Apixaban for the prevention of venous thromboembolism in people ...

when compared to fondaparinux in THR showed no significant differences in terms of any
DVT, xxxxxx xxxx xxxxx xxxxx. Other main outcomes (Total VTE and all-cause mortality,
Major VTE, and Any bleeding) were not reported using indirect comparisons; although, for the
total VTE and all-cause mortality the MTC showed no significant differences. For TKR an
indirect comparison with enoxaparin, 40mg od was not possible.
1.3 Summary of cost effectiveness submitted evidence by the manufacturer
Due to insufficient information from published cost-effectiveness studies as demonstrated by the
literature review in the MS, the manufacturer conducted a de-novo economic analysis. In this analysis
the costs and health outcomes of apixaban, rivaroxaban, dabigatran and enoxaparin (representing al
LMWHs) for the prevention of VTE in adult patients who have undergone elective THR or TKR were
compared. Upon request of the ERG fondaparinux was also included in the analyses.
The manufacturer adopted a two-stage modelling approach. A decision tree was used to model
treatment in the acute phase (surgery to 90 days post surgery) and a Markov model was used to model
the long-term events (35 years). Efficacy and safety of the treatments was modelled in line with the
endpoints in the trials: ‘total VTEs and all deaths’ and ‘total bleeds’. The model did not account for
differences in types of VTEs or types of bleeds between the treatments. Upon request of the ERG, the
manufacturer provided analyses that did take differences in types of VTEs and/or bleeds into account.
The remaining probabilities in the model were assumed to be treatment independent. As a result, the
major model parameters that caused differences between the treatments were the probabilities of ‘total
VTEs and all deaths’ and ‘total bleeds’ in the acute phase.
The probabilities of ‘total VTEs and all deaths’ and ‘total bleeds’ were based on an indirect
comparison with enoxaparin as reference treatment. The results of a MTC were used in a sensitivity
analysis. The values for health related quality of life were based on several studies. These studies used
a large variety of instruments, perspectives and populations. Healthcare resource group 4.0 procedure
codes were used to determine the costs of health states and events.
The manufacturer conducted a full incremental deterministic analysis of the treatment options.
However, for the PSA only selected options were compared, by that deviating from the requested full
incremental analysis. The manufacturer adjusted the PSA in order to allow for a full incremental
analysis after request by the ERG. In THR rivaroxaban was the most effective annd most costly
treatment, followed by apixaban. The ICER of rivaroxaban versus apixaban amounted to 21,661 per
QALY gained. In TKR rivaroxaban was the most effective and least costly treatment option, and
therefore dominated all other treatments. These results were robust.
1.4 ERG commentary on the robustness of evidence submitted by the manufacturer
1.4.1 Strengths
Search methods were clearly presented and reported. The manufacturer searched the required
databases. The MS provided sufficient detail for the ERG to appraise the searches. Additional
searches of conference abstracts were undertaken for the clinical effectiveness and cost effectiveness
sections. The ERG noted that several of the errors identified were not consequential, due to the
comprehensiveness of the rest of the strategies. For the most part, these inconsequential errors would
not have impacted the recall of searching.
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