Holger Schünemann, MD, PhD From Evidence to EMS Practice: Building the National Model Washington,...
-
Upload
lucy-davis -
Category
Documents
-
view
221 -
download
0
Transcript of Holger Schünemann, MD, PhD From Evidence to EMS Practice: Building the National Model Washington,...
Holger Schünemann, MD, PhD
From Evidence to EMS Practice: Building the National ModelWashington, September 4, 2008
1
Disclosure
In the past three years, Dr. Schünemann received no personal payments for service from the pharmaceutical industry. He received research grants and - until April 2008 - fees and/or honoraria that were deposited into research accounts from AstraZeneca, Chiesi Foundation, Lily, Pfizer, Roche and UnitedBioSource for development or consulting regarding quality of life instruments for chronic respiratory diseases or as lecture fees related to the methodology of evidence based practice guideline development and/or research methodology. He is documents editor for the American Thoracic Society and senior editor of the ACCP Antithrombotic and Thrombolytic Therapy Guidelines. Institutions or organizations that he is affiliated with likely receive funding from for-profit sponsors that are supporting infrastructure and research that may serve his work.
3
Why is the GRADE approach emerging as the most useful approach to guideline development in health care?
Content
Study design – bias Levels/quality of evidence - GRADE
Guidelines/Recommendations
Content
Study design – bias Levels/quality of evidence - GRADE
Guidelines/Recommendations
Confidence in evidence
There always is evidence “When there is a question there is
evidence” Better research greater confidence
in the evidence and decisions Evidence alone is never sufficient to
make a clinical decision
Evidence based clinical decisions
Research evidence
Patient valuesand preferences
Clinical state and circumstances
Expertise
Equal for allHaynes et al. 2002
Hierarchy of evidence
STUDY DESIGN
Randomized Controlled Trials
Cohort Studies and Case Control Studies
Case Reports and Case Series, Non-systematic observations
BIAS
Expert Opinion
Exp
ert O
pin
ion
Expert Opinion
Can you explain the following? Concealment of randomization Blinding (who is blinded in a double
blinded trial?) Intention to treat analysis and its
correct application Why trials stopped early for benefit
overestimate treatment effects? P-values and confidence intervals
Reasons for grading evidence? People draw conclusions about the
quality of evidence and strength of recommendations
Systematic and explicit approaches can help protect against errors, resolve disagreements communicate information and fulfil needs
Change practitioner behavior However, wide variation in approaches
GRADE working group. BMJ. 2004 & 2008
Which grading system?
Evidence Recommendation B Class I A 1 IV C
Organization AHA ACCP SIGN
Recommendation for use of oral anticoagulation in patients with atrial fibrillation and rheumatic mitral valve disease
12
A COPD guidelines
13
Another COPD guidelines
14
And another COPD guideline
15
What to do?
16
Grades of Recommendation Assessment,
Development and Evaluation
CMAJ 2003, BMJ 2004, BMC 2004, BMC 2005, AJRCCM 2006, Chest 2006, BMJ 2008
About GRADE
Since 2000 Researchers/guideline developers with
interest in methodology Aim: to develop a common,
transparent and sensible system for grading the quality of evidence and the strength of recommendations
Evaluation of existing systems
GRADE Uptake
World Health Organization Allergic Rhinitis in Asthma Guidelines (ARIA) American Thoracic Society British Medical Journal Infectious Disease Society of America American College of Chest Physicians UpToDate American College of Physicians Cochrane Collaboration National Institute Clinical Excellence (NICE) Infectious Disease Society of America European Society of Thoracic Surgeons Clinical Evidence Agency for Health Care Research and Quality (AHRQ) Over 20 major organizations
Limitations of existing systems
confuse quality of evidence with strength of recommendations
lack well-articulated conceptual framework
criteria not comprehensive or transparent GRADE unique
breadth, intensity of development process wide endorsement and use conceptual framework comprehensive, transparent criteria
Focus on all important outcomes related to a specific question and overall quality
GRADE Evidence Profiles
The GRADE approach
Clear separation of 2 issues:1) 4 categories of quality of evidence:
very low, low, moderate, or high quality? methodological quality of evidence likelihood of bias by outcome and across outcomes
2) Recommendation: 2 grades - weak or strong (for or against)? Quality of evidence only one factor
*www.GradeWorking-Group.org
Determinants of quality
RCTs start high
observational studies start low
what can lower quality?1. detailed design and execution2. inconsistency3. indirectness4. reporting bias5. imprecision
1. Design and Execution
limitations Randomization lack of concealment intention to treat principle violated inadequate blinding loss to follow-up early stopping for benefit
Example: the evidence for the effect of sublingual immunotherapy in children with allergic rhinitis on the development of asthma, comes from a single randomised trial with no description of randomisation, concealment of allocation, and type of analysis, no blinding, and 21% of children lost to follow-up. These very serious limitations would warrant downgrading the quality of evidence by two levels (i.e. from high to low).
