Exploration of time-course combinations of outcome scales for use in a global test of stroke recovery

Authors

  • Fraser C. Goldie,

    Corresponding author
    1. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK
    • Correspondence: Fraser C. Goldie*, Institute of Cardiovascular and Medical Sciences, Western Infirmary, University of Glasgow, 44 Church Street, Glasgow G11 6NT, UK.

      E-mail: 0805712G@student.gla.ac.uk

    Search for more papers by this author
  • Rachael L. Fulton,

    1. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK
    Search for more papers by this author
  • Jesse Dawson,

    1. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK
    Search for more papers by this author
  • Erich Bluhmki,

    1. Department of Statistics, Boehringer Ingelheim, Bieberach, Germany
    Search for more papers by this author
  • Kennedy R. Lees,

    1. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK
    Search for more papers by this author
  • the VISTA Collaboration

    Search for more papers by this author
    • Members of VISTA-Acute Steering Committee: K. R. Lees (Chair), A. Alexandrov, P. W. Bath, E. Bluhmki, L. Claesson, J. Curram, S. M. Davis, G. Donnan, H. C. Diener, M. Fisher, B. Gregson, J. Grotta, W. Hacke, M. G. Hennerici, M. Hommel, M. Kaste, P. Lyden, J. Marler, K. Muir, R. Sacco, A. Shuaib, P. Teal, N. G. Wahlgren, S. Warach, and C. Weimar.

  • Conflicts of interest: Fraser C Goldie, Rachael L. Fulton, and Jesse Dawson declare no conflict of interest. Erich Bluhmki is employed by Boehringer Ingelheim. Kennedy R. Lees chairs the DMCs for DIAS-3, -4, -J trials for Lundbeck; the DMC for Grifols; the DMC for NEST-3 (PhotoThera), and the DMC for ATTEST (University of Glasgow). He also chaired the DMC for ICTUS (Ferrer), and is Associate Editor for Stroke (AHA).

Abstract

Background

Clinical trials for acute ischemic stroke treatment require large numbers of participants and are expensive to conduct. Methods that enhance statistical power are therefore desirable.

Aims

We explored whether this can be achieved by a measure incorporating both early and late measures of outcome (e.g. seven-day NIH Stroke Scale combined with 90-day modified Rankin scale).

Methods

We analyzed sensitivity to treatment effect, using proportional odds logistic regression for ordinal scales and generalized estimating equation method for global outcomes, with all analyses adjusted for baseline severity and age. We ran simulations to assess relations between sample size and power for ordinal scales and corresponding global outcomes. We used R version 2·12·1 (R Development Core Team. R Foundation for Statistical Computing, Vienna, Austria) for simulations and SAS 9·2 (SAS Institute Inc., Cary, NC, USA) for all other analyses.

Results

Each scale considered for combination was sensitive to treatment effect in isolation. The mRS90 and NIHSS90 had adjusted odds ratio of 1·56 and 1·62, respectively. Adjusted odds ratio for global outcomes of the combination of mRS90 with NIHSS7 and NIHSS90 with NIHSS7 were 1·69 and 1·73, respectively. The smallest sample sizes required to generate statistical power ≥80% for mRS90, NIHSS7, and global outcomes of mRS90 and NIHSS7 combined and NIHSS90 and NIHSS7 combined were 500, 490, 400, and 380, respectively.

Discussion

When data concerning both early and late outcomes are combined into a global measure, there is increased sensitivity to treatment effect compared with solitary ordinal scales. This delivers a 20% reduction in required sample size at 80% power. Combining early with late outcomes merits further consideration.

Ancillary