The Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) of the US Food and Drug Administration issued a draft Guidance for Industry on non-inferiority trials in 2010, trying to prevent studies that show a novel drug to be non-inferior to an active control but not superior to placebo.3 They have tried to establish that the effect of the novel treatment must fall within the 95 percent confidence interval of the active control (ie, taking the subjective choice of defining non-inferiority out of the researchers’ hands). Unfortunately, as witnessed by many publications, authors are not adhering to that mandate.

More than 500,000 articles were indexed in Medline in 2015. No one will ever read them all. We have to choose selectively what we’ll read. John Ioannidis, a professor of medicine and health research and policy at Stanford University School of Medicine and a professor of statistics at Stanford University School of Humanities and Sciences, once wrote, “Ultimately, over 95 percent of what is published in the medical literature will be proven to be false.”

Non-inferiority trials cannot show a drug is safe. They can prove a drug is inferior while also proving it’s non-inferior. (This still gives me a headache.) They cannot show a medication to be equivalent or superior. All that leaves as justification for doing these studies is marketing, which is why most of these trials are pharmaceutical industry funded. Given all that I have to read to try and keep up, I’ve decided that the non-inferiority trial class of research is a class I can safely put aside—the quality is just too inferior to be worth it.

Dr. Ducharme is editor in chief of the Canadian Journal of Emergency Medicine, clinical professor of medicine at McMaster University in Hamilton, Ontario, and adjunct professor of family medicine at Queen’s University in Kingston, Ontario.

References

1. Schumi J, Wittes JT. Through the looking glass: understanding non-inferiority. Trials website. Accessed Sept. 14, 2016.
2. Saini P, Loke YK, Gamble C, et al. Selective reporting bias of harm outcomes within studies: findings from a cohort of systematic reviews. BMJ. 2014;348:g501.
3. Guidance for Industry Non-Inferiority Clinical Trials 2010. United States Food and Drug Administration website. Accessed Sept. 14, 2016.