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 .

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.

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.

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.

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.

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.

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.

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.

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.

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.

Evaluation of the Content Validity and Cross-Cultural Validity of the Study Participant Feedback Questionnaire (SPFQ).

OBJECTIVES: The Study Participant Feedback Questionnaire (SPFQ) is a patient-completed tool designed to assess patient experiences and satisfaction with aspects associated with being involved in a clinical trial. Originally developed in oncology and among English-speaking participants, the aim of the current study was to evaluate the content and cross-cultural validity of the SPFQ in other indications and non-English-speaking countries. METHODS: Semi-structured qualitative telephone interviews were conducted with 80 participants across eight non-English-speaking countries (in Europe, South America and Asia) who had received an investigational medicinal product as part of a clinical trial in the past three years. Interviews comprised concept elicitation to identify concepts of importance to participants' trial experiences, and cognitive debriefing to assess understanding and perceived importance of SPFQ instructions, items and response options. RESULTS: Concept elicitation findings supported the content validity of the SPFQ. During cognitive debriefing, SPFQ instructions and the majority of items were well understood by participants. Participants generally considered the SPFQ items important to their clinical trial experience, albeit a handful of items assessed concepts that had not been experienced by trial participants or were redundant with other SPFQ items. The instructions, response options and recall period of the SPFQ were generally well understood. No country-level differences in understanding or importance were apparent. CONCLUSION: Study findings provide evidence for the content and cross-cultural validity of the SPFQ and support implementation of the SPFQ as a means of obtaining participant feedback across global development programmes in a variety of indications.

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.

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.

Patient-Centered Insights on Treatment Decision Making and Living with Acute Myeloid Leukemia and Other Hematologic Cancers.

Expectations relating to treatment and survival, and factors influencing treatment decisions are not well understood in adult patients with acute myeloid leukemia. This study analyzed combined findings from a targeted literature review with patient-reported information shared on YouTube to further understand patient perspectives in hematologic cancers and, in particular, acute myeloid leukemia. The targeted literature review included articles concerning patient (aged ≥ 18 years) experiences or perspectives in acute myeloid leukemia or other hematologic cancers. YouTube video selection criteria included patients (aged ≥ 60 years) with self-reported acute myeloid leukemia. In total, 26 articles (13 acute myeloid leukemia-specific and 14 other hematologic cancers, with one relevant to both populations) and 28 videos pertaining to ten unique patients/caregivers were identified. Key concepts reported by patients included the perceived value of survival for achieving personal and/or life milestones, the emotional/psychological distress of their diagnosis, and the uncertainties about life expectancy/prognosis. Effective therapies that could potentially delay progression and extend life were of great importance to patients; however, these were considered in terms of quality-of-life impact and disruption to daily life. Many patients expressed concerns regarding the lack of treatment options, the possibility of side effects, and how their diagnosis and treatment would affect relationships, daily lives, and ability to complete certain tasks. Both data sources yielded valuable and rich information on the patient experience and perceptions of hematologic cancers, in particular for acute myeloid leukemia, and its treatments. Further understanding of these insights could aid discussions between clinicians, patients, and their caregivers regarding treatment decisions, highlight outcomes of importance to patients in clinical studies, and ultimately, inform patient-focused drug development and evaluation.

Development and First Use of the Patient's Qualitative Assessment of Treatment (PQAT) Questionnaire in Type 2 Diabetes Mellitus to Explore Individualised Benefit-Harm of Drugs Received During Clinical Studies.

