Extract
A commonly used approach to study the association between a time-varying biomarker, such as forced vital capacity (FVC), and a time-to-event outcome, such as new onset of chronic obstructive pulmonary disease (COPD), is to incorporate the biomarker as a time-dependent covariate in a Cox model. This approach, which is known as the time-dependent Cox model (TDCM), requires knowledge of the value of the time-varying biomarker at all time points at which the event of interest occurs [1]. However, in clinical studies, longitudinal biomarker measurements are taken intermittently during scheduled (and sometimes unscheduled) visits, meaning that imputation of missing values is required for those event times at which the biomarker is not observed. In practical application of the TDCM, this is achieved by carrying forward the most recent biomarker measurement. While the use of last observation carried forward (LOCF) is easy to understand and implement, the resulting step function (see fig. 1, panel C for an example) is unlikely to provide a good approximation of the true biomarker trajectory.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Chen has nothing to disclose.
Conflict of interest: Dr. Postmus has nothing to disclose.
Conflict of interest: Dr. Cowie has nothing to disclose.
Conflict of interest: Dr. Woehrle has nothing to disclose.
Conflict of interest: Dr. Wegscheider has nothing to disclose.
Conflict of interest: Dr. Simonds has nothing to disclose.
Conflict of interest: Dr. Boezen has nothing to disclose.
Conflict of interest: Dr. Somers reports other from Steering Committee SERV HF, outside the submitted work.
Conflict of interest: Dr. Teschler has nothing to disclose.
Conflict of interest: Dr. Eulenburg has nothing to disclose.
- Received August 19, 2020.
- Accepted November 4, 2020.
- Copyright ©ERS 2020
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