This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Drug Therapy, Other  • Statistics and Research Methods  • Prognosis/ Outcomes  • Oncology  • Alert me on articles by topic

New Cancer Treatment Successes Identified in Phase 3 Randomized Controlled Trials Conducted by the National Cancer Institute–Sponsored Cooperative Oncology Groups, 1955 to 2006

Benjamin Djulbegovic, MD, PhD; Ambuj Kumar, MD, MPH; Heloisa P. Soares, MD; Iztok Hozo, PhD; Gerold Bepler, MD, PhD; Mike Clarke, DPhil; Charles L. Bennett, MD, PhD, MPP

Arch Intern Med. 2008;168(6):632-642.

Background  The evaluation of research output, such as estimation of the proportion of treatment successes, is of ethical, scientific, and public importance but has rarely been evaluated systematically. We assessed how often experimental cancer treatments that undergo testing in randomized clinical trials (RCTs) result in discovery of successful new interventions.

Methods  We extracted data from all completed (published and unpublished) phase 3 RCTs conducted by the National Cancer Institute cooperative groups since their inception in 1955. Therapeutic successes were determined by (1) assessing the proportion of statistically significant trials favoring new or standard treatments, (2) determining the proportion of the trials in which new treatments were considered superior to standard treatments according to the original researchers, and (3) quantitatively synthesizing data for main clinical outcomes (overall and event-free survival).

Results  Data from 624 trials (781 randomized comparisons) involving 216 451 patients were analyzed. In all, 30% of trials had statistically significant results, of which new interventions were superior to established treatments in 80% of trials. The original researchers judged that the risk-benefit profile favored new treatments in 41% of comparisons (316 of 766). Hazard ratios for overall and event-free survival, available for 614 comparisons, were 0.95 (99% confidence interval [CI], 0.93-0.98) and 0.90 (99% CI, 0.87- 0.93), respectively, slightly favoring new treatments. Breakthrough interventions were discovered in 15% of trials.

Conclusions  Approximately 25% to 50% of new cancer treatments that reach the stage of assessment in RCTs will prove successful. The pattern of successes has become more stable over time. The results are consistent with the hypothesis that the ethical principle of equipoise defines limits of discoverability in clinical research and ultimately drives therapeutic advances in clinical medicine.

Author Affiliation: H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa (Drs Djulbegovic, Kumar, Soares, and Bepler); Department of Mathematics, Indiana University Northwest, Gary (Dr Hozo); UK Cochrane Centre, Oxford, England (Dr Clarke); and Northwestern University Feinberg School of Medicine and Veterans Affairs Center for Management of Complex Chronic Conditions, Chicago, Illinois (Dr Bennett).