Guidelines for Funding Applications to PHARMAC 2010 (text extract)

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Foreword

PHARMAC, the Pharmaceutical Management Agency, is primarily responsible for managing the funding of community pharmaceuticals for New Zealanders, on behalf of the District Health Boards. PHARMAC’s objective is to secure, for eligible people in need of pharmaceuticals, the best health outcomes that are reasonably achievable from pharmaceutical treatment and from within the amount of funding provided. Each year, PHARMAC receives a large number of applications (“Applications”) containing proposals to fund new pharmaceuticals or to widen access to pharmaceuticals that are already funded. As PHARMAC must work within a fixed budget, difficult choices need to be made about which of the proposals should be progressed to a funding decision at any given time. This involves assessing a large amount of often complex information, to identify those proposals that would provide the best health outcomes. In deciding which proposals to fund, PHARMAC assesses each proposal against its nine decision criteria, which include consideration of health need and assessment of cost-effectiveness. All proposals are prioritised against all other funding options according to these criteria. In this context of what we call ‘relative assessment’ (comparing one option against another), it is important that applicants provide good quality, complete and balanced Applications that follow these Guidelines. Good quality Applications will include the following elements: • • • • • critical appraisal of key clinical evidence; information relating to PHARMAC’s nine decision criteria; complete market and epidemiological information; information on cost-effectiveness (based on PHARMAC’s methodology for cost-utility analysis); and disclosure of information on all known ongoing trials and patents.

Good quality Applications will be clear, cite all sources, explain all assumptions, and include all information of material importance. A thorough, yet succinct Application is likely to expedite PHARMAC’s review, potentially enabling the proposal in the Application to be prioritised earlier. Please note that the information requested in these Guidelines is not mandatory. The information we have requested is information that PHARMAC requires when assessing a proposal. The purpose of these Guidelines is to provide you with some guidance on how to compile an application that is useful to us. We do not want to impose any unnecessary burden or create any barriers to submitting an Application. This is why we strongly recommend that you contact PHARMAC first before submitting an Application, as in certain circumstances, less information may be required. If the information requested in these Guidelines is not provided, it is likely that PHARMAC will either contact you for it at some stage or undertake its own searches or analysis (which may result in time delays). Therefore, even though the information

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requested is not mandatory, there are advantages in providing thorough Applications following these Guidelines. If the application is for the funding of a generic pharmaceutical, and the pharmaceutical (including the indication applied for) has previously been assessed by PHARMAC, less information may be required. Please refer to Section 8 of these Guidelines for further details. Anyone can submit a funding Application to PHARMAC. We strongly encourage all applicants to contact PHARMAC (+64 (0)4 460-4990 or 0800-66-00-50) prior to submitting an Application. You will be transferred to the Therapeutic Group Manager who can answer any questions you may have and confirm what the appropriate procedure is and what information needs to be provided.

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First Step

Please call PHARMAC (+64 (0)4 460-4990 or 0800-66-00-50) for all inquiries regarding Applications to fund new pharmaceuticals or to widen access to pharmaceuticals that are already funded. We will direct you to the relevant Therapeutic Group Manager. Send all Funding Applications and supporting information to: Manager, Funding & Procurement PHARMAC Level 9 40 Mercer Street PO Box 10-254 WELLINGTON 6143

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Checklist for Funding Applications

The checklist below outlines the information required when submitting a Funding Application to PHARMAC for an amendment to the Pharmaceutical Schedule. If anything is unclear, please check the glossary in Appendix 1 and contact PHARMAC if you need further clarification.

CHECKLIST FOR FUNDING APPLICATIONS TO PHARMAC Page CRITERIA Application is for an addition or amendment to the Pharmaceutical Schedule STRUCTURE OF APPLICATION Separate synopsis provided Spiral bound copies are clearly labelled and each section indexed Front cover states pharmaceutical name, brand name, date of Application, name of pharmaceutical supplier and name of applicant (including name, phone number and email address of contact person) Table of contents included Three hard copies provided and one electronic copy MAIN CONTENT Pharmacological information Proposed changes to the Pharmaceutical Schedule Epidemiological information Price information Market information Patent information Impact on health sector Search strategy used for identifying clinical trials Summary of the key randomised controlled trials (methods and outcomes) Assessment of the quality of the evidence Incidence and descriptions of adverse drug reactions Applicability of the evidence to the New Zealand health sector Summary of Application evaluated against PHARMAC’s nine decision criteria MAIN ATTACHMENTS Medsafe approved datasheet New Zealand Medicines Assessment Advisory Committee (MAAC) response to the registration application Copies of all identified randomised controlled trials published in peer-reviewed journals, subdivided by grade of evidence and ordered by date of publication One complete hard copy of the clinical study report summaries from the pivotal trials Copies of all errata, editorials and journal correspondence relating to published trials Register of all ongoing trials on the pharmaceutical Declaration that all known unpublished clinical trials have been disclosed One labelled sample of the pharmaceutical inside its packaging (unless Application is for widening of access) 19 19 25 25 25 25 25 31 Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N 19 20 21 22 23 23 24 24 27 27 28 28 29 Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N 16 16 16 Y/N 16 16 Y/N Y/N Y/N Y/N 9 Y/N

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CHECKLIST FOR FUNDING APPLICATIONS TO PHARMAC

ADDITIONAL CONTENT Cost-utility analysis based on the methods outlined in the Prescription for Pharmacoeconomic Analysis (including all costs estimated in $NZ) Additional information on health need and public health significance Additional information on health need by Maori and Pacific peoples ADDITIONAL ATTACHMENTS Copies of relevant EMEA European Public Assessment Reports (EPARs) and FDA Medical reviews Review articles and published critiques International guidance and recommendations Published cost-utility analyses Expert opinion and consensus reports from expert panels Where a cost-utility analysis is included, a CD with a copy of the TreeAge ExcelTM spreadsheet REAPPLICATIONS The Reapplication addresses all of the issues/concerns raised when the original Application was assessed List of all new information provided, along with copies of the new information APPLICATIONS FOR THE FUNDING OF GENERIC PHARMACEUTICALS Registration and indication details Pharmaceutical information (including one labelled sample) Price information Market information Patent information Lead times APPLICATIONS FOR THE FUNDING OF BLOOD GLUCOSE METER SYSTEMS International information Product information Price information Lead times Product testing 41 41 42 42 42 Y/N Y/N Y/N Y/N Y/N 39 39 40 40 40 40 Y/N Y/N Y/N Y/N Y/N Y/N 38 38 Y/N Y/N

33 35 36

Y/N Y/N Y/N

32 32 32 32 32

Y/N Y/N Y/N Y/N Y/N Y/N

model or

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Contents

1. 1.1 1.2 2. 2.1 2.2 2.3 2.3.1 2.4 2.4.1 2.4.2 2.4.3 2.4.4 2.4.5 3. 3.1 4. 4.1 5. 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.8.1 5.8.2 5.8.3 5.8.4 5.8.5 5.8.6 5.9 5.10 5.11 6. 6.1 6.2 6.2.1 6.3 6.4 6.4.1 7. 7.1 8. 8.1 8.2 8.3 8.4 8.5 8.6 9. 9.1 Background.....................................................................................................................................9 What is PHARMAC? ...................................................................................................................9 Purpose of the Funding Application Guidelines ..........................................................................9 The Application Process..............................................................................................................10 Who can initiate an Application? ...............................................................................................10 When do these Guidelines apply? ............................................................................................10 What is the process for submitting an Application?...................................................................11 Confidentiality and application of the Official Information Act ...................................................11 How does PHARMAC process and assess Applications? ........................................................11 PTAC Review of Applications ...................................................................................................12 Economic Assessment..............................................................................................................13 Prioritisation ..............................................................................................................................15 Negotiations ..............................................................................................................................16 Decision 16 Structure of Applications.............................................................................................................17 Submitting an Application .........................................................................................................17 Information Required in the Synopsis to an Application ..........................................................19 Synopsis ...................................................................................................................................19 Information Required in the Application ....................................................................................20 Pharmacological Information.....................................................................................................20 Proposed Changes to the Pharmaceutical Schedule................................................................21 Epidemiological Information ......................................................................................................22 Price Information.......................................................................................................................23 Market Information ....................................................................................................................24 Patent Information.....................................................................................................................24 Impact on Health Sector ...........................................................................................................25 Evidence of Effectiveness and Safety.......................................................................................25 Search Strategy ........................................................................................................................25 Clinical Evidence to Include in Application ................................................................................26 Order of Attachments................................................................................................................27 Presentation of Randomised Controlled Trials..........................................................................28 Critical Appraisal and Grading of Clinical Evidence ..................................................................28 Safety 29 Applicability of Evidence to the New Zealand Health Sector.....................................................29 Decision Criteria........................................................................................................................30 Sample......................................................................................................................................32 Additional Information in Applications.......................................................................................33 Additional Clinical Information...................................................................................................33 Economic Analysis....................................................................................................................34 Recommended Methods for Economic Analysis.......................................................................35 Health Need and Public Health Significance.............................................................................36 Health Need of Māori and Pacific peoples ................................................................................37 Background information ............................................................................................................38 Reapplications ..............................................................................................................................39 Information Requirements.........................................................................................................39 Applications for the Funding of Generic Pharmaceuticals.......................................................40 Registration and Indication .......................................................................................................40 Pharmaceutical Information ......................................................................................................40 Price Information.......................................................................................................................41 Market Information ....................................................................................................................41 Patent Information.....................................................................................................................41 Lead times ................................................................................................................................41 Applications for the Funding of Blood Glucose Meter Systems ..............................................42 International information ...........................................................................................................42

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9.2 9.3 9.4 9.5

Product Information...................................................................................................................42 Price Information.......................................................................................................................43 Lead times ................................................................................................................................43 Product testing ..........................................................................................................................43

Appendix 1 – Glossary .........................................................................................................................44 Appendix 2 – Protocol and evaluation of Self Monitoring Blood Glucose systems .......................51

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1.1

Background

What is PHARMAC?

PHARMAC, the Pharmaceutical Management Agency, is a Crown Entity that is directly accountable to the Minister of Health. Our functions are set out in section 48 of the New Zealand Public Health and Disability Act 2000 (NZPHD Act). One of PHARMAC’s functions is to manage the Pharmaceutical Schedule, which is the list of pharmaceuticals that are publicly funded. Thus, we may refer to a funded pharmaceutical as being “listed,” or to funding applications as containing proposals to “list” a pharmaceutical or to “make amendments to the Pharmaceutical Schedule”. We also negotiate national contracts for some pharmaceuticals and products used by District Health Board (DHB) hospitals and these are also listed in the Pharmaceutical Schedule (section H). PHARMAC's statutory objective is:

‘’to secure for eligible people in need of pharmaceuticals, the best health outcomes that are reasonably achievable from pharmaceutical treatment and from within the amount of funding provided.” Section 47(a) of the NZPHD Act

Further information about PHARMAC can be found at: www.pharmac.govt.nz. 1.2 Purpose of the Funding Application Guidelines

The purpose of these Guidelines is to provide guidance on how to prepare applications to PHARMAC for proposed amendments to the Pharmaceutical Schedule (“Applications”). These Guidelines are subject to the policies and procedures set out in PHARMAC’s Operating Policies and Procedures: http://www.pharmac.govt.nz/AboutPHARMAC/procedures This document is intended to assist anyone wanting to make an Application to PHARMAC for a proposed amendment to the Pharmaceutical Schedule. See section 2.2 of this document for further information on the use of these Guidelines.

