Meyer‑Moock et al.

BMC Neurology (2022) 22:472

https://doi.org/10.1186/s12883-022-02947-0

STUDY PROTOCOL Open Access

Strengthening the occupational and social

participation of multiple sclerosis patients
‑ design of a multicenter, parallel‑group
randomized controlled trial (MSnetWork‑study)
Sandra Meyer‑Moock1* , Susan Raths2, Katharina Strunk3, Bernward Siebert4, Katrin Hinkfoth5, Markus Weih6,
Steffen Fleßa2 and Thomas Kohlmann1

Abstract
Background: Multiple Sclerosis is an autoimmune inflammatory disease of the central nervous system that often
leads to premature incapacity for work. Therefore, the MSnetWork project implements a new form of care and pursues
the goal of maintaining or even improving the state of health of MS patients and having a positive influence on their
ability to work as well as their participation in social life. A network of neurologists, occupational health and reha‑
bilitation physicians, psychologists, and social insurance suppliers provide patients with targeted services that have
not previously been part of standard care. According to the patient’s needs treatment options will be identified and
initiated.
Methods: The MSnetWork study is designed as a multicenter randomized controlled trial, with two parallel groups
(randomization at the patient level with 1:1 allocation ratio, planned N = 950, duration of study participation
24 months). After 12 months, the patients in the control group will also receive the interventions. The primary out‑
come is the number of sick leave days. Secondary outcomes are health-related quality of life, physical, affective and
cognitive status, fatigue, costs of incapacity to work, treatment costs, out-of-pocket costs, self-efficacy, and patient
satisfaction with therapy.
Intervention effects are analyzed by a parallel-group comparison between the intervention and the control group.
Furthermore, the long-term effects within the intervention group will be observed and a pre-post comparison of the
control group, before and after receiving the intervention in MSnetWork, will be performed.
Discussion: Due to the multiple approaches to patient-centered, multidisciplinary MS care, MSnetWork can be
considered a complex intervention. The study design and linkage of comprehensive, patient-specific primary and
secondary data in an outpatient setting enable the evaluation of this complex intervention, both on a qualitative and
quantitative level. The basic assumption is a positive effect on the prevention or reduction of incapacity for work as
well as on the patients’ quality of life. If the project proves to be a success, MSnetWork could be adapted for the treat‑
ment of other chronic diseases with an impact on the ability to work and quality of life.

*Correspondence: sandra.meyer-moock@med.uni-greifswald.de
1
Institute for Community Medicine, University Medicine of Greifswald,
Greifswald, Germany
Full list of author information is available at the end of the article

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
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Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 2 of 12

Trial registration: The trial MSnetWork has been retrospectively registered in the German Clinical Trials Register
(DRKS) since 08.07.2022 with the ID DRKS0​00254​51.
Keywords: Multiple sclerosis, Health-related quality of life (HRQoL), Study protocol, Health economic research, Health
service research, Germany, Incapacity to work, Ability to work

