International Journal of Biostatistics最新文献

While there are many well-developed data science methods for classification and regression, there are relatively few methods for working with right-censored data. Here, we review survival stacking, a method for casting a survival regression analysis problem as a classification problem, thereby allowing the use of general classification methods and software in a survival setting. Inspired by the Cox partial likelihood, survival stacking collects features and outcomes of survival data in a large data frame with a binary outcome. We show that survival stacking with logistic regression is approximately equivalent to the Cox proportional hazards model. We further illustrate survival stacking on real and simulated data. By reframing survival regression problems as classification problems, survival stacking removes the reliance on specialized tools for survival regression, and makes it straightforward for data scientists to use well-known learning algorithms and software for classification in the survival setting. This in turn lowers the barrier for flexible survival modeling.

Biomarker analysis of athletes' urinary steroid profiles is crucial for the success of anti-doping efforts. Current statistical analysis methods generate personalised limits for each athlete based on univariate modelling of longitudinal biomarker values from the urinary steroid profile. However, simultaneous modelling of multiple biomarkers has the potential to further enhance abnormality detection. In this study, we propose a multivariate Bayesian adaptive model for longitudinal data analysis, which extends the established single-biomarker model in forensic toxicology. The proposed approach employs Markov chain Monte Carlo sampling methods and addresses the scarcity of confirmed abnormal values through a one-class classification algorithm. By adapting decision boundaries as new measurements are obtained, the model provides robust and personalised detection thresholds for each athlete. We tested the proposed approach on a database of 229 athletes, which includes longitudinal steroid profiles containing samples classified as normal, atypical, or confirmed abnormal. Our results demonstrate improved detection performance, highlighting the potential value of a multivariate approach in doping detection.

In this paper, we study inference methods for regression analysis of clustered current status data with informative cluster sizes. When the correlated failure times of interest arise from a general class of semiparametric transformation frailty models, we develop a nonparametric maximum likelihood estimation based method for regression analysis and conduct an expectation-maximization algorithm to implement it. The asymptotic properties including consistency and asymptotic normality of the proposed estimators are established. Extensive simulation studies are conducted and indicate that the proposed method works well. The developed approach is applied to analyze a real-life data set from a tumorigenicity study.

Although randomized controlled trials (RCTs) are a cornerstone of comparative effectiveness, they typically have much smaller sample size than observational studies due to financial and ethical considerations. Therefore there is interest in using plentiful historical data (either observational data or prior trials) to reduce trial sizes. Previous estimators developed for this purpose rely on unrealistic assumptions, without which the added data can bias the treatment effect estimate. Recent work proposed an alternative method (prognostic covariate adjustment) that imposes no additional assumptions and increases efficiency in trial analyses. The idea is to use historical data to learn a prognostic model: a regression of the outcome onto the covariates. The predictions from this model, generated from the RCT subjects' baseline variables, are then used as a covariate in a linear regression analysis of the trial data. In this work, we extend prognostic adjustment to trial analyses with nonparametric efficient estimators, which are more powerful than linear regression. We provide theory that explains why prognostic adjustment improves small-sample point estimation and inference without any possibility of bias. Simulations corroborate the theory: efficient estimators using prognostic adjustment compared to without provides greater power (i.e., smaller standard errors) when the trial is small. Population shifts between historical and trial data attenuate benefits but do not introduce bias. We showcase our estimator using clinical trial data provided by Novo Nordisk A/S that evaluates insulin therapy for individuals with type 2 diabetes.

Function on scalar regression models relate functional outcomes to scalar predictors through the conditional mean function. With few and limited exceptions, many functional regression frameworks operate under the assumption that covariate information does not affect patterns of covariation. In this manuscript, we address this disparity by developing a Bayesian functional regression model, providing joint inference for both the conditional mean and covariance functions. Our work hinges on basis expansions of both the functional evaluation domain and covariate space, to define flexible non-parametric forms of dependence. To aid interpretation, we develop novel low-dimensional summaries, which indicate the degree of covariate-dependent heteroskedasticity. The proposed modeling framework is motivated and applied to a case study in functional brain imaging through electroencephalography, aiming to elucidate potential differentiation in the neural development of children with autism spectrum disorder.

