Patient-reported Outcomes Domains Research Articles

Health-related quality of life in patients with triple-class exposed relapsed and refractory multiple myeloma treated with idecabtagene vicleucel or standard regimens: patient-reported outcomes from the phase 3, randomised, open-label KarMMa-3 clinical trial

Chimeric antigen receptor T-cell therapy idecabtagene vicleucel (ide-cel) showed significantly improved progression-free survival compared with standard regimens in adults with relapsed and refractory multiple myeloma who had received two to four previous regimens in the ongoing phase 3 KarMMa-3 trial (NCT03651128). This study analysed patient-reported outcomes (PROs), a KarMMa-3 secondary endpoint. In the randomised, open-label, phase 3 KarMMa-3 trial, 386 patients in hospitals (≥18 years of age, with measurable disease and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who had received two to four previous regimens-including an immunomodulatory agent, a proteasome inhibitor, and daratumumab-and had documented disease progression after receiving their last dose of the last therapy) were randomly assigned to ide-cel (n=254) or standard regimens (daratumumab, pomalidomide, and dexamethasone; daratumumab, bortezomib, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; carfilzomib and dexamethasone; or elotuzumab, pomalidomide, and dexamethasone; n=132). Patients were expected to complete the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire (QLQ-C30), Multiple Myeloma Module (QLQ-MY20), EQ 5 dimensions (EQ-5D), and EQ-5D visual analogue scale (VAS) at baseline and follow-up timepoints (data cutoff April 18, 2022). PROs included nine prespecified primary domains: EORTC QLQ-C30 GHS-quality of life (QoL), physical functioning, cognitive functioning, fatigue, and pain; QLQ-MY20 disease symptoms and side effects of treatment; and five-level EQ-5D (EQ-5D-5L) index score and EQ-5D visual VAS. Differences in overall least-squares mean changes from baseline to month 20 were analysed using post-hoc constrained longitudinal data analysis. Time to confirmed improvement or deterioration from baseline was analysed using Cox proportional hazard models. Patients were randomly assigned between May 6, 2019, and April 8, 2022. Overall, the median age was 63 years (IQR 55-68); 151 (39%) patients were female; and 250 (65%) patients were White, 36 (9%) Black or African American, 19 (5%) Hispanic or Latino, 12 (3%) Asian, and seven (2%) of other race. The median follow-up was 18·6 months (IQR 14·0-26·4). PRO compliance was higher than 75% throughout. Overall least-squares mean changes from baseline favoured ide-cel with Hedges' g effect sizes from 0·3 to 0·7 for most domains. Patients in the ide-cel group showed statistically significant and clinically meaningful improvements across the primary PRO domains of interest, with the exception of QLQ-MY20 disease symptoms, side effects of treatment, and EQ-5D-5L index score, which showed improvement across assessment visits but did not exceed the within-group minimally important difference thresholds. The ide-cel group had shorter times to clinically meaningful improvement than the standard regimens group in QLQ-C30 domains except in role functioning, diarrhoea, and financial difficulties; in QLQ-MY20 domains except body image; and in EQ-5D-VAS. Ide-cel offers improved health-related quality of life compared with standard regimens for patients with relapsed and refractory multiple myeloma after previous lines of therapy. The PRO data highlight the extended QoL benefits of a one-time infusion with ide-cel compared with continuous treatment with standard regimens in the treatment of triple-class exposed patients with relapsed and refractory multiple myeloma. 2seventy bio and Celgene, a Bristol Myers Squibb Company.

Changes over time in patient-reported outcomes in patients with heart failure.

This paper describes the trajectory during 1year of four patient-reported outcomes (PROs), namely, sleep, depressive symptoms, health-related quality of life (HrQoL), and well-being, in patients with heart failure (HF), their relationshipand the patient characteristics associated with changes in these PROs. Data analyses of PROs from 603 patients (mean age 67years; 29% female, 60% NYHA II) enrolled in the HF-Wii study. On short term, between baseline and 3months, 16% of the patients experienced continuing poor sleep, 11% had sustained depressive symptoms, 13% had consistent poor HrQoL, and 13% consistent poor well-being. Across the entire 1-year period only 21% of the patients had good PRO scores at all timepoints (baseline, 3, 6, and 12months). All others had at least one low score in any of the PROs at some timepoint during the study. Over the 12months, 17% had consistently poor sleep, 17% had sustained symptoms of depression, 15% consistently rated a poor HrQoL, and 13% poor well-being. Different patient characteristics per PRO were associated with a poor outcomes across the 12months. Age, education, New York Heart Association, and length of disease were related to two PRO domains and submaximal exercise capacity (6min test), co-morbidity, and poor physical activity to one. In total, 79% of the patients with HF encountered problems related to sleep, depressive symptoms, HrQoL, and well-being at least once during a 1-year period. This underscores the need for continuous monitoring and follow-up of patients with HF and the need for dynamic adjustments in treatment and care regularly throughout the HF trajectory.

