systematic reviews, meta-analysis & evidence based medicine

The Need for Evidence Based
Medicine
Prof. Prathap Tharyan MD, MRCPsych
Professor of Psychiatry & Associate Director
Christian Medical College, Vellore
Director, South Asian Cochrane Network & Centre
Editor, Cochrane Schizophrenia Group
Prof. BV Moses & ICMR Centre for Advanced Research &
Training in Evidence-Informed Healthcare
Christian Medical College, Vellore, Tamil Nadu, India

EVIDENCE BASED MEDICINE
• The integration of
research evidence,
clinical expertise
and patient values
(Sackett et al, 2000)
Evidence-Based Medicine Working Group: Evidence-based medicine. A
new approach to teaching the practice of medicine. JAMA. 1992;268:
2420-5
http://www.cebm.utoronto.ca/

Evidence Based Medicine
• I: Getting the right evidence
• II: Getting the evidence used

Getting the right evidence
What is needed
• Ensure all relevant research is considered
• Critically appraise research for quality and
applicability
• Synthesize research findings using appropriate
methods

Why is reliable evidence important
Hormone replacement therapy for post-menopausal
women provides an instructive example
• For a decade, organizations recommended that clinicians
encourage postmenopausal women to use hormone
replacement therapy believing this would reduce
cardiovascular risks
• Because the data came from observational studies with
inconsistent results, the evidence for a reduction in
cardiovascular risk was of very low quality (unreliable)

Evidence from RCTs

Farquhar C, MarjoribanksJ, LethabyA, Suckling JA, Lamberts Q. Long term hormone
therapy for peri-menopausal and postmenopausal women. Cochrane Database
of Systematic Reviews 2009, Issue 2. Art. No.: CD004143
• Objectives
To assess the effect of long-term HT on mortality,
cardiovascular outcomes, cancer, gallbladder
disease, cognition, fractures and quality of life.
• Selection criteria
Randomised double-blind trials of HT versus
placebo, taken for at least one year by perimenopausal
or postmenopausal women.
HT included oestrogens, with or without
progestogens, via oral, trans-dermal,
subcutaneous or trans-nasal routes.

Farquhar C, MarjoribanksJ, LethabyA, Suckling JA, Lamberts Q.
Long term hormone therapy for peri-menopausal and
postmenopausal women. Cochrane Database of Systematic Reviews
2009, Issue 2. Art. No.: CD004143
• Main results
• Nineteen trials involving 41,904 women were included.
• In relatively healthy women, combined continuous HT
significantly increased the risk of venous thromboembolism
or coronary event (after one year’s use),
stroke (after three years), breast cancer and
gallbladder disease.
• Long-term oestrogen-only HT significantly increased
the risk of venous thrombo-embolism, stroke and
gallbladder disease (after one to two years, three years
and seven years’ use respectively), but did not
significantly increase the risk of breast cancer.

Farquhar C, MarjoribanksJ, LethabyA, Suckling JA, Lamberts Q.
Long term hormone therapy for peri-menopausal and
postmenopausal women. Cochrane Database of Systematic Reviews
2009, Issue 2. Art. No.: CD004143
• Main results (cont..)
• The only statistically significant benefits of HT were a
decreased incidence of fractures and (for combined HT)
colon cancer, with long-term use.
• Among women aged over 65 who were relatively healthy
(i.e. generally fit, without overt disease) and taking
continuous combined HT, there was a statistically
significant increase in the incidence of dementia.
• Among women with cardiovascular disease, long-term
use of combined continuous HT significantly increased
the risk of venous thrombo-embolism.

