Development of a core outcome set for multimorbidity trials in low- and middle-income countries (COSMOS): Study Protocol

Introduction: Multimorbidity describes the presence of two or more long-term conditions, which can include communicable and non-communicable diseases, and mental disorders. The rising global burden from multimorbidity is well-documented, but trial evidence for effective interventions in low- and middle-income countries (LMICs) is limited. Selection of appropriate outcomes is fundamental to trial design to ensure cross-study comparability, but there is currently no agreement on a core outcome set (COS) to include in trials investigating multimorbidity specifically in LMIC. Our aim is to develop international consensus on two COS for trials of interventions to prevent and treat multimorbidity in LMIC settings.
Methods and Analysis: Following methods recommended by the Core Outcome Measures in Effectiveness Trials (COMET initiative), the development of these two COS will occur in three stages: (1) generation of a long list of potential outcomes for inclusion; (2) two-round online Delphi surveys; and (3) consensus meetings. First, to generate an initial list of outcomes, we will conduct a systematic review of multimorbidity intervention and prevention trials and interviews with people living with multimorbidity and their caregivers in LMICs. Outcomes will be classified using an outcome taxonomy. Two-round Delphi surveys will be used to elicit importance scores for these outcomes from people living with multimorbidity, caregivers, healthcare professionals, policy makers, and researchers in LMICs. Finally, consensus meetings will be held to discuss the Delphi survey results and agree outcomes for inclusion in the two COS.
Ethics and dissemination: The study has been approved by the Research Governance Committee of the Department of Health Sciences, University of York, UK [HSRGC/2020/409/D:COSMOS]. Each participating country/research group will obtain local ethics board approval. Informed consent will be obtained from all participants. We will disseminate findings through peer-reviewed open access publications, and presentations at global conferences selected to reach a wide range of LMIC stakeholders
Trial registration PROSPERO ID CRD42020197293
COMET https://www.comet-initiative.org/Studies/Details/1580

Strengths and limitations of this study: The development process follows guidelines and best practice recommendations for developing core outcome sets and integrates four sources of information. Interviews with people living with multimorbidity and caregivers are conducted in several LMICs (in South Asia, Africa and Latin America), by local teams, and in local languages to identify outcomes relevant to them. The Delphi survey and consensus meetings are conducted in English which limits the breadth of participation in these stages of the process. Despite involvement of a wide range of LMIC stakeholders in the process, there may be some limitations to the generalisability of the final core outcome sets due to the heterogeneity of target conditions and the diversity of countries, cultures and experiences.