Pipeline Flex embolisation device with Shield Technology for the treatment of complex intracranial aneurysms

The sponsor submitted a de novo cost analysis for Pipeline for the treatment of complex intracranial aneurysms. Full details of all cost evidence and modelling considered by the committee are available in the assessment report overview.

The sponsor presented a decision tree (for the peri-procedural period) followed by a Markov model (for long-term outcomes) to estimate the costs and consequences associated with Pipeline against 5 comparator interventions: stent-assisted coiling, neurosurgical clipping, endovascular parent vessel occlusion, neurosurgical parent vessel occlusion and conservative management. The patient population included those with unruptured large or giant intracranial aneurysms as outlined in the scope, but did not include fusiform or wide-necked aneurysms.

The decision-tree structure separated patients who had survived initial treatment, based on a mortality rate for the procedure, into 1 of 3 occlusion categories (complete occlusion, residual neck and residual aneurysm). For each occlusion category, patients were tracked through 5 possible health states: 'no complications', 'new non-fatal rupture', 'post rupture', 'fatal rupture' and 'dead (all cause)'. It was assumed that transition probabilities for the health states would be constant over time. The time horizon of the base-case analysis was 10 years.

An NHS and personal social services perspective was used. The cost analysis included the costs associated with the duration of the procedure, staff time (surgeon, radiologist, nurse, anaesthetist), hospital costs (neurology operating or neurosurgical operating room, and recovery ward), imaging (angiography, fluoroscopy or MRI), consumables, drugs; and for conservative management only, long-term monitoring with annual MRI. The cost associated with stroke was assumed to be representative of the cost of rupture. Costs applied to each type of retreatment were assumed to be the same as the full cost if that treatment had been used initially.

The costs and consequences associated with adverse events were not included in the base-case analysis because the sponsor considered there to be insufficient reliable data for each treatment group. However, the sponsor did include costs associated with mortality at 31 days, rupture and retreatment.

In the base case the number of Pipeline embolisation devices used was 1.46, based on data submitted to the sponsor from use of the device in UK hospitals up to August 2011. The number of coils used in the base case was 40 and was derived from an estimate in an editorial review by Wehman in 2006. It was assumed that 1 stent would be needed for each stent-assisted coiling intervention.

The base case presented the total procedure costs over the 10-year time horizon associated with Pipeline as £24,341. For the comparators, the total procedure costs were £37,451 for stent-assisted coiling, £11,658 for neurosurgical clipping, £16,893 for endovascular parent vessel occlusion, £11,654 for neurosurgical parent vessel occlusion and £10,352 for conservative management. The only intervention against which Pipeline was shown to be cost saving was stent-assisted coiling, with a cost saving of £13,110 per patient.

Two scenario analyses were presented. One included costs associated with the adverse events of subarachnoid haemorrhage related to the aneurysm, thromboembolic stroke and intracranial haemorrhagic stroke remote from the aneurysm using data from the PUFS study and data from Darsault et al. (2001) for the comparators. The other scenario analysis restricted the time horizon to 6 months (short-term). Conservative management was excluded from the short-term scenario because it does not have a 'peri-procedural' mortality rate.

In both scenario analyses Pipeline was shown to be cost saving only when compared with stent-assisted coiling. When costs associated with adverse events were included in the model, Pipeline remained a cost-saving intervention compared with stent-assisted coiling, with an associated saving of £13,327. When outcomes were restricted to the short term (6 months), Pipeline remained cost saving compared with stent-assisted coiling (£10,316).

Sensitivity analyses carried out by the sponsor showed that the main factors influencing the cost analysis were the number and cost of consumables, in particular the numbers of Pipeline embolisation devices and endovascular coils. The sponsor carried out sensitivity analysis for the use of 1 to 3 Pipeline embolisation devices and separately for 5 to 100 coils.

