Interview

‘Conducting clinical trials on herbal medicines is challenging’

Charak Pharma's international clinical research initiatives have garnered wide support in the overseas medical fraternity due to constant efforts towards using modern technology and maintaining high quality standards. Pulin Shroff, Managing Director, Charak, reveals more to Sachin Jagdale

What challenges does one face in doing clinical research on herbals/phytomedicines in comparison with allopathic medicines?

Conducting clinical trials on traditional/herbal medicines is challenging due to lot of reasons, for instance, it is very difficult, impracticable or sometimes impossible to have active and control groups with identical colour, smell and taste. Also, the use of placebo involves similar difficulties as the herbal study drug may exhibit its strong aroma, a specific distinguished taste and these can not be imitated while manufacturing a placebo. Using placebo may also involve ethical issues.

Many a times the medicine system advocates other procedures along with oral therapy which again may or may not be standardised. Also, there is no standard single benchmark formulation, especially if a single drug therapy is concerned for various therapeutic areas, as they are present in modern medical science.

Another reason is that the crude raw herb material has various variations as per geographical locations, climatic conditions, environmental hazards, harvesting methods, collection protocols, etc which makes it a difficult task to standardise the end product for a maintained quality. These factors make even making standardised extracts a difficult task.

The system of herbal medicine advocates the choice of herbs, compounding or mixtures, dosage and duration so that it suits the particular psychosomatic constitution (Prakriti) of the patient. This approach, since ancient times, helps in enhancing the therapeutic effect as well as reduces the unwanted effects of the drug. Therefore, administration of a study drug to a subject population of various constitutions may not yield uniform outcomes.

Other reasons include the ftact that integrated approach of many herbal systems does not differentiate the disease from the patient. This approach creates difficulties for the inclusion and exclusion criteria in clinical trial. Also, ayurveda proposes different interventions at different stages of disease in the same patient providing another variable in a clinical trial. Diet component may also affect the treatment outcome in clinical trial.

And in modern conventional medicine, such issues do not exist.

How do practitioners like Charak overcome these challenges?

Charak has been conducting clinical trials since the 50s. Initially, there were no specific guidelines; hence, the research was conducted as per implications followed by other pharma companies. Presently, Charak applies the most recent methodologies and guidelines for clinical trials. Now, the conventional Western approach is adopted. With modern manufacturing technologies and WHO approved, ISO certified units, Charak's products are manufactured by masking the strong smells, fine coating blinds the typical colours and tastes of herbs. This facilitates blinding methods for trials. Identical placebos are also easily made available for all our products. These ensure that all our clinical trials follow GCP guidelines.

Due to the lack of a herbal clinical equipoise, a standard conventional modern drug of respective therapeutic class is used for planning comparative studies. For example, clinical trial on our PCOS drug Hyponidd, metformin is used as a comparator drug, while in male infertility our drug ADDYZOA was evaluated vis a vis to clomiphene and ubiquinone.

Accepting the fact that it is difficult to adopt all ayurvedic therapeutic approaches, the inclusion/exclusion criteria are set as per the international standards for the respective therapeutic area/indications. For example, a hypolipidemic drug is evaluated on subjects enrolled with specific range of abnormal lipid levels.

What guidelines are followed while doing such clinical research?

The WHO has published guidelines in order to define basic criteria for evaluating the quality, safety, and efficacy of herbal medicines aimed at assisting national regulatory authorities, scientific organisations and manufacturers in this particular area (WHO, 2000). Furthermore, the WHO has prepared pharmacopoeia monographs on herbal medicines and the basis of guidelines for the assessment of herbal drugs (WHO, 1999, 2001).WHO guidelines for Good Clinical Practice (GCP) are adapted from ICH guidelines.

When an extract of a plant or 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, sub acute and chronic toxicity data will have to be generated as required by the regulatory authority before it is cleared for clinical evaluation.

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.

What are your overseas clinical research initiatives?

Dr K K Bal from Kenya is conducting a clinical trial on our product Hyponidd in PCOS. Dr Owusu from Ghana has shown interest in our product Hyponidd in type II DM, while another doctor has started a clinical trial on our product Addyzoa in male infertility due to oligo-astheno-teratospermia. Some doctors are conducting clinical trial on our product Kofol in Ukraine.

Recognition of any herbal product by international medical fraternity is an object of honour for any pharma company. This obviously establishes a doctor's confidence in that drug. Charak has gained this acclaim for many of its products through the clinical research initiatives. At present we do not have any tie-ups for international clinical research.

Have you presented any scientific papers at international level?

Yes, we have. One is Dr Gautam Allahabadia's paper on PCOS in international seminar on Reproductive Medicine ‘Volume 26, Number 1, 2008’, which has endorsed Charak’s Hyponidd. Another is Dr Kaushal Kadam's poster presentation.

What is the response to your phyto-medicines in the international markets?

Internationally, Charak's phytomedicines are gaining popularity within a short span from their introduction in the respective country's market. Charak's Kofol is a leading brand in Ukraine. Addyzoa, Evanova, Hyponidd, M2 Tone are also some of the favorite brands of our international prescribers.

Charak's phytomedicines are well appreciated in India and in the countries wherever they are introduced. M2 Tone is the leading brand in India in DUB and infertility. Hyponidd for PCOS is praised at International conferences. Evanova, Addyzoa are the most trusted brands by Indian gynecologists. Livomyn, Manoll, Neo, Vigomax are prescribed by generations of practioners. Many of the products are mentioned in various text books written by eminent doctors. Our Cytozen, Cognium and derma range are also well valued by doctors of various pathies.

sachin.jagdale@expressindia.com