Farquhar C, MarjoribanksJ, LethabyA, Suckling JA, Lamberts Q.
Long term hormone therapy for peri-menopausal and
postmenopausal women. Cochrane Database of Systematic Reviews
2009, Issue 2. Art. No.: CD004143
• Authors’ conclusions
HT is not indicated for the routine management of
chronic disease.
We need more evidence on the safety of HT for
menopausal symptom control, though short-term use
appears to be relatively safe for healthy younger
women

The Need for Evidence:
1. Reliable evidence is needed to optimize healthcare
outcomes and prevent harms

Is bed rest necessary after spinal puncture
Why
• Is bed rest after spinal puncture helpful
A systematic review of trials
Allen, Glasziou, Del Mar. Lancet, 1999
• 10 trials of bed rest after spinal puncture
no change in headache with bed rest
Increase in back pain
• Protocols in UK neurology units - 80% still recommend bed
rest after LP
Serpell M, BMJ 1998;316:1709–10
• …evidence of harm available for 17 years preceding...

The Need for Evidence:
2. A lot of the medicine we practice is not evidence
based

Reduced osmolarity
rehydration solution

Need for unscheduled
intravenous fluid infusion

A large international trial
comparing magnesium
sulphate with placebo for the
treatment of pre-eclampsia;
evaluating the effects on
women and their babies

The Need for Evidence:
3. Reliable evidence improves standards of care

Antenatal care
A reduction in the number of
antenatal care visits with or
without an increased
emphasis on the content of
the visits could be
implemented without any
increase in adverse maternal
and perinatal outcomes.

The need for Evidence:
4. Reliable evidence optimizes resource utilization

The need for evidence:
5. Reliable evidence saves lives

Need for EBM-the Bottom Line:
Scarcity of resources
• Wherever health care is provided and used, it is
essential to know which interventions work,
which do not work, and which are likely to be
harmful.
• This is especially important in situations where
health problems are severe and the scarcity of
resources makes it vital that they are not wasted
• EBM has a particular relevance to the
developing world

“If you are poor, actually you need more
evidence before you invest, rather than
if you are rich.”

Finding reliable evidence

Inadequacy of traditional sources of
information
• Text books rapidly are out of date
Antman et al. A comparison of results of meta-analyses of randomised control trials and
recommendations of clinical experts. JAMA 1992;268:240-8.
• Experts are frequently wrong
Oxman A, Guyatt GH: The science of reviewing research. Ann NY Acad Sci 1993;703:125-
134
• Didactic CME not effective in changing practice
Davis D A, Thomson M A, Oxman A D, Haynes R B: Changing physician performance: a
systematic review of the effect of continuing medical education strategies. JAMA
1997;274:700-5.
• Medical Journals are too many and of variable quality
Haynes RB. Where's the Meat in Clinical Journals [editorial] ACP Journal Club.
1993;119:A-22-3.
EBM. Sackett et al 2000

How much confidence do we place in
evidence
• Not all evidence is equally convincing.
• How convincing evidence is (for effects of
interventions) should be based on criteria such as:
What sort of observations
How well they were done (internal validity)
How directly relevant they are (external validity)
How many there are
How effective is the intervention
How consistent they are
• NOT on who says it or how they say it.

Not all evidence is equally convincing: Levels of Evidence
Level Intervention Prognosis Diagnosis Etiology
Least biased
I
Systematic Review
of level II studies
Systematic Review
of Level II studies
Systematic Review
of Level II studies
Systematic Review
of Level II studies
II RCT Inception cohort
study
Cross sectional
study among
consecutive
patients
Prospective cohort
study
III
•Non-randomized
controlled clinical
trial
•Controlled before
and after study
•Cohort study
•Case control study
•Untreated
controls in an RCT
•Retrospectively
assembled cohort
study
•Cross sectional
study among nonconsecutive
patients
•Case control study
•Retrospective
cohort study
•Case control study
Most biased
IV
Case series Case series Case series
Cohort of patients
at different stages
of disease
Cross sectional
study

What is a systematic review
“A review in which bias has been reduced by the
systematic identification, appraisal, synthesis,
and, if relevant, statistical aggregation of all
relevant studies on a specific topic according
to a predetermined and explicit method.”
Moher et al Lancet 1999
• Many (not all) systematic reviews use meta
analysis to synthesize data

What is meta analysis
• “the statistical method that combines the
results of several independent studies”

