![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
ABSTRACT
Background
Conventional cost-effectiveness analysis [CEA] using cost per QALY thresholds may counteract other incentives introduced to foster development of treatments for rare and ultra-rare diseases. Therefore, alternative economic evaluation methods were explored, namely Discrete Choice Experiment Willingness to Pay (DCE-WTP) and Relative Social Willingness to Pay (RS-WTP), to value interventions for an ultra-rare childhood disease, Neuronal Ceroid Lipofuscinosis type 2 (CLN2).
Research Design and Methods
Treatment for CLN2 was valued from a citizen’s (‘social’) perspective using DCE-WTP and RS-WTP in a survey of 4,009 United Kingdom [UK] adults. Three attributes (initial quality of life, treatment effect, and life expectancy) were used in both analyses. For DCE-WTP, a cost attribute (marginal income tax increase) was also included. Optimal econometric models were identified.
Results
DCE-WTP indicated that UK adults are willing to pay incremental increases through taxation for improvements in CLN2 attributes. RS-WTP identified a willingness to allocate >40% of a pre-assigned healthcare budget to prevent child mortality and approximately 15% for improved health status.
Conclusions
Both techniques illustrate substantive social WTP for CLN2 interventions, despite the small number of children benefitting. This highlights a gap between UK citizens’ willingness to spend on rare disease interventions and current funding policies.
Key issues
The objective was to establish the value from the perspective of society of the benefits associated with a drug treatment for an extremely rare life-threatening neuro-degenerative disease affecting children.
This disease is known as Neuronal Ceroid Lipofuscinosis type 2 (CLN2).
Conventional health economics evaluation techniques (including CEA and Cost-Utility Analysis [CUA]) fail to adequately cater for the additional valuation that members of society might have for prioritizing patients suffering from such rare diseases affecting children.
Therefore, our research employed two complementary preference elicitation techniques (Discrete Choice Experiment Willingness to Pay [DCE-WTP] analysis and Relative Social Willingness to Pay [RS-WTP] analysis), to value preferences for prioritizing the treatment of children with CLN2.
Before undertaking the survey, the fatal and neurodegenerative (especially if not appropriately treated) nature of CLN2 disease was explained to survey respondents in a preamble to the questionnaire.
Both valuation techniques were applied to a large sample (n = 4,009) of adult members of the United Kingdom population, in an attempt to establish potential Social Willingness to Pay [SWTP] for a drug treatment for CLN2.
Considerable experimentation was undertaken with alternative econometric models, to arrive at ‘optimal’ econometric ‘Results’ models for both our DCE-WTP and our RS-WTP analyses contained within this paper.
Due to the methodological limitations associated with aggregating SWTP for a DCE-WTP, when a DCE-WTP analysis incorporates an ‘opt-out’ option, it was impossible to obtain a robust overall estimate of SWTP from the DCE-WTP data.
Nonetheless, the findings obtained from our ‘optimal’ DCE-WTP econometric model indicate that on average respondents are willing to pay high amounts (in terms of additional hypothecated taxation for CLN2) for defined improvements in CLN2 attributes.
Absolute estimates of SWTP obtained using RS-WTP, have the limitation that estimated SWTP may be linearly related to the arbitrary size of the initial hypothetical budget allocation that respondents are asked to assign to either Service 1 [saving a life] or Service 2 [Improving health status]. Therefore, absolute estimates of SWTP obtained using RS-WTP are not informative.
However, the average estimates of the relative percentage share of SWTP obtained using the ‘optimal’ RS-WTP model, imply a willingness to allocate just over 40% of a pre-assigned health-care budget to prevent child mortality, and approximately 15%, for improvements in health status.
In light of the acknowledged methodological limitations of these methods, we tentatively conclude that societal willingness to pay for CLN2 treatment may be high.
This analysis therefore indicates a gap between United Kingdom citizens' willingness to pay for interventions to treat rare life-threatening childhood diseases, and the valuations obtained using conventional techniques of health economic evaluation, which do not consider rarity.
Declaration of interest
D Moro has declared that he has received funding (originally from BioMarin, via Analytica Laser and Certara) to work on the design, data analysis, and interpretation of the DCE-WTP and RS-WTP findings detailed in this paper, and upon the production of this paper. Also, some CLN2 related work-related travel expenditure when attending meetings in London and Frankfurt has been covered by funding emanating from BioMarin.
M Schlander has declared that his institution (InnoValHC) received funding for research projects under an unrestricted educational grant policy for providing consultancy for the present project and for related projects, by BioMarin and Sanofi/Genzyme. His institution has also been receiving unrestricted educational grants from a number of biopharmaceutical companies, including Amgen, BIT Pharma, Celgene, Galenica, Johnson & Johnson (J&J), Novartis, Novocure, Roche, and Vertex, as well as from government, professional, industry, and payer organizations including BPI, curafutura, FAMH, IQWiG, Interpharma, and santésuisse. He also holds shares in J&J (unchanged since 1999).
