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PlanPlan
• GRADE backgroundGRADE background
• confidence in estimates (quality of confidence in estimates (quality of evidence)evidence)
• evidence profilesevidence profiles
• confidence in estimates and confidence in estimates and recommendationsrecommendations
60+ Organizations60+ Organizations
3
2005 2006 2007 2008 2009 2010 2011
GRADE uptake
Confidence in estimateConfidence in estimate(quality of evidence) (quality of evidence)
no confidence
totally confidentHigh
Moderate
Low
Very Low
Randomized trials start high confidence
Observational studies start low confidence
Determinants of confidence
• risk of bias– concealment– blinding– loss to follow-up
• imprecision – wide confidence intervals
• publication bias
Favours Vitamin D Favours Control
10.5 0.1
Study Year Relative Risk (95% CI)
Chapuy 1994 0.79 (0.69, 0.92)
Lips 1996 1.10 (0.87, 1.39)
Dawson-Hughes 1997 0.46 (0.24, 0.88)
Pfeifer 2000 0.48 (0.13, 1.78)
Meyer 2002 0.92 (0.68, 1.24)
Chapuy 2002 0.85 (0.64, 1.13)
Trivedi 2003 0.67 (0.46, 0.99)
Random Effects Estimate: p=0.05 for heterogeneity, I²=53% 0.82 (0.69, 0.98)
Relative Risk with 95% CI for Vitamin D Non-vertebral Fractures
25%
50%75%
Noworries
Someconcern
Seriousconcern
Why arewePooling?
Favours Vitamin D Favours Control
10.5 0.1
Study Year Relative Risk (95% CI)
Chapuy 1994 0.79 (0.69, 0.92)
Lips 1996 1.10 (0.87, 1.39)
Dawson-Hughes 1997 0.46 (0.24, 0.88)
Pfeifer 2000 0.48 (0.13, 1.78)
Meyer 2002 0.92 (0.68, 1.24)
Chapuy 2002 0.85 (0.64, 1.13)
Trivedi 2003 0.67 (0.46, 0.99)
Random Effects Estimate: p=0.05 for heterogeneity, I²=53% 0.82 (0.69, 0.98)
Relative Risk with 95% CI for Vitamin D Non-vertebral Fractures
Quality judgments: Quality judgments: DirectnessDirectness
• populations populations – older, sicker or more co-morbidityolder, sicker or more co-morbidity
• interventions interventions – warfarin in trials and communitywarfarin in trials and community
• outcomes outcomes – important versus surrogate outcomesimportant versus surrogate outcomes– glucose control versus CV eventsglucose control versus CV events
What can raise What can raise confidence?confidence?
• large magnitude can upgrade one levellarge magnitude can upgrade one level– very large two levelsvery large two levels
• common criteriacommon criteria– everyone used to do badlyeveryone used to do badly– almost everyone does wellalmost everyone does well– quick actionquick action
• hip replacement for hip osteoarthritiship replacement for hip osteoarthritis
• mechanical ventilation in respiratory failuremechanical ventilation in respiratory failure
Quality assessment criteriaQuality assessment criteria
Nonfatal MI – Fixed Effects
1 5 10 50 1000.5 0.1 0.05 0.01
Study Year Overall Event Rate Relative Risk (95% CI)
Jakobsen 1997 1 / 36 3.00 (0.13 to 69.09)
Poldermans 1999 9 / 112 0.05 (0.003 to 0.80)
Raby 1999 1 / 26 0.25 (0.01 to 5.62)
Zaugg 1999 3 / 63 0.07 (0.004 to 1.26)
Urban 2000 4 / 120 0.43 (0.07 to 2.81)
Pobble 2005 6 / 103 0.24 (0.04 to 1.39)
DIPOM 2006 5 / 921 1.39 (0.28 to 7.01)
MaVS 2006 38 / 496 1.02 (0.56 to 1.86)
Zaugg 2007 0 / 119 0.99 (0.02 to 49.51)
POISE 2007 366 / 8351 0.70 (0.57 to 0.86)
Fixed Effects Estimate 0.71 (0.59 to 0.86)
p=0.27 for heterogeneity, I²=19%
Quality Assessment
Summary of Findings
QualityRelative Effect
(95% CI)
Absolute risk difference
OutcomeNumber of
participants(studies)
Risk of Bias
Consistency Directness PrecisionPublication
Bias
Myocardial infarction
10,125(9)
No serious limitations
No serious imitations
No serious limitations
No serious limitations
Not detected
High0.71
(0.57 to 0.86)1.5% fewer
