Systematic review of evidence on thrombolytic therapy for acute ischaemic stroke
CommentThe concept of trial heterogeneity is interesting and its application is well illustrated by this review.
When a number of trials studying the same question are performed, they are unlikely to have the exact same outcomes, simply on the basis of sampling error. Just as a small difference between two treatment groups may be due to chance alone, a difference between two trials may also be due to chance. What we need to know is whether discrepancies between trials are greater than we would expect by chance.
A formal analysis of heterogeneity, as was performed in this review, uses statistical tests (such as Chi-square) to determine whether the results of various trials are more different than one would expect by chance alone. If so, further exploratory analyses can help elucidate the specific factors that are at the root of these differences.
Such formal analysis of heterogeneity is one difference between a systematic review such as this one and a more traditional literature review. In the more traditional review, the reviewer will look at a number of trials and try to explain perceived differences between them. This is by nature a very subjective exercise.
Simply inspecting the data from the trials presented here, one would be tempted to concentrate on the differences between trials that showed benefit and those that did not. The difference between these groups seems to be related mainly to the use of streptokinase or tPA. Formal analysis, on the other hand, forces one to consider not only differences between trials that show an effect and those that don't, but also to examine trials that show a markedly different degree of effect. It also reveals that the choice of thrombolytic agent may not be the primary determinant of outcome.
The review presented here concludes that there is insufficient evidence to state that streptokinase is worse than tPA. This may well be the case, but three trials of streptokinase in acute stroke were halted before completion because of safety concerns. If the authors had obtained individual patient data and had been able to show that the entire benefit of tPA over streptokinase was accounted for by other factors (time to reperfusion, use of antiplatelet agents, baseline risk), it might be justifiable to include streptokinase as a treatment arm in future trials. Until such data are obtained, however, it seems unlikely that streptokinase will be tested on a large scale for acute ischemic stroke.
September 30, 1997
ReferencesReferences related to this article from the NLM's PubMed database.
Reader CommentsDate: Mon, 13 Oct 97
From: Masatoshi Matsumoto <firstname.lastname@example.org>
I am a Japanese resident of family practice. I think the heterogeneity of RCTs in this review implies no conclusion about the use of thrombolytic agents for ischemic stroke. A good RCT which is not biased and has a large number of samples should be done in the near future.
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