Table 1.

AAN classification of evidence [9].

Class	Criteria	Level of evidence	Recommendation
I	Prospective, randomized, controlled, outcome masked, representative population with criteria A–E *	A: Two or more Class I studies	Established as effective, ineffective, or harmful
II	Prospective, matched cohort, representative population, masked outcome and meets A–E * OR RCT with one criteria in A–E * lacking	B: At least one Class I or two Class II	Probably effective, ineffective, or harmful and recommended
III	Controlled trial **, representative population, outcome independent of patient treatment	C: At least one Class II	Possibly effective, ineffective or harmful, may be used at discretion of clinician
IV	Uncontrolled study, case series, case report or expert opinion.	U	Data inadequate or conflicting

* Criteria A-DE: A = Primary outcome(s) clearly defined, B = exclusion/inclusion criteria clearly defined, C = Adequate accounting for drop-outs and cross-over with numbers sufficiently low to have minimal potential for bias, D = relevant baseline characteristics or appropriate statistical adjustment for differences, E = For non-inferiority or equivalence trials claiming to prove efficacy for one or both drugs, the following are also required: 1. The standard treatment used in the study is substantially similar to that used in previous studies establishing efficacy of the standard treatment (e.g., for a drug, the mode of administration, dose, and dosage adjustments are similar to those previously shown to be effective); 2. The inclusion and exclusion criteria for patient selection and the outcomes of patients on the standard treatment are substantially equivalent to those of previous studies establishing efficacy of the standard treatment and 3. The interpretation of the results of the study is based on an observed-case analysis. ** Including well-defined natural history controls or patients serving as their own controls.