Abstract
Introduction:
In order to estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated.
Objectives and Methods:
This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015.
Results:
A total of 516 patients (mean age, 53 years) participated in Austria; 72% were below retirement age, and of these, 46% were employed. Employment was related to disability, and MS affected productivity at work for 77% of those working. Overall, 94% and 67% of patients experienced fatigue and cognition as a problem. Mean utility and total annual costs were 0.778 and 25,100€ at Expanded Disability Status Scale (EDSS) 0–3, 0.579 and 44,100€ at EDSS 4–6.5, and 0.244 and 73,800€ at EDSS 7–9. The mean cost of a relapse was estimated at 2563€.
Conclusion:
This study illustrates the burden of MS on Austrian patients and provides current data on MS that are important for development of health policies.
Introduction
Austria recognised the value of economic studies for decision making in health care later than most other European countries. Nevertheless, a consensus paper involving a large group of different stakeholders was developed in 2006, 1 and in 2007, the Federal Institute for Quality in Health Care (BIQG) 2 dedicated to the development and enforcement of clinical guidelines, clinical pathways and health technology assessment was founded. Since then, cost-effectiveness studies for reimbursement decisions of new outpatient drugs are used, with, however, a focus on the impact on the health care budget. Compared to other countries, cost-effectiveness studies and even cost of illness studies are thus relatively scarce. In multiple sclerosis (MS), however, large burden of illness studies using similar methodology were published in 2004 and 2006.3,4
The availability of disease-modifying treatments (DMTs) has led to changes in patient management and to focus on earlier and better diagnosis and adjustments in the diagnostic criteria themselves. One of the consequences in this regard is that the recorded prevalence of the disease is quite different from that estimated two or three decades ago, leading to an increase in prevalence.5,6 Recent estimates for Austria show approximately 12,500 MS cases. 7 With diagnosis possible already after a clinically isolated event, 8 one must also expect a different distribution of the type of MS and the severity of the disease than 10 years ago: a larger proportion of patients with relapsing-remitting disease and thus of patients in the early stages of the disease with less disability.
It is therefore important to update the information on the burden of illness. This study is a continuation of these efforts and is part of a European-wide effort to update information on the burden of illness of MS in 16 countries, endorsed by the European Platform of MS Societies (EMSP) and carried out with the support of national MS societies. 9 It uses a similar methodology as the last European survey in 2005 that also included Austria.10,11
Materials and methods
The detailed methodology for the European survey is published separately. 11 We therefore only provide a short summary of the general methods and issues specific to Austria.
Data
The study aimed to estimate the costs of all health care and other resource utilisation related to MS: hospitalisation, rehabilitation, consultations, diagnostic procedures and tests, medication, community care, family support and production losses (sick leave, early retirement, invalidity). In addition, information on major symptoms such as fatigue and cognition (using visual analogue scales, VAS), health-related quality of life (HRQoL), utility (using the EQ-5D 12 ), as well as patient-assessed disability using descriptions based on the Expanded Disability Status Scale (EDSS), were collected.
Data were collected with a standard questionnaire, at a single point in time, for a retrospective period of time. The latter was varied depending on the question in order to minimise recall bias: 1 month for use of drugs, community services and family help; 3 months for hospitalisation, consultations, tests, sick leave and relapses; 12 months for major investments. Resource utilisation is reported for these time periods, while cost calculations are annualised.
Disease information (type of MS, disability (EDSS), HRQoL, utility (EQ-5D) 12 ), symptoms (fatigue, cognition) and the effect of MS on work related to the current day or week. For comparability across countries, 13 utilities are estimated with the original value set for the EQ-5D developed in the United Kingdom. 14 Contrary to a number of countries, Austria has not developed its own national value set, and the German value set is generally used (not presented).
The handling of missing data for the cost calculation is explained in more detail in the paper describing the methods. 11 For resource use, we present actual answers without any imputation for missing answers. Also, no imputations are made for missing information on disease status, symptoms and HRQoL.
Costs
Costs are calculated in the societal perspective, including all costs regardless of who ultimately is responsible for them. Patient co-payments and patients’ out-of-pocket expenses are thus included.
The cost of a relapse is calculated as the difference in quarterly costs between patients with or without a relapse and an EDSS score of 0–6; patients who were unsure were excluded from the estimation. Invalidity, early retirement and DMT costs are not considered in the calculation, as these are unlikely to be affected within 3 months.
Unit costs for the individual resources were taken from public sources and are described in the methods paper, 11 and results are reported in EUR (2015).
