Wien Med Wochenschr. 2002 ; 152(7-8): 204-8.

[Clinical development of phytopharmaceuticals]

Petrini O.

Therapiegebietsleiter, Medizin (Phytopharmaka und Vitamine), Boehringer Ingelheim, Pharmaton SA, P.O. Box, CH-6903 Lugano, Schweiz. [email protected]

In the past, the proof of efficacy of herbal remedies has relied upon spontaneous reports and the regular use and prescription by a few physicians. Only in the last few decades have reports of clinical trials started to appear in the medical literature. Most reports were based on open, observational trials and were rarely conducted according to the state-of-the-art techniques. Good Clinical Practice (GCP) in clinical studies with herbal remedies has only recently started to be routinely used by a few pharmaceutical companies. The development of herbal remedies differs in a number of aspects from that of chemical entities. On the one hand prolonged and uneventful use of a herbal remedy may testify to its safety and efficacy, on the other, the complex composition of most herbal remedies makes it difficult to carry out pharmacodynamic (PD) and pharmacokinetics (PK) trials. Generally, however, a preclinical and clinical development should be carried out according to the general principles of classical drug development. A particular problem is linked to the issue of the phytoequivalence. While bioequivalence of chemical entities can be assessed in vitro and using comparatively simple pharmacokinetics trials, the equivalence of different extracts must be normally assessed with a proper bioequivalence clinical trial. In the case of herbal remedies the whole extract, and not individual components, has to be considered the active substance. Thus, the results of a clinical trial performed with a given extract or a well-defined mixture of extracts cannot be transferred automatically to other products, unless the ingredients have been produced using the same technology. A complete, state-of-the art clinical development of a new phytopharmaceutical medicine includes the performance of GCP-conform dose-response and double-blind, placebo-controlled, randomised clinical trials. Particular emphasis must be put on the study of efficacy and safety of the phytopharmaceutical product under development. As most herbal remedies aim at improving the well-being, QoL scales are ideally suited for use in the clinical evaluation of herbal remedies.