Comparing patient global impression of severity and patient global impression of change to evaluate test-retest reliability of depression, non-small cell lung cancer, and asthma measures.

PURPOSE: Score reproducibility is an important measurement property of fit-for-purpose patient-reported outcome (PRO) measures. It is commonly assessed via test-retest reliability, and best evaluated with a stable participant sample, which can be challenging to identify in diseases with highly variable symptoms. To provide empirical evidence comparing the retrospective (patient global impression of change [PGIC]) and current state (patient global impression of severity [PGIS]) approaches to identifying a stable subgroup for test-retest analyses, 3 PRO Consortium working groups collected data using both items as anchor measures. METHODS: The PGIS was completed on Day 1 and Day 8 + 3 for the depression and non-small cell lung cancer (NSCLC) studies, and daily for the asthma study and compared between Day 3 and 10. The PGIC was completed on the final day in each study. Scores were compared using an intraclass correlation coefficient (ICC) for participants who reported "no change" between timepoints for each anchor. RESULTS: ICCs using the PGIS "no change" group were higher for depression (0.84 vs. 0.74), nighttime asthma (0.95 vs. 0.53) and daytime asthma (0.86 vs. 0.68) compared to the PGIC "no change" group. ICCs were similar for NSCLC (PGIS: 0.87; PGIC: 0.85). CONCLUSION: When considering anchor measures to identify a stable subgroup for test-retest reliability analyses, current state anchors perform better than retrospective anchors. Researchers should carefully consider the type of anchor selected, the time period covered, and should ensure anchor content is consistent with the target measure concept, as well as inclusion of both current and retrospective anchor measures.

Patients' and clinicians' perspectives on item importance, scoring, and clinically meaningful differences for the Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS).

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.

Understanding the Patient Experience of Severe, Recurrent, Bilateral Nasal Polyps: A Qualitative Interview Study in the United States and Germany.

OBJECTIVES: To qualitatively explore patient experiences of severe, recurrent, bilateral nasal polyps (NP). METHODS: A targeted literature review of published qualitative studies and online blogs describing patient experiences of NP was conducted. Semistructured concept elicitation interviews were conducted in the United States and Germany with participants ≥18 years with severe, recurrent, bilateral NP to explore their symptom experience and impacts on health-related quality of life (HRQoL; NCT03221192). A subset of 10 participants reported symptoms and impacts using a smartphone or tablet application (app) over a 10-day period. RESULTS: A paucity of qualitative evidence regarding patient experience of NP was identified from the literature or blog review. Twenty-seven participant interviews were conducted. Thirty-six symptoms were identified, including 7 primary symptoms (nasal congestion [n = 27 of 27], breathing difficulties [n = 27 of 27], postnasal drip [n = 25 of 27], runny nose [n = 24 of 27], head/facial pressure [n = 23 of 27], loss of smell [n = 23 of 27], loss of taste [n = 22 of 27]) and 29 secondary symptoms (the most common were mucus/catarrh and nose bleeds [both n = 20 of 27]). Most symptoms were reported to vary both within and between days. Sixty impacts of severe NP were reported, including impacts on sleep (n = 22 of 27), physical functioning (n = 21 of 27), activities of daily living (n = 21 of 27), emotional well-being (n = 27 of 27), treatment (n = 23 of 27), social life (n = 26 of 27), and work (n = 19 of 27). Symptoms/impacts reported using the app were consistent with interview findings, although new symptoms were identified (ear pain, throat pain, nasal scabs, and nasal burning). These results supported the development of a conceptual model outlining concepts related to symptoms, impacts, and treatment of NP. CONCLUSIONS: Severe, recurrent, bilateral NP are associated with a range of symptoms that have significant detrimental impact on HRQoL.

Fatigue, treatment satisfaction and health-related quality of life among patients receiving novel drugs suppressing androgen signalling for the treatment of metastatic castrate-resistant prostate cancer.

Clinical studies have demonstrated the benefits of abiraterone acetate + prednisone (AAP) and enzalutamide (ENZ) in significantly improving survival among metastatic castration-resistant prostate cancer (mCRPC) patients. However, evidence regarding patient's real-world experience, particularly with respect to fatigue, treatment satisfaction and health-related quality of life (HRQoL) is limited. Interviews were initially conducted with patients (n = 38) and carers (n = 12) to elicit qualitative data regarding their experiences. Findings informed the design of a quantitative, multinational online survey of mCRPC patients (n = 152) receiving AAP or ENZ. Participants completed validated questionnaires assessing fatigue (Brief Fatigue Inventory), treatment satisfaction (Cancer Therapy Satisfaction Questionnaire) and HRQoL (EuroQol-5-Dimensions). Results indicated that patients were generally satisfied with these therapies, more specifically with reductions in prostate-specific antigen levels and extended survival. Fatigue was commonly linked to poor HRQoL and responses indicated that significantly fewer patients in the AAP group reported feeling usually tired or fatigued in the last week compared to the ENZ group (33% vs. 55%, p = 0.006 respectively). Findings highlight the benefit of AAP and ENZ in promoting the "quality" of extended survival. That fatigue was lower among patients receiving AAP may be important for informing treatment decisions. Further research is needed to gain deeper insights.

