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What could be going wrong? Randomisation and blinding. You can usually find what you ’ re looking for …. 12 graduate psychology students 5 day experiment: rats in T maze with dark arm alternating at random, and the dark arm always reinforced 2 groups – “ Maze Bright ” and “ Maze dull ”. - PowerPoint PPT Presentation
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CAMARADES: Bringing evidence to translational medicine
What could be going wrong?
Randomisation and blinding
CAMARADES: Bringing evidence to translational medicine
CAMARADES: Bringing evidence to translational medicine
You can usually find what you’re looking for …
Group Day 1
Day 2
Day 3
Day 4
Day 5
“Maze bright”
1.33 1.60 2.60 2.83 3.26
“Maze dull”
0.72 1.10 2.23 1.83 1.83
Δ +0.60 +0.50 +0.37 +1.00 +1.43
Rosenthal and Fode (1963), Behav Sci 8, 183-9
• 12 graduate psychology students• 5 day experiment: rats in T maze with dark arm alternating at random, and the
dark arm always reinforced• 2 groups – “Maze Bright” and “Maze dull”
CAMARADES: Bringing evidence to translational medicine
• NXY-059 (Astra Zeneca)
– 11 publications, 29 experiments, 408 animals
– Improved outcome by 44% (35-53%)
Macleod et al, 2008
Effi
cacy
Randomisation
Blinded assessment of outcome
Blinded conduct of experiment
Drugs in animal stroke models
CAMARADES: Bringing evidence to translational medicine
What’s a stroke drug worth?
CAMARADES: Bringing evidence to translational medicine
The same thing happens for other diseases …
Blinded assessment of behavioural outcome
No Yes
Impr
ovem
ent
in b
ehav
iour
al o
utco
me
(S
tand
ardi
sed
Eff
ect
Siz
e)
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Multiple Sclerosis Parkinson´s disease
Alzheimer´s diseaseStroke
CAMARADES: Bringing evidence to translational medicine
Are many studies at risk of bias?
Disease Randomisation
(%)
Blinding(%)
Powercalculation
(%)
Yes No Yes No Yes No
Stroke 37 63 37 63 3 97
Alzheimer’s 16 84 22 78 0 100
Parkinson’s 16 84 15 85 0 100
Multiple Sclerosis
9 91 16 84 0 100
Pain 12 88 26 74 0 100
Disease Randomisation
(%)
Blinding(%)
Powercalculation
(%)
Yes No Yes No Yes No
Stroke 37 63 37 63 3 97
CAMARADES: Bringing evidence to translational medicine
But it’s just the neurosciences, right?
Reporting of measures to reduce bias in 254 reports of in vivo, ex vivo or in vitro studies involving non human animals, identified from random sample of 2000 publications from PubMed
Ioannidis et al, 2014
CAMARADES: Bringing evidence to translational medicine
1173 publications using non human animals, published in 2009 or 2010, from 5 leading UK universities
“an outstanding contribution to the internationally excellent position of the UK in biomedical science and clinical/translational research.”
“impressed by the strength within the basic neurosciences that were returned …particular in the areas of behavioural, cellular and molecular neuroscience”
But not in leading institutions, right?
Rand Blind I/E SSC
CAMARADES: Bringing evidence to translational medicine
But not in journals of repute, right?
Top 10%Bottom 10% Top 10%Bottom 10% Top 10%Bottom 10% Top 10%Bottom 10%
CAMARADES: Bringing evidence to translational medicine
Reporting research detailsThe Morris Water Maze in Alzheimer’s research
CAMARADES: Bringing evidence to translational medicine
Reporting research detailsReporting drop outs
minocycline
control
minocycline
control
