All-Trials – not much to argue with but much to discuss

In this article, Nick Broughton shares his thoughts on the clinical trial data transparency campaign, AllTrials, and considers the ethical justification for data transparency.

A recap

Last year, you may or may not recall, this correspondent wrote, a critical review of Bad Pharma by Ben Goldacre. The basis of the criticism was that, like many external commentaries on pharma, it used examples of bad behaviour by pharma (and in particular the lack of full transparency of clinical trial data) to imply a moral judgement on the industry as a whole i.e. that it was ‘bad’. Occasional text within saying there are good people in pharma or post-hoc claims that the title refers to the bad things within pharma, rather than to pharma as a whole, did not for me correct what I saw as the injustice of a book called and advertised as ‘Bad Pharma – How drug companies mislead doctors and harm patients.’

Dr Goldacre in response took my criticism as an attack on the central tenet of his book regarding the lack of availability of trial data and a minor written spat ensued. You are welcome to read it here: Bad Pharma by Dr Ben Goldacre; the mechanics of a mediocre argument but when you do, read it closely. One I thing I didn’t say is that under-reporting of trial data by pharma hasn’t happened, isn’t happening or won’t happen in the future.

Reflecting on the debate, I then wrote a second piece which received no attention whatsoever probably as I couldn’t craft a reason to criticise Dr Goldacre. Again you are welcome to read it here: Slow e-motion; big things and manners in internet health debates and this article follows on from that. The nub was that argumentative types who engage in social media debate it seems have an inbuilt tendency to read things they don’t like into each other’s arguments. I see the title ‘Bad Pharma‘ on the cover of a book with some reasonable criticisms as giving a very lopsided though populist impression of the industry as a whole and it makes me angry. Dr Goldacre reads a criticism of his book as a criticism of its main argument and it makes him angry. It’s time I proposed for a few more manners in our social media debates whereby we think more closely about our opponent’s perspective to avoid the inertia polarisation brings. So with that in mind…

Why I signed up to All Trials and why I didn’t

Let one thing be clear; I didn’t sign up to it as a result of badgering by some of the wearisome crowd who have picked up on data transparency as another stick with which to beat pharma. In fact rather the opposite; for a couple of months I rejected the idea out-of-hand because of the brow beaters. Ultimately for me as an individual (though not perhaps for companies as I will explain) this was not a sound basis on which to act. Just what is there to argue about in the mission statements of the All Trials group? Well in some ways nothing and perhaps in other ways something. Let me explain.

 

“Important benefit-risk information is lost when study results fail to see the light of day…”

 

The case for publishing all trial results has tended to revolve around the need to understand the true nature of an intervention (usually a medicine) which can only be understood if all results pertaining to it are available. Important benefit-risk information is lost when study results fail to see the light of day and thus the ethical case in favour of complete transparency rests very heavily on our moral obligation to minimise harm to others. Future patients may not benefit or worse be harmed by the use of medicines if that use is as a result of a biased evidence base. The comments on the All Trials website from those who have signed up strongly reflect this theme coupled a sense of outrage that this harm is being perpetrated by ‘big pharma’ for profit.

Not bad so much as human flaw

Harming people is bad, harming people for your own gain is worse. This might be why academic researchers (who fail to publish with the same alacrity as pharma) get off with a relatively light caning in all this. Pharma is hiding data maliciously for profit, whilst academics are doing it through being slightly forgetful scientific sorts may be the view.

The truth I suspect is much more mixed and the same issues underpin the problem everywhere. For both academia and pharma, negative or inconclusive study results may not be actively buried, but on the other hand, no-one is shouting for their publication because, whilst that may be the right thing to do, it isn’t very exciting. The last thing you want to do after the personal disappointment of a negative study is spend months trying to publicise the fact. I’ve been at those congress presentations where multinational studies involving thousands of patients over several years have reported back negative results…I just can’t remember what they were. Non-publication is thus frequently a passive failure resulting from disappointment, apathy and probably a dash of laziness, and not, in the main, a result of venal motivations.

Now the skim readers from the pharma bashing lobby will be thinking that I’m excusing the non-publication of trial data by pharma. I’m not; it’s just that I reject the implication surrounding some of the All Trials related rhetoric that the principle motivation for this ‘scandal’ is profit and that somewhere in companies there are meetings discussing how to hide data to build share price. The importance of this is in the way the case for change is put to achieve its aim, particularly to pharma.

