OBJECTIVES: Compliance with antihypertensives is influenced by various factors, and influences blood pressure (BP) control and cardiovascular outcomes. Differences in compliance, eg. the improvement associated with fixed-dose combinations (FDCs), are acknowledged, but have not been incorporated into cost-effectiveness modeling because the chain of causality between compliance and outcomes is complex. We developed a method to quantify this chain of effects which can use simple compliance parameters such as medication possession ratios, or more sophisticated inputs; it can also be tailored to specific decision problems. METHODS: First the effect of variation in compliance on simulated dosing histories is modeled. Second, the rate of fall/rise in BP on initiating/withdrawing treatment, and the full-compliance BP reduction, are used to estimate corresponding BP trajectories. Finally clinical endpoints are modeled from these BP trajectories, based on existing evidence. In an illustrative example, the effect of choosing an FDC over the corresponding component-based regime was modeled. The FDC effect was modeled as an 11% reduction in missed doses [reference], distributed evenly across interruptions of different lengths. Systolic blood pressure (SBP) trajectories were estimated assuming bioequivalence between FDC and component-based regimes, and the mean SBP calculated. The Framingham risk equation was used to predict the number of strokes which would be expected on the component-based regime, and the expected number which FDC use would avoid through superior compliance. RESULTS: This approach allows quantification of compliance-mediated health effects with great flexibility. CONCLUSIONS: More detailed data on the effects of FDC use on compliance can be incorporated, and different treatment efficacies and/or different durations of action can be substituted, as can different BP summary statistics, different clinical endpoints, and different sources for the relationships between them. Reference: Taylor A and Shoheiber O. Adherence to antihypertensive therapy with fixed-dose amplodipine besylate/benazepril versus comparable component-based therapy. Congestive Heart Failure 2003;9:324-32.