Outcomes validity and reliability of the modified Rankin scale: Implications for stroke clinical trials - A literature review and synthesis

Background and Purpose - The modified Rankin scale ( mRS), a clinician-reported measure of global disability, is widely applied for evaluating stroke patient outcomes and as an end point in randomized clinical trials. Extensive evidence on the validity of the mRS exists across a large but fragmented literature. As new treatments for acute ischemic stroke are submitted for agency approval, an appreciation of the mRS's attributes, specifically its relationship to other stroke evaluation scales, would be valuable for decision-makers to properly assess the impact of a new drug on treatment paradigms. The purpose of this report is to assemble and systematically assess the properties of the mRS to provide decision-makers with pertinent evaluative information. Methods - A Medline search was conducted to identify reports in the peer-reviewed medical literature ( 1957 - 2006) that provide information on the structure, validation, scoring, and psychometric properties of the mRS and its use in clinical trials. The selection of articles was based on defined criteria that included relevance, study design and use of appropriate statistical methods. Results - Of 224 articles identified by the literature search, 50 were selected for detailed assessment. Inter-rater reliability with the mRS is moderate and improves with structured interviews (kappa 0.56 versus 0.78); strong test-re-test reliability (kappa=0.81 to 0.95) has been reported. Numerous studies demonstrate the construct validity of the mRS by its relationships to physiological indicators such as stroke type, lesion size, perfusion and neurological impairment. Convergent validity between the mRS and other disability scales is well documented. Patient comorbidities and socioeconomic factors should be considered in properly applying and interpreting the mRS. Recent analyses suggest that randomized clinical trials of acute stroke treatments may require a smaller sample size if the mRS is used as a primary end point rather than the Barthel Index. Conclusions - Multiple types of evidence attest to the validity and reliability of the mRS. The reported data support the view that the mRS is a valuable instrument for assessing the impact of new stroke treatments.