The Survey of Non-inferiority Trials for Cancer Drugs to Analyze Their Trends Including Guidelines

Abstract

 Background: Non-inferiority (NI) clinical trials are designed to provide the benefits such as enhanced safety, treatment convenience, etc., by demonstrating that the experimental arm is not clinically inferior to the comparator arm statistically. In the area of oncology, the NI trials would provide better treatment options for medical doctors and patients though few anti-cancer drugs have been approved by NI trial despite no opposition in guideline to drug registration by NI. Here, we study the present status of NI trials to clarify the influence of regulation and the intention of investigators and pharmaceutical companies. Methods: We investigated published papers by using PubMed from the search term ‘(tumor OR cancer) AND (non-inferior OR non-inferiority) and (survival) and (species; human) and (published; until Dec 31, 2015)'. 115 papers passed after exclusion criteria were analyzed in terms of regions, sponsors, and drug types. Results: 70% of NI trials was solely conducted in regions, the other was globally done, and only 4% in North America. 65% was categorized as investigator initiated studies (IIS). Eighteen trials were conducted for non-approved drugs and three novel drugs were approved. Conclusions: Each regional guideline describes NI trial differently, and the same tendency of the regional difference in comparison of number of NI trial was confirmed. The majority of NI trials are regional IIS. Approval of non-approved drugs by NI trial indicates that the guidelines do not oppose the design of NI trials for registration.