Table 2.

Summary of challenges, associated uncertainties, and assumptions employed in evaluations

Challenge	Uncertainties	Assumptions used
Modelling long-term BMI trajectories while receiving pharmacotherapies	Limited duration of follow-up from trials for intervention and standard care	Constant absolute difference in BMI after trial ends Natural history increase in BMI for standard care and no change for treatment arm Waning of treatment effect – people on intervention eventually start to gain weight
Modelling time on treatment for pharmacotherapies, and the impact of cessation	Limited follow-up for patients who discontinue for various reasons	Assume time to weight regain of 1–4 years after stopping treatment Use of STEP-1 semaglutide extension study Convergence of both arms to natural history or baseline
Using surrogate relationships to translate the effect of pharmacotherapies on interim endpoints to an impact on clinical events	Clinical trials not long enough to capture clinical events, relationship between surrogate markers and clinical events on pharmacotherapies unclear	Risk equations from different sources (primarily USA and UK) Assuming weight loss reverses risk, or residual effect Annualising multi-year risks
Modelling effects of pharmacotherapies on clinical events that are not solely related to BMI changes	Pharmacotherapies for obesity may affect other outcomes	Including effects on diabetes and cardiovascular events Including other mortality effects

BMI, body mass index