Editorial Review of PBAC Submission Guidelines

Technical GuidelinesforpreparingassessmentreportsfortheMedicalServicesAdvisoryCommittee– Medical Service Type: Therapeutic

(Version2.0)

March 2016

Medical Services Advisory Committee

Foreword

The Medical Services Advisory Committee (MSAC) is an independent committee that provides advice to the Minister for Health on the strength of the evidence relating to the comparative safety, clinical effectiveness and cost-effectiveness of any new or existing medical services or technology, and the circumstances under which public funding should be supported through listing on the Medical Benefits Schedule (MBS).

To achieve this, MSAC undertakes Health Technology Assessments (HTA) using the best available evidence to assess proposals for their comparative safety, clinical effectiveness, and cost effectiveness.

Applications for therapeutic services provide applicants with a number of challenges, requiring them to prove that both the proposed service provides accurate, meaningful information and also that the information improves the subsequent treatment (and health outcomes) of patients.

This document provides detailed advice to assist applicants with determining content and presentation of submissions of evidence for consideration by MSAC and the Evaluation Sub-committee (ESC).

This document provides detailed advice to assist applicants with determining content and presentation of submissions of evidence for consideration by the MSAC and the ESC.

Chair
Medical Services Advisory Committee

Foreword1

Contents

Foreword......

Contacts......

Record of updates

Abbreviations......

PART I General information

1Medical Services Advisory Committee

1.1Purpose and roles of MSAC

1.2Membership of MSAC

1.3MSAC sub-committees

1.4Overview of MSAC processes

1.4.1Regulatory framework

1.4.2The application and assessment process

1.4.3Sources of advice

1.4.4Publication of assessment report

1.4.5Timing of MSAC processes

1.4.6MSAC appraisal

2Introduction to the Guidelines

2.1Structure of these Guidelines

2.2Associated documents

2.3What is a therapeutic medical service?

2.4Writing and style conventions used in these Guidelines

2.5The future

3Rationale and basis for the economic evaluation in the Australian context

3.1Analysis of cost-effectiveness

3.2Australian context

3.3Relevant factors influencing MSAC decision making

3.4Flexibility in interpretation of these Guidelines

4Organisation of a standard assessment report

4.1Choice of information

4.2Overview of a standard assessment report

4.2.1Sections of a standard assessment report

4.3Presentation of the assessment report

4.3.1Standard assessment report

4.3.2Two stage approach to an assessment

4.3.3Co-dependent/integrated assessment reports

5Lodging an assessment report

5.1Assessment report checklist

5.1.1Information requirements

5.1.2Information requests

5.2Provision of information to allow independent verification of computer analyses

5.2.1Information requirements

5.3Provision of information after lodgement of the assessment report

5.3.1Post-lodgement communication with MSAC

5.3.2Provision of information sourced from the TGA after lodgement of the assessment report

Part IIPreferred clinical and economic evidence for proposed medical services to be considered by MSAC

Section ADetails of the proposed therapeutic medical service and its intended use on the Medical Benefits Schedule (or for other public funding)

A1Address all items in the agreed PICO Confirmation

A2Proposed medical service

A3Proposed MBS listing or other public funding sought

A4Proposed population

A5Comparator details

A6Clinical management algorithm(s)

A6.1Algorithms for intended and current contexts

A7Differences between the proposed medical service and the main comparator

A8Clinical claim

A9Summarise the primary elements of the decision analysis (PICO)

Section BClinical evaluation for the proposed therapeutic medical service

B1Description of search strategies

B2Listing all direct randomised trials

B3Assessment of the measures taken by investigators to minimise bias

B4Characteristics of the trials

B5Outcome measures and analysis

B6Systematic overview of the results

B7Extended assessment of comparative harms

B8Interpretation of the clinical evidence

Section CTranslation Issues

C1Identification of issues to be addressed

C2Focused analytical plan

C3Results of pre-modelling studies

C4Relationship of each pre-modelling study to the economic evaluation

Section DEconomic evaluation for the main indication

D.1Overview of the economic evaluation

D2Population and circumstances of use reflected in the economic evaluation

D3Structure and rationale of the economic evaluation

D4Variables in the economic evaluation

D5Results of the economic evaluation

D6Sensitivity analyses

Section EEstimated utilisation and financial implications

E1Justification of the selection of sources of data

E2Estimation of use and costs of the proposed medical service

E3Estimation of changes in use and cost of other medical services

E4Estimated financial implications for the MBS

E5Identification, estimation and reduction of uncertainty

Section FOptions to present additional relevant information

F1Other relevant factors

Part IIIAlternative clinical evidence for proposed medical services to be considered by MSAC

