Study Characteristics

• Study Identifiers

  • Study Name or Acronym
  • Last name of first author
  • Publication Year
• Additional Articles Used in This Abstraction
• Study Objective(s)
• Study Dates

  • Enrollment start (Mon and YYYY)
  • Enrollment end (Mon and YYYY)
  • Follow-up end (Mon and YYYY)
• Study Sites

  • Single center, Multicenter, Unclear/Not reported
  • Number of sites
• Geographic Location (Select all that apply)

  • US, Canada, UK, Europe, S. America, C. America, Asia, Africa, Australia/NZ, Unclear/Not reported, Other (specify)
• Study Design

  • Prospective RCT
  • Prospective Cohort
  • Retrospective Cohort
  • Case-control
  • Cross-sectional
  • Other (specify)
• Funding Source (Select all that apply)

  • Government, Industry, Non-government/non-industry, Unclear/Not reported, Other (specify)
• Setting (Select all that apply)

  • In-patient, Out-patient, Emergency Room, Unclear/Not reported, Other (specify)
• Enrollment Approach (Select all that apply)

  • Consecutive patients, Convenience sample, Unclear/Not reported, Other (specify)
• Study Inclusion and Exclusion Criteria

  • Copy/paste inclusion and exclusion criteria as reported
  • Is the study entirely composed of patients with any of the following characteristics/conditions?

    ▪

    Paroxysmal Atrial Fibrillation (AF)

    ▪

    Persistent AF

    ▪

    Permanent AF

    ▪

    Patients with atrial fibrillation who experience acute coronary syndrome

    ▪

    Age

    ▪

    Women

    ▪

    Pregnant women

    ▪

    Race/ethnicity

    ▪

    Presence of heart disease

    ▪

    Type of AF

    ▪

    Patients in the therapeutic range

    ▪

    Patients with prior bleed

    ▪

    Patients with prior stroke

    ▪

    Patients with comorbid conditions such as dementia, renal failure, or hepatic failure

    ▪

    Patients with multiple coexisting conditions (e.g. combinations of hypertension, diabetes, CHF, CAD, and high cholesterol)

    ▪

    Patients non-compliant with treatment

    ▪

    None of the above

• Study Enrollment/Study Completion

  • N assessed for eligibility
  • N eligible
  • N enrolled/included
  • N completed follow-up (most distal timepoint of the primary outcome)
  • N analyzed
• Key Question Applicability (Select all that apply)

  • KQ1, KQ2, KQ3, KQ4, KQ5, KQ6
• Comments

Baseline Characteristics – Record the following elements for Total Population, Arm 1, Arm 2, Arm 3, and Arm 4 (as applicable)

• Number of Patients, Age, Ethnicity, and Race

  • Number of Patients

    ▪

    Total

    ▪

    Female

    ▪

    Male

  • Percentage

    ▪

    Female

    ▪

    Male

  • Age

    ▪

    Mean

    ▪

    Standard Deviation

    ▪

    Standard Error

    ▪

    Median

    ▪

    IQR

    ▪

    Min

    ▪

    Max

    ▪

    NR

  • Ethnicity

    ▪

    Hispanic or Latino

    ▪

    Not Hispanic or Latino

    ▪

    NR

  • Race

    ▪

    Black/African American

    ▪

    American Indian or Alaska Native

    ▪

    Asian

    ▪

    Native Hawaiian or other Pacific Islander

    ▪

    White

    ▪

    Multiracial

    ▪

    Other (specify)

    ▪

    NR

• Baseline Characteristics

  • Diabetes

    ▪

    N

    ▪

    %

  • Heart failure (NYHA Class), N and % for the following:

    ▪

    Class I

    ▪

    Class II

    ▪

    Class III

    ▪

    Class IV

    ▪

    All classes

  • Sleep apnea

    ▪

    N

    ▪

    %

  • Hyperlipidemia

    ▪

    N

    ▪

    %

  • Hypertension

    ▪

    N

    ▪

    %

  • Kidney disease

    ▪

    N

    ▪

    %

  • Congestive Heart Failure (CHF)

    ▪

    N

    ▪

    %

  • Coronary Artery Disease (CAD)

    ▪

    N

    ▪

    %

  • Prior Myocardial Infarction (MI)

