Research and development: protecting patients
Phytotherapy has its roots in tradition – in a rich heritage of empirical knowledge. So does it essentially belong in a museum? Not at all, because modern phytotherapy combines traditional herbal medicine with the results of modern-day research into medicinal plants and is open to innovation.
The Research and Development department works on the development of remedies that meet the need of our customers and the regulatory authorities. Their scientific work aims to prove and document the quality, efficacy and tolerability of the products.
For proven fresh plant preparations/natural substances, staff work to analyse the constituents and the beneficial profile even more closely and to identify new therapeutic fields.
Apart from professional expertise and financial investment, this requires time, because medicinal regulators require extensive documentation and tests in order to ensure that, ultimately, a safe and effective product is placed on the market for the benefit of patients.
The previous articles have shown how a high-quality herbal medicine is produced. However, many obstacles have to be overcome before a tincture can be poured into bottles or tablets can be filled into jars and sold on the market as a medicine.
These all have a common aim – namely to ensure the well-being and safety of the consumer as far as this is humanly possible.
The articles have also described the prerequisites for ensuring consistent quality in a herbal medicine – i.e. the process of standardisation, which starts during the cultivation of the fresh plant, continuing through validated production processes to result in a medicine that contains the constituents of the fresh plant in a stable composition.
We will now consider the requirements that a product must fulfil in order to be approved for sale on the market.
Uniform admission conditions for traditional herbal medicines
The authorities assessing the quality, efficacy and safety of a medicine (i.e. those who are responsible for approving an application for a medicinal product licence) have sets of rules, with which producers must comply.
For over-the-counter medicines, the "Traditional Herbal Medical Product Directive" (THMPD) has been in force within the European Union since 2004. It regulates the admission of traditional herbal medicinal products under a simplified procedure. An expert report and a registration dossier are required, and data on efficacy relies on traditional use. A seven-year transitional period expired in 2011. In particular, this concerned EU countries that previously had no process for regulating traditional herbal medical products. Since then, only officially registered traditional herbal medical products may be brought onto the market in the EU.
Switzerland permits the simplified registration of herbal medical products with known active substances if proof of therapeutic safety and efficacy can be provided through sufficient evidence in the published literature and at least one clinical study (evidence of use).
The analysis of medicines containing combinations of herbs is often considerably more complex than that for monopreparations. In most cases, proof of efficacy and safety must therefore be provided on the basis of an organisation’s own studies and tests.
Herbal medicines with an indication
For herbal medicines with an indication (eg. to strengthen the immune system, for cardio-vascular complaints), the same guidelines apply as for chemically synthesised medicines.
Physical, chemical, microbiological, toxicological, pharmacological and clinical tests are required to prove efficacy and safety. Firstly, written evidence from existing scientific literature is admissible; secondly, any missing data on the pharmacology of the herbal products must be collected, and thirdly, clinical trials must be conducted on human beings. Scientific reproducibility is ensured through placebo-controlled, randomised double-blind studies.
It goes without saying that such work costs millions, quite apart from the fact that in most cases, more than one trial is required and not every pharmacological study or clinical trial leads to a tangible result.
This financial burden is borne by a few medium-sized businesses - who can only incur this research expense for products that are expected to produce corresponding sales.
Pharmacological studies and clinical trials
Pharmacology is tasked with establishing what the body does with a medicine (pharmacokinetics) and what a medicine does with the body (pharmacodynamics).
It is a fact that, unlike chemically defined medicines, pharmacological studies for herbal active substances quickly reach their limits. It is often not possible to clearly characterise a multicomponent mixture.
Fortunately, for many plants, tradition has already shown us how a medicinal plant works in human beings. Nevertheless, studies on isolated cells make it possible, for example, to study whether and how different plant extracts are effective for rheumatic inflammation, and with a lot of experience, it is in some cases also possible to obtain first indications for correct dosage.
Studies on human beings are conducted once the required pharmacological data concerning efficacy and tolerability have been obtained in cell systems. After preliminary studies have taken place, the medicine is tested on a larger number of patients with specific symptoms in order to ascertain its efficacy.
A certain number of randomly selected test subjects are then divided into two groups. The ‘placebo group’ is given a placebo, while the members of the second group, the ‘verum group’, are given the medicine that is being tested. This process is referred to as a placebo controlled study.
However, test processes also exist where a comparison is made with standard therapies. These are appropriate where the patients are so ill that it would be unethical not to provide appropriate treatment during the period of the trial. The studies are conducted under the supervision of one or more doctors, with most being conducted as double-blind studies.
At the end of the pre-determined period the data undergo statistical analysis to ascertain if the new medicine works better than a placebo or traditional treatment.
People who work in phytotherapy today cannot and must not see themselves as ‘museum curators’ but must instead take an innovative approach to serving the needs of human beings. In recent years, many renowned scientists throughout the world have become involved in phytopharmacological research and conducted many studies.
Without controlled, scientifically based studies it is no longer possible to play in the ‘premier league‘. Throughout the world, and even in countries where the authorities do not regulate the supply of herbal medicines or do not regulate it so strictly, knowledgeable consumers are demanding proof that a herb works.
Bioforce AG also employs a team of doctors and scientists who participate on national and international quality assurance bodies, prepare and carry out clinical trials and conduct research into both new plant combinations and new areas of application for known plants.
Are other approaches also possible?
The foregoing might lead one to conclude that while everything may not be perfect, things are moving in the right direction. Unfortunately, such optimism has to be tempered somewhat.
Phytotherapy is special, because a complex interplay between numerous components creates the overall effect of a medicine. Even if conducted with extreme care and according to best practice, a double-blind study essentially remains a relatively imprecise measuring tool, which hardly does justice to the (holistic) characteristics of a herbal preparation with its broad spectrum of efficacy and often slow onset of effect.
For example, the methods described struggle to cope with combination products (medicines composed of different plants) or the required expense may be disproportionate to the expected result. The development of suitable measurement methods and assessment criteria, which can be integrated into a scientific concept that also finds approval with the authorities, represents a major task for future research.
• Ingrid Zehnder-Rawer
Placebo (lat. ‘I shall please’) is the term used to refer to an imitation of a drug which is identical in appearance, taste and smell but which does not contain any active substance. It is thus a "blank" medicine. Nevertheless, placebos do have effects and side-effects, because it has been proven that even the expectations of a test subject, the individual experiences in taking medicines and also medical attention and control (positive or negative) have effects. Research into the placebo effect has led to deeper knowledge of the healing process and has, in particular, shown that bodies and minds have forces that can make a person healthy (or sick).
Physician and philosopher, Gustave Le Bon’s comment hundreds of years ago that, "Giving people a belief means increasing their strength tenfold", is confirmed by current research results within psychoneuroimmunology.
A relatively high number of positive placebo effects are noted when studying the efficacy of psychopharmaceuticals, for instance, and also, surprisingly, of products to treat veins.
A randomised study is a study in which the test subjects (patients) are divided into the placebo or medicine group not by a doctor but by means of random selection.
In a double-blind study, neither the test subjects nor the treating physician are informed who is taking the placebo and who is not. In a single-blind study, the doctor knows who is taking the placebo. The patients do not know if they are taking the actual medicine or the placebo.