Development of a Conceptual Model for the Patient Experience of Immunoglobulin A Nephropathy (IgAN): A Qualitative Literature Review.

INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is a kidney disorder that can lead to progressive kidney disease. Currently, there lacks a comprehensive overview of the symptoms and impacts experienced by those living with IgAN that would help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in clinical trials. The aim of this study was to develop a conceptual model of the adult and pediatric patient experience of IgAN, including disease signs and symptoms, treatment side effects, and impact on functioning and well-being. METHODS: This study comprised a systematic review and thematic analysis of qualitative studies with adults and children diagnosed with IgAN. Data sources were identified through an electronic database search of journal articles (MEDLINE, Embase, PsycINFO; June 2021), hand-searching of conference proceedings, patient advocacy group websites, and gray literature. Non-English articles were excluded. Identified data (patient/caregiver quotes, author summaries, and interpretations of patient experiences) were extracted from articles. Extracted data were qualitatively analyzed, aided by ATLAS.ti v7. Codes were applied to data; concepts (i.e., symptoms) were identified, named, and refined. A conceptual model was developed by grouping related concepts into domains. RESULTS: In total, five sources were identified for analysis: two journal articles, two online anthologies of patient stories, and one patient organization-sponsored "Voice of the Patient" meeting report. Conceptual model symptom domains included swelling/puffiness (edema), pain/aches/discomfort, fatigue, weight gain, sleep problems, urinary problems, and gastrointestinal problems. Impact domains included emotional/psychological well-being, physical functioning/activities of daily living, social functioning, work/school, and relationships. CONCLUSIONS: Secondary analysis of published qualitative literature permitted development of a novel conceptual model depicting the patient experience of IgAN; however, its depth is limited by a lack of available literature. Further qualitative research is recommended to refine and/or confirm the concepts and domains, determine any relationships between them, and explore the outcomes that are most meaningful to patients. The refined model will provide a useful tool to inform the selection, development, and/or amendment of COAs for use in future IgAN clinical trials.

Development of a Conceptual Model for the Patient Experience of Focal Segmental Glomerulosclerosis (FSGS): A Qualitative Targeted Literature Review.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease and can progress to end stage kidney disease (ESKD). An overview of symptoms and impacts of the disease experienced will help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in FSGS clinical trials. This study aimed to develop a conceptual model (CM) of the adult and pediatric patient experience of FSGS including disease signs/symptoms, treatment side-effects, and impact on functioning and wellbeing. METHODS: This study comprised a systematic review and thematic analysis of qualitative studies with adults and pediatric patients diagnosed with FSGS. Data sources were identified through an electronic database search of journal articles (Medline, Embase, PsycINFO; June 2021) and hand-searching of conference proceedings, patient advocacy group websites, and gray literature. Non-English articles were excluded. Identified data (patient/caregiver quotes, author summaries, and interpretations of patient experiences) were extracted from the articles. Extracted data were qualitatively analyzed aided by ATLAS.ti v7. Codes were applied to data and concepts (symptoms/impacts) were identified, named, and refined. A CM was developed by grouping related concepts into domains. RESULTS: In total, 12 sources were identified for analysis: 6 journal articles and 6 series of patient testimonials. Salient sign/symptom/side-effect domains included swelling/puffiness (edema), pain/aches/discomfort, fatigue, weight changes, skin problems, respiratory problems, and sleep problems. Salient impact domains included emotional/psychological wellbeing, physical functioning/activities of daily living, social functioning, and work/school. CONCLUSION: Secondary analysis of published qualitative literature permitted development of a CM describing the adult and pediatric experience of FSGS. Concept elicitation interviews are recommended to refine the CM, confirm the salient/most bothersome concepts, and confirm the extent of impact on daily life. The refined CM will provide a useful tool to inform the selection, development, and/or amendment of COAs for use in future FSGS clinical trials.

Efficacy and Safety of the TYK2/JAK1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial.

