677. Compliance and Performance Characteristics of Subject Collected Versus Health-care Worker Collected Nasal Swabs for Respiratory Viral Surveillance

Background Self-collection of mid-nasal swabs (SCNS) at home is a convenient alternative to health-care worker-collected nasal swabs (HCWC) for determining the pathogen-specific epidemiology of influenza-like illness (ILI). We evaluated the compliance and performance characteristics of SCNS vs. HCWC for respiratory pathogens during 2019-2020 flu season. Methods Adult Military Health System (MHS) beneficiaries were enrolled in an influenza vaccine effectiveness trial (PAIVED). Following vaccination, subjects were instructed on SCNS and completion of a symptom diary and were contacted weekly to ascertain ILI symptoms (fever, sore throat, and/or cough). In the event of an ILI, subjects completed the symptom diary and SCNS and were scheduled a clinic visit for HCWC. Swabs were tested with the Luminex NxTAG® Respiratory Pathogen Panel. We evaluated compliance with swab collection, positive percent agreement (PPA) of SCNS using PCR detection from either HCWC or SCNS as the reference standard, and agreement between paired swabs using the Cohen Kappa coefficient (Κ). Results 1808 ILI were reported by 972 participants enrolled during the study period. Compliance with HCWC was higher than SCNS (58% [1042] vs. 42% [766]; p< 0.001). SCNS were associated with a shorter interval from symptom onset (median: 4 days [IQR:2-6 days] vs. clinic collect: 7 days [IQR:4-9 days]; p < 0.001). 663 paired swabs were available for 609 participants (Table 1). The overall detection rate was higher in SCNS (36%) than HCWC (26%; p< 0.001) (Figure 1). The overall PPA was 85.7% and a PPA of approximately 80% of greater was observed for influenza, rhino/enterovirus, parainfluenza and respiratory syncytial virus. Agreement between paired swabs was poor due to the lower detection rates in HCWC. Table 1. Demographics and swab collection data for 609 participants who provided 663 paired swabs Figure 1. Detection by pathogen in 663 paired swabs Conclusion SCNS were associated with higher detection rates compared to HCWC, likely due to the shorter interval between symptom onset and swab collection. Strategies to improve compliance with SCNS and minimize the interval between symptom onset and swab collection are needed to optimize detection of respiratory pathogens in this MHS cohort. Disclosures Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) Jitu Modi, MD, GSK (Speaker's Bureau)

488 REST-ON: Efficacy of FT218 for Daytime Sleepiness, Sleep Quality, Hallucinations, and Sleep Paralysis in Patients With Narcolepsy

Introduction Sodium oxybate (SO) is an effective treatment for narcolepsy; however, currently available formulations must be taken twice nightly. FT218 is an investigational once-nightly controlled-release formulation of SO. Here, we evaluated the efficacy of FT218 on excessive daytime sleepiness (EDS), self-reported sleep quality/refreshing nature of sleep, sleep paralysis (SP), and hypnagogic hallucinations (HH) in patients with narcolepsy. Methods In this phase 3, randomized, double-blind, placebo-controlled, multicenter study, patients aged ≥16 years with narcolepsy type 1 or 2 were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night (1 week), 6.0 g/night (2 weeks), 7.5 g/night (5 weeks), and 9.0 g/night (5 weeks). Secondary efficacy endpoints included EDS using the Epworth Sleepiness Scale (ESS), sleep quality/refreshing nature of sleep using a visual analog scale (VAS), and SP and HH using a sleep symptom diary. Results A total of 212 patients were randomized and received study medication (FT218, n=107; placebo, n=105). Patients receiving FT218 had significant improvement vs placebo in EDS on the ESS: LS mean difference on ESS score between FT218 and placebo was −3.86 for 9.0 g (week 13), −3.16 for 7.5 g (week 8), and −2.06 for 6.0 g (week 3) (all P<0.001). Sleep quality/refreshing nature of sleep on VAS was also significantly improved with FT218 vs placebo (P<0.001 for all doses). Patients receiving FT218 reported less SP vs placebo (P<0.05 at all doses). Baseline values for HH were low in both treatment groups; HH was similar for both treatment groups at all study visits. The most common adverse reactions were nausea, dizziness, enuresis, headache, decreased appetite, and vomiting. Conclusion At all evaluated doses, treatment with FT218 significantly improved EDS, sleep quality/refreshing nature of sleep, and SP vs placebo. FT218 was generally well tolerated; the most common adverse events were consistent with known SO side effects. Support (if any) Avadel Pharmaceuticals.

