Evaluating the evidence using GRADE Peter Morley E3 2015 19 th - - PowerPoint PPT Presentation

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Evaluating the evidence using GRADE

Peter Morley E3 2015 19th October 2012

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Conflict of interest disclosure

Commercial/industry Evidence Evaluation Expert (ILCOR/AHA) Potential intellectual conflicts Deputy Chair Australian Resuscitation Council (ARC) Chair ALS Committee ARC ARC rep on International Liaison Committee on Resuscitation (ILCOR) Evidence Evaluation Expert (ILCOR/AHA)

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So what is GRADE?

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Grading of Recommendations Assessment, Development, and Evaluation (GRADE)

Process to take evidence to guidelines Developed by key international groups Widely accepted internationally

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GRADE

Offers a transparent and structured process for developing and presenting summaries of evidence, including its quality, for systematic reviews and recommendations in health care. Provides guideline developers with a comprehensive and transparent framework for carrying out the steps involved in developing recommendations. Use is appropriate and helpful irrespective of the quality of the evidence: whether high or very low. Does not eliminate the inevitable need for judgments.

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GRADE process adopted by:

American College of Physicians The Cochrane Collaboration American College of Chest Physicians European Society of Thoracic Surgeons American Thoracic Society Agency for Healthcare Research and Quality Society of Critical Care Medicine Up to Date WHO NIH NICE Endocrine Society

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GRADE uptake

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Lots of educational material existing

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Journals

Journal of Clinical Epidemiology (2011-2)

• 12 articles (more to come in series)
• extensive review, major reference for GRADE

methodology BMJ Series (2008)

• 7 articles
• initial concepts of GRADE and justification

documents Multiple other publications

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Grade (1997)

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GRADE (1997)

Allows downgrading of quality estimate if involve “indirect evidence” Population groups ? Animals etc! Prognostic or aetiologic studies only useful if their use modifies outcomes! Very good approach to making recommendations

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Grade (1997)

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Comparisons and proposal

GRADE approach closest to our needs Not numerical Needs additional “non-therapy” LOEs OCEBM or NH&MRC

Study type/Approach C2005 Grade SIGN NH&MRC OCEBM Meta-analyses 1 n/a 1++ to 2++ I 1a or 2a RCTs 1 or 2 High/Mod/Low 1/1+/1++ II 1b or 2b Concurrent controls 3 High/Mod/Low 2- to 2++ III-1 or III-2 2b to 4 Retrospective controls 4 Low n/a III-3 ?1c! No controls 5 Very low 3 IV 4 Animal/Mechanical/Model 6 ? As for extrap n/a n/a n/a Extrapolations 7 Downgraded n/a n/a n/a Covers "non-therapy" studies ?1to7 Irrelevant! No Detailed Detailed

C2010 1 2 3 4 5 5 YES 1 or 2

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What are the principles behind GRADE?

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I B II V III

GRADE is outcome-centric

Quality: High Quality: Moderate Quality: Low

Older systems

Outcome #1 Outcome #2 Outcome #3

GRADE

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GRADE: Quality of evidence

GRADE defines 4 categories of quality: High Moderate Low Very low

The extent to which our confidence in an estimate of the treatment effect is adequate to support a particular recommendation.

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Conceptualizing quality

       

We are very confident that the true effect lies close to that of the estimate of the effect. High

    

Low Our confidence in the effect is limited: The true effect may be substantially different from the estimate of the effect.

    

Moderate We are moderately confident in the estimate of effect: The true effect is likely to be close to the estimate of effect , but possibility to be substantially different.

      

Very low We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

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GRADE Recommendations

Strong recommendations strong methods large precise effect few downsides of therapy expect non-variant clinician and patient behavior

• diminished role for clinical expertise

– focus on implementation & barriers

• focused role of patient values and preferences

– emphasis on compliance and barriers

Weak recommendations weak methods imprecise estimate small effect substantial downsides expect variability in clinician and patient actions

• clinical expertise important

– focus on decision-making and implementation

• patient values and preferences important

– focus on determining values and preferences relative to decision Patient Values and Preferences Research Evidence Clinical Experience

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So why adopt GRADE?

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Apart from international consensus

Allows more clarity and consistency when move from evidence to recommendations

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So is this really different to the C2010 approach?

