https://orcid.org/0000-0002-9728-9992
Abstract
Background
Poor treatment adherence in COPD patients is associated with poor clinical outcomes and increased healthcare burden. Personalized approaches for adherence management, supported with technology-based interventions, may offer benefits to patients and providers but are currently unproven in terms of clinical outcomes as opposed to adherence outcomes.
Methods
Maximizing Adherence and Gaining New Information For Your COPD (MAGNIFY COPD study), a pragmatic cluster randomized trial, aims to evaluate the impact of an adherence technology package (interventional package), comprising an adherence review, ongoing provision of a dual bronchodilator but with an add-on inhaler sensor device and a connected mobile application. This will compare time to treatment failure and other clinical outcomes in patients identified at high risk of exacerbations with historic poor treatment adherence as measured by prescription collection to mono/dual therapy over one year (1312 patients) versus usual care. Treatment failure is defined as the first occurrence of one of the following: (1) moderate/severe COPD exacerbation, (2) prescription of triple therapy (inhaled corticosteroid/long-acting β2-agonist/long-acting muscarinic antagonist [ICS/LABA/LAMA]), (3) prescription of additional chronic therapy for COPD, or (4) respiratory-related death. Adherence, moderate/severe exacerbations, respiratory-related healthcare resource utilization and costs, and intervention package acceptance rate will also be assessed. Eligible primary care practices (N=176) participating in the Optimum Patient Care Quality Improvement Program will be randomized (1:1) to either adherence support cluster arm (suitable patients already receiving or initiated Ultibro® Breezhaler® [indacaterol/glycopyrronium] will be offered interventional package) or the control cluster arm (suitable patients continue to receive usual clinical care). Patients will be identified and outcomes collected from anonymized electronic medical records within the Optimum Patient Care Research Database. On study completion, electronic medical record data will be re-extracted to analyze outcomes in both study groups.
Registration Number
ISRCTN10567920.
Conclusion
MAGNIFY will explore patient benefits of technology-based interventions for electronic adherence monitoring.
Abbreviations
ASA, adherence support arm; COPD, chronic obstructive pulmonary disease; CE, Conformité Européenne; EMR, electronic medical record; FEV1, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICC, Intraclass Correlation Coefficient; ICS, inhaled corticosteroids; LAMA, long-acting muscarinic antagonists; LABA, long-acting β2 agonists; MPR, medication possession ratio; OPCRD, Optimum Patient Care Research Database; OPC, Optimum Patient Care; RCTs, randomized clinical trials; TAP, technology adherence package.
Data Sharing Statement
Observational Pragmatic Research Institute (OPRI) will not provide access to patient-level data, if there is a reasonable likelihood that individual patients could be re-identified. In addition, clinical data, in some cases, have been collected subject to contractual or consent provisions that prohibit transfer to third parties. Such restrictions may preclude granting access under these provisions. Where co-development and data sharing agreements or other legal restrictions prevent companies from sharing data, companies will work with qualified requestors to provide summary information where possible.
Acknowledgments
The authors thank Mohammed Najeeb Ashraf, Phani Dantu and Rahul Lad (Novartis Healthcare Pvt. Ltd India) for providing medical writing support/editorial support, which was funded by Novartis, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
Author Contributions
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.
Disclosure
David Price has board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Thermofisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Merck, Zentiva (Sanofi Generics), Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma, Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Thermofisher; funding for patient enrolment or completion of research from Novartis; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; personal fees from Airway Vista Secretariat, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L, Talos Health Solutions, WebMD Global LLC, outside the submitted work; and was an expert witness for GlaxoSmithKline.
Rupert Jones declares grants from Astra Zeneca, GlaxoSmithKline and Novartis and personal fees for consultancy, speaker’s fees or travel support from Astra Zeneca, Boehringer Ingelheim, Glaxo Smith Kline, Novartis, Nutricia and OPRI.
