Have randomized controlled trials of neuroprotective drugs been underpowered? An illustration of three statistical principles - PubMed (original) (raw)
Have randomized controlled trials of neuroprotective drugs been underpowered? An illustration of three statistical principles
G P Samsa et al. Stroke. 2001 Mar.
Abstract
Background and purpose: The results of phase III trials of neuroprotective drugs for acute ischemic stroke have been disappointing. We examine the question of whether these trials may have been underpowered.
Methods: Computer simulations were based on the binomial distribution.
Results: We illustrate that even small overestimates of the efficacy of an intervention can lead to a serious reduction in statistical power, that the use of data from phase II studies tends to lead to such overestimation, and that a minimum clinically important difference derived with cost-effectiveness modeling techniques is considerably smaller than might be suggested by intuition.
Conclusions: We recommend placing more emphasis on minimum clinically important differences when planning stroke trials, with these differences being derived from an assessment of the public health impact obtained in conjunction with the use of epidemiological and cost-effectiveness models. Even small benefits, when averaged over a sufficiently large number of cases, will, in total, accrue to a large positive impact on the public health.
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