Search for: All records

Abstract Observational epidemiological studies often confront the problem of estimating exposure‐disease relationships when the exposure is not measured exactly. Regression calibration (RC) is a common approach to correct for bias in regression analysis with covariate measurement error. In survival analysis with covariate measurement error, it is well known that the RC estimator may be biased when the hazard is an exponential function of the covariates. In the paper, we investigate the RC estimator with general hazard functions, including exponential and linear functions of the covariates. When the hazard is a linear function of the covariates, we show that a risk set regression calibration (RRC) is consistent and robust to a working model for the calibration function. Under exponential hazard models, there is a trade‐off between bias and efficiency when comparing RC and RRC. However, one surprising finding is that the trade‐off between bias and efficiency in measurement error research is not seen under linear hazard when the unobserved covariate is from a uniform or normal distribution. Under this situation, the RRC estimator is in general slightly better than the RC estimator in terms of both bias and efficiency. The methods are applied to the Nutritional Biomarkers Study of the Women's Health Initiative. 

Summary We consider evaluating new or more accurately measured predictive biomarkers for treatment selection based on a previous clinical trial involving standard biomarkers. Instead of rerunning the clinical trial with the new biomarkers, we propose a more efficient approach which requires only either conducting a reproducibility study in which the new biomarkers and standard biomarkers are both measured on a set of patient samples, or adopting replicated measures of the error-contaminated standard biomarkers in the original study. This approach is easier to conduct and much less expensive than studies that require new samples from patients randomized to the intervention. In addition, it makes it possible to perform the estimation of the clinical performance quickly, since there will be no requirement to wait for events to occur as would be the case with prospective validation. The treatment selection is assessed via a working model, but the proposed estimator of the mean restricted lifetime is valid even if the working model is misspecified. The proposed approach is assessed through simulation studies and applied to a cancer study.