FDA speed reviews raises drug safety concerns
A trend towards the use of shorter trials with fewer patients to cut the cost and time of developing new drugs is raising concerns about the safety of approved medicines, say US researchers.
A study by Thomas Moore of the Institute for Safe Medication Practices (ISMP) and epidemiologist Curt Furberg of Wake Forest School of Medicine also found that in many instances post-marketing studies that should have been carried out as a condition of early approval remain uncompleted.
Moore and Furberg looked at 20 drugs approved by the FDA in 2008 and compared those given an expedited review by the agency to those approved using the standard review process.
The expedited drugs spent 50% less time in development - an average of 5.1 years versus 7.5 years - and were tested in less than a fifth of the number of patients compared to standard drugs (104 versus 580).
Moreover four years after approval, 60% of commitments made to the FDA on post-marketing studies were unfulfilled, write the authors of the report, which is published in Journal of the American Medical Association (JAMA) Internal Medicine.
“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”, note the authors.
“Our findings suggest that the shift has made it more difficult to balance the benefits and risks of new drugs.”
The issue of post-marketing trial commitments not being fulfilled has been raised a number of times in the last few years and led to the passage of the Food and Drug Administration Amendments Act (FDAAA) in 2007, when a study found that just over 6% of promised studies were complete.
Moore and Furberg highlighted the problem that same year in a study which found that the number of adverse reactions reported in the US grew at four times the rate of the number of prescriptions between 1998 and 2005.
The two researchers acknowledge there are limitations with the latest comparison. For example, expedited review tended to be for more targeted medicines in diseases with smaller patient populations, which could explain the big disparity in patient numbers, and the sample size was very small.
Nevertheless, an editorial accompanying the study by Daniel Carpenter of Harvard University notes that - at a time when the pressure is on to bring drugs to market more quickly - the report “points to emerging troubles in the regulation of pharmaceuticals in applying the standards used for AIDS, cancer and other life-threatening diseases to a wide variety of disorders”.
Carpenter suggests the FDA has not put in place enough checks to make sure that drugs approved in limited patient populations are only used in those groups.
“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”, he concludes.
“The stakes of the current policy debates could not be higher”.
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