What is the Cochrane Collaboration?

What is a systematic review?

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Archie Cochrane (1909-1988)

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“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 randomized

controlled trials”.

Archie Cochrane, 1979

Collaboration’s Mission Statement

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The Cochrane Collaboration is a unique

worldwide organization that aims to help people make well informed decisions about health care by preparing, maintaining and

promoting the accessibility of systematic reviews of the effects of health care

interventions.

www.cochrane.org

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Centres

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Networks

Methods Groups

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Fields

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Steering Group

Structure of

The Cochrane Collaboration

Review Groups

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Cochrane Centres

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Cochrane Review Groups

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• International group of experts with an

interest in a health problem area

• Prepare and maintain systematic reviews

• Willing and able to review all relevant

research on health care problems related to

their area

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• Back

• Effective Practice and Organization of Care

• Hypertension

• Inflammatory Bowel Disease and Functional Bowel Disorders

• Musculoskeletal

• Upper Gastrointestinal and Pancreatic Diseases

Cochrane Review Groups

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Worldwide there are 52 registered review groups,6 of which have their editorial base in Canada

10 Key Principles….guide the work of Cochranites

1. Collaboration …good communication, open decision-making and teamwork.

2. Building on the enthusiasm of individuals …involving and supporting people based on interest and including consumers.

10 Key Principles (cont)3. Avoiding duplication …maximise efficiency, one

review is enough.

4. Minimising bias …scientific rigour, broad participation, and avoiding conflicts of interest.

5. Keeping up-to-date …up-dating reviews by identifying and adding new trials at least every 2 years.

10 Key Principles (cont)6. Ensuring relevance …choosing outcomes that matter

to patients.

7. Ensuring access …wide dissemination ...appropriate price, content and medium to meet needs of users worldwide.

8. Quality improvement …improving methodology, encouraging feedback and criticism and responding to it.

10 Key Principles (cont)9. Ensuring continuity …responsibility for reviews,

editing, and key functions is maintained and renewed.

10. Enabling wide participation …announced at the 8th Colloquium 2000 in Cape Town, South Africa

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www.thecochranelibrary.com

New Editor-in-Chief: Dr. David Tovey

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What is The Cochrane Library?

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- Main output of

Cochrane Collaboration

- Contains Cochrane

reviews & other

databases

www.thecochranelibrary.com

Cochrane Library

2016

6744 systematic reviews

2439 protocols (reviews in preparation)

>12,000 abstracts of non-Cochrane systematic reviews

> 750,000 controlled clinical trials

Excellent search engine.

The Cochrane Library Search takes place every second

Abstract is viewed every 2 seconds

Full text review is downloaded every 3 seconds.

2014 Impact Factor 6.035

2014 Hypertension Group impact factor 7.571

Systematic Review Definition: A concise summary of the best available

evidence that addresses a sharply defined clinical

question and attempts to answer it using explicit and

rigorous methods to identify, critically appraise and

synthesize all relevant studies.

Only uses scientifically valid evidence. Evidence-based is synonymous with scientifically valid.

Thomas C Chalmers (1917-

1995)

Thomas C Chalmers Outspoken advocate for “randomized controlled trials”.

“Randomize the first patient”

“In the absence of good evidence it is unethical to treat

patients with an unproven intervention except in a

randomised clinical trial comparing the new

intervention with standard therapy.”

Why are randomised

controlled trials

necessary?

Paradigm (mind-set) for decision to

administer or take an intervention

In the absence of good evidence (science), give an

intervention only as part of an RCT.

Otherwise use interventions where the benefits have

been proven to outweigh the harms in a systematic

review of RCTs.

Intervention in the absence of evidence = “snake oil”

Many health interventions are scientifically unproven

and thus no different from “snake oil”

Introduction to Cochrane

systematic reviews

Registering a Title

Use ‘PICOS’ to define the question

•Participants – Describe the specific patient population

characteristics and/or context of the condition or disease.

•Intervention – Define the intervention(s).

•Comparison – Define the control intervention.

•Outcome – Define the outcomes of interest from the most

important to the least

•Study Design – Define the type of study that is acceptable

to answer this question (usually RCTs).

Exercise Your Uncle (age 70) is concerned that he is at risk of

becoming demented as both his parents developed

dementia in their 70’s.

He read in the paper that statins may reduce the risk of

developing dementia and he is asking you if he should

take a statin.

Why would taking a statin reduce the risk of

developing dementia?

Create a systematic

review question (PICOS)

for this review.

PICOS Population Healthy adults

Intervention Statin

Control Placebo

Outcome Dementia

Study design RCT of > 1 year duration.

Cochrane Library

Statins for the Prevention of Dementia

January 2016

Review details Vascular risk factors including high cholesterol levels

increase the risk of vascular dementia or Alzheimer's disease. Observational studies have suggested an association between statin use and lowered incidence of dementia.

Results: 2 trials with 26,340 participants aged 40 to 82 years of whom 11,610 were aged 70 or older.

