IOM calls for more thorough safety monitoring of drugs

At a time when more Americans than ever are taking prescription medications, it is essential that the Food and Drug Administration regularly monitor drugs to watch for any new safety issues, according to an Institute of Medicine report.

To track a medicine’s safety, the FDA should create a comprehensive benefit and risk assessment and management plan that is readily accessible to the public and easy to understand, according to the report, issued May 1. Such a document would give physicians and others greater access to information about drugs on the market than they had in the past, said Eric M. Meslin, PhD, a member of the 12-person IOM committee that wrote the report.

“It’s not that there’s a problem [with the FDA’s postmarketing safety monitoring system]. It’s that the system might have some gaps that could be filled by a more comprehensive and harmonized approach,” said Meslin, director of the Indiana University Center for Bioethics and associate dean for bioethics at the Indiana University School of Medicine.

In recent years, the FDA’s process of ensuring that drugs on the market are safe and effective has improved, due largely to changes in federal law, the IOM committee said. The most influential legislation was the Food and Drug Administration Amendments Act of 2007, which gave the FDA additional postmarketing regulatory tools to better protect the public’s health. One such tool was the authority to require manufacturers to continue studying drugs that are approved for sale.

But with that authority came new challenges, including determining when it is appropriate to require a postmarketing study and how to use information from manufacturers’ studies and other research in making regulatory decisions, the IOM committee said. To help resolve some of those issues, the FDA asked the IOM to evaluate the scientific and ethical issues involved in conducting studies on the safety of approved drugs.

“The main message [of the IOM report], in my view, is that the FDA should be as serious about monitoring the safety of approved drugs on the market as it is about testing drugs before they get to the market,” Meslin said.

To achieve that, the IOM recommends that the FDA:

• Monitor a drug’s safety during its lifetime on the market.
• Use a consistent process for evaluating benefits and risks.
• Consider the perspective of health professionals, patients and others before making a postmarketing decision, such as withdrawing a medication.

The IOM report also encourages the FDA to revisit postmarketing safety decisions that are controversial or difficult. Such reviews should include gauging the public health effects of the FDA’s decision and assessing the decision-making process itself.

Realistic recommendations?

While the FDA described the IOM report as containing thoughtful insights and recommendations, the agency questioned whether some of the suggested changes are realistic, particularly the comprehensive benefit and risk assessment and management plan.

“We support the general concept of enabling the public to be able to clearly monitor relevant safety issues for all drugs,” the FDA’s Center for Drug Evaluation and Research said in a statement issued May 1. “However, we believe it would be very challenging to implement this recommendation within our current resources without seriously compromising other critical regulatory activities.”

The FDA added that it already monitors a drug’s safety through its life cycle on the market.

The agency is analyzing the report to determine which of the recommendations could be enacted. The FDA said its goal is to implement changes “that will have the largest positive impact on public health.”

In 2007 and 2008, 48% of people took at least one prescription medication in the past month, up from 44% in 1999-2000, according to the Centers for Disease Control and Prevention. Also on the rise is the use of multiple drugs, which is most common among people 60 and older, the CDC said. Thirty-seven percent of that population took at least five prescription medications during the past month in 2007-08. The figure was 8% among people 20 to 59.

In this environment of escalating prescription drug use, the public health consequences of drug exposure — both negative and positive — could not be higher, the IOM report said. Complicating matters is that many potential risks of medications cannot be fully identified until after a drug is on the market and used by a large, diverse group of patients over time, the committee said. In many instances, clinical trials that are conducted before a drug is approved are too small or too short to detect all the possible risks of the medications, according to the committee.

“The FDA has a huge job,” said Grace M. Lee, MD, MPH, an IOM committee member. “They have to ensure that drugs are available in a timely fashion, but that means there is going to be some uncertainty about a drug’s benefits and risks.” Dr. Lee also is an associate professor of population medicine and pediatrics at Harvard Pilgrim Health Care Institute and Harvard Medical School in Boston.

Although that uncertainty will continue, the IOM said its recommendations will help make the agency’s postmarketing, decision-making process more proactive and transparent and ultimately improve drug safety.

A key message from the report is that “a medicine being taken off the market is not a failure of [the FDA’s] regulatory system. It’s actually a success,” Meslin said. “It shows the system is working.”