Patient-reported outcomes in the subpopulation of patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer treated with dostarlimab plus chemotherapy compared with chemotherapy alone in the ENGOT-EN6-NSGO/GOG3031/RUBY trial.

OBJECTIVE: In the ENGOT-EN6-NSGO/GOG3031/RUBY trial, dostarlimab+carboplatin-paclitaxel demonstrated significant improvement in progression free survival and a positive trend in overall survival compared with placebo+carboplatin-paclitaxel, with manageable toxicity, in patients with primary advanced or recurrent endometrial cancer. Here we report on patient-reported outcomes in the mismatch repair-deficient/microsatellite instability-high population, a secondary endpoint in the trial. METHODS: Patients were randomized 1:1 to dostarlimab+carboplatin-paclitaxel or placebo+carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo monotherapy every 6 weeks for ≤3 years or until disease progression. Patient-reported outcomes, assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Endometrial Cancer Module, were prespecified secondary endpoints. A mixed model for repeated measures analysis, a prespecified exploratory analysis, was conducted to generate least-squares means to compare between-treatment differences while adjusting for correlations across multiple time points within a patient and controlling for the baseline value. Results are provided with 2-sided, nominal p values. RESULTS: Of 494 patients enrolled, 118 were mismatch repair-deficient/microsatellite instability-high. In this population, mean change from baseline to end of treatment showed visual improvements in global quality of life (QoL), emotional and social function, pain, and back/pelvis pain for dostarlimab+carboplatin-paclitaxel. Meaningful differences (least-squares mean [standard error]) favoring the dostarlimab arm were reported for change from baseline to end of treatment for QoL (14.7 [5.45]; p=0.01), role function (12.7 [5.92]); p=0.03), emotional function (14.3 [4.92]; p<0.01), social function (13.5 [5.43]; p=0.01), and fatigue (-13.3 [5.84]; p=0.03). CONCLUSIONS: Patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer receiving dostarlimab+carboplatin-paclitaxel demonstrated improvements in several QoL domains over patients receiving placebo+carboplatin-paclitaxel. The observed improvements in progression free survival and overall survival while improving or maintaining QoL further supports dostarlimab+carboplatin-paclitaxel as a standard of care in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT03981796.

Understanding the patient experience in hepatocellular carcinoma: a qualitative patient interview study.

PURPOSE: This study aimed to elucidate the patient experience of hepatocellular carcinoma (HCC) to guide patient-centered outcome measurement in drug development. METHODS: Patients with HCC participated in qualitative interviews to elicit disease-related signs/symptoms and impacts, using discussion guides developed from literature searches and discussions with oncologists. Interview participants rated the disturbance of their experiences (0-10 scale). A conceptual model was developed and mapped against patient-reported outcome (PRO) instruments identified from database reviews. RESULTS: Interviews were conducted with 25 individuals with HCC (68% were men; median age: 63 years; 12% Barcelona clinic liver cancer (BCLC) stage A; 32% stage B; and 56% stage C) in the USA. Fifty-one HCC-related concepts were identified from the interviews and were grouped into eight sign/symptom categories (eating behavior/weight changes; extremities [arms, legs]; fatigue and strength; gastrointestinal; pain; sensory; skin; other) and four impact categories (emotional; physical; cognitive function; other) for the conceptual model. The most prevalent and disturbing experiences across the disease stages were fatigue/lack of energy and emotional impacts such as frustration, fear, and depression. Abdominal pain and skin-related issues were particularly common and disturbing in individuals with HCC stage C. The EORTC QLQ-C30 and HCC18 were identified as commonly used PRO instruments in HCC studies and captured the relevant signs/symptoms associated with the patient experience. CONCLUSION: Patients with HCC reported a range of signs/symptoms and impacts that negatively affect daily functioning and quality of life. Including PRO measures in HCC clinical trials can provide meaningful patient perspectives during drug development.

Understanding the patient experience of chronic kidney disease stages 2-3b: a qualitative interview study with Kidney Disease Quality of Life (KDQOL-36) debrief.

