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Mark van der Laan

Publications and source records attributed to Mark van der Laan.

64 records · Page 4Linked to original sources

Estimation of population size based on capture recapture designs and evaluation of the estimation reliability

We propose a modern method to estimate population size based on capture-recapture designs of K samples. The observed data is formulated as a sample of n i.i.d. K-dimensional vectors of binary indicators, where the k-th component of each vector indicates the subject being caught by the k-th sample, such that only subjects with nonzero capture vectors are observed. The target quantity is the unconditional probability of the vector being nonzero across both observed and unobserved subjects. We cover models assuming a single constraint (identification assumption) on the K-dimensional distribution such that the target quantity is identified and the statistical model is unrestricted. We present solutions for linear and non-linear constraints commonly assumed to identify capture-recapture models, including no K-way interaction in linear and log-linear models, independence or conditional independence. We demonstrate that the choice of constraint has a dramatic impact on the value of the estimand, showing that it is crucial that the constraint is known to hold by design. For the commonly assumed constraint of no K-way interaction in a log-linear model, the statistical target parameter is only defined when each of the $2^K - 1$ observable capture patterns is present, and therefore suffers from the curse of dimensionality. We propose a targeted MLE based on undersmoothed lasso model to smooth across the cells while targeting the fit towards the single valued target parameter of interest. For each identification assumption, we provide simulated inference and confidence intervals to assess the performance on the estimator under correct and incorrect identifying assumptions. We apply the proposed method, alongside existing estimators, to estimate prevalence of a parasitic infection using multi-source surveillance data from a region in southwestern China, under the four identification assumptions.

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Sequential causal inference in a single world of connected units

We consider adaptive designs for a trial involving N individuals that we follow along T time steps. We allow for the variables of one individual to depend on its past and on the past of other individuals. Our goal is to learn a mean outcome, averaged across the N individuals, that we would observe, if we started from some given initial state, and we carried out a given sequence of counterfactual interventions for $τ$ time steps. We show how to identify a statistical parameter that equals this mean counterfactual outcome, and how to perform inference for this parameter, while adaptively learning an oracle design defined as a parameter of the true data generating distribution. Oracle designs of interest include the design that maximizes the efficiency for a statistical parameter of interest, or designs that mix the optimal treatment rule with a certain exploration distribution. We also show how to design adaptive stopping rules for sequential hypothesis testing. This setting presents unique technical challenges. Unlike in usual statistical settings where the data consists of several independent observations, here, due to network and temporal dependence, the data reduces to one single observation with dependent components. In particular, this precludes the use of sample splitting techniques. We therefore had to develop a new equicontinuity result and guarantees for estimators fitted on dependent data. We were motivated to work on this problem by the following two questions. (1) In the context of a sequential adaptive trial with K treatment arms, how to design a procedure to identify in as few rounds as possible the treatment arm with best final outcome? (2) In the context of sequential randomized disease testing at the scale of a city, how to estimate and infer the value of an optimal testing and isolation strategy?

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Nonparametric Bootstrap Inference for the Targeted Highly Adaptive LASSO Estimator

The Highly-Adaptive-LASSO Targeted Minimum Loss Estimator (HAL-TMLE) is an efficient plug-in estimator of a pathwise differentiable parameter in a statistical model that at minimal (and possibly only) assumes that the sectional variation norm of the true nuisance functional parameters (i.e., the relevant part of data distribution) are finite. It relies on an initial estimator (HAL-MLE) of the nuisance functional parameters by minimizing the empirical risk over the parameter space under the constraint that the sectional variation norm of the candidate functions are bounded by a constant, where this constant can be selected with cross-validation. In this article, we establish that the nonparametric bootstrap for the HAL-TMLE, fixing the value of the sectional variation norm at a value larger or equal than the cross-validation selector, provides a consistent method for estimating the normal limit distribution of the HAL-TMLE. In order to optimize the finite sample coverage of the nonparametric bootstrap confidence intervals, we propose a selection method for this sectional variation norm that is based on running the nonparametric bootstrap for all values of the sectional variation norm larger than the one selected by cross-validation, and subsequently determining a value at which the width of the resulting confidence intervals reaches a plateau. We demonstrate our method for 1) nonparametric estimation of the average treatment effect based on observing on each unit a covariate vector, binary treatment, and outcome, and for 2) nonparametric estimation of the integral of the square of the multivariate density of the data distribution. In addition, we also present simulation results for these two examples demonstrating the excellent finite sample coverage of bootstrap-based confidence intervals.

