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Tolerability and safety of treatments are important in oncology trials and should be informed by patient assessments. We identified the most relevant patient-reported symptomatic adverse events (AEs) to measure in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.This study selected relevant symptomatic AEs from 78 AEs available in the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Initially, symptomatic AEs were selected based on literature and product labeling reviews, and then core sets of symptomatic AEs were identified by patient and clinician interviews. Qualitative and descriptive analyses were performed using the data collected from three iterative rounds of patient interviews.During concept elicitation interviews involving 29 patients, 12 symptomatic AEs were identified and were then adapted into a 25-item PRO-CTCAE form for use in future clinical trials along with commonly used PRO measures. Cognitive interviews showed that the PRO-CTCAE items were easy to answer and appropriate for assessing the patients' experience with symptomatic AEs. This study also assessed disease symptoms, impacts, and overall patient experience.The 25-item PRO-CTCAE form captures the most relevant symptomatic AEs in this patient population, and it is available for future studies. Baseline characterization of AEs associated with this distinct patient group contributes to our broader knowledge about NSCLC and through platforms like Project Patient Voice will expand our understanding of treatment tolerability and safety for NSCLC. Ultimately, this data collection will help inform decision-making for patients, caregivers, healthcare providers, and regulators.

Background For the treatment of female sexual dysfunction, the most relevant outcome measures are patient-reported treatment effects and changes in symptoms, underscoring the need for reliable, validated patient-reported outcome (PRO) instruments. The aim of this study was to evaluate the psychometric characteristics (validity and reliability) of the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) PRO measure, which was adapted from the validated FSDS-Revised (FSDS-R) questionnaire and added 2 questions involving arousal and orgasm. Methods Psychometric analyses were based on the data from a multicenter phase 2b dose-finding study that compared the safety and efficacy of bremelanotide versus placebo and were conducted in the evaluable modified intent-to-treat population (N = 325) from that study. Psychometric evaluation of the new items in the FSDS-DAO included confirmatory factor analyses, tests of internal consistency and test–retest reliability, examinations of convergent and discriminant validity, and determination of responsiveness. The validity of the FSDS-DAO was evaluated based on previously developed instruments, including the Female Sexual Function Index (FSFI), General Assessment Questionnaire (GAQ), Women’s Inventory of Treatment Satisfaction (WITS-9), and Female Sexual Encounter Profile-Revised (FSEP-R). Results Confirmatory factor analyses demonstrated that the FSDS-DAO items fit very well (Bentler’s comparative fit index of 0.929). Cronbach’s α for the FSDS-DAO total score was ≥ 0.91 at Visits 1, 2, 5, and 12, demonstrating adequate internal consistency reliability. Test–retest reliability was acceptable with an intra-class coefficient of 0.61 and a Spearman’s correlation coefficient score of 0.62 between Visits 1 and 2 (4 weeks). Acceptable construct validity was demonstrated by significant correlations with related PRO scales in the expected directions and magnitude. For example, participants reporting the worst levels of sexual function on the FSFI also showed the worst FSDS-DAO scores at Visits 5 and 12. The FSDS-DAO total score was responsive to change. Conclusions Evidence supports the validity and reliability of the FSDS-DAO for assessing sexually related distress in women with female sexual arousal disorder and/or hypoactive sexual desire disorder; the addition of the arousal and orgasm items did not impact the validity and reliability of the measure. Clinical Trial Registration ClinicalTrials.gov NCT01382719.

Introduction The presence of ring sideroblasts (RS) and mutation of the SF3B1 gene are diagnostic of lower‐risk (LR) myelodysplastic syndromes (MDS) and are correlated with favorable outcomes. However, information on testing and reporting in community‐based clinical settings is scarce. This study from the Connect® MDS/AML Disease Registry aimed to compare the frequency of RS and SF3B1 reporting for patients with LR‐MDS, before and after publication of the 2016 World Health Organization (WHO) MDS classification criteria. Methods Ring sideroblasts assessment and molecular testing data were collected from patients with LR‐MDS at enrollment in the Registry. Patients enrolled between December 2013 and the data cutoff of March 2020 were included in this analysis. Results Among 489 patients with LR‐MDS, 434 (88.8%) underwent RS assessment; 190 were assessed prior to the 2016 WHO guidelines (Cohort A), and 244 after (Cohort B). In Cohort A, 87 (45.8%) patients had RS identified; 29 (33.3%) patients had RS

