Post on 06-Jan-2016
description
Plan
GRADE backgroundcertainty in evidence (quality,
confidence evidence)
evidence profilesstrength of recommendation
exercises in applying GRADE
experience participating guideline panels?
clin epi methodology course?
is grading recommendations a good idea? If so, why?
experience with grading systems used?
Grading good idea, but which grading system to use?
many available Australian National and MRC Oxford Center for Evidence-based
Medicine Scottish Intercollegiate Guidelines
(SIGN) US Preventative Services Task Force American professional organizations
AHA/ACC, ACCP, AAP, Endocrine society, etc....
cause of confusion, dismay
Common international grading system?
GRADE (Grades of recommendation, assessment, development and evaluation)
international group Australian NMRC, SIGN, USPSTF, WHO,
NICE, Oxford CEBM, CDC, CC
~ 35 meetings over last 14 years▪ (~10 – 70 attendants)
GRADE GUIDANCE
2004 BMJ, first description
2008 BMJ six part series for guideline users
2010-13, 21 part series, 15 published for systematic review authors, HTA
practitioners, guideline developers
Grading system – for what?
interventions management strategy 1 versus 2
what grade is not about individual studies (body of evidence)
What GRADE is not primarily about
diagnostic accuracy questions in patients with a sore leg, what is the
accuracy of a blood test (D-Dimer) in sorting out whether a deep venous thrombosis is the cause of the pain
prognosiswhat it is about: diagnostic impact
are patients better off (improved outcomes) when doctors use the d-dimer test
80+ Organizations
9
2005 2006 2007 2008 2009 2010 2011
GRADE uptake
What are we grading?
two components
certainty in estimate of effect adequate to support decision (quality of body of evidence)
high, moderate, low, very low
Likelihood of and confidence in an outcome
Semantic Issue: Label for trustworthiness
Quality Initial choice, defined as confidence natural to clinicians, but confusion with
risk of bias
Confidence what we actually mean, but confusion
with confidence intervals, and experts always confident
Certainty avoids confusion of others, experts might
acknowledge uncertainty - Current preferred term
What are we grading?
two components
certainty in evidence adequate to support decision (quality of body of evidence)
high, moderate, low, very low
strength of recommendation strong and weak weak alternatives
conditional, contingent, discretionary
Health Care Question
(PICO)Systematic reviews
Studies
Outcomes
Important outcomes
Rate the quality of evidence for each outcome, across studies RCTs start high, observational studies start low(-)Study limitationsImprecisionInconsistency of resultsIndirectness of evidencePublication bias likely
Final rating of quality for each outcome: high, moderate, low, or very low
(+)Large magnitude of effectDose responsePlausible confounders would ↓ effect when an effect is present or ↑ effect if effect is absent
Decide on the direction (for/against) and grade strength (strong/weak*) of the recommendation considering:
Quality of the evidenceBalance of desirable/undesirable outcomes
Values and preferencesDecide if any revision of direction or strength is
necessary considering: Resource use*also labeled “conditional”or “discretionary”
Rate overall quality of evidence (lowest quality among critical outcomes)
S1 S2 S3 S4
OC1 OC2 OC3 OC4
OC1 OC3 Critical outcomes
OC4
Generate an estimate of effect for each outcome
OC2
S5
Structured question
patients: Males over 50 presenting with fatigue, malaise
and erecticle dysfunction with laboratory evidence of decreased testosterone
intervention, testosterone
comparator no testosterone
outcomes?
Rating certainty
Where to start RCTs and observational studies (High, moderate, low, very low)?
Recall antioxidant vitamins Observational studies less cancer, CV
outcomes RCTs no difference Result observed repeatedly What went wrong?
Determinants of confidence
RCTs start highobservational studies start low what can lower confidence? risk of bias inconsistency indirectness imprecisionpublication bias
Risk of Bias - RCTs
what to consider? well established
concealment intention to treat principle observed blinding completeness of follow-up
more recent selective outcome reporting bias Stopping early for benefit
RoB – Observational Studies
what to consider?
accurate assessment of exposure
adjusted analysis for all important prognostic factors, accurately measures
accurate assessment of outcome
completeness of follow-up
Risk of Bias differs – what to do?6 studies, 100 patients each
3 studies low risk of bias, 3 high
rate down for risk of bias?
