BETHESDA, MD 24 May 2012—FDA needs to implement a rigorous, consistent approach to overseeing the safety of drugs after they enter the U.S. market, according to a report from the Institute of Medicine (IOM).

The report, "Ethical and Scientific Issues in Studying the Safety of Approved Drugs," was released online May 1.

FDA had commissioned the report to seek guidance on the types of studies needed to address safety issues during the postmarketing period and how to ensure the ethical treatment of study participants.

The report recommends that FDA adopt a patient-centered, three-stage framework for making regulatory decisions about a marketed drug's risk–benefit profile.

First, according to IOM, FDA should define the public health question that prompted the agency to consider making a regulatory decision. Such questions may arise when FDA learns new information about a drug's risks or benefits from surveillance data, published reports, or other sources.

The second stage requires FDA to evaluate the scientific quality of all available risk–benefit information about the drug, including any new information that prompted the regulatory review. The evaluation should include an assessment of the level of uncertainty associated with the available evidence.

During stage three, FDA should make and implement its regulatory decision on the basis of data gathered and assessed during the earlier stages. Regulatory options include requiring manufacturers to change product labeling or disseminate so-called Dear Healthcare Professional letters. FDA may also request or require the manufacturer to conduct new clinical studies, establish or modify a risk evaluation and mitigation strategy, or withdraw a product from the market.

Another option, if the evidence fails to show that a change is needed, is to take no regulatory action at all.

IOM recommended that FDA's decision-making process include "public accountability and transparency to determine the need for a policy decision, the need for new knowledge to support a policy decision, and the policy decision based on the new knowledge."

In its response to IOM, FDA stated that it is "in the process of fully analyzing the report to determine how to implement changes that will have the largest positive impact on public health."

FDA noted that it is already developing a systematic process that includes a risk-and-benefit assessment for communicating new information about drugs after they are approved. The agency stated that proposed legislation to reauthorize the Prescription Drug User Fee Act, which expires in September, "would substantially expand this effort."

According to FDA, many of IOM's recommendations align favorably with the procedures the agency already uses to ensure the safety of drugs that are sold on the U.S. market.

FDA said that it supports the general concept of "enabling the public to be able to clearly monitor relevant safety issues for all drugs." But because of resource constraints, the agency stated, it would be difficult to fully implement this recommendation without seriously compromising other critical regulatory activities.

According to FDA, full public disclosure of safety information held by the agency would require changes to existing laws and regulations.

Allen Vaida, executive vice president of the Institute for Safe Medication Practices (ISMP), said that private groups like his may be able to help FDA increase the transparency of its decision-making process.

Although ISMP is known mainly for its work on medication errors, the organization's QuarterWatch program analyzes data from FDA's Adverse Event Reporting System (AERS) to identify safety signals.

Surveillance data from AERS have known limitations, including underreporting of events and incomplete recording of information. But AERS has captured problems that have led to product labeling changes, market withdrawals, and other regulatory actions.

ISMP's QuarterWatch reports have publicized safety issues with varenicline, fentanyl transdermal patches, and montelukast that preceded regulatory actions on these medications by FDA.

Although AERS data come from FDA, QuarterWatch uses its own processes to filter the information, identify potential safety signals, and decide when to alert the public about a problem. Vaida said the notification process also involves other stakeholders.

"Before we put our report out we share it with the FDA, and we also share it with the industry," he said.

Quarterwatch this year has been following reports of adverse events in users of fingolimod, infliximab, dabigatran, and metoclopramide.

Even when FDA and ISMP are examining the same safety signals, ISMP isn't affected by the intellectual property issues and institutional processes that the agency must consider before making public announcements.

"If the FDA is looking at something, they may not immediately put the word out. We don't have those constraints," Vaida explained. "We may be able to find something and put out the word quicker and easier than FDA."

And, Vaida noted, entities like ISMP provide some level of accountability simply by independently analyzing AERS data.

"There's never any harm in having a couple sets of eyes looking at things," he said.