Multi-classifier prediction of knee osteoarthritis progression from incomplete imbalanced longitudinal data.

Journal: Scientific reports
Published Date:

Abstract

Conventional inclusion criteria used in osteoarthritis clinical trials are not very effective in selecting patients who would benefit from a therapy being tested. Typically majority of selected patients show no or limited disease progression during a trial period. As a consequence, the effect of the tested treatment cannot be observed, and the efforts and resources invested in running the trial are not rewarded. This could be avoided, if selection criteria were more predictive of the future disease progression. In this article, we formulated the patient selection problem as a multi-class classification task, with classes based on clinically relevant measures of progression (over a time scale typical for clinical trials). Using data from two long-term knee osteoarthritis studies OAI and CHECK, we tested multiple algorithms and learning process configurations (including multi-classifier approaches, cost-sensitive learning, and feature selection), to identify the best performing machine learning models. We examined the behaviour of the best models, with respect to prediction errors and the impact of used features, to confirm their clinical relevance. We found that the model-based selection outperforms the conventional inclusion criteria, reducing by 20-25% the number of patients who show no progression. This result might lead to more efficient clinical trials.

Authors

  • PaweÅ‚ Widera
    School of Computing Science, Newcastle University, 1 Science Square, Newcastle, NE4 5TG, UK.
  • Paco M J Welsing
    Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands.
  • Christoph Ladel
    Merck, Frankfurter Str. 250, 64293, Darmstadt, Germany.
  • John Loughlin
    Biosciences Institute, Newcastle University, International Centre for Life, Newcastle, NE1 3BZ, UK.
  • Floris P F J Lafeber
    Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands.
  • Florence Petit Dop
    Immuno-inflammation Center of Therapeutic Innovation, Institut de Recherches Internationales Servier, Suresnes, France.
  • Jonathan Larkin
    Novel Human Genetics Research Unit, GlaxoSmithKline, Collegeville, PA, 19426, USA.
  • Harrie Weinans
    Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628CD Delft, The Netherlands; Department of Orthopedics, UMC Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands; Department of Rheumatology, UMC Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
  • Ali Mobasheri
  • Jaume Bacardit