A weight-loss pill taken by millions of patients in the last two decades has been propped up by problematic clinical studies that “systematically understated” the drug’s potential harms, according to a new analysis. Danish researchers who reviewed data summaries and published journal articles found that seven drug trials funded by the drug maker Roche in the 1990s downplayed the frequency of apparent side effects like diarrhea or incontinence.
The drug, known to scientists as orlistat, and marketed in the US as Alli, has generated hundreds of millions in sales but has slumped in recent years in part because of a reputation for unpleasant gastrointestinal side effects.
The analysis shines light on “something that clinicians often are suspicious of: that the adverse event reporting in clinical trials doesn’t give the whole picture,” said Dr. Raj Padwal, a clinical pharmacologist and internist at the University of Alberta, who was not involved in the analysis.
The new research, published Tuesday in PLOS Medicine, didn’t examine the data reports that were submitted to the Food and Drug Administration when orlistat was approved, first in 1999 as a prescription drug sold by Roche as Xenical or later as a low-dose, over-the-counter pill sold by GlaxoSmithKline as Alli. (The FDA did, however, review the data from the trials in question.)
Those trials, conducted in the 1990s by researchers at academic or medical centers, resulted in journal articles. To evaluate the thoroughness of these articles, the Danish researchers compared them to data summaries submitted to European regulators, which were obtained by filing Freedom of Information Act requests. They found that the publications disclosed just a fraction — between 14 and 33 percent — of patients’ so-called “adverse events” as compared to the data summaries.