Psychometric Evaluation of the Diary for Irritable Bowel Syndrome Symptoms-Constipation in a Prospective Observational Study.

OBJECTIVES: To evaluate the psychometric properties of the Diary for Irritable Bowel Syndrome Symptoms-Constipation (DIBSS-C), which was developed to support primary and secondary endpoints in irritable bowel syndrome (IBS) with predominant constipation (IBS-C) clinical trials. METHODS: Observational data were collected from 108 adults with IBS-C using a smartphone-type device for 17 days. DIBSS-C data regarding bowel movements (BMs) were collected for each event (along with the Bristol Stool Form Scale); abdominal symptoms were rated each evening. Global status items and the Gastrointestinal Symptom Rating Scale-IBS were completed on day 10 and day 17 and the IBS-Symptom Severity Scale on day 17. Item-level performance, internal consistency reliability, test-retest reliability, and construct validity were evaluated. RESULTS: The Abdominal Symptoms Domain score demonstrated high internal consistency reliability (Cronbach's alpha week 1 = 0.98; week 2 = 0.96) and test-retest reliability (intraclass correlation coefficient [ICC] = 0.93). Test-retest reliability was stronger for abdominal symptoms (ICC = 0.91-0.94) than for the frequency-based BM-related outcomes (ICC = 0.54-0.66). Key construct validity hypotheses were supported by moderate to strong correlations with the corresponding Gastrointestinal Symptom Rating Scale-IBS, IBS-Symptom Severity Scale, and Bristol Stool Form Scale items. All known-groups comparisons were statistically significant for the abdominal symptom items and domain score; evidence for known-groups validity of BM-related outcomes was supportive when based on constipation severity. CONCLUSIONS: The results of this study provided key psychometric evidence for the DIBSS-C, ultimately contributing to its qualification by the US Food and Drug Administration for use in IBS-C clinical trials.

Cross-Sectional Quantitative Evaluation of a Novel Patient-Reported Outcome Measure in Familial Chylomicronemia Syndrome.

Background: Familial chylomicronemia syndrome (FCS) is a rare metabolic disorder that impacts physical, emotional, social, and cognitive functioning. The FCS-Symptom and Impact Scale (FCS-SIS) patient-reported outcome (PRO) measure assesses common symptoms and impacts of FCS. This study was conducted to evaluate cross-sectional psychometric properties of the FCS-SIS and its scoring method. Methods: This multisite, cross-sectional, observational study of individuals with FCS was conducted in the United States and Canada. Participants completed a survey composed of 7 PRO measures, including the FCS-SIS, and questions about clinical characteristics and demographics. The structure of the FCS-SIS was evaluated using inter-item and item-scale correlations and internal consistency reliability. Construct, known-groups, and criterion validity were evaluated by examining associations between FCS-SIS item and composite scores and other measures included within the survey. Results: Most of the 33 participants were female (63.6%) and White (78.1%). On average, participants reported first noticing FCS symptoms at ~16 years, with abdominal pain the most frequently reported initial symptom (n=20). Participants reported 2.5 acute pancreatitis attacks on average over the past year. Average FCS-SIS symptom item scores ranged from 1.8 to 3.9 (on a 0-to-10 scale [none-to-worst-possible]) within the 24-hour recall period, with an average Symptom composite score of 2.7. The average impact item scores on the FCS-SIS ranged from 1.6 to 3.0 (on a 0-to-4 scale), with an average Impact composite score of 2.1. Inter-item correlations between the FCS-SIS Symptom items ranged from 0.32 to 0.78. Corrected item-total correlations were highly satisfactory for Impact items, ranging from 0.62 to 0.85. All a priori validity hypotheses were supported by observed correlations and score differences between known groups. Conclusion: The results of this study support the structure, reliability, and validity of the FCS-SIS, laying the psychometric groundwork for longitudinal evaluation of its utility in assessing treatment benefit in FCS clinical studies.

Use of the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events to assess treatment tolerability in pulmonary arterial hypertension: qualitative patient research findings in current and former users of oral selexipag.

BACKGROUND: Understanding patients' perspectives regarding drug tolerability, in addition to effectiveness, provides a complete picture of the patient experience and supports more informed therapeutic decision-making. The item library of the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to measure patient-reported frequency, severity, and interference of adverse events (AEs) associated with cancer therapies. This qualitative interview study assessed the suitability of items selected from the PRO-CTCAE library for assessing tolerability of selexipag, a medication targeting the prostacyclin pathway for patients with pulmonary arterial hypertension (PAH). METHODS: Two rounds of 10 qualitative, web-assisted telephone interviews following a semi-structured guide were conducted in individuals with recent experience taking oral selexipag for PAH. Each interview included concept elicitation to gather participants' perspectives on symptomatic AEs (type, frequency, severity, and interference) and cognitive debriefing of PRO-CTCAE items addressing the most frequently reported AEs of oral selexipag. RESULTS: Interviews were conducted with 20 participants with PAH (mean [range] age 50 [24-68] years; 75% female; 85% in World Health Organization Functional Class II-III), comprising different races/ethnicities, levels of education, and employment status. Fifteen participants were currently treated with selexipag; five had taken selexipag for ≥ 6 months before discontinuing. The most frequently reported AEs included headache, jaw pain, and nausea (n = 15, 12, and 10 participants, respectively). Diarrhea and headache were identified as the most bothersome AEs by 5 and 4 participants, respectively. Some AEs were transitory (e.g., jaw pain); others were long-lasting (e.g., muscle pain). Based on findings from Round 1 interviews, a flushing item was added and the PRO-CTCAE general pain item was modified to be specific to jaw pain for testing in Round 2. Interview findings identified the following AEs as relevant to assess in a PAH clinical trial: nausea, vomiting, diarrhea, flushing, jaw pain, headache, aching muscles, and aching joints. CONCLUSIONS: The PRO-CTCAE items selected in this study and the additional symptomatic AEs identified as patient-relevant have the potential to be included in assessments capturing the patient perspective on tolerability in future studies of selexipag and possibly other PAH therapies.

Evaluation of symptoms in respiratory syncytial virus infection in adults: psychometric evaluation of the Respiratory Infection Intensity and Impact Questionnaire™ symptom scores.

BACKGROUND: The Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) is a patient-reported outcome measure designed to assess symptoms and impacts of respiratory syncytial virus (RSV) infection. This study evaluated the construct validity, reliability, and responsiveness of the RiiQ™ Respiratory and Systemic Symptoms Scale scores. METHODS: Prospective data were analyzed from a total of 1795 participants, including from non-hospitalized patients with acute respiratory infection (ARI) and no coinfections enrolled in a Phase 2b RSV vaccine study (RSV-positive: n = 60; RSV-negative: n = 1615), and two observational studies of patients hospitalized with RSV (n = 20; n = 100). Descriptive statistics, confirmatory factor analysis (CFA), test-retest intraclass correlation coefficients (ICCs), construct validity correlations (between a clinician-assessed clinical questionnaire and the RiiQ™ symptoms scale), known-groups validity, and responsiveness (correlations of change scores) were evaluated. RESULTS: Mean patient age ranged from 66.5 to 71.5 years and the majority of patients were female. Initial assessments in the vaccine trial (ARI Day 1) were suggestive of less severe illness than in the observational studies with hospitalized patients. CFA loadings (> 0.40) supported summary scores. ICCs exceeding the recommended threshold of 0.70 supported test-retest reliability for Respiratory and Systemic Symptoms, except in the small observational study. At the scale level, correlations were moderate to strong (|r| ≥ 0.3) and positive between the Respiratory Symptoms Scale and the related clinical questionnaire scores, reflecting measurement of similar symptoms in support of convergent validity. Correlations with change in Patient Global Impression of Severity > 0.30 supported responsiveness. CONCLUSIONS: Psychometric tests applied to the RiiQ™ Symptoms scales provide evidence of its reliability, construct validity, discriminating ability, and responsiveness for use in clinical studies to assess the onset and severity of RSV symptoms.

Psychometric evaluation of the Symptoms of Infection with Coronavirus-19 (SIC): results from a cross-sectional study and a phase 3 clinical trial.

BACKGROUND: The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome (PRO) measure scored by body system composites to assess signs/symptoms of coronavirus disease 2019 (COVID-19). In addition to cross-sectional and longitudinal psychometric evaluations, qualitative exit interviews were conducted to support the content validity of the SIC. METHODS: In a cross-sectional study, adults diagnosed with COVID-19 in the United States completed the web-based SIC and additional PRO measures. A subset was invited to participate in phone-based exit interviews. Longitudinal psychometric properties were assessed in ENSEMBLE2, a multinational, randomized, double-blind, placebo-controlled, phase 3 trial of the Ad26.COV2.S COVID-19 vaccine. Psychometric properties evaluated included structure, scoring, reliability, construct validity, discriminating ability, responsiveness, and meaningful change thresholds of SIC items and composite scores. RESULTS: In the cross-sectional study, 152 participants completed the SIC (mean age, 51.0 ± 18.6 years) and 20 completed follow-up interviews. Fatigue (77.6%), feeling unwell (65.8%), and cough (60.5%) were symptoms most frequently reported. SIC inter-item correlations were all positive and mostly moderate (r ≥ 0.3) and statistically significant. SIC items and Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) scores correlated as hypothesized (all r ≥ 0.32). Internal consistency reliabilities of all SIC composite scores were satisfactory (Cronbach's alpha, 0.69-0.91). SIC composite scores correlated moderately (r = 0.30-0.49) to strongly (r ≥ 0.50) with PROMIS-29 scores and Patient Global Impression of Severity (PGIS) ratings (all P < 0.01). A variety of signs/symptoms were cited in exit interviews, and participants considered the SIC straightforward, comprehensive, and easy to use. From ENSEMBLE2, 183 participants with laboratory-confirmed moderate to severe/critical COVID-19 were included (51.5 ± 14.8 years). Strong test-retest reliabilities were observed for most SIC composite scores (intraclass correlations ≥ 0.60). Statistically significant differences across PGIS severity levels were found for all but 1 composite score, supporting known-groups validity. All SIC composite scores demonstrated responsiveness based on changes in PGIS. CONCLUSIONS: The psychometric evaluations provided strong evidence for the reliability and validity of the SIC for measuring COVID-19 symptoms, supporting its use in vaccine and treatment trials. In exit interviews, participants described a broad range of signs/symptoms consistent with previous research, further supporting the content validity and format of the SIC.

Coronavirus disease 2019 (COVID-19) is a serious disease that continues to evolve globally. Researchers developed the Symptoms of Infection with Coronavirus-19 (SIC), a 30-item questionnaire designed for patients to report signs and symptoms of COVID-19. In this study, the researchers formally analyzed how well the SIC measures the patient experience with COVID-19, using survey and clinical trial data as well as telephone interviews. Adults with COVID-19 and at least 2 bothersome symptoms completed the web-based survey, and some of these individuals also participated in in-depth interviews. Participants in a clinical trial for a COVID-19 vaccine also completed the SIC measure. The SIC was compared with other commonly used questionnaires that evaluate patient experience. The most commonly reported symptoms of COVID-19 were fatigue, feeling unwell, cough, weakness, and headache. The items for individual symptoms (e.g., "cough") and combined scores for body systems (e.g., "respiratory system") performed well in statistical analyses. Participants found the SIC to be straightforward, comprehensive, and easy to use. The SIC may prove useful in the future for vaccine and treatment trials for COVID-19.

Interview-Based Patient- and Caregiver-Reported Experiences of Hunger and Improved Quality of Life with Setmelanotide Treatment in Bardet-Biedl Syndrome.

INTRODUCTION: Bardet-Biedl syndrome (BBS) is a rare genetic disease associated with hyperphagia, a pathologic insatiable hunger, due to impaired signaling in the melanocortin-4 receptor (MC4R) pathway. The impact of hyperphagia on the lives of patients with BBS and their families has not been fully characterized. METHODS: Patients with BBS or their caregivers who participated in clinical trials of the MC4R agonist setmelanotide (NCT03013543 and NCT03746522) were included in this qualitative study. Telephone interviews were conducted using a semistructured interview guide to explore patient experience and caregiver observations of hyperphagia before and during setmelanotide treatment. RESULTS: Nineteen interviews (8 patients, 11 caregivers) were conducted. The term "hunger" (rather than "hyperphagia") was used in interviews to ensure common terminology. Before setmelanotide treatment, all participants described their (or their child's) hunger as all-consuming, leading to an obsessive focus on food. Nine participants recalled intense, continuous hunger, and most participants (5 patients, 10 caregivers) reported lack of control with eating. Negative impacts on patients' lives included difficulties with concentration, emotional and physical manifestations, and impaired relationships. All participants experienced or observed improvements in hunger and health outcomes during treatment, the most meaningful of which included weight loss and decrease in obsessive focus on food and food-seeking behaviors. All participants reported improvements in either physical and/or emotional well-being and being satisfied with setmelanotide. CONCLUSIONS: Hyperphagia and resulting food-seeking behaviors have notable negative impacts on quality of life in patients with BBS and caregivers. Setmelanotide improved hyperphagia, reduced body weight and obsessive focus on food, and facilitated improvements in physical and emotional well-being for both patients and caregivers. TRIAL REGISTRATION: NCT03013543 and NCT03746522.

Development of patient- and observer-reported outcome measures to assess COVID-19 signs and symptoms in children and adolescents.

BACKGROUND: The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome measure to evaluate the presence and severity of COVID-19 signs/symptoms in adults. This study expanded the context of use of the adult SIC among adolescents aged 12-17 years and supported a pediatric adaptation (the Pediatric SIC [PedSIC]) for caregiver assessment of signs/symptoms in children aged < 12 years. METHODS: Draft versions of the PedSIC and reference materials containing sign/symptom definitions for adolescents, based on an assessment of the reading level of SIC items by a professional linguist, were developed to facilitate accurate completion of the SIC by adolescents and observer-report (PedSIC) by caregivers. For adolescents, reference materials were intended to provide definitions for selected signs/symptoms identified to have a higher reading level. Iterative rounds of cognitive debriefing interviews were conducted from November 2020 to January 2021 to evaluate adolescent understanding of the SIC reference materials and inform refinement of the PedSIC for caregivers of children too young to reliably self-report. Participants were identified via databases of individuals who previously expressed interest in participating in qualitative research and were then screened for eligibility. Recruitment quotas were established to improve sample diversity. Thematic analysis and descriptive statistics were used to assess qualitative and demographic data, respectively. RESULTS: Nine healthy adolescents (mean [SD, range] age, 14 [1.76, 12-17] years, 56% female, 22% non-White; round 1, n = 6; round 2, n = 3) and 17 caregivers (mean [SD, range] age, 34 [6.28, 26-41] years, 59% female, 35% non-White; round 1, n = 9; round 2, n = 8) were interviewed. Adolescents understood the majority of signs/symptoms (22 of the 30 SIC items) without assistance or use of the reference materials during the cognitive debriefing interview. Definitions were added to the reference materials for 5 additional items, and clarifications provided to existing definitions for 3 items. Seven observer-report (PedSIC) items were modified following feedback from caregivers of healthy young children. Reference materials (similar to those for adolescent use) were developed to support caregiver understanding of the intent of the PedSIC items collecting input from children ages ≥ 5- < 12 years. CONCLUSIONS: Results support using the SIC, PedSIC, and their associated reference materials to evaluate the presence and severity of COVID-19 signs/symptoms in adolescents and children aged < 12 years via caregiver-supported report, respectively.

The Prader-Willi Syndrome Anxiousness and Distress Behaviors Questionnaire: Development and Psychometric Validation.

OBJECTIVES: To facilitate the development of new therapies for Prader-Willi syndrome (PWS), we sought to develop a reliable and valid assessment of anxiousness and distress, common characteristics that have a significant negative impact on individuals with PWS and their families. METHODS: The PWS Anxiousness and Distress Behaviors Questionnaire (PADQ) was developed with extensive input from clinical experts, as well as caregivers of individuals with PWS, who participated in iterative sets of qualitative interviews. The psychometric properties of the PADQ were subsequently demonstrated in a cross-sectional evaluation using data from the Global PWS Registry provided by > 400 caregivers and confirmed using data from a phase 3 clinical trial of an oxytocin analogue (intranasal carbetocin, LV-101). RESULTS: Qualitative interview participants consistently endorsed the content of the PADQ and were confident they could accurately respond to each item based on their observations of their child's behavior. Analysis of cross-sectional data supported the computation of a total PADQ score, as well as the reliability and validity of the measure. The results of analyses using longitudinal clinical trial data confirmed these properties and provided evidence for the responsiveness of the PADQ, further supporting its appropriateness for the evaluation of new treatments targeting anxiousness and distress in PWS. CONCLUSIONS: The current body of evidence supports the conclusion that the PADQ measures observable behaviors that are meaningful to patients and their families and provides a valid and reliable method to assess beneficial treatment effects for some of the most challenging behaviors associated with PWS.

Development of an Assessment Tool for Completion by Patients with Overweight or Obesity.

INTRODUCTION: Discussions of weight-management strategies between patients and healthcare providers can yield positive outcomes for people with overweight or obesity. Nonetheless, people with overweight or obesity encounter communication challenges and other barriers to pursuing effective weight-management strategies with their healthcare providers. The aim of this study was to develop a new self-completed assessment tool to initiate and facilitate conversations related to weight management between patients and healthcare providers. METHODS: Developing the assessment tool involved a series of steps and draft versions of the tool, based on feedback from key opinion leaders in the field of obesity (N = 4) and input from people with overweight or obesity (N = 18). Three iterative rounds of qualitative interviews were conducted in the USA. A targeted review of prior qualitative research was conducted to identify common and important impacts of obesity on patients' functioning. Standard qualitative analytical methods were used to identify concepts of importance in a concept elicitation exercise during the interviews and were evaluated for potential inclusion in the tool. Potential problems with the tool were flagged during cognitive debriefing of the draft tool. RESULTS: During 18 individual interviews, participants referenced the impact of their weight on their lives, including health and comorbidities, physical function, emotional/mental functioning, social life, and physical appearance. Over the course of the tool's development, 24 common and important impacts of obesity on patients' functioning were reduced to a final set of eight concepts in the final tool that were deemed important and relevant to both patients and key opinion leaders. CONCLUSIONS: The assessment tool is a five-item, self-completed measure expected to foster patient self-advocacy for individuals with overweight or obesity by giving them an opportunity to define their weight-management goals and discuss these, along with various medical interventions, with a healthcare provider.

Development of a novel patient-reported outcome measure to assess signs and symptoms of COVID-19.

BACKGROUND: Given the urgent need for vaccines and treatments for coronavirus disease 2019 (COVID-19), the Symptoms of Infection with Coronavirus-19 (SIC), a comprehensive, patient-reported outcome (PRO) measure of signs and symptoms associated with COVID-19, was developed in full alignment with current US regulatory guidance to support evaluations of vaccines and treatments in development. METHODS: An initial version of the SIC was developed to address concepts identified through a targeted literature review and consultation with experts in infectious diseases and clinicians routinely managing COVID-19 in a hospital setting. A qualitative study was conducted in sites in the United States among 31 participants aged ≥ 18 years who were English-speaking and willing and able to provide informed consent and a self-reported history by telephone or online method. The measure was refined based on additional feedback from the clinicians and three iterative rounds of combined concept elicitation and cognitive debriefing interviews conducted with patients, caregivers, and healthy volunteers. RESULTS: Among 39 scientific articles identified in the literature review, 35 COVID-19 signs and symptoms were reported and confirmed during interviews with clinicians, patients, and caregivers. Patients and healthy participants suggested changes for refining the draft SIC to ensure consistent interpretation and endorsed both the 24-h recall period and use of an 11-point numeric rating scale (NRS) for capturing change in symptom severity. The final version of the SIC captures the daily presence or absence of 30 symptoms and a rating of severity for 25 of the 30 symptoms using an NRS for those symptoms reported as present. CONCLUSIONS: The SIC comprehensively addresses observations described in the literature, by clinicians, and by patients, and captures patients' experiences with COVID-19 in a manner that minimizes complexity and facilitates completion for both patients and healthy volunteers. This measure is thus appropriate for use in clinical trials of both therapeutics and vaccines for COVID-19.

Qualitative interviews in patients with lipodystrophy to assess the patient experience: evaluation of hunger and other symptoms.

