Cannabinoids in Neurologic Conditions

Appendix. American Academy of Neurology Classification of Evidence

Therapeutic

Class I

A randomized, controlled clinical trial of the intervention of interest with masked or objective outcome assessment, in a representative population. Relevant baseline characteristics are presented and substantially equivalent among treatment groups, or there is appropriate statistical adjustment for differences.

The following are also required:

• (a) Concealed allocation

• (b) Primary outcome(s) clearly defined

• (c) Exclusion/inclusion criteria clearly defined

• (d) Adequate accounting for dropouts (with at least 80% of enrolled subjects completing the study) and crossovers with numbers sufficiently low to have minimal potential for bias

• (e) For non-inferiority or equivalence trials claiming to prove efficacy for one or both drugs, the following are also required∗:

  • 1. The authors explicitly state the clinically meaningful difference to be excluded by defining the threshold for equivalence or non-inferiority.

  • 2. 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).

  • 3. The inclusion and exclusion criteria for patient selection and the outcomes of patients on the standard treatment are comparable to those of previous studies establishing efficacy of the standard treatment.

  • 4. The interpretation of the results of the study is based upon a per protocol analysis that takes into account dropouts or crossovers.

Class II

A randomized controlled clinical trial of the intervention of interest in a representative population with masked or objective outcome assessment that lacks one criteria a–e above or a prospective matched cohort study with masked or objective outcome assessment in a representative population that meets b–e above. Relevant baseline characteristics are presented and substantially equivalent among treatment groups, or there is appropriate statistical adjustment for differences.

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.∗∗

Class IV

Studies not meeting Class I, II, or III criteria including consensus or expert opinion.

∗Note that numbers 1–3 in Class Ie are required for Class II in equivalence trials. If any one of the three is missing, the class is automatically downgraded to Class III.

∗∗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).