Background • occupational health examination by an occupational

Multiple sclerosis (MS) is a chronic inflammatory auto- physician,
immune disease of the central nervous system that affects • psycho-social and legal counseling from a qualified
more than 223,000 statutorily insured people in Germany person,
[1]. The disease is usually diagnosed between the ages of • disease education by a neuropsychologist or a neu-
20 and 40 and is associated with severe physical, cogni- rologist who is specialized in MS,
tive, and social impairments [2]. Treatment options are • MS-specific outpatient and inpatient rehabilitation
defined in guidelines and focus on recovery from attacks, by a rehabilitation physician.
slowing down the disease progression and managing MS
symptoms [3]; by now there is no known cure for MS. Risks of loss of social participation as well as of inability
For many MS patients, the disease leads to a significant to work will be identified and should be reduced by the
reduction in their working ability. As a result, the propor- interventions. The patient will be empowered to make
tion of patients with part-time jobs, disability pensions, informed decisions about their treatment options and
or premature retirement increases in the course and will be supported in upholding the ability to work and to
severity of the MS [2]. Disease-specific factors such as participate in social life.
mobility limitations, fatigue, and cognitive impairments The study was initiated by the Professional Associa-
are primarily responsible here. Comorbid depression, tion of German Neurologists (Berufsverband Deutscher
which is often accompanied with MS, also frequently Neurologen e.V., BDN) and is conducted together with
leads to restrictions on the ability to work. However, GWQ ServicePlus AG as representative of a large num-
working conditions also have an impact on employment ber of statutory health insurance funds and the Profes-
prognosis, as in many cases there is a lack of understand- sional Association of German Occupational Physicians
ing in physically demanding activities in the workplace (Verband Deutscher Betriebs- und Werkärzte e. V.).
and a lack of necessary flexibility to ensure the (contin- The University of Greifswald (UG) and the Institute for
ued) employment of people with MS [4]. This is precisely Community Medicine of the University Medicine of
where the MSnetWork project comes in because it is less Greifswald (UMG) are responsible for the scientific and
about the effect of individual measures or interventions economic evaluation within MSnetWork.
on clinical disease parameters (e.g. relapse frequency),
but rather about the effect on participation in private, Methods / design
social, and, in particular, vocational life and the associ- Research questions and working hypotheses
ated long-term securing of the ability to work. The main aims of the study are (a) to improve or stabilize
The MSnetWork project implements a new form of the health status of patients with MS and (b) to prevent
care and pursues the goal of maintaining or even improv- or reduce their incapacity to work. Therefore, the inter-
ing the state of health of MS patients and having a posi- vention consists of a portfolio of measures to improve the
tive influence on their ability to work as well as their coordination of specialist care as well as the early integra-
participation in social life. A network of neurologists, tion of socio-medical, occupational, psychosocial, reha-
occupational and rehabilitation physicians, psycholo- bilitative, and health care services.
gists, and social insurance suppliers provides patients
with targeted services that have not previously been part
Study design
of standard care and are directly tailored to the personal
The MSnetWork study is designed as a multicenter rand-
needs of the patients. According to the patient’s needs
omized controlled trial (RCT), with two parallel groups.
based on a systematic and regular assessment of func-
The duration of study participation is 24 months. The
tional capacity, the following treatment options will be
patients are consecutively enrolled between January and
identified, initiated, and coordinated by the neurologist:
December 2022, and assigned to an intervention group or
a control group in a ratio of 1:1 after checking the inclu-
• participation-oriented care by the MS-specialized
sion and exclusion criteria. After 12 months, the patients
neurologist,
in the control group will also receive the intervention
Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 3 of 12

