Oxford Centre for
Evidence-based Medicine – Levels of Evidence (March 2009)
What are we to do when the irresistible force of the need to offer clinical advice meets with the immovable object of flawed evidence? All we can do is our best: give the advice, but alert the advisees to the flaws in the evidence on which it is based.
The CEBM ?Levels of Evidence 1′ document sets out one approach to systematising this process for different question types.
(For definitions of terms used see our glossary) Level Therapy / Prevention, Aetiology / Harm Prognosis Diagnosis Differential diagnosis / symptom prevalence study SR (with homogeneity*) of prospective cohort studies Economic and decision analyses 1a SR (with SR (with homogeneityhomogeneity*) *) of RCTs of inception cohort studies; CDR” validated in different populations SR (with homogeneity*) of Level 1 diagnostic studies; CDR” with 1b studies from different clinical centres Validating** cohort study with good” ” ” reference standards; or CDR” tested within one clinical centre SR (with homogeneity*) of Level 1 economic studies 1b Individual RCT (with narrow Confidence Interval”?) Individual inception cohort study with > 80% follow-up; CDR” validated in a single population Prospective cohort study with good follow-up**** Analysis based on clinically sensible costs or alternatives; systematic review(s) of the evidence; and including multi-way sensitivity analyses 1c All or none§ All or none Absolute SpPins All or none Absolute case-series and SnNouts” “ case-series better-value or worse-value analyses ” ” ” “ SR (with homogeneity*) of either retrospective cohort studies or untreated control groups in RCTs 2b Individual cohort study (including low quality Retrospective cohort study or follow-up of untreated Exploratory** Retrospective cohort study with cohort study, or good” ” ” referenpoor follow-up ce standards; Analysis based on clinically sensible costs or alternatives; limited review(s) of the evidence, or single studies; and including multi-way sensitivity analyses 2c “Outcomes” Research; Ecological studies “Outcomes” Research Ecological studies Audit or outcomes research SR (with homogeneity*) of Level >2 diagnostic studies SR (with homogeneity*) of 2b and better studies SR (with homogeneity*) of Level >2 economic studies 2a SR (with homogeneity*) of cohort studies RCT; e.g., control CDR” after <80% patients in an derivation, or follow-up) RCT; validated only on Derivation of split-sample§§§ CDR” or or databases validated on split-sample§§§ only 3a SR (with homogeneity*) of SR (with SR (with SR (with homogeneity*) of homogeneity*) homogeneity3b and better of 3b and *) of 3b and case-control studies 3b Individual Case-Control Study studies better studies better studies Analysis based on limited alternatives or costs, poor quality estimates of data, but including sensitivity analyses incorporating clinically sensible variations. Non-consecutive study; or without consistently applied reference standards Non-consecutive cohort study, or very limited population 4 Case-series (and poor quality cohort and case-control studies§§) Case-series (and poor quality prognostic cohort studies***) Expert opinion without explicit critical appraisal, or Case-control Case-series or Analysis with no sensitivity analysis study, poor or superseded non-independent reference reference standards standard 5 Expert opinion without explicit critical appraisal, or based on physiology, Expert opinion without explicit critical appraisal, or based on Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” Expert opinion without explicit critical appraisal, or based on economic theory or “first principles” based on physiology, bench physiology, research or “first bench principles” research or bench “first research or principles” “first principles” Produced by Bob Phillips, Chris Ball, Dave Sackett, Doug Badenoch, Sharon Straus, Brian Haynes, Martin Dawes since November 1998. Updated by Jeremy Howick March 2009.
Notes
Users can add a minus-sign “-” to denote the level of that fails to provide a conclusive answer because:
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EITHER a single result with a wide Confidence Interval OR a Systematic Review with troublesome heterogeneity.
Such evidence is inconclusive, and therefore can only generate Grade D recommendations. * By homogeneity we mean a systematic review that is free of worrisome variations (heterogeneity) in the directions and degrees of results between individual studies. Not all systematic reviews with statistically significant heterogeneity need be worrisome, and not all worrisome heterogeneity need be statistically significant. As noted above, studies displaying worrisome heterogeneity should be tagged with a “-” at the end of their designated level. Clinical Decision Rule. (These are algorithms or scoring systems that lead to a prognostic estimation or a diagnostic category.) See note above for advice on how to understand, rate and use trials or other studies with wide confidence intervals. Met when all patients died before the Rx became available, but some now survive on it; or when some patients died before the Rx became available, but none now die on it. By poor quality cohort study we mean one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective way in both exposed and non-exposed individuals and/or failed to identify or appropriately control known confounders and/or failed to carry out a sufficiently long and complete follow-up of patients. By poor quality case-control study we mean one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective way in both cases and controls and/or failed to identify or appropriately control known confounders. §§§ Split-sample validation is achieved by collecting all the information in a single tranche, then artificially dividing this into “derivation” and “validation” samples. ” “ 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. Good, better, bad and worse refer to the comparisons between treatments in terms “ “? § §§ “?”? of their clinical risks and benefits. ” ” “ Good reference standards are independent of the test, and applied blindly or objectively to applied to all patients. Poor reference standards are haphazardly applied, but still independent of the test. Use of a non-independent reference standard (where the ?test? is included in the ?reference?, or where the ?testing? affects the ?reference?) implies a level 4 study. ” ” ” “ Better-value treatments are clearly as good but cheaper, or better at the same or reduced cost. Worse-value treatments are as good and more expensive, or worse and the equally or more expensive. ** Validating studies test the quality of a specific diagnostic test, based on prior evidence. An exploratory study collects information and trawls the data (e.g. using a regression analysis) to find which factors are ?significant?. By poor quality prognostic cohort study we mean one in which sampling was biased in favour of patients who already had the target outcome, or the measurement of outcomes was accomplished in <80% of study patients, or outcomes were determined in an unblinded, non-objective way, or there was no correction for confounding factors. **** Good follow-up in a differential diagnosis study is >80%, with adequate time for alternative diagnoses to emerge (for example 1-6 months acute, 1 – 5 years chronic) *** Grades of Recommendation
A consistent level 1 studies B consistent level 2 or 3 studies or extrapolations from level 1 studies C level 4 studies or extrapolations from level 2 or 3 studies D level 5 evidence or troublingly inconsistent or inconclusive studies of any level “Extrapolations” are where data is used in a situation that has potentially clinically important differences than the original study situation.