Won’t get fooled again outlined a stunning propaganda coup by GSK. On the back of a campaign for open access to clinical trial data that has drawn its inspiration from efforts by the Cochrane Tamiflu reviewers to get access to Roche’s clinical trial data, Andrew Witty came out and proclaimed that GSK were all in favor of access to clinical trial data. The BMJ threw its hat in the air and said whoopee.
In fact GSK had only issued a press release. They don’t have a policy. They have at best an aspiration or perhaps more ominously a strategy. Getting such great publicity out of a press release shows considerable tactical skills at the very least.
The GSK press release came a week before a key European Medicines’ Agency meeting on access to clinical trial data. It was aimed at shutting an open door – EMA have granted access, industry want to close it down. Industry representatives at the EMA Access to Data meeting on November 22nd sang from the same song sheet as GSK – of course we are in favor of access and transparency but we have to respect patient privacy and we have to have good governance. Access should be restricted to serious scientists. (These are red herrings – see the next post Access to data: privacy issues).
RxISK has data that GSK should want
At the end of Won’t get fooled again, I said the post had been written against the background of a serious undeclared conflict of interest. Since then, coincidentally probably, I’ve been critiqued by Arthur Schafer on Biojest for an overly casual approach to conflict of interest. This makes it of even greater importance to spell out the conflict (see Medical Partisans).
Here it is. We on Rxisk.org have data GSK should want, should need. We have raised the issue of accessing the data with them. They don’t seem to want access. They do not seem keen to have the issue raised. Interests seem to be conflicting.
Data on hazards – the key to good medical care
So let’s back up a minute. The campaign for access to clinical trial data is about getting a proper picture of the effects of a drug, both the possible therapeutic effects and the hazards. Restricting access is in fact more about restricting access to information about the hazards than about the relative inefficacy of treatment.
Clinical trials are not the correct way to establish the hazards of a drug – the diseases in which they are conducted commonly mask the hazards of treatment (The Spin that no Data can Overcome, Cri de Coeur, Once is Never, The Unbearable Lightness of Being.)
The best approach to hazards is to do what RxISK is trying to do. That is harness the real world experience of people taking a medication to get best quality descriptions of events as well as applying standard approaches to causality such as checking for dose response, challenge-dechallenge-rechallenge and other related methods. The best way to determine risk-benefit ratios is to ask doctors and patients what they think of the possible trade-offs between the effects of a drug – as RxISK asks but clinical trials don’t. We get both doctors and patients to look at the wider impact of an event in a person’s life in addition to reporting on just the event.
There is an industry out there almost it seems aimed at ensuring that we get the most degraded possible descriptions of events with no accompanying details (American Woman, American Woman 2). An industry that has succeeded in building a culture in which even good descriptions of the effects of drugs are dismissed as anecdotes – except of course for patients reporting stunning benefits on treatment. Those who unwittingly repeat the mantra of RCTs offering gold standard evidence on the effects of drugs play straight into industry’s hand in this regard. Words come before numbers – without the right words, the numbers are meaningless.
Andrew Witty eavesdropping on the train
The second consideration is this. If Andrew Witty was to take a train tomorrow and I was sitting in the seat behind him and he overheard me mention a side effect I was having on one of GSK’s drugs he is legally bound to report this to the regulator. Here is Leigh Thompson then the Chief Scientific Officer of Eli Lilly being deposed by Paul Smith on this issue in 1994 for the Fentress trial in Louisville Kentucky after Joseph Wesbecker, shortly after going on Prozac, had shot dead 8 of his co-workers and seriously injured 12 more before killing himself.
Q. The other day you said something that I have a question about. You said something about… employees calling adverse event reports in?
A. I can’t recall that. The rules under the DEN system that I put in place, I think it was ’83 or maybe ’84 — no, it was ’83 we began it, was that any Lilly employee anywhere in the world that learns of any adverse event through any source, and I’ve done it from cocktail parties
and overhearing conversations, should in fact report by telecommunications to DEN within
twenty-four or seventy-two hours, depending on where they are in the world. So, yes, we got a lot of adverse events, including ones I report because I’ve literally called up DEN and said, you know, that I overheard a conversation in the hallway just now that somebody’s wife was taking Ceclor and had an allergic reaction.
