Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: A consensus report fromthe Non-adherence Academic Research Consortium(NARC)

Marco Valgimigli; Hector M. Garcia-Garcia; Bernard Vrijens; Pascal Vranckx; Eugène P. McFadden; Francesco Costa; Karen Pieper; David M. Vock; Min Zhang; Gerrit Anne Van Es; Pierluigi Tricoci; Usman Baber; Gabriel Steg; Gilles Montalescot; Dominick J. Angiolillo; Patrick W. Serruys; Andrew Farb; Stephan Windecker; Adnan Kastrati; Antonio Colombo; Fausto Feres; Peter Jüni; Gregg W. Stone; Deepak L. Bhatt; Roxana Mehran; Jan G.P. Tijssen

doi:10.1093/eurheartj/ehy377

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: A consensus report fromthe Non-adherence Academic Research Consortium(NARC)

Marco Valgimigli, Hector M. Garcia-Garcia, Bernard Vrijens, Pascal Vranckx, Eugène P. McFadden, Francesco Costa, Karen Pieper, David M. Vock, Min Zhang, Gerrit Anne Van Es, Pierluigi Tricoci, Usman Baber, Gabriel Steg, Gilles Montalescot, Dominick J. Angiolillo, Patrick W. Serruys, Andrew Farb, Stephan Windecker, Adnan Kastrati, Antonio ColomboFausto Feres, Peter Jüni, Gregg W. Stone, Deepak L. Bhatt, Roxana Mehran, Jan G.P. Tijssen

Biostatistics

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2070-2085
Number of pages	16
Journal	European heart journal
Volume	40
Issue number	25
DOIs	https://doi.org/10.1093/eurheartj/ehy377
State	Published - Jul 1 2019

Bibliographical note

Funding Information:
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,

Funding 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

Publisher Copyright:
© The Author(s) 2019.

Keywords

Adherence
Clinical trial
Compliance
Medication
Persistence

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Valgimigli, M., Garcia-Garcia, H. M., Vrijens, B., Vranckx, P., McFadden, E. P., Costa, F., Pieper, K., Vock, D. M., Zhang, M., Van Es, G. A., Tricoci, P., Baber, U., Steg, G., Montalescot, G., Angiolillo, D. J., Serruys, P. W., Farb, A., Windecker, S., Kastrati, A., ... Tijssen, J. G. P. (2019). Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: A consensus report fromthe Non-adherence Academic Research Consortium(NARC). European heart journal, 40(25), 2070-2085. https://doi.org/10.1093/eurheartj/ehy377

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: A consensus report fromthe Non-adherence Academic Research Consortium(NARC). / Valgimigli, Marco; Garcia-Garcia, Hector M.; Vrijens, Bernard et al.
In: European heart journal, Vol. 40, No. 25, 01.07.2019, p. 2070-2085.

Research output: Contribution to journal › Article › peer-review

Valgimigli, M, Garcia-Garcia, HM, Vrijens, B, Vranckx, P, McFadden, EP, Costa, F, Pieper, K, Vock, DM, Zhang, M, Van Es, GA, Tricoci, P, Baber, U, Steg, G, Montalescot, G, Angiolillo, DJ, Serruys, PW, Farb, A, Windecker, S, Kastrati, A, Colombo, A, Feres, F, Jüni, P, Stone, GW, Bhatt, DL, Mehran, R & Tijssen, JGP 2019, 'Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: A consensus report fromthe Non-adherence Academic Research Consortium(NARC)', European heart journal, vol. 40, no. 25, pp. 2070-2085. https://doi.org/10.1093/eurheartj/ehy377

Valgimigli M, Garcia-Garcia HM, Vrijens B, Vranckx P, McFadden EP, Costa F et al. Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: A consensus report fromthe Non-adherence Academic Research Consortium(NARC). European heart journal. 2019 Jul 1;40(25):2070-2085. doi: 10.1093/eurheartj/ehy377

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title = "Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: A consensus report fromthe Non-adherence Academic Research Consortium(NARC)",

abstract = "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.",

keywords = "Adherence, Clinical trial, Compliance, Medication, Persistence",

author = "Marco Valgimigli and Garcia-Garcia, {Hector M.} and Bernard Vrijens and Pascal Vranckx and McFadden, {Eug{\`e}ne P.} and Francesco Costa and Karen Pieper and Vock, {David M.} and Min Zhang and {Van Es}, {Gerrit Anne} and Pierluigi Tricoci and Usman Baber and Gabriel Steg and Gilles Montalescot and Angiolillo, {Dominick J.} and Serruys, {Patrick W.} and Andrew Farb and Stephan Windecker and Adnan Kastrati and Antonio Colombo and Fausto Feres and Peter J{\"u}ni and Stone, {Gregg W.} and Bhatt, {Deepak L.} and Roxana Mehran and Tijssen, {Jan G.P.}",

note = "Funding Information: 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{\textquoteright}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{\textquoteright}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 J{\"u}ni: 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 Nestl{\'e}, 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, Funding 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, F{\'e}d{\'e}ration 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{\textquoteright}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, Soci{\'e}t{\'e} 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 Publisher Copyright: {\textcopyright} The Author(s) 2019.",

year = "2019",

month = jul,

day = "1",

doi = "10.1093/eurheartj/ehy377",

language = "English (US)",

volume = "40",

pages = "2070--2085",

journal = "European heart journal",

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TY - JOUR

T1 - Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials

T2 - A consensus report fromthe Non-adherence Academic Research Consortium(NARC)

AU - Valgimigli, Marco

AU - Garcia-Garcia, Hector M.

AU - Vrijens, Bernard

AU - Vranckx, Pascal

AU - McFadden, Eugène P.

AU - Costa, Francesco

AU - Pieper, Karen

AU - Vock, David M.

AU - Zhang, Min

AU - Van Es, Gerrit Anne

AU - Tricoci, Pierluigi

AU - Baber, Usman

AU - Steg, Gabriel

AU - Montalescot, Gilles

AU - Angiolillo, Dominick J.

AU - Serruys, Patrick W.

AU - Farb, Andrew

AU - Windecker, Stephan

AU - Kastrati, Adnan

AU - Colombo, Antonio

AU - Feres, Fausto

AU - Jüni, Peter

AU - Stone, Gregg W.

AU - Bhatt, Deepak L.

AU - Mehran, Roxana

AU - Tijssen, Jan G.P.

N1 - Funding Information: 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, Funding 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 Publisher Copyright: © The Author(s) 2019.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

AB - 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.

KW - Adherence

KW - Clinical trial

KW - Compliance

KW - Medication

KW - Persistence

UR - http://www.scopus.com/inward/record.url?scp=85069231223&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069231223&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehy377

DO - 10.1093/eurheartj/ehy377

M3 - Article

C2 - 29992264

AN - SCOPUS:85069231223

SN - 0195-668X

VL - 40

SP - 2070

EP - 2085

JO - European heart journal

JF - European heart journal

IS - 25

ER -

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: A consensus report fromthe Non-adherence Academic Research Consortium(NARC)

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