The analysis was based on an adaptation of a published mathematical model. A lifetime horizon was considered. The authors stated that the perspective of the NHS and personal social services was adopted.
The efficacy of each treatment over no intervention was a key input for the model. The efficacy of alendronate was from a meta-analysis and the efficacy of vitamin K1
was from a double-blind randomised controlled trial (RCT) that compared vitamin K1
with placebo, in Canada. This RCT was identified by a systematic review of the literature in electronic databases. The other clinical and epidemiological inputs were from the literature. A number of assumptions were required, especially for the waning time for both treatments and the efficacy of vitamin K1
for each type of fracture, which was assumed to be equal.
Monetary benefit and utility valuations:
The disutilities associated with fractures were from a study conducted in Sweden. This study assumed that all fractures combined within a group had the same disutility.
Measure of benefit:
Quality-adjusted life-years (QALYs) were the benefit measure and they were discounted at an annual rate of 3.5%.
The economic analysis included the costs of drugs and fractures. Drug costs were based on NHS prices and conventional dosages. Fracture costs were from a Health Technology Assessment performed by the authors of this study. It was assumed that there was no cost for adverse events. All costs were in UK pounds sterling (£) and a 3.5% annual discount rate was applied.
Analysis of uncertainty:
A probabilistic sensitivity analysis was undertaken, using 1,000 independent Monte Carlo samples for each intervention. Cost-effectiveness thresholds of £20,000 and £30,000 per QALY were considered. In an alternative scenario, vitamin K1
was assumed to have no effect on the risk of hip fracture, while its efficacy against fractures of the vertebrae, wrist, and proximal humerus remained at baseline values. The EVSI was calculated to assess whether a head-to-head clinical trial of alendronate and vitamin K1
could be worthwhile. Sensitivity analyses were performed to check if the EVSI results were robust to variations in the model assumptions.