Levels of Evidence

Level 1 (likely reliable) Evidence - representing research results addressing clinical outcomes and meeting an extensive set of quality criteria which minimizes bias.

DynaMed criteria for level 1 (likely reliable) evidence labels

• DynaMed criteria for level 1 (likely reliable) evidence for conclusions from a systematic review
  1. Full-text report available in English (or language well understood by participating editor)
  2. Clinical outcome (also called patient-oriented outcomes)
  3. Systematic search
  4. Explicit inclusion criteria
  5. Systematic selection of included studies
  6. Evaluation of study quality
  7. Additional criteria if meta-analysis
     • Studies are clinically appropriate for pooled analysis (reasonably similar populations, interventions, methodology and outcomes)
     • Meta-analysis not limited by statistically significant heterogeneity
  8. Conclusion based on primary studies meeting Level 1 evidence criteria (see appropriate criteria set below)
  9. Adequate statistical power
  10. No other factors contributing substantial bias, such as:
      • Inclusion criteria that appear to inappropriately exclude important evidence
      • Subgroup analysis
      • Indirect comparisons
• DynaMed criteria for level 1 (likely reliable) evidence for interventional conclusions (conclusions that an intervention does or does not change an outcome)
  1. Full-text report available in English (or language well understood by participating editor)
  2. Clinical outcome (also called patient-oriented outcomes)
  3. Random allocation method (i.e. not assigned by date of birth, day of presentation, “every other”)
  4. Allocation concealment
  5. Blinding of all persons (patient, treating clinician, outcome assessor) if possible
  6. Intention-to-treat analysis comparing groups according to randomization
  7. Follow-up (endpoint assessment) of at least 80% of study entrants AND adequate such that losses to follow-up could not materially change results
  8. Adequate statistical power
  9. In cases of early trial termination
     • Stopping decision made by independent monitoring board without competing interests
     • Interim analysis is preplanned
     • Statistical stopping rule accounts for multiple assessments (lower p value threshold) for early termination for benefit
     • Clinically significant differences with absolute benefit/harm warranting early termination
     • For classification of level of evidence for a specific outcome (which may be different than outcome used for stopping decision), outcome has sufficient statistical results such that trial continuation would be unlikely to change these results
  10. No other factors contributing substantial bias, such as
      • Differences in management between groups other than the intervention being studied
      • Differential loss to follow-up
      • Posthoc analysis
      • Subgroup analysis
      • Baseline differences between groups
      • Unclear how missing data is accounted for
• DynaMed criteria for level 1 (likely reliable) evidence for diagnostic conclusions
  1. Full-text report available in English (or language well understood by participating editor)
  2. Patient sample represents patients for whom testing would be appropriate (i.e., diagnostic uncertainty)
  3. Reliable reference standard
  4. Reference standard and test under investigation each applied to all study subjects (with and without diagnosis)
  5. Test under investigation conducted blinded to and independent of reference standard results
  6. Reference standard conducted blinded to and independent of results of test under investigation
  7. Adequate follow-up and accounting for subjects
  8. Adequate statistical power
  9. Test studied in independent validation cohort (i.e., a cohort that is independent from the derivation of the test or specific cutoff value being investigated)
  10. No other factors contributing substantial bias, such as
      • Time delay between test under investigation and reference standard sufficient for change in disease status
      • Analysis not accounting for indeterminate results
      • High or unknown variation in test interpretation among observers
• DynaMed criteria for level 1 (likely reliable) evidence for prognostic conclusions
  1. Full-text report available in English (or language well understood by participating editor)
  2. Inception cohort study
  3. Prospective follow-up
  4. Representative sample at similar point in course of disease
  5. Follow-up sufficiently long and complete
  6. Systematic (unbiased) evaluation of outcomes
  7. Adjustments for important confounding factors
  8. Adequate statistical power
  9. Additional criteria for prediction rules
     • Validation in relevant population
     • Validation in sample independent from derivation cohort
  10. No other factors contributing substantial bias

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