    ▪

    N

    ▪

    %

  • Prior Percutaneous Coronary Intervention (PCI)

    ▪

    N

    ▪

    %

  • Prior CABG

    ▪

    N

    ▪

    %

  • Left Ventricular Ejection Fraction (LVEF), Mean or median

    ▪

    Mean or median

    ▪

    SD, SE, or IQR

  • LVEF, Number of patients (<35% or other [define])

    ▪

    N

    ▪

    %

  • Evidence of Left Atrial Appendage (LAA) thrombus

    ▪

    N

    ▪

    %

  • Any Left Ventricular (LV) dysfunction

    ▪

    N

    ▪

    %

  • Prior stroke or Transient Ischemic Attack (TIA), N and % for the following types:

    ▪

    Ischemic

    ▪

    Hemorrhagic

    ▪

    TIA

    ▪

    All types

  • Tobacco use

    ▪

    N

    ▪

    %

  • Obesity (define)

    ▪

    N

    ▪

    %

  • Patients non-compliant with treatment

    ▪

    N

    ▪

    %

  • Prior vascular disease

    ▪

    N

    ▪

    %

  • Prior bleed

    ▪

    N

    ▪

    %

  • CHADS₂ score

    ▪

    Mean or median

    ▪

    SD, SE, or IQR

  • CHADS₂, N and % of patients with the following scores:

    ▪

    0

    ▪

    1

    ▪

    2+

  • CHA₂DS₂-VASc score

    ▪

    Mean or median

    ▪

    SD, SE, or IQR

  • CHA₂DS₂-VASc, N and % of patients with the following scores:

    ▪

    0

    ▪

    1

    ▪

    2+

  • HAS-BLED score

    ▪

    Mean or median

    ▪

    SD, SE, or IQR

  • HAS-BLED, N and % of patients with the following scores:

    ▪

    <3

    ▪

    3+

  • Duration of AF

    ▪

    Mean or median

    ▪

    SD, SE, or IQR

  • Paroxysmal AF

    ▪

    N

    ▪

    %

  • Persistent AF

    ▪

    N

    ▪

    %

  • Permanent AF

    ▪

    N

    ▪

    %

• Comments

Intervention Characteristics – Record the following elements for Total Population, Arm 1, Arm 2, Arm 3, and Arm 4 (as applicable)

• Interventions (Check all that apply)

  • Placebo or control; Clinical & imaging tools for thromboembolic risk; Clinical tools & individual factors for bleeding risk; Anticoagulation therapy (all oral anticoagulants); Procedural interventions; Antiplatelet therapy; Anticoagulation bridging therapies

    ▪

    If ‘Placebo or control’ selected:

    • Placebo/control

      • Placebo, Usual care/Optimal medical therapy (OMT), Other (specify)

    ▪

    If ‘Clinical & imagine tools for thromboembolic risk’ selected:

    • Thromboembolic risk tools

      • CHADS₂ score, CHA₂DS₂-VASc score, Transthoracic echo (TTE), Transesophageal echo (TEE), CT scan, Cardiac MRI, Framingham Score

    ▪

    If ‘Clinical tools & individual factors for bleeding risk’ selected:

    • Intracerebral bleeding risk tools/factors

      • Patient age, Prior stroke, Type of AF (paroxysmal, persistent, permanent), International normalized ratio (INR), Dementia/cognitive impairment, Falls risk, CHADS₂ score, CHA₂DS₂-VASc score, HEMORR₂HAGES, HAS-BLED, ATRIA, Bleeding Risk Index, Framingham

    ▪

    If ‘Anticoagulation therapy (all oral anticoagulants)’ selected:

    • Anticoagulation therapy

      • Vitamin K antagonists

        ▪

        If ‘Vitamin K antagonists’ selected:

        • Warfarin (Coumadin), Other

          • Newer anticoagulants (direct oral anticoagulants [DOACS])
          • Direct thrombin Inh-DTI:

            ▪

            Dabigatran (Pradaxa)

          • Factor Xa inhibitors:

            ▪

            Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (DU-176b)

    ▪

    If ‘Procedural interventions’ selected:

    • Procedural interventions

      • Surgical LAA resection, Surgical LAA ligation, Surgical LAA occlusion, Surgical – other (specify), Minimally invasive – Atriclip, Minimally invasive – LARIAT, Minimally invasive – other (specify), Transcatheter – WATCHMAN, Transcatheter – AMPLATZER, Transcatheter – PLAATO, Transcatheter – Other (specify)

