Comparing two identically protocolized, multicentre, randomized controlled trials on caregiver-mediated exercises poststroke: Any differences across countries?

Marijn Mulder,Maayken Van Den Berg,Maria Crotty,Erwin E H Van Wegen,Rinske H M Nijland,Judith D M Vloothuis,Gert Kwakkel,Abiodun E Akinwuntan

doi:10.1371/journal.pone.0263013

Abstract

BackgroundThe evidence for rehabilitation interventions poststroke lack sufficient robustness. However, variation in treatment effects across countries have been given little attention.ObjectiveTo compare two identically protocolized trials conducted in different western countries in order to identify factors that may have caused variation in secondary trial outcomes.MethodsComparative study based on individual patient data (N = 129) from two randomized controlled trials, conducted in hospitals and rehabilitation facilities in the Netherlands (N = 66) and Australia (N = 63). Patients with stroke and their caregivers were randomly allocated to an 8-week caregiver-mediated exercises intervention (N = 63; 31 Australian and 32 Dutch) or to a control group (N = 66; 32 Australian and 34 Dutch). Patient characteristics, compliance, usual care and process measures were compared across countries. We examined if study setting significantly moderated the trial outcomes: Hospital Anxiety and Depression Scale, Fatigue Severity Scale and General Self-Efficacy Scale, measured at 8- and 12 weeks follow-up. In addition, we explored if factors that were significantly different across countries caused variation in these trial outcomes.ResultsMost patients suffered an ischemic stroke, were in the subacute phase and participated with their partner. Dutch patients were younger (P = 0.005) and had a lower functional status (P = 0.001). Australian patients were recruited earlier poststroke (P<0.001), spent less time in exercise therapy (P<0.001) and had a shorter length of stay (P<0.001). The level of contamination was higher (P = 0.040) among Dutch controls. No effect modification was observed and trial outcomes did not change after controlling for cross-country differences.ConclusionsThe present study highlighted important clinical differences across countries whilst using an identical study protocol. The observed differences could result in a different potential for recovery and variation in treatment effects across trials. We argue that we can proceed faster to evaluating interventions within international pragmatic trials.

Highlights

Stroke affects approximately 104 million people worldwide and the global incidence of stroke is currently estimated at 11.9 million [1]
We examined if study setting significantly moderated the trial outcomes: Hospital Anxiety and Depression Scale, Fatigue Severity Scale and General Self-Efficacy Scale, measured at 8- and 12 weeks follow-up
We explored if factors that were significantly different across countries caused variation in these trial outcomes

Summary

Introduction

Stroke affects approximately 104 million people worldwide and the global incidence of stroke is currently estimated at 11.9 million [1]. The current evidence for specific rehabilitation interventions poststroke lacks sufficient robustness and is largely based on findings from small, phase II, Randomized Controlled Trials (RCTs) [3,4,5]. Conflicting results across trials is assumed to result from either imprecision of effect estimates or true effect variation as a result of clinical heterogeneity [6]. Clinical heterogeneity refers to systematic differences in the outcomes studied or timing of outcome measurement, characteristics of patients (e.g. age, ethnicity, disease severity), interventions (e.g. content, dose, duration), or study setting (e.g. country, healthcare system, cultural context) [7]. Variation in treatment effects across countries with a different healthcare system and cultural context have been given little attention. Variation in treatment effects across countries have been given little attention

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