Suppose that we have 5 possible comparators: A, B, C, D, and E (Figure, bottom panel). First, we eliminate dominated strategies; in this case, treatment C is dominated by D. Second, we eliminate strategies that are subject to extended dominance, which occurs when a less effective intervention has a higher ICER when both are compared with a mutual comparator. Treatment B is less effective than D but has a higher cost per QALY gained when each is compared with A; adopting B would mean paying a higher cost per QALY than is necessary to achieve that level of effectiveness. The third and final step is to look at each remaining intervention, calculate its ICER compared with the next most effective option, and see which ICER (if any) is below the cost-effectiveness threshold. The most cost-effective strategy will be the most effective strategy that has an ICER below the cost-effectiveness threshold. In this example, 3 strategies (A, D, and E) remain. Although treatment E is the most effective, it has a relatively high ICER compared with D. Therefore, as the most effective treatment with an ICER below the threshold, treatment D is the most cost-effective.