Validating Migraine-specific Quality of Life Questionnaire

Christine L. Bagley, PharmD; Regina Rendas-Baum, MS; Gregory A. Maglinte, PhD; Min Yang, MD, PhD; Sepideh F. Varon, PhD; Jeff Lee, PharmD, FCCP; Mark Kosinski, MA

Posted: 04/20/2012; Headache. 2012;52(3):409-421. © 2012 Blackwell Publishing
Abstract and Introduction
Abstract

Objective.— To provide evidence for the reliability and validity of the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ) for use in chronic migraine (CM) in adults.
Background.— MSQ is one of the most frequently utilized disease-specific tools assessing impact of migraine on health-related quality of life (HRQL). However, evidence for its reliability and validity are based on studies in episodic migraine (EM) populations. Additional studies assessing the reliability and validity of the MSQ in patients with CM are needed.
Methods.— Cross-sectional data were collected via web-based survey in 9 countries/regions. Participants were classified as having CM (≥15 headache days/month)

Results.— A total of 8726 eligible respondents were classified: 5.7% CM (n = 499) and 94.3% EM (n = 8227). Subjects were mostly female (83.5%) with a mean (±SD) age of 40.3 ± 11.4, and were similar between the 2 groups. MSQ domain scores for CM and EM groups, respectively, were: RP = 61.4 ± 26.1 and 71.7 ± 24.0; RR = 44.4 ± 22.1 and 56.5 ± 24.1; EF = 48.3 ± 28.1 and 67.2 ± 26.7. Internal consistency of the overall sample for RP, RR, and EF was 0.90, 0.96, and 0.87, respectively. Similar values were observed for CM and EM. MSQ scores for the overall sample correlated moderately to highly with scores from the PHQ-4 (r = −0.21 to −0.42), MIDAS (r = −0.38 to −0.39), and HIT-6 (r = −0.60 to −0.71). Similar values were observed for CM and EM. Known-groups validity indicated significant differences (P < .0001) in the hypothesized direction between CM and EM for RP (F = 86.19), RR (F = 119.24), and EF (F = 235.90).
Conclusion.— The MSQ is a reliable and valid questionnaire in the CM population that can differentiate the functional impact between CM and EM. The MSQ can assist researchers in evaluating treatment effectiveness by obtaining input directly from the patients on multidimensional aspects other than frequency of headache days.

Introduction

Migraine adversely affects an estimated 12% of the US population.^[1–3] Although the clinical course of migraine across a patient’s life span is not yet fully understood, there is increasing evidence that, for some patients, the frequency of headache attacks increases over time.^[4]

Chronic migraine (CM) is currently defined as a complication of migraine characterized by ≥15 headache days per month (HDPM) for at least 3 months, occurring in patients with at least 5 attacks fulfilling criteria for migraine without aura and for whom headache fulfilled criteria for pain and associated symptoms of migraine without aura at least 8 HDPM in the past 3 months.^[5] In addition, the International Classification of Headache Disorders, Revised Second Edition (ICHD-IIR) diagnostic criteria exclude those patients with a diagnosis of medication overuse.^[5] Population-based studies suggest that 1.4–2.2% of the general population suffer from CM.^[6–8] It is estimated that migraine patients transit from episodic migraine (EM) to CM at a rate of 2.5% of patients per year.^[4] Studies have suggested that a higher frequency of headache attacks is associated with significantly greater levels of functional disability and reduced health-related quality of life (HRQL).^[9,10]

Chronic migraine patients have been found to have reduced productivity and more missed days of work, school, housework, or family and leisure activities when compared to patients with EM^[9] and are estimated to incur total costs (both direct and indirect) that are 4 times greater than those for EM patients.^[11] Despite the clinical and economic burden of CM compared to EM, CM is frequently undertreated and underdiagnosed.^[12–14]

Researchers and clinical practitioners alike have become increasingly aware that the impact of migraine cannot be fully assessed through measures that focus exclusively on pain and frequency of headaches. Patient-reported outcome (PRO) instruments are recognized as important tools in assessing the impact of a given disease state on HRQL in clinical practice.^[15]

Both generic and disease-specific PRO measures can be used to evaluate HRQL in migraine patients. Although generic PRO measures allow for a direct comparison of disease burden across different conditions, disease-specific PROs offer a more precise level of measurement, given their focus on limitations or problems that are associated with a particular disease. For this reason, changes in HRQL due to treatment are often better captured by disease-specific PROs. Accordingly, experts have recommended^[16–18] the use of disease-specific PRO measures to quantify the potential benefits of treatment in migraine clinical trials. Previous literature has summarized characteristics of both generic and disease-specific quality of life measures commonly used in headache patients, and these measures were found to vary in their specificity, the dimensions they assess, the time frame they address, as well as their psychometric properties.^[15] Accordingly, as most disease-specific PROs are designed to measure impact on HRQL that is directly attributable to the disease of interest, the reliability of the results obtained with these instruments still requires careful evaluation of their psychometric properties and overall validity among the clinical population of interest.

The Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ) is one of the most frequently utilized disease-specific tools assessing the impact of migraine on HRQL.^[19–23] The MSQ measures the impact of migraine on the patient’s HRQL over the past 4 weeks across 3 dimensions: Role Function-Restrictive (RR), Role Function-Preventive (RP), and Emotional Function (EF). The MSQ was developed from an expert-based item review of the migraine literature and validated in a clinical sample of 458 new and stable EM patients.^[21] In the validation study, the MSQ revealed high internal consistency (Cronbach’s α = 0.79 to 0.85), a moderate to strong convergent validity, as well as an adequate discriminant validity. Martin and Colleagues^[22] performed a multicenter study that further supported the evidence of a high internal consistency (Cronbach’s α = 0.86 to 0.96), strong reliability, and good validity of the 14-item MSQ among 267 participants.

Although there is evidence for reliability and validity of the MSQ, these studies were conducted in EM populations.^[21,22,24] Given the extensive use of the MSQ in migraine research, its integral role within clinical practice, and the emerging evidence regarding the need for practitioners to distinguish CM from EM, additional studies assessing the reliability and validity of the MSQ in patients with CM are needed. The current study aims to provide evidence on the reliability and validity of the MSQ in CM patients and to evaluate its ability to capture differences in HRQL between CM and EM patients.

Methods

Subjects

The International Burden of Migraine Study (IBMS) was a web-based cross-sectional observational study that collected survey data on migraine patients from 9 countries/regions (the USA, Canada, France, Germany, Spain, the UK, Australia, Italy, and Taiwan) between February and April of 2009.^[25] Participants were recruited from a population of panelists, maintained by Synovate Healthcare, who had already reported suffering from headaches and/or migraines. Participants provided consent by “opting-in” using a web link (provided in the email invitation) as a proxy for written informed consent. To be considered for participation in the study, respondents had to meet the following criteria: (1) be 18 years of age or older; (2) have an active email address; (3) report having experienced headaches during the last 3 months not associated with a cold, the flu, a head injury, or a hangover; (4) provide conformed consent by “opting-in” via a web link in the email invitation; (5) have migraine symptoms.

Eligibility and migraine diagnostic features were assessed using validated screening questions^[14] and ICHD-IIR migraine diagnostic criteria.^[26] Eligible participants were further categorized as EM (<15 HDPM) or CM (≥15 headaches days month). A flow diagram of study participants and eligibility is presented in the Figure. A total of 63,001 panelists in 9 countries were contacted. Of those, 30.7% (n = 19,365) responded to the email invitation and completed the eligibility screening and 55.0% (n = 10,650) were eligible to complete the survey based on screening criteria. Surveys were completed by 81.9% (n = 8,726) of eligible responders. Detailed description of study design and methods has been previously published.^[25]

The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Measures

For the respondents who met the screening criteria based on number of headache days in the previous 3 months, the remainder of the survey questions assessed migraine severity, participant socio-demographic and clinical characteristics, healthcare resource utilization, productivity, and HRQL.

Socio-Demographic and Clinical Characteristics Participants reported their age, gender, race, marital status, employment status, education, income, height, and weight. Participants were asked to provide the frequency of the following headache symptoms: severity of pain, throbbing, getting worse with activity, worse on 1 side, nausea, photosensitivity, and phonosensitivity. The survey also included specific questions regarding the typical duration of headaches with and without medication. The presence of comorbidities (pain, vascular disease, vascular events, psychiatric conditions, or other) was also collected as part of the survey. As part of screening, participants were asked to report the number of days in the last 3 months that they had a headache of any intensity.

Migraine-Specific Quality of Life Questionnaire Version 2.1 The 14-item MSQ is designed to measure how migraines affect and/or limit daily functioning across 3 domains: RR (7 items assessing how migraines limit one’s daily social and work-related activities), RP (4 items assessing how migraines prevent these activities), and EF (3 items assessing the emotions associated with migraines). Participants respond to items using a 6-point scale, “none of the time,””a little bit of the time,””some of the time,””a good bit of the time,””most of the time,” and “all of the time,” which are assigned scores of 1 to 6, respectively. Raw dimension scores are computed as a sum of item responses and are rescaled to a 0–100 scale, where higher scores indicate better HRQL.

Multiple studies have demonstrated good reliability and validity of the MSQ in subjects with EM.^{[21,22,24,27]} The MSQ has been administered in several efficacy trials of EM and CM treatment and has shown to be responsive to treatment.^[19,28,29] Results from a study of 119 migraine patients recruited at 4 headache clinics revealed that the effect sizes of the MSQ were moderate to large at 4 and 12 weeks.^[30] More recently, inter- and intra-individual minimally important differences (MID) have been established^[31] using data from 2 randomized clinical trials of migraine prevention therapy and from 1 cross-sectional survey of headache patients.

Headache Impact Test (HIT-6) The HIT-6 assesses the impact of headache on participants’ lives in the past 4 weeks. Six domains are represented by the HIT-6: pain, role functioning, social functioning, energy or fatigue, cognition, and emotional distress.^[32] Responses are provided on a 5-point scale in the categories “never,””rarely,””sometimes,””very often,” and “always,” and are assigned values of 6, 8, 10, 11, and 13, respectively. The HIT-6 total score is obtained from simple summation of the 6 items and ranges between 36 and 78, with larger scores reflecting greater impact. Four groups have been derived to aid in the interpretation of HIT-6 scores: scores ≤49 represent little or no impact, scores between 50 and 55 represent some impact, scores between 56 and 59 represent substantial impact, and score ≥60 indicate severe impact.^[33] The instrument has shown good reliability, construct, and convergent and face validity,^[32,34] and its MID has been evaluated in a sample of patients with chronic daily headache.^[35]

Migraine Disability Assessment Scale (MIDAS) The MIDAS was developed to measure headache-related disability in 3 domains: school/work; household work; and family, social, or leisure activities.^[36] The disability is quantified by the total number of days of activity limitations due to migraine in the past 3 months. Two additional questions assess the frequency and intensity of a headache. A total score is calculated by adding the 5 headache-related disability items, with higher scores indicating increased disability due to headache. The MIDAS has an acceptable internal consistency, and a moderate 3-month test–retest reliability.^[36] MIDAS scores had moderate correlations with equivalent measures derived from 90-day diary data.^[36] Based on physicians’ judgment of MIDAS scores on varying levels of migraine patient’s activity limitation and treatment needs, 4 grades of headache-related disability have been derived from the total MIDAS score: grade I for “minimal or infrequent disability” (0–5), grade II for “mild or infrequent disability” (6–10), grade III for “moderate disability” (11–20), and grade IV for “severe disability” (≥21).^[36] Although this scoring system works well for EM, a previous study found that further subdivision of grade IV allows for a clear examination of variation within CM patients.^[25] Accordingly, for this study, grade IV was subdivided into grade IV-A, severe disability (scores of 21–40), and grade IV-B, very severe (scores of 41–270).

Patient Health Questionnaire (PHQ-4) The PHQ-4 constitutes a brief screening measure for depression and anxiety symptoms in the past 2 weeks. The PHQ-4 scale consists of the 2 core DSM-IV items for major depressive disorder and generalized anxiety disorder, respectively.^[37–39] Each of the 4 items is answered on a 4-point scale: “not at all” (0), “several days” (1), “more than half the days” (2), and “nearly every day” (3). Total scores range from 0 to 12, with a higher score indicating a greater likelihood of an underlying depressive or anxiety disorder. Scores are rated as normal (0–2), mild (3–5), moderate (6–8), and severe (9–12). Two discrete factors of depression and anxiety were found to explain 84% of the total variance in the PHQ-4 and higher scores were strongly associated with functional impairment, disability days, and healthcare use.^[40] Major depressive disorder scores ≥3 have demonstrated sensitivity of 83% and specificity of 90%,^[41] while similar scores on the generalized anxiety disorder items demonstrated good sensitivity (86%) and good specificity (83%) for identifying patients with depression.^[42] Recent studies have confirmed the reliability and validity of the PHQ-4 as a measure of depression and anxiety using a representative sample of the German general population.^[43]

Statistical Analysis

Reliability Analyses Internal consistency reliability was assessed by calculating Cronbach’s α across the 3 MSQ domains, for the whole sample and separately for CM and EM patients. Reliability was determined using the conventional threshold for Cronbach’s α of 0.70.^[44]

Convergent and Discriminant Validity Convergent and discriminant validity was assessed by evaluating the Pearson correlation coefficients of the MSQ scores and HDPM, as well as scores on the following HRQL instruments: HIT-6, MIDAS, and PHQ-4. Given that the HIT-6 and the MIDAS are disease-specific instruments and assess the impact of migraine on HRQL, it was hypothesized that correlations between the MSQ and the HIT-6 and the MSQ and the MIDAS would be higher than those between the MSQ and the PHQ-4. Compared to the MSQ RR and RP scales, it was also hypothesized that the MSQ EF scale would more highly correlate with the PHQ-4. Moderate correlations between HDPM and MSQ scores were expected.

Known-Groups Validity Construct validity of the MSQ was further evaluated using the method of known-groups validity.^[45] Known-groups validity was assessed using analysis of variance (ANOVA) methods to compare mean MSQ score differences across the following criterion measures: (1) patients who differed in headache frequency (CM and EM patients); (2) patients who differed in migraine impact severity, as indicated by the HIT-6 score (little or no impact, some impact, substantial impact, and severe impact); (3) patients who differed in migraine impact severity according to MIDAS grade (I [0–6], II [7–10], III [11–20], and IV [≥21]); (4) patients who differed in risk for depression and anxiety, as indicated by the PHQ-4 score (normal, mild, moderate, and severe). We expected that lower mean MSQ scores would be observed in patients with CM than those with EM. In addition, it was hypothesized that MSQ scores would be monotonically lower across greater impact severity levels and greater levels of depression and anxiety risk.

Results

Subject Characteristics

A total of 8,726 eligible respondents were classified as follows: 5.7% CM (n = 499), 94.3% EM (n = 8,227) (Table 1). Migraine patients were mostly female (83.5%), white/Caucasian (86.1%), with a mean (±SD) age of 40.3 (±11.4) years. Approximately one-quarter of the total sample (24.4%) had completed high school and a similar proportion (25.2%) had some college or had an associate degree. Two-thirds of the total sample (66.4%) had been told by a healthcare provider that they suffered from migraines and the majority (78.9%) reported experiencing severe headache pain. Socio-demographic characteristics were mostly similar across the CM and EM groups, with the exception of the distribution of Asian and Hispanic participants. The proportion of Asians in the CM group was lower (1.8% vs 8.3% in the EM group), while the proportion of Hispanics was higher (5.0% vs 2.5% in the EM group). In addition, a greater proportion of CM patients reported severe headache pain (92.4% vs 78.1% in the EM group).

The MSQ Item Distributional Characteristics

Mean scores for MSQ items on the RR scale (items 1–7) were similar, ranging from 3.0 to 3.4 ( Table 2 ). Mean scores for MSQ items on the RP scale (items 8–11) were lower than those of the items making up the RR scale and ranged from 2.3 to 2.7. Unlike the RR and RP scales, a greater variation in mean scores was observed across the EF scale items (items 12–14) with mean scores of 2.4 in the 2 items concerning “feeling like a burden on others” (item 13) and “being afraid of letting others down” (item 14) and a mean score of 3.3 for the item concerning “feeling fed up or frustrated” (item 12) because of migraines. No ceiling effects were observed among the 14 items (range: 4–12%). However, floor effects were seen for 2 EF scale items (“being a burden on others” and “being afraid of letting others down”) and 3 RP scale items (“canceling work or daily activities,””help with handling routine tasks,” and “being unable to attend social activities”), with over 30% of EM patients obtaining the lowest score in these items.

Reliability and Validity Analyses

Results of the reliability analyses of the MSQ among migraine sufferers are presented in Table 3 . Cronbach’s α indicated excellent^[44] internal consistency reliability for the entire sample (range 0.87 to 0.96) and across migraine frequency groups (CM range: 0.85–0.95; EM range: 0.86–0.96).

The MSQ scales were moderately to highly correlated with the HIT-6 (r = −0.60 to −0.71), MIDAS (r = −0.38 to −0.57), and PHQ-4 (r = −0.30 to −0.47), but had low correlation with HDPM (r = −0.24 to −0.14; Table 4 ). All correlations were statistically significant (P < .01). The higher correlations observed between all scales of the MSQ and the HIT-6 and the MIDAS, as well as the MSQ EF scale and the PHQ-4, supported convergent validity of the MSQ, and the lower correlations observed between the MSQ RR and RP scales and the PHQ-4 supported discriminant validity of the MSQ. Furthermore, correlations of the HIT-6 and the MIDAS with the MSQ tended to be highest for the RR scale, closely followed by the RP and EF scales. Conversely, correlations of the PHQ-4 and HDPM with the MSQ were highest for the EF scale, followed by the RR and RP scales. Although slightly lower correlation values were observed among the EM group when compared to CM, the magnitude of correlations tended to be similar across the 2 groups.

Table 5 presents the means and standard deviations of MSQ scores across several criterion measures that are known to represent different levels of migraine impact. The results indicated that the mean MSQ scale scores decreased with increasing headache severity levels, for all 4 criterion measures. For CM and EM groups, mean (±SD) MSQ were RR = 44.4 (±22.1) and 56.5 (±24.1), RP = 61.4 (±26.1) and 71.7 (±24.1), EF = 48.3 (±28.1) and 67.2 (±26.6), respectively. The differences between CM and EM exceeded the recommended MID values of 3.2, 4.6, and 7.5 for RR, RP, and EF, respectively.^[31] Although all 3 MSQ scales resulted in mean scores that were significantly different across migraine frequency groups, the EF scale appeared to best capture the differences between CM and EM patients, as indicated by a larger F-statistic. In discriminating across migraine impact levels (for both HIT-6 impact groups and MIDAS grades) the RR scale performed the best, whereas the EF scale performed the best in discriminating across groups that differed in risk of anxiety/depression. Overall, these results indicate that the MSQ can adequately differentiate the impact that migraine has on HRQL, overall and across groups varying in headache frequency.

Discussion

The current study demonstrates that the MSQ is a reliable and valid measure of the HRQL among adults with CM and can differentiate the impact of headache across the spectrum of headache frequency as defined for EM and CM. Floor effects were observed for the same 5 items among both CM and EM, while ceiling effects were only observed for 1 item among the CM group. Study results also indicated that the MSQ has high internal consistency and reliability among migraine sufferers, with our results being comparable to those of previous validation studies.^[21,22] Consistent with pre-hypothesized relationships between the MSQ scales and other HRQL instruments, convergent and discriminant validity were supported by relatively higher correlations between the MSQ and the HIT-6 and the MIDAS and lower correlations between the MSQ and the PHQ-4. Construct validity was further confirmed within the framework of known-groups validity, with results showing that MSQ scores differed significantly across CM and EM patients and other important headache severity criterion measures.

