Studies On Placebo Manufacturing Procedures And Specification Evaluation For Placebo-controlled Clinical Trials In Chinese Medicine

Background The placebo-controlled clinical trials on Chinese medicine were rapidly increased in the past decade. A valid placebo should have the same specifications as the trial medicines, but contains nontoxic and inactive ingredients. The investigator needs to explain to the subject the nature, aim, potential risks and hazards of the trial, other available treatment methods and the subject' s rights and responsibilities as prescribed in the Declaration of Helsinki. Informed consent is may be obtained only after the subject fully understands the explanations. However there was no placebo concept in traditional Chinese mediciine, and the articles of clinical trials rarely described the manufacturing procedures, product requirements or the validation methods. Thus the patient compliance becomes a critical issue since it may cause a great variation.Objective To formulate recognized and standardized placebos for placebo controlled clinical studies on Chinese medicine to ensure the implement of blinding.Methods Placebos were formulated in tablet/capsule/granule/powder dosage forms in compliance with GMP guidelines. They were made from herbal powders, pharmaceutical excipients and/or food additives to match up the sensory specifications defined as the trial Chinese medicines. A systematic evaluation method has been established including the specific size and shape, texture, solubility, the color inside and outside, the routine dosage form examinations and packaging, also the sensory evaluations, to get well prepare for blind performance. The four validated placebos were respectively used in four double blind, placebo-controlled clinical studies, which of three for oral use and one for external use.Results The produced placebos well matched in the sensory appearances of trial proprietary Chinese medicines. But the taste and odor still need more development work for improvement of matching the trial medicines. The four placebos were validated by the systematic evaluation method established so that the blind clinical trials were conducted successfully.Conclusion The four placebos were validated to serve in the placebo-controlled clinical trials respectively. The manufacturing procedures, product specifications and the validation methods could be mature to serve as a reference for the invigilators in placebo-controlled clinical trials on Chinese medicine. The placebo product information should be included as part of the documental requirements in the preparation, implementation and verification of a clinical study.