To ensure privacy protection and alleviate computational burden, we propose a fast subsmaling procedure for the Cox model with massive survival datasets from multi-centered, decentralized sources. The proposed estimator is computed based on optimal subsampling probabilities that we derived and enables transmission of subsample-based summary level statistics between different storage sites with only one round of communication. For inference, the asymptotic properties of the proposed estimator were rigorously established. An extensive simulation study demonstrated that the proposed approach is effective. The methodology was applied to analyze a large dataset from the U.S. airlines.

In epidemiological studies, the measurements of disease outcomes are carried out by different evaluators. In this paper, we propose a two-stage procedure for detecting outlier evaluators. In the first stage, a regression model is fitted to obtain the evaluators' effects. Outlier evaluators have different effects than normal evaluators. In the second stage, stepwise hypothesis tests are performed to detect outlier evaluators. The true positive rate and true negative rate of the proposed procedure are assessed in a simulation study. We apply the proposed method to detect potential outlier audiologists among the audiologists who measured hearing threshold levels of the participants in the Audiology Assessment Arm of the Conservation of Hearing Study, which is an epidemiological study for examining risk factors of hearing loss.

Learning individualized treatment rules (ITRs) for a target patient population with mental disorders is confronted with many challenges. First, the target population may be different from the training population that provided data for learning ITRs. Ignoring differences between the training patient data and the target population can result in sub-optimal treatment strategies for the target population. Second, for mental disorders, a patient's underlying mental state is not observed but can be inferred from measures of high-dimensional combinations of symptomatology. Treatment mechanisms are unknown and can be complex, and thus treatment effect moderation can take complicated forms. To address these challenges, we propose a novel method that connects measurement models, efficient weighting schemes, and flexible neural network architecture through latent variables to tailor treatments for a target population. Patients' underlying mental states are represented by a compact set of latent state variables while preserving interpretability. Weighting schemes are designed based on lower-dimensional latent variables to efficiently balance population differences so that biases in learning the latent structure and treatment effects are mitigated. Extensive simulation studies demonstrated consistent superiority of the proposed method and the weighting approach. Applications to two real-world studies of patients with major depressive disorder have shown a broad utility of the proposed method in improving treatment outcomes in the target population.

In previous work, we introduced a framework that combines latent class growth analysis (LCGA) with marginal structural models (LCGA-MSM). LCGA-MSM first summarizes the numerous time-varying treatment patterns into a few trajectory groups and then allows for a population-level causal interpretation of the group differences. However, the LCGA-MSM framework is not suitable when the outcome is time-dependent. In this study, we propose combining a nonparametric history-restricted marginal structural model (HRMSM) with LCGA. HRMSMs can be seen as an application of standard MSMs on multiple time intervals. To the best of our knowledge, we also present the first application of HRMSMs with a time-to-event outcome. It was previously noted that HRMSMs could pose interpretation problems in survival analysis when either targeting a hazard ratio or a survival curve. We propose a causal parameter that bypasses these interpretation challenges. We consider three different estimators of the parameters: inverse probability of treatment weighting (IPTW), g-computation, and a pooled longitudinal targeted maximum likelihood estimator (pooled LTMLE). We conduct simulation studies to measure the performance of the proposed LCGA-HRMSM. For all scenarios, we obtain unbiased estimates when using either g-computation or pooled LTMLE. IPTW produced estimates with slightly larger bias in some scenarios. Overall, all approaches have good coverage of the 95 % confidence interval. We applied our approach to a population of older Quebecers composed of 57,211 statin initiators and found that a greater adherence to statins was associated with a lower combined risk of cardiovascular disease or all-cause mortality.

Traditional methods for Sample Size Determination (SSD) based on power analysis exploit relevant fixed values or preliminary estimates for the unknown parameters. A hybrid classical-Bayesian approach can be used to formally incorporate information or model uncertainty on unknown quantities by using prior distributions according to the Bayesian approach, while still analysing the data in a frequentist framework. In this paper, we propose a hybrid procedure for SSD in two-arm superiority trials, that takes into account the different role played by the unknown parameters involved in the statistical power. Thus, different prior distributions are used to formalize design expectations and to model information or uncertainty on preliminary estimates involved at the analysis stage. To illustrate the method, we consider binary data and derive the proposed hybrid criteria using three possible parameters of interest, i.e. the difference between proportions of successes, the logarithm of the relative risk and the logarithm of the odds ratio. Numerical examples taken from the literature are presented to show how to implement the proposed procedure.