BACKGROUND: Qualitative patient interviews and patient-reported outcome instruments are important tools to understand the patient experience of disease. The aim of this study was to use patient interviews to identify concepts relevant and important to patients living with chronic kidney disease (CKD) stages 2-3b, develop a comprehensive conceptual model of the patient experience and debrief the Kidney Disease Quality of Life 36-item instrument (KDQOL-36) for patients with CKD stages 2-3b. METHODS: Concept elicitation interviews were conducted with patients with CKD stages 2-3b to identify signs/symptoms and impacts most relevant and important to patients (i.e., 'salient' concepts) and develop a conceptual model for the disease. Based on the salient concepts identified in the interviews, new items were proposed to supplement the KDQOL-36. Cognitive debriefing was performed to evaluate the KDQOL-36 and the additional items. RESULTS: A total of 31 patients were interviewed in this study (22 for concept elicitation and 15 for cognitive debriefing). The interviews identified 56 concepts (33 signs/symptoms and 23 impacts), 17 of which had not been identified in a previous literature review. Four signs/symptoms ('fatigue/lack of energy/tiredness', 'sleep problems', 'increased urination [including nocturia]' and 'swelling in legs/ankles/feet') and two impacts ('anxiety/worry' and 'general negative emotional/mental impact') were identified as salient. Of the salient signs/symptoms, three were not covered by the KDQOL-36 (sleep problems, increased urination and swelling in legs/ankles/feet) and were represented during cognitive debriefing interviews through four additional items (trouble falling asleep, trouble staying asleep, increased urination [including nocturia] and swelling in legs/ankles/feet) generated in the style of the KDQOL-36. All patients found the KDQOL-36 plus the four additional items relevant, and the majority found them clear. CONCLUSIONS: By identifying previously unknown concepts and augmenting the understanding of which are most important to patients, a comprehensive conceptual model was developed for patients who have CKD stages 2-3b. This study also demonstrates the suitability of the KDQOL-36 for patients who have CKD stages 2-3b and provides suggestions for how the instrument could be further developed to more comprehensively capture patient experience.

The patient's perspective on treatment with dacomitinib: patient-reported outcomes from the Phase III trial ARCHER 1050.

Aim: Patient-reported symptoms, functioning and overall quality of life (QoL) were compared between dacomitinib and gefitinib in ARCHER 1050. Patients & methods: Patients (n = 448) with advanced EGFR mutation-positive non-small-cell lung cancer completed the EORTC-QLQ-C30 questionnaire and its lung-specific module, LC-13. Mean scores over time were analyzed using a mixed model for repeated measures. Results: Both treatments showed early improvement in disease-related symptoms that was maintained during treatment. Treatment-related diarrhea and sore mouth decreased following dose reduction with dacomitinib. There were no clinically meaningful changes in functioning and overall QoL in either treatment group. Conclusion: Longer treatment duration, enabled by dose reduction, allowed patients on dacomitinib to improve treatment-related symptoms and maintain functioning and overall QoL for longer than gefitinib.

Patient-reported outcomes in patients with metastatic non-squamous non-small cell lung cancer from the randomized Phase II PERLA trial comparing first-line chemotherapy plus dostarlimab or pembrolizumab.

BACKGROUND: PERLA (NCT04581824) compared efficacy and safety of dostarlimab (DCT) or pembrolizumab (PCT) plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer. Here, we report patient-reported outcomes (PROs; exploratory analysis) from PERLA. METHODS: Patients were randomized 1:1 to receive DCT or PCT every 3 weeks (Q3W) for ≤ 35 cycles [C]. PROs (EORTC QLQ-C30 and QLQ-LC13, PRO-CTCAE, FACT-GP5) were collected at baseline, Q3W until C4, Q9W until C16, Q12W until end of treatment and at 30-day safety follow-up. Change from baseline and time to deterioration (TTD) in QLQ-C30 and QLQ-LC13 were analyzed using longitudinal mixed models and Kaplan-Meier estimators, respectively. RESULTS: The PRO (DCT/PCT) datasets included 102/99 patients for QLQ-C30, 96/90 for QLQ-LC13, 96/88 for PRO-CTCAE, and 95/87 for FACT-GP5. Completion rates were > 80 % to C4, then decreased in both arms. For QLQ-C30 and QLQ-LC13, most patients reported stable/improved responses at C13 (∼ 9 months on treatment), with similar responses between arms except more patients reported improvements in dyspnea (QLQ-C30: 36.4 % vs 13.0 %; QLQ-LC13: 40.6 % vs 25.0 %) and chest pain (QLQ-LC13: 34.4 % vs 10.0 %) with DCT vs PCT. TTD per QLQ-C30 and QLQ-LC13 were similar between arms, although TTD in dyspnea was longer with DCT vs PCT (QLQ-LC13: 4.24 vs 1.54 months; p = 0.0168). Most patients in both arms reported that adverse events occurred occasionally/rarely/never with moderate/mild severity. Overall, patients reported little/no bother from treatment side effects. CONCLUSIONS: DCT maintained health-related quality of life similarly to PCT and was well tolerated, supporting the PERLA primary results and dostarlimab use in future regimens.

