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“The James Lind Library:
explaining the rationale for
     and evolution of
   systematic reviews”

        Iain Chalmers
  ichalmers@jameslindlibrary.org


  Opening of the Austrian Branch
   of the Cochrane Collaboration
         14 December 2010
Fund raising
advertisement for the
United Nations
Association, just before I
left the UK to work in
the Gaza Strip in 1969
Gaza

    Learning the hard lesson that
- acting with the best of intentions -
      „do gooders‟ sometimes do
        more harm than good.
One of several
personal examples
Should I have given antibiotics
 prophylactically to children
        with measles?
Severe malnutrition following measles
Some children developing measles in the Gaza Strip
  in 1969 and 1970 suffered and probably died
unnecessarily because I withheld prophylactic
 antibiotics, as my teachers at medical school had
                  told me to do.
Six controlled trials,
  all reported before I went to Gaza,
              showed that:

antibiotics prescribed for children with
   measles can reduce their risk of
         developing pneumonia
Am I the only health professional
    who has been misled by
medical authorities and experts?
JAMA 1992;268:240-248.
Conclusions

“Advice on some life-saving therapies
has been delayed for more than a
decade, while other treatments have
been recommended long after controlled
research has shown them to be harmful.”

Antman et al. JAMA 1992;268:240-248.
In brief…
 science is cumulative,
 and scientists should
cumulate scientifically.

   The process of cumulation
(information synthesis) should
 use methods to reduce
 biases and the play of
        chance.
Lord Rayleigh, 1842-1919
“One of the very few members of the higher nobility
   who won fame as an outstanding scientist.”
“If, as is sometimes supposed, science
consisted in nothing but the laborious
accumulation of facts, it would soon come to
a standstill, crushed, as it were, under its
own weight…The work which deserves,
but I am afraid does not always
receive, the most credit is that in which
discovery and explanation go hand in
hand, in which not only are new facts
presented, but their relation to old ones
is pointed out.”
                     Lord Rayleigh, 1884
Because information about the
 effects of healthcare interventions
      has not been synthesized
systematically and kept up to date,
 people have suffered and died
           unnecessarily
Who was James Lind and
what has he got to do with this?
James Lind, 1716-1794
www.jameslindlibrary.org
Some illustrations of the
  evolution of information
synthesis in health research
Two definitions relevant in discussions
of information synthesis
(Last, Dictionary of Epidemiology, 2001)

Systematic review: The application of
strategies that limit bias in the assembly,
critical appraisal, and synthesis of all
relevant studies on a specific topic.

Meta-analysis: The statistical synthesis of
the data from separate but similar, i.e.
comparable studies, leading to a
quantitative summary of the pooled
results (so reducing the play of chance).
Karl Pearson (1857-1936)
Park WH, Bullowa JGM, Rosenbluth NM (1928).
  The treatment of lobar pneumonia with refined
   specific antibacterial serum. JAMA 91:1503-8.
Jan Stjernswärd
In 1979, Archie Cochrane awards
obstetrics and gynaecology „the
wooden spoon‟ for being the medical
speciality least informed by scientific
evidence, and observes:

"It is surely a great criticism of our
profession that we have not organised a
critical summary, by speciality or
subspeciality, adapted periodically, of
all relevant randomized controlled trials.“
Early 1980s

  An international collaboration
  is established to prepare and
 maintain systematic reviews of
controlled trials in pregnancy and
             childbirth.
1989: publication of:

Effective Care in Pregnancy and
Childbirth (ECPC)

A Guide to Effective Care in
Pregnancy and Childbirth (GECPC)

Oxford Database of Perinatal
Trials (ODPT)
1992
 This ‘pilot experience’ leads the
  NHS R&D Programme to fund
       ‘a Cochrane Centre’
  'to facilitate the preparation of
systematic reviews of randomized
  controlled trials of health care'
The Cochrane Collaboration:
an international, independent, not-for-profit organisation
     of over 27,000 contributors from more than 100
  countries, dedicated to making up-to-date, accurate
   information about the effects of health care readily
                    available worldwide.
A reminder

 “The work which deserves, but I am afraid
 does not always receive, the most credit is
 that in which discovery and explanation go
 hand in hand, in which not only are new
facts presented, but their relation to old
           ones is pointed out.”
                       Lord Rayleigh, 1884
Austin Bradford Hill, 1965

Four questions to which
readers want answers
when reading reports of
research.
1. Why did you start?
2. What did you do?
3. What answer
   did you get?
4. And what does it
   mean anyway?
*



          *actually, the non-use


Only 11 of 24 responding authors of trial reports
that had been added to existing systematic
reviews were even aware of the relevant reviews
when they designed their new studies.
Austin Bradford Hill, 1965

Four questions to which
readers want answers
when reading reports of
research.
1. Why did you start?
2. What did you do?
3. What answer
   did you get?
4. And what does it
   mean anyway?
1. Opening of the Austrian Cochrane Branch - Iain Chalmers
1. Opening of the Austrian Cochrane Branch - Iain Chalmers

