Conversations and Reactions Around Severe Hypoglycemia (CRASH) Study: Results From People With Diabetes and Caregivers in the United States.

A survey was conducted in eight countries to examine conversations around, and experiences and treatments during, severe hypoglycemia among people with diabetes and caregivers of people with diabetes. This article reports a subgroup analysis from the United States involving 219 people with diabetes and 210 caregivers. Most respondents (79.7%) did not use professional health care services during their most recent severe hypoglycemic event, and 40.3% did not report the event to their health care providers at a subsequent follow-up visit. Hypoglycemic events left respondents feeling scared (70.9%), unprepared (42.7%), and helpless (46.9%). These clinically important psychosocial impacts on people with diabetes and caregivers underscore the need for conversations about hypoglycemia prevention and management.

Achieving clinically meaningful response in endometriosis pain symptoms is associated with improvements in health-related quality of life and work productivity: analysis of 2 phase III clinical trials.

BACKGROUND: Endometriosis-related pain symptoms have a negative impact on health-related quality of life and productivity. In fact, as endometriosis-related symptom severity and the number of symptoms experienced increases, health-related quality of life decreases. Dysmenorrhea and nonmenstrual pelvic pain are prominent symptoms experienced by women with endometriosis and were shown to have improved with the oral, nonpeptide gonadotropin-releasing hormone antagonist, elagolix. OBJECTIVE: The objective of this post hoc analysis was to address the question of if patients show a clinical response (in dysmenorrhea or nonmenstrual pelvic pain), do they also have improvements in health-related quality of life and in productivity? STUDY DESIGN: This post hoc analysis used data from the Elaris Endometriosis-I and Elaris Endometriosis-II phase III, randomized, placebo-controlled studies. A surgical diagnosis of endometriosis (in the past 10 years), premenopausal, aged 18-49 years, and moderate to severe endometriosis-associated pain were among the inclusion criteria for both trials. Women self-reported pain daily using a scale ranging from 0 (no pain) to 3 (severe pain); daily pain was assigned to either dysmenorrhea or nonmenstrual pelvic pain based on self-reported bleeding on that particular day. In addition, their self-reported endometriosis-associated pain must have been an average of moderate or severe during the month leading to baseline for inclusion in the trial program. Patients were characterized as achieving a clinical response for dysmenorrhea or nonmenstrual pelvic pain (ie, responder or nonresponder), which was defined as women who did not have an increase in analgesic use and who met the pain reduction score threshold at month 3. Pain reduction score thresholds were defined separately for dysmenorrhea and nonmenstrual pelvic pain in the trial using receiver-operating characteristics analysis. Health-related quality of life was assessed using the Endometriosis Health Profile-30; work productivity was assessed using the Health-Related Productivity Questionnaire. RESULTS: Women enrolled in Elaris Endometriosis-I (n = 871) and Elaris Endometriosis-II (n = 815) were included in this analysis. Patients with a clinical response during treatment to dysmenorrhea or nonmenstrual pelvic pain also experienced a meaningful improvement in all domains of the Endometriosis Health Profile-30 at month 3. Patients who did not show a dysmenorrhea or nonmenstrual pelvic pain clinical response at month 3 did not exhibit mean improvements in Endometriosis Health Profile-30 domain scores that indicate an Endometriosis Health Profile-30 responder. Productivity improved among dysmenorrhea clinical responders. In the Elaris Endometriosis-I study, clinical responders lost a total of 5.9 hours compared with a total of 13.0 hours for nonresponders of employment-related work at month 3 (P < .0001). Among women in the Elaris Endometriosis-II study, a total of 4.1 hours and 10.4 employment-related hours were lost at month 3 for dysmenorrhea responders vs nonresponders (P < .001). Similar results were obtained when analyzed by non-enstrual pelvic pain responder status. CONCLUSION: Women with moderate to severe endometriosis-related pain, who are clinical responders based on dysmenorrhea and nonmenstrual pelvic pain, also experience significant and clinically meaningful improvement in health-related quality of life and productivity as measured by the Endometriosis Health Profile-30 and Health-Related Productivity Questionnaire, respectively.

Clinically Meaningful Reduction in Dyspareunia Is Associated With Significant Improvements in Health-Related Quality of Life Among Women With Moderate to Severe Pain Associated With Endometriosis: A Pooled Analysis of Two Phase III Trials of Elagolix.

