Burosumab Improves Patient-Reported Outcomes in Adults With Tumor-Induced Osteomalacia: Mixed-Methods Analysis.

Tumor-induced osteomalacia (TIO) is an ultra-rare disease caused by tumors that secrete fibroblast growth factor 23, leading to chronic hypophosphatemia, poor skeletal health, and impaired physical function. In a phase 2 trial (UX023T-CL201; NCT02304367; n = 14), 48 weeks of burosumab treatment restored phosphate homeostasis, with improvements in skeletal health, functional mobility, and patient-reported pain, fatigue, and health-related quality of life (HRQL) (SF-36 v2). Here, we report an exploratory mixed-methods analysis of change from baseline after 144 weeks of burosumab treatment alongside qualitative data from exit interviews with 8 of 14 trial participants to evaluate meaningful treatment effects from a patient perspective. The interview subset (n = 8) reported pain and fatigue and compromised HRQL at baseline. In the interviews, participants reported that compromised HRQL and pain were the most important aspects of the disease to treat; both were considered more bothersome than fatigue and compromised physical function and activities of daily living. Improvements in pain and fatigue after treatment were reported, some of which achieved statistically and/or clinically meaningful thresholds. Furthermore, improvements in SF-36 v2 scores were most pronounced in the Physical Component Score and its Physical Function and Bodily Pain domains. Overall, the interview subset provided descriptions of symptomatic improvement and its clinical meaningfulness, including physical function, participation in activities of daily living, and mental well-being. Thus, this exploratory mixed-methods analysis provides deeper understanding of patients' perception of clinical meaningfulness beyond that articulated in validated patient-reported outcome instruments. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Caregiver-reported clinical characteristics and the burden associated with Kabuki syndrome.

Kabuki syndrome is a genetic disorder that can affect multiple body systems and manifest as congenital abnormalities and both developmental and socio-emotional delays. The condition is largely unknown by most primary care physicians and has no available treatment other than symptomatic management. This research sought to obtain caregiver-reported data about the experience of living with and caring for someone with Kabuki syndrome to fill a gap in the available literature. Fifty-seven caregivers participated in an online survey and reported that Kabuki syndrome affected their children in a wide variety of ways, including a high frequency of visits to various healthcare professionals. Caregivers reported their child experienced problems with hearing, eating, eyes, mouth, immune system, anxiety, depression, autism, teeth, joints, seizures, kidneys, and heart. Caregivers also described the challenges of caring for someone with Kabuki syndrome, including an impact on emotional well-being and the ability to work outside the home. This unique research characterizes the caregiver experience of living with and caring for someone with Kabuki syndrome, both through observed manifestations of Kabuki syndrome in their own children and their experience managing their treatment. Additional research is needed to investigate the patient experience of living with Kabuki syndrome.

Development of the pyruvate kinase deficiency diary and pyruvate kinase deficiency impact assessment: Disease-specific assessments.

INTRODUCTION: Currently recommended patient-reported outcome (PRO) measures for patients with pyruvate kinase (PK) deficiency are non-disease-specific. The PK Deficiency Diary (PKDD) and PK Deficiency Impact Assessment (PKDIA) were developed to be more targeted measures for capturing the symptoms and impacts of interest to this patient population. METHODS: The instruments were developed based on concept elicitation interviews with 21 adults and modified based on 20 cognitive interviews. The domain structure and item concepts of the PKDD and PKDIA were compared with currently recommended measures, the EORTC QLQ-C30 and the SF-36v2®. RESULTS: The PKDD is a seven-item measure of the core signs and symptoms of PK deficiency. The PKDIA is a 14-item measure of the impacts of PK deficiency on patients' health-related quality of life (HRQoL). Minimal similarities were found between the new measures and the EORTC QLQ-C30 (eg, 43% of concepts were similar to the PKDD; 42% were similar to the PKDIA) and SF-36v2® (57% of concepts were similar to the PKDD; 17% were similar to the PKDIA). CONCLUSIONS: The PKDD and PKDIA fill a gap in the existing outcomes measurement strategy for PK deficiency. Future work includes psychometric evaluation of these newly developed measures.

The burden of disease in pyruvate kinase deficiency: Patients' perception of the impact on health-related quality of life.

OBJECTIVES: This study explored how signs and symptoms of pyruvate kinase (PK) deficiency, a rare hemolytic anemia caused by mutations in the PKLR gene, impacts patients' health-related quality of life (HRQoL). METHODS: Interviews with 21 adults with PK deficiency in the United States, Netherlands, and Germany were conducted. Participants were asked to describe signs, symptoms, and impacts of the disease on their daily lives. Interviews were transcribed and analyzed using qualitative analysis methods. RESULTS: The most common signs and symptoms reported were yellow eyes (n = 19), tiredness (n = 18), yellow skin (n = 17), fatigue (n = 15), low energy (n = 13), and shortness of breath (n = 13). Furthermore, signs and symptoms of PK deficiency negatively impact the ability to perform physical activities, appearance, social activities, emotional states, activities of daily living, leisure activities, work and/or school, sleep, and cognitive states of those living with PK deficiency. A conceptual model is presented that further demonstrates the profound impact that signs and symptoms of PK deficiency have on dimensions of patients' HRQoL. CONCLUSIONS: This is the first study that provides patient perspective on the burden of living with PK deficiency and lays the foundation for future studies to examine the effect of pharmacologic interventions on overall HRQoL for patients living with PK deficiency.

Development of an overactive bladder assessment tool (BAT): A potential improvement to the standard bladder diary.

AIMS: To develop a comprehensive patient-reported bladder assessment tool (BAT) for assessing overactive bladder (OAB) symptoms, bother, impacts, and satisfaction with treatment. METHODS: Subjects were consented and eligibility was confirmed by a recruiting physician; subjects were then scheduled for in-person interviews. For concept elicitation and cognitive interviews, 30 and 20 subjects, respectively, were targeted for recruitment from US sites. All interviews were conducted face-to-face, audio-recorded, transcribed verbatim, anonymized, and analyzed using a qualitative data analysis software program. A draft BAT was created based on the results of the concept elicitation interviews and further revised based on cognitive interviews as well as feedback from an advisory board of clinical and patient-reported outcome (PRO) experts. RESULTS: Nocturia, daytime frequency, and urgency were reported by all subjects (n = 30, 100.0%), and incontinence was reported by most subjects (n = 25, 83.3%). The most frequently reported impacts were waking up to urinate (n = 30, 100.0%), embarrassment/shame (n = 24, 80.0%), stress/anxiety (n = 23, 76.7%), and lack of control (n = 23, 76.7%). Following analysis, item generation, cognitive interviews, and advisory board feedback, the resulting BAT contains four hypothesized domains (symptom frequency, symptom bother, impacts, and satisfaction with treatment) and 17 items with a 7-day recall period. CONCLUSIONS: The BAT has been developed in multiple stages with input from both OAB patients and clinical experts following the recommended processes included in the FDA PRO Guidance for Industry. Once fully validated, we believe it will offer a superior alternative to use of the bladder diary and other PROs for monitoring OAB patients in clinical trials and clinical practice.