Biomarkers and surrogate endpoints in clinical trials

Stat Med. 2012 Nov 10;31(25):2973-84. doi: 10.1002/sim.5403. Epub 2012 Jun 18.


One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function, and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures, and radiological tests, often are considered as replacement endpoints or 'surrogates' for clinically meaningful endpoints. We discuss the definitions of clinically meaningful endpoints and surrogate endpoints, and provide examples from recent clinical trials. We provide insight into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. We also discuss the nature of evidence that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and provide insights into why this reliability is specific to the context of use of the biomarker.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers*
  • Clinical Trials as Topic*
  • Endpoint Determination*
  • Humans
  • Outcome and Process Assessment, Health Care*
  • Reproducibility of Results
  • Research Design


  • Biomarkers