The process of conducting herbal medicine research through the clinical trials exemption scheme

The primary aims of this study were to develop research methodology in order to investigate the efficacy of herbal medicine in alleviating menopausal symptoms, and to prepare an application for submission to the Medicines Control Agency (MCA) to gain approval to run a randomised, double blind, placebo controlled clinical trial. A research protocol was developed which outlined the key stages of the study for subsequent review and approval by an ethics committee. An operations manual was developed to guide and instruct clinicians on how the study should be implemented. This required the development of case history notes, screening procedures, timetable flow charts and adverse event reporting cards specifically for this study. An original herbal formula was developed for this study based on a literature review of medicinal plants. A 54-page exemption from licences MLA-164 application was completed, which set out in detail the design of the study. The pharmacological properties of the medicinal plants were reviewed from the literature and listed in detail to satisfy the MCA's requirements for scientific evidence of efficacy and safety. Heavy metal analysis was performed for quality control purposes to examine the feasibility of being able to meet specification limits for metal contamination in
medicinal herbs. This was conducted using Inductively Coupled Plasma-Atomic Emission Spectroscopy on a total of 16 herb samples, eight samples of Hypericum perforatum L. and eight samples of Salvia officinalis L. from cultivation sites in the UK and Europe. Mean metal ion concentrations of lead, cadmium, mercury, copper, zinc, nickel and chromium were found to be below statutory limits and guidelines, and would therefore satisfy the requirements of an MLA- 164 application for metal contamination. High Performance Liquid Chromatography was performed using UV detector and Diode-Array detector systems to determine the suitability of each method to provide a `fingerprint' analysis of the medicinal herbs for the purposes of establishing plant authenticity. The diode-array analysis was superior to simple UV detector
methodology because it was able to provide greater accuracy to determine the chemical group for some unknown constituents. However, neither system provided adequate phytochemical profiles to authenticate the medicinal plants. The research study provided a novel insight into the processes required for the design and implementation of a herbal medicine clinical trial, and has expanded the current knowledge of the requirements for completing a clinical trials application (MLA-164) to the MCA.

Submitted in partial fulfilment of the requirement for the degree of Master of Philosophy.