Purpose To systematically estimate the patient-reported outcomes (PROs) and economic burden of sickle cell disease (SCD) among adults in the United States (US). Patients and methods Two systematic literature reviews (SLRs), one each for the PROs and economic topics, were performed using MEDLINE and Embase to identify observational studies of adults with SCD. Included studies were published between 2007 and 2018 and evaluated health-related quality of life (HRQL), function, healthcare resource utilization (HCRU), or costs. Given the high degree of clinical and methodological heterogeneity, findings were summarized qualitatively. Results The SLRs identified 7 studies evaluating the PROs and 15 studies evaluating the economic burden meeting the pre-specified selection criteria. The PRO evidence showed the prevalence of depression and anxiety to be 21-33% and 7-36%, respectively, in adults with SCD. The mean SF-36 physical summary scores ranged from 33.6 to 59.0 and from 46.3 to 61.5 for the mental summary scores. Overall HRQL for adults with SCD was poor and significantly worse in those with opioid use. Adult SCD patients were found to have varying rates of emergency department (ED) utilization (0.3-3.5 annual ED visits), hospitalizations (0.5-27.9 per patient per year), and/or readmission (12-41%). Key factors associated with significant HCRU were age, dental infection, and SCD-related complications. SCD specialized care settings and SCD intensive management strategy were reported to significantly decrease the number of hospitalizations. Conclusion This systematic evidence synthesis found that disease burden measured by PROs and economic burden of SCD on adults in the US are substantial despite the availability of approved SCD treatments during 2007-2018. The use of hydroxyurea, optimal management with opioids, and employing intensive treatment strategies may help decrease the overall burden to patients and healthcare systems. Published data on costs associated with SCD are limited and highlight the need for more economic studies to characterize the full burden of the disease.

Background Triptans are the first-line option for the acute treatment of migraine attacks; however, triptans are contraindicated in people with certain underlying cardiovascular risk factors and are associated with inadequate efficacy or poor tolerability in some individuals. Ubrogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine. Methods This post hoc analysis of the phase 3 ACHIEVE trials examined the impact of ubrogepant on the Functional Disability Scale (FDS), satisfaction with medication, and Patient Global Impression of Change (PGIC) in participants who were self-reported triptan insufficient responders (TIRs), defined as those who are unable to take triptans due to contraindications, tolerability issues, or insufficient efficacy. Responder definitions for the FDS, satisfaction measures, and PGIC were based on qualitative interpretation of the respective response options for the pooled ubrogepant 50 mg and placebo groups. Results In the pooled analysis population (n = 1799), 451 (25%) participants were TIRs, with most (80%) reporting insufficient efficacy with triptan use. A significantly higher proportion of TIRs treated with ubrogepant vs placebo reported being able to function normally from 2 to 8 h post dose (P P = 0.048). A greater proportion of TIRs in the ubrogepant arm vs the placebo arm were satisfied with treatment at 2 (33% vs 21%, P = 0.006) and 24 h (58% vs 28%, P P = 0.006). Results were generally similar in the insufficient efficacy subpopulation of TIRs as in the overall TIRs group. Ubrogepant was safe and well tolerated in TIRs, with no new safety signals identified. Conclusions In people with migraine who are TIRs, individuals treated with ubrogepant had favorable 2-h outcomes, as measured by the FDS, satisfaction with medication, and PGIC, compared with placebo. Trial registration ClinicalTrials.gov: NCT02828020 (ACHIEVE I), registered July 11, 2016; NCT02867709 (ACHIEVE II), registered August 16, 2016.

Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients' symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item's importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs. ispartof: BMJ OPEN vol:11 issue:6 ispartof: location:England status: published

The EORTC QLU-C10D is a new multi-attribute utility instrument derived from the widely used cancer-specific quality of life questionnaire, EORTC QLQ-C30. It contains 10 dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems), each with four levels. The aim of this study was to provide U.K. general population utility weights for the QLU-C10D. A U.K. online panel was quota-sampled to align the sample to the general population proportions of sex and age (≥18 years). The online valuation survey included a discrete choice experiment (DCE). Each participant was asked to complete 16 choice-pairs, each comprising two QLU-C10D health states plus duration. DCE data were analysed using conditional logistic regression to generate utility weights. Data from 2,187 respondents who completed at least one choice set were included in the DCE analysis. The final U.K. QLU-C10D utility weights comprised decrements for each level of each health dimension. For nine of the 10 dimensions (all except appetite), the expected monotonic pattern was observed across levels: Utility decreased as severity increased. For the final model, consistent monotonicity was achieved by merging inconsistent adjacent levels for appetite. The largest utility decrements were associated with physical functioning and pain. The worst possible health state (the worst level of each dimension) is -0.083, which is considered slightly worse than being dead. The U.K.-specific utility weights will enable cost-utility analysis (CUA) for the economic evaluation of new oncology therapies and technologies in the United Kingdom, where CUA is commonly used to inform resource allocation.

