Summary

Submission

from the

Australian and New Zealand Association of

Physicians in Nuclear Medicine

to the

Health Technology Assessment Review

May 2009

PO Box 73 Balmain NSW 2041 AustraliaPhone: +61.2.9818.4824 Fax: +61.2.9818.4806 e-mail: [email protected] web:

www.anzapnm.org.auABN 99 665 425 983

Summary

The ANZAPNM supports the current Review of Health Technology Assessment

as it provides an opportunity to improve the current processes and deliver

more effective outcomes.

Health technology assessment should provide a means of evaluating new

technologies and medicines in a reasonable and timely manner. However at

the same time, it should not be used as a means of rationing access to medical

procedures or medicines that can improve the delivery of health care and

treatment outcomes.

Currently the processes under the Medical Services Advisory Committee

(MSAC) and the Therapeutic Goods Administration (TGA) as defined by their

respective legislation place significant requirements on those seeking approval

of new procedures and products. In some cases, as discussed in this

submission, the requirements are overly burdensome and do not appear to

deliver the intended outcome. For nuclear medicine, there are number of

issues, as outlined below.

The inflexibility of the current processes

Under the MSAC arrangements, the current process that evaluates against

patient outcome disadvantages diagnostic technologies because, while

diagnostic technologies provide information about the presence or absence of

diseases which are used by clinicians to determine initial and ongoing

management of the condition, clinical outcome(s) can only rarely be linked

directly to the result of a diagnostic test. Furthermore, the levels of evidence

applicable to therapeutic procedures do not necessarily have the same

relevance to diagnostic procedures.

2

The current MSAC arrangements do not adequately address situations such as

the evaluation of the reports from the PET Data Collection Project. There

appears to be no mechanism to assess these reports, even though they were

based on MSAC-approved protocols, in a more timely manner. Further, the lack

of “corporate memory” in the area has contributed to difficulties with respect

to why the project was structured in particular ways.

There is concern about the objectivity of the external evaluation process and

the application of inappropriate evidence requirements to diagnostic

technologies, as already noted.

Given that a positive MSAC recommendation remains the first step in having a

procedure included on the Medicare Benefits Schedule, there is no process that

allows the adoption of a technology already in wide use in the public hospital

sector (that is, with public funding) to be funded under the Medicare Scheme

with a Medicare item and available to patients in the private sector.

In the case of the TGA, there are particular issues concerning the availability of

radiopharmaceuticals and the loss of licensing when there is a change of

ownership of the product. The current mechanisms offer some flexibility but it

is inadequate to maintain ready availability of essential radiopharmaceuticals

for patient diagnosis and treatment.

The time and cost of the MSAC process

Under the present arrangements preparation of an application requires

significant work and cost. Once the MSAC evaluation is completed, there are

multiple steps involving preparation of briefings, interdepartmental

consultation concerning cost, regulatory drafting, external consultation through

the MBCC process – all of which add significantly to the timing of introduction

of a new item. The timeframe also has the potential to adversely affect the

funding allocation for the introduction of a new procedure that has taken an

extended time to be implemented, in that costs increase between the time of

the application and the time the decision is made about funding.

3

This extended evaluation and implementation process takes years, not months.

From the perspective of both applicants and the government, there is also

significant cost involved in the process.

Issues around outcome

From the perspective of the medical profession seeking funding for new

diagnostic and therapeutic procedures for which they consider there is robust

evidence that the procedures will improve medical treatment, there remains

potential for significant delays in the implementation of recommendations that

have been approved for public funding.

While it is not clear whether MSAC’s processes represent international best

practice, there would appear to be value in developing cooperative approaches

internationally to facilitate the use of international assessments, particularly in

specialty areas where Australian patient numbers will be small, in order to

facilitate the availability of new diagnostic and therapeutic procedures.

Conclusion

The ANZAPNM believes this review provides the opportunity to develop a

health technology assessment process that provides more flexibility to deal

with different procedures and products and which facilitates involvement in the

process. Health technology assessment must not be used as a means of

restricting access or slowing down the diffusion of diagnostic and therapeutic

procedures that are able to improve the health of the Australian community.

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Recommendations

The ANZAPNM recommends that:

There be a simplified framework and increased flexibility in the health

technology assessment process, in order to facilitate assessment of both new

applications and matters referred for further consideration and to reduce the

need for full external evaluations.

Consideration be given to developing evidence requirements more suited to

diagnostic procedures.

The public interest be considered in all regulation and related documentation

particularly with respect to the availability of radiopharmaceuticals.

Suitable regulatory solutions be identified to facilitate the use of safe, long

established radiopharmaceuticals, particularly where the originally licensed

manufacturer has relinquished ownership of the product.

International cooperative approaches and standardisation and alignment of

processes be developed in order to facilitate the use of international health

technology assessments to augment or substitute for MSAC evaluations.

The PET Data Collection Project be the model for future data collection

arrangements for the evaluation of new technologies.

Ongoing financial support be provided to facilitate such data collection

exercises.

As part of this development consideration be given to funding the

establishment of a diagnostic imaging economics and statistics advisory body

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to improve the quality of applications and reduce the need for external

evaluation.