BACKGROUND: Dyspareunia experienced by women diagnosed with endometriosis is associated with a decreased health-related quality of life (HRQoL). AIM: We evaluated the relationship of clinically meaningful improvements in dyspareunia with HRQoL changes among women with endometriosis. METHODS: This was a post hoc analysis of pooled data from the phase III ELARIS-I and ELARIS-II clinical trials. Women aged 18-49 years with moderate to severe endometriosis-associated pain were randomized to placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily. HRQoL was measured using the validated Endometriosis Health Profile-30 questionnaire (EHP-30), consisting of 5 core domains and a sexual intercourse modular domain. Dyspareunia was ranked 0-3 (none, mild, moderate, or severe) or not applicable using a daily eDiary and averaged monthly. A woman with a clinically meaningful dyspareunia response (dyspareunia responder) was defined as a woman with a reduction from the baseline in dyspareunia score greater than or equal to a predetermined cutoff while maintaining stable/decreased analgesic use. OUTCOMES: Dyspareunia response impact on EHP-30 scores was determined at 3 and 6 months using multivariate linear regression controlling for age, baseline EHP-30 scores, and dysmenorrhea and non-menstrual pelvic pain symptom severity. RESULTS: Analysis included 1,368 women with a mean age of 32.2 years. Dyspareunia responders had significant improvements vs non-responders in all adjusted mean EHP-30 domain scores at months 3 and 6 (control and powerlessness: -17.8 and -18.5; emotional well-being: -10.0 and -10.4; pain: -15.3 and -15.7; self-image: -11.4 and -12.8; social support: -14.3 and -14.0; and sexual intercourse: -18.1 and -19.7; all P < .0001). CLINICAL IMPLICATIONS: Dyspareunia improvements are associated with both personal and psychological benefits. STRENGTHS & LIMITATIONS: This study involved a large sample of women from a well-defined patient population to provide statistical power in evaluating the results. As such, the findings may not be generalizable in a real-world setting. Although the perception of dyspareunia and its severity and the associated effect on HRQoL was subjective, the use of a large patient sample was used to minimize potential issues with this limitation. CONCLUSION: Clinically meaningful responses in dyspareunia are associated with improvements across multiple HRQoL domains among women with endometriosis. Agarwal SK, Soliman AM, Pokrzywinski RM, et al. Clinically Meaningful Reduction in Dyspareunia Is Associated with Significant Improvements in Health-Related Quality of Life Among Women with Moderate to Severe Pain Associated with Endometriosis: A Pooled Analysis of Two Phase III Trials of Elagolix. J Sex Med 2020;17:2427-2433.

Evaluating functional outcomes in adolescents with attention-deficit/hyperactivity disorder: development and initial testing of a self-report instrument.

BACKGROUND: Engaging adolescents in decisions about their health may enhance their compliance with treatment and result in better health outcomes. Treatment outcomes in attention-deficit/hyperactivity disorder (ADHD) are rarely evaluated from the adolescents' point of view. There is also concern that adolescents with ADHD may not have insight about the impacts of their disease. This article describes research conducted to understand the experiences of adolescents with ADHD and how the research was used to develop an adolescent self-report instrument. METHODS: This research involved an iterative process to ensure content validity and was conducted in the following stages: concept identification from literature reviews and interviews with teachers and clinicians; concept elicitation interviews with adolescents with ADHD and their caregivers, review of existing instruments; development of a new instrument and cognitive interviews. Experts in instrument development and translation and clinical practitioners in ADHD also participated. RESULTS: A conceptual framework to measure the impact of ADHD on adolescent functioning identified from concept identification research informed concept elicitation interviews with 60 adolescents with ADHD and their primary caregivers. In the interviews, adolescents discussed difficulties with performing activities in various contexts: school, home, leisure activities and social interactions. Caregivers provided additional insights. The instrument review revealed that none of the existing instruments were suitable to collect data on the elicited concepts; therefore, a new instrument was developed. Revisions were made to the format and content of the instrument (a daily diary) based on feedback received from cognitive testing with 15 adolescents. CONCLUSIONS: Our research helped to obtain a comprehensive understanding of the impacts of ADHD on adolescent functioning, to inform the development of a new instrument for measuring outcomes. Adolescents were able to discuss the impact of ADHD on their lives in concept elicitation interviews and report the impacts of ADHD on a self-report instrument. The new instrument developed to reflect the perspective of adolescents with ADHD can be used to supplement outcome assessments in clinic and research settings. Scientific advocacy for the use of such measures can be valuable to measure outcomes meaningful to adolescents with ADHD and the clinical community.