HJKC3-0006: Outcome of Patients with CML Treated on Second Line or Later Therapy in Routine Clinical Practice

Background: First-line therapies for chronic-phase (CP) CML include the tyrosine kinase inhibitors(TKIs) dasatinib, nilotinib, bosutinib or imatinib, while ponatinib and asciminib are indicated only in later lines. There are typically high response rates to first-line therapy in CP-CML, with responses to second- and third-line therapy lower and highly dependent on the specific TKI. Our goal in this study is to evaluate the role of ponatinib in the treatment of patients with CML using data from routine clinical practice. Study design and methods: Data will come from the H. Jean Khoury Cure CML Consortium (HJKC3) CML registry, a North American multi-site research database. Participating sites include the HJKC3 members (curecml.org). Patient inclusion criteria include a diagnosis CML in chronic phase, receiving second line therapy after initial therapy with a second generation TKI (dasatinib, nilotinib, or bosutinib) or receiving third or later line TKI therapy for CML. Participating patients provide consent to collect their data both retrospectively and prospectively for 1 year. Clinical data, including toxicities and complications of TKI therapy, are abstracted from the electronic health record. Participating patients are invited to complete a questionnaire to assess health-related quality of life. Data are managed using REDCap, a secure web application. Study Objectives: The primary objective is to compare the outcome of patients treated with ponatinib vs. other TKIs as second or later line therapy. Secondary objectives are to evaluate patient-reported outcomes (PRO) for CML treated with second or later line therapy and to determine if there are any patient or disease characteristics that can predict outcomes. Statistical plan for clinical outcomes: Descriptive statistics will be used to compare baseline demographic characteristics. Categorical variables will be compared using the Chi-square test. Continuous variables will be compared using ANOVA. Overall survival will be calculated from the time of diagnosis to death from any cause and patients will be censored if they were alive at the last follow-up. Survival probabilities will be computed using the Kaplan-Meier method and compared with the log-ranktest. Cox regression analyses will be used to determine significant factors that influence survival, and hazard ratios with 95% confidence intervals will be presented. Event free survival (EFS) and transformation free survival (TFS) will be calculated for patients. For EFS, loss of complete hematologic remission, loss of major cytogenetic response, progression to accelerated or blast phase, or death from any cause at any time will be considered an event. For TFS, transformation to accelerated or blast phase while on therapy or death on study will be considered an event. Statistical plan for PRO: Different PRO domains will be analyzed separately (for example, depression separate from fatigue, etc.). Descriptive statistics for each PRO measure will be reported and compared to previously published studies. Differences by treatment type will be evaluated.

HJKC3-007: Outcomes of Patients with Chronic Myeloid Leukemia in Chronic Phase Treated with Asciminib and Other Tyrosine Kinase Inhibitors in Routine Clinical Practice

