Accepted Manuscript Title: Managed entry agreements for pharmaceuticals in Australia Author: Agnes Vitry Elizabeth Roughead PII: DOI: Reference:
S0168-8510(14)00134-1 http://dx.doi.org/doi:10.1016/j.healthpol.2014.05.005 HEAP 3229
To appear in:
Health Policy
Received date: Revised date: Accepted date:
30-7-2013 29-4-2014 20-5-2014
Please cite this article as: Vitry A, Roughead E, agreements for pharmaceuticals in Australia, Health http://dx.doi.org/10.1016/j.healthpol.2014.05.005
Managed entry Policy (2014),
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Managed entry agreements for pharmaceuticals in Australia Agnes Vitrya, Elizabeth Rougheada a
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Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide SA 5001, Australia
Corresponding author:
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Dr Agnes Vitry
GPO Box 2471, Adelaide SA 5001, Australia
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Phone: +61 8 8302 2392 Fax: + 61 8 8302 1087
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E-mail: [email protected]
Keywords
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Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia
pharmaceutical policy; managed entry agreement; medicine subsidization; coverage with
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evidence development.
Funding
Professor Elizabeth Roughead is funded by a Future Fellowship from the Australian Research Council. The views expressed are those of the authors, the sponsor had no role in the preparation of the manuscript.
Competing interests Both authors have completed the ICMJE uniform Disclosure form. Professor Elizabeth Roughead is a member of the Drug Utilisation Sub-Committee (DUSC) of the Pharmaceutical Benefits Advisory Committee (PBAC).
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Abstract
In Australia, a number of managed entry agreementshave been developed to enable national
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coverage of new medicines. Non-outcome based agreementsare usually pricing arrangements that involve price or volume rebate agreements. In February 2013, there were at least 71 special
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pricing arrangements in place,including 26 for medicines restricted to use in hospitals. Health outcome based agreementscan be made at the individual or population level. At the individual
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level, there were 28 medicines funded subject to continuation rules involving documentation of adequate benefit within the individual; some of these medicines also had price agreeements in
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place. At the population level, only one outcome based agreementhas been implementedso far, for bosentan, a medicinemarketed for pulmonary hypertension. In May 2010, a memorandum of understanding signed between the Australian Government and Medicines Australia, the peak
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pharmaceutical industry organisation, includedthe possibility for industry to request consideration of a ‘Managed Entry Scheme’ as part of the funding submission process for
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medicines with high clinical needs. It includes the possibility of a randomised controlled trial (RCT) -based entry scheme.Although this form of managed entry has yet not been trialedin
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Australia, several 2012/2013funding recommendations included requests by the decision making
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committee for further evidence development.
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1. Introduction
The growing ageing population, the raising prevalence of chronic diseases and the high cost of new medicines are all factors contributing to rising pharmaceutical expenditures. The high prices
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requested by pharmaceutical companies for new medicines create further challenges. In
2012,eleven of the twelve cancer medicines approved by the US Food and Drug Administration
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were priced above US$ 100,000 per year[1].The price of ivacaftor, a new medicine marketed in 2012 for a genetic disease, cystic fibrosis, reached US$373,000 per patient in the United
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States[2] and was recommended in Australia with an estimated cost of AU$60 million to $100 million in the fifth year of listing[3, 4]. In 2013, the listing of pregabalin for chronic nerve pain
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will cost the Australian government more than AU$ 450 million over five years and those of three new cancer medicines, ipilimumab for advanced melanoma, abiraterone for advanced prostate cancer and oral vinorelbine for advanced breast cancer,will cost more than AU$430
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million over four years[5].
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Funding decisions by public or private insurance bodies are oftendifficult because of numerousuncertainties around the efficacy, effectiveness, safety or cost-effectiveness of new
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medicines[6]. This uncertainty can create cases where medicines receive a positive coverage
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decision,however, subsequent evidence indicates the medicine is found not to be as effective or as safe as expected and thusresources are wasted (i.e. opportunity costs)or patients harmed.Equally challenging is the negative coverage decision for a breakthrough medicine,which may prevent some patients from accessing the medicine. Moreover, public and private insurersoften operate in a context of intense pressure from stakeholders, pharmaceutical industry and consumer organisations to provide funding for new medicines.
Inthis context, several countries have implemented novel subsidization schemes for new medicines,with the aim of allowing some form of access which is closely managedthough agreements set up with pharmaceutical companies. These managed entry agreements have been defined as “an arrangement between a manufacturer and payer/provider that enables coverage or reimbursement of a health technology subject to specific conditions. These arrangements can use a variety of mechanisms to address uncertainty about the performance of technologies or to 3 Page 3 of 23
manage the adoption of technologies in order to maximise their effective use or limit their budget impact” [7].
1.1 Australia’s public funding system for pharmaceuticals
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In Australia, a nationalpublicpharmaceutical insurance system, the Pharmaceutical Benefits
Scheme (PBS), was established in 1953. By 2011, the PBS subsidised around 4,000 products. In
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2011-12, PBS government expenditure represented AUD $9,193.7 million and 83.4% of the total cost of PBS prescriptions, the remainder being patient contributions[8]. The decision to list new
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medicines on the PBS is taken by the Federal Minister for Health on recommendation from the Pharmaceutical Benefits Advisory Committee (PBAC), an independent expert body that
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determines the effectiveness and cost-effectiveness of new medicines. Australia was the first country to introduce an explicit requirement for economic evaluation in its subsidisation assessment process in 1993. Although there is no capped budget for the PBS, any medicine the
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PBAC recommends for listing that is expected to cost more than $20 million per year in any of the first four years must be approved by Cabinet[9].Medicines listed in the Schedule can fall into
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three broad categories: ‘unrestricted benefits’formedicines with no restrictions on therapeutic use, ‘restricted benefits’ for medicines that can only be prescribed for specific therapeutic uses,
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and ‘authority required benefits’ for medicines that require prior approval from the Department
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of Health. Prescribing restrictions may limit use to indications for which the medicine has been deemed effective or cost-effective and may include rules for initiation or continuation of treatment.
In Australia, managed entry agreements have beenoperating for a number of years. In May 2010, the Australian Government and Medicines Australia, the peak pharmaceutical industry organisation, signed a Memorandum of Understanding which introduced a new type of managed entry agreement[10]. This memorandum focused on the expansion of the price reform policies that had started in Australia in 2007 and included provisions on a ‘Managed Entry Scheme’for pharmaceuticals. Clauses 26 and 27 of the memorandum state that the PBAC ‘may recommend PBS coverage at a price justified by the existing evidence, pending submission of more conclusive evidence of cost-effectiveness to support listing of the drug at a higher price” [10].To support the process, the Australian Department of Health published a framework for the 4 Page 4 of 23
introduction of this form of managed entry agreement [11].The framework states that a submission would be considered for a Managed Entry Scheme when there is ‘a high clinical need for the proposed drug in the indication requested by the sponsor’, and that ‘new clinical data would resolve the issues of uncertainty in relation to the extent or value of the clinical effect
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which would have otherwise prevented an initial positive recommendation’. This includes the possibility of a randomised controlled trial (RCT)-based managed entry scheme with a trial
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protocol available at the time of the original submission. The framework also notes other nonRCT level evidence “may be appropriate, such as data collection for the purpose of confirming
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cost-offsets in economic analyses”.
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In this paper, we examineAustralia’s past and more recent experience with managed entry
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agreements for pharmaceuticals.
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2. Methods Many terms have been used to describe the various types of managed entry agreements but a common feature of the taxonomies that have been proposed is the distinction between outcome based and non-outcome based agreements [12-14]. In this paper we have used a taxonomy
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adapted from those developed by Carlson (2010) and Ferrario (2013) that provides a simple
classification suitable for the Australian setting. It distinguishes non-outcome based agreements
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and outcome-based agreements(Figure 1). Non-outcome based agreements are usually financial in nature and aim to contain the costs without taking into consideration health outcomes. They
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may include price-volume agreements, discounts, price-capping schemes or dose-capping schemes. Outcome-based agreements have been defined as “schemes between healthcare payers
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and medical product manufacturers in which the price, level, or nature of reimbursement are tied to future measures of clinical or intermediate endpoints ultimately related to patient quality or quantity of life” [12]. The outcome-based agreements may be considered at the patient level
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and may include outcome-guarantee schemes (e.g. rebates or reimbursement if the medicine fails to achieve the expected results), or conditional continuation schemes. At the population level,
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coverage with evidence development (CED) schemes have been defined as ‘any policy mechanism that links financial support for medical technologies or treatments to a requirement
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for systematic data collection and analysis with the intent of using that data to modify health
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policy or clinical decision-making’ [15].
We collected data on non-outcome and outcome agreementsoperating in Australiafrom documents publicly available on the Australian government’s website including the Schedule of Pharmaceutical Benefits (edition February 2013), which provides details of medicines subsidised by the Australian Government[16]orthe Therapeutic Relativity Sheets (edition October 2012) released by the Pharmaceutical Benefits Pricing Authority (PBPA), which provides information on therapeutic relativities and pricing comparisons between medicines within a therapeutic group[17]. Funded products that are not medicines (e.g. nutrients) and medicines not listed on the PBS but available through the Life-Saving Drugs Program, which provides subsidised access to some medicines for rare life-threatening conditions, were not considered in this analysis.We compiled a list of all medicines for which there was mention of ‘special pricing arrangements’ either in the Schedule of Pharmaceutical Benefits or the Therapeutic relativity Sheets. 6 Page 6 of 23
Information on conditional treatment continuation was extracted for all medicines included in the Schedule of Pharmaceutical Benefits. Medicines were classified into therapeutic groups using the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification
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system[18].
