Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.
Bibliographical noteFunding Information:
work. Pascal Vranckx: non-financial support from AstraZeneca, nonfinancial support from Bayer Health Care, non-financial support from Boehringer-Ingelheim, non-financial support from Daiichi-Sankyo, non-financial support from The Medicines Co, outside the submitted work. Eugene McFadden: personal fees from null, during the conduct of the study; other from Cardialysis (CRO), other from Abbott Vascular, grants from Astra Zeneca, other from Bayer, other from Terumo, outside the submitted work. Francesco Costa: Nothing to disclose. Bernard Vrijens: Employee of WestRock Healthcare. Gerrit-Anne Van Es: Nothing to disclose. Pierluigi Tricoci: Grant from Merck, CSL, Amgen, Sanofi. Jan G.P. Tijssen: Nothing to disclose. Karen Pieper: Nothing to disclose. Usman Baber: Nothing to disclose. Philippe Gabriel Steg: grants from Merck, Servier, Sanofi, personal fees from Amarin, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, CSL-Behring, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Lilly, Merck Novartis, Pfizer, Regeneron, Sanofi, Servier, The Medicines Company, outside the submitted work. Gilles Montalescot: institutional research grants from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celladon, Daiichi-Sankyo, Eli Lilly, ICAN, Fédération Franc¸aise de Cardiologie, Medtronic, MSD, Pfizer, Sanofi -Aventis, and The Medicines Company; and consulting fees from Amgen, AstraZeneca, Bayer, Berlin Chimie AG, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham and Women’s Hospital, Cardiovascular Research Foundation, CME Resources, Daiichi-Sankyo, Eli Lilly, Europa, Elsevier, Fondazione Anna Maria Sechi per il Cuore, Gilead, Janssen, Lead-Up, Menarini, MSD, Pfizer, Sanofi-Aventis, The Medicines Company, TIMI Study Group, and WebMD. Dominick J. Angiolillo: reports receiving payments as an individual for: (i) Consulting fee or honorarium from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merck, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; (ii) Participation in review activities from CeloNova and St. Jude Medical. Institutional payments for grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli-Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, and Renal Guard Solutions; in addition, Dr Angiolillo is recipient of a funding from the Scott R. MacKenzie Foundation and the NIH/NCATS Clinical and Translational Science Award to the University of Florida UL1 TR000064 and NIH/NHGRI U01 HG007269, outside the submitted work. Pierluigi Tricoci: Grant from Merck, CSL, Amgen, Sanofi. Patrick W. Serruys: Reports consultants fee from: Abbott Laboratories, AstraZeneca Pharmaceuticals, Biotronik, Cardialysis B.V., GLG Research, Medtronic, Sino Medical Sciences Technology Inc. Tianjin China, Société Europa Digital & Publishing, Stentys France, Svelte Medical Systems Inc., Volcano/ Philips Europe, Q3Medical Devices Limited, St. Jude Medical; member of the advisory board of Xeltis. Fortunato Fred Senatore: Nothing to disclose. Stephan Windecker: Reports grant from Abbott, personal fees from AstraZaneca, grants from Biotronik, grants from Biosensors, grants and personal fees from Boston Scientific, personal fees from Daiichi Sankyo, grants from Edwards Lifesciences, grants from Medtronic, personal fees from Sanofi, grants from St. Jude Medical, outside the submitted work. Adnan Kastrati: Reports holding patents related to drug-eluting stent technology. Fausto Feres: Nothing to disclose. Antonio Colombo: Nothing to disclose. Gregg
W. Stone: Reports personal fees from Velomedix, personal fees from Toray, personal fees from Vascular Dynamics, personal fees from Miracor, personal fees from TherOx, personal fees from Reva, personal fees from V-wave, personal fees from Matrizyme, personal fees from Ablative Solutions, personal fees from Neovasc, personal fees from Medical Development Technologies, other from MedFocus family of funds, other from Guided Delivery Systems, other from Micardia, other from Vascular Nonotransfer Technologies, other from Cagent, other from Qool Therapeutics, other from Caliber, other from Aria, other from Biostar family of funds, outside the submitted work; and Consultant on prasugrel patent litigation paid for by Lupin Pharmaceuticals, outside the submitted work. Deepak L. Bhatt: Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St. Jude Medical (now Abbott); Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, PLx Pharma, Takeda, outside the submitted work.Peter Jüni: other from Abbott Vascular, other from Biosensors, other from Medtronic, other from Johnson & Johnson, other from Ablynx, other from Amgen, other from AstraZeneca, other from Boehringer-Ingelheim, other from Eisai, other from Eli Lilly, other from Exelixis, other from Geron, other from Gilead Sciences, other from Nestlé, other from Novartis, other from Novo Nordisc, other from Padma, other from Roche, other from Schering-Plough, other from St. Jude Medical, other from Swiss Cardio Technologies, outside the submitted work; and Unpaid steering committee or statistical executive committee member of trials funded by Abbott Vascular, Biosensors, Medtronic and Johnson & Johnson. Roxana Mehran: institutional research grant support from The Medicines Company, Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, and AstraZeneca and consulting fees from AstraZeneca, Bayer, CSL Behring, Janssen Pharmaceuticals Inc., Merck & Co, Osprey Medical Inc, and Watermark Research Partners and serves on the advisory board of Abbott Laboratories, Boston Scientific Corporation,
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