Clinical Suspicion of TB: A Technology Assessment Tool

描述：(申请人提供)一种新的结核病(TB)诊断测试是一个高度优先的项目，该测试价格低廉，易于执行，而且既敏感又特异。由于结核病的诊断需要结合实验室和临床表现标准，因此对新的结核病诊断试验的评估是一项挑战。此外，由于有许多关于结核病的陈述，一种新的诊断测试在一些关于结核病的陈述中可能比在其他陈述中效果更好。医生评估可以帮助确定特定测试最有用的患者群或子集。临床怀疑结核病(CSTB)仪器根据公认的流行病学、临床、放射学和细菌学标准对结核病治疗前的可能性进行汇总估计，以建立对肺结核(PTB)的推定诊断。CSTB已被该小组用于初步研究，以确定治疗前结核病的患病率。这项研究的第一个目标是使用CSTB表格作为技术评估工具来表征医生在不同环境下对肺结核先验概率的估计。第二个目标是将这一工具应用于评估血清诊断的临床表现，作为经验性治疗决策的辅助。结核病的血清诊断测试为CSTB提供了一个很好的测试案例，因为许多评估过这些测试的研究人员发现这些测试具有良好的操作特性，但对于常规使用来说还不够好。在这项前瞻性、随机、对照试验中，3540名结核病嫌疑人(600名预计患有肺结核)将在7个具有国际代表性的临床地点进行登记。CSTB将在每个地点进行特征描述，并将评估两种新的结核病血清诊断检测模式的临床表现。患者的选择将是为了研究CSTB，并在诊断和筛查肺结核的指征下测试表现。在随机接受现场血清诊断或无血清诊断的标准检查的患者中，将比较CSTB评分和经验性治疗决策的准确性。互补性的实验室研究将评估不同人群的抗原识别图谱。其具体目标是：1)评估CSTB作为估计医生治疗前疾病可能性的工具的可靠性和有效性；2)评估不同测试指征下血清学诊断的敏感性、特异性和预测值；3)描述使用CSTB进行血清学诊断的操作特征；4)评估血清诊断对医生对疾病可能性和经验性治疗决策的估计的影响；以及5)开发用于评估血清诊断测试的临床实用性的决策模型。在这项试验中收集的血清将被用来创建一个血清库，用于测试尚未开发的较新的血清诊断测试。这项研究将：1)验证和简化CSTB作为一种简单的工具，将丰富的临床检查应用于结核病实验室检测的评估和使用；2)就如何使用两种血清诊断测试来协助快速诊断结核病提供见解；以及3)建立血清库，用于筛选未来的结核病血清学测试。这将有助于明确血清学检测在肺结核诊断中的作用。

DESCRIPTION: (provided by applicant) A new diagnostic test for tuberculosis (TB) that is inexpensive, easy to perform and is both sensitive and specific is a high priority. Since the diagnosis of TB requires integrating laboratory and clinical performance standards, the evaluation of new diagnostic tests for TB is a challenge. Further, since there are many presentations of TB, a new diagnostic test may work better in some presentations of TB than in others. Physician evaluations can help to identify clusters, or subsets, of patients where a particular test can be most useful. The Clinical Suspicion of TB (CSTB) instrument provides a summary estimate of the pre-treatment likelihood of TB based on recognized epidemiologic, clinical, radiographic, and bacteriologic criteria for establishing a presumptive diagnosis of pulmonary TB (PTB). The CSTB has been used by this group in preliminary studies to determine the pre-treatment prevalence of TB. The first objective of this study is to characterize the physician's estimation of prior probability of PTB in different settings using the CSTB form as a technology assessment tool. The second objective is to apply this tool in evaluating the clinical performance of serodiagnosis as an aid to empiric treatment decisions. Serodiagnostic tests for TB provide an excellent test case for the CSTB in that many investigators who have evaluated these tests have found good operating characteristics, but not quite good enough for routine use. In this prospective, randomized, controlled trial, 3,540 TB suspects (600 expected to have PTB) will be enrolled at seven internationally representative clinical sites. The CSTB will be characterized at each site and the clinical performance of two new test formats for serodiagnosis of TB will be evaluated. Patients will be selected so as to study CSTB and test performance under both diagnostic and screening indications for PTB. Among patients randomized to receive on-site serodiagnosis or standard work-up without serodiagnosis, CSTB scores and the accuracy of empiric treatment decisions will be compared. Complementary laboratory studies will evaluate antigen recognition profiles in different populations. The specific aims are: 1) to evaluate the reliability and validity of the CSTB as a tool for estimating physicians' pre-treatment likelihood of disease, 2) to evaluate sensitivity, specificity, and predictive values of serodiagnosis under different testing indications, 3) to characterize operating characteristics of serodiagnosis using the CSTB, 4) to evaluate the impact of serodiagnosis on physicians' estimates of disease likelihood and empiric treatment decisions, and 5) to develop a decision model for estimating the clinical utility of serodiagnostic tests. Serum collected in this trial will be used to create a serum bank for testing of newer, as yet to be developed, serodiagnostic tests. This study will: 1) validate and streamline the CSTB as a simple tool to bring the richness of the clinical exam to the evaluation and use of laboratory tests for TB, 2) provide insights into how two serodiagnostic tests can be used to assist in rapid diagnosis of TB, and 3) establish a serum bank for screening of future serologic tests for TB. It will help define the role of serologic testing in the diagnosis of PTB.