measures, during the first 12 months they receive stand- of incapacity to work in a 12-month observation period.
ard care. The study procedure planned is shown in Fig. 1. Hence, the number of cases is calculated with a regres-
The intervention effect is analyzed as follows: sion model for count data with “zero inflation”.
Depending on the assumption about the proportion of
(1) Essentially, the intervention effect is carried out by insured persons without sick leave days (30% vs. 50%),
analyzing the course of the primary and secondary with a statistical power of 80%, and a 2-sided significance
outcomes in the intervention and control groups in level of 0.05, the minimum sample size necessary to iden-
the first 12 months (parallel-group comparison). tify a group difference for the primary outcome of sick
(2) In the following 12 months, the intervention group leave days is between 600 and 860. An expected drop-out
continues to receive the intervention. Further anal- of 20% in the course of the twelve-month comparison
yses of the outcome variables in this time are par- period leads to an increase in the net case numbers to the
ticularly important to be able to check the stability gross case numbers of N = 750 and N = 1075 (Table 1).
of this effect over the time (long-term) to see if an Therefore, we aim for an initial gross sample size of 950
effect of the intervention is present after the first cases in total (475 cases per group). This number of cases
12 months. is somewhat closer to the upper limit and would thus
(3) The control group receives the intervention in the make it possible to achieve the planned power even if the
second half of the study period. The course of the actual conditions deviate from the assumptions made.
primary and secondary outcomes in the control The strategies to achieve adequate recruitment to reach
group between the first and second period (months the target sample size had been.
0 to 12 vs. months 13 to 24) will be analyzed either. based on the number of patients being treated in the
Such a pre-post comparison is methodologically past in the neurological practices who would have ful-
weaker than a parallel group comparison, but it filled the eligibility criteria. Neurological practices will
offers the possibility to examine the effect of the be identified with the help of the BDN, the Professional
intervention once again from an independent per- Association of Neurologists.
spective.
Participant identification / recruitment strategy
and randomization
Subjects and eligibility criteria
Patients are recruited from neurological practices and
Criteria for study inclusion comprise the following: (1)
outpatient clinics in Bavaria, Berlin, Brandenburg, Hesse,
patients with a confirmed diagnosis of multiple sclero-
Baden-Württemberg, Schleswig-Holstein, North Rhine-
sis; (2) patients of working age (aged 18–65 years); (3)
Westphalia and Mecklenburg-Western Pomerania in
patients employed (part-time or full-time) or in study or
Germany. Patients of a centre who fulfill the inclusion
vocational training.
criteria and for whom there are no reasons for exclusion
Criteria for study exclusion comprise the following: (1)
are consecutively included in the study. After informa-
patients with MS who are no longer of working age (older
tion and obtaining consent to participate, patients are
than 65 years); (2) patients who are unable to work; (3)
randomized into the intervention and control groups.
patients with severe impairment of independence (cor-
Concealed randomization with variable block length
responds to care level 4 and 5 in German social law), and
takes place at the patient level using an online tool imple-
(4) patients with severe mental disorders.
mented in the electronic health record system. The allo-
cation sequence is generated by the UMG.
Sample size Patients can be enrolled via managed care contract
The calculation of sample size was done for the analy- with the participating health insurance companies or via
sis of the primary outcome “number of sick leave days” a direct treatment contract with the physician (without
per patient within 12 months. The calculation assumes the participation of a health insurance company).
that the difference in sick leave days is to be an average
of 5 days (or 20% of the average sick leave days for MS
patients in Germany) between the intervention and the Study centres
control group. This number is deduced from the Ger- The study centres take on essential functions in the area
man statistics on types of illness [5], with an annual aver- of patient recruitment (patient information, informed
age number of 25 days of incapacity to work due to MS consent), the management and documentation of study-
among the statutorily insured persons. Further, based on relevant procedures, data collection, and the forward-
a database analysis of the insurances taking part, up to ing of data, in addition to intervention-related services.
50% of the insured persons with MS do not have any days Each practice receives detailed training with the study
Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 4 of 12

