title: Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?
abstract: The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit.
  
  
  
  RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS.
  
  
  
  About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds.
  
  
  
  Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs.
authors.affiliation: Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, Canada.
authors.forename: J C
authors.initials: JC
authors.lastname: Del Paggio
authors.affiliation: Department of Radiation Oncology, Regional Cancer Centre, Trivandrum, Kerala, India.
authors.forename: B
authors.initials: B
authors.lastname: Azariah
authors.affiliation: King's Health Partners Comprehensive Cancer Centre, King's College London, Institute of Cancer Policy, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Sullivan
authors.affiliation: Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, Canada.
authors.forename: W M
authors.initials: WM
authors.lastname: Hopman
authors.affiliation: Department of Radiation Oncology, Regional Cancer Centre, Trivandrum, Kerala, India.
authors.forename: F V
authors.initials: FV
authors.lastname: James
authors.affiliation: Department of Radiation Oncology, Regional Cancer Centre, Trivandrum, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Roshni
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: I F
authors.initials: IF
authors.lastname: Tannock
authors.affiliation: Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, Canada.|Department of Oncology and Public Health Sciences, Queen's University, Kingston, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Booth
mesh_terms: D005060:Europe; D006801:Humans; D008495:Medical Oncology / Q000592:standards*; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D012955:Societies, Medical
keywords: ESMO-MCBS; benefit; meaningful; value