ABSTRACT
In clinical research, it is often of interest to determine whether the observed clinical results from the original target patient population (e.g., adults) or indication can be generalized (extrapolated) to another similar but different patient population (e.g., pediatrics or elderly) or indication. Under certain assumptions, it can be shown that the effect sizes adjusted for the standard deviation between two patient populations differ by a factor, which is usually referred to as a sensitivity index. If the confidence interval of the sensitivity index falls entirely within a pre-specified equivalence limit, then we conclude that the clinical results from the original target patient population or indication can be generalized (extrapolated) to a similar but different patient population or another indication. In this chapter, the generalizability (extrapolation) of clinical results is assessed by evaluating the sensitivity index under different models that (1) a shift in location parameter (population mean) is random, (2) a shift in scale parameter (population standard deviation) is random, and (3) shifts in both location and scale parameters are random. An example concerning an asthma clinical trial is presented for illustration of the proposed method for analysis of sensitivity index for assessing the generalizability of the observed clinical results from adults to the elderly population. The proposed method can be easily applied to evaluate extrapolation from one indication to another indication in clinical trials.
