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BackgroundIntegrated community case management (iCCM) is a child health program designed to provide integrated community-based care for children with pneumonia, malaria, or diarrhea in hard-to-reach areas of low- and middle-income countries. The foundation of the intervention is service delivery by community health workers (CHWs) who depend on reliable provision of drugs and supplies, consistent supervision, comprehensive training, and community acceptance and participation to perform optimally. The effectiveness of the program may also depend on a number of other elements, including an enabling policy environment, financing mechanisms from the national to the local level, data transmission systems, and appropriate monitoring and evaluation. The extent to which these factors act upon each other to influence the effectiveness and viability of iCCM is both variable and challenging to assess, especially across different implementation contexts. ObjectiveIn this paper, we describe a mixed methods systems-based study protocol to assess the programmatic components of iCCM that are associated with intervention effectiveness and report preliminary results of data collection. MethodsThis protocol uses a mixed qualitative and quantitative study design based on a systems thinking approach within four iCCM programs in Malawi, Democratic Republic of the Congo, and Niger State and Abia State in Nigeria. Routine monitoring data are collected to determine intervention effectiveness, namely testing, treatment, and referral outcomes. Surveys with CHWs, supervisors, and caregivers are performed to collect quantitative data on their demographics, activities, and experiences within the program and how these relate to the areas of intervention effectiveness. Focus group discussions are conducted with these stakeholders as well as local traditional leaders to contextualize these data. Key informant interviews are undertaken with national- and district-level program stakeholders and officers knowledgeable in critical program processes. ResultsWe performed 3836 surveys and 45 focus group discussions of 379 participants with CHWs, supervisors, caregivers, and traditional leaders, as well as 120 key informant interviews with district- and national-level program managers, health officers, and ministry officials. Policy and program documents were additionally collected for review. ConclusionsWe expect that evidence from this study will inform child health programs and practice in low- and middle-income settings as well as future policy development within the iCCM intervention. International Registered Report Identifier (IRRID)DERR1-10.2196/33076