Bishal Gyawali, MD, PhD Department of Medicine Brigham and Women's Hospital

More Cancer Drugs Approved Using Non-Inferiority Trials: What Are the Problems with This Approach? Interview with:

Bishal Gyawali, MD, PhD Department of Medicine Brigham and Women's Hospital

Dr. Bishal Gyawali

Bishal Gyawali, MD, PhD
Department of Medicine
Brigham and Women’s Hospital What is the background for this study?

Response: Cancer drugs are prescribed to the patients based on results from trials. Usually, these are superiority trials meaning the cancer drugs prove that they are better than the treatment we already have.

Recently, more and more cancer drugs are approved on the basis of non-inferiority trials. In these trials, the cancer drugs only prove that they are not worse than the treatment we already have ( instead of proving they are better). Such an approach is considered justified if the new drug provides any other benefit such as lower cost, easy to administer or improved quality of life. What are the main findings?

Response: Our research uncovers a number of problems with such trials. We find that in many such cases, using non-inferiority design is not justified. We also found that industry funding of trials was associated with lack of justification. Furthermore, what constituted “not worse” was arbitrary and varied across these trials. What should readers take away from your report?

Response: Because if s/he has cancer, she maybe receiving one of those drugs. A cancer patient should ask whether the drug s/he is receiving is proven superior or only non-inferior. If non-inferior, what was the margin of non-inferiority and consider whether that non-inferiority (not worse) is acceptable. What recommendations do you have for future research as a result of this work? 

Response: This research is significant because it urges regulatory agencies to approve cancer drugs based on NI trials only when non-inferiority is justified. It also recommends REBs(ethics board) to approve such non-inferiority design trials only when such a design is justified Is there anything else you would like to add? 

Response:  Authorities should take steps to

  • a) make sure the non-inferiority trials are justified in their design and
  • b) get patients’ input to define the criteria for non-inferiority 


Gyawali B, Tessema FA, Jung EH, Kesselheim AS. Assessing the Justification, Funding, Success, and Survival Outcomes of Randomized Noninferiority Trials of Cancer DrugsA Systematic Review and Pooled AnalysisJAMA Netw Open. Published online August 30, 20192(8):e199570. doi:10.1001/jamanetworkopen.2019.9570



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Last Updated on September 4, 2019 by Marie Benz MD FAAD