4. RESUMEN DE IMPACTOS SIGNIFICATIVOS
4.1. IMPACTOS SIGNIFICATIVOS EN AGUAS SUPERFICIALES
and motivation for de novo model
The CSs are the only studies that directly assess the decision problem in relation to the new interventions [i.e. the positioning of these treatments within the pathway for PsA (biologic-naive and biologic-experienced populations)]. Although the studies, in relation to the broader comparators, are helpful in terms of
highlighting similarities and possible differences between the approaches being applied by the separate companies and those previously used for previous TA appraisals, they are not directly relevant to the evaluation of SEC and CZP.
In general, the structure and approaches of both models were similar in many key respects to the York model conducted for TA19933(ETN, ADA and INF). The main differences were:
l The timing of the initial response period was assumed to be 24 weeks in the UCB Pharma submission and 3 months (i.e. 12–16 weeks) in both the Novartis submission (with the exception of UST) and the York model. The justification provided by Novartis for assuming 3 months for the initial response period was to ensure consistency with previous NICE appraisals and BSR/British Health Professionals in Rheumatology guidelines and to maximise the data included in the NMA. UCB Pharma justified the 24-week period based on 2011 EULAR guidelines, although results were also reported as part of separate sensitivity analysis assuming a 3-month response period.
l The definition of response in the Novartis base case (PsARC and PASI) differed from that used in the base-case approaches by both UCB Pharma and the previous York model (PsARC only). The Novartis submission presented a separate sensitivity analysis assuming that response was assessed using just PsARC, and this reported only minor differences from its base case.
l The UCB Pharma base case focused on sequences and the incorporation of subsequent lines of
treatments as opposed to presenting this as a separate exploratory scenario (Novartis and York models). l In common with the York model, the Novartis model assumed that the HAQ-DI score gain reported at
3 months was the maximum reduction achieved on treatment and assumed no further change (i.e. increase or decrease) beyond this period for patients while they remained on this treatment. In contrast, the UCB Pharma model employed different assumptions during the initial 9-month treatment (i.e. that the highest rate of change is obtained at 4 weeks, but further improvements in HAQ-DI score are possible during a period of 9 months for a responding patient who remains on treatment). After 9 months, the UCB Pharma model assumed no further change beyond this period for patients while they remained on this treatment.
ASSESSMENT OF EXISTING COST-EFFECTIVENESS EVIDENCE
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l Assumptions related to the rebound effect on HAQ-DI score following treatment withdrawal. The UCB Pharma submission assumes that a patient’s HAQ-DI score rebounds to a worse position than the original baseline value when they switch to the next treatment. Both the Novartis and York models assume that a patient’s HAQ-DI score rebounds to its original baseline value.
l The Novartis and UCB Pharma submissions include additional subpopulations (subpopulations 1 and 3), based on the broader scope for the appraisal of SEC and CZP compared with the scope of TA199.33 l The Novartis submission estimates costs associated with HAQ-DI and PASI based on the same sources
and assumptions previously used in the York model. In contrast, the UCB Pharma submission based costs on a separate study by Poole et al.138and justified this on the basis that the use of a PsA population was more appropriate than deriving costs based on a RA population and employing separate assumptions for PASI costs.
l Although UCB Pharma assumed the same annual withdrawal rate as the York model (16.5% per annum), the UCB Pharma submission applied this only to the first 4 years of a treatment. Thereafter it was assumed that no patient would withdraw. This assumption was justified by UCB Pharma based on the lack of longer-term evidence reported for withdrawal. Novartis utilised withdrawal data from its trial population (FUTURE 2 trial48) and applied a (confidential information has been removed) per annum rate for the first year and (confidential information has been removed) for subsequent years. l By assuming a mean PASI score of > 10 units, the UCB Pharma base-case results relate to an ‘average’
PsA patient with concomitant moderate–severe psoriasis (i.e. ≥ 3% of BSA affected and a PASI score of > 10 units). In contrast, the Novartis base-case results relate to an ‘average’ PsA patient with concomitant mild–moderate psoriasis (≥ 3% of BSA affected and a PASI score of ≤ 10 units), similar to the base case in the York model. Both the UCB Pharma and York model also presented separate sensitivity analyses based on different PASI scores, which reflected subgroups of PsA patients without concomitant psoriasis and with concomitant moderate–severe psoriasis. Separate sensitivity and scenario analyses were not presented in the Novartis submission.
l The time horizon was assumed to be 40 years in the Novartis and York models and 50 years in the UCB Pharma model.
As highlighted in Results, drawing robust conclusions from the results reported from the separate companies is challenging given the differences noted in the approaches and data sources employed. Comparisons in subpopulation 1 are not possible as neither company included the other treatment in their comparisons. The difficulty of comparing results across subpopulations 2 and 3 are further hampered by the different assumptions made concerning the dosage of SEC included and in both subpopulations 2 and 3 based on the use of list prices for SEC in the UCB Pharma submission and Patient Access Scheme prices in the Novartis submission.
Assessments of cross-validity were possible for subpopulations 2 and 3 based on the Novartis results presented for comparator treatment and those reported in previous studies. The results from the Novartis model did not appear consistent with the cost-effectiveness reported for the comparator treatment assessed in previous NICE TAs (see TA199,33TA220133and TA34035). A discussion of possible reasons for this difference was not provided in the Novartis submission. An assessment of cross-validity was possible only in terms of subpopulation 3 for the UCB Pharma submission. Here the reported ICER appeared reasonably consistent for the main comparator treatment (UST) and the ICER reported in the previous NICE TA (TA34035).
Given the different approaches and assumptions employed by the companies, there remains considerable uncertainty regarding the cost-effectiveness of both SEC and CZP in each of the subpopulations and potential implications for the NHS. These differences make it challenging to draw robust conclusions from the current submissions, particularly given the contradictory findings reported for several of the subpopulations in terms of the relative cost-effectiveness of SEC and CZP. Furthermore, neither company incorporated the full range of interventions and comparators as stated in the NICE scope112across all three subpopulations. The following chapter describes the development of a de novo model that attempts to address several areas of remaining uncertainty and to apply a consistent basis for evaluating the cost-effectiveness of the full range of
Chapter 6 Independent economic assessment
Introduction
The review of published models, and the CSs, show that the underlying structure used to model the cost-effectiveness of treatments for PsA has remained largely unaltered since the previous York model for TA199.33Despite the similarity observed across studies in terms of the model structure, important differences were identified in terms of associated assumptions and data sources. None of these can be considered unequivocally superior to the others; however, there are a number of issues with each of the currently available models (see Chapter 5, Relevance of submitted cost-effectiveness evidence for National Institute for Health and Care Excellence decision-making: summary and motivation for de novo model).
In terms of the previous York model, this does not consider all of the subpopulations defined in the NICE scope112for this assessment. Currently available guidance, issued by NICE on the use of biologics in PsA,140 recommends that patients try two cDMARDs over a 6-month period before they can be considered for biologic treatment in accordance with current BSR guidelines. However, as defined in the NICE scope for this appraisal, three subpopulations need to be considered:
1. subpopulation 1 (biologic naive, one prior DMARD)
2. subpopulation 2 (biologic naive, two or more prior DMARDs) 3. subpopulation 3 (biologic experienced or contraindicated).
The two CSs consider these three subpopulations in their economic models; however, neither includes the full range of relevant treatments for all of the subpopulations and neither specifically considers patients contraindicated to existing biologic treatments.
In modelling the cost-effectiveness of available treatments, it is also important to consider the possibility that patients may switch to another active treatment, following primary failure (non-response) or secondary withdrawal (initial response with later withdrawal due to AE or loss of efficacy). Therefore, a key objective of the de novo model is to assess the cost-effectiveness of SEC and CZP for PsA within possible sequences of available treatments.