Criteria for the clinical use of immunoglobulin in Australia: Version 3

The Criteria for the clinical use of immunoglobulin in Australia (the Criteria) identifies the conditions and circumstances for which the use of immunoglobulin (Ig) is clinically appropriate and accessible to patients under the National Blood Agreement Opens new window and within the National Policy: Access to Government Funded Immunoglobulin Products in Australia Opens new window (the National Policy).

Access to Ig products under the National Blood Agreement

In December 2007, Australian Health Ministers agreed to fund Ig products under the National Blood Agreement Opens new window for patients with medical conditions where the indication for use is identified in the Criteria under one of three categories:

  1. Conditions for which Ig has an established therapeutic role
  2. Conditions for which Ig has an emerging therapeutic role
  3. Conditions for which Ig use is in exceptional circumstances only

Ig products are not available under the National Blood Agreement for conditions that have been assessed and identified as conditions for which Ig use is not supported.

To access Ig products under the National Blood Agreement, the National Policy requires that an application must be made by a medical officer through the online system BloodSTAR Opens new window (Blood System for Tracking Authorisations and Reviews). Where eligibility criteria are met, Ig products are supplied at no direct cost to the patient and the cost of the products is met by all Australian governments under the national blood arrangements, managed by the National Blood Authority. Health professionals involved in the prescription, use and management of Ig provided under the National Blood Agreement must comply with the National Policy.

The Criteria, together with BloodSTAR, form part of a broader National Immunoglobulin Governance Program Opens new window (the Program) which ensures that Ig products supplied and funded under the National Blood Agreement are available consistently across Australia to patients who are most likely to benefit and for whom there are no safe and effective alternative treatments, based on reliable evidence, and using the lowest effective dose. The Program aims to ensure the management and use of government-funded Ig reflects appropriate clinical practice, in accordance with relevant safety and quality standards for health care, and represents efficient, effective and ethical expenditure of government funds.

Patients found to be ineligible to access Ig products under the National Blood Agreement or those with a medical condition not covered in the Criteria may be able to access Ig privately or through a Jurisdictional Direct Order.

For more information on the Criteria, the Program, the National Policy, BloodSTAR and access arrangements see the NBA website at https://www.blood.gov.au/Ig-governance Opens new window

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Allocation of Ig products available under the National Blood Agreement

Both domestic and imported Immunoglobulin (Ig) products are available under the National Blood Agreement.

Each year governments agree a National Supply Plan and Budget that sets a specific volume of domestic Ig products to be supplied each year, based on the expected levels of Australian plasma collection and Ig product manufacture. The National Supply Plan and Budget also includes a forecast of the additional volume of imported Ig products expected to be required to meet demand under the Criteria.

To ensure that the planned volume of domestic Ig products is utilised each year, new approved authorisation requests are allocated within BloodSTAR to domestic or imported Ig products based on the patient’s specific condition, according to a pre-determined allocation matrix within BloodSTAR. The allocation matrix is updated as forecasts of demand and supply change over time, and there can be differences in allocation between States and Territories according to patient demographics.

A medical officer making an authorisation request may request a change from the allocated Ig product to an alternative Ig product (available under NBA arrangements) for clinically appropriate reasons, such as patient experience of adverse reaction to a particular Ig product initially allocated by BloodSTAR. Such a change can be requested through BloodSTAR.

All Ig products supplied in Australia are regulated under the Therapeutics Goods Act 1989 by the Therapeutic Goods Administration (TGA) to common standards of safety, quality and efficacy.

For more information regarding allocation of Ig products see https://www.blood.gov.au/Intravenous-Ig Opens new window.

For a full list of products available under the National Blood Agreement see the National Product List at https://www.blood.gov.au/national-product-list Opens new window.

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How to use the Criteria

Medical officers and transfusion medicine professionals can use the Criteria to identify patients who are eligible to receive government-funded Ig products under the National Policy. If the patient is likely to be eligible, a medical officer can submit an application for access to government-funded Ig products using BloodSTAR.

