Pharmacovigilance for CAM

Dr. Harald Matthes

Tell us about the background to the EvaMed project, the German prescription-based electronic pharmacovigilance system in complementary medicine.

The projects EvaMed (Evaluation of Anthroposophic Medicine) and the Oncology Network are two scientific research projects which have been successfully established as nationally active networks on the basis of QuaDoSta, a new software tool for electronic medical networks. The EvaMed Network serves as a modern pharmacovigilance project for the documentation of adverse drug events in complementary medicine (anthroposophic and homeopathic medicine). All prescription data are electronically recorded to assess the relative risk of drugs. The Oncology Network was set up as a documentation system in hospitals and specialist oncology practices where a complete record of all oncological therapies is being carried out to uniform standards on the basis of the ‘basic documentation for tumour patients’ (BDT) developed by the German Cancer Society.

The EvaMed Network included more than 40 CAM practitioners (55% general practitioners and 45% specialists),who were trained to recognise adverse drug reactions (ADRs) according to the Uppsala Monitoring Centre guidelines and WHO System of Organ Classification (SOC). For about ten years, all prescriptions and all serious ADRs (WHO grade III-IV) were documented by all participating doctors while eight of the 40 doctors also documented all non-serious ADRs (WHO grade I-IV).

The EvaMed Network is the largest pharmacovigilance CAM network in Europe. To date, more than 200,000 patients, more than 2,500,000 visits and more than 1,650,000 prescriptions of more than 900,000 remedies have been continuously documented.

What were the key findings of EvaMed?

As is true for allopathic medicines, anthroposophic and homeopathic remedies show a wide range of risk for ADRs. The highest risk in the conventional scientific literature for CAM remedies is accredited to allergic reactions to asteraceae (arguably the largest family of flowering plants). Therefore we examined this special group and found a high rate of prescriptions (e.g. Arnica montana, Matricaria recutita, Chamaemelumnobile, Calendula officials, Echinacea app and Inulahelenium) but a low rate of ADRs. Relative risks (RRs) and proportional reporting ratios (PRRs) were calculated for all asteraceae. The PRR for remedies containing Asteraceae with respect to all other prescriptions was 1.7 for the system organ class 'skin and subcutaneous tissue'. This demonstrates the low risk of asteraceae in daily practice.[1] The discrepancy between scientific literature and these results reflects the need for systematic studies for pharmacovigilance also in CAM. Reports of ADRs only, without the relation to the use of remedies, could not evaluate the realistic risk, which is documented by asteraceae, a group of plants, the use of which is very high and common in Germany.

To bring these findings in a relation to other experience of doctors, the allergic risk for asteraceae containing remedies is 10 to 100-fold lower than the allergic risk of Ampicillin. 

Furthermore, pharmacovigilance data from the EvaMed Project are published in many papers on different groups of drugs and also on different treatment groups such as children, elderly, pregnant women and gender specific prescriptions.

The grants for the EvaMed Project have totalled over€6 million over the last 10 years. No public support or grants were made by the German government for this, the biggest pharmacovigilance network in Germany. This demonstrates the handicap for CAM research in Germany and the EU.

The rate of serious ADRs is many times lower than that of allopathic drugs

How do you perceive safety and risk in relation to these types of medicinal products?

The EvaMed pharmacovigilance network demonstrates that anthroposophic and homeopathic and also many phytotherapy (herbal) medicines are safe, and the rate of serious ADRs is many times lower than that of allopathic medicines. Important for the security of CAM medication is a certain insight from the EvaMed Pharmacovigilance project, that there is no increased risk in the interaction of different combinations of CAM and allopathic drugs. More than 30% of all treated patients in the network get a mixture of CAM and allopathic drugs. Special analysis of combinations of many allopathic medicines, with low CAM (e.g. in the diagnosis of arterial hypertension) or low allopathic with many CAM drugs (e.g. in the diagnosis of dementia) demonstrated the safety of CAM medication in everyday practice.[2]

 What are the implications of the EvaMed findings for the future regulation of anthroposophic medicinal products in Europe?

The safety of drugs is an increasingly important tool in EU regulatory affairs. Pharmacovigilance data from prospective observation data are rare. Therefore in most cases, the toxicology and theoretical security steps of 1:1000 to 1:10,000 diluted concentrations are the fundament of regulatory decisions. The EvaMed project provides such data for CAM. The EvaMed Pharmacovigilance data are a milestone for CAM and future discussions on safety. The pharmacovigilance database for anthroposophic remedies is at this time better than for most allopathic drugs. For the future we need all this pharmacovigilance data for the indication in children, new born infants, pregnancy etc. At this time all data are included in the C-Kids-Project of the BfArM (German regulatory authority) to assess the safety of anthroposophic remedies for children and to fulfil the EU regulatory affairs requirement by 2015 for all remedies applied in children by only national 'registered' drugs.

[2] Lit. Jeschke, E., Ostermann, T., Tabali, M., Bockelbrink, A., Witt, C. M., Willich, S. N., Matthes, H. (2009): Diagnostic profiles and prescribing patterns in everyday anthroposophic medical practice--a prospective multi-centre study. ForschKomplementmed, 16: 325-333. Jeschke, E., Ostermann, T., Tabali, M., Vollmar, H. C., Kroz, M., Bockelbrink, A., Witt, C. M., Willich, S. N., Matthes, H. (2010): Pharmacotherapy of elderly patients in everyday anthroposophic medical practice: a prospective, multicenter observational study. BMC Geriatr, 10: 48. Jeschke, E., Ostermann, T., Tabali, M., Vollmar, H. C., Kroz, M., Bockelbrink, A., Witt, C. M., Willich, S. N., Matthes, H. (2010): Pharmacotherapy of elderly patients in everyday anthroposophic medical practice: a prospective, multicenter observational study. BMC Geriatr, 10: 48. Jeschke, E., Ostermann, T., Vollmar, H. C., Tabali, M., Schad, F., Matthes, H. (2011): Prescribing patterns in dementia: a multicentre observational study in a German network of CAM physicians. BMC Neurology, 11: 99