In practice, not all meta-analyses are conducted as part
of systematic reviews
Metaanalyses
Individual patient
data (IPD) metaanalyses
All reviews
Reviews that
are not
systematic
(traditional,
narrative
reviews)
Systematic
reviews

Traditional Approach To Synthesizing The
Evidence
• Review article
• Written by an expert
• Medline search for trials
• Personal contacts
• Number of trials for and against
• Conclusion
• Influential

Traditional (Narrative)Review
Systematic Review
No Methods section; not reproducible
Limited searching for trials (often limited
to Medline); leads to ‘publication bias’
Include different study designs, often do
not evaluate validity
Over-reliance on p values
Uses ‘vote counting’; each trial given
same weight
Descriptive
Subjective; Biased
Clearly described protocol with detailed
methods
Comprehensive searching for published
and unpublished trials with no language
restrictions
Mostly include only RCTs; evaluates
validity
Estimates size of effect with confidence
intervals (precision)
Differentially weights trials so that larger
trials with more information and precise
results are given more weight
Meta-analysis pools results of similar
trials; provides a ‘tower of power’
Objective ( two or more authors who
independently undertake review)

Problems with traditional
reviews
• Lag behind and often vary significantly from
continuously updated or cumulative metaanalysis
(Lau et al 1992)

33 TRIALS
1959 to 1988
36,974 Pts
I.V.
STREPTOKINASE
FOR ACUTE MI
CUMULATIVE
META-ANALYSIS

Routine
Specific
Rare/Never
Experimental
Not Mentioned
Thrombolysis for Acute MI
Cumulative
Year
RCTs
1960 1
2
1965 3
1970 4
7
10
11
15
17
22
1980 23
27
1985 30
33
43
54
65
1990 67
70
Pts
23
65
149
316
1763
2544
2651
3311
3929
5452
5767
6125
6346
6571
21059
22051
47185
47531
48154
0.5 1.0 2.0
Favors Treatment
Odds Ratio (Log Scale)
P < 0.01
P < 0.001
P < 0.00001
Favors Control
M
M
M
M
M
M
Textbook/Review
Recommendations
21
5
1 10
1 2
2 8
7
8
1 12
1 8 4
1 7 3
5 2 2 1
15 8 1
6 1
Antman et al., JAMA, 1992; 268: 240-248

Prophylactic Lidocaine after acute MI
Antman et al., JAMA, 1992; 268: 240-248

Reduction of perioperative deaths by antibiotic prophylaxis for
colorectal surgery (cumulative meta-analysis)
Conclusive
evidence of
effect
Savulescu, J. et al. BMJ 1996;313:1390-1393
Copyright ©1996 BMJ Publishing Group Ltd.

Putting clinical trials into context
“From August, 2005, we will require authors of clinical trials
submitted to The Lancet to include a clear summary of
previous research findings, and to explain how their
trial’s findings affect this summary.
The relation between existing and new evidence should be
illustrated by direct reference to an existing systematic
review and meta-analysis.
When a systematic review or meta-analysis does not exist,
authors are encouraged to do their own.
Lancet editorial: 2005; July 9, 366: 107-8.

Criticisms of systematic reviews
“Exercise in mega silliness” (Eysenck 1978)
“Adding apples and oranges can render
the exercise fruitless” (Eysenck 1995)

When can meta-analyses
mislead
• When a meta-analysis is done outside of a systematic review
• When poor quality studies are included or when quality issues are
ignored
• When inadequate attention is given to heterogeneity
Indiscriminate data aggregation can lead to inaccurate conclusions
• When reporting biases are a problem
Publication bias
Time lag bias
Duplicate publication bias
Language bias
Outcome reporting bias
Citation bias
Egger M et al. Uses and abuses of meta-analysis. Clinical
Medicine 2001;1:478-84

Can meta-analysis be trusted
• Outcome of 12 large RCTs not predicted
accurately 35% of time by meta-analyses
published previously
(Lelorier et al 1997)

META ANALYSES TEND TO
OVER ESTIMATE EFFECTS

www.cochrane.org

Archie Cochrane
“It is surely a great criticism of our profession that we
have not organised a critical summary, by specialty or
subspecialty, adapted periodically, of all relevant
randomised controlled trials.”

