Developing Clinical Risk Predictions Rules in Early Diffuse Schleroderma

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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.