Rare disease levels of evidence: Time for a new bar?


A report of the Canadian Task Force on the Periodic Health Examination was the first to propose clinical practice recommendations based on evidence in the medical literature, and proposed a rating scheme.1 From that original publication, the categorization of evidence has evolved, with this journal requiring clinical therapeutic studies to provide the level of evidence provided by a report.2 The most rigorous Class I evidence derives from a well-performed randomized controlled clinical trial (RCT). Such trials limit the probability of bias and systematic errors by randomization and masking of treatment assignment. In contrast, Class IV evidence is characterized by retrospective analyses, which have numerous sources of potential bias. However, randomized trials are often not possible because of resource limitations, whether they are financial or organizational. In this issue of Neurology®, Hehir et al.3 identified benefit for rituximab in muscle-specific kinase antibody myasthenia gravis (anti-MuSK MG). Although strictly the report provides Class IV evidence, their unique trial design suggests much greater confidence in rituximab as an effective therapy.


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