Qualitative assessment of the suitability of the Dysphagia Symptom Questionnaire to monitor dysphagia in children aged 7-10 years with eosinophilic esophagitis.

BACKGROUND: The Dysphagia Symptom Questionnaire (DSQ) is a patient-reported outcome measure that assesses the frequency and severity of dysphagia in patients with eosinophilic esophagitis (EoE); however, it has only been validated for use in patients with EoE aged 11-40 years. This study examined the content validity of the DSQ and its usability on an electronic handheld device in children aged 7-10 years with EoE. METHODS: In this qualitative, observational cohort study, participants were recruited to partake in two rounds of interviews. During visit 1, a cognitive interview examined EoE-associated concepts and the appropriateness of the DSQ for assessing dysphagia. Participants completed the DSQ daily for 2 weeks, and DSQ scores were calculated. After 2 weeks, a second interview assessed the usability of the DSQ on the electronic device and the burden associated with completing it daily. RESULTS: Overall, 16 participants were included (aged 7-8 years: n = 8; aged 9-10 years: n = 8); most were male (75%) and white (81%), and the mean (standard deviation [SD]) age was 8.4 (1.3) years. The most commonly reported EoE-associated concept was 'trouble with swallowing' (63% [10/16]). Most participants reported that the questions were 'easy to complete' and 'relevant to someone with EoE and dysphagia'. Overall, participants reported understanding the questions and associated responses; however, further probing demonstrated inconsistent comprehension. Key challenging concepts included 'solid food', 'trouble swallowing', 'vomit', and 'relief'; some participants also reported difficulty differentiating between pain levels (31% [4/13]). Most caregivers reported that their child had experienced dysphagia (94% [15/16]); however, mean (SD) DSQ scores over the study period were low (7.3 [7.4]), suggesting infrequent and mild dysphagia, or a lack of comprehension of the questions. Most participants reported that completing the DSQ on the electronic device was easy (93% [14/15]) and they would be willing to complete it for longer than 2 weeks (73% [11/15]). CONCLUSIONS: Difficulties with comprehension and comprehensiveness suggest that the DSQ may not be sufficiently comprehensive for use in all patients in this population, and wording/phrasing changes are required before use in a clinical trial setting.

Qualitative Interviews to Assess the Content Validity and Usability of the Electronic Raynaud Diary in Patients with Systemic Sclerosis.

OBJECTIVE: To better understand the symptoms and impacts of Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc) and to evaluate the content validity and usability of a new electronic patient-reported outcome (PRO) measure for RP: the Raynaud Diary. METHODS: The Raynaud Diary was developed as a daily eDiary for assessing the number and duration of symptomatic Raynaud attacks; worst pain, numbness, tingling, and discomfort in the fingers; and overall disease severity, captured using the Raynaud's Condition Score. The Raynaud Diary was debriefed in two waves of qualitative interviews with adults with self-reported RP secondary to SSc. All interviews included open-ended questions about participants' experiences of RP. RESULTS: Participants (N = 39) had a mean age of 55.1 years, and 87% were female. Frequently reported RP symptoms were color change (reported by all participants), numbness (90%), tingling (82%), pain (77%), and discomfort (72%). Common attack triggers included temperature-related factors and stress. Participants reported being unable to be outside or do outdoor activities and had problems gripping objects. All participants demonstrated understanding of the Raynaud Diary instructions. Most participants indicated that they would be able to use the Raynaud Diary to record the worst severity of individual RP symptoms in the previous 24 hours. CONCLUSION: Patients with RP secondary to SSc bear a heavy symptom burden. The Raynaud Diary is a content valid PRO measure that captures the most frequent symptoms of RP in patients with SSc.

Cost-effectiveness of combination versus sequential docetaxel and carboplatin for the treatment of platinum-sensitive, recurrent ovarian cancer.

BACKGROUND: In a randomized controlled trial (RCT) of patients with recurrent, platinum-sensitive ovarian cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data. METHODS: An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. RESULTS: The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness-to-pay threshold, cDC was either dominant or cost-effective with an ICER <$50,000 per QALY in 83% of simulations. CONCLUSIONS: Combined weekly cDC appeared to be cost-effective compared with sDC as treatment strategy for patients with platinum-sensitive ovarian cancer, even when accounting for slightly lower QoL during treatment.

