Abstract
BACKGROUND: Physical identical and pharmacological inert are the basic requirements for placebo design, which are essential in clinical trials to evaluate the efficacy of an intervention. However, it is difficult to makeup a placebo of Chinese herbal medicine (CHM) because of special color, taste and smell, etc. Currently, there is no specific requirements and standards for the creation of a CHM-placebo. The purpose of this study is to review the characteristics of the CHM-placebo design and application in registered clinical trials with CHM interventions and identify the common problems, if any. METHODS: The World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) was systematically searched for CHM interventional trials with placebo-controlled design up to 31 December 2017. Registered information of each included trial was collected from specific registries involved in ICTRP through hyperlinks. Descriptive statistics were used to analyze the characteristics of placebo design in CHM trial registrations. RESULTS: A total of 889 CHM interventional trials were registered from 1999 to 2017, and 40.8% (363) of them included CHM-placebo control design. The common ways of their design were: placebo as sole control (191, 52.6%); placebo as add-on control with baseline treatment (84, 23.1%); and placebo as double-dummy control (57, 15.7%). Among 363 included trials, 46 (12.7%) reported the compositions of placebos, including CHM ingredients (17 trials), excipients and other agents (29 trials). 2 (0.6%) reported pharmacological inert testing, and 52 (14.3%) descripted their placebos to be physically identical with the CHMs. 14 (3.9%) reported quality control of placebos, and 2 (0.6%) provided blinding assessment of placebos. CONCLUSIONS: The placebos included in most CHM trial registrations is not optimal in terms of placebo design, application, evaluation and reporting. Specific guidelines or standards of CHM-placebo design, including usage requirements, preparation specifications, quality assessments and reporting guidelines should be developed thus to improve their quality.