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Multivariate meta-analysis of mixed outcomes: a Bayesian approach.

ABSTRACT: Multivariate random effects meta-analysis (MRMA) is an appropriate way for synthesizing data from studies reporting multiple correlated outcomes. In a Bayesian framework, it has great potential for integrating evidence from a variety of sources. In this paper, we propose a Bayesian model for MRMA of mixed outcomes, which extends previously developed bivariate models to the trivariate case and also allows for combination of multiple outcomes that are both continuous and binary. We have constructed informative prior distributions for the correlations by using external evidence. Prior distributions for the within-study correlations were constructed by employing external individual patent data and using a double bootstrap method to obtain the correlations between mixed outcomes. The between-study model of MRMA was parameterized in the form of a product of a series of univariate conditional normal distributions. This allowed us to place explicit prior distributions on the between-study correlations, which were constructed using external summary data. Traditionally, independent 'vague' prior distributions are placed on all parameters of the model. In contrast to this approach, we constructed prior distributions for the between-study model parameters in a way that takes into account the inter-relationship between them. This is a flexible method that can be extended to incorporate mixed outcomes other than continuous and binary and beyond the trivariate case. We have applied this model to a motivating example in rheumatoid arthritis with the aim of incorporating all available evidence in the synthesis and potentially reducing uncertainty around the estimate of interest.

SUBMITTER: Bujkiewicz S

PROVIDER: S-EPMC4015389 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Multivariate meta-analysis of mixed outcomes: a Bayesian approach.

Bujkiewicz Sylwia S Thompson John R JR Sutton Alex J AJ Cooper Nicola J NJ Harrison Mark J MJ Symmons Deborah P M DP Abrams Keith R KR

Statistics in medicine 20130430 22

Multivariate random effects meta-analysis (MRMA) is an appropriate way for synthesizing data from studies reporting multiple correlated outcomes. In a Bayesian framework, it has great potential for integrating evidence from a variety of sources. In this paper, we propose a Bayesian model for MRMA of mixed outcomes, which extends previously developed bivariate models to the trivariate case and also allows for combination of multiple outcomes that are both continuous and binary. We have constructe ...[more]

PMID: 23630081

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Project description:BACKGROUND:Renal transplant patients are mandated to have continuous assessment of their kidney function over time to monitor disease progression determined by changes in blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR). Multivariate analysis of these outcomes that aims at identifying the differential factors that affect disease progression is of great clinical significance. Thus our study aims at demonstrating the application of different joint modeling approaches with random coefficients on a cohort of renal transplant patients and presenting a comparison of their performance through a pseudo-simulation study. The objective of this comparison is to identify the model with best performance and to determine whether accuracy compensates for complexity in the different multivariate joint models. METHODS AND RESULTS:We propose a novel application of multivariate Generalized Linear Mixed Models (mGLMM) to analyze multiple longitudinal kidney function outcomes collected over 3 years on a cohort of 110 renal transplantation patients. The correlated outcomes BUN, Cr, and eGFR and the effect of various covariates such patient's gender, age and race on these markers was determined holistically using different mGLMMs. The performance of the various mGLMMs that encompass shared random intercept (SHRI), shared random intercept and slope (SHRIS), separate random intercept (SPRI) and separate random intercept and slope (SPRIS) was assessed to identify the one that has the best fit and most accurate estimates. A bootstrap pseudo-simulation study was conducted to gauge the tradeoff between the complexity and accuracy of the models. Accuracy was determined using two measures; the mean of the differences between the estimates of the bootstrapped datasets and the true beta obtained from the application of each model on the renal dataset, and the mean of the square of these differences. The results showed that SPRI provided most accurate estimates and did not exhibit any computational or convergence problem. CONCLUSION:Higher accuracy was demonstrated when the level of complexity increased from shared random coefficient models to the separate random coefficient alternatives with SPRI showing to have the best fit and most accurate estimates.

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Dataset Information

Multivariate meta-analysis of mixed outcomes: a Bayesian approach.

Publications

Multivariate meta-analysis of mixed outcomes: a Bayesian approach.

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