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Background Infertility has a negative impact on quality of life (QoL) and well-being of affected individuals and couples. A variety of patient-reported outcome (PRO) measures to assess infertility-related QoL are available; however, there is a concern regarding potential issues with their development methodology, validation and use. This review aimed to i) identify PRO measures used in infertility interventional studies ii) assess validation evidence to identify a reliable, valid PRO measure to assess changes in QoL or treatment satisfaction in clinical studies with female patients following treatment with novel therapies iii) identify potential gaps in evidence for validity. Methods A structured literature search of Medline, Embase, and the Cochrane Library (accessed in September 2015) was conducted using pre-defined search terms. The identified publications were reviewed applying eligibility criteria to select interventional female infertility studies using PROs. Infertility-specific PRO measures assessing QoL, treatment satisfaction or psychiatric health, and included in studies by ≥2 research groups were selected and critically reviewed in light of scientific and regulatory guidance (e.g. FDA PRO Guidance for Industry) for evidence of content validity, psychometric strength, and patient acceptability. Results The literature search and hand-searching yielded 122 publications; 78 unique PRO measures assessing QoL, treatment satisfaction or psychiatric health were identified. Five PRO measures met the selection criteria for detailed review: Fertility Quality of Life (FertiQoL); Fertility Problem Inventory (FPI); Fertility Problem Stress (FPS); Infertility Questionnaire (IFQ); Illness Cognitions Questionnaire adapted for Infertility (ICQ-I). None of the PRO measures met all validation criteria. The FertiQoL was the most widely used infertility-specific PRO measure to assess QoL in interventional studies, with reasonable evidence for adequate content validity, psychometric strength, and linguistic validation. However, gaps in evidence remain including test-retest reliability and thresholds for interpreting clinically important changes. While the FPI demonstrated reasonable evidence for content and psychometric validity, its utility as an outcome measure is limited by a lack of recall period. Conclusion The FertiQoL and the FPI are potentially useful measures of infertility-related QoL in interventional studies. Further research is recommended to address gaps in evidence and confirm both PRO measures as reliable assessments of patient outcomes.

We compared patient-reported outcomes (PROs) with once-weekly carfilzomib 70 mg/m 2 (Kd70 mg/m 2 ) vs. twice-weekly carfilzomib 27 mg/m 2 (Kd27 mg/m 2 ) plus dexamethasone in relapsed or refractory multiple myeloma (RRMM). Patient-reported convenience/satisfaction collected at Cycle 2, Day 1 was compared between groups using logistic regression. European Organization for Research and Treatment of Cancer QOL Questionnaire (QLQ-C30), MM-module (QLQ-MY20), and EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) questionnaires were administered at baseline, then every other cycle. PROs were compared between groups using mixed models for repeated measures. Times from randomization to first deterioration (TTD) in scores were analyzed using Cox regression. PRO analyses included 469 patients. Once-weekly Kd70 mg/m 2 patients reported greater convenience (odds ratio [OR], 4.98; p  < 0.001) and satisfaction (OR, 2.41; p  = 0.059) vs. twice-weekly Kd27 mg/m 2 . The mixed models for repeated measures demonstrated no clinically meaningful differences in scores between treatment arms. Clinically meaningful deterioration in QLQ-C30 Global Health Status/QOL rates were 34.2% (once-weekly Kd70 mg/m 2 ) vs. 40.3% (twice-weekly Kd27 mg/m 2 ). TTD was longer for once-weekly Kd70 mg/m 2 vs. twice-weekly Kd27 mg/m 2 for QLQ-C30 fatigue (HR, 0.79; p  = 0.035), QLQ-MY20 disease symptoms (HR, 0.67; p  = 0.008), EQ-5D-5L index score (HR, 0.58; p  = 0.002), and EQ-5D-5L Visual Analog Scale (HR, 0.75, p  = 0.031). Once-weekly Kd70 mg/m 2 improved convenience/satisfaction, and reduced HRQOL deterioration vs. twice-weekly Kd27 mg/m 2 , supporting convenient, once-weekly Kd70 mg/m 2 dosing in RRMM.

