Hotspot versus clinic-based active case finding for TB in Uganda: A pragmatic randomized trial

乌干达结核病的热点与基于临床的活跃病例发现：一项务实的随机试验

• 批准号: 10387315
• 负责人: David Wesley Dowdy
• 金额: $ 54.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10387315
• 关键词: Africa South of the Sahara; Area; COVID-19; Caring; Catchment Area; Cessation of life; Clinic; Clinical Trials; Communicable Diseases; Communities; Country; Cross-Over Trials; Data; Detection; Devices; Diagnosis; Diagnostic; Diagnostic Sensitivity; Disease; Early Diagnosis; Effectiveness; Epidemiology; Event; Funding; Future; Geography; Health; Health care facility; Heterogeneity; High Prevalence; Household; Incidence; Individual; Infrastructure; Intervention; Lead; Link; Location; Logistics; Maintenance; Measures; Microbiology; Morbidity - disease rate; Mycobacterium tuberculosis; National Heart, Lung, and Blood Institute; Neighborhoods; Notification; Observational Study; Participant; Patient Preferences; Patients; Persons; Population; Prevalence; Preventive therapy; Public Health; Pulmonary Tuberculosis; Randomized; Reading; Regimen; Reporting; Resources; Roentgen Rays; Sputum; Testing; Thoracic Radiography; Time; Translating; Treatment Efficacy; Tuberculosis; Tuberculosis diagnosis; Uganda; Vietnam; Zimbabwe; authority; base; case finding; comparative effectiveness; compare effectiveness; cost; cost effectiveness; digital; disability-adjusted life years; effective intervention; effectiveness implementation design; effectiveness implementation study; evidence base; experience; implementation measures; improved; incremental cost-effectiveness; innovation; intervention effect; models and simulation; mortality; novel; operation; patient oriented; peri-urban; population based; preference; prevent; primary outcome; programs; randomized trial; scale up; screening; secondary analysis; standard of care; technological innovation; transmission process; Africa South of the Sahara; Area; COVID-19; Caring; Catchment Area; Cessation of life; Clinic; Clinical Trials; Communicable Diseases; Communities; Country; Cross-Over Trials; Data; Detection; Devices; Diagnosis; Diagnostic; Diagnostic Sensitivity; Disease; Early Diagnosis; Effectiveness; Epidemiology; Event; Funding; Future; Geography; Health; Health care facility; Heterogeneity; High Prevalence; Household; Incidence; Individual; Infrastructure; Intervention; Lead; Link; Location; Logistics; Maintenance; Measures; Microbiology; Morbidity - disease rate; Mycobacterium tuberculosis; National Heart, Lung, and Blood Institute; Neighborhoods; Notification; Observational Study; Participant; Patient Preferences; Patients; Persons; Population; Prevalence; Preventive therapy; Public Health; Pulmonary Tuberculosis; Randomized; Reading; Regimen; Reporting; Resources; Roentgen Rays; Sputum; Testing; Thoracic Radiography; Time; Translating; Treatment Efficacy; Tuberculosis; Tuberculosis diagnosis; Uganda; Vietnam; Zimbabwe; authority; base; case finding; comparative effectiveness; compare effectiveness; cost; cost effectiveness; digital; disability-adjusted life years; effective intervention; effectiveness implementation design; effectiveness implementation study; evidence base; experience; implementation measures; improved; incremental cost-effectiveness; innovation; intervention effect; models and simulation; mortality; novel; operation; patient oriented; peri-urban; population based; preference; prevent; primary outcome; programs; randomized trial; scale up; screening; secondary analysis; standard of care; technological innovation; transmission process