Consistency
10.5
Relative Risk (95% CI)
0.73 (0.49, 1.07)
0.74 (0.59, 0.94)
0.76 (0.51, 1.12)
0.71 (0.56, 0.90)
0.73 (0.61, 0.88)
Consistency
10.5
Relative Risk (95% CI)
0.44 (0.30, 0.65)
0.45 (0.36, 0.60)
1.25 (0.84, 1.84)
1.17 (0.92, 1.49)
0.73 (0.61, 0.88)
Consistency of results
How did you decide?
Similarity of point estimates less similar, less happy
Overlap of confidence intervals less overlap, less happy
-40 -24 -8 8 24 40 56
RRR (95% CI)
Homogenous
10.5
Relative Risk (95% CI)
0.73 (0.49, 1.07)
0.74 (0.59, 0.94)
0.76 (0.51, 1.12)
0.71 (0.56, 0.90)
0.73 (0.61, 0.88)
test for heterogeneity what is the p-value?
what is the null hypothesis for the test for heterogeneity?
Ho: RR1 = RR2 = RR3 = RR4
p=0.99 for heterogeneity
Heterogeneous
10.5
Relative Risk (95% CI)
0.44 (0.30, 0.65)
0.45 (0.36, 0.60)
1.25 (0.84, 1.84)
1.17 (0.92, 1.49)
0.73 (0.61, 0.88)
p-value for heterogeneity < 0.001
test for heterogeneity what is the p-value?
p-value for heterogeneity < 0.001
I2 Interpretation
No worries 0%
25%Only a little
concerned
50%Getting
concerned
75%Very
concerned
100%Why are
we pooling?
Homogenous
10.5
Relative Risk (95% CI)
0.73 (0.49, 1.07)
0.74 (0.59, 0.94)
0.76 (0.51, 1.12)
0.71 (0.56, 0.90)
0.73 (0.61, 0.88)
p=0.99 for heterogeneity
I2=0%
What is the I2 ?
Heterogeneous
10.5
Relative Risk (95% CI)
0.44 (0.30, 0.65)
0.45 (0.36, 0.60)
1.25 (0.84, 1.84)
1.17 (0.92, 1.49)
0.73 (0.61, 0.88)
p-value for heterogeneity < 0.001I2=89%
What is the I2 ?
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
Relative Risk with 95% CI for Vitamin D (Non-Vertebral Fractures, Dose >400)
Favours Vitamin D Favours Control
10.5 0.1
Study Year Relative Risk (95% CI)
Chapuy 1994 0.79 (0.69, 0.92)
Dawson-Hughes 1997 0.46 (0.24, 0.88)
Pfeifer 2000 0.48 (0.13, 1.78)
Chapuy 2002 0.85 (0.64, 1.13)
Trivedi 2003 0.67 (0.46, 0.99)
Random Effects Estimate: p=0.26 for heterogeneity, I²=24% 0.75 (0.63, 0.89)
Relative Risk with 95% CI for Vitamin D (Non-Vertebral Fractures, Dose = 400)
Favours Vitamin D Favours Control
10.5
Study Year Relative Risk (95% CI)
Lips 1996 1.10 (0.87, 1.39)
Meyer 2002 0.92 (0.68, 1.24)
Random Effects Estimate: p=0.35 for heterogeneity, I²=0% 1.03 (0.86, 1.24)
Should we believe sub-group analysis?
within-study comparison? No unlikely chance Yes, p = 0.006 consistent across studies Yes one of small number a priori hypothesis
with direction Yes biologically compelling Yes shall we believe sub-group analysis?
Credibility of sub-group analysis
no way sure thing
0 100
Confidence judgments: Directness
populations older, sicker or more co-morbidity
interventions warfarin in trials vs clinical practice
outcomes important versus surrogate outcomes glucose control versus CV events
Alendronate
Risedronate
Placebo
Directness
interested in A versus B available data A vs C, B vs C
Imprecision
small sample size small number of events
wide confidence intervals uncertainty about magnitude of effect
how do you decide what is too wide?
primary criterion: would decisions differ at ends of CI
Precision
atrial fib at risk of strokewarfarin increases serious gi
bleeding 3% per year
1,000 patients 1 less stroke 30 more bleeds for each stroke prevented
1,000 patients 100 less strokes 3 strokes prevented for each bleed
where is your threshold? how many strokes in 100 with 3% bleeding?