An argument to pharma which begins ‘Stop doing bad things hiding data for profit…’ will have little resonance when there is no action to hide taking place. The argument rather should begin ‘Act to correct this problem – publish all your data…’ recognising that this more frequently a passive failure than an active one.

“Failure to publish trial data is a significant breach of a patient’s right to make a fully informed decision.”

Pharma and academia alike must be motivated out of their inactivity because, thankless though it may be sometimes, full publication is a very important thing to do. However to me personally the motivation should begin with a moral argument based not on the importance of a complete data record (important though that is), but rather on our obligations to the subjects who have agreed to take part in our studies.

When a patient signs a consent form they are doing a truly noble thing allowing themselves to be used in an experiment to advance medical science for the benefit of humankind. That’s a special thing and the fact people do it in their thousands shouldn’t lessen our appreciation of what each individual is doing. Medical advance frequently equates to company advance and therefore the obligation to each individual subject in pharma studies is possibly even greater than it is for non-pharma research. This is partly recognised in the pretty scrupulous attention pharma companies’ pay within trials to matters of patient safety, but minimising risk of harm is not the only moral obligation researchers have to trial subjects.

Data transparency and patient consent

Failure to publish trial data is to me a significant breach of a patient’s right to make a fully informed decision. Consider a consent form for a study that stated the following;

‘If the experiment with which you will be involved over the next two years produces a positive result we find interesting or helpful we will definitely publish it. If however the result is a bit dull we reserve the right to forget about it such that it is probable the information we have gained from you will be lost forever. In that event you should understand that your participation will have been a complete waste of your time and effort.’

Laughable? Well that’s what has happened and if we feel (and I do) that this information would alter a patient’s willingness to participate in a study it must be communicated explicitly in the consent form. If it isn’t then any consent gained to participate in the trial is invalid because important information the patient needed to make their decision was withheld from them

“Counter-arguments to full data transparency tend to revolve around practicalities such as maintaining patient confidentiality…”

There are two consequences I see from this argument. Prospectively, unless researchers (pharma or otherwise) want to include something along the lines of the statement above in their consent forms then they must commit to publish the results of all research. If they don’t, then every time a patient signs a consent form they are doing so without the full information they need to make a decision; they are being misled.

Thinking retrospectively, the current body of unpublished data is a live moral issue not as may be imagined a matter of history. Each clinical trial that remains unpublished represents numbers of individuals who may have participated without the understanding their participation could be disregarded simply because they had the bad luck to be involved in a dull outcome. That wrong can be righted simply by publication.

Data transparency = All Trials, or not

The case for full availability of trial data is very difficult to argue against credibly. What is more questionable is whether failure to sign-up to All Trials equates to a denial that full data availability is a good thing. Proponents of All Trials would say that it does – failure to sign is failure to agree. Pharma companies however may reasonably argue against joining a bandwagon, even one with a good destination, driven by people whose antipathy towards industry is frequently so palpable. The journey to transparency has very real practical hurdles that need to be tackled by colleagues not combatants.

How the case for full data transparency is made to those in pharma needs more attention than is currently employed. Failure to publish, though wrong, more commonly reflects human disinterest in the uninteresting than it does an act of deception. Unjustified abuse of pharma based on an assumption of its general mal-intent means the day may be delayed when we achieve the data transparency we seek. In the end we all look foolish.

 

About the author:

Transparency statement: Dr Broughton has worked extensively for GSK over the last 2 years. He has not had any involvement with the decision made by GSK to sign the All Trials petition and has not had any discussions with the Company regarding the content of this article.

Nick Broughton is Managing Director at Pharmaceuticalethics.com.

Dr Nick Broughton qualified at Nottingham University Medical School and worked in hospital medicine and primary care for a period of seven years before joining the pharmaceutical industry.

His first role was as a clinical research manager in phase II and III at studies Sanofi Winthrop before moving into a medical adviser role at MSD UK.

The majority of his pharmaceutical career has been at AstraZeneca where he was UK Medical Affairs Manager before becoming UK Head of Medical Affairs. He then gained over 2 years international experience as European Director of Regulatory Affairs.

Nick is co-founder of Pharmaceuticalethics.com, a company that provides ethics and compliance audit, education and consultancy services to pharma and allied agencies.

How will greater data transparency affect patients?