Background Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder with brain iron accumulation (NBIA). Objectives To assess PKAN diagnostic pathway, history, and burden across the spectrum of PKAN severity from patient and/or caregiver perspectives. Methods Caregivers of patients (n = 37) and patients themselves (n = 2) were interviewed in a validation study of the PKAN-Activities of Daily Living (ADL) scale. The current study used quartiles of the PKAN-ADL total score to divide patients by severity of impairment (Lowest, Second Lowest, Third Lowest, Highest). Diagnostic and treatment history, healthcare utilization, disease burden, and caregiver experience were compared between groups. Results The analyses included data from 39 patients. Mean age at PKAN symptom onset (P = 0.0007), initial MRI (P = 0.0150), and genetic testing (P = 0.0016) generally decreased across the PKAN severity spectrum. The mean duration of illness did not differ among PKAN severity groups (range, 9.7–15.2 years; P = 0.3029). First MRI led to diagnosis in 56.4% of patients (range, 30.0–90.0%). A mean (SD) of 13.0 (13.1) medical and 55.2 (78.5) therapy visits (eg, physical, speech) occurred in the past year. More patients in the higher PKAN severity groups experienced multiple current functional losses and/or earlier onset of problems (P-values

Objective: The aim of this study was to determine the clinical meaningfulness of TX-001HR in reducing moderate to severe vasomotor symptoms (VMS) in menopausal women with a uterus. Methods: In the REPLENISH study (NCT01942668), women with moderate to severe hot flushes (≥7/d or ≥50/wk) were enrolled in a VMS substudy and randomized to four doses of daily TX-001HR (17β-estradiol/progesterone) or placebo. Participants assessed improvement of their VMS by the Clinical Global Impression and the Menopause-Specific Quality of Life (MENQOL) questionnaire, which were used to define clinical responders, clinically important differences (CIDs) or minimal CID (MCID) in VMS frequency. Response thresholds were determined by nonparametric discriminant analyses utilizing bootstrapping methods. Results: In the modified intent-to-treat VMS substudy population (n = 726), statistically significantly more Clinical Global Impression–based clinical responders were observed with TX-001HR than placebo for MCID (weekly reduction of ≥25 moderate to severe VMS: 82-88% vs 69%; all, P

Background The purpose of this study is to evaluate the content validity of the National Comprehensive Cancer Network – Functional Assessment of Cancer Therapy – Breast Cancer Symptom Index (NFBSI-16) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b among patients with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Methods Cognitive debriefing interviews sought to evaluate patients’ ability to read, understand, and meaningfully respond to the questionnaires, as well as to evaluate the questionnaires’ relevance in the target patient population. Interviews were conducted by telephone and lasted approximately 90 min. Audio recordings were transcribed, anonymized, and analyzed using qualitative data analysis software. Results Fifteen cognitive debriefing interviews were conducted with women (mean age 66.0 years [standard deviation = 12.4]). Patients reported metastases in the bone (86.7%), liver (20.0%), lung (13.3%), skin (6.7%), and lymph node (6.7%) (not mutually exclusive). All patients for whom data were available demonstrated understanding of the instructions and the recall period of the NFBSI-16 (n = 14/14, 100.0%) and the PROMIS (n = 14/14, 100.0%). Greater than 90% of patients demonstrated understanding of each of the items in the NFBSI-16 and the PROMIS. Greater than 70% of patients demonstrated understanding of the response options of the NFBSI-16, > 90% understood response options of PROMIS Items 1–6, and ≥ 50% understood response options of PROMIS Items 7–10. Conceptual relevance was supported for most items in both questionnaires based on patients’ reports of experiencing the concepts as part of their breast cancer experience. Conclusions The results of the cognitive debriefing interviews provide evidence that the NFBSI-16 and PROMIS Physical Function Short Form 10b have content validity in the HR+/HER2- advanced breast cancer patient population. Patients may benefit from additional instructions at the point the response options reverse direction in the PROMIS.