To identify medicines that may have been proposed for a Managed Entry Scheme, we reviewed
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the outcomes and public summary documents prepared by the PBAC from July 2010 (after the signature of the Memorandum of Understanding) to April 2013 [19]. We also examined the
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literature on managed entry agreements through a comprehensive search of peer-reviewed
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articles on the Web of Science database and grey literature on relevant websites. 3. Results
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3.1 Non-outcome based agreements
in Australia non-outcome based agreements may take the form of price volume arrangements
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that involve price reductions for sales exceeding a pre-agreed volume,or rebate arrangementsthat involve repayment of costs beyond an agreed annual subsidisation cap [20]. These agreements
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are used to manage financial risks due to uncertainties in either estimating the overall usage or
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cost to the PBS, or to reduce risks of paying for medicine use outside of the restricted (or costeffective) listing.The first formal agreement,a legal document called a ‘deed of agreement’,took place in 2003 [6]. Before this date, pricing arrangements were agreed through an exchange of letters between the pharmaceutical company and the PBPA.
Our researchidentified71 medicines with “special pricing arrangements” in February 2013 (Table 1), of which 32 (45%) were mentioned in the Therapeutic Relativity Sheets, 12 (17%) in the Schedule of Pharmaceutical Benefits and 27 (38%) in both sources. Antineoplastic and immunomodulating agents were most frequently represented in these pricing arrangements(33.8%), followed by nervous system (15.5%), alimentary tract and metabolism (9.8%) and cardiovascular system (7%) medicines. Twenty six (37%) pricing arrangements applied to medicines restricted to supply through public and private hospitals (known as Section100).Threeproducts (abacavir, bosentan and efavirenz)have been listed with special 7 Page 7 of 23
bonus arrangements being agreed to with the sponsor rather than a rebate agreement[20].Under these arrangements, the manufacturer has listed the product at its nominated price and been required to provide free goods to the hospital as compensation so that the resultant cost per unit
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is equivalent to the agreed price. The deed of agreements may include the collection and provision of data in relation to a specific
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listing[21]. There are no public data on how many agreements include the requirement for
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collection of additional data.
3.2 Outcome based agreements
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In the February 2013 issue of the Pharmaceutical Benefits Schedule, there were 28 medicines funded subject tocontinuation rules (Table 2). They includedthe tumour necrosis factor (TNFalpha) inhibitors for rheumatoid arthritis, Crohn disease and severe psoriasis, some tyrosine
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kinase inhibitors for several types of cancer, as well as medicines for pulmonary hypertension and for Alzheimer’s disease. Twenty of these medicines (71%) were also included in the special
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pricing arrangements mentioned above. Continuation of treatment is subject to documentation of adequate benefit by some appropriate clinical or biological test. The first continuation rules were
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put in place when anticholinesterase medicines were listedfor the treatment of Alzheimer’s
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disease in 2000. With the exception of medicines for Alzheimer’s disease,patients who start taking medicinessubject to continuation rules are required to sign a patient acknowledgment formindicating that they understand and accept that PBS-subsidised treatment will cease if the criteria defining a satisfactory response to the medicineare not achieved at the pre-specified follow-up clinical assessment[16].
3.3 Coverage with evidence development We were able to identify only one CED schemethat has been implemented in Australia. In 2004, bosentan, a medicineapproved for pulmonary hypertension, was listedon the PBS on the condition that a registry was established to monitor mortality. The agreement was that the price for bosentan would be reduced if the mortality rate observed in the registry cohort was higher than that claimed in the original funding submission [22].The results of the Bosentan Patient Registry were difficult to interpret as the observed annual mortality rate (11.8%) was higher than 8 Page 8 of 23
the estimated rate (5.2%) from the bosentan pivotal randomised controlled trial and also because the 528 patients enrolled (approximately 69% of patients that were prescribed bosentan between 2004 and 2007) were older and hadmore advanced functional deficit than in the clinical trials[23]. In 2008,a new medicine for pulmonary hypertension,sitaxentan,was listed on the PBS
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at a 15% discount to bosentan, which was forced to decrease its price on a cost-minimization basis.Hence, no additional price reduction was required based on analysis of the registry
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data[22].
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In July 2010, the PBAC considered proposals for a Managed Entry Scheme for two medicines, pazopanib and imatinib. In both cases, the PBAC considered that this wasinappropriate in the
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context of the high price requested or high incremental cost-effectiveness ratio. In the case of pazopanib, it also stated that it ‘would be inappropriate to expose patients to a potentially
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inferior drug until evidence has been produced to show the contrary’ [24].
In 2012, the PBAC made onerecommendationrelevant to coverage with evidence development. It
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recommended the listing of ipilimumab for the treatment of melanoma subject to a risk-sharing arrangementthat would involve the ‘implementation of a mechanism to verify the anticipated
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overall survival benefits of ipilimumab in real world clinical practice in Australia... The sponsor
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would be expected to rebate the cost of difference in performance between observed versus predicted benefits of ipilimumab’[25]. In June 2013, the listing was officially announced by the Minister for Health but no details have been released on any coverage with evidence agreement.
In April 2013, the PBAC examined two formal requests for consideration of a Managed Entry Scheme for the listing of everolimus, a treatment for people with subpendymal giant cell astrocytomas caused by tuberous sclerosis, and for the listing of rifaximin, for prevention of hepatic encephalopathy[26]. In both cases, the PBAC recommended listing of these medicines but considered that there was no longer a requirement for a Managed Entry Scheme approach on the basis of the information available.
4. Discussion
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Our research identified 71 medicines with agreements in placein February 2013, 28 medicines subject tocontinuation rules and none with an ongoing CED scheme. These results are consistent with PBPA Annual Report for the 2011/2012 financial year that indicates there were76 deeds of agreement in place or in development[27]. A previous study using similar information sources
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over the period 2004 to 2008 identified 73 medicines with pricing arrangements and showed that47 of the 148 (32%)medicines withmajor submissions (those which include a full economic
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evaluation) to the PBAC had special pricing arrangements in place [28].All special pricing
arrangements apply to patented medicines,andthey are usually discontinued once medicines
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come off-patent and generic products are listed on the PBS.
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Our findings are similar to trends observed in a recent survey of managed entry agreements implemented in European countries between October 2011 and January 2012[14]. Overall, in the 18 European countries surveyed,39% of all the managed entry agreements were price-volume
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agreements; other agreements includedrequirement for data collection (29%), access limited to eligible patients (13 %), conditional continuation of treatment (5.6%), reimbursement or discount
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provided for non-responder patients (5.4%), and a general discount on all doses or an initial discount or free first doses (4.6%). There were important variations in the distributionof schemes
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and Sweden.
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between countries,withthe schemes requiring data collectionmainly used in Italy, Netherlands
We found that the antineoplastic and immunomodulating agents (33.8%), the nervous system (15.5%) and alimentary tract and metabolism agents (9.8%) were the three main therapeutic groups included in Australian non-outcome agreements, a result similar to the European survey that showed that the antineoplastic and immunomodulating agents represented 37% of all the managed entry agreements, followed by alimentary tract and metabolism (15%) and nervous system (10%)[14].These trends may reflect a higherneed to negotiate financial agreements for high cost new medicines such as the targeted medicines usedin oncology or medicines that may be used in large populations, such as insulins analogue for people with diabetes.
Within the PBS listing, there is provision for the cost-effectiveness of medicines as used in realworld clinical practice to be reviewed. The findingsof these post-market reviews may result in 10 Page 10 of 23
changes to the prescribing rules if these are found not to be effective or may result in changes to medicine prices. For example, a review was undertakenfor the biological disease modifying antirheumatic drugs in 2009 and, as a result,eligibility criteria were revised and price reductions required [29]. Another example is the review of the medicines for Alzheimer’s disease in 2013
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that found that they were being used in a much broader population and for longer periods of time than originally agreed as cost-effective[30]. Consequently, the PBAC ended the continuation
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rules that required a demonstrated improvement in cognitive function as measured by a test, the
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mini–mental state examination, and recommended a 40% decrease in the medicine price.
We were able to identify only one past CED scheme and two potential new ones. Three years
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after the signature of the Memorandum of Understanding in 2010, it does not seem that the new Managed Entry Schemehas been trialed yet. The implementation of CED schemes will require all stakeholders, government, industry, clinicians, researchers and consumers to consider
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carefully challenging issues such asthe choice of an appropriate study design, the feasibility of
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the research within a limited time frame, the governance and the funding of the schemes [31-33].
All the deeds of agreement in Australia are ‘commercial in confidence’ documents and detailed
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information is not publicly available. Thus, we were unable to determine the proportion of
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agreements that realised price reductions or rebates, nor how much savings accrued. In the financial statement of the Australian Department of Health’s Annual Report for the 2012- 2013 financial year it was stated that the Department had recovered $300 million ‘under cost-sharing arrangements with pharmaceutical companies’ but no further detail was provided. The confidentiality of the agreements precludes any comparisons with actual prices of individual medicines in other countries and thus, the efficiency of these schemes cannot be assessed [14, 28].
