Opioid therapy for pain in individuals with metastatic cancer: benefits, harms and stakeholder perspectives

项目摘要 阿片类药物治疗转移性癌症患者的疼痛是一个关键但研究不足的领域。痛苦就是 大多数转移性癌症患者在某些时候都会经历这种情况。处方阿片类药物是 治疗疼痛；该领域的流行观点是缓解转移性癌症疼痛的益处 使用阿片类药物几乎总是超过任何潜在的危害。患者做出阿片类药物相关决定的这种方法 转移性癌症意味着患者的预后要么是如此短暂，以至于这些危害不是 有意义的，或者阿片类药物的益处很大，而危害相对很小。关于网络信息技术的研究 阿片类药物治疗的益处和危害在过去十年中呈爆炸式增长，但主要集中在患有 慢性“非癌症”疼痛。然而，癌症患者通常被排除在这些研究之外， 由此产生的建议支持更保守的阿片类药物处方。为数不多的关于慢性阻塞性肺疾病患者的研究 癌症通常支持发生严重危害，但有显著的方法学限制。另外， 在转移性癌症患者中有独特的考虑因素，包括可能会限制生命的疾病 过去几年，高疼痛率和阿片类药物作为公认的护理标准。因此，评估收益和风险 在转移性癌症患者中，阿片类药物相关伤害的因素是文献中的一个关键空白，也是 与阿片类药物相关的决策。这项研究计划的长期目标是开发干预措施 为转移性癌症患者的阿片类药物相关决策提供信息。我们将使用行为决定 研究框架，以建立一个全面的证据基础，这些干预措施可以作为基础； 这是本申请的目的。为了实现我们的目标，我们与NINR合作- 资助姑息治疗研究合作社开发新诊断的前瞻性队列患者 转移性癌。我们在转移性癌症患者中提出了以下目标：目标1：调查 阿片类药物治疗与阿片类药物相关利益的关系。假设1：阿片类药物治疗将是 与疼痛严重程度降低和疼痛干扰(共同初级结果)相关。目标2：调查风险 阿片类药物相关危害的因素。假设2a：某些联合处方药物将与 增加阿片类药物副作用(如苯二氮类药物和嗜睡)的风险。假设2b：年龄较小， 物质使用障碍史和情绪障碍史将与更大的阿片类药物风险相关 误用和使用障碍。方法：我们将使用线性混合效应模型(2a)和事件间隔时间分析 (2B)。目标3：了解利益相关者(患者、家庭护理人员、临床医生)对阿片类药物相关的看法 决策。完成这些目标将直接导致R系列提案开发和测试 为阿片类药物决策提供信息的新干预措施，随后是研究干预措施的R系列建议 有效性和执行力。这项工作有可能改变阿片类药物的处方和疼痛 转移性癌症患者的管理。

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.