Appendix 1 AAN evidence classification scheme for a therapeutic article and linkage to level of recommendation

Rating of therapeutic articleRating of recommendationTranslation of evidence to recommendations
* In exceptional cases, one convincing class I study may suffice for an “A” recommendation if 1) all criteria met, 2) magnitude of effect ≥5, and 3) narrow confidence intervals (lower limit >2).
† Objective outcome measurement—an outcome measure that is unlikely to be affected by an observer’s (patient, treating physician, investigator) expectation or bias (e.g., blood tests, administrative outcome data).
Class I: Prospective, randomized, controlled clinical trial with masked outcome assessment, in a representative population.Level A = Established as effective, ineffective or harmful (or established as useful/predictive or not useful/predictive) for the given condition in the specified populationLevel A rating requires at least two consistent class I studies*
The following are required:
a) primary outcome(s) is/are clearly defined
b) exclusion/inclusion criteria are clearly defined
c) adequate accounting for drop-outs and cross-overs with numbers sufficiently low to have minimal potential for bias
d) relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.
Class II: Prospective matched group cohort study in a representative population with masked outcome assessment that meets a–d above OR a RCT in a representative population that lacks one criteria a–d.Level B = Probably effective, ineffective or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified populationLevel B rating requires at least one class I study or two consistent class II studies
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome is independently assessed, or independently derived by objective outcome measurement.Level C = Possibly effective, ineffective or harmful (or possibly useful/predictive or not useful/predictive) for the given condition in the specified populationLevel C rating requires at least one class II study or two consistent class III studies
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion.Level U = Data inadequate or conflicting. Given current knowledge, treatment (test, predictor) is unprovenStudies not meeting criteria for class I–class III