Only a fraction of side effects associated with the obesity drug orlistat, sold as the prescription drug Xenical and the over-the-counter medicine Alli, were published in papers and summarized clinical study reports submitted to the European Medicines Agency (EMA), according to a study conducted by researchers with the Nordic Cochrane Centre in Copenhagen.
The study used the Freedom of Information Act to acquire clinical study reports from the EMA that included seven randomized placebo-controlled trials of orlistat involving 4,225 patients. The data was reviewed by drug regulators in both the U.K. and the U.S., who voted to approve Xenical in the U.K. in 1998 and the U.S. the following year.
Adverse event data was pulled from the studies and compared to each corresponding published trial paper identified on PubMed. The results, published in PLoS Medicine revealed various ways in which the protocol instructions to trial investigators had the potential to dilute the appearance of side effects. Because of these filters, researchers say that only 3 to 33 percent of adverse events from all trials were reported in the publications even though six of the seven papers claim that “all adverse events were recorded.”
The paper shows that patients treated with orlistat had twice as many, as well as far more severe, side effects than those treated with a placebo. Yet, this information is not relayed in the published papers.
Ben Goldacre, author of Bad Science and founder of AllTrials, says that advances in drug testing technology have not refined the collection of side effects data during drug testing. “We can be confident that this is a much wider problem that just orlistat. This problem is widespread.”
In 2011, the watchdog group Public Citizen petitioned the U.S. Food and Drug Administration (FDA) to ban Xenical and Alli due to health risks that the group said outweighed any benefits of the drugs.
In August 2009, the FDA issued a safety alert regarding cases of severe liver injury in patients who were using both prescription Xenical and OTC Alli.