Fig. 1 Interventions and timeline

Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 5 of 12

Table 1 Results of the calculations for determining sample size to ensure the success of the treatment and to discuss the
Patients without days Net number of cases Gross number of
therapy goal. If the neurologist identifies an acute risk
of incapacity to work ­casesa of incapacity or reduction in earning capacity during
within 12 months (in %) his*her examination, he*she can initiate a case confer-
30% 600 750
ence together with the other players involved to discuss
50% 860 1.075 possible treatment options for acutely avoiding incapac-
a
Drop out of 20% in 12 months
ity and loss of participation. The patient can be included
in the case conference to ensure treatment adherence.
The neurologist has different treatment options to
procedures in the context of virtual training sessions improve health and workability. If the treating neurolo-
before the start of patient inclusion. gist identifies:
Physician practices or participating providers are reim-
bursed for enrolment and performance of individual – health risk from employment and risk for disease
intervention services on a per-service billing basis. The exacerbation, the neurologist initiates an occupa-
individual services provided per patient and the corre- tional health examination by a qualified occupa-
sponding remuneration are presented transparently for tional physician. The focus of the occupational health
the service providers via the patient platform used and examination is to identify health destabilizing influ-
invoiced to the project management. The preliminary ences and to reduce them by occupational medical
calculation of compensation is primarily based on esti- interventions tailored to the patient’s needs.
mates of the time required for single services. – deficits in coping with the disease during the exami-
nation that contribute to worsening health: the neu-
Intervention rologist can initiate disease education. The focus is on
A MS-specialized neurologist examines the cognitive teaching environmental and behavioral strategies for
and physical status of the MS patient using standard- better coping with MS. Patient education promotes
ized assessments like the Symbol Digit Modalities Test active engagement with MS and activation of self-
(SDMT) [6], Expanded Disability Status Scale (EDSS) efficacy and knowledge building. Patient education
[7], 9-Hole Peg Test (9-HPT), and Timed 25-Foot Walk is offered by MS-specialized neurologists or MS-spe-
(T25-FW) of the Multiple Sclerosis Functional Compos- cialized neuro-psychologists, depending on regional
ite (MSFC) [8–10] every six months. Additionally, as part needs. The counseling neurologists and neuro-psy-
of a quarterly consultation on health, affective, and par- chologists are to be qualified by a specialized training
ticipation status, the neurologist examines health-associ- module.
ated participation and workability. The quarterly medical – risk of or present restriction for participation due to
consultation by the neurologist includes participation-, MS or symptoms accompanying MS (affective, cog-
deficit- and resource-oriented therapy planning as well nitive disorders, physical deficits, etc.), which cannot
as progress monitoring with regard to health-associated be eliminated, compensated, or minimized by the
participation and the preservation of the working abil- previous interventions, the neurologist initiates an
ity. In addition, it serves to ensure the stabilization of the inpatient, day-care, or outpatient rehabilitation in an
current treatment success and the optimization or adap- MS-specialized rehabilitation centre, depending on
tation of the therapy. the patient’s need.
As a result, the neurologist identifies risks that influ- – a negative influence of the social and family environ-
ence health status, workability status, family status, and ment during his examination, the neurologist initi-
social status due to the living environment. Together with ates individual psychosocial and legal counseling.
the patient, the physician discusses possible treatment The focus of the consultation is on the individual
options to improve health and prevent workability as well identification of challenges in the family and social
as plans therapy. The neurologist initiates and coordi- environment, support in determining and enforc-
nates the interventions with other health care providers ing legal claims, and support offers. The counseling,
(e.g. occupational physician, psychologist, rehabilitation support, and close follow-up help to improve health
physician, pension insurance, health insurance company) and reduce or eliminate the burden of the disease.
based on the patient’s needs. After the intervention has Depending on the regional situation, counseling is
taken place, or if additional treatment needs have been provided by the MS self-help organization or medical
identified by the service providers during the interven- assistant within the neurological practice. The coun-
tion, the neurologist and the corresponding service pro- selors are qualified by proven MS-specific knowledge
vider can hold a teleconsiliary discussion on the findings as well as by a qualified degree as a social worker; the
Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 6 of 12

