Reproducibility in Preclinical Research:

Activities and Opportunities

Jonathan Kimmelman
Biomedical Ethics / Experimental Medicine
McGill University
cause effect
drug response
ANIMAL
drug response
HUMAN
Photocredit: NIH, Wikimedia
1: problems
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Source: Kilkenny C et al PLoS One 2009; 4: e7824
Random allocation:
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2: activities
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internal validity:
concealed
allocation
sample size
justication
standardize
animal handling
constuct validity:
match co-
interventions
characterization
of animals at
baseline
conrm
mechanism
external validity:
replicate in
different models
replicate in
different disease
severity
planning
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programmatic:
research w/in
multicenter
consortium
standardize
design
Clinical investigators
Patients
Disease
advocates
Lab scientists
Industry
Funding agencies
Regulators
Academic
medical centers
Journals
Referring physicians
Broader medical
community
Trainees
Clinical investigators
Patients
Disease
advocates
Lab scientists
Industry
Funders
Regulators
Academic
medical centers
Journals
Referring physicians
Broader medical
community
Trainees
3: opportunities
1) stakeholders
Clinical investigators
Patients
Disease
advocates
Lab scientists
Industry
Funding agencies
Regulators
Academic
medical centers
Journals
Referring physicians
Broader medical
community
Trainees
lack of potential effectiveness
information should not generally be a
reason for a Phase 1 IND to be placed
on clinical hold

FDA Guidance
Clinical investigators
Patients
Disease
advocates
Lab scientists
Industry
Funding agencies
IRBs / IACUCs
Academic
medical centers
Journals
Referring physicians
Broader medical
community
Trainees
Clinical investigators
Patients
Disease
advocates
Lab scientists
Industry
Funding agencies
IRBs / IACUCs
Academic
medical centers
Journals
Referring physicians
Broader medical
community
Trainees
2) research domains
cancer?
psychiatric?
respiratory?
metabolic disease?
stem cells?
gene transfer?
immunotherapy?
3) programmatic
a) formal process for guidelines
a) formal process for guidelines
b) structured preclinical testing
a) formal process for guidelines
b) structured preclinical testing

c) incentives
planning

design

reporting

uptake

funders

journals

regulators

?
?
?