Pharmacovigilance for alternative medicine

Adam Jacobs explores the pharmacovigilance environment for alternative treatments.

Before drugs are licensed for use in patients, they must go through a rigorous series of clinical trials designed to determine efficacy and safety. Once a drug is licensed, we can usually be pretty confident we have enough efficacy data to know that a drug works, or it wouldn't get a license in the first place. But do we have enough safety data to know that a drug is safe? How much data is enough?

Typically, we would have data on a few hundred patients, or maybe a few thousand if we're lucky, before a drug is licensed. That's certainly enough to tell us about common side effects, but there's always the possibility that rare side effects may be lurking beneath the surface, but which are too rare to have been reliably detected in clinical trials. And if those rare side effects are serious, that can be a problem.

"But do we have enough safety data to know that a drug is safe? How much data is enough?"

That is why a requirement of licensing of drugs is a rigorous programme of post-licensing pharmacovigilance. Pharmaceutical companies are required to continue to monitor the safety of their drugs once they are on the market. This process is important. It sometimes leads to changes in the labelling of drugs when rare side effects are identified after licensing. It occasionally even leads to drugs being taken off the market if rare side effects are sufficiently serious. Vioxx is one of the most famous examples of a drug taken off the market as a result of unfavourable post-licensing safety data, but it's certainly not the only one. Terfenadine and cisapride are two examples of drugs that I have personally been prescribed in the past which have now been withdrawn from the market because of the risk of serious side effects (is my GP trying to get rid of me, I wonder?)

The system is not perfect, of course, but it works pretty well. It would be impracticable to wait until we knew everything we could possibly know about the safety of a drug before licensing it, and even if it were possible, many patients would be denied potentially beneficial treatment in the meantime. While some people may be harmed by drugs with serious side effects reaching the market, the system we have for pharmacovigilance does a good job of keeping their numbers to a reasonable minimum. And it is important to remember that the harm of side effects must be balanced against the harm of denying beneficial treatment.

Everything I've written so far describes the situation for conventional medicines. But conventional medicines are not the only substances to be licensed and used to treat disease. There is also a thriving industry of alternative medicines.

Homeopathy is one part of the alternative medicine industry. There are no requirements for pharmacovigiliance in homeopathy. But, I hear you cry, homeopathy has no active ingredients, so cannot possibly cause side effects, so why would we need pharmacovigilance?

Well, actually, homeopathy may cause direct harms. This may not be very likely if a homeopathic product is of good pharmaceutical quality, but given that Boots famously continued to sell Nelsons homeopathic products even after an FDA inspection revealed broken glass in their production line which may have got into their products, I don't think we can be sure that homeopathic products are always of good quality. How much harm does this actually cause? We don't know, because no-one is systematically collecting the data.

But the real concern with homeopathy is the indirect harm. We may occasionally hear stories in the media where a patient followed a homeopath's advice to treat bowel cancer with homeopathy rather than conventional medicine, with predictably tragic results. Such extreme cases are probably rare, but how often do less serious, but still harmful, consequences result from homeopathy? We don't know, because no-one is systematically collecting the data.

"...it is important to remember that the harm of side effects must be balanced against the harm of denying beneficial treatment."

We should also be concerned about herbal medicines. There is a common perception that herbal medicines must be safe, because they are "all natural". Well, tobacco is "all natural", and probably causes more harm than all synthetic drugs put together. If you ever meet someone who claims that herbs are safe because they are "all natural", the correct response is to challenge them to drink a pint of strychnine.

Now, herbal products registered under the Traditional Herbal Medicines Registration Scheme do have some requirements for pharmacovigilance, which is welcome, albeit that those requirements are less strict than for proper drugs. I do wonder how well pharmacovigilance for herbal medicines works in practice. The lack of good quality safety information on herbal products, even ones with a good evidence base for their efficacy, can be a real problem when trying to offer good advice to patients.

Worryingly, there is an exemption from registration for herbal products made up by herbalists on an individual basis. There are no pharmacovigilance requirements for such products. So how do we know what harms they cause? Unlike homeopathy, herbal remedies contain pharmacologically active substances, so as well as the indirect harms that any form of alternative medicine can cause, herbal remedies can also cause direct harms. And herbal remedies may also contain contaminants, further adding to the risk of harm. How common are these harms?

We don't know, because no-one is systematically collecting the data.

About the author:

Adam is an experienced medical writer and statistician. Before setting up Dianthus Medical in 1999, he worked as a medical writer for both a small contract research organisation and a large medical communication agency. Adam has a PhD in organic chemistry from the University of Cambridge and an MSc in medical statistics from the London School of Hygiene and Tropical Medicine.

He takes an active role in the European Medical Writers Association (EMWA), and was president of the association in 2004-2005. In 2003, he set up EMWA's ghostwriting task force, as a result of which he was co-author of EMWA's guidelines on the role of medical writers in peer-reviewed publications. He is a regular workshop leader for EMWA's training workshops and a columnist in their journal, The Write Stuff, and was among the first few people to be awarded EMWA's advanced professional development certificate. He is also a fellow of the Institute of Clinical Research and a Chartered Scientist.

In his spare time, he enjoys cooking, gardening, karate, long-distance running, travel, and hill walking (but not usually all at the same time).

He can be contacted via Twitter at @dianthusmed

Should safety data be systematically collected for homeopathic remedies?