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Difference between generic and multiple sclerosis-specific quality of life instruments regarding the assessment of treatment efficacy
Journal of the Neurological Sciences 256 (2007) 30 – 34 www.elsevier.com/locate/jns
Difference between generic and multiple sclerosis-specific quality of life instruments regarding the assessment of treatment efficacy S. Özakbas a,⁎, B.B. Akdede b , G. Kösehasanogullari a , Ö. Aksan a , E. Idiman a a b
Department of Neurology, Dokuz Eylul University Faculty of Medicine, Balcova 35340, Izmir, Turkey Department of Psychiatry, Dokuz Eylul University Faculty of Medicine, Balcova 35340, Izmir, Turkey Received 10 May 2006; received in revised form 13 November 2006; accepted 15 January 2007 Available online 26 March 2007
Abstract Multiple sclerosis (MS) is a chronic and stressful disease, which significantly affects the quality of life (QoL) of patients. QoL instruments provide information which traditional outcome measures of MS do not. It is unclear if the longer disease-specific instruments provide more useful information than the shorter. We aimed to investigate whether there was any difference between general QoL instrument and MSspecific one on the basis of detecting the efficacy of pulse therapy. 112 clinically definite MS patients were included in the study. Patients enrolled in the study were in relapse period treated by 1 g/day methyl-prednisolone for 5 days. World Health Organization Quality of Life Brief Form, Turkish Version (WHOQoL-BREF-TR) was given as a generic measure and Multiple Sclerosis Quality of Life-54 (MSQoL-54) as an MS-specific measure to assess the QoL. The same scales were administered 1 month after the therapy. MSQoL-54 was correlated with the EDSS in the pre-treatment period but WHOQoL-BREF was not. On day 30, there was a significant increase in both WHOQoL-BREF and MSQoL-54 scores. Increase was more prominent in MSQoL-54. There was a weak correlation between WHOQoL-BREF and MSQoL-54 (r = 0.17). Correlation between changes in WHOQoL-BREF and MSQoL-54 scores was even weaker (r = 0.11). Correlation between WHOQoL-BREF and EDSS was weaker (r = 0.13), and correlation between MSQoL-54 and EDSS was still moderate (r = 0.46) when compared with day 0. We concluded that although it takes a longer time to administer, MSQoL-54, as a MS-specific QoL instrument, is favorable and reliable for detecting the QoL not only in the remission but also in the relapse period of MS. Our results also indicated that MSspecific measure of QoL might be used for detecting the treatment effects in relapse period of patients with MS. © 2007 Elsevier B.V. All rights reserved. Keywords: Multiple sclerosis; Quality of life; MSQoL-54; WHOQoL-BREF; Relapse; Treatment; EDSS
1. Introduction Multiple sclerosis (MS) is a chronic and stressful disease, which significantly impacts the quality of life (QoL) of patients. QoL instruments can be used as an outcome measure in clinical trials, just like we used Expanded Disability Status Scale (EDSS) [1] or Multiple Sclerosis Functional Composite (MSFC) [2] for assessing disease progression, or magnetic resonance imaging for assessing lesion burden [3–5]. QoL instruments provide information that traditional outcome
⁎ Corresponding author. Tel.: +90 232 4124064; fax: +90 232 2786192. E-mail address: [email protected] (S. Özakbas). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.01.080
measures used in MS studies do not. The two different ways to measure QoL are the generic and disease specific instruments [6]. In the generic instrument, it is aimed to assess universal health concepts thought to be relevant regardless of disease, age group, or treatment. In contrast, in the diseasespecific instrument, it is aimed to reflect factors relevant to a specific disease, in which the content of the measure is more likely to detect change, because it is targeted to the specific disease. A number of disease-specific measures for MS have been developed [7–10]. There are a number of questions to be examined for QoL instruments: Intuitively, it seems reasonable to use MS-specific QoL instrument to evaluate effect of clinical signs or symptoms on QoL of the individual patient. On the other hand, it would be so practical to use lengthy QoL
S. Özakbas et al. / Journal of the Neurological Sciences 256 (2007) 30–34
instruments in the clinical setting. It is unclear if the longer, disease-specific instruments provide more useful information than the shorter. As, one of the most important periods of low levels of QoL is the attack period in patients with MS, we examined how QoL was affected in the attack period in MS patients. But our main question was whether there was any difference between simple, general QoL instrument and MSspecific one on the basis of measurement of the treatment effect of pulse methyl-prednisolone (MP). These questions were examined by conducting a prospective study in patients with MS who were in acute exacerbation period, by comparing two QoL questionnaires: World Health Organization Quality of Life Brief Form, Turkish Version (WHOQoL-REF-TR), as a generic measure and Multiple Sclerosis Quality of Life-54 (MSQoL-54) as a MS-specific measure. 2. Material and methods 2.1. Patients A total of 112 clinically definite MS patients according to the Poser's criteria [11] participated in this longitudinal study. All patients were in an objective acute exacerbation, which was defined as the appearance of new symptom(s) or worsening of existing symptom(s). Symptom(s) should have lasted at least 24 h. Patients were excluded if they were b 18 and N 55 years of age, were unable to reliably complete the questionnaires, had any significant co-morbid illness, such as previous stroke or rheumatoid arthritis which was likely to impact on the patients' QoL or had infectious diseases causing fever. Patients who had an experience with any questionnaires were also excluded. Beck Depression Scale (BDS) was also performed before the attack treatment. Cutoff value was accepted as 17 for significant depression in BDS. 3 patients were found depressed, and excluded from analysis of comparison with QoL scales. All patients received 1000 mg intravenous (i.v.) MP for 5 days, followed by tapering dose of 100 mg oral prednisolone for 25 days. The MSQoL-54, WHOQoL-BREF and EDSS were administered twice in 30 days. All were assessed on day 0, before the first administration of corticosteroid and on day 30, after corticosteroid treatment was finished. Assessment of EDSS and administration of MSQoL-54 and WHOQoLBREF were at the same time of the day, i.e. at 5 and 6 p.m. in the afternoon. 2.2. Instruments Two different QoL instruments were used: the WHOQoLBREF and the MSQoL-54. 2.3. World Health Organization Quality of Life-Brief Form (WHOQoL-BREF) The subjective well being was assessed by the Turkish version of WHO Quality of Life Measure—Abbreviated
31
version. All the participants were administered WHOQoLBREF to assess their quality of life. The WHOQoL is a generic quality of life instrument that was designed to be applicable to people living under different circumstances, conditions and cultures [12,13]. The WHOQoL sets out to be a purely subjective evaluation, assessing perceived QoL, and in this way differs from many other instruments used to assess QoL [14]. WHOQoL also accepts QoL as a multidimensional concept [15]. Two versions are available: i) the full WHOQoL with 100 items, and ii) the WHOQoLBREF with 26 items. WHOQoL-BREF, the generic profile instrument, useful in clinical and service evaluations was used in this study for reasons of brevity. It is suggested that the WHOQoL-BREF is sensitive to the health related quality of life status of those with long-term mental illness [13,16]. It provides unweighted measurement on four domains: physical, psychological, social relationship and environment. The physical domain has questions related to daily activities, treatment compliance, pain and discomfort, sleep and rest, energy and fatigue. In psychological domain, there are questions of positive and negative feelings, selfesteem, body image and physical appearance, personal beliefs and attention. The social relationship domain is related to personal relationships, social support, and sexual activity. The environmental domain explores physical security and safety, financial resources, health and social care and their availability, opportunities for acquiring new information and skills, and participation in and opportunities for recreation and transport. WHOQoL-BREF has acceptable psychometric properties in Turkish population [17]. The MSQoL-54 developed by Vickrey et al. [7] consists of 54 items. Eighteen MS-related specific questions were added to the original Medical Outcome Study 36-Item Short Form Health Survey (SF-36) [18]. SF-36 consists of 36 items divided into 8 scales: physical functioning (10 items), role physical functioning (4 items), bodily pain (2 items), general health (5 items), vitality (4 items), social functioning (2 items), role-emotional functioning (3 items) and mental health (5 items). Vickrey et al. added 18 items on the original SF-36 which address: health distress (4 items), sexual function (4 items), satisfaction with sexual function (1 item), overall quality of life (2 items), cognitive function (4 items), energy (1 item), pain (1 item) and social function (1 item). The MSQoL-54 instrument contains 52 items distributed into 12 scales and 2 single items. As with the SF-36, the individual questions are summed to form the scales, the scores are transformed to a 0 to 100 score both for MSQoL-54 and WHOQoL-BREF, and higher scores indicate better QoL. The patients were interviewed in the neurologist's office. They were given a brief explanation of the objective of the study and were asked for completing the scales after reading the instruction. The same scales were performed 1 month after the therapy. In summary, the same physician administered the MSQoL-54 and WHOQoLBREF to a given patient at each study visit. All examining investigators were trained on administering the scales and
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each neurologist was blinded to the other results of tests or questionnaire. Patients were asked for whether they found the questionnaires very easy/easy/hard or very hard, and whether the instruments acceptable or not. Needing help to complete the questionnaires, average time to complete the questionnaires, and missing data were also recorded. 2.4. Statistics Changes in MSQoL-54 and WHOQoL-BREF scores were assessed by repeated measures of ANOVA. We studied the cross-sectional correlations between MSQoL-54 and WHOQoL-BREF score at baseline and follow-up and longitudinal correlations between ΔMSQoL-54 and Δ WHOQoL-BREF using the Pearson's correlation coefficient (r). Correlations were also performed to assess the relationship between the two questionnaire and demographic and clinical features, e.g., age and duration of disease. The difference between male and female patients was investigated using the chi-squared test. Student's t-test was used for evaluating the difference between the mean time required performing MSQoL-54 and WHOQoL-BREF. We considered p values b 0.01 as significant and b 0.05 as trend only. The strength of correlation was labeled as follows: correlation b 0.40 as weak to marginal; 0.40–0.60 as moderate; 0.60–0.80 as good; and N 0.80 as excellent. The analyses were performed using the Statistical Package for Social Scientists (version 11). 