BloodSTAR Opens new window will guide medical officers submitting an application through the specific criteria required for the medical condition and indication for use for which the authorisation for access to Ig is being sought.

The Criteria are not intended to be clinical practice guidelines. Rather, the Criteria identify the conditions and circumstances for which the use of Ig products is considered to be clinically appropriate and for which Ig products are able to be accessed under the National Policy.

Any advice within the Criteria relating to other forms of treatment for relevant medical conditions has not been subject to a systematic review and should not be relied upon to guide treatment. Furthermore, patients and doctors should not use this information as a substitute for expert medical guidance and advice. The relevance and appropriateness of this information depends, amongst other things, on an accurate diagnosis, the severity of the condition being properly ascertained, the individual response to diagnostic tests and therapies, and other relevant circumstances in each case.

When developing individual treatment plans for patients, medical officers should consider the comparative efficacy, risks and costs associated with Ig products compared with alternative therapies. Furthermore, medical officers should consider suitable adjuvant therapies that may reduce individual patient requirements for Ig products. For some conditions, in recent changes to the Criteria the priority of the use of Ig products has been reduced in favour of alternative therapies, and is now considered exceptional practice. These clinical considerations will assist in avoiding unnecessary growth in demand for Ig.

Categories

Conditions covered in the Criteria are arranged into one of the four categories outlined below, according to the outcome of the evidence assessment undertaken during the development and updating of the Criteria. Ig product use is supported for funding under the National Blood Agreement Opens new window if the medical condition falls into one of categories I, II or III.

  1. Conditions for which Ig has an established therapeutic role (previously Chapter 5)

    For these conditions, Ig product use is supported by reasonable-quality evidence and expert opinion.

    For a number of these conditions Ig products are considered a first-line therapy in selected patients and may be the only established treatment option (for example, as replacement therapy in primary immunodeficiency disease).

    Ig product treatment for conditions identified in this category is funded under the National Policy provided eligibility criteria have been met.

  2. Conditions for which Ig has an emerging therapeutic role (previously Chapter 6)

    For these conditions, there is clinical support for Ig product use in selected patients, although the quality of evidence supporting use is variable.

    For many of these conditions, Ig products are considered a second or third-line therapy only, and are only allowed under the Criteria when standard therapies have proven to be ineffective, become intolerable, or are contraindicated.

    Many of these conditions are rare, and as a result, the evidence of benefit is often incomplete and inconclusive. For other conditions which are often more prevalent, the evidence of benefit is either emerging, uncertain, or conflicting evidence has been identified. In some conditions, Ig products represent a relatively new direction in disease management. More research is required to demonstrate the effectiveness of Ig product treatment in many of these conditions.

    Ig treatment for conditions identified in this category is funded under the National Policy provided eligibility criteria have been met.

  3. Conditions for which Ig use is in exceptional circumstances only (previously Chapter 7)

    These conditions rarely, if ever, require Ig product use, either because there are safe and effective alternative therapies, or because the evidence of benefit does not justify use in most cases.

    Ig products are considered to have a therapeutic role only in exceptional circumstances, such as in urgent or life-threatening circumstances, or in circumstances in which significant morbidity would be expected and other clinically appropriate therapies have been exhausted or are contraindicated.

    Ig product treatment for conditions identified in this category is funded under the National Policy provided eligibility criteria have been met.

  4. Conditions for which Ig use is not supported (previously Chapter 8)

    For these conditions, there is either evidence of no benefit, insufficient evidence of benefit, or some evidence of benefit but preferred alternative therapies are available.

    Funding for Ig therapy for these conditions is not supported under the National Policy at this time.

Medical Condition

Fifty-two medical conditions are supported for funding in Version 3 of the Criteria. In some cases the medical condition is a general term for a group of associated specific conditions. In other cases, the medical condition represents only one specific condition.

Specific Condition

This section lists the specific condition(s) grouped under the medical condition. Each specific condition denotes a disorder within a medical condition that can be determined using specific diagnostic criteria. A number of specific conditions may be grouped under one medical condition.

