Evaluating the Psychometric Properties of the Migraine Functional Impact Questionnaire (MFIQ).

Migraine is a chronic neurologic disease that can be associated with significant migraine-related impact, disability, and burden. Patient-reported outcome measures (PRO) are included in clinical trials of migraine interventions to capture treatment effects from a patient perspective. Clinical and regulatory guidelines also encourage use of PROs in trials. The Migraine Functional Impact Questionnaire (MFIQ) is a novel PRO measure, assessing the impact of migraine on Physical Function (PF), Usual Activities (UA), Social Function (SF), and Emotional Function (EF), in the past 7 days. Scientific methods recommended to meet the requirements of the U.S. Food and Drug Administration were followed, to ensure that the MFIQ content included outcomes that were relevant to adults with migraine and were clinically relevant, specifically to evaluate preventive treatments for migraine. The objective of this study was to conduct item analyses informing item reduction and scoring, and to evaluate the psychometric properties of the MFIQ. In a prospective, observational study, adults with migraine completed the MFIQ as well as additional clinical and PRO instruments, including the Headache Impact Test (HIT-6TM ), Patient-Reported Outcomes Measurement Information System Physical Function Short Form 10a (PROMIS-PF), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and Patient Global Rating of Change (PGIC). Item-level evaluation, item response theory (IRT), and factor analysis were used to select final MFIQ items, identify domains, and inform scoring. Psychometric properties of the MFIQ were evaluated to assess reliability (internal consistency and test-retest), validity (construct and known-groups), and responsiveness. The study enrolled 569 adults with migraine. Subjects had an average age of 39.9 years (SD 12.0), 87.2% were female, and 80.8% were white. Five items were dropped from the draft version based on results of item-level analyses reviewed in the context of previous qualitative research to produce the final 26-item MFIQ (v.2). Four domain scores (PF, UA, SF, and EF) and a global item score for impact on UA were identified. Higher scores on a 0-100 scale represent greater impact. All scores exhibited high internal consistency (α ≥ 0.89) and moderate test-retest reliability among stable subjects (ICCs ≥ 0.47). Construct validity was demonstrated by significant correlations (all P < .0001) between MFIQ domain scores, related PRO scores, and the frequency of migraine days and headache days. All domain scores differentiated between subgroups ("known groups") defined based on established levels of clinical severity: number of monthly migraine and headache days, migraine interference levels and scores on other PRO instruments (P < .05). Improvements in MFIQ scores corresponded with clinical improvement (percent reduction in monthly migraine days), improvement in migraine interference with daily activities, and related improvements in PRO scores (P < .05), demonstrating that the MFIQ was responsive to changes in migraine impact. The MFIQ is a reliable and valid measure that can be used to collect data about migraine impact. The MFIQ is being used to evaluate outcomes of migraine interventions in clinical trials and observational studies. It could potentially also be used in clinical practice both for initial and ongoing assessments for monitoring outcomes and to enhance communication between patients and healthcare professionals for the management of migraine.

Kawata AK ，Hareendran A ，Shaffer S ，Mannix S ，Thach A ，Desai P ，Mikol DD ，Ortmeier B ，Bayliss M ，Buse DC ... -  《-》

Psychometric Evaluation of a Novel Instrument Assessing the Impact of Migraine on Physical Functioning: The Migraine Physical Function Impact Diary.

The objective of this study was to evaluate the measurement properties of the Migraine Physical Function Impact Diary (MPFID), a novel patient-reported outcome (PRO) measure for assessing the impact of migraine on physical functioning. In a prospective, observational study, adults with episodic migraine (EM) or chronic migraine (CM) used an eDiary to complete the MPFID (assessing daily impacts of migraine on physical function) and a headache diary (capturing migraine days, migraine pain intensity, and migraine interference) each day, and other PRO instruments related to migraine. Item-level evaluation, item response theory (IRT), and exploratory factor analysis (EFA) methods were applied to identify domains, select final MPFID items, and develop scoring procedures. Psychometric properties of the final 13-item MPFID were evaluated using confirmatory factor analysis and tests of reliability (Cronbach's α for internal consistency and intra-class correlation [ICC] for test-retest) and validity (convergent and known-groups). The study enrolled 569 adults with chronic or episodic migraine, mean (SD) age 39.9 (12.0) years and 87.2% female. Item-level analyses based on interim data informed selection of a set of 13 items for the MPFID, through evaluation of floor/ceiling effects, item-to-item correlations, factor loadings, and IRT-based fit/misfit statistics. Two domain scores (EA: Impact on Everyday Activities; PI: Physical Impairment) and a global item score for impact on everyday activities were identified. EA and PI domains exhibited high internal consistency (α = 0.97; α = 0.93) and good test-retest reliability among stable subjects (ICCs = 0.74 and 0.77). Convergent validity was demonstrated by moderate correlations (r = ±0.50-0.68; P < .0001) between MPFID domain scores and number of migraine days, headache days, bed days, and other migraine-related PRO instruments. EA and PI scores differentiated between groups who varied by number of migraine days, migraine interference levels, migraine pain intensity, and median split groups of scores based on other PROs instruments (P < .05). The MPFID has robust psychometric properties (ie, reliability and validity). Findings supported two distinct domains about the impact of migraine on physical functioning: Impact on Everyday Activities and Physical Impairment. Both domain scores showed evidence of excellent reliability and construct validity in assessing the impacts of migraine on physical functioning.

