Developing Clinical Risk Predictions Rules in Early Diffuse Schleroderma

描述（由申请人提供）：硬皮病是一种多系统自身免疫性疾病，是风湿病中病例特异性死亡率最高的疾病。关于硬皮病死亡率及其相关预测因素的文献是完全不同的。这种差异的原因包括疾病的罕见性、小样本量和不同的方法方法。因此，没有有效的方法来预测硬皮病的短期或长期死亡率。本研究的目的是为早期弥漫性硬皮病患者制定2年和5年的死亡率风险预测规则，同时采用最先进的方法学指南，并从匹兹堡大学的大量、特征明确、前瞻性随访的硬皮病人群中进行真正的初始队列研究。具体来说，Aim la利用回归分析和分类树分析相结合的方法开发了预测规则。Specific Aim lb使用匹兹堡大学硬皮病队列内部验证规则。特异性目标2a使用来自皇家自由医院和硬皮病临床试验联盟的队列从外部验证了两年死亡率预测规则。特定目标2b使用皇家自由医院硬皮病队列从外部验证5年死亡率预测规则。发展预测规则来计算个体患者2年和5年的死亡风险，并确定与生存相关的因素，将有直接的研究和临床应用。这些预测规则在临床实践中是有用的，当死亡率是一种结果衡量标准时，可以识别短期和长期死亡率高风险的个体，以便将其纳入硬皮病新疗法的临床试验。这一系列研究的最终目标是制定预测规则，以实现为硬皮病患者提供个性化医疗的承诺。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，并帮助我实现成为一名致力于改善硬皮病患者护理和预后的独立内科科学家的目标。

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.