Indication for IVIg use

To be eligible to receive Ig products under the National Blood Agreement, Ig treatment must be prescribed to a patient for an indication described in this section. The indication is applicable once the patient’s clinical condition has been confirmed using the proposed diagnostic parameters described. The indication is the circumstances in which Ig use is permitted, and generally refers to the prevention or management of a particular set of clinical circumstances.

Level of Evidence

The information provided in this section describes the quality of the evidence for each medical condition assessed during the development and updating of the Criteria. The quality of evidence is categorised in accordance with the table below.

Table 1 Level of evidence categories

Level of evidence categories
CategoryStudiesEvidence
1High-quality randomised controlled trials (RCTs)Clear evidence of benefit
2aSome RCTs and/or case studiesEvidence of probable benefit – more research needed
2bSome RCTs and/or case studiesEvidence of no probable benefit – more research needed
2cHigh-quality RCTs with conflicting resultsConflicting evidence of benefit
3High-quality RCTsClear evidence of no benefit
4aSmall case studies onlyInsufficient data
4bNo included studies-

Description and Diagnostic Criteria

This section provides a brief description of the medical condition and methods that should be used to diagnose the condition in a patient. The information provided is based on clinical expert opinion, assessment of better practice, and available evidence.

Justification for Evidence Category

This section provides a brief description of the evidence assessed for each medical condition during the development and updating of the Criteria. The description identifies the key findings that informed decisions about the level of evidence and the inclusion of the medical condition in the Criteria.

Diagnosis Requirements

To be eligible to receive Ig products under the National Blood Agreement, a patient may need to be diagnosed as having a specific condition by a specified type of medical specialist.

Where this applies, this section specifies the type or types of medical specialist that is required to diagnose the specific condition.

Qualifying Criteria for IVIg Therapy

This section describes the Criteria that must be fulfilled to be eligible to receive Ig products under the National Policy. The qualifying criteria generally refer to matters such as patient selection, particular disease characteristics, disease severity, and any requirement for other treatments to have been demonstrably unsuccessful, unavailable or contraindicated before Ig is considered. The qualifying criteria are additional to diagnostic criteria.

Exclusion Criteria

This section describes criteria, if any, that may render a patient ineligible to receive Ig products under the National Policy. The exclusion criteria define the circumstances in which funded Ig therapy will not be supported for a medical condition. In many circumstances, information is included providing guidance to where a patient may be eligible under an alternative medical condition.

Review Criteria for Assessing the Effectiveness of IVIg Use

This section describes the major clinical factors that should be taken into account when reviewing the progress of a patient who is receiving Ig products under the National Policy. The review criteria comprise parameters that indicate a patient’s response to Ig. Evidence of clinical benefit of Ig should be demonstrated to warrant ongoing treatment where required.

Review outcomes may be required in order to determine whether Ig product therapy is to be continued or ceased, or to alter the dose or frequency of administration.

Dose

This section describes the effective dose range that may be prescribed for a patient according to the relevant indication for Ig product use.

Medical officers should prescribe the lowest possible dose, and for the shortest duration, to achieve the appropriate clinical outcome for each patient. As well as conserving the use of Ig, this approach will potentially reduce possible side effects which may be dose related.

The dose of Ig product is calculated based on a patient’s weight. Dose will vary, depending on whether Ig treatment has been prescribed as a replacement therapy or immunomodulation therapy and the individual patient’s condition, clinical presentation, comorbidities, concurrent therapy and response.

Medical officers may adjust the dose for ideal body weight. This is facilitated within BloodSTAR through an algorithmic calculator. Adjusting dose for ideal body weight is not recommended in patients aged less than 18 years, who are less than 152cm in height, or who are pregnant. Furthermore, if the BloodSTAR calculator is applied but the actual weight of the patient is less than the dose determined weight, the Ig dose should be calculated using the patient’s actual weight.

