ABSTRACT Moderate-to-severe cancer pain is common in patients with advanced cancer and is often effectively treated with prescription opioids. Effective pain management is crucial for optimal quality of life and health outcomes in these patients. However, the emergence of the opioid crisis in the United States has sparked widespread fears about the use of opioid pain medications, given the potential for negative outcomes such as addiction and overdose. Despite being exempted from restrictive opioid policies, patients with cancer experience adverse consequences of efforts to address the opioid crisis, including stigma associated with prescription opioid use (“opioid stigma”). Based on our recently published Opioid Stigma Framework, we anticipate that opioid stigma results in several proximal (e.g., impaired patient-provider communication, suboptimal health behaviors, emotional distress, maladaptive coping skills) and long-term health consequences (e.g., less effective pain management, reduced health-related quality of life). Emerging evidence indicates that opioid stigma is common, pervasive, and has the potential to seriously impact patient well-being. However, there are no known interventions to mitigate opioid stigma in patients with advanced cancer. Additionally, perspectives from underserved communities at high risk for pain undertreatment – people of color, people in rural areas, and women – are lacking, and understanding these experiences is critical to build a robust, inclusive opioid stigma intervention Thus, the proposed project will develop and test a novel behavioral intervention for opioid stigma in an effort to fill this unmet need. Together with her mentors, Principal Investigator Dr. Bulls will explore opioid stigma experiences and treatment priorities reported by a diverse group of 75 patients with advanced, painful cancer using rigorous concept mapping methodology (Aim 1). Next, Dr. Bulls will design a theory-based intervention to reduce negative proximal impacts of opioid stigma in patients with advanced cancer, soliciting feedback from patients and community-engaged resources prior to piloting (Aim 2). Finally, Dr. Bulls will conduct a pilot trial of the intervention with 45 patients with advanced cancer pain to evaluate feasibility and acceptability in preparation for a full-scale randomized controlled trial (Aim 3). This project will facilitate training crucial to Dr. Bulls' career development: advanced skills in participatory and stakeholder-engaged research methods, in-depth training in behavioral intervention development, and expertise in conducting clinical trials. Dr. Bulls has convened a dedicated, multidisciplinary 26 mentorship team with expertise in essential content and methodological areas including palliative oncology, 27 opioid pain management, health-related stigma, concept mapping, behavioral intervention development and 28 testing, and research in underserved groups, among others. This proposal represents a comprehensive training, 29 mentoring, and research plan to support Dr. Bulls' transition into a successful independent investigator. At the 30 end of the award period, Dr. Bulls will contribute substantially to the field as a leader in behavioral approaches to 31 improve opioid stigma in patients with advanced cancer. 32 33

PROJECT NARRATIVE Effective pain management is a core element of advanced cancer treatment, as under-treated pain is associated with adverse health consequences and suboptimal quality of life. Cancer-related pain is commonly managed with prescription opioids; however, patients with advanced cancer experience unique challenges associated with this strategy due to the opioid crisis, including stigma surrounding prescription opioid use (“opioid stigma”). The project described in this NCI K08 application will develop and pilot test an intervention to address opioid stigma in patients with advanced cancer, which can then be tested in a randomized controlled trial.