Oxford Centre for Evidence-based Medicine: levels of evidence
| Level | Therapy/prevention/ aetiology/harm | Prognosis | Diagnosis | Differential diagnosis/ symptom prevalence study | Economic and decision analyses |
|---|---|---|---|---|---|
| SR, Systematic review; RCT, randomised controlled trial. | |||||
| *Homogeneity means a systematic review that is free from worrisome variations (heterogeneity) in the results between individual studies. | |||||
| †Clinical decision rules are algorithms or scoring systems leading to a diagnostic category or prognostic estimation. | |||||
| ‡All patients died before the therapy became available, but some survive now on it, or some died before therapy became available, but none now die on it. | |||||
| ¶Validating studies test the quality of a diagnostic test, based on prior evidence. An exploratory study collects information and (for example, using a regression analysis) identifies which factors are significant | |||||
| §Good, better, bad, and worse refer to the comparison between treatments in terms of their clinical benefit and risks. | |||||
| **Poor quality cohort study is one that failed to 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 and control for confounders and/or to complete long follow up. Poor quality case control study is one that failed to 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 and control for confounders. | |||||
| ††Poor quality prognostic cohort study is one with biased sampling in favour of patients who already had the target outcome, or outcomes were measured in <80%, or outcomes were determined in an unblended non-objective way, or there was no correction for the confounders. | |||||
| ‡‡An “absolute SpPin” is a diagnostic finding whose specificity is so high that a positive result confirms the diagnosis. “Absolute SnNout” is a diagnostic finding whose sensitivity is so high that negative results rule out the diagnosis. | |||||
| ¶¶Split sample validation is achieved by collecting all the information in a single tranche and then dividing this into “derivation” and “validation” samples. | |||||
| §§Good follow up is >80%, with adequate time for alternative diagnosis to emerge (for example, 1–8 months acute, 1–5 years chronic). | |||||
| ***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 equally/more expensive | |||||
| 1a | SR (with homogeneity*) of RCTs | SR (with homogeneity*) 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 | SR (with homogeneity*) of prospective cohort studies | 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 | Validating¶ cohort study with good§ reference standards; or CDR† tested within 1 clinical centre | Prospective cohort study with good follow up§§ | Analysis based on clinically sensible costs or alternative systematic reviews of the evidence and including multi-way sensitivity analyses |
| 1c | All or none‡ | All or none case series | Absolute SpPins and SnNouts‡‡ | All or none case series | Absolute better value or worse value analysis*** |
| 2a | SR (with homogeneity*) of cohort studies | SR (with homogeneity*) of either retrospective cohort studies or untreated control groups in RCTs | SR (with homogeneity*) of level >2 diagnostic studies | SR (with homogeneity*) of level 2b and better studies | SR (with homogeneity*) of level >2 economic studies |
| 2b | Individual cohort study (including low quality RCT (<80% follow up) | Retrospective cohort study of follow up of untreated controls in an RCT; Derivation of CDR† or validation on split samples¶¶ only | Exploratory¶ cohort study with good§ reference standards; CDR† after derivation; or validated only on split samples¶¶ or databases | Retrospective cohort study, or poor follow-up | Analysis based on clinically sensible costs or alternatives; limited reviews of the evidence, or single study; and including multi-way sensitivity analysis |
| 2c | “Outcomes” research, ecological studies | “Outcomes” research | Ecological studies | Audit or “outcomes” research | |
| 3a | SR (with homogeneity*) of case control studies | SR (with homogeneity*) of 3b and better studies | SR (with homogeneity*) of 3b and better studies | SR (with homogeneity*) of 3b and better studies | |
| 3b | Individual case control study | Non-consecutive study, or without consistently applied reference standards | Non-consecutive study, or very limited population | Analysis based on limited alternatives or costs, poor quality estimates of data, but including sensitivity analyses incorporating clinically sensible variations | |
| 4 | Case series (and poor quality cohort and case-control studies**) | Case series (and poor quality prognostic cohort studies††) | Case control study, poor or non-dependent reference standards | Case series or supervised reference standards | Analysis with no sensitivity analysis |
| 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” | 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” | Expert opinion without explicit critical appraisal or based on physiology, bench research or “first principles” |