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Although the choice of the comparator is one of the aspects with a highest effect on the results of cost-effectiveness analyses, it is one of the less debated issues in international methodological guidelines. The inclusion of an inappropriate comparator may introduce biases on the outcomes and the recommendations of an economic analysis. Although the rules for cost-effectiveness analyses of sets of mutually exclusive alternatives have been widely described in the literature, in practice, they are hardly ever applied. In addition, there are many cases where the efficiency of the standard of care has never been assessed; or where the standard of care has demonstrated to be cost-effective with respect to a non-efficient option. In all these cases the comparator may lie outside the efficiency frontier, so the result of the CEA may be biased. Through some hypothetical examples, the paper shows how the complementary use of an independent reference may help to identify potential inappropriate comparators and inefficient use of resources.

Some reflections on the use of inappropriate comparators in CEA