Revicki, Dennis A.

Abstract Objective To evaluate the content validity and psychometric properties of the Activity Impairment in Migraine Diary (AIM‐D). Background Measuring treatment effects on migraine impairment requires a psychometrically sound patient‐reported outcome (PRO) measure developed consistent with U.S. Food and Drug Administration guidance. Methods The AIM‐D was created from concepts that emerged during qualitative interviews with five clinicians experienced in treating migraine and concept elicitation (CE) interviews with 40 adults with episodic migraine (EM) or chronic migraine (CM). The initial version was refined based on three waves of cognitive interviews with 38 adults with EM or CM and input from a panel of clinical and measurement experts. The AIM‐D was psychometrically evaluated using data from 316 adults with EM or CM who participated in a 13‐week prospective observational study. Study participants completed PRO assessments including the AIM‐D and a daily headache diary. Exploratory and confirmatory factor analysis were used to determine the factor structure. The reliability, validity, and responsiveness of the AIM‐D were assessed. Additional PRO measures including the Patient Global Impression – Severity (PGI‐S), Migraine Specific Quality of Life Questionnaire, Version 2.1 Role Function‐Restrictive domain, and Headache Impact Test were used for psychometric evaluation of the AIM‐D. Results Based on CE interviews with adults with migraine and input from an expert panel, activity impairment was identified as the target in the preliminary conceptual framework, which had two domains: performance of daily activities (PDAs) and physical impairment (PI). Revision of the draft AIM‐D through multiple rounds of cognitive interviews and expert panel meetings resulted in a content valid 11‐item version. Exploratory factor analysis supported both one‐ and two‐domain structures for the AIM‐D, which were further supported by confirmatory factor analysis (factor loadings all >0.90). The AIM‐D domains (PDA and PI) and total score showed high internal consistency reliability (Cronbach's alpha 0.95–0.97), acceptable test–retest reliability for weekly average scores (intraclass correlation coefficient >0.60 for participants with no change in PGI‐S between baseline and week 2), and good convergent and known‐groups validity. There was evidence of responsiveness based on changes in PGI‐S score and monthly migraine days. Conclusion The AIM‐D is a content valid and psychometrically sound measure designed to evaluate activity impairment and is suitable for use in clinical trials of preventive treatments for EM or CM.

Background: Patient-reported outcome (PRO) data may be used at 2 levels: to evaluate impacts of disease and treatment aggregated across individuals (group-level) and to screen/monitor individual patients to inform their management (individual-level). For PRO data to be useful at either level, we need to understand their clinical relevance. Purpose: To provide clarity on whether and how methods historically developed to interpret group-based PRO research results might be applied in clinical settings to enable PRO data from individual patients to inform their clinical management and decision-making. Methods: We first differentiate PRO-based decision-making required at group versus individual levels. We then summarize established group-based approaches to interpretation (anchor-based and distribution based), and more recent methods that draw on item calibrations and qualitative research methods. We then assess the applicability of these methods to individual patient data and individual-level decision-making. Findings: Group-based methods provide a range of thresholds that are useful in clinical care: some provide screening thresholds for patients who need additional clinical assessment and/or intervention, some provide thresholds for classifying an individual’s level of severity of symptoms or problems with function, and others provide thresholds for meaningful change when monitoring symptoms and functioning over time during or after interventions. Availability of established cut-points for screening and symptom severity, and normative/reference values, may play into choice of PRO measures for use in clinical care. Translatability of thresholds for meaningful change is more problematic because of the greater reliability needed at the individual-level versus group-level, but group-based methods may provide lower bound estimates. Caution is needed to set thresholds above bounds of measurement error to avoid “false-positive changes” triggering unwarranted alerts and action in clinic. Conclusions: While there are some challenges in applying available methods for interpreting group-based PRO results to individual patient data and clinical care—including myriad contextual factors that may influence an individual patient’s management and decision-making—they provide a useful starting point, and should be used pragmatically.

AbstractBackgroundThe purpose of this study was to evaluate the measurement properties of the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index‐Daily Diary, a patient‐reported outcome instrument developed to meet US FDA recommendations for a symptom‐based clinical trial endpoint in gastroparesis. The ANMS GCSI‐DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score from none (0) to very severe (4) and number of vomiting episodes during the past 24 hours. The composite score includes the first four symptoms, the core symptom score includes all five symptoms.MethodsSeventy‐one patients diagnosed with idiopathic or diabetic gastroparesis were recruited for a four‐week observational study. Patients completed the ANMS GCSI‐DD at home between Baseline and Week 4. Statistical analyses included confirmatory factor analysis, item response theory analysis, internal consistency, test‐retest reliability, and construct and known‐groups validity.Key ResultsUnidimensionality for the composite and core symptom scores was supported, and items exhibited good fit. Internal consistency (Cronbach's alpha =0.85 and 0.83) and test‐retest reliability were 0.89 and 0.88, for composite and core symptom scores, respectively. Convergent validity was supported by strong correlations with patient‐reported and clinician measures. Baseline and Week 4 scores differed for three measures used to define disease severity status (P < 0.0001), supporting known‐groups validity.Conclusions & InferencesThe ANMS GCSI‐DD has excellent reliability and validity, supporting its use to assess symptom‐based endpoints in gastroparesis clinical studies. Further analyses will be conducted using clinical trial data to ascertain treatment responsiveness and define a responder.