Project Summary Tuberculosis (TB) is a leading cause of global morbidity and mortality; every year, nearly three million people develop TB disease but are never notified to public health authorities. Studies in Vietnam and Zimbabwe have shown that intensive efforts to find individuals with undiagnosed TB (“active case finding”, ACF) can greatly reduce TB burden. However, in high-burden countries, repeated population-level ACF is not a viable strategy. Therefore, it is critical to understand whether ACF can be implemented in a manner that is both economically/ logistically feasible and epidemiologically impactful. Additionally, as an estimated 23% of the world's population is infected with M. tuberculosis, it is increasingly clear that global targets to end TB cannot be achieved without scaling up TB preventive therapy (TPT). Since ruling out TB disease is essential before providing TPT, ACF offers a unique opportunity to expand TPT by screening a broader population for TB disease; however, most previous ACF campaigns in high-burden countries have not included linkage to TPT. Key recent technological innovations, including mobile chest X-ray devices, AI-based X-ray reading, and novel short-course TPT regimens, have made mass ACF with linkage to TPT feasible for the first time, with potential for transformative impact on TB burden. In our initial R01 study (STOMP-TB), we identified venue-based screening (VBS) as an efficient approach to ACF in an urban Ugandan community; nearly 3% of VBS attendees had undiagnosed TB disease. In this renewal project, we will rigorously evaluate the comparative effectiveness and implementation of two approaches to venue-based ACF with linkage to TPT, each building on specific findings from STOMP- TB. Specifically, we will conduct a multiple period, cluster randomized crossover trial (type 1 hybrid effectiveness-implementation design) comparing a health facility-based approach to ACF/TPT that incorporates existing infrastructure and patients' expressed preferences and a “hotspot”-based approach that brings testing directly to neighborhoods experiencing the highest burden of TB. In Aim 1, we will compare the effectiveness of hotspot-focused versus facility-based ACF/TPT in eight regions near Kampala, Uganda. Our primary outcome will be the number of individuals initiating treatment for confirmed pulmonary TB. Secondary analyses will include the number of people linked to TPT and notifications in the eight intervention regions compared to four control regions. In Aim 2, we will compare implementation (reach, implementation, and maintenance) and incremental cost-effectiveness of hotspot-focused versus facility-based ACF/TPT. In Aim 3, we will use modeling and simulation to estimate intervention effects on the proportion of cases diagnosed, time to TB diagnosis, and projected 10-year TB incidence and mortality. This study will provide randomized yet pragmatic evidence to support the implementation and effectiveness of feasible approaches to TB case-finding and preventive therapy at a critical moment when key innovations (mobile chest x-ray, AI-based interpretation, and short-course TPT regimens) are making such interventions scalable in high-TB-burden settings.

项目摘要 结核病（TB）是全球发病率和死亡率的主要原因。每年，近300万人 开发结核病疾病，但从未通知公共卫生当局。越南和津巴布韦的研究 表明，寻找无诊断结核病的人（“活跃的案例查找”，ACF）的强烈努力可以极大地 减少结核病。但是，在高负年的国家中，反复的人口级ACF并不是可行的策略。 因此，至关重要的是要了解是否可以以经济上的方式/ 从逻辑上可行和流行病学上有影响力。此外，估计占世界人口的23％ 感染了结核分枝杆菌，越来越明显的是，没有结束结核的全球目标就无法实现 扩大TB预防疗法（TPT）。由于排除结核病是必不可少的，在提供TPT之前，ACF 通过筛查更广泛的结核病疾病，提供了一个独特的机会来扩展TPT；但是，大多数 以前在高负责任国家 /地区的ACF运动尚未包括与TPT的联系。关键最近的技术 创新，包括移动胸部X射线设备，基于AI的X射线读数和新颖的短途TPT 方案是首次使质量ACF与TPT链接，并具有变化的潜力 对结核病负担的影响。在我们最初的R01研究（Stomp-TB）中，我们确定了基于场地的筛查（VBS） 在乌干达城市社区中，有效的ACF方法；近3％的VBS参与者患有未诊所的结核病 疾病。在这个续签项目中，我们将严格评估比较效力和实施 与TPT连接的两种基于场地的ACF的方法 tb。特别是，我们将进行多个时期的群集随机跨界试验（1型混合动力 有效实施设计）比较基于医疗机构的ACF/TPT的方法 结合了现有的基础设施和患者表达的偏好和基于“热点”的方法 将测试直接带到经历了结核病负担最高的社区。在AIM 1中，我们将比较 乌干达坎帕拉附近八个地区以热点为中心的ACF/TPT的有效性。我们的 主要结果将是个体开始治疗确认的肺结核的人数。次要 分析将包括与TPT链接的人数以及八个干预区域中的通知 与四个对照区相比。在AIM 2中，我们将比较实施（触及，实施和 维护）和以热点为中心的ACF/TPT的增量成本效益。在AIM 3中， 我们将使用建模和仿真来估计干预对被诊断的病例的比例，时间的影响 进行结核病诊断，并预计10年的结核病事件和死亡率。这项研究将提供随机的 务实的证据支持可行方法的实施和有效性结核病调查 以及关键创新的关键时刻（移动胸部X射线，基于AI的解释， 和短路TPT方案）正在使此类干预措施在高-TB-荷兰设置中可扩展。