Nermina Ferizovic | Health Economics Expert

Given the growing prominence of advanced therapy medicinal products (ATMPs) expected to reach patients in the coming years, it is important to conduct further research in this space to understand all potential impacts and considerations of their economic evaluation. To support this, for my next few blog posts, I will review papers published as part of the “Economics of Gene and Cell Therapies” in PharmacoEconomics.

The first paper I will review is: Capturing the Impact of Constraints on the Cost-Effectiveness of Cell and Gene Therapies: A Systematic Review from Gavan et al., 2023 from The University of Manchester. The article can be found at the following link: https://link.springer.com/article/10.1007/s40273-022-01234-7

Firstly, a summary of the methods. The authors conducted a systematic literature review to identify published cost-effectiveness analyses of gene and cell therapies from 2000 onwards in order to identify examples of where constraints have been considered in analyses. Based on previous research, the authors define constraints as: “any factor that impedes or limits the amount of health status produced for a population of patients receiving specified interventions, or policies, provided by the health care system”. Constraints in any decision-making setting were included (for example, provider, manufacturer, and payer or commissioner settings). The research limits to constraints which are expected to impact cost or health outcomes. 

The authors identified 32 cost-effectiveness analyses: cell (n = 20) and gene therapies (n = 12). In the identified studies, constraints were considered either qualitatively and/or quantitatively. For the former, the authors categorised identifiedqualitative constraints into four themes: single payment models, long-term affordability, delivery by providers and manufacturing capability. For quantitative constraints, two types were defined: alternatives to single payment modelsand improving manufacturing. The authors also assessed whether the consideration of constraints quantitatively led to changes in reimbursement decision making. Four percent of decisions were changed when the constraints on manufacturing were considered quantitatively and 28% of decisions were changed when outcomes-based payment methods were considered. 

Firstly, the definition of constraints. The definition previously defined by the authors is appropriately broad and covers all potential factors which may impede patient access or patient health outcomes but does not limit to ATMPs leaving the door open for other health interventions. Constraints, as defined by the authors, are relevant to the area of ATMPs and it is helpful that the authors separated their findings into qualitative and quantitative constraints, but they do seem to argue that constraints in general should be included in cost-effectiveness analysis to support decision making. This raises several questions which warrant further discussion and research. 

The first question is whether a distinction should be made between constraints which impact on the value of a health intervention and those which do not impact on their value because a cost-effectiveness analysis is an assessment of value. An example of the former is manufacturing times as patients who are waiting long periods of time for their personalised treatments may experience disease progression which would impact on the value of ATMPs. An example of the latter is payment models which would be difficult to argue impact on the value of an ATMP although they obviously impact payer budgets. The definition of economic evaluation requires that all relevant costs and outcomes are considered but how should relevant be defined in this situation? A second question is how, for instance, should manufacturing constraints be incorporated in cost-effectiveness analyses where they do impact on patient outcomes and thereby the value of ATMPs? Given that ATMPs are rapidly evolving, it is difficult to know how long certain constraints would continue to be constraints. For instance, manufacturing processes are continuously evolving. Does this then mean that ATMPs would need to be re-assessed again and how will ethical issues be handled? The authors rightly point out that the cost-effectiveness of an ATMP could change if constraints impact the cost or health consequences of care. 

This study also raises questions about whether cost-effectiveness analyses of other health interventions should incorporate constraints, and the answer is likely a yes, as implied by the authors’ definition of constraints. A final question is whether cost-effectiveness analyses should incorporate ways to resolve capacity and organisational constraints as the authors suggest. A clear link would need to be made between the value of the specific health intervention and any capacity and organisational constraints.

Overall, this article contributes to research on the health economics of ATMPs and generates further research questions which should be explored to advance the field further.