INTRODUCTION: Individualised benefit-harm assessments can help identify patient-perceived benefits and harms of a treatment, and associated trade-offs that may influence patients' willingness to use a treatment. This research presents the first use of a patient-reported outcome measure designed to assess patient-perceived benefits and disadvantages of drugs received during clinical studies. METHODS: The Patient's Qualitative Assessment of Treatment (PQAT) was developed in English and cognitively tested with US (n = 4) and Canadian (n = 3) patients with type 1 and type 2 diabetes mellitus (T2DM). The revised version of the PQAT comprises three qualitative open-ended questions focused on the benefits and disadvantages of treatment and reasons why patients would choose to continue/discontinue treatment. A final quantitative question asks patients to evaluate the balance between benefits and disadvantages using a 7-point scale. The revised version of the questionnaire was administered as an exploratory endpoint in a phase II clinical trial for a new injectable treatment for T2DM. Qualitative data were analysed using thematic analysis, and relationships between qualitative and quantitative data were identified. RESULTS: Patient-reported benefits of treatment administered during the clinical trial included clinical markers of efficacy and subjective markers. Disadvantages reported by patients were mainly related to drug adverse effects or to the mode of administration. Of the 57 patients completing the PQAT, 70.2% reported being willing to continue treatment, with 59.6% reporting that the benefits outweighed the disadvantages. The reported benefits of feeling better and improved energy levels were more likely to be associated with a more positive ratio (70% and 71.4%, respectively), while the disadvantages of fatigue, headaches, and stomach pain were associated with a negative ratio and patients not being willing to continue the treatment. CONCLUSIONS: The PQAT is a unique patient-reported outcome tool designed to aid understanding patients' real experience of benefits and disadvantages of a treatment. It combines the richness of qualitative data with quantitative data-information valuable for various stakeholders to make well-informed treatment decisions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02973321.

Exploring the Impact of Infusion Frequency in Hemophilia A: Exit Interviews with Patients Participating in BAY 94-9027 Extension Studies (PROTECT VIII).

INTRODUCTION: Prophylactic treatment of severe hemophilia A is burdensome, requiring frequent intravenous injections. Extended half-life (EHL) factor VIII replacement therapies offer longer intervals between infusions while still meeting efficacy and safety outcomes; however, patient perspectives following long-term use of such products in the real-world remain unknown. OBJECTIVE: We aimed to explore the importance of infusion frequency and the potential benefits of reduced infusion frequency among patients receiving prophylactic treatment with an EHL product (BAY 94-9027). METHODS: Patients with severe hemophilia A participating in the PROTECT VIII extension study were invited to participate in a semi-structured, concept elicitation 'exit' interview to discuss their experiences. Participants were recruited from Israel, The Netherlands, and the US. Interview transcripts were translated into English and analyzed using thematic analysis methods. RESULTS: Sixteen participants (29-68 years of age) infusing with BAY 94-9027 once every 7 days, once every 5 days, or twice weekly were interviewed. Participants reported infusion frequency (alongside efficacy) as the most important treatment attribute influencing their satisfaction with therapy. Patient-reported benefits of reduced infusion frequency and longer duration of factor coverage included greater ability to participate in physical activities; better vein health; less time to schedule and administer factor VIII; reduced impact on work; and improved emotional well-being. CONCLUSIONS: This study provides rich insights into the experiences of patients with EHL products and the value of reduced infusion frequency. Such data could be of value to a range of stakeholders (e.g. regulators, payers) and facilitate patient-clinician discussions to promote tailored treatment decisions.

The Potential Role of Individual-Level Benefit-Risk Assessment in Treatment Decision Making: A DIA Study Endpoints Community Workstream.

Benefit-risk assessment is the cornerstone of decision making in medical care, playing a critical role in bringing treatments to market by informing decisions regarding drug development, licensing and reimbursement, and informing treatment decisions made by health care professionals and patients in clinical practice. In regulatory approval decision making, benefit and risk attributes are identified and defined based on available, aggregated clinical data from registration trials. In the context of major developments in recent years for involvement of patients as partners in all phases of drug development and in health care improvement, decision makers increasingly recognize the importance of informing treatment decisions by patient needs, values, experiences, and preferences. Using this as a basis, a DIA workstream was convened to explore the potential of individual-level benefit-risk assessment as a supplement to traditional group-level benefit-risk assessment for evaluating treatment. Various approaches as to how this information could be collected, including via patient-reported outcome measures, open-ended questioning, and stated-preference methods are presented. The utility of this information for various stakeholders is discussed.