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

More documents

Recommendations

Info

and the xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx (see section “sufficient compliance” below), txxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx. Compliance would therefore not appear to be likely to provide an explanation for the apparent differences in efficacy, where rivaroxaban appears to have superior efficacy in comparison to enoxaparin/VKA in these subgroups. xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx Subgroup analyses suggested in NICE scope. Nice requested subgroup analyses according to Underlying risk of recurrent VTE including the presence of active cancer Underlying risk of bleeding (for example people over 60 years of age) Only one of the subgroup analyses suggested by NICE were provided, that for the cancer subgroup, via an MTC. The ERG asked for clarification on why other groups were not included in the trial, as the marketing authorisation and draft SmPC do not exclude use in some of the excluded groups (see section 3.1.1above). The manufacturer responded that as the comparator in the trial was enoxaparin with VKA, it would not have been ethical to include groups contraindicated for this treatment. Whilst this is a reasonable argument, it is not an insurmountable obstacle, and the trial could have been designed to allow for use of appropriate treatment in subgroups of patients contraindicated for enoxaparin with VKA. As it is, it is very difficult to draw conclusions as to the safety and efficacy in these patient groups. The manufacturer also argue that risk:benefit of anticoagulation in relation to bleeding was considered when allocating patients to the intended treatment duration, “since patients at higher (lower) risk of 59 Copyright 2012 Queen's Printer and Controller of HMSO. All rights reserved.
leeding may be less suited to longer (shorter) duration anticoagulation.” (page 9, manufacturer’s clarifications), 17 and therefore the need for a subgroup analysis is negated. Whilst this may be an adequate way of dealing with those with a higher risk of bleeding who were included in the trial, it does not provide data on those subgroups who were not included, or provide any indication of how they would have benefited from rivaroxaban. Creatinine clearance. The ERG asked for clarification on the exclusion of patients with creatinine clearance
Page 1 and 2:
Rivaroxaban for the treatment of de
Page 3 and 4:
TABLE OF CONTENTS List of Abbreviat
Page 5 and 6:
Table 12 Time to therapeutic INR (I
Page 7 and 8:
identified in the model). Table 40
Page 9 and 10:
Figures Figure 1 Flow diagram for i
Page 11 and 12:
Figure 23 Exploratory analysis in c
Page 13 and 14:
MS Manufacturer’s submission NE S
Page 15 and 16:
The dose of LMWH used reflects Amer
Page 17 and 18:
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Page 19 and 20: The exploratory analysis in cancer
Page 21 and 22: intended treatment duration of 12 m
Page 23 and 24: VTE therefore has a substantial bur
Page 25 and 26: indefinite treatment. VTE LMWH, low
Page 27 and 28: 3 Critique of manufacturer’s defi
Page 29 and 30: Subgroups to be considered Special
Page 31 and 32: contraindications for the drug (as
Page 33 and 34: 3.1.3 MTC populations The populatio
Page 35 and 36: 3.2.2 Length of treatment As discus
Page 37 and 38: “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: It remains unclear why these patien
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 and 90: 4.4.3 Between study standard deviat
Page 91 and 92: Table 19.2: VTE recurrence (dichoto
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
Page 141 and 142:
5.2.2.2 Subgroup analysis - cancer
Page 143 and 144:
Figure 17: Tornado plot - Net Monet
Page 145 and 146:
5.2.3 Comment on validity of result
Page 147 and 148:
Table 36: Summary of uncertainties
Page 149 and 150:
Summary of uncertainties Has the im
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Superseded - See Erratum 6. ADDITIO
Page 157 and 158:
Superseded - See Erratum Table 37 S
Page 159 and 160:
Superseded - See Erratum Table 38:
Page 161 and 162:
Page 163 and 164:
Superseded - See Erratum Figure 21:
Page 165 and 166:
Page 167 and 168:
Superseded - See Erratum 6.3. Proba
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
6.5. Exploratory analysis in cancer
Page 175 and 176:
Figure 23: Exploratory analysis in
Page 177 and 178:
Table 60: Deterministic base case a
Page 179 and 180:
The ERG also examined the impact of
Page 181 and 182:
days after stopping treatment.(Bull
Page 183 and 184:
Both Phase II studies performed ana
Page 185 and 186:
Appendix 2 Correction of Tables 29
Page 187 and 188:
Appendix 3 Definition of `sufficien
Page 189 and 190:
A bullet on page 42 states that `53
Page 191 and 192:
Both numbers refer to the placebo a
Page 193 and 194:
9. REFERENCES 1. Bayer PLC. Rivarox
Page 195 and 196:
http://www.dh.gov.uk/en/Publication
Page 197 and 198:
51. Department of Health. NHS Refer
Page 199:
77. NICE Guidance. Atrial fibrillat
show all

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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?