Survival analysis using inverse probability of treatment weighted methods based on the generalized propensity score

In survival analysis, treatment effects are commonly evaluated based on survival curves and hazard ratios as causal treatment effects. In observational studies, these estimates may be biased due to confounding factors. The inverse probability of treatment weighted (IPTW) method based on the propensity score is one of the approaches utilized to adjust for confounding factors between binary treatment groups. As a generalization of this methodology, we developed an exact formula for an IPTW log‐rank test based on the generalized propensity score for survival data. This makes it possible to compare the group differences of IPTW Kaplan–Meier estimators of survival curves using an IPTW log‐rank test for multi‐valued treatments. As causal treatment effects, the hazard ratio can be estimated using the IPTW approach. If the treatments correspond to ordered levels of a treatment, the proposed method can be easily extended to the analysis of treatment effect patterns with contrast statistics. In this paper, the proposed method is illustrated with data from the Kyushu Lipid Intervention Study (KLIS), which investigated the primary preventive effects of pravastatin on coronary heart disease (CHD). The results of the proposed method suggested that pravastatin treatment reduces the risk of CHD and that compliance to pravastatin treatment is important for the prevention of CHD. Copyright © 2009 John Wiley & Sons, Ltd.     

On the asymptotic efficiency of moment and maximum likelihood estimators in the three-parameter inverse gaussian distribution

The asymptotic distribution of estimators generated by the methods of moments and maximum likelihood are considered. Simple formulae are provided which enable comparisons of asymptotic relative efficiency to be effected.     

Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies

In a study comparing the effects of two treatments, the propensity score is the probability of assignment to one treatment conditional on a subject's measured baseline covariates. Propensity-score matching is increasingly being used to estimate the effects of exposures using observational data. In the most common implementation of propensity-score matching, pairs of treated and untreated subjects are formed whose propensity scores differ by at most a pre-specified amount (the caliper width). There has been a little research into the optimal caliper width. We conducted an extensive series of Monte Carlo simulations to determine the optimal caliper width for estimating differences in means (for continuous outcomes) and risk differences (for binary outcomes). When estimating differences in means or risk differences, we recommend that researchers match on the logit of the propensity score using calipers of width equal to 0.2 of the standard deviation of the logit of the propensity score. When at least some of the covariates were continuous, then either this value, or one close to it, minimized the mean square error of the resultant estimated treatment effect. It also eliminated at least 98% of the bias in the crude estimator, and it resulted in confidence intervals with approximately the correct coverage rates. Furthermore, the empirical type I error rate was approximately correct. When all of the covariates were binary, then the choice of caliper width had a much smaller impact on the performance of estimation of risk differences and differences in means.     

Variance estimation of the risk difference when using propensity-score matching and weighting with time-to-event outcomes

Observational studies are increasingly being used in medicine to estimate the effects of treatments or exposures on outcomes. To minimize the potential for confounding when estimating treatment effects, propensity score methods are frequently implemented. Often outcomes are the time to event. While it is common to report the treatment effect as a relative effect, such as the hazard ratio, reporting the effect using an absolute measure of effect is also important. One commonly used absolute measure of effect is the risk difference or difference in probability of the occurrence of an event within a specified duration of follow-up between a treatment and comparison group. We first describe methods for point and variance estimation of the risk difference when using weighting or matching based on the propensity score when outcomes are time-to-event. Next, we conducted Monte Carlo simulations to compare the relative performance of these methods with respect to bias of the point estimate, accuracy of variance estimates, and coverage of estimated confidence intervals. The results of the simulation generally support the use of weighting methods (untrimmed ATT weights and IPTW) or caliper matching when the prevalence of treatment is low for point estimation. For standard error estimation the simulation results support the use of weighted robust standard errors, bootstrap methods, or matching with a naïve standard error (i.e., Greenwood method). The methods considered in the article are illustrated using a real-world example in which we estimate the effect of discharge prescribing of statins on patients hospitalized for acute myocardial infarction.     

Correlation and efficiency of propensity score-based estimators for average causal effects

Propensity score-based estimators are commonly used to estimate causal effects in evaluation research. To reduce bias in observational studies, researchers might be tempted to include many, perhaps correlated, covariates when estimating the propensity score model. Taking into account that the propensity score is estimated, this study investigates how the efficiency of matching, inverse probability weighting, and doubly robust estimators change under the case of correlated covariates. Propositions regarding the large sample variances under certain assumptions on the data-generating process are given. The propositions are supplemented by several numerical large sample and finite sample results from a wide range of models. The results show that the covariate correlations may increase or decrease the variances of the estimators. There are several factors that influence how correlation affects the variance of the estimators, including the choice of estimator, the strength of the confounding toward outcome and treatment, and whether a constant or non-constant causal effect is present.     

