title: An integrated approach to evaluating alternative risk prediction strategies: a case study comparing alternative approaches for preventing invasive fungal disease.
abstract: OBJECTIVE
  This article proposes an integrated approach to the development, validation, and evaluation of new risk prediction models illustrated with the Fungal Infection Risk Evaluation study, which developed risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive fungal disease (IFD).
  
  
  METHODS
  Our decision-analytical model compared alternative strategies for preventing IFD at up to three clinical decision time points (critical care admission, after 24 hours, and end of day 3), followed with antifungal prophylaxis for those judged "high" risk versus "no formal risk assessment." We developed prognostic models to predict the risk of IFD before critical care unit discharge, with data from 35,455 admissions to 70 UK adult, critical care units, and validated the models externally. The decision model was populated with positive predictive values and negative predictive values from the best-fitting risk models. We projected lifetime cost-effectiveness and expected value of partial perfect information for groups of parameters.
  
  
  RESULTS
  The risk prediction models performed well in internal and external validation. Risk assessment and prophylaxis at the end of day 3 was the most cost-effective strategy at the 2% and 1% risk threshold. Risk assessment at each time point was the most cost-effective strategy at a 0.5% risk threshold. Expected values of partial perfect information were high for positive predictive values or negative predictive values (£11 million-£13 million) and quality-adjusted life-years (£11 million).
  
  
  CONCLUSIONS
  It is cost-effective to formally assess the risk of IFD for non-neutropenic, critically ill adult patients. This integrated approach to developing and evaluating risk models is useful for informing clinical practice and future research investment.
authors: Department of Health Services Research & Policy, London School of Hygiene and Tropical Medicine, London, UK. Electronic address: Zia.Sadique@lshtm.ac.uk.
authors: Z
authors: Z
authors: Sadique
authors: R
authors: R
authors: Grieve
authors: D A
authors: DA
authors: Harrison
authors: M
authors: M
authors: Jit
authors: E
authors: E
authors: Allen
authors: K M
authors: KM
authors: Rowan
mesh_terms: D003362:Cost-Benefit Analysis; D003422:Critical Care / Q000191:economics / Q000379:methods*; D016638:Critical Illness; D020000:Decision Support Systems, Clinical; D003661:Decision Support Techniques; D006801:Humans; D009181:Mycoses; D019057:Quality-Adjusted Life Years; D018570:Risk Assessment; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
keywords: cost-effectiveness analysis; critical care; invasive fungal disease; risk prediction; value of information analysis