Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the SURMOUNT-1 trial indicates that tirzepatide significantly reduces body weight compared to placebo, with a mean percentage change of -20.1% and a high percentage of participants achieving at least a 5% weight loss. This suggests a clear clinical advantage over standard care, although the lack of long-term data beyond 72 weeks introduces some uncertainty.
Cost effectiveness
The most plausible ICER for tirzepatide is above the acceptable threshold of £20,000 per QALY gained, indicating low cost-effectiveness. The committee noted that the ICERs for the target population were not sufficiently close to the acceptable ICER threshold, suggesting that the cost may not justify the benefits.
Quality of life
While the document does not provide extensive HRQoL data, it suggests that managing obesity can improve quality of life. The evidence indicates that tirzepatide, when combined with diet and exercise, positively impacts physical functioning and mental well-being, although specific validated tools were not mentioned.
Supporting Domains
Safety and Adverse Effects
Tirzepatide has a very good safety profile, with mostly mild or moderate adverse events reported in the trials. The committee noted that the treatment was well tolerated, with a high percentage of participants able to tolerate the maximum dose, indicating a favorable safety profile compared to existing therapies.
Comparator Selection
The comparators selected for the evaluation, including semaglutide and diet and exercise support, are appropriate and relevant to the target population. The committee concluded that these comparators reflect the current standard of care for managing obesity.
Patient Population and Subgroups
The trial population is broadly representative of the intended patient population, including those with relevant comorbidities. The committee acknowledged that while some subgroups were excluded, the overall population included a wide range of comorbidities, enhancing generalizability.
Care Pathway Integration
The integration of tirzepatide into existing care pathways may require significant adjustments, particularly in primary care settings where diet and exercise support is not consistently available. The committee noted that additional services would need to be implemented, indicating a moderate risk of disruption.
Resource Use and Cost Implications
The anticipated costs of implementing tirzepatide exceed the budget impact test of £20 million in the first three years, indicating a high resource burden. The committee expressed concerns about the sustainability of these costs within the Healthcare.
Evidence Quality and Robustness
The evidence base is supported by a well-conducted Phase III trial (SURMOUNT-1) with a robust design. However, the lack of long-term follow-up data introduces some uncertainty regarding the durability of the treatment effects.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the long-term effectiveness of tirzepatide and its impact on broader health outcomes. The committee noted that these uncertainties could affect decision-making and the overall assessment of the treatment’s value.