medical assistant will be qualified by an appropriate Secondary outcomes

advanced training module. The secondary outcomes include primary data col-
lected within the evaluation study and secondary data
provided by the health insurance funds. For patients,
primary data will be collected by a questionnaire at
Control condition baseline and on 6-, 12-, 18-, and 24-month follow-up,
In the first 12 month, participants in the control group that consist of the following:
will not receive trial-related healthcare interventions, but
“treatment as usual”, i.e. the standard healthcare as cur- (1) Health-related quality of life is measured by the
rently applied in the MS standard treatment in Germany. German version of the Multiple Sclerosis Quality
This comparator was chosen because the research ques- of Life (MSQoL)-54 instrument [12], a diagnosis-
tion is whether the new intervention affects outcomes specific MS questionnaire. It contains 52 items
like days of incapacity of work, quality of life, and cost- distributed into 12 scales, and two single items. In
effectiveness and for this a comparison to “usual care” is addition to the generic quality of life items retrieved
warranted. from the SF-36, the questionnaire captures health
However, patients in the control group do also receive aspects that are particularly significant for MS
interventions after 12 months at the same frequency as patients (18 items in the areas of health distress,
participants in the intervention group (Fig. 2). sexual function, satisfaction with sexual function,
overall quality of life, cognitive function, energy,
pain, and social function).
Electronic health record
(2) The EQ-5D-5L is a preference-based HRQoL meas-
Networking and documentation, as well as data exchange
ure and is used to evaluate the generic quality of
between the players involved, take place by using an elec-
life. The EQ-5D-5L contains one item for each of
tronic health record. The online platform contains rele-
the five dimensions mobility, self-care, usual activi-
vant data on the patient’s MS-associated health data and
ties, pain/discomfort, and anxiety/depression. The
information and results on assessments for functional
answers given to EQ-5D-5L can be converted into
capacity as well as examinations from occupational phy-
a utility score, the EQ-5D index. Additionally, the
sicians. In addition, the platform in which the patient’s
EQ-5D-5L includes a Visual Analog Scale (VAS),
record is embedded makes available group offers for dis-
ranging from 0 (the worst possible health status) to
ease education recognizable for the coordinating medi-
100 (the best possible health status) [13]
cal assistant of the neurological practice to enable rapid
(3) Affective status is evaluated by the short form of the
scheduling and therapy assignment. The data exchange is
Depression, Anxiety and Stress Scale (DASS) [14,
based on the already existing and legally provided struc-
15]. The DASS comprises three subscales each con-
tures of the patient’s electronic health record, is used only
sisting of 7 items: depression, anxiety, and stress.
after the patient’s consent, is browser-based, and has the
(4) Fatigue as a common symptom in MS patients [16]
necessary interfaces for demand-oriented care.
is measured with the Fatigue Scale for Motor and
Cognitive Functions (FSMC] [17]. The 20-item
Outcomes scale contains cognitive and motor subscales with
Primary outcome 10 items each.
The primary outcome is the number of MS-associated (5) A short scale measuring the subjective prognosis
sick leave days at 12- and 24-month follow-ups. These of gainful employment (SPE-scale) [18] is used to
data will be provided by the routine data of the health assess the likelihood of reduction of work capacity
insurance funds. In addition, the days of incapacity to (3 Items).
work will be collected with a baseline and follow-up (6) Patients’ adherence to therapy and treatment is
patient questionnaire every six months, as well as via measured by the Adherence Assessment Question-
the digital patient file during the quarterly consultations naire (AAQ) [19]. The AAQ consists of 11 items,
(intervention group) or the functional assessments (con- including a visual analog scale.
trol group). Self-reported primary data can be used for (7) Self-efficacy is carried out with the 13-item short
the analysis of patients with and without secondary data form of the Coping Self-Efficacy Scale (CSES) [20].
from the health insurance funds (inclusion via managed The CSES measures one’s confidence in perform-
care contract or treatment contract), but are somewhat ing coping effectively with life challenges e.g. due
more susceptible to information bias in direct compari- to chronic illness and it can assess changes in cop-
son (e.g. self-reporting bias, recall bias) [11].
Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 7 of 12

Fig. 2 Flow of participants in MSnetWork. * The quarterly medical consultation by the neurologist includes participation-, deficit- and
resource-oriented therapy planning and progress monitoring with regard to health-associated participation and the preservation of the working
ability. In addition, it serves to ensure the stabilization of the current treatment success and the optimization or adaptation of the therapy

ing self-efficacy (CSE) over time in intervention The original version was adapted for use in outpa-
research. tient care.
(8) The level of patient satisfaction with the new inter- (9) Out-of-pocket payments by households due to
vention is measured with an adapted version of the the MS disease are measured with 16 items. These
Patient Satisfaction Questionnaire (ZUF-8) [21, 22] include co-payments, monetary transport costs,
Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 8 of 12

and time losses. The items are based on the Mul- because even if it can be demonstrated that patients ben-
tiple Sclerosis Health Resource Utilization Sur- efit from the new form of care, this alone is no guarantee
vey [23] but were adapted for the specific research that it will be adopted as standard care. In that way the
design in MSnetWork. implementation potential is assessed through:

Additionally, primary data collected as part of the (14) Interviews and surveys with service provid-
intervention at neurological practices will also be used ers (e.g. doctors, psychologists, nurses, medical
for the evaluation as secondary outcomes: assistants) on the acceptance of the intervention.
This analysis aims to record supporting and hin-
(10) The cognitive status is assessed by the Symbol dering factors during the project period as a sec-
Digit Modalities Test (SDMT) at baseline and on ondary outcome because the knowledge of these
6-, 12-, 18- and 24-month follow-up. factors is a basic prerequisite for the subsequent
(11) The physical status is measured using the implementation in regular care.
Expanded Disability Status Scale (EDSS), the (15) Intervention costs: For the study period the
9-Hole Peg Test (9-HPT), and the Timed 25-Foot individual interventions are remunerated to the
Walk (T25-FW) of the Multiple Sclerosis Func- service providers at flat rates. Based on time
tional Composite (MSFC) at baseline and on 6-, records and surveys, the actual costs of the indi-
12-, 18- and 24-month follow-up. vidual interventions are determined to exam-
ine whether the compensatory allowances when
Secondary data of the patients are made available by transferred to standard care will ensure adequate
the participating health insurance companies and con- future financing for the service providers even
sists of the following: after the project duration.

