Chlormethine Gel for Treating Mycosis Fungoides-Type Cutaneous T- Cell Lymphoma [ID1589]
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Chlormethine gel for treating mycosis fungoides-type cutaneous T- cell lymphoma [ID1589] Produced by Aberdeen HTA Group Authors Dwayne Boyers1 Elisabet Jacobsen1 Clare Robertson3 Mari Imamura3 Dolapo Ayansina2 Paul Manson3 Gavin Preston4 Miriam Brazzelli3 1 Health Economics Research Unit, University of Aberdeen, UK 2 Medical Statistics Team, University of Aberdeen, UK 3 Health Services Research Unit, University of Aberdeen, UK 4 NHS Grampian, Aberdeen Royal Infirmary, Aberdeen, UK Correspondence to Miriam Brazzelli, Reader (Research) University of Aberdeen, Health Services Research Unit Foresterhill, Aberdeen, AB25 2ZD Email: [email protected] Date completed: 14 April 2020 Version: 2.0 (revised after factual error check) Copyright belongs to University of Aberdeen HTA Group, unless otherwise stated. : Copyright 2020 Queen's Printer and Controller of HMSO. All rights reserved. Source of funding: This report was commissioned by the NIHR Systematic Reviews Programme as project number 130927. Declared competing interests of the authors No competing interests to disclose. Acknowledgements The authors are grateful to Lara Kemp for providing administrative support. Copyright is retained by Recordati Rare Diseases/Helsinn Healthcare SA for Figures 1, 2, 3, 4, 5 and 6, and Table 8. Rider on responsibility for report The view expressed in this report are those of the authors and not necessarily those of the NIHR HTA Programme. Any errors are the responsibility of the authors. This report should be referenced as follows: Boyers D, Jacobsen E, Robertson C, Imamura M, Ayansina D, Manson P, Preston G, Brazzelli M. Chlormethine gel for treating mycosis fungoides-type cutaneous T-cell lymphoma. Aberdeen HTA Group, 2020. Contribution of authors Clare Robertson and Mari Imamura summarised and critiqued the company’s definition of the decision problem and the clinical effectiveness evidence reported within the company submission. Dolapo Ayansina critiqued the statistical methods and analyses presented in the company submission and checked all the numerical results related to the review of the clinical effectiveness evidence. Dwayne Boyers and Elisabet Jacobsen critiqued the cost-effectiveness evidence submitted by the company, checked their economic model, and conducted further sensitivity analyses. Paul Manson critiqued the methods used for identifying relevant studies and checked the search strategies presented in the company submission. Gavin Preston provided clinical advice during the appraisal. Miriam Brazzelli acted as lead for the clinical effectiveness side of the appraisal. Dwayne Boyers acted as lead for the cost- effectiveness side of the appraisal. All authors contributed to the writing of this report and approved its final version. ii : Copyright 2020 Queen's Printer and Controller of HMSO. All rights reserved. CONFIDENTIAL UNTIL PUBLISHED Table of contents List of tables vi List of figures viii List of abbreviations ix 1 EXECUTIVE SUMMARY 1 1.1 Critique of the decision problem in the company’s 1 submission 1.2 Summary of the key issues in the clinical effectiveness 5 evidence 1.3 Summary of the key issues in the cost-effectiveness evidence 6 1.4 Summary of ERG’s preferred assumptions and resulting 8 ICER 1.5 Summary of exploratory and sensitivity analyses undertaken 10 by the ERG 2 INTRODUCTION AND BACKGROUND 13 2.1 Introduction 13 2.2 Background 13 2.3 Critique of company’s definition of decision problem 16 3 CLINICAL EFFECTIVENESS 22 3.1 Critique of the methods of review(s) 22 3.2 Critique of trials of the technology of interest, the company’s 25 analysis and interpretation (and any standard meta-analyses of these) 3.2.1 Included study 25 3.2.2 Primary and secondary efficacy endpoints 30 3.2.3 Health-related quality of life (HRQOL) measures 38 3.2.4 Adverse effects of treatment 38 iii : Copyright 2020 Queen's Printer and Controller of HMSO. All rights reserved. CONFIDENTIAL UNTIL PUBLISHED 3.2.5 Subgroup analyses 41 3.2.6 Meta-analyses 41 3.3 Critique of trials identified and included in the indirect 43 comparison and/or multiple treatment comparison 3.3.1 Indirect treatment comparison (ITC) 43 3.3.2 Naïve indirect comparison 43 3.4 Critique of the indirect comparison and/or multiple 50 treatment comparison 3.4.1 Indirect treatment comparison (ITC) 50 3.4.2 Naïve indirect comparison 50 3.5 Additional work on clinical effectiveness undertaken by the 50 ERG 3.6 Conclusions of the clinical effectiveness section 54 4 COST-EFFECTIVENESS 55 4.1 ERG comment on company’s review of cost-effectiveness 55 evidence 4.2 Summary and critique of the company’s submitted economic 59 evaluation by the ERG 4.2.1 NICE reference case checklist 59 4.2.2 Model