Abstract
Introduction
Multiple sclerosis (MS) has a considerable social impact and economic consequences. The costs associated with MS are high due to its chronicity, progressive disability and early onset in economically productive years. Furthermore, treatment of MS has changed over the last 15 years, with new disease-modifying drugs (DMDs) introduced. These new treatments come at higher cost than old inexpensive symptomatic treatments and are also associated with more intensive patient management. On the other hand, DMDs have been shown to decrease the incidence of relapses and might have the potential to delay disability progression.1-3 Thus, effective control of disease activity through better treatment not only improves the quality of life of patients but might also decrease the overall cost of MS over time.
A number of cost-of-illness studies in MS were performed in the past decade, including a large study in nine European countries. 4 From the East European countries, the cost-of-illness has only been calculated in Poland. 5 In the Czech Republic, no cost-of-illness studies have been carried out so far.
The aim of this work was therefore to establish the total cost of MS in the Czech Republic from the societal perspective, overall and by the level of disease severity.
Methods
Patients
In this prevalence-based cost-of-illness study, the data were collected both prospectively and retrospectively directly from a sample of patients with MS. A total of 1027 participants were recruited in 7 MS centres in the Czech Republic: General University Hospital in Prague (n = 579), Teplice Hospital (n = 119), Faculty Hospital Olomouc (n = 74), Regional Hospital Pardubice (n = 66), Hospital Ceske Budejovice (n = 50), University Hospital in Pilsen (n = 18) and The University Hospital Brno (n = 3). The criteria of inclusion were definite diagnosis of MS according to the 2005 revised McDonald criteria 6 and absence of any other neurological disorders, and subjects were enrolled from patients who visited the centres in 2007. The resulting sample was representative of the patient population treated in the specialised MS centres in Czech Republic with all stages of disability and types of disability progression represented (Table 1). All subjects gave informed written consent to participation in the study and no sensitive personal information was disclosed. The study protocol was approved by the Ethical Committee of the 1st Faculty of Medicine and General University Hospital in Prague.
Demographics of the sample.
p ≤ 0.05, compared patients with mild, moderate and severe disability; ANOVA, Kruskal-Wallis or χ2 tests.
EDSS, Expanded Disability Status Scale; MS, multiple sclerosis.
Data collection
All data were collected with standardised pre-tested questionnaires. To ensure good compliance and understanding of the protocol, patients first completed sample questionnaires with individual assistance from the investigators. Patients were then asked to complete the questionnaires individually during the subsequent 3-month period; these were collected in person or mailed to the investigators. To ensure the accuracy of the data, all medical information was validated by reviewing patients’ medical records.
The demographic information collected included age, gender, education level, marital status, living situation, current employment status, sick leave and early retirement as well as information on household income. Disease information comprised age at first symptoms, year of diagnosis, clinical course of MS, current Expanded Disability Status Scale (EDSS, evaluated by an experienced scorer) and number of relapses over the 3-month study period. Information on medical conditions other than MS were obtained. Direct medical costs covered inpatient and outpatient medical care, medication (DMDs, other MS therapy, concomitant and over- the-counter medication and drug administration), investigations and tests, inpatient and outpatient rehabilitation, aids and home care. Direct non-medical costs comprised transport, social services, adaptations and major investments directly related to MS. Indirect costs included production loss due to early retirement, sick leave and informal care.
The information on resource use was collected prospectively over a 3-month period, except for inpatient rehabilitation that covered the past year and major investments that covered the time from the disease onset. This predominantly prospective design enhanced the validity of the information collected from patients, and accuracy was further verified for healthcare resource use against patients’ charts. To determine the costs of MS rather than the costs of patients with MS, the resource use not related to MS was excluded from all analyses.
Data analysis
The main analysis estimated the costs of MS from the societal perspective, i.e. regardless of payer. With the exception of major investments and inpatient rehabilitation, the annual costs were estimated by multiplication of the costs calculated over the 3-month period. The major investments since the disease onset were divided by the number of years since diagnosis, while the costs of inpatient rehabilitation were not further adjusted, as they covered the period of one year. The costs were calculated using unit costs based on 2007 prices (see Table 2). Costs of medication were obtained from the Ministry of Health of the Czech Republic (Act 378/2007, www.portal.gov.cz/zakon378/2007). Cost of social services comprised the costs of assistance and food delivery. Income was calculated based on the information provided by each patient individually. Loss of production due to sick leave or full/ partial retirement due to MS was calculated for subjects in productive age (18–65 years) according to the human capital method and using patients’ reported wages. Informal care was calculated as opportunity cost of time for all carers, valuing the hour with the average hourly disposable income (cap at 40 hours per week). All costs are presented in 2007 Euros.
Selected unit costs.