In finalising Medicare item descriptors and fees for Medicare benefit following

an MSAC assessment, consideration be given to replacing the current MBCC

process with a mechanism by which the relevant medical specialty group has

direct involvement and that the recommended fee for Medicare benefit be

adjusted to take account of costs current at the time of introduction of the

item.

Any new provisions for post marketing surveillance take account of and not

duplicate existing State and Federal reporting requirements relating to the

medical use of radiation.

In any realignment of health technology assessment processes the primacy of

the assessment and the importance of ensuring appropriate new technologies

are available for the treatment of Australian patients should outweigh

application fee considerations and accordingly the introduction of application

fees for MSAC applications should not be considered.

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Contents

Page

Background 8

2004 review of MSAC 9

The Australian and New Zealand Association

of Physicians in Nuclear Medicine 10

The Process of Health Technology Assessment in Australia 12

Term of Reference 1 13

Term of Reference 2 20

Term of Reference 3 26

Term of Reference 4 27

Term of Reference 5 30

Attachment

Health Technology Assessment Review – Terms of Reference 32

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Background

In December 2008, the Minister for Health and Ageing and the Minister for

Finance announced there would be a review of health technology assessment

(HTA) as a “Better Regulation Ministerial Partnership” with a stated

commitment to “deregulation, to reduce costs to business and consumers and

contribute to the Government’s productivity agenda”.

The stated objective of the HTA Review is to “recommend options for improving

process efficiency and reducing regulatory burden for Commonwealth HTA

processes to facilitate medical innovation without compromising timely and

affordable patient access to medical services and devices that:

are demonstrated to be safe, effective and cost effective, and

deliver improved health outcomes and value for money.”

The Australian and New Zealand Association of Physicians in Nuclear Medicine

(ANZAPNM) acknowledges the need for ensuring that new technologies are

safe and contribute to improved health outcomes and, at the same time, are

cost effective, as noted in the Discussion Paper. It also recognises that health

technology is one of the drivers of both public and private health expenditure

as new medicines, devices, procedures and tests continue to be developed.

It is further noted that the HTA Review is to present options that are:

sustainable within existing funding levels, and

consistent with Government policy objectives, including:

policy on regulation of therapeutic products

policy on access to and financing of medical procedures and therapeutic

products

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the “interpretation of the term ‘public funding’ to mean direct and indirect

funding of health technologies whether that funding fully or partially covers the

cost”

ensuring the regulatory processes are effective and efficient.

Previous review of MSAC

A review of MSAC was undertaken in 2004. ANZAPNM made a submission to

that review, at a time when there was discussion of the role of MSAC in peer

reviewed medical journals, and associated coverage in the media.

Two particular points were raised by the ANZAPNM in response to that review:

Technology assessment should be conducted on the basis of the best available

evidence, whether it is Australian or from elsewhere.

The evaluation process for diagnostic technologies is necessarily different from

that used for pharmaceuticals or treatment paradigms in general. It is

extremely difficult and in many cases impossible to either use randomised-

controlled trials or provide proof of survival advantage as a result of using new

diagnostic modalities.

It is the ANZAPNM’s view, supported in the international literature, that new

diagnostic technologies should simply demonstrate statistically and clinically

significant improvement in precision, sensitivity and specificity and cost-

effectiveness. These views are reiterated.

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The Australian and New Zealand Association of

Physicians in Nuclear Medicine

The Australian and New Zealand Association of Physicians in Nuclear Medicine

(ANZAPNM) is the peak organisation representing nuclear medicine specialists

and the practice of nuclear medicine in Australia. The membership of the

ANZAPNM includes both physicians with advanced training in nuclear medicine,

and dual-trained radiologists (i.e. radiologists who have undertaken advanced

training in nuclear medicine).

Nuclear medicine is the medical specialty that utilises a range of high

technology imaging equipment, most commonly SPECT and Positron Emission

Tomography (PET) together with medical isotopes to deliver both diagnostic

and therapeutic procedures. Nuclear medicine specialists are highly trained in

the medical application of radiation.

Nuclear medicine is a mature medical specialty in that it is well-established and

its use in a wide range of applications is accepted as both efficient and

effective.

Both pathology and diagnostic imaging, including nuclear medicine, can assist

in more accurately identifying those patient subsets that are more likely to gain

from a therapy, and can enable monitoring of therapy response. Accordingly,

both pathology and diagnostic imaging, including nuclear medicine, are

fundamental to the provision of health care.

The Impact of MSAC and the TGA on Nuclear Medicine

As a high technology medical specialty, diagnostic and therapeutic nuclear

medicine procedures may be subject to assessment under both the MSAC – for

new procedures, or the application of existing technologies for new or

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amended indications, and the TGA – in relation to radiopharmaceutical

production and supply.

Radioisotopes require registration under the TGA. Increasingly, as

radiopharmaceutical manufacturers rationalise their manufacturing operations

and their “radiopharmaceutical portfolios”, well-established, effective

radiopharmaceuticals are losing their registration – not because they have lost

their efficacy, but for the lack of a sponsor in a country where the economics of

serving a relatively small population does not justify a new company spending

significant amounts of money to seek registration. The TGA guidelines provide

for the registration to be transferred between sponsors without the product

having to be re-evaluated at the full fee, with only the annual registration

charge being applicable, but this transfer has to happen simultaneously. The

problem arises when there is no sponsor willing to accept transference of

registration at the same time, resulting in a cancellation of registration.

