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

Records excluded were described in the flow diagram. This stated ‘Most were duplicates,
review articles, editorials, non-English language publications related to included RCTs or
concerning orthopaedic or non-VTE indications.’ This reporting lacks clarity, in that the
numbers of articles excluded for each category are not given. For most categories, this is not
of great importance. However, where English language is used as a selection criterion, it is
usual to list how many potentially includable studies with potentially relevant data were
excluded on this basis, to give some indication of the risk of language bias affecting the
results.
Overall, the above points are thought unlikely by the ERG to introduce any significant bias to the
review.
In relation to study selection, the presentation of two unpublished studies in the “Overview of
rivaroxaban trials” (presented in Table 5, section 5.2.3 of the MS), 1 namely the CYP cohort and
EINSTEIN-PE study, was not necessary, as these studies do not fall within the NICE scope or the
inclusion/exclusion criteria. However, the manufacturer’s provision of information related to them is
appreciated by the ERG, by way of explanation of their exclusion.
The MS presented a list of four RCTs comprising two Phase II studies and two Phase III studies 21,35,36
(Table 6 in MS, page 32, reproduced here as Table 7) comparing the intervention with other therapies
in the population group as defined by the selection criteria, which is reproduced in Table 6.
Of the listed RCTs, the MS highlighted two Phase III randomised controlled trials as the main sources
of clinical evidence for rivaroxaban treatment in patients with DVT and the prophylaxis of recurrent
DVT and PE. The studies were the EINSTEIN-DVT study 21 and the EINSTEIN-Ext study 21 . The
Phase II studies, the Oral Direct Factor Xa Inhibitor BAY-59-7939 in Patients with Acute
Symptomatic Deep-Vein Thrombosis (ODIXa-DVT) study 35 and EINSTEIN dose-ranging Phase II 36
study did not directly contribute data for the review of clinical effectiveness. However, the
manufacturer stated that these were included as they informed the selection of rivaroxaban doses and
also served as supportive evidence on the efficacy and safety of rivaroxaban. These studies are
summarised in Appendix 1.
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