Section B(i)Clinical evaluation for the main indication: indirect comparison of randomised trials

B(i)1Description of search strategies

B(i)2Listing all randomised trials considered for inclusion in indirect comparisons

B(i)3Assessment of the measures taken by investigators to minimise bias

B(i)4Characteristics of the trials

B(i)5Outcome measures

B(i)6Results

B(i)7Extended assessment of comparative harms

B(i)8Interpretation of the clinical evidence

Section B(ii)Clinical evaluation for the main indication: Presenting non-randomised studies

B(ii)1Description of search strategies

B(ii)2Listing all non-randomised studies

B(ii)3Assessment of the measures taken by investigators to minimise bias

B(ii)4Characteristics of the studies

B(ii)5Outcome measures

B(ii)6Results of the comparison involving non-randomised studies

B(ii)7Extended assessment of comparative harms

B(ii)8Interpretation of the clinical evidence

Section C(i)Translating the clinical evaluation: indirect comparisons of randomised trials or non-randomised studies

C(i)1Relevant pre-modelling studies

Section D(i)Economic evaluation for the main indication: presenting a cost-minimisation approach

D(i)1Cost-minimisation analysis

D(i)2Presentation of a cost-minimisation analysis or a cost analysis

Appendices

Appendix 1Relevant factors influencing provision of advice by MSAC

Appendix 2Expert opinion

A2.1Uses of expert opinion

A2.2Presenting expert opinion

A2.3Describing the collection and collation of expert opinion

Appendix 3Assessment of non-inferiority

A3.1Introduction

A3.2Service delivery information

A3.3Non-inferiority threshold

A3.4Method of analysis

A3.5Presenting an assessment of non-inferiority

A3.6Assessing comparative harms in the context of non-inferiority

A3.7Interpretation of the clinical evidence

Appendix 4Utility valuation of health outcomes

A4.1Use of health-related QALYs gained and cost-utility analysis

A4.2Obtaining utility weights

A4.3Trial-based utility valuation of health outcomes

A4.4Scenario-based utility valuation of health outcomes

A4.5Other methods for obtaining utilities

Appendix 5Monetary valuation of healthoutcomes

A5.1Preference for cost-utility analyses over cost-benefit analyses

A5.2Scenario-based monetary valuation of health outcomes

Appendix 6Including non-health care resources and non-health outcomes in a supplementary analysis

A6.1Identifying, measuring and valuing non-health care resources

A6.2Identifying, measuring and valuing non-health outcomes

A6.3Resources and outcomes to be excluded

Appendix 7Measures taken by the investigators to minimise bias in non-randomised studies

A7.1Classical observational designs

A7.2Quasi-experimental designs

Tables and Figures

Figure 4.1Sections of a standard assessment report

Table 5.1Checklist of information to be included in a therapeutic assessment report

FigureB1...... Key information requests for assessment report Section B of an assessment for MSAC

Table B2.1Summary of identification of direct randomised trials from the search of the published literature

Table B2.2Summary of identification of applicants’a direct randomised trials and information from the manual search of retrieved citations

Table B2.3Trials (and associated reports) presented in the assessment report

Table B2.4Reasons to exclude each trial from further detailed assessment

Table B2.5Comparative summary of characteristics of each direct randomised trial

Table B2.6Comparative summary of results of each direct randomised trial

BoxB3.1...... Checklist for assessing the quality (internal validity) of randomised trials

Table B3.1Summary of the measures undertaken to minimise bias in the direct randomised trials

Table B3.2Flow of participants through the direct randomised trials

Table B4.1Eligibility criteria

Table B4.2Characteristics of participants across randomised groups

Table B4.3Therapeutic medical services compared in trials

Table B5.1Primary outcomes and statistical analyses of the direct randomised trials

