OBJECTIVE:To develop a comprehensive, evidence-based, patient-centered conceptual model of migraine and to derive a measurement framework for the development or selection of clinical outcome assessments used in clinical trials of treatments for migraine. BACKGROUND:Improving ways of assessing the outcomes that matter to people who live with migraine is an important goal for treatment development and evaluation. The Migraine Clinical Outcome Assessment System (MiCOAS) project aimed to gather qualitative data directly from people with migraine and develop a patient-centered core set of outcomes and endpoints for migraine clinical trials. Data gathered by the MiCOAS research team was used to develop a patient-centered conceptual model of migraine and a measurement framework designed to capture outcomes that matter to patients. METHODS:A post hoc, pooled secondary interpretive analysis of the results from two MiCOAS qualitative studies (executed in 2020 and 2021 with 71 US adults with migraine) was conducted to develop the conceptual model using iterative diagramming methods to create a visualization. Supporting information exhibits for the visualization were created to record concept definitions and describe their interrelationships. The conceptual model was used to guide development of a measurement framework intended to support the selection or development of patient-reported outcome assessments suitable for regulated clinical trials of both acute and preventive migraine therapies. Input from people with migraine, patient advocates, clinical researchers, and subject matter experts was integrated into the model and the measurement framework. RESULTS:The comprehensive conceptual model diagram organizes patient-reported experiences into domains for symptoms and impacts of migraine and depicts commonly occurring mediating contextual factors (e.g., perceived pain tolerance) that can affect patients' self-reported disease experiences. The measurement framework identifies concepts that are widely experienced or highly disabling to patients with episodic or chronic migraine but also meet the needs of clinical trial endpoint design (e.g., are cross-culturally relevant and amenable to treatment effect within a 3-month trial period) and are capable of capturing experiences during all phases of migraine, including interictal periods. CONCLUSIONS:The patient-centered conceptual model of migraine provides a concise but comprehensive framework for describing and measuring patient experiences of migraine disease and its treatment, including symptoms, daily functioning, and distal outcomes that result from the aggregation of migraine experiences over time. The measurement framework was developed to support comprehensive endpoint design for migraine clinical trials and has been used to guide the development of the MiCOAS measurement instruments.

IntroductionActivated Phosphoinositide 3-Kinase Delta Syndrome (APDS) is a rare disease characterized by progressive symptoms that begin early in life, including lymphoproliferation, recurrent and persistent infections, and early mortality compared with the global population. Delayed diagnosis and inadequate treatment in childhood may exacerbate disease manifestations. This post hoc analysis evaluated caregiver-reported changes in APDS symptoms in pediatric patients after 12 weeks of treatment with leniolisib.MethodsTwenty-one pediatric patients aged 4–11 years with APDS received open-label leniolisib in a single-arm, multicenter, international study (NCT05438407). Study documents received institutional review board approval. In a post hoc analysis, worst-rated dimension scores on the APDS-Symptom Severity Scale (APDS-SSS) at baseline were compared with week 12 scores. Item-level symptom scores, assessed by APDS-SSS, rated moderate to very severe (≥2 on a 0–4 scale) at baseline, were also compared with week 12 scores. Multiple scores per participant were reported in the event of within-person ties.ResultsAfter 12 weeks of leniolisib treatment, APDS-SSS symptom severity scores for dimensions with the worst-rated baseline scores generally decreased, indicating improvement. All patients with infections (n = 4) or gastrointestinal symptoms (n = 3) as their worst baseline dimension improved after 12 weeks of treatment. Among patients with respiratory symptoms as their worst baseline dimension, 10 of 13 (77%) improved at week 12; 1 remained stable, and 2 worsened to mild/moderate severity over time.Among patients with emotional impact as their worst baseline dimension, 3 of 6 (50%) improved at week 12; 1 remained stable, and 2 worsened to mild severity over time. Item-level symptom severity also generally decreased over time. For 3 symptoms, 1 patient each improved from severe/very severe at baseline to “none” at 12 weeks. All patients with visible swollen lymph nodes (n = 3) improved: 1 from severe to moderate and 2 from moderate to none.ConclusionAccording to caregiver ratings, the most severe APDS-related symptoms experienced by pediatric patients aged 4–11 years showed improvements after 12 weeks of leniolisib treatment. These results demonstrate the potential clinical benefit of leniolisib in most pediatric patients.