    ▪

    If ‘Antiplatelet therapy’ selected:

    • Antiplatelet therapy

      • Clopidogrel (Plavix), Aspirin (ASA), ASA + dipyridamole (Aggrenox), Dipyridamole (Persantine), Other (specify)

    ▪

    If ‘Anticoagulation bridging therapies’ selected:

    • Anticoagulation bridging

      • Unfractionated Heparin, Low Molecular Weight Heparin (LMWH), Factor IIa Inhibitors, Factor Xa Inhibitors, Other (specify)

        ▪

        If ‘Unfractionated Heparin’ selected:

        • IV Heparin, Other

        ▪

        If ‘LMWH’ selected:

        • Bemiparin, Certoparin, Dalteparin, Enoxaparin, Nadroparin, Parnaparin, Reviparin, Tinzaparin, Other

        ▪

        If ‘Factor IIa Inhibitors’ selected:

        • Dabigatran, Other

        ▪

        If ‘Factor Xa Inhibitors’ selected:

        • Apixaban, Edoxaban, Rivaroxaban, Other

• Intervention Descriptors

  • Describe the intervention received by each patient group. If the intervention includes medication(s), include pertinent details such as dose, frequency, and potential for adjustment.
• Duration of Follow-up: Record the following elements for Arm 1, Arm 2, Arm 3, and Arm 4 (as applicable)

  • Mean or median (include units)
  • SD, SE, or IQR
  • NR

Clinical/ Patient-Centered Outcomes

• Select the outcome reported on this form:

  • Cerebrovascular infarction
  • Transient ischemic attack (TIA)
  • Systemic embolism (excludes pulmonary embolism and deep vein thrombosis)
  • CV infarction/stroke
  • Ischemic stroke
  • Hemorrhagic stroke
  • Intercerebral hemorrhage
  • Extracranial hemorrhage
  • Subdural hematoma
  • Major bleed
  • Minor bleed
  • Myocardial infarction
  • All-cause mortality
  • CV mortality
  • Infection
  • Heart block
  • Esophageal fistula
  • Cardiac tamponade
  • Health-related QOL/Functional capacity
  • Healthcare utilization – Hospital admissions
  • Healthcare utilization – Other measures
  • Long-term adherence to therapy
  • Cognitive function
  • Time in therapeutic range
  • Composite outcome
  • No clinical or patient-centered outcomes of interest reported
• Define/specify the following for the outcome, if applicable

  • Major bleed type and location
  • Minor bleed type and location
  • Health-related QOL/Functional capacity measure/scale
  • Other Healthcare utilization measure/scale
  • Components of composite outcomes:

    ▪

    Cerebrovascualr infarction; Transient ischemic attach (TIA); Systemic embolism (excludes pulmonary embolism and deep vein thrombosis); CV infarction/stroke; Intercerebral hemorrhage; Subdural hematoma; Major bleed; Minor bleed; Myocardial infarction; All-cause mortality; CV mortality; Infection; Heart block; Esophageal fistula; Tamponade; Dyspepsia; Health-related QOL/Functional capacity; Healthcare utilization – Hospital admissions; Healthcare utilization – Other measures; Long-term adherence to therapy; Time in therapeutic range; Ischemic stroke

• Record additional details to describe outcome measure, as needed
• Timepoints to be abstracted (Check all that apply)

  • Close to 1 month
  • Close to 3 months
  • Close to 6 months
  • Close to 1 yr
  • Most distal timepoint after one year
  • Untimed measure (e.g., time to event)
• For each timepoint, record the following elements as applicable:

  • Specify actual timing of outcome (in months)
  • Group: Arm 1, Arm 2, Arm 3, Arm 4
  • N Analyzed (enter UNK if unknown)
  • Unadjusted Result

    ▪

    Mean

    ▪

    Median

    ▪

    Mean within group change

    ▪

    Mean between group change

    ▪

    Number of patients with outcome

    ▪

    % of patients with outcome

    ▪

    Events/denominator

    ▪

    Odds ratio

    ▪

    Hazard ratio

    ▪

    Relative risk

    ▪

    Other (specify)