A qualitative patient interview study to understand the experience of patients with nonalcoholic steatohepatitis.

NASH is a potentially progressive form of NAFLD characterized by hepatocyte injury and liver inflammation which can cause fibrosis. Currently, there are limited data on the patient experience of NASH. Our aim was to use both literature review and patient interviews to understand the signs/symptoms and life impacts of NASH fibrosis stages F1-F4 that are important to patients, as well as begin to investigate the applicability of an instrument (ie, questionnaire) that may be used to capture patients' experiences. The literature review identified concepts (signs/symptoms and impacts) related to NASH fibrosis stages F1-F4 and the NASH-specific patient-reported outcome instrument (NASH-CHECK) for reporting patient experience of NASH. Interviews with 22 patients from Canada and the USA with NASH fibrosis stages F1-F4 revealed 27 signs/symptoms and 32 impacts that they felt were important, including fatigue, pain in the abdomen, worry, and frustration. Three concepts reported during patient interviews were not identified in the literature review. No concepts appeared to be exclusive to a specific fibrosis stage or presence/absence of obesity and no linear trends were identified between fibrosis stage or presence/absence of obesity and level of disturbance reported for concepts. The patient interviews supported the concepts included in the NASH-CHECK overall, demonstrating that it could be used to report the patient experience of NASH fibrosis stages F1-F4. Interviews with patients with NASH fibrosis stages F1-F4 revealed patients can self-report and elaborate on signs/symptoms and impacts related to the disease regardless of fibrosis stage. The NASH-CHECK was identified as a suitable instrument that could be used by patients with fibrosis stages F1-F4.

Content Validity and Cognitive Debriefing of a Patient-Reported Outcome Instrument Evaluating Symptoms and Disease Impact in Patients with Geographic Atrophy.

INTRODUCTION: Geographic atrophy (GA) occurs in the later stages of dry age-related macular degeneration (AMD) and impairs visual acuity, eventually causing permanent blindness in some patients and impacting patient quality of life. Patient-reported outcome (PRO) measures that assess the experience of patients with visual impairment do not sufficiently capture all concepts salient to patients with GA. In this study the experience of patients with GA secondary to dry AMD was evaluated, and items from the novel 10-item Visual Impairment Symptom Severity Assessment (VISSA-10) PRO instrument were mapped to salient symptoms to assess its content validity, ease of use, and relevance. METHODS: Concept elicitation interviews were conducted with patients with GA to determine salient symptoms and impacts of GA, and a conceptual model was developed to reflect these. The items in the VISSA-10 instrument were then mapped onto the salient symptoms included in this conceptual model. Cognitive debriefing interviews were also conducted with the same cohort to determine the comprehensiveness and comprehensibility of the instrument, and to qualitatively assess levels of change considered meaningful by patients. RESULTS: In total, 25 symptoms and 36 impacts were reported by 19 patients with GA, with seven symptoms and 11 impacts identified as salient. Of these, 12 symptoms and 15 impacts reported were not included in a previously published conceptual model for patients with dry AMD. Overall, eight of the ten items from the VISSA-10 instrument mapped to salient symptoms reported by patients with GA. All patients reported that the instrument was clear and easy to understand. CONCLUSIONS: The VISSA-10 instrument was shown to be content valid, clear, and comprehensible, with sufficient concept coverage to measure the experience of patients with GA. Although further quantitative validation is required, this instrument has demonstrated potential for implementation in future clinical trials to evaluate the efficacy of new treatments for GA.

The Bronchiectasis Exacerbation Diary: a novel patient-reported outcome for non-cystic fibrosis bronchiectasis.

Bronchiectasis is a chronic, progressive lung disease believed to result from a vicious cycle of infection and inflammation, with symptoms of chronic cough with sputum production, chronic fatigue, rhinosinusitis, chest pain, breathlessness and haemoptysis. There are currently no established instruments to monitor daily symptoms and exacerbations for use in clinical trials. Following a literature review and three expert clinician interviews, we conducted concept elicitation interviews with 20 patients with bronchiectasis to understand their personal disease experience. Findings from literature and clinician feedback were used to develop a draft version of the Bronchiectasis Exacerbation Diary (BED), which was designed to monitor key symptoms on a daily basis and during exacerbations. Patients were eligible to be interviewed if they were US residents aged ≥18 years, had a computed tomography scan-confirmed diagnosis of bronchiectasis with ≥two exacerbations in the previous 2 years and had no other uncontrolled respiratory conditions. Four waves of five patient interviews each were conducted. Patients (n=20) had a mean±SD age of 53.9±12.8 years, and most were female (85%) and white (85%). A total of 33 symptoms and 23 impacts arose from the patient concept elicitation interviews. The BED was revised and finalised based upon patient feedback. The final BED is a novel, eight-item patient-reported outcome (PRO) instrument for monitoring key exacerbation symptoms on a daily basis with content validity established through comprehensive qualitative research and direct patient insight. The BED PRO development framework will be completed following psychometric evaluations of the data from a phase 3 bronchiectasis clinical trial.

Impact of Chronic Graft-versus-Host Disease on Patient Employment, Income, and Informal Caregiver Burden: Findings From the Living With Chronic GVHD Patient Survey.

The development of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) results in impaired physical function and quality of life. However, limited data exist regarding the employment and financial impact on patients and caregivers. The objective of this study was to examine the impact of chronic GVHD on patient employment, disability leave, income, reliance on caregivers, and effects on caregiver employment. The Living With Chronic GVHD Patient Survey was a cross-sectional online survey administered from May to August 2020 in the United States to adult HSCT survivors diagnosed with chronic GVHD within the past 5 years. Data on respondent demographics and disease characteristics and the effects of chronic GVHD on employment, income, and need for caregiver assistance were collected. Respondents also were asked to report on the impact of their chronic GVHD on their caregivers' employment. All data were summarized using descriptive statistics; no formal statistical comparisons were conducted. A total of 165 respondents completed the survey (median age, 57.0 years; 63.6% women; 83.0% white). The respondents had been experiencing chronic GVHD for a median of 4.5 years (range, .1 to 36.7 years), with a median of .5 years (range, 0 to 3.6 years) from the most recent transplantation to chronic GVHD diagnosis. Among those employed full- or part-time at the time of their most recent transplantation (n = 80), 61.3% reported taking disability leave, 58.8% worked reduced hours, 27.5% took a less demanding job, and 33.8% left a job because of chronic GVHD. Additionally, 71.3% believed they had lost income due to chronic GVHD. Among all respondents, 72.1% reported receiving regular caregiver assistance. Respondents commonly reported employment changes among unpaid caregivers; 34.5% reduced their working hours, and 16.6% left a job). HSCT survivors who develop chronic GVHD are vulnerable to employment changes and financial hardship. This analysis highlights the need for effective therapies and improved symptom management to reduce the multifaceted burden of chronic GVHD on patients and their caregivers and ultimately improve long-term HSCT outcomes.

Psychometric Validation and Meaningful Change Thresholds of the New Nasal Polyposis Symptom Diary.

OBJECTIVES: The Nasal Polyposis Symptom Diary (NPSD) is a novel and short patient-reported outcome (PRO) tool specifically developed to assess important and relevant symptoms reported by patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). We evaluated the psychometric properties of 4 predefined NPSD-derived scores intended to support symptom-improvement assessments of investigational therapies for inclusion in product labeling. METHODS: Five hundred eighteen patients with severe CRSwNP from a Phase III clinical trial (NCT03401229) completed the NPSD, comprising 11 items: 8 symptom-specific, 2 symptom-impact, and 1 optional medication-compliance. The psychometric characteristics of 3 single-item symptom scores (Nasal Blockage Score [NBS], Nasal Congestion Score [NCS], and Difficulty with Sense of Smell Score [DSS]) and a Total Symptom Score (TSS, summary of the 8 symptom-specific items) were evaluated for reliability, validity, and ability to detect change. Within-patient meaningful change thresholds (MCTs) were established using anchor- and distribution-based methods. Comparative PROs included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Patient Global Impression of Severity (PGI-S). RESULTS: The TSS exhibited strong internal consistency (Cronbach α = .88) and test-retest reliability (intraclass correlation coefficient >.80). Correlation between the TSS and SNOT-22 total score indicated good convergent validity (r = .70). All 4 NPSD scores demonstrated known-groups validity (significant differences among subgroups of patients with predetermined disease severity levels based on PGI-S categories) and were sensitive to detect change in patients' clinical status (significant differences among subgroups of patients with reported changes between 2 time-points in PGI-S and Patient Global Impression of Change scores). MCTs for improvement were established at 1.0 point for NBS, NCS, and DSS, and 4.0 points for TSS. CONCLUSION: These findings support the reliability, validity, and suitability of the 4 NPSD-derived scores for evaluating treatment effect on CRSwNP symptoms and their use in clinical trials with predetermined MCTs for improvement.

Patient-reported symptom burden and impact on daily activities in chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) treatment for hematologic malignancies. There are limited patient-reported data concerning symptom burden and effects on activities of daily living (ADL). METHODS: The cross-sectional Living With Chronic GVHD Patient Survey was administered online in the United States (May-August 2020) to participants aged ≥18 years who underwent allogeneic HSCT, were diagnosed with chronic GVHD by a healthcare provider, and self-reported active chronic GVHD (within past 5 years). Information on patient demographics, disease characteristics, symptom burden, and ability to perform ADL was collected. Symptom burden was assessed using the validated Lee Symptom Scale (range from 0-100 with higher scores indicating greater burden). All data were summarized using descriptive statistics; no formal statistical comparisons were conducted. RESULTS: Out of 580 participants who entered the survey screener, 165 participants (28.4%) across 33 states fulfilled all study eligibility criteria, completed the entire survey, and were included (age: mean [SD], 53.7 (13.8) years; median [range], 57.0 [18-78] years; female, n = 105 [63.6%]; White, n = 137 [83.0%]). Respondents described their chronic GVHD severity primarily as moderate (n = 54 [32.7%]) or severe (n = 102 [61.8%]) at the time when symptoms were at their worst. One-third of respondents (33.9%) indicated that their chronic GVHD symptoms were at their worst for ≥1 year in duration. Mean (SD; range) Lee Symptom Scale score was 44.8 (19.4; 2-100); 44% of respondents considered "dry eye" the most burdensome symptom. Almost half of respondents (n = 73 [44.2%]) rated their overall quality of life (QoL) as poor. Participants reported a detrimental impact of symptoms on ADL, including basic activities (eg, eating, personal hygiene, dressing). CONCLUSIONS: Survey respondents self-reported high chronic GVHD symptom burden and felt that their symptoms severely interfered with physical function and ADL. Effective strategies to mitigate chronic GVHD symptoms are needed to improve QoL among HSCT survivors.

Measuring the patient experience of chronic rhinosinusitis with nasal polyposis: qualitative development of a novel symptom diary.

BACKGROUND: This qualitative study assessed the experience of patients with chronic rhinosinusitis with nasal polyposis (NP) to inform the development of a novel symptom diary for clinical study use. METHODS: Concept elicitation and cognitive interviews were conducted with patients who had a physician-verified diagnosis of NP and a history of intranasal corticosteroid use. Concepts were identified via open-ended and follow-up questions. Relative symptom/impact disturbance level was assessed using a scale of 0 (not at all disturbing) to 10 (extremely disturbing). RESULTS: Patients (n = 30) attributed numerous symptoms and impacts to NP; the most prevalent and disturbing were nasal congestion (identified by 100% of patients; average disturbance rating = 7.9), nasal blockage/obstruction (97%; 8.2), difficulty with sense of smell (97%; 7.6), facial pressure (90%; 6.2), postnasal drip (87%; 6.5), runny nose (87%; 6.2), facial pain (80%; 6.3), and headache (77%; 6.5). These symptoms, along with the impact of NP on sleep and daily activities, were included in the Nasal Polyposis Symptom Diary (NPSD). Cognitive interviews confirmed that patients understood the NPSD items and could select a response reflective of their experience at its worst over the past 24 hours using a four-point scale (none, mild, moderate, or severe). CONCLUSION: The most relevant and disturbing symptoms, according to patients with NP, were included in the NPSD. Interviews confirmed the suitability of NPSD in capturing the daily experience of patients. These findings support the content validity of the NPSD as a suitable tool for capturing NP symptoms and impacts.

Content validity and psychometric evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue scale in patients with chronic lymphocytic leukemia.

PURPOSE: Fatigue is a prominent symptom in individuals with chronic lymphocytic leukemia (CLL). This work evaluates the content validity and psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue) in patients with CLL to determine if it is fit for purpose in CLL research. METHODS: The FACIT-Fatigue yields a 13-item total score from a five-item symptom subscale and an eight-item impact subscale. To evaluate content validity, cognitive debriefing interviews were conducted with 40 patients with CLL in the first-line or relapsed or refractory setting. Psychometric properties, including structural validity, internal consistency, construct and known-groups validity, were investigated using data from a phase 3 trial in relapsed or refractory CLL (NCT02970318). RESULTS: Interviewed patients considered the FACIT-Fatigue items relevant to their CLL experience, understood the terminology and agreed with response options. Confirmatory factor analysis confirmed the presence of symptom and impact subscales, but also supported unidimensionality of the FACIT-Fatigue. The FACIT-Fatigue total, symptom and impact subscales demonstrated good internal consistency (Cronbach's coefficient α > 0.85 and McDonald's omega ω > 0.90), and strong correlations with relevant EORTC QLQ-C30 scales (all Spearman's r ≥ 0.5). Known-groups validity was shown by significant differences between groups defined by baseline performance status, hemoglobin level and constitutional symptoms (all p < .0001). Cluster analysis supported FACIT-Fatigue score thresholds of 30 and 34 to define a severe fatigue population. CONCLUSIONS: Content validity and psychometric evaluation in patients with CLL demonstrated that the FACIT-Fatigue has good psychometric properties and is fit for purpose in CLL.

Patient Global Impression of Benefit-Risk (PGI-BR): Incorporating Patients' Views of Clinical Benefit-Risk into Assessment of New Medicines.

INTRODUCTION: There is a need to understand how patients assess perceived benefits and risks of treatments. OBJECTIVES: The study aimed to (i) elucidate how patients evaluate treatment experiences and (ii) develop a brief patient-reported outcome (PRO) instrument for use across disease areas for perceived benefit-risk evaluation of a new medicine in a clinical trial setting. METHODS: Concepts relating to patient-perceived benefit-risk were identified from literature reviews and qualitative concept elicitation interviews with patients across a variety of primary medical conditions. Draft instrument items were developed from identified concepts and evaluated for clarity, relevance and appropriateness of response options in cognitive interviews. Items were iteratively revised to address patient feedback. RESULTS: Qualitative interviews were conducted with 47 patients (primary condition: 20 oncological, 12 respiratory, 10 metabolic, 5 cardiovascular), of whom 32 contributed to concept elicitation and 42 to cognitive debriefing. Elicited concepts could be grouped into four medication-related categories: effectiveness of treatment, burden of side effects, convenience of use and overall acceptance/satisfaction. Cost, trial experience and altruism were additional concept categories unrelated to medication. The final instrument contained one item each on the medication's effectiveness, side effects and convenience, and an overall item capturing patient benefit-risk assessment. An upfront question was included to separate out non-medication aspects of patients' experiences. CONCLUSION: We developed a brief PRO instrument, the Patient Global Impression of Benefit-Risk (PGI-BR), which can be applied across disease areas to assess patient views of benefit-risk of a new medicine in the clinical trial setting.

Development and content validation of a symptom assessment for eosinophilic gastritis and eosinophilic gastroenteritis in adults and adolescents.

