title: Incorporating biological natural history in simulation models: empirical estimates of the progression of end-stage liver disease.
abstract: OBJECTIVE
  To develop an empiric natural-history model that can predict quantitative changes in the laboratory values and clinical characteristics of patients with end-stage liver disease (ESLD), to be used to calibrate an individual microsimulation model.
  
  
  METHODS
  The authors report the development of a stochastic model that uses cubic splines to interpolate between observed laboratory values over time in a cohort of 1997 patients with ESLD awaiting liver transplantation at the University of Pittsburgh Medical Center. The splines were recursively sampled to provide a stochastic, quantitative natural history of each candidate's disease.
  
  
  RESULTS
  The model was able to simulate the types of erratic disease trajectories that occur in individual patients and was able to preserve the statistical properties of the natural history of ESLD in cohorts of real patients. Moreover, the model was able to predict pretransplant survival rates (87% at 1 year), which were statistically similar to rates observed in the authors' local cohort (92%).
  
  
  CONCLUSIONS
  Cubic splines can be used to generate quantitative natural histories for individual patients with ESLD and may be useful for developing clinically robust microsimulation models of other diseases.
authors.affiliation: Department of Industrial and Systems Engineering, University of Wisconsin, Madison, WI, USA.
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Alagoz
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Bryce
authors.forename: Steven
authors.initials: S
authors.lastname: Shechter
authors.forename: Andrew
authors.initials: A
authors.lastname: Schaefer
authors.forename: Chung-Chou H
authors.initials: CC
authors.lastname: Chang
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
authors.forename: Mark S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D018450:Disease Progression; D036262:Empirical Research; D006801:Humans; D017093:Liver Failure / Q000503:physiopathology*; D008962:Models, Theoretical