(12) Treatment costs and frequency: For each The patients’ primary and secondary data are linked via
included patient, the data set contains the cost a patient pseudonym. For this purpose, a trustee agency
data on inpatient and outpatient care, and if is involved.
applicable rehabilitation costs, medication, rem- Endpoints, outcomes, sources, and follow-ups are pre-
edies (e.g. physiotherapy, occupational therapy), sented in detail in Table 2.
and aids as well as other payments. In addition,
the GWQ Service Plus on behalf of the health
insurance companies directly involved forms a Statistical analyses
match from their patient data of patients with The primary analysis will be performed as an intention-
MS that is as structurally identical as possible to-treat, ITT, analysis.
(propensity score matching by age, gender, 3-st. A regression model for count data with “zero infla-
postcode, among other things), who are not tion”, i.e. with a large proportion of cases without inca-
included in the study. This quasi-experimental pacity to work, is used to analyze the primary outcome.
cohort study design allows further comparison For this purpose, the zip command in the statistical pack-
between MS patients, with and without study age STATA is used. The statistical analyses of the other
participation, meaning between patients with outcome variables are performed with generalized linear
and without receiving intervention services. mixed-effects models [24].
(13) Sick leave days and sickness allowance: The data These models are appropriate for the analysis of cross-
set contains the sick leave days and the paid sick- sectional and longitudinal data on primary and second-
ness allowance for each included patient. This is ary outcomes, which may be continuous (cost, quality of
the basis for calculating the short- and long-term life) or categorical (early retirement) variables. Interde-
social costs of the incapacity to work due to MS. pendencies between measurements in longitudinal data
can be appropriately handled by including mixed effects.
If these secondary data are not available, or not avail- The application of the regression models to variables with
able to a sufficient extent, the frequency of visits to spe- different scale levels is made possible by the appropri-
cialists, inpatient facilities, and other medical service ate choice of the link function (e.g. identity for continu-
providers can be determined from the results of the ous variables, logistic for dichotomous variables) and the
patient questionnaire. error distribution (e.g. normal distribution for continu-
Additionally, the intervention’s implementation poten- ous target variables, binomial distribution for dichoto-
tial into the standard care system will be examined, mous variables).
Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 9 of 12

Table 2 Endpoints, outcomes, sources, and follow-ups

Outcome Measurement instrument or data source Follow-ups

PRIMARY​ Number of sick leave days Routine data from the SHI funds -*)
Patient questionnaire and digital patient health Month 0, 6, 12, 18, 24
record (and during quarterly consultations)
SECONDARY​ Costs of the incapacity to work Routine data from the SHI funds -*)
Human capital or friction costs approach based on Month 0, 6, 12, 18, 24
primary data for sick leave days (and during quarterly consultations)
Treatment costs/ frequency: Routine data from the SHI funds -*)
• Inpatient care Patient questionnaire Month 0, 6, 12, 18, 24
• Outpatient care
• Rehabilitation
• Medication
• Remedies
• Therapeutic appliances
• Others
Out-of-pocket payments Patient questionnaire Month 0, 6, 12, 18, 24
Implementation potential into standard care: Interviews and survey of service providers Study month 24 & 36
• Acceptance Process analysis, time records and surveys Study month 12–36
• Intervention costs
Reduction in earning capacity: Subjective prognosis of gainful employment scale Month 0, 12, 24
•Subjective prognosis of gainful employment (SPE) Month 0, 12, 24
• Employment situation Patient questionnaire
Physical status Expanded Disability Status Scale (EDSS) Month 0, 6, 12, 18, 24
Multiple Sclerosis Functional Composite (MSFC:
T25-FW, 9-HPT)
Cognitive status Symbol Digit Modalities Test (SDMT) Month 0, 6, 12, 18, 24
Affective status Depressions-Anxiety-Stress-Scale (DASS)
Fatigue Fatigue Scale for Motor and Cognitive Functions
(FSMC)
Health-related quality of life Multiple Sclerosis Quality of Life (MSQoL)-54 Month 0, 6, 12, 18, 24
instrument
EuroQol-questionnaire (EQ-5D-5L)
Patients’ adherence to therapy Adherence Assessment Questionnaire (AAQ) Month 0, 6, 12, 18, 24
Self-Efficacy Coping Self-Efficacy Scale (CSES) Month 0, 6, 12, 18, 24
Patient satisfaction with the new intervention Client Satisfaction Questionnaire (ZUF-8) Month 12, 24
*) Continuous recording within the claims data of the statutory health insurers