1. Design and Execution From Cates , CDSR 2008
CDSR 2008
1. Design and Execution
Overall judgment required
2. Consistency of results Look for explanation for inconsistency
patients, intervention, comparator, outcome, methods
Judgment variation in size of effect overlap in confidence intervals statistical significance of heterogeneity I2
3. Directness of Evidence
indirect comparisons interested in A versus B have A versus C and B versus C
differences in patients interventions outcomes
Directness of EvidenceTable 5. Sources of likely indirectness of evidenceSource of indirectness Question of interest ExampleIndirect comparison Early emergency department
systemic corticosteroids to treat acute exacerbations in adult patients with asthma
Both oral and intravenous routes are effective but there is no direct comparison of these two routes of administration in adults.
Differences in populations
Anti-leukotrienes plus inhaled glucocorticosteroids vs. inhaled glucocorticosteroids alone to prevent asthma exacerbations and nighttime symptoms in patients with chronic asthma and allergic rhinitis.
Trials that measured asthma exacerbations and nighttime symptoms did not include patients with allergic rhinitis.
Differences in intervention
Avoidance of pet allergens in non-allergic infants or preschool children to prevent development of allergy.
Available studies used multifaceted interventions directed at multiple potential risk factors in addition to pet avoidance.
Differences in outcomes of interest
Intranasal glucocorticosteroids vs. oral H1-antihistamines in
children with seasonal allergic rhinitis.
In the available study parents were rating the symptoms and quality of life of their teenage children, instead the children themselves.
4. Reporting Bias
reporting bias reporting of studies
publication bias number of small studies
reporting of outcomes
5. Imprecision
small sample size small number of events
wide confidence intervals uncertainty about magnitude of effect
What can raise quality?3 Factors large magnitude can upgrade one level
very large two levels common criteria
everyone used to do badly almost everyone does well
Epinephrin in allergic shock dose response relation
(higher INR – increased bleeding) Residual confounding unlikely to be
responsible for observed effect
Quality assessment criteriaQuality assessment criteria Quality of evidence
Study design Lower if Higher if
High Randomised trial Study quality: Serious limitations Very serious limitations I mportant inconsistency Directness: Some uncertainty Major uncertainty Sparse or imprecise data High probability of reporting bias
Strong association: Strong, no plausible confounders Very strong, no major threats to validity Evidence of a Dose response gradient All plausible confounders would have reduced the eff ect
Moderate
Low Observational study
Very low Any other evidence
Strength of recommendation
“The strength of a recommendation reflects the extent to which we can, across the range of patients for whom the recommendations are intended, be confident that desirable effects of a management strategy outweigh undesirable effects.”
Strong or weak
Evaluating desirable and undesirable effects
Desirable << Undesirable Effects Desirable ?< Undesirable Effects Desirable ?> Undesirable Effects Desirable >> Undesirable Effects
Formulating a recommendation
Against For
Strong
1
Weak ? 2
Weak ? 2
Strong
1
Respiratory disease guidelines ?
Factors determining strength of recommendation
Factors that can strengthen a recommendation
Comment
Quality of the evidence The higher the quality of evidence, the more likely is a strong recommendation.
Balance between desirable and undesirable effects
The larger the difference between the desirable and undesirable consequences, the more likely a strong recommendation warranted. The smaller the net benefit and the lower the certainty for that benefit, the more likely is a weak recommendation.
Values and preferences The greater the variability in values and preferences, or uncertainty in values and preferences, the more likely weak recommendation warranted.
Costs (resource allocation) The higher the costs of an intervention – that is, the more resources consumed – the less likely is a strong recommendation warranted
Determinants of the strength of recommendation
Factors that can strengthen a recommendation
Comment
Quality of the evidence Low
Balance between desirable and undesirable effects
Moderately balance
Values and preferences Fair bit of variability
Costs (resource allocation) Relatively high cost
Conclusion
clinicians, policy makers, decision makers need summaries quality of evidence strength of recommendations
explicit rules transparent, informative
GRADE four categories of quality of evidence two grades for strength of recommendations transparent, systematic by and across outcomes applicable to diagnosis wide adoption
39
Values & Preferences
Patients’ perspectives, beliefs, expectations, and goals for health and life.
Underlying processes used in considering the benefits, harms, costs, and inconveniences patients will experience with each management option and the resulting preferences for each option.
Guideline panels should be explicit about the relative value they place on the range of relevant patient-important outcomes. If values and preferences vary widely, a strong recommendation becomes less likely
Example: Patients vary widely in their view of how aversive they find the risk of a stroke versus the risk of a gastrointestinal bleed when deciding about oral anticoagulation for atrial fibrillation.
Relative importance of outcomes and management approaches
Desirable and undesirable effects desirable effects
Mortality improvement in quality of life, fewer
hospitalizations reduction in the burden of treatment reduced resource expenditure
undesirable consequences deleterious impact on morbidity, mortality
or quality of life, increased resource expenditure