STRATIFIED MEDICINE AND COST-EFFECTIVENESS: STRONG INFLUENCE OF CHOICES IN MODELLING SHORT-TERM, TRIAL-BASED, MORTALITY RISK REDUCTION AND POST-TRIAL LIFE EXPECTANCY

Purpose: Stratified medicine may improve the cost-effectiveness of medical interventions by targeting the right patients. Long-term survival benefit of a one-time treatment may be estimated by multiplying a trial-based short-term mortality risk reduction with the life expectancy after short-term survival. We aimed to study the influence of different modelling choices for the within-trial mortality risk reduction and post-trial life expectancy on estimates of cost-effectiveness for individual patients.

Method: We analyzed 30,510 patients with an acute myocardial infarction who were included in the GUSTO-I trial and treated with different forms of thrombolysis. Estimates of short-term mortality risk reduction were obtained from a logistic regression model with treatment (aggressive vs standard thrombolysis), sex and age as predictor variables. Life expectancy estimates were derived from sex and age-specific US life tables with an additional 2% yearly excess hazard to capture the increased mortality risk of cardiovascular patients. Aggressive thrombolysis was considered cost-effective when incremental costs per life year gained fell below $50,000.

Result: Based on sex and age-specific risk reductions but average population life expectancy, there was a substantial difference in expected life years gained between the lowest and highest quintile of short-term mortality risk (0.04 in first quintile vs 0.43 in fifth quintile; Figure 1). On individual patient level these assumptions imply aggressive thrombolysis to be cost-effective for men above the age of 48 and women above the age of 44 (83% of the population). When both mortality risk reduction and life expectancy were sex and age-specific, the difference in life years gained between the lowest and highest risk quintile was substantially attenuated (0.06 in first quintile vs 0.24 in fifth quintile; Figure 1). Individual cost-effectiveness of aggressive thrombolysis was extended to men above 43 and women above 37 of age (92% of the population).

Conclusion: This case-study illustrates how failure to model short-term risk reduction and life expectancy at a congruent level of detail may mislead our estimates of individualized cost-effectiveness and misallocate resources.

 

Figure 1   Life years gained from aggressive thrombolysis per 100 patients with an acute MI by sex and age specific short-term mortality risk quintile. Based on average population life expectancy (white bars) and on sex and age specific life expectancy (grey bars).