Background The Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance v1.0 item bank (27 items) measures sleep disturbances. Rather than the full item bank, an 8-item short form (PROMIS SD SF 8b) or computerized adaptive testing (CAT) can be used. This study compares the performance of the PROMIS SD SF 8b with two CAT algorithms in postmenopausal women. Methods This is a secondary analysis of data collected for the original psychometric testing of the PROMIS Sleep Disturbance item bank, in a sub-sample of women aged ≥55. A graded response model (GRM) was fitted for the item bank, then simulations evaluated the performance of CAT algorithms and the short form, in terms of root mean square error (RMSE) versus the latent trait estimate derived from the full bank. Two CAT algorithms were tested: CAT1 (stop once standard error <0.3 or 12 items administered) and CAT2 (stop once 8 items administered). Convergent and divergent hypotheses for validity were tested through correlations with the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Known-groups comparisons were made between those with and without self-reported sleep disorder. Results A sample of 337 women was analyzed. Unidimensionality and item-level fit to the GRM was supported; however, the local independence assumption was violated. The CAT1 algorithm showed 4.18 items on average, with a minor decrease in performance (higher RMSE value) compared to CAT2 or the PROMIS SD SF 8b. Administering 8 items adaptively (CAT2) compared to fixed (PROMIS SD SF 8b) performed similarly (RMSE difference = 0.001). Reliability exceeded 0.90 across most of the latent trait for all approaches. Correlations with the PSQI and ESS were largely as hypothesized, with minor differences in coefficient values between the approaches (all within 0.05). Women reporting a sleep disorder had greater sleep disturbance than those who did not ( p  < 0.001 for all). Conclusions The results of this study support using the PROMIS Sleep Disturbance item bank in postmenopausal women. The choice of PROMIS SD SF 8b versus CAT can largely be driven by practical reasons (respondent burden and operational complexity) rather than concerns of differential reliability and validity.

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

Purpose Pancreatic cancer and its treatments impact patients’ symptoms, functioning, and quality of life. Content-valid patient-reported outcome (PRO) instruments are required to assess outcomes in clinical trials. This study aimed to: (a) conceptualise the patient experience of pancreatic cancer; (b) identify relevant PRO instruments; (c) review the content validity of mapped instruments to guide PRO measurement in clinical trials. Methods Qualitative literature and interviews with clinicians and patients were analysed thematically to develop a conceptual model of patient experience. PRO instruments were reviewed against the conceptual model to identify gaps in measurement. Cognitive debriefing explored PRO conceptual relevance and patients’ understanding. Results Patients in the USA ( N  = 24, aged 35–84) and six clinicians (from US and Europe) were interviewed. Pre-diagnosis, pain was the most frequently reported symptom ( N  = 21). Treatments included surgery, radiation, chemotherapy, and immunotherapy. Surgery was associated with acute pain and gastrointestinal symptoms. Chemotherapy/chemoradiation side effects were cyclical and included fatigue/tiredness ( N  = 21), appetite loss ( N  = 15), bowel problems ( N  = 15), and nausea/vomiting ( N  = 15). Patients’ functioning and well-being were impaired. The literature review identified 49 PRO measures; the EORTC QLQ-C30/PAN26 were used most frequently and mapped with interview concepts. Patients found the EORTC QLQ-C30/PAN26 to be understandable and relevant; neuropathic side effects were suggested additions. Conclusions This is the first study to develop a conceptual model of patients’ experience of metastatic/recurrent pancreatic cancer and explore the content validity of the EORTC QLQ-C30/PAN26 following therapeutic advances. The EORTC QLQ-C30/PAN26 appears conceptually relevant; additional items to assess neuropathic side effects are recommended. A recall period should be stated throughout to standardise responses.

Background Refractory chronic cough (RCC) is commonly reported in primary care and associated with significant morbidity. Patient-reported outcome (PRO) measures are important for evaluating the efficacy of antitussive medications for RCC in clinical trials from the patient-perspective. Psychometric properties of Severity of Chronic Cough Diary (SCCD) Cough Severity and Cough Frequency, Leicester Cough Questionnaire (LCQ) Total and Physical Domain and Cough Severity Visual Analogue Scale (VAS) scores using data from a 12-week Phase 2b trial evaluating the efficacy of eliapixant in patients with RCC (NCT04562155) are reported. Results Quality of completion for the SCCD, LCQ and Cough Severity VAS across the study was high, no ceiling or floor effects were observed at baseline. Internal consistency for LCQ Total and Physical domain scores was also high (Cronbach’s alpha = 0.939 and 0.806, respectively). SCCD Cough Frequency and Cough Severity, LCQ Total and Physical domain, and Cough Severity VAS scores demonstrated strong test-retest reliability (Intraclass correlation coefficient ≥ 0.848) among participants defined as stable between Week 3 and Week 4 according to Patient Global Impression of Severity (PGI-S) ratings and Awake Cough Count readings. Construct validity was supported by known-groups comparisons, with large differences (effect sizes 1.99–4.16) observed between groups categorized according to PGI-S ratings and objective Awake Cough Counts. Ability to detect improvement was supported by large effect sizes (≥0.8) observed for mean changes in SCCD, LCQ and Cough Severity VAS scores from baseline to Week 12 among participants classified as ‘improved’ according to PGI-S/PGI-C ratings and Awake Cough Counts. Triangulated thresholds (score range) for meaningful within-patient improvement based on anchor-based assessments were -0.82 for SCCD Cough Frequency (0–4), -0.69 for SCCD Cough Severity (0–4), 2.36 for the LCQ Total (3–21), 0.77 for the LCQ Physical (1–7) and -17.73 for the Cough Severity VAS (0–100) scores. Conclusion Findings support the reliability, validity and responsiveness of the newly developed SCCD Cough Frequency and Severity items as fit-for-purpose PRO measures of cough frequency or severity for use in drug development programs within RCC. The LCQ Total, LCQ Physical Domain and Cough Severity VAS also exhibit acceptable measurement properties for use in this population.

