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Assessed listed medicines evidence guidelines

Version 1.1, August 2018

17 August 2018

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3. Indications

3.1 Risk categorisation

"Indications" are claims that relate to the purpose or health benefit of the product. They are defined in the Act as '‘the specific therapeutic uses of the goods'. All indications on the product label or other advertising must be included in its ARTG entry.

The TGA has a risk hierarchy of indications for complementary medicines. This takes into account the health status and potential vulnerability of the target population; the seriousness of any conditions mentioned; and the probability that a consumer may delay seeking medical treatment based on an indication. On the basis of these risk factors, indications are categorised into three levels of risk: low, intermediate and high.

  • Low level indications are those appropriate for listed medicines, and are specified in the list of Permitted Indications. They include indications for self-diagnosable, self-manageable, and self-limiting conditions where a delay in medical treatment would not be detrimental to the consumer. Low level indications may only refer to general health maintenance, health enhancement, prevention of dietary deficiency, or those that imply a benefit for a non-serious form of a disease or condition.
  • Intermediate level indications exceed the criteria for low level indications but are still appropriate for listed medicines. They are generally more definitive, relate to more serious health conditions, and may present higher risk to consumers than low level indications. These indications include references to prevention or alleviation of non-serious forms of a disease, condition, ailment, defect or injury. Although the conditions captured by these therapeutic uses will generally be naturally self-limiting, self-diagnosable and/or self-manageable, medicines carrying these indications may have the potential to lead to a delay in seeking medical treatment and/or adverse consequences for the consumer.

    Intermediate level indications can also include certain restricted representations[2]. These are indications which, despite referring to a serious disease, condition, ailment or defect specified in the Therapeutic Goods Advertising Code 2015 (as amended from time to time), are permitted on lower risk medicines in acknowledgement of a compelling health benefit from the use of products that refer to them. As such, in addition to demonstrating efficacy of the product, the public interest criteria need to be satisfied to allow a restricted representation to be used.

  • High level indications are those that refer to the treatment, cure or prevention of a serious[3] form of a disease. The diseases referred to by this category of indication may not naturally resolve within a timely manner, and may have undesirable effects that may persist or worsen if effective treatment is not pursued in a timely manner. Products carrying high level indications are not suitable for listing, and must be registered in the ARTG following a complete assessment of their safety, quality and efficacy by the TGA.

The risk hierarchy for indications aligns with the classification of a medicine as a listed, assessed listed, or a registered product. This framework is summarised in Table 1 below.

Table 1: Indication risk classification
Low level Intermediate level High level

Indications drawn exclusively from the list of permitted indications.

A low level indication may refer to:

  • health enhancement
  • health maintenance
  • prevention of dietary deficiency
  • a disease, ailment, defect or injury other than a serious form of those diseases.

A low level indication must not:

  • refer to, or imply, the prevention, alleviation, or cure of any form of a disease, ailment, defect or injury
  • contain a prohibited representation
  • contain a restricted representation[4]
  • have been specified in a non-permitted indications list (if such a list is made).

Indications that are not appropriate for the list of permitted indications, but are not high level indications.

Intermediate level indications may refer to:

  • the prevention, alleviation, or cure of a non-serious disease, ailment, defect or injury
  • restricted representations (i.e. a serious form of a disease).

Intermediate level indications may include those indications specified in a non-permitted indications list (if such a list is made).

An intermediate level indication must not:

  • refer to the prevention, alleviation or cure of a restricted representation (i.e. a serious form of disease)
  • contain a prohibited representation.

Indications that refer to the prevention, alleviation or cure of a serious form of a disease, ailment or injury (i.e. restricted representations).

A high level indication must not:

  • contain a prohibited representation.

See Indications for assessed listed medicines for examples of intermediate and low level indications.

3.2 How to structure an indication

Unlike sponsors of standard listed medicines who must draw exclusively from the list of Permitted Indications, sponsors of assessed listed medicines may submit their own indications. These indications should conform to the required structure and must be supported by appropriate evidence. A valid indication:

  • must describe the specific therapeutic use(s) of the medicine; and
  • must contain three core components: the context (if applicable), action and target.

An indication may also be qualified to specify the severity, population, and timeframes related to the therapeutic use, depending on the specificity of the evidence. Components of an indication are summarised in Table 2.