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Correcting an estimator of a multivariate monotone function with isotonic regression

In many problems, a sensible estimator of a possibly multivariate monotone function may itself fail to be monotone. We study the correction of such an estimator obtained via projection onto the space of functions monotone over a finite grid in the domain. We demonstrate that this corrected estimator has no worse supremal estimation error than the initial estimator, and that analogously corrected confidence bands contain the true function whenever the initial bands do, at no loss to average or maximal band width. Additionally, we demonstrate that the corrected estimator is uniformly asymptotically equivalent to the initial estimator provided that the initial estimator satisfies a stochastic equicontinuity condition and that the true function is Lipschitz and strictly monotone. We provide simple sufficient conditions for our stochastic equicontinuity condition in the important special case that the initial estimator is uniformly asymptotically linear, and illustrate the use of these results for estimation of a G-computed distribution function. Our stochastic equicontinuity condition is weaker than standard uniform stochastic equicontinuity, which has been required for alternative correction procedures. Crucially, this allows us to apply our results to the bivariate correction of the local linear estimator of a conditional distribution function known to be monotone in its conditioning argument. Our experiments suggest that the projection step can yield significant practical improvements in performance for both the estimator and confidence band.

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Kernel Smoothing of the Treatment Effect CDF

The strata-specific treatment effect or so-called blip for a randomly drawn strata of confounders defines a random variable and a corresponding cumulative distribution function. However, the CDF is not pathwise differentiable, necessitating a kernel smoothing approach to estimate it at a given point or perhaps many points. Assuming the CDF is continuous, we derive the efficient influence curve of the kernel smoothed version of the blip CDF and a CV-TMLE estimator. The estimator is asymptotically efficient under two conditions, one of which involves a second order remainder term which, in this case, shows us that knowledge of the treatment mechanism does not guarantee a consistent estimate. The remainder term also teaches us exactly how well we need to estimate the nuisance parameters (outcome model and treatment mechanism) to guarantee asymptotic efficiency. Through simulations we verify theoretical properties of the estimator and show the importance of machine learning over conventional regression approaches to fitting the nuisance parameters. We also derive the bias and variance of the estimator, the orders of which are analogous to a kernel density estimator. This estimator opens up the possibility of developing methodology for optimal choice of the kernel and bandwidth to form confidence bounds for the CDF itself.

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A Fundamental Measure of Treatment Effect Heterogeneity

We offer a non-parametric plug-in estimator for an important measure of treatment effect variability and provide minimum conditions under which the estimator is asymptotically efficient. The stratum specific treatment effect function or so-called blip function, is the average treatment effect for a randomly drawn stratum of confounders. The mean of the blip function is the average treatment effect (ATE), whereas the variance of the blip function (VTE), the main subject of this paper, measures overall clinical effect heterogeneity, perhaps providing a strong impetus to refine treatment based on the confounders. VTE is also an important measure for assessing reliability of the treatment for an individual. The CV-TMLE provides simultaneous plug-in estimates and inference for both ATE and VTE, guaranteeing asymptotic efficiency under one less condition than for TMLE. This condition is difficult to guarantee a priori, particularly when using highly adaptive machine learning that we need to employ in order to eliminate bias. Even in defiance of this condition, CV-TMLE sampling distributions maintain normality, not guaranteed for TMLE, and have a lower mean squared error than their TMLE counterparts. In addition to verifying the theoretical properties of TMLE and CV-TMLE through simulations, we point out some of the challenges in estimating VTE, which lacks double robustness and might be unavoidably biased if the true VTE is small and sample size insufficient. We will provide an application of the estimator on a data set for treatment of acute trauma patients.

