title: Validation of prediction models based on lasso regression with multiply imputed data.
abstract: BACKGROUND
  In prognostic studies, the lasso technique is attractive since it improves the quality of predictions by shrinking regression coefficients, compared to predictions based on a model fitted via unpenalized maximum likelihood. Since some coefficients are set to zero, parsimony is achieved as well. It is unclear whether the performance of a model fitted using the lasso still shows some optimism. Bootstrap methods have been advocated to quantify optimism and generalize model performance to new subjects. It is unclear how resampling should be performed in the presence of multiply imputed data.
  
  
  METHODS
  The data were based on a cohort of Chronic Obstructive Pulmonary Disease patients. We constructed models to predict Chronic Respiratory Questionnaire dyspnea 6 months ahead. Optimism of the lasso model was investigated by comparing 4 approaches of handling multiply imputed data in the bootstrap procedure, using the study data and simulated data sets. In the first 3 approaches, data sets that had been completed via multiple imputation (MI) were resampled, while the fourth approach resampled the incomplete data set and then performed MI.
  
  
  RESULTS
  The discriminative model performance of the lasso was optimistic. There was suboptimal calibration due to over-shrinkage. The estimate of optimism was sensitive to the choice of handling imputed data in the bootstrap resampling procedure. Resampling the completed data sets underestimates optimism, especially if, within a bootstrap step, selected individuals differ over the imputed data sets. Incorporating the MI procedure in the validation yields estimates of optimism that are closer to the true value, albeit slightly too larger.
  
  
  CONCLUSIONS
  Performance of prognostic models constructed using the lasso technique can be optimistic as well. Results of the internal validation are sensitive to how bootstrap resampling is performed.
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 Amsterdam, the Netherlands. z.j.musoro@amc.nl.
authors.forename: Jammbe Z
authors.initials: JZ
authors.lastname: Musoro
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Milo A
authors.initials: MA
authors.lastname: Puhan
authors.forename: Gerben
authors.initials: G
authors.lastname: ter Riet
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Geskus
mesh_terms: D004417:Dyspnea / Q000175:diagnosis*; D005544:Forecasting; D006801:Humans; D015233:Models, Statistical; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis*; D011788:Quality of Life; D012044:Regression Analysis; D011795:Surveys and Questionnaires