Kawata AK ，Hsieh R ，Bender R ，Shaffer S ，Revicki DA ，Bayliss M ，Buse DC ，Desai P ，Sapra S ，Ortmeier B ，Hareendran A ... -  《-》

Development of a New Tool for Evaluating the Benefit of Preventive Treatments for Migraine on Functional Outcomes - The Migraine Functional Impact Questionnaire (MFIQ).

The objective of this study was to develop a method for evaluating patient-relevant outcomes of interventions for preventing migraine attacks, followed by an assessment of the content validity of a new patient-reported outcome (PRO) instrument: the Migraine Functional Impact Questionnaire (MFIQ). The aim of preventive treatments for migraine is not only to reduce migraine frequency, but also to restore patients' ability to function and improve quality of life. A multi-stage process based on best practice methods and regulatory guidelines for ensuring content validity of PRO instruments for evaluating treatment benefit was followed. Qualitative concept elicitation interviews conducted to understand the experiences of adults with migraine underpinned the development of the instrument. The initial stage included the development of a conceptual disease model (CDM) based on information from these interviews. This CDM was used to identify the concepts of interests (COI) to evaluate outcomes of preventive treatments. The results of the interviews were also used in stage 2, to develop a measurement framework for collecting data about these COI. In the third stage, existing instruments were reviewed for coverage of the concepts in the framework and evidence of concept elicitation to the point of saturation, to support content validity. In the fourth stage, an instrument was drafted to evaluate concepts in the framework, based on the qualitative data collected from the interviews. Following a review by clinical and translation experts, the new instrument was tested in adults with migraine in the fifth stage using 2 rounds of cognitive interviews, and was modified based on interview feedback. In the last stage, the instrument was linguistically adapted, using methods recommended for PRO instruments, to ensure conceptual equivalence of language versions for use in international studies. Each language version was tested in at least 5 native speakers using cognitive interviews. Results from the concept elicitation interviews suggested that migraine had an impact on various aspects of functioning. A conceptual framework for evaluating functional outcomes was developed for the concept selected based on a review of the CDM - physical and emotional functioning, every day activities, and social/leisure activities. Existing PROs lacked coverage of some concepts in the conceptual framework, had recall periods that were inappropriate for capturing the experience of COI or did not have evidence of content validity. A novel PRO instrument, the MFIQ, was developed to address these gaps. Cognitive interviews with 9 adults with migraine resulted in minor changes to the items of the MFIQ, and a final round of 8 interviews confirmed the changes were acceptable and supported its validity. The interviews conducted to test linguistic adaptations confirmed conceptual equivalence in the 25 countries evaluated. Development of the MFIQ followed best measurement practices to ensure content validity and followed regulatory guidelines for PRO instruments to evaluate benefits of treatments. The MFIQ was developed for use in clinical trials or clinical practice settings to track outcomes of preventive treatments that are most relevant to adults with migraine.

Hareendran A ，Skalicky A ，Mannix S ，Lavoie S ，Desai P ，Bayliss M ，Thach AV ，Mikol DD ，Buse DC ... -  《-》

Reducing the physical, social, and emotional impact of episodic migraine: Results from erenumab STRIVE and ARISE phase III randomized trials.

The purpose of this study was to examine changes in the functional impact of migraine following treatment with erenumab, as measured by the Migraine Functional Impact Questionnaire (MFIQ). The MFIQ, a novel patient-reported outcome (PRO) measuring the impact of migraine on four domains (physical function, social function, and emotional function [PF, SF, and EF]; usual activities [UAs]) and a single item assessing overall impact on UA, was included in phase III trials evaluating erenumab 70 and 140 mg monthly for migraine prevention among people with episodic migraine (EM). In the ARISE study, 577 patients with EM were randomized to erenumab 70 mg or placebo. In the STRIVE study, 955 patients with EM were randomized to erenumab, 70 mg or 140 mg or placebo. Pairwise comparisons of least-squares mean (LSM) change from baseline in MFIQ scores (with associated 95% confidence interval [CI]) were assessed for each active treatment versus placebo. In ARISE, greater reductions from baseline to month 3 were observed for 70 mg versus placebo for PF (LSM [95% CI]: -3.2 [-6.4 to -0.1]; p = 0.046) and EF (-4.0 [-7.3 to -0.7]; p = 0.019) domain scores. In STRIVE, between-group differences also reflected reductions from baseline to the average of months 4-6 that favored erenumab on all four MFIQ domain scores. Reductions in impact for 70 mg compared to placebo were -4.3 (95% CI: -6.8 to -1.7; p < 0.001) for PF, -4.0 (-6.3 to -1.7; p < 0.001) for UA, -3.7 (-6.1 to -1.2; p = 0.003) for SF, and -5.3 (-7.9 to -2.6; p < 0.001) for EF domain scores. Improvements were also observed for 140 mg versus placebo with between-group differences of -5.7 (95% CI: -8.2 to -3.2; p < 0.001) in PF, -5.1 (-7.5 to -2.8; p < 0.001) in UA, -5.0 (-7.4 to -2.6; p < 0.001) in SF, and -7.2 (-9.9 to -4.5; p < 0.001) in EF domain scores. There were also greater improvements in the overall impact on UA score for 70 mg (LSM [95% CI]: -4.3 [-7.0 to -1.7]; p = 0.001) and 140 mg (-5.3 [-8.5 to -3.2]; p < 0.001) versus placebo. The MFIQ measures the frequency of impacts and level of difficulty on multiple functional domains that provide a more complete picture of the effects of migraine. MFIQ scores showed that in comparison with placebo, patients treated with erenumab had greater reductions in the functional impact of migraine, providing insight into treatment benefits that extend beyond improvements in clinical status and health-related quality of life previously reported based on clinical end points and other PROs.

Kawata AK ，Ladd MK ，Lipton RB ，Buse DC ，Bensink M ，Shah S ，Hareendran A ，Mannix S ，Mikol D ... -  《-》

Functional impairment of chronic migraine with medication overuse: Secondary analysis from the Medication Overuse Treatment Strategy (MOTS) trial.

Chronic migraine exerts substantial negative impacts on daily functioning. Efforts to manage impaired functioning may result in medication overuse, which contributes to the worsening profile and chronification of migraine. The Migraine Functional Impact Questionnaire (MFIQ) is a recently developed measure assessing the impact of migraine on physical, social, and emotional function. The objective of this analysis was to assess changes in MFIQ scores following initiation or modification of migraine preventive medication and determine if changes in function are associated with changes in other aspects of migraine burden, such as headache frequency, headache intensity, and symptoms of anxiety and depression. This is a secondary analysis of data from the Medication Overuse Treatment Strategy (MOTS) trial, a prospective pragmatic clinical trial that investigated two treatment strategies for those with chronic migraine and medication overuse. Data from both treatment arms were pooled and analyzed using a pre-post design. Prior to and 12 weeks following initiation or modification of migraine preventive medication, participants completed a series of questionnaires that captured migraine characteristics, medication use, migraine-related physical impairment (MFIQ), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire 9 [PHQ-9]) symptoms. Changes from baseline in all measures were assessed using the paired t-test. Relationships between changes in MFIQ scores and other measures were assessed using linear regression. Multivariable modeling was performed to determine which additional variables contributed to the change in MFIQ beyond that already explained by an individual variable. Model terms were selected by using elastic net regularization. Only those participants who completed the baseline and 12-week MFIQ were included in this analysis. Of the 537 patients, 88.2% were female, and the average age was 45 years (standard deviation 13). The mean frequency of days with moderate-to-severe headache improved 39.2% from 13.5 per 30 days at baseline to 8.1 per 30 days at week 12. The mean MFIQ Usual Activities Global score improved by 15.0 points (on a 100-point scale). All five domains (Usual Activities Global, Usual Activities, Social Function, Emotional Function, Physical Function) of the MFIQ improved by a mean of at least 13.0 points. Changes in PHQ-9 score, followed by changes in headache frequency, had the strongest associations with change in all domains of the MFIQ. The negative impact of chronic migraine with medication overuse on physical, social, and emotional functioning substantially lessened following initiation or modification of migraine preventive medication. Improved functioning, as measured by the MFIQ, was most strongly associated with reductions in depression scores and headache frequency, highlighting the importance of recognizing and monitoring changes in depressive symptoms, in addition to headache frequency and functional impairment, when evaluating response to preventive medications.

Shao SC ，Hentz J ，Shank P ，Leonard M ，Dodick DW ，Schwedt TJ ... -  《-》