Measuring Outcome in Acute Stroke Trials
To the Editor:
We welcome the article of Sulter and colleagues1 in the August edition of your journal, in which they investigate the use of the Barthel Index (BI) and Modified Rankin scale (MRS) in acute stroke trials.1 The lack of objectivity in defining what is a favorable outcome lends itself to redefining the primary end point should the results of a clinical trial not meet with expectations. The temptation to move the goal posts (MRS <1 to <2) is a clear indication of the ambiguity of the end point.
In the event of a safe, simple, and effective treatment for stroke being discovered, it is likely that this will be given to patients with significant levels of comorbidity and preexisting disability—stroke related or otherwise. In this situation it will be much more difficult to evaluate the clinical effectiveness of the treatment, and use of “poor outcome” as a clinical end point becomes much more relevant. It could be further argued that since the principal objective of stroke treatment is to reduce disability and dependency, it is the avoidance of this poor outcome that is of paramount importance. The clinical relevance of a stroke treatment trial inevitably reflects the trial population; if a highly selected group of patients with no previous disability is selected (MRS=0), it is impossible to be sure what a favourable outcome for such an individual would be. Conversely, we believe there would be little doubt among patients and their carers what a poor outcome would be: death, institutionalization, MRS >3, or BI <60. Dichotomizing outcome to a 3-month MRS of <1 or <2 is even more subjective. In a more pragmatic acute stroke trial (for example, trials of acute stroke unit care or intervention trials for raised glucose or temperature), the inclusion of patients with prior disability (Rankin Scores <3) makes the “good outcome” even less appropriate and emphasizes the practical relevance of the poor outcome. Interestingly, in designing the Glucose Insulin in Stroke Trial (GIST), we sought to determine the effectiveness of maintaining euglycemia in acute stroke in a representative population of patients who might present to any acute stroke unit.2 To recruit patients with prior disability (Rankin <3), we recognized the inappropriateness of the good outcome and opted for poor outcome, defined as death or MRS >3.
In the United Kingdom the results of the Stroke Unit Trialists’ Collaboration (reduced dependency, institutionalization, and mortality) have led to widespread introduction of organized stroke care.3 We believe that the use of a poor outcome in stroke trials deserves wider recognition for its clinical, practical, scientific, and ethical relevance.
- Copyright © 2000 by American Heart Association
Sulter G, Steen C, Dekeyser J. Use of the Barthel Index and Modified Rankin Scale in acute stroke trials. Stroke. 1999;30:1538–1541.
Scott JF, Robinson GM, O’Connell JE, Alberti KGMM, Gray CS. Glucose potassium insulin (GKI) infusions in the treatment of acute stroke patients with mild to moderate hyperglycemia (the GIST Trial). Stroke. 1999;30:739–799.
The Stroke Unit Trialists’ Collaboration. Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. BMJ. 1997;314:1151–1159.