CASCADE Coordinating Center

项目摘要/摘要 艾滋病毒携带者(WLWH)有较高的宫颈获得性、持久性和进展风险 人乳头瘤病毒(HPV)感染到癌前病变，在缺乏有效筛查和治疗的情况下 治疗服务，可能进展为浸润性癌症的几率是没有治疗服务的女性的五到六倍 爱滋病毒。在过去的几十年里，大规模的全球人道主义资源动员， 通过美国总统艾滋病紧急救援计划(PEPFAR)等倡议，已导致 低收入和中等收入国家的数百万WLWH现在正在获得负担得起的抗逆转录病毒治疗 并因此活得更长。然而，自有效以来，他们患宫颈癌的风险仍然有增无减。 在大多数LMIC中，筛查和癌症前治疗服务仍然不可用。 HIV/宫颈癌预防“梯级”临床试验网络计划进行务实的临床试验 评估经临床证实的干预措施优化宫颈癌筛查的有效性的试验， WLWH的管理和癌症前治疗级联。这些临床试验将在预期的- 在低收入国家和健康差距较大的地区，在资源有限的环境中使用环境 各州。CASCADE网络将有四个主要的科学重点领域：增加筛查吸收， 加强阳性筛查管理，促进癌前治疗准入，优化癌前治疗 世界卫生组织宫颈癌预防治疗。CASCADE网络的临床试验将集中在 在预期使用环境中测量干预措施的临床有效性，同时收集关键信息 在各级筛查中通报实施和扩大这类干预措施的信息 以及WLWH的癌症前治疗。这种混合有效性实施设计将主要集中在 临床疗效终点，如HPV阳性率和/或癌前检测/发病率/复发 费率，并将二次收集有关实施的数据-告知成本、可接受性和 在研究实施策略时的干预保真度。 为了支持与NCI癌症预防部门合作的CASCADE临床试验网络， CASCADE研究基地和CASCADE临床站点，CASCADE网络协调中心将(I) 提供全面的网络协调，促进对网络临床试验概念和 协议，(2)为网络临床试验的数据管理提供集中支持，以及(3)进行 网络临床试验的独立风险适当性审计。级联网络协调中心 将作为CASCADE网络的组织和协调中心，并提供多学科 方案和业务管理、临床研究信息学/信息技术方面的专业知识，以及 临床试验审计。

Project Summary/Abstract Women living with HIV (WLWH) have a higher risk for acquisition, persistence, and progression of cervical human papillomavirus (HPV) to precancerous lesions, which, in the absence of effective screening and treatment services, can progress to invasive cancer at five-to-six times higher rates than in women without HIV. The massive global mobilization of humanitarian resources spanning over the past couple of decades, through initiatives such as the US President's Emergency Plan for AIDS Relief (PEPFAR), has resulted in millions of WLWH in low- and middle-income countries (LMICs) now accessing affordable antiretroviral therapy and consequently living longer lives. Yet, their risk for cervical cancer continues unabated since effective screening and pre-cancer treatment services remain unavailable in most LMICs. The HIV/Cervical Cancer Prevention “CASCADE” Clinical Trials Network plans to conduct pragmatic clinical trials evaluating the effectiveness of clinically proven interventions to optimize the cervical cancer screening, management, and pre-cancer treatment cascade for WLWH. These clinical trials will be conducted in intended- use environments in resource-constrained settings in LMICs and in regions with health disparities in the United States. The CASCADE Network will have four major scientific focus areas: increasing screening uptake, improving management of screen positives, facilitating pre-cancer treatment access, and optimizing pre-cancer treatment for cervical cancer prevention in WLWH. The CASCADE Network clinical trials will focus on the measurement of the clinical effectiveness of interventions in intended use settings while gathering crucial information informing the implementation and scale-up of such interventions across the cascade of screening and pre-cancer treatment for WLWH. Such hybrid effectiveness-implementation designs will primarily focus on clinical effectiveness endpoints such as HPV positivity rates and/or pre-cancer detection/incidence/recurrence rates and will secondarily gather data on implementation-informing aspects such as costs, acceptability, and intervention fidelity while studying implementation strategy. To support the CASCADE Clinical Trials Network in partnership with the NCI's Division of Cancer Prevention, CASCADE Research Bases and CASCADE Clinical Sites, the CASCADE Network Coordinating Center will (i) provide overall network coordination and facilitate scientific review of network clinical trial concepts and protocols, (ii) provide centralized support for data management for network clinical trials, and (iii) conduct independent risk-appropriate auditing of network clinical trials. The CASCADE Network Coordinating Center will serve as the organizational and coordination hub for the CASCADE Network and provide multi-disciplinary expertise in program and operations management, clinical research informatics/information technology, and clinical trials auditing.