Malcolm Macleod: What is research waste?

CAMARADES: Bringing evidence to translational medicine
mily Sena, Gillian Currie, Hanna Vesterinen, Kieren Egan, Nicki Sherratt, Cristina Fonseca, Zsannet Bahor, Theo
rst, Kim Wever, Hugo Pedder, Katerina Kyriacopoulou, Julija Baginskaite, Ye Ru, Stelios Serghiou, Aaron McLean,
atherine Dick, Tracey Woodruff, Patrice Sutton, Andrew Thomson, Aparna Polturu, Sarah MaCann, Gillian Mead,
oanna Wardlaw, Rustam Salman, Joseph Frantzias, Robin Grant, Paul Brennan, Ian Whittle, Andrew Rice, Rosie
oreland, Nathalie Percie du Sert, Paul Garner, Lauralyn McIntyre, Gregers Wegener, Lindsay Thomson, David
owells, Ana Antonic, Tori O’Collins, Uli Dirnagl, H Bart van der Worp, Philip Bath, Mharie McRae, Stuart Allan, Ian
arshall, Xenios Mildonis, Konstantinos Tsilidis, Orestis Panagiotou, John Ioannidis, Peter Batchelor, David Howells,
anne Jansen of Lorkeers, Geoff Donnan, Peter Sandercock, A Metin Gülmezoglu, Andrew Vickers, An-Wen Chan,
en Djulbegovic, David Moher,, Davina Ghersi, Douglas G Altman, Elaine Beller, Elina Hemminki, Elizabeth Wager,
ujian Song, Harlan M Krumholz, Iain Chalmers, Ian Roberts, Isabelle Boutron, Janet Wisely, Jonathan Grant,
onathan Kagan, Julian Savulescu, Kay Dickersin, Kenneth F Schulz, Mark A Hlatky, Michael B Bracken, Mike Clarke,
uin J Khoury, Patrick Bossuyt, Paul Glasziou, Peter C Gøtzsche, Robert S Phillips, Robert Tibshirani, Sander
reenland, Sandy Oliver, Silvio Garattini, Steven Julious, Susan Michie, Tom Jefferson, Emily Sena, Gillian Currie,
anna Vesterinen, Kieren Egan, Nicki Sherratt, Cristina Fonseca, Zsannet Bahor, Theo Hirst, Kim Wever, Hugo
edder, Katerina Kyriacopoulou, Julija Baginskaite, Ye Ru, Stelios Serghiou, Aaron McLean, Catherine Dick, Tracey
oodruff, Patrice Sutton, Andrew Thomson, Aparna Polturu, Sarah MaCann, Gillian Mead, Joanna Wardlaw, Rustam
alman, Joseph Frantzias, Robin Grant, Paul Brennan, Ian Whittle, Andrew Rice, Rosie Moreland, Nathalie Percie du
ert, Paul Garner, Lauralyn McIntyre, Gregers Wegener, Lindsay Thomson, David Howells, Ana Antonic, Tori O’Collins,
i Dirnagl, H Bart van der Worp, Philip Bath, Mharie McRae, Stuart Allan, Ian Marshall, Xenios Mildonis, Konstantinos
ilidis, Orestis Panagiotou, John Ioannidis, Peter Batchelor, David Howells, Sanne Jansen of Lorkeers, Geoff Donnan,
eter Sandercock, A Metin Gülmezoglu, Andrew Vickers, An-Wen Chan, Ben Djulbegovic, David Moher,, Davina
hersi, Douglas G Altman, Elaine Beller, Elina Hemminki, Elizabeth Wager, Fujian Song, Harlan M Krumholz, Iain
halmers, Ian Roberts, Isabelle Boutron, Janet Wisely, Jonathan Grant, Jonathan Kagan, Julian Savulescu, Kay
ckersin, Kenneth F Schulz, Mark A Hlatky, Michael B Bracken, Mike Clarke, Muin J Khoury, Patrick Bossuyt, Paul
asziou, Peter C Gøtzsche, Robert S Phillips, Robert Tibshirani, Sander Greenland, Sandy Oliver, Silvio Garattini,
even Julious, Susan Michie, Tom Jefferson, Emily Sena, Gillian Currie, Hanna Vesterinen, Kieren Egan, Nicki
herratt, Cristina Fonseca, Zsannet Bahor, Theo Hirst, Kim Wever, Hugo Pedder, Katerina Kyriacopoulou, Julija
aginskaite, Ye Ru, Stelios Serghiou, Aaron McLean, Catherine Dick, Tracey Woodruff, Patrice Sutton, Andrew
homson, Aparna Polturu, Sarah MaCann, Gillian Mead, Joanna Wardlaw, Rustam Salman, Joseph Frantzias, Robin
rant, Paul Brennan, Ian Whittle, Andrew Rice, Rosie Moreland, Nathalie Percie du Sert, Paul Garner, Lauralyn
cIntyre, Gregers Wegener, Lindsay Thomson, David Howells, Ana Antonic, Tori O’Collins, Uli Dirnagl, H Bart van der
orp, Philip Bath, Mharie McRae, Stuart Allan, Ian Marshall, Xenios Mildonis, Konstantinos Tsilidis, Orestis
anagiotou, John Ioannidis, Peter Batchelor, David Howells, Sanne Jansen of Lorkeers, Geoff Donnan, PeterCAMARADES: Bringing evidence to translational medicine
What is research waste?
Malcolm Macleod
Collaborative Approach to Meta-Analysis and Review of
Animal Data from Experimental Studies
and
University of Edinburgh
CAMARADES: Bringing evidence to translational medicine
Winner of the 2012 Ignoble Prize for Neuroscience
CAMARADES: Bringing evidence to translational medicine
Control half dose full dose
InfarctVolume
0
50
100
150
200
250
300
10-120 M 10-60 M
CAMARADES: Bringing evidence to translational medicine
Biomedical research:
Increasing value, reducing waste
Macleod et al, Lancet 2014
CAMARADES: Bringing evidence to translational medicine
1. Setting research priorities
CAMARADES: Bringing evidence to translational medicine
1. Setting research priorities
Whose priorities?
CAMARADES: Bringing evidence to translational medicine
Biomedical research:
Increasing value, reducing waste
Macleod et al, Lancet 2014
CAMARADES: Bringing evidence to translational medicine
2. Design, conduct and analysis
Failure to replicate published pre-clinical
academic results
64%
36%
89%
11%
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
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”
The scale of the problem
RAE 1173
Rand Blind I/E SSC
CAMARADES: Bringing evidence to translational medicine
Biomedical research:
Increasing value, reducing waste
Macleod et al, Lancet 2014
CAMARADES: Bringing evidence to translational medicine
Delays and inconsistency in ethics and governance
CAMARADES: Bringing evidence to translational medicine
Biomedical research:
Increasing value, reducing waste
Macleod et al, Lancet 2014
CAMARADES: Bringing evidence to translational medicine
CAMARADES: Bringing evidence to translational medicine
Biomedical research:
Increasing value, reducing waste
Macleod et al, Lancet 2014
CAMARADES: Bringing evidence to translational medicine
Use of the Morris Water Maze
CAMARADES: Bringing evidence to translational medicine
Researchers are different …number
quality
F.F.P.
HARKing
Open
Science
Preregistration
Risks of
bias
CAMARADES: Bringing evidence to translational medicine
How we do research integrity
CAMARADES: Bringing evidence to translational medicine
Research Improvement Strategy
CAMARADES: Bringing evidence to translational medicine
If you are planning a systematic review or meta-
analysis of animal data, CAMARADES are here to
help: malcolm.macleod@ed.ac.uk
1 of 21

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Malcolm Macleod: What is research waste?

  • 1. CAMARADES: Bringing evidence to translational medicine
  • 2. mily Sena, Gillian Currie, Hanna Vesterinen, Kieren Egan, Nicki Sherratt, Cristina Fonseca, Zsannet Bahor, Theo rst, Kim Wever, Hugo Pedder, Katerina Kyriacopoulou, Julija Baginskaite, Ye Ru, Stelios Serghiou, Aaron McLean, atherine Dick, Tracey Woodruff, Patrice Sutton, Andrew Thomson, Aparna Polturu, Sarah MaCann, Gillian Mead, oanna Wardlaw, Rustam Salman, Joseph Frantzias, Robin Grant, Paul Brennan, Ian Whittle, Andrew Rice, Rosie oreland, Nathalie Percie du Sert, Paul Garner, Lauralyn McIntyre, Gregers Wegener, Lindsay Thomson, David owells, Ana Antonic, Tori O’Collins, Uli Dirnagl, H Bart van der Worp, Philip Bath, Mharie McRae, Stuart Allan, Ian arshall, Xenios Mildonis, Konstantinos Tsilidis, Orestis Panagiotou, John Ioannidis, Peter Batchelor, David Howells, anne Jansen of Lorkeers, Geoff Donnan, Peter Sandercock, A Metin Gülmezoglu, Andrew Vickers, An-Wen Chan, en Djulbegovic, David Moher,, Davina Ghersi, Douglas G Altman, Elaine Beller, Elina Hemminki, Elizabeth Wager, ujian Song, Harlan M Krumholz, Iain Chalmers, Ian Roberts, Isabelle Boutron, Janet Wisely, Jonathan Grant, onathan Kagan, Julian Savulescu, Kay Dickersin, Kenneth F Schulz, Mark A Hlatky, Michael B Bracken, Mike Clarke, uin J Khoury, Patrick Bossuyt, Paul Glasziou, Peter C Gøtzsche, Robert S Phillips, Robert Tibshirani, Sander reenland, Sandy Oliver, Silvio Garattini, Steven Julious, Susan Michie, Tom Jefferson, Emily Sena, Gillian Currie, anna Vesterinen, Kieren Egan, Nicki Sherratt, Cristina Fonseca, Zsannet Bahor, Theo Hirst, Kim Wever, Hugo edder, Katerina Kyriacopoulou, Julija Baginskaite, Ye Ru, Stelios Serghiou, Aaron McLean, Catherine Dick, Tracey oodruff, Patrice Sutton, Andrew Thomson, Aparna Polturu, Sarah MaCann, Gillian Mead, Joanna Wardlaw, Rustam alman, Joseph Frantzias, Robin Grant, Paul Brennan, Ian