B Seruga1, P C Hertz1, L Wang2, C M Booth3, D W Cescon1, M Krzyzanowska1, I F Tannock4. 1. Departments of Medical Oncology and Hematology. 2. Biostatistics, Princess Margaret Hospital and University of Toronto, Toronto. 3. National Cancer Institute of Canada, Kingston, Ontario, Canada. 4. Departments of Medical Oncology and Hematology. Electronic address: ian.tannock@uhn.on.ca.
Abstract
BACKGROUND: Phase III randomized clinical trials (RCTs) have become larger and are powered to detect small absolute benefits. Temporal changes in absolute benefits of experimental medical therapies reported in RCTs are unknown. METHODS: We identified all RCTs with sample size > or =200 evaluating experimental medical therapies for breast and colorectal cancer published from 1975 to 2007. We assessed changes over three decades in absolute differences in time-to-event end points between experimental and control arms by (i) the usual method (i.e. at one point) and (ii) as the area between time-to-event curves up to a predefined time. RESULTS: We identified 236 eligible RCTs of which 57% (N = 135) evaluated adjuvant treatments. Experimental treatments became more often compared with active treatments (48% versus 59% versus 81%; P < 0.0001). Median absolute benefits of experimental adjuvant treatments decreased but outcomes in control arms improved with time. For RCTs evaluating metastatic disease, there were no changes in absolute benefit over time but incremental monthly costs of new approved treatments increased with time by 100-fold (P < 0.0001). CONCLUSION: In RCTs of breast and colorectal cancer, new effective adjuvant treatments show decreasing absolute benefit, while new treatments of metastatic disease show unchanging levels of benefit at rapidly escalating costs.
BACKGROUND: Phase III randomized clinical trials (RCTs) have become larger and are powered to detect small absolute benefits. Temporal changes in absolute benefits of experimental medical therapies reported in RCTs are unknown. METHODS: We identified all RCTs with sample size > or =200 evaluating experimental medical therapies for breast and colorectal cancer published from 1975 to 2007. We assessed changes over three decades in absolute differences in time-to-event end points between experimental and control arms by (i) the usual method (i.e. at one point) and (ii) as the area between time-to-event curves up to a predefined time. RESULTS: We identified 236 eligible RCTs of which 57% (N = 135) evaluated adjuvant treatments. Experimental treatments became more often compared with active treatments (48% versus 59% versus 81%; P < 0.0001). Median absolute benefits of experimental adjuvant treatments decreased but outcomes in control arms improved with time. For RCTs evaluating metastatic disease, there were no changes in absolute benefit over time but incremental monthly costs of new approved treatments increased with time by 100-fold (P < 0.0001). CONCLUSION: In RCTs of breast and colorectal cancer, new effective adjuvant treatments show decreasing absolute benefit, while new treatments of metastatic disease show unchanging levels of benefit at rapidly escalating costs.
Authors: J Connor Wells; Adam Fundytus; Shubham Sharma; Wilma M Hopman; Joseph C Del Paggio; Bishal Gyawali; Deborah Mukherji; Nazik Hammad; C S Pramesh; Ajay Aggarwal; Richard Sullivan; Christopher M Booth Journal: Curr Oncol Date: 2022-04-07 Impact factor: 3.109