Levels of Evidence

From the Centre for Evidence-Based Medicine, Oxford

For the most up-to-date levels of evidence, see https://www.cebm.net/category/ebm-resources/loe/

Therapy/Prevention/Etiology/Harm:

• 1a: Systematic reviews (with homogeneity ) of randomized controlled trials
• 1a-: Systematic review of randomized trials displaying worrisome heterogeneity
• 1b: Individual randomized controlled trials (with narrow confidence interval)
• 1b-: Individual randomized controlled trials (with a wide confidence interval)
• 1c: All or none randomized controlled trials
• 2a: Systematic reviews (with homogeneity) of cohort studies
• 2a-: Systematic reviews of cohort studies displaying worrisome heterogeneity
• 2b: Individual cohort study or low quality randomized controlled trials <80% follow-up)
• 2b-: Individual cohort study or low quality randomized controlled trials (80% follow-up / wide confidence interval)
• 2c: 'Outcomes' Research; ecological studies
• 3a: Systematic review (with homogeneity) of case-control studies
• 3a-: Systematic review of case-control studies with worrisome heterogeneity
• 3b: Individual case-control study
• 4: Case-series (and poor quality cohort and case-control studies)
• 5: Expert opinion without explicit critical appraisal, or based on physiology, bench research or 'first principles'

Diagnosis

• 1a: Systematic review (with homogeneity) of Level 1 diagnostic studies; or a clinical rule validated on a test set.
• 1a-: Systematic review of Level 1 diagnostic studies displaying worrisome heterogeneity
• 1b: Independent blind comparison of an appropriate spectrum of consecutive patients, all of whom have undergone both the diagnostic test and the reference standard; or a clinical decision rule not validated on a second set of patients
• 1c: Absolute SpPins And SnNouts (An "Absolute SpPin" is a diagnostic finding whose Specificity is so high that a Positive result rules-in the diagnosis. An "Absolute SnNout" is a diagnostic finding whose Sensitivity is so high that a Negative result rules-out the diagnosis).
• 2a: Systematic review (with homogeneity) of Level >2 diagnostic studies
• 2a-: Systematic review of Level >2 diagnostic studies displaying worrisome heterogeneity
• 2b: Any of: 1)independent blind or objective comparison; 2)study performed in a set of non-consecutive patients, or confined to a narrow spectrum of study individuals (or both) all of whom have undergone both the diagnostic test and the reference standard; 3) a diagnostic clinical rule not validated in a test set.
• 3a: Systematic review (with homogeneity) of case-control studies
• 3a-: Systematic review of case-control studies displaying worrisome heterogeneity
• 4: Any of: 1)reference standard was unobjective, unblinded or not independent; 2) positive and negative tests were verified using separate reference standards; 3) study was performed in an inappropriate spectrum of patients.
• 5: Expert opinion without explicit critical appraisal, or based on physiology, bench research or 'first principles'

Prognosis

• 1a: Systematic review (with homogeneity) of inception cohort studies; or a clinical rule validated on a test set.
• 1a-: Systematic review of inception cohort studies displaying worrisome heterogeneity
• 1b: Individual inception cohort study with > 80% follow-up; or a clinical rule not validated on a second set of patients
• 1c: All or none case-series
• 2a: Systematic review (with homogeneity) of either retrospective cohort studies or untreated control groups in RCTs.
• 2a-: Systematic review of either retrospective cohort studies or untreated control groups in RCTs displaying worrisome heterogeneity
• 2b: Retrospective cohort study or follow-up of untreated control patients in an RCT; or clinical rule not validated in a test set.
• 2c: 'Outcomes' research
• 4: Case-series (and poor quality prognostic cohort studies)
• 5: Expert opinion without explicit critical appraisal, or based on physiology, bench research or 'first principles'

Key to interpretation of practice guidelines

Agency for Healthcare Research and Quality:

• A: There is good research-based evidence to support the recommendation.
• B: There is fair research-based evidence to support the recommendation.
• C: The recommendation is based on expert opinion and panel consensus.
• X: There is evidence of harm from this intervention.

USPSTF Guide to Clinical Preventive Services:

• A: There is good evidence to support the recommendation that the condition be specifically considered in a periodic health examination.
• B: There is fair evidence to support the recommendation that the condition be specifically considered in a periodic health examination.
• C: There is insufficient evidence to recommend for or against the inclusion of the condition in a periodic health examination, but recommendations may be made on other grounds.
• D: There is fair evidence to support the recommendation that the condition be excluded from consideration in a periodic health examination.
• E: There is good evidence to support the recommendation that the condition be excluded from consideration in a periodic health examination.

University of Michigan Practice Guideline:

• A: Randomized controlled trials.
• B: Controlled trials, no randomization.
• C: Observational trials.
• D: Opinion of the expert panel.

Other guidelines:

• A: There is good research-based evidence to support the recommendation.
• B: There is fair research-based evidence to support the recommendation.
• C: The recommendation is based on expert opinion and panel consensus.
• X: There is evidence that the intervention is harmful.