What does the Cochrane
Collaboration have to offer
• Largest organization in the world devoted to
producing, disseminating and maintaining
systematic reviews (SRs) of the effects of
interventions
• Also involved in producing SRs of the accuracy
of diagnostic tests
• >20,000 volunteers who share common
principles (www.cochrane.org)
• Main output is The Cochrane Library

Cochrane Centres
Born on the 15 th of July 2008
Canadian
US
UK
Nordic
German
Dutch
Italian
Iberoamerican
SASIANCC
Chinese
Brazilian
South African
Australasian

Conceived 4 years earlier; Goa: December 2004

The South Asian Cochrane Network
South Asian Association of Regional Cooperation
(SAARC)

Network Sites in India
Chandigargh
Delhi
•All India Institute of
Medical Sciences
(New Delhi)
•Post Graduate
Institute, Chandigarh
•Tata Memorial
Hospital, Mumbai
•Manipal University,
Manipal
Mumbai
•Ramaratnam
Epilepsy Foundation,
Chennai
•CMC, Vellore
Manipal
Chennai
Vellore

Network Sites in Pakistan
Aga Khan
University;
Karachi
Khyber
Medical
University;
Peshawar

Network Site in Sri Lanka
University of
Kelaniya;
Ragama
Ragama

Network Site in Bangladesh
Independent
University,
Dhaka
IDDRB:,
Dhaka

July 15, 2008

Prof BV Moses & Indian Council of Medical
Research Centre for Advanced Research &
Training in Evidence Informed Healthcare
Christian Medical College, Vellore

Relevance of the SASIANCC to
health care in South Asia
• Ask questions about efficacy of interventions of relevance to
health care in the region
• Train people to do systematic reviews
• Disseminate evidence from Systematic Reviews
Access to the Cochrane Library
Evidence Based Summaries
• Identify all RCTs and controlled clinical trials from the region
South Asian Database of Controlled Clinical Trials
National Register of Dissertations
Prospective registration of trials
Improve the quality of research conducted
• Orient and train health professions and policy makers in EBM
• Use results of Systematic Reviews to guide health care &
policy

Introduction to Evidence
Based Health Care

Training review authors: protocol
development workshops

Review Completion workshops

SACN participation in systematic
reviews (Cochrane Library Issue 2, 2005
& 2009)
Country Reviews Protocols Titles Total
2005 2009 2005 2009 2005 2009 2005 2009
India 11 36 19 36 33 43 63 109
Pakistan 1 9 3 13 9 12 13 34
Sri Lanka 2 2 1 1 3 3 6
Bangladesh 2 1 1 2 2
Combined 15 48 23 50 42 59 81 151

Growth of contributors in
India
B C AC
2000 2002 2003 2004 2005 2006 2007 2009
Authors 11 15 20 31 42 80 78 248
Editors 2 1 2 5 5 5 5 8
Others 2 15 18 28 19 35 43 284
Total 19 31 40 64 76 120 126 540

www.thecochranelibrary.com

About the Cochrane Collaboration 94
WHAT IS THE COCHRANE LIBRARY`
The Cochrane Library is a collection of Evidence-Based
Medicine databases:
Database Issue 3 2009
The Cochrane Database of Systematic Reviews (CDSR; Cochrane Reviews) 5821
The Cochrane Database of Reviews of Effects (DARE; Other Reviews) 10,894
The Cochrane Central Register of Controlled Trials (CENTRAL; Clinical
Trials)
5,86,829
The Cochrane Methodology Register (CMR; Methods Studies) 11,837
Health Technology Assessment Database (HTA; Technology Assessments) 7947
NHS Economic Evaluation Database (NHSEED; Economic Evaluations) 26,917

