All trials past and present should be registered, and the full methods and the results reported
It is time all clinical trial results are reported. Results from around half of clinical trials have never been published. Information on what was done and what was found in these trials could be lost forever to doctors and researchers, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated. The contributions of the hundreds of thousands of patients who took part in those trials remain unused and unusable.
” I don’t think industry are concerned about patient confidentiality except in so far as they are concerned to avoid being sued for injuries in clinical trials. ”
There is a very informative and fascinating debate going on between Dr David Healy and Ben Goldacre regarding options, thoughts, strategies for better clinical trials access and transparency. Dr. David Healy posted “fucked” here and I posted a summary here. Dr Ben Goldacre responded here and here. I republished his reply here. Dr. David Healy then clarified here – see below – I only added few related links (in the original text response) with the purpose to bring more clarity and/or references to the readers.
Again let me invite you to read “fucked” post 22 comments – about clinical trial data access and pharmaceutical industry transparency.
” The first point to make is this post isn’t about AllTrials. AllTrials is a footnote. It’s about the dismay that many felt at EMA backsliding. It’s about how it was obvious that something like this was on the cards. Against this background uncritical endorsement of industry looked like a bad idea. There was a desperate need to stay awake. It looks like too many of us have been asleep. Ben offers an outline of the AllTrials strategy here. It’s helpful to have this. His accusation that these posts misrepresent campaigns, smear people, shout abuse, and hector from the sidelines looks like a description of posts by others elsewhere. With very few exceptions any comments to the various posts on this blog that in any way fail to support Ben or AllTrials have been deleted. The post repeated an alternate analysis – that the main thing industry wants to hide are adverse event data. In a post 18 months ago I outlined how to achieve this industry would in public deploy the issue of patient confidentiality as a main justification for hiding data. In this it seems to me they have been assisted by Iain Chalmers editorial with Patrick Vaillance and now by Ben. The historical evolution of the confidentiality issue is that the first informed consent forms said nothing about not showing your data to anyone else. Unnoticed industry have slipped in a “we will of course show your data to no-one clause”. At the EMA conference on data access in November 2012, I made two points. The second was that industry would assert the notion of their privacy rights – which they have done. The other was that no one signs to have their data sequestered. Afterwards, Iain Chalmers congratulated me on the point – I thought we were on the same page. Whether adverse event data is key or not, Peter Gotzsche through the European Ombudsman and Tom Jefferson and Peter Doshi through Tamiflu and RIAT seem to me to have done more in practical terms to move the issues forward than anyone else. It leaves me wondering why there is an endless call to celebrate Ben and not Peter or Tom. Some of us have been working the GSK system and can see what the pitfalls are. Even if not redacted, this is a system that will make it close to impossible to analyse CSRs properly. But if it’s not proclaimed by AllTrials first it seems like such insights are unwelcome. In several posts before the latest debacle I outlined how in my opinion there was a real chance that magnificent though he has been and clearly morally right, Peter Gotzsche’s efforts may do more harm than good. Even without taking GSK’s preposterous data access system into account, pushing for data adds to the undue premium being put on RCTs Twenty years ago the moral case for access was as strong and the risks consequent on failing were much less in that we were less hypnotized by RCTs than we are now. Far from responding shrilly, Peter Gotzsche recognized the risk and we have been collaborating ever more closely since. The issues are so complex we might all be making mistakes – the only people unwilling to concede this seem to be AllTrials. The push for data access remains morally compelling but there are other things that can be done that might be more effective. As the BBC program a week ago on Thalidomide, and previous posts here, make clear, industry fear a boycott more than anything else. It is the only thing they have ever responded to. At the moment the focus is on a bunch of bureaucrats in EMA, who aren’t there with a brief to protect us other than by regulating the wording of advertisements. The focus should be on doctors who treat patients. We could refuse to use drugs where there is no access to the data. It shouldn’t even take courage to do this. In my opinion, this is the call that’s needed now rather than a call to support more of what AllTrials have been doing. But who will lead such a call? Along with colleagues I put forward a softer version of a boycott – an AbbVie – which encouraged doctors and patients to use drugs but to report on the adverse events which would in fact make these chemicals better medicines. It would be difficult for government or anyone else to gainsay this win-win option in the way they might come out against the lose-lose of a boycott. There is a conflict of interest here. RxISK.org has a stake in this idea. It was set up before AllTrials to move ideas like this forward. I suspect those of us working on RxISK in the evenings and at weekends have been putting far more hours into the effort than the AllTrials team have. At the end of the day, I may well be wrong on this, but I personally think AllTrials have been naïve. I don’t think industry are concerned about patient confidentiality except in so far as they are concerned to avoid being sued for injuries in clinical trials. Recent decades have seen industry put Litigation Support Defences in place. As outlined a decade ago in Let Them Eat Prozac, putting a premium on clinical trials has been a key element in their litigation support strategy. Seen from this vantage point AllTrials offers Pharma a lot – all without the effort of having to conspire or fund a conspiracy. Playing straight into industry’s hands is a hazard for all of us. Good intentions aren’t enough to save us. I’d rest more comfortably if the key players in AllTrials had a track record in bringing adverse events to light or even a record of supporting those trying to do so – if they’d really antagonized industry good and proper. It’s not that partnership isn’t nice but perhaps after playing hard to get first. ”
The AllTrials campaign is really simple: it calls for all trials to be registered, with their full methods and results made publicly available. Where CSRs have been made, we call for those to be placed in the public domain.
