title: Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions.
abstract: Well-defined and reliable clinical outcome assessments are essential for determining whether a drug provides clinically meaningful treatment benefit for patients. In 2015, FDA convened a workshop, "Assessing Neurocognitive Outcomes in Inborn Errors of Metabolism." Topics covered included special challenges of clinical studies of inborn errors of metabolism (IEMs) and other rare diseases; complexities of identifying treatment effects in the context of the dynamic processes of child development and disease progression; and the importance of natural history studies. Clinicians, parents/caregivers, and participants from industry, academia, and government discussed factors to consider when developing measures to assess treatment outcomes, as well as tools and methods that may contribute to standardizing measures. Many issues examined are relevant to the broader field of rare diseases in addition to specifics of IEMs.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Shapiro & Delaney, LLC, Mendota Heights, MN, USA. Electronic address: shapi004@umn.edu.
authors.forename: Elsa
authors.initials: E
authors.lastname: Shapiro
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: jessica.bernstein@fda.hhs.gov.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bernstein
authors.affiliation: Department of Neurology, Division of Child Neurology, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: Heather_Adams@URMC.Rochester.edu.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Adams
authors.affiliation: Shire, Lexington, MA, USA. Electronic address: annjbarbier@aol.com.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Barbier
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: teresa.buracchio@fda.hhs.gov.
authors.forename: Teresa
authors.initials: T
authors.lastname: Buracchio
authors.affiliation: Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: peter.como@fda.hhs.gov.
authors.forename: Peter
authors.initials: P
authors.lastname: Como
authors.affiliation: Shapiro & Delaney, LLC, Mendota Heights, MN, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: kate.delaney@shapiroanddelaney.com.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Delaney
authors.affiliation: Department of Neurology, Center for Rare Neurological Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: feichler@partners.org.
authors.forename: Florian
authors.initials: F
authors.lastname: Eichler
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: jonathan.goldsmith@fda.hhs.gov.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Goldsmith
authors.affiliation: Saving Case & Friends, Inc., Thompson's Station, TN, USA. Electronic address: melissa@savingcase.com.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hogan
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: sarrit.kovacs@fda.hhs.gov.
authors.forename: Sarrit
authors.initials: S
authors.lastname: Kovacs
authors.affiliation: Department of Neurology, Division of Child Neurology, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: Jonathan_Mink@URMC.Rochester.edu.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Mink
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: jo21x@nih.gov.
authors.forename: Joanne
authors.initials: J
authors.lastname: Odenkirchen
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: parisima@mail.nih.gov.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Parisi
authors.affiliation: Clinical Outcomes Research and Evaluation, Ultragenyx Pharmaceutical Inc., Novato, CA, USA. Electronic address: ASkrinar@ultragenyx.com.
authors.forename: Alison
authors.initials: A
authors.lastname: Skrinar
authors.affiliation: Metabolism Program, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: Susan.Waisbren@childrens.harvard.edu.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Waisbren
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: andrew.mulberg@fda.hhs.gov.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Mulberg
mesh_terms: D017028:Caregivers; D002648:Child; D002657:Child Development; D002986:Clinical Trials as Topic; D018450:Disease Progression; D006801:Humans; D000073216:Mental Status and Dementia Tests / Q000592:standards*; D008661:Metabolism, Inborn Errors / Q000188:drug therapy*; D009316:National Institutes of Health (U.S.); D017063:Outcome Assessment, Health Care; D010290:Parents; D035583:Rare Diseases / Q000188:drug therapy*; D058998:Remote Sensing Technology; D014481:United States; D014486:United States Food and Drug Administration
keywords: Clinical outcome assessment; Drug development; Inborn errors; Natural history studies; Neurocognitive; Rare diseases