Comments on: Hidden Data: Merck, Schering-Plough & Zetia

By: BPW

BPW — Sat, 29 Dec 2007 16:59:23 +0000

All,

This finding by the NYT should not surprise anyone who has knowledge about how Big Pharma operates. If it’s good news, shout it from the mountaintop. If it’s bad news, hide it in the closet. As the FDA is woefully underfunded, they need to be able to trust the Big Pharma companies to be honest. Unfortunately, as long as money is involved, this trust is misplaced. The Big Pharma companies will never be trustworthy. They’ve demonstrated over and over again that they just can’t do it. It’s a crime when human lives are affected, but there’s money to be made. With all the recent bad news on Schering-plough, they now top the list of the most mistrusted.

By: Hank

Hank — Sun, 23 Dec 2007 18:17:32 +0000

Much thanks. Consistent with every report on FDA that’s been issued, I guess (for the past forty years).

Has the NNT question re: Alz. studies been raised in context of Vioxx “wider discussion”? As I recall (could be wrong), Merck talked about unblinding those studies after VIGOR to see if the same pattern showed itself. Claiming not, used that as a reason to minimize response to VIGOR (along with theory that naproxen lowers MI rate, etc.)

By: Emil

Emil — Sun, 23 Dec 2007 17:40:14 +0000

The FDA has all the data analysis plans but does not seem to have the wherewithal to ensure the plans are carried out.

By: Hank

Hank — Sun, 23 Dec 2007 17:06:52 +0000

Great point, Emil. From what you say, I take it that there is no pre-specification of analysis type that a company files with FDA? Or, if they do, still easy for FDA to “miss” and/or let it be?

By: Emil

Emil — Sun, 23 Dec 2007 15:28:20 +0000

In the case of Vioxx, Merck didn’t hide studies per se, but
they failed to report pre-specified analyses to the FDA and to the world. For example, in the key Alzheimer’s studies,
Merck never reported the so-called “intention-to-treat” (ITT) analysis (which was pre-specified). The ITT analysis
shows a clear signal against placebo for thrombotic adverse
events long before the withdrawal. Merck instead reported an
“on-drug” analysis, that, for various reasons, looks much
better. The FDA would need a staff of millions to catch this
level of subterfuge.

So, its not just about hidden data. Its also about
hidden analyses. To this day, Merck has never published
an ITT analysis of the Vioxx Alzheimer’s studies.

By: Hank

Hank — Fri, 21 Dec 2007 18:09:00 +0000

Again thanks, Jack.

Todd - Rather than attack, why don’t you tell us what you found misinformed, misguided, etc.. No doubt, many of us could learn from you.

By: Jack

Jack — Fri, 21 Dec 2007 16:32:20 +0000

Hank:
My understanding is basically all human phase II-IV trials will require at least a posting to clinicaltrials.gov. This was common practice before, since if things turned out well the company would want it to show up somewhere prestigious (eg JAMA), and the editors of these journals all agreed a few years ago not to publish trials that hadn’t been posted on the website. Now the FDA requires it and can legally penalize (fines?) companies that don’t comply with the strict deadlines. The NIH is also under certain legally required timelines for maintaining the site. I don’t really know how detailed the postings will need to be, and haven’t seen any hard guidelines. It’s entirely possible the synopsis on the website could be short enough or vague enough to hide something like this example. But on the other hand, it’s tough to legislate exactly what companies need to post, since trial design varies.

Anyway, it prevents companies (and universities - I think it applies to them too) from conducting a trial in a certain indication and, when the results don’t turn out right, not telling anyone about it. I personally don’t think this was common practice (but I do think companies might drag their feet a little about publishing failed efficacy results - and journals don’t exactly like to publish it either), but I’m sure it happened.

However, please also keep in mind, previously, all data from registration trials got sent to the FDA, and companies needed to send all adverse event reports to the FDA as well.

Ed: I saw some stuff in my post before that looked unclear after I reread it too. How about an edit button?

By: TOdd

TOdd — Fri, 21 Dec 2007 15:54:37 +0000

Hank, please tell me you are not a clinician. If you are practicing medicine with this knowledge base, please consider retiring this year.

By: Hank

Hank — Fri, 21 Dec 2007 15:39:50 +0000

Thanks to Jack - didn’t see that message when posted my last.

Re: Todd’s comment, we obviously have much to find out. NYT piece “suggests” interaction issue may be part of it - like statins, fibrates, and rhabdo. Or, indeed, could be independent issue of zetia alone, compared with statins, re: liver function.

By: Hank

Hank — Fri, 21 Dec 2007 15:30:45 +0000

I see enough typos in my message that I should clarify the main question:

Even though they would not apply in this case, do potential FDAAA sanctions apply to published/unpublished studies in general, in contrast with submission of studies to FDA? Are they tied into what is posted on relevant websites?

Otherwise, agree with Atlex in principle, but it also comes down to what FDA actually got - raw data, interepretations, summaries, etc.. As we learned with Baycol, fen-phen, et. al., there are lots of ways data can be submitted that still leave OND/ODS with a good deal of “detective work.”