Challenges in Modelling the Cost Effectiveness of Pharmacotherapies for Obesity.

The cost effectiveness of pharmacotherapies for obesity (such as semaglutide, tirzepatide, liraglutide, and newer agents) is increasingly being appraised by health technology assessment (HTA) bodies. Modelling is required to extrapolate weight change observed over relatively short clinical trial durations to long-term weight loss and associated cardio-metabolic outcomes and costs. Extrapolation is a common issue in HTA, but there is a unique challenge for anti-obesity drugs because of the number of interacting uncertainties. This is a particular concern given the substantial eligible population sizes and associated high financial decision risk of providing lifetime treatment. We describe four key challenges in modelling pharmacotherapies for obesity: (1) modelling long-term body mass index (BMI) trajectories with and without obesity pharmacotherapy, (2) modelling time on treatment, (3) using risk equations to link changes in BMI to clinical outcomes, and (4) modelling clinical outcomes not (solely) related to BMI changes. We discuss each of these challenges and the impact they have had in global HTA appraisals for pharmacotherapies. We speculate how these challenges relating to short-term clinical trials could be overcome to more robustly predict long-term outcomes and the role that observational data may play. As clinical trial and real-world evidence for technologies for obesity evolves, analysts and decision-makers need to determine which evidence sources are most appropriate and how they should be combined.