To the Editor: In the January issue of the Journal, Harvey et al raised some serious concerns about the listing system for complementary medicines.1 In particular, they suggest scrapping the listing system (AUST L) and requiring complementary medicine (CM) products to be evaluated by the Therapeutic Goods Administration (TGA) for efficacy.

Scrapping the system would be a significant setback for natural medicines, which have an important role to play in the health system. Such a move would be likely to remove products from the market, while the problem outlined by Harvey et al is more about the claims made for products rather than the products themselves. Certain CM products play a valuable role in many chronic diseases, in situations where existing synthetic products are often lacking. The regulatory system should encourage evidence-based CM products, and appropriate sanctions and enforcement should downgrade the claims made on products that don’t have a specific evidence base.

CMs, especially herbal medicines, are complex products with numerous biologically active components. This means that the evidence is specific to the product and cannot be extrapolated. This fact has two important consequences for practitioners and the health system as a whole:

• the “generic” concept of synthetic pharmaceuticals (eg, interchangeability of paracetamol-containing products) is invalid for CM, meaning that a prescription for “St John’s wort” for example is not reliable, as St John’s wort is not one substance; and

• meta-analyses and systematic reviews of a “substance” (eg, a herb, or glucosamine) are easily misinterpreted because the products made from that “substance” are so different, any conclusions drawn can only be applied to the particular products that have been trialled.2

While the health system fails to discriminate between products that have specific trial evidence and those that do not, practising evidence-based complementary medicine will remain difficult. Encouraging evidence-based use of CM products, including supporting specifically clinically proven products, will lead to further research and better integration of CM into our health system for the benefit of the Australian public.

To the Editor: I am writing in response to the recent article by Harvey and colleagues about complementary medicines in Australia.1

Rottapharm is the developer and manufacturer of DONA glucosamine, a patented form of glucosamine. DONA is a registered medicine in 54 countries, in many on the equivalent of the Pharmaceutical Benefits Scheme. DONA is the leading glucosamine product in the world measured by specific trial evidence, sales and registration approvals.

The fundamental issue is that different products that contain glucosamine and other complementary medicine (CM) products should be considered to be distinct products. Standards of active ingredients and methods of manufacture of finished products are substantially different between companies.

Specific clinical trial evidence for glucosamine is essential because of:

• formulation differences (DONA glucosamine is a patented formulation of crystalline glucosamine sulfate, which is not comparable with glucosamine hydrochloride or other glucosamine sulfate formulations);

• bioavailability of glucosamine sulfate (unlike all other formulations on the Australian market, DONA has proven plasma concentrations and synovial fluid levels consistent with a clinical effect at a dosage of 1500 mg once a day, and is the only glucosamine product available with proven human bioavailability and pharmacokinetics);2 and

• results of specific clinical trials (studies of non-DONA glucosamine products [unknown formulations] have had mixed results while DONA has shown consistent efficacy across all trials, and has been assigned level 1A evidence by the European League Against Rheumatism).2-6

Not requiring sponsors to have evidence to support claims made about their products encourages low quality. For example, the market-leading glucosamine products in Australia have not been subject to independent peer review to establish whether they are effective. As the claims allowed on such products are identical to the claims allowed on DONA, there is no incentive for the industry to source the “real thing” or conduct their own clinical trials.

In the interests of their patients, we believe that health professionals have a right to be able to identify specific products that have been clinically proven. Use of CMs that is not evidence-based is likely to lead to failure to realise significant health benefits of CM for the Australian public.

To the Editor: The article by Harvey et al raises important concerns about the complementary medicine (CM) industry, particularly with respect to inappropriate marketing and advertising by some sponsors.1

The role of the Therapeutic Goods Administration (TGA) in setting standards and regulation of CMs should not be taken lightly. Australia has one of the highest quality standards for CMs internationally. Many CM products in Australia are assessed by expert authorities within the Office of Complementary Medicines and the Complementary Medicines Evaluation Committee of the TGA for safety and (where appropriate) efficacy relating to claims made for products.2 This is not fully appreciated by the authors.

While many CMs may lack high-quality research to validate efficacy, this does not necessarily mean they are not clinically effective. Many clinicians and consumers find CMs to be of clinical value in improving health status. By suggesting that “the listing system should be scrapped, and CAMs [complementary and alternative medicines] . . . be assessed for efficacy and delisted if evidence is lacking” would be to deny consumers choice of treatment and potential health benefits, and lead to a “black market” or buying products from overseas which may not compare in quality. The authors fail to acknowledge that much of the drive for CM sales is actually coming from consumers through their choice of health care treatment.3 Consumers have the right to trial CMs. It is our role to ascertain safety issues and encourage clinical trials where they are lacking. For thousands of years, populations have relied on some CMs for health benefits, not having the advantage of any trials, but relying solely on traditional use. If the risk of harm to human health from the use of a CM outweighs any proven or unproven efficacy, consideration should be given to delisting the product or restricting its use. More research is required to assess safety data and efficacy for CMs.