Patients
The objective was to include a sample where all levels of disease severity (defined by EDSS) were represented in sufficient numbers to permit analysis, rather than a prevalence sample. This allows highlighting how costs and HRQoL change as the disease progresses and provides the necessary data for cost-effectiveness analysis of treatments that are expected to change the course of the disease. Due to this approach, in addition to the enrolment method, mean results, in particular cost estimates, may not be representative and should neither be extrapolated directly to national costs nor be compared directly to the results in earlier studies. We therefore report results by disease severity groups only (mild MS EDSS, 0–3; moderate MS EDSS, 4–6.5; severe MS EDSS, 7–9).
Data collection
In anonymous surveys, it is difficult to include a fully representative patient population, and changes in the management of MS, in particular earlier diagnosis, have increased this challenge. In addition, participation will depend heavily on the methods used for the survey: collecting data in MS centres tends to overestimate the number of patients with early but severe disease and on treatment with DMTs; 15 collecting data from members in patient organisations may lead to the opposite. Internet surveys will bias towards younger patients with better education, while postal mailing may bias towards older patients.
The Austrian data were collected during spring 2015. The national MS patient association (ÖMSG) distributed the invitation to participate in the study with an insert into their quarterly news bulletin sent to 3500 members, followed by a reminder in the subsequent bulletin.
Results
A total of 516 evaluable responses were received. The majority of patients returned the paper questionnaire (85%), which implies a certain quantity of missing data. All regions of Austria were well represented, with however an overrepresentation of Tirol, Vorarlberg and in particular Vienna. 16
Table 1 provides details on demographics, employment and disease.
Sample demographics and disease information.
MS: multiple sclerosis; SD: standard deviation; EDSS: Expanded Disability Status Scale; RRMS: relapsing-remitting multiple sclerosis; DMT: disease-modifying treatment.
Of total sample (N = 516).
Of patients of working age (N = 371).
Of patients working (N = 173).
Demographics and employment
The age of respondents in Austria ranged from 20 to 89 years (mean and median, 53; standard deviation (SD), 12.4). Women represented 73% of the sample; 75% lived with their family and only 10 patients lived in a nursing home at the time of the survey. Education levels in our sample were slightly higher than in the general population of that age: 9% of patients had basic education, 74% had a secondary or a professional degree and 16% a university degree. This compares to 19% of the population with primary education, 68% with upper secondary education and 14% with tertiary education in 2015 (23%, 64% and 13% for women; 15%, 71% and 14% for men, respectively). 17
The majority of patients in the sample was below retirement age (defined as effective retirement age, 59.4 years for women and 61.9 for men 18 ): 371 patients (72%). Of these, 170 patients (46%) were employed or self-employed. Three patients above retirement age also worked, bringing this group to 173 patients (or 34% of the full sample), with a mean age of 44 years. This compares to an employment rate of 71.3% in the general population aged 15–64 in 2015 (67% for women and 75% for men). 19 However, 62% of employed patients worked part time, on average 24 hours per week, and 63% of these did so due to MS. In the general population in Western Europe, only around 21% of employed work part time, confirming indeed the effect of MS not only on employment but also on working time. 20 Short-term sick leave during the past 3 months was reported by 37 patients (21%), with a mean duration of 18 days.
Employment decreased rapidly with advancing disease, as shown in Figure 1. Of non-employed patients below retirement age, 43% indicated MS as the reason for leaving the workforce.
Employment by disease severity.
Most employed patients felt that MS affected their productivity at work (73%), and only 18% indicated that they had no problems related to work, while 9% had not answered this question. The severity of the effect covered the entire VAS range from 0 to 10, with a mean of 2.7 (SD, 2.4) (Figure 2). Fatigue was considered the most bothersome symptom (60%), followed by mobility (30%), difficulties with thinking (25%), pain (19%) and low mood (18%).
Fatigue, cognitive difficulties and effect of MS on productivity at work.
Disease characteristics
Data on disease characteristics are summarised in Table 1. The mean EDSS in the sample was 4.4 (SD, 2.5), with the mild group representing 40% of the sample, the moderate group 35% and the severe group 22%. The number of patients at each EDSS level exceeded 30 except at EDSS 9 (6 patients only), with, however, a surprisingly large group at EDSS 8 (66 patients).