Background and significance: There are typically high response rates to first line TKI therapies in chronic phase chronic myeloid leukemia (CP-CML). However, responses in later lines (second line and beyond) are diminished and highly dependent on the specific tyrosine kinase inhibitors (TKIs) used. Asciminib received FDA approval in October 2021 for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) CML-CP who were previously treated with two or more TKIs, and in patients with Ph+ CML-CP with the T315I mutation. Our goal in this study is to evaluate the role of asciminib therapy for patients with CML beyond clinical studies, in routine clinical practice. Study Design and methods: Data for this study will be abstracted from the HJKC3 (H. Jean Khoury Cure CML Consortium) CML registry project (HJKC3-0005); the HJKC3 CML Registry is a collaborative academic multi-site registry. Patients will be consented to allow collection of both retrospective and prospective data for the HJKC3 CML Registry. The data forms and surveys will be built and managed through the Research Electronic Data Capture (REDCap), a secure web application managed by the Clinical & Translational Science Institute. Participating sites include members of the HJKC3 (curecml.org). This study will be an opportunity to evaluate asciminib usage in ‘real-world’ academic practices across the United States. This observational study will include cohorts of patients diagnosed with CP-CML previously treated with two or more tyrosine kinase inhibitors and/or receiving asciminib and/or those with a T315I mutation, not currently enrolled in a randomized controlled trial. The HJKC3 CML Registry intends to collect clinical and patient reported outcome (PRO) data. After obtaining patient consent, patients will be invited to complete PRO assessments. The study will attempt to collect PRO data regardless of disease or treatment status. PRO assessments will be primarily administered online, though study staff will offer alternatives (e.g., phone) for participants without internet access. Study subjects will be emailed a link to access a secure platform hosted by one of the study sites, Medical College of Wisconsin (MCW), using the REDCap platform. Study Objectives: The primary objective of the study is to describe characteristics of patients who were previously treated with two or more TKIs and treated with asciminib or with any other TKIs. The secondary objectives are to describe the clinical outcomes and PRO of those patients. Exploratory objectives include description of characteristics, treatment outcome and PRO for patients with T315I mutation. Statistical plan: The sample size of approximately 225 participants during the 5-year recruitment period is based on the available clinical expertise and ongoing recruitment data in the HJKC3 CML registry in lieu of statistical power analysis. We estimate that 150 patients in the HJKC3 CML registry will be treated with other TKI and 75 treated with asciminib. Among a total of 225 patients, we estimate that 75 patients with the T315I mutation will be enrolled in the registry. No formal statistical inference will be drawn to compare the outcomes between these two groups. Bayesian predictive probability (PP) will be utilized for the exploratory analysis of Major Molecular Response (MMR). Survival probabilities will be computed using the Kaplan-Meier method, and the p-values from the log-rank test will be provided. Different PRO domains of the patient's symptoms and functioning will be analyzed separately (e.g., depression separate from fatigue, separate from GI symptoms, etc.) since combining them into a summary score may dilute the effects of the individual (and not necessarily related) components and mask actual change. The main objective for the analyses of PRO data from the registry is to describe any differences by treatment type in patients treated with asciminib and other TKIs.

Longitudinal Trends in Physical Functioning Patient-Reported Outcome Domains for Children with Sickle Cell Disease

Background: Children with sickle cell disease (SCD) often experience pain and have impaired physical functioning. Patient Reported Outcomes Measurement Information System (PROMIS) tools have previously been shown to be valid and responsive to varied states of health for children with SCD. However, there is limited understanding of the trend of patient-reported outcomes (PROs) over time and the factors associated with this trend and time-dependent changes. The objective of this study was to determine the longitudinal trends in physical functioning domains in children with SCD over a three-year time period and identify factors associated with worse PROs. Methods: Our study included a convenience sample of children with SCD recruited from a tertiary care facility during 2017 - 2020. Eligible children with SCD to self-report PROs were 8 years and older and cognitively capable. Validated PROMIS measures were used to assess fatigue, physical stress experience, strength impact and functioning/mobility over time. The PRO questionnaires were administered every 6 months (with time windows to facilitate completeness of data) for three years to obtain longitudinal data. In addition, we collected clinical data including disease management strategy (hydroxyurea use, chronic transfusion), pain medication, prior acute care use for pain (3 years at baseline and 6 months at follow-up) disease complications (overt stroke, acute chest syndrome, priapism) and other comorbidities. Generalized Estimating Equations with patients as clusters were used to determine changes in PROs over time. This model used compound symmetry covariance structure to account for correlations over time and was adjusted for age and other clinical data. Stepwise regression model was used to identify the significant variables associated with PROs. Results: We recruited 170 children with SCD into our study. Of these, 145 (85.3%) had self-report PRO data for more than one time point. The mean age of the cohort was 10.6 (SD 3.3) years, 53.1% were female. Table 1 shows the demographic and clinical characteristics of our study population. The average T-score for fatigue, physical functioning/mobility, stress experience and strength impact were 47.9, 49.1, 57.2 and 41.5 respectively. Figure 1 shows the unadjusted T-scores over time for each of the listed domains. The regression models showed there were no significant changes in scores for fatigue and physical function mobility over time. However, the stress experience [β (time in months) = -0.13 (95% CI = -0.20 - - 0.07), p-value <0.0001] and strength impact B estimate [β (time in months) = 0.13 (95% CI = 0.08 - 0.18), p-value <0.0001] improved over time. Age at enrollment was significantly associated with strength impact where older kids had a higher strength impact [β (age) = 0.49 (95% CI = 0.15 - 0.83), p = 0.005]. However, age was not associated with any of the other physical functioning domains. Disease severity at baseline, as determined by acute care use in the past three years, was significantly associated with stress experience [β (3 or more acute care visits for pain vs none) = 6.32 (95% CI = 1.71 - 10.93), p-value =.007] and fatigue [β (3 or more acute care visits for pain vs none) = 5.31 (95% CI = 0.95 - 9.66), p-value =.03]. The extent of acute care use within 6 months at follow-up time points was significantly associated with worse fatigue [β (acute care for pain within past 6 months) = 2.19 (95% CI = 0.19 - 4.20), p-value = 0.03] and physical functioning/mobility [β (acute care for pain within past 6 months)=-1.76 (95% CI = -3.24 - - 0.28), p-value = 0.02]. Conclusions: Fatigue and functioning/mobility did not change over time in children with SCD. There were slight improvements in stress experience and strength impact, but the clinical significance of these improvements is unknown. Disease severity, as measured by acute care use at baseline, was significantly associated with worse physical health across all domains.