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The Application Process

PHARMAC has an established process for deciding which pharmaceuticals, and which of their possible uses (indications), to fund. The decision-making process described in this document is the process that PHARMAC generally follows with an Application for a proposed change to the Pharmaceutical Schedule. PHARMAC may occasionally adopt a different process, or vary the process (for example, we decide whether or not it is appropriate to undertake consultation on a case-by-case basis). 2.1 Who can initiate an Application?

There are no restrictions on who can make an Application. Applications are usually made by pharmaceutical suppliers; however, clinicians, interest groups, PHARMAC committees and consumers (patients) may also make Applications. Before making an Application for a proposed amendment to the Pharmaceutical Schedule, please call PHARMAC on +64 (0)4 460-4990 or 0800-66-00-50. We will direct you to the relevant Therapeutic Group Manager who will discuss the nature of the proposed amendment with you. They will confirm what the appropriate procedure is, and what information needs to be provided to PHARMAC. 2.2 When do these Guidelines apply?

Proposed amendments to the Pharmaceutical Schedule where these Guidelines apply include Applications for: (i) (ii) (iii) (iv) (v) (vi) funding of new pharmaceuticals for use in the community; funding of new hospital oncology pharmaceuticals; changing funded access to an already listed pharmaceutical (e.g. for new uses or patient groups); funding generic pharmaceuticals where an application to fund the pharmaceutical has not previously been considered by PHARMAC; funding new formulations or strengths of already funded pharmaceuticals; and funding combination products (products that consist of two or more pharmaceuticals).

Funding Applications relating to a generic pharmaceutical where funding of the pharmaceutical has previously been considered by PHARMAC should follow Section 8 of these Guidelines only. These Guidelines do not apply to the following: (i) (ii) community funding for hospital pharmaceuticals funded by District Health Boards (DHBs); or funding of pharmaceuticals for individual patients.

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If you have concerns regarding the safety of a pharmaceutical funded by PHARMAC, or consider that a pharmaceutical should be removed from the Pharmaceutical Schedule, please write to PHARMAC outlining your concerns. PHARMAC staff will inform you of what course of action will be taken. Please note that it is Medsafe (the New Zealand Medicines and Medical Devices Safety Authority; a business unit of the Ministry of Health) that is responsible for pharmaceutical regulation and safety matters (under the Medicines Act 1981 and Regulations 1984), so Medsafe should be approached in the first instance on all issues related to the safety of a pharmaceutical. Applications to PHARMAC should be for Medsafe-registered products and indications. If the pharmaceutical is not registered, or if the Application is for a registered pharmaceutical for use in an unregistered indication, please contact PHARMAC to discuss the Application with the relevant Therapeutic Group Manager prior to submitting an Application to PHARMAC. 2.3 What is the process for submitting an Application?

Please ensure that Applications adhere to the content, format and organisation stipulated in this document. Section 3 of these Guidelines gives details on the required format of Applications to PHARMAC. 2.3.1 Confidentiality and application of the Official Information Act

Some of the information submitted to PHARMAC, or held by us, may be considered by the applicant to be confidential and/or commercially sensitive. While we respect the confidentiality and commercial sensitivity of information provided, applicants should be aware that PHARMAC must balance this against the need to provide information when we consider that consultation with affected parties is appropriate. Further, as a public organisation, PHARMAC is subject to the Official Information Act 1982 (OIA). Applications and all correspondence PHARMAC holds related to Applications may therefore be the subject of requests under OIA. If PHARMAC receives such requests under the OIA it would generally consult with Applicants, prior to releasing any of the information they have provided. PHARMAC will, at all times, act in good faith where we consider it necessary or appropriate to release information, including in any consultation with affected parties. 2.4 How does PHARMAC process and assess Applications?

When an Application is received, PHARMAC reviews the Application to ensure that it contains the information PHARMAC requires in order to assess the proposal. If an Application is incomplete in any way, or if clarification is required, PHARMAC may contact the applicant and may defer consideration of the Application until the applicant has resolved any outstanding issues. Application details will be published on PHARMAC’s website, including the name of the pharmaceutical and the proposed indication for funding: http://www.pharmac.govt.nz/fundingapps If PHARMAC considers that clinical advice on the Application is required, the first step in the assessment process will be a review of the Application by the

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Pharmacology and Therapeutics Advisory Committee (PTAC) or, in some cases, one of the specialist PTAC Subcommittees. PHARMAC, in consultation with the PTAC Chair, may consider: (i) (ii) (iii) whether a particular Application should be referred directly to PTAC for advice; or whether a particular Application should be referred directly to the relevant Subcommittee (i.e. prior to its consideration by PTAC); or whether they wish to invite relevant medical groups and other interested parties to comment on the pharmaceutical that is the subject of the Application before the Application is considered by PTAC or a Subcommittee. Where we seek comments, the main objective will be to enable interested parties to outline specific issues relating to the pharmaceutical (in relation to PHARMAC’s decision criteria) early in the PHARMAC decision making process. These comments will then be considered by PTAC or a Subcommittee when it considers the Application.

The decision to submit an Application to PTAC (including the decision about which PTAC meeting to send it to) following receipt of the Application is at the discretion of PHARMAC in consultation with the PTAC Chair. If PHARMAC decides not to submit the Application to PTAC, PHARMAC will inform the applicant of the reasons for this. If an Application is submitted for consideration at a particular PTAC or Subcommittee meeting, PHARMAC staff will usually draft a cover paper for the Application, which generally includes (but is not limited to) the following information: • • • • • • • • • 2.4.1 summary of the proposal (the pharmaceutical, indications, pharmaceutical supplier, proposed subsidy, etc.); questions to PTAC and/or the Subcommittee; previous PTAC and/or Subcommittee minutes (if relevant); brief description of the disease and current treatment in New Zealand; brief description of the pharmaceutical under consideration (including clinical evidence and any proposed restrictions or changes to access); international prices of the pharmaceutical; estimated cost of funding; cost-effectiveness (if available and relevant); and PHARMAC’s decision criteria and Government priorities for funding. PTAC Review of Applications

PTAC is PHARMAC’s primary clinical advisory committee. Its role is to provide objective advice to PHARMAC on pharmaceuticals and their benefits. PTAC's members are appointed by the Director-General of Health in consultation with the PHARMAC Board. PTAC comprises senior health practitioners with expertise in critical appraisal and broad experience and knowledge of pharmaceuticals and their therapeutic uses. There are also a number of PTAC Subcommittees, made up of

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experts in specialist clinical fields such as cardiology and oncology. PHARMAC and/or PTAC often seek advice from a specialist PTAC Subcommittees. When considering an Application, PTAC will review and critically appraise the clinical evidence. It uses the same decision criteria as PHARMAC when evaluating Applications. PTAC makes recommendations to PHARMAC regarding amendments to the Pharmaceutical Schedule and assigns priority ratings to these recommendations (typically, high, medium or low). PTAC may also recommend that an Application be declined or deferred, giving reasons for the deferral, such as supply of further information. When making recommendations to PHARMAC, PTAC indicates which decision criteria it has given particular weight to. These recommendations are taken into account when PHARMAC sets its funding priorities. Generally, if a proposal in an Application is given a high PTAC priority and the proposed amendment to the Pharmaceutical Schedule is relatively cost-effective, it may be progressed sooner than a proposal that has been given a low PTAC priority or one that is not as cost-effective. A positive recommendation by PTAC and/or its Subcommittees, however, is no guarantee of funding as the role of PTAC and PTAC Subcommittees is to advise PHARMAC on matters referred to them. PHARMAC is not bound to follow the recommendations made. If PTAC considers that further specialist advice is needed prior to making a recommendation to PHARMAC, the Application may be referred to a PTAC Subcommittee. Applications may also be referred to PTAC Subcommittees for advice on developing or refining access criteria. If PTAC considers that further information is required from the applicant, this will be referred back to the applicant. A copy of the relevant part of the PTAC/subcommittee minute is sent to the applicant. The applicant then has two weeks to review the minute and to make a request for the withholding of all or part of the minute from public release. When we consider requests for withholding part or all of the PTAC/Subcommittee minutes, PHARMAC is guided by the grounds for withholding information specified in the Official Information Act. In some instances where the Application has not been made by the pharmaceutical supplier, the minute may be sent to the relevant pharmaceutical supplier as well as the applicant for review and feedback. This usually occurs if we consider that there is a possibility that the supplier may object to the release of part or all of the minute. Following this review, the minutes may be published on the PHARMAC website. Further details about PTAC and PTAC Subcommittees can be found in the PTAC Terms of Reference, which are available on the PHARMAC website http://www.pharmac.govt.nz/PTAC or by contacting PHARMAC on +64 (0)4 4604990. 2.4.2 Economic Assessment

PHARMAC generally will undertake or review two forms of analysis on a proposal: (i) (ii) a cost-utility analysis (CUA); and a budget-impact analysis (BIA).

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PHARMAC estimates the budgetary impact of the proposed change to the Pharmaceutical Schedule, usually over a period of five years (discounted at 8%)1. In some cases a longer time horizon is required. The methods PHARMAC uses when undertaking CUA are outlined in PHARMAC’s Prescription for Pharmacoeconomic Analysis (PFPA) – www.pharmac.govt.nz/2007/06/19/PFPAFinal.pdf We encourage applicants to provide a CUA when submitting an Application. Providing good quality analysis, following the methods outlined in the PFPA, may help the review and information acquisition process, enabling your Application to be prioritised earlier. When PHARMAC receives a CUA from an applicant, our analysts review it, and amend it if required. In order to be able to review CUAs more efficiently, applicants should provide a CD with a copy of the TreeAge model and/or Microsoft Excel spreadsheet. If PHARMAC has made amendments to the analysis, PTAC will usually be supplied with a copy of the applicant’s CUA and PHARMAC’s amended CUA, with the differences between them clearly explained. If an economic analysis has not been provided in the Application to illustrate the cost -effectiveness of the proposed amendment to the Pharmaceutical Schedule, PHARMAC will undertake a CUA. The stage at which this occurs depends on availability of health economist resources and its PTAC priority. Very few Applications receive a detailed CUA assessment, as these take around 2–6 months to complete and, tend therefore to be too slow and resource-intensive for a purchasing environment. The process is usually iterative, meaning that rapid assessments are conducted first; then preliminary assessments; then if this is insufficient to inform a recommendation, an indicative or detailed analysis is undertaken. The level of analysis undertaken depends on the factors outlined in Table 1 below.