Therefore, nuclear medicine is one of a number of medical specialties that is

significantly affected by regulatory and non-regulatory health technology

assessment requirements in Australia.

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The Process of Health Technology Assessment in

Australia

The following issues will be discussed by the ANZAPNM in this submission

under the relevant term of reference. The majority of the ANZAPNM’s

comments relate to the operation of MSAC, although a number of issues

concerning TGA’s processes are also raised.

the opportunity provided by the Review of Health Technology Assessment to

improve the current processes and deliver more effective outcomes;

the inflexibilities built into the MSAC assessment processes that need to be

addressed, including the application of different levels of evidence, the use of a

range of data to support applications including international data and

evaluations, enhanced processes for “references” in place of full evaluations;

the cumbersome nature and significant work and cost involved in the

application and assessment requirements for all involved in both MSAC and

TGA applications;

the extended evaluation and implementation timelines;

the need for transparency in all the processes;

the need for flexibility in TGA’s processes and mechanisms to ensure that

access to clinically valuable radiopharmaceuticals is facilitated, particularly

where there has been a loss of licensing through a change in owners.

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Term of Reference 1

1 Simplification and better coordination between the Commonwealth HTA

processes (as identified in the Review scope), which includes:

consideration of a single entry point and tracking system for applications for

market regulation and funding;

making time to affordable access as short as possible for new technologies

while maintaining or improving the rigour of evaluation processes; and

examination of the feasibility of conducting concurrent assessments for market

registration and funding and coverage purposes, noting current work in this

area.

The Discussion Paper comments that the “lack of high quality evidence for new

medical procedures and associated devices is a shared problem that affects

the medical industry, health professionals, consumers and governments”. This

is true in relation to Level 1 evidence (RCTs), and governments need to

recognise that for many reasons this standard is unlikely to be reached. In the

absence of level 1 evidence, there is significant clinical investigation underway

and published in the scientific literature, on most, if not all new medical

procedures and associated devices. The ANZAPNM supports the continuing use

of available data, both Australian and international, in health technology

assessments.

In Australia, applicants are requested to submit a significant set of data to

support the safety, clinical effectiveness and cost effectiveness of the

diagnostic or therapeutic service for which they seek public funding under

Medicare. In reality, an externally contracted evaluating agency (or agencies)

undertakes what is essentially a parallel process. The Department of Health

and Ageing has indicated that the data provided in applications are poor and

cannot be used – this is not unique to Australia. Other than rejecting all such

applications, the department’s contracted evaluating agency searches,

documents and evaluates all available relevant information as part of

conducting a review of the evidence for MSAC’s consideration. This accounts

for much of the cost and time associated with assessments.

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14

In 2007-08 MSAC received 14 requests for assessment:

four from the medical industry

one from a professional college

two from individuals

seven references from government including the states and the Department of

Health and Ageing.

From this data, government is the single largest user of MSAC and this is

understandable given its responsibilities. All parties recognise the factors that

inhibit the ability of applicants to prepare submissions comparable to the

pharmaceutical and devices industries. At the same time, the parallel work

undertaken by the external evaluators is a time consuming, inefficient and

costly process.

There is a reluctance to rely on health technology assessment undertaken in

other countries, and in Australia a full assessment of current Australian and

international evidence is undertaken, irrespective of the results of overseas

HTAs.

The ANZAPNM undertook an extensive review of health technology assessment

processes in a number of countries comparable to Australia. These processes

did not offer any one perfect model, and health technology assessment was

undertaken for a range of reasons. Nevertheless, there would appear to be

value in a formal review of these approaches being undertaken, particularly

with respect to increasing Australia’s ability to utilise the results of

international health technology assessment in order to avoid duplication.

The limitations, risks and opportunities associated with using overseas health

technology assessments relate to whether the actual processes are

comparable and whether the ultimate purpose of the assessment is the same

or different. The ANZAPNM appreciates the need for assessments to consider

diagnostic or therapeutic procedures in the Australian context. However, this

element could supplement the findings of overseas health technology

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assessment agencies, particularly those undertaken in the recent past and

which align with Australian imperatives, rather than duplicate them.

As noted above, the acceptability or otherwise of overseas based health

technology assessments could be based on a comprehensive evaluation of the

processes of other agencies undertaking health technology assessment

internationally, against a set of agreed requirements for Australia’s purposes.

Where one or more international agencies whose approaches to assessment

were found to align with those of Australia, formal agreements could be made

to access their assessments. This could pave the way for applicants and MSAC

to focus on the Australian aspects of the diagnostic and therapeutic service,

such as epidemiological considerations, limitations of current interventions,

and cost effectiveness, where appropriate. In the continuing challenge posed

by data quality issues, MSAC could take on a stronger role in defining interim

funding arrangements where a pre-requisite to funding is local data collection.

The benefits of using relevant aspects of overseas health technology

assessments would be shorter assessment timeframes overall, earlier

introduction of services found to be of value, and data collection for services

where the evidence base needs to be strengthened. It would also result in cost

savings from process efficiencies.

The other consideration is that Australia’s population does not necessarily

support the recruitment of large numbers of patients to studies where the

condition may be relatively rare. In these cases, international data will be

important.

The ANZAPNM would be willing to work with the department on exploring

collaborative approaches to data collection, particularly under interim funding

arrangements to build the evidence base.

