Evidence guidelines

Guidelines on the evidence required to support indications for listed complementary medicines

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24 July 2014

Traditional indications: What evidence do you need to support your traditional indication?

Evidence of traditional use

Traditional indications present factual statements of a health benefit relating to a historical record of use within a traditional paradigm. Traditional indications cannot make a scientific claim of efficacy; as such indications require supportive scientific evidence.

Evidence of traditional use to support your traditional indication can be based on the medicine itself as a whole, or on evidence for the individual ingredient about which the indication is made. Each ingredient should be clearly identified and you must hold evidence for each indication. If you chose a traditional indication that is linked to a specific ingredient in the medicine's formulation, then that ingredient should be linked to that indication on the medicine's label.

To claim evidence of traditional use you should ensure that your medicine or ingredient is an established part of a tradition of medicinal use within a particular paradigm or culture for over three generations.

Evidence of traditional use

Traditional indications are based on evidence of a history of medicinal use of the ingredients or medicines that exceeds three generations (75 years) of use.

Many traditional ingredients have a well-established period of widespread traditional use extending well over 75 years, which is extensively recorded in recognised evidence sources for traditional medicine such as materia medica, monographs and publications from various international regulatory authorities.

Factors that should be taken into account to establish that a medicine or active ingredient has a well-established tradition of use for its intended purpose include the:

  • time over which the medicine or active ingredient has been used
  • therapeutic use/s during that time
  • continuity of its use
  • geographical extent of its use ; and
  • use of the medicine is recorded in recognised traditional medicine evidence sources.

Well established traditional of use

Traditional indications based on

  • evidence of a history of widespread medicinal use of the ingredient/s or medicine that well exceeds three generations of use (75 years); and
  • the traditional use is extensively recorded in internationally recognised evidence sources for traditional medicine use.

If the traditional indication is non-specific (general) and is associated with a well-established tradition of use for a particular ingredient or medicine, then the evidence to support the traditional indication is easier to assess and establish.

Homoeopathic medicines

Homoeopathic medicine is a traditional paradigm where the manufacturing process of serial dilution and succussion or serial trituration is a major component of the tradition of use. Provided that a substance is prepared according to principles described in a recognised homoeopathic pharmacopoeia and safety requirements are satisfied, indications may be based on traditional use. Evidence of traditional use for homoeopathic medicines can include independent written histories of use in traditional or contemporary homoeopathic literature.

Evidence package checklists will assist you in compiling an evidence package for your traditional indication.

Multi-traditional paradigm medicines

A listed medicine may contain multiple traditional ingredients that are supported by evidence of therapeutic use within different traditional paradigms (multiple traditional paradigms). Each indication must be supported by evidence and include the traditional context of use (see traditional context in 'What does an indication look like?').

The resulting medicine or formulation is not traditional in the context of either of the original traditional paradigms. For example, an ingredient from traditional Chinese medicine may be combined with another ingredient from traditional Ayurvedic medicine. However, since the new formulation is neither a traditional Chinese nor Ayurvedic medicine, the formulation as a whole cannot claim a history of use. Therefore, each indication must refer to the relevant ingredient and specify the traditional paradigm of use.

Your evidence package should include a rationale for the combination of the ingredients in the new formulation which is justifiable in terms of therapeutic use; this includes the dose of each ingredient based on their respective traditional uses.

Example of a traditional indication for a multi traditional paradigm medicine:

  • 'These herbs are used traditionally in Chinese medicine and Ayurvedic medicine to promote relaxation'.

What are the sources of evidence of traditional use?

Many traditional medicines and ingredients with a long and coherent history of use are well documented in monographs, materia medica and other texts. Some traditional medicine paradigms have been recorded by people outside the tradition's indigenous origin and culture. Other traditional medicine paradigms, particularly those that have been developed within smaller and more localised groups are not well documented; rather they are based on knowledge transmitted orally from generation to generation.

In some instances, you may need different sources of evidence of traditional use to support a particular indication for a traditional ingredient or formulation. Together these sources should form a combined collective of evidence that will be relevant and of high quality.

