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Abstract Statistical analysis of longitudinal data often involves modeling treatment effects on clinically relevant longitudinal biomarkers since an initial event (the time origin). In some studies including preventive HIV vaccine efficacy trials, some participants have biomarkers measured starting at the time origin, whereas others have biomarkers measured starting later with the time origin unknown. The semiparametric additive time-varying coefficient model is investigated where the effects of some covariates vary nonparametrically with time while the effects of others remain constant. Weighted profile least squares estimators coupled with kernel smoothing are developed. The method uses the expectation maximization approach to deal with the censored time origin. The Kaplan–Meier estimator and other failure time regression models such as the Cox model can be utilized to estimate the distribution and the conditional distribution of left censored event time related to the censored time origin. Asymptotic properties of the parametric and nonparametric estimators and consistent asymptotic variance estimators are derived. A two-stage estimation procedure for choosing weight is proposed to improve estimation efficiency. Numerical simulations are conducted to examine finite sample properties of the proposed estimators. The simulation results show that the theory and methods work well. The efficiency gain of the two-stage estimation procedure depends on the distribution of the longitudinal error processes. The method is applied to analyze data from the Merck 023/HVTN 502 Step HIV vaccine study.
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Functional principal component analysis with informative observation times
Summary Functional principal component analysis has been shown to be invaluable for revealing variation modes of longitudinal outcomes, which serve as important building blocks for forecasting and model building. Decades of research have advanced methods for functional principal component analysis, often assuming independence between the observation times and longitudinal outcomes. Yet such assumptions are fragile in real-world settings where observation times may be driven by outcome-related processes. Rather than ignoring the informative observation time process, we explicitly model the observational times by a general counting process dependent on time-varying prognostic factors. Identification of the mean, covariance function and functional principal components ensues via inverse intensity weighting. We propose using weighted penalized splines for estimation and establish consistency and convergence rates for the weighted estimators. Simulation studies demonstrate that the proposed estimators are substantially more accurate than the existing ones in the presence of a correlation between the observation time process and the longitudinal outcome process. We further examine the finite-sample performance of the proposed method using the Acute Infection and Early Disease Research Program study.
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- Award ID(s):
- 2242776
- PAR ID:
- 10568408
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Biometrika
- Volume:
- 112
- Issue:
- 1
- ISSN:
- 1464-3510
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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