To evaluate the psychometric properties of the Neuro-QoL Fatigue patient-reported outcome measure and its short form when used to assess fatigue in adults living with generalized Myasthenia Gravis (gMG). Data from Vivacity-MG3 (ClinicalTrials.gov Identifier: NCT04951622), a double-blind placebo-controlled phase 3 study of nipocalimab enrolled 196 participants living with gMG were analyzed. Psychometric analyses of Neuro-QoL Fatigue scores (19-item version and short-form version) focused on data from Baseline and the 24-week double-blind interventional phase of the trial. Factor analytic and classical test theory (CTT) analyses were performed to investigate support for intended Neuro-QoL Fatigue score use, along with convergent and discriminant relationships, known groups analyses, and sensitivity to change analyses. Thresholds to define meaningful within-person change (improvement) over time were also investigated. The full form factor analytic analyses showed evidence that a unidimensional model adequately fits the data (TLI = 0.99, RMSEA = 0.07), CTT analyses showed high internal consistency (alpha = 0.95), and high test–retest reliability for stable participants (r = 0.92); similar results were observed for the short form. Both versions’ scores were correlated with a variety of reference variables at expected levels, demonstrated the ability to differentiate between clinically meaningfully distinct groups, and were significantly correlated with changes in other reference variables. Analyses suggested 19-item and short-form score changes of 6.7 and 7.6, respectively, as showing meaningful improvement over time. Results provided robust psychometric evidence that supports the use of Neuro-QoL Fatigue scores for assessing fatigue in adults living with gMG.

Physical functioning and symptom severity are important factors in the experience of people with living with non-small cell lung cancer (NSCLC). This study evaluates the reliability, validity, and meaningful within-person change (MWPC) thresholds of 2 patient-reported outcome (PRO) measures in NSCLC: the Patient-Reported Outcomes Measurement Information System (PROMIS®) Physical Function (PF) short form (SF) 8c and the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ). Data came from 2 Phase 3 clinical trials among people living with NSCLC. PROMIS PF-SF analyses included data from 300 participants in the PAPILLON trial, and NSCLC-SAQ analyses included 615 participants in the MARIPOSA 2 trial. Prespecified expected relationships between target PRO measures and relevant study variables were used to evaluate validity evidence. Additionally, MWPC thresholds were estimated using anchor- and distribution-based analyses. Both PRO measures exhibited adequate internal consistency for clinical trial use. All examined correlations with reference variables and score differences between clinically meaningful groups conformed to expectations for both measures. Estimated thresholds for meaningful worsening were a decrease of 6–7 points on the PROMIS PF-SF and an increase of 2–3 points on NSCLC-SAQ. This study is the first to examine longitudinal measurement properties of PROMIS PF-SF and investigates thresholds for meaningful change on the PROMIS PF-SF and NSCLC-SAQ measures. Results support the validity of these measures in NSCLC and aid the interpretation of clinically meaningful change in scores over time.