Assessing Asthma Symptoms in Adolescents and Adults: Qualitative Research Supporting Development of the Asthma Daily Symptom Diary.

BACKGROUND: Despite the widespread availability of patient-reported asthma questionnaires, instruments developed in accordance with present regulatory expectations are lacking. To address this gap, the Patient-Reported Outcome (PRO) Consortium's Asthma Working Group has developed a patient-reported asthma daily symptom diary (ADSD) for use in clinical research to assess outcomes and support medical product labeling claims in adults and adolescents with asthma. OBJECTIVES: To summarize the qualitative research conducted to inform the initial development of the ADSD and to provide evidence for content validity of the instrument in accordance with the Food and Drug Administration's PRO Guidance. METHODS: Research informing the initial development and confirming the content validity of the ADSD is summarized. This comprised a review of published qualitative research, semi-structured concept elicitation interviews (n = 55), and cognitive interviews (n = 65) with a diverse and representative sample of adults and adolescents with a clinician-confirmed diagnosis of asthma in the United States to understand the asthma symptom experience and to assess the relevance and understanding of the newly developed ADSD. RESULTS: From the qualitative literature review and concept elicitation interviews, eight core asthma symptoms emerged. These were broadly categorized as breathing symptoms (difficulty breathing, shortness of breath, and wheezing), chest symptoms (chest tightness, chest pain, and pressure/weight on chest), and cough symptoms (cough and the presence of mucus/phlegm). Conceptual saturation was achieved and differences in the experience of participants according to socio-demographic or clinical characteristics were not observed. Subsequent testing of the ADSD confirmed participant relevance and understanding. CONCLUSIONS: The ADSD is a new patient-reported asthma symptom diary developed in accordance with the Food and Drug Administration's PRO Guidance. Evidence to date supports the content validity of the instrument. Item performance, reliability, and construct validity will be assessed in future quantitative research.

The humanistic, economic and societal burden of herpes zoster in Europe: a critical review.

BACKGROUND: Herpes zoster (HZ) or "shingles" is common in persons aged 50 years or over. HZ is characterised by a painful dermatological rash which typically resolves in approximately one month. Persistent pain for months or years after rash onset, however, is a common complication of HZ; referred to as post-herpetic neuralgia (PHN). Both HZ and PHN have a significant impact on patients' lives, with considerable implications for healthcare systems and wider society. The aim of the present review is to provide comprehensive documentation and critical appraisal of published data concerning the humanistic, economic and societal burden of HZ in Europe. METHODS: Systematic literature searches were conducted in Medline, EMBASE, PsycINFO, EconLit, HEED and CRD databases. Searches were conducted in July 2014 and restricted to articles published in the past 20 years. Articles were selected for full review by two independent researchers in accordance with predefined eligibility criteria. RESULTS: From a review of 1619 abstracts, 53 eligible articles, were identified which reported data concerning healthcare resource use (n = 38), direct costs (n = 20), indirect costs (n = 16), total costs (n = 10) and impact on health-related quality of life (HRQoL) (n = 21). Findings highlight that PHN is associated with greater impairments in HRQoL and higher costs of management than HZ. For both HZ and PHN, pain severity is a significant predictor of impact on individuals, healthcare systems and society. While the incidence of HZ and PHN increase with age, age does not appear to be a key driver of overall costs for HZ and PHN. Specifically, while direct costs (e.g. GP, specialists, medications, hospitalisations) tend to be higher for older patients, indirect costs (e.g. work time missed) are higher for younger patients. CONCLUSIONS: Available evidence highlights that HZ and PHN result in significant humanistic and economic burden for patients, healthcare systems and wider societies. A tendency to focus upon healthcare resource use and the direct costs of management at the expense of other impacts (e.g. informal caregivers and formal social care) may result in an underestimation of the true burden of HZ and PHN.

Burden of herpes zoster in the UK: findings from the zoster quality of life (ZQOL) study.

