arXiv subjects

Christina D. Chambers

Publications and source records attributed to Christina D. Chambers.

4 recordsLinked to original sources

arXiv2022

Causal Effects of Prenatal Drug Exposure on Birth Defects with Missing by Terathanasia

A recent cohort study revealed a positive correlate between major structural birth defects in infants and a certain medication taken by pregnant women. To draw valid causal inference, an outstanding problem to overcome was the missing birth defect outcomes among pregnancy losses resulting from spontaneous abortion. This led to missing not at random since, according to the theory of "terathanasia", a defected fetus is more likely to be spontaneously aborted. Other complications in the data included left truncation, right censoring, observational nature, and rare events. In addition, the previous analysis stratified on live birth against spontaneous abortion, which was itself a post-exposure variable and hence did not lead to a causal interpretation of the stratified results. In this paper we aim to estimate and provide inference for the causal parameters of scientific interest, including the principal effects, making use of the missing data mechanism informed by "terathanasia". The rare events with missing outcomes led to multiple sensitivity analyses where the causal parameters can be estimated with better confidence in each setting. Our findings should shed light on how studies on causal effects of medication or other exposures during pregnancy may be analyzed using state-of-the-art methodologies.

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arXiv2017

Semiparametric Sieve Maximum Likelihood Estimation Under Cure Model with Partly Interval Censored and Left Truncated Data for Application to Spontaneous Abortion Data

This work was motivated by observational studies in pregnancy with spontaneous abortion (SAB) as outcome. Clearly some women experience the SAB event but the rest do not. In addition, the data are left truncated due to the way pregnant women are recruited into these studies. For those women who do experience SAB, their exact event times are sometimes unknown. Finally, a small percentage of the women are lost to follow-up during their pregnancy. All these give rise to data that are left truncated, partly interval and right-censored, and with a clearly defined cured portion. We consider the non-mixture Cox regression cure rate model and adopt the semiparametric spline-based sieve maximum likelihood approach to analyze such data. Using modern empirical process theory we show that both the parametric and the nonparametric parts of the sieve estimator are consistent, and we establish the asymptotic normality for both parts. Simulation studies are conducted to establish the finite sample performance. Finally, we apply our method to a database of observational studies on spontaneous abortion.

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arXiv2017

The Impact of Confounder Selection in Propensity Scores for Rare Events Data - with Applications to Birth Defects

Our work was motivated by a recent study on birth defects of infants born to pregnant women exposed to a certain medication for treating chronic diseases. Outcomes such as birth defects are rare events in the general population, which often translate to very small numbers of events in the unexposed group. As drug safety studies in pregnancy are typically observational in nature, we control for confounding in this rare events setting using propensity scores (PS). Using our empirical data, we noticed that the estimated odds ratio for birth defects due to exposure varied drastically depending on the specific approach used. The commonly used approaches with PS are matching, stratification, inverse probability weighting (IPW) and regression adjustment. The extremely rare events setting renders the matching or stratification infeasible. In addition, the PS itself may be formed via different approaches to select confounders from a relatively long list of potential confounders. We carried out simulation experiments to compare different combinations of approaches: IPW or regression adjustment, with 1) including all potential confounders without selection, 2) selection based on univariate association between the candidate variable and the outcome, 3) selection based on change in effects (CIE). The simulation showed that IPW without selection leads to extremely large variances in the estimated odds ratio, which help to explain the empirical data analysis results that we had observed. The simulation also showed that IPW with selection based on univariate association with the outcome is preferred over IPW with CIE. Regression adjustment has small variances of the estimated odds ratio regardless of the selection methods used.

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arXiv2016

A Nonparametric Maximum Likelihood Approach for Partially Observed Cured Data with Left Truncation and Right-Censoring

Partially observed cured data occur in the analysis of spontaneous abortion (SAB) in observational studies in pregnancy. In contrast to the traditional cured data, such data has an observable `cured' portion as women who do not abort spontaneously. The data is also subject to left truncate in addition to right-censoring because women may enter or withdraw from a study any time during their pregnancy. Left truncation in particular causes unique bias in the presence of a cured portion. In this paper, we study a cure rate model and develop a conditional nonparametric maximum likelihood approach. To tackle the computational challenge we adopt an EM algorithm making use of "ghost copies" of the data, and a closed form variance estimator is derived. Under suitable assumptions, we prove the consistency of the resulting estimator involving an unbounded cumulative baseline hazard function, as well as the asymptotic normality. Simulation results are carried out to evaluate the finite sample performance. We present the analysis of the motivating SAB study to illustrate the power of our model addressing both occurrence and timing of SAB, as compared to existing approaches in practice.

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