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Evaluation of adaptive treatment strategies in an observational study where time-varying covariates are not monitored systematically

In studies based on electronic health records (EHR), the frequency of covariate monitoring can vary by covariate type, across patients, and over time. This can lead to major challenges: first, the difference in monitoring protocols may invalidate the extrapolation of study results obtained in one population to the other, and second, monitoring can act as a time-varying confounder of the causal effect of a time-varying treatment on the outcomes of interest. This paper demonstrates how to account for non-systematic covariate monitoring when evaluating dynamic treatment interventions, and how to evaluate joint dynamic treatment-censoring and static monitoring interventions, in a real world, EHR-based, comparative effectiveness research (CER) study of patients with type II diabetes mellitus. First, we show that the effects of dynamic treatment-censoring regimes can be identified by including indicators of monitoring events in the adjustment set. Second, we demonstrate the poor performance of the standard inverse probability weighting (IPW) estimator of the effects of joint treatment-censoring-monitoring interventions, due to a large decrease in data support resulting in a large increase in standard errors and concerns over finite-sample bias from near-violations of the positivity assumption for the monitoring process. Finally, we detail an alternate IPW estimator of the effects of these interventions using the No Direct Effect assumption. We demonstrate that this estimator can result in improved efficiency but at the cost of increased bias concerns over structural near-violations of the positivity assumption for the treatment process. To conclude, this paper develops and illustrates new tools that researchers can exploit to appropriately account for non-systematic covariate monitoring in CER, and to ask new causal questions about the joint effects of treatment and monitoring interventions.

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A machine learning-based approach for estimating and testing associations with multivariate outcomes

We propose a method for summarizing the strength of association between a set of variables and a multivariate outcome. Classical summary measures are appropriate when linear relationships exist between covariates and outcomes, while our approach provides an alternative that is useful in situations where complex relationships may be present. We utilize ensemble machine learning to detect nonlinear relationships and covariate interactions and propose a measure of association that captures these relationships. A hypothesis test about the proposed associative measure can be used to test the strong null hypothesis of no association between a set of variables and a multivariate outcome. Simulations demonstrate that this hypothesis test has greater power than existing methods against alternatives where covariates have nonlinear relationships with outcomes. We additionally propose measures of variable importance for groups of variables, which summarize each groups' association with the outcome. We demonstrate our methodology using data from a birth cohort study on childhood health and nutrition in the Philippines.

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Finite Sample Inference for Targeted Learning

The Highly-Adaptive-Lasso(HAL)-TMLE is an efficient estimator of a pathwise differentiable parameter in a statistical model that at minimal (and possibly only) assumes that the sectional variation norm of the true nuisance parameters are finite. It relies on an initial estimator (HAL-MLE) of the nuisance parameters by minimizing the empirical risk over the parameter space under the constraint that sectional variation norm is bounded by a constant, where this constant can be selected with cross-validation. In the formulation of the HALMLE this sectional variation norm corresponds with the sum of absolute value of coefficients for an indicator basis. Due to its reliance on machine learning, statistical inference for the TMLE has been based on its normal limit distribution, thereby potentially ignoring a large second order remainder in finite samples. In this article, we present four methods for construction of a finite sample 0.95-confidence interval that use the nonparametric bootstrap to estimate the finite sample distribution of the HAL-TMLE or a conservative distribution dominating the true finite sample distribution. We prove that it consistently estimates the optimal normal limit distribution, while its approximation error is driven by the performance of the bootstrap for a well behaved empirical process. We demonstrate our general inferential methods for 1) nonparametric estimation of the average treatment effect based on observing on each unit a covariate vector, binary treatment, and outcome, and for 2) nonparametric estimation of the integral of the square of the multivariate density of the data distribution.

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Controlling Familywise Error When Rejecting at Most One Null Hypothesis Each From a Sequence of Sub-Families of Null Hypotheses

We present a procedure for controlling FWER when sequentially considering successive subfamilies of null hypotheses and rejecting at most one from each subfamily. Our procedure differs from previous procedures for controlling FWER by adjusting the critical values that are applied in subsequent rejection decisions by subtracting from the global significance level $α$ quantities based on the p-values of rejected null hypotheses and the numbers of null hypotheses considered.

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