On Discounting of Health Gains from Human Papillomavirus Vaccination: Effects of Different Approaches

Westra, Tjalke A.; Parouty, M.; Brouwer, Werner; Beutels, Philippe; Rogoza, Raina M.; Rozenbaum, Mark H; Daemen, Toos; Wilschut, Jan; Boersma, Cornelis; Postma, Maarten J.

doi:10.1016/j.jval.2012.01.005

Cited by 31 publications

(23 citation statements)

References 33 publications

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“…The appropriateness of employing different discount rates and/or different rates over time is an area that requires further consideration, particularly for potentially curative regenerative medicines and cell-based therapies. Westra et al 139 explored the impact of employing alternative discount rate approaches for human papillomavirus vaccination based on different time-varying methods: a stepwise approach (a constant rate is applied for a set period and lowered in subsequent periods), a hyperbolic approach (the discount rate declines over time) and a time-shifted approach. A recent review by Jit and Mibei 140 also noted that the UK Treasury currently recommends stepwise discounting to all public sector bodies, but at a very slowly declining rate (3.5% for the first 30 years, declining to 3.0% from year 31, with further declines from year 76).…”

Section: Possible Implications For National Institute For Health and mentioning

confidence: 99%

The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal

Hettle

Corbett

Hinde

et al. 2017

Health Technol Assess

106

143

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BackgroundThe National Institute for Health and Care Excellence (NICE) commissioned a ‘mock technology appraisal’ to assess whether changes to its methods and processes are needed. This report presents the findings of independent research commissioned to inform this appraisal and the deliberations of a panel convened by NICE to evaluate the mock appraisal.MethodsOur research included reviews to identify issues, analysis methods and conceptual differences and the relevance of alternative decision frameworks, alongside the development of an exemplar case study of chimeric antigen receptor (CAR) T-cell therapy for treating acute lymphoblastic leukaemia.ResultsAn assessment of previous evaluations of regenerative medicines found that, although there were a number of evidential challenges, none was unique to regenerative medicines or was beyond the scope of existing methods used to conceptualise decision uncertainty. Regarding the clinical evidence for regenerative medicines, the issues were those associated with a limited evidence base but were not unique to regenerative medicines: small non-randomised studies, high variation in response and the intervention subject to continuing development. The relative treatment effects generated from single-arm trials are likely to be optimistic unless it is certain that the historical data have accurately estimated the efficacy of the control agent. Pivotal trials may use surrogate end points, which, on average, overestimate treatment effects. To reduce overall uncertainty, multivariate meta-analysis of all available data should be considered. Incorporating indirectly relevant but more reliable (more mature) data into the analysis can also be considered; such data may become available as a result of the evolving regulatory pathways being developed by the European Medicines Agency. For the exemplar case of CAR T-cell therapy, target product profiles (TPPs) were developed, which considered the ‘curative’ and ‘bridging to stem-cell transplantation’ treatment approaches separately. Within each TPP, three ‘hypothetical’ evidence sets (minimum, intermediate and mature) were generated to simulate the impact of alternative levels of precision and maturity in the clinical evidence. Subsequent assessments of cost-effectiveness were undertaken, employing the existing NICE reference case alongside additional analyses suggested within alternative frameworks. The additional exploratory analyses were undertaken to demonstrate how assessments of cost-effectiveness and uncertainty could be impacted by alternative managed entry agreements (MEAs), including price discounts, performance-related schemes and technology leasing. The panel deliberated on the range of TPPs, evidence sets and MEAs, commenting on the likely recommendations for each scenario. The panel discussed the challenges associated with the exemplar and regenerative medicines more broadly, focusing on the need for a robust quantification of the level of uncertainty in the cost-effective estimates and the potential value of MEAs in limiting the exposure of the NHS to high upfront costs and loss associated with a wrong decision.ConclusionsIt is to be expected that there will be a significant level of uncertainty in determining the clinical effectiveness of regenerative medicines and their long-term costs and benefits, but the existing methods available to estimate the implications of this uncertainty are sufficient. The use of risk sharing and MEAs between the NHS and manufacturers of regenerative medicines should be investigated further.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Possible Implications For National Institute For Health and mentioning

confidence: 99%

The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal

Hettle

Corbett

Hinde

et al. 2017

Health Technol Assess

106

143

View full text Add to dashboard Cite

show abstract

“…First, there are often long delays between vaccine administration (when costs are incurred) and disease averted (when benefits are obtained), so benefits are greatly affected by discounting. For example, vaccination against human papillomavirus [15] or hepatitis B [14] involves decadeslong delays between initial costs and eventual benefits. In contrast, interventions without long-lasting effects (such as pain relief that provides immediate but short-term relief of symptoms) may be largely insensitive to discounting.…”

Section: Distinctive Intertemporal Features Of Vaccinationmentioning

confidence: 99%

“…Murray and Acharya propose an exponentially declining rate in the short term to reflect concern for proximal generations, and then a constant (but extremely low) rate thereafter [53]. Westra et al [15] examined the cost-effectiveness of human papillomavirus vaccination using different several different discounting models.…”