Health-related quality of life outcomes of docetaxel/carboplatin combination therapy vs. sequential therapy with docetaxel then carboplatin in patients with relapsed, platinum-sensitive ovarian cancer: results from a randomized clinical trial.

OBJECTIVES: A phase II clinical trial compared docetaxel in combination with carboplatin to sequential single agent docetaxel followed by carboplatin for treatment of recurrent platinum-sensitive ovarian, peritoneal, or tubal cancer. This manuscript reports prospectively collected health-related quality of life (HRQL). METHODS: Participants were randomized to either weekly docetaxel 30 mg/m(2)/days 1 and 8 and carboplatin AUC 6/day 1 every 3 weeks (cDC) or docetaxel 30 mg/m(2)/days 1 and 8, repeated every 3 weeks for 6 cycles followed by carboplatin AUC 6/day 1 every 3 weeks for 6 cycles or until disease progression (sDC). The primary HRQL endpoint was the trial outcome index (TOI) score of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) instrument, and was assessed as an intent-to-treat analysis. The secondary HRQL endpoints included the FACT-O total score, the FACT-General, and several domain scores of the FACT-O instrument (physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and the ovarian cancer specific (OCS) module). The FACT-O was administered at randomization, prior to each of 6 cycles of treatment, and at study endpoint. RESULTS: One hundred forty-eight participants were randomized to each group. Sequential docetaxel followed by carboplatin (sDC) was associated with significant improvements in the FACT-O TOI (p=0.013), FACT-O total score (p=0.033), and OCS (p=0.029) compared to the combination docetaxel and carboplatin group (cDC). CONCLUSIONS: Sequential single agent docetaxel followed by carboplatin is associated with improved HRQL when compared to cDC. The improved progression-free survival observed with cDC should be weighed against lower quality of life during treatment.

Development and validation of the living with chronic obstructive pulmonary disease questionnaire.

PURPOSE: Available patient-reported outcome (PRO) measures for chronic obstructive pulmonary disease (COPD) focus primarily on impairment (symptoms) and activities (functioning). The purpose of the study was to develop a patient-based PRO measure for COPD that captures the overall everyday impact of living with COPD from the patient's perspective. METHODS: LCOPD items (Living with COPD Questionnaire) were generated from qualitative interviews in the U.K. and focus groups in the U.S.A. The draft measure was tested for face and content validity in both countries. Item reduction and testing for reproducibility and construct validity was conducted via Rasch and traditional psychometric analyses. RESULTS: The draft LCOPD was found to be relevant and acceptable to patients in the U.K. (N = 19) and U.S. (N = 16). Application of Rasch analysis to data collected in validation studies (n = 162 in the U.K. and 145 in U.S.) identified a 22-item scale that measured a single construct in both countries. Psychometric analyses indicated that this version was internally consistent and reproducible. Scores on the measure were related as expected to clinician ratings of disease severity and patient ratings of COPD severity and general health. CONCLUSIONS: The LCOPD is a new measure examining the everyday impact of living with COPD. It demonstrates good scaling properties and may prove valuable in understanding treatment benefits.

Evaluating functional disability in clinical trials of lisdexamfetamine dimesylate in binge eating disorder using the Sheehan Disability Scale.

OBJECTIVES: This study examined Sheehan Disability Scale (SDS) performance in binge eating disorder (BED) and explored relationships between SDS and BED outcomes using data from three placebo-controlled lisdexamfetamine (LDX) studies (two short-term, dose-optimized studies and one double-blind, randomized-withdrawal study) in adults with Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR)-defined BED. METHODS: Analyses evaluated the psychometric properties of the SDS. RESULTS: Confirmatory factor analysis supported a unidimensional total score in the short-term studies, with internal consistency (Cronbach's α) being 0.878. Total score exhibited good construct validity, with moderate and statistically significant correlations observed with Yale-Brown Obsessive Compulsive Scale modified for binge eating, Binge Eating Scale (BES), and EuroQol Group 5-Dimension 5-Level health status index scores. Known-groups validity analysis for the short-term studies demonstrated a significantly lower total score at end of study in participants considered "not ill" versus "ill" based on Clinical Global Impressions-Severity scores. SDS total score changes in the short-term studies were greater in responders than nonresponders based on binge eating abstinence or BES score. In the randomized-withdrawal study, SDS scores increased relative to baseline to a greater extent in participants randomized to placebo than LDX. CONCLUSIONS: These analyses support the reliability, validity, and responsiveness to change of the SDS in individuals with BED.