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Differences between processes

2010 ILCOR

Identify PICO question Search for studies Clear inclusion exclusion criteria Identify studies for detailed review Identify key (critical)

• utcomes of relevance

2015 ILCOR (GRADE)

Identify PICO question Search for studies Clear inclusion exclusion criteria Identify studies for detailed review Identify key (critical)

• utcomes of relevance

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Differences between processes

2010 ILCOR

Allocate study LOE: from LOE 1 to LOE 5 Allocate “methodological quality” for each study All studies (with outcomes) into grid according to direction for specific question

2015 ILCOR (GRADE)

Allocate study type: RCTs

• r observational

Assess “risk of bias” for each study All studies (with outcomes) into “risk of bias” table (including overall “risk of bias” for each study)

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Assessment of methodological quality (risk of bias) of RCTs: similar

2010: ILCOR Quality RCTs (not clearly documented)

Adequacy of randomization Allocation concealment Blinding Loss to follow up Intention to Treat (IT) analysis Groups treated equally? Groups similar at the start?

2015: GRADE Risk of bias RCTs (clearly documented)

Adequacy of randomization Allocation concealment Blinding Loss to follow-up, Intention to Treat (IT) analysis Any other risks?

• Early stopping for positive benefit
• thers

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Allocation of quality vs downgrading for RCTs: similar

2010: Quality for individual RCT

Good studies

• most/all of the relevant quality

items

Fair studies

• have some of the relevant

quality items

Poor studies

• have few of the relevant quality

items (but sufficient value to include for further review).

Excluded

• insufficient relevant quality

items to be included

2015: Overall risk of bias for individual RCT

Low (?Good) Unclear (?Fair) High (?Poor)

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Published limitations (extras at 5)

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Remember our evidence table

Summary of evidence

Evidence Supporting Clinical Question

Good Fair Poor 1 2 3 4 5 Level of evidence A = Return of spontaneous circulation C = Survival to hospital discharge E = Other endpoint

B = Survival of event D = Intact neurological survival Italics = Animal studies

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Overall risk of bias for study: Low, Moderate or High

“Low” risk of bias = most or all key criteria listed are met, and any violations are not crucial. “Moderate” risk of bias if have a crucial limitation in one criterion or some limitations in multiple criteria, sufficient to lower the confidence in the estimate of effect. “High” risk of bias if have a crucial limitation in

• ne or more criteria, sufficient to substantially

lower the confidence in the estimate of effect.

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Differences between processes

2010 ILCOR

Narrative description of key information from all studies

2015 ILCOR (GRADE)

Narrative description of key information from all studies Plus specific information regarding evidence for each key outcome

• “Evidence profile” table(s)
• “Summary of findings” table(s)

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Major difference in approach for GRADE

Key outcome measures are allocated a numerical rating Critical 9, 8, 7 Important 6, 5, 4 Limited importance 3, 2, 1 Quality of evidence is assessed (across studies) for each key outcome

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How is the evidence for each outcome collated?

Evidence Profile table(s) Summary of Findings table(s) Narrative description Consensus on Science statement

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Evidence Profile table(s)

PICO question Outcome to which evidence applies No of studies that report data for that outcome Study Design (RCT, Observational etc) Risk of bias (limitations: no serious, serious, very serious) Inconsistency (limitations: no serious, serious, very serious) Indirectness (limitations: no serious, serious, very serious) Imprecision (limitations: no serious, serious, very serious) Other including publication bias (Undetected, strongly suspected) Overall Quality of evidence for outcome High, Moderate, Low, Very low

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Evidence profile table

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Classification across all studies for each outcome

Risk of Bias/Inconsistency/Indirectness/Imprecision No serious limitations: Most information is from studies at low risk of bias. Do not downgrade Serious limitations: Most information is from studies at moderate risk of bias. Rate down one level Very serious limitations: Most information is from studies at high risk of bias. Rate down two levels

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Classification across all studies for each outcome

Publication Bias Undetected Strongly suspected Quality of Evidence across all included studies for outcome High Moderate Low Very Low

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Quality of evidence for outcome (across all studies)

Four final categories

High Moderate Low Very low

Start with “high” for RCTs Start with “low” for observational Can be modified according to a number of factors

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RCTs can be downgraded

all or most of the studies had sufficient problems to make estimate unreliable or uncertain design and execution (risk of bias) consistency of results directness of comparisons precision publication bias

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Overall quality of evidence: for each key outcome across studies

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What about even lower levels of evidence?

Case series (LOE 4) Manikin/Models/Animals (LOE 5)

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Case series

Start at low/very low quality Can be upgraded

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Case series

Start at low quality Can be upgraded BUT not if would be downgraded first!

