ABSTRACT Multimorbidity is increasing throughout the world. In many high-income countries (HICs), it is the norm rather than the exception, and low-and-middle-income countries (LMICs) are heading in this direction.1 Multiple studies have shown that patients with multimorbidity suffer from worse clinical outcomes.2 Part of this is due to the fact that they experience a higher burden of treatment (BOT), which is defined as how their healthcare workload - or all of the things they must do to comply with their medical treatment - affects their functionality and well-being. One of the many factors that increases healthcare workload and consequently BOT is the presence of healthcare system-related barriers. In LMICs, healthcare systems have evolved to treat acute conditions rather than manage chronic ones and consequently are replete with numerous barriers preventing successful multimorbidity management.1, 2 In order to improve outcomes in multimorbidity, it is crucial to create patient-centered interventions minimize these barriers. Sustainable implementation of these changes, however, requires the use of quality indicators, one of which is BOT. Although several patient-reported outcome measures have been identified to measure BOT in clinical settings, their use in LMICs has been limited. In this study, we will evaluate BOT in multimorbid patients in Peru using a mixed-methods approach. Both semi-structured interviews and a validated survey, the Treatment Burden Questionnaire (TBQ), will be applied to patients in different healthcare settings and geographic regions. Our overarching goal is to gain an in-depth understanding of what patient- reported barriers to multimorbidity management exist in Peru, and we aim to achieve the following specific objectives: 1) To use BOT to identify and compare patient-reported barriers to multimorbidity management in groups receiving care in private versus public healthcare sectors in Peru. 2) To use BOT to identify and compare patient-reported barriers to multimorbidity management in patients receiving care in different geographic regions in Peru. 3) To use semi-structured interviews with patients to gain additional, in-depth information about barriers to multimorbidity management in Peru. We believe that the novel approaches used in this study have significant potential to advance the field of global multimorbidity. The use of the TBQ to compare BOT in patients receiving different types of healthcare and in different locations will advance its use as an indicator of healthcare quality. Moreover, the use of qualitative methods will allow us to understand what barriers exist in Peru and how well they are captured by the TBQ. This unique approach will will serve as a model for how the TBQ can be adapted for use in other unique healthcare contexts. Using a reliable tool to understand the relationship between BOT and healthcare systems - particularly those in LMICs - has the potential to provide a foundation for patient- centered interventions that target the most burdensome and costly aspects of multimorbidity care. 1

NARRATIVE In LMICs, healthcare systems lack the infrastructure, organization, and resources to address the growing burden of multimorbidity, resulting in numerous barriers to care that augment burden of treatment (BOT) and perpetuate poor clinical outcomes. Implementation of patient-centered interventions to minimize these barriers is crucial to prevent the negative downstream consequences of poorly-managed multimorbidity. We propose to use a mixed- methods approach to evaluate which subgroups of patients in Peru - particularly those in different healthcare sectors and geographic regions - experience the highest BOT and what barriers contribute most. 1