Table B5.2Patient-relevant secondary outcomes and analyses

Table B6.1Results of [patient-relevant outcome] (available as dichotomous data) across the direct randomised trials (relative risk)

Table B6.2Results of [patient-relevant outcome] (available as dichotomous data) across the direct randomised trials (risk difference)

Table B6.3Results of [patient-relevant outcome] (available as continuous data) across the direct randomised trials (end point)

Table B6.4Results of [patient-relevant outcome] (available as continuous data) across the direct randomised trials (change)

Table B6.5Results of [patient-relevant outcome] across the direct randomised trials (available as time-to-event data)

TableB8.1...... Classification of the comparative effectiveness and safety of the proposed therapeutic medical service compared with its main comparator and guide to the suitable type of economic evaluation

Table C2.1Assessment of treatment effect variation across subgroups

Table C2.2Assessment of relative treatment effect variation across subgroups

Table C2.3Assessment of absolute treatment effect variation across subgroups

Table C2.4Summary of assessment of treatment effect variation across subgroups

Table C2.5Reasons to exclude each direct randomised trial

Table C4.1Summary of results of pre-modelling studies and their uses in the economic evaluation

Figure D1Key information requests for assessment report Section D of a standard assessment for MSAC

TableD1.1...... Classification of a service under MSAC consideration/Classification of the effectiveness of the proposed medical service over its main comparator and guide to the suitable type of economic evaluation

TableD1.2...... Type of economic evaluation that should be presented for various classifications of a service under MSAC consideration

Table D2.1Definitions for populations and circumstance of use that should be taken into account in the evaluation

Table D2.2Comparison of characteristics of trial and requested populations and circumstances of use

TableD2.3...... Example of a comparison of the characteristics of target, study and wider populations and settings

FigureD3.1...... Example of the structure of a basic economic evaluation

TableD3.1...... Key elements of the base-case economic evaluation

Table D4.1List of health care resource items and unit costs included in the economic evaluation

Table D5.1List of health care resource items and summary of cost impacts in the economic evaluation

Table D5.2List of health care resource items and summary of cost impacts for each health state in a state transition model

Table D5.3List of health states and summary of cost impacts included in the economic evaluation

Table D5.4List of health states and summary of health outcomes included in the economic evaluation

Table D5.5Assessment of the implications for the economic evaluation of applying the clinical evaluation (Step1 then Step2)

Table D5.6Assessment of the implications for the economic evaluation of extrapolating and transforming the clinical evaluation (Step3)

Table D6.1Analyses of the implications for the economic evaluation of usage beyond the requested populations and circumstances of use

Figure E1Key information requests for assessment report Section E of a standard assessment for MSAC

TableE1.1...... Categories of data sources

Figure B(i)1Key information requests for assessment report Section B of a standard assessment for MSAC with clinical data from an indirect comparison of randomised trials

Table B(i)2.1Trials (and associated reports) presented in the assessment report

Table B(i)2.2Reasons to exclude each trial from the indirect comparison

Table B(i)2.3Summary of randomised trials used to conduct the indirect comparison

Table B(i)6.1Summary of results of the indirect comparison of randomised trials

Figure B(ii)1Key information requests for assessment report SectionBof a standard assessment for MSAC with clinical data from non-randomised studies

Table B(ii)2.1Studies (and associated reports) presented in the assessment report

Table B(ii)2.2Reasons to exclude each study

Figure C(i)1 Key information requests for assessment report Section C of a standard assessment for MSAC with clinical data from an indirect comparison of randomised trials (SectionB(i)) or from non-randomised studies (Section B(ii))

Figure D(i)1Key information requests for assessment report Section D of a standard assessment for MSAC in which the therapeutic conclusion from assessment report Section B is non-inferior

TableA1.1...... Factors that are more readily quantified

TableA1.2...... Examples of factors that are less readily quantified

Table A2.1Methods to collect and collate expert opinion

Contents1

Contacts

The Medical Services Advisory Committee (MSAC) and its two sub-committees have secretariats within the Australian Government Department of Health.

