In designing and analyzing any clinical study, two issues related to patient heterogeneity must be remembered: the effect of chance, and the effect of bias. These issues are addressed by (1) having adequate numbers of patients in the study, and (2) randomizing treatment assignment. Adequate sample size allows the control of the probability of a false-positive result and the probability of a false-negative result. Randomization avoids bias (whether conscious or unconscious); with randomized allocation, predictive factors (known and unknown) tend on average to be balanced between treatment groups.<sup>3 Byar D.P., Simon R.M., Friedewald W.T. , e al. Randomized clinical trials: Perspectives on some recent ideas N Engl J Med 1976 ;  295 : 74-80  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 8 Green S.B. Patient heterogeneity and the need for randomized clinical trials Control Clin Trials 1982 ;  3 : 189-198  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 11 Green S.B., Byar D.P. Using observational data from registries to compare treatments: The fallacy of omnimetrics Stat Med 1984 ;  3 : 361-370  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> Also, randomization provides a valid basis for statistical tests of significance.<sup>3 Byar D.P., Simon R.M., Friedewald W.T. , e al. Randomized clinical trials: Perspectives on some recent ideas N Engl J Med 1976 ;  295 : 74-80  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> These concepts are discussed further later.