ABSTRACT
RMs are typically investigated in non-randomized controlled trials with small patient numbers and short-term durations, making HTA agencies question the representatives of study populations and the generalization of study results. Most importantly, evidence limitations generate great uncertainties in assessing the relative effectiveness magnitude of the RMs against alternative therapies and the maintenance of long-term clinical benefits. Consequently, economic analyses of RMs have to rely on intensive extrapolations and assumptions on the long-term outcomes, which compromises the robustness of economic analyses due to the paucity of reliable model inputs for rare diseases. In addition, other factors including cost estimation (additional administrative costs and indirect cost reductions), the selection of appropriate discount rates, and time horizons will also significantly affect the conclusion of economic analysis. Precise value assessments of RM are hindered by the methodology for utility elicitation and quality-adjusted life-year (QALY) generation because the potential indirect health benefits related to RMs, such as improved professional opportunities and reduced lifetime caregiver burdens, are largely neglected. Constricted budgets determine that payers have to put strict reimbursement restrictions on RMs, which potentially lead to limited clinical adoption and inequitable patient access. Innovative payment mechanisms were proposed to mitigate the financial risk, while outcome-based payments will require substantial investments to establish the infrastructures to capture the reliable and unbiased outcome measurements. Installment payments show promise to spread the total cost over multiple years and facilitate the timely patient access, while the determination of country-specific standards and criteria for the application of amortization needs further discussion.