OBJECTIVE: Brepocitinib is a TYK2/JAK1 inhibitor in development for the treatment of several immunologic diseases. The efficacy and safety of oral brepocitinib were assessed in participants with moderately-to-severely active psoriatic arthritis (PsA) for up to 52 weeks. METHODS: In this placebo-controlled, dose-ranging, phase IIb study, participants were randomized to receive 10 mg, 30 mg, or 60 mg of brepocitinib once daily or placebo, advancing to 30 mg or 60 mg of brepocitinib once daily at week 16. The primary endpoint was the response rate according to the American College of Rheumatology criteria for 20% improvement (ACR20) in disease activity at week 16. Secondary endpoints included response rates according to the ACR50/ACR70 response criteria, 75% and 90% improvement in the Psoriasis Area and Severity Index (PASI75/PASI90) score, and minimal disease activity (MDA) at weeks 16 and 52. Adverse events were monitored throughout the study. RESULTS: Overall, 218 participants were randomized and treated. At week 16, the brepocitinib 30 mg and 60 mg once daily groups had significantly greater ACR20 response rates (66.7% [P = 0.0197] and 74.6% [P = 0.0006], respectively), versus the placebo group (43.3%), and significantly higher ACR50/ACR70, PASI75/PASI90, and MDA response rates. Response rates were maintained or improved through week 52. Adverse events were mostly mild/moderate; serious adverse events (15) in 12 participants (5.5%) included infections in 6 participants (2.8%) in the brepocitinib 30 mg and 60 mg once daily groups. No major adverse cardiovascular events or deaths occurred. CONCLUSION: Treatment with brepocitinib at dosages of 30 mg and 60 mg once daily was superior to placebo at reducing signs and symptoms of PsA. Brepocitinib was generally well tolerated throughout the 52-week study, with a safety profile consistent with those found in other brepocitinib clinical trials.

A Review of Labeling Based on Patient-Reported Outcome Endpoints for New Oncology Drugs Approved by the European Medicines Agency (2017-2021).

OBJECTIVE: A review of new oncology indications approved by the European Medicines Agency (EMA) for 2012-2016 showed that 33% of new drugs had labeling based on patient-reported outcomes (PROs). We reviewed labeling text based on PRO endpoints for new oncology indications approved during 2017-2021. METHODS: New oncology drugs approved by EMA to treat indications of cancers during 2017-2021 were identified from the EMA website. PRO-related language reported in EMA summaries of product characteristics (SmPCs) were summarized and compared with similar findings reported for oncology indications approved during 2012-2016. RESULTS: Review documents by the EMA during 2017-2021 were available for 49 new oncology drugs for 70 cancer indications. Submissions for 52 (74.3%) of the 70 indications included PRO data for EMA review. Of all submissions, 14 (20.0%) approvals contained PRO-related language in the SmPC. Broad concepts such as health-related quality of life were most common and found in 8 of 14 (57.1%) PRO-related labels. CONCLUSION: PRO-related language appeared in SmPCs for 20% of all indications of new oncology drugs approved by EMA during 2017-2021 compared with approximately 33% of EMA approvals during 2012-2016. PRO-related labeling during the same periods showed a greater decline (from 47% to 27%) for indications of new oncology drugs that also included PRO data. One possible reason for this decline may be the increase in open-label studies from 62% between 2012 and 2016 to approximately 79% between 2017 and 2021.

Validation of the Alopecia Areata Patient Priority Outcomes (AAPPO) Questionnaire in Adults and Adolescents with Alopecia Areata.

INTRODUCTION: Individuals with alopecia areata (AA) may experience significant impacts on their health-related quality of life. The novel Alopecia Areata Patient Priority Outcomes (AAPPO) questionnaire has been developed to assess hair loss signs, emotional symptoms, and activity limitations associated with AA. The objective of this study was to evaluate psychometric properties and establish scoring of the AAPPO in adults and adolescents with AA. METHODS: Scoring and measurement properties of the AAPPO were examined using baseline and 2-week follow-up data from a prospective, noninterventional, web-based study of 121 patients with AA (85 adults aged ≥ 18 years, 36 adolescents aged 12-17 years) with Severity of Alopecia Tool (SALT) ≥ 25% scalp hair loss. RESULTS: Exploratory and confirmatory factor analysis supported four single Hair Loss (HL) items, an Emotional Symptoms domain (ES; 4 items), and an Activity Limitations domain (AL; 3 items). Among all patients, the multi-item ES and AL domains had strong internal consistency (α ≥ 0.87); all HL items and domain scores had strong test-retest reliability (weighted kappa or intraclass correlation coefficients ≥ 0.78). All HL item scores demonstrated strong construct validity (r ≥ 0.52) compared with the patient-reported Alopecia Areata Symptom and Impact Scale (AASIS) hair loss subscale score; ES and AL domain scores exhibited strong construct validity (r ≥ 0.66) compared with the SF-36 Mental Component Summary (MCS) score. Using SALT scores, HL mean item scores were better (lower) in the 25-49% SALT subgroup versus those with highest SALT scores (76-100%); however, ES mean domain scores were better in the SALT 76-100% subgroup in the same comparison (p < 0.0001). Using AASIS and MCS score-created subgroups, ES and AL mean domain scores demonstrated hypothesized differences across subgroups (all p values < 0.0001). CONCLUSION: The AAPPO questionnaire is a reliable, valid disease-specific measure of hair loss severity and impact in individuals with AA.

