Clinical Suspicion of TB: A Technology Assessment Tool

描述：（由申请人提供）一种价格低廉、易于实施、既敏感又具有特异性的新型结核病诊断检测是当务之急。由于结核病的诊断需要综合实验室和临床表现标准，因此评估新的结核病诊断检测是一项挑战。此外，由于结核病有多种表现形式，一种新的诊断测试可能对某些表现形式的结核病比对其他表现形式的结核病更有效。医生的评估可以帮助确定特定测试最有用的患者群或亚群。结核病临床怀疑（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总结估计，以建立肺结核（PTB）的推定诊断。CSTB已被该组用于初步研究，以确定治疗前结核病的患病率。本研究的第一个目的是利用CSTB表格作为技术评估工具，表征医生在不同情况下对PTB先验概率的估计。第二个目标是将该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。结核病血清诊断测试为CSTB提供了一个极好的测试案例，因为许多对这些测试进行评估的调查人员发现这些测试具有良好的操作特性，但还不够好，不能作为常规使用。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地点招募3540名结核病疑似患者（其中600人预计患有肺结核）。将在每个地点对CSTB进行特征描述，并将评估两种用于结核病血清诊断的新检测格式的临床性能。将选择患者，以研究CSTB和在肺结核诊断和筛查指征下的测试表现。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。补充实验室研究将评估不同人群的抗原识别概况。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信度和效度，2)评估不同检测适应症下血清诊断的敏感性、特异性和预测值，3)表征使用CSTB进行血清诊断的操作特征，4)评估血清诊断对医生估计疾病可能性和经验治疗决策的影响。5)建立评估血清诊断试验临床效用的决策模型。在这项试验中收集的血清将用于建立一个血清库，用于测试尚待开发的较新的血清诊断测试。本研究将：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测的评估和使用；2)为如何使用两种血清诊断检测来协助结核病的快速诊断提供见解；3)建立一个血清库，用于筛选未来的结核病血清学检测。这将有助于确定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.