When politicians talk clinical trials: Nine takeaways from the recent UK parliamentary enquiry
Many scientists secretly believe that politicians are too daft to understand the complexities and challenges of doing science well.
Last week, UK parliamentarians proved them wrong when they quizzed universities and regulators about their progress on making more clinical trial results public.
Below nine takeaways from the session.
Back story: In 2018, politicians were dismayed to learn that most clinical trials conducted by UK universities were missing results on the European trial registry, in violation of EU transparency rules. During an earlier enquiry in 2013, the very same parliamentary committee had produced a set of excellent recommendations to fix the problem, but these recommendations had been ignored, and nothing much had changed. In early 2019, the chair of the committee then wrote to all institutions with missing results and told them that they would be asked to explain themselves during a follow-on session if they had not fixed the problem by the end of summer. That session took place last week.
Takeaway 1: Politicians expect all clinical trials to report their results – without exceptions.
Chair: “The reason we are supposed to be reporting all clinical trials is that not doing so lacks accountability for public money, puts public health at risk and distorts the research record. The bottom line is the need to improve to get 100% reporting on all these registers. Whether it is for drug trials or anything else, presumably the argument is the same: it is paramount.”
Takeway 2: Political solutions to scientific problems can work extremely well.
The 2018-2019 enquiry has already led to major improvements: four times as many trial results were uploaded by UK universities in 2019 than during the four previous years combined, the national medicines regulator MHRA has updated registry entries, and the national ethics regulator (the Health Research Authority) is drawing up a transparency strategy.
This month, King’s College London became the first major medical research university in Europe to have posted 100% of due trial results onto the registry, and other UK universities are close on its heels. Meanwhile, in other European countries (excepting Ireland), universities continue to perform badly.
Takeway 3: Most universities were not even aware they had a problem until politicians raised the alarm.
Sile Lane, AllTrials campaign: “At the institution level, the problem was that, broadly, there was no one person at an institution who was taking responsibility and control for the reporting rates and record of their institution… There were all these things that nobody in the institution was aware of until the letters you sent, when you flagged all of it up to them, suddenly made people aware of them. There wasn’t anybody there in control.”
Takeway 4: There is nothing like a letter from politician to get academics to take a problem seriously.
Professor: “When I saw that letter [from parliament], I thought, ‘Oh, my goodness, look at that.’ There is nothing like being on 0% to focus people’s attention. The next response was to get my team together and say, ‘What are we going to do to sort this out?’”
Takeway 5: Some academics think academics should enjoy impunity. Politicians and the public think this is “a ridiculous argument”.
Professor: “I understand why there might be a feeling that some kind of sanction is required. Maybe it is true that it should be in some cases. My experience of dealing with researchers is that, if you try to push them around, they will just say, ‘I’m not doing this any more.’”
Chair: “Well, they shouldn’t have public money.”
Professor: “I agree, but they will.”
Chair: “That is a ridiculous argument, surely. This is public money, and we have already had evidence that human health is put at risk by non-reporting. I think there is a culture that hitherto has not regarded this as serious enough. Performance against a legal requirement to report is woeful. What do you expect Parliament to conclude, other than that something needs to change? The idea of gentle encouragement seems to me not to have worked hitherto.”
Sile Lane, AllTrials: “It flummoxes people who have been part of clinical trials and take and use medicines all the time that there are medicine regulators who are purportedly about safeguarding public health and safety but do not seem to be bothered about bringing in sanctions for those who break the rules. It flummoxes people that no one takes responsibility.”
Takeaway 6: The Health Research Authority is still opposing sanctions with teeth.
HRA: “In terms of regulation, we want to be what would be called right-touch regulation, proportionate. Start with making it easy, educating people, and making our expectations clearer. The next stage would be telling people what we are going to put in the public domain, and then perhaps league tables, moving on to telling people that future approval would be contingent on
past performance.”
Chair: “Are you suggesting that this is a two or three-year programme?”
HRA: “It is a regulatory ladder that any regulator would use. They would start with trying to change behaviour and sharing good practice.”
Chair: “You have had that duty in the HRA for some time. Behaviour has improved, but it has not changed enough. It sounds to me as if you are saying you are resistant to deciding that there should be some consequences for total flouting of the rules.”
HRA: “Financial penalties require legislation, which does not seem very likely in the present climate. Why go for something that is undoable? Why not start with the low-hanging fruit, the things we can get on with quite quickly?”
Note: Achieving 100% clinical trial registration and reporting rates is achievable in the UK without changing any laws.
Takeaway 7: Uploading the results of clinical trials onto registries is excessively complex.
Professor 1: “The design of some of those studies is very complicated. To be able to lift some of those into the European database is incredibly difficult.”
Professor 2: “[The European trial registry EudraCT] is much more complicated than it needs to be. Battling with that is a worry because, moving forward, I see us dealing with a whole load of different databases and that becoming even more complicated and confused.”
Takeaway 8: In future, journals may require results to be posted onto trial registries
Fiona Godlee, BMJ: “The International Committee of Medical Journal Editors [ICMJE] is very clear that the posting of summary results is not considered prior publication, and that is very clearly stated in several parts of the ICMJE guidelines. I will take back to my colleagues on the ICMJE whether we could make it not a sanction as such, but a requirement in submitting a clinical trial, that the summary data are already on the database. I cannot see a reason why we should not do that.”
Takeaway 9: Parliament has to remain engaged.
Due to the upcoming UK election, the committee has now ceased its work, but in an open letter, the chair has encouraged the next committee to resume the enquiry, noting that:
“There is a risk of this [positive momentum] diminishing if scrutiny of relevant bodies and organisations is not maintained. This is particularly crucial as the Health Research Authority’s new Research Transparency Strategy is expected in 2020 and will require further scrutiny from the Committee.”
Cochrane calls for "coordinated action on clinical trial transparency in other countries" too
Commenting on progress in the UK, Cochrane Editor in Chief, Dr Karla Soares-Weiser, said:
“At Cochrane, we rely on the availability of clinical trial data to produce high-quality and relevant systematic reviews. We welcome this effort among UK-based non-commercial clinical trial sponsors to improve reporting rates – though there is still clearly much more to be done for all sponsors to meet their full ethical obligations and achieve 100% compliance.
"Given that this issue goes far beyond the UK, we think it’s time for similar coordinated action on clinical trial transparency in other countries. We encourage researchers, healthcare professionals, patients and members of the public to get involved and to hold clinical trial sponsors to account on their reporting rates.”
The full transcript of the parliamentary session is online and makes for fascinating reading. Some of the passages cited above were edited for brevity and clarity. A letter the committee wrote to the European Medicines Agency about its efforts to make trial reporting easier is worth reading. A collection of letters that universities and NHS Trusts wrote to the committee explaining their successes and challenges in reporting trial results is also online.
Universities that want to improve their clinical trial reporting can find a collection of transparency tools, tips and tricks on the TranspariMED website.