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

项目摘要/摘要 目前的烟草治疗受限于医生不经常开戒烟药物(&lt；20%)， 患者不经常使用戒断药物(~33%)，药物疗效有限(&lt；30%)。一个 多层次干预以个性化烟草治疗，以大量数据为基础，将遗传信息联系起来 治疗反应的标记物，有可能通过解决多个靶点来解决这些关键差距 在一连串的治疗成功中。首先，精确治疗可能会通过以下方式提高治疗效果 将吸烟者与最大限度提高疗效和安全性的药物相匹配。其次，它可能会增加 医生开处方的可能性，因为他们希望精确的治疗比 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引导治疗和 增加了坚持使用它的动力。新出现的证据，包括最近的Cochrane审查和我们的 研究表明，患者戒烟的能力和对戒烟药物的反应有关 多个生物标志物参与尼古丁代谢(即尼古丁代谢物比率，核磁共振)和尼古丁 受体功能(即，CHRNA5变异体rs16969968的基因型)。评估精准治疗的基础上 利用行为改变理论进行多水平干预的多标记物将推动烟草领域的发展 治疗。我们的初步工作表明：1)同时使用遗传和代谢标记的前景 指导治疗，2)对基因引导治疗的高度兴趣及其提高用药的潜力 在吸烟者中，3)使用遗传风险交流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。这项拟议的研究旨在测试一种多水平干预精确治疗干预，使用两种方法 针对医生和患者的遗传和代谢标记，以增加对药物的吸收和有效性 初级保健中的烟草治疗。我们提出了一项包含40名医生的双臂整群随机对照试验 800名吸烟患者随机接受常规护理(UC)和精确治疗(PT)，这两组患者的核磁共振和 初级保健中的遗传学。我们假设PT将通过增加内科医生来提高戒烟成功率 用药处方、患者依从性和治疗效果。在目标1和目标2中，我们将测试 PT对医生处方、患者用药和患者戒烟的影响。在目标3中，我们 将评估行为改变的机制和实施结果。这项研究反映了一个重要的 创新的治疗模式从传统的治疗模式向包括两者的精确治疗转变 代谢和遗传标记，以激励和指导医生和患者的烟草治疗， 纳入初级保健。

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.