Life After FDA

From his new post, former FDA commissioner Mark McClellan talks about the current safety equation
Sep 30, 2007

You have to admit: Mark McClellan, MD, has quite a resumé. But after you've been the commissioner of FDA and the administrator of the Centers for Medicare and Medicaid Services (CMS), what comes next?

For McClellan, who was awarded a fellowship at the AEI-Brookings Joint Center for Regulatory Studies after leaving CMS, it's about finishing what he started. Under his leadership, the think tank launched the new Engelberg Center for Health Care Reform, which seeks to find practical solutions to the very big questions surrounding the safety, affordability, and quality of medical care.

Industry insiders see McClellan as a "less talk, more action" kind of guy and hope his new post will add horsepower to moving discussions about public policy reforms into action. (After all, Medicare Part D was enacted under his watch.) Here, Pharm Exec talks to McClellan about what it will take to improve the drug safety system and the challenges that face industry and regulators alike.

From your new position, how do you view the issues associated with drug safety?

This has been a big year for FDA reform with the FDA Revitalization Act. And one of the more challenging elements in there has been what to do about gaps in the nation's drug safety system. The usual debate at FDA is that you need more regulation because you need oversight of the drug companies and further government assurances to make sure that drugs are being used appropriately. On the flip side, if you put in too many regulatory barriers, it raises costs and reduces access to cures.

Part of the problem with drug safety is that we don't have a good system for learning about safety problems in a timely way. FDA has tried very hard, but it's difficult to rely on very busy doctors and hospitals and patients who don't always call into the so-called spontaneous reporting system to report adverse drug events. Take the case of Vioxx: It's unlikely that the doctor whose patients have heart disease and heart attacks would see that as a reportable adverse event for the drug. The result has been that we don't find out nearly as quickly as we need to about potential safety signals—and that's what's led to calls for alternative approaches for more intensive regulation.

What role could the Engelberg Center play?

We developed some ideas with researchers at Harvard, like Richard Platt, on how we could implement an active drug-surveillance system. If we had an active surveillance system, there could be more confidence that if there were an adverse event associated with a drug in actual use, it would be detected quickly.

These are ideas that get broad bipartisan support. On the one hand, it gives some real assurances that the safety problems are going to be identified and can be acted upon more quickly and reliably. On the other hand, it's about gaining better evidence about drugs using the electronic data systems that are already out there.

What would such a system look like?

There are pieces of it in place now. A number of health insurance plans have already been collecting electronic population-based data on the utilization of drugs and subsequent results for patients. Just look at the recent Avandia advisory-panel meeting. WellPoint presented data on something like 160,000 beneficiaries who have been on Avandia in comparison with other treatments for diabetes and found that there wasn't a higher rate of adverse cardiovascular occurrences.

It is possible now to pool together not just the experience of individual health plans like WellPoint, but also a much broader range of health plans that collectively cover more than 100 million patients. That's a much stronger database to use for surveillance of these safety signals.

This approach is focused on data mining, rather than conducting clinical trials. What are the potential issues there?

These are observational data sets, so just because you see an association does not mean that it's a causal relationship. It will be very important for there to be careful oversight of active surveillance systems by the FDA and expert advisors to the FDA to help identify which signals really are likely to be meaningful.

I mean, there are some adverse events that just shouldn't happen. Maybe you start seeing a significant number of cases of aplastic anemia or liver failure. That's a sign that we ought to be able to detect quickly and take action on. But often, there may be an association between a drug and adverse event that may just occur by chance. If you have large enough sample sizes, lots of things look statistically significant but may not be clinically meaningful.

Any safety surveillance system will require careful expert oversight to make sure that we're using these new data opportunities appropriately. Sometimes—or maybe often—this will be just a signal detection process. It won't resolve the issue, but it will help us identify where further clinical studies and more careful clinical evaluation is needed.