Introduction
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by the degeneration of alpha motor neurons in the anterior horns of the spinal cord. SMA is the second most common severe hereditary disease of infancy and early childhood, with an estimated incidence of 1/5000 to 1/10,000 births and a carrier frequency of 1/35 to 1/50 [
1,
2].
The difficulties of living with SMA begin with the long and often arduous process of diagnosis. Therefore, as is the case with other rare diseases [
3], SMA imposes a considerable economic burden on society. Substantial health-care costs are associated with its management in terms of treatment, hospitalizations, emergency consultations, visits to General Practitioners (GPs) and other specialists, etc. Additionally, due to the considerable disability that SMA causes, most of the patients are unable to fulfill their activities of daily living (ADLs) and they rely on family for support and/or social services. Therefore, quantification of the economic burden of SMA needs not only to consider the costs to the healthcare systems but also, the costs of formal care, unpaid care provided by relatives and other household costs.
To our knowledge, few studies have delved into the cost of SMA from a social point of view [
4]. Therefore, the main aim of this study was two-fold. First, to estimate the economic costs related to SMA from a societal perspective in Spain Second, to assess the HRQOL of SMA patients and their caregivers. This information provides valuable information on the real economic impact that SMA has in Spain.
Results
A total of 95 completed questionnaires were collected related to individuals with SMA, of which 14 were excluded because the patients did not fulfill the inclusion criteria. Thus, a total valid sample of 81 patients was studied. The main characteristics of the participants and their caregivers are shown in Table
1. The average age of the children was 7.22 years (SD = 5.47) and 42% were boys. In this sample, 10% of patients had type I SMA, 74% of patients had SMA type II and 16% type III SMA. It is noteworthy that it seems to take a long time to obtain a diagnosis for this condition, perhaps because the average age of the first symptom is 4.32 years (SD = 2.5).
Table 1
Demographic characteristic of the study participants (N = 81 patient-caregiver pairs)
Type I | 8 (9.87) |
Type II | 60 (74.07) |
Type III | 13 (16.06) |
Gender |
Female | 47 (58.02) |
Male | 34 (41.98) |
Age (mean) | 7.22 (5.47)a
|
Age from the first symptom, mean (SD) | 4.32 (2.50) |
Type I | 1.55 (1.06) |
Type II | 4.26 (2.35) |
Type III | 5.35 (2.79) |
Education |
Educated at an ordinary school | 21 (25.93) |
Educated at an ordinary center with special sessions | 39 (48.15) |
Educated at a special needs education center | 3 (3.70) |
Home schooled | 5 (6.17) |
Nursery school | 0.00 |
Not received education | 10 (12.35) |
Missing | 3 (3.70) |
Caregivers |
No. of caregivers (N) | 81 (100) |
Gender | |
Male | 7 (8.64) |
Female | 36 (44.44) |
Missing | 38 (46.92) |
Age | 40.29 (7.30)a
|
Working situation |
Employed | 25 (30.87) |
Retired or pensioner | 0 |
Housewife/house husband | 16 (19.75) |
Missing | 40 (49.38) |
Caregiving time (daily hours) | 4.05b (8.22)c
|
Barthel Index, median | 39.1 (22.50)a
|
Zarit-caregiver burden, median | 34.53 (13.41)a
|
Regarding the patient’s caregivers, the weight of female relatives in this role should be noted. Caregivers in Spain spent around 8.22 h per day providing care to the children due to the limitations caused by the disease. The average Barthel Index score for patients reflected severe dependence (39), while the burden for caregivers was mild to moderate as the average Zarit Burden Interview score was 35.
The health-related quality of life of the patients and caregivers was assessed (time trade off -TTO- social tariff, as well as the VAS: Table
2). The proxy EQ-5D social tariff show a score of 0.16 (max. of 1) for patients, while the EQ-5D VAS produced a score of 54.1. For caregivers, the mean EQ-5D social tariff score was 0.49 and the mean EQ-5D VAS score was 69.1. However, when considering only patients type II, it is observed that the mean EQ-5D social tariff decreased significantly, obtaining a score equal to −0.012.