Are Cochrane Systematic Reviews
different from other systematic
reviews
• Only about 20% of reviews published each year are Cochrane
Systematic Reviews
• Cochrane Systematic Reviews emphasize methodological rigour
Found to be of better quality, more up to date, & less biased in
methods and interpretation than non-Cochrane systematic
reviews
Free of conflicted sources of funding
• Used to inform practice guidelines of the WHO, many policy making
bodies world-wide; have changed health practices too
Jadad et al. Methodology and reports of systematic reviews and meta-analyses: a
comparison of Cochrane reviews with articles published in paper-based journals. JAMA
1998;280:278-280.
Moher D, et al. Epidemiology and reporting characteristics of systematic reviews. PLoS
Med 2007; 4(3): e78. doi:10.1371/journal. pmed.0040078

Access to reliable evidence is crucial
The Cochrane Library
Evidence Based Journals and Text Books
Evidence Based Summaries

Free access to the Cochrane
Library to anyone in India
The Telegraph, Kolkatta; Feb 3, 2007

Free access to the Cochrane
Library to anyone in India

Do Indians use the Cochrane Library

Country Visits 2006 Visits 2007 Visits 2008 % Growth 2007-
2008
United States 608,712 1,012,389 1,545,125 52.62%
United Kingdom 595,807 948,750 856,522 -9.72%
Australia 309,487 373,486 457,584 22.52%
Canada 280,124 181,775 203,699 12.06%
Netherlands 183,298 121,935 143,901 18.01%
Taiwan 133,259 89,185 120,529 35.14%
Sweden 68,243 85,416 87,192 2.08%
Italy 61,483 83,198 97,865 17.63%
Germany 53,209 82,071 98,537 20.06%
Norway 53,142 68,694 74,335 8.21%
Japan 52,936 62,649 69,228 10.50%
India 48,940 53,041 63,679 20.06%
Ireland 42,625 50,726 59,642 17.58%
Visits to the Cochrane Library 2006-2008
India shows same growth rate as Germany on visits.

10000
Usage in India: Abstracts
2006-2008
9000
8000
7000
6000
5000
4000
Abstracts 2008
Abstracts 2007
Abstracts 2006
3000
2000
1000
0
January February March April May June July August
September
October
November December

Full Text 2008
Full Text 2007
Full Text 2006
Searches 2008
Searches 2007
Searches 2006
Abstracts
2008
Abstracts 2007
Abstracts
2006
0 10000 20000 30000 40000 50000 60000 70000

Overall growth on Full text Downloads for the
whole of The Cochrane Library for India.
Total
2006 2007 Growth
2006/2007
2008 Growth
2007/2008
9,338 62,621 571% 66,303 6%
•Full text downloads are up by 3% on the same period last
year (Jan to August 2008 versus 2009)
•The average number of full text downloads per month in
2008 was 5,845 by 2009 August it had risen to 5,919 per
month
People are reading evidence from the Cochrane Library
National subscription due for renewal in February 2010

Role of the media in EBM
• Media coverage of new and updated
Cochrane reviews are also an effective
dissemination method
• News media in India now cover each
new issue of The Cochrane Library
• Media in India constitute 17% of world
media that cover each issue of The
Cochrane Library
• 2 nd in media coverage in the world next
to the US

Is the evidence relevant to us
Making trials from the region available to
systematic review authors
Improving the quality of trials from the region

www.cochrane-sadcct.org

Improving the quality of research

Sources of Bias in RCTs
Biases
Minimized by
Trial Population
Allocation
Selection
Randomization &
Allocation
concealment
Intervention group
Control group
Performance
Blinding of
Investigator/
participant
Exposed to
intervention
Not exposed
to intervention
Detection
Blinding of
outcome
assessment
Outcome
Outcome
Attrition
Intention-to-treat
Follow up
Follow up
Follow up

Randomization is a two stage process:
1. Generating the randomization sequence
2. Concealing allocation to intervention arms
•Allocation concealment is not the same as blinding
•Allocation concealment is a pre-requisite to blinding
•Without allocation concealment, blinding may be difficult or impossible
•Blinding may not be always possible but allocation concealment is
always possible (even in surgical trials)
randomisation
time
Concealment
of allocation
Blinding
Selection bias
Performance bias