01.0%
01.0%
01.0%
01.0%
Example: clopidogrel or ASA?
pts with threatened strokeRCT of clopidogrel vs ASA
19,185 patients
ischaemic stroke, MI, or vascular death compared 939 events (5·32%) clopidogrel 1021 events (5·83%) with aspirin
RR 0.91 (95% CI 0.83 – 0.99) (p=0·043)
rate down for precision?
01.0%
Clopidogrel or ASA for threatened vascular events
RCT 19,185 patients
1.7% - 0.9 – 0.1%
RR 0.91 (95% CI 0.83 – 0.99)
small trials, large effect likely to be overestimate
analogy to stopping early lack of prognostic balancesolution: optimal information size
# of pts from conventional sample size calculation
specify control group risk, α, β, Δ
Fluoroquinolone prophylaxis in neutropenia: infection-related mortality
Total number of events: 47
Fluoroquinolone prophylaxis in neutropenia: infection-related mortality
sample size 1,002α 0.05, β 0.20, Δ 0.25 RRR, CER 7%
N = 6,000
Publication bias
high likelihood could lower quality
when to suspect number of small studies industry sponsored
Funnel PlotFish oil on mortality
What can raise confidence?What do you do high certainty, no
RCTs?common criteria
everyone used to do badly almost everyone does well quick action
insulin for diabetic ketoacidosis? thyroxine for thyroid deficiency?hydrocortisone for adrenal
insufficiency?
Dose-response gradient
childhood lymphoblastic leukemia
risk for CNS malignancies 15 years after cranial irradiation
no radiation: 1% (95% CI 0% to 2.1%) 12 Gy: 1.6% (95% CI 0% to 3.4%) 18 Gy: 3.3% (95% CI 0.9% to 5.6%).
Cetainty assessment criteria
Overall level of evidence
What to do when certainty differs across outcomes?
options ignore all but primary
previous approach least certainty of any outcome some blended approach least certainty of critical outcomes
what do patients/clinicians need to know relative risk reduction? absolute risk difference?
Toxic treatment, 50% RRR mortality? OK?
1% to 1/2% OK?
40% to 20%, OK?
body of evidence how do we get risk difference?
Trading off desirable and undersirable
How to get absolute?
meta-analysis get pooled relative risk
obtain baseline risk and multiply
BR 10%, RRR 50%, RD 5%
why not get risk difference directly?
RR 0.67RD 10%
RR 0.67RD 3.3%
RR 0.67RD 1%
Population No. of participants (trials) †
Higher PEEP
Lower PEEP
Adjusted Relative Risk (95% CI; P-
value) ‡
Adjusted Absolute Risk Difference (95%
CI)
Quality
Patients with ARDS
1892 (3) 324/951
(34.1%)
368/941
(39.1%)
0.90 (0.81 to 1.00; 0.049)
-3.9% (-7.4% to -0.04%)
High
Patients without ARDS
404 (3) 50/184 (27.2%)
41/220 (18.6%)
1.37 (0.98 to 1.92; 0.065)
6.9% (-0.4% to 17.1%) Moderate (imprecision)
High versus low PEEP in ALI and ARDS
Strength of Recommendationstrong 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
Risk/Benefit tradeoff
aspirin after myocardial infarction 25% reduction in relative risk side effects minimal, cost minimal benefit obviously much greater than
risk/cost
warfarin in low risk atrial fibrillation warfarin reduces stroke vs ASA by 50% but if risk only 1% per year, ARR 0.5% increased bleeds by 1% per year
Aspirin after MI – do it
Warfarin rather than ASA in Afib -- probably do it -- probably don’t do it
Strength of Recommendations
Significance of strong vs weak
variability in patient preference strong, almost all same choice (> 90%) weak, choice varies appreciably
interaction with patient strong, just inform patient weak, ensure choice reflects values
use of decision aid strong, don’t bother; weak, use the aid
quality of care criterion strong, consider; weak, don’t consider
When evidence is low confidence
choice more preference dependent
risk aversion
steroids for pulmonary fibrosis low quality evidence in support of benefit high quality evidence of toxicity
When confidence is low
recommendation to the hopeful patient
I’m likely to deteriorate if something might work, let’s try it damn the torpedoes
recommendation to the fearful patient doctor, you mean you know it’s toxic
diabetes, skin changes, body habitus, infection, osteoporosis
you don’t know for sure it works? are you crazy?
