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| Journal of the New Zealand Medical Association,
25-November-2011, Vol 124 No 1346
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Access to new medicines in New Zealand compared to
Australia
Michael Wonder, Richard Milne
Access to new medicines is an ongoing public health issue in
most developed countries. Many new medicines are costly and unaffordable for
many patients; therefore public access is very limited. Governments are under
continual pressure to provide timely access to new medicines, many of which are
costly.
In New Zealand (NZ) the governmental Pharmaceutical
Management Agency (PHARMAC) manages purchasing of pharmaceuticals on behalf of
District Health Boards (DHBs) following their registration by Medsafe. PHARMAC
develops and maintains the NZ Pharmaceutical Schedule (the ‘NZ
Schedule’) of pharmaceuticals available in the community on prescription
by a medical doctor, dentist, registered midwife, designated nurse practitioner
or optometrist, and partly or fully subsidised from a national pharmaceutical
budget. It also includes some pharmaceuticals purchased by DHBs for use in their
hospitals, for which national prices have been negotiated by
PHARMAC.1
In Australia, pharmaceuticals that are subsidised by the
Federal Government are listed in the Schedule of Pharmaceutical Benefits (the
‘Australian Schedule’) and funded by the Pharmaceuticals Benefits
Scheme (PBS) following their registration by the Therapeutic Goods
Administration (TGA). A PBS prescription must be written by a doctor, a dentist,
an optometrist, a midwife or a nurse practitioner. There are separate
arrangements for PBS prescriptions in certain public hospitals in most
States.2
New prescription-only medicines become available after the
results of their Phase 3 clinical trials become known and pharmaceutical
suppliers make submissions to the NZ and Australian governments for public
funding. In NZ, decisions on listing, indication, subsidy levels, prescribing
guidelines and conditions are made by the Board of PHARMAC with input from its
Pharmacology and Therapeutics Advisory Committee (PTAC), its specialist
sub-committees, the Hospital Pharmaceutical Advisory Committee (HPAC) and
PHARMAC staff.
In Australia, a statutory body called the Pharmaceutical
Benefits Advisory Committee (PBAC) reviews all submissions by pharmaceutical
suppliers. The PBAC then makes recommendations to the Minister for Health and
Ageing on the listing and subsidisation of medicines in the Australian Schedule.
Restrictions may be applied to limit the use of medicines to certain registered
indications.
The aim of this study was to compare access to new
prescription-only medicines in NZ with Australia in the period January 2000 to
December 2009. For the purposes of this analysis we define ‘access’
to a new medicine in NZ or Australia as listing in the respective Pharmaceutical
Schedule.3,4
MethodsA ‘new medicine’ was defined as:
This definition includes
a medicine that was registered some time ago, only to be deregistered and
subsequently reregistered (ostensibly for use by a different patient
population).
The analysis excluded any existing medicine in the
same presentation that was subsequently reimbursed for use by a
different patient population (i.e. a new indication). It also excluded
any existing medicine that was given access to a wider patient group, but in the
same indication (e.g. moved from second-line to first-line use).
The following were also excluded from the
analysis:
For Australia, we examined serial
editions of Section 2 (Ready-Prepared Medicines) of the Australian Schedule
issued during the study period to identify new medicines and their respective
dates of reimbursement. Medicines listed only in Section 4
(Extemporaneously-Prepared Medicines) or the Repatriation Schedule of
Pharmaceutical Benefits were excluded. New combination products were also
excluded from the sample as we assumed that patients should be able to access
the respective components separately. Vaccines and medicinal products, such as
test strips and infant formulae, were also excluded.
A medicine was considered to be ‘new’ if
its first listing in the Australian Schedule occurred no more than 10 years
after its initial registration by the TGA. This was done to exclude medicines
that were likely to be out of patent in Australia when they were first listed in
the Schedule.
TGA registration dates are not readily available. When
the initial registration date for a medicine could not be determined, the
on-line version of the Australian Register of Therapeutic Goods (ARTG) was used
to determine the date a medicine was first entered into the register; this date
was used as a proxy for the TGA registration date. Medicines are generally
entered in the ARTG within days of
registration.5 The core data set for Australia
comprised new prescription-only medicines that were first listed in the Schedule
in the study period.
