A Bayesian Analysis of Bisphosphonate Effects and Cost-Effectiveness in Post-menopausal Osteoporosis

OBJECTIVE - Effects of oral bisphosphonates on the rate of vertebral
fractures in post-menopausal osteoporotic women have been found in
clinical trials. We wanted to compare the effects of two
bisphosphonates, alendronate and etidronate, and calculate the price
difference that would give the same cost-effectiveness for the two
drugs. We also intended to give by means of Bayesian statistics,
probability distributions and point and interval estimates for key
parameters. METHODS - We used published, double blind, randomized
placebo controlled studies describing the results of occurrence of
vertebral fractures at 3-year follow-up in postmenopausal women taking
bisphosphonates. Four studies were identified, including altogether
3510 women. The women had either suffered a fracture at entry or had a
bone density at least 2.5 SD below the mean value for young women. Two
of the studies dealt with alendronate and two with etidronate. RESULTS
- According to three of the studies, the number of women out of a 100
avoiding vertebral fractures during a 3-year observation period varied
from two to seven. The fourth study did not contain the necessary data.
The four studies showed that, for the incidence rate, the
multiplicative treatment effects were respectively 0.45, 0.74, 0.40 and
0.36, where values less than 1 indicate positive treatment effects.
Using data from all four studies, a comparison of the two drugs gave a
point estimate of 0.247 with 95% credibility interval (CI): -0.051 to
0.496 for a difference in effect in favour of alendronate measured in
terms of risk ratio of fracture and 0.302 (CI: 0.099 to 0.539) measured
as incidence rate ratio. Based on two studies, showing about the same
prevalence of fractures in the control groups, the difference in the
risk difference between the two drugs was 0.028 (CI: -0.039 to 0.079).
CONCLUSIONS - Bisphosphonates effectively reduce risk of new vertebral
fractures, but alendronate is somewhat more effective than etidronate.
To obtain equal cost-effectiveness alendronate should be priced 40-70%
higher than etidronate.