One of the issues frequently raised is the time taken for an application to go

through the MSAC process.

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As an example, the submission dates of the reports of the PET Data Collection

Project and the date of implementation of the resultant Medicare items

indicates the extended time taken in completing evaluations:

Date Report Submittedto MSAC

Indication Date Medicare

Item Available

Elapsed time in months from submission to available item

30 May 2006 Colorectal Cancer 1 Dec 2008 30 months14 June 2006 Ovarian Cancer 1 Dec 2008 29 month10 July 2006 Melanoma 1 Dec 2008 28 months13 Oct 2006 Oesophageal cancer

Gastro-oesophageal junction cancer1 July 2009(anticipated)

33 months

9 May 2007 Head and Neck cancer 1 July 2009(anticipated)

26 months

19 July 2007 Low Grade Non-Hodgkin’s Lymphoma Not completed > 22 months for MSAC evaluation phase only

13 Nov 2007 Glioma Not completed > 18 months for MSAC evaluation phase only

23 April 2008 Sarcoma Not completed > 13 months for MSAC evaluation phase only

Given the clinical protocols for each of the indications were approved by MSAC

prior to the commencement of the study, the duration of these evaluations

could not be considered timely.

As indicated above, it is difficult to demonstrate cost effectiveness for

diagnostic technologies. What is needed is an evaluation mechanism that

recognises that it is not possible to demonstrate an outcome based on the use

of a diagnostic technology; it is possible to demonstrate changed management

that affects outcome.

The PET Data Collection Project is a case in point. Any amended MSAC or

similar process needs to have a distinct evaluation process for diagnostic

technologies or a mechanism to recognise the differences between evaluating

diagnostic and therapeutic procedures. The development of economic data is

also frequently the stumbling block for MSAC assessments; and the availability

of health economic advice presents a significant problem.

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Assessing diagnostic technology, Fryback and Thornbury1 proposed a hierarchy

of diagnostic efficacy as follows.

1. Technical Technical imaging quality2. Diagnostic accuracy Sensitivity, specificity, positive predictive value,

negative predictive value3. Diagnostic thinking Likelihood ratio (Bayesian approach using pre-test and

post-test probabilities)4. Therapeutic Changes in therapeutic choices (patient management)5. Patient outcome Improvement in morbidity/mortality6. Societal Cost–benefit analysis

This hierarchy continues to be used as a framework for assessing diagnostic

technologies.2 The link between diagnostic accuracy and patient outcome is

not direct. Diagnostic test accuracy influences diagnosis which in turn

influences treatment decisions; outcome depends on treatment effectiveness.

Thus, there is only an indirect link between diagnostic accuracy and patient

outcome, particularly medium to long-term outcome. The Canadian Institute of

Clinical Evaluative Sciences, in an assessment of PET, shared this view,

concluding that it was difficult to conclusively assess the impact of PET on

morbidity and mortality but intermediate outcomes such as the avoidance of

inappropriate surgery could be assessed.3

A further issue raised with respect to the consideration of the PET data has

been the decision that for every indication for which PET may be used a

separate MSAC application must be developed and assessed. It is difficult to

find a comparable decision in relation to other diagnostic technologies. From

the demographic data collected during the PET project, additional data was

provided to the clinician that resulted in a change in clinical management in

most cases. From this, it is reasonable to assume that PET’s impact on patient

management is significant in the majority of cases.1 Fryback, D.G. & Thornbury, J.R. The efficacy of diagnostic imaging. Medical Decision Making, 1991, 11:88-94.2 Facey, K., Bradbury, I., Laking, G. & Payne, E. Overview of the clinical effectiveness of positron emission tomography imaging in selected cancers. Health Technology Assessment, 2007; Vol. 11: No. 44.3 Institute for Clinical Evaluative Sciences. Health Technology Assessment of Positron Emission Tomography (PET) – A Systematic Review, 2001.

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Therefore, the decision that PET will not be accepted as useful across all cancer

indications is disappointing. The ANZAPNM believes there is sufficient evidence

for this aspect of the MSAC process to be re-assessed, particularly where there

is data generated in consultation with the department and MSAC that supports

wider application of this technology.

Ideally the health technology assessment process aims to deliver information

that is accurate in terms of the ultimate cost. However the problem with the

current process is that the costings included in the application may be directed

more towards eliciting a successful outcome in a comparison with any existing

funded technology, than the longer-term objective of ensuring that the final

funding model reflects the true costs of the procedure. As a result, because

this same set of costings is used in the ministerial briefing (assuming a positive

recommendation) the actual projected outlays are under-estimated and the

resulting fee for Medicare benefit has not reflected all relevant costs.

The nature of the evaluation process encourages the minimisation of costs and

is consistent with the government’s position that it may choose to fully or

partially fund or subsidise a medical service. However, the consequence of

underfunding new and existing services, particularly those that may be

considered expensive, is that the difference has to be met through out of

pocket costs by patients. One interpretation of the implications of government

policy on minimising costs may be that applicants have to submit cost data

that underestimates actual costs in order to enhance the chances of the

submission being successful.

