Project Summary Opioid therapy for pain in patients with metastatic cancer is a critical yet understudied area. Pain is experienced at some point by most patients with metastatic cancer. Prescribed opioids are a cornerstone of treating pain; the prevalent belief in the field has been that the benefits of palliating pain in metastatic cancer with opioids nearly always outweigh any potential harms. This approach to opioid-related decisions in patients with metastatic cancer implies that patients’ prognoses are either so short that these harms are not meaningful, or that benefits of opioids are substantial while harms are relatively minimal. Research on the benefits and harms of opioid therapy has exploded in the past decade but primarily focuses on individuals with chronic “non-cancer” pain. However, patients with cancer have been routinely excluded from these studies and resulting recommendations that favor more conservative opioid prescribing. The few studies of patients with cancer generally support that serious harms occur, but have significant methodologic limitations. Additionally, there are unique considerations in individuals with metastatic cancer, including life-limiting disease that may last years, high pain rates, and opioids as accepted standard of care. Therefore, assessing benefits and risk factors for opioid-related harms in individuals with metastatic cancer is a critical gap in the literature and key to opioid-related decision-making. The long-term goal of this program of research is to develop interventions that inform opioid-related decision-making for patients with metastatic cancer. We will use the Behavioral Decision Research framework to create a comprehensive evidence base on which these interventions can be grounded, which is the objective of the present application. To accomplish our aims, we have partnered with the NINR- funded Palliative Care Research Cooperative to develop a prospective cohort of patients newly diagnosed with metastatic cancer. We propose the following Aims in patients with metastatic cancer: Aim 1: Investigate the relationship between opioid therapy and opioid-related benefits. Hypothesis 1: Opioid therapy will be associated with decreased pain severity and pain interference (co-primary outcomes). Aim 2: Investigate risk factors for opioid-related harms. Hypothesis 2a: Certain co-prescribed medications will be associated with increased risk of opioid side effects (e.g., benzodiazepines and somnolence). Hypothesis 2b: Younger age, history of substance use disorder, and history of mood disorders will be associated with greater risk of opioid misuse and use disorder. Approach: We will use linear mixed effects models (2a) and time-to-event analyses (2b). Aim 3: Understand stakeholder (patient, family caregiver, clinician) perspectives on opioid-related decision-making. Completion of these aims will lead directly to an R-series proposal to develop and test a novel intervention to inform opioid decision-making, followed by R-series proposals to study intervention effectiveness and implementation. This work has the potential to transform opioid prescribing and pain management for patients with metastatic cancer.

Project Narrative By investigating opioid-related benefits and risk factors for harms in individuals with metastatic cancer, the proposed study will provide evidence that patients, family caregivers, and clinicians need when engaged in opioid-related decision-making. This has the potential to transform pain and opioid care for patients with metastatic cancer, and as such, is directly responsive to National Institute of Nursing Research priorities to improve the health of individuals with serious illness and the National Cancer Institute’s mission of helping people with cancer lead longer, healthier lives.