Statistical inference on asymptotic properties of two estimators for the partially linear single-index models

The outer product of gradients (OPG) estimation procedure based on least squares (LS) approach has been presented by Xia et al. [An adaptive estimation of dimension reduction space. J Roy Statist Soc Ser B. 2002;64:363–410] to estimate the single-index parameter in partially linear single-index models (PLSIM). However, its asymptotic property has not been established yet and the efficiency of LS-based method can be significantly affected by outliers and heavy-tailed distributions. In this paper, we firstly derive the asymptotic property of OPG estimator developed by Xia et al. [An adaptive estimation of dimension reduction space. J Roy Statist Soc Ser B. 2002;64:363–410] in theory, and a novel robust estimation procedure combining the ideas of OPG and local rank (LR) inference is further developed for PLSIM along with its theoretical property. Then, we theoretically derive the asymptotic relative efficiency (ARE) of the proposed LR-based procedure with respect to LS-based method, which is shown to possess an expression that is closely related to that of the signed-rank Wilcoxon test in comparison with the t-test. Moreover, we demonstrate that the new proposed estimator has a great efficiency gain across a wide spectrum of non-normal error distributions and almost not lose any efficiency for the normal error. Even in the worst case scenarios, the ARE owns a lower bound equalling to 0.864 for estimating the single-index parameter and a lower bound being 0.8896 for estimating the nonparametric function respectively, versus the LS-based estimators. Finally, some Monte Carlo simulations and a real data analysis are conducted to illustrate the finite sample performance of the estimators.     

Comparison of adjusted and unadjusted marginal probabilities for estimating binomial parameters in observational studies

In this study, we demonstrate how generalized propensity score estimators (Imbens’ weighted estimator, the propensity score weighted estimator and the generalized doubly robust estimator) can be used to calculate the adjusted marginal probabilities for estimating the three common binomial parameters: the risk difference (RD), the relative risk (RR), and the odds ratio (OR). We further conduct a simulation study to compare the estimated RD, RR, and OR using the adjusted and the unadjusted marginal probabilities in terms of the bias and mean-squared error (MSE). Although there is no clear winner in terms of the MSE for estimating RD, RR, and OR, simulation results surprisingly show thatthe unadjusted marginal probabilities produce the smallest bias compared with the adjusted marginal probabilities in most of the estimates. Hence, in conclusion, we recommend using the unadjusted marginal probabilities to estimate RD, RR, and OR, in practice.     

Propensity score prediction for electronic healthcare databases using super learner and high-dimensional propensity score methods

ABSTRACT

The optimal learner for prediction modeling varies depending on the underlying data-generating distribution. Super Learner (SL) is a generic ensemble learning algorithm that uses cross-validation to select among a ‘library’ of candidate prediction models. While SL has been widely studied in a number of settings, it has not been thoroughly evaluated in large electronic healthcare databases that are common in pharmacoepidemiology and comparative effectiveness research. In this study, we applied and evaluated the performance of SL in its ability to predict the propensity score (PS), the conditional probability of treatment assignment given baseline covariates, using three electronic healthcare databases. We considered a library of algorithms that consisted of both nonparametric and parametric models. We also proposed a novel strategy for prediction modeling that combines SL with the high-dimensional propensity score (hdPS) variable selection algorithm. Predictive performance was assessed using three metrics: the negative log-likelihood, area under the curve (AUC), and time complexity. Results showed that the best individual algorithm, in terms of predictive performance, varied across datasets. The SL was able to adapt to the given dataset and optimize predictive performance relative to any individual learner. Combining the SL with the hdPS was the most consistent prediction method and may be promising for PS estimation and prediction modeling in electronic healthcare databases.     

Bayesian misclassification and propensity score methods for clustered observational studies

Bayesian propensity score regression analysis with misclassified binary responses is proposed to analyse clustered observational data. This approach utilizes multilevel models and corrects for misclassification in the responses. Using the deviance information criterion (DIC), the performance of the approach is compared with approaches without correcting for misclassification, multilevel structure specification, or both in the study of the impact of female employment on the likelihood of physical violence. The smallest DIC confirms that our proposed model best fits the data. We conclude that female employment has an insignificant impact on the likelihood of physical spousal violence towards women. In addition, a simulation study confirms that the proposed approach performed best in terms of bias and coverage rate. Ignoring misclassification in response or multilevel structure of data would yield biased estimation of the exposure effect.     

On the asymptotic non‐equivalence of efficient‐GMM and MEL estimators in models with missing data

The generalized method of moments (GMM) and empirical likelihood (EL) are popular methods for combining sample and auxiliary information. These methods are used in very diverse fields of research, where competing theories often suggest variables satisfying different moment conditions. Results in the literature have shown that the efficient‐GMM (GMM_E) and maximum empirical likelihood (MEL) estimators have the same asymptotic distribution to order n^?1/2 and that both estimators are asymptotically semiparametric efficient. In this paper, we demonstrate that when data are missing at random from the sample, the utilization of some well‐known missing‐data handling approaches proposed in the literature can yield GMM_E and MEL estimators with nonidentical properties; in particular, it is shown that the GMM_E estimator is semiparametric efficient under all the missing‐data handling approaches considered but that the MEL estimator is not always efficient. A thorough examination of the reason for the nonequivalence of the two estimators is presented. A particularly strong feature of our analysis is that we do not assume smoothness in the underlying moment conditions. Our results are thus relevant to situations involving nonsmooth estimating functions, including quantile and rank regressions, robust estimation, the estimation of receiver operating characteristic (ROC) curves, and so on.     