Healy says we’ve created a situation where people are withholding CSRs: that’s simply absurd, this is precisely what we campaign against.
Healy says we’ve created a situation where CSRs are inappropriately redacted: that’s absurd, again, this is specifically what we campaign against.
Healy says we have created a situation where drug companies get to choose who has access to CSRs: again, that is ridiculous, this is exactly what we campaign against.
GSK have signed up to the AllTrials campaign: they join over a hundred patient groups, more than 75,000 members of the public, NICE, Wellcome, MRC, almost all academic and medical professional bodies in the UK, and a growing number around the world. When Bad Pharma came out, industry and others were able to pretend that information about clinical trials is no longer withheld. We’ve transformed that, triggered two select committees and put the policy issue on the map, created a coalition, unpicked a web of dangerous false reassurances by professional bodies, and made it impossible for industry to engage in glib denialism.
I’m delighted that GSK have signed up to AllTrials, along with all the other organisations. There are lots of problems in medicine. There lots of people and organisations who’ve done – and continue to do – things I think are harmful to public health. But where people do the right thing, I will applaud them for it. I genuinely think that’s the right thing to do. It doesn’t mean you’re part of an elaborate and complex conspiracy with people. It doesn’t mean you approve of everything they do at work and at home.
It’s easy, and attractive, to scream from the sidelines, and carry on screaming forever. It’s also possible to shout out clearly and succinctly about problems, try to set out and discuss clear solutions, floodlight the path forwards, and encourage people to go down it.
Lastly, and specifically, the issue of individual personal data. The AllTrials campaign doesn’t call for all the rich individual patient data from all trials to be simply posted publicly in the public domain: that poses too much of a privacy risk, because patients are identifiable in this data. This privacy risk isn’t as big as is claimed by some of those who seek to block transparency, but we decided that the issues around graded access control to IPD are too complex for a simple headline campaign, and we didn’t want to risk industry using the issues around protecting participants’ privacy as an excuse to derail discussion on the very important separate issue of access to methods and summary results. We were absolutely right: industry have repeatedly tried to pretend that AllTrials calls for individual trial participants’ personal data to be posted online, even though AllTrials is specifically focused on registration, methods, results, and CSRs. But as David Healy knows, most of the people involved in the AllTrials campaign, myself, Iain Chalmers and the BMJ included, are closely involved in pushing for greater transparency on IPD too. It is simply absurd to claim otherwise.
The comments section on this blog is clearly the worst place to say this, but it really is a big waste of everyone’s time to have to deal with the kind of misrepresentation and abuse that David Healy keeps posting. From past experience, I don’t believe that David will engage constructively with my taking the time to correct these repeated misrepresentations, and I honestly think that’s a shame. We’re all – most of us at any rate – trying to get things improved. Everyone’s time is short, and people run things like AllTrials in their spare time. If Healy has a better way to make things better, that’s great, he should crack on with it and get others behind him. If it involves misrepresenting campaigns, smearing people, shouting abuse, and hectoring from the sidelines, then I won’t be in.
As an addendum, three brief specifics, since time is short:
David Healy, above: “Consent processes in clinical trials were about telling you you were on a new drug that might be dangerous or might be involved in a marketing trial. Instead they have become a way for companies to justify hiding your data on the basis of a confidentiality clause they have slipped into the forms. Iain Chalmers, Ben Goldacre and AllTrials appear to have signed up to this.” – This is complete and utter fantasy. Neither I nor AllTrials have signed up to this. David Healy will be unable to provide any evidence to show that we have. Consent forms being used to justify withholding information is exactly what I’ve campaigned against.
David Healy, above: “That what would be put in place was a mechanism that gave the appearances of transparency but in fact would lock academics into agreeing with GSK and other companies as to what the outcomes of their trials have been.” – This is completely bizarre. AllTrials simply calls for all trials to be registered, with their full methods and results made freely publicly available, and CSRs where they’ve been created. It is impossible to argue that this “locks academics into agreeing with GSK and other companies as to what the outcomes of their trials have been”.
David Healy, above: “Rape is a loaded word these days”. It’s always been a loaded word, David. “
It’s impossible to have a drug with no side effects
Most medical research aims to discover more about health and to find new ways to treat or prevent diseases. Within this, the science of how to make drugs safer has received relatively little research funding and attention. This is despite the fact that side effects (known as adverse drug reactions) are both a big public health concern and a major barrier to the development of new medicines.
