IOM: FDA should strengthen post-approval drug safety management

A new report released by the Institute of Medicine this week urges the Food and Drug Administration to adopt a full life cycle approach to drug safety oversight that would include strengthening data collection and the monitoring of drugs after they have received FDA approval.

The report, Ethical and Scientific Issues in Studying the Safety of Approved Drugs, notes that while the current approval process for a new drug is based on determining whether its benefits outweigh its risks, it is often the case that the full range of a new medication’s effects may not become apparent until it has been used by a larger, more diverse population over time.

"It is not possible to know what the full range of a drug's benefits and risks will be until it is used by many different kinds of patients over time, so it is critical that FDA continue to monitor and learn about the effects of drugs after they are marketed," said IOM committee co-chair Ruth Faden, a professor of biomedical ethics and executive director, Berman Institute of Bioethics at Johns Hopkins University in Baltimore, in a press release detailing the recommendations.

Among the recommendations from the IOM committee is one that urges the FDA to create a benefit and risk assessment and management plan for each drug it approves. This would be a single publicly available document that serves as a central repository of findings both pre- and post-approval. Currently, the FDA is already gathering much of this information, but it is scattered across the agency in any number of different records.

The study authors point out that the high-profile problems associated with a number of big name drugs, including diabetes medication Avandia, pain reliever Vioxx and cholesterol-lowering drug Crestor, bolsters the argument that FDA needs to a more systematic approach that will allow it to collect, assess and act on data about a medication's benefit-risk profile throughout its entire "life cycle" from approval until it is no longer marketed.

"We believe that the adoption of a life-cycle approach to drug approval and monitoring will help the agency strengthen its oversight, better tackle these complex decisions and increase public confidence in the agency's ability to protect public health," added committee co-chair Steven N. Goodman, professor of medicine, health research and policy and associate dean for clinical and translational research at Stanford University School of Medicine in Stanford, Calif., in a prepared statement. "This will become increasingly important as FDA looks for ways to safely expedite the drug approval process."

The committee also noted the difficulty in how to determine which drugs should require post-approval studies since there are too many individual factors involved in the approval of each drug as well as too broad a variety of approved drugs to create a universal set of criteria.

However, the report does make a number of suggestions about how the FDA manages those risk factors associated with greater uncertainty about a drug’s benefit-risk profile in the postmarketing setting.

These risk factors may include:

• drugs approved through the use of several surrogate endpoints that provide conflicting evidence about likely health outcomes associated with the drug;
• a first-in-class approval that used surrogate endpoints employed for medicines from a different drug class; and
• a medicine associated with a worrisome safety profile that could affect a large number of people, that could trigger severe side effects, or that carries a strong biological rationale for a particular side effect.

With an estimated 48 percent of all Americans taking at least one prescription drug, the report concludes that the FDA’s current approach to post-approval oversight is not sufficiently systematic and does not ensure a drug’s safety over its marketing lifetime. Further, broader powers granted the FDA in 2007 to proactively monitor drugs after approval and to act, if necessary, would allow the agency to make the recommended changes.

“Adopting a regulatory framework that is standardized across all drugs, yet flexible enough to adapt to regulatory decisions of differing complexity, could help make the agency’s decision making process more predictable, transparent, and proactive, allowing the FDA to better anticipate post-approval research needs and improving drug safety for all Americans,” a report brief concluded.