Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions

Elsa Shapiro; Jessica Bernstein; Heather R Adams; Ann J Barbier; Teresa Buracchio; Peter Como; Kathleen A Delaney; Florian Eichler; Jonathan C Goldsmith; Melissa Hogan; Sarrit Kovacs; Jonathan W Mink; Joanne Odenkirchen; Melissa A Parisi; Alison Skrinar; Susan E Waisbren; Andrew E Mulberg

doi:10.1016/j.ymgme.2016.04.006

Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions

Mol Genet Metab. 2016 Jun;118(2):65-9. doi: 10.1016/j.ymgme.2016.04.006. Epub 2016 Apr 14.

Authors

Elsa Shapiro¹, Jessica Bernstein², Heather R Adams³, Ann J Barbier⁴, Teresa Buracchio⁵, Peter Como⁶, Kathleen A Delaney⁷, Florian Eichler⁸, Jonathan C Goldsmith⁹, Melissa Hogan¹⁰, Sarrit Kovacs¹¹, Jonathan W Mink¹², Joanne Odenkirchen¹³, Melissa A Parisi¹⁴, Alison Skrinar¹⁵, Susan E Waisbren¹⁶, Andrew E Mulberg¹⁷

Affiliations

¹ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Shapiro & Delaney, LLC, Mendota Heights, MN, USA. Electronic address: shapi004@umn.edu.
² Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: jessica.bernstein@fda.hhs.gov.
³ Department of Neurology, Division of Child Neurology, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: Heather_Adams@URMC.Rochester.edu.
⁴ Shire, Lexington, MA, USA. Electronic address: annjbarbier@aol.com.
⁵ Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: teresa.buracchio@fda.hhs.gov.
⁶ Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: peter.como@fda.hhs.gov.
⁷ Shapiro & Delaney, LLC, Mendota Heights, MN, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: kate.delaney@shapiroanddelaney.com.
⁸ Department of Neurology, Center for Rare Neurological Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: feichler@partners.org.
⁹ Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: jonathan.goldsmith@fda.hhs.gov.
¹⁰ Saving Case & Friends, Inc., Thompson's Station, TN, USA. Electronic address: melissa@savingcase.com.
¹¹ Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: sarrit.kovacs@fda.hhs.gov.
¹² Department of Neurology, Division of Child Neurology, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: Jonathan_Mink@URMC.Rochester.edu.
¹³ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: jo21x@nih.gov.
¹⁴ Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: parisima@mail.nih.gov.
¹⁵ Clinical Outcomes Research and Evaluation, Ultragenyx Pharmaceutical Inc., Novato, CA, USA. Electronic address: ASkrinar@ultragenyx.com.
¹⁶ 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.
¹⁷ Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: andrew.mulberg@fda.hhs.gov.

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.

Keywords: Clinical outcome assessment; Drug development; Inborn errors; Natural history studies; Neurocognitive; Rare diseases.

Published by Elsevier Inc.

MeSH terms

Caregivers
Child
Child Development
Clinical Trials as Topic
Disease Progression
Humans
Mental Status and Dementia Tests / standards*
Metabolism, Inborn Errors / drug therapy*
National Institutes of Health (U.S.)
Outcome Assessment, Health Care*
Parents
Rare Diseases / drug therapy*
Remote Sensing Technology
United States
United States Food and Drug Administration

Grants and funding

U54 HD061221/HD/NICHD NIH HHS/United States