The confidentiality agreements creates challenges for countries that rely on external reference pricingto determine their own prices as the real price to othercountries is unknown[34]. A recent survey of policy makers involved in negotiating reimbursement contracts for pharmaceuticals in nine high-income countries found that they felt isolated as pharmaceutical companies had a substantial advantage in knowing discounts offered to other insurers [35]. Some policy makers 11 Page 11 of 23
also highlighted that some degree of secrecy could be justified to obtain price reductions, but Canadian policy makers expressed concerns that secret rebates could increase inequities in medicine pricing and coverage between jurisdictions [34]. Further, limited information on the
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technicalities and outcomes of the agreements restrict cross-country learning [36].
This study has a number of limitations. We were only able to obtain data publicly accessible on
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the Australian Department of Health’s websites and because of the limited information available, we cannot be sure to have identified all of the agreements in place. It was also not possible to
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examine the details of the agreements and the outcomes in terms of savings or impact on cost-
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effective use.
5. Conclusion
Australia’s pharmaceutical subsidisation system is highly regarded internationally for having
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developed and implemented rigorous methodologies for the appraisal of the effectiveness and cost-effectiveness of medicines[37]. Most managed entry agreements that have been
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implemented in Australia arenon-outcome based agreements.The confidential nature of these agreements limits the evaluation of their benefits with regards to coverage and pricing of new
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medicines compared with other countries.
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Figure 1.
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Taxonomy of managed entry agreementsadapted from those developed by Carlson (2010) and Ferrario (2013)
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Table 1 Medicines with special pricing arrangementsmentioned either in the Schedule of Pharmaceutical Benefits or the Therapeutic Relativity Sheets Names of medicines
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Number of medicines (%) 7 (9.8)
methylnaltrexone, exenatide, insulin detemir, insulin glargine, pioglitazone, rosiglitazone, sitagliptin
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Anatomical Therapeutic Chemical (ATC) classification system Alimentary tract and metabolism
3 (4.2)
rivaroxaban, eltrombopag, romiplostim
5 (7.0)
ambrisentan,bosentan, clopidogrel, iloprost, prasugrel
Dermatologicals
1 (1.4)
Genito urinary system and sex hormones
4 (5.6)
dutasteride, oxybutynin, choriogonadotropin, progesterone
Systemic hormonal preparations Anti-infectives
3 (4.2)
cinacalcet, teriparatide, somatropin
4 (5.6)
darunavir co-administered with ritonavir, efavirenz, tipranavir, tobramycin solution for inhalation
Musculo-skeletal system
Nervous system
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Antineoplastic and immunomodulating agents
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Blood and blood forming organs Cardiovascular system
24 (33.8)
3 (4.2)
11 (15.5)
imiquimod
peginterferon alfa-2a, azacitidine, bortezomib, certolizumab, dasatinib, docetaxel, erlotinib, imatinib, lenalidomide, pazopanib, sorafenib, sunitinib, fludarabine, trastuzumab, adalimumab, ustekinumab, abatacept, etanercept, golimumab, infliximab, rituximab, tocilizumab, fingolimod, natalizumab zoledronic acid, risedronate, botulinum toxin type A fentanyl,lacosamide, levodopa with carbidopa intestinal gel, pramipexole, topiramate, pregabalin, atomoxetine, desvenlafaxine, olanzapine powder for
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injectiona, paliperidone, risperidoneinjectiona 1 (1.4)
omalizumab
Sensory organs
2 (2.8)
aflibercept, ranibizumab
Various
3 (4.2)
deferasirox, lanthanum carbonate, sevelamer
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the oral form is not subject to a special pricing arrangement.
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Respiratory system
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Table 2
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Health outcome-based schemes involving conditional treatment continuation (Schedule of Pharmaceutical Benefits edition February 2013) Continuing treatment metastatic or unresectable malignant gastrointestinal stromal tumour
Satisfactory response a decrease from baseline in the sum of the products of the perpendicular diameters of all measurable lesions of 50% or greater (Response definition based on the Southwest Oncology Group standard criteria, see Demetri et al. N Engl J Med 2002; 347: 472-80.) demonstrating a response following the initial 18 months of treatment and at 12 monthly intervals thereafter. A major cytogenetic response is defined as less than 35% Philadelphia positive bone marrow cells. A peripheral blood BCR-ABL level of less than 1% on the international scale (Blood 108: 28-37, 2006) also indicates a response, at least the biological equivalent of a major cytogenetic response. Definitions of loss of response: loss of a previously documented major cytogenetic response (demonstrated by the presence of greater than 35% Ph positive cells on bone marrow biopsy), during ongoing tyrosine kinase inhibitor (TKI) therapy. Loss of a previously demonstrated molecular response (demonstrated by peripheral blood BCR-ABL levels increasing consecutively in value by at least 5 fold to a level of greater than 0.1% confirmed on a subsequent test), during ongoing tyrosine kinase inhibitor therapy. complete haematological response, with a normal eosinophil count
imatinib, dasatinib, nilotinib
chronic phase of chronic myeloid leukaemia expressing the Philadelphia chromosome or the transcript, BCR-ABL tyrosine kinase
imatinib
hypereosinophilic syndrome or chronic eosinophilicleukaemiarequiring treatment and confirmed to carry the Fip1-like1-plateletderived growth factor receptor alpha (FIP1L1-PDGFRA) fusion gene complete haematological response platelet-derived growth factor receptor beta (PDGFRB) fusion gene-positive myelodysplastic or myeloproliferative disorder FIP1L1-PDGFRA fusion gene- complete haematological response positive aggressive systemic mastocytosis
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Drug imatinib, sunitinib
imatinib
imatinib
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immunosuppressants (abatacept, rituximab, tocilizumab)
adalimumab, etanercept, infliximab, ustekinumab adalimumab, infliximab
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i rheumatoid arthritisand other types of arthritis
TNF-alpha antagonists (adalimumab, certolizumab, etanercept, infliximab, golimumab)
Satisfactory response Response Evaluation Criteria In Solid Tumours (RECIST) is defined as follows: Complete response (CR) is disappearance of all target lesions. Partial response (PR) is a 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) is a 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) is small changes that do not meet above criteria. An adequate response to treatment is defined as: an erythrocyte sedimentation rate(ESR) no greater than 25 mm per hour or a C-reactive protein (CRP) level no greater than 15 mg per L or either marker reduced by at least 20% from baseline; AND either of the following: (i) a reduction in the total active (swollen and tender) joint count by at least 50% from baseline, where baseline is at least 20 active joints; or (ii) a reduction in the number of the following major active joints, from at least 4, by at least 50%: — elbow, wrist, knee and/or ankle (assessed as swollen and tender); and/or — shoulder and/or hip (assessed as pain in passive movement and restriction of passive movement, where pain and limitation of movement are due to active disease and not irreversible damage such as joint destruction or bony overgrowth). The joint count and ESR and/or CRP must be determined at the completion of the 6 month intensivedisease-modifying antirheumatic drug(DMARD) trial, but prior to ceasing DMARD therapy. All measures must be no more than one month old at the time of initial application. If the above requirement to demonstrate an elevated ESR or CRP cannot be met, the application must state the reason this criterion cannot be satisfied. Where the baseline active joint count is based on total active joints (i.e. more than 20 active joints), response will be determined according to the reduction in the total number of active joints. Where the baseline is determined on total number of major joints, the response must be demonstrated on the total number of major joints. If only an ESR or CRP level is provided with the initial application, the same marker will be used to determine response. Psoriasis Area and Severity Index (PASI) calculation sheets and face, hand, foot area diagrams including the dates of assessment of the patient's condition
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Continuing treatment stage IV clear cell variant renal cell carcinoma
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Drug sunitinib, pazopanib
severe chronic plaque psoriasis
Crohn disease
Crohn Disease Activity Index (CDAI) calculation 17 Page 17 of 23
i ambrisentan, bosentan, epoprostenol, iloprost, sildenafil, tadalafil
pulmonary hypertension
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thrombocytopenic purpura
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eltrombopag, romiplostim
Satisfactory response An adequate response is defined as: (a) a decrease from baseline in the number of open draining fistulae of greater than or equal to 50%; and/or (b) a marked reduction in drainage of all fistula(e) from baseline, together with less pain and induration as reported by the patient. (a) use of rescue medication (corticosteroids or immunoglobulins) on no more than one occasion during the most recent 24 week period of PBSsubsidised treatment with eltrombopag, AND either of the following: (b) a platelet count greater than or equal to 50,000 million per L OR (c) a platelet count greater than 30,000 million per L and which is double the baseline platelet count. (i) Right heart catheterisation (RHC) composite assessment; and (ii) Echocardiograph (ECHO) composite assessment; and (iii) 6 minute walk test (6MWT). The results of the same tests as conducted at baseline should be provided with each written continuing treatment application (i.e. every 6 months), except for patients who were able to undergo all 3 tests at baseline, and whose subsequent ECHO and 6MWT results demonstrate disease stability or improvement, in which case RHC can be omitted. In all other patients, where the same test(s) conducted at baseline cannot be performed for assessment of response on clinical grounds, a patient specific reason why the test(s) could not be conducted must be provided with the application.