Table 1: Determinants of Level of Analysis Undertaken by PHARMAC Determinants of level of analysis Timeframes Impact on pharmaceutical budget Reliability of results Extent of information available for analysis Impact of CUA on funding decision Availability of health economist resources

Details In some cases a CUA result may be required within a week; hence a more detailed analysis cannot be undertaken. A high expenditure pharmaceutical is more likely to require a detailed CUA, especially if the pharmaceutical is highly effective. If the results of a CUA are very sensitive to key assumptions a higher level of analysis may be required. Pharmaceuticals for rare conditions are more likely to undergo rapid analysis due to unavailability of data. In some cases the pharmaceutical may be funded based on other decision criteria, hence a detailed analysis may not be required. Given limited analyst resources, it may not be cost-effective to undertake a detailed analysis when a number of other CUAs are also required.

Note that the discount rate used by BIA differs from the rate used for CUA (the (nominal) discount rate for BIA is 8%, and the (real) discount rate for CUA is 3.5% for both costs and benefits). The rationale for using these rates is outlined in the Prescription for Pharmacoeconomic Analysis (PFPA) www.pharmac.govt.nz/2007/06/19/PFPAFinal.pdf

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Most CUAs are written up as ‘Technology Assessment Reports’ following a template. CUAs are then peer-reviewed internally and examination of the economic methodology is conducted. Analyses may also be reviewed by PTAC or the relevant specialist PTAC Subcommittee, or by other relevant external experts. PHARMAC has no threshold below which a proposed amendment to the Pharmaceutical Schedule is considered “cost-effective”. The main reason for this is that cost effectiveness is only one of the decision criteria we use. One Application may be more cost effective than another but rate poorly on other decision criteria and, therefore, may not be progressed since, on ‘successfulness grounds’, it will not be considered cost effective. Another reason for not having a threshold value is that spending on community pharmaceuticals is required to be kept within a fixed budget. Given this constraint, and all other things being equal, what is and is not considered “cost-effective” will vary with the amount of funding available (not just in terms of the total budget each year, but the available budget at any point in time). An Application to fund a pharmaceutical can, therefore, only be considered “cost-effective” in comparison with other Applications under consideration by PHARMAC at any one particular time. 2.4.3 Prioritisation

Once full information on an Application is available (including PTAC priority and costeffectiveness where necessary), it is compiled and considered by PHARMAC according to our nine Decision Criteria (outlined below).

PHARMAC’s Decision Criteria are: 1. The health needs of all eligible people within New Zealand. 2. The particular needs of Māori and Pacific peoples. 3. The availability and suitability of existing medicines, therapeutic medical devices and related products and related things. 4. The clinical benefits and risks of pharmaceuticals. 5. The cost-effectiveness of meeting health needs by funding pharmaceuticals, rather than by using other publicly-funded health and disability support services. 6. The budgetary impact (in terms of the pharmaceutical budget and the Government's overall health budget) of any changes to the Pharmaceutical Schedule. 7. The direct cost to health service users. 8. The Government's priorities for health funding, as set out in any objectives notified by the Crown to PHARMAC, in PHARMAC's Funding Agreement, or elsewhere. 9. Any other criteria that PHARMAC thinks are relevant. PHARMAC will carry out the necessary consultation whenever we intend to take any 'other criteria' into account.

All Applications are prioritised against other funding options (either listing of new pharmaceuticals or widening access to pharmaceuticals that are already listed), whether received via Application or via PHARMAC initiated proposals. The overall aim is to identify potential amendments to the Pharmaceutical Schedule that would provide the greatest possible health benefits. PHARMAC conducts regular prioritisation reviews of all outstanding Applications.

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2.4.4

Negotiations

Therapeutic Group Managers are responsible for negotiating listing and supply agreements with pharmaceutical supplier(s), where these are relevant to a proposed change to the Pharmaceutical Schedule. This commercial activity may include: price negotiations; Special Authority or other targeting criteria; expenditure caps; rebates on the pharmaceutical price; and/or multi-product agreements. Negotiation outcomes may lead to re-prioritisation of an Application. 2.4.5 Decision

Section 49(a) of the NZPHD Act requires that PHARMAC must, when it considers it appropriate to do so, consult on matters that relate to the management of pharmaceutical expenditure with any sections of the public, groups or individuals that may be affected by decisions on those matters. Prior to PHARMAC making a decision on a proposed change to the Pharmaceutical Schedule, we will, when we consider it appropriate, consult with people that may be affected by the proposed change (which may, according to the circumstances, include suppliers, PTAC and PTAC Subcommittees, health professionals or patients groups, Maori, Pacific peoples and other groups). Consultation responses are considered by PHARMAC with an open mind and, if appropriate, the proposal may be amended. Decisions regarding any amendments to the Pharmaceutical Schedule are made by the PHARMAC Board, or PHARMAC’s Chief Executive acting under delegated authority.

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Structure of Applications

Applications to PHARMAC for the listing of new pharmaceuticals, new indications and/or new formulations should be separated into the following three sections: (i) (ii) (iii) synopsis; the main body of the Application; and supporting information.

Hard copies of the Applications should be provided in separate spiral bound volumes. It is particularly important that copies of the synopsis are provided separately from the rest of the Application. Each binder should be clearly labelled and the Application indexed so that information can be easily located. Please provide a table of contents in each binder. It is also useful if the Application has labelled tabs for each of the sections it contains (i.e. pharmacology, epidemiology, etc.). The front cover of the Application should include the following information: (i) (ii) (iii) pharmaceutical, brand name and indication; date of the Application; and the name of the pharmaceutical supplier and (if different) the name of the applicant (including name, phone number and email address of contact person).

The Application must include all relevant information known to the applicant, including data that is contrary to, or does not necessarily support, the case presented in the Application. Any information required for the Application (as outlined below) that is not available or is otherwise not supplied, should be stated explicitly under the relevant heading(s). Explain all sources and assumptions. If PHARMAC is not provided with information it considers necessary to assess the Application, this is likely to result in delays. Please be clear and succinct, yet thorough. Applications must also include one labelled sample of the pharmaceutical inside its New Zealand packaging, as appropriate. Sometimes more samples may be required. A sample is not required with Applications for widening access to treatments already listed on the Pharmaceutical Schedule. Please refer to Section 5.10 for further details on the provision of samples. 3.1 Submitting an Application

Applicants must initially provide three hard copies and one electronic copy of the Application to PHARMAC. PHARMAC will undertake an initial screening of the Application (as outlined in section 2.4), usually within ten working days of receiving it, to ensure that it is complete and includes the key information that PHARMAC requires in order to assess the proposal. If the Application is incomplete or further clarification is required, PHARMAC may contact the applicant and may defer consideration of the Application until any outstanding issues are resolved.

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If an Application is approved for consideration by PTAC, PHARMAC will notify the applicant. Following notification, the applicant must provide fifteen copies of the Application. Applicants must also supply one additional electronic copy of the entire Application on Compact Disk (CD). If an economic analysis is included in the Application, please also provide a copy of the analysis on the CD, along with the Excel spreadsheet and/or TreeAge model as outlined in Section 2.4.2. If you have any questions, please contact the relevant Therapeutic Group Manager at PHARMAC.

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Information Required in the Synopsis to an Application

Sections 4 and 5 outline the information required for Applications to PHARMAC for new pharmaceuticals, new indications (expanded access) and new formulations. Applications for generic pharmaceuticals (where the pharmaceutical has previously been considered by PHARMAC) should refer to Section 8. Please refer to Section 7 of these Guidelines for details on the format and content required for reapplications. 4.1 Synopsis

The synopsis should include a high-level summary of key aspects and issues presented in the Application. This should generally not be more than 10 pages long and should include the following information: (i) (ii) (iii) (iv) (v) (vi) (vii) (viii) (ix) (x) (xi) (xii) (xiii) (xiv) official or approved names of the pharmaceutical; form(s), strength(s), pack size(s); registered indication(s); proposed restriction(s) for listing; recommended course of treatment; main comparator(s) and the main expected changes in the clinical management algorithm; numbers of patients treated (restricted and unrestricted listing); proposed price; net cost of the proposed drug each year over five years; the number and date of expiry for all relevant New Zealand patents (both granted and pending); cost per patient per course (for acute therapy) or the cost per patient per year (for chronic therapy); any wider health sector resources affected by the listing of the proposed drug; main results of the clinical evaluation in terms of comparative effectiveness and comparative toxicity, including key data sources; and if available, a summary of the cost-utility analysis, including the main sources of uncertainty in the structure and variables in the economic evaluation and the results of associated sensitivity analyses.

The synopsis will be used as a general information guide for PHARMAC and will be provided to PTAC members.

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5.1

Information Required in the Application

Pharmacological Information

Please provide the following information: (i) (ii) (iii) (iv) (v) (vi) official or approved names of the pharmaceutical; pharmaceutical form (e.g. ampoule, vial, sustained-release tablet); pharmaceutical strength; arranged pack sizes (in the case of a preparation such as an aerosol, state the number of doses available from the container); principal pharmacological action of the pharmaceutical; indications registered for use in New Zealand – attach the Medsafe approved data sheet and the New Zealand Medicines Assessment Advisory Committee (MAAC) response to the registration application; where known, details of OECD countries where registration has been approved (names only) or declined; where known, details of OECD countries where an application for funding has been approved (names only) or declined; other presentations or formulations of the pharmaceutical that have been submitted for approval, or are already approved, in other OECD countries; recommended dosages for each of the indications provided in connection with (vi) above. In the case of a pharmaceutical that is not used for chronic therapy, provide information on the average length of a treatment course and anticipated frequency of repeat courses of treatment; any contra-indications and drug interactions. Include information on any necessary dosage adjustments and cautions required when using the pharmaceutical in conjunction with other pharmaceuticals; common adverse effects (including frequency); serious adverse effects; and a summary statement of the main pharmaceutical and its proposed use. therapeutic claims for the

(vii) (viii) (ix) (x)

(xi)

(xii) (xiii) (xiv)

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5.2

Proposed Changes to the Pharmaceutical Schedule

Please provide the following information: (i) (ii) (iii) (iv) (v) the therapeutic group and/or subgroup where the applicant considers the pharmaceutical should be listed on the Pharmaceutical Schedule; details of any proposed restrictions to access (e.g. Special Authority criteria or endorsement criteria); details of the comparator treatments available in New Zealand (funded and unfunded); present the current clinical treatment algorithm (or pathway) and outline the main expected changes in the treatment algorithm; describe how pharmaceuticals including: • the pharmaceutical compares clinically with already listed on the Pharmaceutical Schedule,

what (if any) advantages the pharmaceutical offers over existing listed pharmaceuticals in terms of efficacy and/or side effects: whether the pharmaceutical is equivalent to existing listed pharmaceuticals whether the pharmaceutical is more effective than existing listed pharmaceuticals whether the pharmaceutical has a similar efficacy to existing listed pharmaceuticals but has fewer side effects

•

whether the pharmaceutical is associated with similar, greater or fewer side effects and/or toxicity than existing listed pharmaceuticals whether the pharmaceutical offers greater compliance (e.g. once daily dosing) than existing listed pharmaceuticals (include evidence supporting this claim);

•

(vi)

if available, include dose equivalencies with comparator pharmaceuticals (whether listed or not) and justify these. State whether dose equivalencies were derived from direct or indirect comparisons; whether the pharmaceutical has a longer shelf life than existing listed pharmaceuticals, or other points of difference; and other pharmaceuticals, medical devices, related products or things, if any, likely to be prescribed for use in conjunction with the pharmaceutical as part of a course of treatment (whether listed or not). Include pharmaceuticals that may be used to manage any side effects.

