SIngle-saMPLE tuberculosis evaluation to facilitate linkage to care: The SIMPLE TB trial

 描述（由申请人提供）：在高负担国家，许多到社区卫生中心就诊的结核病（TB）患者在结核病得到诊断或治疗之前就失去了随访，导致持续传播。一个主要原因是，在多天内收集痰标本进行显微镜检查的标准方法不仅不敏感，而且对患者来说不方便且昂贵。Xpert MTB/RIF（Xpert）是一种半自动化分子检测，可在2小时内识别90%的结核病病例。Xpert现在被推荐作为肺结核的初始诊断测试，但由于成本和基础设施要求，不能在社区卫生中心部署。为了实现对健康结果的访问、利用和影响，从社区卫生中心到部署Xpert的设施的成功转诊策略至关重要。我们的总体目标是评估简化的单样本（SIMPLE）结核病诊断评价策略的有效性、实施情况和影响。简单结核病战略是在对结核病诊断评价的提供者和患者层面的障碍进行理论评估之后，通过利益相关者参与的过程制定的。其组成部分包括：1）单样本LED荧光显微镜（两小时内分析并报告初始标本的涂片结果）; 2）每天将涂片阴性痰液样本运送至Xpert检测中心; 3）基于短信向患者和卫生中心报告Xpert检测结果; 4）向卫生中心工作人员常规反馈结核病评估指标。我们的中心假设是，简单结核病策略将增加开始治疗的活动性结核病患者的数量。为了验证这一假设，我们将在乌干达的20个社区卫生中心进行一项随机分组试验，以确定相对于现行标准治疗（目标1），SIMPLE TB策略是否能提高结核病诊断和治疗的启动率。在干预和控制健康中心接受结核病诊断评估的成人中收集的常规数据将用于评估试验结果。在临床试验的同时，我们将采用 一种混合方法的方法来详细评估实施过程（目标2），重点是影响干预组件的采用和维护以及对我们的概念模型的忠诚度的因素。最后，我们将进行经济和流行病学建模，以估计成本效益和流行病学影响（即，未来的结核病发病率）。仅仅依靠新的诊断技术而不支持卫生系统干预措施以促进其吸收和使用，不太可能在目前的结核病防治工作中取得持续和有意义的进展。该综合研究计划将产生指导结核病政策制定者决定是否采用简单结核病战略以及如何在其他卫生中心最好地实施该战略所需的高质量证据。这项研究还将有助于更好地了解与在低收入、结核病负担高的国家成功实施新型结核病诊断相关的干预措施的因素和类型。

 DESCRIPTION (provided by applicant): In high burden countries, many patients with tuberculosis (TB) who present to community health centers are lost to follow-up before TB can be diagnosed or treated, leading to ongoing transmission. A primary reason is that the standard approach of collecting sputum specimens over multiple days for microscopic examination is not only insensitive but also inconvenient and costly for patients. Xpert MTB/RIF (Xpert) is a semi-automated molecular test that identifies 90% of TB cases within 2 hours. Xpert is now recommended as the initial diagnostic test for pulmonary TB but cannot be deployed at community health centers because of cost and infrastructure requirements. To achieve access, utilization and impact on health outcomes, strategies for successful referrals from community health centers to facilities in which Xpert is being deployed are essential. Our overall objective s to assess the effectiveness, implementation and impact of a streamlined, single- sample (SIMPLE) TB diagnostic evaluation strategy. The SIMPLE TB strategy was developed after a theory-informed assessment of provider- and patient-level barriers to TB diagnostic evaluation and through a process of stakeholder engagement. Its components include: 1) Single-sample LED fluorescence microscopy (analysis and reporting of smear results from the initial specimen within two hours); 2) Daily transport of smear-negative sputum samples to Xpert testing sites; 3) SMS-based reporting of Xpert test results to patients and health centers; and 4) Routine feedback of TB evaluation metrics to health center staff. Our central hypothesis is that the SIMPLE TB strategy will increase the number of patients with active TB for whom treatment is initiated. To test this hypothesis, we will conduct a cluster-randomized trial at 20 community health centers in Uganda to determine whether the SIMPLE TB strategy improves TB diagnosis and treatment initiation rates relative to the prevailing standard-of-care (Aim 1). Routine data collected on adults undergoing TB diagnostic evaluation at intervention and control health centers will be used to assess trial outcomes. Concurrently with the clinical trial, we will employ a mixed methods approach to evaluate in detail the process of implementation (Aim 2), focusing on factors that influence the adoption and maintenance of intervention components and faithfulness to our conceptual model. Last, we will perform economic and epidemic modeling to estimate the cost-effectiveness and epidemiological impact (i.e., future TB incidence) of the SIMPLE TB strategy (Aim 3). Relying solely on novel diagnostic technologies without also supporting health system interventions to facilitate their uptake and use is unlikely to result in sustained and meaningful progress in the ongoing fight against TB. The comprehensive research plan will generate the high-quality evidence needed to guide TB policy makers in deciding whether to adopt the SIMPLE TB strategy, and on how best to implement it at other health centers. This research will also lead to a better understanding of the factors and types of interventions associated with successful implementation of novel TB diagnostics in low- income, high TB burden countries.