Simon Finfer is a leading critical care clinical researcher. Hear his candid talk on the reality of research and publication and why it's relevant to you!

1. Research and Publication:
The light and the dark side
Simon Finfer
sfinfer@georgeinstitute.org.au
Royal North Shore Hospital

2. @icuresearch

3. Disclosures
http://www.nejm.org/doi/suppl/10.1056/
NEJMra1208705/suppl_file/
nejmra1208705_disclosures.pdf
or see @icuresearch

4. What will I talk about?
• Research
– Why do it? Gattinoni vs. Finfer
– Testable vs. untestable hypotheses
– “Industrial plant”
– How to do it well – collaborators and industry
– How to mess it up
• Publication
– What do journals want
– Is peer review a good idea
– Could I make it all up and get away with it?
– Things you won’t believe (or at least shouldn’t happen)
– Don’t take “No” for an answer
– Protect yourself
– What’s next …………… ?

5. Eminence based medicine
Evidence based medicine
Charisma based
medicine?

6. Am I qualified?
• Research
– Lead SAFE, NICE SUGAR,
– MC – RENAL, CHEST, ADRENAL ETC.
– Grant reviews – NHMRC, NZHRC, CIHR, NIHR (UK),
MRC (UK), ICF, etc
– SC – PROWESS SHOCK, ACCESS, EUROTHERM
• Publication
– Only 120 papers but…..
– 20% (24) in NEJM, JAMA, Lancet or BMJ
– Editor OTCC, section editor OTM, Guest Editor NEJM
• What can’t I tell you?
– I can’t tell you that …………

7. Why do we do research?
• We do it for
– Power
– Money
– SEX

8. But seriously…….

9. Why do we do research?
– To understand
– To change behaviour
– To improve patients’
outcomes

10. • How much certainty do we want?
• Few treatments produce dramatic effects
• Most claims for large benefits prove evanescent

11. Strict control of random error
• large numbers of deaths or other relevant outcome
And Bias
• Strict randomisation with allocation concealment
• Appropriate analysis, with no unduly data-dependent
emphasis on specific parts of the overall evidence

12. TBI Research

13. 13 13
IIT-TC – Eligible but not included
Eligible but not included (16 Trials - 5320 participants)
Other
IIT
trials
(n=16)
Country
Sample
size
UNABLE
provide
data
(n=4)
Ma
2008
China
510
Yu
2005
China
54
He
2007
China
188
Fernandez
2005
USA
207
CollaboraEon
denied
(n=2)
Yang
2009
China
240
Yan
2009
China
356
Withdrew
(n=2)
Van
den
Berghe
2001
Belgium
1,548
Van
den
Berghe
2006
Belgium
1,200
No
response
(n=8)
Grey
2004
USA
61
He
2008
China
122
Taslimi
2009
Iran
129
Lacherade
2008-­‐2010
France
440
Benito
2008
Spain
28
De
Azevedo
2007
Brazil
48
Stecher
2006
Slovenia
n/a
Desai
2012
USA
189

14. So, how to do it well …….

15. Build a team and collaborate… even with industry

16. “can’t be done ……”
“never been done ……..”
“pick a patient group – think small ……”
“can’t be blinded…….”

17. Institute for International Health
The University of Sydney
Faculty of Medicine
and
Royal North Shore Hospital
Northern Sydney Area Health Service

19. Study Treatments:
4% albumin
(ALBUMEX®) or saline
Manufactured by CSL
Limited, Melbourne,
Australia.

20. Study fluid distribution and tracking

21. SAFE – Belfast 2005
Study Design
• Packaging and distribution

22. Data management

23. SAFE Study: Actual v Target Recruitment
8,000
7,000
6,000
5,000
4,000
3,000
2,000
1,000
0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 63 65 67 69
Week of Study
Number Recruited
Actual Recruitment Target Recruitment

24. It’s your data, don’t compromise!

26. V

28. How to mess it up ……..

29. How to mess it up?
• Launch into it unprepared….
– Without knowing incidence, outcome, realistic effect or
minimal clinically important effect
• Choose an untestable hypothesis
– Dopamine / Frusemide to reverse early AKI
• Work with people seeking to prove something
– “we are not interested in funding you because your
proposed study is not designed to show our product in a
favourable light”
– “can we arrange for these two hospitals to be randomised
to the same group?”
– “can we analyze the data in all three ways and publish the
analysis that shows our product is better?”
• Do your sample size calculation backwards …….

30. Who is behind it?

31. Who is behind it??

32. Who is behind it??

33. Who is behind it??

34. Who is behind it??

35. Research……..
Converting b*llsh*t into FF points.

36. Writing and publication ……..

37. What do journals want?
• Advertising revenue
• Advertising revenue
• Advertising revenue …..

38. What do journals want?
• Revenue from reprints
• Revenue from reprints
• Revenue from reprints

39. What do journals want?
• High quality papers or
• Papers that will be bought in the thousands by
company marketing departments or
• Papers that will be widely cited because they will
generate ……
• Advertising revenue ……..
• And publication fees

40. Is peer review a good thing?

41. Is peer review a good thing?

43. Reviewer 1 – the results appear to be robust
Reviewer 2 – this is a very important study
Reviewer 3 – the authors should be commended on
a well thought out and executed clinical trial
Reviewer 4 – effects of HES on renal function is a
never ending story
Reviewer 5 – “this is not a randomised trial, there
was no allocation concealment, the study was not
blinded, I doubt one can draw meaningful
inferences from these data with any acceptable
degree of certainty.”

46. Reviewer 3

48. Reviewer 3

50. Too many journals?
• Editor - “We can’t ask them to change it all …..
• Finfer - “Well, it’s the wrong design, the wrong
outcome, the wrong analysis. It’s meaningless. You
can’t publish it.”
• Editor – “It’s better than 90% of the stuff I’m sent,
if I don’t publish this I may as well close the journal
down”
• Finfer – “Sounds like a good idea”

51. SURPRISE!!

52. SURPRISE!!

56. Some good news

59. Cochrane albumin Review:
Reactions from industry
Manufacturers allocated $2.2 million:
• To prepare literature reviews supporting the use of
albumin, to be sent to leading regulatory agencies
• To prepare and disseminate a Cochrane critique
dossier
• To establish a medical advisory panel to write
articles supporting the use of albumin

60. Who is behind it??

62. § Issues?
§ Unblinded
§ Marked baseline imbalance
§ Insufficient data re resuscitation and renal function
§ Stopped for futility but reports “positive” findings
§ Changing P values
§ Senior industry (HES) employee on trial advisory board

65. What’s next?

68. My view of the world ….
Goodness