Capturing the Impact of Constraints on the Cost-Effectiveness of Cell and Gene Therapies: A Systematic Review

Objective: Decision-makers need to resolve constraints on delivering cell and gene therapies to patients as these treatments move into routine care. This study aimed to investigate if, and how, constraints that affect the expected cost and health consequences of cell and gene therapies have been included in published examples of cost-effectiveness analyses (CEAs).

Method: A systematic review identified CEAs of cell and gene therapies. Studies were identified from previous systematic reviews and by searching Medline and Embase until 21 January 2022. Constraints described qualitatively were categorised by theme and summarised by a narrative synthesis. Constraints evaluated in quantitative scenario analyses were appraised by whether they changed the decision to recommend treatment.

Results: Thirty-two CEAs of cell (n = 20) and gene therapies (n = 12) were included. Twenty-one studies described constraints qualitatively (70% cell therapy CEAs; 58% gene therapy CEAs). Qualitative constraints were categorised by four themes: single payment models; long-term affordability; delivery by providers; manufacturing capability. Thirteen studies assessed constraints quantitatively (60% cell therapy CEAs; 8% gene therapy CEAs). Two types of constraint were assessed quantitatively across four jurisdictions (USA, Canada, Singapore, The Netherlands): alternatives to single payment models (n = 9 scenario analyses); improving manufacturing (n = 12 scenario analyses). The impact on decision-making was determined by whether the estimated incremental cost-effectiveness ratios crossed a relevant cost-effectiveness threshold for each jurisdiction (outcome-based payment models: n = 25 threshold comparisons made, 28% decisions changed; improving manufacturing: n = 24 threshold comparisons made, 4% decisions changed).

Conclusion: The net health impact of constraints is vital evidence to help decision-makers scale up the delivery of cell and gene therapies as patient volume increases and more advanced therapy medicinal products are launched. CEAs will be essential to quantify how constraints affect the cost-effectiveness of care, prioritise constraints to be resolved, and establish the value of strategies to implement cell and gene therapies by accounting for their health opportunity cost.