Allocation concealment & effect on outcome
• Inadequately concealed or trials with unclear
allocation concealment treatment
overestimate effects by ~ 30%
( 95% CI- 21% to 38%) (Schulz et al, 1994)
• Most important source of bias in a trial
Schulz KF et al. JAMA 1994; 272:125-128

www.consort-statement.org

Assessing and improving the
quality of trials

Editorial Policy of Indian
Medical Journals
Editorial
Policy
Endorsed
ICMJE
Endorsed
CONSORT
2005 (%) 2008 (%)
38 (59) 37 (57)
20 (31) 22(34)
Indian medical journals

Reporting of CONSORT items
pertaining to internal validity
(2004-2005 versus 2007 – 2008)
CONSORT ITEM
Random
sequence
generation
Concealing
Allocation
Blinding
ITT
2004-2005
(151 RCTs)
57
(38%)
24
(16%)
96
(64%)
73
(48%)
2007-2008
(145 RCTS)
79
(55%)
30
(21%)
67
(46%)
62
(43%)
OR (95% CI) 2.0
(1.2 -3.1)
1.4
(0.8-2.5)
0.5
(0.3-0.8)
0.8
(0.5-1.3)

Reporting ICMJE requirements: Indian Journals 2004-2005

Catch them younger

Using prospective trials
registration to improve the
quality of design of trials
Scientific Advisory Group of the WHO ICTRP

International Advisory Board

,PTI
Clinical Trial Registry-
India
National Institute of Medical Statistics
(ICMR)
The CTRI is a
primary register of
the WHO-ICTRP
India launches Clinical Trials Registry
20 Jul 2007, 1858 hrs IST
Vision:
Use trials
registration to
improve design
and ethical
conduct of trials
Cochrane inside
www.ctri.in

Registration Data Set:
CTRI specific items
Trial registration data set with explanations can be downloaded

Ethics
committee
approval:100%
Random sequence
generation:
82.6%
Allocation
concealment:
76%
Blinding 85%

Working with Medical Journal Editors in India
to endorse trials registration
Meeting with Medical Journal
Editors (ICMR)
October 9 2007

Editorial policy on trials registration
Meeting with medical journal editors
about trials registration ( ICMR)
October, 2007

2008 revision of the Declaration of
Helsinki

De facto legislation in India
• Schedule Y of the Drugs and Cosmetics Act
requires researchers to abide by Helsinki & the
ICMR guidelines
• ICMR bioethics guidelines will soon endorse
registration specifically in the CTRI
• Regulators and ethics committees will now be
obliged to support trials registration as a legal
and an ethical requirement.
Tharyan P, IJME 2007

DCGI announcement
Prospective registration
in CTRI of all new drug
applications is
mandatory from July
15, 2009

Knowledge translation:
From clinical research to practice decisions
Evidence-based
healthcare
Evidence
generation
Evidence
synthesis
Clinical policy
(guidelines)
Clinical
trials
Cochrane
Collaboration,
others
Professional
societies,
others
Application of policy:
Evidence
Clinician expertise
Patient values
Knowledge translation

“Seeing through a dark glass dimly”
Addressing the gaps between evidence and practice
Getting the evidence straight
Getting the evidence used
Glasziou P, Haynes B. ACP J Club. 2005

Using evidence to inform health policy and
practice
From systematic reviews
From pragmatic trials when evidence is scant

Asking questions of relevance to
the region
• Effective Health Care Research Partnership
Consortium (Infectious Diseases Group)
Malaria,
TB
Shigella
Leishmaniasis
Snake bite
• ICMR
Vaccines
TB

Addressing gaps between policy and
evidence

Radical cure of P Vivax malaria
• A combination of chloroquine and primaquine
is used to treat P. vivax malaria.
• Chloroquine acts on the blood stages of the
parasite and primaquine eliminates the liver
forms.