Measuring health-related quality of life in patients with rare disease.

BACKGROUND: There has been a growing emphasis on health-related quality of life (HRQoL) as an important outcome in rare disease drug development, although its assessment may be useful outside the drug development context, including in clinical applications or natural history studies. Central to assessing quality of life in health research is utilizing outcome measures that capture symptoms and impacts of the disease and treatment that are important and relevant to patients. Identifying and implementing valid and reliable tools to measure HRQoL in rare diseases poses unique challenges that often require creative solutions. MAIN BODY: In this commentary, we explore some of the challenges in HRQoL assessment in rare disease, propose solutions, and consider regulatory issues. Some of the solutions discussed entail the use of item banks, adapting existing measures from phenotypically similar disease contexts, use of multi-domain measurement indices, and adapting methods for assessing content validity of existing measures. Current regulatory considerations are discussed and resources outlined. CONCLUSION: Quality of life may be the most important endpoint for patients with rare diseases, and the challenges of valid assessment require effort and innovative thinking specific to each context to improve measurement and clinical outcomes.

The Patient Experience of Premenopausal Women Treated with Bremelanotide for Hypoactive Sexual Desire Disorder: RECONNECT Exit Study Results.

Background: Hypoactive sexual desire disorder (HSDD) has a significant negative impact on women's overall health and relationships with their partners. Primary analyses from the RECONNECT clinical trials demonstrated statistically significant and clinically meaningful improvements in sexual desire and related distress with bremelanotide relative to placebo in premenopausal women with HSDD. Exit surveys and patient interviews were conducted to evaluate the impact of HSDD and bremelanotide treatment from the patient's perspective. Materials and Methods: Upon completion of the double-blind study but before participation in the open-label extension, up to 250 participants were recruited to complete the quantitative exit survey (17 questions). A subset of up to 90 patients was invited to participate in the telephone interview (17 questions). Patients who volunteered to participate remained blinded to study drug until the survey and interviews were completed. Results: Quantitative exit surveys were completed by 242 RECONNECT participants; 80 of these women also completed qualitative telephone exit interviews. Participants who received bremelanotide described increased feelings of sexual desire, physical arousal, and improvements in overall quality of their sexual activities in their partner relationship. In comparison, women taking placebo reported benefits that did not include the physiological responses described by women receiving bremelanotide, such as positive experiences of seeking HSDD treatment and improved communication with their partner. Conclusions: Exit surveys and patient interviews support the primary findings from RECONNECT and provide quantitative and qualitative assessments of the impact of HSDD on patients' quality of life and the patients' perspectives on the impact of bremelanotide. Clinical trial numbers NCT02333071, NCT02338960.

Impact and burden of acid sphingomyelinase deficiency from a patient and caregiver perspective.

Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease (NPD) types A, A/B, and B, is a rare, progressive, potentially fatal lysosomal storage disease with a spectrum of phenotypes. Little is known about how ASMD symptoms affect the lives of patients and their caregivers. In a cross-sectional qualitative study conducted in the US and UK, and in collaboration with the National Niemann-Pick Disease Foundation (US) and Niemann-Pick UK, we investigated the symptom experience of patients with ASMD types B and A/B and explored how the disease impacts their and their caregivers' lives. The study included 17 adult patients (mean age 38.7 years, 12 female), three caregivers of adults with ASMD, 12 pediatric/adolescent patients with ASMD (mean age 10.5 years, six female), and 12 caregivers of pediatric/adolescent patients with ASMD. The most commonly reported disease manifestations were respiratory (n = 26, 89.7%), abdominal (n = 25, 86.2%), and musculoskeletal symptoms (n = 23, 79.3%); excessive bleeding or bruising (n = 20, 69%); fatigue (n = 20, 69%); gastrointestinal symptoms (n = 18, 62.1%); and headache (n = 15, 51.7%). ASMD was reported to negatively impact patients' physical function (n = 23, 79.3%), self-esteem (n = 18, 62.1%), emotions (n = 16, 55.2%), social function and relationships (n = 16, 55.2%), and personal care (n = 9, 31%). Providing care for individuals with ASMD negatively affected caregivers' emotional well-being (n = 12, 80%), social function (n = 4, 26.7%), relationships (n = 6, 40%), and financial security (n = 7, 46.7%). The physical toll of providing care, the need for lifestyle changes, and the responsibility for making medical decisions added to the burden for caregivers. Alternatively, some caregivers noted that caring for a loved one enhanced their spirituality, providing them with a different outlook on life and a deeper personal resolve. This study showed that ASMD is a substantial burden for patients and caregivers, with long-term physical, emotional, social, and financial impacts. The study confirmed commonly known manifestations of ASMD, especially respiratory problems, but also identified less recognized ones, such as dermatological complications. The data collected and insight gained from this study should enhance clinical care, help evaluate new treatments, and inform health care decision making for patients with ASMD.