BACKGROUND: Herpes zoster (HZ) is a painful condition that can have a substantial negative impact on patients' lives. However, UK-specific data on the debilitating impact of HZ, in terms of patients' experience of pain and impairments in Health-Related Quality of Life (HRQoL) are limited. The Zoster Quality of Life (ZQOL) study, a large-scale UK cross-sectional study, was conducted to quantify the burden of HZ in UK patients. METHODS: A total of 229 HZ patients aged 50 years or over were recruited from primary and secondary/tertiary care centres throughout the UK. Patients completed a battery of validated questionnaires, including the Zoster Brief Pain Inventory (ZBPI), the Medical Outcomes Study Short-Form 36 (SF-36) and the EuroQol-5 Dimensions (EQ-5D) on initial presentation to the doctor and again 7-14 days later. At follow-up patients also completed the Treatment Satisfaction with Medication (TSQM) questionnaire. Where available, mean questionnaire scores in the HZ population were compared to scores for age-matched norms to investigate the burden associated with HZ. RESULTS: Pain was prominent among patients, with 57.9% at the initial study visit reporting pain in the preceding 24 hours at levels typically considered to have a significant impact on HRQoL (i.e. ZBPI worst pain ≥ 5). This was reflected in SF-36 and EQ-5D scores that were significantly lower for patients when compared to age-matched norms (p < 0.05) - except for the SF-36 domain of physical functioning. HRQoL was inversely associated with levels of reported pain, with those patients in the greatest amount of pain reporting the greatest HRQoL impact. However, there was no association between pain severity and participant age. The majority of patients (69.4%) received antivirals within 72 hours of rash appearing and 69.9% of patients were also taking analgesics for the management of HZ pain. TSQM scores indicated that patients were least satisfied with the effectiveness of their prescribed treatment. CONCLUSIONS: The acute presentation of HZ is a painful experience that can have a significant impact on the physical and mental wellbeing of sufferers. Findings highlight significant unmet need among patients, particularly in terms of the effectiveness of therapies for the management of HZ.

Burden of post-herpetic neuralgia in a sample of UK residents aged 50 years or older: findings from the Zoster Quality of Life (ZQOL) study.

BACKGROUND: Post-herpetic neuralgia (PHN) is the most common complication of herpes zoster (shingles). As a chronic condition, PHN can have a substantial adverse impact on patients' lives. However, UK-specific data concerning the burden of PHN on individual patients, healthcare systems and wider society, are lacking. As the first UK-wide cross-sectional study of its kind, The Zoster Quality of Life (ZQOL) study was designed to address these concerns. METHODS: Patients (n = 152) with a confirmed diagnosis of PHN (defined as pain persisting ≥ 3 months following rash onset) and aged ≥50 years were recruited from primary and secondary/tertiary care centres throughout the UK. All patients completed validated questionnaires, including the Zoster Brief Pain Inventory (ZBPI), the Medical Outcomes Study Short-Form 36 (SF-36), the EuroQol-5 Dimensions (EQ-5D) and the Treatment Satisfaction with Medication (TSQM) questionnaire. Where available, mean patient population scores on these questionnaires were compared to scores derived from age-matched normative samples to quantify the burden associated with PHN. RESULTS: Despite numerous consultations with healthcare professionals and receiving multiple medications for the management of their PHN, the majority of patients reported being in pain 'most of the time' or 'all of the time'. A total of 59.9% (n = 91) of all PHN patients reported pain in the preceding 24 hours to assessment at levels (ZBPI worst pain ≥ 5) typically considered to have a significant impact on Health Related Quality of Life (HRQoL). Accordingly, scores for SF-36 and EQ-5D indicated significant deficits in HRQoL among PHN patients compared to age-matched norms (p < 0.05) and patients reported being dissatisfied with the perceived efficacy of therapies received for the management of PHN. Increased pain severity was observed among older participants and higher levels of pain severity were associated with greater HRQoL deficits. CONCLUSIONS: The inadequate relief provided by PHN therapies available in the UK is associated with a significant burden among PHN patients in terms of pain severity and deficits in HRQoL which may persist for years. Therefore, alternative means such as prevention of shingles and PHN, are essential for reducing the impact on individual patients, healthcare systems and society as a whole.

Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and muscle weakness can cause impaired physical function, significantly impacting patients' health-related quality of life (HRQoL). Loss of muscle strength is usually assessed through clinical and performance outcome (PerfO) assessments, which consists of tasks performed in a standardized manner, providing evidence of a patient's functional ability. However, evidence documenting the patient experience of COPD and muscle weakness is limited. METHODS: This two-stage qualitative study used semi-structured interviews in patients aged 45-80 years with COPD (post-bronchodilator forced expiratory volume in 1s [FEV1]/forced vital capacity ratio < 0.70, and FEV1% predicted of 30-80%) and muscle weakness. In Stage 1, 30-minute concept elicitation interviews were conducted with participants recruited across three US sites to explore impacts on physical functioning and activities of daily living. In Stage 2, interviews were performed with participants exiting a Phase IIa trial investigating the efficacy of a selective androgen receptor modulator (GSK2881078) on leg strength, whereby PerfOs were used to evaluate strength and physical functioning endpoints. These participants completed either 60-minute in-depth (n = 32) or 15-minute confirmatory (n = 35) interviews exploring trial experience, completion of outcome measures, disease experience and treatment satisfaction. RESULTS: In Stage 1 (n = 20), most participants described their muscles as weak (83.3%). Difficulties with walking (100%) and lifting heavy objects (90%) were reported. In Stage 2, 60-minute interviews, all participants (n = 32) reported a positive trial experience. Most participants reported that the home exercise program was easy to fit into daily life (77.8%), the PROactive daily diary was easy to complete (100%) and wearable sensors were easy to use (65.6%). However, technical issues were reported (71%), and few participants (19.4%) found physical assessments easy to complete. Improvements in muscle strength and functional limitations were reported by most participants. The shorter 15-minute confirmatory interviews (n = 35) supported the in-depth interview results. CONCLUSION: The qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies. TRIAL NUMBER: GSK Stage 1: 206869; Stage 2: 200182, NCT03359473; Registered December 2, 2017, https://clinicaltrials.gov/ct2/show/NCT03359473 .

Development and Psychometric Validation of the 27 Item Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD-27).

BACKGROUND: Caring for an individual with Alzheimer's disease (AD) is an allencompassing challenge that affects daily life. Assessment of the care partner experience is needed to support the development and evaluation of successful interventions for people with AD and their care partners. We developed the 27-item Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD-27) to assess the impact of informal caregiving in the context of AD. OBJECTIVE: We assessed the psychometric validity of the ZCI-AD-27 in a population of care partners for individuals with moderate AD, and established thresholds for meaningful score change. METHODS: Secondary data were obtained from informal care partners of participants in a clinical trial (NCT01677754). Psychometric analyses were conducted to assess validity, reliability, and responsiveness of the ZCI-AD-27. Anchor-based and distribution-based methods were performed to determine clinically meaningful score change. RESULTS: The ZCI-AD-27 had a 12-domain factor structure, including a second-order domain termed Humanistic impact that included four key domains (Physical, Emotional, Social, and Daily life) as confirmed by confirmatory factor analysis with the adequate fit. Internal consistency (Cronbach's alpha ranging from 0.66 to 0.93 for domains), convergent validity, and discriminant validity indicated the good performance of the ZCI-AD-27. Known-groups validity analyses showed a greater impact on care partners with increasing disease severity. Responsiveness results demonstrated that the ZCI-AD- 27 is sensitive to change over time and meaningful change analyses indicated a range of meaningful score changes in this population. CONCLUSION: The ZCI-AD-27 is a comprehensive, psychometrically valid measure to assess the impact of caring for individuals with moderate AD.

Patient-Reported Outcome Measures for Severe Recurrent Bilateral Nasal Polyps: Psychometric Evaluation and Content Validity.

Objective: To date, no patient-reported outcome measures have been specifically developed to assess pharmacological treatment effect in participants with severe chronic rhinosinusitis (CRS) with recurrent bilateral nasal polyps (NP). These studies aimed to assess (1) the psychometric properties and (2) content validity of Visual Analogue Scales (VAS) assessing NP symptom severity. Study Design: (1) Retrospective psychometric validation study using clinical trial data and (2) cross-sectional qualitative patient interview study. Setting: (1) Multicentre trial; (2) real-world. Methods: (1) Psychometric validation was performed using data from a randomized, double-blind, placebo-controlled, Phase II study (NCT01362244) investigating the effect of mepolizumab in 105 participants with severe, recurrent bilateral NP currently needing polypectomy surgery. (2) Content validity was explored through cognitive debriefing interviews in 27 adults with severe CRS with recurrent bilateral NP who had received NP surgery in the past 10 years (NCT03221192). Results: (1) Acceptable reliability, validity, and responsiveness were shown for individual VAS items, although the loss of smell VAS item performed poorly in several analyses, suggesting further evaluation of this item is needed. (2) All individual VAS items were well understood, considered relevant and were consistently interpreted by most participants, providing evidence for their content validity. Conclusion: These findings support the use of symptom VAS measures to evaluate disease experience and treatment effect in clinical trials of participants with severe CRS with recurrent bilateral NP.

