Comparing medication adherence in patients receiving bisphosphonates for preventing fragility fractures: a comprehensive systematic review and network meta-analysis

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Abstract

Background

Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits.

Objective

To investigate persistence and compliance to oral and intravenous bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate).

Methods

Searches of 12 databases, unpublished sources, and trial registries were conducted, covering the period from 2000 to April 2021. Screening, data extraction, and risk of bias assessment (Cochrane Collaboration risk-of-bias tool 1.0 & ROBINS-I) were independently undertaken by two study authors. Randomised controlled trials (RCTs) and observational studies that used prescription claim databases or hospital medical records to examine patients’ adherence were included. Network meta-analyses (NMA) embedded within a Bayesian framework were conducted, investigating users’ likelihood in discontinuing bisphosphonate treatment. Where meta-analysis was not possible, data were synthesised using the vote-counting synthesis method.

Results

Fifty-nine RCTs and 43 observational studies were identified, resulting in a total population of 2,656,659 participants. Data from 59 RCTs and 24 observational studies were used to populate NMAs. Zoledronate users were the least likely to discontinue their treatment HR = 0.73 (95%CrI: 0.61, 0.88). Higher rates of compliance were observed in those receiving intravenous treatments. The paucity of data and the heterogeneity in the reported medication possession ratio thresholds precluded a NMA of compliance data.

Conclusions

Users of intravenously administered bisphosphonates were found to be the most adherent to treatment among bisphosphonates’ users. Patterns of adherence will permit the more precise estimation of clinical and cost-effectiveness of bisphosphonates.

Trial registration

PROSPERO 2020 CRD42020177166

Supplementary Information

The online version contains supplementary material available at 10.1007/s00198-022-06350-w.

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Most cited references 22

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Rayyan—a web and mobile app for systematic reviews

Mourad Ouzzani, Hossam Hammady, Zbys Fedorowicz … (2017)

Background Synthesis of multiple randomized controlled trials (RCTs) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions. Filtering of searches is time consuming, and no single method fulfills the principal requirements of speed with accuracy. Automation of systematic reviews is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making. We developed Rayyan (http://rayyan.qcri.org), a free web and mobile app, that helps expedite the initial screening of abstracts and titles using a process of semi-automation while incorporating a high level of usability. For the beta testing phase, we used two published Cochrane reviews in which included studies had been selected manually. Their searches, with 1030 records and 273 records, were uploaded to Rayyan. Different features of Rayyan were tested using these two reviews. We also conducted a survey of Rayyan’s users and collected feedback through a built-in feature. Results Pilot testing of Rayyan focused on usability, accuracy against manual methods, and the added value of the prediction feature. The “taster” review (273 records) allowed a quick overview of Rayyan for early comments on usability. The second review (1030 records) required several iterations to identify the previously identified 11 trials. The “suggestions” and “hints,” based on the “prediction model,” appeared as testing progressed beyond five included studies. Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements. The survey respondents reported 40% average time savings when using Rayyan compared to others tools, with 34% of the respondents reporting more than 50% time savings. In addition, around 75% of the respondents mentioned that screening and labeling studies as well as collaborating on reviews to be the two most important features of Rayyan. As of November 2016, Rayyan users exceed 2000 from over 60 countries conducting hundreds of reviews totaling more than 1.6M citations. Feedback from users, obtained mostly through the app web site and a recent survey, has highlighted the ease in exploration of searches, the time saved, and simplicity in sharing and comparing include-exclude decisions. The strongest features of the app, identified and reported in user feedback, were its ability to help in screening and collaboration as well as the time savings it affords to users. Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of reviewers.

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The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.

Brian Hutton, Georgia Salanti, Deborah M Caldwell … (2016)

The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement was developed specifically to improve the reporting of systematic reviews incorporating network meta-analyses. A group of experts participated in a systematic review, Delphi survey, and face-to-face discussion and consensus meeting to establish new checklist items for this extension statement. Current PRISMA items were also clarified. A modified, 32-item PRISMA extension checklist was developed to address what the group considered to be immediately relevant to the reporting of network meta-analyses. This document presents the extension and provides examples of good reporting, as well as elaborations regarding the rationale for new checklist items and the modification of previously existing items from the PRISMA statement. It also highlights educational information related to key considerations in the practice of network meta-analysis. The target audience includes authors and readers of network meta-analyses, as well as journal editors and peer reviewers.

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Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial.