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1. Opening of the Austrian Cochrane Branch - Iain Chalmers

  • 1. “The James Lind Library: explaining the rationale for and evolution of systematic reviews” Iain Chalmers ichalmers@jameslindlibrary.org Opening of the Austrian Branch of the Cochrane Collaboration 14 December 2010
  • 2. Fund raising advertisement for the United Nations Association, just before I left the UK to work in the Gaza Strip in 1969
  • 3. Gaza Learning the hard lesson that - acting with the best of intentions - „do gooders‟ sometimes do more harm than good.
  • 5. Should I have given antibiotics prophylactically to children with measles?
  • 7. Some children developing measles in the Gaza Strip in 1969 and 1970 suffered and probably died unnecessarily because I withheld prophylactic antibiotics, as my teachers at medical school had told me to do.
  • 8. Six controlled trials, all reported before I went to Gaza, showed that: antibiotics prescribed for children with measles can reduce their risk of developing pneumonia
  • 9. Am I the only health professional who has been misled by medical authorities and experts?
  • 11.
  • 12. Conclusions “Advice on some life-saving therapies has been delayed for more than a decade, while other treatments have been recommended long after controlled research has shown them to be harmful.” Antman et al. JAMA 1992;268:240-248.
  • 13. In brief… science is cumulative, and scientists should cumulate scientifically. The process of cumulation (information synthesis) should use methods to reduce biases and the play of chance.
  • 14. Lord Rayleigh, 1842-1919 “One of the very few members of the higher nobility who won fame as an outstanding scientist.”
  • 15.
  • 16. “If, as is sometimes supposed, science consisted in nothing but the laborious accumulation of facts, it would soon come to a standstill, crushed, as it were, under its own weight…The work which deserves, but I am afraid does not always receive, the most credit is that in which discovery and explanation go hand in hand, in which not only are new facts presented, but their relation to old ones is pointed out.” Lord Rayleigh, 1884
  • 17. Because information about the effects of healthcare interventions has not been synthesized systematically and kept up to date, people have suffered and died unnecessarily
  • 18. Who was James Lind and what has he got to do with this?
  • 20.
  • 21.
  • 23.
  • 24. Some illustrations of the evolution of information synthesis in health research
  • 25. Two definitions relevant in discussions of information synthesis (Last, Dictionary of Epidemiology, 2001) Systematic review: The application of strategies that limit bias in the assembly, critical appraisal, and synthesis of all relevant studies on a specific topic. Meta-analysis: The statistical synthesis of the data from separate but similar, i.e. comparable studies, leading to a quantitative summary of the pooled results (so reducing the play of chance).
  • 27.
  • 28.
  • 29. Park WH, Bullowa JGM, Rosenbluth NM (1928). The treatment of lobar pneumonia with refined specific antibacterial serum. JAMA 91:1503-8.
  • 31.
  • 32.
  • 33.
  • 34. In 1979, Archie Cochrane awards obstetrics and gynaecology „the wooden spoon‟ for being the medical speciality least informed by scientific evidence, and observes: "It is surely a great criticism of our profession that we have not organised a critical summary, by speciality or subspeciality, adapted periodically, of all relevant randomized controlled trials.“
  • 35. Early 1980s An international collaboration is established to prepare and maintain systematic reviews of controlled trials in pregnancy and childbirth.
  • 36.
  • 37.
  • 38.
  • 39.
  • 40. 1989: publication of: Effective Care in Pregnancy and Childbirth (ECPC) A Guide to Effective Care in Pregnancy and Childbirth (GECPC) Oxford Database of Perinatal Trials (ODPT)
  • 41. 1992 This ‘pilot experience’ leads the NHS R&D Programme to fund ‘a Cochrane Centre’ 'to facilitate the preparation of systematic reviews of randomized controlled trials of health care'
  • 42. The Cochrane Collaboration: an international, independent, not-for-profit organisation of over 27,000 contributors from more than 100 countries, dedicated to making up-to-date, accurate information about the effects of health care readily available worldwide.
  • 43. A reminder “The work which deserves, but I am afraid does not always receive, the most credit is that in which discovery and explanation go hand in hand, in which not only are new facts presented, but their relation to old ones is pointed out.” Lord Rayleigh, 1884
  • 44. Austin Bradford Hill, 1965 Four questions to which readers want answers when reading reports of research. 1. Why did you start? 2. What did you do? 3. What answer did you get? 4. And what does it mean anyway?
  • 45. * *actually, the non-use Only 11 of 24 responding authors of trial reports that had been added to existing systematic reviews were even aware of the relevant reviews when they designed their new studies.
  • 46. Austin Bradford Hill, 1965 Four questions to which readers want answers when reading reports of research. 1. Why did you start? 2. What did you do? 3. What answer did you get? 4. And what does it mean anyway?