Systematic validation of disease models for pharmacoeconomic evaluations

Pharmacoeconomic evaluations are often based on computer models which simul ate the course of disease with and without medical interventions. The purpo se of this study is to propose and illustrate a rigorous approach for valid ating such disease models. For illustrative purposes, we applied this appro ach to a computer-based model we developed to mimic the history of HIV-infe cted subjects at the greatest risk for Mycobacterium avium complex (MAC) in fection in Switzerland. The drugs included as a prophylactic intervention a gainst MAC infection were azithromycin and clarithromycin. We used a homoge nous Markov chain to describe the progression of an HIV-infected patient th rough six MAC-free states, one MAC state, and death. Probability estimates were extracted from the Swiss HIV Cohort Study database (1993-95) and rando mized controlled trials. The model was validated testing for (1) technical validity (2) predictive validity (3) face validity and (4) modelling proces s validity. Sensitivity analysis and independent model implementation in DA TA(TM) (PPS) and self-written Fortran 90 code (BAC) assured technical valid ity. Agreement between modelled and observed MAC incidence confirmed predic tive validity. Modelled MAC prophylaxis at different starting conditions af firmed face validity. Published articles by other authors supported modelli ng process validity. The proposed validation procedure is a useful approach to improve the validity of the model.