As expected, with 60% of the sample at an EDSS of 4 and above, and a mean disease duration of 20 years (Table 1), the proportion of patients with relapsing-remitting multiple sclerosis (RRMS) was low (42%). However, only 25% thought they had secondary-progressive multiple sclerosis (SPMS), while 23% indicated that they had primary-progressive multiple sclerosis (PPMS) and 2% were missing. The proportion with PPMS is higher than expected even for this sample, considering what is seen in recent studies, 21 and suggests that patients were insecure in their answers regarding the type of disease. The same issue was identified in both previous studies in Austria.3,4 We therefore did not include the disease course in our analyses and focused on EDSS levels instead, as in these earlier analyses. Despite the large proportion of patients with advanced disease, DMTs were used by 63% of the sample, and as many as 33% of patients in the severe group were on treatment (Table 1). Among users, 29% were on their first DMT treatment; first-generation DMTs were used by 56% of users (Table 2).
Type of DMTs used (N = 326 a ).
DMT: disease-modifying treatment.
Missing information on DMT for 11 patients.
Relapses in the preceding 3 months were reported by 56 patients (11%) of which about half occurred in the past month (Table 1). However, 55 patients (11%) were unsure whether they had a relapse or not, and we assumed that the answer was no. Thus, the mean relapse rate over a 3-month period was estimated at 0.1 (SD, 0.4). Corticosteroids were administered to 70% of patients with relapses, most often as infusion.
Symptoms and HRQoL
Fatigue and cognitive difficulties were an issue for the majority of patients, and both were related to disease severity (Figure 2). Fatigue was present in 94% of patients (2% missing). The mean VAS score was 5.1 (SD, 2.4) for the whole sample, 4.4 for patients with mild disease and 5.6 for patients in the moderate and severe groups. Cognitive difficulties were present in 67% of all patients (3% missing). The mean VAS score in the group with difficulties was 4.4 (SD, 2.0) overall, 4.0 in the mild, 4.5 in the moderate and 5.0 in the severe group. For the full study sample (assigning 0 to the group with no problems), the mean score was 3.0 (SD, 2.6), with scores of 2.8 in the mild and 3.2 in the moderate and 3.1 in the severe group.
All five domains of HRQoL included in the EQ-5D displayed problems for a large number of patients: pain/discomfort for 71%, usual activities for 64%, mobility for 61%, anxiety/depression for 49% and self-care for 35%. Both the severity and the affected domains changed with advancing disease. Self-care was basically unaffected in patients with mild disease, but declined very rapidly with advancing disease, with less than 10% of the severe group experiencing no difficulty. Mobility, pain and usual activities presented problems for almost all patients already with moderate disease and difficulties increased with advancing disease; most noticeably, however, anxiety was present in about 50% of the patients at all levels of disease severity (Figure 3).
Problems in different domains of QoL (EQ-5D), N = 457.
Utility
Utility scores declined with increasing disability (EDSS) (Figure 4). Mean utility in this specific sample of patients was 0.602 (SD, 0.371), and 0.778, 0.579 and 0.244 in the mild, moderate and severe groups, respectively.
Utility by EDSS (N = 457).
Resource utilisation
Resource use data are presented in Table 3. Inpatient admissions were required for 47 patients (9%) in the preceding 3 months, most often to the neurology ward, 1.4 times on average and for a mean of 13.1 (SD, 13.8) days. Day admissions were reported by 25 patients (5%), on average once a month. Inpatient or day admissions to rehabilitation centres occurred for 66 patients (13%).
Resource utilisation, health care and community services.
SD: standard deviation; MS: multiple sclerosis; MRI: magnetic resonance imaging; DMT: disease-modifying treatment; OTC: over-the-counter drug.
A majority of patients (386 patients, 75%) had a consultation during the past 3 months, most often with neurologists (58%), general practitioners (34%) and physiotherapists (22%). Investigations and tests were done for 44% patients, with 121 patients (23%) undergoing magnetic resonance imaging (MRI) of the brain and 91 patients (18%) of the spine. Medications for MS and MS-related symptoms were used by 86% of patients during the past month. Drugs other than DMTs and corticosteroids were used by 44% of patients, predominantly treatments for walking, spasticity and pain (29%) and depression (19%). Non-prescription drugs were purchased by 53% of patients.
Investments in equipment and devices to aid patients’ mobility were made during the past 12 months for or by 37% of patients, most often for walking/mobility aids and modifications to the house or the car.
Community and social services were used by 30% of patients, most frequently home help. Help from family was used by 52% of patients, on average 19.6 (SD, 11.6) days per month and 4.2 (SD, 5.1) hours per day. Both community services and informal care were related to disease severity (Figure 5).
Use of informal care (days per month and hours per day, per user).
Costs
Total mean annual costs per patient for patients with mild, moderate and severe disease and by EDSS score are presented in Figure 6 and Table 4.
