Originally published as JCO Early Release 10.1200/JCO.2008.16.5456 on October 27 2008

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Evolution of the Randomized Controlled Trial in Oncology Over Three Decades

Christopher M. Booth, David W. Cescon, Lisa Wang, Ian F. Tannock, Monika K. Krzyzanowska

From the National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston; and Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada

Corresponding author: Monika Krzyzanowska, MD, MPH, Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Ave, Toronto, ON, M5G 2M9, Canada; e-mail: monika.krzyzanowska{at}uhn.on.ca

Purpose The randomized controlled trial (RCT) is the gold standard for establishing new therapies in clinical oncology. Here we document changes with time in design, sponsorship, and outcomes of oncology RCTs.

Methods Reports of RCTs evaluating systemic therapy for breast, colorectal (CRC), and non–small-cell lung cancer (NSCLC) published 1975 to 2004 in six major journals were reviewed. Two authors abstracted data regarding trial design, results, and conclusions. Conclusions of authors were graded using a 7-point Likert scale. For each study the effect size for the primary end point was converted to a summary measure.

Results A total of 321 eligible RCTs were included (48% breast, 24% CRC, 28% NSCLC). Over time, the number and size of RCTs increased considerably. For-profit/mixed sponsorship increased substantially during the study period (4% to 57%; P < .001). There was increasing use of time-to-event measures (39% to 78%) and decreasing use of response rate (54% to 14%) as primary end point (P < .001). Effect size remained stable over the study period. Authors have become more likely to strongly endorse the experimental arm (P = .017). A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent (odds ratio [OR] = 19.6, 95% CI, 8.9 to 43.1, and OR = 3.5, 95% CI, 1.6 to 7.5, respectively).

Conclusion RCTs in oncology have become larger and are more likely to be sponsored by industry. Authors of modern RCTs are more likely to strongly endorse novel therapies. For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm.

published online ahead of print at www.jco.org on October 27, 2008

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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