In an outrageous commentary in the British Medical Journal, Sid Wolfe cites a JAMA study that claims “new black-box warnings and safety withdrawals have increased following PDUFA’s enactment, perhaps as a result of an expedited review process that may not adequately detect serious drug safety problems in the preapproval period.”
Statistics, the saying goes, are like a bikini. What they show you is interesting, but what they conceal is essential. In the case of Dr. Wolfe, it’s a case (in fact, the latest in a series) of taking evidence and selectively using it to prove a long-held theory. In the case of Sid Wolfe, the theory is that PDUFA puts FDA in industry’s pocket. Nothing could be further from the truth.
Much has changed since the introduction of user fees in 1992 and one of the most important changes has been in the medical innovation. Since 1992 both small and large molecules have become more complex. Since 1992 these new medicines have addressed the unmet medical needs of many orphan and serious chronic diseases.
But new drugs are more than about just reward. Many of these new FDA-approved medicines have a higher risk profile. And with better data management tools, the FDA is now able to capture adverse event information in a more timely and accurate manner. This is especially important when it comes to the approval of medicines with a higher risk profile. Post-marketing pharmacovigilance, whether in the form of more targeted REMS or more sophisticated surveillance techniques allows the FDA to pursue expedited approval pathways for those medicines it feels fill a void in the therapeutic armamentarium. The voice of patients supports this approach, as does that or practitioners. And it also supports innovation.
As Paul J. Seligman, former chief of post-marketing drug surveillance at the FDA, commented back in 2005, it’s important to “develop the science for monitoring adverse events in ways that will allow us to give adequate warnings.”
No pharmaceutical company wants its product brought to market more swiftly if that will lead to a rapid recall. The fact that there are more products with boxed warnings is a direct consequence of the FDA’s efforts to better inform physicians and patients to the risk/reward ratio of these new products. It’s 21st century safe use or, as the French refer to it, bon usage. In that respect, more product withdrawals are the natural consequence of better pharmacoviiglance – the counterweight to expedited approvals of higher risk medicines.And nothing to do with PDUFA fees.