Combining risk difference and risk ratio in noninferiority trials of safety

J Biopharm Stat. 2013;23(1):261-71. doi: 10.1080/10543406.2011.616966.

Abstract

Prior to marketing, the long-term safety profile of a new therapy is often uncertain. One recommendation for premarket safety studies is to compare the new therapy to an appropriate control to determine whether the 95% confidence interval of the risk ratio is entirely less than a prespecified threshold (e.g., 1.8). The restriction to the risk ratio, however, has consequences that may not be intended. Risk difference may be a more appropriate measure of risk in this setting when event rates are very low. We propose using a suitable combination of risk ratio and risk difference in demonstrating noninferiority.

MeSH terms

  • Clinical Trials as Topic / adverse effects*
  • Clinical Trials as Topic / standards*
  • Humans
  • Odds Ratio*
  • Patient Safety / standards*
  • Risk Factors