How generalizable are rehabilitation trials? The results of a large international rehabilitation trial (AVERT).

Introduction: Generalizability of the results of randomized controlled trials (RCTs) could be compromised when recruitment is poor. We aimed to examine potential threats to generalizability of a multicenter RCT using data from A Very Early Rehabilitation Trial (AVERT). Method(s): AVERT is a prospective, parallel group, assessor-blinded, randomized, clinical trial. The trial setting is acute stroke units at 44 hospitals in 8 countries. Among the first 20,000 patients screened for AVERT, 1158 were recruited and randomized. We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalizability. As well as comparing the recruited patients to the target population, we performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment. Result(s): The demographics and stroke characteristics of the included patients in the trial were broadly similar to population based norms, with the exception that men featured more often in those recruited (63%) than not recruited (53%, p<0.001). The most common reason for non-recruitment was late arrival to hospital (i.e. >24 hours). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95%CI: 9.27-11.65). Conclusion(s): A model which explores person, place and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials.