Validity and reliability of the Finnish version of the Multiple Sclerosis Impact Scale‐29

Abstract Background The Multiple Sclerosis Impact Scale‐29 (MSIS‐29) has been increasingly used to evaluate the self‐perceived impact of multiple sclerosis (MS) on a patient. Objectives The aim of this study was to evaluate the psychometric properties of the Finnish version of MSIS‐29 in patients with MS. Methods A total of 553 patients with MS completed the MSIS‐29 and self‐administered questionnaires capturing information on demographics, disease characteristics and severity, perceived quality of life (EuroQol 5D‐3L instrument), and fatigue (Fatigue Severity Scale). Results The data quality for MSIS‐29 was excellent, with 99.5% computable scores for the MSIS‐29 physical scale and 99.3% for the MSIS‐29 psychological scale. Floor and ceiling effects were minimal. Excellent Cronbach's alpha values of 0.97 and 0.90 were seen for MSIS‐29 physical and psychological subscales, respectively. The physical subscale showed highest correlations with measures of physical functioning, such as disease severity and the mobility domain of the quality of life. Similarly, the psychological subscale showed highest correlations with self‐reported fatigue and the anxiety/depression domains of the quality of life. MSIS‐29 physical scores related strongly to disease severity, whereas the MSIS‐29 psychological scores increased in mild disease but declined in more severe disease forms. Conclusion The Finnish version of MSIS‐29 has satisfactory psychometric properties. Consistent with the previous recommendations, the use of two MSIS‐29 subscale scores instead of a total score was supported.

is an increasing need for sensitive and clinically relevant assessment methods to describe the effects of MS on patients. Psychometrically robust methods to evaluate physical and psychological disease burden of MS are also needed in population-based and rehabilitation studies as well as for the continuous evaluation of individual patients.
Several measurement scales, both disease specific and generic, have been used to evaluate functioning and quality of life of patients with MS. Clinician outcomes, that primarily capture functional disability include Expanded Disability Status Scale (EDSS) (Kurtzke, 1983) and Multiple Sclerosis Functional Composite (MSFC) score (Cutter et al., 1999). Patient-reported outcomes, that can capture broader effects on patient's quality of life, include Functional Assessment of Multiple Sclerosis (FAMS) (Cella et al., 1996), Multiple Sclerosis Quality of Life (MSQOL-54) (Vickrey, Hays, Harooni, Myers, & Ellison, 1995), and the Medical Outcomes 36-item Short-Form Health Survey (Hobart, Freeman, Lamping, Fitzpatrick, & Thompson, 2001). For decades, outcome measurement in MS has relied particularly on EDSS. While EDSS is the most widely used assessment tool to capture the level of physical disability, it has a poor ability to take into account other aspects, such as fatigue and cognition. While the generic patient-reported outcome measures, such as quality of life or perceived health or disability questionnaires, enable comparisons across diseases and with normative population, they do not recognize MS-specific symptoms.
Furthermore, none of the aforementioned MS-specific questionnaires have been developed using the standard psychometric approach of reducing a large item pool generated de novo from the people with MS.
The Multiple Sclerosis Impact Scale-29 (MSIS-29) was developed in 2001, and since then has been used increasingly in both research and clinical settings (Hobart, Lamping, Fitzpatrick, Riazi, & Thompson, 2001). MSIS-29 is a measure of the perceived physical T A B L E 1 The Multiple Sclerosis Impact Scale-29: English and Finnish versions In the past 2 weeks, how much has your MS limited your ability to:/Miten paljon MS-tauti on viimeisen kahden viikon aikana rajoittanut kykyäsi: and psychological impact of MS from the patient's perspective. It was developed as a MS-specific scale using a standardized psychometric approach of reducing an item pool generated from patient interviews, expert opinion, and literature review . It is a questionnaire structured in two subscales -a 20-item scale for the physical impact and a 9-item scale for the psychological impact of the disease. The items are answered in a five-point Likert scale ranging from one ("not at all") to five ("extremely") ( Table 1). The two subscale scores are generated by summing individual items and then transformed to a 0-100 scale. Higher scores indicate a more severe disease burden. The total score can be reported, but is not recommended . MSIS-29 has been suggested for use in cross-sectional studies to describe the impact of MS, in longitudinal studies to monitor the natural history of the disorder, and in clinical trials to evaluate therapeutic effectiveness from the patients' perspective . and Persian (Ayatollahi, Nafissi, Eshraghian, Kaviani, & Tarazi, 2007) versions. Additionally, preliminary findings have supported the stability of MSIS-29 across eight European countries (Hobart et al., 2004).  Huh et al., 2014;Learmonth, Hubbard, McAuley, & Motl, 2014;Riazi, Hobart, Lampling, Fitzpatrick, & Thompson, 2002). Similarly, high correlations have been found between MSIS-29 psychological scores and depressive symptoms (McGuigan & Hutchinson, 2004) and the psychological domains of quality of life questionnaires Huh et al., 2014;Learmonth et al., 2014;Riazi et al., 2002). MSIS-29 has shown high internal consistency, as analyzed using Cronbach's alpha (Gray, McDonnell, & Hawkins, 2009;Huh et al., 2014;Jones et al., 2013;McGuigan & Hutchinson, 2004;Riazi et al., 2002;Smedal et al., 2010), as well as a high test-retest reliability (Learmonth et al., 2014;Smedal et al., 2010). The MSIS-29 physical scale has been found responsive to change in EDSS (McGuigan & Hutchinson, 2004), steroid therapy, and rehabilitation (Hobart, Riazi, Lampling, Fitzpatrick, & Thompson, 2005). Furthermore, MSIS-29 has been found to be a reliable and valid instrument when used by proxies (van der Linden et al., 2005) and via the internet (Jones et al., 2013).
The purpose of this study was to evaluate the psychometric properties of the Finnish version of MSIS-29 in terms of data quality, scaling assumptions, acceptability, validity, and reliability in a large sample of MS patients including all clinical phenotypes, and with a wide range of disability. Additionally, the dimensional structure of MSIS-29 was evaluated.