Table 2: Components of an indication
Component Explanation Examples
Action The action, effect, mechanism or benefit of the product. Reduces, relieves, supports, increases, maintains etc.
Action qualifier Terms that ensure the action is suitable for the level of evidence the sponsor holds. They often specify effectiveness. Helps, temporary relief of, etc.
Target The physiological/ psychological factor or process; or disease, ailment, condition, defect or injury. General health and well-being, headache, muscle cramps and spasms, fever, pain, etc.
Target qualifier Terms that ensure that the target is suitable for the evidence the sponsor holds. Mild, symptoms of, healthy/normal, moderate, excess, etc.
Indication qualifier Terms that may provide information relating to the evidence held by the sponsor. This includes terms that specify a target population and/or times of use. In the elderly, in sports athletes, in women, after strenuous exercise, etc.
Context This specifies the traditional paradigm for indications where the sponsor holds evidence of traditional use. Traditionally used in Western herbal medicines

The structure of a valid indication is illustrated below. The action and target are mandatory. The context is mandatory for traditional indications.

Context (if applicable) plus action qualifier (optional) plus Action (mandatory) plus target qualifier (optional) plus Target (mandatory) plus indication qualifier (optional)

Note that the use of indication qualifiers requires sponsors to hold more specific evidence for their medicine.

3.3 Indications for assessed listed medicines

3.3.1 Intermediate (primary) indications

Intermediate level indications may only be used on products that have undergone pre-market assessment by the TGA. Assessed medicines must have at least one approved intermediate indication.

Please note that:

  • Intermediate indications can be linked to individual ingredients or the entire medicine, provided that the evidence for the finished product supports the indications i.e. if the intermediate indication is associated with a specific ingredient (e.g. folic acid), evidence from clinical trials and/or biopharmaceutic studies on the product must be provided rather than literature based evidence for the specific ingredient (refer to Evidence requirements).
  • As all indications for an assessed listed medicine must be supported by scientific evidence, indications that belong to a recognised paradigm outside modern conventional medicine ("traditional indications") are not suitable as intermediate indications. They can, however, be included on products as secondary indications (see Low level (secondary) indications).
  • Intermediate level indications can imply clinical efficacy where they are supported by evidence.

Intermediate indications may refer to:

  • Preventing, curing or alleviating a non-serious form of a disease, ailment, defect or injury

The indication may refer to or imply the prevention, alleviation or cure of a non-serious form of a disease, ailment, defect or injury. 'Cure' is considered to imply the complete resolution of the disease, ailment, defect or injury.

These indications may relate to:

  • reduction in risk, frequency, duration or severity;
  • relief or reduction of symptoms; and/or
  • complete resolution;

of a non-serious form of a disease, condition, ailment, defect or injury.

Examples:

'Prevents muscular cramps and spasms'

'Alleviates mild dermatitis'

'Prevents cold sores'

  • A serious form of a disease, condition, ailment or defect

The indication can refer to a serious form of a disease, condition, ailment or defect (e.g. a restricted representation) other than prevention, alleviation or cure of that disease, condition, ailment or defect.

These indications may relate to:

  • relief or reduction of symptoms, without implying resolution, cure, alleviation (reduction in severity) or prevention of the disease, condition, ailment or defect.

Examples:

'Reduces symptoms of tinnitus'

'Relieves rheumatoid arthritis symptoms, such as inflammation and pain'

'Relieves symptoms of gastroesophageal reflux disease'

The list of permitted indications includes the indications covered by the substance-based restricted representation exemptions linked to vitamin D and calcium (referring to osteoporosis) and folic acid (referring to neural tube defects) on the basis of their public health importance, safe history of use and well-established evidence base. Current listed medicines can use these indications and are not required to transition to the assessed listed medicines pathway.

All other indications that refer to a restricted representation will require assessment and approval through a pre-market assessment pathway.

3.3.2 Low level (secondary) indications

Low level 'secondary' indications such as those drawn from the list of permitted indications may be included on assessed listed medicines in addition to the primary intermediate level indication(s). The secondary indications must meet the requirements for low level indications as described in the Permitted indications for listed medicines guidance.

