What's new in trial design: propensity scores, equivalence, and non-inferiority

Abstract

Recent modifications to traditional clinical research designs include propensity scores, equivalence, and non-inferiority trials, as well as greater use of pooled endpoints for primary outcome measures. Each of these innovations offers benefits, but they have been misused. Propensity score techniques can account for imbalance in treatment group allocation to provide more accurate estimates of benefit or risk. Unlike clinical trials, they typically represent real world, everyday practice and so their findings may in fact be less biased. Equivalence and non-inferiority designs can tailor clinical trials to address clinically meaningful questions: Is a proposed new technique at least as good as current treatment? Pooled endpoints can summarize a range of beneficial outcomes as well as reduce the required sample size. A clearer understanding of bias and confounding, and the interpretation of the 95% confidence interval of the estimated treatment effect are central to proper use of these techniques.

Figure 1.

Six scenarios describing results of a clinical trial comparing two treatment groups. Each displays estimated treatment difference and its 95% CI, p-value, strength of evidence, and suggested phraseology to use in conclusions. For non-inferiority scenarios, non-inferiority margin delta (?) is shown, and pNI is the p-value for the test of non-inferiority. Reproduced with permission from The Lancet 2009;373:1926–8 (27).