Measurement Errors in Times for Blood Sampling in Population Pharmacokinetic Models

• Activity Number: 614
• Type: Contributed
• Date/Time: Thursday, August 2, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Biometrics Section
• Author(s): Leena Choi*+
• Companies: Vanderbilt University
• Keywords: pharmacokinetic ; nonlinear mixed effects models ; errors-in-variables ; measurement error ; sampling time error

Abstract

Observational population pharmacokinetic (PK) data collected from routine clinical practice can provide valuable information. In contrast to PK data collected from a clinical trial, the analysis of observational PK data has several challenges. One of the challenges is measurement error in variables in PK models. An example is the time at which blood concentrations were measured or medications were administered, which is assumed to be known without error. However, time information for blood sample draw is often missing or inaccurately recorded in observational PK studies. Errors-in-variables and their bias correction using measurement error models has been widely discussed in linear and nonlinear regressions. As of yet, the measurement error problem has not been extensively studied in population PK models, an important area of nonlinear mixed effects models. Thus, we studied the effect of measurement errors in time at blood draw in population PK models. We conducted simulations studies to examine the bias in parameter estimates in the presence of measurement errors in variables, and compared bias correction methods and made recommendations.