A further issue that influences the overall time taken from an assessment -

from submission, through to final recommendation by MSAC to a new item on

the MBS - is the number of steps that need to be undertaken. These include:

preparation of a briefing by DoHA for the Minister,

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consideration of the financial impact on Medicare outlays by the Department of

Finance and Regulation

the Minister’s consideration

the DoHA’s preparation of items including liaison with legislative drafting and

with clinicians about technical issues

the involvement of the AMA through the convening of an MBCC meeting

subsequent work by DoHA and

Executive Committee approval.

All of these steps contribute to the time taken to make a diagnostic or

therapeutic service available to patients via the MBS.

The value of the involvement of the MBCC has been questioned on a number of

occasions, particularly with respect to health technology assessment in areas

where the AMA has no particular expertise other than as a convenor of a

meeting and has, on occasions, not ensured the relevant specialty groups have

been involved in the meetings. While the AMA through the MBCC has had an

important role in negotiations about Medicare fees in the past, the ANZAPM

believes that this might not be the most effective arrangement into the future.

In summary, the ANZAPNM makes the following points:

it is possible to conduct national studies to collect and collate clinical data in

order to gather data for the evaluation of health technologies;

there is value in having a single coordinating body / organisation;

there is value in the government providing support for these exercises;

there would be value in there being additional support, such as economic and

statistical advice; and

consideration should be given as to whether the MBCC process is the most

effective mechanism for review and input at the final stages of the process.

There may be value in establishing a broader evaluation framework in order to

facilitate the use of international health technology assessment reports and

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data to speed up the evaluation process. There may also be value in further

review of the practicalities of using multi-centre studies to gather evidence and

the introduction of mechanisms to facilitate this process, such as enhancing

the capacity for ethics approvals across a number of sites and providing

support for protocol development. While there are strengths in having

individual site assessment and protocol development, there is also a need for a

mechanism to facilitate approvals when the site is involved in a national study.

Term of Reference 2Improving role clarity and addressing duplication between processes, where it

exists, including consideration of consolidating functions with the Australian

HTA system.

The ANZAPNM has no particular experience of difficulties associated with the

duplication between the different health technology assessment processes for

drugs, medical services and devices. However, recent experiences in relation

to the availability of certain radiopharmaceuticals has highlighted the need for

a more responsive capability to allow for the use of radiopharmaceuticals

different from those specifically identified in Medicare item descriptors. While

this issue does not necessarily fall under the focus of this review it does

however highlight the need for greater adaptability across a range of processes

not just those associated with health technology assessment.

Standardisation and alignment of processes, consolidation of application

information, greater cooperation between agencies and committees are

appropriate objectives for health technology assessment. However, at the

same time, consideration needs to be given to the size and coverage of a

single agency and potential inefficiencies if all the above processes were

carried out within the one agency.

Therapeutic Goods Administration (TGA)

The ANZAPNM has had no involvement in submitting applications involving

approval or recognition across two or more assessment schemes. However,

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the ANZAPNM has a number of problems with the current process of

registration of radiopharmaceuticals by the TGA.

These problems relate to the situation where a manufacturer who holds

registration for a particular product sells the licence for that product to another

manufacturer who is disinclined to retain the registration. The product then

become unregistered – for no other reason than the want of a sponsor – and

then may only be available through arrangements such as the Special Access

Scheme (SAS) or by individuals obtaining endorsement as Authorised

Prescribers under Section 19(5) of the Therapeutic Goods Act. Such

endorsements relate to the use of the product for which application is made.

The most prominent and ongoing recent example of this problem is

cholecystokinin (CCK) for nuclear medicine hepatobiliary scans. CCK is used in

patients

with suspected chronic acalculous cholecystitis, to make the gallbladder

contract.

to clear sludge (caused by prolonged fasting) from the gallbladder, prior to

imaging.

(iii) to diagnose sphincter of Oddi dysfunction.

The clinical justification for the use of CCK is that, although a number of agents

can make the gallbladder contract, CCK is the only agent to mimic the

evacuation of bile that occurs in normal physiology, i.e. a prompt contraction

that is limited in duration. Simulation of the normal physiological response of

the gallbladder is highly desirable in patients with complex gallbladder

pathology. The gallbladder ejection obtained from infusion of CCK is used by

surgeons to select patients who are likely to benefit from cholecystectomy or

sphincterotomy.

There is no alternative supplier of the drug locally or internationally. There are

no alternative drugs that do not require an authorised prescriber licence.

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While there are provisions for products registered on ARTG to be transferred to

another sponsor without cancelling the registration and thereby having to go

through the process of submitting a new full application with full application

and/or evaluation fees payable to ensure continuing supply of products, this

requires action by both the relinquishing company and by the accepting

company. This process simply requires completion of documentation to

transfer the therapeutic product to another sponsor. However, the reality is

that, as noted above, increasingly the new company is disinclined to take over

the product – probably due to the relatively low number of doses that would be

sold in Australia, compared with overseas countries where the sale of the

product has occurred.

The question arises as to whether, in the case of products such as

radiopharmaceuticals that have proven efficacy and very few adverse

reactions, and where the only reason they become unregistered is because of

the sale of a suite of products from one manufacturer to another, there should

be a different process applicable from the one currently existing.

The impact of the current registration problem for products such as CCK is that:

there is significant additional workload for nuclear medicine specialists to

individually seek authorised prescriber status, or to obtain approval for single

use of a product under the Special Access Scheme;

there is added workload for the TGA that should be able to be eliminated; and

patients who will benefit from the use of products, such as CCK, do not undergo

those procedures because of the difficulties associated with using the product –

an outcome that disadvantages the patients.

