Relevance to target population Population studied is identical to the target population. Population studied is comparable to the target population. Some differences between study and target populations but ‘clinically reasonable’ to extrapolate evidence to the target population. Major differences or differences of uncertain clinical significance exist between study and target populations. Relevance to health benefit Study directly measures health benefit in listable indication as primary outcome. Study directly measures health benefit in listable indication as secondary outcome. Study directly measures health benefit in listable indication as analysis. Study does not directly measure health benefit in listable indication. Relevance to context of use context directly applicable to Australian self care context. Study context applicable to Australian self care context with few caveats. Probably applicable to Australian self care context. Study context not applicable to Australian self care context. When an indication is directed at a specific of the population, eligibility criteria will reflect the indication. When an indication is directed at a sub-group of the population, the sub-group must be specified in the indication. The results of studies that target specific subgroups cannot be generalised to the general population Only studies achieving ratings of ‘satisfactory’ or above in ALL four relevance categories are considered relevant to a proposed listable indication. All studies achieving four ratings of ‘satisfactory’ or above must be included in the analysis of evidence, and studies not achieving this ranking must be excluded. 3.2.1.6 of relevant evidence Each relevant item of evidence must be categorised according to the National Health and Medical Research Council (NHMRC) hierarchy of evidence for intervention studies, prognosis or aetiology. The hierarchy for prognosis or aetiology may only be used where randomised controlled trials are impractical or unavailable. Table 3: NHMRC Levels of Evidence Intervention Prognosis Aetiology I 4 A systematic review of level II studies A systematic review of level II studies A systematic review of level II studies
II A randomised controlled A prospective cohort study A prospective cohort study III-1 A pseudo-randomised controlled trial(i.e. alternate allocation or some other method) All or none All or none III-2 A comparative study with concurrent controls: Non-randomised, experimental Cohort study Case-control study Interrupted time series with a control group Analysis of prognostic factors amongst persons in a single arm of a randomised controlled A retrospective cohort study III-3 A comparative study without concurrent controls: Historical control study Two or more single arm study Interrupted time series without a parallel control group A retrospective cohort study A case-control study IV Case series with either post-test or pre-test/post-test outcomes Case series, or cohort study of persons at different stages of disease A cross-sectional study or case series 3.2.1.7 Quality of relevant evidence The quality of relevant item of evidence must be assessed utilising a published, critical appraisal instrument that is appropriate for the type of evidence being considered. The instrument must include as a minimum an assessment of the following: characterisation of the ingredient/s study design/methods participant eligibility (inclusion/exclusion criteria) randomisation and blinding of participants (for Randomised Controlled Trials (RCT)) sample size justification/power calculations controlling for potential confounders
reasonable’ to extrapolate evidence to the target population. exist between traditional and target populations. Relevance to traditional health benefit The wording of the indication is identical to item of evidence, including, the use of traditional terminology. The wording of the indication is identical in intent to item of evidence, including, the use of traditional terminology (traditional synonym used to describe the indication). The wording for the indication is identical in intent to item of evidence, but using contemporary terminology (modern synonym used to describe the traditional indication). The wording and intent for the indication is inconsistent with the item of evidence. Relevance to traditional context Clearly identified and used continuously within the relevant traditional paradigm over at 75 years. Identified within the relevant traditional paradigm but with disclarity regarding consistency of use over a period of 75 years. Identified within the relevant traditional paradigm with some disclarity regarding characterisation of the active ingredients or formulation. Not consistent with the relevant traditional paradigm. Only of evidence achieving ratings of ‘satisfactory’ or above in ALL four relevance categories are considered relevant to a proposed listable indication. All items achieving four ratings of ‘satisfactory’ or above must be included in the analysis of evidence, and those not achieving this ranking must be excluded. 3.2.2.6 Quality of relevant evidence When supporting evidence includes independent written histories of use in the classical or traditional literature, the significance and clarity of references to any health benefit must be assessed. The assessment of quality must consider how well the: traditional paradigm has been defined ingredient(s)/product has been characterised preparation has been described dose and dosing details have been documented route of administration has been specified target population has been defined; and trial
