title: Clinical prediction in defined populations: a simulation study investigating when and how to aggregate existing models.
abstract: Clinical prediction models (CPMs) are increasingly deployed to support healthcare decisions but they are derived inconsistently, in part due to limited data. An emerging alternative is to aggregate existing CPMs developed for similar settings and outcomes. This simulation study aimed to investigate the impact of between-population-heterogeneity and sample size on aggregating existing CPMs in a defined population, compared with developing a model de novo.
  
  
  
  Simulations were designed to mimic a scenario in which multiple CPMs for a binary outcome had been derived in distinct, heterogeneous populations, with potentially different predictors available in each. We then generated a new 'local' population and compared the performance of CPMs developed for this population by aggregation, using stacked regression, principal component analysis or partial least squares, with redevelopment from scratch using backwards selection and penalised regression.
  
  
  
  While redevelopment approaches resulted in models that were miscalibrated for local datasets of less than 500 observations, model aggregation methods were well calibrated across all simulation scenarios. When the size of local data was less than 1000 observations and between-population-heterogeneity was small, aggregating existing CPMs gave better discrimination and had the lowest mean square error in the predicted risks compared with deriving a new model. Conversely, given greater than 1000 observations and significant between-population-heterogeneity, then redevelopment outperformed the aggregation approaches. In all other scenarios, both aggregation and de novo derivation resulted in similar predictive performance.
  
  
  
  This study demonstrates a pragmatic approach to contextualising CPMs to defined populations. When aiming to develop models in defined populations, modellers should consider existing CPMs, with aggregation approaches being a suitable modelling strategy particularly with sparse data on the local population.
authors.affiliation: Health e-Research Centre, University of Manchester, Vaughan House, Portsmouth Street, M13 9GB, Manchester, UK. glen.martin@manchester.ac.uk.
authors.forename: Glen P
authors.initials: GP
authors.lastname: Martin
authors.affiliation: Health e-Research Centre, University of Manchester, Vaughan House, Portsmouth Street, M13 9GB, Manchester, UK.|Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent, UK.
authors.forename: Mamas A
authors.initials: MA
authors.lastname: Mamas
authors.affiliation: Health e-Research Centre, University of Manchester, Vaughan House, Portsmouth Street, M13 9GB, Manchester, UK.|NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre, University of Manchester, Manchester, UK.
authors.forename: Niels
authors.initials: N
authors.lastname: Peek
authors.affiliation: Health e-Research Centre, University of Manchester, Vaughan House, Portsmouth Street, M13 9GB, Manchester, UK.|NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre, University of Manchester, Manchester, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: Buchan
authors.affiliation: Health e-Research Centre, University of Manchester, Vaughan House, Portsmouth Street, M13 9GB, Manchester, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Sperrin
mesh_terms: D003198:Computer Simulation; D003661:Decision Support Techniques; D006801:Humans; D016018:Least-Squares Analysis; D015233:Models, Statistical; D025341:Principal Component Analysis; D012044:Regression Analysis; D018401:Sample Size
keywords: Clinical prediction models; Computer simulation; Contextual heterogeneity; Model aggregation; Validation