Objectives. The aim of this dissertation is to develop and apply methods to make more valid estimates of treatment effect using observational data in uncommon disease. The objectives were 1) using strategies that reduce the threat of potential biases on the elicited response, to develop and evaluate the feasibility, validity and reliability of a revised belief elicitation method for Bayesian priors; 2) to determine expert clinicians’ beliefs regarding the effect of warfarin on survival in systemic sclerosis associated pulmonary arterial hypertension (SSc-PAH) and idiopathic pulmonary arterial hypertension (IPAH) (expressed as prior probability distributions), and determine the importance of factors that influence experts’ use of warfarin for SSc-PAH and IPAH; 3) a) use data from experts to derive a propensity score in a Bayesian context, and, b) combine observed survival data from 2 large, inception cohorts with the prior probability distributions derived from experts, to evaluate the effect of warfarin on survival in SSc- PAH and IPAH.
Methods. The methods include systematic review of the literature, application of principles of psychometric science, cross-sectional elicitation of experts’ beliefs, analysis of retrospective observational cohort data with a survival outcome using propensity score modeling and Bayesian inference.
Results. I have developed a scientific method to quantifiably elicit experts’ beliefs in the form of Bayesian priors that can be included in models of treatment effect. This method incorporates strategies that reduce the effect of potential biases, and has demonstrable feasibility, validity and reliability. I have developed methods in a Bayesian framework to make propensity-score adjusted estimates of treatment effect using observational data with a survival end point. I have determined experts’ beliefs regarding the effect of warfarin on survival on SSc-PAH and IPAH, and have determined factors that influence experts’ use of warfarin in SSc-PAH and IPAH. Using these methods, I have found that warfarin has a low probability of improving survival in SSc-PAH and IPAH.
Conclusion. I have demonstrated that making more valid estimates of treatment effect using observational data of an uncommon disease can be successfully achieved. Given the low probability that warfarin improves survival in SSc-PAH and IPAH, and availability of other PAH therapies with demonstrable benefits, there is little role for warfarin in these patients.