Postmenopausal Osteoporotic Women at High Risk of Fracture: METHODS part 2
As with hip fracture, vertebral fracture rates for the general population were adjusted to reflect a PMO population. Efficacy values (in terms of relative risk of fracture) of 0.51 and 0.53 were used for patients treated with alendronate, respectively. These efficacy rates were obtained from randomized clinical trials with similar patient populations as the base case cohort. Excess mortality caused by vertebral fractures was not incorporated because of the lack of comprehensive data on the degree of increased risk of death.
The cost of a radiographic vertebral fracture was estimated at $1,880 and was based on a weighted average of clinical vertebral fracture costs in hospitalized patients and nonhospitalized patients. Because the proportion of radiographic vertebral fractures that are clinically detected and treated ranges from 35% to 50%, we adjusted the clinical fracture cost downward (by a multiplier factor of 12.3% for hospitalized patients and 42.5% for nonhospitalized patients) to avoid overestimating vertebral fracture costs. The expected costs of clinical vertebral fractures included costs of inpatient facilities, emergency room visits, inpatient physician services, outpatient care, and nursing home care. Expected costs related to disability in subsequent years were $71 (after adjustments to the National Osteoporosis Foundation Working Group’s 1992 figure of $120).
The utility decrement applied to patients during the year of a vertebral fracture was 0.16, whereas in all subsequent years a decrement of 0.08 was assumed. For women with a history of hip fracture, the utility decrease is 0.55 in the year of the vertebral fracture and 0.09 in all subsequent years.
Other Fracture Types
In randomized clinical trials, risedronate significantly reduced the number of nonvertebral fractures (defined as a composite of six bone sites: leg, humerus, clavicle, pelvis, hip and wrist) between 36% and 39%, whereas alendronate produced a nonsignificant reduction in fractures of 21%. However, sufficient data were lacking on the incidence and expected costs of non-hip/non-vertebral fractures; therefore, we excluded these types of fractures from the analysis. Fractures of the wrist or forearm were also excluded from the analysis because neither risedronate nor had consistent and statistically significant efficacy values across their clinical trials.
AND BUDGET IMPACT ANALYSIS
The cost-effectiveness of each therapy was assessed in terms of the incremental cost per hip fracture averted and per QALY gained. The cost-effectiveness ratios were calculated by dividing the difference in total discounted costs between two treatment groups (e.g., A and B) by the difference in discounted treatment effectiveness.
Costs A – Costs B
Incremental cost per effect gained = ” ~ “
Effects A – Effects B
In the base case analysis, both costs and outcomes were discounted at a rate of 3%. Costs included all fracture-related costs in the year of fracture and all subsequent years as well as the cost of therapy over the entire observation period. In addition to comparing risedronate to alendronate canadian, both therapies were compared to an untreated cohort. Total budgetary impacts of each therapy over the three-year period were also calculated using the discounted costs.
Table 2 Parameter Values Used in the Sensitivity Analyses
|Hip Fracture||Year of Fracture||Subsequent Years|
|Low||$27,648||$2,874||Base values +/- 25%|
|Low||$1,410||$53||Base values +/- 25%|
|Hip Fracture||Year of Fracture||Subsequent Years|
|Low||0.09||0.045||Base values x 0.5|
|High||0.27||0.l35||Base values x l.5|
|Low||0.08||0.04||Base values x 0.5|
|High||0.24||0.l2||Base values x l.5|
|First 3 months||25%||Analysis of General Practice Research Database38|
|Rest of lst year||23%||Data on file, Procter & Gamble Pharmaceuticals|
|During 2nd year||l8%|
|During 3rd year||l0%|
|Cumulative over 3 years||76%|
|Hip Fracture||Vertebral Fracture|
|Risedronate (Actonel®)||80%, 20%||64%, 27%||McClung et al., 20016/ Reginster et al., 200028|
|Alendronate||99%, 23%||59%, 32%||Black et al., 199620|
|Relative Risk of Fracture|
|Both hip and vertebral||4, 5, 6, 7|
|Observation Period||Lifetime (death or age l00 years)|
|Starting Age of Therapy||55, 60, 70, 75 years|
To assess the sensitivity of the results to the uncertainty in the input variables, one-way sensitivity analyses were conducted. Variables explored in these analyses included fracture costs, RR, utility values, therapy efficacy, therapy discontinuation rates, and patient age (see Table 2 for data ranges). The lifetime risks of hip fracture for a population with a RR of 4.0 and 5.0 were estimated as 49.6% and 56%, respectively. In addition to these analyses, a sensitivity analysis was conducted in which the base case three-year treatment duration was used, but the observation period for costs and consequences was extended to include the lifetime of patients in the cohort (defined as death or 100 years of age). This analysis was particularly important as it illustrates the long-term treatment benefits in terms of cost-savings and QALYs gained, and is consistent with methodologies employed previously in cost-effectiveness evaluation guidelines and with previous analyses of osteoporosis.