Serial issues of the NZ Schedule were then searched for
medicines in the core data set. A medicine listed in the NZ Schedule was
considered to be the same medicine as that listed in the Australian Schedule if
its registered form was the same chemical entity in the same or similar
registered form. Tablets and capsules were considered to be sufficiently
similar, and differences in registered dosage were ignored. A medicine listed in
NZ was deemed to be different from that listed in Australia if it was available
in a different presentation for use by a different patient
population.
A new medicine was considered to be
‘accessible’ in New Zealand if it was listed in Section B (Community
Pharmaceuticals) and/or in Part II (Pharmaceuticals Under National Contract) of
Section H. Accessible medicines also include oncology products included in Part
V (Pharmaceutical Cancer Treatments) of Section H (Hospital Pharmaceuticals) in
the period January 1, 2000 to June 30, 2008 or into Section B or H after June
30, 2008. It was considered to be ‘accessible’ in Australia if it
was listed in the Australian Schedule. A medicine listed in the NZ
Pharmaceutical Schedule only under ‘Special Access’ provisions (i.e.
reimbursed despite not yet being registered) was not considered to be
‘accessible’ as there are no such provisions in Australia.
The New Zealand Gazette and Data Sheets
(Consumer Medicine Information) were examined to determine the registration
status of all medicines in the core data set. Data Sheets were also used to
determine which medicines in the core data set were prescription-only in New
Zealand.6
The date that a medicine first appeared in the New
Zealand Gazette was considered to be its registration date.
Medicines in the core data set that have been reimbursed in NZ comprised the
common data set.
The following descriptive analyses were performed on
the medicines on the common data set.
The medicines in the core data set
that were reimbursed only in Australia in the study period (unique data set)
were then analysed by their ATC main group and therapeutic area (reimbursed
use).
Finally, listings of all the new, prescription-only
medicines that were reimbursed in NZ were compared with listings in Australia in
the study period.
Single sample t-tests of differences were used for
between-country comparisons of registration dates, reimbursement dates and the
time from registration to listing. Analyses were conducted as two sided tests
with an α of 0.05, using GraphPad.8
ResultsBreadth of access—136 new,
prescription-only medicines (core data set) were listed in the Australian
Schedule in the study period (Table 1).
Table 1. New medicines listed in the Australian
Schedule of Pharmaceutical Benefits in the period 2000–2009
a WHO ATC
classification system.
Another medicine (troglitazone) was listed in the 1 May 2000
issue of the Schedule but it was deregistered before the listing took
effect.
Timeliness of
access—Table 2 shows all 59 medicines that were listed in both NZ
and Australia in the period 2000-2009 (common data set; Table 2).
((view Table 2 and Table 3 here))
Registration occurred on average sooner in Australia than in
NZ (mean difference 9.0 months; 95% CI 3.6 to 14.4 months; p=0.0012). 43 (73%)
of the 59 medicines in the common data set were registered in Australia before
NZ and 53 (90%) of the 59 medicines in the common data set were reimbursed in
Australia before NZ (mean difference 32.7 months; 95% CI 24.2 to 41.2 months;
p<0.0001).
Importantly, the lag between registration and listing was
almost 2 years longer in NZ than in Australia (mean difference 23.7 months; 95%
CI 14.9 to 32.4 months; p<0.0001).
Earlier registration of ursodeoxycholic acid, dorzolamide
and ezetimibe in NZ was followed by earlier reimbursement. In the case of four
medicines in the common data set (pravastatin, meloxicam, donepezil and
levetiracetam), their listing in the NZ Pharmaceutical Schedule was so delayed
that the first entrant was a generic brand.
77 medicines of the core data set were reimbursed only in
Australia in the study period (unique data set; Table 3). They encompass most
therapeutic areas; the largest group is WHO ATC Main Group L (anti-neoplastic
and immunomodulating agents) with 15 (20%).
Limited access to new medicines in NZ cannot be attributed
to non-registration because 64 (84%) of the new medicines registered in
Australia are currently registered in NZ. The medicines in the unique data set
that are not registered in NZ have not been reimbursed by way of ‘Special
Access’ provisions.
Other new medicines
listed in NZ—In total, 80 new prescription-only medicines were
listed in the NZ Pharmaceutical Schedule in the period 2000–2009.
Excluding the 59 new medicines listed in both countries during this period (see
Table 2 above), most of the remainder were registered in Australia prior to the
study period and two (rizatriptan and mirtazipine) were registered in Australia
subsequent to the study period. Five new medicines were reimbursed in NZ but not
in Australia (Table 4).