Table 2
Health-related quality of life (HRQOL) of patients and caregivers
HRQOL (TTO social tariff score) | 0.158 (0.44)a
| −0.012 (0.347)a
|
Be confined to bed | 19 (23.46%) | 18 (30.0%) |
Unable to wash or dress by themselves | 30 (37.04%) | 26 (43.33%) |
Unable to perform their usual activities | 13 (16.05%) | 11 (18.33%) |
Surfer anxiety or mid depression | 10 (12.35%) | 5 (8.33%) |
Difficulties for usual activities or selfcare | 40 (49.38%) | 18 (30.0%) |
HRQOL (VAS score) | 54.09 (26.30)a
| 53.03 (25.03)a
|
Caregivers |
HRQOL (TTO social tariff score) | 0.484 (0.448)a
| 0.472 (0.475)a
|
HRQOL (VAS score) | 69.1 (21.96)a
| 69.9 (20.03)a
|
The average annual cost associated with SMA reached € 33,721 (SD = 38,700) in Spain (Table
3). While 32.2% of this total cost was attributed to direct healthcare costs, which amounted to € 10,882, the average direct non-healthcare costs were € 22,839 (representing 67.7% of the total cost). Within the category of direct healthcare costs, the largest component was that of the visits to medical specialists, valued at € 7732. The next most significant direct healthcare cost was hospitalizations, estimated at € 1297. The family caregiving costs represented the largest component reaching € 21,127 (62.7% of the total cost of the illness in Spain).
Table 3
Average annual costs per patient (€, 2014)
Drugs | 83 (262) | 0.76% | 0,25% |
Medical tests | 603 (721) | 5.54% | 1,79% |
Medical visits | 7732 (11,211) | 71.05% | 22,93% |
Hospitalizations | 1297 (5856) | 11.92% | 3,85% |
GP & Emergency | 244 (956) | 2.24% | 0,72% |
Health material | 920 (1183) | 8.45% | 2,73% |
Healthcare transport | 3 (13.48) | 0.03% | 0,01% |
Direct healthcare costs | 10,882 (14,974) | 100.00% | 32,27% |
Social services | 746 (2511) | 3.27% | 2,21% |
Direct non-healthcare formal costs | 746 (2511) | 3.27% | 2,21% |
Main informal career | 11,508 (19,855) | 54.47% | 34,13% |
Other informal careers | 9619 (18,666) | 45.53% | 28,52% |
Direct non-healthcare informal costs | 21,127 (30,253) | 92.50% | 62,65% |
Other non-healthcare family costs a
| 966 (1240) | 4.23% | 2,86% |
Direct non-healthcare costs | 22,839 (31,340) | 100.00% | 67,73% |
TOTAL COST | 33,721 (38,700) | 100.00% | 100,00% |
When taking into consideration individuals with type II, it was observed the fact that the mean costs are higher compared with those obtained with all patients (Table
4). Concretely, mean total cost of individuals with type II was € 37,670 (€ 33,721 for all individuals). Informal care cost reached € 24,099 (€21,127 for all), formal care cost arrived at € 827 (€ 746 for all) and direct healthcare cost was € 11,580 (€ 10,882 for all individuals). The reason that explains mainly such difference in costs, especially those related to personal care (informal and formal care), might be associated with the poorer quality of life of individuals with type II.
Table 4
Average annual costs per patient type II (€, 2014)
Direct healthcare costs | 11,580 (14,436) | 30.74 |
Direct non-healthcare formal costs | 827 (2700) | 2.20 |
Direct non-healthcare informal costs | 24,099 (33,240) | 63.97 |
Direct non-healthcare costs | 26,089 (34,366) | 69.26 |
TOTAL COST | 37,670 (42,579) | 100.00 |
Discussion
This study analyzed the social/economic burden of SMA in terms of costs and decreased HRQOL. Specifically, the average annual cost associated with SMA reaches € 33,721, of which 32.2% was attributed to direct healthcare costs and 67.8% to direct non-healthcare costs. Moreover, according to the results obtained, informal caregiving constituted a major cost component.
HRQOL is another source of information that helps define the overall societal impact of a specific health problem. The estimated average EQ-5D social tariff score for patients was 0.16. This score is significantly lower than that for young Spanish people between 16 and 20 years of age (the youngest age range available: 0.987) as estimated from the Spanish Health Survey (2011-2012), or for that of pediatric patients with Type 1 Diabetes Mellitus (0.94) [
33]. Alternatively, the estimated average EQ-5D social tariff score for caregivers was 0.49 while that of the general population of the same age was 0.959 (estimated from the Spanish Health Survey, 2011-2012). These data demonstrate that patients and caregivers experience a strong deterioration in HRQOL relative to the general population. In fact, caregivers have a significantly lower quality of life than the general population after controlling for age [
34], mostly due to economic factors and a lack of appropriate support. Our results reveal areas in which improvements can be made, accentuating the need for family support through social care as well as civic, patient and/or organizational support.