Measuring dengue illness intensity: Development and content validity of the dengue virus daily diary (DENV-DD).

BACKGROUND: Dengue is the most prevalent arboviral infection causing an estimated 50-60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel 'Dengue Virus Daily Diary (DENV-DD)', designed to measure symptom intensity and disease burden within outpatient infant to adult populations. METHODS: The Dengue Illness Index Report Card was used as a foundation to create the DENV-DD, consisting of patient- and observer-reported outcome (PRO/ObsRO) instruments. In two South American dengue-endemic communities, qualitative combined concept elicitation and cognitive debriefing interviews were conducted among individuals and caregivers of children with symptomatic laboratory-confirmed dengue. Interviews were conducted across two rounds allowing DENV-DD modifications. A small-scale quantitative assessment of the DENV-DD was also conducted with data from an independent Dengue Human Infection Model (DHIM) to generate early evidence of feasibility of DENV-DD completion, instrument performance and insight into the sign/symptom trajectory over the course of illness. RESULTS: Forty-eight participants were interviewed (20 adults, 20 older children/adolescents with their caregivers, 8 caregivers of younger children). A wide spectrum of signs/symptoms lasting 3-15 days were reported with fever, headache, body ache/pain, loss of appetite, and body weakness each reported by > 70% participants. DENV-DD instructions, items and response scales were understood, and items were considered relevant across ages. DHIM data supported feasibility of DENV-DD completion. CONCLUSIONS: Findings demonstrate content validity of the DENV-DD (PRO/ObsRO instruments) in dengue-endemic populations. Psychometric and cultural validity studies are ongoing to support use of the DENV-DD in clinical studies.

Dengue is the most common viral infection transmitted to humans by mosquitos, and affects an estimated 50­60 million individuals globally per year. However, there are few resources for understanding and capturing the patient experience of dengue throughout illness. Most research studies are based on healthcare provider assessment, which lack consistency in terms of assessment time points and the signs/symptoms assessed. The 'Dengue Illness Index Report Card (DII-RC)' was used as a foundation to create the new 'Dengue Virus Daily Diary (DENV-DD)' to better capture the patient experience of symptom intensity and dengue disease burden for the duration of illness. Forty-eight individuals and caregivers of younger children from Peru and Ecuador who recently had symptomatic dengue were interviewed to understand the patient experience over the time of illness and to test whether the DENV-DD is understood by patients and caregivers and includes all relevant and important signs/symptoms and health-related quality of life impacts. Nine individuals with active dengue infection also completed the DENV-DD daily for 28-days as part of a clinical study. We found that > 70% of patients experienced fever, headache, body ache/pain, loss of appetite and body weakness. The DENV-DD instructions, questions and response option(s) were well understood, feasible to complete and the concepts assessed by the DENV-DD were relevant to the dengue experience. Our study adds to the understanding of the dengue illness experience and supports the DENV-DD for use in future dengue studies as an assessment of signs/symptoms throughout the duration of illness.

Qualitative evaluation of the symptoms and quality of life impacts of long-chain fatty acid oxidation disorders.

BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare autosomal-recessive genetic disorders characterized by metabolic deficiencies in which the body is unable to convert long-chain fatty acids into energy. To date, however, there is limited understanding of the patient experience of LC-FAOD. METHODS: The symptoms, observable signs, and quality of life (QoL) impacts associated with LC-FAOD were explored via a focus group (n = 8) and semi-structured interviews (n = 6) with patients and caregivers of patients with LC-FAOD, and interviews (n = 4) with expert clinicians. Data were analyzed via thematic analysis and summarized in a conceptual model. RESULTS: Participants reported a wide range of signs and symptoms associated with LC-FAOD, broadly categorized as musculoskeletal, endocrine/nutritional/metabolic, neurological, gastrointestinal/digestive, sensory, cardiovascular, respiratory, urological, and constitutional. LC-FAOD were reported to have a significant impact on various aspects of patients' lives including physical functioning, participation in daily activities, emotional/psychological wellbeing, and social functioning. Lifestyle modifications (such as diet and exercise restrictions) were necessary because of the condition. Symptoms were typically episodic in presentation often arising or exacerbated during catabolic conditions such as prolonged exercise, fasting, physiological stress, and illness/infection. Symptoms were also commonly reported to lead to emergency room visits, hospitalization, and clinical complications. CONCLUSION: LC-FAOD have a considerable impact on patients' lives. There is a high degree of concordance in the signs, symptoms, and impacts of LC-FAOD reported by patients, caregivers, and clinicians; however, there were many symptoms and impacts that were only reported by patients and caregivers, thus demonstrating that insights from patient/caregiver experience data are integral for informing medical product development and facilitating patient-centered care.

Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD): Measurement Properties of Novel Patient-Reported Symptom Measures.

BACKGROUND: The Asthma Daytime Symptom Diary (ADSD) and the Asthma Nighttime Symptom Diary (ANSD) were developed to meet the need for standardized patient-reported measures of asthma symptoms to assess treatment trial outcomes in adults and adolescents. OBJECTIVE: To determine scoring and evaluate the measurement properties of the ADSD/ANSD. METHODS: Adolescents (12-17 years) and adults (18+ years) with asthma completed draft 8-item electronic versions of the ADSD/ANSD for 10 days alongside the Adult Asthma Symptom Daily Scales (AASDS) and a Patient Global Impression of Severity (PGIS). Using classical and modern psychometric methods, initial analyses evaluated the performance of ADSD/ANSD items to inform scoring. Subsequent analyses evaluated the reliability and validity of ADSD/ANSD scores. RESULTS: A demographically and clinically diverse sample (n = 130 adolescents; n = 89 adults) was recruited. Item performance was generally strong. However, items assessing chest pressure and mucus/phlegm demonstrated redundancy and poorer performance and were removed. Principal-components analysis, confirmatory factor analysis, and item response theory supported combining items to form 6-item total ADSD/ANSD scores. Internal consistency (α = 0.94-0.95) and test-retest reliability (intraclass correlation coefficient = 0.86-0.95) were strong. Strong correlations (r = 0.72-0.80) were observed between ADSD scores and AASDS items assessing asthma symptom frequency, bother, and impact on activities. Significant differences (P < .001) in mean ADSD/ANSD scores were observed between groups categorized by asthma severity (PGIS), asthma control, inhaler use, nebulizer use, activity limitations, and nighttime awakenings. CONCLUSIONS: The ADSD/ANSD items and scores demonstrated strong reliability and validity. Implementation of the measures in interventional studies will enable the evaluation of responsiveness and meaningful within-patient change.

Generation of evidence supporting the content validity of SF-36, FACIT-F, and LupusQoL, and novel patient-reported symptom items for use in patients with systemic lupus erythematosus (SLE) and SLE with lupus nephritis (LN).

OBJECTIVE: SLE and lupus nephritis (LN) have significant impacts on the health-related quality of life of patients living with the condition, which are important to capture from the patient's perspective using patient-reported outcomes (PROs). The objectives of this study were to evaluate the content validity of PROs commonly used in SLE and LN (36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Lupus Quality of Life (LupusQoL), as well as novel PRO symptom severity items measuring skin rash, joint pain, joint stiffness and swelling of the legs and/or feet, in both populations. METHODS: Qualitative, semi-structured, cognitive interviews were conducted with 48 participants (SLE=28, LN=20). Understanding and relevance of symptom and impact PRO concepts from existing PROs were assessed, alongside novel PRO symptom severity items with different recall periods (24 hours vs 7 days) and response scales (Numerical Rating Scale (NRS) vs Verbal Rating Scale). Interviews were conducted in multiple rounds to allow for modifications to the novel PRO items. Analysis of verbatim interview transcripts was performed. RESULTS: Symptom and impact concepts assessed by the SF-36, FACIT-F, and LupusQoL were well understood by both participants with SLE and LN (≥90.0%), with most considered relevant by over half of the participants asked (≥51.9%). All participants asked (100%) understood the novel PRO symptom severity items, and the majority (≥90.0%) considered the symptoms relevant. Minor modifications to the novel PRO items were made between rounds to improve clarity based on participant feedback. The selected 7-day recall period and NRS in the final iteration of the PRO items were understood and relevant. No differences in interview findings between the SLE and LN samples were identified. CONCLUSIONS: Findings provide evidence of content validity for concepts assessed by the SF-36, FACIT-F, LupusQoL and the novel PRO symptom severity items, supporting use of these PROs to comprehensively assess disease impact in future SLE and LN clinical trials.

Patient, Family Member and Physician Perspectives and Experiences with AML Treatment Decision-Making.