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Continuing treatment complex refractory fistulisingCrohn disease
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Drug adalimumab
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i omalizumab
severe allergic asthma
anticholinesterases (donepezil, galantamine, rivastigmine)
Alzheimer’s disease
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Continuing treatment chronic hepatitis C
Satisfactory response Patients with genotype 1, 4, 5 or 6 who are eligible for 48 weeks of treatment may only continue treatment after the first 12 weeks if the result of an HCV RNA quantitative assay (performed at the same laboratory using the same test) shows that the plasma HCV RNA has become undetectableor the viral load has decreased by at least a 2 log drop. (An HCV RNA assay at week 12 is unnecessary for genotype 2 and 3 patients because of thehigh likelihood of early viral response by week 12). Patients with genotype 1, 4, 5 or 6 who are viral positive at week 12 but have attained at least a 2 log drop in viral load may only continue treatment after the first 24 weeks of treatment if plasma HCV RNA is not detectable by an HCV RNA qualitative assay at week 24. Similarly, genotype 2 or 3 patients with hepatic cirrhosis or bridging fibrosis may only continue treatment after the first 24 weeks if plasma HCV RNA is not detectable by an HCV RNA qualitative assay at week 24. An HCV RNA qualitative assay at week 24 is unnecessary for those patients with genotype 1, 4, 5 or 6 who became viral negative at week 12 (a) a reduction in the Asthma Control Questionnaire (ACQ-5) score of at least 0.5 from baseline, or (b) maintenance oral corticosteroid dose reduced by at least 25% from baseline, and no deterioration in ACQ-5 score from baseline. demonstrated improvement in cognitive function as measured by: (a) for patients with a baseline Mini-Mental State Examination (MMSE) or Standardised Mini-Mental State Examination (SMMSE) score of 10 or more and less than 25, an increase of at least 2 points from baseline on the MMSE or SMMSE; (b) for patients with a baseline MMSE or SMMSEscore of at least 25 points, a decrease of at least 4 points from baseline on the Alzheimer's Disease Assessment Scale, cognitive sub-scale (ADAS-Cog) or an increase of at least 2 points from baseline on MMSE orSMMSE. demonstrated improvement in cognitive function as measured by an increase of at least 2 points from baseline on the MMSE or SMMSE.
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[1] Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood 2013; 121:4439‐42. [2] O'Sullivan BP, Orenstein DM, Milla CE. Pricing for orphan drugs will the market bear what society cannot? Jama 2013; 310:1343‐4. [3] Pharmaceutical Benefit Advisory Committee. Public Summary Document. Ivacaftor, tablet, 150 mg, Kalydeco® ‐ July 2013. http://www.pbs.gov.au/info/industry/listing/elements/pbac‐ meetings/psd/2013‐07/ivacaftor. [last accessed 28 April 2014]. [4] Pharmaceutical Benefit Advisory Committee. Public Summary Document. Ivacaftor, tablet, 150 mg, Kalydeco® ‐ November 2013. http://www.pbs.gov.au/info/industry/listing/elements/pbac‐ meetings/psd/2013‐11/ivacaftor. [last accessed 28 April 2014]. [5] Australian Government, Department of Health and Ageing. Annual report 2012‐2013. http://www.health.gov.au/internet/main/publishing.nsf/Content/annual‐report2012‐13. [last accessed 18 December 2013]. [6] Australian National Audit Office, Commonwealth of Australia. Selected measures for managing subsidised drug use in the Pharmaceutical Benefits Scheme. Audit Report no. 44 2005‐06 Performance Audit. http://www.anao.gov.au/uploads/documents/2005‐06_Audit_Report_44.pdf. [last accessed 17 April 2012]. [7] Klemp M, Frønsdal KB, Facey K. What principles should govern the use of managed entry agreements? Int J Technol Assess Health Care 2011; 27:77‐83. [8] PBS Information Management Section, Pharmaceutical Policy Branch, Department of Health and Ageing. Expenditure and prescriptions twelve months to June 2012. http://www.pbs.gov.au/statistics/2011‐2012‐files/expenditure‐and‐prescriptions‐2011‐2012.pdf. [last accessed 3 January 2014]. [9] The Hon Peter Dutton MP, Minister for Health, Minister for Sport. Media release. Australians to access more affordable medicines sooner. http://www.health.gov.au/internet/ministers/publishing.nsf/Content/4084C89B3E2171EBCA257C14000 1CA8C/$File/PD007.pdf. [last accessed 18 December 2013]. [10] Australian Government, Department of Health. Memorandum of understanding between the Commonwealth of Australia and Medicines Australia. http://www.health.gov.au/internet/main/publishing.nsf/Content/further‐PBS‐reforms‐Agreement. [last accessed 14 June 2013]. [11] Australian Government, Department of Health. Framework for the introduction of a Managed Entry Scheme for submissions to the Pharmaceutical Benefits Advisory Committee. http://www.pbs.gov.au/info/publication/factsheets/shared/framework‐for‐introduction‐of‐managed‐ entry‐scheme‐for‐PBAC‐submissions. [last accessed 14 June 2013]. [12] Carlson JJ, Sullivan SD, Garrison LP, Neumann PJ, Veenstra DL. Linking payment to health outcomes: a taxonomy and examination of performance‐based reimbursement schemes between healthcare payers and manufacturers. Health Policy 2010; 96:179‐90. [13] Adamski J, Godman B, Ofierska‐Sujkowska G, Osinska B, Herholz H, Wendykowska K, Laius O, Jan S, Sermet C, Zara C, Kalaba M, Gustafsson R, Garuoliene K, Haycox A, Garattini S, Gustafsson LL. Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers. BMC Health Serv Res 2010; 10:153. [14] Ferrario A, Kanavos P. Managed entry agrements for pharmaceuticals: the European experience. http://ec.europa.eu/enterprise/sectors/healthcare/files/docs/mea_report_en.pdf. [last accessed 27 November 2013]. [15] Health Technology Assessment International (HTAi) interest subgroup ‐ Conditional coverage/access with evidence development. http://www.htai.org/. [last accessed 14 June 2013]. 20 Page 20 of 23
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[16] Australian Government, Department of Health. Schedule of Pharmaceutical Benefits February 2013. http://www.pbs.gov.au/browse/publications. [last accessed 14 June 2013]. [17] Australian Government, Department of Health, Pharmaceutical Benefits Pricing Authority (PBPA). Therapeutic relativity sheets ‐ 1 October 2012. http://www.pbs.gov.au/info/industry/pricing/pbs‐items/therapeutic‐relativity‐sheets. [last accessed 14 June 2013]. [18] WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD index 2014. http://www.whocc.no/atc_ddd_index/. [last accessed 28 April 2014]. [19] Pharmaceutical Benefit Advisory Committee. PBAC outcomes and public summary documents. http://www.health.gov.au/internet/main/publishing.nsf/Content/pbac‐outcomes‐and‐public‐summary‐ documents. [last accessed 14 June 2013]. [20] Australian Government, Department of Health, Pharmaceutical Benefits Pricing Authority (PBPA). PBPA Policies, Procedures and Methods. Pricing of new products proposed for listing on the Pharmaceutical Benefits Scheme (PBS). http://www.health.gov.au/internet/publications/publishing.nsf/Content/pbs‐pbpa‐policies‐ contents~pbs‐pbpa‐policies‐ch3. [last accessed 14 June 2013]. [21] Australian Government, Department of Health. Guidelines for deeds of agreement for the Pharmaceutical Benefits Scheme. Version 1.3. http://www.pbs.gov.au/industry/listing/elements/deeds‐ agreement/Guidelines_for_Deeds_of_Agreement.pdf. [last accessed 14 June 2013]. [22] Wlodarczyk J, Reid CM, Pater G. Funding Linked to Ongoing Research: Impact of the Bosentan Patient Registry on Pricing in Australia. Value Health 2011; 14:961‐3. [23] Keogh A, Strange G, McNeil K, Williams TJ, Gabbay E, Proudman S, Weintraub RG, Wlodarczyk J, Dalton B. The bosentan patient registry: long‐term survival in pulmonary arterial hypertension. Intern Med J 2011; 41:227‐34. [24] Pharmaceutical Benefits Advisory Committee. Public summary document. PAZOPANIB, tablets, 200 mg and 400 mg (as hydrochloride), Votrient®, July 2010. http://www.health.gov.au/internet/main/publishing.nsf/Content/pbac‐psd‐Pazopanib‐july10. [last accessed 18 December 2013]. [25] Pharmaceutical Benefits Advisory Committee. November 2012 PBAC Outcomes ‐ Positive Recommendations. http://www.health.gov.au/internet/main/publishing.nsf/content/health‐pbs‐ general‐listing‐committee3.htm. [last accessed 14 June 2013]. [26] Pharmaceutical Benefits Advisory Committee. Avril 2013 PBAC Outcomes ‐ Positive Recommendations. http://www.pbs.gov.au/info/industry/listing/elements/pbac‐meetings/pbac‐ outcomes/2013‐04/positive‐recommendations. [last accessed 24 July 2013]. [27] Australian Government, Department of Health and Ageing. Annual report 2011‐2012. Appendix 2: Pharmaceutical Benefits Pricing Authority Annual Report for the year ended 30 June 2012. http://www.health.gov.au/internet/annrpt/publishing.nsf/Content/annual‐report‐1112‐toc~11‐ 12append~11‐12app2. [last accessed 14 June 2013]. [28] Robertson J, Walkom EJ, Henry DA. Transparency in pricing arrangements for medicines listed on the Australian Pharmaceutical Benefits Scheme. Aust Health Rev 2009; 33:192‐9. [29] Pharmaceutical Benefit Advisory Committee. PBAC Review of bDMARDs for the treatment of severe active rheumatoid athritis. http://www.health.gov.au/internet/main/publishing.nsf/Content/pbac‐psd‐bdmards‐dec09. [last accessed 14 June 2013]. [30] Pharmaceutical Benefit Advisory Committee. PBAC Recommendations from the Review of Pharmaceutical Benefits Scheme Anti‐dementia Drugs to Treat Alzheimer Disease. http://www.pbs.gov.au/info/reviews/pbac‐minutes‐alzheimers. [last accessed 14 June 2013].