Background Patients with breast cancer experience a variety of disease symptoms and treatment-related side effects that can adversely affect functioning. The breast cancer experience may differ across disease stages and biomarker subtypes. This study identified relevant disease symptoms, treatment-related side effects, and physical functioning impacts in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Methods One-on-one concept elicitation interviews were conducted with 15 patients with HR+/HER2- advanced breast cancer. Open-ended questions about patient experience with breast cancer and its treatment were drawn from a semi-structured interview guide. All interviews were audio-recorded and transcribed verbatim, and codes were used to document and organize patient descriptions of their experiences. Coded concepts were defined, supported by exemplary patient quotes, and analyzed for frequency of mention and saturation. Five interviews with experienced oncologists were conducted to supplement the concept elicitation interviews. Results The average age of the patients was 66 years. Most (53%) self-identified as White/Caucasian; 40%, as Black/African American. Patients were reported to have metastases to bone (87%), liver (20%), lung (13%), skin (7%), and lymph nodes (7%). The most frequently reported disease-related concepts were fatigue and lump in breast (47% each) and pain (40%), while the most frequently reported treatment-related side effects were hair loss (67%), fatigue/tiredness (47%), and nausea (40%). Patients identified 10 concepts associated with both breast cancer and its treatment, including fatigue/tiredness, shortness of breath, weakness, and nausea. The most frequently reported impacts on physical function included working around home (73%), walking (73%), and cooking (53%). The most frequently reported symptoms and side effects from the expert perspective included fatigue, pain, and hot flashes (n = 5 each, 100%), while the ability to work (n = 5, 100%) and walk (n = 3, 60%) were reported impacts, aligning with those concepts reported by patients. The resulting concepts were organized into a patient-based conceptual model. Conclusions Patients have varied experiences due to HR+/HER2- advanced breast cancer and its treatment, and commonly experience fatigue/tiredness, hair loss, general pain, lump in breast, and nausea, as well as impacts to physical functioning (specifically, activities of daily living and mobility). Electronic supplementary material The online version of this article (10.1186/s41687-019-0098-1) contains supplementary material, which is available to authorized users.

Objective Pantothenate kinase‐associated neurodegeneration (PKAN) is an autosomal‐recessive, neurodegenerative disorder with a mixed‐motor phenotype caused by a defective PanK2 enzyme, for which there are few adequate treatment options. Clinimetrically sound measures of patient‐reported outcomes are necessary to facilitate therapeutic development for this debilitating disease. This study's objective was to develop such a scale and assess its clinimetric properties. Methods A conceptually driven, iterative, content development process incorporating input from experts, caregivers, and patients was used. Scale items were initially adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) Part II resulting in the 12‐item Pantothenate Kinase‐Associated Neurodegeneration Activities of Daily Living (PKAN‐ADL). The PKAN‐ADL scale was administered to caregivers (n = 37) and patients (n = 2) twice over 2 weeks, along with selected Quality of Life in Neurological Disorders (Neuro‐QoL) measures, selected attributes of the Health Utilities Index (HUI)‐2/3, and the Stroke Aphasia Depression Questionnaire (SADQ‐10) to assess construct validity. Results Internal consistency was 0.93, with excellent test‐retest reliability (intraclass correlation coefficient = 0.99). Of the 12 items, 25% (n = 3) showed a ceiling effect >30% (range, 31–54) and 42% (n = 5) showed a floor effect >30% (range, 31–46), reflecting disease heterogeneity. Convergent validity was shown with Neuro‐QoL measures (rs > 0.90) and HUI‐2/3 attributes (rs ≥ 0.48); divergent validity was demonstrated with the SADQ‐10 (r = 0.11). Participants reported a high level of comprehension (98%), and average item relevance ratings (0–10 scale) ranged from 7.0 to 9.9. Conclusion The PKAN‐ADL scale demonstrated acceptable content validity, with evidence of construct validity and excellent reliability. Overall results support the use of the PKAN‐ADL scale in clinical trials.

