Validation%20of%20predictive%20regression%20models

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Validation of predictive regression models

• Ewout W. Steyerberg, PhD
• Clinical epidemiologist
• Frank E. Harrell, PhD
• Biostatistician

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Personal background

• Ewout Steyerberg Erasmus MC, Rotterdam, the
  Netherlands
• Frank Harrell Health Evaluation Sciences, Univ
  of Virginia, Charlottesville, VA, USA
• Validation of predictions from regression models
  is of paramount importance

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Learning objectives knowledge of

• common types of regression models
• fundamental assumptions of regression models
• performance criteria of predictive models
• principles of different types of validation

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Performance objectives

• To be able to explain why validation is necessary
  for predictive models
• To be able to judge the adequacy of a validation
  procedure

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Predictive models provide quantitative estimates
of an outcome, e.g.

• Quality of life one year after surgery
• Death at 30 days after surgery
• Long term survival

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Predictive models are often based on regression
analysis

• y a sum(bixi)
• y outcome variable
• a intercept
• bi regression coefficient i
• xi predictor variable i
• i in 1,many, usually 2 to 20

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3 examples of regression

• Quality of life one year after surgery
• continuous outcome, linear regression
• Death at 30 days after surgery
• binary outcome, logistic regression
• Long term survival
• time-to-outcome, Cox regression

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Predictive models make assumptions

• Distribution
• Linearity of continuous variables
• Additivity of effects

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Example a simple logistic regression model

• 30day mortality a b1sex b2age
• Assumptions
• Distribution of 30day mortality is binomial
• Age has a linear effect
• The effects of sex and age can be added

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Assessing model assumptions

• Examine model residuals
• Perform specific tests
• add nonlinear terms, e.g. ageage2
• add interaction terms, e.g. sexage

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Model assumptions and predictions

• Better predictions if assumptions are met
• Some violation inherent in empirical data
• Evaluate predictions in new data

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Evaluation of predictions

• Calibration
• average of predictions correct?
• low and high predictions correct?
• Discrimination
• distinguish low risk from high risk patients?

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Example predicted probabilities
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3 types of validation

• Apparent performance on sample used to develop
  model
• Internal performance on population underlying
  the sample
• External performance on related but slightly
  different population

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Apparent validity

• Easy to calculate
• Results in optimistic performance estimates

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Apparent estimates optimistic since same data
used for

• Definition of model structure e.g. selection
  and coding of variables
• Estimation of model parameters e.g. regression
  coefficients
• Evaluation of model performance e.g.
  calibration and discrimination

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Internal validity

• More difficult to calculate
• Test model in new data, random from underlying
  population

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Why internal validation?

• Honest estimate of performance should be
  obtained, at least for a population similar to
  the development sample
• Internal validated performance sets an upper
  limit to what may be expected in other settings
  (external validity)

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External validity

• Moderately easy to calculate when new data are
  available
• Test model in new data, different from
  development population

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Why external validation?

• Various factors may differ from development
  population, including
• different selection of patients
• different definitions of variables
• different diagnostic or therapeutic procedures

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Internal validation techniques

• Split-sample
• development / validation
• Cross-validation
• alternating development / validation
• extreme n-1 develop / 1 validate (jack-knife)
  
• Bootstrap

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Bootstrap is the preferred internal validation
technique

• bootstrap sample for model development n
  patients drawn with replacement
• original sample for validation n patients
• difference optimism
• efficiency development and validation on n
  patients

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Example bootstrap results for logistic
regression model

• 30-day mortality a b1sex b2age
• Apparent area under the ROC curve 0.77
• Mean area of 200 bootstrap samples0.772
• Mean area of 200 tests in original 0.762
• Optimism in apparent performance 0.01
• Optimism-corrected area 0.76

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External validation techniques

• Temporal validation same investigators, validate
  in recent years
• Spatial validation (other place) same
  investigators, cross-validate in centers
• Fully external other investigators, other centers

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Example external validity of logistic regression
model

• 30-day mortality a b1sex b2age
• Apparent area in 785 patients 0.77
• Tested in 20,318 other patients 0.74
• Tested by other investigators ?

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Example external validation
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Summary

• Apparent validity gives an optimistic estimate of
  model performance
• Internal validity may be estimated by
  bootstrapping
• External validity should be determined in other
  populations

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Key references

• tutorial and book on multivariable
  models(Harrell 1996, Stat Med 15361-87
  Harrell regression modeling strategies,
  Springer 2001)
• empirical evaluations of strategies (Steyerberg
  2000 Stat Med19 1059-79)
• internal validation (Steyerberg 2001JCE 54
  774-81)
• external validation (Justice 1999 Ann Intern
  Med 130515-24 Altman 2000 Stat Med 19 453-73)

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Links

• Interactive text book on predictive
  modelinghttp//www.neri.org/symptom/mockup/Chapte
  r_8/
• Harrells Regression modeling strategieshttp//he
  sweb1.med.virginia.edu/biostat/rms/