Drug Safety Tools for the Full Development Lifecycle Posted November 23, 2015Accutane AEs Highlight the Need for Better and Faster Insights Over time, the pharmaceutical and life sciences sector has come to recognize that drug safety is not strictly a concern during research or clinical trials, but rather an ongoing objective. Further, there is an increasing sense that pharmaceuticals can do more to ensure their drugs perform as intended once they are launched onto the market and begin to be used by actual patients. The famous example of Accutane (isotretinoin) – a prescription drug created by Hoffman-La Roche, a Swiss healthcare company, to treat severe cystic acne – highlights the need for closer monitoring of signals related to adverse effects, even after drugs are launched. Accutane was approved by the U.S. Food and Drug Administration (FDA) in 1982 and was regarded as a miracle cure by some patients. For 80 percent of patients, Accutane provided was highly effective. The drug’s known side effects included Crohn’s disease and suicidal thoughts. But, within a year of Accutane’s release, there were reports of additional adverse effects – including a baby born with malformations to a mother who took Accutane during pregnancy. In 1983, two “Dear Doctor letters” were released. These are special communications the FDA requires drug manufacturers to send out if the drug label is not complete in covering the extent and severity of side effects. In the case of Accutane, physicians were alerted to the possibility of birth defects. From 1984 to 1988, seven more of these letters went out. According to DrugWatch.com: The FDA was not alone in noting the dangers of Accutane. Dr. Frank Yoder, one of the scientists involved in the discovery of Accutane, wrote a letter to the Journal of American Medicine in 1983, informing the public of the possibility that Roche was not clear in alerting users of the toxicity associated with Accutane. That same year, a nonprofit health advocacy group, Public Citizen, petitioned the FDA to add warnings of birth defects to Accutane labels. The FDA took action in 1985, when a black-box warning, indicating that Accutane can cause fetal deformities and possibly fetal death, was added to the medication. By 1988, a pregnancy prevention program had been put into place, with the goal of decreasing the number of woman getting pregnant while taking the drug. A Centers for Disease Control (CDC) report led to a 1998 recommendation to the FDA that the drug be taken off the market. Additional reports of infant death following maternal exposure to Accutane came to light. By 2006, a link between Accutane and irritable bowel syndrome was discovered, leading to significant lawsuits in 2008, 2010 and 2012. Roche stopped manufacturing Accutane in 2009, by which time the drug had been recalled in 11 countries. Could better data and more powerful insights have prevented these adverse effects? Certainly, they could have made more people – including pharmacovigilance, risk management and clinical affairs professionals at Roche – aware of the risks sooner. At a minimum, this case and others demonstrate the need tools that enable the tracking of real-world inputs and feedback from patients. That is especially true given that the FDA’s streamlined approval cycles have coincided with an increase in black-box warnings and market withdrawals, according to Health Affairs. Given the high cost and brand impact surrounding market withdrawals, pharmas need ready access to a range of validated data, from multiple sources and tools for analyzing the data. Such tools would be useful for researchers during development cycles, but also to pharmacovigilance specialists and risk and medical affairs teams, who are tasked with monitoring drugs during post-marketing phases. Beyond the “holy grail” of drug safety, the benefits extend from more focused and cost-effective clinical studies to more efficient regulatory reporting and lower risk of fines. And it’s important to note that drug safety and innovation are not mutually exclusive goals; in fact, tools that are used to detect signals regarding adverse events may also uncover positive side effects and potential new indications.