Hilda Bastian is cartoonist and writer at StatisticallyFunny blog
” It’s the Catch-22 of clinical trials: to protect pregnant women and children from the risks of untested drugs….we don’t test drugs adequately for them.
In the last few decades, we’ve been more concerned about the harms of research than of inadequately tested treatments for everyone, in fact. But for “vulnerable populations,” like pregnant women and children, the default was to exclude them. ”
Hilda Bastian is Editor etc at PubMed Health, blogger at Scientific American, commenting on the science of unbiased health research with cartoons at Statistically funny.
Clinical trials: clearer rules, better protection for patients
Exciting news from Brussels this morning – law that would mean researchers running a clinical trial in Europe have to register the trial before it begins and to publish summary results within a year of its end is a step closer. The committee of representatives from every EU member state government has agreed with the text of the Clinical Trials Regulation proposed by MEPs led by Glenis Willmott. This agreement now has to be formally ratified by the European Parliament and the Council of Ministers (probably in early 2014) but today’s provisional agreement is a fantastic result at a very important stage of negotiation and is down to the hard work of the MEPs and thanks to your input. The legislation will need final approval from the European Parliament.
The proposals agreed today include:
A publicly accessible EU database, set up and run by European Medicines Agency, containing:
A register of all trials carried out in the EU
A summary of results for all trials, uploaded 1 year after the end of the trial at the latest
As well as a summary understandable for a layperson
Clinical Study Reports for all trials used in a marketing authorisation request, whether it is approved, rejected or withdrawn
A statement that Clinical Study Reports should, in general, not be considered commercially confidential
Fines to be imposed by Member States for non-compliance with the transparency requirements
A requirement for all trials to be registered or published in order to be used to back up a new clinical trial authorisation (will encourage the retrospective registering/publishing of old trials)
The Clinical Trial Master File retained for at least 25 years.
Glenis Willmott MEP said: “For too long, unflattering studies on new medicines have gone undisclosed. Around half of all trials are never published, usually those with negative or disappointing results. It is vital we know about negative outcomes, otherwise trials can be conducted repeatedly before it becomes public knowledge they are ineffective, or even dangerous.
We are determined to finalise this before the European elections in May. This legislation will set the global gold standard for transparency in clinical trials, and I call on all EU governments to support the agreement”.
Síle Lane, Director of Campaigns, Sense About Science said: “We are very pleased to hear that EU governments have agreed the draft Clinical Trials Regulation which contains proposals that would mean all clinical trials done in Europe will have to be registered and results reported. Well done to Glenis Willmott MEP who has worked very hard to get this agreement. We know Glenis was helped enormously by the hundreds of individuals and organisations who got involved and told MEPs and Ministers their reasons why transparency is vital. Now is the time for companies and academics to listen to all these voices and commit to registering and reporting results from trials done in the past too. There’s no excuse for not publishing results but a huge public health benefit to having a complete picture of what was found in trials conducted on treatments currently available to patients.”
Ben Goldacre, co-founder of AllTrials said: ”This is great news, and patients around the world should be grateful for the fantastic work that has been done on this by politicians in Europe. However we must remember that it only covers new trials, starting from 2014. The vast majority of medicines prescribed today came on the market 5, 10, or 20 years ago. This new law will do nothing to improve the evidence base for those treatments. We still cannot get all the results of all the trials on even the simplest everyday treatments, the antidepressants, the statins, the blood pressure treatments, and more. Those are the drugs that doctors are using right now, and will continue to use for at least a generation. Notably, the law would also do nothing to ensure that researchers and doctors can access all the results of trials on controversial drugs such as Tamiflu.
The campaign for access to trial results began over 20 years ago. Throughout the 1990s and 2000s, industry promised that everything had changed, and that everything had become more transparent. We now know that this wasn’t true. It is unacceptable that results from the 1990s and 2000s should continue to be withheld from doctors, researchers and patients. It is unacceptable to say that these trial results were allowed to somehow continue “disappearing”, even while some of the industry was publicly promising greater transparency. With their reckless belief that they could stonewall forever, too much of the industry have stored up a big problem for themselves, and for patients. We need the results of all trials, of all uses, of all the treatments we prescribe today. Without that, we cannot practice medicine safely and effectively.”
Mark Wilson, CEO, Cochrane Collaboration said: “Cochrane is delighted with today’s agreement on clinical trials transparency; a victory for patients, practitioners and policy-makers across Europe, and a clear and compelling message to decision-makers worldwide. The ratification of the agreement in 2014 will be a key milestone on the AllTrials journey to ‘all results reported’ becoming a reality.”
How withholding clinical trials degrades the evidence base
Science & the City interviews Dr Ben Goldacre – author of Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients – who discusses the pervasive bias in reporting clinical trials of medications.
Dr Ben Goldacre calls for all trials to be registered and for all trial results to be reported. Otherwise, he says, doctors, researchers, and patients are prevented from making discerning decisions about treatments and the field of evidence-based medicine is pointlessly hobbled.