Satisfaction of the uncertainty principle in cancer clinical trials: retrospective cohort analysis.

OBJECTIVE: To assess whether publicly funded adult cancer trials satisfy the uncertainty principle, which states that physicians should enroll a patient in a trial only if they are substantially uncertain which of the treatments in the trial is most appropriate for the patient. This principle is violated if trials systematically favour either the experimental or the standard treatment. DESIGN: Retrospective cohort study of completed cancer trials, with randomisation as the unit of analysis. SETTING: Two cooperative research groups in the United States. STUDIES INCLUDED: 93 phase III randomised trials (103 randomisations) that completed recruitment of patients between 1981 and 1995. MAIN OUTCOME MEASURES: Whether the randomisation favoured the experimental treatment, the standard treatment, or neither treatment; effect size (outcome of the experimental treatment compared with outcome of the standard treatment) for each randomisation. RESULTS: Three randomisations (3%) favoured the standard treatment, 70 (68%) found no significant difference between treatments, and 30 (29%) favoured the experimental treatment. The average effect size was 1.20 (95% confidence interval 1.13 to 1.28), reflecting a slight advantage for the experimental treatment. CONCLUSIONS: In cooperative group trials in adults with cancer, there is a measurable average improvement in disease control associated with assignment to the experimental rather than the standard arm. However, the heterogeneity of outcomes and the small magnitude of the advantage suggest that, as a group, these trials satisfy the uncertainty principle.

Duke Scholars

Author Stephen L. George Biostatistics & Bioinformatics, Division of Biostatistics