Developing Clinical Risk Predictions Rules in Early Diffuse Schleroderma

描述(申请人提供)：硬皮病是风湿性疾病中病死率最高的一种多系统自身免疫性疾病。关于硬皮病死亡率及其相关预测因素的文献各不相同。这种差异的原因包括疾病的罕见、样本量小和不同的方法方法。因此，目前还没有有效的方法来预测硬皮病的短期或长期死亡率。这项建议的目的是为早期弥漫性硬皮病患者制定一项为期两年和五年的死亡风险预测规则，同时使用最先进的方法学指南和来自匹兹堡大学大量、特征良好、前瞻性跟踪的硬皮病患者的真正初始队列。具体地说，LA使用回归分析结合分类树分析来开发预测规则。SPECIAM LB使用匹兹堡大学硬皮病队列对规则进行内部验证。具体目标2a使用皇家自由医院和硬皮病临床试验联盟的队列在外部验证了两年死亡率预测规则。具体目标2b使用皇家自由医院硬皮病队列在外部验证了五年死亡率预测规则。开发预测规则以计算单个患者两年和五年死亡率的风险，并确定与生存相关的因素，将具有直接的研究和临床应用。这些预测规则将在临床实践中有用，并在死亡率作为结果衡量标准的情况下，识别具有短期和长期死亡率的高风险个体，以便纳入硬皮病新疗法的临床试验。这项研究的最终目标是开发预测规则，以实现为硬皮病患者提供个性化药物的承诺。开发和评估预测规则的经验，加上通过教学课程和指导教程进行的先进方法培训，将提供宝贵的临床研究培训，并帮助我实现我的目标，即成为一名独立的内科科学家，致力于改善硬皮病患者的护理和预后。

DESCRIPTION (provided by applicant): Scleroderma is a multisystem autoimmune disease with the highest case specific mortality rate of the rheumatic diseases. Literature on scleroderma mortality and its associated predictors has been disparate. The reasons for this variability include the rarity of the disease, small sample sizes and different methodologic approaches. As such, there is no validated method for predicting short or long term mortality in scleroderma. The objective of this proposal is to develop both a two- and five-year mortality risk prediction rule for patients with early diffuse scleroderma while using state of the art methodologic guidelines and a true inception cohort from a large, well- characterized, prospectively followed scleroderma population at the University of Pittsburgh. Specific Aim la develops the prediction rules using regression analysis augmented by classification tree analysis. Specific Aim lb internally validates the rules using the University of Pittsburgh Scleroderma cohort. Specific Aim 2a externally validates the two-year mortality prediction rule using cohorts from the Royal Free Hospital and the Scleroderma Clinical Trials Consortium. Specific aim 2b externally validates the five-year mortality prediction rule using the Royal Free Hospital scleroderma cohort. The development of prediction rules to calculate an individual patient's risk of two- and five-year mortality and ascertain factors associated with survival will have direct research and clinical applications. These prediction rules will be useful in clinical practice and to identify individuals at high risk of short and longer term mortality for inclusion in clinical trials of new therapies for scleroderma when mortality is an outcome measure. The ultimate goal of this line of research is to develop prediction rules that will fulfill the promise of personalized medicine for patients with scleroderma. The experience of developing and vaUdating prediction rules, combined with advanced methodologic training through didactic coursework and directed tutorials, will provide invaluable clinical research training, and help me attain my goal of becoming an independent physician scientist dedicated to improving the care and outcomes of scleroderma patients.