These are proven therapeutic and diagnostic products that should be available

under normal circumstances.

The SAS refers to arrangements that provide for the import and/or supply of an

unapproved therapeutic good for a single patient, on a case-by-case basis.

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Patients are defined as either Category A patients or Category B patients. For

Category A patients, medical practitioners can supply unapproved goods to

very seriously ill patients without the approval of the TGA as long as the

medical practitioner notifies the TGA within 28 days. These patients are

defined in the legislation as "persons who are seriously ill with a condition from

which death is reasonably likely to occur within a matter of months, or from

which premature death is reasonably likely to occur in the absence of early

treatment".

For Category B patients, approval of an application by the TGA to supply an

unapproved product is required on a patient-by-patient basis to reflect the

needs of different patients. Applications should be made in writing.

The document Access to Unapproved Therapeutic Goods, TGA 2004 explains

the rationale for TGA’s approach to monitoring access to unregistered

products, as: In keeping with its charter, the TGA also has a responsibility to

encourage at all times the availability of approved (evaluated) products. Thus

the various mechanisms for supply of unapproved products are intended to be

temporary measures pending general market approval of the product. TGA

requires that applications to use unapproved products justify adequately why

available approved unapproved (fully evaluated products) are not suitable for

use. Unfettered access to unapproved products amounts to de-facto marketing

and would remove any incentive for a sponsor to seek registration of the

unapproved product or for other sponsors to seek of alternative similar

products.

The supplier has to provide the TGA with six monthly reports on access and

supply of the unregistered product. Clearly, where long-term use is

anticipated, it is expected that the product becomes registered. However, this

again raises the problem of manufacturers supplying products for a small

population and balancing the relatively low number of sales against the

significant cost of developing and maintaining registration. It may be

reasonably asked why a new owner would not simply take the step of

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transferring registration, as currently allowed – ANZAPNM is unable to speak on

behalf of the manufacturers in this regard, but assumes it relates to ongoing

cost.

Radiopharmaceuticals are classed as chemical entities and are considered

under Category 1 which is provided for under the Therapeutic Goods

Regulations sub-regulation 16(C)(3)(b) and 16 (D)(3)(b). The evaluation fee for

Category 1, New chemical entity (including radiopharmaceuticals) where they

have not been included previously on the ARTG, is $176, 000. However, if a

sponsor can show that the new isomer, mixture of isomers, complex or

derivative of or salt of a registered substance does not change the

pharmacokinetics, pharmacodynamics and/or toxicity of the moiety in a way

which could change the safety/efficacy profile, the new product may be

considered to be essentially similar and the fee level would be for a generic

product rather than a new chemical entity. If not, then the application would

be considered as a new chemical entity.

There are other provisions for “extension of indication” ($104,800) and new

generic product (essentially the same as a registered medicine chemically,

same form, bioequivalent and same safety and efficacy properties) ($67,300).

There are annual charges of $5,250 for biologics and $3,140 for non-biologics.

Change in ownership of the sponsor/supplier does not in itself incur a charge –

it is the lapsing or cancellation of registration that results in the need to re-

register the product that incurs the evaluation fee. Transfer provisions allow

for continuity of registration with payment of the annual fee as advised by the

TGA.4

4 It is noted that amendments to the Therapeutic Goods Amendment (2009 Measures No. 1) Bill 2009 will be considered by Parliament in the 2009 winter sittings. These include clarifying the arrangements for setting conditions on medicines so these are more transparent, and also to enable sponsors who have asked for the registration or listing of a medicine to be cancelled to apply for this to be revoked (within 90 days) to keep the medicine on the register. However, these amendments if passed, will do little to address the current problems.

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On that basis, it is difficult to see why a manufacturer/supplier would not – in

the case of a radiopharmaceutical – simply organise to transfer the registration

but, as noted above, the ANZAPNM is not in a position to comment on why this

does not occur.

The answer may be for a provision to be introduced that deals specifically with

this issue in the case of radiopharmaceuticals – i.e. where there is no sponsor

available at the time the registration lapses and a new sponsor comes forward

within a year or so, re-registration of the product is allowed under the same

provisions, without incurring the evaluation fee. This would reduce the

significant financial disincentive for another company to seek re-registration of

a product that is used for a relatively small population.

Similarly, the possibility of recognition of certain radiopharmaceuticals as

“orphan drugs” has been raised. However, given an orphan drug is defined in

the legislation as a medicine, vaccine or in vivo diagnostic agent which is

intended to treat, prevent or diagnose a rare disease or must not be

commercially viable to supply to treat, prevent or diagnose another disease or

condition, this provision does not assist with the radiopharmaceutical problem.

It is noted that the TGA also has provisions for considering products for use of

medicines in special population groups, e.g. geriatrics, paediatrics, hepatic or

renal impairment which may involve less than 2,000 users a year. However,

for products such as CCK, the condition they are treating is not rare.

