Adjusting for misclassification in a stratified biomarker clinical trial

Stat Med. 2014 Aug 15;33(18):3100-13. doi: 10.1002/sim.6164. Epub 2014 Apr 14.

Abstract

Clinical trials utilizing predictive biomarkers have become a research focus in personalized medicine. We investigate the effects of biomarker misclassification on the design and analysis of stratified biomarker clinical trials. For a variety of inference problems including marker-treatment interaction in particular, we show that marker misclassification may have profound adverse effects on the coverage of confidence intervals, power of the tests, and required sample sizes. For each inferential problem, we propose methods to adjust for the classification errors.

Keywords: biomarkers; classification error; correction for error; personalized medicine; power and sample size; prevalence; randomized controlled clinical trials; sensitivity and specificity.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / classification*
  • Biostatistics
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / secondary
  • Clinical Trials as Topic / statistics & numerical data*
  • Clinical Trials, Phase III as Topic / statistics & numerical data
  • Confidence Intervals
  • Humans
  • Interleukin-6 / analysis
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / immunology
  • Models, Statistical
  • Neoplasms / therapy
  • Precision Medicine
  • Sample Size

Substances

  • Biomarkers, Tumor
  • IL6 protein, human
  • Interleukin-6