Rationale and design of the validation of bladder health instrument for evaluation in women (VIEW) protocol

Background Bladder health is an understudied state and difficult to measure due to lack of valid and reliable instruments. While condition specific questionnaires assess presence, severity and degree of bother from lower urinary tract symptoms, the absence of symptoms is insufficient to assume bladder health. This study describes the methodology used to validate a novel bladder health instrument to measure the spectrum of bladder health from very healthy to very unhealthy in population based and clinical research. Methods Three samples of women are being recruited: a sample from a nationally representative general population and two locally recruited clinical center samples—women with a targeted range of symptom severity and type, and a postpartum group. The general population sample includes 694 women, 18 years or older, randomly selected from a US Postal delivery sequence file. Participants are randomly assigned to electronic or paper versions of the bladder health instrument along with a battery of criterion questionnaires and a demographic survey; followed by a retest or a two-day voiding symptom diary. A total of 354 women around 7 clinical centers are being recruited across a spectrum of self-reported symptoms and randomized to mode of completion. They complete the two-day voiding symptom diary as well as a one-day frequency volume diary prior to an in-person evaluation with a standardized cough stress test, non-invasive urine flowmetry, chemical urine analysis and post void residual measurement. Independent judge ratings of bladder health are obtained by interview with a qualified health care provider. A total of 154 postpartum women recruited around 6 of the centers are completing similar assessments within 6–12 weeks postpartum. Dimensional validity will be evaluated using factor analysis and principal components analysis with varimax rotation, and internal consistency with Cronbach’s alpha. Criterion validity will be assessed using multitrait-multimethod matrix including correlations across multiple data sources and multiple types of measures. Discussion We aim to validate a bladder health instrument to measure the degree of bladder health within the general population and among women (including postpartum) recruited from local clinical centers. Trial registration NCT04016298 Posted July 11, 2019 (https://www.clinicaltrials.gov/ct2/show/NCT04016298?cond=bladder+health&draw=2&rank=1).

Patients’ and clinicians’ perspectives on item importance, scoring, and clinically meaningful differences for the Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS)

Background The Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS) are patient-reported outcome measures developed to evaluate efficacy in clinical trials and clinical practice. The ESD is a daily electronic diary assessing symptom severity; the EIS is a weekly electronic diary assessing symptom impact. This study explored the importance of symptoms (ESD items) and impacts (EIS domains), perspectives on scoring algorithms, and clinically important difference (CID) thresholds to inform clinical trial score interpretation. Methods Endometriosis patients in Germany (n = 8) and the US (n = 17), and expert clinicians (n = 4) in Germany, the US, Spain, and Finland participated in semi-structured qualitative interviews comprising structured tasks. Interview transcripts were analyzed using thematic analysis techniques. Results Quality and severity of endometriosis-associated pelvic pain varied considerably among patients; some experienced pelvic pain daily, others during menstrual bleeding (dysmenorrhea) only. Patients and clinicians ranked “worst pelvic pain” as the most meaningful pain concept assessed by the ESD, followed by constant and short-term pelvic pain. Preferences for summarizing daily pain scores over the 28-day menstrual cycle depended on individuals’ experience of pain: patients experiencing pain daily preferred scores summarizing data for all 28 days; patients primarily experiencing pain during selected days, and their treating clinicians preferred scores based on the most severe pain days. Initial CID exploration for the “worst pelvic pain” 0–10 numerical rating scale (0–10 NRS) revealed that, for most patients, a 2- or 3-point reduction was considered meaningful, depending on baseline severity. Patients and clinicians ranked “emotional well-being” and “limitations in physical activities” as the most important EIS domains. Conclusions This study informs the use of the ESD and EIS as clinically relevant measures of endometriosis symptoms and their impact. Findings from the ESD highlight the importance of individual-patient assessment of pain experience and identify “worst pelvic pain” as the most meaningful symptom assessed. Aggregating scores over the 28-day menstrual cycle may inform meaningful endpoints for clinical trials. Diverse EIS concepts (e.g. impact on emotional well-being and physical activities) are meaningful to patients and clinicians, emphasizing the importance of evaluating the impact on both to comprehensively assess treatment efficacy and decisions. Trial registration Not applicable. Qualitative, non-interventional study; registration not required.