H Telser has declared that his institution (Polynomics) received consultancy payments from BioMarin relating to this submitted work, this was for sitting on the expert advisory board for designing and conducting the discrete choice experiment for this study.
O Sola-Morales has declared receipt of payments from BioMarin relating to the preparation of this manuscript, and for other purposes not directly related to this matter, but which could be considered as potentially influential.
M Clark has declared he has received funding (originally from BioMarin, but paid via Apple Education Limited) for his work upon interpretation of data for this project, and for his input into this publication. Also, some CLN2 related work-related travel expenditure (traveling to work for work on this project) has been covered by funding emanating from BioMarin.
A Olaye was a salaried employee and shareholder of BioMarin when this study was undertaken.
C Camp, M Jain, and T Butt are salaried employees and shareholders of BioMarin, who have contributed to this CLN2 project and this paper whilst working for BioMarin.
S Bakshi who works for Certara Evidence & Access (EvA) disclosed that Certara EvA (previously Analytica Laser) has received financial support in the form of Consultancy payments from BioMarin toward the design and implementation of the study detailed in this paper and for medical writing support.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Authors contributions
D Moro, A Olaye, M Jain, T Butt, and S Bakshi were involved in the conception and design of the study. M Clark was involved in pinpointing key methodological literature to assist D Moro with study design. D Moro, A Olaye, T Butt, and S Bakshi were involved in the analysis of the study data. D Moro, M Schlander, H Telser, O Sola-Morales, M Clark, A Olaye, C Camp, M Jain, T Butt, and S Bakshi were involved in the interpretation of the data. All authors were involved in revising the paper critically for intellectual content, and agreed for the final version of the manuscript to be published.
A statement of originality of this research
This paper has been submitted for consideration for publication as an ‘Original Research’ paper within the journal ‘Expert Review of Pharmacoeconomics & Outcomes Research.’ The research underpinning this paper can lay legitimate claims to originality in a number of respects.
First, it relates to new primary research that the co-authors of this paper have been involved in undertaking, which elicits the preferences and monetary valuations of United Kingdom members of the general population relating to the value of treating a very rare disease affecting children (Neuronal Ceroid Lipofuscinosis type 2 - CLN2).
Second, to our knowledge, this is the first joint application of both Discrete Choice Experiment Willingness to Pay [DCE-WTP], and also Relative Social Willingness to Pay [RS-WTP] analysis that has ever been applied to the same sample of respondents, to value the same condition (in this case CLN2).
Third, we have conducted this experimental research (which applied both DCE-WTP alongside RS-WTP analysis) because of our perception that most other conventional techniques for health economics evaluation are ill-equipped to assess any additional value that members of society might place upon treatments targeted at rare conditions. A key issue that this paper therefore addresses is that if you develop a new treatment for a rare disease, by implication because the potential market for such an intervention is very limited, this may provide a disincentive for commercial organizations to develop drugs to treat rare diseases such as CLN2. This would be the case unless commercial organizations could charge sufficiently high prices to reimburse them for the research and development costs incurred. This novel research was therefore conducted to establish whether members of the general population might be willing to fund higher prices for products that treat rare life-threatening diseases affecting children (such as CLN2), through hypothecated taxation.
Finally, our RS-WTP analysis to our knowledge was the first to use an appropriate main effect design (D-optimal RS-WTP design for RS-WTP attributes) to facilitate assessment of the impact of changes in RS-WTP attribute levels upon econometric estimates obtained using the RS-WTP technique. Therefore, the application of multivariate analysis for RS-WTP to ascertain the impact of changing attribute levels upon allocations to the imperfect CLN2 health state contained in this paper is underpinned by an appropriate underlying RS-WTP questionnaire design.
Complying with research ethics requirements
This study was conducted using a sample of the UK general public who did not suffer from CLN2. The issue of whether UK National Health Service ethical approval was required was considered before this research was conducted. However, it was concluded that NHS ethical approval was not required. This was because it was a survey of general population preferences, and our sample did not contain CLN2 patients, CLN2 carers, or prisoners. Moreover, our enquiries indicated that no other forms of approval were needed for this UK-based study.
Data availability statement
As the underlying preference data cannot be utilized without elaborate econometric modeling, and without providing considerable time-consuming explanations of the data, the underlying data supporting this analysis is not being made publicly available alongside this publication.
However, in principle if peer reviewers or others request access to the data within 2 years of the date of first publication, then we may be prepared to facilitate access to data relating to the actual RS-WTP or DCE-WTP analyses, which are outlined in detail within this paper. Any requested disclosures that we could facilitate, must, however, be in line with any relevant legislation relating to data protection (e.g. including the United Kingdom General Data Protection Act 2018).
Data deposition
As indicated above, this is ‘Not applicable.’
Reviewer disclosures
Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.
Supplemental data
Supplemental data for this article can be accessed here.
