Addressing the health economic challenges of evaluating genome-targeted therapies with uncertain costs and benefits

Advancements in genomic medicine have catalysed the development of genome‑targeted therapies (GTTs), which are therapies that directly modify the genome or influence gene expression. Because these therapies target the root genetic cause of disease, rather than merely treating symptoms, many GTTs are potentially curative, offering transformative opportunities to improve the health of populations with rare genetic conditions. However, GTTs can only improve population health if they are accessible to patients, and their prices (£1 million plus) raise questions about the value of introducing them into both public and private health systems.

A key barrier to the reimbursement of these therapies is that significant long‑term uncertainties remain around their lifelong impacts on health outcomes and resource utilisation. Economic evaluations of disease‑modifying or curative therapies may need to extrapolate lifelong costs and benefits on the basis of clinical trial evidence that may only have followed patients for five years or less. While decision‑making bodies routinely make reimbursement decisions under uncertainty, and a range of health economic methods exist to measure, summarise and communicate this uncertainty, the nature and scale of uncertainty associated with GTTs may differ in important ways from those typically encountered in economic evaluations.

This project aims to characterise the distinct sources of uncertainty in the economic evaluation of GTTs, examine how these uncertainties are perceived and managed by policymakers, and assess the extent to which existing methodological frameworks and policy tools are adequate in this context. We aim to better understand how to bring together various sources of information to quantify and reduce uncertain costs and outcomes. A comprehensive understanding of these issues is essential to ensure that uncertainty does not lead to unnecessary delays in reimbursement or undue restrictions on patient access.

Funder: Medical Research Council, UKRI