The development and application of a normative framework for considering uncertainty and variability in economic evaluation

Abstract

The focus of this thesis is in the development and application of a normative framework for handling both variability and uncertainty in making decisions using economic evaluation. The framework builds on the recent work which takes an intuitive Bayesian approach to handling uncertainty as well as adding a similar approach for the handling of variability. The technique of stratified cost effectiveness analysis is introduced as an innovative, intuitive and theoretically sound basis for consideration of variability with respect to cost effectiveness. The technique requires the identification of patient strata where there are differences between strata but individual strata are relatively homogenous. For handling uncertainty, the normative framework requires a twofold approach. First, the cost effectiveness of therapies within each patient stratum must be assessed using probabilistic analysis. Secondly, techniques for estimation of the expected value of perfect information should be applied to determine an efficient research plan for the disease of interest. For the latter, a new technique for estimating EVPI based on quadrature is described which is both accurate and allows simpler calculation of the expected value of sample information. In addition the unit normal loss integral method previously ignored as a method of estimating EVPPI is shown to be appropriate in specific circumstances. The normative framework is applied to decisions relating to the public funding of the treatment of osteoporosis in the province of Ontario. The optimal limited use criteria would be to fund treatment with alendronate for women aged 75 years and over with previous fracture and 77 years and over with no previous fracture. An efficient research plan would fund a randomised controlled trial comparing etidronate to no therapy with a sample size of 640. Certain other research studies are of lesser value. Subsequent to the analysis contained in this thesis, the province of Ontario revised there limited use criteria to be broadly in line with the conclusions of this analysis. Thus, the application of the framework to this area demonstrates both its feasibility and acceptability. The normative framework developed in this thesis provides an optimal solution for decision makers in terms of handling uncertainty and variability in economic evaluation. Further research refining methods for estimating information value and considering other forms of uncertainty within models will enhance the framework.