(vii) (viii)

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5.3

Epidemiological Information

For each requested indication(s), please provide estimates for the first five years of the proposal (shown on a year-by-year basis) of: (i) (ii) the number of people in New Zealand with the particular condition(s); where available, the number of Māori people in New Zealand with the particular condition(s), along with their age-standardised prevalence rate per 1000 population; where available, the number of Pacific people in New Zealand with the particular condition(s) , along with their age-standardised prevalence rate per 1000 population; where available, the number of non Māori / non Pacific people in New Zealand with the particular condition(s) , along with their age-standardised prevalence rate per 1000 population; the number of additional people in New Zealand likely to be prescribed the pharmaceutical under the proposal; and a breakdown of the number of people in New Zealand treated for the condition, including: • • those who can be successfully treated by the pharmaceutical only; those who can be treated by both the pharmaceutical and other pharmaceuticals (whether listed or not) that treat the same condition; those who can be treated by only other pharmaceuticals (whether listed or not); those who can be treated, completely or partially, by other therapies.

(iii)

(iv)

(v) (vi)

• •

In all cases where estimates and assumptions are made or used, please clearly and explicitly state what underlies them, including sources. These may be indicated in ranges (i.e. the minimum and maximum plausible range of values). Further information on deriving numbers of Maori and Pacific people with the particular condition(s) can be found in Section 6.6. When estimating the likely number of patients eligible under access scenarios, please use an epidemiological approach. This means the prevalence and/or incidence of the condition to be treated; current patterns of how the pharmaceutical is used across different disease/indications; patterns over time in usage across diseases/indications; and patterns seen in other pharmaceutical markets internationally with the introduction of the new pharmaceuticals. Please cite data sources, and clearly and explicitly state the bases of the assumptions made for the estimated numbers, including the quality of the data and relevance to the New Zealand setting. Estimates and assumptions can be indicated in ranges or similar.

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The table below provides a suggested format for presenting this information.

Assumption/ parameter Central estimate Type of estimator used (mean, median, mode, etc.) Variation (as a range, percentile, standard deviations, 95% confidence interval, etc.) Source (e.g. publication, reference from the literature - state; expert estimate (who/credentials) Rationale for using this/these particular source/s

As with evidence of effectiveness (Section 5.8), all prevalence estimates and assumptions should be obtained systematically. Please supply details of the search strategies used to identify these (the medium used; databases searched; time period when undertaken; search strategy and keywords/MeSH headings used). Also specify the pre-defined inclusion and exclusion criteria for selecting the relevant epidemiological data used for estimates and assumptions. Prevalence and outcomes data may be located using relevant on-line Medline searches (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) using search terms that incorporate [the disease/indication], (epidemiology OR prevalence OR risk factors OR natural history OR prognosis OR outcomes OR survival), and specific outcomes relevant to the disease/indication. Local epidemiology/outcomes data can be located more specifically by including the terms (Austral* OR Zealand OR NZ OR Aotearoa) in the search. If you are unsure about how to do such searches (including search strategy and keywords/MeSH headings), you may wish to discuss with a medical librarian or PHARMAC. You may find useful sources of New Zealand mortality and morbidity data in cancer registry data, hospitalisation episode data, mental health episode data, and mortality data. These are available from NZ Health Information Service (http://www.nzhis.govt.nz). Details on the range of data available can be obtained from the Ministry of Health’s Public Health Metadata Database (see http://www.moh.govt.nz/PHMetadata.nsf/). 5.4 Price Information

Please provide the following price information: (i) (ii) the supplier’s selling price in $NZ (ex-manufacturer, GST exclusive); the supplier’s selling prices to wholesalers in other OECD countries where the pharmaceutical is marketed (in local currencies (excluding local taxes) and New Zealand dollar equivalents – please specify the exchange rates used); and alternative pricing proposals (e.g., possible price/volume trade-offs).

(iii)

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5.5

Market Information

Please provide the following market information: (i) estimated average daily dose (ADD) information for New Zealand (and other markets where possible) and estimated average daily cost (ADC) of treatment for New Zealand; expected sales (dollars and volume) for the first five years of listing, to be shown on a year-by-year basis with anticipated market segments and projected market shares; and estimate the change in the extent of use of other pharmaceuticals.

(ii)

(iii)

The ADD, ADC and expected sales information referred to in (i) and (ii) above should be supported by data from major OECD markets and other markets where the pharmaceutical is available (i.e. therapeutic indication(s) and use, ADD information, ADC of treatment, and sales). These data should cover the time period from product launch within each market to the date of the Application, on a year-by-year basis. 5.6 Patent Information

Please provide the information set out below on each patent (granted and pending) that has claims relating to the pharmaceutical that is the subject of the Application, and with respect to which a claim of patent infringement could reasonably be asserted if a person, not licensed by the owner of the patent, distributed or sold the pharmaceutical in New Zealand. This information is required to help inform PHARMAC’s assessment of the budget impact associated with the Application. Please submit the following information for each pharmaceutical substance (ingredient) patent and finished pharmaceutical product (formulation and composition) patent and method of use and “Swiss-type” claim patents: (i) (ii) (iii) (iv) (v) patent number and the date on which the patent will (or would, if granted) expire; type of patent (i.e. drug substance, finished drug product, method of use or “Swiss-type” claim); name of the patent owner; if you are not the patent owner, details of your right to sell or distribute the pharmaceutical in New Zealand; and if you or the patent owner do not reside or have a place of business within New Zealand, the name of your representative or the representative of the patent owner who resides or maintains a place of business within New Zealand and who is authorised to receive notices related to the patent.

PHARMAC does not require information on manufacturing process patents.

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If a patent is issued after the Application is made to PHARMAC but before funding is approved, please submit the required patent information in an amendment to the Application within 30 days of the date of issuance of the patent. If you believe that there are no relevant patents with respect to which a claim of patent infringement could reasonably be asserted if a person, not licensed by the owner of the patent, distributed or sold the pharmaceutical in New Zealand, please specify this in your Application. PHARMAC recognises that some applicants, particularly those that are not pharmaceutical suppliers, may not have access to this information. If this is the case, please specify it in your Application. PHARMAC may subsequently seek such information from the relevant pharmaceutical supplier. 5.7 Impact on Health Sector

Please provide information on the following: (i) hospital outpatient or community-based services required for administration of the pharmaceutical (e.g. nurse and specialist time required for infusions); laboratory and diagnostic tests; inpatient hospitalisation; emergency department visits; specialist visits and primary care services; and community-based services (e.g. nurse home visits, residential care (specify), home help, hospice care).

(ii) (iii) (iv) (v) (vi)

If possible, please quantify this impact (refer to Section 7 of the PFPA for details on how to estimate these costs). 5.8 Evidence of Effectiveness and Safety

Please use key clinical data sources when estimating relative treatment effects, including published randomised controlled trials (RCTs) and meta-analyses. Other possible sources include observational studies, unpublished trial data, expert opinion, and case reports. 5.8.1 Search Strategy

All evidence should be obtained systematically. Describe the search strategy used to identify clinical studies, including: (i) (ii) (iii) who carried out the search? Using which medium? what databases were searched? over what time period was the search undertaken? what search strategy and keywords/MeSH headings were used?

Please specify the pre-defined inclusion and exclusion criteria used for selecting relevant studies.

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5.8.2

Clinical Evidence to Include in Application

When presenting clinical data to PHARMAC on relative treatment effects, please include the following: (i) all identified RCTs published as full articles in peer-reviewed journals in the English language that report (or give sufficient data to calculate) outcomes by intention-to-treat (ITT); one complete hard copy of the clinical study report summaries from the pivotal RCTs; a register of all ongoing trials on the pharmaceutical for the relevant indication(s) known to the applicant, including trials not directly funded by the pharmaceutical supplier (this can be in the form of a print-out from clinicaltrials.gov); copies of all published errata (or corrections), retractions, editorials, and journal correspondence directly relating to the published trials included in the Application; if including data from unpublished trials, specify why each trial has not been published and expected dates of publication (if applicable); and a declaration that all unpublished clinical trials known to the applicant have been disclosed, including those known to the applicant to have been undertaken by other companies that may distribute, market or licence the pharmaceutical in New Zealand.

(ii) (iii)

(iv)

(v) (vi)

In evaluating therapeutic effectiveness and safety, we place greater weight on welldesigned RCTs than other data sources. Of particular interest are head-to-head comparison RCTs between the proposed product and principal comparators. Please include unpublished articles or studies that have been submitted for publication in peer-reviewed journals. In cases where the study is published after the Application has been submitted, applicants may substitute the draft submitted version with the final published version. Note however, PHARMAC may place greater weight on trials registered on public trial registers. PHARMAC is committed to international efforts to mitigate publication bias through the provision of central trial registries. Details on supplementary information that may be provided in a separate section of the Application are included in Section 6 of these Guidelines. Please do not include the following information in the Application as such information will not be reviewed: • • information unrelated to the pharmaceutical and disease(s)/indications under consideration; and phase I clinical trials relating to the pharmaceutical.

Abstracts and posters are not usually appropriate sources for descriptions of the study methodology or primary outcomes of studies. However, if they are adequately detailed, they may be used as references to update information after the primary analyses or any analyses of secondary outcomes not detailed in the published report.

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5.8.3

Order of Attachments

To make it easier for us to deal with attachments, please subdivide copies of articles, with their accompanying appraisals (see 5.8.5 below), into the three categories outlined in table 2. Within each group, please order articles by date of publication, starting with the most recent.