Table 4. New medicines listed in NZ during the
study period, and their reimbursement status in
Australiaa
a Excluding those
listed in both countries during 2000-2009 (Table 2);
b Intra-uterine device (Mirena) listed
for heavy menstrual bleeding but not contraception in NZ;
c Unregistered medicine
Inclusion of levonorgestrel in the form of an intrauterine
device to prevent heavy menstrual bleeding (Mirena) is perhaps
controversial, as levonorgestrel (in tablet form) was already listed in the NZ
Schedule as a contraceptive (Microlut). Nonetheless, the tablet form is
listed for systemic use as a contraceptive whereas the IUD is listed for
localised slow release of levonorgestrel to prevent heavy menstrual bleeding.
Levonorgestrel (as Mirena) was first listed in the Australian Schedule
for use as a contraceptive device on 1 February 2003. It was not considered to
be a new medicine, as the tablets were already listed in the Australian Schedule
for use as a contraceptive.
The PBAC recommended the listing of ropinirole for the
treatment of Parkinson’s disease at its December 1997 meeting; however, it
remains unreimbursed because its sponsor decided not to proceed with the
listing. An application to list ropinirole for the treatment of patients
suffering with severe primary restless legs syndrome was rejected by the PBAC in
March 2006.9
Anagrelide was first registered in Australia on 23 November
1999.5 At least 2 applications seeking its
listing on the PBS have been rejected by the PBAC, the last in June
2003.10 Finasteride was first registered in
Australia on 26 October 1993 but it has never been listed in the Schedule of
Pharmaceutical Benefits.5 No application has
been made since June 2003.9
Although pentostatin was designated as an orphan drug by the
TGA on 15 May 2009, it remained unregistered as at December
2010.5,11
DiscussionOver the previous 10 years, the NZ public has been given
access through Government funding to less than half of the new medicines that
have been reimbursed in Australia. The remaining 77 new medicines that are
reimbursed in Australia but not in NZ cover a wide range of therapeutic areas,
including some diseases for which there are no reimbursed medicines in NZ. For
the new medicines that were listed in both countries, registration occurred on
average 9.0 months later in NZ and listing occurred 32.7 months later, giving a
23.7 month difference in the interval between registration and listing (95% CI
14.9 to 32.4 months; p<0.0001). Sixteen of the new medicines listed in both
countries (27%) were registered first in NZ but only three of these
(ursodeoxycholic acid, dorzolamide and ezetimibe) were listed first in NZ.
Differences in access are probably due to both the financial
constraints on the reimbursement agencies and the methods of assessment used.
Both PHARMAC and the PBS aim to provide ‘value for money’; however,
PHARMAC is legislated to operate on a capped
budget1 whereas the Australian Government
allows the expansion of the PBS budget in order to accommodate as many new
medicines as can demonstrate clinical importance, clear evidence of
effectiveness, affordability, cost-effectiveness and other
qualities.12
PHARMAC assesses and prioritises new medicines against each
other and against widened access to older medicines annually, and declines or
defers listing of new medicines in the NZ Schedule in order to stay within its
budget.1 The result for the NZ public is delays
in listing of new medicines, an expanding list of new medicines that are
acceptable but deferred, and more predictable pharmaceutical expenditures. In
contrast, the PBAC judges each new medicine on merit, regardless of other
medicines that are competing for the same
budget.2 The result for Australia is better
access to new medicines along with an expanding pharmaceuticals budget.
The methodologies for achieving value for money also differ.
