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

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4.5 Additional work on clinical effectiveness undertaken by the ERG Two further pieces of work were undertaken by the ERG. 4.5.1 Reanalysis of the MTC data The ERG undertook a reanalysis of the MTC data, using a uniform prior distribution for the between- study standard deviation. The results of these analyses are presented in Tables 18 to 21. Table 18.1: VTE recurrence (time to event, hazard ratio) - U(0,5) Node mean SD 2.5% Median 97.5% hr[1,2] 4257.0 913800.0 0.05213 1.413 36.73 hr[1,3] 204.5 36370.0 0.04103 0.6809 11.65 hr[2,3] 1.05 24.82 0.09175 0.481 2.665 SD 0.8579 0.9667 0.02001 0.5008 3.818 1, rivaroxaban; 2, long term LMWH; 3, dual heparin/VKA; SD, standard deviation; HR, hazard ratio. Table 18.2: VTE recurrence (time to event, hazard ratio) - U(0,2) Node mean SD 2.5% Median 97.5% hr[1,2] 2.579 13.32 0.1825 1.397 10.1 hr[1,3] 1.028 3.577 0.1262 0.6744 3.641 hr[2,3] 0.5614 0.4551 0.1694 0.4834 1.465 SD 0.5654 0.4812 0.0197 0.4226 1.781 1, rivaroxaban; 2, long term LMWH; 3, dual heparin/VKA; SD, standard deviation; HR, hazard ratio. Table 18.3: VTE recurrence (time to event, hazard ratio) - U(0, 0.6) Node mean SD 2.5% Median 97.5% hr[1,2] 1.6 0.8766 0.5388 1.425 3.761 hr[1,3] 0.7305 0.3047 0.3136 0.679 1.481 hr[2,3] 0.4988 0.1546 0.2634 0.4771 0.8666 SD 0.2575 0.1673 0.01116 0.2379 0.5753 1, rivaroxaban; 2, long term LMWH; 3, dual heparin/VKA; SD, standard deviation; HR, hazard ratio. Table 19.1: VTE recurrence (dichotomous, odds ratio) - U(0,5) Node mean sd 2.5% Median 97.5% OR[1,2] 19.26 2634.0 0.3259 1.581 8.435 OR[1,3] 4.246 702.8 0.1686 0.6932 2.893 OR[2,3] 0.4745 0.4347 0.1954 0.4371 0.9269 SD 0.4643 0.5073 0.0126 0.3127 1.851 1, rivaroxaban; 2, long term LMWH; 3, dual heparin/VKA; SD, standard deviation; OR, odds ratio. 79 Copyright 2012 Queen's Printer and Controller of HMSO. All rights reserved.
Table 19.2: VTE recurrence (dichotomous, odds ratio) - U(0,2) Node mean sd 2.5% median 97.5% OR[1,2] 2.252 9.066 0.3722 1.584 7.045 OR[1,3] 0.8805 2.129 0.1894 0.6921 2.487 OR[2,3] 0.4623 0.1921 0.208 0.4359 0.8791 SD 0.4209 0.3839 0.0123 0.3094 1.49 1, rivaroxaban; 2, long term LMWH; 3, dual heparin/VKA; SD, standard deviation; OR, odds ratio. Table 19.3: VTE recurrence (dichotomous, odds ratio) - U(0,0.6) node mean sd 2.5% median 97.5% OR[1,2] 1.761 0.9156 0.6393 1.574 4.018 OR[1,3] 0.741 0.2956 0.3236 0.6925 1.453 OR[2,3] 0.4529 0.123 0.2543 0.4391 0.734 SD 0.2451 0.1634 0.01065 0.2216 0.5708 1, rivaroxaban; 2, long term LMWH; 3, dual heparin/VKA; SD, standard deviation; OR, odds ratio. Table 20.1: Major bleeding - U(0,5) Node mean SD 2.5% median 97.5% OR[1,2] 928.1 133100.0 0.01326 0.6181 23.07 OR[1,3] 210.4 45210.0 0.02496 0.6895 18.93 OR[2,3] 2.034 18.77 0.2127 1.112 6.936 SD 1.179 0.9652 0.05568 0.9129 3.872 1, rivaroxaban; 2, long term LMWH; 3, dual heparin/VKA; SD, standard deviation; OR, odds ratio. Table 20.2: Major bleeding - U(0,2) Node mean SD 2.5% median 97.5% OR[1,2] 1.486 8.315 0.05049 0.6249 7.029 OR[1,3] 1.32 4.627 0.0781 0.6875 6.001 OR[2,3] 1.323 1.04 0.3503 1.1 3.748 SD 0.8268 0.505 0.04997 0.7602 1.877 1, rivaroxaban; 2, long term LMWH; 3, dual heparin/VKA; SD, standard deviation; OR, odds ratio. Table 20.3: Major bleeding - U(0,0.6) Node mean SD 2.5% median 97.5% OR[1,2] 0.7642 0.5353 0.188 0.6373 2.114 OR[1,3] 0.7856 0.4423 0.2464 0.6899 1.904 OR[2,3] 1.145 0.3875 0.5686 1.087 2.069 SD 0.3279 0.1693 0.02132 0.342 0.5874 1, rivaroxaban; 2, long term LMWH; 3, dual heparin/VKA; SD, standard deviation; OR, odds ratio. 80 Copyright 2012 Queen's Printer and Controller of HMSO. All rights reserved.
