Abstract
Background:
In order to assess the value of management strategies in multiple sclerosis (MS), outcome data have to be combined with cost data. This, in turn, requires that cost data be regularly updated.
Objective and methods:
This study is part of a cross-sectional retrospective study in 16 countries collecting current data on resource consumption, work capacity and health-related quality of life (HQoL). Descriptive analyses are presented by level of severity; costs are estimated in the societal perspective, in RUB 2015.
Results:
A total of 208 patients (mean age: 38.5 years) participated in the Russian study; 97% were below retirement age, and of these, 49% were employed. MS was reported to affect productivity at work in 63% of patients. Overall, 87% and 41% of patients felt that fatigue and cognition were a problem. The mean utility and costs were 0.769 and 578,000 RUB at Expanded Disability Status Scale (EDSS) 0–3, 0.509 and 826,000 RUB at EDSS 4–6.5, and 0.071 and 1,013,000 RUB at EDSS 7–9. The average cost of a relapse was 33,000 RUB.
Conclusion:
This study illustrates the burden of MS on Russian patients and provides current data that are important for developing health policies.
Introduction
Few cost of illness studies in multiple sclerosis (MS) have been published for Russia. All of them were published in Russian and were parts of small pharmacoeconomic studies of disease-modifying treatments (DMTs) to show differences among them.1–4 The mean cost of MS in 2002–2009 was generally estimated to be nearly US$5000 per year but greatly depended on the severity of the disease and the DMTs used.1,2,4
The availability of new treatment options has led to changes in patient management and a 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.5,6 The most recent estimate suggests that the prevalence in Russia is at around 80 cases per 100,000 population, 7 while 10–20 years ago it was below 50 per 100,000.8–10 With wide use of magnetic resonance imaging (MRI) and earlier diagnosis after a clinically isolated event,11,12 one must also expect a different distribution of the type of MS and the severity of the disease: a larger proportion of patients with relapsing-remitting disease and thus of patients in the early stages of Expanded Disability Status Scale (EDSS).
It is therefore important to update the information on the burden of MS, and this study is part of a European-wide effort in 16 countries, endorsed by the European Platform of MS Societies (EMSP) and carried out with the support of national MS societies and clinical experts. 13 It uses a similar methodology as a previous European survey in 2005 that, however, did not include Russia. 14
Materials and methods
The detailed methodology for the European survey is published separately, as introduction to this series of country reports. 15 We therefore only provide a short summary of the general methods and issues specific to Russia.
Data
The study aimed to estimate all costs 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, health-related quality of life (HRQoL) and self-assessed disability using descriptions based on the EDSS, was 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 such as the type of MS, disability (EDSS), HRQoL, utility (EuroQol five-dimensions (EQ-5D) 16 ), symptoms (fatigue, cognition) and the effect of MS on work related to the current day or week. For comparability across countries, 13 utilities were estimated with the original value set development in the United Kingdom. 17
The handling of missing data for the cost calculation is explained in more detail in the paper describing the methods. 15 For resource use, we present actual answers without any imputation for missing answers. Also, no imputations are made for missing information on disease status and HRQoL.
Costs
Costs are calculated in the societal perspective, including all costs regardless of who ultimately is responsible for paying 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 of 0–6; patients who were unsure were excluded from the estimation. Invalidity, early retirement and DMT costs are not considered in this calculation as they are unlikely to be affected directly within 3 months.
Unit costs for the defined resource items were taken from public sources and are described elsewhere; 15 results are reported in Russian Ruble (100 RUB = 1.469 EUR 2015 average).
Patients
The objective was to include a sample where all levels of disease severity (defined by EDSS) were represented in sufficient numbers to highlight how costs and HRQoL change as the disease progresses. This provides the necessary data for cost-effectiveness analysis of treatments that are expected to change the course of the disease. As a consequence, our study population does not represent the prevalence of MS, and average results for the sample are not meaningful. They can neither be extrapolated to national costs without careful adjustment, nor can they be compared directly to the results in other studies or other countries. We therefore report results by disease severity only, for patients with mild (EDSS 0–3), moderate (EDSS 4–6.5) and severe MS (EDSS 7–9).
Data collection
In anonymous surveys, it is difficult to include a fully representative patient population, and changes in 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 clinical MS centres tends to overestimate the number of patients with early disease and on treatment with DMTs; collecting data from members in a patient organisation may be influenced by the structure and the activities of the organisation. Internet surveys will bias towards younger patients with higher education, while postal mailings may do the opposite.
As in the other countries of this study, participants were to be enrolled by the MS Society. The Russian Multiple Sclerosis Society (RuMSS) has around 100,000 official members organised into 75 chapters, which made it difficult to cover the entire country with our survey. Invitations for participation posted on the website and the patient forum yielded very limited results. We therefore also made paper questionnaires available at the Moscow MS Centre at the 11th City Hospital.
Results
The Russian data were collected for a period of 6 months in 2015–2016, after approval by the ethics commission at the Russian State Medical University. A total of 208 evaluable answers were received: The electronic invitation by RuMSS resulted in 17 online answers, while 191 paper questionnaires were collected at the Moscow MS Centre. Thus, our results do not represent the entire MS population in the country, but rather an urban population mostly from the Moscow area.