Note that in general, web searches will not provide sufficient evidence to substantiate traditional indications.

What are the primary sources of evidence of traditional use?

Primary sources of evidence to support traditional indications for your medicine can be derived from sources such as:

  • materia medica
  • official pharmacopoeias
  • monographs
  • publications from various international regulatory authorities
  • texts that are relevant to the traditional paradigm; and
  • well recognised evidence-based reference texts.

A pharmacopoeia contains a comprehensive list of medicines and describes their properties and how they are prepared.

A materia medica sets out the body of knowledge on the therapeutic properties of medicines. Different materia medica relate to different types of complementary medicines, for example: Traditional Chinese Medicine and homoeopathy.

While the TGA does not have a list of approved sources of information, Appendix 3 provides some examples of internationally recognised resources and texts.

Each item of evidence must be considered on its own merit in relation to your medicine. An item of evidence can only be considered a primary source of evidence if it establishes a tradition of use and is credible and relevant for your medicine/indication.

Some monographs refer to clinical studies or pharmacology of a particular ingredient using citations and reporting study outcomes of auxiliary scientific papers. Such information would be considered a secondary source of scientific evidence and is often associated with scientific indications. Such information is not consistent with evidence of tradition of use and traditional indications.

Can non-reference textbooks be used as sources of evidence?

Non-reference textbooks cite, comment on or build on primary sources of evidence. As such, non-reference textbooks do not usually provide sufficient evidence to substantiate traditional indications. If you use a non-reference textbook, you should locate the original or primary source of evidence of traditional use; that is find copies or quotations from the original documents cited in footnotes. If this is not possible then include the footnotes in your evidence summary to clearly indicate that the textbook is based on original historic records.

Where it is impossible to find the original reference that describes the traditional use, evidence of traditional use may be supported by more recent references reporting the original tradition. However, these references should provide enough information to support that your medicine is consistent, as far as possible, with the one described in the original reference.

Can you use modern textbooks and monographs to support your traditional indication?

Many modern textbooks and monographs include a combination of both traditional and scientific evidence. If you are using a textbook, monograph or similar source to support an indication, you must determine whether the information in the source is traditional (over three generations of use) or scientific.

In a situation where a traditional indication is used in combination with a scientific statement relating to the mechanism of action of the ingredients, the combined indications must not imply clinical efficacy unless supported by primary sources of scientific evidence.

Mechanistic studies [in vitro studies or non-clinical (animal studies)] are types of secondary sources of evidence and are appropriate to provide information regarding the biological plausibility of a mechanism of action. However, non-clinical studies are rarely a supportive form of evidence in isolation and cannot be used to imply efficacy of a medicine in the absence of clinical studies.

Can you use independent written histories to support your traditional indication?

When supporting evidence includes independent written histories of use in the classical or traditional literature (such as in relation to oral evidence or testimonials), the significance and clarity of references to any health benefit should be assessed by whether the:

  • traditional paradigm is defined
  • ingredient(s)/medicine is/are fully characterised (for example: chemically, biologically)
  • preparation is described
  • dose and dosing details are documented
  • route of administration is specified
  • target population is defined; and
  • traditional indication is described.

Can you use evidence in languages other than English to support your traditional indication?

Evidence in a language other than English can be used, if you provide in your evidence package a:

  • copy of the relevant pages in the original language; and
  • verified English translation of the relevant pages.

A verified translation is one that is accompanied by a signed statement from an accredited translator, fluent in both languages, verifying that the translation is true and complete.

Are there any other evidence sources you can use to support your traditional indication?

If the traditional indication is from an oral culture, video footage (stored in a digital format, not on film) may be appropriate. To be regarded as high quality, oral evidence must be corroborated from at least two separate sources in different locations.

Assessing the relevance of evidence to your indication

You must ensure that the evidence of traditional use for your indication is comparable to your medicine in terms of:

  • ingredient/s
  • method of preparation
  • dosage; and
  • conditions of use (route of administration, frequency and duration of use, target population and risks).

