The UK Health Research Authority yet again seems poised to let patients down.
A document that appeared online in December suggests that the UK's medical research ethics regulator is determined to let clinical trial sponsors off the hook for failing to adhere to its own rules on clinical trial registration and reporting - defying the wishes of patients, parliament, and the wider public.
There is overwhelming evidence that hidden medical evidence harms patients and undermines public health. The Health Research Authority's (HRA) mission is ostensibly to “protect and promote the interests of patients and the public in health and social care research.” However, the regulatory agency appears to have forgotten whose interests it was created to protect and promote.
The document summarises the results of HRA’s 2019 #MakeItPublic consultation on how to improve clinical trial registration and reporting. In its report, the HRA disaggregates responses according to the type of respondents, allowing us to distinguish between patient and industry perspectives.
Here is what patients, trial participants and members of the public told the HRA:
92% wanted the HRA to ‘take into consideration’ past transparency performance when reviewing new studies for approval
81% supported the publication of an annual ‘transparency league table’ highlighting studies whose results are overdue
57% supported fining trial sponsors with ‘very poor transparency compliance rates’ (only 26% opposed this approach)
Having been told what patients and the public want, the HRA then applies a staggering amount of spin to invalidate their views.
Below some excerpts from the document.
HRA spin: “Whilst there was a strong feeling that the use of fines would ‘focus minds’ many cited a lack of evidence that fines would promote compliance. It was felt that they would not address the current barriers to compliance and, instead, would damage good will, alienate the research community, and potentially make the UK a less attractive place to do research… and make the HRA the ‘bad guys’.”
Fact: Voluntary compliance has not worked in the past, and will not work in the future. The HRA should focus on its mission of protecting patient interests, rather than on making itself popular with those it is supposed to regulate. Note that a recent policy paper by the Association of the British Pharmaceutical Industry identifies “high standards for transparency” as one of seven key factors required to maintain the UK’s position as an "attractive destination for global investment in the sector".
HRA spin: “The need for cultural change was frequently emphasised in workshops. This would support raising awareness of the social and moral responsibility to report findings, ending the current bias for only reporting positive results, [and] reporting research findings in ways other than peer-reviewed journals.”
Fact: ‘Cultural change’ has been discussed since the 1980s. Researchers did not have to wait for ‘cultural change’ before legislation was adopted against sexual discrimination within research institutions, so why should patients have to wait for another generation or two? World Health Organisation best practices clearly state that the results of all clinical trials should be uploaded onto trial registries within 12 months of trial completion, for the simple reason that this is the only way to ensure that the results of all trials are reported in a timely fashion. The HRA’s thinking is outdated.
HRA spin: “The transparency vison set out by the HRA and the associated cultural change required can only be delivered if all relevant stakeholders cooperate. Everyone involved in research whether funders, researchers, sponsors, coordinators or publishers has a part to play in promoting transparency and openness in health and social care research.”
Fact: The HRA is the body responsible for promoting transparency in research in the UK. Passing the buck to other actors (many of which are located abroad) is inappropriate.
HRA spin: “[I]t was suggested that issues around copyright mean that researchers may be unable to report their results until after the publication of their research.”
Fact: Making trial results public on registries has never led to a journal subsequently rejecting a paper for publication. The HRA should help to debunk this harmful urban legend, not perpetuate it.
HRA spin: We have already decided to make the following changes… Giving sponsors and researchers feedback on their transparency performance… Sharing transparency performance data with funders, other regulators and registries.”
Fact: Sharing data behind closed doors does not constitute transparency. This data should be visible to everyone, including trial participants, patients, and taxpayers (who currently foot the bill for hundreds of millions of pounds’ in wasted medical research funding).
HRA spin: “[S]ome cautioned that the publication of [league] tables could deter patients from taking part in research at certain institutions and thus should only be visible to professionals… [T]here may be valid reasons for non-compliance… [I]nterpretation of the information would be dependent on who is reading the league table, particularly in the absence of any information to place the data in context.”
Fact: This is beyond parody.
HRA spin: “Several considerations were raised regarding the introduction of any financial penalties, notably that reasons for non-compliance would need to be taken into account... Others suggested that charities should be exempt.”
Fact: Trial participant and patient interests are violated whenever a sponsor fails to make trial results public, regardless of which sponsor breaks the rules and for what reasons. Many UK trial sponsors have already achieved full compliance with reporting rules - patients volunteering to participate in trials can and should expect all institutions conducting medical research with humans to do the same.
HRA spin: “It was noted that fines may not be appropriate for non-commercial organisations and would have little impact on commercial organisations for whom withholding approval would carry more weight.”
Fact: Fines could be coupled with withholding approval. Note that under United States law, trial sponsors who fail to make the results of certain types of clinical trials public face a fine of over $11,000 for every day that the results are late.
The Health Research Authority seems to believe that even though most patients support introducing sanctions with teeth on pharmaceutical companies and universities that break long-standing transparency rules, it would somehow be inappropriate to enforce those rules.
This not only lets patients down, but also shows that the UK’s ethics regulator is years behind the times. In response to the HRA’s own survey, around 60% of research managers, researchers and Contract Research Organisations supported the introduction of a ‘transparency league table’, and 30% of them even supported the introduction of fines. Times they are a’changin' indeed, at least among those the HRA regulates.
The reason for this is simple: Most large pharmaceutical companies have achieved near-perfect compliance with European and American clinical trial disclosure regulations, and many major non-commercial trial sponsors in the UK are catching up fast. Well-run institutions with strong clinical trial management systems have nothing to fear from sanctions that will only affect those that break the rules.
Oxford scholar and AllTrials campaign co-founder Dr Ben Goldacre commented in a Tweet that:
The HRA has long tried to undermine accountability measures
First, the HRA refused to release information on its legal powers to impose sanctions, thereby precluding informed public debate.
Then, according to meeting minutes released by the HRA, an advisory group it set up "felt" that “discussing firmer [sic] sanctions was premature”. The AllTrials campaign, which had participated in the advisory group session in question, later made clear that it actually strongly supports sanctions.
A consultation document issued by the HRA in 2019 stated that before imposing sanctions, the HRA would perform yet another round of consultations.
Till Bruckner, founder of TranspariMED, said:
"The Health Research Authority is tasked with protecting patient interests and promoting transparency in medical research. However, the Health Research Authority has consistently ignored calls by parliament, patients and the public to impose sanctions with teeth on trial sponsors who betray clinical trial participants' trust and harm patient interests. Experience shows that voluntary compliance and talk of 'cultural change' will not solve the problem.
"UK patients and taxpayers deserve better. The Science and Technology Committee of the House of Commons should resume its 2018-2019 enquiry into Clinical Trial Transparency and keep a close eye on the forthcoming HRA Transparency Strategy to ensure that patient interests are not sidelined.
"The year 2020 presents a unique policy window. Either we continue with impunity as usual, or we fix this problem once and for all."
IMPORTANT: TranspariMED opposes imposing backward-looking punitive sanctions on individual researchers.
Instead, TranspariMED advocates for the phased introduction of smart sanctions geared towards driving improvements in institutional performance. Sanctions should be effective, efficient, support consistent compliance against clear standards, and - crucially - not prevent or delay life-saving research.