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Longitudinal natural history studies based on real-world data in rare diseases: Opportunity and a novel approach.
Adang, Laura Ann; Sevagamoorthy, Anjana; Sherbini, Omar; Fraser, Jamie L; Bonkowsky, Joshua L; Gavazzi, Francesco; D'Aiello, Russel; Modesti, Nicholson B; Yu, Emily; Mutua, Sylvia; Kotes, Emma; Shults, Justine; Vincent, Ariel; Emrick, Lisa T; Keller, Stephanie; Van Haren, Keith P; Woidill, Sarah; Barcelos, Isabella; Pizzino, Amy; Schmidt, Johanna L; Eichler, Florian; Fatemi, Ali; Vanderver, Adeline.
Afiliação
  • Adang LA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: adangl@chop.edu.
  • Sevagamoorthy A; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Sherbini O; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Fraser JL; Rare Disease Institute, Children's National Medical Center, Washington, DC, USA; Leukodystrophy and Myelin Disorders Program, Children's National Medical Center, Washington, DC, USA.
  • Bonkowsky JL; Division of Pediatric Neurology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA; Center for Personalized Medicine, Primary Children's Hospital, Salt Lake City, UT, USA.
  • Gavazzi F; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • D'Aiello R; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Modesti NB; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Yu E; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Mutua S; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Kotes E; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Shults J; Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.
  • Vincent A; CHOP Research Institute, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Emrick LT; Division of Neurology and Developmental Neuroscience in Department Pediatrics, Baylor College Medicine and Texas Children's Hospital, Houston, TX, USA; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Keller S; Children's Healthcare of Atlanta Scottish Rite Hospital, Emory University School of Medicine, Atlanta, GA, USA.
  • Van Haren KP; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Woidill S; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Barcelos I; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Pizzino A; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Schmidt JL; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Eichler F; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
  • Fatemi A; Moser Center for Leukodystrophies, Kennedy Krieger Institute, Baltimore, MD, USA; Departments of Neurology & Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Vanderver A; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Mol Genet Metab ; 142(1): 108453, 2024 May.
Article em En | MEDLINE | ID: mdl-38522179
ABSTRACT
Growing interest in therapeutic development for rare diseases necessitate a systematic approach to the collection and curation of natural history data that can be applied consistently across this group of heterogenous rare diseases. In this study, we discuss the challenges facing natural history studies for leukodystrophies and detail a novel standardized approach to creating a longitudinal natural history study using existing medical records. Prospective studies are uniquely challenging for rare diseases. Delays in diagnosis and overall rarity limit the timely collection of natural history data. When feasible, prospective studies are often cross-sectional rather than longitudinal and are unlikely to capture pre- or early- symptomatic disease trajectories, limiting their utility in characterizing the full natural history of the disease. Therapeutic development in leukodystrophies is subject to these same obstacles. The Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) comprises of a network of research institutions across the United States, supported by a multi-center biorepository protocol, to map the longitudinal clinical course of disease across leukodystrophies. As part of GLIA-CTN, we developed Standard Operating Procedures (SOPs) that delineated all study processes related to staff training, source documentation, and data sharing. Additionally, the SOP detailed the standardized approach to data extraction including diagnosis, clinical presentation, and medical events, such as age at gastrostomy tube placement. The key variables for extraction were selected through face validity, and common electronic case report forms (eCRF) across leukodystrophies were created to collect analyzable data. To enhance the depth of the data, clinical notes are extracted into "original" and "imputed" encounters, with imputed encounter referring to a historic event (e.g., loss of ambulation 3 months prior). Retrospective Functional Assessments were assigned by child neurologists, using a blinded dual-rater approach and score discrepancies were adjudicated by a third rater. Upon completion of extraction, data source verification is performed. Data missingness was evaluated using statistics. The proposed methodology will enable us to leverage existing medical records to address the persistent gap in natural history data within this unique disease group, allow for assessment of clinical trajectory both pre- and post-formal diagnosis, and promote recruitment of larger cohorts.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Raras Limite: Humans País/Região como assunto: America do norte Idioma: En Revista: Mol Genet Metab Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / METABOLISMO Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Raras Limite: Humans País/Região como assunto: America do norte Idioma: En Revista: Mol Genet Metab Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / METABOLISMO Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos