gryffron wrote:According to newsnight, AstraZeneca were specifically asked by the US regulator to make trial data available as soon as possible. Then they get slammed by peer reviewers for publishing incomplete data.
Its almost as if US big pharma is trying to rubbish them to keep the much cheaper AstraZeneca product out of the market. Who'd have thought it.
Gryff
It's even worse than that, they got slammed by their own advisory board!
I got another mini tutorial from a friend of mine yesterday on clinical trials yesterday, in particular on data safety and monitoring boards. As it happens she has just moved onto a project to write the DSMB charters for a couple of new trials after her current trials got slowed down due to lack of ICU beds and has written quite a few DSMB charters for other trials in the past.
This is not in reaction to your post but I see a few people seem to think the DSMB is part of or closely associated with the FDA. It isn't. A DSMB is actually recruited for a specific trial by the drug company running that trial, AZ in this case, and is specific to that trial. There are strict rules on the composition of a DSMB for a trial and steps to attempt to ensure the members' independence e.g. they have to declare shareholdings and they are not allowed to have worked for the company within a certain period of time prior to being appointed to the DSMB. A DSMB is not some big organisation, it is typically 7 or 8 people and must include at least one statistician and one medic with expertise in the therapeutic area under investigation. Another possibly biased observation (from my friend) is that they tend to be academics so sometimes ask some "pretty stupid questions". Is that comment born of the arrogance of a clinical scientist with decades of industry experience or is it indicative of the "ivory tower" attitude of some academics who can be somewhat divorced from practical realities? I have no way to judge that.
The key fact though is that the primary communications interface is supposed to be with the company. During the running of the trial the people on the DSMB actually have the best visibility of anyone in the world of the trial data, better than the drug company itself, because they are the only people who get to see all the data unblinded from the outset so that they can raise an alarm privately to the clinical trials team at the drug company if they see something in the data that makes them think that the drug is giving worrying safety signals (or even too many side effects in the placebo possibly indicating a contaminated manufacturing batch of whatever is being used for the placebo). The drug company would then be expected to react appropriately of course.
This is what makes this episode all the more strange. These conversations that we're seeing played out in public really should have been happening in private between AZ and the DSMB and if those discussions had been going on in private between the DSMB and AZ in the few days or weeks before the DSMB made its public announcement was AZ saying the same thing, i.e. that the interim results were fulfilling a commitment and that the later data would be integrated and released only days later? If yes then why on earth did the DSMB feel it appropriate to blow a whistle in public when it dic? It seems similar to some Lemon Fool owing me £100 where in private PM discussions he/she has agreed to pay me back £50 today and the remaining £50 on Friday yet, as soon as I am paid the first £50 instalment today, I make a post on this board about that Fool not repaying his/her debts because I have only been paid £50 of the £100 I am owed.
I've seen a few people post theories that the DSMB might have been compromised in some way by other pharma companies or simply parochial "US vaccines are best" politics and I suppose that could well be the case. Alternatively maybe the grubby and disappointing truth is that this is all simply because of some really serious personality clashes between one or more people on the DSMB and one or more people in AZ causing this DSMB to behave so aggressively.
- Julian