  • Unadjusted Result Variability

    ▪

    Standard Error (SE)

    ▪

    Standard Deviation (SD)

    ▪

    IQR

    ▪

    95% CI

    ▪

    Other % CI (specify)

    ▪

    Other (specify)

  • Unadjusted Result, p-value between groups
  • Unadjusted Result, Reference group (for comparison between groups)
  • Adjusted Result

    ▪

    Mean

    ▪

    Median

    ▪

    Mean within group change

    ▪

    Mean between group change

    ▪

    Number of patients with outcome

    ▪

    % of patients with outcome

    ▪

    Events/denominator

    ▪

    Odds ratio

    ▪

    Hazard ratio

    ▪

    Relative risk

    ▪

    Other (specify)

  • Adjusted Result Variability

    ▪

    Standard Error (SE)

    ▪

    Standard Deviation (SD)

    ▪

    IQR

    ▪

    95% CI

    ▪

    Other % CI (specify)

    ▪

    Other (specify)

  • Adjusted Result, p-value between groups
  • Adjusted Result, Reference group (for comparison between groups)
  • If adjusted data is recorded, indicate the adjustments applied
• Does the study report any subgroup analyses for this outcome? (Yes/No)

  • If Yes, describe the subgroup analyses and summarize results
• Comments

Adverse Events

• Are adverse events reported? (Yes/No)
• Record the Number of patients, % of patients, and exact p-value for the Total Population, Arm 1, Arm 2, Arm 3, and Arm 4 (as applicable) for the following:

  • Infection
  • Heart block
  • Esophageal fistula
  • Tamponade
  • Dyspepsia
• Does the study report any AE subgroup analyses? (Yes/No)

  • If Yes, describe the subgroup analyses and summarize results
• Comments

KQ1/2 Diagnostic Efficacy

• Type of risk being evaluated

  • Thromboembolic risk
  • Intracerebral hemorrhage bleeding risk
• Tool or individual risk factor being tested

  • CHADS₂ score
  • CHA₂DS₂-VASc score
  • ABC stroke risk score
  • Transthoracic echo (TTE)
  • Transesophageal echo (TEE)
  • CT scan
  • Cardiac MRI
  • HEMORR₂HAGES
  • HAS-BLED
  • ATRIA
  • Framingham score
  • Bleeding Risk Index
  • Patient age
  • Prior stroke
  • Type of AF (paroxysmal, persistent, permanent)
  • International normalized ratio (INR)
  • Dementia/cognitive impairment
  • Falls risk
  • INR level
  • Duration and frequency of AF
  • Presence of heart disease
  • Presence and severity of CKD
  • DM
  • Sex
  • Race/ethnicity
  • Cancer
  • HIV
• Additional details describing risk being evaluated
• Outcomes reported on this form for this tool or risk factor (Select all that apply): Diagnostic Accuracy; Diagnostic Thinking/Therapeutic Efficacy; Patient Outcome Efficacy

  • If Diagnostic Accuracy:

    ▪

    Timing of the outcome data reported

    ▪

    Total Population, Group 1, Group 2, Group 3, Group 4, Group 5, Group 6

    • N and %
    • C statistic
    • C statistic CI (Lower – Upper bound)

      • 95% CI
      • Other % (specify)
    • Hazard Ratio
    • Hazard Ratio (Lower – Upper bound)

      • 95% CI
      • Other % (specify)
    • Event rate (define)
    • Event rate (Lower – Upper bound)

      • 95% CI
      • Other % (specify)
    • True positive (# patients)
    • True negative (# patients)
    • False positive (# patients)
    • False negative (# patients)
    • Indeterminate/inadequate results (# patients)
    • Sensitivity (%)
    • Sensitivity (SD)
    • Sensitivity CI (Lower – Upper bound)

      • 95% CI
      • Other % (specify)
    • Specificity (%)
    • Specificity (SD)
    • Specificity CI (Lower – Upper bound)

      • 95% CI
      • Other % (specify)
    • Positive predictive value (%)
    • Positive predictive value (Std dev)
    • Positive predictive value (Lower – Upper bound)

      • 95% CI
      • Other % (specify)
    • Negative predictive value (%)
    • Negative predictive value (SD)
    • Negative predictive value (Lower – Upper bound)

