ReviewSocio-economic burden of rare diseases: A systematic review of cost of illness evidence
Introduction
Most rare diseases are associated with high unmet need due to the lack of available and effective treatments and the relative lack of research to discover and develop such treatments. In the European Union (EU), a rare disease is defined as one affecting less than 1 in 2,000 people, and it is estimated that over 6,000 different, life-threatening or chronic, rare diseases exist today [1]. Although rare diseases are by definition associated with low prevalence, considering that 6–8% of the population are affected by a rare disease, the total number of patients in the EU is estimated to be between 27 and 36 million [2]. With the majority of rare disease patients suffering from less frequent conditions with a prevalence of 1 in 100,000 population, and with many rare diseases being of genetic origin, there is a strong public health interest relating to their cost and broader socioeconomic impact in order to develop sustainable health policy options.
Cost-of-illness (COI) studies measure the socio-economic burden of a disease and can be used as a public policy tool to assist in prioritisation and justification of healthcare and prevention policies [3]. COI studies can indicate which interventions are more valuable by comparing averted economic burden, and consequently lead to shifts in distribution of public and private investments. Different stakeholders can utilise COI studies differently. Governments can estimate the financial impact of a disease on public budgets for resource allocation purposes, whereas pharmaceutical corporations can identify diseases with high management costs to direct research and development (R&D) investments towards accordingly.
In addition, COI studies provide information for other types of economic evaluations, including a framework for cost estimation in cost-utility and cost-effectiveness analyses, frequently used by policy makers [3], [4]. They are increasingly cited in clinical and epidemiological research to emphasise the importance of studying a particular disease and the scale of a health-related problem, conveying the aggregate burden of illness on society by estimating the maximum amount that could potentially be saved if a disease were to be eradicated [5], [6].
While COI studies can identify and measure all costs of a particular disease, they do not address issues of inefficiency or waste; nor do they weigh up costs and benefits of interventions [6]. Caution is also advisable when interpreting COI estimates as potential savings if a disease were systematically targeted, because not all conditions can be fully eradicated, and some proportion of economic burden will remain despite effective interventions [6]. For optimal resource allocation, COI studies should be used in combination with full economic evaluations such as cost-benefit or cost-utility analyses which assess both costs and outcomes [7].
COI studies employ a wide range of different designs and methodologies, often limiting comparability and usefulness of results [8]. Variations include data sources, perspectives (healthcare, societal, etc.), cost types, costing approach and discount rate [9]. While standardisation of methodology through implementation of guidelines is becoming increasingly important, some flexibility may be required for diseases with special characteristics to be adequately described [3], [9].
Numerous COI studies have been conducted over the past three decades across a range of diseases, however few have addressed rare diseases. In this context, the aim of the BURQOL-RD project (“Social Economic Burden and Health-Related Quality of Life in patients with Rare Diseases in Europe”) was to provide new tools and knowledge for 10 rare diseases (RDs), including socio-economic burden and health related quality of life for patients and their caregivers [10].
As part of this initiative, the objective of this study is to systematically review the relevant literature on the socioeconomic burden of RDs and identify all costs, both direct and indirect, related to ten specifically identified RDs from the perspective of patients, families and society.
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Data and methods
The BURQOL-RD project participants adopted a Delphi consensus approach in combination with a Carroll diagram for the selection of the 10 RDs to be studied [10]. An expert panel involved 23 individuals as representatives of each associated and collaborating project partner. Initially, the selection criteria for the potential RDs were defined and were summarised under the acronym BOSCARE and included: a broad spectrum of RDs being suitably represented, including some ultra-rare and less
Disease characteristics and prevalence in Europe
By reviewing the available evidence on disease characteristics and their prevalence/rarity, a better understanding of the burden of the different diseases can be gained. In turn, the limited availability of COI evidence suggests the need for further research on the selected RDs. Prevalence for each disease is shown in Table 1.
CF is the most frequent paediatric autosomal recessive disease in Caucasian populations [13], [14], [15], occurring in 1 in 2,500–3,600 births, with a European Union (EU)
Evidence and policy implications
In this review, we identified 77 studies that provide some level of information on the economic burden of ten selected RDs. An overall summary of the cost results is shown in Table 3. For some conditions (PWS and EB) no COI information was available despite relatively high prevalence (see Table 2). For other conditions (DMD, MPS I and VI, histiocytosis, FXS, scleroderma) COI information was very limited, and with the exception of MPS for which rhASB has undergone clinical trials as a treatment,
Conclusions
Although methodological variations prevent any detailed comparison between conditions, most of the rare diseases examined in this study are associated with significant economic burden. Indirect costs associated with loss of productivity in most cases approach or exceed the level of direct costs. The level of evidence available is highest for conditions that have specific pharmaceutical treatments available and is not necessarily associated with disease rarity. The study raises awareness about
Acknowledgements
This paper is an output from the BURQOL-RD project, funded by the 2nd Programme of Community Action in the Field of Public Health, promoted by the Directorate General for Health and Consumer Affairs (DG Sanco) of the European Commission. The views represented in the paper do not reflect the views of the European Commission. We are grateful to the BURQOL partner network for comments and feedback on earlier versions of this paper as well as to two anonymous referees for constructive comments. We
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