This section also indicates whether an authorisation may be sought to prescribe subcutaneous Ig (SCIg) as an alternative to IVIg under the National Policy. SCIg is currently available for four specific indications within the Criteria.

Bibliography

This section lists the resources used to inform the development of the Criteria for each medical condition.

For more information on SCIg access see https://www.blood.gov.au/SCIg Opens new window.

For more information information on the BloodSTAR calculator for adjusting Ig dose for ideal body weight see https://www.blood.gov.au/bloodstar-calculator-adjusting-ig-dose-ideal-body-weight Opens new window.

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Development of the Criteria

The Criteria is based on evidence identified through systematic reviews of the literature. Where insufficient evidence was found to exist, the Criteria is based on the opinions provided by clinical experts as individuals, clinical colleges and clinical societies.

First and second editions of the Criteria (now withdrawn)

The first edition of the Criteria was developed in response to a recommendation that arose from a review conducted in 2000 by the Blood and Blood Products Committee of the Australian Health Ministers’ Advisory Council (AHMAC). The recommendation stipulated that conditions for access to Ig products undergo regular review to ensure that the therapeutic use of Ig is kept current.

The term ‘criteria for use’ was chosen specifically to indicate a more directive framework to describe the circumstances, based on evidence and clinical experience, under which the clinical use of Ig products is considered appropriate to be funded in Australia.

The first edition of the Criteria was published in 2007 following a systematic review that was completed in mid-2006. It followed the methods described in the National Health and Medical Research Council (NHMRC) handbook, How to review the evidence: systematic review and assessment of the scientific literature (NHMRC 2000) 4 Opens new window and the Evidence-based practice workbook published by BMJ Books (Glasziou et al 2007) 5 Opens new window . The review aimed to:

  • identify and critically appraise the scientific literature regarding the efficacy and risks of Ig therapy;
  • analyse scientific publications (including existing guidelines) that identify the key therapeutic issues in Ig therapy; and
  • include studies comparing Ig with other treatments, including immunoglobulin administered by other routes, when such other treatments have been studied in comparison with intravenous administration.

Following its release, Health Ministers, through the then Australian Health Ministers’ Conference (AHMC) granted approval to limit access to intravenous Ig funded under the National Blood Agreement to only those conditions and their associated criteria as set out in the Criteria.

In 2010 a public consultation period was held to identify areas in the first edition of the Criteria that required updating. A systematic review of a limited number of indications was subsequently undertaken in 2010-11 to update the Criteria This review resulted in the addition of a small number of indications, removal of a small number of indications, and a rewording of a limited number of indications. The second edition of the Criteria was published in 2012 and the continuance of the effect of the Funding Statement was confirmed by Health Ministers at this time.

The second edition of the Criteria was adapted for use within BloodSTAR Opens new window (Blood System for Tracking Authorisations and Reviews) in preparation for the BloodSTAR rollout which commenced in 2016.

More information about the development of the first and second editions of the Criteria can be found within the archived versions of those publications, and on the NBA website at https://www.blood.gov.au/ivig-criteria Opens new window.

Version 3 of the Criteria (current)

A further review of the Criteria commenced in 2014 and has followed a comprehensive process to result in Version 3 of the Criteria, released nationally and into BloodSTAR in 2018.

This review addressed recommendations that arose from the Review of the clinical governance and authorisation process for intravenous Ig Opens new window commissioned by the NBA and undertaken by Ernst and Young in 2012. The review recommended the next development of the Criteria apply more consistent qualifying and review criteria across the conditions.

The development of Version 3 involved a review of all qualifying, review and dose criteria, along with evidence items and system controls. To ensure accurate translation into the BloodSTAR system, the definition and description of each evidence item and its associated system controls were subject to a comprehensive quality assurance analysis. Approximately 22,000 descriptor and system controls have been defined for Version 3 of the Criteria to ensure the system functions as intended. Amongst other things, the descriptors determine:

  • what the requestor sees;
  • what the requestor is asked to provide;
  • whether or not the requirement is mandatory; and
  • instructions that will be provided to assessors.

