Regulatory Focus™ > News Articles > Researchers: FDA Needs to Take More Control over Postmarketing Studies

Researchers: FDA Needs to Take More Control over Postmarketing Studies

Posted 23 August 2012 | By Alexander Gaffney, RAC 

The manner in which US regulators assess the safety of prescription drug products after approval is in serious need of reform, opines a trio of researchers writing in the New England Journal of Medicine (NEJM).

The authors, Michelle Mello, Steven Goodman and Ruth Faden-all of whom were associated with the Institute of Medicine's (IOM) May 2012 report, Ethical and Scientific Issues in Studying the Safety of Approved Drugs-argue that scientific and ethical issues are at the forefront of problems with the safety of drugs. They point to the prominent safety failures of several drugs-GlaxoSmithKline's Avandia, Merck's Vioxx, and Pfizer's Celebrex-as evidence of both.

A Paradox for Regulators

A particular tension for drugs with known safety concerns lies in a paradox for US regulators, the authors said. "The public health mission of the FDA gives rise to potentially competing ethical obligations, 'To protect the public's health by having strong science on which to base regulatory decisions,' and, 'To protect participants in research that it requires.'"

In other words, the safety of the public at large must be balanced with the safety of those enrolled in clinical trials.

When regulators at the US Food and Drug Administration (FDA) require a postmarketing study for a drug known to be associated with serious adverse events, they assume "a measure of ethical responsibility for the welfare of the study participants," the authors write. "Exercise of that responsibility cannot be handed off to contractors of the industry sponsor."

Researchers: FDA Must Take More Responsibility

FDA, they continue, should only mandate a randomized, controlled study design if observational studies are infeasible or could not provide the necessary amount of information to determine the safety of a drug. The IOM committee on which they served ultimately recommended FDA rely more upon such observational studies in light of serious ethical concerns about subjecting patients to unnecessary risks without the possibility of enhanced benefit.

"Such trials can be justified only if they are necessary to answer a critically important public health question, if the potential risk is acceptable and minimized, and if special safeguards are in place, including a highly explicit informed-consent process to ensure that patients understand that they are potentially shouldering additional risk solely to contribute to the public good," the authors wrote.

As part of this ethical responsibility, FDA should also be more heavily involved in setting the terms of all postmarketing trials, including the design, title, end points, features, primary analysis and safety monitoring scheme, they explained.

"As the pace of the translation of discoveries from bench to bedside continues to intensify, so too does the imperative for thoughtful ethical governance throughout the life cycle of a drug," concluded the authors.

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