Responsiveness and thresholds for clinically meaningful changes in worst pain numerical rating scale for dysmenorrhea and nonmenstrual pelvic pain in women with moderate to severe endometriosis.

OBJECTIVE: To evaluate the utility, responsiveness, and thresholds for clinically meaningful change of a numerical rating scale for worst pain associated with dysmenorrhea (NRS-DYS) and nonmenstrual pelvic pain (NRS-NMPP) in women with moderate to severe endometriosis-associated pain. DESIGN: Analysis of data from two phase III randomized clinical trials (EM-I [NCT01620528] and EM-II [NCT01931670]). SETTING: Not applicable. PATIENT(S): Premenopausal women ages 18-49 years with moderate to severe endometriosis-associated pain. INTERVENTION(S): Participants in both trials were randomized 3:2:2 to receive placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily for 6 months. MAIN OUTCOME MEASURE(S): NRS-DYS and NRS-NMPP. RESULT(S): EM-I enrolled 871 women and EM-II enrolled 815 women. For patients with a global impression of improvement at month 3, the least-squares mean change between baseline and month 3 was -3.6 (EM-I and EM-II) for NRS-DYS and -1.9 (EM-I) and -2.0 (EM-II) for NRS-NMPP. Standard errors of measurement were 2.99 (EM-I) and 2.86 (EM-II) for NRS-DYS and 1.74 (EM-I) and 1.71 (EM-II) for NRS-NMPP. Baseline half standard deviations were 0.78 (EM-I) and 0.85 (EM-II) for NRS-DYS and 0.92 (EM-I) and 0.96 (EM-II) for NRS-NMPP. Based on these results, clinically meaningful changes were defined as a reduction of 4 points for NRS-DYS and 2 points for NRS-NMPP. CONCLUSION(S): This study demonstrated the utility and responsiveness of separate numerical rating scales to assess worst pain for dysmenorrhea and NMPP in women with moderate to severe endometriosis-associated pain and identified initial thresholds for clinically meaningful change.

Conversations and Reactions Around Severe Hypoglycaemia (CRASH): Spanish results of a global survey of people with type 1 diabetes or insulin-treated type 2 diabetes and caregivers.

INTRODUCTION: Information on experience/management of severe hypoglycaemic events (SHEs) among people with insulin-treated diabetes (PWD) and caregivers (CGs) providing care to PWD was sought. MATERIALS AND METHODS: An online cross-sectional survey was conducted in eight countries. INCLUSION CRITERIA: PWD (aged≥18 years; self-reported type 1 [T1D] or insulin-treated type 2 [T2D] diabetes; experienced ≥1 SHE [hypoglycaemia requiring external assistance] in past 3 years); CGs (layperson aged ≥18 years; caring for PWD meeting all criteria above except age [≥4 years]). This descriptive analysis provides data from Spain. SHE-associated data relate to the most recent SHE. RESULTS: Across all groups (T1D PWD, n=106; T2D PWD, n=88, T1D CG, n=87; T2D CG, n=96), 76-89% reported that the SHE occurred at home; most common cause was eating less than planned (38-53%). Most usual action during the SHE was to intake carbohydrates (67-84%); glucagon use was low (9-36%). Discussion of the SHE with their healthcare provider (HCP) was reported by 70-75% of PWD. During the SHE, 35-69% of PWD/CGs reported feeling scared, unprepared and/or helpless. CONCLUSIONS: Most SHEs occurred outside the healthcare setting; treatment therefore depends greatly on CGs. SHEs have a negative emotional impact on PWD/CGs, underscoring the need for HCPs to discuss SHEs with PWD/CGs, and to provide tools and strategies to prevent and effectively manage SHEs.

