Tuesday, March 1, 2005

U.S. Senator Johnny Isakson (R-GA)
Hearing on FDA’s Drug Approval Process
Health, Education, Labor, and Pensions Committee

Sen. Johnny Isakson (R-GA): Thank you, Mr. Chairman.  I apologize to the panel for being late.

Dr. Fleming, I'd like to ask you, do you concur in general with Mr. Schultz' remarks with regard to advertising limitations?

Mr. Thomas Fleming: I think the reality here is that we want to get the truth to the public.  And the advertising to the public and direct-to-consumer advertising is certainly one aspect, but in many instances, it doesn't reflect the essence of the truth.

And one of the comments that I had made in my recommendations was to encourage the FDA reviewers to be more forthcoming in their communication.

One experience that I've had on FDA monitoring committees – FDA advisory committees -- is that it's striking how often what you read in the clinical literature is not fully capturing the essence of really what is known in the evidence about benefit to risk.  There's what I call a sponsor spin in what gets into the clinical literature, because much of what's written is influenced by academics and industry that have some conflicts of interest.

Certainly, even more so, what gets presented in direct-to-consumer advertising can't be expected to be an independent, objective assessment of the truth.

And in some instances, particularly in settings where there are significant concerns about safety risk, as have been identified by the COX-2s, there are real concerns, then, about direct-to-consumer advertising giving a misrepresentation of the true benefit of what's
truly known about benefit to risk.

Sen. Isakson: That being said, I take it that in part is some of the reason for your recommendation in the conclusions, that the one thing we should not do is have an external review panel established.  Is that correct?

Mr. Fleming: Well, part of my concern here is not only the fact that I think FDA brings the greatest overall insight into regulatory issues, clearly FDA is benefited greatly by having external advice from industry and from the academic community.

And yet, the reality is, there are conflicts of interest.  And I believe that it's one of the issues that concerns me, as to the influence of that on the objectivity of the input that would occur in that process.

Sen. Isakson: Thank you.  One last question of Dr. Fleming.

In recommendation number three that begins, when a safety signal is found, frequently from non-controlled, post-marketing data, the FDA should -- and I didn't hear the testimony, so I apologize if I an behind the curve here -- but that tells me, or portends to me, that a
post-marketing situation is a drug that's already on the market.

And then they get some notice that there may be a problem, or there was an episode or there were a sequence of episodes.

What, currently -- your solution begs that question that currently there's not a standard timeline and methodology upon which that's measured and tested.  Is that true or not true?

Mr. Fleming: Well, I don't -- I'm not sure about the standard timeline.  What I know is that there's a clear recognition and acceptance that there must be post-marketing safety assessment.  And there are many levels for that, as we've discussed.

Passive surveillance using MedWatch is useful at a certain level. More effective are large-linked databases that allow us to more reliably get assessments of signals.  But ultimately when you see those signals, the most reliable way to asses the degree of benefit
and risk is through randomized trials.

And my concern is, there are settings, such as in the COX-2 inhibitors, where there is great need for having post-marketing, randomized trials of sufficient size and duration, that we're going to be able to detect safety risks that could be sufficiently rare, that you wouldn't be able to reliably assess them except in the randomized trials, but could have the influence to tip the scale in benefit-to-risk.

And I believe the FDA should have the authority in those settings to indicate that those studies should be done in a timely way.

Sen. Isakson: Thank you very much.

And not a question, Mr. Chairman, but a comment to Ms. Davenport-Ennis.  I had the chance to skim most of your testimony, although I didn't get to hear it.  I want to commend you on your advocacy in balancing safety and timeliness, and also not thwarting research and
development, cancer survivors, of which my sister is one, from radical treatments and things like that.

Appreciate the dynamics of the pharmaceutical industry and new innovation.  And safety is important, but we've got to recognize the balance for those that life is in the balance at any one given point in time.

So, I appreciate your testimony.

Thank you, Mr. Chairman.