Patient-reported symptoms and interest in symptom monitoring in HCC treated with locoregional therapies: A qualitative study.

Patient-reported outcomes (PRO) measures relevant to domains most important to patients with HCC who received locoregional therapies are needed to advance patient-centered research. Furthermore, electronic PRO monitoring in clinical care has been shown to reduce hospitalizations and deaths in patients with other cancers. We conducted a qualitative study among patients with HCC who recently received locoregional therapies to (1) identify common and distressing posttreatment symptoms to prioritize PRO domain selection and (2) gauge interest in an electronic PRO symptom monitoring system. We performed semi-structured telephone interviews among adult patients who received locoregional therapies (median of 26 days after treatment) for treatment-naïve HCC at a single tertiary care center. Interviews were conducted until thematic saturation was reached. Qualitative content analysis was conducted to identify emerging themes and sub-themes. Ten of 26 patients (38%) reported at least 1 symptom before treatment. In contrast, all participants (n = 26) with recently treated HCC reported at least 1 posttreatment physical symptom, with the most common being appetite loss (73%), fatigue (58%), abdominal pain (46%), and nausea (35%). Most participants (77%) stated they saw potential benefits in posttreatment ePRO symptom monitoring. Posttreatment symptoms after HCC locoregional therapies are common and often severe. These data can inform and prioritize PRO domain selection. Patients are interested in ePRO monitoring to monitor and proactively address posttreatment symptoms. Given the clinical benefits in patients with metastatic cancers, ePRO monitoring warrants investigation in patients with HCC.

Patient-reported outcomes in clinical HIV care: protocol for a single-centre, multistage, mixed-methods study in Denmark

IntroductionPeople with HIV-1 (PWH) have worse health-related quality of life (HRQoL) compared with the general population. Using patient-reported outcomes (PROs) may help reorient the focus of HIV care towards improving...

Patient-reported outcomes in clinical studies of patients with hypertrophic cardiomyopathy

ObjectivesThis study aimed to characterize patient-reported outcomes (PROs) in registered clinical studies of participants with hypertrophic cardiomyopathy (HCM). BackgroundTherapy for HCM is primarily targeted toward alleviation of symptoms and improvement in function and quality of life. Yet, the contemporary landscape of PROs in HCM clinical research has not been investigated. MethodsClinicalTrials.gov was queried to identify clinical studies of HCM that reported PROs as outcome measures. All studies of HCM as the disease condition were included, and PROs were identified using specific search terms in the Outcome Measures field. Study characteristics were collected and compared between those that did versus did not report PROs. ResultsFrom November 1987 to February 2022, 181 studies including participants with HCM were registered on ClinicalTrials.gov. Of these, 35 (19%) included PROs as outcome measures. Studies reporting PROs were more likely to be designated as interventional (85.7% vs. 46.6%; p < 0.001) and to involve randomization (65.7% vs. 24.7%; p = 0.003) compared with those that did not report PROs. Prior to 2007, no clinical studies that reported PROs were registered in ClinicalTrials.gov; however, PRO reporting has increased over the last 15 years. Of the 66 PRO tools or domains included as outcome measures, the Kansas City Cardiomyopathy Questionnaire was the most often used. ConclusionsOnly approximately one in five registered clinical studies of participants with HCM report PROs. As medical, percutaneous, and surgical therapies for HCM continue to advance, HCM-specific PRO tools that assess the impacts of these new treatments on meaningful patient-related endpoints are urgently needed.

Association between patient-reported outcomes and therapeutic outcomes in patients with breast cancer: A pooled individual-participant data analysis.

