Surrogate endpoints in randomized cardiovascular clinical trials.
Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. However, assurance that use of a surrogate endpoint will result in a correct conclusion regarding treatment effect on a CEI requires prior rigorous validation of the surrogate. Surrogate endpoints can also be of substantial use in Phase I and II studies to assess whether the intended therapeutic pathway is operative, thus providing assurance regarding the reasonableness of proceeding to a Phase III trial. This paper discusses the uses and validation of surrogate endpoints.
Domanski
Michael
M
The National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
Pocock
Stuart
S
Bernaud
Corine
C
Borer
Jeffrey
J
Geller
Nancy
N
Revkin
James
J
Zannad
Faiez
F
D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D023381:Endpoint Determination / Q000379:methods*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D015203:Reproducibility of Results
D015415:Biomarkers