OBJECTIVES : Generating evidence for health technology assessment (HTA) submissions in an orphan drug can be challenging. Hurdles may include limited clinical trial data, lack of comparators, established endpoints or outcome measures, and absence of validated disease-specific quality-of-life (QoL) tools. In this study, we established an evidence generation plan (EGP) for a drug under development for a rare congenital disorder for the purpose of informing its value story and preparing for the future.

METHODS : To develop the EGP, we performed four tasks: (a) evaluated published European HTA reports of the drugs currently holding marketing authorization in the disease area; (b) obtained insights in HTA, health economics and outcome research (HEOR), patient-reported outcomes (PRO), real-world evidence (RWE), and pricing and market access from an expert panel; (c) identified and classified EGP actions according to priority; (d) provided recommendations on the EGP strategy.

RESULTS : The HTA landscape assessment revealed that a validated disease-specific PRO instrument is of high importance; economic models should be comprehensive, capturing relevant clinical data and in accordance with HTA guidelines; long-term efficacy and safety data are essential; and treatment benefit should be assessed using objective measures rather than subjective tools (e.g., patient diaries). Expert insights highlighted the importance of PRO, HEOR, RWE, and pricing in informing the value proposition of an orphan drug. Based on the HTA findings and expert feedback, three levels of priority actions were identified for the EGP (high=key steps; middle=steps to be taken after the key priorities; and low=optional steps). The recommendations included early development of conceptual PRO and HE models, which would identify evidence gaps and drive evidence generation, and EGP validation via early scientific advice from the European Medicines Agency (EMA) and HTA agencies.

CONCLUSIONS : A well-established EGP is critical for overcoming payer uncertainty and facilitating a successful launch of an orphan drug treatment in Europe.