Randomized controlled trials (RCTs) are the gold standard for assessing treatment efficacy because their design optimizes internal validity. Participants of these trials are often not representative of patients for whom treatment is delivered in practice, however, so external validity is reduced. Early implementation in patient-centered outcomes research (PCOR) and comparative-effectiveness research (CER) has largely ignored differences in the characteristics of the populations in trial and target population and how care is delivered in these settings. Hybrid studies use data from both trials and real-world practice. This design takes advantage of randomization, thus preserving internal validity, but incorporates real-world (or observational) data, thus enhancing external validity. In addition, little practical guidance exists for implementation by applied researchers.
