jonathan kimmelman ilar presentation

8/12/2019 Jonathan Kimmelman ILAR Presentation

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Reproducibility in Preclinical Research:Activities and Opportunities

Jonathan KimmelmanBiomedical Ethics / Experimental MedicineMcGill University


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cause effect


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drug response

ANIMAL

drug response

HUMAN


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Photocredit: NIH, Wikimedia


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1: problems


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pl nningplanning

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design

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ratio


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Source: Kilkenny C et al PLoS One2009; 4: e7824

Random allocation:


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unanalyzable

Source: Henderson V, in preparation


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Source: Henderson V, in preparation


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2: activities


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internal validity:

concealedallocation

sample size

justification

standardize

animal handling


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constuct validity:match co-

interventions

characterizationof animals at

baseline

confirmmechanism


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external validity:replicate in

different models

replicate indifferent diseaseseverity


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n

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programmatic:

research w/inmulticenter

consortium

standardizedesign


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Clinical investigators

Patients Diseaseadvocates

Lab scientists

Industry

Fundingagencies

Regulators

Academicmedical centers

Journals

Referringphysicians

Broader medicalcommunity

Trainees


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Lab scientists

Industry

Funders

Regulators


Journals

Referringphysicians


Trainees


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3: opportunities


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1) stakeholders


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Lab scientists

Industry

Fundingagencies

Regulators


Journals

Referringphysicians


Trainees


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lack of potential effectiveness

information should not generally be areason for a Phase 1 IND to be placed

on clinical holdFDA Guidance


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Lab scientists

Industry

Fundingagencies

IRBs / IACUCs


Journals

Referringphysicians


Trainees


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Lab scientists

Industry

Funding agencies

IRBs / IACUCs


Journals

Referringphysicians


Trainees


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2) research domains


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cancer?psychiatric?respiratory?metabolic disease?


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stem cells?gene transfer?immunotherapy?


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3) programmatic


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a) formal process for guidelines


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a) formal process for guidelinesb) structured preclinical testing


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a) formal process for guidelinesb) structured preclinical testingc) incentives


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planningdesignreportinguptake

fundersjournalsregulators ?

?

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jonathan kimmelman ilar presentation

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