Exploring threats to generalisability in a large international rehabilitation trial (AVERT)

Abstract

Objective: The purpose of this paper is to examine potential threats to generalisability of the results of a multicentre randomised controlled trial using data from A Very Early Rehabilitation Trial (AVERT).

Design: AVERT is a prospective, parallel group, assessor-blinded randomised clinical trial. This paper presents data assessing the generalisability of AVERT.

Setting: Acute stroke units at 44 hospitals in 8 countries.

Participants: The first 20,000 patients screened for AVERT, of whom 1158 were recruited and randomised.

Model: We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalisability. As well as comparing the recruited patients with the target population, we also performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment.

Results: The demographics and stroke characteristics of the included patients in the trial were broadly similar to population-based norms, with the exception that AVERT had a greater proportion of men. The most common reason for non-recruitment was late arrival to hospital (ie, >24 h). 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 to 11.65).

Conclusions: 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.

Trial registration number: Australian New Zealand Clinical Trials Registry (ACTRN12606000185561) and Clinicaltrials.gov (NCT01846247).

Keywords: Generalisability; Proximal Similarity Model; Randomised Control Trial; Rehabilitation.

Figure 1

Proximal similarity framework applied to the AVERT trial: a model for conceptualising the dimensions along which the sample of patients may be similar to the target population. Each dimension (person, place and setting and practice) is affected by specific factors which may threaten external validity (AVERT, A Very Early Rehabilitation Trial; ICU, intensive care unit).

Figure 2

Relationship between trial inclusion/exclusion criteria and screening log categories (AVERT, A Very Early Rehabilitation Trial).

Figure 3

Methods of explorative analysis using the first reason for non-recruitment (arrived after 24 h) as an example. Bold boxes indicate data grouping. Analyses were repeated for all 10 reasons for non-recruitment, with four patient demographic and clinical factors. Trial site and month of trial were controlled for in each analysis (ICU, intensive care unit; mRS, modified Rankin Scale).