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

y intended treatment duration given the small sample size when splitting patients by treatment arms
and intended treatment duration.
The manufacturer assumed that the probability that a major bleeding event is an IC bleeding event
(conditional on one occurring) was the same between the two treatment arms in the economic model
(12.5%). It is unclear why the manufacturer assumed this to be the same irrespective of the treatment
arm (and intended treatment duration). No data was presented to support or reject this assumption.
The split between intracranial/extracranial (IC/EC) bleeds is likely to affect the ICER as IC bleeds are
associated with greater cost implication and reduction in QoL compared with EC bleeds. The impact
of this assumption in the model has not been formally examined in the economic model by the ERG
in the absence of data by treatment arm. This remains an area of uncertainty in the model. If the
proportion of major bleeding events that are IC bleeds is higher in the rivaroxaban arm, this
assumption will favour rivaroxaban. If the proportion is higher in the dual therapy LMWH/VKA arm,
this assumption will favour the dual therapy arm.
Discontinuation rate
The discontinuation rate whilst on treatment was taken from the EINSTEIN-DVT trial, 50 and was
assumed to be the same irrespective of the initial treatment received and intended treatment duration. 1
The manufacturer included the following reasons for discontinuation: non compliant with study
medication, protocol violation, patient convenience, switch to commercial drug, insufficient
therapeutic effect and bleeding adverse events. The manufacturer reported the total discontinuation for
those reasons: xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx. This equated to an overall 3 month probability of xxxxxxxxx.
The model additionally assumes that all patients with IC bleeds, xxx of patients with major EC bleeds
and xxx of patients with CRNM bleeds discontinue treatment, based on
xxxxxxxxxxxxxxxxxxxxxxxxxxxx.
The MS stated that assuming the same discontinuation rate irrespective of the initial treatment was a
conservative assumption; 1 however the ERG disagrees with this xxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx.
There is also double counting as the manufacturer included bleeding events to calculate the
discontinuation rate whilst this was already included in the economic model. The discontinuation rate
was calculated from the whole trial population, rather than specifically by intended treatment
duration. There was also a mismatch between the economic model and the report, as the manufacturer
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