Implementing Interventions with Varying Marginal Cost-Effectiveness: An Application in Precision Medicine.

. A range of barriers may constrain the effective implementation of strategies to deliver precision medicine. If the marginal costs and consequences of precision medicine vary at different levels of implementation, then such variation will have an impact on relative cost-effectiveness. This study aimed to illustrate the importance and quantify the impact of varying marginal costs and benefits on the value of implementation for a case study in precision medicine. . An existing method to calculate the value of implementation was adapted to allow marginal costs and consequences of introducing precision medicine into practice to vary across differing levels of implementation. This illustrative analysis used a case study based on a published decision-analytic model-based cost-effectiveness analysis of a 70-gene recurrence score (MammaPrint) for breast cancer. The impact of allowing for varying costs and benefits for the value of the precision medicine and of implementation strategies was illustrated graphically and numerically in both static and dynamic forms. . The increasing returns to scale exhibited by introducing this specific example of precision medicine mean that a minimum level of implementation (51%) is required for using the 70-gene recurrence score to be cost-effective at a defined threshold of €20,000 per quality-adjusted life year. The observed variation in net monetary benefit implies that the value of implementation strategies was dependent on the initial and ending levels of implementation in addition to the magnitude of the increase in patients receiving the 70-gene recurrence score. In dynamic models, incremental losses caused by low implementation accrue over time unless implementation is improved. . Poor implementation of approaches to deliver precision medicine, identified to be cost-effective using decision-analytic model-based cost-effectiveness analysis, can have a significant economic impact on health systems. Developing and evaluating the economic impact of strategies to improve the implementation of precision medicine will potentially realize the more cost-effective use of health care budgets.