Evidence map›Paper›PMID 33156354›Full record

Trial reportOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2021

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

J A Kanis, N C Harvey, M Lorentzon, E Liu, L Vandenput, E V McCloskey, H Johansson

Abstract readClinical Trial, Phase III
PubMed Publisher
In one paragraph

Trial report in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 2 pooled it
1.2field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 2 syntheses or guidelines pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

J A KanisMary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia. w.j.pontefract@shef.ac.uk.
N C HarveyMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
M LorentzonGeriatric Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
E LiuMary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
L VandenputMary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
E V McCloskeyCentre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK.
H JohanssonMary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
Australian Catholic University · AUUniversity of Sheffield · GBUniversity Hospital Southampton NHS Foundation Trust · GBUniversity of Gothenburg · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

introductionThe 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.

methodsData 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.

resultsTreatment 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).

conclusionsDenosumab 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.

Indexed as

Bone Density Conservation AgentsDenosumabOsteoporosis, PostmenopausalAntibodies, Monoclonal, HumanizedFemaleHumansPostmenopauseTreatment OutcomeAntibodies, Monoclonal, HumanizedBone Density Conservation AgentsDenosumabDenosumabDisutilityFracturePhase 3 studyQuality of life years

Identifiers

PMID33156354
OpenAlexW3096909793

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.