3. Results Demographic and clinical features of patients were summarized in Table 1. Four patients (3.5%) required assistance to fill in the questionnaires. For the MSQoL-54, 10 (8.9%) patients had difficulty understanding the items related to sexual function and satisfaction, 1 km walking distance and facial expressions on one of the overall quality of life items. The acceptability of each instrument was shown in Table 2. Questionnaires with missing data was significantly low (p = 0.009) and average time to complete the questionnaire was shorter (p = 0.008) for WHOQoL-BREF. For MSQoL-54, the mean physical health composite score increased from 61.78 ± 11.5 on day 0 to 75.10 ± 10.07
MSQoL-54 WHOQoL-BREF Subjects found instrument easy or very easy to complete (%) Subjects found instrument acceptable (%) Average time to complete the questionnaire (min ± SD) Questionnaires with missing data (%)
94
96
88 92 32.4 ± 13.70 24.5 ± 11.65 12
8
on day 30. This improvement was statistically significant (p = 0.003). Mental health composite had also a significant improvement from 65.59 ± 9.7 on day 0 to 77.49 ± 11.16 on day 30 (p = 0.004). Overall MSQoL-54 score improved from 63.89 ± 11.76 on day 0 to 76.34 ± 10.65 on day 30. Overall WHOQoL-BREF score increased from 57.70 ± 12.02 to 64.60 ± 9.81 (p = 0.046). Similar trend was seen for domains of WHOQoL-BREF (Table 3). There was a very weak correlation between both QoL scales and BDS (r = −0.11 for MSQoL-54 and r = 0.13 for WHOQoL-BREF). Both WHOQoL-BREF-TR and MSQoL-54 scores showed weak correlations with age (r = 0.21, p = 0.041 and r = 0.31, p = 0.022, respectively) and duration of disease (r = 0.28, p = 0.032 and r = 0.39, p = 0.028, respectively). 3.1. MSQoL-54–WHOQoL-BREF, MSQoL-54–EDSS, WHOQoL-BREF–EDSS correlations When compared the WHOQoL-BREF and MSQoL-54, there was a weak correlation in the pretreatment period (r= 0.37). It was even weaker on day 30 (r= 0.19). In subgroup analysis, both physical and mental composites of MSQoL-54 correlated weakly with WHOQoL-BREF (r= 0.10, r= 0.12, respectively). The four domains of WHOQoL-BREF correlated weakly with MSQoL-54 (r= 0.29 for physical domain, r= 0.31 for psychological domain, p = 0.22 for social domain, and p = 0.11 for environmental domain). Physical and mental composites of MSQoL-54 were also weakly correlated with WHOQoL-BREF (r = 0.21 and r = 0.19, respectively). Correlation between changes in the WHOQoL-BREF and MSQoL-54 (ΔWHOQoL-BREF, ΔMSQoL-54) scores was even weaker (r= 0.11). Table 3 Comparison of the WHOQoL-BREF domain scores between pretreatment period and on day 30 after treatment in MS patients with relapse
Table 1 Demographic features of patients Patients (n) Females n (%) Males n (%) Course of disease n (%) RRMS SPMS Mean age (years ± SD) Mean duration of MS (years ± SD) Mean attack rate Mean EDSS score (±SD)
Table 2 The acceptability of the instruments to the subjects
112 74 (66%) 38 (34%) 98 (85.7%) 16 (14.3%) 32.14 ± 9.87 5.21 ± 6.29 4.76 ± 3.10 4.7 ± 3.71 (range 2 and 6.5)
Overall MSQoL-54 Physical health composite Mental health composite Overall WHOQoL-BREF Physical Psychological Social Environmental
Day 0 ± SD
Day 30 ± SD
p
63.89 ± 11.76 61.78 ± 11.5 65.59 ± 9.7 57.70 ± 12.02 55.01 ± 10.97 56.60 + 11.54 60.76 ± 10.10 54.43 ± 15.80
76.34 ± 10.65 75.10 ± 10.07 77.49 ± 11.16 64.60 ± 9.81 66.72 ± 11.85 68.54 ± 14.75 63.94 ± 10.92 61.68 ± 16.50
0.004 0.003 0.004 0.046 0.015 0.018 0.061 0.047
S. Özakbas et al. / Journal of the Neurological Sciences 256 (2007) 30–34
There was a moderate negative correlation between MSQoL-54 and EDSS (r = −0.48, p = 0.006). Correlation was stronger in physical health composite – EDSS relation than mental health composite – EDSS relation (r = − 0.58 and r = − 0.44, respectively). Correlation between WHOQoLBREF and EDSS was very weak in the pre-treatment period (r = − 0.17). On day 30, it was even weaker (r = − 0.13), and correlation between MSQoL-54 and EDSS was still moderate (r = − 0.46) when compared with day 0. There was not any correlation between QoL scales and attack rate (r = −0.10 for WHOQoL-BREF and r =−0.11, respectively) and there was no gender difference on the basis of QoL, either. 4. Discussion There have been a number of studies investigating the difference between generic and MS-specific QoL instruments in terms of measurement of severity of MS as perceived by patients [19,20], which was the main objective of the present study. Some authors compared an MS-specific QoL instrument (MSQoL-54) with either SF-36 [19] or both SF-36 and EuroQoL EQ-5D [20]. Freeman et al. [19] concluded that adding clinically chosen items might not be as useful as expected, in their study. In a cross-sectional design, Moore and his colleagues [20] also could not find any difference between MS-specific and generic measures. These results suggested that MS-specific QoL instruments do not necessarily have an advantage over the generic measures. As our observations were not the same, we conducted a longitudinal study of QoL in the relapse period of MS patients. We prefer WHOQoL-BREF, as a generic QoL instrument, because it is based on a cross-culturally sensitive concept and is available in most of the world's languages, including Turkish. Its multidimensional profile provides us to compare with MSQoL-54. In our study, the majority of subjects found both instrument easy to respond and acceptable. Number of missing data was greater in MSQoL-54. Most of them were due to questions relating to sexual function, which has been reported previously [20–22]. It might be due to the fact that the sexual function is a highly personal issue, and people with MS had some difficulties answering these questions. On the other hand, most of patients (88%) responded to all questions, and because of importance of sexual function in MS it should be asked in the QoL instruments. The other significant difference between two questionnaires was time to complete: WHOQoL-BREF was one-forth shorter then MSQoL-54. It is a clear advantage of a shorter and generic instrument to measure the QoL of MS patients, especially in a brief visit. The most important difference of our study was to establish the QoL of MS patients in the attack period, in which patients had the least QoL level during their disease. This might provide us to measure the QoL in a very critical episode, when the patients are so motivated to answer the questions in the scale more properly than the other periods of
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the disease. We also measured them in the 30th day after the treatment finished, and investigated the correlation between changes in the WHOQoL-BREF and MSQoL-54 scores. In the pretreatment period, there was a weak correlation between these two instruments. We suggested that WHOQoL-BREF and MSQoL-54 might not have measured the same parameters in the patients' QoL. Weaker correlation on day 30 made our suggestion stronger. Similar results in subgroup analysis supported this conclusion. Weak correlation between changes in the WHOQoL-BREF and MSQoL-54 scores also supports the fact that they cannot be used together. Significant correlations between the EDSS and the MSQoL54 measures indicate that EDSS reflects the severity of MS as perceived by patients. There was a weaker correlation between the EDSS and WHOQoL-BREF scores in the pretreatment period. Therefore we suggest that WHOQoL-BREF, as a generic QoL instrument, could not reflect the severity of MS as perceived by patients. Stronger correlation in physical health composite – EDSS relation than mental health composite – EDSS relation might be interpreted as EDSS scores reflect physical health status more than mental health, which is also reported in the previous studies [20,23,24]. The original result in our study is the significant correlation between the changes in EDSS scores and MSQoL-54 on day 30 compared with day 0 but not between the changes in EDSS and WHOQoL-BREF. We concluded that in spite that the lengthy time of administration is a disadvantage of MSQoL-54 it is still favorable and reliable for detecting the QoL in any period of MS, including remission. Our results also indicated that MSspecific measure of QoL might be used for detecting the treatment effects in relapse period of patients with MS. References [1] Kurtzke JF. Rating neurological impairment in multiple sclerosis: an Expanded Disability Status Scale. Neurology 1983;33:1444–52. [2] Cutter GR, Baier ML, Rudick RA, Cookfair DL, Fischer JS, Petkau J, et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain 1999;122:871–82. [3] Fletcher A, Gore S, Jones D, Fitzpatrick R, Spiegelhalter D, Cox D. Quality of life measures in health care. II: Design, analysis, and interpretations. Br Med J 1992;305: 1145–8. [4] Bulpitt CJ. Quality of life as an outcome measure. Postgrad Med J 1997;73:613–6. [5] Rothwell PM. Quality of life in multiple sclerosis. J Neurol Neurosurg Psychiatry 1998;65:433. [6] Patrick DL, Deyo RA. Generic and disease-specific measures in assessing health status and quality of life. Med Care 1989;27:S217–32. [7] Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A healthrelated quality of life measure for multiple sclerosis. Qual Life Res 1995;4:187–206. [8] Cella DF, Dineen K, Arnason B, Reder A, Webster KA, Karabatsos G, et al. Validation of the Functional Assessment of Multiple Sclerosis quality of life instrument. Neurology 1996;47:129–39. [9] Fischer JS, LaRocca NG, Miller DM, Ritvo PG, Andrews H, Paty D. Recent developments in the assessment quality of life in multiple sclerosis. Mult Scler 1999;5:251–9. [10] Gulick EE, Cook SD, Troiano R. Comparison of patient and staff assessment of MS patients' health status. Acta Neurol Scand 1993;88:87–93.
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[11] Poser CM, Paty DW, Scheinberg L, Mcdonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis guidelines for research protocols. Ann Neurol 1983;13:227–31. [12] WHOQoL Group. The World Health Organization Quality of Life Assessment (WHOQoL): development and general psychometric properties. Soc Sci Med 1998;46:1569–85. [13] WHOQoL Group. The World Health Organization WHOQoL-BREF Quality of Life Assessment. Psychol Med 1998;28:551–8. [14] Orley J, Saxena S, Herrman H. Quality of life and mental illness. Br J Psychiatry 1998;172:291–3. [15] Saxena S, Orley J. Quality of life assessment: the World Health Organization perspective. Eur Psychiatr 1997;12:263–6. [16] O'Carroll RE, Smith K, Couston M, Cossar JA, Hayes PC. A comparison of the WHOQoL-100 and the WHOQoL-BREF in detecting change in quality of life following liver transplantation. Qual Life Res 2000;9:121–4. [17] Eser E, Fidaner H, Fidaner C, Eser SY, Elbi H, Göker E. Psychometric properties of the WHOQoL-100 and WHOQoL-BREF. J Psychiatr Psychol Psychopharmacol 1999;7:23–40 [Turkish]. [18] Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 Health Survey: Users Manual and Interpretation Guide. Boston, MS: The Health Institute, New England Medical Center; 1993.
[19] Freeman JA, Hobart JC, Thompson AJ. Does adding MS-specific items to a generic measure (the SF-36) improve measurement? Neurology 2001;57:68–74. [20] Moore F, Wolfson C, Alexandrov L, Lapierre Y. Do general and multiple sclerosis-specific quality of life instruments differ? Can J Neurol Sci 2004;31:64–71. [21] Solari A, Filippini G, Mendozzi L, et al. Validation of Italian multiple sclerosis quality of life-54 questionnaire. J Neurol Neurosurg Psychiatry 1999;67:158–62. [22] Solari A, Radice D. Health status of people with multiple sclerosis: a community mail survey. Neurol Sci 2001;22:307–15. [23] Ozakbas S, Cagiran I, Ormeci B, Idiman E. Correlations between multiple sclerosis functional composite, expanded disability status scale and health-related quality of life during and after treatment of relapses in patients with multiple sclerosis. J Neurol Sci 2004;218:3–7. [24] Ozakbas S, Ormeci B, Idiman E. Utilization of the multiple sclerosis functional composite in follow-up: relationship to disease phenotype, disability and treatment strategies. J Neurol Sci 2005;232:65–9.
Difference between generic and multiple sclerosis-specific quality of life instruments regarding the assessment of treatment efficacy S. Özakbas a,⁎, B.B. Akdede b , G. Kösehasanogullari a , Ö. Aksan a , E. Idiman a a b
Department of Neurology, Dokuz Eylul University Faculty of Medicine, Balcova 35340, Izmir, Turkey Department of Psychiatry, Dokuz Eylul University Faculty of Medicine, Balcova 35340, Izmir, Turkey Received 10 May 2006; received in revised form 13 November 2006; accepted 15 January 2007 Available online 26 March 2007
Abstract Multiple sclerosis (MS) is a chronic and stressful disease, which significantly affects the quality of life (QoL) of patients. QoL instruments provide information which traditional outcome measures of MS do not. It is unclear if the longer disease-specific instruments provide more useful information than the shorter. We aimed to investigate whether there was any difference between general QoL instrument and MSspecific one on the basis of detecting the efficacy of pulse therapy. 112 clinically definite MS patients were included in the study. Patients enrolled in the study were in relapse period treated by 1 g/day methyl-prednisolone for 5 days. World Health Organization Quality of Life Brief Form, Turkish Version (WHOQoL-BREF-TR) was given as a generic measure and Multiple Sclerosis Quality of Life-54 (MSQoL-54) as an MS-specific measure to assess the QoL. The same scales were administered 1 month after the therapy. MSQoL-54 was correlated with the EDSS in the pre-treatment period but WHOQoL-BREF was not. On day 30, there was a significant increase in both WHOQoL-BREF and MSQoL-54 scores. Increase was more prominent in MSQoL-54. There was a weak correlation between WHOQoL-BREF and MSQoL-54 (r = 0.17). Correlation between changes in WHOQoL-BREF and MSQoL-54 scores was even weaker (r = 0.11). Correlation between WHOQoL-BREF and EDSS was weaker (r = 0.13), and correlation between MSQoL-54 and EDSS was still moderate (r = 0.46) when compared with day 0. We concluded that although it takes a longer time to administer, MSQoL-54, as a MS-specific QoL instrument, is favorable and reliable for detecting the QoL not only in the remission but also in the relapse period of MS. Our results also indicated that MSspecific measure of QoL might be used for detecting the treatment effects in relapse period of patients with MS. © 2007 Elsevier B.V. All rights reserved. Keywords: Multiple sclerosis; Quality of life; MSQoL-54; WHOQoL-BREF; Relapse; Treatment; EDSS
1. Introduction Multiple sclerosis (MS) is a chronic and stressful disease, which significantly impacts the quality of life (QoL) of patients. QoL instruments can be used as an outcome measure in clinical trials, just like we used Expanded Disability Status Scale (EDSS) [1] or Multiple Sclerosis Functional Composite (MSFC) [2] for assessing disease progression, or magnetic resonance imaging for assessing lesion burden [3–5]. QoL instruments provide information that traditional outcome
⁎ Corresponding author. Tel.: +90 232 4124064; fax: +90 232 2786192. E-mail address: [email protected] (S. Özakbas). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.01.080
measures used in MS studies do not. The two different ways to measure QoL are the generic and disease specific instruments [6]. In the generic instrument, it is aimed to assess universal health concepts thought to be relevant regardless of disease, age group, or treatment. In contrast, in the diseasespecific instrument, it is aimed to reflect factors relevant to a specific disease, in which the content of the measure is more likely to detect change, because it is targeted to the specific disease. A number of disease-specific measures for MS have been developed [7–10]. There are a number of questions to be examined for QoL instruments: Intuitively, it seems reasonable to use MS-specific QoL instrument to evaluate effect of clinical signs or symptoms on QoL of the individual patient. On the other hand, it would be so practical to use lengthy QoL
S. Özakbas et al. / Journal of the Neurological Sciences 256 (2007) 30–34
instruments in the clinical setting. It is unclear if the longer, disease-specific instruments provide more useful information than the shorter. As, one of the most important periods of low levels of QoL is the attack period in patients with MS, we examined how QoL was affected in the attack period in MS patients. But our main question was whether there was any difference between simple, general QoL instrument and MSspecific one on the basis of measurement of the treatment effect of pulse methyl-prednisolone (MP). These questions were examined by conducting a prospective study in patients with MS who were in acute exacerbation period, by comparing two QoL questionnaires: World Health Organization Quality of Life Brief Form, Turkish Version (WHOQoL-REF-TR), as a generic measure and Multiple Sclerosis Quality of Life-54 (MSQoL-54) as a MS-specific measure. 2. Material and methods 2.1. Patients A total of 112 clinically definite MS patients according to the Poser's criteria [11] participated in this longitudinal study. All patients were in an objective acute exacerbation, which was defined as the appearance of new symptom(s) or worsening of existing symptom(s). Symptom(s) should have lasted at least 24 h. Patients were excluded if they were b 18 and N 55 years of age, were unable to reliably complete the questionnaires, had any significant co-morbid illness, such as previous stroke or rheumatoid arthritis which was likely to impact on the patients' QoL or had infectious diseases causing fever. Patients who had an experience with any questionnaires were also excluded. Beck Depression Scale (BDS) was also performed before the attack treatment. Cutoff value was accepted as 17 for significant depression in BDS. 3 patients were found depressed, and excluded from analysis of comparison with QoL scales. All patients received 1000 mg intravenous (i.v.) MP for 5 days, followed by tapering dose of 100 mg oral prednisolone for 25 days. The MSQoL-54, WHOQoL-BREF and EDSS were administered twice in 30 days. All were assessed on day 0, before the first administration of corticosteroid and on day 30, after corticosteroid treatment was finished. Assessment of EDSS and administration of MSQoL-54 and WHOQoLBREF were at the same time of the day, i.e. at 5 and 6 p.m. in the afternoon. 2.2. Instruments Two different QoL instruments were used: the WHOQoLBREF and the MSQoL-54. 2.3. World Health Organization Quality of Life-Brief Form (WHOQoL-BREF) The subjective well being was assessed by the Turkish version of WHO Quality of Life Measure—Abbreviated
31
version. All the participants were administered WHOQoLBREF to assess their quality of life. The WHOQoL is a generic quality of life instrument that was designed to be applicable to people living under different circumstances, conditions and cultures [12,13]. The WHOQoL sets out to be a purely subjective evaluation, assessing perceived QoL, and in this way differs from many other instruments used to assess QoL [14]. WHOQoL also accepts QoL as a multidimensional concept [15]. Two versions are available: i) the full WHOQoL with 100 items, and ii) the WHOQoLBREF with 26 items. WHOQoL-BREF, the generic profile instrument, useful in clinical and service evaluations was used in this study for reasons of brevity. It is suggested that the WHOQoL-BREF is sensitive to the health related quality of life status of those with long-term mental illness [13,16]. It provides unweighted measurement on four domains: physical, psychological, social relationship and environment. The physical domain has questions related to daily activities, treatment compliance, pain and discomfort, sleep and rest, energy and fatigue. In psychological domain, there are questions of positive and negative feelings, selfesteem, body image and physical appearance, personal beliefs and attention. The social relationship domain is related to personal relationships, social support, and sexual activity. The environmental domain explores physical security and safety, financial resources, health and social care and their availability, opportunities for acquiring new information and skills, and participation in and opportunities for recreation and transport. WHOQoL-BREF has acceptable psychometric properties in Turkish population [17]. The MSQoL-54 developed by Vickrey et al. [7] consists of 54 items. Eighteen MS-related specific questions were added to the original Medical Outcome Study 36-Item Short Form Health Survey (SF-36) [18]. SF-36 consists of 36 items divided into 8 scales: physical functioning (10 items), role physical functioning (4 items), bodily pain (2 items), general health (5 items), vitality (4 items), social functioning (2 items), role-emotional functioning (3 items) and mental health (5 items). Vickrey et al. added 18 items on the original SF-36 which address: health distress (4 items), sexual function (4 items), satisfaction with sexual function (1 item), overall quality of life (2 items), cognitive function (4 items), energy (1 item), pain (1 item) and social function (1 item). The MSQoL-54 instrument contains 52 items distributed into 12 scales and 2 single items. As with the SF-36, the individual questions are summed to form the scales, the scores are transformed to a 0 to 100 score both for MSQoL-54 and WHOQoL-BREF, and higher scores indicate better QoL. The patients were interviewed in the neurologist's office. They were given a brief explanation of the objective of the study and were asked for completing the scales after reading the instruction. The same scales were performed 1 month after the therapy. In summary, the same physician administered the MSQoL-54 and WHOQoLBREF to a given patient at each study visit. All examining investigators were trained on administering the scales and
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each neurologist was blinded to the other results of tests or questionnaire. Patients were asked for whether they found the questionnaires very easy/easy/hard or very hard, and whether the instruments acceptable or not. Needing help to complete the questionnaires, average time to complete the questionnaires, and missing data were also recorded. 2.4. Statistics Changes in MSQoL-54 and WHOQoL-BREF scores were assessed by repeated measures of ANOVA. We studied the cross-sectional correlations between MSQoL-54 and WHOQoL-BREF score at baseline and follow-up and longitudinal correlations between ΔMSQoL-54 and Δ WHOQoL-BREF using the Pearson's correlation coefficient (r). Correlations were also performed to assess the relationship between the two questionnaire and demographic and clinical features, e.g., age and duration of disease. The difference between male and female patients was investigated using the chi-squared test. Student's t-test was used for evaluating the difference between the mean time required performing MSQoL-54 and WHOQoL-BREF. We considered p values b 0.01 as significant and b 0.05 as trend only. The strength of correlation was labeled as follows: correlation b 0.40 as weak to marginal; 0.40–0.60 as moderate; 0.60–0.80 as good; and N 0.80 as excellent. The analyses were performed using the Statistical Package for Social Scientists (version 11). 3. Results Demographic and clinical features of patients were summarized in Table 1. Four patients (3.5%) required assistance to fill in the questionnaires. For the MSQoL-54, 10 (8.9%) patients had difficulty understanding the items related to sexual function and satisfaction, 1 km walking distance and facial expressions on one of the overall quality of life items. The acceptability of each instrument was shown in Table 2. Questionnaires with missing data was significantly low (p = 0.009) and average time to complete the questionnaire was shorter (p = 0.008) for WHOQoL-BREF. For MSQoL-54, the mean physical health composite score increased from 61.78 ± 11.5 on day 0 to 75.10 ± 10.07
MSQoL-54 WHOQoL-BREF Subjects found instrument easy or very easy to complete (%) Subjects found instrument acceptable (%) Average time to complete the questionnaire (min ± SD) Questionnaires with missing data (%)
94
96
88 92 32.4 ± 13.70 24.5 ± 11.65 12
8
on day 30. This improvement was statistically significant (p = 0.003). Mental health composite had also a significant improvement from 65.59 ± 9.7 on day 0 to 77.49 ± 11.16 on day 30 (p = 0.004). Overall MSQoL-54 score improved from 63.89 ± 11.76 on day 0 to 76.34 ± 10.65 on day 30. Overall WHOQoL-BREF score increased from 57.70 ± 12.02 to 64.60 ± 9.81 (p = 0.046). Similar trend was seen for domains of WHOQoL-BREF (Table 3). There was a very weak correlation between both QoL scales and BDS (r = −0.11 for MSQoL-54 and r = 0.13 for WHOQoL-BREF). Both WHOQoL-BREF-TR and MSQoL-54 scores showed weak correlations with age (r = 0.21, p = 0.041 and r = 0.31, p = 0.022, respectively) and duration of disease (r = 0.28, p = 0.032 and r = 0.39, p = 0.028, respectively). 3.1. MSQoL-54–WHOQoL-BREF, MSQoL-54–EDSS, WHOQoL-BREF–EDSS correlations When compared the WHOQoL-BREF and MSQoL-54, there was a weak correlation in the pretreatment period (r= 0.37). It was even weaker on day 30 (r= 0.19). In subgroup analysis, both physical and mental composites of MSQoL-54 correlated weakly with WHOQoL-BREF (r= 0.10, r= 0.12, respectively). The four domains of WHOQoL-BREF correlated weakly with MSQoL-54 (r= 0.29 for physical domain, r= 0.31 for psychological domain, p = 0.22 for social domain, and p = 0.11 for environmental domain). Physical and mental composites of MSQoL-54 were also weakly correlated with WHOQoL-BREF (r = 0.21 and r = 0.19, respectively). Correlation between changes in the WHOQoL-BREF and MSQoL-54 (ΔWHOQoL-BREF, ΔMSQoL-54) scores was even weaker (r= 0.11). Table 3 Comparison of the WHOQoL-BREF domain scores between pretreatment period and on day 30 after treatment in MS patients with relapse
Table 1 Demographic features of patients Patients (n) Females n (%) Males n (%) Course of disease n (%) RRMS SPMS Mean age (years ± SD) Mean duration of MS (years ± SD) Mean attack rate Mean EDSS score (±SD)
Table 2 The acceptability of the instruments to the subjects
112 74 (66%) 38 (34%) 98 (85.7%) 16 (14.3%) 32.14 ± 9.87 5.21 ± 6.29 4.76 ± 3.10 4.7 ± 3.71 (range 2 and 6.5)
Overall MSQoL-54 Physical health composite Mental health composite Overall WHOQoL-BREF Physical Psychological Social Environmental
Day 0 ± SD
Day 30 ± SD
p
63.89 ± 11.76 61.78 ± 11.5 65.59 ± 9.7 57.70 ± 12.02 55.01 ± 10.97 56.60 + 11.54 60.76 ± 10.10 54.43 ± 15.80
76.34 ± 10.65 75.10 ± 10.07 77.49 ± 11.16 64.60 ± 9.81 66.72 ± 11.85 68.54 ± 14.75 63.94 ± 10.92 61.68 ± 16.50
0.004 0.003 0.004 0.046 0.015 0.018 0.061 0.047
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There was a moderate negative correlation between MSQoL-54 and EDSS (r = −0.48, p = 0.006). Correlation was stronger in physical health composite – EDSS relation than mental health composite – EDSS relation (r = − 0.58 and r = − 0.44, respectively). Correlation between WHOQoLBREF and EDSS was very weak in the pre-treatment period (r = − 0.17). On day 30, it was even weaker (r = − 0.13), and correlation between MSQoL-54 and EDSS was still moderate (r = − 0.46) when compared with day 0. There was not any correlation between QoL scales and attack rate (r = −0.10 for WHOQoL-BREF and r =−0.11, respectively) and there was no gender difference on the basis of QoL, either. 4. Discussion There have been a number of studies investigating the difference between generic and MS-specific QoL instruments in terms of measurement of severity of MS as perceived by patients [19,20], which was the main objective of the present study. Some authors compared an MS-specific QoL instrument (MSQoL-54) with either SF-36 [19] or both SF-36 and EuroQoL EQ-5D [20]. Freeman et al. [19] concluded that adding clinically chosen items might not be as useful as expected, in their study. In a cross-sectional design, Moore and his colleagues [20] also could not find any difference between MS-specific and generic measures. These results suggested that MS-specific QoL instruments do not necessarily have an advantage over the generic measures. As our observations were not the same, we conducted a longitudinal study of QoL in the relapse period of MS patients. We prefer WHOQoL-BREF, as a generic QoL instrument, because it is based on a cross-culturally sensitive concept and is available in most of the world's languages, including Turkish. Its multidimensional profile provides us to compare with MSQoL-54. In our study, the majority of subjects found both instrument easy to respond and acceptable. Number of missing data was greater in MSQoL-54. Most of them were due to questions relating to sexual function, which has been reported previously [20–22]. It might be due to the fact that the sexual function is a highly personal issue, and people with MS had some difficulties answering these questions. On the other hand, most of patients (88%) responded to all questions, and because of importance of sexual function in MS it should be asked in the QoL instruments. The other significant difference between two questionnaires was time to complete: WHOQoL-BREF was one-forth shorter then MSQoL-54. It is a clear advantage of a shorter and generic instrument to measure the QoL of MS patients, especially in a brief visit. The most important difference of our study was to establish the QoL of MS patients in the attack period, in which patients had the least QoL level during their disease. This might provide us to measure the QoL in a very critical episode, when the patients are so motivated to answer the questions in the scale more properly than the other periods of
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the disease. We also measured them in the 30th day after the treatment finished, and investigated the correlation between changes in the WHOQoL-BREF and MSQoL-54 scores. In the pretreatment period, there was a weak correlation between these two instruments. We suggested that WHOQoL-BREF and MSQoL-54 might not have measured the same parameters in the patients' QoL. Weaker correlation on day 30 made our suggestion stronger. Similar results in subgroup analysis supported this conclusion. Weak correlation between changes in the WHOQoL-BREF and MSQoL-54 scores also supports the fact that they cannot be used together. Significant correlations between the EDSS and the MSQoL54 measures indicate that EDSS reflects the severity of MS as perceived by patients. There was a weaker correlation between the EDSS and WHOQoL-BREF scores in the pretreatment period. Therefore we suggest that WHOQoL-BREF, as a generic QoL instrument, could not reflect the severity of MS as perceived by patients. Stronger correlation in physical health composite – EDSS relation than mental health composite – EDSS relation might be interpreted as EDSS scores reflect physical health status more than mental health, which is also reported in the previous studies [20,23,24]. The original result in our study is the significant correlation between the changes in EDSS scores and MSQoL-54 on day 30 compared with day 0 but not between the changes in EDSS and WHOQoL-BREF. We concluded that in spite that the lengthy time of administration is a disadvantage of MSQoL-54 it is still favorable and reliable for detecting the QoL in any period of MS, including remission. Our results also indicated that MSspecific measure of QoL might be used for detecting the treatment effects in relapse period of patients with MS. References [1] Kurtzke JF. Rating neurological impairment in multiple sclerosis: an Expanded Disability Status Scale. Neurology 1983;33:1444–52. [2] Cutter GR, Baier ML, Rudick RA, Cookfair DL, Fischer JS, Petkau J, et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain 1999;122:871–82. [3] Fletcher A, Gore S, Jones D, Fitzpatrick R, Spiegelhalter D, Cox D. Quality of life measures in health care. II: Design, analysis, and interpretations. Br Med J 1992;305: 1145–8. [4] Bulpitt CJ. Quality of life as an outcome measure. Postgrad Med J 1997;73:613–6. [5] Rothwell PM. Quality of life in multiple sclerosis. J Neurol Neurosurg Psychiatry 1998;65:433. [6] Patrick DL, Deyo RA. Generic and disease-specific measures in assessing health status and quality of life. Med Care 1989;27:S217–32. [7] Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A healthrelated quality of life measure for multiple sclerosis. Qual Life Res 1995;4:187–206. [8] Cella DF, Dineen K, Arnason B, Reder A, Webster KA, Karabatsos G, et al. Validation of the Functional Assessment of Multiple Sclerosis quality of life instrument. Neurology 1996;47:129–39. [9] Fischer JS, LaRocca NG, Miller DM, Ritvo PG, Andrews H, Paty D. Recent developments in the assessment quality of life in multiple sclerosis. Mult Scler 1999;5:251–9. [10] Gulick EE, Cook SD, Troiano R. Comparison of patient and staff assessment of MS patients' health status. Acta Neurol Scand 1993;88:87–93.
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