Background: Novel clinical measures assessed by a digital health technology tool require thresholds to interpret change over time, such as the minimal clinically important difference. Establishing such thresholds is a key component of clinical validation, facilitating understanding of relevant treatment effects. Summary: Many of the approaches to derive interpretative thresholds for patient-reported outcomes can be applied to digital clinical measures. We present theoretical background to the use of interpretative thresholds, including the distinction between thresholds based on perceived importance versus measurement error, and thresholds for group- versus individual-level interpretations. We then review methods to estimate such thresholds, including anchor-based approaches. We illustrate the methods using data on cough frequency counts as measured by a wearable device in a clinical trial. Key Messages: This paper provides an overview of statistical methodologies to estimate thresholds for the interpretation of change.

Background Medication non-adherence is a common issue in chronic illness. The World Health Organization has recognized a need for a valid and reliable method of measuring adherence to understand and mitigate non-adherence. This study aimed to psychometrically evaluate the English version of the Adelphi Adherence Questionnaire (ADAQ©), a questionnaire designed to assess patient-reported medication adherence across multiple therapy areas, in patients with Osteoarthritis (OA). Methodology Data from the Adelphi OA Disease Specific Programme™, a survey of physicians and their consulting adult patients with OA conducted in the United States, November 2020 to March 2021, was used to assess the psychometric properties of the ADAQ. Patients completed the ADAQ, Adherence to Refills and Medication Scale (ARMS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and EQ-5D-3L. The measurement model of the 13-item ADAQ was assessed and refined using latent variable modelling (Multiple Indicator Multiple Cause, confirmatory and exploratory factor analyses, item response theory, Mokken scaling, and bifactor analyses). Correlational analyses (Spearman’s rank and polyserial as appropriate) with ARMS, WOMAC, and EQ-5D-3L scores assessed construct validity. Anchor- and distribution-based analyses were performed to estimate between-group clinically important differences (CID). Results Overall, 723 patients were included in this analysis (54.5% female, 69.0% aged ≥ 60). Latent variable modelling indicated a unidimensional reflective model was appropriate, with a bifactor model confirming an 11-item essentially unidimensional score. Items 12 and 13 were excluded from scoring as they measured a different concept. The ADAQ had high internal reliability with omega hierarchical and Cronbach’s alpha coefficients of 0.89 and 0.97, respectively. Convergent validity was supported by moderate correlations with items of the ARMS, and physician-reported adherence and compliance. Mean differences in ADAQ score between high and low adherence groups yielded CID estimates between 0.49 and 1.05 points, with a correlation-weighted average of 0.81 points. Conclusion This scoring model showed strong construct validity and internal consistency reliability when assessing medication adherence in OA. Future work should focus on confirming validity across a range of disease areas.

Background: Assessment of reliability is one of the key components of the validation process designed to demonstrate that a novel clinical measure assessed by a digital health technology tool is fit-for-purpose in clinical research, care, and decision-making. Reliability assessment contributes to characterization of the signal-to-noise ratio and measurement error and is the first indicator of potential usefulness of the proposed clinical measure. Summary: Methodologies for reliability analyses are scattered across literature on validation of PROs, wet biomarkers, etc., yet are equally useful for digital clinical measures. We review a general modeling framework and statistical metrics typically used for reliability assessments as part of the clinical validation. We also present methods for the assessment of agreement and measurement error, alongside modified approaches for categorical measures. We illustrate the discussed techniques using physical activity data from a wearable device with an accelerometer sensor collected in clinical trial participants. Key Messages: This paper provides statisticians and data scientists, involved in development and validation of novel digital clinical measures, an overview of the statistical methodologies and analytical tools for reliability assessment.

In this paper we show that to some extent several arguments misrepresent Thorstein Veblen's original conception of conspicuous consumption and take it out of context in relation to his overall framework. In addition, in order to develop a contemporary response to these arguments we examine the possible contribution that can be made using the work of Pierre Bourdieu, the sociologist and anthropologist who has been described as France's leading living social theorist (Shusterman 1999). The contribution of this paper is to develop a defense and extension of the theory of conspicuous consumption by exploring the writings of Veblen and Bourdieu. An introduction to Veblen's theory of conspicuous consumption in the first part of the paper is followed in the second part by a presentation of the main arguments against it. In the third part a response to each argument is developed using Veblen and Bourdieu.