The transitive property across randomized controlled trials: if B is better than A, and C is better than B, will C be better than A?

In everyday practice, clinicians are faced with questions on the comparative benefits and risks of the various health interventions available to treat patients. When performed well and reported completely, randomized controlled trials (and systematic reviews of such trials) are generally considered to be the most scientifically rigorous approach to determine whether a cause-effect relationship exists between an intervention and a given outcome. However, clinical trials are hampered by their tendency to focus on simultaneous comparison of no more than 2 or 3 alternatives (eg, treatment vs no treatment, treatment with option A vs B and A vs C). To make more informed decisions, knowledge of the existing evidence on the numerous alternatives available in clinical practice, as well as quantitative recapitulation of this information, is often required to estimate the comparative efficacy and safety of health interventions. Ideally, approach would require clinical trials with as many treatment arms as there are available alternatives, allowing diverse comparisons to be made between option A and B, B and C, C and D, and so forth, and not only the determination of whether A is simply better (or not worse) than B. This information would also be useful for guiding clinical decision making through the use of systematic reviews and clinical practice guidelines that stringently evaluate the evidence and clearly state which are the best choices for treating a specific patient. However, the information required is often only partially available and/or has major associated uncertainties. Limited resources and the need to determine in relative terms the beneficial or potentially harmful effects of multiple treatments have meant that, consciously or not, the transitive property is always present in clinical reasoning when choosing a treatment, in the planning and design of a new clinical trial, or, more recently,