Statistical Methods for Evaluation and Validation of Diagnostic Tests

描述（由申请人提供）：这项由生物统计学家、放射学家和医学物理学家共同开展的多学科合作，旨在开发创新的统计方法，以评估和验证新的低成本诊断模式。具体目标是：(1)确定诊断技术非劣效性的统计方法；(2)统计设计和分析方法，以快速准确地评估新的放射学标志物与疾病结局的时间相关性和治疗效果；(3)将统计学方法应用于临床研究，开发人性化软件。具体目标1研究基于不同条件下（缺失数据、混合数据类型和聚类数据）的受试者工作特征曲线、协变量的影响（协变量调整后的非劣效性和确定新测试在其中的劣、优或等效亚组）和贝叶斯实用新型对新诊断测试的非劣效性评价。特异性目的2研究了一种新的横断面病例对照短期随访（CSCCSTFU）设计和分析方法，以估计一种新的诊断试验对罕见结果的时间优势比。它还将提出估算新测试诊断的患者治疗效果下边界的方法。数学理论和模拟研究将用于了解CSCCSTFU设计的估计比值比可以普遍化的条件。Specific Aim 3将把Specific Aim 1的结果应用于骨质疏松性骨折研究和骨质疏松与超声研究的数据，以测试定量超声、外周骨密度（BMD）和骨生化标志物是否以及何时可以作为髋关节和脊柱骨密度的非劣势或等效技术来评估骨质疏松性骨折的风险。它还将使用Specific Aim 2的结果来确定新的单x射线吸收测定技术的乳腺体积密度和结构参数是否可以在一项正在进行的研究中预测15000名女性的乳腺癌。由国际公认的骨质疏松症和乳腺癌研究领域的领导者组成的咨询委员会将为研究团队提供咨询医生和辅助研究机会的建议。研究成果将通过在临床和统计杂志上发表软件、研究和指导论文以及通过影响专业组织的立场文件来传播。

DESCRIPTION (provided by applicant): This multi-disciplinary effort by biostatisticians, radiologists, and medical physicists aims to develop innovative statistical methods for evaluation and validation of new and low cost diagnostic modalities. Specific Aims are (1) statistical methods for determining non-inferiority of diagnostic techniques; (2) statistical design and analysis methods for rapid and accurate evaluation of the chronological association and treatment efficacy of new radiological markers with disease outcome; (3) applying the statistical methods to clinical research and developing user-friendly software. Specific Aim 1 studies evaluation of non- inferiority for a new diagnostic test based on the receiver operating characteristics curve under various conditions (missing data, mixed data types, and clustered data), effects of covariates (non-inferiority after adjustment of covariates and identification of subgroups within which the new test is inferior, superior or equivalent), and Bayesian utility models. Specific Aim 2 studies a new cross-sectional case-control short- term follow-up (CSCCSTFU) design and analysis methods to estimate the chronological odds ratio of a new diagnostic test for a rare outcome. It will also propose methods to estimate the lower boundary of treatment efficacy for patients diagnosed by the new test. Mathematical theory and simulation studies will be used to understand the conditions in which the estimated odds ratio of the CSCCSTFU design can be generalized. Specific Aim 3 will apply results from Specific Aim 1 to data from the Study of Osteoporotic Fractures and the Osteoporosis and Ultrasound Study to test whether and when quantitative ultrasound, peripheral bone mineral density (BMD), and biochemical bone markers can serve as non-inferior or equivalent techniques to BMD of hip and spine for assessing osteoporotic fracture risks. It will also use results of Specific Aim 2 to determine whether the volumetric breast density and structural parameters of the new single X-ray absorptiometry technique can prospectively predict breast cancer in an on-going study of 15,000 women. An advisory committee of internationally recognized leaders in osteoporosis and breast cancer research will advise the research team on outreach to physicians and opportunities for ancillary studies. Research results will be disseminated through publication of software, research and tutorial papers in both clinical and statistical journals and by influencing position papers of professional organizations.