Better options for chronic cancer pain: a SMART study

Background: Twenty-four percent of Veterans who survive cancer remain on long term opioid therapy (LTOT) after completing cancer treatment, placing them at significant risk of opioid addiction, overdose, and other opioid- related health conditions. To reduce opioid use in this population, we will examine the impacts of multimodal pain care and buprenorphine rotation – two strategies that have demonstrated efficacy in Veterans with musculoskeletal pain on LTOT but have not been tested in cancer survivors on LTOT, revealing a critical knowledge gap. The overall scientific premise of this project is that these two approaches can effectively reduce LTOT in cancer survivors without worsening chronic pain, and that they are better than pain medication optimization and opioid tapering. Our primary objective is to examine which treatment strategy or combination of strategies is most successful at achieving a reduction in LTOT without worsening chronic pain over 6 and 9 months. We will also identify the key challenges and strategies in the implementation of each treatment strategy to facilitate future translation of study findings into VA practice. Significance: There are currently no care pathways at the VHA to help cancer survivors on LTOT find alternatives to opioids for managing chronic pain, nor evidence to guide which interventions to include. By addressing these unmet needs, this work aligns with POU-AMP’s priority to examine clinical interventions for tapering opioid medications. Innovation: We are among the first to examine multimodal care and buprenorphine rotation to reduce LTOT in cancer survivors. Also, we are among the first to apply VHA’s evidence-based, stepped care model of multidisciplinary pain care to cancer survivors on LTOT. Aim 1: To test if Veterans who receive multimodal pain care will be more likely to decrease total daily opioid use by at least 20% at 6 and 9 months without experiencing worsened pain interference compared to those who receive optimization of non-opioid pain medications. Aim 2: To test if Veterans who do not respond to 6 months of multimodal care or medication optimization are more likely to achieve the desired outcome at 9 months when they are offered buprenorphine rotation as opposed to opioid tapering. Exploratory Aim 3: To examine which combination of interventions is most likely to achieve the desired outcome at 9 months. Aim 4: To understand the key challenges and strategies in the implementation of each intervention to facilitate future translation of study findings into practice. Methodology: We plan a two-site, two-stage, response-adaptive, comparative effectiveness trial following SMART (Sequential, Multiple-Assignment Randomized Trial) principles. We will enroll 294 Veteran cancer survivors on LTOT who receive their care at the Indianapolis or Ann Arbor VAMC. Subjects will be randomized to either multimodal pain care or pain medication optimization at Stage 1. After 6 months, non-respondents will be randomized to buprenorphine rotation or opioid tapering in Stage 2. Our primary outcome is a composite variable combining one objective outcome (opioid dose reduction) and one subjective outcome (pain interference), assessed at 6 and 9 months. Our secondary outcomes are opioid dose reduction and pain interference individually. Next Steps/Implementation: Successful execution of this project will provide actionable information, including an implementation strategy, that VHA’s Offices of Pain Management and Oncology can put in place to support over 240,000 cancer survivors on LTOT for chronic pain. Project Number: 1I01CX002902-01 | Fiscal Year: 2025 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Maria Silveira (+1 co-PI) | Institution: VETERANS HEALTH ADMINISTRATION, ANN ARBOR, MI | Activity Code: I01 | Study Section: Special Emphasis Panel[ZRD1 NURP-N (01)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11054164