Levels of evidence. From the Oxford Centre for Evidence-based Medicine, available from http://www.cebm.net/index.aspx?o=1047; with permission.
| Level | Therapy/Prevention, Etiology/Harm | Prognosis |
|---|---|---|
| 1a | SR (with homogeneity*) of RCT | SR (with homogeneity*) of inception cohort studies; CDR† validated in different populations |
| 1b | Individual RCT (with narrow confidence interval‡) | Individual inception cohort study with ≥ 80% followup; CDR† validated in a single population |
| 1c | All or none§ | All or none case series |
| 2a | SR (with homogeneity*) of cohort studies | SR (with homogeneity*) of either retrospective cohort studies or untreated control groups in RCT |
| 2b | Individual cohort study (including low quality RCT; e.g., < 80% followup) | Retrospective cohort study or followup of untreated control patients in an RCT; derivation of CDR† or validated on split-sample§§§ only |
| 2c | “Outcomes” research; ecological studies | “Outcomes” research |
| 3a | SR (with homogeneity*) of case-control studies | |
| 3b | Individual case-control study | |
| 4 | Case series (and poor quality cohort and case-control studies§§) | Case-series (and poor quality prognostic cohort studies**) |
| 5 | Expert opinion without explicit critical appraisal, or based on physiology, bench research, or “first principles” | Expert opinion without explicit critical appraisal, or based on physiology, bench research, or “first principles” |
Users can add a minus sign “–” to denote the level if that fails to provide a conclusive answer because of: EITHER a single result with a wide confidence interval (such that, for example, an ARR in an RCT is not statistically significant but whose confidence intervals fail to exclude clinically important benefit or harm); OR a SR with troublesome (and statistically significant) heterogeneity. Such evidence is inconclusive, and therefore can generate only Grade D recommendations.
↵* Homogeneity: A SR free of worrisome variations (heterogeneity) in the directions and degrees of results between individual studies. Not all SR 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. (Algorithms or scoring systems that lead to a prognostic estimation or a diagnostic category).
↵‡ See note no. 2 for advice on how to understand, rate, and use trials or other studies with wide confidence intervals.
↵§ Met when all patients died before the prescription became available, but some now survive on it; or when some patients died before the prescription became available, but none now die on it.
§§ Poor quality cohort study: 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 followup 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.
↵** Poor quality prognostic cohort study: one in which sampling was biased in favor 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, nonobjective way, or there was no correction for confounding factors.
“Extrapolations”: where data are used in a situation that has potentially clinically more important differences than the original study situation.
SR: systemic review; RCT: randomized controlled trial; CDR: clinical decision rule.