Voice Analysis of Cancer Experiences Among Patients With Breast Cancer: VOICE-BC.

Patient experience literature in early-stage breast cancer (eBC) is limited. This study used a mixed-methods approach to examine patient conversations from public online forums to identify and evaluate eBC-related themes. Among 60,000 eBC-related posts published September 2014-2019, text from a random subset of 15,000 posts was extracted and grouped into linguistically similar, mutually exclusive clusters using an advanced natural language processing (NLP) algorithm. Clusters were characterized using four quantitative metrics: betweenness centrality (linguistic similarity to other areas of the cluster network), sentiment (general attitude toward a topic), recency (average date of posts), and volume (total number of posts). This analysis represented 3906 unique users (67% and 33% obtained from cancer-specific and general health/nonhealth forums, respectively). Of the 27 clusters identified, most important were "discussing recurrence & progression," "understanding diagnosis & prognosis," and "understanding cancer, biomarkers, and treatments." Several major themes related to recurrence risk, diagnosis, monitoring, and treatment were identified. Additional emphasis on communicating the disease recurrence risk and shared decision-making could strengthen patient-clinician partnerships.

Patient Perspectives of the Social, Emotional and Functional Impact of Alopecia Areata: A Systematic Literature Review.

INTRODUCTION: Alopecia areata (AA) is a chronic, autoimmune disease of hair loss, which can significantly affect the emotional and psychological well-being of patients. A systematic literature review was conducted to better understand the burden of AA from the patient perspective. METHODS: Embase, MEDLINE and Cochrane databases were searched for published studies (2008-2018) reporting on assessments of health-related quality of life (HRQoL) for patients with AA. Qualitative, and quantitative data were collected. RESULTS: The review included 37 studies encompassing a range of clinical outcome assessment (COA) tools. None of the COA tools were specific for AA, and only one study used the Hairdex scale, which was designed to evaluate HRQoL in patients with disorders of the hair and scalp. All studies reported substantial impact on HRQoL due to AA, both overall and in domains related to personality (i.e. temperament and character), emotions and social functioning. Acute stress was also noted, and several studies identified lack of emotional awareness (alexithymia) in 23-50% of the patients with AA. CONCLUSIONS: Although it is well-established that patients with AA experience anxiety and depression, they also experience a decrease in HRQoL in many other areas, including personality, emotions, behaviors and social functioning, and these changes may be accompanied by acute stress and alexithymia. There is a need to achieve consensus on a core set of measures for AA and to develop and validate AA-specific measurement tools for use in future studies, to attain a clearer understanding of the impact of AA on patients. TRIAL REGISTRATION: PROSPERO registration number; CRD42019118646.

STUDY DESIGN: We reviewed published studies to better understand how AA affected people socially, emotionally and in their day-to-day functioning. We also looked at how healthcare providers measured these social, emotional and day-to-day effects on people with AA. Our review included 37 published studies that used several evaluation tools to measure the impacts of AA. These included a variety of questionnaires that were answered by people with AA. RESULTS: The studies reported that AA negatively affected the personality, emotions, behaviors and/or social functioning of many people with AA. However, none of the evaluation tools that were used in those studies were specific for AA, and most of the evaluation tools did not include questions about the hair or scalp. CONCLUSIONS: We recommend that a group of people familiar with AA (practitioners, researchers and patients) work together to develop an evaluation tool that is designed specifically for people with AA. This evaluation tool can then be used in future studies to better understand how AA affects people socially, emotionally and in their day-to-day functioning.

Alopecia areata (AA) is a disease in which a person's immune system attacks their hair follicles, from which hairs grow, causing hair loss. Studies have shown that people with AA may have a lower quality of life, and studies have reported higher rates of depression and anxiety in people with AA than in people without AA.

Development of the Alopecia Areata Patient Priority Outcomes Instrument: A Qualitative Study.

