Jill Wechsler
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The development of more complex therapies to treat chronic illnesses and complex diseases warrants a whole new approach to
testing and regulating prescription drugs, according to a much anticipated report from the Institute of Medicine (IOM). Several
high-profile drug withdrawals and safety alerts in recent years have undermined public confidence in the Food and Drug Administration
and the pharmaceutical industry and raised concerns about the agency's ability to assure the safety of critical medicines,
according to a panel of health experts assessing "The Future of Drug Safety." The study says that FDA needs more funding,
stronger regulatory authority, and many internal reforms to enhance its ability to monitor and implement changes in drug use
after a product comes to market.
"The world has changed" since FDA was established 100 years ago, commented panel member Alta Charo, lawyer and ethicist at
the University of Wisconsin. Current agency operations reflect the old model, which focused on screening out highly toxic
drugs designed to treat acute conditions. Today most drugs are used by patients with chronic conditions for long periods of
time, making it impossible for sponsors to ascertain all possible side effects and safety issues from investigational studies.
Ongoing review
Strengthening Leadership
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The panel acknowledges that added regulatory requirements could delay patient access to needed therapies and further increase
the cost of drug development. But because randomized controlled clinical trials can yield only limited information on the
long-term impact of new medicines, these experts advocate a "lifecycle approach" to drug regulation that would soften the
sharp line between pre- and postapproval product status. While FDA has considerable clout in shaping clinical trials, drug
labeling, and Phase IV study commitments prior to NDA approval, it has limited "tools" for compelling changes and compliance
later on. FDA's main recourse is to pull a troubling product off the market or use its "bully pulpit" to sway sponsor behavior,
an approach that can be lengthy and ultimately unsatisfactory.
The recommended remedy lies in an ongoing, periodic review process that authorizes FDA to reassess accumulated safety and
efficacy data within five years of product approval. Sponsors would submit reports of accumulated safety and efficacy data,
including publications in peer-reviewed journals and updates on postapproval studies.
In addition, the panel proposes to highlight the limited safety experience of a newly approved drug by requiring it to carry
a special symbol, similar to the black triangle required for new drugs in the United Kingdom, during the first two years on
the market. FDA also would restrict direct-to-consumer advertising during this "black triangle" period, which could be shorter
or longer depending on the nature of the product.
Insufficient resources, weak legal authority, and too little data on drugs' risks and benefits make it difficult for FDA to
fully evaluate and address postapproval safety concerns, according to these experts from academia and health care organizations.
A main challenge for the agency is to establish a regulatory system that better balances resources for postmarket oversight
with those for pre-approval assessment.
Interoffice tensions
The current organization foments tensions between the two operations because the Office of New Drugs (OND) in the Center for
Drug Evaluation and Research (CDER) has ample resources to assess efficacy data from clinical trials, while the task of reviewing
safety and risk information falls to the much smaller and disproportionately underfunded Office of Surveillance and Epidemiology
(OSE), formerly the Office of Drug Safety. The resulting "interoffice polarization" has marginalized OSE staffers and produced
considerable "friction" between these two review staffs.
Instead of establishing a separate FDA drug safety office, as some members of Congress have advocated, the IOM panel seeks
a more integrated regulatory process that would give OSE a more prominent role in CDER approvals and drug oversight. To obtain
a more balanced assessment of a product's risks and benefits throughout development and application review, FDA would:
