Ken Harvey: CM evidence is testing

LATE last year, Choice, the Consumers Health Forum and several health professionals asked the Therapeutic Goods Administration for a list of properly evaluated registered complementary medicines in order to aid consumer (and health professional) decision making.

In Australia, the Therapeutic Goods Administration (TGA) is responsible for regulating complementary medicines (CMs). More than 10 000 complementary medicine products are listed by the TGA (AUST L). There is a much smaller number of registered (AUST R) products which, in theory, should have had some evidence of efficacy approved by the TGA.

In reality, only a small number of registered CMs have been thoroughly assessed for quality, safety and efficacy.

However, a larger number of registered CMs appear to have been grandfathered onto the Australian Register of Therapeutic Goods (ARTG) without any assessment of efficacy. In short, despite TGA assertions, not all AUST R labelled products have been evaluated to see if they work. In addition, most listed AUST L CM products are never evaluated for efficacy prior to marketing.

The TGA has now published a list of what they consider to be properly evaluated CMs.

Of the 25 products on the list most are unsurprising — iron, calcium and/or vitamin D, calcium ascorbate complex (a form of vitamin C), psyllium fibre and ispaghula husk for constipation, eucalyptus oil with lemon tea tree oil for head lice and clove oil for toothache.

More innovative products with robust evidence are:

• Iberogast (manufactured by Flordis). A specific nine-herb mixture “for the treatment of gastric and abdominal discomfort associated with functional and motility-conditioned gastrointestinal disturbances such as functional dyspepsia and irritable bowel syndrome”.

• Kaloba (Schwabe) containing a specific extract of Pelargonium sidoides (EPs 7630) for “for the treatment of acute bronchitis and sinusitis”. This product may help to conserve antibiotic use.

• Flexagil (Blackmores). A specific extract of Symphytum officinale (comfrey) for topical application for the “relief of lower back pain, painful joints and strains”.

I asked the TGA why Omacor (Abbott) was not on the list as I understood this is the only AUST R omega-3 product, although many are listed. They said the application had been made as a prescription medicine not a CM. There is good evidence for the benefits of omega-3 polyunsaturated fatty acids and many listed products are also of good quality.

I also asked the TGA about the one AUST R glucosamine hydrochloride product — Arthro-Aid Arkopharma) — on the list, as there are 330 AUST L glucosamine products. Reviews of the scientific literature report that glucosamine hydrochloride formulations are more likely to be associated with negative trial results than specific preparations of glucosamine sulphate.

In addition, an attempt by the sponsor to get Arthro-Aid on the Pharmaceutical Benefits Schedule for the symptomatic treatment of osteoarthritis was rejected because of lack of evidence demonstrating clinical efficacy with an appropriate comparator.

The TGA told me this product was evaluated against the evidence base current at the time of assessment (1998). This is an example of another problem with registration — there is no process (apart from resubmission by the sponsor) to update the assessment in light of new knowledge.

The confusion surrounding the efficacy of glucosamine formulations highlights the fact that the concept of therapeutic equivalence that is applicable to generic prescription products does not apply to CMs.

Just as not all red wine is Grange Hermitage neither are all preparations of St John’s wort or glucosamine, for example, therapeutically equivalent. Clinical trial results only apply to the specific, well characterised product that was tested. They cannot be extrapolated to other products containing the same generic ingredient.

Unfortunately, there is currently little incentive for sponsors to undertake expensive research, compile an extensive dossier and pay the higher fees required for TGA registration as the public does not understand the subtleties of AUST R and AUST L and registration provides little or no market advantage.

A better return on investment comes from spending money on marketing.

While there are evidence-based listed CMs on the ARTG it is very difficult to distinguish this evidence-based wheat from the much more voluminous hype-driven chaff.

In response to the difficulties of identifying effective CMs based on their TGA listing or registration, Professor Paul Komesaroff, director of the centre of ethics in medicine and society and Monash University, and colleagues have set up a broad-based collaboration to assist the quality use of CMs.

One component of this will be an opt-in system, funded by an additional fee, which will independently (non-TGA) assess the evidence supporting specific CMs.

Products that have gone through the process will be awarded a trademark symbol of assessment and review. The concept has received support from industry partners and health professional and consumer organisations who are committed to evidence-based use of CMs. A management team is currently being established and the project will soon be underway.

Dr Ken Harvey is adjunct associate professor at the School of Public Health, La Trobe University. He can be contacted through his website http://medreach.com.au.

Posted 26 March 2012

[poll id="169"]