Table 2: Categories for Order of Attachments Category Grade 1 evidence Examples Randomised controlled trials (RCTs) of efficacy (individual RCTs and metaanalyses of RCTs) Controlled but non-randomised experimental studies and non-analytic uncontrolled descriptive data for efficacy or prognosis/natural history Grade 2-3 evidence Adverse effects (prospective cohort studies, case control studies, before-andafter studies, longitudinal studies, uncontrolled observational studies, case reports) Non-systematic reviews Expert opinion Economic modelling/analyses and intervention logic in absence of direct empirical data Other background epidemiology and natural history of the disease/indication Other published material relevant to the proposal

Grade 4 evidence

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5.8.4

Presentation of Randomised Controlled Trials

For each direct RCT, provide the following details of the trial: (i) (ii) objective of trial; study design including eligibility criteria, sample size, interventions (including dose and treatment duration), methods for randomisation and blinding, duration of follow-up, and outcomes measures and methods; results including number of withdrawals and dropouts; and results for prospectively-defined primary outcomes, secondary outcomes and adverse effects for ITT population.

(iii)

Clinical trials should be analysed using data from the ITT population in order to take into account outcomes of all patients irrespective of whether they received treatment. Where ITT analysis has not been reported, ideally recalculate effectiveness rates by adding to the “on treatment” participant population for the group (i.e. the denominator) all of the patients who withdrew, dropped-out, or were otherwise lost to follow-up. This is the group’s true ITT starting participant population. In addition, information should be provided on Numbers Needed to Treat (NNT) and Numbers Needed to Harm (NNH). The prospectively-defined primary and secondary outcome measures (as determined in the study protocol) should include both published and unpublished outcomes. Published outcomes data should be obtained from the complete published reports of the trials. If these are not available, use clinical study reports. These should be clearly highlighted and will be treated as commercial- or academic-in-confidence. Where clinical trial data have been taken from more than one source, this should be made clear. Examples include: • • • 5.8.5 a clinical trial report and a published paper; an open-label extension to a trial; and additional analyses (e.g. interim or post-hoc). Critical Appraisal and Grading of Clinical Evidence

Where possible, critically appraise and grade the evidence using the methods described in PHARMAC’s Prescription for Pharmacoeconomic Analysis (PFPA). PHARMAC recommends the use of the Graphic Appraisal Tool for Epidemiology (GATE) for the critical appraisal of clinical trials, and the use of the Scottish Intercollegiate Guidelines Network (SIGN) to grade clinical evidence. Details on the GATE framework, including critical appraisal spreadsheets, are available at: www.epiq.co.nz, and it is described further in Evidence Based Medicine at http://ebm.bmj.com/cgi/content/full/11/2/35. Further details on these tools are also included in the PFPA: www.pharmac.govt.nz/2007/06/19/PFPAFinal.pdf The following table outlines a number of issues to consider when critically appraising a clinical trial.

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Table 3: Factors to Consider in Critical Appraisal of Trials Validity Factors for appraisal Availability of data Number of patients Questions to consider Was the trial published in a peer-reviewed journal? Was the sample size large enough to indicate efficacy (i.e. that the results did not occur due to chance)? Or was the effect large enough to be statistically significant even in a small sample size? Was there likely to be any selection bias or confounding? Were patients, clinicians and assessors blinded? Were patients followed for an adequate time period? How often were patients assessed? Was analysis undertaken on the ITT population? Was the selection of endpoints relevant? Was the patient population in the trial similar to those considered for funding? Was the comparator consistent with current clinical practice in New Zealand? Were these consistent with recommended treatment regimes in New Zealand?

Internal validity

Method of randomisation, including adequate concealment Length and completeness of follow-up

Selection of endpoints Patient population

External validity

Comparator

Dose, formulation and administration regimen

5.8.6 Safety Information on the incidence and descriptions of adverse drug reactions should include data collected from: • • • • 5.9 observational longitudinal clinical studies; RCTs; case reports on adverse drug reactions and expected/unexpected side effects; and post-marketing surveillance data. Applicability of Evidence to the New Zealand Health Sector

For each clinical study provided in the Application, please assess how applicable the study is to the New Zealand health sector and pharmaceutical funding environment. Please try to answer the following questions: (i) (ii) (iii) Are there any known biological factors that may alter the effect of the pharmaceutical? What effects does the time of taking the pharmaceutical have? What effects do variations in the nature and severity of the disease have?

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(iv)

Does the effectiveness of the pharmaceutical depend on the way it is administered and/or by whom (e.g. by a nurse rather than by the patient)? Is the giving or taking of the pharmaceutical part of a complex procedure with many components? Is any infrastructure required/available, such as monitoring with regular blood tests? Are there any other factors that may affect transferability of study results to the New Zealand clinical setting? Decision Criteria

(v) (vi) (vii)

5.10

When making decisions on proposals, PHARMAC uses the decision criteria set out below and weights each criterion. These decision criteria are set out in Section 2.2 of PHARMAC’s OPPs which are available on the PHARMAC website. The criteria are also used by PTAC when it assesses Applications. Please provide a summary of the Application, evaluated against as many as possible of PHARMAC’s nine decision criteria, described below. The questions included for each criterion have been included to help applicants to address each criterion. We have also identified some potentially relevant supporting information, which would be helpful for applicants to provide in relation to each criterion. The questions and supporting information identified below do not limit either the application of each criterion or the factors PHARMAC may consider under each criterion.

Table 4: PHARMAC Decision Criteria Decision Criteria Questions to address Supporting information How many people are there with the disease/condition that may benefit from the treatment? Criterion 1 - the health needs of all eligible people within New Zealand What health need(s) are relevant to this proposal? What is the morbidity and premature mortality of the condition in New Zealand? Refer to sections 5.3 and 6.3 for further information. Describe the extent of disparity in disease prevalence and incidence between Māori, Pacific people and non Māori/non Pacific people. Refer to sections 5.3 and 6.4 for further information. What other interventions are currently available to meet these health needs – if there are none, what other health sector resources are used managing the need(s)?

Criterion 2 - the particular health needs of Māori and of Pacific peoples

What particular health need(s) of Māori and of Pacific peoples are relevant to this proposal?

Criterion 3 - the availability and suitability of existing medicines, therapeutic medical devices and related products and related things

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Decision Criteria

Questions to address

Supporting information What would be the absolute risk reductions (ARR) in events (specify) or improvement in health states (specify) caused by the proposal? What other benefits would be conferred for patients (e.g. evidence of improved efficacy through increased compliance)? Refer to section 5.8 for further information

Criterion 4 - the clinical benefits and risks of pharmaceuticals

What health benefits and risks would the proposal provide, including in comparison with the other interventions outlined above?

Criterion 5 - the costeffectiveness of meeting health needs by funding pharmaceuticals rather than using other publicly funded health and disability support services

What is the incremental cost (or saving) and incremental benefit (or risk) compared with other interventions?

What is the estimated cost per QALY associated with funding the proposal? Refer to Section 6.2 for further information.

Criterion 6 - the budgetary impact (in terms of the pharmaceutical budget and the Government’s overall health budget) of any changes to the Pharmaceutical Schedule

What impact would this proposal have on the pharmaceutical budget and the overall health budget, both for the current financial year and the net present value (NPV) of the effects over future years? How would patients’ out-ofpocket expenses be changed by the proposal?

Criterion 7 - the direct cost to health service users

Criterion 8 - the Government’s priorities for health funding, as What Government priorities set out in any objectives notified for health funding are by the Crown to PHARMAC, or relevant to the proposal? in PHARMAC’s Funding Agreement, or elsewhere

Information on Government priorities for health funding is available at: http://www.moh.govt.nz/nzhs.html

Criterion 9 - such other criteria as PHARMAC thinks fit.

Note that PHARMAC is not bound to accept the applicant’s evaluation of the Application against the decision criteria, and may attribute different weightings to the criteria.

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5.11

Sample

Please provide one labelled sample of the pharmaceutical inside its New Zealand packaging, as appropriate (more samples may be required). If the pharmaceutical is cytotoxic or a controlled pharmaceutical, please send a sample separately directly to the PHARMAC Medical Director with clearly labelled packaging. Nothing in this requirement to send samples acts as an exemption for the applicant from relevant legislation relating to the importation or distribution of pharmaceuticals, including but not limited to the Medicines Act 1981 (and its Regulations), the Misuse of Drugs Act 1975 or relevant patents legislation. You do not need to provide a sample with Applications for widening of access for treatments already listed on the Pharmaceutical Schedule.

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Additional Information in Applications

This section outlines the information that would be useful to provide in addition to the core information detailed in Section 5 of these Guidelines. Some of this information may not be relevant or necessary for every Application. While not compulsory, however, providing this information may reduce delays in the assessment and prioritisation of the Application. Please provide this information in a separate section from the main body of the Application. 6.1 Additional Clinical Information

The following supplementary clinical information may be provided in a separate section: (i) (ii) review articles and published critiques; publications produced by international regulatory authorities, including European Public Assessment Reports (EPARs) produced by the European Medicines Agency (EMEA) and Medical reviews produced by the American Food and Drug Administration (FDA); international guidance and assessments by regulatory authorities or health technology assessment agencies (for example, reports produced by the National Institute of Health and Clinical Excellence, Canadian Agency for Drugs and Technologies in Health, Scottish Medicines Consortium, and the Pharmaceutical Benefits Advisory Committee); published CUAs; reviews by expert bodies such as specialist colleges/professional bodies; consensus reports from expert panels; and expert opinion.

(iii)

(iv) (v) (vi) (vii)

“Expert opinion” is provided by groups with any relevant expertise in the area of concern, for example, specialist professional societies or consumer support groups. Expert opinion cannot substitute for sound scientific evidence, but will help interpret data, particularly the relevance and potential impact of clinical trial results and economic aspects. Where expert opinion is provided, applicants should justify the need for any such expert opinion, and describe the methods used to obtain and collate those opinions, which must be systematic and robust. Applications with expert opinion should include the following information: (i) (ii) (iii) (iv) criteria for selecting the experts; number of experts approached; number of experts who participated; whether a declaration of potential conflict(s) of interest was sought from all experts;

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(v) (vi) (vii) (viii) (ix) (x) (xi)

medical specialty groups whose opinions were sought; background information provided and its consistency with the totality of the evidence provided in the submission; method and medium used to collect the opinions; questions asked; whether iteration was used in the collation of opinions and, if so, how it was used; number of responses received for each question; whether all experts agreed with each response, and, if not, then the approaches used to both finalise the estimates and present the variability of the opinions; whether the experts received benefits (monetary or non-monetary) for the advice provided; and relevant conflicts of interest.

