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Safety Issues Found in 24% of Newly Approved Drugs

Serious safety issues were found after regulatory approval in approximately one quarter of new active substances (NASs) introduced in Canada between 1995 and 2010, and priority-review drugs were more likely than standard-review drugs to acquire serious safety warnings.

Joel Lexchin, MD, from the School of Health Policy and Management, York University, Toronto, Ontario, Canada, published the results in a research letter online October 8 in the Archives of Internal Medicine.

To determine what percentage of drugs approved in Canada go on to acquire serious safety warnings or to be withdrawn from the market for safety reasons, Dr. Lexchin used the Therapeutic Products Directorate and the Biologic and Genetic Therapies Directorate to identify 434 NASs approved between January 1, 1995, and December 31, 2010. Approximately three quarters (74.4%) of NASs underwent standard review and one quarter (25.6%) underwent priority review. (The US Food and Drug Administration has a similar priority-review process known as an "Expedited Drug Development Pathway.")

Overall, 23.7% of the drugs approved during the study period had a postapproval safety issue. Of those that underwent standard review, Dr. Lexchin estimated that 19.8% (95% confidence interval [CI], 14.8% - 24.8%) subsequently gained a serious safety issue compared with 34.2% (95% CI, 24.3% - 44.2%; P = .005 log rank test) of the products that underwent priority review.

Certain drugs are given priority review as potential treatments for important clinical problems and may gain regulatory approval with a lower benefit-to-harm threshold. Health Canada approved 87 NASs for 5 serious diseases during the period of the study. Of those, 42 NASs underwent priority review and 45 underwent standard review. Among these NASs, there was no difference in the probability of acquiring a safety issue (31.1% [95% CI, 14.3 - 46.0] for priority-review NASs vs 34.9% [95% CI, 16.8 - 52.9] for standard-review NASs; P = .96, log-rank test).

The study highlights the fact that many drugs had serious safety issues that were not understood at the time of approval.

Monitoring drug safety is a major public health issue, noted Thomas J. Moore, AB, from the Institute for Safe Medication Practice in Horsham, Pennsylvania, in an invited commentary that was also published online October 8 in the Archives of Internal Medicine.

In the commentary, Moore explained that regulators in Health Canada and the US Food and Drug Administration are required to make difficult scientific judgments that may affect the health of hundreds of thousands of patients within months after drug launch.

To approve an NAS, regulators pore over piles of densely written scientific reports. Although fast approval of new drugs may benefit some patients, for most it is a mixed blessing, Moore writes.

Dr. Lexchin and Moore have disclosed no relevant financial relationships.
Arch Intern Med. Published online October 8, 2012. Research letter abstract, Commentary extract

Medscape Medical News © 2012 WebMD, LLC
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