A Positive-Sum Game

The job of a medicines regulator is a precarious balancing act. The primary concern has to be the safety of patients but, if the barriers to approval are too high, it can reduce the number of lifesaving therapies available to those patients. And that’s where pharmacovigilance comes into play. By monitoring the effects of drugs post-approval, warning signs can be recognized and appropriate action taken, such as changing safety information or, in extreme cases, removing a drug from the market. Two recent studies highlight the importance of pharmacovigilance; the first looked at the total number of post-market safety events in the US over a period of 10 years (1), and the second analyzed the monetary cost associated with failing to invest in fully functional pharmacovigilance programs (2).

The scale of the issue

A collaborative team comprising six different institutions from the US and France analyzed the number of post-market safety events between 2001 and 2010 (1). Of the 222 novel therapeutics approved during this period, 32 percent were affected by a post-market safety event. Overall, there were 123 safety events, including three withdrawals, 61 boxed warnings, and 59 safety communications, during a mean follow up of 11.7 years.

The research team also found that post-market safety events were statistically more frequent among biologics and drugs used to treat psychiatric disease, as well as those receiving accelerated approval and those with near-regulatory deadline approval. Post-market safety events were less frequent among therapeutics approved with a regulatory review time of less than 200 days, which, according to the authors, suggests that some approval packages provide clearer evidence of safety – leading to fewer post-market safety events. 
In the discussion, the authors argue that additional pre-market review may only delay approval without identifying therapeutics that pose future safety concerns. They advocate greater collaboration between the FDA and other stakeholders, as well as the sharing of pre-market clinical trial data.

The return on investment

What about the financial cost of failing to invest in pharmacovigilance? Researchers from Brigham and Women’s Hospital looked into cases studies of three drugs – rofecoxib, cerovastatin, and troglitazone – and suggested that the early signals of safety hazards were not adequately recognized (2). The lack of vigilance resulted in continued exposure of a large number of patients to the drugs, when safer and effective alternative treatments were available.

The authors stated, “Earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773-$884 million for rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone in the US through the prevention of adverse events.” They contrast the figures with the amount the FDA spends on population-based pharmacovigilance activities in the US – around $42.5 million – and concluded, “Our analyses demonstrate a pivotal and economically justifiable role for active pharmacovigilance in protecting the health of the public.”