(xii) (xiii)

Applicants should indicate how the opinions have been used in the Application, and state the extent to which opinions may have varied. Any clinicians providing expert advice must declare all potential conflicts of interest, including (but not limited to) financial interests in the development of the technology, likely financial gains arising from the proposed technology and research funding. Experts must not supply any data able to identify individual patients. 6.2 Economic Analysis

PHARMAC encourages applicants to provide a cost-utility analysis (CUA) when submitting a funding Application. Providing a good quality analysis, based on the methods outlined in the PFPA, will help the Application be assessed and prioritised more quickly. If a CUA has been submitted to the Pharmaceutical Benefits Advisory Committee (PBAC) in Australia, PHARMAC will accept the same CUA in the Application to PHARMAC, providing an electronic copy of the Excel spreadsheet and/or TreeAge model are included. This ensures that PHARMAC can amend the costs (and any other relevant inputs) so the model is applicable to the New Zealand clinical and funding environment. If available, please also provide a copy of any reviews undertaken by PBAC-contracted reviewers. When PHARMAC receives a CUA from an applicant it is reviewed, and often amended. The guidelines PHARMAC uses to review analyses are included in Appendix 4 of the PFPA http://www.pharmac.govt.nz/pdf/PFPAFinal.pdf In order for PHARMAC to be able to review CUAs more efficiently, please provide a CD with a copy of the TreeAge model and/or Excel spreadsheet. If amendments have been made to the analysis, PTAC will usually be supplied with a copy of the applicant’s CUA and PHARMAC’s amended CUA, with the differences between them clearly explained.

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6.2.1

Recommended Methods for Economic Analysis

Economic analyses should be in the form of a CUA, with benefits measured in terms of quality-adjusted life years (QALYs). In cases where the clinical outcomes of the drug and the comparator have been shown to be equivalent, a cost-minimisation analysis may be appropriate. Other forms of cost-effectiveness or cost-benefit analyses (CBA) should not be provided to PHARMAC. Please avoid unnecessary complexity in the economic models, and ensure that they are transparent, well described and reproducible. The structure, data and process of building the model should be detailed enough to enable competent analysts, who are not familiar with the model, to reproduce it. The key recommendations to consider when undertaking CUAs for funding Applications (as outlined in the PFPA) are summarised in Table 5 below.

Table 5: CUA Inputs/Outputs Input / Output Perspective Target population Recommendation PHARMAC’s decision criteria. Population most likely to receive treatment. Treatment that most prescribers would replace in New Zealand clinical practice, and the treatment prescribed to the largest number of patients (if this differs from the treatment most prescribers would replace). Statistically and clinically significant outcomes obtained, preferably, from highquality RCTs, systematic reviews or meta-analyses (grade of evidence of 1+ or 1++). Include impact of non-compliance if significant. Base on NZ EQ-5D Tariff 2. Use of GBD weights to check for consistency. Pharmaceutical costs should take into account any proposed rebate, and should be based on the dose used in the key clinical trials (unless there is evidence of efficacy for different doses in clinical practice). Dispensing fees and pharmacy mark-up should be included if these are likely to differ between treatment arms. The analysis should also include the lower cost of a future generic pharmaceutical. Hospital, outpatient and direct patient costs should be included. Direct patients should be restricted to healthcare costs that the government partially subsidises, and should be based on the cost to government plus the additional cost to the patient. These costs include General Practitioner visits, pharmaceutical co-payments and continuing care. Costs to non-healthcare government departments and indirect patient costs should not be included in CUAs for PHARMAC. Discount all costs and benefits in CUAs at a 3.5% discount rate. Include rates of 0%, 5%, and 10% in sensitivity analyses. The overall incremental cost per QALY result should be reported as a point estimate as well as the range over which the cost per QALY is likely to vary. In addition, information on discounted real and nominal costs, savings, lifeexpectancy and quality of life gains/losses resulting from treatment should be reported separately.

Comparator

Clinical outcomes

HR-QOL

Pharmaceutical Costs

Other Costs

Discount rate

Results

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Input / Output

Recommendation Sensitivity analysis should include univariate (simple) analysis, multivariate analysis and extremes (scenario) analysis.

Sensitivity Analysis

6.3

Health Need and Public Health Significance

PHARMAC encourages applicants to provide further information on health needs and public health significance (beyond the information provided in Section 5.3) when submitting a funding Application. This information relates to PHARMAC’s Decision Criterion 1, and may include: (i) Description of the burden of the disease or condition (impact of the disease or condition on the individual and the community), including: • • • the annual incidence of the disease/condition in New Zealand (number of new cases each year); the morbidity associated with the condition (e.g. annual number of hospitalisations); the premature mortality associated with condition in New Zealand (e.g. annual number of deaths; number of potential years of life lost before age 80 (PYLL(80))2); the average disability-adjusted life years (DALYs) lost by an individual patient due to the disease(s)3; the population loss of disability-adjusted life years (DALY loss) for the disease(s); and the population DALY loss attributable to the disease as a percent of all diseases (where in 1996 there were 543,000 total DALY lost from all diseases4).

• • •

(ii)

Description of the estimated uptake rate of the pharmaceutical (i.e. the number of people likely to be prescribed the pharmaceutical, divided by number of people with the particular disease or condition who should benefit from the pharmaceutical). This should use both the epidemiological data above and in section 5.3 and the estimates of likely usage from section 5.3.

PYLL80 = sum across all individuals of (80 years minus age at death for an individual) Where an individual’s normal life expectancy minus their loss of disability-adjusted life years (DALY loss) from their disease/condition equals their disability-adjusted life expectancy (DALE) 4 The Burden of Disease and Injury in New Zealand. Public Health Intelligence Occasional Bulletin No. 1. Wellington: Ministry of Health, 2001. http://www.moh.govt.nz/moh.nsf/82f4780aa066f8d7cc2570bb006b5d4d/a313645fbc60bf02cc2569f400791b9b/$FILE /BurdenofDisease.pdf

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6.4

Health Need of Māori and Pacific peoples

The health needs of Māori and Pacific peoples is something PHARMAC is particularly keen to improve. This is reflected in our decision criteria (Criterion 2). PHARMAC encourages applicants, where possible, to provide information on health needs and public health significance specific to Māori and Pacific peoples when submitting a funding Application. This information should include the following: (i) A description of the availability and quality of data indicating the extent of disparity between Māori, Pacific peoples and non Māori/non Pacific people. This may include further data on disease prevalence, incidence, notifications of new cases, public hospital hospitalisations, and/or deaths. Where available, show the degree of impact of the disease on Māori and Pacific people relative to non Māori/non Pacific peoples. Please use ageadjusted relative risks for annual incidence rates for notifications, hospitalisations and mortality. In each instance this could include: • the annual number of events occurring amongst Māori, along with the age-standardised annual incidence rate per 1000 (further details below); the annual number of events occurring in Pacific people, along with the age-standardised annual incidence rate per 1000; the annual number of events in non Māori/non Pacific peoples, along with the age-standardised annual incidence rate per 1000; both risk differences for age-standardised annual incidence rates and age-adjusted rate ratios with 95% confidence limits for Māori vs. non Māori/non Pacific peoples; and both risk differences for age-standardised annual incidence rates and age-adjusted rate ratios with 95% confidence limits for Pacific peoples vs. non Māori/non Pacific peoples.

(ii)

• • •

•

(iii)

You may include, where available, the key age-specific differences in annual incidence between Māori or Pacific people and non Māori/non Pacific people. This may include data on particular age-sex specific groups for Māori/Pacific that have the greatest age-specific risk differences when compared with non Māori/non Pacific people. Comment on the extent to which annual incidence rates (notification, hospitalisation and mortality rates) correlate with the need for pharmaceuticals.

(iv)

Please use standard sources for this information (e.g. NZHIS mortality, hospitalisation and mental health data), supplemented where required by discussion with relevant experts and/or Medline searches. Sources could include prevalence data, incidence/notifications data, hospitalisation data, mental health episode data, and mortality data for relevant indicator(s). This could be combined with New Zealand age-ethnic-specific populations (available at http://www.stats.govt.nz/). Where possible, please calculate age-standardised prevalence and annual incidence rates using the direct method against Segi’s Standard World population. You can calculate age-standardised rate ratios (relative risks) and 95% confidence limits using standard binomial techniques. (Age-standardised rate ratios summarise disparity for

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Māori or Pacific people over all ages when compared with non-Māori/non Pacific, mitigating bias due to differences between ethnic groups’ age structures.) Applicants providing such information need to be aware that the use of annual incidence (notification) rates to proxy need for pharmaceuticals is valid only if survival times are similar between ethnic groups. This is often not the case with Māori and Pacific peoples, who have worse mortality and case fatality rates. In addition, hospitalisation rates do not necessarily correlate well with prevalence (here, the need for pharmaceuticals), although they might indicate the total burden of disease. 6.4.1 Background information

Historically, there have been major problems with the accuracy and validity of the data available within the New Zealand health sector, especially with ethnicity data. In general there is little relevant information available about the types of patients, disease/disability rates and pharmaceuticals used to treat primary care conditions, particularly when subdividing ethnicity by disease/indications. Mortality data are less timely than hospitalisations data and give less precise estimates of risk (because of smaller numbers of deaths). Māori death rates have in past decades been substantially under-represented because their ethnicity was often miscoded. Causes of death described on death certificates can be inaccurate. Routinely collected hospitalisations data are less accurate than mortality data-historically over onequarter of discharge diagnoses were incorrectly coded. Because hospitals had systematically under-counted Māori admissions, there were numerator-denominator mismatches. Hospital admissions only indirectly measure need, being also affected by supply factors (such as regional variations in admitting practices relating to bed/service availability and clinical protocols). This in turn affects ethnic rates. Double counting of readmissions and of inter-hospital transfers as “new” admissions further biases the data. Describing Māori or Pacific peoples’ representation (i.e. what proportion of patients in the community are Māori or Pacific peoples) has only partial relevance to PHARMAC’s decision-making. Disease prevalence does not necessarily correlate with need for pharmaceuticals. In addition, deviations from expected need for ethnic groups have little relevance if these ethnic groups are not accessing appropriate treatment. This is where accessing appropriate treatment means being able to visit a GP or similar primary care professional, the disease being identified and treatment prescribed – all equally available to non Māori. There is evidence with many aspects of healthcare that Māori access is lower than that for non-Māori.

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Reapplications

Key reasons for Reapplications include: • • new information has become available (e.g. clinical trials, cost-utility analyses); and the applicant wishes to respond to issues or questions raised by PTAC or specialist PTAC Subcommittees (as recorded in the minutes of the meeting). Information Requirements

7.1

It is important that Reapplications address all of the concerns raised by PTAC or the PTAC Subcommittee when the original Application was considered. Please provide a list of all new information (not included in the original Application or previous reapplications) along with copies of all new information and supporting documentation. Applicants are not required to provide copies of their original Application, however PHARMAC may contact you if this information is required.