Objective: To characterize the impact of TX-001HR on the relationship between vasomotor symptom (VMS) improvement and quality of life and sleep. Methods: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial, which evaluated four daily doses of 17β-estradiol and progesterone (E2/P4) combined in a single, oral, softgel capsule in postmenopausal women (40-65 years) with a uterus and moderate to severe VMS (≥7/day or ≥50/week). In post hoc analyses, growth models were used to examine relationships between linear changes in VMS frequency and severity over 12 weeks and changes from baseline in the Menopause-Specific Quality of Life (MENQOL; total score and VMS domain) and the Medical Outcomes Study-Sleep (total score, sleep problems indices I and II) questionnaire outcomes at 12 weeks with treatment compared with placebo. Results: Outcomes with all four E2/P4 doses were combined (n = 591) and compared with placebo (n = 135). In all 5 growth models, the effects of TX-001HR on MENQOL total score and vasomotor domain were significantly associated with changes in VMS frequency and severity observed over 12 weeks (all, P

Background The EORTC QLU-C10D is a multiattribute utility measure derived from the cancer-specific quality-of-life questionnaire, the EORTC QLQ-C30. The QLU-C10D contains 10 dimensions (physical, role, social and emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems). The objective of this study was to develop a United States value set for the QLU-C10D. Methods A US online panel was quota recruited to achieve a representative sample for sex, age (≥18 y), race, and ethnicity. Respondents undertook a discrete choice experiment, each completing 16 choice-pairs, randomly assigned from a total of 960 choice-pairs. Each pair included 2 QLU-C10D health states and duration. Data were analyzed using conditional logistic regression, parameterized to fit the quality-adjusted life-year framework. Utility weights were calculated as the ratio of each dimension-level coefficient to the coefficient for life expectancy. Results A total of 2480 panel members opted in, 2333 (94%) completed at least 1 choice-pair, and 2273 (92%) completed all choice-pairs. Within dimensions, weights were generally monotonic. Physical functioning, role functioning, and pain were associated with the largest utility weights. Cancer-specific dimensions, such as nausea and bowel problems, were associated with moderate utility decrements, as were general issues such as problems with emotional functioning and social functioning. Sleep problems and fatigue were associated with smaller utility decrements. The value of the worst health state was 0.032, which was slightly greater than 0 (equivalent to being dead). Conclusions This study provides the US-specific value set for the QLU-C10D. These estimated health state scores, based on responses to the EORTC QLQ-C30 questionnaire, can be used to evaluate the cost-utility of oncology treatments.

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

Research in gastroparesis hinges on validated outcome measures. This chapter will focus on patient reported outcome measures and survey instruments, so that the readers will be aware of common outcome measures used in gastroparesis clinical trials and be familiar with the options should they choose to initiate investigation in this field.

Objective: The aim of the study was to evaluate the clinically meaningful effect of oral TX-001HR (17β-estradiol [E2]/progesterone [P4]) capsules on hot flushes severity (vasomotor symptoms [VMS] severity scale) using the patient-reported Clinical Global Impression (CGI). Methods: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR in postmenopausal women (40-65 y) with a uterus. Those with frequent moderate to severe hot flushes (≥7/d or ≥50/wk) were randomized in a VMS substudy to daily E2/P4 (1/100, 0.5/100, 0.5/50, or 0.25/50 mg/mg), or placebo. Patients rated VMS severity from 1 (mild) to 3 (severe) and symptom improvements with the CGI. CGI results were an anchor in a nonparametric discriminant analysis to define clinically important differences (CIDs) and minimal CID in VMS severity at weeks 4 and 12. Results: In the VMS substudy (n = 726), determined CID and minimal CID severity thresholds were reductions of 0.525 and 0.350 points at week 4, respectively, and 0.775 and 0.225 points at week 12. Significantly more women taking the two highest E2/P4 doses (1/100 and 0.5/100) versus placebo met CID severity thresholds at weeks 4 (40% and 44% vs 17%; P