Departmental Staff are available through the Health Technology Assessment (HTA) Team on the contact numbers and email below to discuss proposals for MSAC consideration or related matters. Any correspondence or assessment reports should also be lodged at via the address below. Staff within the HTA Team are also the first point of contact concerning the relevant committee or sub-committee’s discussions and decisions.

HTA Team

Australian Government Department of Health

MDP 851

GPO Box 9848

CANBERRA ACT 2601

Or courier

Sirius Building

23 Furzer Street

PHILLIP ACT 2602

Phone: +61 2 6289 7550

Fax: +61 2 6289 5540
Website:

Email:

1

Recordofupdates

1

Abbreviations

1

PARTI
Generalinformation

1

1Medical Services Advisory Committee

1.1Purpose and roles of MSAC

The Medical Services Advisory Committee (MSAC) is a non-statutory committee established by the Australian Government Minister for Health in 1998. MSAC appraises new medical services proposed for public funding, and provides advice to Government about the level and quality of evidence relating to the comparative safety, clinical effectiveness, and cost-effectiveness of such services. Amendments and reviews of existing services funded by the Medicare Benefit Schedule (MBS) or other programs (for example, blood products or screening programs) are also considered by MSAC.

The MSAC advises the Minister for Health on medical services in relation to:

• the strength of evidence about the comparative safety, effectiveness, cost-effectiveness and total cost of the medical service;
• whether public funding should be supported for the medical service and, if so, the circumstances under which public funding should be supported;
• the proposed MBS item descriptor and fee for the service where funding through the MBS is supported; and
• other matters related to the public funding of health services referred by the Minister for Health.

MSAC also advises the Australian Health Ministers’ Advisory Council (AHMAC) on health technology assessments referred under AHMAC arrangements.

There is no obligation on Government to accept or implement the advice MSAC provides.

1.2Membership of MSAC

MSAC is an independent expert committee comprising professionals from the fields of clinical medicine, health economics and consumer matters. The Minister for Health determines the size and composition of MSAC. Members are drawn from a wide range of experts, constituted from time-to-time to address the likely type of applications for the committee’s consideration. The current membership of MSAC is available on the MSAC website

1.3MSAC sub-committees

MSAC currently has two sub-committees: the PICO Advisory Sub-committee (PASC) and the Evaluation Sub-committee (ESC). MSAC also has an Executive Committee (made up of the chairs of MSAC, ESC and PASC, and also the Deputy Chair of MSAC) to manage MSAC activities between formal committee meetings.

1.4Overview of MSAC processes

1.4.1Regulatory framework

All therapeutic goods used in the provision of medical services must be assessed by the Therapeutic Goods Administration (TGA) and included on the Australian Register of Therapeutic Goods (ARTG) before they can be marketed in Australia.

As a general rule, MSAC does not support public funding for a service that uses a therapeutic good for indications beyond those for which it was included on the ARTG.

An application to MSAC can be lodged before relevant therapeutic goods are included on the ARTG provided that the applicant has evidence that the relevant sponsor has commenced the TGA process. Confirmation of inclusion on the ARTG is required before MSAC can finalise its own appraisal of the corresponding medical service.

In considering whether to advise listing a service on the MBS, MSAC considers whether the service meets the criteria laid down in the Health Insurance Act 1973, and takes advice from the Department of Health on legal and policy matters as required.

1.4.2The application and assessment process

The approach to seeking MSAC advice to government for public funding is broken up into stages that provide stakeholders and the general public with opportunities to be actively engaged in the consultation phases, as well as opportunities for further applicant engagement throughout the process.

Unlike applications to the Pharmaceutical Benefits Advisory Committee (PBAC) and the Prostheses List Advisory Committee (PLAC), the costs incurred in submitting an application to MSAC isnot recovered from the applicant. To ensure that only relevant information is collected, the scope of every application is determined before evidence is compiled.

MSAC may seek co-applicants or co-sponsors to broaden the scope of an application. In some instances, a professional body and more than one commercial company might be co-applicants in a combined application.

1.4.3Sources of advice

In formulating its advice, MSAC and its sub-committees may seek expert opinion from relevant professional bodies or appropriate specialists, and input from appropriate consumer bodies. Where external advice is obtained, the applicant is informed of the advice and given an opportunity to reply.