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Original Investigation
June 3, 2021

Defining Nonadherence and Nonpersistence to Anti–Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration

Author Affiliations
  • 1Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
  • 2Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
  • 3Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore
  • 4Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
  • 5Department of Ophthalmology, Hacettepe University, Ankara, Turkey
  • 6The Newcastle upon Tyne Hospitals NHS Foundation, Newcastle upon Tyne, United Kingdom
  • 7Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, The University of Manchester School of Health Sciences, Manchester, United Kingdom
  • 8Montpellier University Hospital, Montpellier, France
  • 9Fundación Oftalmologica Nacional, Universidad del Rosario School of Medicine, Bogotá, Colombia
  • 10Department of Ophthalmology, York Teaching Hospital NHS Foundation Trust, York, United Kingdom
  • 11International Federation on Ageing, Toronto, Ontario, Canada
  • 12Department of Ophthalmology, University of Bonn, Bonn, Germany
  • 13Division of Ophthalmology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
JAMA Ophthalmol. Published online June 3, 2021. doi:10.1001/jamaophthalmol.2021.1660
Key Points

Question  What is the definition of adherence to and persistence with intravitreal therapy in neovascular age-related macular degeneration?

Findings  This expert consensus survey used a modified Delphi technique to establish a set of definitions for the terms adherence, nonadherence, persistence, nonpersistence, planned discontinuation, and transfer of care. A classification system based on the World Health Organization dimensions of adherence was developed for the reasons for nonadherence and nonpersistence.

Meaning  These definitions provide a framework when assessing patient engagement to intravitreal therapy, which may be useful in future studies identifying rates or risk factors for patient nonadherence or nonpersistence.

Abstract

Importance  Poor adherence or persistence to treatment can be a barrier to optimizing clinical practice (real-world) outcomes to intravitreal injection therapy in patients with neovascular age-related macular degeneration (nAMD). Currently, there is a lack of consensus on the definition and classification of adherence specific to this context.

Objective  To describe the development and validation of terminology on patient nonadherence and nonpersistence to anti–vascular endothelial growth factor therapy.

Design, Setting, and Participants  Following a systematic review of currently used terminology in the literature, a subcommittee panel of retinal experts developed a set of definitions and classification for validation. Definitions were restricted to use in patients with nAMD requiring intravitreal anti–vascular endothelial growth factor therapy. Validation by the full nAMD Barometer Leadership Coalition was established using a modified Delphi approach, with predetermined mean scores of 7.5 or more signifying consensus. Subsequent endorsement of the definitions was provided from a second set of retinal experts, with more than 50% members agreeing or strongly agreeing with all definitions.

Main Outcomes and Measures  Development of consensus definitions for the terms adherence and persistence and a classification system for the factors associated with treatment nonadherence or nonpersistence in patients with nAMD.

Results  Nonadherence was defined as missing 2 or more treatment or monitoring visits over a period of 12 months, with a visit considered missed if it exceeded more than 2 weeks from the recommended date. Nonpersistence was defined by nonattendance or an appointment not scheduled within the last 6 months. The additional terms planned discontinuation and transfer of care were also established. Reasons for treatment nonadherence and nonpersistence were classified into 6 dimensions: (1) patient associated, (2) condition associated, (3) therapy associated, (4) health system and health care team associated, (5) social/economic, and (6) other, with subcategories specific to treatment for nAMD.

Conclusions and Relevance  This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti–vascular endothelial growth factor treatments. This may have additional importance, given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD.

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