SUMMARY Social determinants of health and its downstream social risks such as housing instability, food insecurity, and financial strain, are key drivers of cancer health inequities. Healthcare systems’ engagement in identifying and addressing social needs is a new and evolving field. In particular, limited resources exist to guide healthcare clinics in selecting, implementing, and optimizing social service resource locators (SSRLs) for their specific context. The purpose of this supplement is to draw on learnings from our team’s previous pilot efforts in supporting clinics’ adoption of different SSRL approaches to develop a pragmatic guide for implementation of social risk referral-making and documentation. This supplement is a collaborative effort across four ISC3 Centers: BRIDGE-C2, Harvard ISCCCE, OPTICC (Optimizing Implementation in Cancer Control) Center, and Washington University-ISC3. We propose to: (1) develop a pragmatic, applied guidebook (the Guide) for clinics seeking to implement, expand, or optimize efforts to address patient-reported social risks using Assistance strategies; (2) use rapid-cycle testing to identify best practices for implementing the Guide; and (3) iterate and disseminate the refined Guide. In Aim 1, we will develop a pragmatic Guide to help primary care practices: 1) select an Assistance strategy and a related SSRL approach, and associated workflows for conducting these strategies in practice, including documenting social risk referrals; and 2) adopt, optimize, and sustain these workflows. Subsequently, in Aim 2 we will 1) provide the Guide to diverse clinics (urban and rural Federally Qualified Health Centers; primary care clinics) at different stages of SSRL implementation, in three ISC3 laboratories; 2) identify facilitators and barriers to implementing the Guide; and 3) identify the support needed to use the Guide. ISCCCE, OPTICC, and WU-ISC3 will use a series of rapid cycle turns with their clinical partner sites. We will use the Phase I supplement outer context dataset to identify key social resource needs that should be addressed in each clinic setting and rapid cycle testing using user-centered designed methods will be used to refine the Guide based on pilot learnings. Rapid tests using OPTICC state II methods of small changes for improvement will be tracked systematically. We will also track the implementation strategies used to support the Guide’s use, whether provided by ISC3 center staff or participating clinic sites. Clinics were selected to ensure variation in the ‘community vital signs’ associated with the populations they serve, as determined using our outer contextual database that was developed in Phase 1, and in the stages of implementing Assistance strategies, increasing generalizability. Finally, in Aim 3, we will finalize refining the Guide based on the findings of Aim 2, and disseminate it as a public good. Ultimately, this proposal will lead a public guide that can immediately be disseminat...