Technical Guidelines for preparing assessment reports for the Medical Services Advisory Committee – Medical Service Type: Therapeutic

(Version 2.0)

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

Foreword i

Contents

Foreword i

Contacts xi

Record of updates xii

Abbreviations xiv

PART I General information 1

1 Medical Services Advisory Committee 2

1.1 Purpose and roles of MSAC 2

1.2 Membership of MSAC 2

1.3 MSAC sub-committees 2

1.4 Overview of MSAC processes 3

1.4.1 Regulatory framework 3

1.4.2 The application and assessment process 3

1.4.3 Sources of advice 3

1.4.4 Publication of assessment report 3

1.4.5 Timing of MSAC processes 4

1.4.6 MSAC appraisal 4

2 Introduction to the Guidelines 5

2.1 Structure of these Guidelines 5

2.2 Associated documents 5

2.3 What is a therapeutic medical service? 6

2.4 Writing and style conventions used in these Guidelines 6

2.5 The future 7

3 Rationale and basis for the economic evaluation in the Australian context 8

3.1 Analysis of cost-effectiveness 8

3.2 Australian context 8

3.3 Relevant factors influencing MSAC decision making 8

3.4 Flexibility in interpretation of these Guidelines 9

4 Organisation of a standard assessment report 10

4.1 Choice of information 10

4.2 Overview of a standard assessment report 11

4.2.1 Sections of a standard assessment report 11

4.3 Presentation of the assessment report 11

4.3.1 Standard assessment report 11

4.3.2 Two stage approach to an assessment 13

4.3.3 Co-dependent/integrated assessment reports 13

5 Lodging an assessment report 14

5.1 Assessment report checklist 14

5.1.1 Information requirements 14

5.1.2 Information requests 14

5.2 Provision of information to allow independent verification of computer analyses 16

5.2.1 Information requirements 16

5.3 Provision of information after lodgement of the assessment report 16

5.3.1 Post-lodgement communication with MSAC 16

5.3.2 Provision of information sourced from the TGA after lodgement of the assessment report 16

Part II Preferred clinical and economic evidence for proposed medical services to be considered by MSAC 17

Section A Details of the proposed therapeutic medical service and its intended use on the Medical Benefits Schedule (or for other public funding) 18

A1 Address all items in the agreed PICO Confirmation 18

A2 Proposed medical service 18

A3 Proposed MBS listing or other public funding sought 18

A4 Proposed population 18

A5 Comparator details 18

A6 Clinical management algorithm(s) 19

A6.1 Algorithms for intended and current contexts 19

A7 Differences between the proposed medical service and the main comparator 20

A8 Clinical claim 20

A9 Summarise the primary elements of the decision analysis (PICO) 20

Section B Clinical evaluation for the proposed therapeutic medical service 21

B1 Description of search strategies 23

B2 Listing all direct randomised trials 24

B3 Assessment of the measures taken by investigators to minimise bias 30

B4 Characteristics of the trials 33

B5 Outcome measures and analysis 34

B6 Systematic overview of the results 38

B7 Extended assessment of comparative harms 46

B8 Interpretation of the clinical evidence 46

Section C Translation Issues 49

C1 Identification of issues to be addressed 51

C2 Focused analytical plan 56

C3 Results of pre-modelling studies 68

C4 Relationship of each pre-modelling study to the economic evaluation 69

Section D Economic evaluation for the main indication 71

D.1 Overview of the economic evaluation 73

D2 Population and circumstances of use reflected in the economic evaluation 80

D3 Structure and rationale of the economic evaluation 85

D4 Variables in the economic evaluation 93

D5 Results of the economic evaluation 100

D6 Sensitivity analyses 107

Section E Estimated utilisation and financial implications 110

E1 Justification of the selection of sources of data 112

E2 Estimation of use and costs of the proposed medical service 114

E3 Estimation of changes in use and cost of other medical services 117

E4 Estimated financial implications for the MBS 118

E5 Identification, estimation and reduction of uncertainty 119

Section F Options to present additional relevant information 122

F1 Other relevant factors 122

Part III Alternative clinical evidence for proposed medical services to be considered by MSAC 125