Section: Non-constant Discountingmentioning

confidence: 99%

“…Constant rate discounting is supported by the discounted utility model, which states that the utility derived from consumption at a future time t is the same as the utility now multiplied by a discounting factor (1 + r) −t . However, this standard model of discounting has been challenged [4][5][6][7][8][9][10], particularly for the case of vaccines [11][12][13][14][15][16], since they have distinct characteristics not shared by many other health interventions and hence their costeffectiveness can be particularly sensitive to discounting. In light of the importance of discounting to economic evaluations of vaccines, this paper aims to survey the methodological basis and merits of alternatives to standard discounting schemes, as well as to consider how they may apply to vaccination.…”

Section: Introductionmentioning

confidence: 99%

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Discounting in the evaluation of the cost-effectiveness of a vaccination programme: A critical review

Jit

Mibei

2015

Vaccine

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Discounting future costs and health benefits usually has a large effect on results of cost-effectiveness evaluations of vaccination because of delays between the initial expenditure in the programme and the health benefits from averting disease. Most guidelines currently recommend discounting both costs and health effects at a positive, constant, common rate back to a common point in time. A review of 84 published economic evaluations of vaccines found that most of them apply these recommendations. However, both technical and normative arguments have been presented for discounting health at a different rate to consumption (differential discounting), discounting at a rate that changes over time (non-constant discounting), discounting intra-generational and inter-generational effects at a different rate (two-stage discounting), and discounting the health gains from an intervention to a different discount year from the time of intervention (delayed discounting). These considerations are particularly acute for vaccines, because their effects can occur in a different generation from the one paying for them, and because the time of vaccination, of infection aversion, and of disease aversion usually differ. Using differential, two-stage or delayed discounting in model-based cost-effectiveness evaluations of vaccination raises technical challenges, but mechanisms have been proposed to overcome them.

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“…Reliable evidence suggests that OPC associated with HPV (HPV OPC) has a better prognosis than non-HPV-associated OPC (non-HPV OPC) [ 4 – 6 ]. HPV OPC may have different epidemiological and histopathological characteristics than other head and neck cancers, which are usually associated with smoking and alcohol use [ 7 , 8 ]. The molecular profiles of HPV OPC are characterized by p53 degradation, retinoblastoma RB pathway inactivation by E6 and E7 oncoprotein overexpression, respectively and p16 upregulation [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Different protein expression associated with chemotherapy response in oropharyngeal cancer according to HPV status

Kim

et al. 2014

BMC Cancer

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BackgoundOropharyngeal cancer (OPC) associated with human papilloma virus (HPV OPC) shows better treatment outcomes than non-HPV OPC. We investigated the expression of p53, β-tubulin, bcl-2 and ERCC 1, which are well-known biomarkers to predict the chemotherapy response, according to HPV status in OPC patients.MethodsPatients who treated with at least 2 cycles of induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced oropharyngeal cancer were reviewed. HPV PCR and immunohistochemical stain was done in paraffin embedded tumor tissue and evaluated the relation with the chemotherapy response and survival outcomes according to HPV status.ResultsSeventy-four patients were enrolled for this study and all patients received induction chemotherapy with docetaxel, 5-FU and cisplatin. After induction chemotherapy, complete response (CR) was shown in 22 patients (30%) and partial response (PR) in 46 patients (62%). HPV + was detected in 21 patients (28%), while 35 patients (47%) showed p16+ expression by IHC analysis. p16 positive patients showed better overall response, PFS and OS than p16 negative patients. p53 and class III beta-tubulin expression were significantly higher in HPV- and p16- than HPV + and p16+ patients. Conversely, bcl-2 expression was greater in HPV + or p16+ than HPV- or p16- patients. ERCC1 expression did not differ significantly according to HPV status. In multivariate analyses, early T stage (p = 0.036) and good PS (PS 0) (p = 0.029) showed a better 3Y-PFS rate, and low p53 expression (p = 0.012) and complete response after induction chemotherapy (p = 0.026) were highly associated with 3Y-OS rate. Low expression of p53 and p16 positive patients showed significantly prolonged OS than others (p = 0.010).ConclusionP53, class III beta-tubulin and bcl-2 were differently expressed in OPC according to HPV status and present study suggested the underlying mechanism of better response to chemotherapy in case of HPV OPC than non-HPV OPC. Among these biomarkers, p53 is the strongest prognostic marker in OPC and p53 in addition to p16 support the rationale to study of de-escalation strategy for OPC.

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On Discounting of Health Gains from Human Papillomavirus Vaccination: Effects of Different Approaches

Cited by 31 publications

References 33 publications

The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal

The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal

Discounting in the evaluation of the cost-effectiveness of a vaccination programme: A critical review

Different protein expression associated with chemotherapy response in oropharyngeal cancer according to HPV status

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