PHARMAC relies heavily on a wide range of relatively blunt commercial tools
including reference pricing, expenditure caps, tendering for sole supply, multi
product agreements, confidential rebates to suppliers and Special Authority
provisions to restrict access.1 Whilst
reference pricing and prior authorisation provisions are also used in Australia,
deeds of agreement containing risk sharing arrangements are increasingly being
used by the Government to manage financial risk and to contain PBS
costs.13
Both the PBAC and PHARMAC take into account the
cost-effectiveness of new medicines as one of several listing criteria. The PBAC
Guidelines require suppliers to provide a detailed cost-effectiveness and budget
impact analysis of each new medicine compared with the treatment most likely to
be replaced in practice. These analyses are scrutinised by PBAC’s
Economics Sub-Committee (ESC) comprised of academics and clinicians. Economic
models are evaluated by the Pharmaceutical Evaluation Section (PES) in detail,
including all clinical and economic data used to populate the model, its
construction and the auditing of any formulae. Suppliers are given the
opportunity to comment on the PES report before this goes to the ESC, as well as
the opportunity to comment on the ESC report before it goes to the
PBAC.14
In contrast, PHARMAC encourages suppliers of new medicines
to provide detailed cost-effectiveness and budget impact analyses of their
products, then undertakes (generally) rapid economic analyses in-house,
comparing new medicines with submissions for other new medicines and widened
access to older medicines.15,16 In short, while
the PBAC evaluates each new medicine against current medical practice in a given
therapeutic area, PHARMAC evaluates each new medicine against the range of
funding options that are currently available to it across all medicines (old and
new) and all therapeutic areas. Budget impact plays an important role in the
listing decision in both countries.12,15
Since mid 2005, the PBAC has published all its decisions
relating to submissions to list new medicines on the PBS in the form of public
summary documents.17 PHARMAC has defended some
of its decisions to list or decline to list certain new medicines (or classes of
medicines) in the NZ Schedule, including some that are now listed in both NZ and
Australia 18-29 and others that are listed only
in Australia.30-36 However, most of
PHARMAC’s listing decisions have not been open to public scrutiny except
for a limited number of unpublished health technology assessments.
Restrictions in access to new medicines have an opportunity
cost for patients in terms of preventable mortality and morbidity and potential
quality-adjusted life year (QALY) gains forgone. PHARMAC has estimated QALY
gains achieved by listing or declining to list selected new
medicines29,37 but information is not available
concerning the overall QALY gains and losses across all major funding decisions.
Restricting access to new medicines also limits the opportunity to improve the
overall efficiency of healthcare delivery through reducing hospital admissions
and length of stay.38
On the other hand, expanded access to new medicines has a
monetary opportunity cost. The cost of the PBS has increased steadily over the
last decade39 whereas PHARMAC has been
successful in containing growth in the community pharmaceuticals budget in the
face of volume growth, by driving down prices and limiting
access.40 Funds within PHARMAC’s budget
that are preserved by limiting access to new medicines are used to widen access
to other medicines, and funds that might have been allocated to pharmaceuticals
can potentially be used for non pharmaceutical healthcare
delivery.30
A secondary benefit to PHARMAC of deferring the listing of
new medicines is that prices inevitably decline with time and they can fall
precipitously when a generic ultimately becomes
available.10 However, most of the medicines
that are reimbursed in Australia but not NZ (Table 3) are unlikely to cause
undue stress on PHARMAC’s budget. Only 4 medicines that were listed in
Australia but not NZ (ranibizumab, rosuvastatin, rabeprazole and celecoxib) were
in the top 50 highest PBS cost items for the year ended 30 June
2010.13
The results from our study have some limitations. We chose
new prescription-only medicines as our study sample because they are a major
focus of current public discourse on access to healthcare in both countries. We
may well have obtained different results had we chosen a broader sample of
medicines and medicinal preparations. We defined access as being listed in the
respective national pharmaceutical schedules; we did not attempt to study the
quality of access such as indications and patient groups. While the initial
listing of most of the medicines in our study came with restrictions, we did not
compare restrictions or examine whether restrictions were changed over time
(within and/or across indications). These are all worthy areas of future
research.
Our definition of access did not consider prescription costs
because we were more interested in studying whether (and when) new medicines
were listed than whether patients could afford the requisite prescription
co-payment. When they are reimbursed, medicines are more affordable to the NZ
patient because patient contributions are lower and 3 months’ supply may
be dispensed for some medicines.3,4
We chose 2000-2009 as our study period rather than any
single point in time. This strategy improved the size of our study sample and
also showed that access to new medicines in NZ compared to Australia has been
restricted and delayed over the recent decade.
Whilst others have also compared access to medicines in NZ
and Australia (as well as in other selected countries), none have been as
comprehensive as ours in terms of study sample and study period.
Danzon and colleagues recently published the results of
their study on the impact of price regulation on the timing of the launch of new
medicines in 25 major countries, including NZ and Australia. The study was
conducted on 85 new chemical entities (NCEs). The outcome of interest was the
launch date (i.e. the first possible date of supply), which could well be more
of a registration issue than a reimbursement issue. Unfortunately, data
limitations did not enable the analysts to distinguish between a delay due to
market authorisation versus price/reimbursement approval.
