Head-to-head Comparative Studies: Challenges and Opportunities?

Therapeutic advances need a high level of evidence, such as that provided by placebo-controlled randomised clinical trials. These trials are also required for marketing authorisation by the health authorities. However, in the development of several novel drugs, the performance of a placebo-controlled trial may be unethical due to a potential loss of opportunity for patients included in the placebo group. There seem to be fewer head-to-head studies in the feld of inflammatory bowel diseases [IBD] than in specialties such as digestive oncology and hepatology. However, IBD trials have a number of characteristics, including a large placebo effect with a high clinical response rate. This paradigm could change in the near future, with the introduction of strong outcomes [endoscopic remission and mucosal healing, for example]. There are several reasons for performing head-to-head trials. The health authorities may request an active comparator when considering the reimbursement of novel treatments. Once a drug is approved, other more clinically relevant questions may arise. A new drug that is as effcient as the reference drug might be safer, cheaper or easier to administer. These considerations have recently prompted a dramatic increase in the number of non-inferiority studies. However, these studies have several statistical particularities, and many have limitations and are diffcult to interpret. Last, the increased use of biologics to treat IBD will necessarily lead to the introduction of superiority trials that compare the effcacy of various active compounds. In the present article, we review the different types of head-to-head studies [as illustrated by examples from the literature] and consider their respective strengths and limitations. © 2016 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved.