Assumption on Non-inferiority
The economic model assumed equal efficacy between rivaroxaban and enoxaparin plus VKA based on the non-inferiority results from the EINSTEIN PE trial. However, the assumption of non-inferiority is uncertain (see CADTH Common Drug Review [CDR] Clinical Report).
Assumption on Long-Term Efficacy
The economic model continued to assume equal efficacy between rivaroxaban and enoxaparin plus VKA after 12 months, which might not be the case, as indicated in the CDR Clinical Report, because of premature discontinuation in the trial. If the efficacy assumptions do not persist beyond 12 months, the cost-effectiveness of rivaroxaban will be less attractive. If rivaroxaban net efficacy over the long term (≥ 12 months) is less than that of LMWH plus VKA, rivaroxaban would be dominated (more costly and less effective).
Assumption on Monitoring Cost
While there is some uncertainty in the true cost of VKA monitoring, the costs of physician consultations and PT tests are obtained from a Canadian study, and are tested in the sensitivity analysis. As above, if actual monitoring costs are less than estimated, the cost savings of rivaroxaban are attenuated. This is fully explored in CDR sensitivity analysis (Table 5 and Table 6 in Appendix 1); rivaroxaban is no longer cost saving at six months if there are five physician consultations (versus eight in the base case) during the first three months. Further, if a greater proportion of patients are monitored through an anticoagulation clinic (estimated to have lower per-consultation costs), the cost savings are attenuated. In addition, almost 38% of the rivaroxaban patients in the EINSTEIN PE trial received VKA or heparin in addition to their assigned treatment, which may attenuate monitoring cost and drug (versus LMWH) savings. However, VKA or heparin are likely used for a short duration and would be unlikely to meaningfully alter conclusions.
Interpretation of Time of Duration
While not explicitly described in the manufacturer’s submission, it appears that the treatment time durations used represent duration for all patients (and not a maximum duration, with some patients having shorter duration). Therefore, if 60% of patients are treated for six months and 40% are treated for 12 months [(60% × −$113) + (40% × $152)], net cost may be similar (rivaroxaban leads to $6 cost saving).
