Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study

Ciani, Oriana, Buyse, Marc, Garside, Ruth, Pavey, Toby, Stein, Ken, Sterne, Jonathan A. C. and Taylor, Rod S. (2013) Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study. BMJ, 346 7898: . doi:10.1136/bmj.f457


Author Ciani, Oriana
Buyse, Marc
Garside, Ruth
Pavey, Toby
Stein, Ken
Sterne, Jonathan A. C.
Taylor, Rod S.
Title Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study
Journal name BMJ
ISSN 1756-1833
0959-535X
Publication date 2013-01-29
Sub-type Article (original research)
DOI 10.1136/bmj.f457
Open Access Status DOI
Volume 346
Issue 7898
Total pages 12
Place of publication London, United Kingdom
Publisher BMJ Group
Collection year 2014
Language eng
Formatted abstract
Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes.
Design Meta-epidemiological study.
Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine.
Study selection Two independent reviewers selected trials.
Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes.
Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses.
Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.
Keyword Cell lung cancer
End points
Clinical trials
Hierarchical levels
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Human Movement and Nutrition Sciences Publications
 
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