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Missing exposure information is a very common feature of many observational studies. Here we study identifiability and efficient estimation of causal effects on vector outcomes, in such cases where treatment is unconfounded but partially missing. We consider a missing at random setting where missingness in treatment can depend not only on complex covariates, but also on post-treatment outcomes. We give a new identifying expression for average treatment effects in this setting, along with the efficient influence function for this parameter in a nonparametric model, which yields a nonparametric efficiency bound. We use this latter result to construct nonparametric estimators that are less sensitive to the curse of dimensionality than usual, e. g. by having faster rates of convergence than the complex nuisance estimators they rely on. Further we show that these estimators can be root-n consistent and asymptotically normal under weak nonparametric conditions, even when constructed using flexible machine learning. Finally we apply these results to the problem of causal inference with a partially missing instrumental variable.

In randomized clinical trials, researchers are often interested in identifying an inexpensive intermediate study endpoint (typically a biomarker) that is a strong effect modifier of the treatment effect on a longer-term clinical endpoint of interest. Motivated by randomized placebo-controlled preventive vaccine efficacy trials, within the principal stratification framework a pseudo-score type estimator has been proposed to estimate disease risks conditional on the counter-factual biomarker of interest under each treatment assignment to vaccine or placebo, yielding an estimator of biomarker conditional vaccine efficacy. This method can be used for trial designs that use baseline predictors of the biomarker and/or designs that vaccinate disease-free placebo recipients at the end of the trial. In this article, we utilize the pseudo-score estimator to estimate the biomarker conditional vaccine efficacy adjusting for baseline covariates. We also propose a perturbation resampling method for making simultaneous inference on conditional vaccine efficacy over the values of the biomarker. We illustrate our method with datasets from two phase 3 dengue vaccine efficacy trials.

Infectious disease transmission between individuals in a heterogeneous population is often best modelled through a contact network. However, such contact network data are often unobserved. Such missing data can be accounted for in a Bayesian data augmented framework using Markov chain Monte Carlo (MCMC). Unfortunately, fitting models in such a framework can be highly computationally intensive. We investigate the fitting of network-based infectious disease models with completely unknown contact networks using approximate Bayesian computation population Monte Carlo (ABC-PMC) methods. This is done in the context of both simulated data, and data from the UK 2001 foot-and-mouth disease epidemic. We show that ABC-PMC is able to obtain reasonable approximations of the underlying infectious disease model with huge savings in computation time when compared to a full Bayesian MCMC analysis.

Bioequivalence (BE) studies are an integral component of new drug development process, and play an important role in approval and marketing of generic drug products. However, existing design and evaluation methods are basically under the framework of frequentist theory, while few implements Bayesian ideas. Based on the bioequivalence predictive probability model and sample re-estimation strategy, we propose a new Bayesian two-stage adaptive design and explore its application in bioequivalence testing. The new design differs from existing two-stage design (such as Potvin’s method B, C) in the following aspects. First, it not only incorporates historical information and expert information, but further combines experimental data flexibly to aid decision-making. Secondly, its sample re-estimation strategy is based on the ratio of the information in interim analysis to total information, which is simpler in calculation than the Potvin’s method. Simulation results manifested that the two-stage design can be combined with various stop boundary functions, and the results are different. Moreover, the proposed method saves sample size compared to the Potvin’s method under the conditions that type I error rate is below 0.05 and statistical power reaches 80 %.

Understanding treatment heterogeneity is essential to the development of precision medicine, which seeks to tailor medical treatments to subgroups of patients with similar characteristics. One of the challenges of achieving this goal is that we usually do not have a priori knowledge of the grouping information of patients with respect to treatment effect. To address this problem, we consider a heterogeneous regression model which allows the coefficients for treatment variables to be subject-dependent with unknown grouping information. We develop a concave fusion penalized method for estimating the grouping structure and the subgroup-specific treatment effects, and derive an alternating direction method of multipliers algorithm for its implementation. We also study the theoretical properties of the proposed method and show that under suitable conditions there exists a local minimizer that equals the oracle least squares estimator based on a priori knowledge of the true grouping information with high probability. This provides theoretical support for making statistical inference about the subgroup-specific treatment effects using the proposed method. The proposed method is illustrated in simulation studies and illustrated with real data from an AIDS Clinical Trials Group Study.