All secondary indications for use with assessed listed medicines require pre-market assessment by the TGA. Sponsors are required to submit evidence to support these indications alongside evidence submitted in support of the intermediate (primary) indications. The level of evidence required to support low level (secondary) indications for assessed listed medicines is consistent with the requirements for standard listed medicines.

Low level (secondary) indications can be linked to individual ingredients or the entire medicine, provided that the evidence for the finished product supports the indications.

Secondary indications may:

  • be associated with individual ingredients or the whole medicine. If an indication 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;
  • be general (non-specific) or specific in nature. General indications are those relating to health maintenance and supplementation or relief of symptoms not related to a named condition (e.g. 'helps soothe dry skin'). Specific indications refer to named conditions or symptoms, health enhancement or specific therapeutic effects (e.g. 'helps relieve indigestion');
  • include both scientific and traditional indications, provided there is scientific evidence to demonstrate efficacy for all indications and evidence to show use in a traditional context for traditional indications.
Scientific indications

Scientific indications are those that refer to modern conventional medicine paradigms and which are supported by quantitative scientific data derived from human clinical trials, observational studies and/or systematic reviews.

Scientific indications cannot:

  • imply a higher level of certainty in the implied health benefit than warranted by the supporting evidence, i.e. terms such as 'clinically' and 'scientifically' in combination with 'proven', 'tested', 'trialled' etc. are not appropriate unless supported by unequivocal data from robust clinical trials on the product;
  • refer to traditional paradigms, or be based on evidence of traditional or historical use.

Examples:

'Helps relieve mild dermatitis'

'Helps maintain blood levels of vitamin D'

'Aids/assists healthy red blood cell production'

Vitamin or mineral supplementation indications are only permitted where the recommended daily dose of the product provides at least 25% of the Australian Recommended Dietary Intake (RDI) for that vitamin or mineral. If there is no Australian RDI for a vitamin or mineral, an RDI from another country may be used. Indications should not refer to the presence of vitamins or minerals unless they are present in the recommended daily dose of the product to at least the level of 10% of the RDI, unless there is evidence to support a therapeutic effect below this level. The dose must be consistent with the evidence to support the indication being made.

Traditional indications

Traditional indications are those that belong to a recognised paradigm outside modern conventional medicine. These include – among many others - traditional Chinese medicine, Aboriginal and Torres Strait Islander healing practices, Ayurvedic medicine, and Western herbal medicine. Traditional indications must be based on long-term use (in excess of three generations - 75 years) within a specific paradigm. The traditional use should be extensively documented in internationally recognised evidence sources for traditional medicine use.

Please note, all indications for an assessed listed medicine must be supported by scientific evidence of efficacy. Claims of use in a traditional context may be used if the therapeutic use of the indication is supported by scientific evidence of efficacy. For example, 'traditionally used in Ayurvedic medicine to soothe an upset stomach' can be used if supported by; scientific evidence that the product relieves the relevant stomach condition; and evidence of a tradition of use in Ayurvedic medicine.

Traditional indications must refer to the traditional paradigm in which the medicine has been used, must use terms consistent with the specific traditional paradigm, and must be based on the experiences/use within the specific paradigm. They may include multiple traditions if the ingredient/product has been used within more than one tradition for the same benefit.

Examples:

'Ingredients in this medicine have been traditionally used in Ayurvedic and Chinese medicine for relieving symptoms of the common cold'

Traditional indications must not:

  • refer to scientific terminology, or use terms belonging to other traditional paradigms
  • refer to anatomical, physiological or pharmacological effects not envisaged in the traditional paradigm (e.g. 'lowers cholesterol'), or requiring scientific substantiation; or
  • refer to conditions that cannot be diagnosed within that paradigm.

It is important to ensure that your indication aligns with the evidence you have to support it. The supporting studies need to refer to medicines with the same formulation, preparation, dosage, and duration of use, and must have been carried out in a similar population group and context (refer to Alignment and Presentation for more information).


Footnotes

  1. A restricted representation is any reference expressly or by implication, to a serious disease, condition, ailment or defect. Prior approval is required by the TGA before an advertisement may refer to a restricted representation.
  2. A serious form of a disease or condition is one which is generally accepted to be beyond the ability of the average consumer to diagnose, evaluate, and/or safely treat without consulting a suitably qualified health care professional.
  3. Excludes approved restricted representations for sunscreens, folic acid, vitamin D and calcium.

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