The fragility of cardiovascular clinical trial results.
BACKGROUND
Clinical trials that have their prospective analysis plan altered are difficult to interpret.


RESULTS
After providing 4 examples of problematic trial results that have had their findings reversed, the necessity of a fixed research protocol is developed. Investigators generally wish to extend the results from their research sample to the larger population; however, this delicate extension is complicated by the presence of sampling error. No computational or statistical tools can remove sampling error--the most that researchers can do is to provide to the medical and regulatory communities a measure of the distorting effect that sampling error can produce. Investigators accomplish this by providing an estimate of how likely it is that the population produced a misleading sample for them to study. However, studies in which the data determine the analysis plan damage these estimators. When they are damaged, these estimators produce untrustworthy assessments of the degree to which the study results reflect the population findings.


CONCLUSIONS
The way to avoid these complications is to design the experiment carefully, then carefully execute the experiment as it was designed.
Moyé
Lemuel A
LA
University of Texas School of Public Health, Houston, Texas 77030, USA.
Deswal
Anita
A
D002317:Cardiovascular Agents / Q000592:standards / Q000627:therapeutic use*; D004311:Double-Blind Method; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012107:Research Design / Q000592:standards; D014481:United States
D002317:Cardiovascular Agents