Australia has come a long way in regulating CMs. To say the “listing system should be scrapped” does not appreciate the tremendous efforts and gains made by the TGA compared with international efforts to enforce good manufacturing practice and various methods to better safeguard consumers.

The authors do raise a valid point in saying that sponsors should provide “key evidence supporting each indication of the ARTG [Australian Register of Therapeutic Goods] . . . [which] should be publicly available on the Internet”. This may be useful for consumers and health practitioners, but requires appropriate funding to be viable. Furthermore, codes of conduct and complaints procedures for CMs, such as through the Complaints Resolution Panel, need to be strengthened, particularly with respect to breaches in the advertising code.4 To date, the Parliamentary Secretary has asked the TGA for advice on the proposals put forward by Harvey and colleagues.1,5 The government will consider its response to these proposals in the context of taking forward legislative changes that were deferred in anticipation of the establishment of an Australian New Zealand Therapeutic Products Agency (TGA advice, 28 May 2008).

To the Editor: Harvey et al1 have a right to be concerned about the parlous state of regulation in the billion-dollar complementary medicine (CM) industry. They are not alone, with various leaders from CM doctor groups and other leaders also expressing concern.2,3

Predictably, those in the CM industry itself are denying any problems exist, and just repeat their mantra that their products are safe and effective.3

As business people, the leaders of the CM industry must be pleased with the unchallenged run they have had over the past 20 years (except for one challenge with the Pan Pharmaceuticals debacle4).

Consider one company (Mannatech) whose multilevel marketed products are promoted by their associates (natural drug representatives) as useful for arthritis, diabetes, dementia, attention deficit hyperactivity disorder, Parkinson’s disease, asthma, cancer and various other chronic diseases. The associates promoted claims that a product, Ambrotose, would assist with the above conditions using literature that did not carry the company logo, and used the company literature for non-specific claims and testimonials, thus absolving the company of responsibility.

The Therapeutic Goods Administration is helpless in such a situation, and it was only when a medical practitioner started selling Mannatech products, including Ambrotose, from his surgery that the state medical board took an interest.5 However, the medical board has no jurisdiction over the company, and when the doctor was deregistered, he would have been able to keep marketing the product for the company.

Mannatech launched Ambrotose in Australia, quoting the benefits of their product from a trial conducted and published in the Journal of the American Nutraceutical Association by American immunologist Dr See and colleagues.6 Eighteen months later, the published trial was the subject of much controversy.7 There was little if any effect on the company from this, in stark contrast with what one would expect in the pharmaceutical industry.

Yes, Harvey and colleagues are just starting to scratch the surface of controversies that are decades old in this unregulated industry. For the good of the public and for the good of the CM industry, there needs to be a watchdog, similar to Medicines Australia, to regulate CM.

In reply: We agree with Kotsirilos that the current listing process of the Therapeutic Goods Administration (TGA) provides some protection for consumers by ensuring that complementary medicines (CMs) are manufactured in accordance with good manufacturing practice.

The TGA claims that about 25% of new listings are assessed in detail each year for compliance with requirements, including that sponsors must hold evidence to support promotional claims made.1 However, we understand that the TGA does not assess this evidence for quality, and that literature searches are not performed to see if more recent evidence2 contradicts that submitted by the sponsor.3

In addition, sponsors can make a conservative claim at the time of listing but then make very different claims in promotional campaigns. An under-resourced, laboriously slow and largely impotent complaint system provides little disincentive to such unethical (but profitable) behaviour.

While the Medicines Australia code of conduct (for prescription medicines) still has room for improvement, we agree with Masters that it currently provides more effective sanctions for breaches (eg, fines up to $200 000) than the options currently available to the TGA. Medicines Australia also proactively monitors compliance with the code of conduct and provides useful annual reports.4

Regardless, claims for CM that cannot be substantiated by appropriate evidence are better dealt with at the time of a marketing application rather than many months after advertisements have been published and when consumers have long been misled. We also recommended that therapeutic equivalence of the product in question should also be assessed at this time; a point reiterated by Santoro and Pollard.

We support the right of consumers to choose from a variety of therapeutic modalities offered in the market place. However, good decision making requires evidence-based information about risks and benefits, regardless of whether the medicine in question requires a prescription, can be obtained over the counter or is a CM. Even if the risks of CMs are relatively low, the financial and opportunity cost for consumers can be significant.

A pragmatic compromise to delisting CMs that lack evidence of effectiveness would be an opt-in system, funded by an additional fee, that would independently evaluate the effectiveness of specific CM products. A product with reasonable evidence of effectiveness could be awarded a symbol similar to the the National Heart Foundation “red tick”. Implementing this measure, together with the disclaimer and other recommendations we made in our article,5 would assist consumer choice and provide a market advantage for the sponsors of evidence-based, ethically promoted CMs.

These proposals have received support from health professional and consumer organisations as well as sections of the CM industry. They have been put to the Parliamentary Secretary who assists the Minister for Health and Ageing.3