Georgia Salanti, A E Ades, John Ioannidis (2011)

To present some simple graphical and quantitative ways to assist interpretation and improve presentation of results from multiple-treatment meta-analysis (MTM). We reanalyze a published network of trials comparing various antiplatelet interventions regarding the incidence of serious vascular events using Bayesian approaches for random effects MTM, and we explore the advantages and drawbacks of various traditional and new forms of quantitative displays and graphical presentations of results. We present the results under various forms, conventionally based on the mean of the distribution of the effect sizes; based on predictions; based on ranking probabilities; and finally, based on probabilities to be within an acceptable range from a reference. We show how to obtain and present results on ranking of all treatments and how to appraise the overall ranks. Bayesian methodology offers a multitude of ways to present results from MTM models, as it enables a natural and easy estimation of all measures based on probabilities, ranks, or predictions. Copyright © 2011 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

A. Bastounis:

ORCID: http://orcid.org/0000-0001-5861-9373

Anastasios.Bastounis1@nottingham.ac.uk

T. Langley: tessa.langley@nottingham.ac.uk

S. Davis: s.davis@sheffield.ac.uk

Z. Paskins: z.paskins@keele.ac.uk

N. Gittoes: Neil.Gittoes@uhb.nhs.uk

J. Leonardi-Bee: jo.leonardi-bee@nottingham.ac.uk

O. Sahota: opinder.sahota@nuh.nhs.uk

Journal

Journal ID (nlm-ta): Osteoporos Int

Journal ID (iso-abbrev): Osteoporos Int

Title: Osteoporosis International

Publisher: Springer London (London )

ISSN (Print): 0937-941X

ISSN (Electronic): 1433-2965

Publication date (Electronic): 21 February 2022

Publication date PMC-release: 21 February 2022

Publication date (Print): 2022

Volume: 33

Issue: 6

Pages: 1223-1233

Affiliations

[1 ]GRID grid.412920.c, ISNI 0000 0000 9962 2336, Division of Epidemiology & Public Health, School of Medicine, , University of Nottingham, City Hospital, ; Nottingham, NG5 1PB UK

[2 ]GRID grid.11835.3e, ISNI 0000 0004 1936 9262, School of Health and Related Research, Regent Court (ScHARR), , University of Sheffield, ; Sheffield, S1 4DA UK

[3 ]GRID grid.9757.c, ISNI 0000 0004 0415 6205, School of Medicine, , Keele University, ; Keele, ST5 5BG UK

[4 ]GRID grid.500956.f, Haywood Academic Rheumatology Centre, , Midlands Partnership NHS Foundation Trust, ; Stoke-on-Trent , Staffordshire UK

[5 ]GRID grid.6572.6, ISNI 0000 0004 1936 7486, Centre for Endocrinology, Diabetes and Metabolism (CEDAM), , University of Birmingham, ; Birmingham, UK

[6 ]GRID grid.412563.7, ISNI 0000 0004 0376 6589, Queen Elizabeth Hospital, , University Hospitals Birmingham NHS Foundation Trust, ; Birmingham, B15 2TH UK

[7 ]GRID grid.240404.6, ISNI 0000 0001 0440 1889, Queens Medical Centre (QMC), , University of Nottingham, Nottingham University Hospitals NHS Trust, ; Nottingham, NG7 2UH UK

Author information

A. Bastounis http://orcid.org/0000-0001-5861-9373

Article

Publisher ID: 6350

DOI: 10.1007/s00198-022-06350-w

PMC ID: 9106630

PubMed ID: 35188591

SO-VID: adac642e-9a82-4570-a8b4-26ba312c5746

License:

Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 30 September 2021

Date accepted : 14 February 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100000664, Health Technology Assessment Programme;

Award ID: NIHR127550

Award Recipient : O. Sahota

Custom metadata

ScienceOpen disciplines: Orthopedics

Keywords: adherence,bisphosphonates,compliance,discontinuation,network meta-analysis

Data availability:

ScienceOpen disciplines: Orthopedics

Keywords: adherence, bisphosphonates, compliance, discontinuation, network meta-analysis

Comparing medication adherence in patients receiving bisphosphonates for preventing fragility fractures: a comprehensive systematic review and network meta-analysis

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Abstract

Background

Objective

Methods

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Conclusions

Trial registration

Supplementary Information

Related collections

Orthopedics

Most cited references 22

Rayyan—a web and mobile app for systematic reviews

The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.

Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial.

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