INTRODUCTION: Treatment decisions in older adults with acute myeloid leukemia (AML) are challenging, particularly for those who are not candidates for intensive chemotherapy (IC), and the trade-offs patients, their families and physicians consider when choosing a treatment option are not well understood. This qualitative research explored the value of extending survival and the treatment decision-making process from a multi-stakeholder perspective. METHODS: Overall, 28 patients with AML (≥ 65 years old, unsuitable for IC), 25 of their relatives and 10 independent physicians from the US, UK and Canada took part in one-on-one, 60-minute qualitative interviews. RESULTS: Across all stakeholders, improved health-related quality of life (HRQoL), extended survival and relief of AML symptoms were recognized as most important in AML treatment decision-making. However, extending survival in 'good health' was more important than extending survival alone, particularly because of the extra time it gives patients and their relatives together, and allows patients to achieve important goals. Patients' limited understanding of available treatment options, paired with incorrect perceptions of treatment side effects, impacted their involvement in the treatment decision-making process. Patients and physicians perceived physicians to have the most influence in the decision-making process despite their priorities not always aligning. CONCLUSION: These findings illustrate the importance of having structured discussions which explicitly assess patients' goals and their understanding and expectations of treatments and also the need for patient friendly resources about the lived experience of AML and available treatment options. These measures will help to ensure that patients are fully involved in the shared decision-making process.

Pain in castration-resistant prostate cancer with bone metastases: a qualitative study.

BACKGROUND: Bone metastases are a common painful and debilitating consequence of castration-resistant prostate cancer (CPRC). Bone pain may predict patients' prognosis and there is a need to further explore CRPC patients' experiences of bone pain in the overall context of disease pathology. Due to the subjective nature of pain, assessments of pain severity, onset and progression are reliant on patient assessment. Patient reported outcome (PRO) measures, therefore, are commonly used as key endpoints for evaluating the efficacy of CRPC treatments. Evidence of the content validity of leading PRO measures of pain severity used in CRPC clinical trials is, however, limited. METHODS: To document patients' experience of CRPC symptoms including pain, and their impact on health-related quality of life (HRQL), semi-structured in-depth qualitative interviews were conducted with 17 patients with CRPC and bone metastases. The content validity of the Present Pain Intensity (PPI) scale from the McGill Pain Questionnaire (MPQ), and the 'Average Pain' and 'Worst Pain' items of the Brief Pain Inventory Short-Form (BPI-SF) was also assessed. RESULTS: Patients with CRPC and bone metastases present with a constellation of symptoms that can have a profound effect on HRQL. For patients in this study, bone pain was the most prominent and debilitating symptom associated with their condition. Bone pain was chronic and, despite being generally well-managed by analgesic medication, instances of breakthrough cancer pain (BTcP) were common. Cognitive debriefing of the selected PRO measures of pain severity highlighted difficulties among patients in understanding the verbal response scale (VRS) of the MPQ PPI scale. There were also some inconsistencies in the way in which the BPI-SF 'Average Pain' item was interpreted by patients. In contrast, the BPI-SF 'Worst Pain' item was well understood and interpreted consistently among patients. CONCLUSIONS: Study findings support the importance of PRO measures of pain severity as key endpoints for evaluating the efficacy of treatments for CRPC, particularly for patients with bone metastases where episodes of BTcP are common. Qualitative evidence from CRPC patients supports the content validity of the BPI-SF ''Worst Pain' item and promotes use of this item for measuring pain severity in this population.

Development and Content Validation of Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) in Adolescents and Adults with Moderate-to-Severe AD.

INTRODUCTION: Most patient-reported outcome (PRO) instruments that measure atopic dermatitis (AD) symptoms do not have sufficient documented evidence of content validity to satisfy regulatory agency guidance for inclusion in product-labelling claims in the USA or Europe. The objective of this study was to develop a PRO instrument in accordance with regulatory agency guidance to assess daily AD symptoms during the course of therapy and to establish its content validity and psychometric properties. METHODS: The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) daily diary was developed based on qualitative interviews with US adolescents and adults with mild-to-severe AD. Content validity, test-retest reliability, internal consistency reliability, clinically important difference, clinically important responder, convergent validity, and known-group validity were evaluated using correlational and regression methods from phase 2b data from US adults with moderate-to-severe AD who were treated with abrocitinib. RESULTS: Patient interviews conducted with US adolescents and adults with mild-to-severe AD identified 11 relevant symptoms (itch, dryness, redness, flaking, discolouration, pain, bleeding, cracking, bumps, swelling, and weeping/oozing) for inclusion in the PSAAD instrument. All PSAAD psychometric parameters were acceptable based on phase 2b data from US adults with moderate-to-severe AD. Convergent validity and known-group validity were confirmed by significant correlations between PSAAD and six other PRO measures (r = 0.24-0.91, all p ≤ 0.01) and Dermatology Life Quality Index category (p ≤ 0.0001), respectively. CONCLUSIONS: Evidence supports the PSAAD instrument validity, reliability, responsiveness and definitions of clinically important changes/differences for adults with moderate-to-severe AD.

