With no universal agreement on what constitutes adherence to intravitreal injection therapy in neovascular AMD (nAMD), researchers sought to lay the groundwork for development and validation of terminology on patient nonadherence and nonpersistence to treatment of this disease.

Nonadherence was defined as missing two or more treatments or monitoring visits over a period of 12 months, with a visit considered missed if it exceeded more than two weeks from the recommended date. Nonpersistence was defined as nonattendance or an appointment not scheduled within the last six months. The additional terms “planned discontinuation” and “transfer of care” were also established by the group.

Reasons for treatment nonadherence and nonpersistence were classified into six dimensions: (1) patient-associated, (2) condition associated, (3) therapy associated, (4) health system and health care team associated, (5) social/economic and (6) other. The system also includes subcategories specific to treatment for nAMD.

“The definitions proposed here are designed to be sufficiently flexible to cover all currently used injection regimens,” the authors explain in their study. “Although there has been a transition to favoring the treat-and-extend protocol in recent years, using timing of scheduled visits rather than the number of injections enables these definitions to be used by practitioners across different health systems.” The proposed terms and classification system may be applicable to other uses of anti-VEGF but the team decided to restrict the approach to wet AMD for now, “because intravitreal injection is usually more time critical in this condition compared with other indications, such as diabetic macular edema.”

This new classification system also addresses some of the shortcomings of previous definitions, one of which was the grouping of patient death or planned discontinuation because of treatment futility with other reasons for nonpersistence. The authors note these represent different scenarios than patients who are nonpersistent because of factors such as lack of transportation, for example. In addition, the distinction between the terminology of adherence and persistence is also clarified here, because patients can be nonadherent yet still persistent.

The approach was also modeled on the World Health Organization dimensions of adherence, but had subcategories specific to patients receiving intravitreal injections.

“This helps to align this system with other discussions of adherence in the health literature yet keeps it relevant to the management of nAMD,” the authors noted in their study. “However, it is worth noting that although factors have been classified into distinct dimensions, causes can be bidirectional or interdependent. For example, a patient’s perceived treatment burden may be associated with system issues, such as the distance to specialist treatment, which is also associated with social barriers, such as access to transportation. Therefore, for an individual patient, there can be multiple attributable reasons.”

Okada M, Yin Wong T, Mitchell P, et al. Defining nonadherence and nonpersistence to anti-vascular endothelial growth factor therapies in neovascular age-related macular degeneration. JAMA Ophthalmology. Epub ahead of print.