Victoria Carter is an employee of the study sponsor Observational & Pragmatic Research International Ltd (OPRI), the study sponsor, which has conducted paid research in respiratory disease on behalf of the following other organizations in the past 5 years: Aerocrine, AKL Ltd, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Orion, Sanofi, Takeda and Teva.
Alan Kaplan received fee for advisory board or speakers bureau for Astra Zeneca, Boehringer Ingelheim, Covis, GSK, Merck Frosst, Pfizer, Purdue, Novartis, Sanofi, Teva, Trudel.
David MG Halpin has received personal fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Pfizer and Sanofi, and non-financial support from Boehringer Ingelheim and Novartis.
Anu Kemppinen and Allan Clark have nothing to disclose.
Hilary Pinnock was paid an honorarium for writing an on-line piece on supported self-management for Teva website. She is involved with several professional or educational organisations which receive multi-company sponsorship.
Job van Boven receives funding from the European Commission to Chair the European Network to Advance Best practices & technoLogy on medication adherencE (COST Action CA19132, ENABLE). His institution (Medication Adherence Expertise Center of the northern Netherlands, MAECON, University Medical Center Groningen, Groningen, the Netherlands) has received consultancy fees, speaking fees, and/or research grants from AstraZeneca, Boehringer Ingelheim, Chiesi, eLucid mHealth, Menarini, Novartis, Teva and Trudell Medical related to medication adherence but all unrelated to this study.
Kai M. Beeh declares personal or institutional compensations from the following in the past 5 years: Kai Beeh is a full time employee of insaf Respiratory Research Institute. The institution has received compensation for services on advisory boards or consulting for AstraZeneca, Berlin Chemie, Boehringer, Chiesi, Cytos, GSK, Mundipharma, Novartis, Pohl Boskamp, Sanofi, Zentiva. The institution has received compensation for speaker activities in scientific meetings supported by AstraZeneca, Berlin Chemie, Boehringer, ERT, GSK, Novartis, Pfizer, Pohl Boskamp, Sanofi, Takeda. The institution has further received compensation for design and performance of clinical trials from AstraZeneca, Boehringer, GSK, Infinity, Mundipharma, Novartis, Parexel, Pearl Therapeutics, Pfizer, Revotar, Teva, Sterna, and Zentiva.
Konstantinos Kostikas was an employee and shareholder of Novartis Pharma AG until October 31, 2018. He have received honoraria for presentations and consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GSK, Menarini, Novartis and Sanofi; his department has received funding and grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GSK, Menarini, Novartis and NuvoAir.
Nicolas Roche reports research grants from Boehringer Ingelheim, Novartis, Pfizer and personal fees for consultancy, advisory boards, lectures and education, participation to steering committees from Boehringer Ingelheim, Novartis, Pfizer, Teva, GSK, AstraZeneca, Chiesi, Sanofi, Trudell, Zambon.
James Chalmers reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Chiesi, grants and personal fees from Gilead Sciences, grants and personal fees from GlaxoSmithKline, grants and personal fees from Novartis, personal fees from Zambon, from null, outside the submitted work; Dr. Chalmers reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim and Insmed, personal fees from Chiesi, grants and personal fees from Gilead Sciences, grants and personal fees from GlaxoSmithKline, grants and personal fees from Novartis, personal fees from Zambon, personal fees from Janssen, outside the submitted work.
Omar Usmani reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Chiesi, grants and personal fees from GlaxoSmithKline, personal fees from Napp, personal fees from Mundi Pharma, personal fees from Sandoz, personal fees from Takeda, grants from Edmond pharma, personal fees from Cipla, personal fees from Covis, personal fees from Novartis, personal fees from Mereo BioPharma, personal fees from Orion, personal fees from Menarini, personal fees from Deva, personal fees from Roche, personal fees from, Trudel, personal fees from UCB outside the submitted work.
Björn Holzhauer, Pascal Pfister, Hui Cao and Paul Mastoridis are employees of Novartis and holds stock in Novartis Pharma AG. The authors report no other conflicts of interest in this work.