weak recommendation mandated
Challenge
Comparator often not clearChildren with suspected or confirmed
tuberculous meningitis should be treated with a four-drug regimen (HRZE) for 2 months, followed by a two-drug regimen (HR) for 10 months
Offer and promote postpartum and post-abortion contraception to adolescents through multiple home visits and/or clinic visits
Experts use often
Why? What are the possibilities?
Strong recommendations, Low certainty: Discordant recs
Why all the inappropriate strong recommendations?
panels don’t believe their own confidence ratings
personal conviction trumps evidence
believe weak recommendations ignored
influence funders
good practice
mistaken judgment
inappropriate
exceptional situation they got it right
Discordant recommendations:What are the possibilities?
Good Practice Statements
For patients with congenital adrenal hyperplasia, we recommend monitoring patients for signs of glucocorticoid excess
Wealth of indirect linked evidenceHigh confidence in net benefit
Benefit clear Minimal harms or costs
Poor use of guideline panel time effort summarize
Summarizing evidence poor use of time
symptoms and signs appear not infrequently Collect cohort studies of incidence Studies of accuracy of symptoms and signs
patients suffer if clinicians fail to recognize Reports of untreated glucocorticoid excess
clinical action can ameliorate the problem Evidence supporting therapy
describe how evidence is linked
Questions panels considering good practice statement should ask
Is the statement clear and actionable? Is the message really necessary? Is the net benefit large and
unequivocal? Is the evidence difficult to collect and
summarize? If a public health guideline, are there
specific issues that should be considered (e.g. equity)
Have you made the rationale explicit? Is this better to be formally GRADEd?
Clear and actionable
For patients with congenital adrenal hyperplasia, we recommend monitoring patients for signs of glucocorticoid excess
Monitor how often?
Nature of monitoring
What to do if signs of excess found
Really necessary?
For patients with congenital adrenal hyperplasia, we recommend monitoring patients for signs of glucocorticoid excess
Really plausible that clinicians won’t monitor?
If not, not necessary
Provide Rationale
relevant symptoms and signs appear not infrequently
patients will suffer if clinicians fail to recognize these signs
clinical action can ameliorate the problem.
1 LQE in a life-threatening situation
Fresh frozen plasma and intracranial bleed
2 LQoE benefit and HQoE suggests harm
Head-to-toe CT/MRI screening for cancer.
3 LQoE suggests equivalence, HQoE less harm for one alternative
Helicobacter pylori eradication early stage gastric MALT lymphoma
4 HQoE suggests equivalence, LQoE suggests harm in one alternative
ACEI in hypertension in women planning conception and in pregnancy.
5 HQoE suggests benefit in one outcome, LQoE suggests harm in more highly valuedoutcome
Testosterone in males with or at risk of prostate cancer
1 LQE in a life-threatening situation
Fresh frozen plasma and intracranial bleed
2 LQoE benefit and HQoE suggests harm
Head-to-toe CT/MRI screening for cancer.
3 LQoE suggests equivalence, HQoE less harm for one alternative
Helicobacter pylori eradication early stage gastric MALT lymphoma
4 HQoE suggests equivalence, LQoE suggests harm in one alternative
ACEI in hypertension in women planning conception and in pregnancy.
5 HQoE suggests benefit in one outcome, LQoE suggests harm in more highly valuedoutcome
Testosterone in males with or at risk of prostate cancer
1 LQE in a life-threatening situation
Fresh frozen plasma and intracranial bleed
2 LQoE benefit and HQoE suggests harm
Head-to-toe CT/MRI screening for cancer.
3 LQoE suggests equivalence, HQoE less harm for one alternative
Helicobacter pylori eradication early stage gastric MALT lymphoma
4 HQoE suggests equivalence, LQoE suggests harm in one alternative
ACEI in hypertension in women planning conception and in pregnancy.