BACKGROUND: A patient reported outcome (PRO) instrument with evidence of validity and reliability for assessing symptoms of eosinophilic gastritis (EG) and eosinophilic gastroenteritis (EGE) is needed to measure treatment benefit in clinical trials. The aim of this research is to develop an EG/EGE symptom PRO instrument for patients aged 12 and above. METHODS: The Symptom Assessment for Gastrointestinal Eosinophilic Diseases (SAGED) was developed through a literature review, discussions with expert clinicians, and concept elicitation and cognitive debriefing interviews with patients. Patients (n = 28) were recruited based on confirmed diagnosis and self-reported symptoms. The final instrument was translated and linguistically validated with additional cognitive debriefing interviews (n = 105). RESULTS: SAGED is a 24-h recall questionnaire consisting of eight items evaluating the core symptoms of EG and EGE (abdominal pain, nausea, bloating, early satiety, loss of appetite, vomiting, and diarrhea). Seven of the eight items are evaluated on an 11-point numerical rating scale ranging from 'none' to 'worst imaginable'. Cognitive debriefing interviews showed that adults and adolescents understand the content and are able to select a response that reflects their experience. The linguistic validation process produced 21 translations that are understandable to patients and conceptually equivalent to the source version. CONCLUSIONS: SAGED is suitable for measuring symptom improvement in adult and adolescent patients with EG and/or EGE. The content validity of SAGED has been established through best practices in qualitative research for PRO instrument development. The psychometric properties of SAGED will be evaluated in a future study.

Understanding Patient Experience in Biliary Tract Cancer: A Qualitative Patient Interview Study.

INTRODUCTION: Patients living with biliary tract cancer (BTC) experience a decline in health-related quality of life (HRQoL). This study aimed to obtain a comprehensive understanding of the patient experience of BTC-related signs/symptoms and the impacts of these on daily functioning and HRQoL. METHODS: Patients with BTC participated in qualitative semi-structured concept elicitation interviews. Signs/symptoms and impacts of BTC were initially explored by targeted literature searches and interviews with five clinicians. Patient interviews were transcribed and coded using qualitative research software. Concept saturation was assessed over five interview waves. A sign/symptom or impact was defined as "salient" if mentioned by ≥ 50% of patients, with a mean disturbance rating of ≥ 5 (0-10 scale). A conceptual model of the patient experience of BTC-related signs/symptoms and impacts was produced. RESULTS: Twenty-three patients from the USA (78% women; median age: 54 years), diagnosed as having early (n = 3), locally advanced (n = 11) or metastatic (n = 9) disease, were interviewed. Sixty-six signs/symptoms and 12 impacts were identified. Of these, 46 signs/symptoms and 8 impacts were not identified from the targeted literature or clinician interviews. Concept saturation was reached by the fourth of five interview waves. Fourteen disease-related signs/symptoms (including fatigue/lack of energy, abdominal pain, lack of appetite, insomnia and diarrhoea) and three impacts (physical, emotional and cognitive impacts) were deemed "salient". The conceptual model included 50 signs/symptoms and 12 impacts. CONCLUSION: Patients with BTC reported a range of signs/symptoms and impacts that negatively affect daily functioning and HRQoL.

Comparing the effects of sampling designs on the diagnostic accuracy of eight promising screening algorithms for pediatric bipolar disorder.

BACKGROUND: Past studies have used markedly different inclusion and exclusion criteria to form samples used to evaluate diagnostic tests, making it difficult to compare results across studies. The present investigation compared eight screening algorithms in the same sample but under two different design strategies. METHODS: The DSM-IV diagnoses were based on a semi-structured diagnostic interview (KSADS) with the parent and youth sequentially. Raters were blind to index test scores. Participants were 216 youths with bipolar spectrum diagnoses and 284 youths with other Axis I diagnoses or no diagnosis. T-tests evaluated whether areas under the curve (AUC) from receiver operating characteristic analyses differed under the two design conditions. RESULTS: All of the instruments discriminated bipolar cases better when inclusion and exclusion criteria duplicated those used in phenomenological research studies selecting narrow phenotypic cases (AUCs ranging from .90 to .81). The measures performed less well when more heterogeneous clinical presentations were included [AUCs ranging from .86 to .69, t(8) = 4.99, p = 001]. CONCLUSIONS: Results indicate that checklists perform less well discriminating pediatric bipolar disorder under conditions that more closely resemble clinical practice. Test users must consider whether the sampling strategies and participant characteristics used to evaluate tests match the characteristics of their own patients.

Costs and Resource Utilization Among Medicaid Patients with Schizophrenia Treated with Paliperidone Palmitate or Oral Atypical Antipsychotics.

