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Qualitative research methods can be used to obtain a deeper understanding of patient experience by collecting information in the patients' own words about their encounters, perspectives, and feelings. In this study, patients with schizophrenia were interviewed to capture their voice and to complement the quantitative data typically obtained in clinical trials. Semi-structured exit interviews were conducted with 41 patients who completed or prematurely discontinued from a phase 3, open-label trial (NCT02873208). The interview guide included open-ended questions on current and prior disease burden, symptoms, quality of life, and treatment experiences. Steps taken to reduce interview stress and secure the validity of data included interviewer sensitivity training specific to mental health conditions and schizophrenia, use of in-person interviews whenever possible and use of videoconferencing for remote interviews to promote trust and comfort, and working closely with clinical site staff to identify patient eligibility and willingness to participate. Transcripts based on audio recordings were content coded and analyzed using thematic analysis; a post-hoc quantitative content analysis was conducted. Patients reported that the symptoms of schizophrenia negatively impacted their work, relationships, self-esteem, emotional health, and daily activities. Most patients had positive experiences with medications that alleviated hallucinations, depression, and anxiety. However, side effects of medications were associated with negative impacts on physical, emotional, behavioral, and cognitive health. Lack of energy/drowsiness, weight gain, mood changes, and involuntary movements were the most common side effects reported with the use of antipsychotic medications. Patients reported unmet treatment needs related to better symptom control and to improved social and physical functioning. Collection of qualitative information within a schizophrenia clinical development process provides value and insights into patients' views on burden of illness, experiences with previous medications, and experiences following participation in a clinical trial and can inform design for future studies.

e13785 Background: Unprecedented cancer treatment efficacy has led to high rates of disease sequelae. Lancet recently declared the failure to care for the human dimensions of cancer treatment a "humanitarian crisis." To address this humanitarian crisis, real-world economic evidence can improve patient access to whole person care through insurance reimbursement policies. Methods: We implemented a virtual primary cancer survivor care clinic that follows ASCO and NCCN guidelines for cancer survivors with emphasis on mental health, nutrition, physical activity, and sleep optimization. Our clinic utilizes medical oncologists, physician associates, mental health therapists, registered dietitians, and occupational therapists. Patient reported outcomes (PRO) monitor health status and inform treatment pathways. To reduce test fatigue, we use the SF12 Vitality Enhanced scale (SF12v2). The SF12v2 measures physical functioning, activities of daily living, pain, vitality, social functioning, and mental health. Total medical expenditures (MEs) is the sum of payments for hospital inpatient events, emergency room visits, home care, prescribed medicines, office-based and out-patient visits, and medical equipment. Patient SF12v2 summary scores predict a patient's total MEs. A one-point better physical component summary score and mental component summary score are associated with 2% lower MEs; 3 and 5 point score increases are associated with 10% and 18% lower MEs. Results: Patients were referred from a Utah community oncology clinic, other medical clinics, or self-referred (N=99). The mean patient age was 52 years. 84% were female, 16% were male. At enrollment, 35% had started treatment, 21% were on post treatment aromatase therapy or adjuvant hormonal therapy, 65% were post treatment. Baseline PRO reveal significant disease burden: 82% report poor mental health; 72% report poor physical health; 79% report poor cognitive health; 83% report sleep disorders. For patients who completed at least three PRO measurement time points (n=54): 91% had a positive clinical outcome for mental health; 70% had a positive clinical outcome for physical health; 89% had a positive clinical outcome for cognitive health; 76% had a positive clinical outcome for sleep health. As a result of these extraordinary outcomes, 74% of patients had lower predicted MEs. The average predicted reduction in MEs was 16% with an average annual savings of $1,629.49. Conclusions: Cancer is associated with high disease sequelae and high MEs. We believe this is the first study that reports real-world clinical evidence and predicts MEs for patients enrolled in a virtual primary cancer survivor care clinic. Real-world evidence demonstrates both clinically significant improvements in HRQoL and reductions in patient MEs. These results can inform insurance reimbursement policies, ensuring equitable access to cancer survivor care.