Introduction The Neuro-QoL is a standardized approach to assessing health-related quality of life in people with neurological conditions, including multiple sclerosis (MS). Item banks were developed with item response theory (IRT) methodology so items are calibrated along a continuum of each construct. The purpose of this study was to develop a preference-based scoring algorithm for the Neuro-QoL to derive utilities that could be used in economic modeling. Methods With input from neurologists, 6 Neuro-QoL domains were selected based on relevance to MS and used to define health states for a utility elicitation study in the United Kingdom. General population participants and individuals with MS valued the health states and completed questionnaires (including Neuro-QoL short forms). The Neuro-QoL Utility Scoring System (NQU) was derived based on multi-attribute utility theory using data from the general population sample. Single-attribute disutility functions for 6 Neuro-QoL domains were estimated using isotonic regression with linear interpolation and then combined with a multiplicative model. NQU validity was assessed using MS participant data. Results Interviews were completed with 203 general population participants (50.2% female; mean age = 45.0 years) and 62 participants with MS (62.9% female; mean age = 46.1 years). Mean (SD) NQU scores were 0.94 (0.06) and 0.82 (0.13) for the general population and MS samples, respectively. The NQU demonstrated known-groups validity by differentiating among subgroups categorized based on level of disability. The NQU demonstrated convergent validity via correlations with generic measures (0.66 and 0.63 with EQ-5D-5L and Health Utilities Index Mark 3, respectively; both P < 0.001). Discussion With the NQU, utilities can be derived from any MS treatment group, subgroup, or patient sample who completes items from 6 Neuro-QoL domains. Because the Neuro-QoL is frequently used with MS patients, the NQU greatly expands the options for quantifying outcomes in cost-utility analyses conducted to inform allocation of resources for MS treatment.

Hormonal therapies effectively reduce the frequency and severity of vasomotor symptoms (VMS) in menopausal women; however, whether the effect is clinically meaningful to women is typically not determined. Oral estradiol/progesterone (E2/P4; mg/mg) 1/100 and 0.5/100 significantly improved moderate to severe VMS versus placebo at weeks 4 and 12. The objective of these analyses was to determine the clinical importance (meaningfulness) of E2/P4 treatment versus placebo in menopausal women. REPLENISH, a phase 3, randomized, double-blind, placebo-controlled trial, evaluated the safety and efficacy of E2/P4 oral capsules in symptomatic, postmenopausal women with a uterus. Clinically meaningful reductions in weekly VMS frequency were determined using 3 patient-reported outcomes as anchors (VMS severity score, clinical global impression [CGI], and question 1 from the vasomotor domain of the menopause-specific quality of life questionnaire). The proportion of women who had a clinically important response with 0.5/100 was compared with placebo using the Fisher’s exact test. Spearman correlations were also performed across the 3 anchors. Clinically meaningful reductions in weekly VMS frequency ranged from 32 to 43 at week 4, and from 32 to 48 at week 12. Significantly more responders were observed with 0.5/100 than with placebo for all 3 anchors at both weeks 4 (all, P Treatment with E2/P4 0.5/100 provided consistent clinically meaningful improvements in the weekly frequency of moderate to severe VMS in menopausal women, similar to what has been observed with the CGI-anchor for E2/P4 1/100.

Screening, diagnosis, and management of hypoactive sexual desire disorder (HSDD) and research into the condition have been challenging due to its biopsychosocial complexity and lack of consensus on relevant measures. Although physician interviews yield much clinically valid information, self-reported questionnaires appear more acceptable to patients and physicians. Consequently, validated patient-reported outcome (PRO) tools are essential for evaluation and management of HSDD, including any therapeutic intervention. The US Food and Drug Administration (FDA) has issued guidance on the use of appropriate endpoints and associated measures for female sexual dysfunction, including HSDD. Although many of the available measures were not designed specifically for HSDD assessment, as per FDA guidelines, most clinical studies have used individual domains or items from established tools, such as the Female Sexual Function Index-desire domain and Item 13 of the revised Female Sexual Distress Scale. For clinical practice, several professional societies recommend the Decreased Sexual Desire Screener and/or a sexual history as tools to diagnose HSDD. This review discusses frequently used PRO tools as well as the newly developed and validated Elements of Desire Questionnaire, which may be appropriate for clinical trials or clinical practice.

Introduction: The primary objective of the study was to evaluate the measurement properties of the patient-reported four-item Psoriasis Symptom Scale (PSS).Methods: Analysis of phase-III data on th...

Background. Health-related quality of life (HRQL) preference-based scores are used to assess the health of populations and patients and for cost-effectiveness analyses. The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS®) consists of patient-reported outcome measures developed using item response theory. PROMIS is in need of a direct preference-based scoring system for assigning values to health states. Objective. To produce societal preference-based scores for 7 PROMIS domains: Cognitive Function–Abilities, Depression, Fatigue, Pain Interference, Physical Function, Sleep Disturbance, and Ability to Participate in Social Roles and Activities. Setting. Online survey of a US nationally representative sample ( n = 983). Methods. Preferences for PROMIS health states were elicited with the standard gamble to obtain both single-attribute scoring functions for each of the 7 PROMIS domains and a multiplicative multiattribute utility (scoring) function. Results. The 7 single-attribute scoring functions were fit using isotonic regression with linear interpolation. The multiplicative multiattribute summary function estimates utilities for PROMIS multiattribute health states on a scale where 0 is the utility of being dead and 1 the utility of “full health.” The lowest possible score is –0.022 (for a state viewed as worse than dead), and the highest possible score is 1. Limitations. The online survey systematically excludes some subgroups, such as the visually impaired and illiterate. Conclusions. A generic societal preference-based scoring system is now available for all studies using these 7 PROMIS health domains.

