Generalizability of cognitive results from clinical trial participants to an older adult population: Addressing external validity.

Abstract

Study inclusion criteria and recruitment practices limit the generalizability of randomized-controlled trial (RCT) results. Statistical modeling could enhance generalizability of outcomes. To illustrate this, the cognition-depression relationship was assessed with and without adjustment relative to the target population of older women. Randomized participants from four RCTs and non-randomized participants from two cohorts were included in this study. Prediction models estimated probability of being randomized into trials from target populations. These probabilities were used for inverse odds weighting relative to target populations. Weighted linear regression was used to assess the depression-cognition relationship. There was no depression-cognition relationship in the combined randomized sample. After applying weights relative to a representative cohort, negative relationships were observed. After applying weights relative to a non-representative cohort, bias of estimates increased. Quantitative approaches to transportability using representative samples may explain the absence of a-priori established relationships in RCTs.