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![Page 1: Risk/Benefit Evaluation in FIH Trials: implications for gene editing in human embryos Jonathan Kimmelman Biomedical Ethics / Experimental Medicine McGill.](https://reader036.fdocuments.us/reader036/viewer/2022062423/5697bfde1a28abf838cb21ca/html5/thumbnails/1.jpg)
Risk/Benefit Evaluation in FIH Trials:
implications for gene editing in human embryos
Jonathan KimmelmanBiomedical Ethics / Experimental MedicineMcGill University
![Page 2: Risk/Benefit Evaluation in FIH Trials: implications for gene editing in human embryos Jonathan Kimmelman Biomedical Ethics / Experimental Medicine McGill.](https://reader036.fdocuments.us/reader036/viewer/2022062423/5697bfde1a28abf838cb21ca/html5/thumbnails/2.jpg)
risk
benefit
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?
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part 1: overview
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part 2: framework
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part 3: extending to embryos
![Page 7: Risk/Benefit Evaluation in FIH Trials: implications for gene editing in human embryos Jonathan Kimmelman Biomedical Ethics / Experimental Medicine McGill.](https://reader036.fdocuments.us/reader036/viewer/2022062423/5697bfde1a28abf838cb21ca/html5/thumbnails/7.jpg)
part 1: overview
![Page 8: Risk/Benefit Evaluation in FIH Trials: implications for gene editing in human embryos Jonathan Kimmelman Biomedical Ethics / Experimental Medicine McGill.](https://reader036.fdocuments.us/reader036/viewer/2022062423/5697bfde1a28abf838cb21ca/html5/thumbnails/8.jpg)
2
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1) prior evidence
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2) trial design
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(1) (2)
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risk Benefit:a) subjects +b) society
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clinical promise
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part 2: framework
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2
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1. animal efficacy evidence
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treatmt effect
ANIMAL
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treatmt effect
ANIMAL
effect
HUMAN
treatmt
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treatmt effect
ANIMAL
a)
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
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treatment “generalizable” effect
noisebias
cause specific effect
b)
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treatment effect
animal
confound
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treatment effect
animal
treatment effect
human
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cause effect cause effect
human
cause effect
cause effect
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context specific
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PLoS Medicine 2013
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2. clinical evidence
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reference class
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Dementia
amyloid precursor protein
b-secretase
g-secretase
Aß
Aß
X
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Source: Kimmelman J, London AJ, PLoS Med 2010
¯ confidence
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treatmt effect
HUMAN
a)
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
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b)
p(RC)
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PLoS Medicine 2011
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b)
p(Effrc) x p(Effpc)
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3. moral evaluation
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- risk / benefit- direct social
value- fecundity…
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part 3: extending to embryos
![Page 39: Risk/Benefit Evaluation in FIH Trials: implications for gene editing in human embryos Jonathan Kimmelman Biomedical Ethics / Experimental Medicine McGill.](https://reader036.fdocuments.us/reader036/viewer/2022062423/5697bfde1a28abf838cb21ca/html5/thumbnails/39.jpg)
4
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1. safety, not efficacy
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2. reference class
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1st generation:integrating vectors into pluripotent cells?
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3. identity
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4. long tail
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EVENT RATE
p(E)
p(E)
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