530 Background: Patient-reported outcomes (PROs) are captured in validated tools to provide the patients’ perspective and voice on their physical, social, emotional, functional, and cognitive abilities. Pre-treatment PROs have shown prognostic importance in other cancer types, however, the prognostic value of PROs in breast cancer has been minimally explored. Methods: In a pooled analysis of contemporary clinical trial IPD from patients with breast cancer, cox-proportional hazard analysis and binary logistic regression was used to assess the association between potential predictors with overall survival (OS) and adverse event (grade ≥ 3) outcomes, respectively. PROs were recorded using the EORTC QLQ-C30 version 3.0 questionnaire in the pooled cohort. Statistical significance was set at a threshold of P&lt;0.05 and was determined via the likelihood ratio test. Model fit and linearity of variable associations were assessed via the Akaike information criterion (AIC). All analyses were stratified by age, performance status, treatment arm, and study. The primary assessed outcome was OS, with grade ≥ 3 adverse events assessed as a secondary outcome. A forward inclusion process (starting with the variable of lowest AIC, PRO domains were retained in the model if they decreased the AIC by 2 or more on addition, and remained statistically significant) was used to evaluate the value of multiple PRO domains on prognostic performances. Results: Within data available, the EORTC QLQ-C30 version 3.0 questionnaire was used in a pooled cohort of 8,544 patients across 8 clinicals trials. In the pooled cohort, the association between PROs and outcomes was best described by a linear association. Patient-reported physical functioning, appetite loss, and pain were significantly associated with OS. On forward-inclusion, only physical functioning remained within the OS prognostic model. Except for patient-reported financial difficulties, all PRO domains were significantly associated with grade ≥ 3 adverse events. On forward-inclusion, physical functioning, pain, and constipation all remained statistically significant. Conclusions: Within large high-quality IPD, pre-treatment PROs demonstrated significant prognostic relationships with therapeutic outcomes in patients with breast cancer initiating contemporary anticancer treatments. Patient-reported physical functioning was found to be the most prognostic PRO domain for OS, while patient-reported physical functioning, pain, and constipation were retained in a multivariable model prognostic of grade ≥ 3 adverse events.

Assessment of Real-World Patient-Reported Outcomes in Patients Initiating Biologic Agents for the Treatment of Autoimmune Diseases: An Observational Study in Four Patient-Powered Research Networks.

The most reliable and meaningful approach for inclusion of patient-reported outcomes (PROs) in the evaluation of real-world clinical effectiveness of biologics in the treatment of autoimmune diseases is u ncertain. This study aimed to assess and compare the proportions of patients who had abnormalities in PROs measuring important general health domains at the initiation of treatment with biologics, as well as the effects of baseline abnormalities on subsequent improvement. PROs were collected for patient participants with inflammatory arthritis, inflammatory bowel disease, and vasculitis using Patient-Reported Outcomes Measurement Information System instruments. Scores were reported as T-scores normalized to the general population in the United States. Baseline PROs scores were collected near the time of biologic initiation, and follow-up scores were collected 3 to 8 months later. In addition to summary statistics, the proportion of patients with PROs abnormalities (scores ≥5 units worse than the population norm) was determined. Baseline and follow-up scores were compared, and an improvement of ≥5 units was considered significant. There was wide variation across autoimmune diseases in baseline PROs scores for all domains. For example, the proportion of participants with abnormal baseline pain interference scores ranged from 52% to 93%. When restricted to participants with baseline PROs abnormalities, the proportion of participants experiencing an improvement of ≥5 units was substantially higher. As expected, many patients experienced improvement in PROs following initiation of treatment with biologics for autoimmune diseases. Nevertheless, a substantial proportion of participants did not exhibit abnormalities in all PROs domains at baseline, and these participants appear less likely to experience improvement. For PROs to be reliably and meaningfully included in the evaluation of real-world medication effectiveness, more knowledge and careful consideration are needed to select the most appropriate patient populations and subgroups for inclusion and evaluation in studies measuring change in PROs.

Use of PROMIS to capture patient reported outcomes over time for patients on I-SPY2.

611 Background: Patient reported outcomes (PROs) capture direct feedback from patients in clinical trials. The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) is an open source and validated PRO platform. Data on PROMIS score trajectories over time for breast cancer patients undergoing neoadjuvant chemotherapy (NAC) are limited. Methods: We administered paper surveys to patients enrolled on the I-SPY2 trial, a multicenter, randomized phase 2 trial comparing novel agents to standard NAC in high-risk breast cancer. PRO domains included PROMIS Physical Function, Anxiety, Depression, Applied Cognition and Fatigue. Surveys were administered at baseline (post-consent), C1D1, inter-regimen (~12 wks into NAC), pre-surgery and at 1, 6, 12, and 24 months post-surgery. Responses were scored using the HealthMeasures Scoring Service to generate a standardized T score, with a score of 50 representing the general US population mean. Higher Anxiety, Depression and Fatigue scores represent worse symptoms; higher Physical Function and Applied Cognition scores represent better symptoms. We calculated average scores by time-point and compared changes from baseline to various grouped time points using a paired t-test. Results: From 1/2012 to 7/2020, 1631 patients enrolled in I-SPY 2 with 959 completing the baseline survey. 62% had at least two “on-treatment” surveys, and 52% had at least one follow-up time-point. Average baseline PROMIS scores for Physical Function, Anxiety, Depression, Applied Cognition and Fatigue were 46.7, 55.1, 47.2, 53.3 and 46.0 respectively. Between baseline and the latest on-treatment time point we observed improvement in Anxiety (-5.2) and worsening in Physical Function, Applied Cognition and Fatigue (-5.4, -6.9 and +8.2 respectively). Between baseline and the latest post-surgery time point, we saw improved Anxiety (-5.9) and worsened Physical Function, Applied Cognition and Fatigue (-5.9, -3.6 and +4.3). Depression changed minimally. Conclusions: Using PROMIS, patients on I-SPY2 experienced worse Physical Function, Applied Cognition and Fatigue but improved Anxiety during and after treatment compared to baseline. While changes in Applied Cognition and Fatigue recovered partially after treatment, Physical Function scores did not, suggesting potential for longer term impact on quality of life. Clinical trial information: NCT01042379 . [Table: see text]

