Rivaroxaban for the treatment of deep vein thrombosis and ...

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Rider on responsibility for report: The views 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: Harnan, S, Rafia, R, Poku, E, Stevens, J W, Stevenson, M, Wong, R. Rivaroxaban for the treatment of deep vein thrombosis and secondary prevention of venous thromboembolism: A Single Technology Appraisal. ScHARR, The University of Sheffield, 2012. Contributions of authors The review of the clinical evidence was undertaken by Sue Harnan and Edith Poku. The review of the cost-effectiveness evidence was undertaken by Rachid Rafia and Matt Stevenson. John Stevens undertook the review of the mixed treatment comparison meta-analysis. Ruth Wong re-ran the searches included in the manufacturer’s submission. Matt Stevenson advised the project. Acknowledgements Dr Raj Patel (Consultant Haematologist, Kings Thrombosis Centre) and Dr Eddie Hampton (Senior Lecturer in Haematology, University of Sheffield) provided advice during the project. Matt Stevenson (Technical Director, ScHARR Technology Assessment Group) and Kumar Perampaladas (Technical Lead, NICE) commented on a draft version of the report. The authors wish to thank all of the above. We would also like to thank Gill Rooney, Project Administrator, ScHARR, for her help in preparing and formatting the report. Declared competing interests of the authors: Dr Raj Patel declared no competing interests. Dr Eddie Hampton declared no competing interests. Copyright 2012 Queen's Printer and Controller of HMSO. All rights reserved.
TABLE OF CONTENTS List of Abbreviations 1 1 SUMMARY 3 2 BACKGROUND 11 3 Critique of manufacturer’s definition of decision problem 16 3.1 Population 16 3.2 Intervention 22 3.3 Comparators 24 3.4 Outcomes 28 3.5 Other relevant factors 31 4 CLINICAL EFFECTIVENESS 32 4.1 Critique of the methods of review(s) 32 4.2 Critique of trials of the technology of interest, their analysis and interpretation (and any standard meta-analyses of these) 4.3 Critique of trials identified and included in the indirect comparison and/or multiple treatment comparison 4.4 Critique of the indirect comparison and/or multiple treatment comparison 4.5 Additional work on clinical effectiveness undertaken by the ERG 79 4.6 Conclusions of the clinical effectiveness section 81 5 COST EFFECTIVENESS 85 5.1 Review of the cost-effectiveness evidence 85 5.2 Summary and critique of the manufacturer’s submitted economic evaluation 6 ADDITIONAL WORK UNDERTAKEN BY THE ERG 144 6.1 6.2 6.3 Probabilistic cost-effectiveness results in patients for whom 3 months of anticoagulation treatment is appropriate – exploratory analyses conducted by the ERG. Probabilistic cost-effectiveness results in patients for whom 6 months of anticoagulation treatment is appropriate – exploratory analyses conducted by the ERG. Probabilistic cost-effectiveness results in patients for whom 12 months of anticoagulation treatment is appropriate – exploratory Copyright 2012 Queen's Printer and Controller of HMSO. All rights reserved. 41 70 74 85 145 151 156
Page 1: Rivaroxaban for the treatment of de
Page 5 and 6: Table 12 Time to therapeutic INR (I
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o EINSTEIN-DVT dose-ranging study 3
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Trial name References, study type E
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4.2.1 Critique of pivotal EINSTEIN-
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However, the study design did not i
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Table 10: Summary of outcomes for E
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Chi-square analyses were undertaken
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clarification on this matter, the m
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Both of these factors are likely to
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It remains unclear why these patien
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leeding may be less suited to longe
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may account for the apparent differ
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Table 13: Criteria used to define a
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DVT and/or PE xxxxxxxxx xxxxxxxxxxx
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There is some doubt about the appro
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Subgroup analyses - EINSTEIN-Ext Su
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o It is clear that bleed events wer
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is likely to be small as the outcom
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depends on the specific parameteris
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4.4.3 Between study standard deviat
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Table 19.2: VTE recurrence (dichoto
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Table 22 Uncertainties in clinical
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The ERG are of the understanding th
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For the primary analysis, the rates
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In the economic model, the manufact
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Finally, in cancer patients, the ma
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Our experts believed that patients
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Similarly, the manufacturer used da
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Table 25: baseline risk of events f
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y intended treatment duration given
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eflect the current long term risk o
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survival of 70% in the 148 non-surg
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Monitoring xxxxxxxxxxxxxxxxxxxxxxxx
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The ERG acknowledges that the monit
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For patients managed in the inpatie
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The searches identified 2,811 poten
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The health state utility value for
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xxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxx
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few occasions for both VTEs and ble
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2) the values used in the PSA for t
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5.2.1 Results included in the manuf
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Figure 8: Tornado plot - Net Moneta
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5.2.2.1.2. Results for patients for
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Figure 12: Cost-effectiveness plane
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Figure 14: Tornado plot - Net Monet
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5.2.2.2 Subgroup analysis - cancer
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Figure 17: Tornado plot - Net Monet
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5.2.3 Comment on validity of result
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Table 36: Summary of uncertainties
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Summary of uncertainties Has the im
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Superseded - See Erratum 6. ADDITIO
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Superseded - See Erratum Table 37 S
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Superseded - See Erratum Table 38:
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Superseded - See Erratum Figure 21:
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Superseded - See Erratum 6.3. Proba
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6.5. Exploratory analysis in cancer
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Figure 23: Exploratory analysis in
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Table 60: Deterministic base case a
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The ERG also examined the impact of
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days after stopping treatment.(Bull
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Both Phase II studies performed ana
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Appendix 2 Correction of Tables 29
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Appendix 3 Definition of `sufficien
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A bullet on page 42 states that `53
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Both numbers refer to the placebo a
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9. REFERENCES 1. Bayer PLC. Rivarox
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http://www.dh.gov.uk/en/Publication
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51. Department of Health. NHS Refer
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77. NICE Guidance. Atrial fibrillat
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