Functional Outcome Measures in Contemporary Stroke Trials

Various instruments are used to describe poststroke functional outcome, with limited consensus as to optimal end-point for clinical trial use. Many of the popular assessment tools are administered with little formal guidance on best practice. Thus there is potential for substantial heterogeneity in functional outcome assessment poststroke, with consequent effects on trial quality. We examined functional assessment methodology in recent stroke trials. We reviewed six journals representing high-impact international publications in the fields of: stroke (Stroke); neurology (Neurology, Lancet Neurology) and internal medicine (Lancet, New England Journal Medicine; Journal of the American Medical Association). Journals were hand searched for all interventional studies in stroke patients between 2001 and 2006 inclusive. Chosen manuscripts were then analyzed for outcome assessment methodology. We identified 126 trials, comprising a mix of early hypothesis generating studies through to multicentre trials (phase I: four trials; phase II: 46 trials; phase III: 20 trials; noninvestigational medicinal product studies: 56 trials). The median number of patients assessed per trial was 100. Across the trials, 47 different outcome measures were used. One hundred trials had functional outcome assessment as the primary study end-point. The median number of outcome measures was two per trial (range 1–9). The modified Rankin scale was the most prevalent outcome assessment (64·3%); followed by Barthel index (40·5%). A minority of trials (33·3%) provided full details on outcome assessment methodology. Among these trials there was substantial heterogeneity in data collection procedures. There is heterogeneity in the use of functional outcome measures in stroke trials. This compromises comparison and meta-analysis. Trialists continue to use poorly validated approaches to outcome assessment. Given the potential effects on data quality, explicit description of methodology should be mandatory for all trials and rigour is desirable.

[1]  R. Bloch,et al.  Interobserver agreement for the assessment of handicap in stroke patients. , 1988, Stroke.

[2]  J. De Keyser,et al.  Use of the Barthel index and modified Rankin scale in acute stroke trials. , 1999, Stroke.

[3]  J. Coast,et al.  Inter-rater reliability of the Barthel ADL Index: how does a researcher compare to a nurse? , 2000, Clinical rehabilitation.

[4]  D. Liebeskind,et al.  Acute ischemic stroke trials. , 2001, Stroke.

[5]  D. Liebeskind,et al.  Trends in Acute Ischemic Stroke Trials Through the 20th Century , 2001, Stroke.

[6]  P. Duncan,et al.  Stroke Recovery Profile and the Modified Rankin Assessment , 2001, Neuroepidemiology.

[7]  U. Schulz,et al.  Improving the Assessment of Outcomes in Stroke: Use of a Structured Interview to Assign Grades on the Modified Rankin Scale , 2002, Stroke.

[8]  Jan Potter,et al.  Reliability of the Modified Rankin Scale Across Multiple Raters: Benefits of a Structured Interview , 2005, Stroke.

[9]  J. Grotta,et al.  NIHSS Training and Certification Using a New Digital Video Disk Is Reliable , 2005, Stroke.

[10]  Christopher J Weir,et al.  Comparison of the National Institutes of Health Stroke Scale With Disability Outcome Measures in Acute Stroke Trials , 2005, Stroke.

[11]  M. Flaster,et al.  tPA by telephone: Extending the benefits of a comprehensive stroke center , 2005, Neurology.

[12]  Jeffrey L Saver,et al.  Frequency and Determinants of Nonpublication of Research in the Stroke Literature , 2006, Stroke.

[13]  Vincent M. Vacca,et al.  Acute ischemic stroke. , 2006, Nursing.

[14]  Y. Ohashi,et al.  Modified Rankin Scale with Expanded Guidance Scheme and Interview Questionnaire: Interrater Agreement and Reproducibility of Assessment , 2006, Cerebrovascular Diseases.

[15]  Scott E Kasner,et al.  Clinical interpretation and use of stroke scales , 2006, The Lancet Neurology.

[16]  M. Walters,et al.  Initial Experience of a Digital Training Resource for Modified Rankin Scale Assessment in Clinical Trials , 2007, Stroke.

[17]  A. Boonen,et al.  The international classification for functioning, disability and health , 2007, Clinical Rheumatology.

[18]  S. Pocock,et al.  Can We Improve the Statistical Analysis of Stroke Trials?: Statistical Reanalysis of Functional Outcomes in Stroke Trials , 2007, Stroke.

[19]  J. Saver.  Novel End Point Analytic Techniques and Interpreting Shifts Across the Entire Range of Outcome Scales in Acute Stroke Trials , 2007, Stroke.

[20]  Marion F Walker,et al.  Stroke rehabilitation: evidence-based or evidence-tinged? , 2007, Journal of rehabilitation medicine.

[21]  S. Warach,et al.  Recommendations from the STAIR V meeting on acute stroke trials, technology and outcomes. , 2007, Stroke.

[22]  L. Gray.  Optimising the analysis of stroke trials , 2008 .

[23]  Terence J Quinn,et al.  Exploring the Reliability of the Modified Rankin Scale , 2009, Stroke.