Delays Between Post-Marketing Studies and FDA Approvals

A new study reveals that drugs cleared under an accelerated U.S. Food and Drug Administration (FDA) program do not always fully study sufficient patient demographics.

In fact, of 20 new drugs that received clearance for marketing by the FDA in 2008, just eight received expedited reviews after a significantly small number of patients were studied. The report appears in the October 28 online issue of JAMA Internal Medicine. Also, 50 of 85 post-marketing study commitments involved conditions for approvals that were still not fulfilled as of this January, according to Medscape.

The descriptive study, led by Thomas J. Moore, AB, from the Institute for Safe Medication Practices, Alexandria, Virginia, and Curt D. Furberg, MD, PhD, from the Wake Forest School of Medicine, Winston-Salem, North Carolina, involved 2008 FDA new molecular entity approvals, FDA documentation, drug information databases, prescribing information, and other data, Medscape reported.

The researchers found that drugs approved under the accelerated approval program received approval after just a median period of 5.1 years—from 1.6 to 10.6 years—when compared to a range of 4.7 to 19.4 years (median 7.5 years) for drugs approved under the standard review process. Expedited drug approvals following efficacy testing were conducted in a median of 104 patients—the range was 23 to 599 patients)—compared to a median of 580 patients (75 to 1207 patients) under standard review protocols, Medscape reported.

Of 20 drugs approved in 2008, half were for inpatient and half were for outpatient use. Of those, seven were approved with orphan drug status for rare diseases, which included six, which underwent expedited review. All 20 were being marketed as of January 2013. Meanwhile, drug sponsors only completed 26 of 85 (31 percent) of their post-marketing studies and only submitted data for FDA review for just eight (nine percent) of the drugs. This means that drug sponsors had met their commitments for more than half—50 of 83—post-marketing agency-mandated commitments, according to Medscape.

According to the researchers, post-marketing commitment take place about 11 years following approval; however, the research only covered a four-year period, Medscape noted.

At approval, five of 20 medications included a boxed warning concerning a significant safety risk; eight included a special risk management mandate and another eight included a warning or contraindication for hypersensitivity. Since approval, another five medications received either a new or expanded boxed warning; one drug received new contraindications and four received additional warnings or precautions, Medscape reported.

“The testing of new drugs has shifted from a situation in which most testing was conducted prior to initial approval to a situation in which many innovative drugs are more rapidly approved after a small trial in a narrower patient population, with extensive additional testing conducted after approval,” the researchers concluded. “Our findings suggest that the shift has made it more difficult to balance the benefits and risks of new drugs,” he added, according to Medscape.

“If the FDA’s requirements for new drugs, both pre-market and post-market, are weakened, trust in both the efficacy and safety of prescription drugs is likely to be weakened,” wrote Daniel Carpenter, PhD, from the Radcliffe Institute for Advanced Study, Harvard University, Cambridge, Massachusetts, in a commentary accompanying the study. “The stakes of the current policy debates could not be higher. There is scarcely a feature of the American health care system that does not depend on evidence-based trust in prescription drugs, ratified and enforced by the FDA,” he added.