Issue 11 / 26 March 2012

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

Posted 26 March 2012

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6 thoughts on “Ken Harvey: CM evidence is testing

  1. Rob Loblay says:

    I strongly support all of what Ken says. TGA listing is useless. Leaving aside questions of efficacy, when it comes to ‘safety assessment’ of CM’s what they mean is ‘a history of safe use’ – i.e. no dead bodies in the street as far as they know – not a well designed clinical trial where the safety profile has been properly documented. IMO, most herbal medicines remain:

    UNKNOWN mixtures; of
    UNKNOWN substances; in
    UNKNOWN concentrations; with
    UNKNOWN actions,
    UNKNOWN interactions,
    UNKNOWN side-effects, and
    UNKNOWN toxicities.

    CMs should all be subject to the same safety & efficacy standards as regular medicines before getting marketing approval from TGA. I’ll be interested to see how many CM manufacturers ‘opt-in’ to the Monash group’s assessment program if the bar is set at the correct height.

  2. Ray T says:

    I would add a 4th option to the poll on CMs:
    * It might if I thought the TGA adequately tested products.

    I chased up issues over generic equivalents a few years ago.
    Most bureaucrats and pharmacists assure us drugs ARE tested after any formulation change.
    The Act the last time I read it said “MAY be tested” at the TGA’s decision.
    A member of the TGA board admitted on the phone: “Well we don’t have the funding to test every time we would like to, and largely rely on manufacturer supplied data…”

  3. cboughton says:

    The community obviously expects CMs to be therapeutically effective and safe. Unless these preparations are submitted to the same safety and efficacy checks as are new “orthodox” drugs, they should not be listed by the TGA, as such listing gives the TGA’s imprimatur to their use. The composition of some CMs varies from batch to batch and some have contained prescription only drugs, or even heavy metals, eg, lead. These comments certainly relate to herbal medicines ordered via the internet. In brief the whole CM situation is unsatisfactory and I support the comments of Ken Harvey, Ray and Rob Loblay.

  4. Sue says:

    I am starting to wonder whether the terms CM or CAM are actually useful. Firstly, they are umbrella terms for wide-ranging practices from nineteenth century theories about dilution (homeopathy) to manipulative therapies with some evidence (chiropractic). Secondly, I wonder whether it is useful to have a dichotomy of “orthodox” vs “other” – perhaps it would be more useful to have “proven efficacy” vs “unproven” and “regulated practitioner” vs “unregulated”. All practitioners and all “remedies” could then be held to the same standards.

  5. Rob Loblay says:

    @ Sue, “proven” vs “unproven” is just as problematic a dichotomy as “orthodox” and “other/unorthodox”. Treatments are only “proven” until the next contradictory study comes along; some are applicable to patients selected for RCT but may not be generalizable to the wider population. In medicine, “proof” (like “safety”) is relative, not absolute. These days people prefer to speak of “levels (or quality) of evidence”, so maybe we should invent a new level which applies to “unsubstantiated beliefs & practices of CAM practitioners”. The problem with “regulated practitioner” is that chiropractors are regulated but many of them cling to unsubstantiated beliefs & dodgy practices (e.g. diagnosis and treatment of ‘subluxation’)! That said, I too wonder about the value of the term “CAM” when it includes such things as meditation & prayer…

  6. Sue says:

    I agree, Rob – perhaps “proven” was the wrong term to use. Conceptually, I like the idea of “supported by current science.” I don’t think every therapy needs an RCT to be supported by science – it can be supported by the CLINICAL sciences – such as consistent with physiological or pharmacological principles. Some of the so-called CAMs, like infinitely dilute solutions of homeopathy, are just not feasible in light of what we know about physiology. Although chiropractic does still perpetuate the “subluxation” theory, manipulation is a “feasible” therapy and there is some evidence that it is useful for low back pain. That doesn’t validate the theory, but we can say that manipulative therapy is feasible and probably effective for this condition. That makes it “therapy” – not “alternative”. Manipulation for treatment of other organ systems, however, is not science-based.

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