BackgroundChildren with sickle cell disease (SCD) experience a multiplex of disease-related symptoms and complications, including vaso-occlusive crises (VOCs), episodes characterized by extreme pain.MethodsA cross-sectional observational survey examined the health-related quality of life (HRQoL) and school experiences of children with SCD 2 months–11 years, burden experienced by their caregivers, and associations between these outcomes and VOC frequency. Caregivers (N=167) of children with SCD in the US completed the Infant-Toddler Quality of Life-Short Form 47 (ITQoL-SF47) for children 2 months–4 years, the Child Health Questionnaire–Parent Form 50 (CHQ-PF50) and PROMIS Pain Interference and Sleep Disturbance Parent Proxy short forms for children 5–11 years, and a study-specific survey of school experiences.ResultsChildren with SCD 2 months–4 years had lower ITQoL-SF47 scores (ie, worse HRQoL, p<0.001) than a normative sample of children; across domains, differences ranged from 18.73–45.03 points and exceeded minimal important difference (MID) thresholds. Except for the behavior domain, children with SCD 5–11 years had lower scores on all CHQ-PF50 domains than the normative sample (p<0.001); differences ranged from 6.78–36.37 points and exceeded MID thresholds. Children with more frequent VOCs had lower HRQoL and worse school experiences than children with less frequent VOCs (p<0.05, except for behavior domains). The largest differences based on VOC frequency were observed for overall health and bodily pain/discomfort among children 2 months–4 years (differences=40.88 and 32.50 points, respectively), and bodily pain and role/social limitations due to physical health among children 5–11 years (differences=38.99 and 37.80, respectively). Caregivers of children with more frequent VOCs experienced greater burden than caregivers of children with less frequent VOCs, though specific areas of impact (eg, caregiver emotions, time) differed across child age groups.ConclusionVOC frequency is negatively associated with HRQoL, highlighting the burden experienced by children with SCD and their caregivers.

Systemic AL (light chain) amyloidosis is a rare protein misfolding disorder associated with plasma cell dyscrasia affecting various organs leading to organ dysfunction and failure. The Amyloidosis Forum is a public-private partnership between the Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research with the goal of accelerating the development of effective treatments for AL amyloidosis. In recognition of this goal, 6 individual working groups were formed to identify and/or provide recommendations related to various aspects of patient-relevant clinical trial endpoints. This review summarizes the methods, findings, and recommendations of the Health-Related Quality of Life (HRQOL) Working Group. The HRQOL Working Group sought to identify existing patient-reported outcome (PRO) assessments of HRQOL for use in clinical trials and practice deemed relevant across a broad spectrum of patients with AL amyloidosis. A systematic review of the AL amyloidosis literature identified 1) additional signs/symptoms not currently part of an existing conceptual model, and 2) relevant PRO instruments used to measure HRQOL. The Working Group mapped content from each identified instrument to areas of impact in the conceptual model to determine which instrument(s) provide coverage of relevant concepts. The SF-36v2® Health Survey (SF-36v2; QualityMetric Incorporated, LLC) and Patient-Reported Outcomes Measurement Information System-29 Profile (PROMIS-29; HealthMeasures) were identified as instruments relevant to patients with AL amyloidosis. Existing evidence of reliability and validity was evaluated with a recommendation for future work focused on estimating clinically meaningful within-patient change thresholds for these instruments. For sponsors, the context of use-including specific research objectives, trial population, and investigational product under study-should inherently drive selection of the appropriate PRO instrument and endpoint definitions to detect meaningful change and enable patient-focused drug development.

PurposeMeaningful thresholds are needed to interpret patient-reported outcome measure (PROM) results. This paper introduces a new method, based on item response theory (IRT), to estimate such thresholds. The performance of the method is examined in simulated datasets and two real datasets, and compared with other methods.MethodsThe IRT method involves fitting an IRT model to the PROM items and an anchor item indicating the criterion state of interest. The difficulty parameter of the anchor item represents the meaningful threshold on the latent trait. The latent threshold is then linked to the corresponding expected PROM score. We simulated 4500 item response datasets to a 10-item PROM, and an anchor item. The datasets varied with respect to the mean and standard deviation of the latent trait, and the reliability of the anchor item. The real datasets consisted of a depression scale with a clinical depression diagnosis as anchor variable and a pain scale with a patient acceptable symptom state (PASS) question as anchor variable.ResultsThe new IRT method recovered the true thresholds accurately across the simulated datasets. The other methods, except one, produced biased threshold estimates if the state prevalence was smaller or greater than 0.5. The adjusted predictive modeling method matched the new IRT method (also in the real datasets) but showed some residual bias if the prevalence was smaller than 0.3 or greater than 0.7.ConclusionsThe new IRT method perfectly recovers meaningful (interpretational) thresholds for multi-item questionnaires, provided that the data satisfy the assumptions for IRT analysis.

