Definition and rationale for placebo composition: Cross-sectional analysis of randomized trials and protocols published in high-impact medical journals.

There is no accessible record of the composition of placebos for approximately half of high-impact RCTs, even with access to study protocols. This impedes reproducibility and raises unanswerable questions about what effects-beneficial or harmful-the placebo may have had on trial participants, potentially confounding an accurate assessment of the experimental intervention's safety and efficacy. Considering that study protocols are unabridged, detailed documents describing the trial design and methodology, the fact that less than half of the study protocols described the placebo contents raises concerns about clinical trial transparency. To improve the reproducibility and potential of placebo-controlled RCTs to provide reliable evidence on the efficacy and safety profile of drugs and other experimental interventions, more detail regarding placebo contents must be included in trial documents.