CHRIS REDMAN

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Introduction to Critical Appraisal
CHRIS REDMAN ALEX SANCHEZ-VIVAR
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Presentation Overview

• Introduction to critical appraisal
• Definition, differences, strengths and weaknesses
  of systematic reviews and meta-analyses
• Sources of systematic reviews/meta-analyses
• Levels of Evidence
• Interpretation of basic statistics in
  meta-analyses confidence intervals, forest
  plots
• Critical appraisal of systematic
  reviews/meta-analyses

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What is critical appraisal?

• Critical appraisal is the process of
  systematically examining research evidence to
  assess its validity, results, and relevance
  before using it to inform a decision
• (Hill and Spittlehouse, 2001, p.1)
• Consideration of quantitative and qualitative
  aspects

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Critical appraisal is not

• Negative dismissal of any piece of research
• Assessment on results alone
• Based entirely on statistical analysis
• Undertaken by experts only

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Why critically appraise?

• To find out the validity of the study
• are the methods robust?
• To find out the reliability of the study
• what are the results and are they credible?
• To find out the applicability of the study
• is it important enough to change my practice?

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How do I critically appraise research?

• Be (critically) open to everything
• Believe (in principle) papers from high quality
  journals
• Read decide yourself
• Let other people read and decide for (with) you
• Read for yourself and make a structured appraisal

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Critical appraisal

• Advantages
• systematic way of assessing validity, results
  usefulness of research
• contributes to improving practice (quality)
• encourages objective assessment of information
• not difficult to develop skills
• Disadvantages
• time consuming
• not always any easy answers or what you hoped to
  find
• dispiriting if good evidence is lacking i.e.
  little / poor research done

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What do I need to know?
Critical appraisal

• BUT you can all do it with the right tools
  guidance

• Awareness of study designs
• Levels of evidence
• Statistics!!
• CA checklists
• CA resources

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Awareness of study design
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Observational study design measures of disease,
measures of risk, and temporality
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What is a systematic review?

• A review that has been prepared
• using some kind of systematic approach
• to minimising biases and random errors,
• and that the components of the approach
• will be documented
• in a materials and methods section
• Chalmers et al, 1995

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What is a systematic review
Reviews
Systematic reviews
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Rationale for systematic reviews

• Information overload
• Publication bias
• Poor quality of reviews
• Vitamin C and the prevention of the common cold
  (Pauling 1986)
• Missing link
• Inhalation of hexamethonium (comment by Clark et
  al, 2001)

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Sources of systematic reviews

• The Cochrane Library
• www.library.nhs.uk
• DARE (in Cochrane Library Other reviews)
• Health Technology Assessments (in Cochrane
  Library Technology Assessments)
• Medline, Cinahl, Embase search on systematic
  review in title, abstract
• PubMed Systematic Review in Limits gt Topic
• TRIP
• www.tripdatabase.com
• Evidence Based Reviews - Journals and Databases
• https//www.library.nhs.uk/evidence
• NHS Evidence
• https//www.evidence.nhs.uk/

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Format of a systematic review

• Formulation of a review question
• Define inclusion/exclusion criteria
• Locate studies
• Select studies (inclusion/exclusion)
• Assess study quality
• Data extraction
• Analyse and present results
• Interpretation of results
• Egger et al, 2001

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Formulation of review question

• Is the question focused in terms of
• Population studied
• Intervention/exposure given
• Outcomes considered
• Do anticoagulants prevent strokes in patients
  with atrial fibrillation?

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Define inclusion/exclusion criteria

• Were the right types of studies included to
  answer the question? Depends on the question.
• Can have observational studies (cohort,
  case-control), diagnostic/screening tests,
  prognostic, non-randomised trials
• Studies should be defined according to their
  design, participant characteristics,
  interventions and outcomes

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Locate studies

• Comprehensive search
• Databases
• Conference proceedings
• Hand searching
• Grey literature (reports, research registers)
• Foreign language
• Follow-up references
• Contacting experts/authors
• Publication bias unpublished studies
• Explicit

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Select and Assess Studies

• Eligibility criteria for study selection can be
  applied
• More than one reviewer can help reduce bias
• Checklists/scoring systems

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What do the findings mean?

• Effect measures odds ratios, relative risk,
  mean difference
• P-values
• Confidence intervals

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Using statistics

• Assess the weight of the evidence that a
  treatment works (or doesnt)
• Give an estimate (and likely range) of the
  treatment effect
• Test to see how likely it is that this effect
  would have been seen by chance

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Odds ratio (OR)

• Expresses the odds of having an event compared
  with not having an event in two different groups
• OR odds in the treated group / odds in the
  control group

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• OR1 treatment has identical effect to control
• ORlt1 event is less likely to happen than not
  (i.e. the treatment reduces the chance of having
  the event)
• ORgt1 event is more likely to happen than not
  (increases the chances of having the event)
• Clinical trials typically look for treatments
  which reduce event rates, and which have odds
  ratios of less than one

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Importance of defining the outcome
Type of outcome Type of outcome Type of outcome
Value of OR/RR Adverse outcome (e.g. death) Beneficial outcome (e.g. stopped smoking)
lt1 New intervention better New intervention worse
1 New intervention no better/no worse New intervention no better/no worse
gt1 New intervention worse New intervention better
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P-values significance test

• A p-value is a measure of statistical
  significance which tells us the probability of an
  event occurring due to chance alone
• P-value results range from 0 to 1
• The closer the p-value is to zero, the less
  chance there is that the effects of two
  interventions are the same

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Statistical significance

• In general, p-values of either 0.05 or 0.01 are
  used as a cut-off value, although this value is
  arbitrary
• P-value of lt0.05 indicates the result is
  unlikely to be due to chance
• P-value of gt0.05 indicates the result might have
  occurred by chance.