Section B(i) Clinical evaluation for the main indication: indirect comparison of randomised trials 126

B(i)1 Description of search strategies 128

B(i)2 Listing all randomised trials considered for inclusion in indirect comparisons 128

B(i)3 Assessment of the measures taken by investigators to minimise bias 132

B(i)4 Characteristics of the trials 132

B(i)5 Outcome measures 133

B(i)6 Results 133

B(i)7 Extended assessment of comparative harms 134

B(i)8 Interpretation of the clinical evidence 135

Section B(ii) Clinical evaluation for the main indication: Presenting non-randomised studies 136

B(ii)1 Description of search strategies 138

B(ii)2 Listing all non-randomised studies 138

B(ii)3 Assessment of the measures taken by investigators to minimise bias 140

B(ii)4 Characteristics of the studies 142

B(ii)5 Outcome measures 142

B(ii)6 Results of the comparison involving non-randomised studies 142

B(ii)7 Extended assessment of comparative harms 142

B(ii)8 Interpretation of the clinical evidence 143

Section C(i) Translating the clinical evaluation: indirect comparisons of randomised trials or non-randomised studies 144

C(i)1 Relevant pre-modelling studies 145

Section D(i) Economic evaluation for the main indication: presenting a cost-minimisation approach 147

D(i)1 Cost-minimisation analysis 147

D(i)2 Presentation of a cost-minimisation analysis or a cost analysis 149

Appendices 151

Appendix 1 Relevant factors influencing provision of advice by MSAC 152

Appendix 2 Expert opinion 154

A2.1 Uses of expert opinion 154

A2.2 Presenting expert opinion 155

A2.3 Describing the collection and collation of expert opinion 155

Appendix 3 Assessment of non-inferiority 158

A3.1 Introduction 158

A3.2 Service delivery information 158

A3.3 Non-inferiority threshold 158

A3.4 Method of analysis 159

A3.5 Presenting an assessment of non-inferiority 159

A3.6 Assessing comparative harms in the context of non-inferiority 160

A3.7 Interpretation of the clinical evidence 160

Appendix 4 Utility valuation of health outcomes 161

A4.1 Use of health-related QALYs gained and cost-utility analysis 161

A4.2 Obtaining utility weights 162

A4.3 Trial-based utility valuation of health outcomes 163

A4.4 Scenario-based utility valuation of health outcomes 165

A4.5 Other methods for obtaining utilities 172

Appendix 5 Monetary valuation of healthoutcomes 175

A5.1 Preference for cost-utility analyses over cost-benefit analyses 175

A5.2 Scenario-based monetary valuation of health outcomes 176

Appendix 6 Including non-health care resources and non-health outcomes in a supplementary analysis 181

A6.1 Identifying, measuring and valuing non-health care resources 181

A6.2 Identifying, measuring and valuing non-health outcomes 181

A6.3 Resources and outcomes to be excluded 184

Appendix 7 Measures taken by the investigators to minimise bias in non-randomised studies 185

A7.1 Classical observational designs 185

A7.2 Quasi-experimental designs 187

Tables and Figures

Figure 4.1 Sections of a standard assessment report 12

Table 5.1 Checklist of information to be included in a therapeutic assessment report 15

FigureB1 Key information requests for assessment report Section B of an assessment for MSAC 22

Table B2.1 Summary of identification of direct randomised trials from the search of the published literature 25

Table B2.2 Summary of identification of applicants’a direct randomised trials and information from the manual search of retrieved citations 26

Table B2.3 Trials (and associated reports) presented in the assessment report 27

Table B2.4 Reasons to exclude each trial from further detailed assessment 28

Table B2.5 Comparative summary of characteristics of each direct randomised trial 28

Table B2.6 Comparative summary of results of each direct randomised trial 29

BoxB3.1 Checklist for assessing the quality (internal validity) of randomised trials 30

