Thibang Diphatlha: Testing adaptive strategies to close the gap from cervical cancer diagnosis to treatment in Botswana

项目摘要 延误和错过及时治疗的机会是造成低收入和中等收入国家（LMIC）与高收入国家（HIC）宫颈癌死亡率差异的重要原因。宫颈癌是全球最常见的女性癌症之一，约90%的病例和死亡发生在中低收入国家，特别是艾滋病毒感染率高的国家。造成这种全球差异的部分原因是高收入国家成功地实施了注重早期发现和及时护理的循证做法。在博茨瓦纳，艾滋病毒和宫颈癌患病率极高的低收入国家，我们发现从诊断到治疗的癌症护理严重延误，这是由无数个人和系统层面的障碍造成的。迄今为止，博茨瓦纳和其他中低收入国家的大多数实施和癌症控制研究都侧重于预防和筛查，对诊断出艾滋病毒相关恶性肿瘤后的治疗关注有限。因此，迫切需要确定有效的战略，以确保及时的护理，并了解影响战略反应的背景因素。如果没有这些基本知识，宫颈癌将仍然是博茨瓦纳和其他中低收入国家的公共卫生危机。为了帮助填补这一关键空白，本研究将使用序贯多重分配随机试验（SMART）设计来测试适应性策略对及时采用治疗的有效性，并使用定性比较分析来评估促成每种适应性策略成功或失败的背景机制。适应性策略旨在针对我们初步数据中确定的个人和系统层面的决定因素，包括结果的延迟沟通，获得治疗的个人和结构性障碍，以及转诊和癌症治疗诊所之间的次优护理协调，并得到临床护理中轻推策略有效性的系统证据的支持。主要实施成果将是采用，定义为在90天内开始治疗。次要实施成果包括保真度（即，完成推荐的治疗），覆盖范围，可接受性，实施成本，以及癌症和艾滋病毒相关的临床结果。这项研究的基本原理是，通过集中外展加强协调、沟通和导航，既能增加及时的治疗采用，又能在项目完成后实现可扩展性和可持续性。这项创新的研究直接响应了国家癌症研究所的呼吁，即在中低收入国家制定和测试癌症控制的实施策略。此外，这种高效的设计使人们能够在一项研究中比较不同的适应性策略，帮助人们进一步了解在资源较低的环境中改善和维持癌症控制所需的最低干预水平。如果成功，这些策略可以很容易地转化为解决癌症控制的其他领域。该项目的长期目标是通过制定和实施有效和可持续的战略，降低中低收入国家的宫颈癌死亡率。

PROJECT SUMMARY Delays and missed opportunities for timely treatment contribute significantly to disparities in cervical cancer mortality in low- and middle-income countries (LMICs) compared to high-income countries (HICs). Cervical cancer is one of the most common female cancers globally, with approximately 90% of cases and deaths occurring in LMICs, particularly those with high rates of HIV. This global disparity is partly driven by successful efforts in HICs to implement evidence-based practices focused on early detection and timeliness of care. In Botswana, a LMIC with an extremely high prevalence of HIV and cervical cancer, we identified substantial delays in cancer care from diagnosis to treatment, driven by a myriad of individual- and system-level barriers. To date, most of the implementation and cancer control research in Botswana and other LMICs has focused on prevention and screening, with limited focus on treatment following diagnosis of HIV-associated malignancies. As such, there is a critical need to identify effective strategies to ensure timely care, and to understand contextual factors that shape the response to strategies. Without this fundamental knowledge, cervical cancer will remain a public health crisis in Botswana and other LMICs. To help fill this critical gap, this study will test the effectiveness of adaptive strategies on timely treatment adoption using a Sequential Multiple Assignment Randomized Trial (SMART) design and evaluate contextual mechanisms contributing to the success or failure of each adaptive strategy using qualitative comparative analysis. The adaptive strategies are designed to target individual- and system-level determinants identified in our preliminary data, including delayed communication of results, individual and structural barriers to accessing treatment, and suboptimal care coordination between referring and cancer treatment clinics, and are supported by systematic evidence of the effectiveness of nudge strategies in clinical care. The primary implementation outcome will be adoption, defined as the initiation of treatment within 90 days. Secondary implementation outcomes include fidelity (i.e., completion of recommended treatment), reach, acceptability, implementation costs, and cancer and HIV-related clinical outcomes. The rationale for the study is that enhancing coordination, communication, and navigation through centralized outreach will both increase timely treatment adoption and be scalable and sustainable after the project is completed. This innovative study responds directly to the call by the National Cancer Institute to develop and test implementation strategies in cancer control in LMICs. Furthermore, the highly efficient design enables the comparison of different adaptive strategies within one study, helping to advance an understanding of the minimum level of intervention needed to improve and sustain cancer control in lower resource settings. If successful, these strategies can be easily translated to address other areas of cancer control. The long-term goal of this project is to decrease cervical cancer mortality in LMICs by developing and implementing effective and sustainable strategies.