BMJ, doi: 10.1136/bmj.38118.685289.55, (Published 26 May 2004)

PAPERS

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

Steven Joffe ¹, David P Harrington ², Stephen L George ³, Ezekiel J Emanuel ⁴, Lindsay A Budzinski ⁵, Jane C Weeks ⁶

¹ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
² Department of Biostatistical Science, Dana-Farber Cancer Institute, Boston
³ Cancer and Leukemia Group B Statistical Center, Durham, NC 27710, USA
⁴ Department of Clinical Bioethics, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1156, USA
⁵ Lesley College, Cambridge, MA 02138, USA
⁶ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston

Objective To assess whether publicly funded adult cancer trials satisfy the uncertainty principle, which states that physicians should enrol 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.

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(Accepted 2 April 2004)
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