      • 95% CI
      • Other % (specify)
    • Positive likelihood ratio
    • Negative likelihood ratio
    • Other (specify)

  • If Diagnostic Thinking/Therapeutic Efficacy: Describe
  • If Patient Outcome Efficacy: Describe
• Does the study report any subgroup analyses for this tool/ outcome? (Yes/No)

  • If Yes, describe the subgroup analyses and summarize results
• QUADAS 2 Tool for Quality Assessment of Study of Diagnostic Accuracy. (2017 and 2013 Studies) Indicate Yes, No, or Unclear for the following:

  • Signaling questions

    ▪

    Patient Selection

    • Was a consecutive or random sample of patients enrolled?
    • Was a case-control design avoided?
    • Did the study avoid inappropriate exclusions?

    ▪

    Index Test

    • Were the index test results interpreted without knowledge of the results of the reference standard?
    • If a threshold was used, was it pre-specified?

    ▪

    Reference Standard

    • Is the reference standard likely to correctly classify the target condition?
    • Were the reference standard results interpreted without knowledge of the results of the index test?

    ▪

    Flow & Timing

    • Was there an appropriate interval between index test(s) and reference standard?
    • Did all patients receive a reference standard?
    • Did all patients receive the same reference standard?
    • Were all patients included in the analysis?

  • Risk of bias

    ▪

    Patient Selection

    • Could the selection of patients have introduced bias?

    ▪

    Index Test

    • Could the conduct or interpretation of the index test have introduced bias?

    ▪

    Reference Standard

    • Could the reference standard, its conduct or its interpretation have introduced bias?

    ▪

    Flow & Timing

    • Could the patient flow have introduced bias?

  • Concerns regarding applicability

    ▪

    Patient Selection

    • Are there concerns that the included patients do not match the review question?

    ▪

    Index Test

    • Are there concerns that the index test, its conduct, or interpretation differ from the review question?

    ▪

    Reference Standard

    • Are there concerns that the target condition as defined by the reference standard does not match the review question?

• Overall study rating

  • High risk of bias/ Low risk of bias/ Unclear
• Comments
• ROBINS-I (The Risk of Bias in Non-Randomized Studies—of Interventions). (2017 Studies Only) Indicate Yes, No, or Unclear for the following:

  • Bias due to confounding

    ▪

    Was there any bias arising in the randomization process or due to confounding?

  • Bias in selection of participants into the study

    ▪

    Was there any bias in selecting participants into the study?

  • Bias in classification of interventions

    ▪

    Was there any bias in classifying interventions?

  • Bias due to deviations from intended intervention

    ▪

    Was there any bias due to departures from intended interventions?

  • Bias due to missing data

    ▪

    Was there any bias due to missing data?

  • Bias in measurement of outcomes

    ▪

    Was there any bias in the measurement of outcomes?

  • Bias in selection of the reported result

    ▪

    Was there any bias in reporting results selectively?

• Overall Bias

  • Risk of Bias Judgment:

    ▪

    Low/Moderate/High

• Overall ROB outcome-specific quality rating

  • Do you think that any of the outcomes abstracted for this study should be assigned a quality rating DIFFERENT from the overall study rating?

    ▪

    No/Yes

  • Comments
• Cochrane Quality Tool (2017 Studies Only). Select Low/High/Unclear risk of bias for each of the following questions:

  • Random sequence generation

    ▪

    Low risk/High risk/Unclear risk

    ▪

    Describe the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups

  • Allocation concealment

    ▪

    Low risk/High risk/Unclear risk

    ▪

    Describe the method used to conceal the allocation sequence in sufficient detail to determine whether intervention allocations could have been foreseen before or during enrollment

  • Blinding of participants and personnel

    ▪

    Low risk/High risk/Unclear risk

    ▪

    Describe all measures used, if any, to blind trial participants and researchers from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective

  • Blinding of outcome assessment

    ▪

    Low risk/High risk/Unclear risk

    ▪

    Describe all measures used, if any, to blind outcome assessment from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective

  • Incomplete Outcome Data

    ▪

    Low risk/High risk/Unclear risk

    ▪

    Describe the completeness of the outcome data for each main outcome, including attrition and exclusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition or exclusions where reported, and any reinclusions in analyses for the review

  • Selective Reporting

    ▪

    Low risk/High risk/Unclear risk

    ▪

    State how selective outcome reporting was examined and what was found

  • Other Bias

    ▪

    Low risk/High risk/Unclear risk

    ▪

    State any important concerns about bias not covered in the other domains in the tool

• Overall Study Quality Rating

  • Good/Fair/Poor
• Overall ROB Quality Rating

  • Do you think that any of the outcomes abstracted for this study should be assigned a quality rating DIFFERENT from the overall study rating?