Within the European study, the Russian sample was the youngest and least severely affected. 13 Age and EDSS drive the proportion of patients with relapsing disease indicated for DMT treatment, the number of patients actually on DMTs and, to some extent, the proportion reporting a relapse and the proportion of patients of working age. Thus, a majority of patients in the Russian sample had relapsing disease and an EDSS between 0 and 3, a high proportion was on DMT treatment, and almost all were below retirement age (97%). The group with severe disease (EDSS 7–9) was extremely small (n = 11), with only one patient at EDSS 9 and three at EDSS 8. Consequently, our results for this group are presented for reasons of completeness only as the results cannot be interpreted.
Table 1 provides details on demographics, employment and disease.
Sample demographics and disease information.
MS: multiple sclerosis; EDSS: Expanded Disability Status Scale; SD: standard deviation; RRMS: relapsing-remitting multiple sclerosis; DMTs: disease-modifying treatments.
Of total sample (N = 208).
Of patients of working age (n = 201).
Of patients working (n = 101).
Demographics and employment
The age of respondents in Russia ranged from 20 to 64 years (mean = 38.5 years, median = 37 years, SD = 10.5 years); women represented 65%; 88% lived with their family and only three patients were in a nursing home at the time of the survey. Education levels in the sample were high: 64% of patients had university education, while 30% had a secondary or professional degree and only one patient had primary education (5% missing answers). This is, however, not fundamentally different from the national average for the population between 25 and 64 years, where 53% have tertiary education and 94% a secondary degree. 18
In the sample, 201 patients were below the official retirement age of 60 and of these, 49% patients were employed or self-employed. Two patients above the retirement age also worked, bringing this group to 101 patients with a mean age of 36.2 years. This compares to an employment rate in the population aged 15–72 of 73.2% for women and 73.4% for the total population of Moscow in 2015. 19 The impact of MS on work is further illustrated by the fact that only 12 patients worked full-time (mean 50 hours per week), while 81% worked on average 29 hours per week. For comparison, less than 10% of the general population of Moscow have only part-time employment. Sick leave during the past 3 months was reported by 14% of patients, with a mean duration of 19.4 days. Among patients not working, slightly over half (56%) declared that this was due to MS.
Employment decreased rapidly with advancing disease, as shown in Figure 1.
Employment by disease severity.
A majority of employed patients felt that MS affected their productivity at work (63%), but few patients rated the severity of the effect higher than 4 on the visual analogue scale (VAS), resulting in a mean impact of 2.8 (SD = 2.7; Figure 2). Fatigue was considered the most disabling functional loss (47%), followed by mobility (23%), low mood (17%), difficulties in thinking (15%) and pain (7%).
Fatigue, cognitive difficulties and effect of MS on productivity at work.
Disease information
The mean EDSS was 2.9 (SD = 2.1) as the majority of patients had early disease (Table 1). The proportion of patients with relapsing-remitting multiple sclerosis (RRMS) was 55%, 15% had secondary progressive multiple sclerosis (SPMS) and 7% had primary progressive disease. However, the information was missing for 22% of patients, indicating that it is difficult for patients to answer this question. Thus, we ignore the disease type in our analyses and focus instead on EDSS levels, despite the fact that DMTs are mostly indicated for relapsing disease.
DMTs were used by 66% of the sample, with usage declining sharply at higher EDSS levels, as expected (Table 1). Among users, 48% were on their first DMT treatment. First-generation DMTs were used by 75% (12% missing; Table 2).
Type of DMTs used (n = 137 a ).
DMT: disease-modifying treatment.
Missing information on DMT for 16 patients.
Relapses in the preceding 3 months were reported by 60 patients (29%), of which 53% occurred in the past month, and corticosteroids were used for 33 patients, mostly as infusions. In total, 20% of respondents were unsure whether they had a relapse or not, and we assumed that the answer was no. The mean number of relapses over a period of 3 months in the sample was thus estimated to be 0.4 (SD = 0.8).
Symptoms and HRQoL
Fatigue was an issue for 87% patients with a mean score of 4.9 (SD = 2.6) for the sample and increased with disease severity: 4.0, 6.4 and 8.0 for patients with mild, moderate and severe disease, respectively (Figure 2).
Cognitive difficulties were an issue for 42% of the patients. The mean VAS score among this group with difficulties was 4.4 (SD = 2.1) and increased with disease severity: 4.0 in the mild, 4.3 in the moderate and 5.8 in the severe group (Figure 2). For the full study sample (assigning 0 to the group with no problems), the mean score was 2.0 (SD = 2.6) and 1.8, 2.4 and 4.4 in the three groups, respectively.
All five domains of HRQoL included in the EQ-5D represented problems for a large proportion of patients: pain and anxiety both represented problems for 55%, mobility for 51%, usual activities for 47% and self-care for 22%. Difficulties increased with advancing disease, as expected. Self-care was mainly affected for patients with severe disease, while pain/discomfort and anxiety/depression are present already very early in the disease, indicating the difficulties in managing these symptoms (Figure 3).