For data analysis with generalized linear mixed mod- costs for MS patients is compared to the effectiveness of
els, corresponding procedures are available in all relevant the measures (cost-effectiveness analysis), to give infor-
statistical packages (e.g. SPSS, SAS, Stata, R). Beyond mation on the intervention’s advantageousness compared
these advantages of the chosen analysis model, it should to other health policy instruments.
be emphasized that with these models it is possible to Institutional conditions: Based on the survey of the
specify and statistically test relevant hypotheses about intervention costs and the acceptance of the intervention
the group, time, period, and interaction effects. These by the health care providers, the conditions for a suc-
models also allow the handling of missing follow-up data. cessful implementation of the intervention as part of the
For the analysis of cost data, special gamma regression standard care are elaborated and evaluated.
models can be used according to the distributional prop- An interim analysis is not planned.
erties of the dependent variable. With the help of suit-
able methods, the dispersion of costs and efficiencies is Monitoring and data management
explained, i.e., those parameters are determined which Before the start of recruitment, the neurological prac-
have a significant influence on the costs and efficiencies tices receive training on the interventions, use of the
of the measures. assessment instruments, the study documentation, the
Cost-benefit analysis: Based on the intervention costs forwarding of the study documentation to the evaluating
and the saved costs (if applicable), the profitability of institutions, as well as the process and obligations regard-
the measures is determined. In addition, the difference ing data validation. Online training is required, addition-
between intervention costs and the potentially saved ally, written and video-based training material is made
Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 10 of 12

available via the electronic health record platform and an socioeconomic factors and the providers’ perspective to
access-restricted website. ensure such future treatment for MS patients.
Monitoring is carried out by the central project coor- If the project proves to be a success, a transfer for the
dinator (BDN) and the evaluating institutions (UG and treatment of other chronic diseases with an impact on
UMG). It starts directly after recruitment and the inclu- the ability to work is conceivable and desirable.
sion of the first patients. The principle of data Man-
agement has been described in a comprehensive data
Abbreviations
management plan. 9-HPT: 9-Hole Peg Test; AAQ: Adherence Assessment Questionnaire; BDN: Bun‑
desverband Deutscher Neurologen (Professional Association of Neurologists);
CSE: Coping self-efficacy; CSES: Coping Self-Efficacy Scale; DASS: Depression,
Anxiety and Stress Scale; EDSS: Expanded Disability Status Scale; EQ-5D-5L:
Discussion EuroQol questionnaire, 5 dimensions, 5 level; FSMC: Fatigue Scale for Motor
To the best of our knowledge, this is the first study to and Cognitive Functions; GWQ: Gesellschaft für Wirtschaftlichkeit und Qualität
consider multidisciplinary care in MS patients and its bei Krankenkassen (Society for Efficiency and Quality in Health Insurance
Funds); HRQoL: Health-related quality of life; ITT: Intention-to-treat; MS:
effects on health, gainful employment, and sick leave Multiple sclerosis; MSFC: Multiple Sclerosis Functional Composite; MSQoL-54:
in Germany. In the project, patients with MS receive Multiple Sclerosis Quality of Life-54 instrument; RCT​: Randomized controlled
a bundle of interventions aiming to positively influ- trial; SDMT: Symbol Digit Modalities Test; SF-36: Short Form Health 36; SHI:
Statutory Health Insurance; SPE-scale: Short scale measuring the subjective
ence their ability to work and to participate in a self- prognosis of gainful employment; T25-FW: Timed 25-Foot Walk; UG: University
determined life. The neurologist at the centre of the of Greifswald; UMG: University Medicine of Greifswald; VAS: Visual Analog
newly established network coordinates the care services Scale; ZUF-8: Patient Satisfaction Questionnaire.