Predictors and Interrelationship of Patient-Reported Outcomes in Antiphospholipid Syndrome: A Cross-Sectional Study.

This study assessed patient-reported outcomes (PROs) in individuals with persistently positive antiphospholipid antibodies (aPL) to better understand how living with aPL may affect their quality of life. Patients completed Patient-Reported Outcomes Measurement Information System Physical Function (PF) and Cognitive Function (CF) Short Forms as well as the pain intensity (PI) rating (scale of 1-10). Patients were characterized for demographics, clinical manifestations of antiphospholipid syndrome (APS), cardiovascular risk factors, laboratory test results, and medication usage. Multivariate modeling was done via linear regression. Of 139 patients, 89 had primary APS, 21 had secondary APS, and 29 had persistent aPL without meeting clinical criteria for APS. The average T scores (±SD) for PF and CF were 45.4 ± 9.2 and 48.6 ± 11.6, respectively; the average for PI was 3.0 ± 2.6. Approximately half of the patients (47%) endorsed at least mild impairment in PF (T score < 45). Mean PF, CF, and PI did not differ between diagnostic groups. Individuals who endorsed more impairment on one measure also tended to endorse more impairment on another (Pearson r= 0.43-0.59). In the multivariate models, age, smoking, pain medications, and serotonergic medications were associated with impairment in at least one PRO domain. The Damage Index for APS was significantly correlated with both PF and CF. Individuals living with APS endorsed more impairment in PF (and potentially CF) than expected for the general population. The relationship between certain medications and PROs warrants further study, as does the longitudinal trajectory of these and other PROs.

Abstract 12321: Patient-Reported Outcomes in Clinical Studies of Patients With Hypertrophic Cardiomyopathy

Introduction: Therapy for hypertrophic cardiomyopathy (HCM) is primarily targeted toward alleviation of symptoms and improvement in function and quality of life. Yet, the contemporary landscape of patient-reported outcomes (PROs) in HCM clinical research has not been investigated. Methods: ClinicalTrials.gov was queried to identify clinical studies of HCM that reported PROs as outcome measures. All studies of HCM as the disease condition were included, and PROs were identified using specific search terms in the Outcome Measures field. Study characteristics were collected and compared between those that did versus did not report PROs. Results: From November 1987 to February 2022, 181 studies including participants with HCM were registered on ClinicalTrials.gov. Of these, 35 (19%) included PROs as primary or secondary outcome measures. Studies reporting PROs were more likely to be interventional (85.7% vs. 46.6%; p&lt;0.001) and to involve randomization (65.7% vs. 24.7%; p=0.003) compared with those that did not report PROs. Prior to 2007, no clinical studies that reported PROs were registered in ClinicalTrials.gov; however, PRO reporting has increased over the last 15 years. Ninety-four percent of studies that reported PROs as outcomes enrolled fewer than 500 participants. In total, 66 PRO tools or domains were listed as outcome measures. Of these, the Kansas City Cardiomyopathy Questionnaire (KCCQ) was the most often used. Conclusion: Only approximately one in five registered clinical studies of participants with HCM report PROs. Only one PRO tool, the KCCQ, has been validated in studies of patients with HCM. HCM-specific symptoms such as palpitations, dizziness, angina, syncope, and psychiatric impacts are not adequately assessed by existing PRO tools. Future research is needed to develop and validate PRO tools that adequately capture HCM-specific symptoms and longitudinal health status trajectories in patients with varying HCM subphenotypes.

Socioeconomic deprivation and patient-reported outcomes in symptom management trials for patients with breast cancer.

