One of the key elements of comparative treatment effectiveness research is head-to-head trials. We herein describe the control arms and the treatment received by patients in recently conducted or ongoing randomized controlled trials of biologic disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis.We identified all protocols recorded in ClinicalTrials.gov to October 1, 2009. We extracted trial length and funding, prior treatment, disease activity in eligible patients, and the treatment received in both trial arms.Among the 91 trials identified (15 DMARD-naive trials, 63 biologic-naive trials, and 13 biologic-second-line trials) involving 18, 554 patients in control arms (3059, 13 095, and 2400 patients, respectively), only 5 compared biologic DMARDs head-to-head (2 of 7 noncommercially funded trials and 3 of 84 commercially funded trials). Two-thirds (66%) of these trials are ongoing. Networks of treatment comparisons reflect a predominant use of placebo as a comparator (81 of 102 comparisons among the 91 trials). In all 15 DMARD-naive trials, all control patients received a new treatment. In 54 of the 63 biologic-naive trials, 9224 of the 13, 095 control patients received their previously ineffective treatment, 3848 for more than 6 months, despite high levels of disease activity and contrary to guidelines. In biologic-second-line trials, 851 of the 2400 control patients received treatment comparable to their previously ineffective one.Head-to-head trials of biologic DMARDs are still exceptions. Exposing patients in control arms who had a previous partial response or nonresponse to an inadequate treatment could lead to irreversible deterioration in condition.