Whittle, Andrew Rice, Rosie Moreland, Nathalie Percie du ert, Paul Garner, Lauralyn McIntyre, Gregers Wegener, Lindsay Thomson, David Howells, Ana Antonic, Tori O’Collins, i Dirnagl, H Bart van der Worp, Philip Bath, Mharie McRae, Stuart Allan, Ian Marshall, Xenios Mildonis, Konstantinos ilidis, Orestis Panagiotou, John Ioannidis, Peter Batchelor, David Howells, Sanne Jansen of Lorkeers, Geoff Donnan, eter Sandercock, A Metin Gülmezoglu, Andrew Vickers, An-Wen Chan, Ben Djulbegovic, David Moher,, Davina hersi, Douglas G Altman, Elaine Beller, Elina Hemminki, Elizabeth Wager, Fujian Song, Harlan M Krumholz, Iain halmers, Ian Roberts, Isabelle Boutron, Janet Wisely, Jonathan Grant, Jonathan Kagan, Julian Savulescu, Kay ckersin, Kenneth F Schulz, Mark A Hlatky, Michael B Bracken, Mike Clarke, Muin J Khoury, Patrick Bossuyt, Paul asziou, Peter C Gøtzsche, Robert S Phillips, Robert Tibshirani, Sander Greenland, Sandy Oliver, Silvio Garattini, even Julious, Susan Michie, Tom Jefferson, Emily Sena, Gillian Currie, Hanna Vesterinen, Kieren Egan, Nicki herratt, Cristina Fonseca, Zsannet Bahor, Theo Hirst, Kim Wever, Hugo Pedder, Katerina Kyriacopoulou, Julija aginskaite, Ye Ru, Stelios Serghiou, Aaron McLean, Catherine Dick, Tracey Woodruff, Patrice Sutton, Andrew homson, Aparna Polturu, Sarah MaCann, Gillian Mead, Joanna Wardlaw, Rustam Salman, Joseph Frantzias, Robin rant, Paul Brennan, Ian Whittle, Andrew Rice, Rosie Moreland, Nathalie Percie du Sert, Paul Garner, Lauralyn cIntyre, Gregers Wegener, Lindsay Thomson, David Howells, Ana Antonic, Tori O’Collins, Uli Dirnagl, H Bart van der orp, Philip Bath, Mharie McRae, Stuart Allan, Ian Marshall, Xenios Mildonis, Konstantinos Tsilidis, Orestis anagiotou, John Ioannidis, Peter Batchelor, David Howells, Sanne Jansen of Lorkeers, Geoff Donnan, PeterCAMARADES: Bringing evidence to translational medicine What is research waste? Malcolm Macleod Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and University of Edinburgh
  • 3. CAMARADES: Bringing evidence to translational medicine Winner of the 2012 Ignoble Prize for Neuroscience
  • 4. CAMARADES: Bringing evidence to translational medicine Control half dose full dose InfarctVolume 0 50 100 150 200 250 300 10-120 M 10-60 M
  • 5. CAMARADES: Bringing evidence to translational medicine Biomedical research: Increasing value, reducing waste Macleod et al, Lancet 2014
  • 6. CAMARADES: Bringing evidence to translational medicine 1. Setting research priorities
  • 7. CAMARADES: Bringing evidence to translational medicine 1. Setting research priorities Whose priorities?
  • 8. CAMARADES: Bringing evidence to translational medicine Biomedical research: Increasing value, reducing waste Macleod et al, Lancet 2014
  • 9. CAMARADES: Bringing evidence to translational medicine 2. Design, conduct and analysis Failure to replicate published pre-clinical academic results 64% 36% 89% 11%
  • 10. 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”
  • 11. 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” The scale of the problem RAE 1173 Rand Blind I/E SSC
  • 12. CAMARADES: Bringing evidence to translational medicine Biomedical research: Increasing value, reducing waste Macleod et al, Lancet 2014
  • 13. CAMARADES: Bringing evidence to translational medicine Delays and inconsistency in ethics and governance
  • 14. CAMARADES: Bringing evidence to translational medicine Biomedical research: Increasing value, reducing waste Macleod et al, Lancet 2014
  • 15. CAMARADES: Bringing evidence to translational medicine
  • 16. CAMARADES: Bringing evidence to translational medicine Biomedical research: Increasing value, reducing waste Macleod et al, Lancet 2014
  • 17. CAMARADES: Bringing evidence to translational medicine Use of the Morris Water Maze
  • 18. CAMARADES: Bringing evidence to translational medicine Researchers are different …number quality F.F.P. HARKing Open Science Preregistration Risks of bias
  • 19. CAMARADES: Bringing evidence to translational medicine How we do research integrity
  • 20. CAMARADES: Bringing evidence to translational medicine Research Improvement Strategy
  • 21. CAMARADES: Bringing evidence to translational medicine If you are planning a systematic review or meta- analysis of animal data, CAMARADES are here to help: malcolm.macleod@ed.ac.uk