Understanding and quantifying uncertainty due to multiple biases in meta-analyses of observational studies

• Main Author: Mak, Timothy Shin Heng
• Format: Dissertation
• Language: English
• Published: Imperial College London 2013
• DOI: 10.25560/11666

There has been considerable interest recently in quantifying uncertainty beyond that due to random error in meta-analyses. This is particularly relevant to meta-analyses of observational studies, since error in estimates from these studies cannot be attributed to a randomization mechanism. Typically, observational studies are also subject to error due to measurement error, non-participation, and incomplete adjustment for confounding. Errors due to these sources are often referred to as bias. To quantify uncertainty due to bias, researchers have proposed using "bias models" and giving subjectively elicited probability distributions to parameters that are not identifiable in the models. In a typical meta-analysis, probability distributions involving tens of parameters will have to be elicited. At the same time, the resulting estimate and uncertainty interval of the overall (meta-analytic) effect measure will generally be very sensitive to this multi-dimensional subjectively-elicited distribution. To overcome some of the problems associated with the use of such a distribution, I propose an alternative method for eliciting and quantifying uncertainty due to bias. In the method of this thesis, the lower and upper bounds of bias parameters are elicited instead of probability distributions. The most extreme Bayesian posterior inference for the target parameter of interest within the specified bounds is sought through an algorithm. The resulting lower and upper bounds for the target parameter of interest have interpretation of a Robust Bayes analysis. In this thesis, the method is applied to a meta-analysis of childhood leukaemia and exposure to electromagnetic fields. The method of this thesis was found to produce uncertainty intervals that are generally more conservative in comparison with the standard approach. It is also proposed that the method be used as a tool for sensitivity analysis, and some interesting insight is gained from the childhood leukaemia data. [For supplementary files please contact author].