IOM Issues Report on Studying Safety of Approved Drugs

Posted 01 May 2012 | By Alexander Gaffney, RAC 

The Institute of Medicines (IOM) has released a consensus report on ways to improve the US Food and Drug Administraiton's (FDA) oversight of the safety of already-approved drug products.

The report, entitled Ethical and Scientific Issues in Studying the Safety of Approved Drugs, explores a paradox often faced by FDA: only products that are safe should be approved, but the true safety profile of a product is difficult to ascertain until it has been used in real-world conditions and with numerous patients.

"Often, [a product's] benefits and risks cannot be fully identified until after a drug is on the market and has been used by a large, diverse group of patients over time, mainly because clinical trials conducted before approval may be too small or too short to detect all possible risks," wrote IOM in an accompanying press release.

The good news, says IOM, is that advances in information technology are making postmarketing tracking of pharmaceutical products increasingly easy and new-found regulatory authority granted to FDA under the FDA Amendments Act of 2007 allows the agency to require postmarketing studies if they are deemed necessary.

These postmarketing studies are the focus of IOM's report, which raises a number of ethical issues, including when such studies are appropriate, which types of studies to conduct, how the rights of study participants are to be best protected and how to use information obtained from the studies.

Among the recommendations proposed by the IOM report is the adoption of a "life cycle approach to drug safety oversight," which would see FDA formulate advanced planning for postmarketing drug safety monitoring.

Integral to this advanced planning is the establishment of a "consistent process" that takes into account both scientific and ethical considerations, wrote IOM in the report. These issues must bridge the concerns of patients, industry and other stakeholders, added IOM.

To accomplish this, IOM recommends the formation of a "comprehensive benefit and risk assessment and management plan (BRAMP) to track the medicine's benefits and harms during its entire life cycle."

"The BRAMP should be a living document that is publicly available and easy to understand," explains IOM.  The system should also incorporate periodic and need-specific reviews, such as when a controversial decision occurs or a safety issue emerges.

The IOM report is quick to add while "no general algorithm can dictate when the FDA should require a postmarketing study or which type of study to require," there are numerous red flags and risk factors that could help to provide advanced warning to regulators and patients alike.

Suck risk factors include products approved via surrogate endpoints, first-in-class compounds, and drugs known to have a "worrisome safety profile," explained IOM.

IOM's report also highlights the difficulties associated with enrolling patients into postmarketing clinical trials. Many patients may be averse to enrolling, particularly when the medicine is freely available and participating in the trial could hypothetically subject them to an inferior treatment regimen.

In cases where it is particularly difficult to enroll patients, observational studied may be the preferred method of postmarketing surveillance, notes IOM.

All of these issues highlight what IOM says are deficiencies within FDA's regulatory approach.

"FDA's current approach to drug oversight in the postmarketing setting is not sufficiently systematic and does not ensure that it assesses the benefits and risks of drugs consistently over a drug's life cycle," concludes IOM. "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 decisionmaking process more predictable, transparent, and proactive, allowing the FDA to better anticipate post-approval research needs and improving drug safety for all Americans."

Read more:

IOM - Ethical and Scientific Issues in Studying the Safety of Approved Drugs (Report Brief)

IOM - Ethical and Scientific Issues in Studying the Safety of Approved Drugs (Report Main Page)

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