(0.7% fewer to 2.1% fewer)
)
Beta blockers in non-cardiac surgery
Mortality – Fixed Effects
1 5 10 50 1000.5 0.1 0.05
Study Year Overall Event Rate Relative Risk (95% CI)
Wallace 1998 6 / 200 1.84 (0.40 to 8.41)
Bayliff 1999 3 / 99 1.70 (0.23 to 12.39)
Poldermans 1999 11 / 112 0.24 (0.06 to 0.91)
Pobble 2005 5 / 103 1.23 (0.25 to 5.93)
DIPOM 2006 35 / 921 1.31 (0.69 to 2.51)
MaVS 2006 8 / 496 0.20 (0.04 to 1.16)
Zaugg 2007 1 / 219 2.97 (0.12 to 72.19)
POISE 2007 226 / 8351 1.33 (1.03 to 1.72)
Fixed Effects Estimate 1.24 (0.99 to 1.56)
p=0.14 for heterogeneity, I²=36%
Quality Assessment
Summary of Findings
QualityRelative Effect
(95% CI)
Absolute risk difference
OutcomeNumber of
participants(studies)
Risk of Bias
Consistency Directness PrecisionPublication
Bias
Myocardial infarction
10,125(9)
No serious limitations
No serious imitations
No serious limitations
No serious limitations
Not detected
High0.71
(0.57 to 0.86)1.5% fewer
(0.7% fewer to 2.1% fewer)
Mortality10,205
(7)No serious limitations
Possiblly inconsistent
No serious limitations
ImpreciseNot
detectedModerate
or low1.23
(0.98 – 1.55)
0.5% more(0.1% fewer
to 1.3% more)
Beta blockers in non-cardiac surgery
Stroke – Fixed Effects
1 5 10 50 1000.5 0.1
Study Year Overall Event Rate Relative Risk (95% CI)
Wallace 1998 5 / 200 3.06 (0.49 to 19.02)
Pobble 2005 1 / 103 2.63 (0.11 to 62.97)
DIPOM 2006 2 / 921 4.97 (0.24 to 103.19)
MaVS 2006 6 / 496 1.83 (0.39 to 8.50)
Zaugg 2007 1 / 119 2.97 (0.12 to 72.19)
POISE 2007 60 / 8351 2.13 (1.25 to 3.64)
Fixed Effects Estimate 2.22 (1.39 to 3.56)
p=0.99 for heterogeneity, I²=0%
Total events 75/10,290
Quality Assessment
Summary of Findings
QualityRelative Effect
(95% CI)
Absolute risk difference
OutcomeNumber of
participants(studies)
Risk of Bias
Consistency Directness PrecisionPublication
Bias
Myocardial infarction
10,125(9)
No serious limitations
No serious imitations
No serious limitations
No serious limitations
Not detected
High0.71
(0.57 to 0.86)1.5% fewer
(0.7% fewer to 2.1% fewer)
Mortality10,205
(7)No serious limitations
Possiblly inconsistent
No serious limitations
ImpreciseNot
detectedModerate
or low1.23
(0.98 – 1.55)
0.5% more(0.1% fewer
to 1.3% more)
Stroke10,889
(5)No serious limitaions
No serious limitations
No serious limitations
No serious
limitations
Not detected
High2.21
(1.37 – 3.55)0.5% more
(0.2% more to 1.3% more0
Beta blockers in non-cardiac surgery
Significance of strong vs Significance of strong vs weakweak• variability in patient preferencevariability in patient preference
– strong, almost all same choice (> 90%)strong, almost all same choice (> 90%)– weak, choice varies appreciablyweak, choice varies appreciably
• interaction with patientinteraction with patient– strong, just inform patientstrong, just inform patient– weak, ensure choice reflects valuesweak, ensure choice reflects values
• use of decision aiduse of decision aid– strong, don’t botherstrong, don’t bother– weak, use the aidweak, use the aid
• quality of care criterionquality of care criterion– strong, considerstrong, consider– weak, don’t considerweak, don’t consider
Strength of Recommendation
• strong recommendation– benefits clearly outweigh risks/hassle/cost– risk/hassle/cost clearly outweighs benefit
• what can downgrade strength?
• low confidence in estimates
• close balance between up and downsides
ConclusionConclusion
• clinicians, policy makers need summariesclinicians, policy makers need summaries– quality of evidencequality of evidence
• explicit rulesexplicit rules– transparent, informativetransparent, informative
• GRADEGRADE– simple, transparent, systematicsimple, transparent, systematic
