Adapting Preclinical Benchmarks for First‐in‐Human Trials of Human Embryonic Stem Cell‐Based Therapies
As research on human embryonic stem cell (hESC)‐based therapies is moving from the laboratory to the clinic, there is an urgent need to assess when it can be ethically justified to make the step from preclinical studies to the first protocols involving human subjects. We examined existing regulatory...
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doaj-6562fc4f9ab748f4b570772e58bff84b2020-11-25T02:16:35ZengWileyStem Cells Translational Medicine2157-65642157-65802016-08-01581058106610.5966/sctm.2015-0222Adapting Preclinical Benchmarks for First‐in‐Human Trials of Human Embryonic Stem Cell‐Based TherapiesGaia Barazzetti0Samia A. Hurst1Alexandre Mauron2Institut Universitaire d'Histoire de la Medicine et de la Santé Publique (IUHMSP), University of Lausanne–CHUV Lausanne University Hospital, Lausanne, SwitzerlandiEH2–Institut Ethique Histoire Humanités, Geneva University Medical School, Geneva, SwitzerlandiEH2–Institut Ethique Histoire Humanités, Geneva University Medical School, Geneva, SwitzerlandAs research on human embryonic stem cell (hESC)‐based therapies is moving from the laboratory to the clinic, there is an urgent need to assess when it can be ethically justified to make the step from preclinical studies to the first protocols involving human subjects. We examined existing regulatory frameworks stating preclinical requirements relevant to the move to first‐in‐human (FIH) trials and assessed how they may be applied in the context of hESC‐based interventions to best protect research participants. Our findings show that some preclinical benchmarks require rethinking (i.e., identity, purity), while others need to be specified (i.e., potency, viability), owing to the distinctive dynamic heterogeneity of hESC‐based products, which increases uncertainty and persistence of safety risks and allows for limited predictions of effects in vivo. Rethinking or adaptation of how to apply preclinical benchmarks in specific cases will be required repeatedly for different hESC‐based products. This process would benefit from mutual learning if researchers included these components in the description of their methods in publications. Significance To design translational research with an eye to protecting human participants in early trials, researchers and regulators need to start their efforts at the preclinical stage. Existing regulatory frameworks for preclinical research, however, are not really adapted to this in the case of stem cell translational medicine. This article reviews existing regulatory frameworks for preclinical requirements and assesses how their underlying principles may best be applied in the context of human embryonic stem cell‐based interventions for the therapy of Parkinson's disease. This research will help to address the question of when it is ethically justified to start first‐in‐human trials in stem cell translational medicine.https://doi.org/10.5966/sctm.2015-0222First-in-human trialsHuman embryonic stem cellsPreclinical benchmarksResearch ethicsTranslational research |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gaia Barazzetti Samia A. Hurst Alexandre Mauron |
spellingShingle |
Gaia Barazzetti Samia A. Hurst Alexandre Mauron Adapting Preclinical Benchmarks for First‐in‐Human Trials of Human Embryonic Stem Cell‐Based Therapies Stem Cells Translational Medicine First-in-human trials Human embryonic stem cells Preclinical benchmarks Research ethics Translational research |
author_facet |
Gaia Barazzetti Samia A. Hurst Alexandre Mauron |
author_sort |
Gaia Barazzetti |
title |
Adapting Preclinical Benchmarks for First‐in‐Human Trials of Human Embryonic Stem Cell‐Based Therapies |
title_short |
Adapting Preclinical Benchmarks for First‐in‐Human Trials of Human Embryonic Stem Cell‐Based Therapies |
title_full |
Adapting Preclinical Benchmarks for First‐in‐Human Trials of Human Embryonic Stem Cell‐Based Therapies |
title_fullStr |
Adapting Preclinical Benchmarks for First‐in‐Human Trials of Human Embryonic Stem Cell‐Based Therapies |
title_full_unstemmed |
Adapting Preclinical Benchmarks for First‐in‐Human Trials of Human Embryonic Stem Cell‐Based Therapies |
title_sort |
adapting preclinical benchmarks for first‐in‐human trials of human embryonic stem cell‐based therapies |
publisher |
Wiley |
series |
Stem Cells Translational Medicine |
issn |
2157-6564 2157-6580 |
publishDate |
2016-08-01 |
description |
As research on human embryonic stem cell (hESC)‐based therapies is moving from the laboratory to the clinic, there is an urgent need to assess when it can be ethically justified to make the step from preclinical studies to the first protocols involving human subjects. We examined existing regulatory frameworks stating preclinical requirements relevant to the move to first‐in‐human (FIH) trials and assessed how they may be applied in the context of hESC‐based interventions to best protect research participants. Our findings show that some preclinical benchmarks require rethinking (i.e., identity, purity), while others need to be specified (i.e., potency, viability), owing to the distinctive dynamic heterogeneity of hESC‐based products, which increases uncertainty and persistence of safety risks and allows for limited predictions of effects in vivo. Rethinking or adaptation of how to apply preclinical benchmarks in specific cases will be required repeatedly for different hESC‐based products. This process would benefit from mutual learning if researchers included these components in the description of their methods in publications. Significance To design translational research with an eye to protecting human participants in early trials, researchers and regulators need to start their efforts at the preclinical stage. Existing regulatory frameworks for preclinical research, however, are not really adapted to this in the case of stem cell translational medicine. This article reviews existing regulatory frameworks for preclinical requirements and assesses how their underlying principles may best be applied in the context of human embryonic stem cell‐based interventions for the therapy of Parkinson's disease. This research will help to address the question of when it is ethically justified to start first‐in‐human trials in stem cell translational medicine. |
topic |
First-in-human trials Human embryonic stem cells Preclinical benchmarks Research ethics Translational research |
url |
https://doi.org/10.5966/sctm.2015-0222 |
work_keys_str_mv |
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