The three countries that did not require price approval
before launch had the highest number of launches. The USA led with 73 launches,
followed by Germany (n=66) and the United Kingdom (n=64). At the other extreme,
only 13 NCEs were launched in Japan, followed by Portugal (n=26) and NZ (n=28).
Australia had 43 launches.41
A wide-ranging study (the Castalia Report) compared the
number of new listings (new chemical entities, new products and new items) in
Australia and NZ from June 1999 to June 2004.42
The results for NZ were poorer for all three categories. Whilst some aspects of
the findings of the Castalia Report have been challenged, criticisms were not
directed at the results on the access to new
listings.43,44
Morgan and colleagues compared the centralised drug review
processes in four Commonwealth countries, including Australia and NZ. They
examined the outcomes of the listing decisions by comparing the subsidised
access, cost and use of 17 of the world’s top-selling medicines in 2003 in
each of the countries. They found that 15 of the 17 medicines were reimbursed in
Australia whereas only 8 were reimbursed in
NZ.45 One of these was a combination product
and another was already available in both countries as a generic. These results
have since been updated. All of the 17 medicines were reimbursed in Australia
and 9 were reimbursed in NZ.46
Researchers from the Karolinska Institute in Sweden studied
the market introduction and total sales of 67 oncology products in 25 countries
including the USA, UK, Canada, Australia and NZ. Uptake was slower in NZ than in
Australia and Canada, and comparable to or slower than the
UK.47
Our results contrast with those from a media release by
PHARMAC showing that as at March 2006, NZ had listed more unique therapeutic
chemicals than Australia (267 versus 217). NZ also had more funded chemicals or
formulations of the same chemical entity with distinctly different uses (e.g.
ketoconazole tablets versus ketoconazole shampoo) [717 versus
655].48
The methods and definitions used by PHARMAC have not been
published, however the differences in results between PHARMAC’s study and
ours are not surprising given the differences in the questions being addressed
and the study design. PHARMAC’s study: (a) considered access only at one
time point; (b) included both new and old medicines; (c) included medicines and
medicinal preparations, such as nutrients/special foods, vitamins, non-hormonal
contraceptives, barrier creams, emollients, etc, (d) included multiple strengths
of the same or similar presentations of the same medicine/medicinal preparation
and (e) excluded hospital pharmaceuticals that were not listed in the community
pharmaceutical schedule.
Finally, declining to list highly cost-effective
pharmaceuticals because of a pharmaceuticals budget cap, as in NZ, implies that
such pharmaceuticals are intrinsically less cost-effective than any
non-pharmaceutical interventions that they might displace if they were funded.
This implicit assumption is clearly unsupported because rigorous economic
evaluation is not available for most non-pharmaceutical healthcare
interventions. There is a case for the expansion of PHARMAC’s
pharmaceuticals budget when highly cost-effective pharmaceutical interventions
become available, rather than delaying listing indefinitely. PHARMAC would still
benefit when the patent expires, and in the meantime patients would
benefit.
ConclusionSince 2000, the NZ public has been able to access fewer new
medicines via its national medicines reimbursement programme than the Australian
public. Access to new medicines in NZ is considerably slower than in Australia.
The population health implications of the differences in access need further
research.
Disclaimer:
Any views expressed in this paper are those of the authors and do not
necessarily represent the views or practices of Novartis and its
affiliates.
Source of funding: Funding for RM was
provided by Novartis New Zealand Ltd. Novartis took no part in the design,
analysis or interpretation of results.
Disclosures of interest: MW was
employed until recently by Novartis Pharmaceuticals Australia Pty Ltd., a
pharmaceutical company that made numerous applications to the PBAC during the
study period. RM has acted as a consultant to the Ministry of Health and PHARMAC
and to various New Zealand companies that made submissions to these
agencies.
Author
information: Michael Wonder, Consultant Health Economist, Sydney,
Australia; Richard Milne, Honorary Associate Professor, School of Population
Health, University of Auckland; Managing Director, Health Outcomes Associates
Ltd, Auckland, New Zealand
Correspondence:
Michael Wonder, PO Box 470, Cronulla, NSW 2230, Australia. Fax: +61 (0)2
95015855; email: mwonder@optusnet.com.au
References:
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