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Manikin/Models/Animals (LOE 5)

(NB. GRADE not created for these)

Starting point depends on methodology RCTs at high quality Observational at low quality BUT Even RCTs can be downgraded Very serious “indirectness” = -2 Can be explained in comments

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Summary of Findings table: columns

PICO Key Outcomes Illustrative comparative risks (categorical or continuous with 95% CI) Control group Intervention group Relative effect (95% CI) No of Participants (studies) Overall quality of the evidence (GRADE) Comments/Footnotes

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Summary of findings table

Present a key summary graph or table Citation #1 Citation #2

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Next = CoSTR

Consensus on Science statement and Treatment Recommendations

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Differences between processes

2010

Consensus on Science statement (based on listing

• f levels of evidence for

specific outcomes) Treatment recommendation: using behavioral wording, based largely on quality of evidence

2015

Consensus on Science statement (based on “overall quality” of evidence for “critical

• utcomes”)

Treatment recommendation: strong or weak (with behavioral correlates), based on evidence quality (high, moderate, low, very low)

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So how will our Consensus on Science statement and Treatment Recommendations differ?

COS: Quality level of evidence (GRADE) TR: Strength of Recommendation (GRADE)

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GRADE Strength of Recommendation

Strong: the desirable effects of an intervention clearly outweigh the undesirable effects, or clearly do not. Weak: the trade-offs are less certain—either because of low quality evidence or because evidence suggests that desirable and undesirable effects are closely balanced.

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Strong Recommendation

For patients—most people in your situation would want the recommended course of action and only a small proportion would not; request discussion if the intervention is not offered For clinicians—most patients should receive the recommended course of action

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Weak Recommendation

For patients—most people in your situation would want the recommended course of action, but many would not For clinicians—you should recognize that different choices will be appropriate for different patients and that you must help each patient to arrive at a management decision consistent with her or his values and preferences

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So what might a GRADE review for ILCOR look like?

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Worksheet identifier: TBA Author: Peter Morley Affiliation: ANZCOR Taskforce: ALS/BLS Other Worksheet Authors: TBA

In adult cardiac arrest (prehospital [OHCA], in-hospital [IHCA]), does the use

• f an ITD (I) compared with no ITD (C),

improve any outcomes (e.g. survival) (O)?

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C2015 PICO

Population: adult cardiac arrest (prehospital [OHCA], in-hospital [IHCA]) Intervention: the use of an ITD Comparison: compared with no ITD Outcomes Neurologically intact survival (critical 9) Discharge from hospital alive (critical 8) Return of spontaneous circulation (important 6)

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Inclusion/Exclusion/Articles Found

Included all studies with concurrent controls. Excluded review articles, studies with historical controls, animal studies, and studies that did not specifically answer the

• question. Excluded unpublished studies,

studies only published in abstract form, unless accepted for publication. 8 Articles Finally Evaluated

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Risk of Bias in studies table(s)

Impedance Threshold Device + Standard CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, Intention to Treat (IT) analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Aufderheide 2005, 734

ITD+SCPR vs ShamITD+SCPR

Low Low Low Low Discontinued early. Indirectness: 2000 guidelines. All Low Pirallo 2005, 13

ITD+SCPR vs ShamITD+SCPR

Low Unclear Low Low Changed device halfway into

• study. Equipment problems

Indirectness: 2000 guidelines. All Low Aufderheide 2011, 798

ITD+SCPR vs ShamITD+SCPR

Low Low Low Low Indirectness: 2005 guidelines All Low

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Active Compression Decompression CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Plaisance 2000, 989

ITD+ACD vs ACD

Low Low Low Low No description primary

• utcome/power. Indirectness:

1992 guidelines All Low Plaisance 2004, 265

ITD+ACD vs ShamITD+ACD

Low Low Low Low Automatic ventilator. Indirectness: 2000 guidelines. All Low Plaisance 2005, 990

ITD+ACD vs ShamITD+ACD

Low (order of use) Low Low Low Crossover trial. Indirectness: 2000 guidelines All Moderate

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Risk of Bias in studies table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Study Random

• ization

Allocation concealment Blinding Loss to follow-up, IT principle

• bserved or per

protocol analysis Any other risks Outcomes to which these assessments apply Overall risk

• f bias for
• utcome(s)

for study** Wolcke 2003, 2201

ITD+ACD vs SCPR

Low High High Low Indirectness: ?1992/2000 guidelines All High Aufderheide 2011, 301

ITD+ACD vs SCPR

Low Unclear High (only

• utcome

assessor) Unclear, some exclusions based on difficultly with airway border on deviation from IT analysis. High: Significant differences in real time feedback about CPR