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[31] Tunis SR, Pearson SD. Coverage options for promising technologies: Medicare's 'coverage with evidence development'. Health Aff 2006; 25:1218‐30. [32] Menon D, McCabe CJ, Stafinski T, Edlin R. Principles of design of access with evidence development approaches: a consensus statement from the Banff Summit. Pharmacoeconomics 2010; 28:109‐11. [33] Trueman P, Grainger DL, Downs KE. Coverage with Evidence Development: applications and issues. Int J Technol Assess Health Care 2010; 26:79‐85. [34] Cheema PK, Gavura S, Migus M, Godman B, Yeung L, Trudeau ME. International variability in the reimbursement of cancer drugs by publically funded drug programs. Current oncology 2012; 19:e165‐76. [35] Morgan S, Daw J, Thomson P. International best practices for negotiating 'reimbursement contracts' with price rebates from pharmaceutical companies. Health Aff (Millwood) 2013; 32:771‐7. [36] Robertson J, Walkom EJ, Bevan MD, Newby DA. Medicines and the media: news reports of medicines recommended for government reimbursement in Australia. BMC Public Health 2013; 13:489. [37] Lopert R, Elshaug AG. Australia's 'Fourth Hurdle' Drug Review Comparing Costs And Benefits Holds Lessons For The United States. Health affairs (Project Hope) 2013; 32:778‐87.
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Highlights
• In Australia, managed entry agreements enable coverage of new medicines.
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In February 2013, there were at least 71 special pricing arrangements in place.
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28 medicines were subject to continuation rules.
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One health outcome based agreement has been implemented so far.
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A new ‘Managed Entry Scheme’ has not been trialedyet.
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S0168-8510(14)00134-1 http://dx.doi.org/doi:10.1016/j.healthpol.2014.05.005 HEAP 3229
To appear in:
Health Policy
Received date: Revised date: Accepted date:
30-7-2013 29-4-2014 20-5-2014
Please cite this article as: Vitry A, Roughead E, agreements for pharmaceuticals in Australia, Health http://dx.doi.org/10.1016/j.healthpol.2014.05.005
Managed entry Policy (2014),
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Managed entry agreements for pharmaceuticals in Australia Agnes Vitrya, Elizabeth Rougheada a
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Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide SA 5001, Australia
Corresponding author:
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Dr Agnes Vitry
GPO Box 2471, Adelaide SA 5001, Australia
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Phone: +61 8 8302 2392 Fax: + 61 8 8302 1087
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E-mail: [email protected]
Keywords
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Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia
pharmaceutical policy; managed entry agreement; medicine subsidization; coverage with
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evidence development.
Funding
Professor Elizabeth Roughead is funded by a Future Fellowship from the Australian Research Council. The views expressed are those of the authors, the sponsor had no role in the preparation of the manuscript.
Competing interests Both authors have completed the ICMJE uniform Disclosure form. Professor Elizabeth Roughead is a member of the Drug Utilisation Sub-Committee (DUSC) of the Pharmaceutical Benefits Advisory Committee (PBAC).
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Abstract
In Australia, a number of managed entry agreementshave been developed to enable national
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coverage of new medicines. Non-outcome based agreementsare usually pricing arrangements that involve price or volume rebate agreements. In February 2013, there were at least 71 special
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pricing arrangements in place,including 26 for medicines restricted to use in hospitals. Health outcome based agreementscan be made at the individual or population level. At the individual
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level, there were 28 medicines funded subject to continuation rules involving documentation of adequate benefit within the individual; some of these medicines also had price agreeements in
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place. At the population level, only one outcome based agreementhas been implementedso far, for bosentan, a medicinemarketed for pulmonary hypertension. In May 2010, a memorandum of understanding signed between the Australian Government and Medicines Australia, the peak
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pharmaceutical industry organisation, includedthe possibility for industry to request consideration of a ‘Managed Entry Scheme’ as part of the funding submission process for
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medicines with high clinical needs. It includes the possibility of a randomised controlled trial (RCT) -based entry scheme.Although this form of managed entry has yet not been trialedin
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Australia, several 2012/2013funding recommendations included requests by the decision making
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committee for further evidence development.
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1. Introduction
The growing ageing population, the raising prevalence of chronic diseases and the high cost of new medicines are all factors contributing to rising pharmaceutical expenditures. The high prices
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requested by pharmaceutical companies for new medicines create further challenges. In
2012,eleven of the twelve cancer medicines approved by the US Food and Drug Administration
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were priced above US$ 100,000 per year[1].The price of ivacaftor, a new medicine marketed in 2012 for a genetic disease, cystic fibrosis, reached US$373,000 per patient in the United
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States[2] and was recommended in Australia with an estimated cost of AU$60 million to $100 million in the fifth year of listing[3, 4]. In 2013, the listing of pregabalin for chronic nerve pain
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will cost the Australian government more than AU$ 450 million over five years and those of three new cancer medicines, ipilimumab for advanced melanoma, abiraterone for advanced prostate cancer and oral vinorelbine for advanced breast cancer,will cost more than AU$430
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million over four years[5].
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Funding decisions by public or private insurance bodies are oftendifficult because of numerousuncertainties around the efficacy, effectiveness, safety or cost-effectiveness of new
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medicines[6]. This uncertainty can create cases where medicines receive a positive coverage
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decision,however, subsequent evidence indicates the medicine is found not to be as effective or as safe as expected and thusresources are wasted (i.e. opportunity costs)or patients harmed.Equally challenging is the negative coverage decision for a breakthrough medicine,which may prevent some patients from accessing the medicine. Moreover, public and private insurersoften operate in a context of intense pressure from stakeholders, pharmaceutical industry and consumer organisations to provide funding for new medicines.
Inthis context, several countries have implemented novel subsidization schemes for new medicines,with the aim of allowing some form of access which is closely managedthough agreements set up with pharmaceutical companies. These managed entry agreements have been defined as “an arrangement between a manufacturer and payer/provider that enables coverage or reimbursement of a health technology subject to specific conditions. These arrangements can use a variety of mechanisms to address uncertainty about the performance of technologies or to 3 Page 3 of 23
manage the adoption of technologies in order to maximise their effective use or limit their budget impact” [7].
1.1 Australia’s public funding system for pharmaceuticals
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In Australia, a nationalpublicpharmaceutical insurance system, the Pharmaceutical Benefits
Scheme (PBS), was established in 1953. By 2011, the PBS subsidised around 4,000 products. In
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2011-12, PBS government expenditure represented AUD $9,193.7 million and 83.4% of the total cost of PBS prescriptions, the remainder being patient contributions[8]. The decision to list new
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medicines on the PBS is taken by the Federal Minister for Health on recommendation from the Pharmaceutical Benefits Advisory Committee (PBAC), an independent expert body that
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determines the effectiveness and cost-effectiveness of new medicines. Australia was the first country to introduce an explicit requirement for economic evaluation in its subsidisation assessment process in 1993. Although there is no capped budget for the PBS, any medicine the
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PBAC recommends for listing that is expected to cost more than $20 million per year in any of the first four years must be approved by Cabinet[9].Medicines listed in the Schedule can fall into
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three broad categories: ‘unrestricted benefits’formedicines with no restrictions on therapeutic use, ‘restricted benefits’ for medicines that can only be prescribed for specific therapeutic uses,
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and ‘authority required benefits’ for medicines that require prior approval from the Department
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of Health. Prescribing restrictions may limit use to indications for which the medicine has been deemed effective or cost-effective and may include rules for initiation or continuation of treatment.
In Australia, managed entry agreements have beenoperating for a number of years. In May 2010, the Australian Government and Medicines Australia, the peak pharmaceutical industry organisation, signed a Memorandum of Understanding which introduced a new type of managed entry agreement[10]. This memorandum focused on the expansion of the price reform policies that had started in Australia in 2007 and included provisions on a ‘Managed Entry Scheme’for pharmaceuticals. Clauses 26 and 27 of the memorandum state that the PBAC ‘may recommend PBS coverage at a price justified by the existing evidence, pending submission of more conclusive evidence of cost-effectiveness to support listing of the drug at a higher price” [10].To support the process, the Australian Department of Health published a framework for the 4 Page 4 of 23
introduction of this form of managed entry agreement [11].The framework states that a submission would be considered for a Managed Entry Scheme when there is ‘a high clinical need for the proposed drug in the indication requested by the sponsor’, and that ‘new clinical data would resolve the issues of uncertainty in relation to the extent or value of the clinical effect
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which would have otherwise prevented an initial positive recommendation’. This includes the possibility of a randomised controlled trial (RCT)-based managed entry scheme with a trial
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protocol available at the time of the original submission. The framework also notes other nonRCT level evidence “may be appropriate, such as data collection for the purpose of confirming
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cost-offsets in economic analyses”.
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In this paper, we examineAustralia’s past and more recent experience with managed entry
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agreements for pharmaceuticals.
