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Randomized, blinded, controlled experiments have often been considered the highest level of evidence in the methodological hierarchy. This Viewpoint discusses the strengths and limitations of both observational studies and randomized controlled trials, and the benefits that can be gained by researchers and clinicians through the appreciation of both methods.
The introduction of tumor necrosis factor antagonist therapies has transformed expectations for the management of rheumatoid arthritis. Although all available agents have demonstrated comparable clinical efficacy, heterogeneity of response and treatment failure has been observed in up to 40% of patients. This Viewpoint will discuss the use of alternative TNF-blocking therapy in patients who have failed treatment.
Both systemic and local biomechanical factors contribute to joint degeneration in osteoarthritis, and diverse molecular mechanisms of the disease pathogenesis are being uncovered. Can mechanism-based treatments be developed for patients with this disease, as has happened with rheumatoid arthritis, and what are the challenges in drug development?
Nonpharmacological treatments cannot be assessed according to the same standards used for pharmacological treatments. This Review gives guidance on trial designs that address specific methodological issues encountered in assessment of nonpharmacological treatments, and on interpretation of data from such trials.
The risk of cardiovascular disease is increased in patients with rheumatoid arthritis, as discussed in this Review. Joan M Bathon and colleagues outline some preliminary recommendations for how these complications can be prevented and managed by aggressive control of both synovitis and conventional cardiovascular risk factors.
Our comprehension of the role of the complement system in autoimmunity and tissue injury in systemic lupus erythematosus has progressed since mice lacking early components of the complement pathway were developed. Elucidation of these disease mechanisms might lead to the development of improved therapeutic approaches.