In cases where the traditional terminology may be unclear to consumers, the information should (also) be communicated using appropriate conventional terminology. The use of appropriate contextual qualifiers and the inclusion of a statement to the effect that the health benefit is based exclusively on long-term use and experience, ensures that such information is readily available to consumers. In situations where the requirements for both scientific evidence and evidence of traditional use are met for an active ingredient or product, traditional and/or scientific indications may be made. If an indication is solely supported by scientific evidence, it must not use the words ‘traditionally used’. The guidance regarding the assessment of evidence for scientific and traditional indications is provided in Section 3. 2.2 Types of indication according to type of health benefit Listable indications may be further classified according to type of health benefit. In broad terms, indications may target biological factors or processes, health states or clinical conditions. The following diagram provides a schematic representation of all states of health through healthy to symptomatic illness. It also includes a description of the different types of indications according to the action or effect on the indication target. Indications can be conveniently separated into three clusters – indications targeting: a generally healthy state; risk reduction/prevention; and illness. All indications must be supported by evidence that is appropriate and valid. Figure 1: Schematic diagram showing relationships of different types of indications Cluster 1: Health indications Health indications target healthy individuals and assist in maintaining or improving their state of health and wellbeing. The health indication cluster includes the following types of indications: health maintenance: normal physiological effects of nutrients and substances in growth, development and normal functions of the body. health enhancement: specific beneficial effects of nutrients and other substances on physiological and psychological activities beyond their role in normal growth, development and normal functions of the body. Cluster 2: Risk reduction and prevention indications Risk reduction/prevention indications target individuals at risk of illness and partially or completely reduce the risk. The risk reduction/prevention indication cluster includes the following types of indications: risk reduction: favourable modification of a known risk factor for a specified illness. condition, disease or disorder. prevention: prevents the development of a named illness. trial
within that specific context fulfils the requirements of the subsequent sections of this document. Example: The evidence base surrounding a modulating effect of Factor X on levels of calcium demonstrate a consistent increase in bone density but all studies have been conducted in postmenopausal women. The indication would need to include a contextual qualifier such as ‘Used in postmenopausal women’. Determining which studies to include for further analysis It is important that only studies that are relevant to proposed listable indications are included in any subsequent analysis. The following table provides guidance regarding the inclusion and exclusion of studies from further analysis based on relevance to a proposed listable indication. Excellent Good Satisfactory Unsatisfactory Relevance to medicine Identical active ingredient, dosing details, formulation and route of administration. Identical active ingredient and route of administration, Comparable dosing details and formulation. Identical route of administration Comparable active ingredient, or formulation and dosing details. Different active ingredient or of administration. Relevance to target population Population studied is identical to the target population. Population studied is comparable to the target population. Some differences between study and target populations but ‘clinically reasonable’ to extrapolate evidence to the target population. Major differences or differences of uncertain clinical significance exist between study and target populations. Relevance to health benefit Study directly measures health benefit in listable indication as primary outcome. Study directly measures health benefit in listable indication as secondary outcome. Study directly measures health benefit in listable indication as post-hoc analysis. Study does not directly measure health benefit in listable indication. trial
Determining which sources of evidence of traditional use are relevant All (and only) information that is relevant to proposed listable indications must be considered as part of the relevant body of evidence. The following table provides guidance on the inclusion and exclusion of items of evidence from further analysis based Excellent Good Satisfactory Unsatisfactory Relevance to medicine Identical active ingredient, dosing details and route of administration. Identical active ingredient and route of administration, comparable dosing details, dose form and formulation. Identical of administration, comparable active ingredient or formulation dosing details and dose form. Different active ingredient or of administration. Relevance to target population Traditional population is identical to the target population. Traditional population is comparable to the target population. Some differences between traditional population and target populations but ‘clinically reasonable’ to extrapolate evidence to the target population. Major differences or differences of uncertain clinical significance exist between traditional and target populations. Relevance to traditional health benefit The wording of the indication is identical to item of evidence, including, the use of traditional terminology. The wording of the indication is identical in intent to item of evidence, including, the use of traditional terminology (traditional synonym used to describe the indication). The wording for the indication is identical in intent to item of evidence, but using contemporary terminology (modern synonym used to describe the traditional indication). The wording and intent for the indication is inconsistent with the item of evidence. Relevance to traditional context Clearly identified and used continuously within the relevant traditional paradigm over Identified within the relevant traditional paradigm but with disclarity regarding consistency of Identified within the relevant traditional paradigm with disclarity regarding consistency of Not consistent with the relevant traditional paradigm.
