AHFS Levels of Evidence Rating System

Evidence Levels

Level 1: High Strength/Quality

• Evidence consists of at least one randomized, double-blind trial without important limitations (i.e., large treatment effect); intent-to-treat analysis used, confidence intervals reported. If one more than one trial is available, these trials have consistent results.

  or

• A meta-analysis of such trials with consistent results (i.e., low heterogeneity)

Evidence consisting of a non-blinded or single-blinded trial that meets study objective endpoints may be considered as Level 1 evidence in some cancer-related cases (e.g., NCI-sponsored cooperative group study or a multi-center trial)

Level 2: Moderate Strength/Quality

• Evidence consists of at least one non-blinded or single-blinded, randomized clinical trial

  or

• Evidence consists of at least one non-blinded or single-blinded, non-randomized clinical trial

  or

• A meta-analysis of randomized, controlled clinical trials with heterogenous results if reasons for heterogeneity in individual trials are adequately discussed

  or

• Evidence consists of at least one randomized, controlled clinical trial, but with important methodological limitations (e.g., large number of patients lost to follow-up and/or no intent-to-treat analysis and/or important data not recorded).

  or

• Evidence is inconsistent (i.e., two or more randomized controlled trials with unexplained, widely varying estimates of treatment effects, even if results of individual trials would constitute a strong Level 1 evidence when considered alone)

Evidence consisting of a non-blinded, non-randomized trial (e.g., a phase II study) may be considered as Level 2 in some cancer-related cases (e.g., rare cancers or cancers with limited available treatment options)

Level 3: Low Strength/Quality

• Evidence consists of observational studies, case reports or case series; may also include randomized-clinical trials with multiple serious deficiencies or study limitations.

Level 4: Opinion/Experience

• Expert consensus panel reports or expert reviewer’s comments

Strength of Study End Points

(listed in descending order)

• Overall Survival (total mortality)
• Cause-specific Mortality
• Quality of Life
• Indirect Surrogates
  • Overall response rate (ORR)
  • Progression-free survival (PFS)
  • Disease-free survival (DFS)

AHFS Grades of Recommendation

A- Recommended - Accepted
(e.g., should be used, is recommended, is useful/effective/beneficial in most cases)

B- Reasonable Choice (Accepted, with Possible Conditions) (e.g., option)
(e.g., is reasonable to use in certain subgroups or clinical scenarios)

C- Not Fully Established (Unclear risk/benefit, equivocal evidence, inadequate data and/or experience)
(e.g., usefulness/effectiveness unknown/unclear/uncertain or not well established relative to standard of care)

D- Not Recommended (Unaccepted)
(e.g., considered inappropriate, obsolete, or unproven)