TY - JOUR
T1 - Developments in evidence creation for treatments of inborn errors of metabolism
AU - Stockler-Ipsiroglu, Sylvia
AU - Potter, Beth K.
AU - Yuskiv, Nataliya
AU - Tingley, Kylie
AU - Patterson, Marc
AU - van Karnebeek, Clara
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - evidence-based medicine
KW - orphan drugs
KW - participatory research
KW - personalized medicine
KW - rare diseases
UR - http://www.scopus.com/inward/record.url?scp=85092150123&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jimd.12315
DO - https://doi.org/10.1002/jimd.12315
M3 - Review article
C2 - 32944978
SN - 0141-8955
VL - 44
SP - 88
EP - 98
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 1
ER -