dosing details, formulation and route of administration route of administration, Comparable dosing details and formulation Comparable active ingredient, or formulation and dosing details route of administration Relevance to target population Population studied is identical to the target population Population studied is comparable to the target population Some differences between study and target populations but ‘clinically reasonable’ to extrapolate evidence to the target population differences or differences of uncertain clinical significance exist between study and target populations Relevance to health benefit Study directly measures health benefit in listable indication as primary outcome Study directly measures health benefit in listable indication as secondary outcome Study directly measures health benefit in listable indication as post-hoc analysis Study does not directly measure health benefit in listable indication Relevance to context of use Study context directly applicable to Australian self care context Study context applicable to Australian self care context with few caveats Probably applicable to Australian self care context Study context not applicable to Australian self care context Only studies achieving ratings of ‘satisfactory’ or above in ALL four relevance categories are considered relevant to a proposed listable indication. 4. Evidence level and quality (for each included study) (sections 3.2.1.6-7) Level of evidence: Quality of experimental studies (e.g. randomised controlled clinical trials) Item Parameter Yes (1) or No (0)
Characterisation of the ingredient/s Ingredient named (genus, species and plant part if herb)? Yes No Extraction/preparation described? Yes No Dose and of administration? Yes No criteria Inclusion and exclusion criteria reported? Yes No Sample size Power calculation performed? Yes No Attrition reported?* Yes No Reasons for attrition given?* Yes No Exposure Was the methodology used to measure the exposure reported? Yes No Was the exposure assessed more than once? Yes No Blinding Were the researchers blinded to the exposure status? Yes No Baseline comparison Were the subjects in different exposure groups compared at baseline? Yes No Health outcome Was the methodology used to measure the health outcome reported? Yes No Was the health outcome verified (e.g. through assessment of medical records, confirmation by a health practitioner)? Yes No Potential confounders Were potential confounders considered? Yes No
with respect to a SS positive effect Clinical impact Meaningful health benefit very likely to achieved by consumers Meaningful health benefit likely at the individual or population level Clinical impact uncertain- meaningful health benefit possible. Unlikely to be meaningful SS=statistically significant Additional comments (eg Justification re effect size):
and route of administration administration, Comparable dosing details, dose form and formulation ingredient or formulation dosing details and dose form route of Relevance to target population Traditional population is identical to the target population Traditional population is comparable to the target population Some differences between traditional population and target populations but ‘clinically reasonable’ to extrapolate evidence to the target population differences or differences of uncertain clinical significance exist between traditional and target populations Relevance to traditional health benefit The wording of the indication is identical to item of evidence, including, the use of traditional terminology. The wording of the indication is identical in intent to item of evidence, including, the use of traditional terminology (traditional synonym used to describe the indication). The wording for the indication is identical in intent to item of evidence, but contemporary terminology (modern synonym used to describe the traditional indication). The wording and intent for the indication is inconsistent with the item of evidence. Relevance to traditional context Clearly identified and used continuously within the relevant traditional paradigm over at 75 years Identified within the relevant traditional paradigm but with disclarity regarding consistency of use over a period of 75 years Identified within the relevant traditional paradigm with some disclarity regarding characterisation of the active ingredients or formulation Not consistent with the relevant traditional paradigm 4. Quality of evidence (Section 3.2.2.6) trial