A note on the asymptotic relative efficiency of estimators from the additive hazards model

In this note, the asymptotic variance formulas are explicitly derived and compared between the parametric and semiparametric estimators of a regression parameter and survival probability under the additive hazards model. To obtain explicit formulas, it is assumed that the covariate term including a regression coefficient follows a gamma distribution and the baseline hazard function is constant. The results show that the semiparametric estimator of the regression coefficient parameter is fully efficient relative to the parametric counterpart when the survival time and a covariate are independent, as in the proportional hazards model. Relative to a more realistic case of the parametric additive hazards model with a Weibull baseline, the loss of efficiency of the semiparametric estimator of survival probability is moderate.     

Maximum entropy in the mean methods in propensity score matching for interval and noisy data

Abstract

In this paper, we propose maximum entropy in the mean methods for propensity score matching classification problems. We provide a new methodological approach and estimation algorithms to handle explicitly cases when data is available: (i) in interval form; (ii) with bounded measurement or observational errors; or (iii) both as intervals and with bounded errors. We show that entropy in the mean methods for these three cases generally outperform benchmark error-free approaches.     

Second order efficiency for a class of estimators within the multinomial family

All the estimators considered by Rao (1961; 1963) belong to a certain class of minimum discrepancy estimators. A new representation of Rao s second measure of second order efficiency is given for estimators belonging to this class.     

A Note on the Role of the Propensity Score for Estimating Average Treatment Effects

Hahn [Hahn, J. (1998). On the role of the propensity score in efficient semiparametric estimation of average treatment effects. Econometrica 66:315-331] derived the semiparametric efficiency bounds for estimating the average treatment effect (ATE) and the average treatment effect on the treated (ATET). The variance of ATET depends on whether the propensity score is known or unknown. Hahn attributes this to “dimension reduction.” In this paper, an alternative explanation is given: Knowledge of the propensity score improves upon the estimation of the distribution of the confounding variables.     

The efficiency of a test based on the asymptotic distribution of the mle for a linear functional relationship

A rigorous derivation is given of the asymptotic normality of the MLE of a linear functional relationship. Using these results, it is shown that the test proposed by VILLEGAS (1964) has Pitman efficiency zero w.r.t, a test based on the asymptotic distribution of the MLE.     

Nonnull asymptotic distributions of the LR,Wald, score and gradient statistics in generalized linear models with dispersion covariates

The class of generalized linear models with dispersion covariates, which allows us to jointly model the mean and dispersion parameters, is a natural extension to the classical generalized linear models. In this paper, we derive the asymptotic expansions under a sequence of Pitman alternatives (up to order n ^?1/2) for the nonnull distribution functions of the likelihood ratio, Wald, Rao score and gradient statistics in this class of models. The asymptotic distributions of these statistics are obtained for testing a subset of regression parameters and for testing a subset of dispersion parameters. Based on these nonnull asymptotic expansions, the power of all four tests, which are equivalent to first order, are compared. Furthermore, we consider Monte Carlo simulations in order to compare the finite-sample performance of these tests in this class of models. We present two empirical applications to two real data sets for illustrative purposes.     

Modeling the Effects of Genetic Factors on Late-Onset Diseases in Cohort Studies

Many late-onset diseases are caused by what appears to be a combination of a genetic predisposition to disease and environmental factors. The use of existing cohort studies provides an opportunity to infer genetic predisposition to disease on a representative sample of a study population, now that many such studies are gathering genetic information on the participants. One feature to using existing cohorts is that subjects may be censored due to death prior to genetic sampling, thereby adding a layer of complexity to the analysis. We develop a statistical framework to infer parameters of a latent variables model for disease onset. The latent variables model describes the role of genetic and modifiable risk factors on the onset ages of multiple diseases, and accounts for right-censoring of disease onset ages. The framework also allows for missing genetic information by inferring a subject's unknown genotype through appropriately incorporated covariate information. The model is applied to data gathered in the Framingham Heart Study for measuring the effect of different Apo-E genotypes on the occurrence of various cardiovascular disease events.     

The effect of tapering on the semiparametric estimators for nonstationary long memory processes

In this paper, we study, by a Monte Carlo simulation, the effect of the order p of “Zhurbenko-Kolmogorov” taper on the asymptotic properties of semiparametric estimators. We show that p  =  [d + 1/2] + 1 gives the smallest variances and mean squared errors. These properties depend also on the truncation parameter m. Moreover, we study the impact of the short-memory components on the bias and variances of these estimators. We finally carry out an empirical application by using four monthly seasonally adjusted logarithm Consumer Price Index series.