offered by various service providers and, for the first Acknowledgments

time, works together with a preventive occupational The publication was prepared within the framework of the German innovation
physician. Tele-consultations and case discussions sup- fund project MSnetWork. In this context, the authors would like to thank all
responsible persons as well as the participating centres and their staff for their
port this cooperation. support. Responsible persons and parties are:
This complex intervention needs a highly integrated • Dr. med. Bernd Brockmeier, BDN (Professional Association of Neurologists),
collaborative evaluation of health and health economic Berlin.
• Dr. Martin Delf, BDN (Professional Association of Neurologists), Brandenburg.
effects. In that way, primary and secondary data will be • Prof. Dr. Wolfgang Freund BDN (Professional Association of Neurologists),
primarily matched, but due to the extensive collection Baden-Württemberg.
of primary data within the project, a comprehensive • Dr. med. Stephen Kaendler/Dr. Specht, BDN (Professional Association of
Neurologists), Hessen.
evaluation of the new intervention is possible even in • Dr. med. Uwe Meier/Prof. Dr. Gereon Nelles, BDN (Professional Association of
the absence of secondary data. The patient questionnaire Neurologists), Nordrhein.
and the documentation of MS-specific days of incapac- • Dr. Gehring, BDN (Professional Association of Neurologists),
Schleswig-Holstein.
ity to work by the treating neurologists within the digital • Dr. Martin Bauersachs, BDN (Professional Association of Neurologists),
patient file make sufficient data available to analyze the Westfalen.
primary endpoint, costs of incapacity to work and the • Charlotte Müller and Barbara Prodanovic for their cooperation and support,
BDN (Professional Association of Neurologists).
course of treatment independently. • Pathways Public Health GmbH.
Complementing the patient perspective and the social • IVPnetWorks GmbH.
and occupational participation outcomes achieved
Protocol version
through the interventions, the perspective of service The latest version of the study protocol (Evaluation study amendment No. 2)
providers is also highlighted. Even though the new and dating from 06/04/2022 is serving as the basis of the publication.
comprehensive care for MS patients with the managing Date and version identifier:
• Grand application study protocol (23/04/2021): Original.
neurologist in the middle of the network can be under- • Amendment 01 (13/10/2021): Change in follow-up; specification of item
stood as an innovation that goes beyond the current level selection in the CRF.
of care. It is therefore of central importance that the new • Amendment 02 (06/04/2022): Opening the project to patients enrolled via
direct treatment contract with the physicians; including further states.
form of care is seen as useful and reasonable by the pro- Protocol modifications (e.g., changes to eligibility criteria, outcomes, analyses)
viders on the one hand, and that adequate financing can to relevant.
be ensured in the future on the other. The determination parties (e.g., investigators, institutional review board, trial participants, trial
registry) are.
of the actual costs is thus indispensable for the transfer communicated by the study coordinating centre (BDN).
of this pilot implementation within the framework of
MSnetWork.
Authors’ contributions
Against this background, the study aims to improve KH, MW, BS, TK, and SF designed the trial. All authors were involved in the
the current employment situation of MS patients, con- discussion of the trial design. KH, MW, and BS are responsible for conducting
sidering disease-specific, therapeutic, psychosocial, and the interventions. KS is in charge of organising, providing and transmitting the
routine data of the health insurance funds to evaluators. SMM, SR, SF, and TK
Meyer‑Moock et al. BMC Neurology (2022) 22:472 Page 11 of 12

are responsible for scientific and economic evaluation. SMM and SR drafted Association of Neurologists Bavaria, MVZ Medic Center Schöll&Kollegen,
the first manuscript. All authors read and reviewed the manuscript, and Nürnberg, Germany.
approved the final version.
Received: 2 August 2022 Accepted: 28 October 2022
Funding
Open Access funding enabled and organized by Projekt DEAL. The study is
funded by the German Federal Joint Committee’s Innovation Fund (Innova‑
tionsausschuss beim G-BA, Postfach 120606, 10596 Berlin, Germany, grant
number 01NVF20025) from 1 July 2021 to 30 June 2025. The Study Protocol References
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