Evaluation of designs for clinical trials of neuroprotective agents in head injury. European Brain Injury Consortium.
In a study involving the statistical modeling of potential head injury trials, we explore approaches to trial design that could enhance their power to detect treatment-related effects on clinical outcome. The study uses a survey organized by the European Brain Injury Consortium of over 1,000 head-injured patients to characterize the population from which trial participants can be selected. A variety of models are postulated for the effects of "neuroprotective" treatment on outcome, and their interaction with a range of strategies for targeting patients for inclusion in the trial is evaluated. A very simple strategy of targeting patients with an intermediate prognosis was found to allow a reduction in sample size by 30%, with no reduction in statistical power. This paper illustrates an important methodology for studying the characteristics of competing trial designs.
Machado
S G
SG
Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland, USA.
Murray
G D
GD
Teasdale
G M
GM
D000293:Adolescent; D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D006259:Craniocerebral Trauma / Q000188:drug therapy*; D005069:Evaluation Studies as Topic; D006801:Humans; D008875:Middle Aged; D008962:Models, Theoretical; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010560:Personnel Selection; D011379:Prognosis; D012107:Research Design / Q000592:standards; D013223:Statistics as Topic
D018696:Neuroprotective Agents