There is currently a lack of publicly driven research into the economic burden of SMA. One previous study on the cost of SMA in Germany estimated the average annual cost per patient to be €70,566 in 2013 [
4]. Major cost drivers were proposed to be informal care cost and overall, the results were very similar to those presented here. However, there were important differences in the direct health costs that probably reflect the distinct populations studied. While we carried out a population survey, the German study was a hospital survey, which is also likely to produce an overestimation of these direct costs, in particular for type I patients that place stronger demands on hospital resources. Thus, we feel that our study provides a more representative approach to estimate e healthcare costs associated with SMA patients.
This study represents the first complete and realistic costing to date of the burden of SMA patients in Spain. The main added value of the study lies in the bottom-up approach to costing. In addition, the costs were estimated for a period of 1 year and therefore, they provide a more accurate outlook of the medium-term burden of SMA. Among rare diseases, SMA is a significant health problem with important social consequences in high-income countries. The incidence and prevalence of SMA, and its consequences in terms of mortality, morbidity, economic costs and loss of quality of life justify the attention received from health authorities and society in general. Particularly, we show that the estimated average annual cost per patient in 2014 was € 33,721 for patients in Spain. The estimated cost of SMA is higher than the social costs of other chronic diseases in Spain, such as stroke (€27,711, base year 2012) [
35], symptomatic chronic heart failure (€12,995 − €18,220, base year 2012) [
36] or HIV/AIDS (€17,300, base year 2010) [
37]. In addition, the estimated cost of SMA is higher than the social costs of other rare diseases as ataxia (€18,776, base year 2004) [
11] and similar to fragile X syndrome (€31,008, base year 2012) [
38], amyotrophic lateral sclerosis (€36,194) [
12] and Duchenne muscular dystrophy (€36,970, base year 2012) [
39].
The findings in this study have several limitations, in particular regarding the study sample, the recruitment process and the validity of caregivers as proxy. However, other studies on rare diseases have used smaller sample sizes due to the low frequency of these diseases and the refusal rates for participation. Patients with SMA were recruited by the Spanish patient association (FUNDAME,
http//www.fundame.net), and although the sample was almost evenly distributed in terms of severity or dependency, we cannot guarantee the absence of selection bias as tends to occur in studies on rare diseases. There is also a potential recall bias given that patient-based data were obtained through a questionnaire. Another potential limitation when assigning health status to children is the fact that this might be a misrepresentation. As concluded elsewhere, the values for health states when ascribed to adults are higher than when those same states are associated to children [
40]. Additionally, due to the information available, the most appropriate technique to be applied in the analysis to estimate the informal care cost was proxy good method. Other alternative methods such as opportunity cost method and contingent valuation [
18‐
20,
41] were not considered in this study.
Finally, our study was based on cross-sectional data, whereas ideally the study would be a prospective longitudinal study of a cohort of people with SMA. However, this type of study was beyond our current means. To our knowledge, no study into the cost of SMA of this nature has been carried out to date and therefore, the challenge to researchers, authorities and patient associations is to carry out such a longitudinal study in the future. It is quite frequent that cost of illness studies are criticized due to the nature of the information they provide, as well as the types of resources included and the way in which they are valued [
42,
43]. Nevertheless, cost of illness studies continue to attract the particular interest of policy makers and for society as a whole [
44]. Firstly, because they provide information on the real economic burden that some chronic diseases cause (not only including healthcare costs but also, non-healthcare costs), which can be useful when designing policies, programs or strategies. As shown here, the non-healthcare cost of SMA is higher than the healthcare cost (68% vs 32% respectively). Thus, the failure to take into consideration non-healthcare costs might underestimate the real impact that some chronic diseases. Furthermore, cost of illness studies complement epidemiological information and in recent years, several clinical trials on SMA have been performed and others are ongoing (see
http//www.clinicaltrials.gov). In particular, advanced therapies such as intrathecal antisense oligonucleotide administration to modify splicing of the SMN2 gene [
45] and intravenous gene therapy based on self complementary AAV-SMN1 [
46] appear to be very promising approaches to therapy, which will surely change the epidemiological landscape of SMA types and the natural history of the disease. These advances will influence the future healthcare of SMA patients, switching to a more proactive approach as opposed to the reactive measures of complications and palliative care.