Abstract
BackgroundIn the absence of head-to-head trials, indirect comparisons of randomized placebo-controlled trials may provide a viable option to assess relative efficacy. The purpose was to estimate the relative efficacy of reduction of fractures in post-menopausal women, and to assess robustness of the results.MethodsA systematic literature review of multiple databases identified randomized placebo-controlled trials with nine drugs for post-menopausal women. Odds ratio and 95% credibility intervals for the rates of hip, non-vertebral, vertebral, and wrist fractures for each drug and between drugs were derived using a Bayesian approach. A drug was ranked as the most efficacious if it had the highest posterior odds ratio, or had the highest effect size.Results30 studies including 59,209 patients reported fracture rates for nine drugs: alendronate (6 studies), denosumab (1 study), etidronate (8 studies), ibandronate (4 studies), raloxifene (1 study), risedronate (7 studies), strontium (2 study), teriparatide (1 study), and zoledronic acid (1 study). The drugs with the highest probability of reducing non-vertebral fractures was etidronate and teriparatide while the drugs with the highest probability of reducing vertebral, hip or wrist fractures were teriparatide, zoledronic acid and denosumab. The drugs with the largest effect size for vertebral fractures were zoledronic acid, teriparatide and denosumab, while the drugs with the highest effect size for non-vertebral, hip or wrist fractures were alendronate or risedronate. Estimates were consistent between Bayesian and classical approaches.ConclusionTeriparatide, zoledronic acid and denosumab have the highest probabilities of being most efficacious for non-vertebral and vertebral fractures, and having the greatest effect sizes. The estimates from indirect comparisons were robust to differences in methodology.
Highlights
In the absence of head-to-head trials, indirect comparisons of randomized placebo-controlled trials may provide a viable option to assess relative efficacy
Literature Search An electronic search of the following databases restricted to English was conducted from January 1990 to October 2009, and the search was continually updated by alerts until September 2010: EMBASE, Medline, Medline in Process, and Cochrane Database for Systematic Reviews, Evidence Based Reviews-American College of Physicians Journal, National Health Service (NHS) Database of Assessment of Reviews and Effectiveness (DARE), CINAHL
Baseline Bone Mineral Density (BMD) in the hip ranged from 0.28 to 1.08 and the percentage of participants that had previous vertebral fractures were from 0% to 100%
Summary
In the absence of head-to-head trials, indirect comparisons of randomized placebo-controlled trials may provide a viable option to assess relative efficacy. To reduce the risk of fractures due to osteoporosis, drugs have been introduced to reduce the rate of bone loss and to increase the strength of the bones. In Canada in 2010 about 9% of the population age 50 years and over were receiving an osteoporosis drug. These drugs include the bisphosphonates (alendronate, etidronate, risedronate or ibandronate), Selective Estrogen Receptor Modulators (raloxifene) and anabolic agents (teriparatide). All of these have shown to be effective in reducing the rate of fractures relative to placebo [4]. A major gap in the evidence to identify the most efficacious drugs is the lack of randomized active-controlled trials, i.e., direct treatment comparison (DTC) evidence [4]
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