BACKGROUND: New treatments are being evaluated for lipodystrophy; however, limited information is available on the patient experience. Results of a prior patient panel showed that hunger and temperature-related symptoms were an issue for participants. Therefore, evaluation of any changes in these symptoms is recommended for inclusion in new treatment options. The objective of this study was to further understand the patient experience and to evaluate newly developed items of hunger and temperature regulation. METHODS: Individual, in-depth telephone interviews were conducted via semi-structured discussion guide. Telephone interviews were conducted with 21 US patients with generalized lipodystrophy (GLD) or partial lipodystrophy (PLD). Eligibility requirements included self-reported PLD or GLD. Interviews included open-ended concept elicitation followed by a review of newly developed items assessing hunger, temperature sensations, and patient globals. Interviews were conducted in two rounds, with the newly developed items assessing hunger revised after each round of interviews based on participant feedback. RESULTS: Results indicated that hunger-related symptoms were considered a current issue for greater than half (N = 11) of participants, and all but one reported this as an issue at some point in their lives. Specifically, participants most often reported symptoms of increased appetite and not feeling full. The cognitive debriefing process indicated that the hunger-related symptoms, temperature, and global impression of change and severity items were correctly interpreted and easily completed by the participants. While not a focus of the interviews, the concept elicitation results demonstrated that pain was a frequently reported and bothersome symptom in this patient population. CONCLUSIONS: This qualitative research provided evidence to support the use of clinical outcomes assessments such as hunger and temperature-related items in clinical trials.

Understanding the Patient Experience of Hunger and Improved Quality of Life with Setmelanotide Treatment in POMC and LEPR Deficiencies.

INTRODUCTION: In patients with pro-opiomelanocortin (POMC) or leptin receptor (LEPR) deficiency, managing obesity and hyperphagia can be burdensome for patients and caretakers. The impacts on health-related quality of life are under-recognized and are not well characterized. METHODS: We conducted in-depth qualitative interviews in patients with POMC (n = 3) and LEPR (n = 2) deficiencies participating in an ongoing open-label extension of phase 3 clinical trials with the melanocortin receptor 4 agonist setmelanotide to describe the patient experience of hyperphagia and characterize changes following treatment with setmelanotide. RESULTS: Prior to setmelanotide treatment, all five patients described abnormal sensations of hunger with none indicating feeling satiated after meals and also reported that the burden of hyperphagia impacted their families, emotions, and work and/or school functioning. Following setmelanotide treatment, all five patients reported consistent reductions in hunger and weight, decreased eating, and feeling satiated after meals in addition to substantial improvements in each area of functioning they had previously reported. All five patients indicated they were very satisfied with the impact of setmelanotide on their quality of life and would be upset if treatment was discontinued. CONCLUSIONS: In patients with POMC or LEPR deficiency, hyperphagia and the inability to feel satiety negatively impacted quality of life. By reducing hunger and improving satiety, setmelanotide facilitated important changes in the lives of these patients. This qualitative research study suggests that the impact of setmelanotide goes beyond favorable clinical changes (e.g., weight and hunger) to also include quality of life improvements that are highly meaningful to patients.

Development of a novel PRO instrument for use in familial chylomicronemia syndrome.

BACKGROUND: Familial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by high levels of circulating triglycerides, negatively impacts multiple organs, including the liver and pancreas. OBJECTIVE: The objective of this study was to develop and support the content validity of a novel patient-reported outcome (PRO) measure addressing FCS symptoms and impacts. To facilitate use in clinical trials of new treatments, evidence supporting the new measure needed to be consistent with regulatory guidance and requirements. METHODS: A pool of items addressing symptoms and impacts of FCS was initially developed based on data from a large burden-of-illness study with patients with FCS as well as a review of available literature and existing PRO measures. Two rounds of qualitative interviews were conducted with patients with FCS (N = 10) to refine the draft items and support the measure's content validity. Each interview began with concept elicitation followed by cognitive debriefing of the draft FCS measure. RESULTS: Patient-reported symptoms and impacts of FCS were generally consistent with those identified by the burden-of-illness study; abdominal pain was particularly prevalent and salient for patients. Suggested changes to the draft item pool were generally minor. Comprehensibility and ease of completion for the final instrument were confirmed during the second set of interviews. CONCLUSION: The content validity of the final 17-item FCS Symptoms and Impacts Scale is strongly supported by patient input gathered through both a large burden-of-illness study and qualitative research. To further support use in clinical trials, psychometric evaluation of the measure is underway.

Confirmatory psychometric evaluations of the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT).

The Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) was developed to assess weight-related physical and psychosocial functioning in the context of clinical trials. Data from two pivotal trials of once-weekly subcutaneous semaglutide for the purpose of weight management (NCT03548935 and NCT03552757) were analysed to confirm the structure, reliability, validity, and responsiveness of the IWQOL-Lite-CT and evaluate the magnitude of meaningful within-patient change in patients with overweight or obesity, with and without type 2 diabetes. Factor analyses and inter-item correlations confirmed the IWQOL-Lite-CT structure and scoring algorithm. Each composite score (physical, physical function, psychosocial, and total) demonstrated excellent internal consistency (Cronbach's alphas ≥ 0.82) and test-retest reliability (intraclass correlation coefficients ≥ 0.85) in both trials. Patterns of cross-sectional and longitudinal construct validity correlations were generally consistent with hypotheses. Each of the IWQOL-Lite-CT composites was able to discriminate between known groups. Effect sizes and paired t tests comparing IWQOL-Lite-CT scores at baseline and Week 68 were statistically significant for all composites in both trials (P < 0.0001), providing strong support for the ability to detect change. Results of anchor-based analyses supported responder thresholds ranging from 13.5 to 16.6 across composite scores. The IWQOL-Lite-CT, a comprehensive assessment of weight-related functioning from the patient perspective, is appropriate for use in clinical trials evaluating the efficacy of new treatments for weight management.

Development of the impact of weight on daily activities questionnaire: A patient-reported outcome measure.

While patient-reported outcome measures are available to evaluate health-related quality of life and functioning in obesity, existing measures do not evaluate the impact of excess weight and weight loss on the ability to perform regularly occurring daily activities. Three iterative sets of qualitative interviews were conducted in two countries (United States, n = 23; United Kingdom, n = 23) with individuals with body mass index ≥30 kg/m2 to inform development of the Impact of Weight on Daily Activities Questionnaire (IWDAQ) for use in clinical trials to evaluate daily activity limitations associated with excess weight. Candidate concepts were selected based on the literature, expert opinion, and previously conducted qualitative research, after which the draft IWDAQ was developed and tested. Interviews included a brief concept elicitation phase, followed by cognitive debriefing during which the IWDAQ was refined based upon participants' feedback. The IWDAQ uses a novel, adaptive questionnaire design, such that clinical trial participants choose the three IWDAQ activities they would most like to improve with weight loss and rate the degree of limitation in each of these activities at baseline. By allowing individuals participating in trials to identify and monitor changes in the activities they most want to see improve with weight loss, the 19-item IWDAQ has the potential to detect the benefits of weight-loss treatment that individuals with obesity value most.

The atopic dermatitis itch scale: development of a new measure to assess pruritus in patients with atopic dermatitis.

Introduction: Pruritus is the primary symptom of atopic dermatitis (AD). The objective of this study was to develop a patient-reported outcome (PRO) instrument for daily administration in clinical trials to measure AD-related itch in adolescents and adults that would meet the standards described in the US Food and Drug Administration's (FDA's) PRO Guidance.Materials and methods: Six focus groups were conducted with 49 patients with AD (32 adults; 17 adolescents). Three iterative rounds of cognitive debriefing interviews were conducted in 26 patients with AD (17 adults; 9 adolescents) to pretest and refine the instrument.Results: AD-related itching was considered the most bothersome AD symptom by nearly two-thirds of the focus group participants. The items in the initial version of the instrument, named the Atopic Dermatitis Itch Scale (ADIS), were developed to reflect concepts most relevant to the assessment of itching as described during the focus groups. Based on results of the cognitive debriefing interviews, an 8-item final version of the ADIS was created.Conclusion: The ADIS is a content valid PRO instrument addressing the concepts critical to the measurement of AD-related itching. To our knowledge, it is the first instrument developed to assess AD-related itch in patients as young as 12 years following the recommendations of the PRO Guidance.

Validation of a new measure of quality of life in obesity trials: Impact of Weight on Quality of Life-Lite Clinical Trials Version.