Problems in different domains of QoL (EQ-5D), n = 151.
Utility
The utility decreased with increasing EDSS (Figure 4). The mean score in this sample was 0.663 (using the UK value set 17 ).
Utility by EDSS (n = 168).
Resource utilisation
Resource utilisation is presented in Table 3. Health care resources (except medication) were collected for a 3-month period. Hospitalisation was relatively frequent, with 35 patients (17%) indicating an inpatient admission; 31 of these were admitted on average 2.4 times to the neurology ward for a mean of 16.2 days. Day admission was necessary for 32 patients (15%), on average 2.5 times, and rehabilitation centres were used by 3% of patients. Roughly 61% of patients had consultations, and of these, 91% saw a neurologist; 53.4% had investigations and tests. Medication for MS or MS-related symptoms was used by 82% of patients during the past month. Most often used prescription medicines for related symptoms were spasticity and pain treatments. Non-prescription drugs were purchased by 47% of patients.
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.
Details on the ward missing for some patients.
Community services were only used by 19.7% of the sample during the past month, most often transportation. Help from family was used by 34.1% of patients, on average 15.3 days per month and 4.8 hours per day. Informal care increased as expected with disease severity (Figure 5).
Use of informal care (days per month and hours per day, per user).
Investments in equipment and devices to aid patients’ mobility were made during the past 12 months for or by 30 patients (14%), most often for walking aids and modifications to the car or the house.
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 and by level of EDSS (N = 208).
Total mean annual cost per patient by disease severity (mild, moderate, severe), N = 208 (RUB 2015).
EDSS: Expanded Disability Status Scale; SD: standard deviation; DMTs: disease-modifying treatments.
The average cost of a relapse for patients with an EDSS below 6.5 was estimated at 33,000 RUB. All types of costs increased during a relapse, with hospital care representing 32% of the additional cost, consultations 18%, community services 12% and informal care 11% (Figure 7).
Relapse costs (3 months).
Discussion
The distribution of the clinical signs of MS was very close to previously reported for the same and other European populations.7,20 The possible bias in age, EDSS, work status, DMT and intensity of care might be associated with the selection bias as the mostly urban active population of the megalopolis of Moscow with well-organised medical care and an experienced MS Centre participated in this study. At the same time, the situation in Moscow is now very similar to that seen in the majority of large cities in Russia, which are now 74.2% of the total population of Russia (https://ru.wikipedia.org/wiki/; in Russian).
The cost of MS in our study is significantly higher than in previous studies in the Russian MS population (mean rate USD to RUB in 2015 was 64, so the rates were nearly US$9000 for mild, US$13,000 for moderate and US$16,000 for severe MS). This increase is mainly due to the changes in the USD to RUB rate, increase in total direct health care costs (mainly DMTs) and long-term absence and invalidity costs. The mean total annual costs for the Russian MS patients in our study were still significantly lower than in the majority of Western European countries, 5 while the prices of DMTs were very close. The difference is due to overall lower prices for health care resources and lower employment cost, and also due to a reduced availability of certain services compared with Western European countries.
Costs in our study are heavily dependent on the distribution of the sample over the EDSS range, which confirm previous findings in this population.1,2 In addition, although age is correlated with EDSS, it has an independent effect on production losses, as these are only relevant for patients below retirement age. In view of the young age and high proportion of patients with early disease, average costs per patient in the study are meaningless. We therefore present our results only by EDSS or in three groups of patients with mild, moderate and severe disease.
In this study, DMTs represent a large proportion of costs (57% of costs). However, this proportion has to be considered with caution, as we have used list prices for the DMTs, even though discounts might exist (but are not publicly available). The cost of DMTs in this study may thus be overestimated.
As in all countries of our study, costs are correlated with EDSS. However, due to the small sample and thus a very small number of patients at each EDSS level, particularly in the more severe ranges, the cost increase with increasing EDSS is not perfectly linear.
In conclusion, our study provides for the first time information on resource utilisation and costs in Russia. It highlights the importance of MS-related symptoms such as fatigue, cognition and pain and suggests that the impact of these symptoms on HRQoL and also particularly on daily activities, workforce participation and support should be studied more in depth.
Footnotes
Acknowledgements
The authors are grateful to Pavel Zlobin (Russian Federation of MS Societies) for support with data collection, to Elena Potapchik (HSE, Moscow) for providing unit costs, to Johan Dalén and Mia Gannedahl (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: A.B. has received consulting fees and participated in clinical trials sponsored by Biogen, Merck Serono, Novartis, Biocad, Gereium, Rosh, Sanofi Genzyme and 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 J.E. were at the time of the study employed by the Mapi Group, a research company acting as consultants to pharmaceutical companies. O.B. has received consulting fees and participated in clinical trials sponsored by Biogen, Merck Serono, Rosh, Sanofi Genzyme and Teva. E.P. has received consulting fees and participated in clinical trials sponsored by Biogen, Merck Serono, Novartis, Biocad, Gereium, Rosh, Sanofi Genzyme and Teva.
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.