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Be careful

• A p-value in the non-significant range tells you
  that either there is no difference between the
  groups or there were too few subjects to
  demonstrate such a difference (ideally need to
  report confidence intervals)
• There is not much difference between p0.049 and
  p0.051
• P-values do not indicate the magnitude of the
  observed difference between treatments that is
  needed to determine the clinical significance

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Interpretation of Confidence Intervals

• Confidence interval is the range within which we
  have a measure of certainty that the true
  population value lies
• OR
• The confidence interval around a result obtained
  from a study sample (point estimate) indicates
  the range of values within which there is a
  specific certainty (usually 95) that the true
  population value for that result lies.
• (MeReC Briefing 2005)

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What can a CI tell us?

• Tells us whether the result is significant or not
• The width of the interval indicates precision.
  Wider intervals suggest less precision
• Shows whether the strength of the evidence is
  strong or weak.
• The general confidence level is 95. Therefore,
  the 95 CI is the range within which we are 95
  certain that the true population value lies

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Confidence Intervals reported on Ratios (odds
ratio, etc)

• The line of no effect centres around 1
• If a CI for an RR or OR includes 1
• (the line of no effect)
• then we are unable to demonstrate statistically
  significant difference between the two groups

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What is a meta-analysis?

• A statistical analysis of the results
  from independent studies,
  which generally aims to produce
  a single estimate of the treatment
  effect
• Egger et al, 2001

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Interpretation of forest plots
Effect of probiotics on the risk of antibiotic
associated diarrhoea
D'Souza, A. L et al. BMJ 20023241361
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Interpretation of forest plots

• Look at the title of the forest plot, the
  intervention, outcome effect measure of the
  investigation and the scale
• The names on the left are the authors of the
  primary studies included in the MA
• The small squares represent the results of the
  individual trial results
• The size of each square represents the weight
  given to each study in the meta-analysis
• The horizontal lines associated with each square
  represent the confidence interval associated with
  each result
• The vertical line represents the line of no
  effect, i.e. where there is no statistically
  significant difference between the
  treatment/intervention group and the control
  group
• The pooled analysis is given a diamond shape. The
  horizontal width of the diamond is the confidence
  interval

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Advantages of a systematic review/meta-analysis

• Limits bias in identifying and excluding studies
• Objective
• Good quality evidence, more reliable and accurate
  conclusions
• Added power by synthesising individual study
  results
• Control over the volume of literature

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Drawbacks to systematic reviews/meta-analyses

• Can be done badly
• 2 systematic reviews on same topic can have
  different conclusions
• Inappropriate aggregation of studies
• A meta-analysis is only as good as the papers
  included
• Tend to look at broad questions that may not be
  immediately applicable to individual patients

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Conclusion

• Critical appraisal of systematic reviews and
  other research is well within your capabilities
• Use a recognised checklist (i.e. SIGN)
• Update your literature searching skills regularly
  (contact your library skills trainer)

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D'Souza, A. L et al. BMJ 20023241361
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(Other) Critical appraisal checklists

• CASP (Critical Skills Appraisal Programme)
• http//www.phru.nhs.uk/casp/critical_appraisal_too
  ls.htm
• JAMA Users Guides to the Medical Literature
• http//www.cche.net/usersguides/main.asp
• Crombie I (1996) The Pocket Guide to Critical
  Appraisal, BMJ Books, London
• Greenhalgh T (2001) How to Read a Paper, BMJ
  Books, London
• BestBETs CA database
• http//www.bestbets.org/cgi-bin/browse.pl?showap
  praisal

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References

• Systematic reviews in health care electronic
  resource meta-analysis in context / edited by
  Matthias Egger, George Davey Smith, and Douglas
  G. Altman. BMJ Books 2001 (ebook)
• What is a systematic review?, What is a
  meta-analysis?, What are confidence intervals?
• http//www.evidence-based-medicine.co.uk/what_is_s
  eries.html
• Understanding systematic reviews and
  meta-analysis. Akonberg AK. Archives of Disease
  in Childhood 200590845-848.

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References

• Cochrane Open Learning Material Systematic
  Reviews and Meta-analyses (useful Forest Plot
  interpretation PDF)
• http//www.cochrane-net.org/openlearning/HTML/mod3
  -2.htm
• Funnel plots
• Bias in meta-analysis detected by a simple,
  graphical test. Egger M, et al BMJ 1997
  (315)629-634
• The case of the misleading funnel plot. Lau J, et
  al. BMJ 2006 (333)597-600
• Heterogeneity
• What is heterogeneity and is it important?
  Fletcher J BMJ 200733494-6

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The label tells you what the comparison and
outcome of interest are
Effect of probiotics on the risk of antibiotic
associated diarrhoea
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Scale measuring treatment effect. Take care when
reading labels!
Effect of probiotics on the risk of antibiotic
associated diarrhoea
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Each study has an ID (author)
Effect of probiotics on the risk of antibiotic
associated diarrhoea
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Treatment effect sizes for each study (plus 95
CI)
Effect of probiotics on the risk of antibiotic
associated diarrhoea
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Horizontal lines are confidence intervals
Diamond shape is pooled effectHorizontal width
of diamond is confidence interval
Effect of probiotics on the risk of antibiotic
associated diarrhoea
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The vertical line in middle is the line of no
effectFor ratios this is 1, for means this is 0
Effect of probiotics on the risk of antibiotic
associated diarrhoea
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Rationale for meta-analysis
Conventional and cumulative meta-analysis of 33
trials of intravenous streptokinase for acute
myocardial infarction.
Mulrow, C D BMJ 1994309597-599