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

xxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxx
Once the manufacturer calculated the baseline risk of events for patients treated with
rivaroxaban, the next step was to estimate the risk of events for patients treated with
LMWH. This was done by applying a HR/RR to the baseline risk of events. The
manufacturer conducted an MTC in the absence of direct evidence and applied the
reciprocated HR/RR for rivaroxaban vs. LMWH in the economic model to estimate the
risk of events in LMWH patients. The HR/RR were calculated from the median and
assuming a between study variability of U(0,5).
Before inversion, the HR/RRs for rivaroxaban against LMWH were:
o VTE recurrence: HR of 1.440 (95% CI 0.070 to 31.400)
o Major bleeding: HR of 0.640 (95% CI 0.010 to 30.100)
o CRNM bleeding: RR of 1.320 (95% CI 0.090 to 18.700)
The manufacturer assumed that cancer patients are treated with LMWH only (dalteparin)
and did not include monitoring costs.
The manufacturer also included some costs associated with transportation and
administration by district nurses for patients treated with LMWH.
Finally, the manufacturer assumed a median survival of 5 years for cancer patients based
on data from Rachet et al (2010) 75 to reflect the poorer prognosis (lower life expectancy)
of patients with cancer.
The ERG acknowledges the positive response from the manufacturer and the efforts made to provide
an exploratory analysis in the subgroup of patients with cancer. Nevertheless, the ERG has some
concerns with the approach used by the manufacturer and the robustness of the analysis.
1) The ERG has some concerns on the robustness of the estimated treatment effect (taken from
the MTC conducted by the manufacturer). As previously described (Section 4.4), the
manufacturer used a uniform prior distribution for the between-study standard deviation of
U(0,5) when synthesising hazard ratios and odds ratios in the MTC. The ERG believes that a
smaller between-study standard deviation is more appropriate, such as U(0,2) or U(0,0.6).
2) In addition, the manufacturer used the treatment effect calculated from the median instead of
the mean, which is believed to be more appropriate by the ERG in an economic evaluation.
114
Copyright 2012 Queen's Printer and Controller of HMSO. All rights reserved.