1 What is the Cochrane Collaboration? What is a systematic review?
Archie Cochrane (1909-1988) 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 2
Collaboration s Mission Statement 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 3
Structure of The Cochrane Collaboration Centres 12 Review Groups 52 Networks Steering Group Methods Groups 13 Fields 16 4
5 Cochrane Centres
Cochrane Review Groups 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 6
Cochrane Review Groups Worldwide there are 52 registered review groups, 6 of which have their editorial base in Canada Back Effective Practice and Organization of Care Hypertension Inflammatory Bowel Disease and Functional Bowel Disorders Musculoskeletal Upper Gastrointestinal and Pancreatic Diseases 7
10 Key Principles.guide the work of Cochranites 1. Collaboration good communication, open decisionmaking 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
www.thecochranelibrary.com New Editor-in-Chief: Dr. David Tovey 12
What is The Cochrane Library? - Main output of Cochrane Collaboration - Contains Cochrane reviews & other databases 13 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.
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 29
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.
Publication bias Other biases Patient selection bias (limited to patients known to respond to or tolerate the intervention). Early termination of trial bias. Sponsor bias.
What have I learned from the Cochrane Collaboration? Life is full of trials. 40
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?
A Cochrane Systematic Review Compression stockings for preventing deep vein thrombosis in airline passengers.
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.