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2. Methods Many terms have been used to describe the various types of managed entry agreements but a common feature of the taxonomies that have been proposed is the distinction between outcome based and non-outcome based agreements [12-14]. In this paper we have used a taxonomy
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adapted from those developed by Carlson (2010) and Ferrario (2013) that provides a simple
classification suitable for the Australian setting. It distinguishes non-outcome based agreements
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and outcome-based agreements(Figure 1). Non-outcome based agreements are usually financial in nature and aim to contain the costs without taking into consideration health outcomes. They
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may include price-volume agreements, discounts, price-capping schemes or dose-capping schemes. Outcome-based agreements have been defined as “schemes between healthcare payers
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and medical product manufacturers in which the price, level, or nature of reimbursement are tied to future measures of clinical or intermediate endpoints ultimately related to patient quality or quantity of life” [12]. The outcome-based agreements may be considered at the patient level
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and may include outcome-guarantee schemes (e.g. rebates or reimbursement if the medicine fails to achieve the expected results), or conditional continuation schemes. At the population level,
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coverage with evidence development (CED) schemes have been defined as ‘any policy mechanism that links financial support for medical technologies or treatments to a requirement
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for systematic data collection and analysis with the intent of using that data to modify health
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policy or clinical decision-making’ [15].
We collected data on non-outcome and outcome agreementsoperating in Australiafrom documents publicly available on the Australian government’s website including the Schedule of Pharmaceutical Benefits (edition February 2013), which provides details of medicines subsidised by the Australian Government[16]orthe Therapeutic Relativity Sheets (edition October 2012) released by the Pharmaceutical Benefits Pricing Authority (PBPA), which provides information on therapeutic relativities and pricing comparisons between medicines within a therapeutic group[17]. Funded products that are not medicines (e.g. nutrients) and medicines not listed on the PBS but available through the Life-Saving Drugs Program, which provides subsidised access to some medicines for rare life-threatening conditions, were not considered in this analysis.We compiled a list of all medicines for which there was mention of ‘special pricing arrangements’ either in the Schedule of Pharmaceutical Benefits or the Therapeutic relativity Sheets. 6 Page 6 of 23
Information on conditional treatment continuation was extracted for all medicines included in the Schedule of Pharmaceutical Benefits. Medicines were classified into therapeutic groups using the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification
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system[18].
To identify medicines that may have been proposed for a Managed Entry Scheme, we reviewed
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the outcomes and public summary documents prepared by the PBAC from July 2010 (after the signature of the Memorandum of Understanding) to April 2013 [19]. We also examined the
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literature on managed entry agreements through a comprehensive search of peer-reviewed
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articles on the Web of Science database and grey literature on relevant websites. 3. Results
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3.1 Non-outcome based agreements
in Australia non-outcome based agreements may take the form of price volume arrangements
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that involve price reductions for sales exceeding a pre-agreed volume,or rebate arrangementsthat involve repayment of costs beyond an agreed annual subsidisation cap [20]. These agreements
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are used to manage financial risks due to uncertainties in either estimating the overall usage or
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cost to the PBS, or to reduce risks of paying for medicine use outside of the restricted (or costeffective) listing.The first formal agreement,a legal document called a ‘deed of agreement’,took place in 2003 [6]. Before this date, pricing arrangements were agreed through an exchange of letters between the pharmaceutical company and the PBPA.
Our researchidentified71 medicines with “special pricing arrangements” in February 2013 (Table 1), of which 32 (45%) were mentioned in the Therapeutic Relativity Sheets, 12 (17%) in the Schedule of Pharmaceutical Benefits and 27 (38%) in both sources. Antineoplastic and immunomodulating agents were most frequently represented in these pricing arrangements(33.8%), followed by nervous system (15.5%), alimentary tract and metabolism (9.8%) and cardiovascular system (7%) medicines. Twenty six (37%) pricing arrangements applied to medicines restricted to supply through public and private hospitals (known as Section100).Threeproducts (abacavir, bosentan and efavirenz)have been listed with special 7 Page 7 of 23
bonus arrangements being agreed to with the sponsor rather than a rebate agreement[20].Under these arrangements, the manufacturer has listed the product at its nominated price and been required to provide free goods to the hospital as compensation so that the resultant cost per unit
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is equivalent to the agreed price. The deed of agreements may include the collection and provision of data in relation to a specific
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listing[21]. There are no public data on how many agreements include the requirement for
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collection of additional data.
3.2 Outcome based agreements
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In the February 2013 issue of the Pharmaceutical Benefits Schedule, there were 28 medicines funded subject tocontinuation rules (Table 2). They includedthe tumour necrosis factor (TNFalpha) inhibitors for rheumatoid arthritis, Crohn disease and severe psoriasis, some tyrosine
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kinase inhibitors for several types of cancer, as well as medicines for pulmonary hypertension and for Alzheimer’s disease. Twenty of these medicines (71%) were also included in the special
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pricing arrangements mentioned above. Continuation of treatment is subject to documentation of adequate benefit by some appropriate clinical or biological test. The first continuation rules were
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put in place when anticholinesterase medicines were listedfor the treatment of Alzheimer’s
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disease in 2000. With the exception of medicines for Alzheimer’s disease,patients who start taking medicinessubject to continuation rules are required to sign a patient acknowledgment formindicating that they understand and accept that PBS-subsidised treatment will cease if the criteria defining a satisfactory response to the medicineare not achieved at the pre-specified follow-up clinical assessment[16].
3.3 Coverage with evidence development We were able to identify only one CED schemethat has been implemented in Australia. In 2004, bosentan, a medicineapproved for pulmonary hypertension, was listedon the PBS on the condition that a registry was established to monitor mortality. The agreement was that the price for bosentan would be reduced if the mortality rate observed in the registry cohort was higher than that claimed in the original funding submission [22].The results of the Bosentan Patient Registry were difficult to interpret as the observed annual mortality rate (11.8%) was higher than 8 Page 8 of 23
the estimated rate (5.2%) from the bosentan pivotal randomised controlled trial and also because the 528 patients enrolled (approximately 69% of patients that were prescribed bosentan between 2004 and 2007) were older and hadmore advanced functional deficit than in the clinical trials[23]. In 2008,a new medicine for pulmonary hypertension,sitaxentan,was listed on the PBS
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at a 15% discount to bosentan, which was forced to decrease its price on a cost-minimization basis.Hence, no additional price reduction was required based on analysis of the registry
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data[22].
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In July 2010, the PBAC considered proposals for a Managed Entry Scheme for two medicines, pazopanib and imatinib. In both cases, the PBAC considered that this wasinappropriate in the
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context of the high price requested or high incremental cost-effectiveness ratio. In the case of pazopanib, it also stated that it ‘would be inappropriate to expose patients to a potentially
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inferior drug until evidence has been produced to show the contrary’ [24].
In 2012, the PBAC made onerecommendationrelevant to coverage with evidence development. It
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recommended the listing of ipilimumab for the treatment of melanoma subject to a risk-sharing arrangementthat would involve the ‘implementation of a mechanism to verify the anticipated
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overall survival benefits of ipilimumab in real world clinical practice in Australia... The sponsor
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would be expected to rebate the cost of difference in performance between observed versus predicted benefits of ipilimumab’[25]. In June 2013, the listing was officially announced by the Minister for Health but no details have been released on any coverage with evidence agreement.
In April 2013, the PBAC examined two formal requests for consideration of a Managed Entry Scheme for the listing of everolimus, a treatment for people with subpendymal giant cell astrocytomas caused by tuberous sclerosis, and for the listing of rifaximin, for prevention of hepatic encephalopathy[26]. In both cases, the PBAC recommended listing of these medicines but considered that there was no longer a requirement for a Managed Entry Scheme approach on the basis of the information available.
4. Discussion
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Our research identified 71 medicines with agreements in placein February 2013, 28 medicines subject tocontinuation rules and none with an ongoing CED scheme. These results are consistent with PBPA Annual Report for the 2011/2012 financial year that indicates there were76 deeds of agreement in place or in development[27]. A previous study using similar information sources
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over the period 2004 to 2008 identified 73 medicines with pricing arrangements and showed that47 of the 148 (32%)medicines withmajor submissions (those which include a full economic
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evaluation) to the PBAC had special pricing arrangements in place [28].All special pricing
arrangements apply to patented medicines,andthey are usually discontinued once medicines
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come off-patent and generic products are listed on the PBS.
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Our findings are similar to trends observed in a recent survey of managed entry agreements implemented in European countries between October 2011 and January 2012[14]. Overall, in the 18 European countries surveyed,39% of all the managed entry agreements were price-volume
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agreements; other agreements includedrequirement for data collection (29%), access limited to eligible patients (13 %), conditional continuation of treatment (5.6%), reimbursement or discount
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provided for non-responder patients (5.4%), and a general discount on all doses or an initial discount or free first doses (4.6%). There were important variations in the distributionof schemes
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and Sweden.
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between countries,withthe schemes requiring data collectionmainly used in Italy, Netherlands
We found that the antineoplastic and immunomodulating agents (33.8%), the nervous system (15.5%) and alimentary tract and metabolism agents (9.8%) were the three main therapeutic groups included in Australian non-outcome agreements, a result similar to the European survey that showed that the antineoplastic and immunomodulating agents represented 37% of all the managed entry agreements, followed by alimentary tract and metabolism (15%) and nervous system (10%)[14].These trends may reflect a higherneed to negotiate financial agreements for high cost new medicines such as the targeted medicines usedin oncology or medicines that may be used in large populations, such as insulins analogue for people with diabetes.
