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

5.2.11 Model validation
The MS stated that “quality assurance was assessed by modellers that were not involved in
producing the model. Two primary criteria were used in quality assessment, internal
(verification) and external consistency (validation). Verification was assessed using the
techniques of extreme value analysis (substituting minimum and maximum values for
appropriate parameter values), using parallel inputs for all interventions for efficacy, costs and
utilities. These techniques help reveal inappropriate algorithms in a model and identify any
irregularities between the programming of treatment arms. External consistency was assessed
by assessing the results of the model against published results.” (MS-section 6.8)
Comment
– The results were comparable to earlier evaluations (described in section 5.1.4) in that
dabigatran was found to dominate enoxaparin and that rivaroxaban was found to
dominate both dabigatran and enoxaparin. Clinical experts were not used to validate the
model structure or input values. However, clinical experts called in by the ERG
confirmed that in general the assumptions that were made were deemed valid.
– The ERG noted some internal errors within the model which were disclosed to the
manufacturer. These included the distributions for relative risk not properly reflecting the
uncertainty as found in the original papers and incorrect use of standard errors instead of
standard deviations in informing distributions. These errors were fixed to the satisfaction
of the ERG.
5.3 Additional work undertaken by the ERG
Provide details of any additional work conducted by the ERG in relation to cost effectiveness.
If the results of any of the additional work affect the size of the ICER, refer the reader to the
summary table in Section 6.
The ERG found that in the inclusion of fondaparinux as a comparator, the extra postdischarge
costs were not included, while these were included for the other injections
(enoxaparin). Therefore, the ERG performed additional analyses including post-discharge
costs. After including post discharge costs, fondaparinux was still the least expensive
comparator in THR. However, as the difference in costs between fondaparinux and apixaban
was smaller, the ICER decreased to £4,958 (Table 5.21). The corresponding CEACs showed
that at a threshold of £20,000 per QALY, fondaparinux no longer had the highest probability
of being cost-effective (Figure 5.12). This was now apixaban with 43%, followed by
rivaroxaban (39%) and fondaparinux (19%). At a threshold of £30,000 per QALY these
probabilities were 40%, 46% and 14%, respectively.
Additionally, the ERG analysed the cost-effectiveness including evidence from the recently
published RE-NOVATE-II study for the dabigatran relative risk of bleeding 22 (see paragraph
4.2.7). A comparison was made between all comparators, including the total costs of
fondaparinux as described above. The updated RR resulted in total costs of dabigatran of
£266.12, which was £2.23 higher than in the previous analysis. The update did not affect the
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