• quality. Increase enrollment

numbers then stop early. All High

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Next create an “Evidence Profile” table

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Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision) Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

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Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision) Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

76

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision)

77

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision)

78

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision)

79

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision)

80

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision)

81

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision)

82

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision)

83

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision)

84

85

86

Overall quality of evidence: for each key outcome across studies

87

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 1 Aufderheide 2011 301 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations No serious limitations Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement). More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias and imprecision)

88

89

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

90

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

91

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

92

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

93

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

94

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

95

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

96

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

97

Evidence profile table: ITD+ACDCPR vs Standard CPR

Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Population: Patients in cardiac arrest Settings: OOHCA Intervention: Impedance Threshold Device + Active Compression Decompression CPR Comparison: Standard CPR

Outcome No of studies Author Year 1

st page

Study Design Risk of bias* Inconsistency* Indirectness* Imprecision* Other (including publication bias)** Quality of evidence for

• utcome***

Outcome 2 Survival to hospital discharge Critical (8) 2 Aufderheide 2011 301 Wolcke 2003 2201 RCT Very serious limitations (blinding, feedback about CPR quality, exclusions/ IT analysis) No serious limitations Serious limitations (Wolcke 2003 2210: 1992/2000 guidelines) Serious limitations (ARR CI

• verlap 1%)

Undetected (sponsor involvement) More pulmonary

• edema I

94/840 (11%) vs C 62/813 (7%) 0.015. Low (rated down for risk of bias, indirectness and imprecision)

98

Next create a “summary of findings” table

99

100

Summary of findings table(s)

Present a key summary graph or table Citation #1 Citation #2

101

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

102

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

103

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

104

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

105

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

106

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

107

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

108

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

109

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

110

Summary of findings table: 1

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 1 Neurologically intact survival (survival to hospital discharge with modified Rankin ≤ 3) Critical (9) 47/813 (5.8%) 75/840 (8.9%) Difference 3.15% (0.64 to 5.66) NNT 31.8 OR 1.60 (1.09 to 2.33) 2470 (1)** Low

1

Unblinded study with unbalanced control for quality

• f

CPR.

111

Summary of findings table: 2

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 2 Survival to hospital discharge Critical (8) 94/920 (10.2%) 123/943 (13%) Difference 2.83% (-0.08 to 5.73) NNT 35.4 OR 1.32 (0.99 to 1.75) 2680 (2)*** Low

1

Unblinded studies with unbalanced control for quality

• f

CPR.

112

Summary of findings table: 2

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 2 Survival to hospital discharge Critical (8) 94/920 (10.2%) 123/943 (13%) Difference 2.83% (-0.08 to 5.73) NNT 35.4 OR 1.32 (0.99 to 1.75) 2680 (2)*** Low

1

Unblinded studies with unbalanced control for quality

• f

CPR.

113

Summary of findings table: 2

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 2 Survival to hospital discharge Critical (8) 94/920 (10.2%) 123/943 (13%) Difference 2.83% (-0.08 to 5.73) NNT 35.4 OR 1.32 (0.99 to 1.75) 2680 (2)*** Low

1

Unblinded studies with unbalanced control for quality

• f

CPR.

114

Summary of findings table: 2

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 2 Survival to hospital discharge Critical (8) 94/920 (10.2%) 123/943 (13%) Difference 2.83% (-0.08 to 5.73) NNT 35.4 OR 1.32 (0.99 to 1.75) 2680 (2)*** Low

1

Unblinded studies with unbalanced control for quality

• f

CPR.

115

Summary of findings table: 2

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 2 Survival to hospital discharge Critical (8) 94/920 (10.2%) 123/943 (13%) Difference 2.83% (-0.08 to 5.73) NNT 35.4 OR 1.32 (0.99 to 1.75) 2680 (2)*** Low

1

Unblinded studies with unbalanced control for quality

• f

CPR.

116

Summary of findings table: 2

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 2 Survival to hospital discharge Critical (8) 94/920 (10.2%) 123/943 (13%) Difference 2.83% (-0.08 to 5.73) NNT 35.4 OR 1.32 (0.99 to 1.75) 2680 (2)*** Low

1

Unblinded studies with unbalanced control for quality

• f

CPR.

117

Summary of findings table: 2

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 2 Survival to hospital discharge Critical (8) 94/920 (10.2%) 123/943 (13%) Difference 2.83% (-0.08 to 5.73) NNT 35.4 OR 1.32 (0.99 to 1.75) 2680 (2)*** Low

1

Unblinded studies with unbalanced control for quality

• f

CPR.

