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ObjectiveTo assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM).MethodsParticipants (aged 36-85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV infusions every 4 weeks). The co-primary outcome measures were 6-minute walk distance (6MWD) and safety.ResultsBetween November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24-104 in all treatment groups. Overall, 91.0% (n = 142) of participants in the pooled bimagrumab group and 89.1% (n = 49) in the placebo group had ≥1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group vs 10 mg/kg, 1 mg/kg, and placebo groups (69.2% [n = 36 of 52] vs 56.6% [n = 30 of 53], 58.8% [n = 30 of 51], and 61.8% [n = 34 of 55], respectively). The most frequently reported AEs in the pooled bimagrumab group were diarrhea 14.7% (n = 23), involuntary muscle contractions 9.6% (n = 15), and rash 5.1% (n = 8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18.6% [n = 29] vs 14.5% [n = 8], respectively).ConclusionExtended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint.Clinical trial registrationClinicaltrials.gov identifier NCT02573467.Classification of evidenceThis study provides Class IV evidence that for patients with sIBM, long-term treatment with bimagrumab was safe, well-tolerated, and did not provide meaningful functional benefit. The study is rated Class IV because of the open-label design of extension treatment period 2.

Abstract Background The objective of this study was to develop and validate a daily electronic Endometriosis Pain and Bleeding Diary (EPBD) for assessing treatment-related changes in endometriosis symptoms from the patient's perspective in a clinical trial setting. Methods The EPBD items were developed based on clinician input and the results of 5 focus groups (N = 38) and 3 iterative sets of cognitive interviews (N = 22). The psychometric properties were evaluated using data collected in a usual-practice, non-intervention study conducted at 4 sites in the United States. Existing questionnaires were also administered to explore the construct validity of the EPBD. The development and validation processes were consistent with the recommendations in the 2009 FDA Patient Reported Outcomes Guidance to Industry. Results Focus group participants described 2 distinct types of pain (intermittent and continuous), which they felt were relevant and important to monitor. Participants also indicated that pain and bleeding/spotting associated with intercourse were important symptoms related to endometriosis. Cognitive interviews with additional endometriosis patients served to optimize item content, wording, and response options. Psychometric analyses found the EPBD items to behave as expected, for example, item-level means for subjects with severe endometriosis symptoms were higher (i.e., worse) compared with subjects with mild symptoms. Item-total correlations for the EPBD pain items (range 0.40-0.89) indicated that the items were related but not redundant. EPBD pain ratings correlated highly with the modified Brief Pain Inventory-Short Form Pain Intensity score (range 0.46-0.61). Women with severe endometriosis symptoms reported significantly higher intermittent and continuous dysmenorrhea and intermittent and continuous pelvic pain ratings and greater interference with daily activities compared with women with mild symptoms (all p < 0.01). Conclusions The results of this study show that the 17-item EPBD reliably and validly characterizes the types of pain that endometriosis patients identified as being important. As a daily patient-reported assessment, it overcomes the significant potential for intra- and inter-rater variability and rater and recall bias that is inherent in the Biberoglu and Behrman Scale. Additional studies are required to confirm the dimensionality and optimal scoring of the EPBD, to corroborate the present results, and to assess other important measurement properties, such as responsiveness.

Abstract Background Fast-acting medications for the management of anxiety are important to patients and society. Measuring early onset, however, requires a sensitive and clinically responsive tool. This study evaluates the psychometric properties of a patient-reported Global Anxiety - Visual Analog Scale (GA-VAS). Methods Data from a double-blind, randomized, placebo-controlled study of lorazepam and paroxetine in patients with Generalized Anxiety Disorder were analyzed to assess the reliability, validity, responsiveness, and utility of the GA-VAS. The GA-VAS was completed at clinic visits and at home during the first week of treatment. Targeted psychometric analyses—test-retest reliabilities, validity correlations, responsiveness statistics, and minimum important differences—were conducted. Results The GA-VAS correlates well with other anxiety measures, at Week 4, r = 0.60 (p < 0.0001) with the Hamilton Rating Scale for Anxiety and r = 0.74 (p < 0.0001) with the Hospital Anxiety and Depression Scale - Anxiety subscale. In terms of convergent and divergent validity, the GA-VAS correlated -0.54 (p < 0.0001), -0.48 (p < 0.0001), and -0.68 (p < 0.0001) with the SF-36 Emotional Role, Social Function, and Mental Health subscales, respectively, but correlated much lower with the SF-36 physical functioning subscales. Preliminary minimum important difference estimates cluster between 10 and 15 mm. Conclusions The GA-VAS is capable of validly and effectively capturing a reduction in anxiety as quickly as 24 hours post-dose.

Background: Measures assessing treatment outcomes in previous CC clinical trials have not met the requirements described in the US Food and Drug Administration's guidance on patient-reported outcomes., Aim: Psychometric analyses using data from one Phase IIb study and two Phase III trials of linaclotide for the treatment of chronic constipation (CC) were conducted to document the measurement properties of patient-reported CC Symptom Severity Measures., Study Methods: Each study had a multicenter, randomized, double-blind, placebo-controlled, parallel-group design, comparing placebo to four doses of oral linaclotide taken once daily for 4 weeks in the Phase IIb dose-ranging study (n=307) and to two doses of linaclotide taken once daily for 12 weeks in the Phase III trials (n=1,272). The CC Symptom Severity Measures addressing bowel function (Bowel Movement Frequency, Stool Consistency, Straining) and abdominal symptoms (Bloating, Abdominal Discomfort, Abdominal Pain) were administered daily using interactive voice-response system technology. Intraclass correlations, Pearson correlations, factor analyses, F-tests, and effect sizes were computed., Results: The CC Symptom Severity Measures demonstrated satisfactory test-retest reliability and construct validity. Factor analyses indicated one factor for abdominal symptoms and another for bowel symptoms. Known-groups F-tests substantiated the discriminating ability of the CC Symptom Severity Measures. Responsiveness statistics were moderate to strong, indicating that these measures are capable of detecting change., Conclusion: In large studies of CC patients, linaclotide significantly improved abdominal and bowel symptoms. These psychometric analyses support the reliability, validity, discriminating ability, and responsiveness of the CC Symptom Severity Measures for evaluating treatment outcomes in the linaclotide clinical studies.