La integración del programa de televisión en la enseñanza de ELE Ventajas e inconvenientes

The ERG has made a number of revisions to the economic model, and for the ERG SoC resource use scenario based upon Fonia et al 201058 this significantly worsens the cost effectiveness estimate for secukinumab compared to SoC to £52,760 per QALY. For the company SoC resource use scenario, the ERG revisions to the company model still worsen the cost effectiveness estimate for secukinumab compared to SoC from £7,076 per QALY to £14,902 per QALY.

If among SoC patients with a PASI <50 response the mean annual numbers of day case admissions and the days as an inpatient total around 1, the cost effectiveness estimate for secukinumab compared to SoC is around £30,000 per QALY. If this total is around 14 days, the cost effectiveness estimate for secukinumab compared to SoC is around £20,000 per QALY.

For the ERG SoC resource use scenario the pairwise cost effectiveness estimates of secukinumab compared to etanercept, adalimumab, ustekinumab 45mg and ustekinumab 90mg are £42,367, £38,684, £26,321 and £17,717 per QALY respectively. Secukinumab is estimated to dominate infliximab.

For the company SoC resource use scenario the pairwise cost effectiveness estimates of secukinumab compared to etanercept and adalimumab are £8,899 and £6,979 per QALY respectively. Secukinumab is estimated to dominate ustekinumab 45mg, ustekinumab 90mg and infliximab.

The application of the quality of life values from the other NICE assessments in the area also tends to improve the cost effectiveness estimates. This applies particularly to the quality of life values from the TA180 ustekinumab,45 and the TA134 infliximab.46

Results are not particularly sensitive to the other variables explored by the ERG, though varying the clinical effectiveness inputs and the direct drug costs of the biologics would obviously have an impact.

There are a number of issues that cannot be quantified within the current modelling: • The model structure assumes that only one biologic is tried and when this fails the

patient reverts to SoC. ERG expert opinion suggests that patients failing on one biologic tend to be treated with another one. Modelling a sequence of treatments with biologics would explore whether the treatment sequences are cost effective compared to SoC, whether adding an additional biologic within the treatment sequences is cost effective and what the most cost effective sequencing of biologics was. While speculation on the part of the ERG:

- If the individual biologics are not cost effective compared to SoC, it is difficult to imagine that a treatment sequence of these biologics will be cost effective compared to SoC.

- If secukinumab is not individually cost effective compared to SoC and treatment sequences of current biologics are not cost effective compared to SoC, it is difficult to imagine that adding secukinumab to a treatment sequence of current biologics will be cost effective compared to SoC.

- If secukinumab is cost effective compared to the other biologics but is not cost effective compared to SoC, it is not difficult to imagine that if secukinumab displaces an existing biologic that the cost effectiveness of that treatment sequence compared to SoC will improve. However, if it is an addition to the treatment sequence, it is more difficult to imagine that this will improve the cost effectiveness of the treatment sequence.

- If secukinumab is cost effective compared to SoC, it is not difficult to imagine that adding secukinumab to a treatment sequence will improve the cost

effectiveness of that treatment sequence compared to SoC.

• The model may strip some of the placebo effect from SoC while retaining it for more effective treatments. If a patient receiving SoC has a PASI 50-75 response but would have had a PASI 75 response on a biologic, it could be argued that the biologic PASI 75 response is in some sense on the back of the placebo PASI 50-75 response. Those with a PASI 50-75 response are assumed to fall back to a PASI <50 response while those with a PASI 75 response are assumed to maintain it. If this is a concern, it seems likely to have biased the ICER(s) in favour of secukinumab.

• The analysis of the EQ-5D data does not explore a treatment effect. It is possible that the distribution among week 12 PASI <50 patients in the SoC arm is worse than that

in the biologic arms, given the other response categories’ data. This might suggest a lower EQ-5D QoL value in the PASI <50 SoC arm patients than in the PASI <50 biologic arms patients, though whether this could be demonstrated statistically is a moot point. If this occurred and was applied within the modelling it could increase the patient benefits from the biologics compared to SoC. However, there would be

problems in terms of taking the two biologics into consideration. The possible existence of such an effect is pure speculation by the ERG. If this is a concern, it seems likely to have biased the ICER(s) against secukinumab.

• The model does not take into account possible changes in PASI response categories among week 12 PASI 75-89 responders between week 12 and week 52. Given the discontinuation rate of the model which could be assumed to apply to those with a worsening PASI response, there is a suggestion that this might tend to increase the patient benefits from secukinumab and etanercept over SoC as some of these patients may move into the PASI 90 response category. If this is a concern, it seems likely to have biased the ICER(s) in favour of SoC.

• The ERG has not parsed the partial responder analysis of the company. But this apparently assumes that those with a PASI 50-74 response continue on treatment, in effect lowering the bar for a response to a PASI 50. It may have been appropriate to have considered the evolution of PASI responses within this category. The model structure might then have had two response evaluations: one at 12 weeks when week 12 PASI <50 response patients have treatment withdrawn, and one at 52 weeks when week 52 PASI <75 response patients have treatment withdrawn. This might be the more logical partial PASI response model structure. This analysis would only be possible for the FIXTURE trial comparators. This might increase the patient benefits from secukinumab over both etanercept and SoC. But as the company points out, patient numbers within the week 12 PASI 50-74 category are not large and some caution would be required. If this is a concern, it seems likely to have biased the ICER(s) in favour of SoC