Version 3 of the Criteria more clearly articulates and standardises the diagnostic, qualifying and review criteria, initial and continuing authorisation periods, dosing controls and supporting evidence for access to Ig under the National Blood Agreement. These changes enhance consistency in access and further support the use of Ig products for clinically appropriate purposes, and for the treatment of patients whose health is most likely to be improved with Ig therapy.

Process established to develop Version 3 of the Criteria

The clinical disciplines of immunology, haematology, neurology and transplantation define the key specialty areas for the highest use of Ig in Australia. Specialist working groups (SWGs) consisting of representative clinical experts for each of the key Ig specialty areas were established to undertake the review work. Members of the SWGs worked in their own time to review the available evidence and identify potential changes to the Criteria. Teleconference meetings were convened to discuss proposed changes and develop recommendations for the NBA’s consideration. The extensive revision process commenced in early 2015 and was completed in mid-2018.

The reviews conducted by SWG members resulted in changes to the Criteria to more clearly articulate and standardise the diagnostic, qualifying and review criteria, initial and continuing authorisation periods, and dosing controls to align with recent evidence, publications and international standards. Evidence involving the use of alternative therapies in each diagnostic group was considered and incorporated into qualifying and review criteria where appropriate for cost effectiveness or clinical benefit.

Indications were defined to provide further clarity and separate indications that required assessment against different criteria, for example if a patient should relapse. Consideration was given to minimum effective dosing and upper dosing limits and whether a trial off Ig therapy should be encouraged after a determined treatment period.

Public consultation on proposed changes

Public consultation was conducted as each part of the Version 3 Criteria was developed that allowed the broader community to consider proposed revisions and provide feedback. As part of the public consultation, the NBA specifically invited medical specialist societies, associations and colleges, consumer groups and active Ig prescribers to comment.

The consultation process was very successful with constructive feedback being provided of high quality from a broad range of stakeholders. Submissions received were considered by SWGs and, informed the final/subsequent draft of the Criteria.

Endorsement and approval of Version 3 of the Criteria

All changes to the Criteria as proposed by SWGs were reviewed and endorsed by the National Immunoglobulin Governance Advisory Committee (NIGAC) prior to consideration by the Jurisdictional Blood Committee (JBC).

For more information on the National Ig Governance Advisory Committee and the Jurisdictional Blood Committee please see https://www.blood.gov.au/Ig-committees Opens new window.

Acknowledgements

The development and subsequent revisions to the Criteria have been funded through the national blood arrangements by Australian governments.

The NBA established four SWGs and engaged a clinical consultant to assist the Project Team with the development of Version 3 of the Criteria. A number of colleges and societies also provided additional expert advice. The NBA gratefully acknowledges the contributions of all parties involved in the development of Version 3 of the Criteria, with thanks in particular to the individuals and groups listed below.

Neurology SWG

  • A/Prof Lyn Kiers (since December 2014)
  • A/Prof Stephen Reddel (since December 2014)
  • A/Prof Pamela McCombe (since December 2014)
  • A/Prof Bruce Taylor (since December 2014)
  • A/Prof Russell Dale (since May 2016)
  • A/Prof Andrew Kornberg (December 2014 – October 2016)
  • A/Prof Janakan Ravindran (December 2014 – February 2016)

Haematology SWG

  • Dr Cameron Curley (since December 2014)
  • Dr Philip Crispin (since December 2014)
  • Dr Ashish Bajel (since December 2014)
  • Prof John Gibson (since December 2014)
  • Dr Philip Choi (since June 2016)
  • Dr Anthea Greenway (since August 2016)
  • Prof Catherine Cole (December 2014 – October 2017)
  • A/Prof Huyen Tran (December 2014 – March 2016)

Immunology SWG

  • Dr Melanie Wong (since December 2014)
  • A/Prof Richard Loh (since December 2014)
  • A/Prof Jane Peake (since December 2014)
  • Prof Matthew Cook (since December 2014)
  • Dr Pravin Hissaria (since December 2014)
  • Dr Daman Langguth (since December 2014)
  • Prof Martyn French (December 2014 – February 2017)
  • Prof Jo Douglass (December 2014 – February 2016)