Background: The 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32), a measure of IBD-specific health-related quality of life (HRQoL), with scores ranging from 32-224 and higher scores indicating better HRQoL, has been shown to be reliable and valid in patients with ulcerative colitis (UC). Previous reviews produced weak evidence to support its responsiveness or ability to detect changes in UC health indicators. Given the need for accurate assessment in clinical trials, this review and meta-analysis provide an updated synthesis of the literature on IBDQ-32 responsiveness. Methods: A systematic literature review using the PubMed, Embase, and CENTRAL databases identified articles published since the IBDQ-32’s inception through 2021 that either 1) linked change in IBDQ-32 to change in UC health indicators in adults, or 2) reported IBDQ-32 responder analyses in randomized control trials (RCTs) of adults with UC. Studies that fit criteria 1 were summarized in a narrative review. Studies that fit criteria 2 were included in a random effects meta-analysis that compared the proportions of patients who showed a response on the IBDQ-32 (typically ≥16 points) between active treatment and placebo arms. A moderator analysis (Cochran’s Q-test, significance level = 0.10) compared the proportion of IBDQ-32 responders between efficacious treatments (those that met the primary endpoint) and non-efficacious treatments (those that did not meet the primary endpoint). A linear meta-regression examined the association between a continuous predictor of treatment efficacy (primary endpoint odds ratios) and proportions of IBDQ-32 responders in active treatment compared with placebo groups. Results: This review identified 15 articles that linked changes in IBDQ-32 to change in UC health. Change in IBDQ-32 total scores showed consistent moderate-to-strong correlations in the expected direction with change in other UC health measures. Change in IBDQ-32 total scores were correlated with changes in patient-reported symptoms (correlations: r = 0.57, ρ = -0.64), clinical response/remission on disease activity indices (e.g., partial Mayo score; correlations: ρ = -0.53, -0.59), and remission/mucosal healing on endoscopic activity indices (correlations: ρ = -0.37, -0.50). Further, changes in patient-reported symptoms or disease activity indices were linked to clinically meaningful (>16 points) mean changes in IBDQ-32 total scores (ranging from 22.3 to 50.1 points). Patients achieving clinical remission (based on disease activity indices) or mucosal healing (based on Mayo endoscopic sub-scores) experienced significantly larger mean changes in IBDQ-32 total scores than those who did not achieve remission or mucosal healing (p. Conclusion(s): Evidence supports the ability of the IBDQ-32 to detect change and response to treatment among patients with UC, supporting the use of the IBDQ-32 in clinical trials. Future research should examine IBDQ-32 responsiveness in the context of real-world evidence studies.

IntroductionPatients with generalized myasthenia gravis (gMG) experience functional impairment due to MG symptoms. This study aimed to assess, from the patient perspective, the symptoms, impacts, and treatment goals of individuals diagnosed with gMG.MethodsSemi-structured, in-depth concept-elicitation interviews were conducted with 28 individuals diagnosed with gMG in the United States.ResultsParticipants reported gMG symptoms that affected many body regions and functions, with an average of 16 symptoms per participant. The most frequently reported symptoms were eyelid drooping (93%), physical fatigue (89%), symptoms affecting the legs (82%), difficulty breathing (82%), and difficulty holding head up (82%). Nearly all participants (96%) reported fluctuations in symptoms and severity. Participants’ most bothersome symptoms were blurry/double vision (43%), breathing difficulties (36%), all-over fatigue (36%), and swallowing problems (29%). Impacts on physical functioning included an inability to participate in hobbies/sports, need for increased planning, and difficulties performing activities of daily living. All participants reported emotional impacts and impacts on their work and finances. Their treatment goals included reduced fatigue and weakness, improved symptom stability, and minimization of the impact of symptoms, in particular the emotional impact.ConclusionsThe fluctuating and unpredictable nature of gMG symptoms was found to have a substantial impact on patients’ emotional, social, and economic well-being. Participants’ goals for symptom management suggest that greater focus is needed to help them quickly resume a normal lifestyle by achieving symptom stability. Impacts of fluctuating and unpredictable symptoms are difficult to measure, but it is important to consider symptom fluctuation as well as ongoing symptomatology when making treatment decisions, and to recognize the impact of uncontrolled symptoms on patients, their partners/caregivers, and family/friends. These factors are often not reflected in burden/cost-of-illness studies.

ObjectivePatient-reported transition ratings are supposed to reflect the change between a previous baseline health state and a present follow-up state, but may reflect the present state to a greater extent. This so-called “present state bias” (PSB) potentially threatens the validity of transition ratings. Several criteria have been proposed to assess PSB. We examined how well these criteria perform and to which extent confirmatory factor analysis (CFA) for categorical data provides an accurate assessment of the degree of PSB. Study Design and SettingWe simulated multiple samples with baseline and follow-up item responses to a hypothetical questionnaire, and transition ratings. The samples varied with respect to various distributional characteristics and the degree of PSB. The performance of criteria proposed in the literature, and a new CFA-based criterion, were evaluated by the proportion of explained variance in PSB. In addition, four real datasets were analyzed. ResultsThe known criteria explained 36–74% of the variance in PSB. A new CFA-based criterion, namely the ratio of the factor loadings of the transition ratings plus one, explained 81–98% of the variance in PSB across the samples. ConclusionPresent state bias in transition ratings can be estimated accurately using CFA.