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Rivaroxaban for the treatment of de
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TABLE OF CONTENTS List of Abbreviat
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Table 12 Time to therapeutic INR (I
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identified in the model). Table 40
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Figures Figure 1 Flow diagram for i
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Figure 23 Exploratory analysis in c
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MS Manufacturer’s submission NE S
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The dose of LMWH used reflects Amer
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xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
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The exploratory analysis in cancer
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intended treatment duration of 12 m
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VTE therefore has a substantial bur
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indefinite treatment. VTE LMWH, low
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3 Critique of manufacturer’s defi
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Subgroups to be considered Special
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contraindications for the drug (as
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3.1.3 MTC populations The populatio
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3.2.2 Length of treatment As discus
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“No preventative therapy” is th
Page 39 and 40: It could be argued that poor TTR ma
Page 41 and 42: 3.4.2 Outcomes recommended by EMA r
Page 43 and 44: 4 CLINICAL EFFECTIVENESS 4.1 Critiq
Page 45 and 46: competitor products were excluded f
Page 47 and 48: Figure 1 Flow diagram for identifyi
Page 49 and 50: Table 7: Table showing list of rele
Page 51 and 52: The approach taken to quality asses
Page 53 and 54: o EINSTEIN-DVT dose-ranging study 3
Page 55 and 56: Trial name References, study type E
Page 57 and 58: 4.2.1 Critique of pivotal EINSTEIN-
Page 59 and 60: However, the study design did not i
Page 61 and 62: Table 10: Summary of outcomes for E
Page 63 and 64: Chi-square analyses were undertaken
Page 65 and 66: clarification on this matter, the m
Page 67 and 68: Both of these factors are likely to
Page 69 and 70: It remains unclear why these patien
Page 71 and 72: leeding may be less suited to longe
Page 73 and 74: may account for the apparent differ
Page 75 and 76: Table 13: Criteria used to define a
Page 77 and 78: DVT and/or PE xxxxxxxxx xxxxxxxxxxx
Page 79 and 80: There is some doubt about the appro
Page 81 and 82: Subgroup analyses - EINSTEIN-Ext Su
Page 83 and 84: o It is clear that bleed events wer
Page 85 and 86: is likely to be small as the outcom
Page 87 and 88: depends on the specific parameteris
Page 89: 4.4.3 Between study standard deviat
Page 93 and 94: Table 22 Uncertainties in clinical
Page 95 and 96: The ERG are of the understanding th
Page 97 and 98: For the primary analysis, the rates
Page 99 and 100: In the economic model, the manufact
Page 101 and 102: Finally, in cancer patients, the ma
Page 103 and 104: Our experts believed that patients
Page 105 and 106: Similarly, the manufacturer used da
Page 107 and 108: Table 25: baseline risk of events f
Page 109 and 110: y intended treatment duration given
Page 111 and 112: eflect the current long term risk o
Page 113 and 114: survival of 70% in the 148 non-surg
Page 115 and 116: Monitoring xxxxxxxxxxxxxxxxxxxxxxxx
Page 117 and 118: The ERG acknowledges that the monit
Page 119 and 120: For patients managed in the inpatie
Page 121 and 122: The searches identified 2,811 poten
Page 123 and 124: The health state utility value for
Page 125 and 126: xxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxx
Page 127 and 128: few occasions for both VTEs and ble
Page 129 and 130: 2) the values used in the PSA for t
Page 131 and 132: 5.2.1 Results included in the manuf
Page 133 and 134: Figure 8: Tornado plot - Net Moneta
Page 135 and 136: 5.2.2.1.2. Results for patients for
Page 137 and 138: Figure 12: Cost-effectiveness plane
Page 139 and 140: 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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