Unexpectedly, the MSQ scales had low correlations with HDPM. The low correlations may be at least partially explained by the fact that the MSQ is designed to capture the multifaceted construct of migraine impact, which includes not only the frequency but also the intensity and the duration of headaches and the patient’s own evaluation of how migraines impact their quality of life. Indeed, other studies^[46,47] have reported disability to be more strongly associated with headache pain severity rather than with headache frequency, which further concurs with our findings. In the MSQ development and validation study,^[21] frequency of headaches over the past 12 months had low to moderate correlations with the MSQ scales. In that study, from among the 3 MSQ scales, the EF scale was the most strongly correlated (r = −0.48) with headache frequency, followed by the RR (r = −0.27) and lastly the RP (r = −0.14), a ranking of correlations that was mirrored in our results (for CM and EM combined only).

One limitation of the study was that the migraine diagnosis was not based on physician report but used the participants’ self-report to the migraine screening questions.^[25] Therefore, it is possible that some respondents were misclassified. Furthermore, electronic data collection conducted in this study design may have introduced participation bias because individuals lacking appropriate computer skills, access, or willingness may not have been included.^[25] Finally, given the cross-sectional study design, certain psychometric properties, such as test–retest reliability and responsiveness, could not be assessed.

Despite these limitations, the results of this study provide important new evidence for the psychometric reliability and validity of the MSQ. Although the MSQ has been shown to be a valid tool for measuring functional status and the effect of treatment among general migraine patients,^[20–22,24] the present study expands the scope of these findings by providing quantitative indicators of the validity of the MSQ specifically among CM adults, a group that has traditionally been understudied in validation analyses of headache- or migraine-specific HRQL measures.

The MSQ has been successfully used to assess the effect of therapy in several randomized clinical trials of migraine treatment,^[19,29] including clinical trials among patients with CM.^[28,48,49] HRQL instruments are most effective when they can capture clinically meaningful data while minimizing respondent burden without compromising validity.^[50] Accordingly, the combination of these key elements makes the MSQ a valuable tool, not only for use in clinical trials, but also for clinicians who manage treatment of CM and EM patients.

The importance of differentiating between headache subtypes in order to optimize treatment is an increasingly relevant issue for clinical practitioners. PRO instruments can be integrated within clinical practice to guide diagnosis and treatment^[15] that is targeted to the correct subtype of migraine. The growing interest^[51] in using HRQL measures to characterize differences between EM and CM patients supports the need to study the psychometric properties of these tools. Although several studies have examined the validity of the MSQ using samples of EM patients or general migraine patients, this was the first study that examined the validity of the MSQ in capturing distinct domains of migraine impact, across patients with different headache frequency levels.

Longitudinal studies exploring test–retest and responsiveness are recommended in the future to assess the reliability and validity of the MSQ in CM patients. In addition, continued examination of the psychometric properties of HRQL instruments that characterize the impact of migraine in CM and EM patients is needed to expand the current understanding of differences across these 2 groups.

Conclusions

The MSQ has been shown to be a reliable and valid measure of HRQL among adults with CM and can differentiate the functional impact of headache across the spectrum of headache frequency as defined for EM and CM. The MSQ can assist researchers in evaluating treatment effectiveness by obtaining input directly from the patients on multidimensional aspects other than frequency of headache days.

Sidebar

Statement of Authorship

Category 1

(a) Conception and Design
Christine L. Bagley; Sepideh F. Varon; Gregory A. Maglinte

(b) Acquisition of Data
Christine L. Bagley; Sepideh F. Varon; Gregory A. Maglinte; Regina Rendas-Baum; Min Yang

(c) Analysis and Interpretation of Data
Christine L. Bagley; Gregory A. Maglinte; Regina Rendas-Baum; Min Yang; Sepideh F. Varon

Category 2

(a) Drafting the Article
Christine L. Bagley; Regina Rendas-Baum; Min Yang; Gregory A. Maglinte; Sepideh F. Varon; Jeff Lee; Mark Kosinski

(b) Revising It for Intellectual Content
Christine L. Bagley; Regina Rendas-Baum; Min Yang; Gregory A. Maglinte; Sepideh F. Varon; Jeff Lee; Mark Kosinski

Category 3

(a) Final Approval of the Completed Article
Christine L. Bagley; Regina Rendas-Baum; Min Yang; Gregory A. Maglinte; Sepideh F. Varon; Jeff Lee; Mark Kosinski