Anastasios Skroumpelos

Background: Rare diseases affect more than 400 million people globally with only a small number having currently approved treatments. Drugs for rare diseases (medications developed to treat conditions affecting small patient populations), which may include innovative drugs (medications with novel mechanisms/new active ingredients) can face access challenges as they are often found not to be cost-effective under conventional health technology assessment methods. In this review we provide a comprehensive and up-to-date understanding of challenges associated with the economic evaluation of innovative drugs for severe-rare diseases, and any proposed solutions and associated barriers to solution adoption. Methods: This review included searches of electronic databases and select health technology assessment agency websites to identify relevant publications, guidelines or recommendations from 1st January 2014 to 29th July 2024. A pre-authorised protocol, including detailed eligibility criteria, was used to ensure robust methodology in the capture of materials. Relevant data extracted from included publications were synthesised thematically to support identification of the most prominent concepts within current literature. Results: Of the 1,803 records identified, 31 publications and eight health technology assessment guidance were included. Main challenges were related to the utilitarian principle underlying cost-effectiveness analysis, the limited scope of the quality-adjusted life year and the value elements assessed. Associated solutions included the incorporation of a societal willingness-to-pay or inclusion of equity in healthcare decision making, reduced weighting of the economic evaluation in resource allocation, consideration of additional value elements, and introducing a quality-adjusted life year weighting or alternative measures of health outcomes. While some payers have implemented modifications to economic evaluation guidelines in an attempt to address the challenges, for example including the consideration of additional value elements, the solutions employed are not consistent across payers and often do not address the root issue. Economic evaluation as part of health technology assessment therefore remains challenging for manufacturers of drugs for rare diseases. Conclusion: Conventional methods of economic evaluation contribute to the access challenge for innovative drugs for rare diseases. Collaboration between payers, manufacturers, and healthcare decision makers to foster greater understanding of how to evolve and adopt these novel solutions will be key to ensuring timely patient access.

The COVID-19 pandemic has caused significant disruptions to healthcare, including reduced administration of routinely recommended HPV vaccines in a number of European countries. Because the extent and trends of accumulated vaccine dose deficits may vary by country, decision-makers need country-specific information regarding vaccine deficits to plan effective catch-up initiatives. To address this knowledge gap in Switzerland and Greece, this study used a previously published COVID-19 recovery calculator and historical vaccine sales data to quantify the cumulative number of missed doses and the catch-up rate required to clear the deficit in Switzerland and Greece. The resultant cumulative deficit in HPV doses for Switzerland and Greece were 24.4% and 21.7%, respectively, of the total number of doses disseminated in 2019. To clear the dose deficit by December 2025, monthly vaccination rates must be increased by 6.3% and 6.0% compared to 2019 rates in Switzerland and Greece, respectively. This study demonstrates that administration rates of routine HPV vaccines decreased significantly among Swiss and Greek adolescents during the COVID-19 pandemic and that a sustained increase in vaccination rates is necessary to recover the HPV dose deficits identified and to prevent long-term public health consequences.