OBJECTIVE:To describe the impact of migraine on functioning based on comprehensive data collection, analysis, and reporting of patients' experiences. BACKGROUND:Qualitative research conducted to understand patients' perspectives on living with migraine has often focused on narrow topics or specific groups of patients or has been selectively reported. METHODS:Qualitative interviews with 71 participants were conducted during two concept elicitation studies as part of the Migraine Clinical Outcome Assessment System (MiCOAS) project, an FDA grant-funded program designed to develop a core set of patient-centered outcome measures for migraine clinical trials. Participants self-reported being diagnosed with migraine by a healthcare professional and participated in semi-structured qualitative interviews about their experiences with the symptoms and impacts of migraine. Interview transcripts were coded to identify and define concepts, which were then grouped into broad domains based on conceptual similarities. RESULTS:A total of 66 concepts were identified: 12 for physical functioning, 16 for cognitive functioning, 10 for social role functioning, 19 for emotional and psychological functioning, and 9 related to migraine management. Participants described a complex and varied relationship between migraine attack symptoms and impacts on functioning. Impacts from migraine were further influenced by numerous contextual factors, such as people's individual social environments and the level of day-to-day demand for functioning they face. CONCLUSION:Findings showed that migraine impacted individual functioning in multiple ways and the nature of these impacts was dependent on social-contextual factors. The results are being used in the development of core measures designed to improve our understanding of the burden of migraine and the efficacy of migraine therapies. The results also offer new insights and raise new questions about migraine experience that can be used to guide future research.

OBJECTIVE:To better understand the breadth and frequency of symptoms across the phases of the migraine cycle using data captured from qualitative patient interviews conducted through the Migraine Clinical Outcome Assessment System (MiCOAS) project. BACKGROUND:People living with migraine experience a range of symptoms across the pre-headache, headache, post-headache, and interictal phases of the migraine cycle. Although clinical diagnostic criteria and clinical trial endpoints focus largely on cardinal symptoms or monthly migraine days, migraine symptom profiles are far more complex. As a part of the MiCOAS project, semi-structured qualitative interviews were undertaken to better understand the migraine-related symptomology from the patient's viewpoint. METHODS:This concept elicitation study used iterative purposeful sampling to select 40 people with self-reported medical diagnosis of migraine for interviews that were conducted via audio-only web conferencing. Key topics related to migraine symptoms, including mood/emotion symptoms, were identified using content analysis. Interview transcripts were also coded to reflect the phase of migraine under discussion, so that patient experiences could be compared by phase. RESULTS:Forty participants (50%, n = 20 episodic migraine; 50%, n = 20 chronic migraine), aged from 21 to 70 years old reported a total of 60 unique symptoms, which were categorized into 30 broader symptom categories. Participants reported between 7 and 22 unique symptom categories across all phases. During pre-headache and headache, participants reported a median of 7.5 (interquartile range [IQR] = 5.5) and 8 (IQR = 4.0) different symptom categories compared to 4 (IQR = 3.0) and 1.5 (IQR = 2.5) for the post-headache and interictal periods, respectively. Head pain during the headache phase was the only universally reported symptom (100%, n = 40). Pooling across all phases, the next most reported symptoms were light sensitivity (93%, n = 37), nausea (88%, n = 35), irritability/impatience (83%, n = 24), sound sensitivity (80%, n = 32), and fatigue/exhaustion (80%, n = 32). One or more interictal symptoms were reported by 73% (n = 29) of participants and included mood/emotion symptoms, such as anxiety (30%, n = 12), depression (18%, n = 7), and anger (15%, n = 6), as well as cardinal symptoms, such as light sensitivity (13%, n = 5) and nausea (13%, n = 5). CONCLUSIONS:Patients experience a range of symptoms across the phases of the migraine cycle. Results often aligned with clinical expectations, but non-cardinal migraine-related symptoms were reported both inside and outside the headache phase, including between attacks. These discoveries highlight the importance of assessing a range of symptoms and timing when developing patient-reported outcome measures for migraine clinical trials.

