Related Experiment Video
Updated: May 14, 2026
The Adjuvant Efficacy of Angong Niuhuang Pill in the Treatment of Viral Encephalitis: A Meta-Analysis of Randomized Controlled Trials
Published on: April 19, 2024
Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised
Oriana Ciani1, Marc Buyse, Ruth Garside
1PenTAG, Institute for Health Services Research, University of Exeter Medical School, University of Exeter, Exeter EX2 4SG, UK. oriana.ciani@pcmd.ac.uk
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.
Related Concept Videos
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
01:20Comparing the Survival Analysis of Two or More Groups
01:26Introduction to Epidemiology
01:20Study Designs in Epidemiology
Observational studies are those where the researcher does not intervene but rather observes natural variations. They include cross-sectional, cohort, and case-control studies.
01:12Hazard Ratio
For example, in a clinical trial evaluating a...
01:24Kaplan-Meier Approach