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Applications for the Funding of Generic Pharmaceuticals

This section of the Guidelines should be used only for Applications to fund a generic pharmaceutical where the pharmaceutical, including the indication applied for, has previously been assessed by PHARMAC. If PHARMAC has not assessed other brands of the pharmaceutical, a full application is required. You can confirm this by contacting the relevant Therapeutic Group Manager at PHARMAC (+64 (0)4 4604990). Please provide as much of the following information as possible in your Application. 8.1 Registration and Indication

Please provide a copy of the Medsafe gazette notice and approved New Zealand data sheet. If the pharmaceutical is not registered for use in New Zealand, please outline the date, or likely date, of submission of the dossier, and whether or not this would be subject to any of Medsafe’s abbreviated registration processes. If known, please indicate the expected date of registration. Please state whether there are any differences, or likely to be any differences, in the approved indications for the pharmaceutical compared with the other brand(s) of the pharmaceutical previously considered by PHARMAC. Please also state the indication for which funding is being sought. 8.2 Pharmaceutical Information

Please provide the following pharmaceutical information: (i) (ii) the official or approved names of the pharmaceutical; available forms, strengths, pack sizes and packaging for which funding is sought (In the case of a preparation such as an aerosol, state the number of doses available from the container); whether there are any other available forms, strengths and pack sizes; if available, provide one labelled sample of the pharmaceutical inside its New Zealand packaging. If the pharmaceutical is cytotoxic or a controlled pharmaceutical, please send the sample separately directly to the PHARMAC Medical Director (note that more samples may be required later);5 detail any differences between the pharmaceutical and any other brand(s) of the pharmaceutical previously considered by PHARMAC, including (but not limited to): • • •

(iii) (iv)

(v)

differences in the efficacy, side effect and toxicity profiles; differences in the pharmacokinetic profile with respect to age, concomitant pathological status, or polymorphic metabolism; differences in the shelf-life;

Nothing in this requirement to send samples acts as an exemption for the applicant from relevant legislation relating to the importation or distribution of pharmaceuticals, including but not limited to the Medicines Act 1981 (and its Regulations), the Misuse of Drugs Act 1975 or relevant patents legislation.

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• • •

differences in appearance/taste (e.g., colour, shape, size, coating, ability to be split); difference in excipients (i.e. the inactive substances used to carry the active ingredients); and any other differences that the applicant is aware of that could be of relevance.

8.3

Price Information

Please provide the following price information: (i) (ii) the selling price (GST exclusive); and any alternative pricing proposals (e.g., possible price/volume trade-offs).

8.4

Market Information

Please provide the following market information: (i) (ii) (iii) (iv) which (if any) international markets the generic pharmaceutical is registered for use; which (if any) international markets where registration of the generic pharmaceutical has been declined; the market share of the generic pharmaceutical in international markets; and a description of uptake and acceptance of the generic in international markets. Patent Information

8.5

Please provide the information set out in Section 5.6 on each patent (granted and pending) that has claims relating to the generic pharmaceutical that is the subject of the Application, and with respect to which a claim of patent infringement could reasonably be asserted if a person, not licensed by the owner of the patent, distributed or sold the pharmaceutical in New Zealand. If you believe that there are no relevant patents with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner of the patent distributed or sold the pharmaceutical in New Zealand, please specify this in your Application. 8.6 Lead times

Please provide information about the length of time following a funding decision required to obtain sufficient stock to supply the market in New Zealand.

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9. Applications for the Funding of Blood Glucose Meter Systems

This section of the Guidelines should be used only for Applications to fund a blood glucose diagnostic test meter and/or blood glucose diagnostics test strip where the brand has not previously been assessed by PHARMAC. We recommend you discuss your blood glucose meter system by contacting the relevant Therapeutic Group Manager at PHARMAC (+64 (0)4 460-4990) before submitting your Application. Please provide as much of the following information as possible in your Application. 9.1 International information

Please provide information advising where your brand is marketed and supplied overseas and include any relevant international regulatory evaluation reports (e.g. CE Certification or FDA approval). Please state whether there are any differences in your brand of blood glucose diagnostic test meter and/or blood glucose diagnostic test strip that differ from the currently funded brands in the Pharmaceutical Schedule. 9.2 Product Information

Please provide the following product information: (i) (ii) (iii) (iv) (v) the official or approved names of the blood glucose diagnostic test meter and/or blood glucose diagnostic test strip; date of notification to WAND database; available pack sizes and packaging for which funding is sought; whether there are any other available forms, strengths and pack sizes; operating information about your brand of blood glucose diagnostic test meter and/or blood glucose diagnostic test strip, including: a. b. c. d. e. f. (vi) coding volume of blood required time taken for test temperature range of operation open and unopened strip vial stability strip expiry detection

computer software information (including the ability to download information, compatibility of software and availability of software to healthcare providers and patients); other relevant information: a. b. c. availability of an 0800 number (incl. hours of operation) repair/replacement policy other customer services

(vii)

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(viii)

if available, provide two samples of the blood glucose diagnostic test meter and/or blood glucose diagnostic test strip inside its New Zealand packaging.

9.3

Price Information

Please provide the following price information: (i) (ii) 9.4 the selling price (GST exclusive); and any alternative pricing proposals (e.g., possible price/volume trade-offs). Lead times

Please provide information about the length of time following a funding decision required to obtain sufficient stock to supply the market in New Zealand. 9.5 Product testing

Please provide local and independent testing results for your blood glucose diagnostic test meter and/or blood glucose diagnostic test strip to help determine decisions on funding of your brand by PHARMAC (and, where deemed necessary, the Pharmacology and Therapeutics Advisory Committee (PTAC) or one of the specialist PTAC Subcommittees). Details of an acceptable protocol and evaluation to compare the analytical performance of blood glucose meters on capillary whole blood samples versus reference laboratory analysis of venous plasma glucose are in Appendix 2. PHARMAC has an agreement for the provision of services relating to capillary glucose meter studies with the Canterbury District Health Board. Details for the provider and costs are also in Appendix 2. Suppliers may opt to use this provider or opt to seek the services from an alternative local and independent provider. Finally please supply eight samples to PHARMAC to allow separate field testing (including ease of use for all age groups) and associated computer software by the Diabetes Subcommittee of the Pharmacology and Therapeutic Advisory Committee (PTAC).

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Appendix 1 – Glossary

Term Definition

Absolute Risk Reduction (ARR) or Absolute Risk Increase (ARI)

The absolute difference in event rates between an intervention and its comparator.

Adherence

Continuation and consistency with recommended treatment regimen.

Applicant

Any person or organisation making an application to PHARMAC.

Application

An application or proposal made by a third party to PHARMAC for (a) the funding of a pharmaceutical; or (b) changes to the funding of a pharmaceutical that is already on the Pharmaceutical Schedule (e.g. a proposal to widen or restrict access).

Average cost

Total cost divided by total number of units.

Budget impact analysis (BIA)

Estimate of planned resource use and impact on budget over a period of time.

Community pharmaceutical

A pharmaceutical that is funded from the Pharmaceutical Budget and used in the community (i.e. outside of the hospital).

Combination product

Products that consist of two or more pharmaceuticals.

Comparator

Treatment most prescribers would replace in New Zealand clinical practice, and the treatment prescribed to the largest number of patients (if this differs from the treatment most prescribers would replace). Numerical measure of the range within which the true treatment effect is likely to lie. Result of cost-utility analysis. Monetary cost per quality-adjusted life year (QALY).

Confidence interval

Cost/QALY gained

Cost-benefit analysis (CBA)

Cost-benefit analysis (CBA) measures costs and benefits in monetary terms, and expresses the results as one figure representing the difference between benefits and costs (B-C>0), or as a ratio (B/C).

Cost-effectiveness analysis (CEA)

Cost-effectiveness analysis (CEA) compares the relative costs of interventions against some clearly definable outcome; such an outcome may be, for example, hospitalisation days avoided, strokes prevented or hip fractures averted. The final result is a value called the incremental costeffectiveness ratio (ICER).

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Term

Definition

Cost-minimisation analysis (CMA)

Cost-minimisation analysis (CMA) assumes that there is no net health change between different treatment options (i.e. there is no significant difference in the effectiveness of the treatments). In this case the analysis is essentially a search for the least costly alternative.

Cost-utility analysis (CUA)

Cost-utility analysis (CUA) is similar to CEA, but health outcomes are measured using a common denominator - quality-adjusted life-years (QALYs) gained. The incremental cost-utility ratio (ICUR) is defined as the change in the costs and benefits (where benefits are measured in terms of quality-adjusted life years) resulting from substituting one treatment for another.

Decision tree

Graphical representation of alternative treatments for use under conditions of uncertainty.

Diagnosis Related Group (DRG)

Patient classification scheme which provides a clinically meaningful way of relating the number and types of patients treated in a hospital to the resources required by the hospital.

Age standardisation (age adjustment) is a technique to better compare populations when their age profiles differ. It uses a weighting approach to match the age distribution of a common reference population, thereby obtaining a weighted average of age-specific rates to derive a summary event rate. Direct age standardisation Methods of age standardisation can be direct or indirect. Direct age standardisation gives a summary rate of events that would have been observed had the study population had the same age structure as the reference group (e.g. the number of cases of disease that would be expected if the disease rates in the study population were applied to the reference population). Further details are available in standard epidemiology texts.

Direct cost

Fixed and variable costs (medical and non-medical) directly related to the treatment.

Discount rate

Rate used to convert future costs and benefits into present values (current dollars and benefits have greater value than future dollars and benefits).

Disinvestment

May involve reduction in eligibility to a treatment (i.e. tightening of access), or cessation of treatment.

Disability-adjusted life year (DALY)

Burden of disease measure that combines years of life lost due to premature mortality and years of life lost due to time lived in states of less than full health.

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Term

Definition

District Health Board (DHB)

The Crown entities responsible for ensuring the provision of publicly funded health and disability support services for the population of a specific geographic area in New Zealand. There are currently 21 DHBs.

Health-related quality of life Hospital pharmaceutical

Physical, social and emotional aspects of patient’s well-being. Pharmaceutical that is predominantly administered within the hospital and is funded by DHBs. Benefit of treatment in ‘real world’ setting.

Effectiveness

Efficacy

Benefit of treatment in defined population in controlled or ideal circumstances (e.g. randomised controlled trials).

Exceptional Circumstances (EC) process

Exceptional Circumstances offers individuals access to medicines that aren't otherwise funded through the Pharmaceutical Schedule, or through DHB Hospitals. Separate schemes, with distinct criteria, operate for community, hospital and cancer medicines.

