To summarize the key methodological challenges identified by health technology assessment (HTA) agencies assessing gene therapy (GT) and consideration of broad elements of value.

Economic evaluations (EEs) of voretigene neparvovec (VN) in RPE65-mediated inherited retinal disease (IRD) published in English were selected. HTA evaluations from Australia, Canada, Ireland, Scotland, England, and the United States were reviewed. An existing methodological framework was used to identify the challenges and considerations.

Eight unique EEs were identified of which six were evaluated by HTA agencies. Incremental cost-effectiveness ratios ranged from $68,951 to $643,813 per quality-adjusted life-years (QALY) gained (healthcare perspective) and dominant to $480,130 per QALY gained (societal perspective). The key challenges were the lack of validated surrogate outcome, utility values and indirect costs from IRD patients, and limited evidence of the long-term treatment effect. Two HTA agencies reviewed a range of novel broader elements of value and whether they were associated with VN while other agencies discussed some elements of broader value. Caregiver disutility was included in some, but not all, evaluations.

The methodological challenges were consistent with innovative interventions for rare diseases and managed using standard methods. Broader value was important to decision-makers but inconsistently applied across agencies. Possible reasons are limitations in the evidence available of the broader benefits that VN offers and how to incorporate these within an EE. A need exists for greater guidance and consistency across jurisdictions regarding the consideration of broader value that considers latest best practice.

Viral gene therapy is a promising new treatment modality for head and neck cancer. This paper provides the reader with a review of the relevant literature in this field.

There are government licensed viral gene therapy products currently in use for head and neck cancer, utilised in conjunction with established treatment modalities. The viruses target tumour-associated genes, with the first licensed virus replacing p53 gene function, which is frequently lost in tumourigenesis. Oncolytic viruses selectively destroy cancer cells through viral replication and can be armed with therapeutic transgenes.

Despite considerable advances in this field over the last 40 years, further research is needed to improve the overall efficacy of the viruses and allow their widespread utilisation in the management of head and neck cancer.