July 10, 2006

The FDA's Slippery Slope

Who could be against making the process of getting new drugs through the Food and Drug Administration more efficient as long as the end products were still safe and effective? Today’s Wall Street Journal reports that the FDA has launched yet another program to help its primary client – the drug industry. It’s called “adaptive clinical trials,” which, if I understand them correctly, are trials that switch protocols mid-stream if early results suggest the change is warranted.

There’s no doubt that more flexibility in clinical trial design could teach drug makers and physicians a lot during the early stages of drug testing. Dosing could be adjusted, for instance, or patient-types on whom the drug has no effect could be eliminated from the trial so that it could be tested in more people for whom it looks like it is working. One could even imagine a safety problem arising in a subset of patients, who could then be eliminated from a trial when the drug looked promising for another subset or even majority of patients.

I have no problem with the FDA moving toward this approach for some drugs as long as it understands the pitfalls and builds in protective mechanisms. One such mechanism mentioned in the story was requiring these trials to have totally independent data monitoring committees with the power to set these mid-course corrections. That seems like a fair tradeoff to me.

But I was struck by a related piece of FDA news today, this one from the Reuters newswire. The inspector general of the Health and Human Services department says the FDA doesn’t closely monitor the status of the post-marketing trials that it ordered (these are trials designed to get real world feedback from patients who are on drugs whose recent approval had been based on skimpy data). The FDA has requested post-marketing trials for nearly half of all drugs approved since 1990.

According to Reuters, 35 percent of 336 annual reports due in 2004 "were missing entirely or contained no information.” The FDA politely disagreed with the report’s conclusions, but didn’t contradict the data.

Bottom line: the agency is moving toward more flexibility in pre-approval testing and conducting less follow-up on post-marketing testing. If I were running the FDA right now, I would want to tread carefully on this slippery slope. One more misstep – another Vioxx, for instance – will shred what’s left of its reputation.

Posted by gooznews at July 10, 2006 03:28 PM
Comments

Merrill--

I still think if a lawyer/investigator would look carefully into the shenanigans used by Eli Lilly to essentially monopolize the U.S. market--and the result on their captive audience of insulin-using diabetics, the details (though perhaps more difficult to obtain) would make the Vioxx debacle pale in comparison.

Because the treatment of diabetes is so patient-intensive, the harm that has been done can easily (though not necessarily truthfully) be shifted to the non-compliant patient. A dead-in-bed diabetic can't pursue a remedy.

As with all things, though, (just like these 2 FDA articles) IT'S ABOUT THE MONEY . . . and not just in the pharmaceutical arena. Several law firms HAVE investigated the "insulin crisis" and determined that while there is "a case" it would be too costly and too time-consuming for the firm to pursue. (IT'S ABOUT THE MONEY.)

Posted by: Melody at July 10, 2006 08:07 PM

Not sure I am so gung ho about this. The propagandists might call this adaptive clinical trials and claim this is like police having a warrant to search for one thing and finding another. But i suspect this is really more about allowing the sponsors to datamine their trials.

We could certainly lower our standards from drugs that have been proven to be safe and effective when used as directed to drugs that seem like they are safe and effective, but I don't think that is a great idea.

Posted by: Scott at July 10, 2006 09:17 PM

...and I would agree and disagre with the following:

Bottom line: the agency is moving toward more flexibility in pre-approval testing and conducting less follow-up on post-marketing testing. If I were running the FDA right now, I would want to tread carefully on this slippery slope. One more misstep – another Vioxx, for instance – will shred what’s left of its reputation.


You are right...this is the new business model for the FDA. This is what people voted for in 2004 (certainly in the minds of policymakers) and the role of the FDA is to get out of the way and let physicians decide what is best for their patients (which is laughable when you consider how little time doctors have for research after they finish with the paperwork from running their business and get a lot of their medical information from former cheerleaders).

But you are wrong...Vioxx is inevitable, particularly under this new business model. If doctors want to overprescribe Vioxx, that is the business of doctors and it is not FDA's role to get between doctors and patients. There is simply too much money to be made in prescription drugs and with FDA now backing out of the drug safety business and now eliminating the "gold standard"....there will be more Vioxxes. And I don't think people will really care.

You are going to get approvals based on targeted subpopulations (uh, maybe like the subpopulation of people who can't tolerate other pain relievers) and then detailers and marketing will get physicians to expand the prescribing. (Sound familiar?)

Posted by: Scott at July 11, 2006 07:07 AM