Randomized and nonrandomized clinical studies: statistical considerations.

THE article in this issue of ANESTHESIOLOGY by O'Hara et aL1 provides a good opportunity to review different clinical study designs and statistical issues associated with analyzing data from randomized and nonrandomized comparative studies. Statistics are necessary to analyze clinical data because the response to intervention usually varies widely among patients.' Most biostatisticians favor the use of randomized trials to compare interventions. To understand why, consider the question posed by O'Hara et aZ.:' whether either of two interventions-regional or general anesthesia-led to greater mortality in hip fracture patients. Ideally one would compare mortality after all patients received regional, and then, after turning back the clock, after the same patients all received general. Such a study design would eliminate the possibility that different outcomes in regional or general resulted from differences inherent to the patients. Of course, this study design is impossible to implement, but it sets a standard for evaluation. Randomly assigning subjects to regional or general anesthesia comes closest to the ideal situation. Instead of comparing regional and general in the same subjects, a randomized trial compares regional and general in subjects with the same distribution of observed and unobserved risk factors. In other words, in a randomized trial, observed or unobserved risk factors would have the same chance of occurrence in subjects who receive regional anesthesia as in subjects who receive general. In