In general, active ingredients may be considered as sufficiently identical if there are no relevant differences in the method of preparation and if the medicine has the same intended purpose, dosage and the same route of administration. This includes traditional medicines in which the therapeutic indication, dosage and administration are based on traditional knowledge but the dosage forms have been modified to modern dosage forms, for example: capsules or tablets.

When evidence relates to an herb or herbal substance, the species (and subspecies where applicable), plant part and route of administration should be identical to that described in the evidence. The method of preparation and processing, the equivalent dry weight and the dose of active component described in the evidence should be consistent with that in the medicine. Traditional methods of preparation include:

  • the use of a whole organism or specific parts (leaf, root, fruiting body, etc.)
  • fresh, dried, or preserved with alcohol, honey or sugar
  • extracts produced by the application of pressure to the source material
  • aqueous extracts such as infusions, decoctions and syrups
  • ethanol-based extracts such as tinctures
  • glycerine-based extracts
  • vinegar-based extracts
  • oil, grease or fat-based infusions; and
  • beeswax salves and ointments.

Other methods of preparation may be considered traditional if supported by an appropriate reference describing the use of the method within the traditional medicine paradigm. However, non-traditional methods of preparation of otherwise traditional materials, including the use of non-traditional solvents, can change the chemical profile of the preparation. Such changes may affect the efficacy (and safety) of the product. Medicines that have been altered significantly in their constituent profile from the traditional medicine on which the indication is based will require scientific evidence to substantiate their claimed action.

Additional guidance on the equivalence of herbal extracts in complementary medicines is available on the TGA website.

Medicinal preparations described in early pharmacopoeias, materia medica and other traditional references may pre-date modern analytical techniques. These are unlikely to provide a comprehensive and satisfactory specification (for the characterisation and establishment of the quality of the ingredient or medicine). In such situations, your active ingredients and method of preparation should be identical to that described in the classical literature.

Modification of traditional formulations

Modification to the traditional formulations in Traditional Chinese Medicine (TCM) and Ayurvedic medicine should ensure that the traditional method of preparation, traditional formulation principles and dosage for the therapy remain in order for these medicines to make a traditional indication.

That is, to meet the criteria for a traditional claim using a history of TCM use, the overall medicine formulation should reflect the traditional principles of ingredient combinations or substitution of herbal species.

For traditional ingredients or medicines which have been altered significantly in their constituent profile from the classical traditional medicine on which the indication is based, further information may be required to justify the alteration in order to substantiate their claimed indication.

What indication sub-type does your evidence of traditional use support?

The sub-type of the indication will affect the level of evidence required to substantiate the indication. The more non-specific the traditional indication, the greater likelihood that the evidence to support the indication can be found in primary sources of evidence of traditional use and the more straightforward the evidence assessment process will be.

Table 3 provides information on the level of evidence generally required to substantiate non-specific and specific traditional indications.

Table 3: Levels of evidence generally required to support sub-types of traditional indications
Level of indication Evidentiary support required
Traditional non-specific (general) indications Two primary sources of evidence of traditional use.
Traditional specific indications At least two primary sources of evidence of traditional use as well as other relevant and credible items of evidence to support the specificity of the indication.

An example of a non-specific indication for a traditional ingredient:

  • Allium sativum (garlic) (that has a well established tradition of use): 'Traditionally used in Western herbal medicine to support immune system function in healthy individuals'.

An example of non-supportive evidence for a traditional specific indication:

  • A listed medicine contains a number of herbs commonly used in TCM and has the indication: 'Traditionally used for the symptomatic relief of heartburn'.
  • The only evidence the sponsor holds that the ingredients have a tradition of use within TCM is a copy of the relevant pages from a contemporary Chinese reference that indicate one of the herbs present in the medicine was used in ancient times for symptoms such as 'stomach fire with rebellious stomach qi'. However, there is no information on the plant part of the herbal species used, the method of preparation or the recommended dosage.
  • In this instance, the evidence item is not sufficient to support the proposed indication at the dose recommended.

