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Randomised Controlled Trials (RCTs) produce relative treatment effects that have high internal validity. However they may suffer from lack of external validity when used as inputs to cost-effectiveness analyses (CEA). If differences in RCT and CEA populations can be described by a set of observed covariates, then it is possible to adjust for these differences. A common approach is to estimate effects at the mean covariate values. For non-linear models this introduces bias, even if the RCT and CEA populations are comparable.

External validity of rct evidence in cost-effectiveness analyses. A review of recent technology appraisals for nice and proposed methods of adjustment