The Impact of Weight on Quality of Life-Lite (IWQOL-Lite) is widely used in evaluations of weight-loss interventions, including pharmaceutical trials. Because this measure was developed using input from individuals undergoing intensive residential treatment, the IWQOL-Lite may include concepts not relevant to clinical trial populations and may be missing concepts that are relevant to these populations. An alternative version, the IWQOL-Lite Clinical Trials Version (IWQOL-Lite-CT), was developed and validated according to the US Food and Drug Administration's (FDA's) guidance on patient-reported outcomes. Psychometric analyses were conducted to validate the IWQOL-Lite-CT using data from two randomized trials (NCT02453711 and NCT02906930) that included individuals with overweight/obesity, with and without type 2 diabetes. Additional measures included the SF-36, global items, weight and body mass index. The IWQOL-Lite-CT is a 20-item measure with two primary domains (Physical [seven items] and Psychosocial [13 items]). A five-item Physical Function composite and Total score were also supported. Cronbach's alpha and intraclass correlation coefficients exceeded 0.77 at each time point; patterns of construct validity correlations were consistent with hypotheses; and scores demonstrated treatment benefit. The IWQOL-Lite-CT is appropriate for assessing weight-related physical and psychosocial functioning in populations commonly targeted for obesity clinical trials. Qualification from the FDA is being sought for use of the IWQOL-Lite-CT in clinical trials to support product approval and labelling claims.

Development and psychometric evaluation of the Diabetic Gastroparesis Symptom Severity Diary.

BACKGROUND: Diabetic gastroparesis (DG) is defined as delayed gastric emptying with associated gastrointestinal symptoms, without mechanical obstruction. Patient-reported symptoms are critical for diagnosis and evaluation of treatment benefit in DG. The Diabetic Gastroparesis Symptom Severity Diary (DGSSD), a new patient-reported outcome measure, was developed for use in clinical trials to support product approval and labeling claims for DG treatments. MATERIALS AND METHODS: Initial DGSSD development was based on a review of the existing instruments and qualitative research (focus groups and cognitive debriefing interviews) in 41 patients with DG. Psychometric evaluations (individual items and composite scores) were conducted using data from Phase IIa and IIb relamorelin clinical trials. RESULTS: Qualitative research in patients with DG resulted in a six-item DGSSD, included in the Phase IIa trial, addressing symptom severity for nausea, vomiting, abdominal pain, early satiety, and bloating, as well as vomiting frequency. An item addressing severity of postprandial fullness (PPF) was subsequently added based on regulatory advice and included in the Phase IIb trial. Measurement properties were generally strong for weekly averages of daily item and composite scores. Item-level intraclass correlation coefficients ranged from 0.79 to 0.97 and correlations with other measures matched hypothesized patterns; the discriminating ability and responsiveness of the DGSSD were also supported. Multiple methods supported the computation of a composite score based on items addressing nausea, abdominal pain, bloating, and PPF severity. CONCLUSION: Qualitative and quantitative evidence support use of the DGSSD as a reliable and valid measure from which to derive endpoints to evaluate treatment benefit in future DG interventional trials.

Exploring the Diabetic Gastroparesis Patient Experience: Patient Exit Interviews.

INTRODUCTION: To improve understanding of the diabetic gastroparesis (DGP) patient experience and inform the patient-reported outcome measurement strategy for future trials in DGP, qualitative interviews were conducted with participants in a phase 2 clinical trial of a novel DGP treatment. METHODS: Trial participants were invited to participate in interviews at both the pretreatment visit (PTV) and the end-of-treatment visit (EOTV). The interviews were conducted by experienced qualitative researchers and followed a semistructured interview guide. The PTV interviews focused on patients' DGP symptoms and the impact of DGP on their lives, and the EOTV interviews focused on any symptom changes patients experienced during the trial. RESULTS: Of 90 enrolled trial participants, 78 (86.7%) opted to participate in the interview study. Bloating, stomach fullness, upper abdominal pain, vomiting, constipation, and heartburn or reflux were each reported spontaneously by a majority of the 73 PTV interview participants with evaluable data. These patients commonly reported bloating (n = 20), upper abdominal pain (n = 12), and nausea (n = 11) as their most bothersome DGP symptom. Of 51 EOTV interview participants, 44 (86.3%) reported improvement in at least one DGP symptom either spontaneously or when asked about specific symptoms reported during their PTV interview. CONCLUSION: Bloating, abdominal pain, nausea, constipation, stomach fullness, vomiting, and heartburn were frequently reported by patients as the most bothersome and important-to-treat symptoms. These results support the assessment of these symptoms in future DGP clinical trials, whether for symptom improvement or worsening. FUNDING: Ironwood Pharmaceuticals. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02289846.