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 more than one trial is available, these trials have consistent results. or
- Evidence consists of 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 end points may be considered as Level 1 evidence in some cancer-related cases (e.g., NCI-sponsored cooperative group study or a multicenter 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
- Evidence consists of 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 strong Level 1 evidence when considered alone).
Evidence consisting of a non-blinded, non-randomized trial (i.e., a phase II study) may be considered as Level 2 evidence in some cancer-related cases (i.e., 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
- Evidence consists of expert consensus panel reports or expert reviewers’ 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
- Recommended (Accepted)
The drug or biologic should be used, is recommended/indicated, or is useful/effective/beneficial in most cases. - Reasonable Choice (Accepted, with Possible Conditions) (e.g., treatment option)
The drug or biologic is reasonable to use under certain conditions (e.g., in certain patient groups), can be useful/effective/beneficial, or is probably recommended or indicated. - Not Fully Established (Unclear Risk/Benefit, Equivocal Evidence, Inadequate Data and/or Experience)
Usefulness and/or effectiveness is unknown, unclear, or uncertain or is not well established relative to the standard of care. - Not Recommended (Unaccepted)
The drug or biologic is considered inappropriate, obsolete, or unproven; is not recommended, is not indicated, or is not useful/effective/beneficial; or may be harmful.