5 HQoE suggests benefit in one outcome, LQoE suggests harm in more highly valuedoutcome
Testosterone in males with or at risk of prostate cancer
1 LQE in a life-threatening situation
Fresh frozen plasma and intracranial bleed
2 LQoE benefit and HQoE suggests harm
Head-to-toe CT/MRI screening for cancer.
3 LQoE suggests equivalence, HQoE less harm for one alternative
Helicobacter pylori eradication early stage gastric MALT lymphoma
4 HQoE suggests equivalence, LQoE suggests harm in one alternative
ACEI in hypertension in women planning conception and in pregnancy.
5 HQoE suggests benefit in one outcome, LQoE suggests harm in more highly valuedoutcome
Testosterone in males with or at risk of prostate cancer
1 LQE in a life-threatening situation
Fresh frozen plasma and intracranial bleed
2 LQoE benefit and HQoE suggests harm
Head-to-toe CT/MRI screening for cancer.
3 LQoE suggests equivalence, HQoE less harm for one alternative
Helicobacter pylori eradication early stage gastric MALT lymphoma
4 HQoE suggests equivalence, LQoE suggests harm in one alternative
ACEI in hypertension in women planning conception and in pregnancy.
5 HQoE suggests benefit in one outcome, LQoE suggests harm in more highly valuedoutcome
Testosterone in males with or at risk of prostate cancer
Methods
systematic survey of all published ES guidelines between 2005 and 2011
screening and extraction in duplicate for each recommendation: confidence in
estimates, strength of recommendation strong recommendations based on LQE
taxonomy for paradigmatic recommendations applied
Condition Example
1 Best practice statementsFor patients with Congenital Adrenal Hyperplasia, we recommend monitoring patients for signs of glucocorticoid excess
2 Additional researchWe recommend additional investigation using rodents and primates to further define the specific targets of androgen action
3 Mistaken judgment
For overweight and obese children and adolescents, intensive lifestyle modification for the patient and entire family
4 Inappropriate strong recommendation
In patients with primary aldosteronism who are unable or unwilling to undergo laparascopic adrenalectomy, we recommend medical treatment with mineralocorticoids
If they did not fit one of 5 paradigms
Strong recommendations (n=206):
n (%) Weak recommendations
(n=151):
n (%)
High/moderate confidence in estimates
85 (41%)
High/moderate confidence in estimates
16(8%)
Very low/low confidence in estimates
121(59%)
Very low/ low confidence in estimates
135(92%)
Totals (%) 206 (100%)
Totals (%) 151 (100%)
Guidelines Strenght and Confidence
Ap-pro-
priate29%
Inap-propri-
ate71%
N - 35 Condition
1 LQE in a life-threatening situation
13 LQoE benefit and HQoE suggests harm or a very high cost
7LQoE suggests equivalence, HQoE less harm for one of the competing alternatives.
5HQoE suggests equivalence of two alternatives and LQoE suggests harm in one alternative
9 HQoE suggests modest benefits and LQoE suggests possibility of catastrophic harm
Appro-priate29%
Inap-propri-
ate71%
N = 86 Condition
43 Best practice
5 Mistaken judgment
5 Additional research
33 Inappropriate strong recommendation
Summary
majority ES recommendations strong 121 (59%) discordant
35/121 (29%) of discordant appropriate
of 86 inappropriate, 43 (50%) best practice statements
33/86 inappropriate, should have been weak recommendations
Value and preference statements
underlying values and preferences always present
sometimes crucial
important to make explicit
Values and preferences
Stroke guideline: patients with TIA clopidogrel over aspirin (Grade 2B).
Underlying values and preferences: This recommendation to use clopidogrel over aspirin places a relatively high value on a small absolute risk reduction in stroke rates, and a relatively low value on minimizing drug expenditures.
Values and preferences
peripheral vascular disease: aspirin be used instead of clopidogrel (Grade 2A).
Underlying values and preferences: This recommendation places a relatively high value on avoiding large expenditures to achieve small reductions in vascular events.