Within the PBS listing, there is provision for the cost-effectiveness of medicines as used in realworld clinical practice to be reviewed. The findingsof these post-market reviews may result in 10 Page 10 of 23
changes to the prescribing rules if these are found not to be effective or may result in changes to medicine prices. For example, a review was undertakenfor the biological disease modifying antirheumatic drugs in 2009 and, as a result,eligibility criteria were revised and price reductions required [29]. Another example is the review of the medicines for Alzheimer’s disease in 2013
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that found that they were being used in a much broader population and for longer periods of time than originally agreed as cost-effective[30]. Consequently, the PBAC ended the continuation
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rules that required a demonstrated improvement in cognitive function as measured by a test, the
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mini–mental state examination, and recommended a 40% decrease in the medicine price.
We were able to identify only one past CED scheme and two potential new ones. Three years
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after the signature of the Memorandum of Understanding in 2010, it does not seem that the new Managed Entry Schemehas been trialed yet. The implementation of CED schemes will require all stakeholders, government, industry, clinicians, researchers and consumers to consider
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carefully challenging issues such asthe choice of an appropriate study design, the feasibility of
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the research within a limited time frame, the governance and the funding of the schemes [31-33].
All the deeds of agreement in Australia are ‘commercial in confidence’ documents and detailed
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information is not publicly available. Thus, we were unable to determine the proportion of
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agreements that realised price reductions or rebates, nor how much savings accrued. In the financial statement of the Australian Department of Health’s Annual Report for the 2012- 2013 financial year it was stated that the Department had recovered $300 million ‘under cost-sharing arrangements with pharmaceutical companies’ but no further detail was provided. The confidentiality of the agreements precludes any comparisons with actual prices of individual medicines in other countries and thus, the efficiency of these schemes cannot be assessed [14, 28].
The confidentiality agreements creates challenges for countries that rely on external reference pricingto determine their own prices as the real price to othercountries is unknown[34]. A recent survey of policy makers involved in negotiating reimbursement contracts for pharmaceuticals in nine high-income countries found that they felt isolated as pharmaceutical companies had a substantial advantage in knowing discounts offered to other insurers [35]. Some policy makers 11 Page 11 of 23
also highlighted that some degree of secrecy could be justified to obtain price reductions, but Canadian policy makers expressed concerns that secret rebates could increase inequities in medicine pricing and coverage between jurisdictions [34]. Further, limited information on the
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technicalities and outcomes of the agreements restrict cross-country learning [36].
This study has a number of limitations. We were only able to obtain data publicly accessible on
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the Australian Department of Health’s websites and because of the limited information available, we cannot be sure to have identified all of the agreements in place. It was also not possible to
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examine the details of the agreements and the outcomes in terms of savings or impact on cost-
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effective use.
5. Conclusion
Australia’s pharmaceutical subsidisation system is highly regarded internationally for having
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developed and implemented rigorous methodologies for the appraisal of the effectiveness and cost-effectiveness of medicines[37]. Most managed entry agreements that have been
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implemented in Australia arenon-outcome based agreements.The confidential nature of these agreements limits the evaluation of their benefits with regards to coverage and pricing of new
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medicines compared with other countries.
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Figure 1.
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Taxonomy of managed entry agreementsadapted from those developed by Carlson (2010) and Ferrario (2013)
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Table 1 Medicines with special pricing arrangementsmentioned either in the Schedule of Pharmaceutical Benefits or the Therapeutic Relativity Sheets Names of medicines
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Number of medicines (%) 7 (9.8)
methylnaltrexone, exenatide, insulin detemir, insulin glargine, pioglitazone, rosiglitazone, sitagliptin
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Anatomical Therapeutic Chemical (ATC) classification system Alimentary tract and metabolism
3 (4.2)
rivaroxaban, eltrombopag, romiplostim
5 (7.0)
ambrisentan,bosentan, clopidogrel, iloprost, prasugrel
Dermatologicals
1 (1.4)
Genito urinary system and sex hormones
4 (5.6)
dutasteride, oxybutynin, choriogonadotropin, progesterone
Systemic hormonal preparations Anti-infectives
3 (4.2)
cinacalcet, teriparatide, somatropin
4 (5.6)
darunavir co-administered with ritonavir, efavirenz, tipranavir, tobramycin solution for inhalation
Musculo-skeletal system
Nervous system
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Antineoplastic and immunomodulating agents
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Blood and blood forming organs Cardiovascular system
24 (33.8)
3 (4.2)
11 (15.5)
imiquimod
peginterferon alfa-2a, azacitidine, bortezomib, certolizumab, dasatinib, docetaxel, erlotinib, imatinib, lenalidomide, pazopanib, sorafenib, sunitinib, fludarabine, trastuzumab, adalimumab, ustekinumab, abatacept, etanercept, golimumab, infliximab, rituximab, tocilizumab, fingolimod, natalizumab zoledronic acid, risedronate, botulinum toxin type A fentanyl,lacosamide, levodopa with carbidopa intestinal gel, pramipexole, topiramate, pregabalin, atomoxetine, desvenlafaxine, olanzapine powder for
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injectiona, paliperidone, risperidoneinjectiona 1 (1.4)
omalizumab
Sensory organs
2 (2.8)
aflibercept, ranibizumab
Various
3 (4.2)
deferasirox, lanthanum carbonate, sevelamer
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the oral form is not subject to a special pricing arrangement.
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Respiratory system
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Table 2
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Health outcome-based schemes involving conditional treatment continuation (Schedule of Pharmaceutical Benefits edition February 2013) Continuing treatment metastatic or unresectable malignant gastrointestinal stromal tumour
Satisfactory response a decrease from baseline in the sum of the products of the perpendicular diameters of all measurable lesions of 50% or greater (Response definition based on the Southwest Oncology Group standard criteria, see Demetri et al. N Engl J Med 2002; 347: 472-80.) demonstrating a response following the initial 18 months of treatment and at 12 monthly intervals thereafter. A major cytogenetic response is defined as less than 35% Philadelphia positive bone marrow cells. A peripheral blood BCR-ABL level of less than 1% on the international scale (Blood 108: 28-37, 2006) also indicates a response, at least the biological equivalent of a major cytogenetic response. Definitions of loss of response: loss of a previously documented major cytogenetic response (demonstrated by the presence of greater than 35% Ph positive cells on bone marrow biopsy), during ongoing tyrosine kinase inhibitor (TKI) therapy. Loss of a previously demonstrated molecular response (demonstrated by peripheral blood BCR-ABL levels increasing consecutively in value by at least 5 fold to a level of greater than 0.1% confirmed on a subsequent test), during ongoing tyrosine kinase inhibitor therapy. complete haematological response, with a normal eosinophil count
imatinib, dasatinib, nilotinib
chronic phase of chronic myeloid leukaemia expressing the Philadelphia chromosome or the transcript, BCR-ABL tyrosine kinase
imatinib
hypereosinophilic syndrome or chronic eosinophilicleukaemiarequiring treatment and confirmed to carry the Fip1-like1-plateletderived growth factor receptor alpha (FIP1L1-PDGFRA) fusion gene complete haematological response platelet-derived growth factor receptor beta (PDGFRB) fusion gene-positive myelodysplastic or myeloproliferative disorder FIP1L1-PDGFRA fusion gene- complete haematological response positive aggressive systemic mastocytosis
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Drug imatinib, sunitinib
imatinib
imatinib
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immunosuppressants (abatacept, rituximab, tocilizumab)
adalimumab, etanercept, infliximab, ustekinumab adalimumab, infliximab
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i rheumatoid arthritisand other types of arthritis
TNF-alpha antagonists (adalimumab, certolizumab, etanercept, infliximab, golimumab)
Satisfactory response Response Evaluation Criteria In Solid Tumours (RECIST) is defined as follows: Complete response (CR) is disappearance of all target lesions. Partial response (PR) is a 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) is a 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) is small changes that do not meet above criteria. An adequate response to treatment is defined as: an erythrocyte sedimentation rate(ESR) no greater than 25 mm per hour or a C-reactive protein (CRP) level no greater than 15 mg per L or either marker reduced by at least 20% from baseline; AND either of the following: (i) a reduction in the total active (swollen and tender) joint count by at least 50% from baseline, where baseline is at least 20 active joints; or (ii) a reduction in the number of the following major active joints, from at least 4, by at least 50%: — elbow, wrist, knee and/or ankle (assessed as swollen and tender); and/or — shoulder and/or hip (assessed as pain in passive movement and restriction of passive movement, where pain and limitation of movement are due to active disease and not irreversible damage such as joint destruction or bony overgrowth). The joint count and ESR and/or CRP must be determined at the completion of the 6 month intensivedisease-modifying antirheumatic drug(DMARD) trial, but prior to ceasing DMARD therapy. All measures must be no more than one month old at the time of initial application. If the above requirement to demonstrate an elevated ESR or CRP cannot be met, the application must state the reason this criterion cannot be satisfied. Where the baseline active joint count is based on total active joints (i.e. more than 20 active joints), response will be determined according to the reduction in the total number of active joints. Where the baseline is determined on total number of major joints, the response must be demonstrated on the total number of major joints. If only an ESR or CRP level is provided with the initial application, the same marker will be used to determine response. Psoriasis Area and Severity Index (PASI) calculation sheets and face, hand, foot area diagrams including the dates of assessment of the patient's condition
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Continuing treatment stage IV clear cell variant renal cell carcinoma
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Drug sunitinib, pazopanib
severe chronic plaque psoriasis
Crohn disease
Crohn Disease Activity Index (CDAI) calculation 17 Page 17 of 23
i ambrisentan, bosentan, epoprostenol, iloprost, sildenafil, tadalafil
pulmonary hypertension
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eltrombopag, romiplostim
Satisfactory response An adequate response is defined as: (a) a decrease from baseline in the number of open draining fistulae of greater than or equal to 50%; and/or (b) a marked reduction in drainage of all fistula(e) from baseline, together with less pain and induration as reported by the patient. (a) use of rescue medication (corticosteroids or immunoglobulins) on no more than one occasion during the most recent 24 week period of PBSsubsidised treatment with eltrombopag, AND either of the following: (b) a platelet count greater than or equal to 50,000 million per L OR (c) a platelet count greater than 30,000 million per L and which is double the baseline platelet count. (i) Right heart catheterisation (RHC) composite assessment; and (ii) Echocardiograph (ECHO) composite assessment; and (iii) 6 minute walk test (6MWT). The results of the same tests as conducted at baseline should be provided with each written continuing treatment application (i.e. every 6 months), except for patients who were able to undergo all 3 tests at baseline, and whose subsequent ECHO and 6MWT results demonstrate disease stability or improvement, in which case RHC can be omitted. In all other patients, where the same test(s) conducted at baseline cannot be performed for assessment of response on clinical grounds, a patient specific reason why the test(s) could not be conducted must be provided with the application.
