A multilevel intervention to personalize and improve tobacco treatment in primary care

项目总结/摘要 目前的烟草治疗受到医生不经常开戒烟药物的限制（<20%）， 患者很少使用戒烟药物（约33%），药物有效性有限（<30%）。一 多层次的干预，以个性化的烟草治疗，基于大量的数据连接遗传信息 治疗反应的标志物，有可能通过解决多个目标来解决这些关键差距 在治疗成功的级联中。首先，精确治疗可以通过以下方式提高治疗效果： 使吸烟者与最大限度地提高疗效和安全性的药物相匹配。第二，可能会增加 医生开处方的可能性，因为他们希望精确治疗比 标准治疗。第三，精准医疗可能会增加患者发起和坚持的动力。 戒烟药物，因为有证据表明，吸烟者表达了对基因指导治疗的渴望， 增加了坚持使用它的动机。新出现的证据包括最近的科克伦综述和我们的 研究表明，患者戒烟的能力和对戒烟药物的反应是相关的， 具有参与尼古丁代谢的多种生物标志物（即，尼古丁代谢物比率，NMR）和烟碱 受体功能（即，CHRNA 5变体rsl 6969968的基因型）。根据以下方面评估精密治疗 使用行为改变理论的多层次干预中的多个标志物将推动烟草领域的发展 治疗我们的初步工作表明：1）使用遗传和代谢标记在 指导治疗，2）对基因指导治疗的高度兴趣及其提高药物使用的潜力 在吸烟者中，3）使用遗传风险沟通反馈的戒烟动机更高 工具，以及4）成功地利用健康信息学在临床上实施多层次的烟草干预 设置.这项研究旨在测试一种多层次的干预精确治疗干预， 遗传和代谢标记，针对医生和患者，以增加吸收和有效性， 初级保健中的烟草治疗。我们提出了一个2臂集群随机对照试验的40名医生 和800名吸烟患者，根据NMR随机分为常规治疗（UC）和精确治疗（PT）， 初级保健中的遗传学我们假设PT将通过增加医生来提高戒烟成功率 药物处方、患者依从性和治疗有效性。在目标1和2中，我们将测试 PT对医生处方、患者用药和患者戒烟影响。在目标3中， 将评估行为改变机制和实施结果。这项研究反映了一个重要的 从传统的治疗模式到精确治疗的创新范式转变， 代谢和遗传标记来激励和指导医生和患者的烟草治疗， 与初级保健相结合。

PROJECT SUMMARY/ABSTRACT Current tobacco treatment is limited by physicians infrequently prescribing cessation medication (<20%), patients infrequently using cessation medication (~33%), and limited medication effectiveness (<30%). A multilevel intervention to personalize tobacco treatment, based on substantial data linking genetically informed markers to treatment response, has the potential to address these critical gaps by addressing multiple targets in the cascade of treatment success. First, precision treatment may increase treatment effectiveness by matching the smoker with the medication that maximizes efficacy and safety. Second, it may increase physicians’ likelihood of prescribing because they expect precision treatment to be more effective than standard treatment. Third, precision medicine may increase patients’ motivation to initiate and adhere to cessation medication, as evidence suggests that smokers express desire for gene-guided treatment and increased motivation to use it adherently. Emerging evidence including a recent Cochrane review and our research suggests that patients’ ability to quit smoking and respond to cessation medication are associated with multiple biomarkers involved in nicotine metabolism (i.e., nicotine metabolite ratio, NMR) and nicotinic receptor function (i.e., genotype of CHRNA5 variant rs16969968). Evaluating precision treatment based on multiple markers in a multilevel intervention using behavior change theories will advance the field of tobacco treatment. Our preliminary work demonstrated: 1) promise of using both genetic and metabolic markers in guiding treatment, 2) high interest in gene-guided treatment and its potential for enhancing medication use among smokers, 3) higher motivation for smoking cessation with use of genetic risk communication feedback tools, and 4) successful use of health informatics to implement a multilevel tobacco intervention in clinic settings. The proposed study aims to test a multilevel intervention precision treatment intervention using both genetic and metabolic markers, directed at physicians and patients, to increase the uptake and effectiveness of tobacco treatment in primary care. We propose a 2-arm cluster randomized controlled trial of 40 physicians and 800 patients who smoke randomized to usual care (UC) vs. precision treatment (PT) based on NMR and genetics in primary care. We hypothesize that PT will enhance cessation success via increased physician prescription of medication, patient adherence, and treatment effectiveness. In Aims 1 and 2, we will test the impact of PT on physician prescribing, patient use of medication, and patient smoking abstinence. In Aim 3, we will evaluate mechanisms of behavior change and implementation outcomes. The study reflects a significant and innovative paradigm shift from a traditional treatment model to precision treatment that includes both metabolic and genetic markers to motivate and guide tobacco treatment for both physicians and patients, integrated within primary care.