Combining fracture outcomes in phase 3 trials of osteoporosis: an analysis of the effects of denosumab in postmenopausal women

• This paper explores use of metrics that combine fracture outcomes that add power to phase 3 studies and provide a surrogate outcome for regulatory agencies. Introduction The aim of this study was to develop an analytic framework that would combine information from all fracture outcomes (including radiographic vertebral fractures) in phase 3 studies to provide a metric for the assessment of treatment efficacy. Methods Data from the phase 3 study of denosumab were used as an exemplar comparing the effects of active intervention with placebo on the risk of all fractures associated with osteoporosis. Fracture outcomes were assigned utility weights drawn from the published literature and applied to age-specific health state values of the general population. For each fracture outcome in each arm of the study, cumulative disutility was computed to serve as the principal end point. The hypothesis tested was that treatment with denosumab results in a significant reduction in mean fracture-related disutility. Results Treatment with denosumab was associated with significantly lower utility loss compared with placebo. For patients treated with denosumab, mean utility loss was 42% less than with placebo (4.5 vs. 7.5 QALYs/1000 patient years, respectively, p < 0.001). Conclusions Denosumab significantly decreased utility loss. The use of metrics that combine fracture outcomes may provide added power to phase 3 studies and provide a surrogate outcome for regulatory agencies.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Denosumab

Disutility

Fracture

Phase 3 study

Quality of life years

health technology-assessment

bone-density

worldwide prevalence

vertebral fractures

increased mortality

excess mortality

meta-regression

risk

hip

reduction

Endocrinology & Metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)