Dataset Information

Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety.

ABSTRACT: Genome editing tools have already revolutionized biomedical research and are also expected to have an important impact in the clinic. However, their extensive use in research has revealed much unpredictability, both off and on target, in the outcome of their application. We discuss the challenges associated with this unpredictability, both for research and in the clinic. For the former, an extensive validation of the model is essential. For the latter, potential unpredicted activity does not preclude the use of these tools but requires that molecular evidence to underpin the relevant risk:benefit evaluation is available. Safe and successful clinical application will also depend on the mode of delivery and the cellular context.

SUBMITTER: Teboul L

PROVIDER: S-EPMC7264426 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety.

Teboul Lydia L Herault Yann Y Wells Sara S Qasim Waseem W Pavlovic Guillaume G

Molecular therapy : the journal of the American Society of Gene Therapy 20200320 6

Genome editing tools have already revolutionized biomedical research and are also expected to have an important impact in the clinic. However, their extensive use in research has revealed much unpredictability, both off and on target, in the outcome of their application. We discuss the challenges associated with this unpredictability, both for research and in the clinic. For the former, an extensive validation of the model is essential. For the latter, potential unpredicted activity does not pre ...[more]

PMID: 32243835

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Project description:BackgroundThe ability to reproduce experiments is a defining principle of science. Reproducibility of clinical research has received relatively little scientific attention. However, it is important as it may inform clinical practice, research agendas, and the design of future studies.MethodsWe used scoping review methods to examine reproducibility within a cohort of randomized trials examining clinical critical care research and published in the top general medical and critical care journals. To identify relevant clinical practices, we searched the New England Journal of Medicine, The Lancet, and JAMA for randomized trials published up to April 2016. To identify a comprehensive set of studies for these practices, included articles informed secondary searches within other high-impact medical and specialty journals. We included late-phase randomized controlled trials examining therapeutic clinical practices in adults admitted to general medical-surgical or specialty intensive care units (ICUs). Included articles were classified using a reproducibility framework. An original study was the first to evaluate a clinical practice. A reproduction attempt re-evaluated that practice in a new set of participants.ResultsOverall, 158 practices were examined in 275 included articles. A reproduction attempt was identified for 66 practices (42%, 95% CI 33-50%). Original studies reported larger effects than reproduction attempts (primary endpoint, risk difference 16.0%, 95% CI 11.6-20.5% vs. 8.4%, 95% CI 6.0-10.8%, P = 0.003). More than half of clinical practices with a reproduction attempt demonstrated effects that were inconsistent with the original study (56%, 95% CI 42-68%), among which a large number were reported to be efficacious in the original study and to lack efficacy in the reproduction attempt (34%, 95% CI 19-52%). Two practices reported to be efficacious in the original study were found to be harmful in the reproduction attempt.ConclusionsA minority of critical care practices with research published in high-profile journals were evaluated for reproducibility; less than half had reproducible effects.

Dataset Information

Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety.

Publications

Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety.

Similar Datasets

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