Weight loss drug risks under-reported

Adverse events associated with the weight-loss drug orlistat are often understated in trial reports, according to an analysis published today.

Orlistat is sold as a prescription drug as Xenical, and over-the-counter as Alli. It was approved in Europe in 1998 and is widely used globally.

Dr Jeppe Schroll and colleagues at the Nordic Cochrane Centre in Copenhagen, Denmark, set out to understand the accuracy and potential bias, in reporting for trials of orlistat.

In PLoS Medicine, they write that detailed information on adverse events in trials is usually considered confidential.

The team acquired clinical study reports from seven randomised controlled trials from the European Medicines Agency via the Freedom of Information Act.

This showed that none of the protocols or clinical study reports contained instructions for investigators on how to ask participants about adverse events. Only 3% to 33% of the total number of investigator-reported adverse events were reported in the trial’s publications.

The authors write: "For one trial, we identified an additional 1,318 adverse events that were not listed or mentioned in the clinical study report itself but could be identified through manually counting individual adverse events reported in an appendix."

They add: "We discovered that the majority of patients had multiple episodes of the same adverse event that were only counted once. We also discovered that participants treated with orlistat experienced twice as many days with adverse events as participants treated with placebo.

"None of this was stated in the clinical study reports or in the published paper."

Overall, they conclude that reports of these trials seemed to have systematically understated adverse events. They call for protocols and clinical study reports to be routinely published.

Schroll, J. B. et al. Assessment of Adverse Events in Protocols, Clinical Study Reports, and Published Papers of Trials of Orlistat: A Document Analysis. PLoS Medicine 16 August 2016; doi:10.1371/journal.pmed.1002101 [abstract]