Background The clinical course of ulcerative colitis (UC) and the effects of treatment are assessed through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Ulcerative Colitis Patient-Reported Outcomes Signs and Symptoms (UC-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of UC in clinical trials through direct report from patient ratings. Design The UC-PRO/SS was developed by collecting data from concept elicitation (focus groups, and individual interviews), then refined through a process of cognitive interviews of 57 UC patients. Measurement properties, including item-level statistics, scaling structure, reliability, and validity, were evaluated in an observational, four-week study of adults with mild to severe UC (N = 200). Results Findings from qualitative focus groups and interviews identified nine symptom items covering bowel and abdominal symptoms. The final UC-PRO/SS daily diary includes two scales: Bowel S&S (six items) and Abdominal Symptoms (three items), each scored separately. Each scale showed evidence of adequate reliability (α = 80 and 0.66, respectively); reproducibility (intraclass correlation coefficient = 0.81, 0.71) and validity, including moderate-to-high correlations with the Partial Mayo Score (0.79; 0.45) and Inflammatory Bowel Disease Questionnaire (IBDQ) total score (− 0.70; − 0.61). Scores discriminated by level of disease severity, as defined by the Partial Mayo Score, Patient Global Rating, and Clinician Global Rating (p

Daisy Ng-Mak,1 Jiat-Ling Poon,2 Laurie Roberts,2 Leah Kleinman,2 Dennis A Revicki,2 Krithika Rajagopalan1 1Global Health Economics and Outcomes Research, Sunovion Pharmaceuticals Inc., Marlborough, MA, 2Patient-Centered Research, Evidera, Bethesda, MD, USA Purpose: The purpose of this study was to assess patient preferences regarding pharmacological treatment attributes for bipolar depression using a discrete choice experiment (DCE).Methods: Adult members of an Internet survey panel with a self-reported diagnosis of bipolar depression were invited via e-mail to participate in a web-based DCE survey. Participants were asked to choose between hypothetical medication alternatives defined by attributes and levels that were varied systematically. The six treatment attributes included in the DCE were time to improvement, risk of becoming manic, weight gain, risk of sedation, increased blood sugar, and increased cholesterol. Attributes were supported by literature review, expert input, and results of focus groups with patients. Sawtooth CBC System for Choice-Based Conjoint Analysis was used to estimate the part-worth utilities for the DCE analyses.Results: The analytical sample included 185 participants (50.8% females) from a total of 200 participants. The DCE analyses found weight gain to be the most important treatment attribute (relative importance =49.6%), followed by risk of sedation (20.2%), risk of mania (13.0%), increased blood sugar (8.3%), increased cholesterol (5.2%), and time to improvement (3.7%).Conclusion: Results from this DCE suggest that adults with bipolar depression considered risks of weight gain and sedation associated with pharmacotherapy as the most important attributes for the treatment of bipolar depression. Incorporating patient preferences in the treatment decision-making process may potentially have an impact on treatment adherence and satisfaction and, ultimately, patient outcomes. Keywords: bipolar depression, treatment preference, adverse events, weight gain

