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Ann Oncol. 2017 Jan 1;28(1):157-162. doi: 10.1093/annonc/mdw538.

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

Author information

1
Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, Canada.
2
Department of Radiation Oncology, Regional Cancer Centre, Trivandrum, Kerala, India.
3
King's Health Partners Comprehensive Cancer Centre, King's College London, Institute of Cancer Policy, London, UK.
4
Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
5
Department of Oncology and Public Health Sciences, Queen's University, Kingston, Canada.

Abstract

Background:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

KEYWORDS:

ESMO-MCBS; benefit; meaningful; value

PMID:
27742650
DOI:
10.1093/annonc/mdw538
[Indexed for MEDLINE]
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