Incidence of dementia: odds ratio (OR) 1.00, [0.61 to 1.65]

No differences between statin and placebo groups on five different cognitive tests.

Clinical answer Advise your uncle that there is reasonable evidence

that taking a statin will have no effect on his risk of

dementia.

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Advantages of a Cochrane review

Rigour of methodology

Broad scope of literature included

Updated and maintained

Inclusiveness of perspectives

Plain language summary

Independence from commercial interests

Risk of bias is estimated and included in the interpretation of the evidence

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Steps in doing Systematic

Review Identifying a question (PICOS)

Registering the Title

Writing the protocol

Search to find all trials (Cochrane Library etc)

Choosing and entering relevant trials

Characteristics of included and excluded trials

Steps in doing Systematic

Review (cont) Risk of bias of included trials

Extracting and entering data

Interpreting findings (subgroup analysis, sensitivity

analysis)

Writing results and discussion

Summary of Findings Table, conclusions and abstract

Submit review for publication

Risk of Bias tool Sequence generation (randomization)

Allocation concealment

Blinding (participants, investigators, outcomes)

Incomplete outcome data

Selective reporting

Other biases

Proper randomization reduces the risk of imbalance in known and

unknown important prognostic factors which could influence the course of the process under evaluation.

Allocation concealment Inadequate or unclear concealment of allocation

produces effect estimates that exaggerate the true effect by 29%.

Blinding

Trials with inadequate blinding produce

effect estimates that on average exaggerate

the effect by 14% (Egger 2003) to 17%

(Schultz 1995).

Incomplete outcome data Data must be reported according to the intention to

treat principle.

Loss to follow-up potentially invalidates the results.

It is common that adverse effects are incompletely

reported.

Selective reporting bias Multiple scales in a trial are measured and the only

ones reported are those that achieve statistically

significant positive effects.

Other biases Publication bias

Patient selection bias (limited to patients known to

respond to or tolerate the intervention).

Early termination of trial bias.

Sponsor bias.

Life is full of trials.

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What have I learned

from the Cochrane

Collaboration?

Is the Cochrane Library useful

for you? When you were 18 after a minor basketball injury you

developed a swollen painful right leg.

You went to the emergency and were found to have a

deep venous thrombosis.

You were treated with anticoagulants for a short time

and are now fine.

Next week you are booked on a trip to Hong Kong.

Is there anything you should do?

Compression stockings for preventing deep vein thrombosis in

airline passengers.

A Cochrane Systematic

Review

Compression stockings for preventing deep vein thrombosis

in airline passengers

Air travel might increase the risk of deep vein thrombosis (DVT). It

has been suggested that wearing compression stockings might

reduce this risk.

Objectives

To assess the effects of wearing compression stockings versus not

wearing them among people travelling on flights lasting at least four

hours.

Search methods

The Cochrane Peripheral Vascular Diseases Group searched their

Specialized Register (last searched April 2007) and the Cochrane

Central Register of Controlled Trials (CENTRAL) in The Cochrane

Library (inception to Issue 1, 2007). The authors searched

MEDLINE (January 1966 to November 2005), EMBASE (January

1980 to December 2005) and several other electronic or grey

literature sources, detailed in full in the review.

Selection criteria

Randomized trials of compression stockings versus no stockings in

passengers on flights lasting at least four hours. Trials in which

passengers wore a stocking on one leg but not the other, or those

comparing stockings and another intervention were also eligible.

Data collection and analysis

At least two authors independently assessed the quality of each study

and extracted data. We sought additional information from trialists.

Main results

Ten randomized trials (n = 2856) were included; nine (n = 2821)

compared wearing stockings on both legs versus not wearing them, and

one (n = 35) compared wearing a stocking on one leg for the outbound

flight and on the other leg on the return flight. Of the nine trials, seven

included people judged to be at low or medium risk (n = 1548) and two

included high risk participants (n = 1273). All flights lasted at least seven

hours.

Main results (cont)

Fifty of 2637 participants with follow-up data available in the trials

of wearing stockings on both legs had a symptomless DVT; three

wore stockings, 47 did not (odds ratio 0.10, 95% confidence

interval 0.04 to 0.25, P < 0.00001). There were no symptomless

DVTs in three trials. No deaths, pulmonary emboli or symptomatic

DVTs were reported. Wearing stockings had a significant impact

in reducing oedema (based on six trials). No significant adverse

effects were reported.

Authors' conclusions

Airline passengers similar to those in this review can expect a

substantial reduction in the incidence of symptomless DVT and

leg oedema if they wear compression stockings. We cannot

assess the effect of wearing stockings on death, pulmonary

embolus or symptomatic DVT because no such events occurred

in these trials. Randomized trials to assess these outcomes

would need to include a very large number of people.

Exercise Search the Cochrane Library to find out whether

ACE inhibitors or ARBs are better for treating patients with hypertension.