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A Bayesian dose-response meta-analysis model: A simulations 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 develop our model assuming normal or binomial likelihood and accounting for exposures grouped in clusters. To allow maximum flexibility, the dose-response association is modelled using restricted cubic splines. 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 lower bias than the Bayesian model with normal likelihood and the frequentist one-stage model when studies have small sample size. When the true underlying shape is log-log or half-sigmoid, the performance of all models depends on choosing an appropriate location for the knots. In all other examined situations, all 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 serotonin-specific reuptake inhibitor (SSRI) antidepressant drugs. All models suggest that the dose-response curve increases between zero dose and 30-40 mg of fluoxetine-equivalent dose, and thereafter shows small decline. 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 approach and offers maximum flexibility to accommodate features of the data.

SUBMITTER: Hamza T

PROVIDER: S-EPMC8209313 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:When assessing the human risks due to exposure to environmental chemicals, traditional dose-response analyses are not straightforward when there are numerous high-quality epidemiological studies of priority cancer and non-cancer health outcomes. Given this wealth of information, selecting a single "best" study on which to base dose-response analyses is difficult and would potentially ignore much of the available data. Therefore, systematic approaches are necessary for the analysis of these rich databases. Examples are meta-analysis (and further, meta-regression), which are well established methods that consider and incorporate information from multiple studies into the estimation of risks due to exposure to environmental contaminants. In this paper, we propose a hierarchical, Bayesian meta-analysis approach for the dose-response analysis of multiple epidemiological studies. This paper is the second of two papers detailing this approach; the first covered "pre-analysis" steps necessary to prepare the data for dose-response modeling. This paper focuses on the hierarchical Bayesian approach to dose-response modeling and extrapolation of risk to populations of interest using the association between bladder cancer and oral inorganic arsenic (iAs) exposure as an illustrative case study. In particular, this paper addresses the modeling of both case-control and cohort studies with a flexible, logistic model in a hierarchical Bayesian framework that estimates study-specific slopes, as well as a pooled slope across all studies. This approach is akin to a random effects model in which no assumption is made a priori that there is a single, common slope for all included studies. Further, this paper also details extrapolation of the estimates of logistic slope to extra risk in a target population using a lifetable analysis and basic assumptions about background iAs exposure levels. In this case, the target population was the general United States population and information on all-cause mortality and incidence and mortality from bladder cancer was used to perform the lifetable analysis. The methods herein were developed for general use in investigating the association between any pollutant and observed health-effects in epidemiological studies. In order to demonstrate these methods, inorganic arsenic was chosen as a case study given the large epidemiological database that exists for this contaminant.

Project description:In vivo functional neuroimaging, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), is becoming increasingly important in defining the pathophysiology of psychiatric disorders such as schizophrenia, major depression, and Alzheimer's disease. Furthermore, recent studies have begun to investigate the possibility of using functional neuroimaging to guide treatment selection for individual patients. By studying the changes between a patient's pre- and post-treatment brain activity, investigators are gaining insights into the impact of treatment on behavior-related neural processing traits associated with particular psychiatric disorders. Furthermore, these studies may shed light on the neural basis of response and nonresponse to specific treatments. The practical limitation of such studies is that the post-treatment scans offer little guidance to treatment selection in clinical settings, since treatment decisions precede the availability of post-treatment brain scans. This shortcoming represents the impetus for developing statistical methodology that would provide clinicians with predictive information concerning the effect of treatment on brain activity and, ultimately, symptom-related behaviors. We present a prediction algorithm that uses a patient's pretreatment scans, coupled with relevant patient characteristics, to forecast the patient's brain activity following a specified treatment regimen. We derive our predictive method from a Bayesian hierarchical model constructed on the pre- and post-treatment scans of designated training data. We perform estimation using the expectation-maximization algorithm. We evaluate the accuracy of our proposed prediction method using K-fold cross-validation, quantifying the error using two new measures that we propose for neuroimaging data. The proposed method is applicable to both PET and fMRI studies. We illustrate its use with a PET study of working memory in patients with schizophrenia and an fMRI data example is also provided.

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

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