For any health technology, this is a difficult question to answer. How do you predict the number of QALYs gained by an intervention? Health economic modelling looks at clinical efficacy results and breaks down the patient group into distinct clinical subpopulations. These are then analysed regarding their potentially different responses to treatment, their reliance on healthcare systems, and the likelihood and level of certainty around these outcomes and how they may change or stabilise over time.
When looking at cell and gene therapies, the equation is unique. Often these therapies are used to treat rare conditions, so the patient populations are smaller and there is less data available. In addition, the costs are much higher, and thus, the cost per QALY that is considered cost-effective needs to be looked at differently. NICE has a specific appraisal process for highly specialised technologies (HSTs) that are meant for very rare and severe diseases and thus require an appraisal that acknowledges the novelty of the innovation and the gaps in evidence. Compared to a standard appraisal, for which NICE set a threshold of £20,000-30,000 per QALY, highly specialised technologies can cost up to £100,000 per QALY to be deemed cost-effective.
Another unique characteristic of genomic technologies like CGTs is that they can have QALY gains of a high magnitude. Libmeldy, for example, is life saving and could provide many healthy years to patients who would otherwise have died young. This is accounted for in the evaluation of impact on not only the individual patient but their families, carers and environments, and ultimately the cost-effectiveness estimate. However, since the data available on these long-term effects is limited, there is some uncertainty around how stable and frequent that treatment response is, making the prediction of the QALYs gained challenging and subject to scrutiny. To account for this uncertainty, the highly specialised technology appraisal may include a recommendation to the NHS only on certain conditions. Libmeldy is recommended on the condition of a confidential commercial arrangement with the manufacturing company, providing a discount to the NHS. This helps share some risk and accommodate uncertainty.
This recommendation from NICE on the use of Libmeldy in the NHS specifies that only specific subpopulations of patients with metachromatic leukodystrophy (MLD) may be prescribed it – children with late infantile or early juvenile types. This is in line the marketing authorisation for use of the intervention in Europe by the European Medicine’s Agency (EMA), which states the populations for which Libmeldy is approved for use. NICE’s recommendation also requires the manufacturer to gather of long-term evidence, another condition stimulated by EMA in the approval of Libmeldy. In order for it to be approved for use in Europe, the manufacturer had to commit to conducting studies to assess long-term efficacy and safety, helping to address the evidence gap mentioned previously around long-term effects of the intervention. This serves as a reminder that health economic evaluations and regulatory approvals are distinct, but inextricably linked – any recommendation for use in a hospital system based on a health economic assessment has to fall within the remit of the intervention’s marketing authorisation.