Just shy of a year since the US Institute of Medicine implored the Food and Drug Administration to “embrace a culture of safety”, an article in the latest New England Journal of Medicine says that the agency’s response shows a lack of understanding of the problems.

Sheila Weiss Smith, an associate professor at the Center on Drugs and Public Policy at the University of Maryland who has served on a number of FDA advisory committees, notes that the IoM’s September 2006 report commissioned by the agency, The Future of Drug Safety, identified “weaknesses in the laws, regulations, resources and practice” of ensuring that goal. In the report, the IoM implored the agency to "embrace a culture of safety" but “sadly, the FDA's official response falls far short of what the American public expects and deserves”.

Dr Smith says that the FDA’s response “highlights the very reason that the agency – with which I have had some first-hand experience – is in need of monumental change: its philosophy is no longer aligned with its regulatory mandate”. She goes on to note that the 1992 Prescription Drug User Fee Act led to resources being provided to accelerate access to new treatments, and the FDA shortened review times and “safety was affected in several ways”.

As a result, “mechanisms intended to speed access to potentially lifesaving medicines were broadly interpreted” and led to approvals for drugs that were later withdrawn for safety reasons, such as the diabetes therapy Rezulin (troglitazone) and the COX-2 inhibitor Vioxx (rofecoxib). Dr Smith says that “the public expects the FDA to be the final arbiter of drug safety” but by “pitting safety directly against ‘access and innovation,’ the agency betrays its mandate to ensure that US drugs are both safe and effective”.

Agency structure marginalises safety

She also claims that “the very structure of the FDA marginalises safety”. All regulatory authority lies within the drug-evaluation divisions of the Office of New Drugs but the agency’s safety experts work in a separate Office of Surveillance and Epidemiology “and serve only as consultants to the review divisions, having no direct regulatory authority”. The IOM report suggested changing the role of the safety expert “from occasional consultant to vital participant in the day-to-day work of regulatory decision-making” but this has not happened.

Dr Smith also says that postmarketing surveillance is crucial, “but although responsibility for these activities falls to the OSE, all regulatory authority remains with the division that approved the drug”. The “sidelining of safety experts” extends to the FDA's external advisory committees, and the IOM recommended that scientists with expertise in pharmacoepidemiology or public health be included as regular members of all committees. However the agency has proposed that it include such expertise "when safety issues are an important component of the issues before the Committee," but Dr Smith declares that “safety should always be on the agenda,” adding that “the FDA's response once again highlights the low priority it assigns to its responsibility for arbitrating drug safety”.

She concludes by saying that the FDA's response to the IOM report “demonstrates a lack of understanding of the magnitude of the changes required to create a culture of safety. Apparently, the agency's leadership has yet to recognise that the adoption of such a culture would benefit all stakeholders – industry, the community of scientists, and most important, the American public.”