Personalized treatment selection via the covariate-specific treatment effect curve for longitudinal data

Abstract

Treatment selection based on patient characteristics has been widely recognised in modern medicine. In this paper, we propose a generalised partially linear single-index mixed-effects modelling strategy for treatment selection and heterogeneous treatment effect estimation in longitudinal clinical and observational studies. We model the treatment effect as an unknown functional curve of a weighted linear combination of time-dependent covariates. This method enables us to investigate covariate-specific treatment effects and make personalised treatment selection in a flexible fashion. We develop a method that combines local linear regression and penalised quasi-likelihood to estimate the weight for each covariate, the unknown treatment effect curve and the parameters for mixed-effects. Based on pointwise confidence intervals for the treatment effect curve, we can make individualised treatment decisions from the information of patient characteristics. A simulation study is conducted to evaluate finite sample performance of the proposed method. We also illustrate the method via analysis of a real data example.

Keywords:

• personalized medicine
• treatment selection
• semiparametric model
• longitudinal data

Acknowledgments

We are grateful to the Editor-in-Chief, Prof. Jun Shao, an Associate Editor and anonymous reviewers for their thorough reading of our manuscript and insightful comments that have led to significant improvement of this work. We also thank the US National Alzheimer's Coordinating Center for providing the data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Natural Science Foundation of Shanghai (17ZR1409000). The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428-01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P30 AG062422-01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429-01 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).

Notes on contributors

Yanghui Liu

Yanghui Liu is a Ph.D. candidate in Statistics at East China Normal University.

Riquan Zhang

Riquan Zhang is a Professor in School of Statistics at East China Normal University.

Shujie Ma

Shujie Ma is an Associate Professor in Department of Statistics at University of California, Riverside.

Xiuzhen Zhang

Xiuzhen Zhang is a Ph.D. candidate in Statistics at East China Normal University.