Gazette notice

Announcement of Medsafe approval for the marketing of a pharmaceutical in New Zealand.

Generic pharmaceutical

A pharmaceutical that contains the same active ingredients as the original branded (and usually patented) formulation. Generic pharmaceuticals are bioequivalent to the branded pharmaceutical with respect to pharmacokinetic and pharmacodynamic properties.

Graphic Appraisal Tool for Epidemiology (GATE)

Tool developed for the critical appraisal of clinical literature.

Incidence

The count of new cases of disease in a defined population during specified period of time.

Incidence rate

The count of new cases of disease in a defined population within a specified period of time, divided by the number of persons (i.e. population) at risk (or person-time) of developing the disease during that time period. The difference between the cost of an intervention and the cost of the comparator. A valid, or generally accepted, use of a medicine.

Incremental cost

Indication

Marginal cost

The additional cost of one extra unit of product or treating one additional patient.

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Term

Definition

Markov model

A statistical representation of discrete, recurrent events over time in which the probability of transition from one to another depends on the current state.

Medsafe

New Zealand Medicines and Medical Devices Safety Authority.

Medsafe datasheet

Prescribing information provided by the pharmaceutical supplier (and approved by Medsafe) on a specific medicine registered by Medsafe.

Meta-analysis

A systematic process for finding, evaluating and combining the results of data from independent sources. Simulation modelling that uses random numbers to capture effects of uncertainty. The number of patients who are treated that would lead to one additional person being harmed compared with patients who receive the control treatment. NNH=1/ARI The number of patients who need to be treated in order to prevent or create one additional event occurring over a predefined period of time. NNT=1/ARR An Act (i) to increase the availability of information to the people of New Zealand in order to (a) to enable their more effective participation in the making and administration of laws and policies and (b) to promoted the accountability of Ministers of the Crown & officials; (ii) to provide for proper access by each person to official information relating to that person; and (iii) to protect official information to the extent consistent with the public interest and the preservation of personal privacy.

Monte Carlo simulation

Number needed to harm (NNH)

Number needed to treat (NNT)

Official Information Act 1982 (OIA)

Opportunity cost

Value of the alternative options that could be undertaken with the same resources.

Patent

The official document (also known as letters patent) setting out the Government’s grant of an exclusive right to an inventor to manufacture, use, or sell an invention for a certain number of years.

Perspective

Viewpoint of analysis (e.g. funder, society, government, individual).

Pharmaceutical

Medicine, therapeutic medical device, or related product.

Pharmaceutical Benefits Advisory Committee (PBAC)

Independent statutory body in Australia that makes recommendations and gives advice to the Australian Minister of Health about which drugs and medicinal preparations should be made available as pharmaceutical benefits.

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Term

Definition

Pharmaceutical Budget

The budget set by the Minister of Health for the funding of community pharmaceuticals – those medicines dispensed by a community pharmacist. It does not include funding for hospital or cancer medicines (both of which are funded by District Health Boards); funding for PHARMAC’s operations; or payments for distribution (such as the fees a pharmacist receives).

Pharmaceutical Management Agency (PHARMAC)

The New Zealand Crown Entity directly accountable to the Minister of Health for, amongst other things, the management of the Pharmaceutical Schedule.

Pharmaceutical Schedule

List of pharmaceuticals available in the community and subsidised with funding from the Pharmaceutical Budget, and also the list of some pharmaceuticals purchased by DHBs for use in their hospitals (including those where PHARMAC has negotiated a national price).

Pharmacology and Therapeutic Advisory Committee (PTAC)

An expert committee of senior health practitioners which provides objective advice to PHARMAC on pharmaceuticals and their benefits.

Prescription for Pharmacoeconomic Analysis (PFPA)

The document that provides an overview of PHARMAC’s cost-utility analysis methodology.

Prevalence

The number of existing cases of disease in a defined population at a notional point in time.

Prevalence rate

The number of existing cases of disease in a defined population at a notional point in time, divided by the number of persons in the population at that time.

PYLL(80)

Potential Years of Life Lost before the age of 80. PYLL measures the time (in years) lost by a population due to premature death. This involves choosing an arbitrary limit to life, so that the duration of life lost due to each death is that potential limit minus the age at death. In the case of PYLL(80), the arbitrary age limit chosen is 80 years. Note that the subtraction is truncated, so that any deaths occurring after people attain that arbitrary age limit have a potential loss of life of zero years.

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Term

Definition

A QALY (‘quality adjusted life year’) is a standard economic measure, which combines the effects of changes in the length and quality of life that result from treatment. Quality-adjusted life-years help compare gains in the quality of life with gains in the quantity (length) of life, in a simple and direct manner. Quality-adjusted life years Quality of life weightings (or utilities) are typically measured on a scale of 0 (QALY) to 1, where 0 is equivalent to death and 1 to perfect health. These weights can then be summed over life expectancy in order to calculate the total number of QALYs. The difference in QALYs and overall costs gained between two treatments informs the relative cost-effectiveness of an intervention.

Relative risk

Ratio of incidence of disease in exposed group divided by incidence of disease in non-exposed (control) group.

Relative Risk Increase (RRI)

Proportional increase in rates of events between the experimental group and control group.

Relative Risk Reduction (RRR)

The relative (not absolute) difference in events between two treatment groups, expressed as a proportion of the event rate in the untreated group. Similar to RRI, a RRR is therefore a proportional decrease in rates of events between the control and experimental group.

Sensitivity analysis

Process through which the robustness of an economic model is assessed by examining the changes in the result of the analysis when key variables are varied over a specified range.

Special Authority criteria

A Subsidy or additional Subsidy may only be claimed for certain pharmaceuticals if an application, relating to the specific patient, meeting the Special Authority criteria specified in the Schedule has been approved, and the valid Special Authority number is present on the prescription.

Subsidy

The maximum amount paid to a person, entitled to receive payment from the Crown (usually a pharmacy), for the supply of a pharmaceutical to a patient (this may not be the same as the final cost paid by the Crown, depending on the nature of PHARMAC’s contractual arrangements with the pharmaceutical supplier).

Technology Assessment Report (TAR)

Documentation of the economic analysis (including cost-utility analysis).

Therapeutic Group Manager (TGM)

PHARMAC staff member responsible for managing PHARMAC’s processes for pharmaceutical funding, within an assigned therapeutic group.

TreeAge

Decision analysis software used for modelling cost-effectiveness.

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Term

Definition

Utility

Values of the strength of preferences for, or desirability of, a specific level of health status or a specific health outcome.

Value for money

Refers to whether the benefits of a pharmaceutical are considered significant enough to compensate for the cost.

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Appendix 2 – Protocol and evaluation of Self Monitoring Blood Glucose systems

PHARMAC has an agreement for the provision of services relating to capillary glucose meter studies with the Canterbury District Health Board. Suppliers may opt to use this agreement or opt to seek the services from an alternative local and independent provider. The aim of the evaluation is to compare the analytical performance of the blood glucose meter on capillary whole blood samples versus reference laboratory analysis of venous plasma glucose. The performance of self monitoring blood glucose (SMBG) meters should be assessed by comparing capillary blood sample results from two meters of each make, with a simultaneously collected venous sample. The venous samples should be spun down immediately and analysed promptly by a reference laboratory. Samples should be collected from 50 outpatients with diabetes, with either type 1 or type 2 diabetes (aiming to have a wide spread of glucose results) and a current haematocrit >0.30. The sample size should be increased to 100 patients if results from the evaluation of 50 patients are inconclusive or uncertain. The capillary glucose result used in the final analysis should be the mean of the two results collected from each make of meter. Imprecision of the meters should be assessed by repeating glucose estimation 20 times on high and low test solutions as supplied by the supplier and also using patient’s venous whole blood samples stabilised in a fluoride tube. The supplier is responsible for all costs of an evaluation. PHARMAC has a fixed price agreement with the Christchurch Diabetes Centre (an operating unit of Canterbury District Health Board) to perform these evaluations if a supplier wishes to utilise this service agreement. The cost (exclusive of GST) of full formal evaluations and indicative timelines involved are as follow:

Service One capillary glucose meter study completed within 4 months One capillary glucose meter study ‘fast tracked’ within 2 months Two capillary glucose meter studies completed simultaneously within 4 months Two capillary glucose meter studies ‘fast tracked’ simultaneously within 2 months Three capillary glucose meter studies completed simultaneously within 4 months Three capillary glucose meter studies ‘fast tracked’ simultaneously within 2 months Service Fee $20,000 $30,000 $25,000 $35,000 $26,000 $36,000

PHARMAC may be aware of other suppliers wishing to undertake a study and where possible will help try to coordinate such studies to reduce costs. The Service Fee will be discounted by 15% (inclusive of GST) in the event that the supplier agrees that the Christchurch Diabetes Centre may use results of the study in an independent academic study looking at variation in the difference between venous and capillary glucose in relation to postprandial states. Suppliers would be responsible for providing the evaluator with sufficient consumables (including two different batches of test strips). Please note that the time frames above exclude delays outside the Christchurch Diabetes Centre’s control, such as unforeseen delays in ethics approval or delays in the supply of meter testing equipment.

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The supplier has the opportunity to provide the evaluator with a face-to-face instruction on the use of the meter and test strips but any additional communications with the supplier should be made via PHARMAC only to ensure the independence of the study. Meter performance should be assessed in the ambulatory (outpatient) setting only; i.e. there is no expectation that performance should be assessed in specialist settings such as neonatal ICU. Accuracy should be assessed relative to the reference method by Bland–Altman plots, Passing and Bablok regression analysis, and both Clarke and consensus (Parkes) error grid analyses. The results from the Christchurch Diabetes Centre will be provided to the supplier and PHARMAC. The Christchurch Diabetes Centre will obtain regional ethics committee approval for an evaluation. The Christchurch Diabetes Centre is bound to a confidentiality agreement with PHARMAC relating to the data and information provided to it during the evaluation. Bench-top evaluations performed to assess minor changes in performance claims for existing funded products should be discussed with PHARMAC. These will be considered on a case-by-case basis following a summary from the supplier of the proposed changes. The paper referenced below6 provides full details of the methodology used by the Christchurch Diabetes Centre.

Comparison of blood glucose meters in a New Zealand diabetes centre. Florkowski et al. Ann Clin Biochem.2009; 46: 302-305 (http://acb.rsmjournals.com/cgi/content/full/46/4/302)

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Metadata

Title

Guidelines for Funding Applications to PHARMAC 2010

Abstract

Guidelines for Funding Applications to PHARMAC Version 2 2009 Foreword PHARMAC, the Pharmaceutical Management Agency, is primarily responsible for managing the funding of community pharmaceuticals for New Zealanders, on behalf of the District Health Boards. PHARMAC’s objective is to secure,…

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