Search arXivSearch

arXiv · 2004.12737

A Bayesian dose-response meta-analysis model: simulation study and application

Abstract

Dose-response models express the effect of different dose or exposure levels on a specific outcome. In meta-analysis, where aggregated-level data is available, dose-response evidence is synthesized using either one-stage or two-stage models in a frequentist setting. We propose a hierarchical dose-response model implemented in a Bayesian framework. We present the model with cubic dose-response shapes for a dichotomous outcome and take into account heterogeneity due to variability in the dose-response shape. We develop our Bayesian model assuming normal or binomial likelihood and accounting for exposures grouped in clusters. We implement these models in R using JAGS and we compare our approach to the one-stage dose-response meta-analysis model in a simulation study. We found that the Bayesian dose-response model with binomial likelihood has slightly lower bias than the Bayesian model with the normal likelihood and the frequentist one-stage model. However, all three models perform very well and give practically identical results. We also re-analyze the data from 60 randomized controlled trials (15,984 participants) examining the efficacy (response) of various doses of antidepressant drugs. All models suggest that the dose-response curve increases between zero dose and 40 mg of fluoxetine-equivalent dose, and thereafter is constant. We draw the same conclusion when we take into account the fact that five different antidepressants have been studied in the included trials. We show that implementation of the hierarchical model in Bayesian framework has similar performance to, but overcomes some of the limitations of the frequentist approaches and offers maximum flexibility to accommodate features of the data.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Tasnim Hamza, Andrea Cipriani, Toshi A. Furukawa, Matthias Egger, Nicola Orsini, Georgia Salanti. 2020-04-27. A Bayesian dose-response meta-analysis model: simulation study and application. https://doi.org/10.1177/0962280220982643

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

KEEP EXPLORING

Related papers

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 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.

stat.ME

Interpretable Deep Neural Network for Modeling Functional Surrogates

Developing surrogates for computer models has become increasingly important for addressing complex problems in science and engineering. This article introduces an artificial intelligent (AI) surrogate, referred to as the DeepSurrogate, for analyzing functional outputs with vector-valued inputs. The relationship between the functional output and vector-valued input is modeled as an infinite sequence of unknown functions, each representing the relationship at a specific location within the functional domain. These spatially indexed functions are expressed through a combination of basis functions and their corresponding coefficient functions, both of which are modeled using deep neural networks (DNN). The proposed framework accounts for spatial dependencies across locations, while capturing the relationship between the functional output and scalar predictors. It also integrates a Monte Carlo (MC) dropout strategy to quantify prediction uncertainty, enhancing explainability in the deep neural network architecture. The proposed method enables efficient inference on datasets with approximately 50,000 spatial locations and 20 simulations, achieving results in under 10 minutes using standard hardware. The approach is validated on extensive synthetic datasets and a large-scale simulation from the Sea Lake and Overland Surge from Hurricanes (SLOSH) simulator. An open-source Python package implementing the method is made available.

stat.ME

Bayesian inference for the learning rate in Generalised Bayesian inference

In Generalised Bayesian Inference (GBI), the learning rate and hyperparameters of the loss must be estimated. These inference-hyperparameters can't be estimated jointly with the other parameters, from the data, by giving them a prior. However, in some settings there exist unknown ``true'' hyperparameter-values about which it is meaningful to have prior belief. It is then possible to use Bayesian inference with held-out data to get hyperparameter-posteriors. We define two hyperparameter posteriors, one based on an Expected Log Pointwise Predictive Density (ELPPD)-utility and one aiming to cover the pseudo-true parameter. The new framework supports estimation and uncertainty quantification for multiple hyperparameters jointly. Experiments show that the resulting GBI-posteriors outperform Bayesian inference on simulated test data and select optimal or near-optimal hyperparameter values in a large real problem of text analysis. Generalised Bayesian inference is particularly useful for combining multiple data sets and most of our examples belong to that setting. We also give asymptotic results for some of the special ``multi-modular'' Generalised Bayes posteriors which we use in our examples.

stat.ME