    ▪

    No/Yes

  • Comments

Quality (2013 Studies Only)

• Study Type (select one): RCT, Cohort, Case-control, Cross-sectional
• If RCT, select Yes/No/Unclear for each of the following questions:

  • Selection Bias

    ▪

    Was the allocation sequence generated adequately (e.g., random number table, computer-generated randomization)?

    ▪

    Was the allocation of treatment adequately concealed (e.g., pharmacy-controlled randomization or use of sequentially numbered sealed envelopes)?

    ▪

    Were participants analyzed within the groups they were originally assigned to?

    ▪

    Does the design or analysis control account for important confounding and modifying variables through matching, stratification, multivariable analysis, or other approaches?

  • Performance Bias

    ▪

    Did researchers rule out any impact from a concurrent intervention or an unintended exposure that might bias results?

    ▪

    Did the study maintain fidelity to the intervention protocol?

  • Attrition Bias

    ▪

    If attrition (overall or differential nonresponse, dropout, loss to follow-up, or exclusion of participants) was a concern, were missing data handled appropriately (e.g., intention-to-treat analysis and imputation)?

  • Detection Bias

    ▪

    In prospective studies, was the length of follow-up different between the groups, or in case-control studies, was the time period between the intervention/exposure and outcome different for cases and controls?

    ▪

    Were the outcome assessors blinded to the intervention or exposure status of participants?

    ▪

    Were interventions/exposures assessed/defined using valid and reliable measures, implemented consistently across all study participants?

    ▪

    Were outcomes assessed/defined using valid and reliable measures, implemented consistently across all study participants?

  • Reporting Bias

    ▪

    Were the potential outcomes prespecified by the researchers? Are all prespecified outcomes reported?

• If Cohort, select Yes/No/Unclear for each of the following questions:

  • Selection Bias

    ▪

    Were participants analyzed within the groups they were originally assigned to?

    ▪

    Did the study apply inclusion/exclusion criteria uniformly to all comparison groups?

    ▪

    Did the strategy for recruiting participants into the study differ across study groups?

    ▪

    Does the design or analysis control account for important confounding and modifying variables through matching, stratification, multivariable analysis, or other approaches?

  • Performance Bias

    ▪

    Did researchers rule out any impact from a concurrent intervention or an unintended exposure that might bias results?

    ▪

    Did the study maintain fidelity to the intervention protocol?

  • Attrition Bias

    ▪

    If attrition (overall or differential nonresponse, dropout, loss to follow-up, or exclusion of participants) was a concern, were missing data handled appropriately (e.g., intention-to-treat analysis and imputation)?

  • Detection Bias

    ▪

    In prospective studies, was the length of follow-up different between the groups, or in case-control studies, was the time period between the intervention/exposure and outcome different for cases and controls?

    ▪

    Were the outcome assessors blinded to the intervention or exposure status of participants?

    ▪

    Were interventions/exposures assessed/defined using valid and reliable measures, implemented consistently across all study participants?

    ▪

    Were outcomes assessed/defined using valid and reliable measures, implemented consistently across all study participants?

    ▪

    Were confounding variables assessed using valid and reliable measures, implemented consistently across all study participants?

  • Reporting Bias

    ▪

    Were the potential outcomes prespecified by the researchers? Are all prespecified outcomes reported?

• If Case-Control, select Yes/No/Unclear for each of the following questions:

  • Selection Bias

    ▪

    Were cases and controls selected appropriately (e.g., appropriate diagnostic criteria or definitions, equal application of exclusion criteria to case and controls, sampling not influenced by exposure status) (Yes/No/Unclear)

    ▪

    Does the design or analysis control account for important confounding and modifying variables through matching, stratification, multivariable analysis, or other approaches?

  • Performance Bias

    ▪

    Did researchers rule out any impact from a concurrent intervention or an unintended exposure that might bias results?

