Biomarkers and surrogate endpoints in clinical trials
Top Cited Papers
- 18 June 2012
- journal article
- research article
- Published by Wiley in Statistics in Medicine
- Vol. 31 (25), 2973-2984
- https://doi.org/10.1002/sim.5403
Abstract
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. Copyright © 2012 John Wiley & Sons, Ltd.Keywords
This publication has 29 references indexed in Scilit:
- Content Validity—Establishing and Reporting the Evidence in Newly Developed Patient-Reported Outcomes (PRO) Instruments for Medical Product Evaluation: ISPOR PRO Good Research Practices Task Force Report: Part 2—Assessing Respondent UnderstandingValue in Health, 2011
- Content Validity—Establishing and Reporting the Evidence in Newly Developed Patient-Reported Outcomes (PRO) Instruments for Medical Product Evaluation: ISPOR PRO Good Research Practices Task Force Report: Part 1—Eliciting Concepts for a New PRO InstrumentValue in Health, 2011
- Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73 913 patientsJournal of Hypertension, 2011
- K-rasMutations and Benefit from Cetuximab in Advanced Colorectal CancerThe New England Journal of Medicine, 2008
- Effects of Intensive Glucose Lowering in Type 2 DiabetesThe New England Journal of Medicine, 2008
- Effects of Torcetrapib in Patients at High Risk for Coronary EventsThe New England Journal of Medicine, 2007
- Correction of Anemia with Epoetin Alfa in Chronic Kidney DiseaseThe New England Journal of Medicine, 2006
- Progressive Multifocal Leukoencephalopathy after Natalizumab Therapy for Crohn's DiseaseThe New England Journal of Medicine, 2005
- Comparison of Ximelagatran with Warfarin for the Prevention of Venous Thromboembolism after Total Knee ReplacementThe New England Journal of Medicine, 2003
- Preliminary Report: Effect of Encainide and Flecainide on Mortality in a Randomized Trial of Arrhythmia Suppression after Myocardial InfarctionThe New England Journal of Medicine, 1989