Incorporating biological natural history in simulation models: empirical estimates of the progression of end-stage liver disease.
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.
Alagoz
Oguzhan
O
Department of Industrial and Systems Engineering, University of Wisconsin, Madison, WI, USA.
Bryce
Cindy L
CL
Shechter
Steven
S
Schaefer
Andrew
A
Chang
Chung-Chou H
CC
Angus
Derek C
DC
Roberts
Mark S
MS
D018450:Disease Progression; D036262:Empirical Research; D006801:Humans; D017093:Liver Failure / Q000503:physiopathology*; D008962:Models, Theoretical