    ▪

    Did the study maintain fidelity to the intervention protocol?

  • Attrition Bias

    ▪

    If attrition (overall or differential nonresponse, dropout, loss to follow-up, or exclusion of participants) was a concern, were missing data handled appropriately (e.g., intention-to-treat analysis and imputation)?

  • Detection Bias

    ▪

    In prospective studies, was the length of follow-up different between the groups, or in case-control studies, was the time period between the intervention/exposure and outcome different for cases and controls?

    ▪

    Were the outcome assessors blinded to the intervention or exposure status of participants?

    ▪

    Were interventions/exposures assessed/defined using valid and reliable measures, implemented consistently across all study participants?

    ▪

    Were outcomes assessed/defined using valid and reliable measures, implemented consistently across all study participants?

    ▪

    Were confounding variables assessed using valid and reliable measures, implemented consistently across all study participants?

  • Reporting Bias

    ▪

    Were the potential outcomes prespecified by the researchers? Are all prespecified outcomes reported?

• If Cross-sectional, select Yes/No/Unclear for each of the following questions:

  • Selection Bias

    ▪

    Did the study apply inclusion/exclusion criteria uniformly to all comparison groups?

    ▪

    Does the design or analysis control account for important confounding and modifying variables through matching, stratification, multivariable analysis, or other approaches?

  • Performance Bias

    ▪

    Did researchers rule out any impact from a concurrent intervention or an unintended exposure that might bias results?

  • Attrition Bias

    ▪

    If attrition (overall or differential nonresponse, dropout, loss to follow-up, or exclusion of participants) was a concern, were missing data handled appropriately (e.g., intention-to-treat analysis and imputation)?

  • Detection Bias

    ▪

    Were the outcome assessors blinded to the intervention or exposure status of participants?

    ▪

    Were interventions/exposures assessed/defined using valid and reliable measures, implemented consistently across all study participants?

    ▪

    Were outcomes assessed/defined using valid and reliable measures, implemented consistently across all study participants?

    ▪

    Were confounding variables assessed using valid and reliable measures, implemented consistently across all study participants?

  • Reporting Bias

    ▪

    Were the potential outcomes prespecified by the researchers? Are all prespecified outcomes reported?

• Other Bias

  • If applicable, describe any other concerns that may impact risk of bias
• Overall Study Rating (Good/Fair/Poor)

  • Good (low risk of bias). These studies have the least bias, and the results are considered valid. These studies adhere to the commonly held concepts of high quality, including the following: a clear description of the population, setting, approaches, and comparison groups; appropriate measurement of outcomes; appropriate statistical and analytical methods and reporting; no reporting errors; a low dropout rate; and clear reporting of dropouts.
  • Fair. These studies are susceptible to some bias, but not enough to invalidate the results. They do not meet all the criteria required for a rating of good quality because they have some deficiencies, but no flaw is likely to cause major bias. The study may be missing information, making it difficult to assess limitations and potential problems.
  • Poor (high risk of bias). These studies have significant flaws that may have invalidated the results. They have serious errors in design, analysis, or reporting; large amounts of missing information; or discrepancies in reporting.
  • If the study is rated as “Fair” or “Poor,” provide rationale.

Applicability – Use the PICOS format to identify specific issues, if any, that may limit the applicability of the study to this review.

• Population (P)

  • Narrow eligibility criteria and exclusion of those with comorbidities
  • Large differences between demographics of study population and community patients
  • Narrow or unrepresentative severity, stage of illness, or comorbidities
  • Run-in period with high-exclusion rate for nonadherence or side effects
  • Event rates much higher or lower than observed in population-based studies
• Intervention (I)

  • Doses or schedules not reflected in current practice
  • Monitoring practices or visit frequency not used in typical practice
  • Older versions of an intervention no longer in common use
  • Cointerventions that are likely to modify effectiveness of therapy
  • Highly selected intervention team or level of training/proficiency not widely available
• Comparator (C)

  • Inadequate comparison therapy
  • Use of substandard alternative therapy
• Outcomes (O)

  • Composite outcomes that mix outcomes of different significance
  • Short-term or surrogate outcomes
• Setting (S)

  • Standards of care differ markedly from setting of interest
  • Specialty population or level of care differs from that seen in community
• Comments