Clinical Suspicion of TB: A Technology Assessment Tool

产品说明：（由申请人提供）一种新的结核病（TB）诊断检测方法是一个高度优先事项，该方法价格低廉，易于执行，既敏感又特异。由于结核病的诊断需要整合实验室和临床性能标准，因此评估结核病的新诊断测试是一项挑战。此外，由于结核病有许多表现，新的诊断测试可能在某些结核病表现中比其他表现更好。医生的评估可以帮助确定特定测试最有用的患者群或子集。临床疑似结核病（CSTB）工具根据公认的流行病学、临床、放射学和细菌学标准提供了治疗前结核病可能性的汇总估计，用于建立肺结核（PTB）的推定诊断。该小组在初步研究中使用了CSTB，以确定结核病治疗前的患病率。本研究的第一个目的是使用CSTB表作为技术评估工具，描述医生在不同环境下对PTB先验概率的估计。第二个目标是应用该工具评价血清学诊断的临床表现，作为经验性治疗决策的辅助手段。TB的血清诊断试验为CSTB提供了一个极好的试验案例，因为许多评价这些试验的研究人员发现了良好的操作特性，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，将在7个具有国际代表性的临床研究中心招募3，540名结核病疑似患者（预计600人患有PTB）。将在每个研究中心对CSTB进行表征，并将评价两种新的结核病血清学诊断检测形式的临床性能。将选择患者，以便研究CSTB并在PTB的诊断和筛选适应症下测试性能。 在随机接受现场血清学诊断或标准检查（无血清学诊断）的患者中，将比较CSTB评分和经验性治疗决策的准确性。补充实验室研究将评估不同人群的抗原识别特征。具体目标是：1）评估CSTB作为估计医生的疾病治疗前可能性的工具的可靠性和有效性，2）评估不同测试适应症下血清诊断的灵敏度、特异性和预测值，3）表征使用CSTB的血清诊断的操作特征，4）评估血清诊断对医生的疾病可能性估计和经验性治疗决策的影响，以及5）开发用于估计血清诊断测试的临床效用的决策模型。本试验中采集的血清将用于建立血清库，用于检测更新的、尚未开发的血清诊断检测。这项研究将：1）验证和简化CSTB作为一种简单的工具，将临床检查的丰富性引入结核病实验室检查的评估和使用，2）提供关于如何使用两种血清学诊断测试来帮助快速诊断结核病的见解，以及3）建立用于筛选未来结核病血清学测试的血清库。这将有助于明确血清学检测在PTB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.