Objectives: To capture patients' perspectives on migraine-related cognitive symptoms during pre-headache, headache, post-headache, and interictal periods.Background: Migraine-related cognitive symptoms are reported by people with migraine both during and between attacks. Associated with disability, they are increasingly viewed as a priority target for treatment. The Migraine Clinical Outcome Assessment System (MiCOAS) project is focused on developing a patient-centered core set of outcome measures for the evaluation of migraine treatments. The project focuses on incorporating the experience of people living with migraine and the outcomes most meaningful to them. This includes an examination of the presence and functional impact of migraine related cognitive symptoms and their perceived impact on quality of life and disability.Methods: Forty individuals with self-reported medically diagnosed migraine were recruited via iterative purposeful sampling for semi-structured qualitative interviews conducted using audio only web conferencing. Thematic content analysis was performed to identify key concepts around migraine-related cognitive symptoms. Recruitment continued until concept saturation was achieved.Results: Participants described symptoms consistent with migraine-related deficits in language/speech, sustained attention, executive function, and memory that manifest during pre-headache (36/40 [90%] reported >= 1 cognitive feature), headache (35/40 [88%] reported >= 1 cognitive feature), post-headache (27/40 [68%] reported >= 1 cognitive feature), and interictal periods (13/40 [33%] reported >= 1 cognitive feature). Among participants reporting cognitive symptoms during pre-headache, 32/40 (81%) endorsed 2- 5 cognitive symptoms. Findings were similar during the headache phase. Participants reported language/speech problems consistent with, for example, impairments in receptive language, expressive language, and articulation. Issues with sustained attention included fogginess, confusion/disorientation, and trouble with concentration/focus. Deficits in executive function included difficulty processing information and reduced capacity for planning and decision-making. Memory issues were reported across all phases of the migraine attack.Conclusions: This patient level qualitative study suggests that cognitive symptoms are common for persons with migraine, particularly in the pre-headache and headache phases. These findings highlight the importance of assessing and ameliorating these cognitive problems.

Objective: To describe differences in within-person patterns of cardinal migraine-associated symptoms across the phases of the migraine cycle. Background: Cardinal migraine-associated symptoms can impose significant disability and are a central focus of clinical care and research, but little is known about how they unfold across the full migraine cycle from the patient perspective. As a part of the Migraine Clinical Outcome Assessment System (MiCOAS) project, qualitative interviews were undertaken to elicit a description of symptom occurrence by migraine phase. We applied a novel analytic framework to these data to examine within-person patterns of migraine-related symptoms. Design/Methods: Forty individuals with self-reported, medically diagnosed migraine were screened to confirm diagnosis before participating in semi-structured interviews. Interviews explicitly probed symptoms by headache phase using standardized open-ended questions. Responses were transcribed and coded using content and thematic analysis methods. Within-person patterns of symptom endorsement were described across migraine phases (pre-headache, headache, post-headache, interictal) for specific cardinal symptoms (nausea/vomiting, photophobia, and phonophobia) using descriptive statistics (n, %) and innovative conditional branching pattern analyses with tree diagrams. Results: Participants were 77.5% female and 67.5% white with an average age of 44. Participants varied greatly in their specific within-person symptom patterns across phases. Although results showed that the most common pattern entailed symptoms exclusively occurring during both pre-headache and headache phases, this pattern applied to a minority of individuals (nausea/vomiting: 27.5%[n=11]; photophobia: 40%[n=16]; phonophobia 27.5%[n=11]). Symptoms were regularly reported in the pre-headache phase without being endorsed in the headache phase (nausea/vomiting: 17.5%[n=7]; photophobia: 12.5%[n=5]; phonophobia 20.0%[n=8]). Conclusions: There were common within-person patterns of symptom endorsement across phases that may support potential patient phenotypes. However, results also suggested heterogeneity in the patient experience and potential shortcomings of focusing solely on the headache phase. Findings highlight the importance of leveraging patient-centered research to better inform clinical practice and research. Disclosure: James McGinley has received personal compensation for serving as an employee of Vector Psychometric Group, LLC. An immediate family member of James McGinley has received personal compensation for serving as an employee of UPMC Children's Community Pediatrics. James McGinley has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for McGinley Statistical Consulting, LLC. James McGinley has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Cephalalgia (journal). James McGinley has stock in various companies. The institution of James McGinley has received research support from National Headache Foundation. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. An immediate family member of Ms. Mangrum has received personal compensation for serving as an employee of GSK. Ms. Mangrum has received personal compensation for serving as an employee of Vector Psychometric Group. Dr. Buse has received personal compensation for serving as an employee of Vector Psychometric Group. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie-Allergan. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Collegium. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie-Allergan. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Buse has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Pain and Headache Reports. The institution of Dr. Buse has received research support from Amgen. Dr. Hall has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Virginia Sexual and Domestic Violence Action Alliance. Carrie R. Houts has received personal compensation for serving as an employee of Vector Psychometric Group, LLC. Dr. Nishida has received personal compensation for serving as an employee of VPG. RJ Wirth has received personal compensation for serving as an employee of Vector Psychometric Group, LLC.

