Analytical approach:
The economic evaluation was based on one clinical trial. A Markov model was used for the ongoing risks of treatment discontinuation, disease progression, and death, over five years. The costs and benefits were aggregated over this period. The authors stated that a health care system perspective was adopted.
Effectiveness data:
The primary clinical data were the probability of reaching the minimum improvement at four weeks, on Sativex, and the probability of disease progression each month, over the five years. The probability of death and treatment discontinuation were incorporated. There were two stages to the clinical trial. At four weeks, 241 of the initial 572 patients had responded to Sativex and were randomised to Sativex or placebo. After the 12 weeks of the second part of the trial, patients were assumed to remain at the same spasticity severity up to the five years of the study, unless they discontinued treatment. Discontinuation rates were from the trial and from a long-term, open-label UK study.
Monetary benefit and utility valuations:
The utility values were obtained for mild, moderate and severe spasticity states. They were from the 241 trial participants, who completed the EQ-5D questionnaire at the end of the 12-week second part of the trial. Any quality-of-life effects associated with adverse events were assumed to be captured in the utility questionnaire.
Measure of benefit:
The measure of benefit was the quality-adjusted life-year (QALY). Benefits were discounted at an annual rate of 3.5%.
Cost data:
The resources included the medications; administration of botulinum toxin and intrathecal baclofen; tenotomy and rhizotomy surgery; health care visits for the management of MS; and tests that included the identification of responders at four weeks. The percentage of patients receiving each treatment in standard practice, was estimated by a Delphi survey of 16 neurologists (eight from Germany and eight from Spain). The resource consumption was estimated separately for patients with mild, moderate, and severe MS spasticity. The annualised resource use was valued using 2010 unit costs. Drug price lists, published sources and public information were used for the unit costs. Separate unit costs were derived for Germany and for Spain. The costs were reflated to 2010 prices, where necessary, using published country-specific inflation rates. They were reported in Euros (EUR) and discounted at an annual rate of 3.5%.
Analysis of uncertainty:
One-way sensitivity analyses were conducted to investigate the impact on the results of varying the input parameters across a defined range of values. The results were presented in tornado diagrams. The range of parameter values was defined as ±20% of the initial estimate. Alternative resource use data from a German retrospective study were tested.