Surrogate disease markers as substitutes for chronic disease outcomes in studies of diet and chronic disease relations

Am J Clin Nutr. 2017 Nov;106(5):1175-1189. doi: 10.3945/ajcn.117.164046. Epub 2017 Oct 11.

Abstract

Surrogate biomarkers for clinical outcomes afford scientific and economic efficiencies when investigating nutritional interventions in chronic diseases. However, valid scientific results are dependent on the qualification of these disease markers that are intended to be substitutes for a clinical outcome and to accurately predict benefit or harm. In this article, we examine the challenges of evaluating surrogate markers and describe the framework proposed in a 2010 Institute of Medicine report. The components of this framework are presented in the context of nutritional interventions for chronic diseases. We present case studies of 2 well-accepted surrogate markers [blood pressure within sodium intake and cardiovascular disease (CVD) context and low density lipoprotein-cholesterol concentrations within a saturated fat and CVD context]. We also describe additional cases in which the evidence is insufficient to validate their surrogate status. Guidance is offered for future research that evaluates or uses surrogate markers.

Keywords: biomarker qualification; diet and chronic disease; diet and health relations; surrogate disease marker qualification; surrogate disease markers.

MeSH terms

  • Biomarkers / blood*
  • Blood Pressure / drug effects
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Chronic Disease
  • Diet*
  • Fatty Acids / adverse effects
  • Humans
  • National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division
  • Neoplasms / blood
  • Neoplasms / epidemiology
  • Observational Studies as Topic
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Sodium, Dietary / adverse effects
  • Sodium, Dietary / blood
  • United States

Substances

  • Biomarkers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fatty Acids
  • Sodium, Dietary