Transplantation SWG

  • A/Prof Kate Wyburn (since December 2014)
  • A/Prof Scott Campbell (since December 2014)
  • Prof Stephen Alexander (since December 2014)
  • A/Prof Toby Coates (since December 2014)
  • A/Prof Shlomo Cohney (since December 2014)
  • Prof Peter Hopkins (since December 2014)
  • Prof Peter MacDonald (since December 2014)
  • Prof Josette Iris (December 2014 – April 2016)

Observer to the SWGs

  • Dr Janet Wong (Australian Red Cross Blood Service)

Colleges and societies

  • The Australasian College of Dermatologists
  • Australian College of Emergency Medicine
  • Australian College of Nursing
  • Australian Haemophilia Centre Directors' Organisation
  • Australian and New Zealand Association of Neurologists
  • Australian and New Zealand Intensive Care Society
  • Australian and New Zealand Society of Blood Transfusion
  • Australian Rheumatology Association
  • Australian Society for Clinical Immunology and Allergy
  • Australian Society for Infectious Diseases
  • See THSANZ (new acronym) formerly Australasian Society of Thrombosis and Haemostasis
  • Cardiac Society of Australia and New Zealand
  • Endocrine Society
  • Haematology Society of Australia and New Zealand
  • Perinatal Society of Australia and New Zealand
  • Royal Australasian College of Physicians
  • Royal Australian College of General Practitioners
  • Royal Australian and New Zealand College of Ophthalmologists
  • Royal Australian and New Zealand College of Obstetricians and Gynaecologists
  • Royal College of Pathologists of Australasia
  • Rural Doctors Association
  • Thrombosis and Haemostasis society of Australia and New Zealand
  • Transplantation Society of Australia and New Zealand

Consultant

  • Dr Philippa Hetzel (December 2013 – February 2018)

NBA Project Team

  • Mr Michael Stone (Deputy Chief Executive and General Counsel)
  • Ms Jo Cameron (Director, Ig Governance from April 2016)
  • Ms Jennifer Roberts (Director, Clinical Evidence and Assessment)
  • Ms Melody Black (Program Manager, Ig Governance until April 2016)
  • Ms Vesna Morosin (Assistant Director, Ig Governance from July 2017)
  • Ms Lyndsay Wall (Assistant Director, Ig Governance from July 2017)
  • Ms Karla Grant (Senior Project Officer, Ig Governance from July 2017)
  • Ms Angela Byron (Senior Project Officer, Ig Governance from July 2018)
  • Ms Tara Stevens (Project Officer, Ig Governance from July 2017)
  • Ms Nicole Wicks (Project Officer, Ig Governance from March 2016)
  • Ms Amitha Jason (Data Entry Officer, Ig Governance from July 2018)
  • Ms Rhea Donaldson (Data Entry Officer, Ig Governance from July 2018)
  • Ms Petra Chitsaka (Project Officer, Ig Governance until March 2016)
  • Ms Casey Bruning (Project Officer, Ig Governance until April 2015)

Each of the parties involved in the development of the Criteria expressly disclaims and accepts no responsibility for any consequences arising from relying upon the information or content contained within the Criteria as clinical guidance. The Criteria describe the circumstances in which patients may be eligible to access government-funded Ig and should not be relied upon as a substitute for expert medical opinion and advice or to guide treatment.

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Maintenance of the Criteria

Under the National Blood Agreement, governments review expenditure twice a year and health ministers revised funding annually. The prescription, use and management of Ig, as guided by the latest edition of the Criteria for the clinical use of intravenous immunoglobulin in Australia, will be reviewed regularly. Reviews will ensure the qualifying, exclusion, review criteria and indicative dosages for each condition remain, in the light of emerging evidence, appropriate and in keeping with an evidence-based approach.

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