Economic Burden of Haemophilia from a Societal Perspective: A Scoping Review

Abstract

Introduction: Haemophilia is a rare genetic bleeding disorder that leads to musculoskeletal complications. The high cost of haemophilia treatment necessitates a thorough evaluation of its economic burden. However, due to the difficulty of estimating direct non-medical, indirect, and intangible costs, studies often underestimate the actual economic burden of haemophilia. This scoping review aims to summarise economic studies in haemophilia conducted from a societal perspective.

Methods: A systematic search across eight scholarly databases, grey literature, and reference lists until the 5^th of July 2023 was conducted to identify relevant studies. The inclusion criteria encompassed full-text, English-language publications of economic analyses in congenital haemophilia from a societal perspective. Model-based studies and those adopting a payer perspective were excluded. Costs were adjusted to international dollars (I$) and US dollars (US$) in 2022 for comparability.

Results: Out of 2993 potential sources identified, 25 studies met the inclusion criteria, covering 7226 persons with haemophilia across 22 countries. All studies reported direct medical costs, with four excluding the cost of haemostatic therapy. Fifteen studies reported direct formal non-medical costs, while eight reported direct informal non-medical costs. All but one study reported the indirect costs. The average annual costs of haemophilia varied widely based on treatment modality, disease severity, geographical location, and included cost categories. When including the cost of clotting factor replacement therapy (CFRT), the total cost for severe haemophilia without inhibitors ranged from 1566 I$ to 700,070 I$ per person per year (lowest value reported in India and highest in the United States). CFRT represented up to 99.9% of the total cost for those receiving prophylaxis and up to 95.1% for episodic treatment. Haemostatic therapies accounted for 82% of the total cost in patients with inhibitors.

Conclusion: There is a significant heterogeneity in defining cost categories required for a comprehensive economic analysis from a societal perspective. While haemostatic therapies constitute a substantial portion of the overall cost, direct non-medical and indirect costs are crucial as they are often paid out-of-pocket and may impede access to treatment. It is essential for haematologists and economists to establish a standardised costing framework for future studies, particularly in the era of novel therapies.

Fig. 1

Types of cost categories that should be reported in economic analyses from a societal perspective. The cost of haemostatic therapies may be reported as part of the direct medical cost, which includes the cost of other medications, medical, dental, and surgical procedures, medical devices, outpatient services (including all healthcare specialities, laboratory services), inpatient services (including hospitalisation), and paid caregivers, e.g., a skilled nurse [–, , –79]. Direct formal non-medical cost refers to the out-of-pocket expenditure incurred by people with haemophilia (PwH) and caregivers to receive haemophilia care, such as transportation, accommodation, and meals [, , , –79]. Direct informal non-medical cost relates to the unpaid cost of informal care provided by non-professional caregivers, such as family members, relatives, friends, or community health volunteers [22, 38, 76, 78, 84]. Indirect cost consists of the productivity loss by PwH, caregivers, and society due to haemophilia morbidity and mortality or treatment, including loss of work, school, and leisure time. Additionally, the cost of other aspects of social life, such as education, housing, and the environment, should be considered to ensure the application of a wider societal perspective [79, 85]. Intangible cost is the cost of the reduced quality of life, such as pain, anxiety, and other sufferings of PwH. Because these costs are difficult to quantify in monetary value, a willingness-to-pay threshold may be used as a proxy method to estimate the amount people would be willing to pay to avoid disease morbidity or mortality [22, 24, 75, 77, 78]. Total (societal) cost is the sum of all direct costs, indirect costs, and intangible costs [–, , –78]

Fig. 2

PRISMA flow chart [27, 28, 160, 161]

Fig. 3

Socioeconomic burden of severe haemophilia across countries included in this review, A) in I$ for 2022, B) in US$ for 2022. Values reported in figures are the highest values reported for each country in Tables 5 and 6, respectively. I$ International dollar, LMICs low- and middle-income countries, US$ United States dollar