Factors Contributing to the Efficacy-Effectiveness Gap in the Case of Orphan Drugs for Metabolic Diseases

INTRODUCTION: Authorization of orphan medicinal products (OMPs) is often based on studies with several methodological shortcomings. Hence, data are difficult to interpret and efficacy does not always correspond to real-world effectiveness. We investigated to what extent an efficacy-effectiveness gap exists for OMPs for metabolic diseases and set out to explore which factors contribute to it. METHODS: We included all OMPs for rare metabolic diseases authorized in the EU up to 1 January 2016. Efficacy data were obtained from European Public Assessment Reports, relative effectiveness data from the Dutch National Healthcare Institute website, and real-world effectiveness data from literature and interviews with experts and patients. Efficacy and effectiveness were scored as ‘no effect’, ‘unclear’ or ‘good’ based upon a prespecified scoring system. RESULTS: We identified 31 authorized OMPs, of which 21 had post-marketing studies available, thus making it possible to score real-world effectiveness. Eight of 21 (38%) OMPs had a ‘good’ real-world effectiveness. The use of a clinical or validated surrogate primary endpoint and a representative study population seemed to be related to good effectiveness in the real world, as were type of marketing authorization, study population and disease prevalence. CONCLUSIONS: This study revealed that less than half of the authorized OMPs are effective in the real world. Since the type of primary endpoint used in the pivotal study seems to be associated with good real-world effectiveness, it is important to agree upon study endpoints through early dialogues among relevant stakeholders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40265-017-0788-z) contains supplementary material, which is available to authorized users.