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1.
Mol Genet Metab. 2017 Jun;121(2):57-69. doi: 10.1016/j.ymgme.2017.05.005. Epub 2017 May 8.

Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature.

Author information

1
Oregon Health & Science University, Institute on Development & Disability, United States.
2
Shapiro & Delaney LLC, United States.
3
Shapiro & Delaney LLC, United States; University of Minnesota, Department of Pediatrics and Neurology, United States. Electronic address: shapi004@umn.edu.

Abstract

Sensitive, reliable measurement instruments are critical for the evaluation of disease progression and new treatments that affect the brain in the mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical phenotypes that affect the brain during development and result in devastating cognitive decline and ultimately death without treatment. Comparisons of outcomes are hindered by diverse protocols and approaches to assessment including applicability to international trials necessary in rare diseases. We review both cognitive and adaptive measures with the goal of providing evidence to a Delphi panel to come to a consensus about recommendations for clinical trials for various age groups. The results of the consensus panel are reported in an accompanying article. The following data were gathered (from internet resources and from test manuals) for each measure and summarized in the discussion: reliability, validity, date and adequacy of normative data, applicability of the measure's metrics, cross cultural validity including translations and adaptations, feasibility in the MPS population, familiarity to sites, sensitivity to change, and interpretability. If, resulting from this consensus, standard protocols are used for both natural history and treatment studies, patients, their families, and health care providers will benefit from the ability to compare study outcomes.

KEYWORDS:

Adaptive skills; Clinical trials; Mucopolysaccharidosis; Neurocognition

PMID:
28506702
DOI:
10.1016/j.ymgme.2017.05.005
[Indexed for MEDLINE]
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2.
Mol Genet Metab. 2017 Jun;121(2):70-79. doi: 10.1016/j.ymgme.2017.05.004. Epub 2017 May 6.

Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure.

Author information

1
Pediatric Clinical Research Office, Emma Children's Hospital, Academic Medical Center, Amsterdam, Netherlands.
2
Comradis Limited, Oxford, UK.
3
Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
4
British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
5
Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, Netherlands.
6
Department of Pediatrics, Pittsburgh School of Medicine, Pittsburgh, PA, USA.
7
Department of Genetics/UFRGS, Medical Genetic Service/HCPA, Porto Alegre, Brazil.
8
UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
9
Saving Case & Friends, Thompsons Station, TN, USA.
10
Willink Biochemical Genetic Unit, Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester, UK.
11
Clinical Paediatric Psychology, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
12
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
13
Paediatric Psychosocial Department, Royal Manchester Children's Hospital, Manchester, UK.
14
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
15
Department of Pediatrics, Academic Medical Center, Amsterdam, Netherlands.
16
Statistics Collaborative, Inc., Washington, DC, USA.
17
Institute on Development & Disability, Oregon Health & Science University, Portland, OR, USA.
18
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Shapiro Neuropsychology Consulting, LLC, Portland, OR, USA. Electronic address: shapi004@umn.edu.

Abstract

The design and conduct of clinical studies to evaluate the effects of novel therapies on central nervous system manifestations in children with neuronopathic mucopolysaccharidoses is challenging. Owing to the rarity of these disorders, multinational studies are often needed to recruit enough patients to provide meaningful data and statistical power. This can make the consistent collection of reliable data across study sites difficult. To address these challenges, an International MPS Consensus Conference for Cognitive Endpoints was convened to discuss approaches for evaluating cognitive and adaptive function in patients with mucopolysaccharidoses. The goal was to develop a consensus on best practice for the design and conduct of clinical studies investigating novel therapies for these conditions, with particular focus on the most appropriate outcome measures for cognitive function and adaptive behavior. The outcomes from the consensus panel discussion are reported here.

KEYWORDS:

Adaptive behavior; Clinical trial; Cognitive; Mucopolysaccharidoses; Neurological; Protocol

PMID:
28501294
DOI:
10.1016/j.ymgme.2017.05.004
[Indexed for MEDLINE]
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