Different dosing regimens in use
• Several dosing regimens are used for
primaquine, such as 15 mg/day for five, seven, or
fourteen days.
• WHO recommends 14 days of Primaquine
following chloroquine
• India and Sri Lanka recommends 5 days of
primaquine following chloroquine

When in doubt do a systematic
review!
• Objectives
1. To compare primaquine plus chloroquine
with chloroquine alone for preventing
relapses in people with P. vivax malaria.
2. To compare the standard primaquine
regimen (15 mg/day for 14 days)
recommended by the World Health
Organization with other primaquine
regimens for preventing relapses in people
with P. vivax malaria.

Main results
• Nine RCTs (3423 participants) met the inclusion
criteria.
• Eight trials were conducted in Asia:
three in India (Gogtay 1999; Yadav 2002; Rajgor 2003);
three in Afghan refugee camps in Pakistan (Rowland
1999i; Rowland1999ii; Leslie 2004);
two in Thailand (Pukrittayakamee 1994; Walsh 2004).
The other was conducted in South America in Brazil
(Villalobos 2000).

Conclusions
• Primaquine (14 days) plus chloroquine is
more effective than chloroquine alone or
primaquine (5 days) plus chloroquine in
preventing relapses of P. vivax malaria.
• Primaquine (five days) plus chloroquine
appears no better than chloroquine alone.

Recommendations
• Countries advocating the five-day
regimen should follow the World
Health Organization's
recommendation of the 14-day
primaquine plus chloroquine regimen.

Influencing health policy in
India
• Workshop for senior faculty of the Indian Council
of Medical Research (ICMR) (October 10, 2006)
Using Cochrane reviews to inform health policy and
care
• Review published Jan 2007
• Policy unchanged Feb 2007
• Disseminated results of review

May 2007

Getting the evidence used:
Changing health policy
• Within 6 months of publication of the
Cochrane Review
Revised National Malaria Control Guidelines 2007
for India changed Primaquine dosing regimen for
radical cure of P. vivax malaria from 5 days to 14
days
Sri Lankan guidelines changed within 2 months of
publication

Dissemination and implementation
• Local malaria control programmes are
implementing the policy and have adequate
supply of medicines
• Park & Park 2009 ( Text book of Preventive
and Social Medicine) recommends 14 days of
primaquine

Gawrie Galappaththy wins the Kenneth Warren
Prize at the XV Cochrane Colloquium at Sao
Paulo, Brazil in October 2007

Evidence Based Healthcare
Evidence does not automatically transform into guidelines or practice
Quality of
Evidence

Case management for people with severe mental
disorders
Comparisons: Case Management versus standard care
Outcome: Admitted to hospital during study
Case Management increases odds of re-admission
compared to standard care

Assertive community treatment for people with mental
disorders
Comparisons: Assertive community treatment VS Standard care for
people with severe mental disorders
Outcome: Admitted to hospital during study
Do we have any assertive community teams

The river of evidence flows
both ways….
From India…

The river flows both ways….
From Brazil….

Pragmatic trials in developing countries
• Both sets of trials were preceded by a systematic review that
demonstrated the need for RCTs
• Both sets of trials were conducted in real world settings and
during routine working conditions, excluded few patients and
used outcomes of relevance to clinicians and carers
• Both sets utilized central randomization and allocation
concealment and assessed adequacy of blinding of primary
outcomes
• They demonstrated that investigator driven and locally funded,
good quality trials that answer questions of relevance to the
developing world are feasible

Lessons learnt
• Reliable and valid evidence from well done systematic
reviews is essential to inform healthcare decisions
• Relevant evidence may not be easily located; mechanisms
to increase access is needed
• Relevant evidence may not be of good quality and may
mislead; the methods of the primary studies must be good
• Evidence does not automatically translate into guidelines
• Evidence may not always be available; Local research is
often needed to provide local answers
• “International” guidelines are not always meant for
international use
• Effective collaboration and strategic partnerships are
important

Lessons learned
• “Never doubt that a small group of
thoughtful, committed citizens can change
the world. Indeed, it’s the only thing that
ever has.”
[Margaret Mead]

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The power of collaboration
Portrait of Sir Iain Chalmers- founder of the Cochrane
Collaboration- National Art Gallery, London, UK