Documenting the Journey of Patients with Eosinophilic Esophagitis and the Impact of the Disease on Patients and their Caregivers: A Cross-sectional, Qualitative Research Study.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease for which there is currently no approved treatment in the USA and only one approved therapy in Europe. EoE can significantly affect the lives of patients and caregivers; however, little has been published about patients' experiences from symptom onset to diagnosis and treatment. METHODS: This was a cross-sectional, qualitative research study. During one-on-one semi-structured interviews, patients with EoE in the USA and their caregivers provided information about their experiences of EoE before and during diagnosis, and their current experiences. Qualitative data were analyzed using a content analysis approach. RESULTS: The study included children aged 6-11 years with EoE (n = 4) and their caregivers (n = 4); adolescents aged 12-17 years with EoE (n = 7) and their caregivers (n = 7); and adults aged ≥ 18 years with EoE (n = 20). The diagnosis of EoE was often arduous and took many years. Patients and caregivers were frequently frustrated with the complexities of diagnosing EoE, which often involved multiple healthcare providers and procedures. Patients reported physical and psychosocial burdens associated with EoE before diagnosis, including interference with social activities, school, and work. Patients also reported feeling frustrated or anxious. These burdens frequently remained after diagnosis. Caregivers also reported anxiety and, in some cases, interference with their ability to work. CONCLUSION: This study of EoE describes the difficult journey faced by patients and their caregivers from symptom onset to diagnosis and beyond.

Psychometric assessment of the PROMIS Fatigue Short Form 6a in women with moderate-to-severe endometriosis-associated pain.

BACKGROUND: Endometriosis is a common problem in women of reproductive age and has impacts on health-related quality of life and productivity. Fatigue is an important part of the burden of endometriosis, it is not often included as an endpoint in clinical trials. OBJECTIVES: The study assessed the psychometric properties of the PROMIS Fatigue Short Form 6a in women with moderate-to-severe endometriosis-associated pain. METHODS: In a phase III double-blind, placebo-controlled clinical trial (NCT01620528), women aged 18-49 years with moderate-to-severe endometriosis-related pain were randomized to elagolix 150 mg once daily, elagolix 200 mg twice daily, or placebo for 6 months. PROMIS Fatigue and dysmenorrhea and non-menstrual pelvic pain (NMPP) scores were assessed at baseline and months 1, 3, and 6, and Patient Global Impression of Change (PGIC) was assessed at months 1, 3, and 6. Reliability (internal consistency and test-retest reliability), construct validity (convergent and known groups validity), and responsiveness were evaluated. RESULTS: The analysis included 871 women, mean age 31.5 years. Internal consistency supported a single concept (Cronbach's alpha 0.93). For the 238 patients with no change in PGIC at month 1, the intraclass correlation coefficient for the PROMIS Fatigue T-score was 0.7 and paired t-test statistically significant (2.84, p = 0.0049). Correlations with other measures were expected to be fairly low as concepts were not redundant. The PROMIS Fatigue discriminated among known groups with mean scores of 55.3, 62.3, and 65.8 at month 3 (PGIC improvement, no change, worsening, respectively). Statically significant discrimination, and change score responsiveness, were seen using clinically relevant anchors (dysmenorrhea and NMPP) at months 3 and 6 between responders and non-responders. Anchor-based (PGIC) responsiveness showed significant improvement from baseline to months 3 and 6 (p < 0.0001). CONCLUSIONS: PROMIS Fatigue has good reliability, validity, and responsiveness in women with moderate-to-severe endometriosis-associated pain.

Health-Related Quality of Life Improvements in Patients With Endometriosis Treated With Elagolix.

