Public rarely knows full reason FDA rejects new drugs

A view shows the U.S. Food and Drug Administration (FDA) headquarters in Silver Spring, Maryland August 14, 2012. REUTERS/Jason Reed

By Lisa Rapaport (Reuters Health) - Drug companies generally don’t disclose all the reasons new medicines fail to win U.S. marketing approval, even though regulators often reject treatments over concerns about safety or effectiveness, a study finds. Researchers compared the details companies made public in press releases with confidential documents from the U.S. Food and Drug Administration known as complete response letters, which explain why a new medicine can’t be sold. Often, companies made no announcement when a drug was rejected, or omitted most of the reasons the FDA cited for denying approval, the study found. “Only a minority of the press releases clearly stated that receipt of a complete response letter meant that marketing could not commence, and most findings associating the drug with a higher mortality rate went unmentioned,” lead study author Dr. Peter Lurie, FDA associate commissioner for public health strategy and analysis, said by email. Lurie and colleagues analyzed 61 complete response letters issued from August 2008 through June 2013, assessing what elements of the letters, if any, companies disclosed in press releases. When multiple letters were issued as part of the same application process, the researchers only included the initial letter from the FDA in the analysis, not subsequent ones issued after companies responded to the original concerns. If, however, companies received separate letters on the same new drug for two different uses, the researchers counted those as separate and included both in their analysis. In 11 instances, or 18 percent of complete response letters, companies didn’t issue any press release, the study found. For 13 releases, none of the statements matched what was said in the complete response letter. About half of the time, the complete response letters cited shortcomings in both safety and effectiveness. Out of 191 concerns about effectiveness raised in the letters, drugmakers disclosed a total of 30 in press releases, while companies shared 22 of 150 safety concerns. Roughly half of the letters asked for new clinical trials to study safety or effectiveness; and in 59 percent of these cases companies disclosed this in a press release. While seven letters reported that drugs had higher mortality rates in treated people compared to those not treated with the medicine, only one press release shared this detail. Publicly-traded companies, which may need to share details on the drug rejection under securities regulations, were more likely to issue press releases about complete response letters. These releases also tended to include more statements that matched points made in the letters. Companies were also more likely to issue press releases when their drug application was for the first in a new family of medicines. Making the full contents of complete response letters public would allow the FDA to increase transparency and combat misconceptions about why regulators refuse approval for new drugs, Lurie said. Doing this would probably require a change in FDA regulations, he added. Public access to these letters would help patients better understand the risks and benefits of medications, particularly when the complete response letters are issued for new uses of previously approved drugs, said Barbara Mintzes, a professor of pharmacy at the University of Sydney and author of an editorial accompanying the study in the journal BMJ. Even though companies aren’t allowed to advertise drugs for unapproved uses in the U.S., doctors are free to prescribe medicines for what’s know as off-label use, Mintzes said by email. “Doctors who are considering prescribing a drug for a specific use would likely reconsider if they knew the FDA had rejected an application for marketing for that specific use,” Mintzes said. “Medicines are important treatments but they are capable of causing harm as well as benefit, and harmful drug reactions are a leading cause of death and hospitalizations,” she said. SOURCE: BMJ, online June 10, 2015.