| Patients
This was a retrospective, cross-sectional mail survey. The study protocol was approved by the ethics committee of the Hospital District of South-Western Finland and all participants provided written informed consent. The study population included patients registered with the Finnish Neuro Society, a national patient association in Finland. The inclusion criteria comprised diagnosis of MS, age ≥ 18 years, a membership in the Finnish Neuro Society for at least 1 year, a permission to receive mail from the association, ability to complete the survey in the Finnish language, no illness other than MS that could limit their participation, and not enrolled in any other clinical trial.

| Outcome measures
The study population and methods have been described in detail previously (Ruutiainen, Viita, Hahl, Sundell, & Nissinen, 2016). Briefly, the patients were required to complete the survey questionnaire or were interviewed via telephone using the Finnish questionnaire adapted from previous, multinational studies (Karampampa, Gustavsson, & Miltenburger, 2013). The questionnaire included demographic background variables and disease information (e.g., year of diagnosis, type of MS, and self-assessment of disease severity by Patient Assessment of Expanded Disability Status Scale (EDSS) Levels, a method widely used in cost-of-illness studies in MS (Kobelt, Berg, Lindgren, & Jönsson, 2006). The perceived quality of life was evaluated using the generic EuroQol 5D-3L instrument (EQ-5D) including five domains of well-being (mobility, personal care, usual activities, pain/discomfort, and anxiety/depression) using a social tariff established with the general population in UK (Euroqol Group, 1990). The visual analogue scale (VAS) was used to assess patients' perceived health state on a scale of 0 (worst imaging health state) to 100 (best imaginable health state) (Euroqol Group, 1990). The perceived severity of fatigue was evaluated using the Fatigue Severity Scale (FSS) (Krupp, Larocca, Muir-Nash, & Steinberg, 1989). In addition, the physical and psychological impacts of the disease were assessed using MSIS-29 .

| Statistical methods
The following psychometric properties of MSIS-29 were evaluated using standard methods (Nunnally & Bernstein, 1994): • Data quality: The percentage missing data and percentage computable scores were determined.
• Scaling assumptions: Item mean scores and standard deviations (SD), skewness, and item to total correlations were determined.
• Acceptability: Score range, mean scores, floor/ceiling effects, and skewness were estimated.
• Reliability: Cronbach's alpha with 95% confidence intervals (CIs) and Cronbach's alpha when one item is deleted were calculated.

| Demographic and clinical characteristics of the sample
Overall, 553 patients completed the questionnaire and were included in the analysis. The study sample was representative of all ages, MS phenotypes, and levels of disability (Table 2).

| Data quality
The percentage of missing data for items was low (1.3%), and the percentage of computable scale scores was high for both MSIS-29 physical (99.5%) and psychological (99.3%) scales (Table 3).

| Scaling assumptions
Frequency distributions for item response were relatively symmetrical.
For the MSIS-29 physical, skewness was, however, outside the skewness range of −1 to +1 for item numbers 9, 13, 15, and 17, which were

| Acceptability
The scores ranged from 0 to 98.8 for the MSIS-29 physical scale and from 0 to 91.7 for the psychological scale. The mean (SD) scores were lower than the scale mid-points (MSIS-29 physical mean 33.9 [24.8], psychological mean 24.0 [19.8]). Floor effects were low (MSIS-29 physical, 3.5%; psychological, 7.7%) and there were no ceiling effects to either of the subscales. Mean scale scores were not notably skewed (Table 3).

| Validity
The correlations between the subscales as well as MSIS-29 and other outcomes are summarized in Table 4 The MSIS-29 scores also supported known-group validity ( Table 5).
As predicted, mean MSIS-29 were significantly higher for patients who were retired due to their MS than for those who were employed, when limiting the comparison to groups with patients aged <63 years (working age population). Additionally, mean MSIS-29 were higher for patients with higher disease severity than for those with mild disease severity. Similarly, mean MSIS-29 scores for patients with progressive disease phenotypes (secondary or primary progressive) were higher than for those with relapsing-remitting form of the disease. In addition,  mean MSIS-29 physical scores were higher for older patients than for younger patients. Mean MSIS-29 psychological scores were slightly higher for older patients, but the difference did not reach statistical significance. The MSIS-29 psychological score did not differ between men and women, but men reported higher MSIS-29 physical scores than women.
Further, when the relationship between the EDDS and MSIS-29 subscales were evaluated more specifically, it was found that the MSIS-29 physical scores related strongly to disease severity but the MSIS-29 psychological scores increased synchronously with the EDDS score only in mild disease, peaked at EDDS 5, and declined thereafter.
In case of most severe disability (EDDS 8-9) the MSIS psychological score was as high as that in EDDS 4 (Figure 1).
MSIS-29 showed adequate convergent and divergent validity. The MSIS-29 physical scale correlated most strongly with disease severity (r = .80), followed by overall (r = .70-.79) and the mobility domain of quality of life (r = .70), and fatigue (r = .61). In contrast, the correlation was weak with the anxiety/depression domain of quality life (r = .26).
Accordingly, the MSIS-29 psychological scale correlated most strongly with fatigue (r = .64), followed by anxiety/depression domain (r = .57) and overall quality of life (r = .49-.52), while correlation was weak with disease severity (r = .28) and moderate with the mobility domain of quality of life (r = .33). Progressive disease (higher disability and progressive phenotype) as well as retirement due to MS were found to be associated with higher MSIS-29 scores. Interestingly, MSIS-29 psychological scores increased with the EDDS scores in mild disease but declined in more severe disease forms. In a previous study by Gray et al. (2009), MSIS-29 physical scores were also found to increase with disease duration, but psychological scores were significantly lower in patients with symptoms for more than 40 years. The decrease in the self-assessed psychological burden in patients with most advanced disease may refer to adjustment to the disability. In contrast, it may also imply that the psychological subscale is insensitive to change. Older patients reported significantly higher physical but not psychological subscale scores than did younger patients. The association to age may at least partly be explained especially by increased physical disease burden along with age. As predicted, MSIS-29 psychological scores were not affected by gender differences; instead, against our predictions and in contrast to previous findings Huh et al., 2014;van der Linden et al., 2005;Ramp et al., 2009;Riazi et al., 2002), men reported higher MSIS-29 physical scores than women. In line with the present findings, men with MS may have a poorer prognosis than would women with MS (Vasconcelos et al., 2016) and have been found to be less physically active than were women (Anens, Emtner, Zerrerberg, & Hellström, 2014). The direction, magnitude, and pattern of correlations were, however, generally consistent with previous findings Hoogervorst et al., 2004;Learmonth et al., 2014;McGuigan & Hutchinson, 2004;Riazi et al., 2002).
Additionally, Rasch analysis has supported the use of two subscale scores instead of a total score (Ramp et al., 2009). A CFI of 0.90 or greater has been suggested as a criterion for an acceptable fit of the scale in a unidimensional model (Hu & Bentler, 1999). The CFA results in this study did not support the unidimensionality of the MSIS-29 total score (CFI 0.74). The CFIs were higher for the MSIS-29 physical and psychological subscales-0.88 and 0.89, respectively. Additionally, our finding on the differences in MSIS-29 physical and psychological subscales according to disease severity supports the view that two separate subscale scores should be used instead of a total score. Cross-sectional data did not allow evaluation of test-retest reliability or responsiveness to change in MSIS-29.
In conclusion, the Finnish version of MSIS-29 seems to be culturally well adapted and to have sound psychometric properties, such as convergent and divergent validity and internal consistency. MSIS-29 F I G U R E 1 Relationship between EDDS and MSIS-29 subscales offers the opportunity to evaluate the physical and psychological impacts of MS rigorously from the patient's perspective.