Review of head-to-head study designs in rheumatoid arthritis.
Treatment options available to patients with rheumatoid arthritis (RA) are ever-changing, and understanding the similarities and differences of efficacy and safety between different RA therapies is of key importance in order to facilitate treatment decisions by both the patient and physician. Very few head-to-head, peer-reviewed trials exist; instead, evidence for efficacy of treatments is often ascertained from placebo-controlled trials, registries and meta-analyses, which often do not sufficiently address the relative effectiveness of two medications.



A targeted review of indirect comparison methods, and ongoing and published clinical studies assessing the efficacy and safety, and the comparative efficacy and safety of biologic disease modifying antirheumatic drugs in RA.



Critical elements that should be considered when designing head-to head trials are described using examples of true head-to-head and placebo-controlled randomized controlled trials (RCTs). The appropriate use of head-to-head trial designs is demonstrated by reviewing different examples of well-designed clinical trials, and an overview is presented of the challenges associated with indirect comparisons. This review also examines the use of studies comparing therapies to placebo, highlighting the difficulties associated with the interpretation of these studies.



For comparative trials to contribute to evidence-based decision making in the treatment of RA, patient populations and treatment regimens as similar as possible to those used in routine clinical practice should be employed and the trial should be appropriately designed to answer the specific question asked.
Metroplex Clinical Research Center, Dallas, TX, USA; University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: RFleischmann@arthdocs.com.
Fleischmann
F
R
Academic Medical Center, Amsterdam, The Netherlands; Atrium Medical Center, Heerlen, The Netherlands.
Landewé
L
R
Medical University of Vienna, Vienna, Austria; Hietzing Hospital, Vienna, Austria.
Smolen
S
J S
D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
D018501:Antirheumatic Agents
Anti-TNF drugs; Biologicals; DMARDs; Rheumatoid arthritis