MARTINGALE RESEARCH CORPORATION — Department of Health and Human Services SBIR Phase I: 400

Description

The Persistent Inflammation Immunosuppression and Catabolism Syndrome PICS is a newly identified medical condition involving extended stays in intensive care units that reduces quality of life for over surgical patients in the U S each year and adds nearly $ billion annually in health related costs The availability of new clinical data characterizing PICS provides the opportunity to develop patient level PICS risk models for trauma and emergency surgery research epidemiologic clinical diagnostic and therapeutic studies Such models are invaluable as decision tools that better inform practitioners administrators and policy makers in order to effectuate improved patient quality of life and reduced health care costs Despite widespread use of patient level prediction models for clinical events patient level multivariate PICS risk models are not currently available Moreover recent advances in statistics that can be applied to robust risk modeling of underlying pathologies are required but not readily accessible to researchers Thus utilizing improved statistical methods for developing a PICS risk model that can reveal the etiology for the disease not merely predict onset would significantly help scientists understand assess prevent and treat PICS This Phase I study investigates the feasibility of applying a Best Approximating Model BAM method to develop PICS risk models on a NIGMS sponsored research center dataset The BAM method is a systematic model development approach that combines robust estimation specification analyses stochastic exhaustive model search and model validation within the single model selection validation framework of a generalized additive model A BAM is designed to handle common problems encountered in developing predictive and explanatory risk models including possible model misspecification missing values and overfitting as well as multicollinearity small sample size bias and Type I error inflation due to multiple model comparisons In this Phase I study the BAM software functionality will be extended to support development of robust PICS risk models followed by a series of simulation studies designed to evaluate its performance The simulation studies will also characterize the advantages of the BAM strategy for developing a robust PICS risk model over conventional statistical methods such as stepwise regression Feasibility study results will develop and evaluate the performance of a PICS risk model on a NIGMS sponsored research center dataset disseminate findings to scientists studying PICS establish feasibility for Phase II PICS risk model development validation evaluation and dissemination and provide the foundation for Phase III commercialization of an advanced risk modeling technology The Persistent Inflammation Immunosuppression and Catabolism Syndrome PICS is a newly identified medical condition replacing late multiple organ failure MOF failure as a predominant phenotype of chronic critical illness PICS involves extended stays in intensive care units that reduces quality of life for over surgical patients in the U S each year that survive sepsis or MOF and adds nearly $ billion annually in health related costs Developing improved risk models of clinical predictors would thus provide the opportunity to test clinical interventions designed to prevent PICS Extending recent advances in robust statistical modeling this Phase I study will develop and evaluate the performance of a PICS risk model on a NIGMS sponsored research center dataset disseminate findings to scientists studying PICS establish feasibility for Phase II PICS risk model development validation evaluation and dissemination and provide the foundation for Phase III commercialization of an advanced risk modeling technology