BACKGROUND: Non-adherence to antipsychotic therapy among patients with schizophrenia is a key driver of relapse, which can lead to costly inpatient stays. Long-acting injectables (LAIs) may improve adherence, thus reducing hospitalizations, but inpatient cost reductions need to be balanced against higher drug acquisition costs of LAIs. Real-world evidence is needed to help quantify the economic value of oral atypical antipsychotics compared with LAIs. OBJECTIVE: The objective of this study was to compare healthcare costs and resource utilization between once-monthly paliperidone palmitate (PP) and oral antipsychotic therapy (OAT) in a population of Medicaid beneficiaries with schizophrenia. METHODS: A retrospective, observational study was performed using Truven Health MarketScan Medicaid claims data from 2009 to 2012. Marginal structural modeling, a form of weighted repeated measures analysis to control for differences between cohorts and time-varying confounding, was used to estimate monthly costs of care in 2012 US dollars and resource utilization over a 12-month period for patients in each cohort. RESULTS: While per-month mental-health prescription costs were US$1019 higher in the PP cohort, approximately 55 % of this premium was offset by lower inpatient and outpatient care costs, producing a mean monthly total cost differential of US$434 (95 % CI 298-569, p < 0.0001) for all-cause costs and US$463 (95 % CI 374-552, p < 0.0001) for mental-health-related costs. Use of PP also resulted in a 0.44 and 0.47 reduction in the odds of all-cause and mental-health-related hospitalizations and a 0.09 reduction in the odds of all-cause emergency department visits (p < 0.0001, p < 0.0001, and p = 0.0134, respectively) over the 12-month follow-up period. CONCLUSIONS: Treatment with long-acting injectable antipsychotics, such as PP, may reduce inpatient and outpatient healthcare services utilization and associated costs. These findings also suggest that patients with schizophrenia taking once-monthly PP may stand a lower risk of hospitalization than patients on OAT.

Quality of life in pediatric bipolar disorder.

OBJECTIVE: Bipolar disorder is a common mood disorder associated with significant disability and impairment in quality of life in adults. Little research has examined the impact of the disorder on quality of life in children and adolescents. The current study examines the quality of life in children and adolescents with bipolar disorder compared with other physical and psychiatric illnesses. METHODS: This study included 529 youth and caregiver pairs who sought services at a community mental health center or an academic medical center. Diagnoses were based on semistructured interviews of caregivers and youths, and quality of life was determined by the parent-reported Revised Children Quality of Life Questioinnaire (KINDL) questionnaire and compared with published benchmarks for many medical illnesses. RESULTS: Mean age of the youths was 12.0 years, 57% were boys, 72% were black, 22% were white, and 17% had received bipolar disorder diagnoses. Youths with bipolar disorder had significantly lower quality-of-life scores than youths with asthma, atopic dermatitis, obesity, arthritis, oxygen dependence, heart surgery during infancy, depression, behavior disorders, and nonmood and nonbehavior psychiatric diagnoses. CONCLUSIONS: Youths with bipolar disorder reported lower quality of life than other youths encountered in pediatric practice. Pediatricians should attend not only to the child's mood symptoms but also to the overall impairment of the disorder.

A Parent General Behavior Inventory subscale to measure sleep disturbance in pediatric bipolar disorder.

OBJECTIVE: Sleep disturbance is a reliable marker for differentiating children with bipolar spectrum disorders from those with attention-deficit/hyperactivity disorder. Sleep-related items were extracted from the Parent General Behavior Inventory (P-GBI) to determine whether these items, as a scale unto themselves, demonstrate adequate psychometrics to be useful as a possible endophenotypic marker for bipolar spectrum disorders. METHOD: From July 2003 to July 2007, 625 youths and their parents completed semistructured Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version interviews. Parents also completed the 73-item P-GBI. RESULTS: Participants with bipolar spectrum disorders (DSM-IV criteria) scored significantly higher than all other participants on all 7 of the sleep variables (p < .005). On receiver operating characteristic (ROC) analysis, the sleep subscale did substantially as well at discriminating participants with bipolar spectrum disorders as did either of the 2 built-in GBI scales, depression and hypomanic/biphasic (area under the ROC curve = 0.74 vs. 0.75 and 0.77, respectively). CONCLUSION: The P-GBI sleep subscale, developed in this study, is a reliable measure of a wide range of mood-related sleep problems in youths diagnosed with bipolar spectrum disorders. Sleep disturbance appears to be a promising endophenotype for further clinical investigation, and the P-GBI sleep scale may provide an inexpensive way of quantifying this trait for research. Further research needs to evaluate how parent report compares to objective measures of sleep efficiency, such as actigraphy or polysomnography.