Quantitative retrospective natural history modeling for orphan drug development.

Autor: Garbade SF; Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Center for Rare Diseases, University Hospital Heidelberg, Heidelberg, Germany., Zielonka M; Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Center for Rare Diseases, University Hospital Heidelberg, Heidelberg, Germany., Komatsuzaki S; Institute of Human Genetics, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany., Kölker S; Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Center for Rare Diseases, University Hospital Heidelberg, Heidelberg, Germany., Hoffmann GF; Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Center for Rare Diseases, University Hospital Heidelberg, Heidelberg, Germany., Hinderhofer K; Institute of Human Genetics, Heidelberg University, Heidelberg, Germany., Mountford WK; Department of Clinical Research, School of Nursing, College of Health and Human Services, University of North Carolina at Wilmington, Wilmington, North Carolina, USA., Mengel E; SphinCS Clinical Science for LSD, Hochheim, Germany., Sláma T; Department of Pediatrics, Oberwallis Hospital, Visp, Switzerland., Mechler K; Pediatric Psychopharmacology, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Ries M; Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Center for Rare Diseases, University Hospital Heidelberg, Heidelberg, Germany.; Center for Virtual Patients, Medical Faculty, University of Heidelberg, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2021 Jan; Vol. 44 (1), pp. 99-109. Date of Electronic Publication: 2020 Sep 08.
DOI: 10.1002/jimd.12304
Abstrakt: The natural history of most rare diseases is incompletely understood and usually relies on studies with low level of evidence. Consistent with the goals for future research of rare disease research set by the International Rare Diseases Research Consortium in 2017, the purpose of this paper is to review the recently developed method of quantitative retrospective natural history modeling (QUARNAM) and to illustrate its usefulness through didactically selected analyses examples in an overall population of 849 patients worldwide with seven (ultra-) rare neurogenetic disorders. A quantitative understanding of the natural history of the disease is fundamental for the development of specific interventions and counseling afflicted families. QUARNAM has a similar relationship to a published case study as a meta-analysis has to an individual published study. QUARNAM relies on sophisticated statistical analyses of published case reports focusing on four research questions: How long does it take to make the diagnosis? How long do patients live? Which factors predict disease severity (eg, genotypes, signs/symptoms, biomarkers)? Where can patients be recruited for studies? Useful statistical techniques include Kaplan-Meier estimates, cluster analysis, regression techniques, binary decisions trees, word clouds, and geographic mapping. In comparison to other natural history study methods (prospective studies or retrospective studies such as chart reviews), QUARNAM can provide fast information on hard clinical endpoints (ie, survival, diagnostic delay) with a lower effort. The choice of method for a particular drug development program may be driven by the research question and may encompass combinatory approaches.
(© 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
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