structure 61 4.2.3 Population 64 4.2.4 Interventions and comparators 65 4.2.5 Perspective, time horizon and discounting 67 4.2.6 Treatment effectiveness and extrapolation 67 4.2.7 Health related quality of life 75 4.2.8 Resources and costs 78 5 COST-EFFECTIVENESS RESULTS 84 5.1 Company’s cost-effectiveness results 84 iv : Copyright 2020 Queen's Printer and Controller of HMSO. All rights reserved. CONFIDENTIAL UNTIL PUBLISHED 5.2 Company’s sensitivity analyses 85 5.3 Model validation and face validity check 93 6 EVIDENCE REVIEW GROUP’S ADDITIONAL 95 ANALYSES 6.1 Exploratory and sensitivity analyses undertaken by the ERG 95 6.2 Impact on the ICER of additional clinical and economic 103 analyses undertaken by the ERG 6.3 ERG’s preferred assumptions 109 6.4 Conclusions of the cost-effectiveness section 117 7 REFERENCES 120 8 APPENDICES 127 v : Copyright 2020 Queen's Printer and Controller of HMSO. All rights reserved. CONFIDENTIAL UNTIL PUBLISHED List of tables Table 1 Differences between the company decision problem 2 and final scope issued by NICE Table 2 ICER resulting from ERG’s preferred assumptions 10 Table 3 Exploratory analyses undertaken by ERG 11 Table 4 Summary of the decision problem 17 Table 5 ERG appraisal of the systematic review methods 23 presented in the CS Table 6 Quality assessment of the company’s systematic 24 review of clinical effectiveness evidence Table 7 Characteristics of Study 201, Study 202 and relevant 28 observational studies that provide additional data on the effectiveness and safety of chlormethine gel Table 8 Outcome definitions in Study 201 (reproduced from 30 Table 9, Document B of the CS) Table 9 Secondary endpoints in Study 201 (ITT including 34 NYU population) Table 10 Summary response data for Study 201, French ATU 37 study and PROVe study Table 11 Summary of adverse events (AEs) reported in Study 42 201, Study 202, MIDAS study, French ATU study and PROVe study Table 12 Summary of the characteristics of the 9 comparator 45 RCTs considered for the indirect treatment comparison (ITC) [adapted from Table 26, Section B.2.9, and Tables 12 and 13, Appendix D.5.1, of the CS] Table 13 Summary of the 7 phototherapy efficacy studies (3 48 RCTs and 4 non-RCTs) considered for the naïve unadjusted indirect comparison (adapted from Table 26, Section B.2.9, and Tables 12 and 13, Appendix D.5.1, of the CS) vi : Copyright 2020 Queen's Printer and Controller of HMSO. All rights reserved. CONFIDENTIAL UNTIL PUBLISHED Table 14 Summary of the studies comparing psoralen–UV-A 52 phototherapy (PUVA) with narrowband UV-B (NBUBV) included in the Phan et al. (2019) systematic review Table 15 Relevance of studies identified in company’s 56 literature review Table 16 NICE reference case checklist 59 Table 17 Definitions of skin burden health status 62 Table 18 Alternative sources of transition probabilities for 69 underlying disease progression Table 19 Sources of alternative CR and PR considered for use 71 in the economic model Table 20 Transition to 2nd line treatment following a CR and 74 PR on phototherapy, comparing company and ERG alternative assumptions. Table 21 Health state utility values applied in the economic 75 model Table 22 Summary of modelled adverse events and costs 82 Table 23 Company preferred deterministic base-case results 84 Table 24 Probabilistic sensitivity analysis results (company’s 86 preferred base case analysis) Table 25 Scenario analysis results – applied to company’s 89 revised preferred base case analysis Table 26 Black box’ verification checks conducted on the 94 company submitted model Table 27 ERG justification for additional exploratory and 96 sensitivity analyses Table 28 ERG’s scenario analyses surrounding company’s base 104 case (ERG’s preferred assumptions in bold) Table 29 Cumulative impact of ERG preferred assumptions on 111 the ICER Table 30 Scenario analyses surrounding ERG preferred base- 113 case vii : Copyright 2020 Queen's Printer and Controller of HMSO. All rights reserved. CONFIDENTIAL UNTIL PUBLISHED List of figures Figure 1 A summary of the treatment options for MF-CTCL 15 (both SDTs and systemic therapies) in UK clinical practice [reproduced from Figure 2, Document B of the C] Figure 2 Scatter plot of PSA results on the cost-effectiveness 87 plane (company’s preferred base case analysis) Figure 3 CEAC (company’s preferred base case analysis) 87 Figure 4 ICER tornado diagram (company’s preferred base 88 case analysis) Figure 5 Scatter plot of the cost-effectiveness plane for ERG’s 116 preferred base case analysis Figure 6 CEAC for ERG’s preferred base case analysis 117 viii : Copyright 2020 Queen's Printer and Controller of HMSO. All rights reserved. CONFIDENTIAL UNTIL PUBLISHED List of abbreviations AE Adverse event BAD British Association of Dermatologists BSA Body surface area CAILS Composite Assessment of Index Lesion