158 Background: Patient-reported outcomes (PROs) provide important metrics to guide treatment decision making and have been shown to be predictive of clinical outcomes. Neighborhood socioeconomic deprivation, characterized by lower levels of income, education, and housing quality, has been shown to be associated with worse outcomes in clinical trials. However, the relationship between deprivation and PROs in clinical trials has not been systematically examined. Methods: We examined the relationship between multiple PRO domains and deprivation using data from 3 randomized trials (S0927, S1200, S1202) of interventions for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) among female breast cancer patients. The studies were conducted by the SWOG Cancer Research Network. Deprivation was measured using patients’ residential zip code linked to the area deprivation index (ADI), measured on a 0-100 scale and categorized into tertiles based on national ADI distribution. Multivariable linear regression was used with adjustment for patient age, race, ethnicity, cancer stage, days on AI, and body mass index (BMI). Secondary models adjusted for rurality and insurance (Medicaid/no insurance v. private/Medicare). Average joint pain and pain interference (each on 0-10 scales) based on the Brief Pain Inventory, and physical and functional wellbeing (PWB, FWB) based on the FACT-ES (on 0-28 scales), at baseline were analyzed. Results: Overall, 761 patients were examined. Median age was 60 years, 8% of patients were Black, 5.5% were Hispanic, 87% had Stage I or II disease, and median duration on AI was 365 days. 51% of patients were from least deprived areas (bottom tertile of ADI), while 15% were from the most deprived areas (top tertile). Compared with patients from the least deprived areas, patients in the most deprived areas had worse FWB (β = -1.53, 95% CI: -2.7, -0.4; p =.01) and average pain scores (β = 0.51, 95% CI: 02, 0.8; p = 0.002) at baseline. Patients from more deprived areas (middle tertile of ADI) had worse FWB (β = -1.3, 95% CI: -2.1, -0.4; p =.005) and pain interference (β = 0.5, 95% CI: 0.2, 0.9; p =.002) compared to those from least deprived areas. For pain outcomes, the ADI coefficient was attenuated but statistically significant with adjustment for insurance. The association of FWB with ADI was not statistically significant after adjusting for insurance. No statistically significant differences were noted for PWB. Conclusions: Patients with AIMSS who live in neighborhoods with higher social needs had slightly worse FWB joint pain, and pain interference at baseline, but similar PWB. The effect of insurance on the PRO-ADI association indicates that individual access to healthcare explains some of the area-level differences in PROs. Future work will examine differences in PRO trajectory by ADI, adjusted for insurance, over the course of patient participation in these trials.

Severe impairment of patient-reported outcomes in patients with chronic hepatitis C virus infection seen in real-world practices across the world: Data from the global liver registry.

Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N=12,171 CHC patients were included (GLR n=3146, clinical trial subjects n=9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p < 0.001). Out of 15 PRO domain and summary scores, 12 were lower in GLR patients than in subjects enrolled in clinical trials (p < 0.001). In multiple regression models, anxiety, depression, and fatigue were associated with significant PRO impairment in CHC patients (p < 0.05). After adjustment for the clinico-demographic confounders, the association of PRO scores of CHC patients with enrolment settings was no longer significant (all p > 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.

Quality of Life and Other Patient-Reported Outcomes Across the Life Span Among People With Fontan Palliation.

Traditional congenital heart disease (CHD) outcomes include mortality (survival to adulthood and life expectancy) as well as cardiac and noncardiac morbidity. Strategies to identify and manage sequelae have primarily focused on objective data obtained though invasive and noninvasive diagnostic approaches. In contrast, patient-reported outcomes (PROs) provide subjective information, using standardized measures, about patients' health and well-being as reported directly by patients, without interpretation, interference, or assumptions made by clinicians or others. Selection of PRO measures entails thoughtful consideration of who the individuals being surveyed are, why assessment is occurring (eg, what are the domains of interest; clinical vs research), and what processes are in place for acquisition, administration, interpretation, and response. In this review, we focus on 3 domains of PROs for pediatric and adult patients with Fontan physiology: physical health status, psychological functioning, and quality of life. Infants, children, adolescents, and adults with CHD face a spectrum of challenges that might influence PROs across the life span. In general, patients with Fontan palliation tend to have lower physical health status, experience more psychological distress, and have equivalent or reduced quality of life compared with healthy peers. Herein, we provide an overview of PROs among people with Fontan circulation as a group, yet simultaneously emphasize that the optimal way to understand the experiences of any individual patient is to ask and listen. We also offer clinical and research initiatives to improve the adoption and utility of PROs in CHD settings, which show commitment to capturing, understanding, and responding to the patient voice.