Objective: To investigate individual differences in two cognitive features across phases of the migraine cycle. Background: Previous qualitative work from the Migraine Clinical Outcome Assessment System (MiCOAS) project showed that persons with migraine experience a broad array of cognitive-related features. Little is known about how specific cognitive features differ within-person across the phases of the migraine cycle. The current work evaluates individual differences in two specific cognitive areas. Design/Methods: Forty individuals with migraine participated in semi-structured interviews that probed typical symptoms by migraine phases (pre-headache, headache, post-headache and interictal). Responses were transcribed and coded using content and thematic analysis methods, and 12 cognition-related concepts emerged. The current work focuses on two cognitive areas not attributed to pain interference (fogginess and memory issues). Descriptive statistics (n, %) and conditional branching pattern analyses with tree diagrams illustrated how the selected cognitive symptoms manifested across migraine phases. Results: The sample was 77.5% female, 67.5% white, average age 44 (50% episodic migraine, 50% chronic migraine) with about two-thirds reporting the symptoms (fogginess: n=25, 62.5%; memory issues: n=27, 67.5%). Participants' symptom patterns varied across phases, but important trends occurred. Of those reporting fogginess, only one participant reported the symptom solely in the headache phase (4.0%) compared to 16 participants (64%) uniquely in phases outside the headache phase. Of those reporting memory issues, the majority (88.9%) had memory issues for ≥1 phase outside of the headache phase and few were impacted only within the headache phase (11.1%;). Conclusions: Most participants reported memory issues or fogginess during ≥1 migraine phase. Intraindividual patterns of symptoms provided unique insights into symptom timing and may provide insights into possible phenotypes. Results highlight possible drawbacks of concentrating only on the headache phase. Future research should consider other cognition areas and how heterogeneity should be handled in clinical practice and trials. Disclosure: James McGinley has received personal compensation for serving as an employee of Vector Psychometric Group, LLC. An immediate family member of James McGinley has received personal compensation for serving as an employee of UPMC Children's Community Pediatrics. James McGinley has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for McGinley Statistical Consulting, LLC. James McGinley has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Cephalalgia (journal). James McGinley has stock in various companies. The institution of James McGinley has received research support from National Headache Foundation. An immediate family member of Ms. Mangrum has received personal compensation for serving as an employee of GSK. Ms. Mangrum has received personal compensation for serving as an employee of Vector Psychometric Group. Dr. Buse has received personal compensation for serving as an employee of Vector Psychometric Group. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie-Allergan. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Collegium. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie-Allergan. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Buse has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Pain and Headache Reports. The institution of Dr. Buse has received research support from Amgen. Dr. Hall has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Virginia Sexual and Domestic Violence Action Alliance. Carrie R. Houts has received personal compensation for serving as an employee of Vector Psychometric Group, LLC. Dr. Nishida has received personal compensation for serving as an employee of VPG. RJ Wirth has received personal compensation for serving as an employee of Vector Psychometric Group, LLC. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care.

