Biostatistics and epidemiology
Trial endpoints: primary, surrogate and composite
Primary and secondary endpoints, multiplicity, when a surrogate can be trusted (CAST, ILLUMINATE, ACCORD), and how to dissect a composite endpoint with a worked example.
Tier 1Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- The primary endpoint is chosen before the trial, drives the sample size calculation and is the only outcome the trial is powered to test.
- Secondary endpoints support or explain the primary result. Without a prespecified plan for multiplicity they are hypothesis-generating.
- Surrogate endpoints (BP, LDL, HbA1c, tumour shrinkage, viral load) are quicker and cheaper but can mislead badly.
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Sources
- CONSORT 2025 statement: updated guideline for reporting randomised trialsBMJ (Hopewell et al., 2025), 2025
- ICH E9 Statistical principles for clinical trialsInternational Council for Harmonisation (adopted by the TGA)
- Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice (3rd ed.)JAMA Evidence / McGraw-Hill (Guyatt et al., 2015)
- Surrogate end points in clinical trials: are we being misled?Annals of Internal Medicine (Fleming and DeMets, 1996;125:605-13)
- Validity of composite end points in clinical trialsBMJ (Montori et al., 2005;330:594-6)
- Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression TrialNEJM (Echt et al., 1991;324:781-8)
- Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction (CAST)NEJM (CAST Investigators, 1989;321:406-12)
- Effects of torcetrapib in patients at high risk for coronary events (ILLUMINATE)NEJM (Barter et al., 2007;357:2109-22)
- Effects of intensive glucose lowering in type 2 diabetes (ACCORD)NEJM (Gerstein et al., 2008;358:2545-59)
- The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical prioritiesEuropean Heart Journal (Pocock et al., 2012;33:176-82)
- Last updated
- 14 November 2026
What changed
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