Tiago A Mestre1, Shirley Eberly2, Caroline Tanner3, David Grimes4, Anthony E Lang5, David Oakes2, Connie Marras5. 1. Parkinson's Disease and Movement Disorders Center, Division of Neurology, Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. Electronic address: tmestre@toh.ca. 2. Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA. 3. Parkinson's Disease Research, Education and Clinical Center, Neurology, San Francisco Veterans Affairs Medical Center & Department of Neurology, University of California - San Francisco, San Francisco, CA, USA. 4. Parkinson's Disease and Movement Disorders Center, Division of Neurology, Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. 5. Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Canada.
Abstract
INTRODUCTION: PD subtype classification systems attempt to address heterogeneity in PD, a widely recognized feature of the disease with implications in prognosis and therapeutic development. There is no consensus on a valid PD subtype classification system, and its use in clinical research is sparse. Reproducibility has not been systematically assessed as a step for the validation of a PD subtype classification system. We aimed at assessing reproducibility of previously published data-driven PD subtype classification systems in a well-characterized cohort created for clinical research purposes, the Longitudinal and Biomarker Study in Parkinson's Disease (LABS-PD). METHODS: We identified all published studies of data-driven PD subtype classification systems and included those with variables that conceptually matched the variables available in LABS-PD. We reproduced the cluster analyses of the included studies in LABS-PD. Reproducibility was determined by a panel of experts using a modified Delphi consensus process. RESULTS: We included eight studies of data-driven PD subtype classification systems and completed the replication in LABS-PD of the analyses conducted in each original study. After two iterations of the modified Delphi consensus process, no study was reproducible in LABS-PD. CONCLUSIONS: Currently published data-driven PD subtype classification systems lack reproducibility in a well-characterized cohort of patients initially recruited for a clinical trial of a disease-modifying intervention. The results raise concerns about the utility of the widely-discussed concept of data-driven PD subtypes. This gap is a barrier for a meaningful use of PD subtypes and calls for the establishment of standards for the validation and use of these subtype classification systems.
INTRODUCTION:PD subtype classification systems attempt to address heterogeneity in PD, a widely recognized feature of the disease with implications in prognosis and therapeutic development. There is no consensus on a valid PD subtype classification system, and its use in clinical research is sparse. Reproducibility has not been systematically assessed as a step for the validation of a PD subtype classification system. We aimed at assessing reproducibility of previously published data-driven PD subtype classification systems in a well-characterized cohort created for clinical research purposes, the Longitudinal and Biomarker Study in Parkinson's Disease (LABS-PD). METHODS: We identified all published studies of data-driven PD subtype classification systems and included those with variables that conceptually matched the variables available in LABS-PD. We reproduced the cluster analyses of the included studies in LABS-PD. Reproducibility was determined by a panel of experts using a modified Delphi consensus process. RESULTS: We included eight studies of data-driven PD subtype classification systems and completed the replication in LABS-PD of the analyses conducted in each original study. After two iterations of the modified Delphi consensus process, no study was reproducible in LABS-PD. CONCLUSIONS: Currently published data-driven PD subtype classification systems lack reproducibility in a well-characterized cohort of patients initially recruited for a clinical trial of a disease-modifying intervention. The results raise concerns about the utility of the widely-discussed concept of data-driven PD subtypes. This gap is a barrier for a meaningful use of PD subtypes and calls for the establishment of standards for the validation and use of these subtype classification systems.
Authors: Robert S Eisinger; Daniel Martinez-Ramirez; Adolfo Ramirez-Zamora; Christopher W Hess; Leonardo Almeida; Michael S Okun; Aysegul Gunduz Journal: Parkinsonism Relat Disord Date: 2019-05-19 Impact factor: 4.891
Authors: Alberto J Espay; Lorraine V Kalia; Ziv Gan-Or; Caroline H Williams-Gray; Philippe L Bedard; Steven M Rowe; Francesca Morgante; Alfonso Fasano; Benjamin Stecher; Marcelo A Kauffman; Matthew J Farrer; Chris S Coffey; Michael A Schwarzschild; Todd Sherer; Ronald B Postuma; Antonio P Strafella; Andrew B Singleton; Roger A Barker; Karl Kieburtz; C Warren Olanow; Andres Lozano; Jeffrey H Kordower; Jesse M Cedarbaum; Patrik Brundin; David G Standaert; Anthony E Lang Journal: Neurology Date: 2020-02-26 Impact factor: 9.910