BackgroundThere is renewed emphasis on including patients in determining, defining, and prioritizing outcomes for migraine treatment.ObjectivesTo obtain insights directly from people living with migraine on their priorities for treatment.MethodsA total of 40 qualitative interviews were conducted as part of the Migraine Clinical Outcome Assessment System project, a United States Food and Drug Administration grant-funded program to develop a core set of patient-centered outcome measures for migraine clinical trials. Interviews included a structured exercise in which participants rank-ordered pre-defined lists of potential benefits for acute and preventive migraine therapy. The 40 study participants who reported being diagnosed with migraine by a clinician ranked the benefits and explained their rationale.ResultsStudy participants consistently ranked either pain relief or absence of pain as their top priority for acute treatment. Relief/absence of other migraine symptoms and improved functioning were also prioritized. For preventive treatment, participants prioritized reductions in migraine frequency, symptom severity, and attack duration. Few differences were found between participants with episodic migraine and those with chronic migraine. However, participants with chronic migraine ranked "increased predictability of attacks" much higher than those with episodic migraine. Participants' rankings were influenced by prior expectations and experiences of migraine treatments, which caused many participants to deprioritize desired benefits as unrealistic. Participants also identified several additional priorities, including limited side-effects and reliable treatment efficacy in both acute and preventive treatments.ConclusionThe results showed the participants prioritized treatment benefits aligned with existing core clinical outcomes used in migraine research, but also valued benefits that are not typically assessed, such as predictability. Participants also deprioritized important benefits when they believed treatment was unlikely to deliver those outcomes.

Abstract Background The Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) is a 10-item patient-reported outcome (PRO) measure designed to assess the severity of mitochondrial disease symptoms. Analyses of data from a clinical trial with PMM patients were conducted to evaluate the psychometric properties of the PMMSA and to provide score interpretation guidelines for the measure. Methods The PMMSA was completed as a daily diary for approximately 14 weeks by individuals in a Phase 2 randomized, placebo-controlled crossover trial evaluating the safety, tolerability, and efficacy of subcutaneous injections of elamipretide in patents with mitochondrial disease. In addition to the PMMSA, performance-based assessments, clinician ratings, and other PRO measures were also completed. Descriptive statistics, psychometric analyses, and score interpretation guidelines were evaluated for the PMMSA. Results Participants (N = 30) had a mean age of 45.3 years, with the majority of the sample being female (n = 25, 83.3%) and non-Hispanic white (n = 29, 96.6%). The 10 PMMSA items assessing a diverse symptomology were not found to form a single underlying construct. However, four items assessing tiredness and muscle weakness were grouped into a “general fatigue” domain score. The PMMSA Fatigue 4 summary score (4FS) demonstrated stable test–retest scores, internal consistency, correlations with the scores produced by reference measures, and the ability to differentiate between different global health levels. Changes on the PMMSA 4FS were also related to change scores produced by the reference measures. PMMSA severity scores were higher for the symptom rated as “most bothersome” by each subject relative to the remaining nine PMMSA items (most bothersome symptom mean = 2.88 vs. 2.18 for other items). Distribution- and anchor-based evaluations suggested that reduction in weekly scores between 0.79 and 2.14 (scale range: 4–16) may represent a meaningful change on the PMMSA 4FS and reduction in weekly scores between 0.03 and 0.61 may represent a responder for each of the remaining six non-fatigue items, scored independently. Conclusions Upon evaluation of its psychometric properties, the PMMSA, specifically the 4FS domain, demonstrated strong reliability and construct-related validity. The PMMSA can be used to evaluate treatment benefit in clinical trials with individuals with PMM. Trial registration ClinicalTrials.gov identifier, NCT02805790; registered June 20, 2016; https://clinicaltrials.gov/ct2/show/NCT02805790 .

The coronavirus disease 2019 (COVID‐19) pandemic is an ongoing global health crisis that has had a range of impacts on people living with migraine.