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Review
. 2021 Jan;44(1):88-98.
doi: 10.1002/jimd.12315. Epub 2020 Oct 4.

Developments in evidence creation for treatments of inborn errors of metabolism

Sylvia Stockler-Ipsiroglu  1 , Beth K Potter  2 , Nataliya Yuskiv  1 , Kylie Tingley  2 , Marc Patterson  3 , Clara van Karnebeek  4   5   6
Affiliations
Review

Developments in evidence creation for treatments of inborn errors of metabolism

Sylvia Stockler-Ipsiroglu et al. J Inherit Metab Dis. 2021 Jan.

Abstract

Inborn errors of metabolism (IEM) represent the first group of genetic disorders, amenable to causal therapies. In addition to traditional medical diet and cofactor treatments, new treatment strategies such as enzyme replacement and small molecule therapies, solid organ transplantation, and cell-and gene-based therapies have become available. Inherent to the rare nature of the single conditions, generating high-quality evidence for these treatments in clinical trials and under real-world conditions has been challenging. Guidelines developed with standardized methodologies have contributed to improve the practice of care and long-term clinical outcomes. Adaptive trial designs allow for changes in sample size, group allocation and trial duration as the trial proceeds. n-of-1 studies may be used in small sample sized when participants are clinically heterogeneous. Multicenter observational and registry-based clinical trials are promoted via international research networks. Core outcome and standard data element sets will enhance comparative analysis of clinical trials and observational studies. Patient-centered outcome-research as well as patient-led research initiatives will further accelerate the development of therapies for IEM.

Keywords: evidence-based medicine; orphan drugs; participatory research; personalized medicine; rare diseases.

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Conflict of interest statement

S. S.‐I. received educational grants from Biomarin, Shire, Recordati, and serves/served as PI in clinical trials and postmarketing registries sponsored by Actelion, Biomarin, Shire, Ultragenyx. M. P. has consulted for Actelion, Amicus, IntraBio, Novartis, Orphazyme, Shire, and Vtesse, and has received research funding from Actelion and Orphazyme. He owns stock in IntraBio. C. van K. serves as PI for clinical trials sponsored by Vitaflo. B. K. P., N. Y., K. T., and C. van K. have no conflicts to declare.

References

    1. Scriver CR. Garrod's Croonian lectures (1908) and the charter 'inborn errors of metabolism: albinism, alkaptonuria, cystinuria, and pentosuria at age 100 in 2008. J Inherit Metab Dis. 2008;31(5):580‐598. 10.1007/s10545-008-0984-9. - DOI - PubMed
    1. Bickel H, Gerrard J, Hickmans EM. Influence of phenylalanine intake on phenylketonuria. Lancet. 1953;265(6790):812‐813. - PubMed
    1. van Karnebeek CD, Stockler S. Treatable inborn errors of metabolism causing intellectual disability: a systematic literature review. Mol Genet Metab. 2012;105(3):368‐381. - PubMed
    1. Sun W, Zheng W, Simeonov A. Drug discovery and development for rare genetic disorders. Am J Med Genet A. 2017;173(9):2307‐2322. 10.1002/ajmg.a.38326. - DOI - PMC - PubMed
    1. Potter BK, Khangura SD, Tingley K, Chakraborty P, Little J. Translating rare‐disease therapies into improved care for patients and families: what are the right outcomes, designs, and engagement approaches in health‐systems research? Genet Med. 2016;18:117‐123. - PubMed

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