Methodological challenges in Dutch HTA of non-oncological orphan drugs: a retrospective analysis and price comparison using different pricing models

Cost-effectiveness analyses can have limited informative value for pricing and reimbursement decisions for orphan drugs. In cases where cost-effectiveness cannot be reliably assessed or achieved, value-based pricing principles may not be applicable. As a result, alternative pricing models have been proposed. It remains unclear how these alternative approaches compare to one another and to traditional value-based pricing. This study aims to explore and compare these pricing models in the context of orphan drugs. All cost-effectiveness assessments of non-oncological orphan drugs published by the Dutch National Health Care Institute between 2015 and 2024 were analyzed to identify methodological challenges and recommended value-based price estimates. For each treatment, prices were also estimated using a cost-plus pricing model and a discounted cash flow model. These estimates were then compared to value-based prices and public list prices. Cost-effectiveness assessments of 13 different therapies were found, 12 of which provide information for determining a value-based price. All assessment reports cite major uncertainties or unresolved issues in one or more of the following areas: (1) lack of a suitable comparator, (2) sub-optimal disease understanding, (3) limited evidence to inform models, (4) effect uncertainty and (5) flawed QoL measurement. Only one single treatment was found to be cost-effective at the appropriate threshold. Value-based prices were found to fall below, within or above the price ranges of the two alternative models. Challenges cited in literature are present in Dutch assessments of the cost-effectiveness of orphan drugs. Although these issues cause considerable uncertainty, they did not negate CEA’s ability to inform decision-making. Still, orphan drugs tend to be far from cost-effective, providing a challenge for patient access that is both timely and financially feasible. Alternative models like cost-plus pricing and discounted cash flow tend to generate even lower price estimates and rely on considerable assumptions, making them unlikely to offer a viable solution in their current state.