The number of Pipeline embolisation devices used in the base case was 1.46 per patient. On receipt of more data from UK hospitals, the sponsor submitted a revised number of 1.658 in October 2011. The external assessment centre reviewed the data and concluded that when 1.658 Pipeline embolisation devices were used, Pipeline was more costly compared with stent-assisted coiling if 22 coils were used (an estimated cost increase of £19), but cost saving when 23 coils were used. The cost saving when using 1.658 Pipeline embolisation devices compared with stent-assisted coiling with 23 coils was estimated to be £588 (total procedure costs of £26,546 and £27,134 respectively). When 2 Pipeline embolisation devices were used, Pipeline was more costly by an estimated £185 than stent-assisted coiling using 28 coils, but was less costly than stent-assisted coiling when 29 coils were used. The cost saving when using 2 Pipeline embolisation devices compared with stent-assisted coiling with 29 coils was estimated to be £421 (total procedure costs of £30,354 and £30,775 respectively).

During consultation, expert advisers expressed doubts about 5 parameters in the cost model: the cost of microcatheters; the use of a balloon in stent-assisted coiling; drug costs; the procedure duration; and the cost of additional endovascular equipment. Additional exploratory analyses were carried out by the external assessment centre to examine the impact of changing these parameters, in ways which the expert advisers suggested were more appropriate.

In the sponsor's economic model, the cost of microcatheters used in stent-assisted coiling was comparable to the cost of a Marksman catheter (£1,030) used to insert Pipeline. However, the expert advisers stated that cheaper microcatheters (average cost £460.50) would be used for stent-assisted coiling than for Pipeline in UK practice. The external assessment centre's exploratory analyses demonstrated that reducing the cost of 2 microcatheters for stent-assisted coiling from £1,030 to £460.50 reduced the total procedure cost for stent-assisted coiling from £37,451 to £36,137.

The sponsor's economic modelling also assumed that a balloon is used in 50% of stent-assisted coiling procedures and is not used to insert Pipeline. However, the expert advisers stated that use of a balloon is relatively uncommon in the UK for stent-assisted coiling procedures. In the exploratory analyses carried out by the external assessment centre, removing the cost of a balloon reduced the total procedure cost for stent-assisted coiling from £36,137 to £35,725, while the total procedure cost for Pipeline (with 2 devices) remained at £30,354.

The sponsor's economic model assumed different drug use for patients having stent-assisted coiling and those having Pipeline (18,000 mg aspirin and 6,750 mg clopidogrel compared with 25,000 mg aspirin and 13,500 mg clopidogrel respectively). The expert advisers stated that in clinical practice drug use in the 2 groups is likely to be equal. The external assessment centre noted that in the sponsor's economic model drug use was calculated from 2 non-comparative studies, but that few published data are available on clinical use. The external assessment centre stated that the low cost of these drugs means that relatively small differences in drug use are unlikely to have a significant impact on the overall procedure costs for stent-assisted coiling and Pipeline. In the absence of a systematic review the external assessment centre stated that the drug costs used in the model were appropriate.

In its exploratory analysis the external assessment centre identified 2 calculation errors in the sponsor's economic model, both relating to the number of days of drug therapy. The external assessment centre stated that correcting these calculation errors made only a very small difference in the total procedure costs for both Pipeline and stent-assisted coiling, reducing them from £30,354 to £30,346 and £35,725 to £35,724 respectively.

In the sponsor's economic model, the average duration of the procedure (in hours) and therefore the use of additional endovascular equipment were different for stent-assisted coiling and insertion of Pipeline. The expert advisers stated that the procedures are likely to take the same amount of time in clinical practice. The external assessment centre noted that the time taken for stent-assisted coiling was derived from 1 non-comparative study and the time for inserting Pipeline from another. However the external assessment centre was not able to judge which study was the best source for duration of procedure and no systematic review was carried out. The external assessment centre stated that because both studies were appropriately and accurately used in the model no changes were justified with regard to procedure time for stent-assisted coiling or Pipeline. The external assessment centre also noted that the sponsor included the use of additional endovascular equipment in the model based on the duration of procedure, but provided no justification for why it was included only for stent-assisted coiling and not for Pipeline or the other comparators. Furthermore, there was no justification for why the cost of additional equipment was only included in calculating the retreatment cost but not the cost of the initial procedure. The exploratory analyses demonstrated that removing the costs of additional endovascular equipment from the model reduced the total procedure cost of stent-assisted coiling from £35,724 to £35,693 while the total procedure cost for Pipeline remained at £30,346.