Table B3.1 Summary of the measures undertaken to minimise bias in the direct randomised trials 32

Table B3.2 Flow of participants through the direct randomised trials 32

Table B4.1 Eligibility criteria 33

Table B4.2 Characteristics of participants across randomised groups 33

Table B4.3 Therapeutic medical services compared in trials 34

Table B5.1 Primary outcomes and statistical analyses of the direct randomised trials 35

Table B5.2 Patient-relevant secondary outcomes and analyses 36

Table B6.1 Results of [patient-relevant outcome] (available as dichotomous data) across the direct randomised trials (relative risk) 41

Table B6.2 Results of [patient-relevant outcome] (available as dichotomous data) across the direct randomised trials (risk difference) 41

Table B6.3 Results of [patient-relevant outcome] (available as continuous data) across the direct randomised trials (end point) 42

Table B6.4 Results of [patient-relevant outcome] (available as continuous data) across the direct randomised trials (change) 42

Table B6.5 Results of [patient-relevant outcome] across the direct randomised trials (available as time-to-event data) 44

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 47

Table C2.1 Assessment of treatment effect variation across subgroups 60

Table C2.2 Assessment of relative treatment effect variation across subgroups 61

Table C2.3 Assessment of absolute treatment effect variation across subgroups 62

Table C2.4 Summary of assessment of treatment effect variation across subgroups 63

Table C2.5 Reasons to exclude each direct randomised trial 67

Table C4.1 Summary of results of pre-modelling studies and their uses in the economic evaluation 70

Figure D1 Key information requests for assessment report Section D of a standard assessment for MSAC 72

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 75

TableD1.2 Type of economic evaluation that should be presented for various classifications of a service under MSAC consideration 77

Table D2.1 Definitions for populations and circumstance of use that should be taken into account in the evaluation 80

Table D2.2 Comparison of characteristics of trial and requested populations and circumstances of use 82

TableD2.3 Example of a comparison of the characteristics of target, study and wider populations and settings 84

FigureD3.1 Example of the structure of a basic economic evaluation 87

TableD3.1 Key elements of the base-case economic evaluation 89

Table D4.1 List of health care resource items and unit costs included in the economic evaluation 97

Table D5.1 List of health care resource items and summary of cost impacts in the economic evaluation 102

Table D5.2 List of health care resource items and summary of cost impacts for each health state in a state transition model 102

Table D5.3 List of health states and summary of cost impacts included in the economic evaluation 102

Table D5.4 List of health states and summary of health outcomes included in the economic evaluation 103

Table D5.5 Assessment of the implications for the economic evaluation of applying the clinical evaluation (Step1 then Step2) 106

Table D5.6 Assessment of the implications for the economic evaluation of extrapolating and transforming the clinical evaluation (Step3) 107

Table D6.1 Analyses of the implications for the economic evaluation of usage beyond the requested populations and circumstances of use 109

Figure E1 Key information requests for assessment report Section E of a standard assessment for MSAC 111

TableE1.1 Categories of data sources 113

Figure B(i)1 Key information requests for assessment report Section B of a standard assessment for MSAC with clinical data from an indirect comparison of randomised trials 127

Table B(i)2.1 Trials (and associated reports) presented in the assessment report 130

Table B(i)2.2 Reasons to exclude each trial from the indirect comparison 131

Table B(i)2.3 Summary of randomised trials used to conduct the indirect comparison 132

Table B(i)6.1 Summary of results of the indirect comparison of randomised trials 134

Figure B(ii)1 Key information requests for assessment report SectionBof a standard assessment for MSAC with clinical data from non-randomised studies 137

Table B(ii)2.1 Studies (and associated reports) presented in the assessment report 139

Table B(ii)2.2 Reasons to exclude each study 140

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)) 144

Figure D(i)1 Key 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 148

TableA1.1 Factors that are more readily quantified 152

TableA1.2 Examples of factors that are less readily quantified 153

Table A2.1 Methods to collect and collate expert opinion 156

Contents iii

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