OBJECTIVE: To evaluate the effects of elagolix on clinically meaningful improvements in health-related quality of life (HRQOL) measured by the EHP-30 (Endometriosis Health Profile-30). METHODS: Data from two phase III trials of elagolix for moderate to severe pain associated with endometriosis were pooled and analyzed as three groups: placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily. Patients were administered the EHP-30 questionnaire at baseline, and at months 1, 3, and 6 of treatment. Previously established responder definitions were applied to determine percentages of patients with clinically meaningful EHP-30 improvements. The probability of meeting EHP-30 responder definitions with elagolix compared with placebo at months 3 and 6 was determined by Poisson regression analysis, controlling for baseline scores. RESULTS: At month 6, the probabilities of meeting EHP-30 subscale responder definitions for pain, control and powerlessness, self-image, social support, emotional well-being, and sexual intercourse were 169% (adjusted relative risk [aRR]: 2.69, 95% CI 2.26-3.21), 129% (aRR 2.29, 95% CI 1.96-2.67), 80% (aRR 1.80, 95% CI 1.54-2.11), 70% (aRR 1.70, 95% CI 1.47-1.97), 67% (aRR 1.67, 95% CI 1.45-1.92), and 62% (aRR 1.62, 95% CI 1.36-1.92) greater, respectively (all P<.001), in the 200-mg group than in the placebo group. Although lower in magnitude than the 200-mg group, the 150-mg group also had greater probabilities of meeting responder definitions than the placebo group for all subscales except sexual intercourse. The probabilities of meeting responder definitions for pain, control and powerlessness, self-image, social support, and emotional well-being were 75% (aRR 1.75, 95% CI 1.44-2.14), 50% (aRR 1.50, 95% CI 1.25-1.80), 22% (aRR 1.22, 95% CI 1.01-1.47), 30% (aRR 1.30, 95% CI 1.09-1.53), and 35% (aRR 1.35, 95% CI 1.16-1.57) greater, respectively (all P<.05), in the 150-mg group than in the placebo group. CONCLUSION: Patients with moderate to severe pain associated with endometriosis and were treated with elagolix experienced clinically meaningful HRQOL improvements. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01620528 and NCT01931670. FUNDING SOURCE: AbbVie Inc.

Psychometric assessment of the health-related productivity questionnaire (HRPQ) among women with endometriosis.

Objective: Endometriosis impacts health-related quality of life. The objective was to assess the validity and responsiveness of the Health-Related Productivity Questionnaire, version 2 (HRPQ). Methods: Outcome measures (Endometriosis Health Profile-30; pain scales; and global assessment) from Elaris Endometriosis I and II clinical trials (EM-I, EM-II) were used. Validity testing using Cohen's conventions was assessed. Known-groups validity was evaluated using generalized linear models comparing clinical responders, assessment of change, and the endometriosis impact. The effect size (ES) and standard error of means were calculated to evaluate responsiveness. Results: 871 and 815 women participated in the EM-I and EM-II trials. The total hours of lost work among employed women were 16.5 (±11.4) hours per week for EM-I and 15.2 (±11.3) for EM-II. The total hours of lost work among the household group were 8.3 (±8.7) hours for EM-I and 8.4 (±9.0) hours for EM-II. HRPQ discriminated between all known group assessments tested. Correlations for the HRPQ compared to other measures were small to moderate. Moderate to large ES was observed and the ability of the HRPQ to detect change was strong using patient-reported impressions. Conclusion: The HRPQ is a valid and responsive tool for evaluating patient-reported productivity at work and at home among women with endometriosis.

Responsiveness Evaluation and Recommendation for Responder Thresholds for Endometriosis Health Profile-30: Analysis of Two Phase III Clinical Trials.

Objective: To evaluate the responsiveness of the Endometriosis Health Profile-30 (EHP-30) and ascertain score changes that are indicative of response to treatment. A post hoc analysis of two Phase III, double-blind, placebo-controlled, randomized clinical trials among women with moderate-to-severe endometriosis-associated pain (Elaris Endometriosis I and II [EM-I and EM-II]). Materials and Methods: EHP-30 core items and sexual relationship module were administered at day 1, month 3 (M3), and month 6 (M6) to monitor patient-reported impacts of endometriosis-related pain. A seven-response level Patient Global Impression of Change (PGIC) was administered at M3 and M6. Dysmenorrhea (DYS), nonmenstrual pelvic pain (NMPP), and dyspareunia (DYSP) were collected using a daily diary. Three psychometric approaches, "triangulation," were used to suggest responder thresholds for the EHP-30 domains. The three approaches were anchor- and distribution-based analyses and use of clinically relevant indicators (DYS, NMPP, DYSP). Results: EM-I and EM-II enrolled 871 and 815 women, respectively. All EHP-30 domains improved during the trials (M3, M6). Differences (p < 0.001) for all EHP-30 domains were found among the PGIC responses at M3 and M6, indicating greater change was associated with greater EHP-30 improvements. Large effect sizes were noted for all EHP-30 domains (EM-I range -0.59 to -1.80; EM-II range -0.52 to -1.59). EHP-30 thresholds of meaningful change ranged from -20 to -35, with greater changes indicating greater improvement in health status. Conclusion: Responder thresholds by EHP-30 domain are recommended to evaluate treatment efficacy. Clinicians can individualize goals of treatment by EHP-30 domain and track changes using the EHP-30.