Guidelines for Clinical Evaluation of Herbal Remedies and Medicinal Plants

For the herbal remedies and medicinal plants that are to be clinically evaluated for use in the Allopathic System and which may later be used in allopathic hospitals, the procedures laid down by the office of the Drugs Controller General of India for allopathic drugs should be followed. This does not pertain to guidelines issued for clinical evaluation of Ayurveda, Siddha or Unani drugs by experts in hospitals and clinics. All the general principles of clinical trials pertain also to herbal remedies. However, when clinical trials of herbal drugs used in recognized Indian Systems of Medicine and Homeopathy are to be undertaken in Allopathic Hospitals, association of physicians from the concerned system as co-investigators/collaborators/members of the expert group is desirable for designing and evaluating the study.
Important Points:
The herbal products can belong to either of the three categories given below

1.
A lot is known about the use of a plant or its extract in the ancient Ayurveda, Siddha or Unani literature or the plant may actually be regularly used by physicians of the traditional systems of medicine for a number of years. The substance is being clinically evaluated for same indication for which it is being used or as has been described in the texts.
2.
When an extract of a plant or a compound isolated from the plant has to be clinically evaluated for a therapeutic effect not originally described in the texts of traditional systems or, the method of preparation is different, it has to be treated as a new substance or new chemical entity (NCE) and the same type of acute, subacute and chronic toxicity data will have to be generated as required by the regulatory authority before it is cleared for clinical evaluation.
3.
An extract or a compound isolated from a plant which has never been in use before and has not ever been mentioned in ancient literature, should be treated as a new drug, and therefore, should undergo all regulatory requirements before being evaluated clinically.

It is important that plants and herbal remedies currently in use or mentioned in literature of recognized Traditional System of Medicine is prepared strictly in the same way as described in the literature while incorporating GMP norms for Standardization It may not be necessary to undertake phase I studies. However, it needs to be emphasis ed that since the substance to be tested is already in use in Indian Systems of Medicine or has been described in their texts, the need for testing its toxicity in animals has been considerably reduced. Neither would any toxicity study be needed for phase II trial unless there are reports suggesting toxicity or when the herbal preparation is to be used for more than 3 months. It should be necessary to undertake 4-6 weeks toxicity study in 2 species of animals in the circumstances pointed out in the preceding sentence or when a larger multicentric phase III trial is subsequently planned based on results of phase II study.

Clinical trials with herbal preparation should be carried out only after these have been standardized and markers identified to ensure that the substances being evaluated are always the same. The recommendations made earlier regarding informed consent, inducements for participation, information to be provided to the subject, withdrawal from study and research involving children or persons with diminished autonomy, all apply to trials on plant drugs also. These trials have also got to be approved by the appropriate scientific and ethical committees of the concerned Institutes. However, it is essential that such clinical trials be carried out only when a competent Ayurvedic, Siddha or Unani physician is a co-investigator in such a clinical trial. It would neither ethically acceptable nor morally justifiable, if an allopathic physician, based on references in ancient literature of above-mentioned traditional systems of Medicine, carries out clinical evaluation of the plant without any concept or training in these systems of medicine. Hence, it is necessary to associate a specialist from these systems and the clinical evaluation should be carried out jointly.