The Appalachia Mind Health Initiative (AMHI): a pragmatic randomized clinical trial of adjunctive internet-based cognitive behavior therapy for treating major depressive disorder among primary care patients.

Background: Major depressive disorder (MDD) is a leading cause of disease morbidity. Combined treatment with antidepressant medication (ADM) plus psychotherapy yields a much higher MDD remission rate than ADM only. But 77% of US MDD patients are nonetheless treated with ADM only despite strong patient preferences for psychotherapy.

The optimal dynamic treatment rule superlearner: considerations, performance, and application to criminal justice interventions.

The optimal dynamic treatment rule (ODTR) framework offers an approach for understanding which kinds of patients respond best to specific treatments - in other words, treatment effect heterogeneity. Recently, there has been a proliferation of methods for estimating the ODTR. One such method is an extension of the SuperLearner algorithm - an ensemble method to optimally combine candidate algorithms extensively used in prediction problems - to ODTRs.

An omnibus non-parametric test of equality in distribution for unknown functions.

We present a novel family of nonparametric omnibus tests of the hypothesis that two unknown but estimable functions are equal in distribution when applied to the observed data structure. We developed these tests, which represent a generalization of the maximum mean discrepancy tests described in Gretton et al. [2006], using recent developments from the higher-order pathwise differentiability literature.

Toward computerized efficient estimation in infinite-dimensional models.

Despite the risk of misspecification they are tied to, parametric models continue to be used in statistical practice because they are simple and convenient to use. In particular, efficient estimation procedures in parametric models are easy to describe and implement. Unfortunately, the same cannot be said of semiparametric and nonparametric models.

Assessing the incremental value of new biomarkers based on OR rules.

In early detection of disease, a single biomarker often has inadequate classification performance, making it important to identify new biomarkers to combine with the existing marker for improved performance. A biologically natural method for combining biomarkers is to use logic rules, e.g.

Statistical Learning Methods to Determine Immune Correlates of Herpes Zoster in Vaccine Efficacy Trials.

Using Super Learner, a machine learning statistical method, we assessed varicella zoster virus-specific glycoprotein-based enzyme-linked immunosorbent assay (gpELISA) antibody titer as an individual-level signature of herpes zoster (HZ) risk in the Zostavax Efficacy and Safety Trial. Gender and pre- and postvaccination gpELISA titers had moderate ability to predict whether a 50-59 year old experienced HZ over 1-2 years of follow-up, with equal classification accuracy (cross-validated area under the receiver operator curve = 0.65) for vaccine and placebo recipients.

Parametric-rate inference for one-sided differentiable parameters.

Suppose one has a collection of parameters indexed by a (possibly infinite dimensional) set. Given data generated from some distribution, the objective is to estimate the maximal parameter in this collection evaluated at the distribution that generated the data. This estimation problem is typically non-regular when the maximizing parameter is non-unique, and as a result standard asymptotic techniques generally fail in this case.

Evaluating the impact of treating the optimal subgroup.

Suppose we have a binary treatment used to influence an outcome. Given data from an observational or controlled study, we wish to determine whether or not there exists some subset of observed covariates in which the treatment is more effective than the standard practice of no treatment. Furthermore, we wish to quantify the improvement in population mean outcome that will be seen if this subgroup receives treatment and the rest of the population remains untreated.

Super-Learning of an Optimal Dynamic Treatment Rule.

We consider the estimation of an optimal dynamic two time-point treatment rule defined as the rule that maximizes the mean outcome under the dynamic treatment, where the candidate rules are restricted to depend only on a user-supplied subset of the baseline and intermediate covariates. This estimation problem is addressed in a statistical model for the data distribution that is nonparametric, beyond possible knowledge about the treatment and censoring mechanisms. We propose data adaptive estimators of this optimal dynamic regime which are defined by sequential loss-based learning under both the blip function and weighted classification frameworks.

Optimal Individualized Treatments in Resource-Limited Settings.

An individualized treatment rule (ITR) is a treatment rule which assigns treatments to individuals based on (a subset of) their measured covariates. An optimal ITR is the ITR which maximizes the population mean outcome. Previous works in this area have assumed that treatment is an unlimited resource so that the entire population can be treated if this strategy maximizes the population mean outcome.

Racial/Ethnic Differences in the Role of Childhood Adversities for Mental Disorders Among a Nationally Representative Sample of Adolescents.

Background: Childhood adversities may play a key role in the onset of mental disorders and influence patterns by race/ethnicity. We examined the relations between childhood adversities and mental disorders by race/ethnicity in the National Comorbidity Survey-Adolescent Supplement.

Methods: Using targeted maximum likelihood estimation, a rigorous and flexible estimation procedure, we estimated the relationship of each adversity with mental disorders (behavior, distress, fear, and substance use), and estimated the distribution of disorders by race/ethnicity in the absence of adversities.

STATISTICAL INFERENCE FOR THE MEAN OUTCOME UNDER A POSSIBLY NON-UNIQUE OPTIMAL TREATMENT STRATEGY.

We consider challenges that arise in the estimation of the mean outcome under an optimal individualized treatment strategy defined as the treatment rule that maximizes the population mean outcome, where the candidate treatment rules are restricted to depend on baseline covariates. We prove a necessary and sufficient condition for the pathwise differentiability of the optimal value, a key condition needed to develop a regular and asymptotically linear (RAL) estimator of the optimal value. The stated condition is slightly more general than the previous condition implied in the literature.

Discussion of Identification, Estimation and Approximation of Risk under Interventions that Depend on the Natural Value of Treatment Using Observational Data, by Jessica Young, Miguel Hernán, and James Robins.

Young, Hernán, and Robins consider the mean outcome under a dynamic intervention that may rely on the natural value of treatment. They first identify this value with a statistical target parameter, and then show that this statistical target parameter can also be identified with a causal parameter which gives the mean outcome under a stochastic intervention. The authors then describe estimation strategies for these quantities.

Targeted Learning of the Mean Outcome under an Optimal Dynamic Treatment Rule.

We consider estimation of and inference for the mean outcome under the optimal dynamic two time-point treatment rule defined as the rule that maximizes the mean outcome under the dynamic treatment, where the candidate rules are restricted to depend only on a user-supplied subset of the baseline and intermediate covariates. This estimation problem is addressed in a statistical model for the data distribution that is nonparametric beyond possible knowledge about the treatment and censoring mechanism. This contrasts from the current literature that relies on parametric assumptions.