Q. Do you usually stop and ask for more information about that adverse event or do you just report what you overheard in a conversation in the hallway?
A. Depending on who the individual is, but, for example, you remember you showed me the document about that meeting of the expert opinion leaders that I had gone to wherever it was, I had another Lilly employee come to that meeting and follow me around so that that
person could in fact report all the adverse events that I was hearing, so that I wouldn’t have to do it myself.
A. I think it fulfills a regulatory requirement… if you right now told me that you had heard of a patient who had taken one of our drugs and who had their hair turn blue, I will guarantee you that I would call DEN up within two days and that would be in the DEN database. And I may or may not ask you for more information, but I would identify you.
Q. What if their hair turned loose?
A. You’re the lawyer, but if you read the law and the regulations, I think that’s exactly what it requires. The NDA, for example, requires all information…
Q. So let me make sure I understand. You feel it is your absolute duty to report a conversation that you have overheard in the hallway, but you don’t necessarily feel it’s your duty to report an issue raised by another regulatory agency and the analyses that were done
by the drug company in response to that issue being raised?
A. Under the FDA laws and regulations, I think you’ve stated it correctly.
Writing to GSK about access to data
Against this background it seemed appropriate to alert Andrew Witty last March to the fact that we expected RxISK to start generating data on GSK’s and other drugs – mentioning that despite everything many still considered GSK to be among the more responsible pharmaceutical companies. GSK’s response was to misattribute the remark that they were a responsible company to me and to thank me for this recognition, but to turn down a possible collaboration while in a follow up letter stating their full commitment to their regulatory obligations.
The growing data set
It is now November and RxISK.org has been up and functioning for two months. It is getting on average 10 treatment effects reported per day directly from the public. In two months it has had more patients report effects to it than the Irish Medicine’s Board has had since opening up for patient adverse event reporting in 2009. RxISK has had more treatment effects reported to it by Germans than Germany has ever had – reporting by the public is still not facilitated in Germany. Within a year we expect to have more treatment effect reports from the public than anyone except FDA.
RxISK & free appetizers?
FDA have 4.1 million adverse event reports from around the world collected since 2004. A number of companies have set up businesses, selling these reports to doctors, patients or anyone else for $200 for basic information on a drug and a possible problem linked to it – we make this information available for free to anyone who accesses RxISK.
We are on our way to having a substantial amount of RxISK data. We will make the key components of this available for free from the get-go. We are particularly keen not just to give people the number of reports of Leigh Thompson’s side effect – Hair turning blue on Prozac – but want to make the data local in the belief that if people in Baltimore, Brisbane, Birmingham or Bordeaux find its happening there and not in Calgary, Cologne, Chicago or Chenai, they may be able to bring local knowledge to bear on the issue and help work out what is going on.
We also want to bring the stories to life so that people can identify their own stories with those of others. These collected stories can help us all understanding the real story about these drugs. We think everyone can play a part in understanding and interpreting the stories – that access should not be restricted to just a few people who want to “guide” the narrative.
Leigh Thompson is now dead. But from his testimony above it seems like he would probably have been delighted to know we have a Hair Zone opening up soon, to complement the Violence and Suicide Zones already on RxISK, and the Skin and Sex and Relationships Zones still to come.
But then again maybe not. There are endless ways to adhere to the letter of a regulation but not its spirit. This is why you hire lawyers. Or perhaps GSK thought we were at the press release before the policy stage. Or perhaps they don’t have a policy on access to data yet.
How does RxISK move forward?
The issues for anyone reading this blog from Arthur Schafer to Andrew Witty, to Aetna Insurance, to lawyers like Andy Vickery, to Anne-Marie and all the people who have reported on RxISK stories and our still anonymous American Woman are:
- what interests conflict,
- where exactly do the conflicts arise, and
- what should RxISK be doing with its data?
We welcome your ideas and will respond.