Discounting the cost and effect for health intervention is a controversial topic over the last two decades. In particular, the cost-effectiveness of gene therapies is especially sensitive to the discount rate because of the substantial delay between the upfront cost incurred and long-lasing clinical benefits received. This study aims to investigate the influence of employing alternative discount rates on the incremental cost-effectiveness ratio (ICER) of gene therapies.

A systematic review was conducted to include health economic evaluations of gene therapies that were published until April 2023.

Sensitivity or scenario analysis indicated that discount rate represented one of the most influential factors for the ICERs of gene therapies. Discount rate for cost and benefit was positively correlated with the cost-effectiveness of gene therapies, that is, a lower discount rate significantly improves the ICERs. The alternative discount rate employed in some cases could be powerful to alter the conclusion on whether gene therapies are cost-effective and acceptable for reimbursement.

Although discount rate will have substantial influence on the ICERs of gene therapies, there lacks solid evidence to justify a different discounting rule for gene therapies. However, it is proposed that the discount rate in the reference case should be updated to reflect the real-time preference, which in turn will affect the ICERs and reimbursement of gene therapies more profoundly than conventional therapies.

Implicit factors can be defined as any criteria that play a role in the health technology assessment (HTA) deliberative process but are not part of the HTA framework. To date, very few studies have explored the influence of implicit factors on this process. This survey of HTA experts in five European countries aimed to analyze the influence of implicit factors on the HTA deliberative process.

Semi-structured interviews with 20 HTA experts from five European countries (France, Germany, Italy, Spain, and the United Kingdom) were conducted from February to May 2021. The main topics of the interviews were: the HTA deliberative process; the degree of influence on the HTA deliberative process of a set of factors previously identified in a systematic literature review performed by the authors; and recommendations for improving the deliberative process.

All but two of the experts concurred that implicit factors played a role in the deliberative process. German experts considered that the factors explored had a low influence on the process. Burden of disease and unmet need scored highest, followed by the professional experience of the people involved in the HTA deliberative process. To improve the deliberative process, experts suggested expanding the external stakeholder perspective (i.e., including patients, the pharmaceutical industry, and the public), increasing transparency when revealing implicit factors, and implementing a methodology to mitigate the influence of implicit factors.

Our survey indicates a need to increase external involvement in the process and to develop a methodology for unmasking the implicit factors in the deliberative process. This may be achieved by either updating the current frameworks to include these implicit factors or by developing new methods to address them. Further research may explore approaches to acknowledge the implicit factors in the HTA deliberative process in a systematic manner.