Several statistical issues associated with health care costs, such as heteroscedasticity and severe skewness, make it challenging to estimate or predict medical costs. When the interest is modeling the mean cost, it is desirable to make no assumption on the density function or higher order moments. Another challenge in developing cost prediction models is the presence of many covariates, making it necessary to apply variable selection methods to achieve a balance of prediction accuracy and model simplicity. We propose Spike-or-Slab priors for Bayesian variable selection based on asymptotic normal estimates of the full model parameters that are consistent as long as the assumption on the mean cost is satisfied. In addition, the scope of model searching can be reduced by ranking the Z-statistics. This method possesses four advantages simultaneously: robust (due to avoiding assumptions on the density function or higher order moments), parsimonious (feature of variable selection), informative (due to its Bayesian flavor, which can compare posterior probabilities of candidate models) and efficient (by reducing model searching scope with the use of Z-ranking). We apply this method to the Medical Expenditure Panel Survey dataset.

We propose autoregressive Bayesian semi-parametric models for gap times between recurrent events. The aim is two-fold: inference on the effect of possibly time-varying covariates on the gap times and clustering of individuals based on the time trajectory of the recurrent event. Time-dependency between gap times is taken into account through the specification of an autoregressive component for the frailty parameters influencing the response at different times. The order of the autoregression may be assumed unknown and is an object of inference. We consider two alternative approaches to perform model selection under this scenario. Covariates may be easily included in the regression framework and censoring and missing data are easily accounted for. As the proposed methodologies lie within the class of Dirichlet process mixtures, posterior inference can be performed through efficient MCMC algorithms. We illustrate the approach through simulations and medical applications involving recurrent hospitalizations of cancer patients and successive urinary tract infections.

We consider the situation where a temporal process is composed of contiguous segments with differing slopes and replicated noise-corrupted time series measurements are observed. The unknown mean of the data generating process is modelled as a piecewise linear function of time with an unknown number of change-points. We develop a Bayesian approach to infer the joint posterior distribution of the number and position of change-points as well as the unknown mean parameters. A-priori, the proposed model uses an overfitting number of mean parameters but, conditionally on a set of change-points, only a subset of them influences the likelihood. An exponentially decreasing prior distribution on the number of change-points gives rise to a posterior distribution concentrating on sparse representations of the underlying sequence. A Metropolis-Hastings Markov chain Monte Carlo (MCMC) sampler is constructed for approximating the posterior distribution. Our method is benchmarked using simulated data and is applied to uncover differences in the dynamics of fungal growth from imaging time course data collected from different strains. The source code is available on CRAN.

We present new methods for cell line classification using multivariate time series bioimpedance data obtained from electric cell-substrate impedance sensing (ECIS) technology. The ECIS technology, which monitors the attachment and spreading of mammalian cells in real time through the collection of electrical impedance data, has historically been used to study one cell line at a time. However, we show that if applied to data from multiple cell lines, ECIS can be used to classify unknown or potentially mislabeled cells, factors which have previously been associated with the reproducibility crisis in the biological literature. We assess a range of approaches to this new problem, testing different classification methods and deriving a dictionary of 29 features to characterize ECIS data. Most notably, our analysis enriches the current field by making use of simultaneous multi-frequency ECIS data, where previous studies have focused on only one frequency; using classification methods to distinguish multiple cell lines, rather than simple statistical tests that compare only two cell lines; and assessing a range of features derived from ECIS data based on their classification performance. In classification tests on fifteen mammalian cell lines, we obtain very high out-of-sample predictive accuracy. These preliminary findings provide a baseline for future large-scale studies in this field.

Merging databases is a strategy of paramount interest especially in medical research. A common problem in this context comes from a variable which is not coded on the same scale in both databases we aim to merge. This paper considers the problem of finding a relevant way to recode the variable in order to merge these two databases. To address this issue, an algorithm, based on optimal transportation theory, is proposed. Optimal transportation theory gives us an application to map the measure associated with the variable in database A to the measure associated with the same variable in database B . To do so, a cost function has to be introduced and an allocation rule has to be defined. Such a function and such a rule is proposed involving the information contained in the covariates. In this paper, the method is compared to multiple imputation by chained equations and a statistical learning method and has demonstrated a better average accuracy in many situations. Applications on both simulated and real datasets show that the efficiency of the proposed merging algorithm depends on how the covariates are linked with the variable of interest.