Class I: evidence provided by a prospective, randomized, controlled clinical trial with masked outcome assessment, in a representative population. The following are required: (a) Primary outcome(s) is/are clearly defined; (b) exclusion/inclusion criteria are clearly defined; (c) adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias; and (d) relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.
Class II: evidence provided by a prospective matched group cohort study in a representative population with masked outcome assessment that meets a–d above or a randomized control trial in a representative population that lacks one criteria of a–d.
Class III: all other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment.
Class IV: evidence from uncontrolled studies, case series, case reports, or expert opinion.