The problem with follow-on studies is that they take time—and leave physicians and patients hanging on without answers. My
hope is that we'll be able to do that much more quickly than in the past and, as a result, be able to more effectively target
the postmarket follow-up studies that are needed.
We shouldn't have to wait five years, until a drug is used by millions of patients, and still not be able to get to a more
definitive answer—like what happened with Vioxx. So I don't think we should expect to wait a long time to get the needed information.
We ought to have a mechanism in place to quickly conduct any follow-up confirmatory clinical studies that are needed.
What are the most promising ways to integrate surveillance systems with what's already in place today?
You can begin the surveillance process at the time when the drug is approved. For example, in the case of Vioxx, there were
concerns about possible cardiovascular adverse events during development and at the time of FDA approval. There was a relative
signal that [made it seem] plausible that events could occur with long-term use and maybe in certain patients. There was also
the possibility that it may not have been a real effect at all. If we had this system in place when the drug was approved,
the FDA could have highlighted the importance of tracking the occurrence of cardiovascular events in patients using the drug
who had heart disease.
According to some simulations done by Richard Platt in conjunction with this work we're doing, the safety signal for a higher
rate of serious cardiovascular events with Vioxx could have been detected in three months—rather than four to five years—with
this kind of large-scale population network in place.
When it comes to execution of a drug safety surveillance system, where are the places FDA can fall down?
We're entering a new era here—and not just because FDA is now moving to active surveillance and much more routine and systemic
oversight. But we're entering into a new era in terms of the ability of anyone to look on the Web or run an analysis and find
a statistically significant association between a drug used and an adverse event. A lot of times, that won't be a causal association.
Did it occur by chance?
And if FDA doesn't have an aggressive mechanism in place to help the public distinguish between adverse-event associations
that occur by chance and those that may really mean something, then it doesn't have a way of giving the public confidence
that they will be able to get to the bottom of the issue in a timely and effective way. That's going to lead to real challenges
for effective drug development.
Does FDA have what it needs to make the change?
I think the good news is that the agency is finally getting a down payment on all the additional resources that it desperately
needs [through the FDA Revitalization Act] and all the additional opportunities to develop new scientific and technical capabilities
to deal with these new challenges. But it also presents some major adjustment challenges.
That will include developing new skills. It will also include developing new ways of interacting with companies and the approval
process, especially in the postmarketing process. Things are changing. It will not be business as usual in terms of drug approval
and even postmarket planning.
What impact do you predict on new systems for adverse-event reporting and detection?
There may not be any immediate effect—but there's at least the potential for some significant improvements for a couple of
reasons. If FDA is able to implement an effective active surveillance follow-up system, issues that are properly dealt with
in the postmarket setting will be dealt with in the postmarket setting. In other words, you won't see as much reluctance to
approve a new drug when there are some slight doubts that are, again, best resolved when you can see how a drug is used in
practice. I think it might actually speed up the approval process.
Also, the new Revitalization Act includes a framework for FDA to develop the premarket science of showing that drugs are safe
and effective and can be used reliably.