OBJECTIVE The objective of this study was to evaluate the measurement properties of the Migraine Physical Function Impact Diary (MPFID), a novel patient-reported outcome (PRO) measure for assessing the impact of migraine on physical functioning. METHODS In a prospective, observational study, adults with episodic migraine (EM) or chronic migraine (CM) used an eDiary to complete the MPFID (assessing daily impacts of migraine on physical function) and a headache diary (capturing migraine days, migraine pain intensity, and migraine interference) each day, and other PRO instruments related to migraine. Item-level evaluation, item response theory (IRT), and exploratory factor analysis (EFA) methods were applied to identify domains, select final MPFID items, and develop scoring procedures. Psychometric properties of the final 13-item MPFID were evaluated using confirmatory factor analysis and tests of reliability (Cronbach's α for internal consistency and intra-class correlation [ICC] for test-retest) and validity (convergent and known-groups). RESULTS The study enrolled 569 adults with chronic or episodic migraine, mean (SD) age 39.9 (12.0) years and 87.2% female. Item-level analyses based on interim data informed selection of a set of 13 items for the MPFID, through evaluation of floor/ceiling effects, item-to-item correlations, factor loadings, and IRT-based fit/misfit statistics. Two domain scores (EA: Impact on Everyday Activities; PI: Physical Impairment) and a global item score for impact on everyday activities were identified. EA and PI domains exhibited high internal consistency (α = 0.97; α = 0.93) and good test-retest reliability among stable subjects (ICCs = 0.74 and 0.77). Convergent validity was demonstrated by moderate correlations (r = ±0.50-0.68; P

Pain behaviors are important indicators of functioning in chronic pain; however, no self-reported pain behavior instrument has been developed for pediatric populations. The purpose of this study was to create a brief pediatric measure of patient-reported pain behaviors as part of the Patient-Reported Outcome Measurement Information System (PROMIS). A pool of 47 candidate items for this measure had been previously developed through qualitative research. In this study, youth with chronic pain associated with juvenile fibromyalgia, juvenile idiopathic arthritis, or sickle cell disease (ages 8-18 years) from 3 pediatric centers completed all 47 candidate items for development of the pain behavior item bank along with established measures of pain interference, depressive symptoms, fatigue, average pain intensity, and pain catastrophizing. Caregivers reported on sociodemographic information and health history. Psychometric properties of the pain behavior items were examined using an item response theory framework with confirmatory factor analysis and examination of differential item functioning, internal consistency, and test information curves. Results were used along with expert consensus and alignment with the adult PROMIS pain behavior items to arrive at an 8-item pediatric pain behavior short form, and all 47 items were retained in a calibrated item bank. Confirmatory factor analysis and correlations with validated measures of pain, pain interference, and psychosocial functioning provided support for the short form's reliability and validity. The new PROMIS pediatric pain behavior scale provides a reliable, precise, and valid measure for future research on pain behavior in school-aged children with chronic pain.

This series of articles, Standards for Clinical Trials in Male and Female Sexual Dysfunction, began with the discussion of a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for the selection of study population and study duration in male and female sexual dysfunction. The second article in this series discussed fundamental principles in development, validation, and selection of patient- (and partner-) reported outcome assessment. The third and present article in this series discusses selected aspects of sexual dysfunction that are that are unique to male sexual dysfunctions and relevant to the conduct of clinical trials of candidate treatments for men.

Background To evaluate the measurement properties (e.g., content validity, reliability, and ability to detect change) of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale in patients with active psoriatic arthritis (PsA). Methods One-on-one semi-structured qualitative interviews with adult patients with active PsA evaluated the content validity of FACIT-Fatigue. Quantitative measurement properties were evaluated using data from phase III tofacitinib randomized controlled trials (RCTs) in PsA: OPAL Broaden (NCT01877668) and OPAL Beyond (NCT01882439). Results Of 12 patients included in the qualitative study, 2 (17%) had mild, 8 (67%) had moderate, and 2 (17%) had severe PsA disease activity; 7 (58%) attributed fatigue to PsA, and 7 (58%) rated fatigue as important or extremely important. Most patients considered the FACIT-Fatigue items relevant to their PsA experience, and understood item content and response options as intended. In the psychometric analysis of RCT data, a second-order confirmatory factor model fit the data well (Bentler’s Comparative Fit Index ≥0.92). FACIT-Fatigue demonstrated good internal consistency (Cronbach’s coefficient α ≥ 0.90), test-retest reliability (Intraclass Correlation Coefficient ≥ 0.80) and a strong correlation with SF-36 Vitality (r > 0.80). A robust relationship between disease activity (based on Patient’s Global Assessment of Psoriasis and Arthritis) and FACIT-Fatigue was observed (effect sizes > 1.4), with clinically important difference for the FACIT-Fatigue total score estimated as 3.1 points, and the responder definition estimated as a 4-point improvement for FACIT-Fatigue total score. Conclusion Fatigue was confirmed to be an important symptom to patients with PsA, and FACIT-Fatigue was found to be a reliable and valid measure in this population. Electronic supplementary material The online version of this article (10.1186/s41687-019-0115-4) contains supplementary material, which is available to authorized users.