Affiliation:
1. Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel
Abstract
Summary
The causal effects of Apolipoprotein E $\epsilon4$ allele (APOE) on late-onset Alzheimer’s disease (AD) and death are complicated to define because AD may occur under one intervention but not under the other, and because AD occurrence may affect age of death. In this article, this dual outcome scenario is studied using the semi-competing risks framework for time-to-event data. Two event times are of interest: a nonterminal event time (age at AD diagnosis), and a terminal event time (age at death). AD diagnosis time is observed only if it precedes death, which may occur before or after AD. We propose new estimands for capturing the causal effect of APOE on AD and death. Our proposal is based on a stratification of the population with respect to the order of the two events. We present a novel assumption utilizing the time-to-event nature of the data, which is more flexible than the often-invoked monotonicity assumption. We derive results on partial identifiability, suggest a sensitivity analysis approach, and give conditions under which full identification is possible. Finally, we present and implement nonparametric and semiparametric estimation methods under right-censored semi-competing risks data for studying the complex effect of APOE on AD and death.
Funder
National Institute on Aging
Israel Science Foundation
U.S.-Israel Binational Science Foundation
Publisher
Oxford University Press (OUP)
Subject
Statistics, Probability and Uncertainty,General Medicine,Statistics and Probability
Reference30 articles.
1. Estimation of bivariate and marginal distributions with censored data;Akritas,;Journal of the Royal Statistical Society: Series B (Statistical Methodology),2003
2. 2019 Alzheimer’s disease facts and figures;Alzheimer’s & Dementia,2019
3. Nonparametric regression with randomly censored survival data. Technical Report, Department of Statistics;Beran,,1981
4. Survivor average causal effects for continuous time: a principal stratification approach to causal inference with semi-competing risks;Comment,,2019
5. Gene dose of Apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families;Corder,;Science,1993
Cited by
9 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献