An example of supportive evidence item for a traditional specific indication:

  • A listed medicine contains a number of herbs commonly used in TCM and has the indication: 'Traditionally used for the symptomatic relief of dry cough'.
  • All ingredients are included in the Pharmacopoeia of the People's Republic of China (PPRC). The formulation is referred to in a TCM Materia medica. Ingredients in the medicine are the same plant part, preparation type and quantity as that referred to in the traditional formula in the Materia medica. However, one of the herbal ingredients is not a permitted ingredient in listed medicines in Australia. This ingredient has been substituted in the medicine available in Australia by another herbal ingredient, which is listed in the PPRC as a widely accepted medicinal substitute for the original herbal ingredient.
  • In this instance, this evidence item is likely to support the proposed indication.

Choosing or deciding upon your traditional indication

Due to the discordance between traditional and contemporary contexts and the potential for consumers to assume that medicines have been assessed scientifically, traditional indications are required to include the traditional context of use in the indication (refer to 'What does an indication look like?'). Evidence of traditional use must clearly identify the traditional paradigm which it refers to, and this context must be conveyed clearly to the consumer. When traditional use is limited to a particular paradigm or geographical region, then this limitation must be referenced in the indication.

Compare your chosen indication with the reported health benefit and context of use in your evidence of traditional use. Your indication should have the same meaning and intent specified in the evidence (including any traditional terminology). The terms used in your indication should be consistent with the specified paradigm to ensure that the indication is not misleading and appropriately supported by the evidence you hold. The use of common English terms in addition to traditional terminology provides clarity to the average consumer regarding the therapeutic use of the medicine.

You should ensure that each ingredient (for which a traditional indication is made) has been prepared using a traditional method for that paradigm (for example: dilution and succussion of mother tinctures for homoeopathic medicines). Where your medicine has been modified from a classic formula or individual ingredient - you should show that the formula or ingredient, as modified, is still acceptable within the specified tradition.

When choosing or deciding upon your traditional indication you should:

  • clearly identify the traditional paradigm that supports the traditional formulation
  • base any statement about the medicine's therapeutic benefit on experiences or theories specific to the particular tradition, not on scientific cinical evidence; and
  • use the same logic and terminology (in English terms or accompanied by English terms) that belongs to the specified traditional paradigm.

Your traditional indication should not:

  • refer to anatomical, physiological or pharmacological effects that are not envisaged within the specified paradigm, for example: 'raise haemoglobin levels'
  • imply efficacy based on scientific evidence for the medicine, for example: 'clinically tested'
  • use specialist terminology that belongs to a different paradigm, for example: 'damp heat' is a specific Chinese medicine term and would be inappropriate for an Ayurvedic medicine
  • include indications that require scientific substantiation, for example: 'assists to increase bone density by 10%'; or
  • refer to conditions that cannot be diagnosed within the specified paradigm, for example: 'Traditionally used in Chinese medicine to increase bone mineral density' is inappropriate as increased bone mineral density cannot be monitored or determined without conventional medical intervention.

If you are aware that there is conflicting evidence between the history of traditional use and contemporary scientific evidence for your medicine, then it is advisable to include a statement to this effect in any labelling and advertising associated with the medicine, for example: 'this traditional use is not supported by scientific evidence'. This will ensure that the advertised information relating to your medicine is truthful, valid and not misleading.

In deciding your traditional indication, ask yourself

  • Is the indication suitable for use in listed medicines?
  • Are the terms used to describe your indication the same as those in your evidence of traditional use?
  • If the terms are different from those in the evidence of traditional use, can you justify the change?

How to compile a summary of the evidence to support your traditional indication

You should compile an evidence summary demonstrating that you have conducted an objective, comprehensive review of the literature relating to your traditional indication/s. The resulting evidence you hold should be:

  • relevant to your medicine
  • be of high quality; and
  • adequately demonstrate that all traditional indications you make for your medicine are true, valid and not misleading.

Evidence package checklists provided on the TGA website assist you to collate your evidence summary and filter evidence items to those that are credible and relevant to your medicine. Refer to Appendix 1: How to use evidence package checklists for assistance with the process. While presentation in this manner is not compulsory, it will expedite the compliance review process should your medicine be selected for an evidence compliance review.

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