The Food and Drug Administration recently issued a final rule regarding safety-reporting requirements for Investigational New Drug Applications, including biologic drugs.
The rule, to go into effect early next year, mandates that applicants submit for review only those adverse events "for which there is evidence to suggest a causal relationship between the drug and the adverse event," according to a guidance issued by the agency. In the past, drug makers and investigators had to report any and all adverse events, regardless of whether causality was likely.
Dr. Daniel E. Furst
The new system is meant to "expedite FDA’s review of critical safety information," said Dr. Rachel E. Behrman, associate director for medical policy at the agency’s Center for Drug Evaluation and Research (CDER).
Efficient, timely analysis and action are worthy goals, and it is true that the FDA is currently lacking in these areas. Indeed, it has been 7 years since the current rule was first proposed and opened for comment in 2003, a long time even by the standards of an agency that takes 3-4 years to issue many of its final rules.
But the slow, ponderous process by which rules are made is necessitated by the need to gather comments and feedback from an incredibly large number of constituencies. The agency must then assess and weigh them all, and create a careful policy that takes them into account. And maybe this is the model to follow for drug safety reporting, too.
Take the case of the link between phocomelia and thalidomide, or the discovery of rare cases of myocardial infarction occurring after exposure to nonsteroidal anti-inflammatory drugs. These events probably would not have been caught under the new system of event reporting, or would not have been caught as quickly. A pattern is difficult to discern when there is a lot of noise, but that does not mean the pattern does not exist. Rare events can still be meaningful.
The rule’s intention – to increase efficiency – is good. But instead of simply lightening the load, government, patients, and physicians alike must realize that the actual solution is to give the FDA the resources it needs to do the full job.
My preference, therefore, would be to have a system that allows periodic screening, via computer, for very rare events. This would mean, however, that the reporting of events is comprehensive.
The new rule does definitely succeed in one respect: It brings U.S. safety-reporting requirements in line with those of other international agencies, including the World Health Organization. Uniformity is important.
I hope that this rule continues to make sense in a couple of years, and fulfills its goal of expediting safety reviews. However, if looking back on it we find that it does not, I hope the FDA will not hesitate to revisit the issue in order to keep new drugs safe for the public and to help prescribers embrace new therapies with confidence.
Dr. Furst is the Carl M. Pearson Professor of Rheumatology at the University of California, Los Angeles. He has disclosed a number of grants and honoraria from several pharmaceutical makers and has also acted as a consultant.
The final rule is published at Federal Register 75;188:59935-63 (http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2010_register&docid=fr29se10-3.pdf).