Biomarker data with measurement error in medical research: A literature review

A biomarker is a measurable indicator of the severity or presence of a disease or medical condition in biomedical or epidemiological research. Biomarkers may help in early diagnosis and prevention of diseases. Several biomarkers have been identified for many diseases such as carbohydrate antigen 19‐9 for pancreatic cancer. However, biomarkers may be measured with errors due to many reasons such as specimen collection or day‐to‐day within‐subject variability of the biomarker, among others. Measurement error in the biomarker leads to bias in the regression parameter estimation for the association of the biomarker with disease in epidemiological studies. In addition, measurement error in the biomarkers may affect standard diagnostic measures to evaluate the performance of biomarkers such as the receiver operating characteristic (ROC) curve, area under the ROC curve, sensitivity, and specificity. Measurement error may also have an effect on how to combine multiple cancer biomarkers as a composite predictor for disease diagnosis. In follow‐up studies, biomarkers are often collected intermittently at examination times, which may be sparse and typically biomarkers are not observed at the event times. Joint modeling of longitudinal and time‐to‐event data is a valid approach to account for measurement error in the analysis of repeatedly measured biomarkers and time‐to‐event outcomes. In this article, we provide a literature review on existing methods to correct for estimation in regression analysis, diagnostic measures, and joint modeling of longitudinal biomarkers and survival outcomes when the biomarkers are measured with errors. This article is categorized under: Statistical and Graphical Methods of Data Analysis > Robust Methods Statistical and Graphical Methods of Data Analysis > EM Algorithm Statistical Models > Survival Models Left: Clinic assay versus research assay from two labs. Right: logarithmic transform of clinic assay versus logarithmic transform of research assay from two labs.