Have randomized controlled trials of neuroprotective drugs been underpowered? An illustration of three statistical principles.
OBJECTIVE
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.
Center for Clinical Health Policy Research, Department of Medicine, Duke University Medical Center, Durham, NC 27705, USA. samsa001@mc.duke.edu
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D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D015233:Models, Statistical; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012107:Research Design / Q000592:standards*; D018401:Sample Size; D012680:Sensitivity and Specificity; D013223:Statistics as Topic / Q000379:methods; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
D018696:Neuroprotective Agents