Act number 532/2005 – adjusted by Notice from 20/12/2006, www.mzcr.cz
Act number 108/2006, www.mzcr.cz
Act number 48/1997, www.mzcr.cz
To evaluate the effect of disability on the costs of MS, patients were stratified into three groups: those with mild (EDSS 0–3.5), moderate (EDSS 4–6.5) and severe (EDSS 7–9.5) disability. The relapse costs were estimated as the difference in costs between all patients with and without relapses (not stratified by EDSS), as shown elsewhere. 7
Statistical analysis was carried out with PASW 18 (SPSS Inc.) and Statistica 9 (StatSoft) software packages. Data are given throughout as mean ± standard deviation. All comparisons were evaluated on the 95% level of statistical significance. In all variables, basic descriptive analysis was carried out. One-way analysis of variance (ANOVA) or the Kruskal–Wallis test were used to compare demographic and clinical data as well as costs between the groups stratified by EDSS. Demographics and costs in patients with and without relapses were compared with Student’s t-test and Mann–Whitney U-test. For the categorical variables, a χ 2 test was used. To control the false-discovery rate, Benjamini–Hochberg correction was applied.
Results
Of the recruited 1027 patients, 909 completed the questionnaires and were included in the study; i.e. the response rate reached 89% (varying between 80% and 100% depending on the centre). Demographics of the study population are summarized in Table 1. Mean EDSS was 3.4 ± 2.2, with median 3 and interquartile range 1.5–5. Distribution of EDSS within the patient sample is shown in Figure 1. When stratified by disease severity, 67% of patients had mild, 27% had moderate and 10% had severe disability. Patients with more severe MS were older with a longer disease history compared with those with milder MS (p ≤ 2 × 10−50, F2,906 ≥ 127, one-way ANOVA). The proportion of patients with relapses tended to be lower in the group with severe disability, however, this trend was not statistically significant (p = 0.5, χ22 = 1.4, χ2 test). While 54% of the patients with mild MS were treated with DMDs, the patients with severe MS received DMDs only occasionally (3%). It can be seen in Table 1 that the work capacity decreased and the dependence on pension increased with the increasing disability (p ≤ 5 × 10−48, χ24 ≥ 231, χ2 test).
Distribution of patients by disability. Stratification of the subjects into three severity groups is indicated by the dashed lines. Each strata was represented by at least 85 patients.
Figure 2 shows that the mean annual costs of MS per patient reached €12,272 ± 9430 in our sample. These costs consisted of 51% of direct medical costs, 4% of direct non-medical costs and 45% of indirect costs. Full account of the costs is given in Table 3 (for the costs in Czech Koruna, see Supplementary Table 1). It can be seen that the treatment with DMDs (administered to 41% of patients), production loss due to early retirement (in 49% of patients) and informal care (in 28% of patients) constituted the most substantial portions of the overall costs (see Figure 3). While 7% of patients were hospitalised during the study period, 82% visited a neurologist and 72% were seen by other specialist (together amounting to 5% of the total costs).
Mean annual costs of multiple sclerosis per patient in the unstratified sample (overall) and in the three EDSS strata. Total costs as well as direct and indirect costs are given.
Estimated annual costs of multiple sclerosis per patient.
p ≤ 0.05, compared patients with mild, moderate and severe disability; analysis of variance (ANOVA) or Kruskal–Wallis tests.
EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; OTC, over the counter.
Distribution of expenses in multiple sclerosis, societal perspective.
The costs of relapses were estimated by comparing the expenses in the groups with (n = 109) and without relapses (n = 800) over the 3-month period. There was no significant difference in either MS duration (p = 0.4, t907 = 0.9, t-test) or EDSS (p = 0.2, U = 40,207, Mann–Whitney U-test) between the relapsing and non-relapsing sub-groups. The difference in the annualized mean overall costs amounted to €2054 ± 12,533 (p = 0.04, t907 = 2.1, t-test) and was attributed to the increase in indirect costs (€1325 ± 8307) and direct medical costs (€819 ± 9517), diminished by a mild decrease in direct non-medical costs (€90 ± 2439).
When comparing the patients stratified by the severity of MS (see Figure 2 and Table 3), it is apparent that the annual costs increased by 42% and 131% in those with moderate and severe disability, respectively, compared with the patients with mild disability (p = 6 × 10−39, F2,906 = 179, one-way ANOVA). While direct non-medical and indirect costs increased with the MS severity, direct medical costs decreased in moderate disability and increased again in severe disability. The changes in direct medical costs were attributed to the decreasing use of DMDs in the moderately and severely impaired and the higher use of other resources (other medication, rehabilitation, aids, ambulatory, hospital and home care) in the severely impaired (see Figure 4). In patients with the most severe disability, the hospital care was replaced with rehabilitation and more extensive ambulatory care. The increase in the direct non-medical costs was driven predominantly by the increment in the costs of social services. Of the indirect costs, the production losses increased mainly in the moderately impaired (with the balance shifting from sick leave to early retirement), while the costs of informal care increased mainly in the severely impaired patients.