The use of the special TGA arrangements under which a number of

radiopharmaceuticals are supplied generates significant work which, in the

case of radiopharmaceuticals, is mostly related to products that have

previously been registered by the TGA. The ANZAPNM wishes to acknowledge

efforts by the TGA to facilitate the requirements for authorisation and special

access. It is recognised that, in the long term, utilising such arrangements for

very safe and effective radiopharmaceuticals is not desirable. However, given

there has been no inclination to transfer registration it is highly unlikely there

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will be moves to re-register these radiopharmaceuticals. This means that to

maintain access to currently unregistered radiopharmaceuticals other

mechanisms need to be developed to ensure that patients continue to have

access to the diagnostic and therapeutic procedures for which they are used.

Therefore, the ANZPANM firmly believes that, in the same way that

government makes very high cost medicines available to prolong life for some

cancer sufferers, equally there are public interest arguments to identify a

suitable regulatory solution that enables low use, safe radiopharmaceuticals to

retain registration independent of the originally licensed manufacturer when

that manufacturer has relinquished ownership of the product.

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Term of Reference 3

Enhancing post marketing surveillance mechanisms to ensure the ongoing

safety and efficacy of medical devices.

The ANZAPNM notes that data on adverse events (that equates to post

marketing surveillance) is collected in relation to both radiopharmaceutical use

and on nuclear medicine procedures. In both cases, the number of adverse

events is negligible. However, it is relevant to note that nuclear medicine can

be identified as having a high number of incidents reported to state radiation

advisory councils, for example. The reason is that nuclear medicine has a

strong culture of reporting any accidents and has generally adopted a systemic

risk approach like that of the aviation industry rather than a “name and blame”

approach common in the rest of the medical profession. This approach has

encouraged good practice and minimisation of serious accidents.

At the same time, other diagnostic modalities using radiation have not yet

developed this same approach and do not automatically categorise incidents

such as repeating a scan or Xray to expand the area scanned, or to ensure the

image is satisfactory, as a reportable incident – this is merely classified as

“taking another view”. In this regard, there would be value in developing some

uniformity of reporting, although we question whether this would be a role for

an enhanced post-marketing surveillance capacity.

In initiating any additional post-marketing surveillance it is important to

recognise that, in the case of nuclear medicine (and presumably many other

specialties), there are already multiple regulatory requirements relating to the

submission of data (at both federal and state levels) and these must be

coordinated, rather than duplicated by any post marketing surveillance

exercise.

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Term of Reference 4

Strengthening transparency and procedural fairness in the assessment,

decision making and fee negotiation arrangements for processes (as outlined in

the Review scope) through improved communication with stakeholders about

processes, methodologies, outcomes and performance against key indicators.

The Review has asked what aspects of Australia’s health technology

assessment system work well in relation to transparency and procedural

fairness, what improvements could be made, and what performance indicators

could be instituted.

Concerns about procedural fairness and transparency have been examined in

detail elsewhere in relation to the assessment of two applications concerning

PET.

With respect to issues raised in those examinations, concerns are expressed to

the ANZAPNM in relation to:

the objectivity of the technical evaluation process;

the need for an evaluation methodology that is specifically designed to

assess diagnostic technologies and which is different from that applicable

to therapeutic technologies;

the potential for politicisation of elements of the process;

the inter-relationship of the roles of the main MSAC and the supporting

committees.

The ANZAPNM appreciates that changes have been made to some MSAC

processes in response to the issues raised in relation to the early PET

assessments.

The ANZAPNM understands the government's rationale for considering any

further scope for aligning processes for pharmaceuticals, devices, diagnostic

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technology and therapeutic procedures/interventions and there is sense in

considering this. 

It is also noted that one area that would be under consideration is the

introduction of fees for lodging and assessing applications for funding under

Medicare in a similar fashion to the way that fees currently apply to

assessments by the TGA and PBAC. On the surface this would seem a logical

step. However PBAC and TGA applicants are manufacturers, suppliers or

distributors of products. In the majority of cases their request for MBS or PBS

listing is the culmination of multi-year and multi-million dollar research and

development investment projects.

MSAC applicants tend to be less homogeneous than the TGA and PBAC

applicants, comprising individuals, professional organisations, governments

and some from medical industry who have been through the TGA and/or PBAC

process.

For the medical industry group, MSAC is the end of the line where the product’s

therapeutic value has to be established before medical and other health

professionals can perform a service (using that product) that attracts a patient

benefit. In many cases the final amount of the determined schedule fee for the

procedure using the new product includes a professional component (taking

into account the training of the professional), a technical component (allowing

for the complexity of the service), and a capital component (the costs of the

equipment to provide the service and its running costs etc). Consequently the

MSAC process focuses on the value of the service (involving the use of an

approved product) to health care - be it diagnostic and/or therapeutic.

Particular procedures provided by medical practitioners not involving new

products require assessment by MSAC before the procedure can attract a

patient benefit.

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The ANZAPNM supports the need for assessment of new medical technologies

to establish their diagnostic and therapeutic value and assess the acceptability

of their risk to the community.

In 2007, of 14 applications received by MSAC seven were from government

agencies including the Department of Health and Ageing, applications from

governments likely to continue to increase as they seek to contain costs

through various demand and supply measures.