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Continuing treatment complex refractory fistulisingCrohn disease
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Drug adalimumab
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severe allergic asthma
anticholinesterases (donepezil, galantamine, rivastigmine)
Alzheimer’s disease
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Continuing treatment chronic hepatitis C
Satisfactory response Patients with genotype 1, 4, 5 or 6 who are eligible for 48 weeks of treatment may only continue treatment after the first 12 weeks if the result of an HCV RNA quantitative assay (performed at the same laboratory using the same test) shows that the plasma HCV RNA has become undetectableor the viral load has decreased by at least a 2 log drop. (An HCV RNA assay at week 12 is unnecessary for genotype 2 and 3 patients because of thehigh likelihood of early viral response by week 12). Patients with genotype 1, 4, 5 or 6 who are viral positive at week 12 but have attained at least a 2 log drop in viral load may only continue treatment after the first 24 weeks of treatment if plasma HCV RNA is not detectable by an HCV RNA qualitative assay at week 24. Similarly, genotype 2 or 3 patients with hepatic cirrhosis or bridging fibrosis may only continue treatment after the first 24 weeks if plasma HCV RNA is not detectable by an HCV RNA qualitative assay at week 24. An HCV RNA qualitative assay at week 24 is unnecessary for those patients with genotype 1, 4, 5 or 6 who became viral negative at week 12 (a) a reduction in the Asthma Control Questionnaire (ACQ-5) score of at least 0.5 from baseline, or (b) maintenance oral corticosteroid dose reduced by at least 25% from baseline, and no deterioration in ACQ-5 score from baseline. demonstrated improvement in cognitive function as measured by: (a) for patients with a baseline Mini-Mental State Examination (MMSE) or Standardised Mini-Mental State Examination (SMMSE) score of 10 or more and less than 25, an increase of at least 2 points from baseline on the MMSE or SMMSE; (b) for patients with a baseline MMSE or SMMSEscore of at least 25 points, a decrease of at least 4 points from baseline on the Alzheimer's Disease Assessment Scale, cognitive sub-scale (ADAS-Cog) or an increase of at least 2 points from baseline on MMSE orSMMSE. demonstrated improvement in cognitive function as measured by an increase of at least 2 points from baseline on the MMSE or SMMSE.
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Drug peginterferon alfa-2a and ribavirin
Alzheimer’s disease
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[1] Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood 2013; 121:4439‐42. [2] O'Sullivan BP, Orenstein DM, Milla CE. Pricing for orphan drugs will the market bear what society cannot? Jama 2013; 310:1343‐4. [3] Pharmaceutical Benefit Advisory Committee. Public Summary Document. Ivacaftor, tablet, 150 mg, Kalydeco® ‐ July 2013. http://www.pbs.gov.au/info/industry/listing/elements/pbac‐ meetings/psd/2013‐07/ivacaftor. [last accessed 28 April 2014]. [4] Pharmaceutical Benefit Advisory Committee. Public Summary Document. Ivacaftor, tablet, 150 mg, Kalydeco® ‐ November 2013. http://www.pbs.gov.au/info/industry/listing/elements/pbac‐ meetings/psd/2013‐11/ivacaftor. [last accessed 28 April 2014]. [5] Australian Government, Department of Health and Ageing. Annual report 2012‐2013. http://www.health.gov.au/internet/main/publishing.nsf/Content/annual‐report2012‐13. [last accessed 18 December 2013]. [6] Australian National Audit Office, Commonwealth of Australia. Selected measures for managing subsidised drug use in the Pharmaceutical Benefits Scheme. Audit Report no. 44 2005‐06 Performance Audit. http://www.anao.gov.au/uploads/documents/2005‐06_Audit_Report_44.pdf. [last accessed 17 April 2012]. [7] Klemp M, Frønsdal KB, Facey K. What principles should govern the use of managed entry agreements? Int J Technol Assess Health Care 2011; 27:77‐83. [8] PBS Information Management Section, Pharmaceutical Policy Branch, Department of Health and Ageing. Expenditure and prescriptions twelve months to June 2012. http://www.pbs.gov.au/statistics/2011‐2012‐files/expenditure‐and‐prescriptions‐2011‐2012.pdf. [last accessed 3 January 2014]. [9] The Hon Peter Dutton MP, Minister for Health, Minister for Sport. Media release. Australians to access more affordable medicines sooner. http://www.health.gov.au/internet/ministers/publishing.nsf/Content/4084C89B3E2171EBCA257C14000 1CA8C/$File/PD007.pdf. [last accessed 18 December 2013]. [10] Australian Government, Department of Health. Memorandum of understanding between the Commonwealth of Australia and Medicines Australia. http://www.health.gov.au/internet/main/publishing.nsf/Content/further‐PBS‐reforms‐Agreement. [last accessed 14 June 2013]. [11] Australian Government, Department of Health. Framework for the introduction of a Managed Entry Scheme for submissions to the Pharmaceutical Benefits Advisory Committee. http://www.pbs.gov.au/info/publication/factsheets/shared/framework‐for‐introduction‐of‐managed‐ entry‐scheme‐for‐PBAC‐submissions. [last accessed 14 June 2013]. [12] Carlson JJ, Sullivan SD, Garrison LP, Neumann PJ, Veenstra DL. Linking payment to health outcomes: a taxonomy and examination of performance‐based reimbursement schemes between healthcare payers and manufacturers. Health Policy 2010; 96:179‐90. [13] Adamski J, Godman B, Ofierska‐Sujkowska G, Osinska B, Herholz H, Wendykowska K, Laius O, Jan S, Sermet C, Zara C, Kalaba M, Gustafsson R, Garuoliene K, Haycox A, Garattini S, Gustafsson LL. Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers. BMC Health Serv Res 2010; 10:153. [14] Ferrario A, Kanavos P. Managed entry agrements for pharmaceuticals: the European experience. http://ec.europa.eu/enterprise/sectors/healthcare/files/docs/mea_report_en.pdf. [last accessed 27 November 2013]. [15] Health Technology Assessment International (HTAi) interest subgroup ‐ Conditional coverage/access with evidence development. http://www.htai.org/. [last accessed 14 June 2013]. 20 Page 20 of 23
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[31] Tunis SR, Pearson SD. Coverage options for promising technologies: Medicare's 'coverage with evidence development'. Health Aff 2006; 25:1218‐30. [32] Menon D, McCabe CJ, Stafinski T, Edlin R. Principles of design of access with evidence development approaches: a consensus statement from the Banff Summit. Pharmacoeconomics 2010; 28:109‐11. [33] Trueman P, Grainger DL, Downs KE. Coverage with Evidence Development: applications and issues. Int J Technol Assess Health Care 2010; 26:79‐85. [34] Cheema PK, Gavura S, Migus M, Godman B, Yeung L, Trudeau ME. International variability in the reimbursement of cancer drugs by publically funded drug programs. Current oncology 2012; 19:e165‐76. [35] Morgan S, Daw J, Thomson P. International best practices for negotiating 'reimbursement contracts' with price rebates from pharmaceutical companies. Health Aff (Millwood) 2013; 32:771‐7. [36] Robertson J, Walkom EJ, Bevan MD, Newby DA. Medicines and the media: news reports of medicines recommended for government reimbursement in Australia. BMC Public Health 2013; 13:489. [37] Lopert R, Elshaug AG. Australia's 'Fourth Hurdle' Drug Review Comparing Costs And Benefits Holds Lessons For The United States. Health affairs (Project Hope) 2013; 32:778‐87.
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Highlights
• In Australia, managed entry agreements enable coverage of new medicines.
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In February 2013, there were at least 71 special pricing arrangements in place.
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28 medicines were subject to continuation rules.
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One health outcome based agreement has been implemented so far.
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A new ‘Managed Entry Scheme’ has not been trialedyet.
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