically relevant evidence on repurposed Covid drugs than all other countries combined.
The Health Research Authority’s latest move appears to form part of an effort to apply the lessons of Covid across the country’s entire clinical trials landscape.
While researchers have been warning of rampant research waste in clinical trials for decades – according to one estimate, medical research worth $170 billion is wasted every year – the issue has only gained high-level attention in the wake of the global Covid drug research fiasco.
While regulators worldwide are now acutely aware of the problem, it is often unclear who is responsible for stopping weak trials from going ahead. In the past, regulators, funders, ethics committees and individual researchers have passed the buck among themselves.
A copy of the letter sent out by the UK Department of Health and Social Care can be downloaded below.