Clinical and economic issues complicating cost-effectiveness evaluation of orphan diseases

Cost-effectiveness evaluation of orphan medicinal products is confronted with a large confidence interval on the incremental cost-effectiveness ratios (ICERs), or extremely high ICERs and therefore rejection of products for uptake in the health insurance package (coverage) by health authorities in Europe. Examples from the United Kingdom (UK) and The Netherlands illustrated that straightforward application of the decision criteria might not always be possible, resulting in a large variety of coverage decisions that were neither transparent nor consistent with the criteria. This observation required more insight into what drives the high ICERs and what policies may support the appropriate use of orphan medicinal products. The most relevant clinical and economic issues that are perceived to complicate the cost-effectiveness evaluation of orphan medicinal products are discussed. Theoretically, two possible solutions are available: 1) circumvent or 2) keep the standard assessment criterion costeffectiveness. In analogy to the Europe Medicine Agency (EMA) registration approach of orphan medicinal products that are hampered by limitations in the clinical data at the time of registration, we suggest to stick to the use of standard uniform criteria, but that efforts should be directed at optimising the input to the cost-effectiveness evaluation. Subsequently potential policy approaches are developed.