Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence from the ARCH trial indicates that romosozumab followed by alendronic acid significantly reduces the risk of fractures compared to alendronic acid alone, with a 50% lower relative risk of vertebral fractures and a statistically significant reduction in clinical fractures. However, the extent of the benefit is uncertain due to differences in trial populations in indirect comparisons.
Cost effectiveness
The cost-effectiveness estimates for romosozumab followed by alendronic acid are within what NICE considers acceptable, particularly when considering the ICER is likely below £30,000 per QALY gained. However, uncertainties in the model persist, particularly regarding treatment persistence and utility values.
Quality of life
The committee concluded that severe osteoporosis can substantially affect quality of life, and preventing fragility fractures would improve this. While the ARCH trial did not provide robust utility values, the use of fracture utility multipliers from the ICUROS study suggests a moderate improvement in HRQoL.
Supporting Domains
Safety and Adverse Effects
Romosozumab has a generally acceptable safety profile, although there is a concern regarding an increased risk of serious cardiovascular events compared to alendronic acid. The committee noted that balancing benefits and risks is essential, but overall, the adverse effects are manageable.
Comparator Selection
The treatment was compared against appropriate standard-of-care alternatives, including bisphosphonates and other osteoporosis treatments. The committee concluded that both bisphosphonates and non-bisphosphonates are relevant comparators for romosozumab.
Patient Population and Subgroups
The trial population in the ARCH study is broadly generalizable to the intended patient population of postmenopausal women with severe osteoporosis at high risk of fracture. However, there are some limitations regarding the company’s narrower definition of imminent fracture risk.
Care Pathway Integration
Romosozumab can be integrated into existing healthcare pathways with minor adjustments, such as training for administration. The committee noted that the treatment is self-administered, which facilitates integration into current clinical practice.
Resource Use and Cost Implications
The economic model indicates that romosozumab is likely to have a manageable budget impact, with the potential for cost savings in the long term due to reduced fracture rates. The committee concluded that the resource implications are justifiable given the expected benefits.
Evidence Quality and Robustness
The evidence base is primarily derived from the ARCH trial, which is a well-designed RCT. However, there are some concerns regarding the generalizability of results to the imminent fracture risk population and the reliance on indirect comparisons.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties in the economic model, particularly regarding treatment persistence and the impact of cardiovascular events. The committee noted that these uncertainties could affect the overall decision-making process.
