Evidence-based herbal medicinesFebruary 5, 2019
Globally, herbal medicine has become a popular therapy. Many modern drugs, e.g. aspirin or anticancer paclitaxel and vinblastine, are derived from plants. Nevertheless, the path of developing a modern drug from herbal therapy is long and arduous. The alternative of generating clinical evidence through the conduct of randomized placebo-controlled trials is also fraught with scientific challenges, some of which are discussed here.
Selection of herbal medicine: In traditional practice, many herbs are used for one indication and each herb has multiple uses. This is compounded by 2 plant species having the same name e.g. Bacopa monnieri and Centella asiatica are both called Brahmi. Many herbal medicines in practice are a mixture of multiple plants. Choosing such a polyherbal medicine for a clinical trial will make design and quality control complex and demanding. Herbal medicines with long documentation of safety in human use can undergo pilot clinical trials in a small number of subjects, without undergoing pre-clinical animal studies.
Preparation of herbal extract: Hot water extracts of Artemisia annua – the plant containing artemisinin – were ineffective against mice infected with malarial parasite. But cold ethereal extracts were active. Hence preparation of the herbal formulation of an active aqueous or ethanol extract is a must before initiating a clinical trial.
Deciding dose: Traditional textbooks recommend the use of the fresh plant in high doses – grams. However, the herbal medicine formulations are extracts of the whole plant. The relationship between these doses may be difficult to establish. Phase 2 proof-of-concept studies using biomarker-based efficacy endpoints would be useful in dose searching.
Placebo control: Some herbs have a distinct taste, odour and appearance, which makes the creation of matching placebo difficult. In such situations, bias could be reduced by blinding the assessor and having endpoints which are objective.
Duration of treatment: A short-term trial for a chronic indication e.g., rheumatoid arthritis, cannot be conclusive for long-term benefits. Duration of clinical trials in such conditions could be 12-24 weeks, to obtain meaningful conclusions.
Safety issues: Herbal medicines are usually considered safer than synthetic drugs. But there are reports of serious adverse drug reactions e.g. hepatotoxicity of kava, nephrotoxicity of plants containing aristolochic acid and adverse drug interactions, e.g. increase clotting time with garlic in patients on warfarin. Hence the assessment of safety by recording adverse events, frequent clinical examination and laboratory tests should be included in the clinical trial.
Quality control: For the safe and effective use of herbal drugs, quality control is essential to ensure consistency in composition and biologic activity and the reduction of contamination and adulteration with toxic metals, microorganisms, microbial toxins, pesticides and fumigation agents. Hence, before initiating clinical trials, quality specifications and tests should be available for raw herb, the formulation process for extraction and the subsequent fractionation and purification, as well as the manufacturing process. The formulation should be stable for the duration of the clinical trial.
If herbal drugs have to compete and complement modern drugs, the herbal industry and medical experts should collaborate to develop robust evidence, based on randomized controlled clinical trials.