Total mean annual cost per patient by disease severity (N = 516).
Total mean annual cost per patient by disease severity (mild, moderate, severe), N = 516 (EUR 2015).
EDSS: Expanded Disability Status Scale; SD: standard deviation; DMT: disease-modifying treatment.
The average cost of a relapse for patients with an EDSS between 0 and 6 was estimated at 2563€. All types of costs increased during a relapse, with hospital care representing 44% of the additional cost, community services 19%, informal care 14% and sick absence 7% (Figure 7).
Relapse costs (3 months).
Discussion
This study provides an update to current understanding of the burden of MS on patients, the health care system and society in general in Austria based on a cross-sectional survey conducted in 2015. The survey follows the same methodology as earlier studies, and a number of findings are surprisingly similar. Demographic data of the sample in this study are very similar to those in the earlier studies, likely due to the same approach to patient recruitment. The level of disability was consequently also comparable, but not necessarily representative of prevalence in Austria. Rather, it represents the members of the Austrian MS patient association.
Nevertheless, the sample was geographically representative despite a slight dominance of an urban population, with educational levels only slightly above the general population and well spread over the entire disease severity. Despite responses being mainly on paper, missing answers were relatively limited, never exceeding 1%–2%. Thus, while the sample may not match prevalence in terms of disease severity or type of MS, the results by EDSS can be considered representative. Also, disease symptoms and utility were very similar to those found in all the other countries, attesting that the severity of the disease affects patients in the same way regardless of jurisdiction or heath care systems.
Resource consumption, while reflecting the clinical needs of patients, has also to be seen in the light of the organisation of the Austrian health care system, general medical traditions, cultural norms, but also general trends. As an example, 26% of patients were admitted as inpatients in the survey in 2005, 4 while this was the case for only 9% in 2015, reflecting the general trend towards outpatient treatment and the implementation of a nation-wide MS centre network in Austria over the past 15 years. MRIs were more frequent in 2015 as MRI is increasingly used for managing patients. The use of DMTs was substantially higher in 2015 (63% compared to 40%), in line with better access to treatment and an increased choice of different treatments. On the other hand, the use of symptomatic medication and non-prescription medicines was essentially the same.
An important finding of this study is the overwhelming presence of fatigue in almost all patients and the importance of cognitive difficulties, regardless of disease severity. Similarly, problems with anxiety and depression are present at the same level (in around 50% of patients) throughout the disease. While our data do not allow an investigation of causal effects, it is of note that in all 16 countries in the study a substantial number of patients are not able to work due to MS already very early in the disease and with basically no physical disability. In Austria, 11.5% of patients in the mild group (EDSS, 0–3) receive an invalidity pension. Thus, the results of our study corroborate previous findings in a study with German MS patients that ‘invisible’ symptoms such as fatigue, cognitive difficulties and mood disorders may have an enormous impact on work ability. 22 These results have important consequences, both for the management of MS patients, for example, focus on symptomatic treatment or even prevention of these symptoms, and legal bodies, such as sick funds and health policy, for recognition of the socioeconomic impact of these debilitating symptoms on working capabilities and premature retirement.
In conclusion, these data characterise various aspects of the burden of MS on patients and society and capture patterns of resource utilisation that could inform future policy recommendations. In addition, these data provide input into cost-effectiveness analyses for reimbursement decisions.
Footnotes
Acknowledgements
The authors are grateful to Andrea Dürmoser and Dr Ulf Baumhackl (ÖMSG) and Sigrid Redl (MedMedia) for making the survey available to members, to Jennifer Eriksson and Johan Dalén (MAPI Group) for organisational and statistical support, to Markas Gedminas (Medscinet) for construction of the online platform, to Barbara Rosengren for language editing and to Cara Harley for formatting.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: T.B. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for multiple sclerosis: Almirall, Biogen, Celgene, Genzyme, Merck, Novartis, Octapharma, Roche and Sanofi Aventis/TEVA. His institution has received financial support by unrestricted research grants (Biogen, Novartis, Roche and Sanofi Aventis/TEVA) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche and Sanofi Aventis/TEVA. G.K. has received consulting fees from Almirall, Bayer, Biogen, Merck Serono, Novartis, Oxford PharmaGenesis, Sanofi Genzyme and Teva. J.B., D.C. and M.G. were at the time of the study employed by the MAPI Group, a research company acting as consultants to pharmaceutical companies.
Funding
The author(s) declared receipt of the following financial support for the research, authorship and/or publication of this article: European Health Economics and MAPI have received funding for the full research and production of the manuscripts from Biogen.