Cost recovery of all costs relating to processing and assessing applications is

one such measure. However, if the average cost of an MSAC assessment is

$250,000 full cost recovery to this amount for professional services would be

prohibitive for individual professionals and for professional organizations. The

effect of this would be a stifling of the introduction of new and potentially safer

and more cost effective diagnostic and therapeutic services. With the opening

up of the MBS to health professionals other than the medical profession, and

the pressure to expand roles on the basis of equivalent safety and

effectiveness but greater cost-effectiveness, the burden of cost on those health

professionals or professional associations to put forward their case will be even

more onerous than it is now.

This is an area that needs to be explored carefully, including the possibility of

introducing a financial contribution, to ensure that the original objective of

establishing MSAC as a public interest facility is not lost in the face of

budgetary pressures.

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Term of Reference 5

Enhanced arrangements for assessment of co-dependent5 and hybrid

technologies6.

The process whereby the ANZAPNM was able to coordinate the national PET

Data Collection Project provides a valuable model for future assessment. While

this project was very large, involving multiple sites and multiple indications –

with a cost that reflected the extensive nature of the project – it nonetheless

represents a useful approach in developing a dataset on particular

technologies. In this case, there was a need to assess the role of PET in

relation to a number of cancer indications; Commonwealth funding provided

the opportunity to conduct several protocols in parallel.

The terms of reference for this Review seek examples to illustrate points. One

such example relates to the usefulness of having an extensive data set. The

PET Data Collection Project had an additional benefit in that from the extensive

data collected and analysed it was possible for ANZAPNM to provide additional

information to further inform the MSAC process in relation to the lymphoma

evaluation. Concerns were expressed by MSAC when it was reviewing the

report from the Project about the selection of low grade rather than high-grade

lymphoma for review. The ANZAPNM was also in a position to provide

additional data on the stage change information for low grade, high grade and

Hodgkins disease patients, both for initial staging and for restaging, from the

PET Data Collection Project database.

It is understood these additional data enabled the MSAC evaluation to

progress.

5 Where therapy involving the use of one health technology to directly improve health (eg a medicine or a medical device or a procedure) is improved by the use of another health technology (eg a pathology or imaging diagnostic technology), which might more accurately identify patient subsets most likely to gain from the therapy or monitors therapy response.6 Where the characteristics of different health technologies (eg a medicine or a medical device or a biologic) are combined in one intervention (eg laser activated medicines such as photodynamic therapy, or drug eluting stents.

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The ability to respond to such enquiries from MSAC significantly enhances the

evaluation of new technologies and reinforces the value of government support

for similar clinical research activities.

While the PET Data Collection Project process presented a number of difficulties

over the life of the project, not the least of which was the time taken to finalise

protocols, it still provided valuable lessons in how to undertake such a multi-

centre research program to inform government policy.

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Attachment

Terms of Reference

The terms of reference for the Review, issued in April 2009, seek a report on:

1 Simplification and better coordination between the Commonwealth HTA processes (as identified in the Review scope), which includes:

consideration of a single entry point and tracking system for applications for market regulation and funding;making time to affordable access as short as possible for new technologies while maintaining or improving the rigour of evaluation processes; andexamination of the feasibility of conducting concurrent assessments for market registration and funding and coverage purposes, noting current work in this area.

2 Improving role clarity and addressing duplication between processes, where it exists, including consideration of consolidating functions within the Australian HTA system.

3 Reviewing post marketing surveillance mechanisms to ensure the ongoing safety and efficacy of medical devices.

4 Strengthening transparency and procedural fairness in the assessment, decision making and fee negotiation arrangements for processes (as outlined in the Review scope) through improved communication with stakeholders about processes, methodologies, outcomes and performance against key indicators.

5 Enhanced arrangements for assessment of co-dependent7 and hybrid technologies8.

Scope of the Review

The Scope of the Review includes:

regulation of therapeutic goods approval of funding under the Medicare Benefits Scheme currently informed by the MSAC and relevant implementation consultative committees 7 Where therapy involving the use of one health technology to directly improve health (eg a medicine or a medical device or a procedure) is improved by the use of another health technology (eg a pathology or imaging diagnostic technology) which might more accurately identify patient subsets most likely to gain from the therapy or monitors therapy response.8 Where the characteristics of different health technologies (eg a medicine or a medical device or a biologic) are combined in one intervention (eg laser activated medicines such as photodynamic therapy, or drug eluting stents.

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listing of prostheses for private health insurance coverage, as currently informed by the PDC; andlisting of hybrid and co-dependent technologies as currently informed by the MSAC, Pharmaceutical Benefits Advisory Committees (PBAC) and PDC.

MSAC’s current role is defined by its Terms of Reference, namely:

Advise the Minister for Health and Ageing on the strength of evidence pertaining to new and emerging medical technologies and procedures in relation to their safety, effectiveness and cost-effectiveness and under what circumstances public funding should be supported.

Advise the Minister for Health and Ageing on which new medical technologies and procedures should be funded on an interim basis to allow data to be assembled to determine either safety, effectiveness and cost-effectiveness.

Advise the Minister for Health and Ageing on references related either to new and/or existing medical technologies and procedures.

Undertake health technology assessment work referred by the Australian Health Ministers’ Advisory Council (AHMAC) and report its finding to the AHMAC.

Under these Terms of Reference, MSAC has the responsibility of accepting applications in relation to new medical technologies and procedures, or where there are significant changes in the use of already publicly-funded medical technologies. However it may also accept “references” from both the Minister and from the Australian Health Ministers’ Advisory Council.

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