PubMed Health⌕ Search

PubMed · 9567053

Assessing placebo response using Bayesian hierarchical survival models.

Abstract

The National Institute of Mental Health (NIMH) Collaborative Study of Long-Term Maintenance Drug Therapy in Recurrent Affective Illness was a multicenter randomized controlled clinical trial designed to determine the efficacy of a pharmacotherapy for the prevention of the recurrence of unipolar affective disorders. The outcome of interest in this study was the time until the recurrence of a depressive episode. The data show much heterogeneity between centers for the placebo group. The aim of this paper is to use Bayesian hierarchical survival models to investigate the heterogeneity of placebo effects among centers in the NIMH study. This heterogeneity is explored in terms of the marginal posterior distributions of parameters of interest and predictive distributions of future observations. The Gibbs sampling algorithm is used to approximate posterior and predictive distributions. Sensitivity of results to the assumption of a constant hazard survival distribution at the first stage of the hierarchy is examined by comparing results derived from a two component exponential mixture and a two component exponential changepoint model to the results derived from an exponential model. The second component of the mixture and changepoint models is assumed to be a surviving fraction. For each of these first stage parametric models sensitivity of results to second stage prior distributions is also examined.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

D K Stangl, J B Greenhouse. 1998. Assessing placebo response using Bayesian hierarchical survival models.. https://doi.org/10.1023/a%3A1009644308160

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

A Bayesian framework for multivariate differential analysis.

Differential analysis is a routine procedure in the statistical analysis toolbox across many applied fields, including quantitative proteomics, the main illustration of the present paper. The state-of-the-art limma approach uses a hierarchical formulation with moderated-variance estimators for each analyte directly injected into the t-statistic. While standard hypothesis testing strategies are recognised for their low computational cost, allowing for quick extraction of the most differential among thousands of elements, they generally overlook key aspects such as handling missing values, inter-element correlations, and uncertainty quantification. The present paper proposes a fully Bayesian framework for differential analysis, leveraging a conjugate hierarchical formulation for both the mean and the variance. Inference is performed by computing the posterior distribution of compared experimental conditions and sampling from the distribution of differences. This approach provides well-calibrated uncertainty quantification at a similar computational cost as hypothesis testing by leveraging closed-form equations. Furthermore, a natural extension enables multivariate differential analysis that accounts for possible inter-element correlations. We also demonstrate that, in this Bayesian treatment, missing at random data should generally be ignored in univariate settings, and further derive a tailored approximation that handles multiple imputation for the multivariate setting. We argue that probabilistic statements in terms of effect size and associated uncertainty are better suited to practical decision-making. Therefore, we finally propose simple and intuitive inference criteria, such as the overlap coefficient, which express group similarity as a probability rather than traditional, and often misleading, p-values. The performance of this approach is evaluated through an extensive empirical study using both synthetic and controlled real-world proteomics datasets. Overall, we believe that this Bayesian framework for (multivariate) differential analysis provides a valuable and intuitive counterpart to standard methods at a comparable computational cost.

Bayes Theorem↗

NExON-Bayes: a Bayesian approach to network estimation informed by ordinal covariates.

MOTIVATION: In heterogeneous disease settings, accounting for intrinsic sample variability is crucial for obtaining reliable and interpretable omic network estimates. However, most graphical model analyses of biomedical data assume homogeneous conditional dependence structures, potentially leading to misleading conclusions. To address this, we propose a joint Gaussian graphical model that leverages sample-level ordinal covariates (e.g. disease stage) to account for heterogeneity and improve the estimation of partial correlation structures. RESULTS: Our modelling framework, called NExON-Bayes, extends the graphical spike-and-slab framework to account for ordinal covariates, jointly estimating their relevance to the graph structure and leveraging them to improve the accuracy of network estimation. To scale to high-dimensional omic settings, we develop an efficient variational inference algorithm tailored to our model. Through simulations, we demonstrate that our method outperforms the vanilla graphical spike-and-slab (with no covariate information), as well as other state-of-the-art network approaches which exploit covariate information. Applying our method to reverse phase protein array data from patients diagnosed with stage I, II or III breast carcinoma, we estimate the behaviour of proteomic networks as cancer progresses. Our model provides insights not only through inspection of the estimated proteomic networks, but also of the estimated ordinal covariate dependencies of key groups of proteins within those networks, offering a comprehensive understanding of how biological pathways shift across disease stages. AVAILABILITY AND IMPLEMENTATION: A user-friendly R package for NExON-Bayes with tutorials is available on Github at github.com/jf687/NExON, and archived at https://doi.org/10.5281/zenodo.20312938. The source of the dataset used is cited in the relevant section.

Bayes Theorem↗

BaGGLS: a Bayesian shrinkage framework for interpretable modeling of interactions in high-dimensional biological data.

MOTIVATION: Biological data is often high dimensional, noisy, and governed by complex interactions among sparse signals. This poses major challenges for interpretability and reliable feature selection. Tasks such as identifying motif interactions in genomics exemplify these difficulties, as only a small subset of biologically relevant features (e.g. motifs) are typically active, and their effects are often non-linear and context-dependent. While statistical approaches often result in more interpretable models, deep learning models have proven effective in modeling complex interactions and prediction accuracy, yet their black-box nature limits interpretability. RESULTS: We introduce BaGGLS, a flexible and interpretable probabilistic binary regression model designed for high-dimensional biological inference involving feature interactions. BaGGLS incorporates a Bayesian group global-local shrinkage prior, aligned with the group structure introduced by interaction terms. This prior encourages sparsity while retaining interpretability, helping to isolate meaningful signals and suppress noise. To enable scalable inference, we employ a partially factorized variational approximation that captures posterior skewness and supports efficient learning even in large feature spaces. In extensive simulations, we compare BaGGLS to frequentist probit regressions (unconstrained and with L1-penalty) as well as a probit model with Markov Chain Monte Carlo (MCMC) sampling under a horseshoe prior. We can show that BaGGLS outperforms the other methods with regard to interaction detection and is many times faster than MCMC sampling under the horseshoe prior. We also demonstrate the usefulness of BaGGLS in the context of interaction discovery from motif scanner outputs (e.g. Find Individual Motif Occurrences (FIMO)) and noisy attribution scores from deep learning models. This shows that BaGGLS is a promising approach for uncovering biologically relevant interaction patterns, with potential applicability across a range of high-dimensional tasks in computational biology. AVAILABILITY: Code is available at gitlab.com/dacs-hpi/baggls.

Bayes Theorem↗