INTRODUCTION: Although alopecia areata (AA) profoundly impacts patients' physical appearance, emotional state, and daily activities, no treatment approved for AA currently exists. Patient-reported outcome (PRO) instruments currently used to capture patients' AA experiences do not meet the requirements to support claims of treatment benefit as described in the US Food and Drug Administration's 2009 PRO guidance. Our objective was to explore the consequences and priority treatment outcomes among individuals with AA and develop a PRO measure consistent with regulatory requirements that assesses these priorities and represents clinical benefit from the AA patient perspective. METHODS: Targeted literature and instrument reviews informed an initial concept set. Concept elicitation interviews with 20 adults with AA confirmed the relevance and importance of the initial concepts, identified additional relevant concepts, and informed an AA consequence model. Thematic analysis yielded a draft item pool, which was evaluated through two iterative rounds of cognitive debriefing interviews with 16 patients with AA (9 adults; 7 adolescents). RESULTS: Hair loss was the primary consequence of importance to patients with AA. Patients emphasized the need to differentiate hair loss by location: scalp, eyebrows, eyelashes, and body. Consequences of AA include difficulty conducting daily activities, particularly outdoor activities and exercise, and emotional impacts such as sadness, frustration, and negative self-image. Following cognitive debriefing interviews, 11 items were included to form the Alopecia Areata Patient Priority Outcome (AAPPO), assessing AA-related symptoms and impacts over the past week. CONCLUSIONS: The AAPPO is a novel, content-valid PRO that captures the consequences of AA of the highest priority to patients.

The Patient Experience with Soft Tissue Sarcoma: A Systematic Review of the Literature.

BACKGROUND: Soft tissue sarcomas (STS) are a heterogenous group of rare tumors that involve the connective tissue in the body (e.g. muscle, tendons). As with many rare tumors, little is known about the impact of STS on patient well-being. OBJECTIVE: The aim of this review was to better understand current knowledge related to patient experience and quality of life (QOL) following diagnosis of STS. METHODS: A systematic review of English-language articles published from 2005 to 2015 was conducted in the PubMed/MEDLINE, Embase, PsychINFO, and Evidence-Based Medicine databases. The review included recent conference proceedings and advocacy websites. Articles were eligible if they included adult STS patient-reported outcomes (PROs) or details on patient experience. RESULTS: Overall, 3430 articles were identified and 20 were eligible for inclusion. Of these, 14 were clinical studies that included PRO measures, 1 summarized PRO measures used in STS studies, and 5 described the STS patient experience. Patients with STS report a range of impacts on QOL, including emotional well-being, body image, functional deficit following surgery, and practical considerations such as child care and work. CONCLUSIONS: Few studies have published either qualitative or quantitative data on the patient experience with STS. While STS has a measurable impact on QOL, there is a lack of detailed information in the published literature. Although PROs are used in clinical studies of STS, they are not STS-specific and may not capture the unique needs of this population. There is a need for qualitative research to better understand both patient and caregiver experiences in STS.

Patient-Reported Outcomes in Latin America: Implementation in Research and Role in Emerging HTA Systems.

BACKGROUND: Patient-reported outcomes (PROs) are increasingly used to demonstrate the value of interventions and support health technology assessment (HTA). OBJECTIVE: The objective of this work was to analyze trends regarding PROs in Latin America (LatAm), highlight challenges in the application of PROs in this region, and suggest solutions. METHODS: A team of researchers with expertise in PROs conducted a nonsystematic PubMed literature search pertaining to the use of PROs in LatAm. The experts also drew on their experience working with PROs to assess the application of PROs in LatAm. RESULTS: The literature search yielded more than 4000 publications, with an increasing publication rate in recent years. PROs are being used in LatAm in various study types: instrument validation, phase III international clinical trials, health service research. A large Inter-American Development Bank study demonstrates the growing importance of PROs in the region. The growth in local value sets for the EuroQol five-dimensional questionnaire in LatAm reflects the regional emergence of HTA systems. Operational challenges relate to ensuring the use of good-quality questionnaires that, at a minimum, have undergone appropriate cultural adaptation and ideally have established psychometric properties. CONCLUSIONS: PROs are increasingly important in LatAm. Future efforts should aim to strengthen the operational and research infrastructure around PROs in the region. Innovation should be encouraged, including studying alternative methods of eliciting health utilities for economic evaluation. A wider scope around PRO uses for decision making by HTA bodies is an international trend with potential positive prospects in LatAm.

Proposing a standardized method for evaluating patient report of the intensity of dyspnea during exercise testing in COPD.

BACKGROUND: Measuring dyspnea intensity associated with exercise provides insights into dyspnea-limited exercise capacity, and has been used to evaluate treatment outcomes for chronic obstructive pulmonary disease (COPD). Three patient-reported outcome scales commonly cited for rating dyspnea during exercise are the modified Borg scale (MBS), numerical rating scale for dyspnea (NRS-D), and visual analogue scale for dyspnea (VAS-D). Various versions of each scale were found. Our objective was to evaluate the content validity of scales commonly used in COPD studies, to explore their ability to capture patients' experiences of dyspnea during exercise, and to evaluate a standardized version of the MBS. METHODS: A two-stage procedure was used, with each stage involving one-on-one interviews with COPD patients who had recently completed a clinic-based exercise event on a treadmill or cycle ergometer. An open-ended elicitation interview technique was used to understand patients' experiences of exercise-induced dyspnea, followed by patients completing the three scales. The cognitive interviewing component of the study involved specific questions to evaluate the patients' perspectives of the content and format of the scales. Results from Stage 1 were used to develop a standardized version of the MBS, which was then subjected to further content validity assessment during Stage 2. RESULTS: Thirteen patients participated in the two-stage process (n = 6; n = 7). Mean forced expiratory volume in 1 second (FEV(1)) percent predicted was 40%, mean age 57 years, and 54% were male. Participants used a variety of terms to describe the intensity and variability of exercise-induced dyspnea. Subjects understood the instructions and format of the standardized MBS, and were able to easily select a response to report the level of dyspnea associated with their recent standardized exercise. CONCLUSION: This study provides initial evidence in support of using a standardized version of the MBS version for quantifying dyspnea intensity associated with exercise in patients with COPD.

Capturing patients' perspectives of treatment in clinical trials/drug development.

The patient's perspective of treatment outcomes is increasingly important to consumers and providers of healthcare. Recent studies have shown that traditional clinical endpoints may not accurately reflect the patient experience with treatment. Often patients' experience of their disease and associated treatment differs from the perspective of their physicians. When implemented with a clear and effective assessment strategy, patient-reported outcome (PRO) measures can be used to collect data directly from patients in the clinical setting. These data can be applied to a range of outcomes, such as treatment efficacy, safety, and patient satisfaction. Such information is valuable at various stages of drug development and can be used to understand the patient's perspective of the treatment for evaluating the treatment benefit of new products and to engage patients to make decisions about treatment options and ultimately to support commercialization of pharmaceutical products. Recognizing the value of these data, various regulatory agencies have recently released guidelines on how to best implement these measures in clinical trials to support label claims. The purpose of this paper is to discuss the benefits of collecting PRO data for evaluating the outcomes of treatments in clinical trials, through the product life cycle.

Development of the EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): a patient-reported outcome (PRO) measure.

BACKGROUND: This article describes the qualitative methods used to develop the EXAcerbation of Chronic Pulmonary Disease Tool (EXACT), a new patient-reported outcome (PRO) instrument for evaluating frequency, severity, and duration of exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: Focus groups and interviews were conducted in the United States with COPD patients treated for exacerbations during the past 6 months. Participants were asked to describe exacerbation attributes, care-seeking cues, and indications of progression and recovery. An iterative process was used to identify themes in the data to inform instrument content and structure. Cognitive debriefing interviews were performed to evaluate and revise the draft item pool. Experts in COPD, instrument development, and clinical research participated in the process. RESULTS: Eighty-three subjects participated in elicitation focus groups or interviews (n=48); elicitation interviews with cognitive debriefing (n=23), or cognitive interviews alone (n=12). Mean age of the sample was 65 years (SD=10); 45% were male; mean FEV-1% predicted was 44% (SD=16). Participants characterized exacerbations as a persistent increase in the severity of respiratory symptoms and other systemic manifestations accompanied by a dramatic reduction in activity. Specific attributes included shortness of breath, chest congestion, cough, sputum, chest discomfort, feeling weak or tired, sleep disturbances, and concern or worry. The diary card of 23 candidate items was debriefed in booklet and electronic format. CONCLUSIONS: Qualitative data from patients and input from experts formed the basis of the EXACT's structure and item pool, ready for empirically based item reduction and reliability and validity testing.