David T Eton,1,2 Jennifer L Ridgeway,1,2 Jason S Egginton,1,2 Kristina Tiedje,3 Mark Linzer,4,5 Deborah H Boehm,4 Sara Poplau,6 Djenane Ramalho de Oliveira,7 Laura Odell,8 Victor M Montori,1,9 Carl R May,10 Roger T Anderson11 1Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 2Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA; 3Department of Sociology and Anthropology, Université Lumière Lyon 2, Lyon, France; 4Division of General Internal Medicine, Hennepin County Medical Center, Minneapolis, MN, USA; 5University of Minnesota Medical School, University of Minnesota, Minneapolis, MN, USA; 6Minneapolis Medical Research Foundation, Minneapolis, MN, USA; 7Department of Social Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 8Pharmacy Services, Mayo Clinic, Rochester, MN, USA; 9Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA; 10Faculty of Health Sciences and NIHR CLAHRC Wessex, University of Southampton, Southampton, UK; 11School of Medicine, University of Virginia, Charlottesville, VA, USA Purpose: The workload of health care and its impact on patient functioning and well-being is known as treatment burden. The purpose of this study was to finalize a conceptual framework of treatment burden that will be used to inform a new patient-reported measure of this construct. Patients and methods: Semi-structured interviews were conducted with 50 chronically ill patients from a large academic medical center (n=32) and an urban safety-net hospital (n=18). We coded themes identifying treatment burden, with the themes harmonized through discussion between multiple coders. Four focus groups, each with five to eight participants with chronic illness, were subsequently held to confirm the thematic structure that emerged from the interviews. Results: Most interviewed patients (98%) were coping with multiple chronic conditions. A preliminary conceptual framework using data from the first 32 interviews was evaluated and was modified using narrative data from 18 additional interviews with a racially and socioeconomically diverse sample of patients. The final framework features three overarching themes with associated subthemes. These themes included: 1) work patients must do to care for their health (eg, taking medications, keeping medical appointments, monitoring health); 2) challenges/stressors that exacerbate perceived burden (eg, financial, interpersonal, provider obstacles); and 3) impacts of burden (eg, role limitations, mental exhaustion). All themes and subthemes were subsequently confirmed in focus groups. Conclusion: The final conceptual framework can be used as a foundation for building a patient self-report measure to systematically study treatment burden for research and analytical purposes, as well as to promote meaningful clinic-based dialogue between patients and providers about the challenges inherent in maintaining complex self-management of health. Keywords: treatment burden, conceptual framework, adherence, questionnaire, self-management, multi-morbidity