Evolution of the randomized clinical trial in the era of precision oncology

Abstract

IMPORTANCE The randomized clinical trial (RCT) in oncology has evolved since its widespread adoption in the 1970s. In recent years, concerns have emerged regarding the use of putative surrogate end points, such as progression-free survival (PFS), and marginal effect sizes. OBJECTIVE To describe contemporary trends in oncology RCTs and compare these findings with earlier eras of RCT design and output. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of systemic therapy RCTs in breast, colorectal, and non-small cell lung cancer published in 7 major journals between 2010 and 2020. This strategy replicates prior work and allows for comparison of trends with RCTs published between 1995 to 2004 and 2005 to 2009. MAIN OUTCOMES AND MEASURES Data on RCT design, funding, results, and reporting were extracted from the published RCT report. Findings from the current period (2010-2020) were compared with data from RCTs published from 1995 to 2004 and 2005 to 2009. Descriptive and bivariate statistics were used to analyze temporal trends. RESULTS The cohort included 298 RCTs (132 [44%] breast, 111 [37%] non-small cell lung cancer, 55 [19%] colorectal cancer). Experimental treatment included molecular inhibitor (171 of 298 [57%]), cytotoxic (83 of 298 [28%]), hormone (15 of 298 [5%]), and immune (24 of 298 [8%]) therapies. Sixty-nine percent (206 of 298) of RCTs were of palliative intent. The most common primary end point is now PFS; this has increased substantially over time (from 0% [0 of 167] to 18% [25 of 137] to 42% [125 of 298]; P