Definitions of the strength of the recommendations (A, B, C, U) and classification of the evidence (Class I through Class IV) are provided at the end of the "Major Recommendations" field.
Practice Recommendations
- On the basis of evidence from a single Class I study and a few Class II or III studies, it appears that mitoxantrone may have a beneficial effect on disease progression in patients with multiple sclerosis (MS) whose clinical condition is deteriorating (Type B recommendation). In general, however, this agent is of limited use and of potentially great toxicity. Therefore, it should be reserved for patients with rapidly advancing disease who have failed other therapies.
- On the basis of several consistent Class II and III studies, mitoxantrone probably reduces the clinical attack rate and reduces attack-related magnetic resonance imaging (MRI) outcomes in patients with relapsing MS (Type B recommendation). The potential toxicity of mitoxantrone, however, considerably limits its use in patients with relapsing forms of MS.
- Because of the potential toxicity of mitoxantrone, it should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapeutic agents (Type A Recommendation). In addition, patients being treated with mitoxantrone should be monitored routinely for cardiac, liver, and kidney function abnormalities (Type A Recommendation).
Definitions:
Rating of Recommendations
A = Established as effective, ineffective, or harmful for the given condition in the specified population.
B = Probably effective, ineffective, or harmful for the given condition in the specified population.
C = Possibly effective, ineffective, or harmful for the given condition in the specified population.
U = Data inadequate or conflicting; given current knowledge, treatment is unproven.
Translation of Evidence to Recommendations
Level A rating requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating requires at least one convincing class II study or at least three consistent class III studies.
Level C rating requires at least two convincing and consistent class III studies.
Rating of therapeutic article
Class I: Prospective, randomized, controlled clinical trial (RCT) with masked outcome assessment, in a representative population. The following are required:
- Primary outcome(s) is/are clearly defined.
- Exclusion/inclusion criteria are clearly defined.
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias.
- 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 criterion 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.