Distribution of expenses in multiple sclerosis stratified by the disease severity.
Discussion
In this work we present the outcomes of the COMS study, the first cost-of-illness study of MS in the Czech Republic. Using the societal perspective, we have shown that the average annual costs amount to €12,272 per patient, varying between €9905 and €22,880 depending on the disease severity. With current prevalence of 170/100,000 (i.e. overall 17,000 patients; Dr Marta Vachova, unpublished results), the total costs of MS in the Czech Republic are estimated at €208.6 million per year.
These costs are a factor of 1.5–3.5 lower in comparison with other countries with available data, such as UK, Germany, Australia or USA.8-11 The costs are lower proportionally across all of the categories of expenses which are based on the unit costs. Therefore, large proportion of the observed differences is attributed to the markedly lower unit costs in the Czech Republic compared with other Western countries. For example, the unit costs of a neurology visit and an inpatient stay amount to €13 and €31.5 in the Czech republic versus €65 and €360 in the Netherlands, respectively. 7 Furthermore, the less pronounced productivity losses, which result from the relatively lower average wages, also contribute substantially to the lower overall MS costs. In contrast, the average annual costs of DMDs in Czech Republic (€4267) are comparable with those in Italy or Austria (€4722–4957),12,13 and thus constitute markedly larger proportion of the direct medical costs (68% versus 28–42%, respectively). i On the other hand, the costs of MS in Czech Republic are a factor of 4–5 higher compared with those calculated in Poland in 2002. 5 The Polish study was the first cost-of-illness study in MS in the East European region and was carried out in 148 patients from 3 centres. Apart from lower unit costs and changes in market prices, an important reason for the markedly lower costs in Poland was the fact that no patients using DMDs were included in the 2002 study. In contrast, DMD-treated patients constituted substantial proportion of our sample population (41%) with the costs of DMDs accounting for 33% of the overall MS costs. For more comprehensive overviews of the MS costs in other countries see Kobelt et al. 4 and Sharac et al. 14
The present study was carried out in 7 MS centres in various regions of the Czech Republic, however, more than half of the patients were recruited from the MS Centre of the General University Hospital in Prague. As a result of this, patients with higher disease activity and with mild disability could be slightly over-represented in the sample. Compared with the studies completed in other European countries, the proportion of patients with relapses over the 3-month period was lower in our sample (12% versus 16–29%). 4 Also the mean EDSS as well as the proportion of severely impaired patients were lower in our study (EDSS: 3.4 versus 3.8–5.1; severely impaired: 10% versus 5–39%).4,15 This could explain the relatively low total costs of MS compared with those estimated in the 2009 Comparator report by Kobelt and Kasteng. 16 This difference in total costs is driven by the indirect and direct non-medical costs, which are, as we have shown here, strongly associated with disability. Finally, as a result of predominance of patients from large MS centres in our sample, the proportion of patients on DMDs was higher than that estimated in the Czech Republic in 2008. 16
Stratifying our patients according to their EDSS, we have observed an apparent increase in the total MS costs with the increasing severity of MS. In the patients with severe MS the total costs are approximately a factor of 2.5 higher than in those with mild MS. This increase is similar to that observed in Germany, Austria or Belgium (a factor of 2.2–2.5), while in other countries (e.g. Sweden, Switzerland or UK) the disability-dependent escalation of costs is even more prominent (a factor of 3.9–4.9) due to high provision of social services by the healthcare or social systems. 4 The changes in direct medical costs reflect gradual shift from DMDs to other treatment and increasing consumption of rehabilitation, hospital, ambulatory and home care with increasing disability (see Table 1). It is consistent with trends observed in other European countries. In addition to this, the higher disability leads to increased use of services and in decreased work capacity. Similar to European data, the proportion of employed patients drops from 67% in those with mild disability to 5% in those with severe disability. Finally, the most severe disability is associated with increased major investments and costs of aids, and the hospital care is replaced with rehabilitation and ambulatory care.
While we have not used any instruments to evaluate and quantify the quality of life in this study, the strong relation between the disability and utility is well known. 17 Commonly used DMDs have the potential to reduce the activity and progression of MS and thus may improve the utility in MS patients. In fact, a number of studies investigated their cost-effectiveness, however, DMDs such as interferons or glatiramer acetate proved to be only marginally cost-effective (for review see Phillips 18 ). Advanced clinical markers, such as individual predictors of treatment non-response, constitute a promising instrument to further enhance the efficacy of DMDs through individually tailored therapeutic regimens.
Footnotes
Acknowledgements
The authors are grateful to Dr Marta Vachova, Dr Vladimira Sladkova, Dr Alena Novotna, Dr Libuse Lhotakova and Dr Jiri Fiedler from the associated institutions, which have provided the patient data.
Funding
The study was supported by the Czech Ministry of Education (grant number MSM 0021620849).
Notes
References
Supplementary Material
Please find the following supplemental material available below.
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