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