118

Summary of findings table: 2

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 2 Survival to hospital discharge Critical (8) 94/920 (10.2%) 123/943 (13%) Difference 2.83% (-0.08 to 5.73) NNT 35.4 OR 1.32 (0.99 to 1.75) 2680 (2)*** Low

1

Unblinded studies with unbalanced control for quality

• f

CPR.

119

Summary of findings table: 2

Topic title: Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR (C)

Patient

• r

population: Patients in cardiac arrest Settings: OOHCA Intervention: Use

• f

Impedance Threshold Device in addition to Active Compression Decompression CPR Comparison: Use

• f

Standard CPR Outcomes Illustrative comparative risks*

• (95%

CI) Relative effectOR (95% CI) No

• f

Participants (studies) Quality

• f

the evidence (GRADE) Comments Assumed risk Comparison Corresponding risk Intervention Outcome 2 Survival to hospital discharge Critical (8) 94/920 (10.2%) 123/943 (13%) Difference 2.83% (-0.08 to 5.73) NNT 35.4 OR 1.32 (0.99 to 1.75) 2680 (2)*** Low

1

Unblinded studies with unbalanced control for quality

• f

CPR.

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So what might a 2015 COS statement look like?

121

Consensus on Science statements

• Impedance Threshold Device + Active Compression Decompression

CPR (I) vs Standard CPR (C)

• One RCT enrolling over 2000 OOHCAs [Aufderheide 2011,

301]reported improved neurologically intact survival when the unblinded use of an Impedance Threshold Device and Active Compression Decompression CPR was compared with manual standard CPR.

• Two RCTs enrolling over 2000 OOHCAs [Aufderheide 2011, 301;

Wolcke 2003, 2201] were unable to demonstrate any improvements in survival to hospital discharge when the unblinded use of an Impedance Threshold Device and Active Compression Decompression CPR was compared with manual standard CPR.

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What about a Treatment Recommendation?

123

GRADE Strength of Recommendation

Strong: the desirable effects of an intervention clearly outweigh the undesirable effects, or clearly do not. Weak: the trade-offs are less certain—either because of low quality evidence or because evidence suggests that desirable and undesirable effects are closely balanced.

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So what might a 2015 TR look like?

125

2015 Draft Treatment Recommendations

• Impedance Threshold Device + Active Compression

Decompression CPR (I) vs Standard CPR (C)

• There is insufficient evidence to recommend the routine

use of the combination of an Impedance Threshold Device and manual active compression decompression cardiopulmonary resuscitation instead of standard CPR (weak recommendation, low quality of evidence).

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Systematic review Guideline development

P I C O

Outcome Outcome Outcome Outcome Critical Important Critical Not Summary of findings & estimate of effect for each outcome Rate

• verall quality of evidence

across outcomes based on lowest quality

• f critical outcomes

RCT start high,

• bs. data start low
• 1. Risk of bias
• 2. Inconsistency
• 3. Indirectness
• 4. Imprecision
• 5. Publication

bias Grade down Grade up

• 1. Large effect
• 2. Dose

response

• 3. Confounders

Very low Low Moderate High Formulate recommendations:

• For or against (direction)
• Strong or weak (strength)

By considering:  Quality of evidence  Balance benefits/harms  Values and preferences Revise if necessary by considering:  Resource use (cost)

• “We recommend using…”
• “We suggest using…”
• “We recommend against using…”
• “We suggest against using…”

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Journals

Journal of Clinical Epidemiology (2011-2)

• 12 articles (more to come in series)
• extensive review, major reference for GRADE

methodology BMJ Series (2008)

• 7 articles
• initial concepts of GRADE and justification

documents Multiple other publications

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Online resources

http://ims.cochrane.org/revman/other-resources/gradepro/resources Provides numerous webinars, videos, Powerpoint’s, and PDFs on the topic of GRADE. http://www.gradeworkinggroup.org/toolbox/index.htm General website for all things ‘GRADE’ Pro: video at site provides 10 minute quick review Con: lacking an executive summary or ‘user guides’ as have been created for other ‘User Guides to the Medical Literature’ http://ims.cochrane.org/revman/gradepro Software and PDF website Pro: provides both software and PDF tools Con: unknown usability at this point http://www.cochrane-handbook.org/ Online tool available to reviewers. Pro: thorough and compreshensive Con: difficult to navigate through

129 http://cebgrade.mcma ster.ca/

130