Tuberculosis continues to be a leading cause of infectious disease mortality, and effective screening and diagnosis remains crucial. Despite progress made, diagnostic gaps remain due to poor access to diagnostic tools and testing, particularly in rural and remote areas. As such, the development of target product profiles is essential in guiding the development of new diagnostic tools, however target product profiles often lack evidence-based information and do not consider trade-offs between test accuracy and accessibility. A simulation-based model, in the form of a decision tree, was used to map out the baseline patient tuberculosis diagnostic pathway for individuals in Kenya, South Africa, and India. The model was then used to adapt this pathway to evaluate the trade-offs between increased access to testing and varying accuracy of new tuberculosis diagnostic tools within the health-care contexts of Kenya, South Africa, and India. The model aims to support target product profile development by quantifying the impact of new diagnostics on the standard of care. The model considered three diagnostic attributes, namely sample type (sputum non-sputum), site of testing (point of care, near point of care, and health setting) and turnaround time. Our results indicate that per sample type, novel point-of-care tests would be the most accessible and even with lower sensitivities can achieve comparable or better case detection than the current standard of care in each country. Non-sputum diagnostics also have lower sensitivity requirements. Overall, target product profile parameters with reduced sensitivities from 70% for non-sputum and 78% for sputum tests could be accepted. Diagnostics which bring tuberculosis tests and test results closer to the patient could reduce overall diagnostic loss despite potential reductions in sensitivity. This work provides a novel framework for guiding the future development of diagnostics, with an approach towards balancing accessibility and test performance. The Bill and Melinda Gates Foundation (INV-045721).

中文翻译：

---

结核病诊断中临床表现和测试可及性之间的权衡：目标产品概况开发的多国建模方法


结核病仍然是传染病死亡的主要原因，有效的筛查和诊断仍然至关重要。尽管取得了进展，但由于难以获得诊断工具和检测，诊断差距仍然存在，特别是在农村和偏远地区。因此，目标产品概况的开发对于指导新诊断工具的开发至关重要，但是目标产品概况通常缺乏基于证据的信息，并且不考虑测试准确性和可访问性之间的权衡。使用决策树形式的基于模拟的模型为肯尼亚、南非和印度的个人绘制了基线患者结核病诊断路径。然后使用该模型来调整该路径，以评估肯尼亚、南非和印度医疗保健环境中增加检测机会与新结核病诊断工具的不同准确性之间的权衡。该模型旨在通过量化新诊断对护理标准的影响来支持目标产品概况的开发。该模型考虑了三个诊断属性，即样本类型（痰液非痰液）、检测地点（护理点、附近护理点和健康环境）和周转时间。我们的结果表明，对于每种样本类型，新颖的即时护理测试将是最容易获得的，即使灵敏度较低，也可以实现与每个国家当前护理标准相当或更好的病例检测。非痰诊断的灵敏度要求也较低。总体而言，可以接受目标产品概况参数，其灵敏度从非痰测试的 70% 和痰测试的 78% 降低。 尽管敏感性可能会降低，但使结核病检测和检测结果更接近患者的诊断可以减少总体诊断损失。这项工作为指导诊断的未来发展提供了一个新颖的框架，并提供了一种平衡可访问性和测试性能的方法。比尔和梅琳达·盖茨基金会 (INV-045721)。