Development and content validation of two new patient-reported outcome measures for endometriosis: the Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS).

BACKGROUND: Endometriosis is a common, chronic, impactful condition in women of reproductive age. In the absence of established sensitive and specific biomarkers, disease severity is determined by patient-reported symptoms and impacts. This article details the development of two new patient-reported outcome (PRO) measures designed to assess efficacy endpoints in clinical studies: The Endometriosis Symptom Diary (ESD) and the Endometriosis Impact Scale (EIS). METHODS: The ESD and EIS were developed according to best practice and scientific standards (including the Food and Drug Administration (FDA) PRO Guidance) and with extensive input from women with surgically-confirmed endometriosis. Research included: a review of published qualitative literature; concept elicitation interviews in the US, Germany and France (n = 45) to explore the experiences of women with endometriosis and to inform ESD and EIS development; and cognitive interviews in the US and Germany (n = 31) to assess relevance and understanding of the ESD and EIS and usability of administration using an electronic handheld device. The FDA and the European Medicines Agency (EMA) as well as PRO and clinical experts were consulted throughout the process. RESULTS: Pelvic pain was identified as the most frequent, severe and bothersome symptom for women with endometriosis. Pain was reported to be greatest during menstruation (dysmenorrhea) and during or after sexual intercourse (dyspareunia). Pain resulted in significant impairments in physical activities, work/study, social/leisure activities, household activities and sexual functioning. All women highlighted the emotional impact of endometriosis. Descriptions of pain and associated impacts were largely consistent across participants from the US and Europe, with the most notable differences being the words used to describe the location of pain (e.g., 'pelvis' vs. 'abdomen'). Testing during cognitive interviews indicated that the ESD and EIS were well understood and consistently interpreted. Furthermore, all participants found the ePRO devices easy to use and no issues regarding visual presentation, selection of responses or navigation were identified. CONCLUSIONS: Evidence from extensive qualitative research supports the content validity of the ESD and EIS as patient-reported measures of the disease-defining symptoms of endometriosis and the associated impact on women's lives. Future research will seek to establish the measurement properties of the measures.

Content validity of patient-reported outcomes for use in lower-risk myelodysplastic syndromes.

BACKGROUND: The lower-risk (low and intermediate-1 risk based on IPSS) myelodysplastic syndrome (MDS) has a negative impact on patients' health-related quality of life (HRQoL). Patient Reported Outcomes (PROs) instruments, which are used to collect patients' HRQoL data, should have established content validity in the target population to ensure that the instrument is comprehensive and comprehensible. The present study was conducted to evaluate the content validity of the Quality of Life in Myelodysplasia Scale (QUALMS) and the Functional Assessment of Cancer Therapy-Anemia (FACT-An) PRO instruments in patients with lower-risk MDS. METHODS: In this cross-sectional, qualitative study, 16 patients aged ≥18 years with lower-risk MDS, who were RBC transfusion dependent, literate and fluent in US-English were interviewed. Interviews were semi-structured comprising of two parts: concept elicitation (CE) explored symptoms and impacts important to patients, and cognitive debriefing (CD) assessed understanding and relevance of the QUALMS and FACT-An. A conceptual model was developed, which was used to map the concepts that emerged during CE onto the QUALMS and FACT-An to assess concept coverage and suitability of the instruments. RESULTS: The median age of participants was 67.5 years (range: 51-91), with half being female (n = 8). Nine (56.2%) participants had intermediate-1-risk MDS and 10 (62.5%) were relapsed or refractory to erythropoiesis-stimulating agent treatment. Fatigue/tiredness (100.0%), shortness of breath (87.5%), weakness (81.2%), and low energy (75.0%) were reported most commonly and were the most bothersome symptoms as well. Of seven high-level HRQoL domains identified, activities of daily living (n = 16, 100.0%), physical functioning (n = 15, 93.8%), emotional wellbeing (n = 13, 81.3%), social functioning (n = 12, 75.0%), sleep disturbance (n = 9, 56.3%), and impact on work (n = 9, 56.3%) were the most commonly reported. For CD, the QUALMS and FACT-An were found to be mostly relevant and very well understood; response options were easy to use, and recall period was appropriate. CONCLUSION: Both QUALMS and FACT-An demonstrated a strong face and content validity in patients with lower-risk MDS, suggesting that these instruments are appropriate for assessing HRQoL in this population.