Values and preferences
Consider UpToDate style of values and preferences
Weak recommendation low certainty evidence for trial of testosterone in men with apparent testosterone deficiency and cardiovascular disease
Men who place a high value on minimizing risk of an adverse cardiovascular event and a relatively low value in ameliorating the symptoms of testosterone deficiency are likely to choose against testoserone use
Flavanoids for Hemorrhoids
venotonic agents mechanism unclear, increase venous
return
popularity 90 venotonics commercialized in France none in Sweden and Norway France 70% of world market
possibilities French misguided rest of world missing out
Systematic Review
14 trials, 1432 patients
key outcome risk not improving/persistent symptoms 11 studies, 1002 patients, 375 events RR 0.4, 95% CI 0.29 to 0.57
minimal side effects
is France right?
what is the certainty of evidence?
What can lower confidence?
risk of bias lack of detail re concealment questionnaires not validated
indirectness – no problem
inconsistency, need to look at the results
Review : Phlebotonics for hemorrhoidsComparison: 01 Venotonics vs placebp Outcome: 08 Overall improvement: no improvement/some improvement
Study RR (random) Weight RR (random)or sub-category log[RR] (SE) 95% CI % 95% CI
01 Up to seven daysChauvenet -0.8916 (0.2376) 12.67 0.41 [0.26, 0.65] Cospite -2.2073 (0.6117) 5.51 0.11 [0.03, 0.36] Thanapongsathorn -0.4308 (0.2985) 11.18 0.65 [0.36, 1.17]
Subtotal (95% CI) 29.36 0.37 [0.18, 0.77]Test for heterogeneity: Chi² = 6.92, df = 2 (P = 0.03), I² = 71.1%Test for overall effect: Z = 2.67 (P = 0.008)
02 Up to four w eeksAnnoni F -1.6094 (0.7073) 4.50 0.20 [0.05, 0.80] Clyne MB -0.9943 (0.3983) 8.94 0.37 [0.17, 0.81] Pirard J -1.1712 (0.3086) 10.94 0.31 [0.17, 0.57] Thanapongsathorn -1.1087 (1.1098) 2.18 0.33 [0.04, 2.91] Thorp 0.2624 (0.3291) 10.46 1.30 [0.68, 2.48] Titapan -0.8916 (0.3691) 9.56 0.41 [0.20, 0.85] Wijayanegara -0.5978 (0.1375) 14.97 0.55 [0.42, 0.72]
Subtotal (95% CI) 61.54 0.48 [0.32, 0.72]Test for heterogeneity: Chi² = 13.87, df = 6 (P = 0.03), I² = 56.7%Test for overall effect: Z = 3.57 (P = 0.0004)
03 Further than four w eeksGodeberg -1.7719 (0.3906) 9.10 0.17 [0.08, 0.37]
Subtotal (95% CI) 9.10 0.17 [0.08, 0.37]Test for heterogeneity: not applicableTest for overall effect: Z = 4.54 (P < 0.00001)
Total (95% CI) 100.00 0.40 [0.29, 0.57]Test for heterogeneity: Chi² = 28.66, df = 10 (P = 0.001), I² = 65.1%Test for overall effect: Z = 5.14 (P < 0.00001)
0.001 0.01 0.1 1 10 100 1000
Favours treatment Favours control
Publication bias?
size of studies40 to 234 patients, most around
100
all industry sponsored
Review : Phlebotonics for hemorrhoidsComparison: 01 Venotonics vs placebp Outcome: 08 Overall improvement: no improvement/some improvement
0.001 0.01 0.1 1 10 100 1000
0.0
0.4
0.8
1.2
1.6
RR (fixed)
What can lower confidence?
risk of bias lack of detail re concealment questionnaires not validated
inconsistency almost all show positive effect, trend heterogeneity p < 0.001; I2 65.1%
indirectness imprecision
RR 0.4, 95% CI 0.29 to 0.57 publication bias
40 to 234 patients, most around 100
Is France right?
recommendationyesno against use
strengthstrong weak
Quality Assessment
Summary of Findings
QualityRelative Effect
(95% CI)
Absolute risk difference
OutcomeNumber of
participants(studies)
Risk of Bias
Consistency Directness Precision Publication 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
No serious limiations
No serious limitations
ImpreciseNot
detectedModerate
1.23(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
Where to from here?
GRADE values and preferences
GRADE diagnosis
Aspirin for primary prevention
Culprit only vs complete revascularization in STEMI
Management of esophageal varices