P1725: OBSERVATIONAL STUDY TO EVALUATE PATIENT-REPORTED OUTCOMES IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Background: Paroxysmal Nocturnal Hematuria (PNH) is a rare acquired hematopoietic stem cell disorder with non-specific clinical features and onset prevalent at young adult age. Main symptoms are fatigue (80%) and dyspnea (64%). Treatment for symptomatic and/or predominantly haemolytic PNH patients is associated with an improvement in survival and quality of life (QoL). To date, cancer-specific patient-reported outcome (PRO) measures (PROMS) have been used in PNH. A novel PNH-specific PROM, EORTC QLQ-AA/PNH, consisting of 54 items has undergone initial Phase 2-3 evaluation. We present preliminary results of the first 31 cases enrolled. Aims: The aim of this observational non-interventional prospective multicenter Italian study is to evaluate whether PROMs can identify patients’ biological response to treatment and factors associated with health-related QOL. The primary endpoint is differences in EORTC QLQ-C30 scores between patients with versus without hemolysis. Secondary endpoints include further validation of EORTC QLQ-AA/PNH Italian version, differences in scale scores between patients experiencing hemolysis versus those not experiencing hemolysis and factors associated with PROs by EORTC QLQ-AA/PNH. Methods: 110 adult patients age ≥ 18 years with PNH will be included. Exclusion criteria consists of bone marrow failure, history of treatment for cancer within the last 5 years and clinically significant comorbidities that impact PROs. Patients complete both PROMs on the day of visit to the clinic for the scheduled treatment and re-test after 2 weeks. For EORTC QLQ-AA/PNH higher scores identified higher impact or symptoms. Demographics and disease features are collected at baseline. Hemolysis is defined by a lactate dehydrogenase (LDH) ≥ 1.5 times upper limit of normal (ULN) at baseline. Results: Patient characteristics are shown in the Table 1. The EORTC QLQ-C30 scores did not distinguish patients with or without hemolysis, probably due to the small sample size. Baseline Global Function was good with median score 83 (IQR 50-100). Fatigue and dyspnea were not frequently reported with median scores 33 (IQR 11-33) and 0 (0-33), respectively. The EORTC QLQ-AA/PNH showed good reliability with Chronbach alpha standardized scores for all domains except Body Image (BI), Infections (IN) and Social Support (SS), confirmed at retest. There were strong correlations between the 2 questionnaires. QLQ-AA/PNH Cognitive Functioning (CF) median score was 0 (IQR 0-25), Emotional Functioning 20 (IQR 5-35), Fatigue (FA) 20 (IQR 10-30), Illness Intrusiveness (II) 11 (IQR 4-32), other symptoms (OS) 11 (0-21), Physical Functioning (PF) 17 (0-33), Role Functioning (RF) 14 (9-32), Stigmatisation (ST) 12 (0-25) and Fear of Progression (PAF) 123 (4-29). Hemoglobin levels correlated with QLQ C30 physical function (R=0.505, P=0.006), role function (R=0.450, P= 0.014), Fatigue (R=-0.520, P=0.004), Dyspnea (R=-0.410, P=0.027) and Pain (R0-0.409, P0 0.028). They correlated with EORTC QLQ-AA/PNH PF (R=0.499, P=0.006), ST (R=0.395, P=0.034) and FA (r=-0.517, p=0.004). Image:Summary/Conclusion: The preliminary analysis confirms the validity of the EORTC QLQ-AA/PNH as a PROM for PNH. Hemoglobin is an important factor which correlates with many PRO domains. Further analyses at study completion will inform on the impact of PNH in patients’ lives.

Patient reported outcomes in adult patients with neuroendocrine neoplasms.

e24122 Background: Neuroendocrine neoplasm (NEN) is a broad term that includes both neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). These rare malignancies most often occur in the gastrointestinal tract, pancreas, lung, adrenal medulla, and thyroid. Clinical symptoms depend upon several factors including tumor location, length of time since diagnosis, secretion of hormones, and tumor growth. Physical symptoms may include fatigue, gastrointestinal complaints, shortness of breath, and fluctuations in blood pressure, weight, and appetite. Patient reported outcomes (PROs) are critical in understanding the clinical spectrum of patients with NENs including their physical and social-emotional response to disease course and treatments. The aim of the current study was to assess physical, social, and emotional domains of PROs amongst a cohort of adult participants with NENs over time. Methods: Patients were enrolled on an ongoing NIH natural history study (NCT03739827). Annual PROs were electronically administered to adult participants (≥18 years) using the PRO Measurement Information System (PROMIS) forms for Anxiety, Depression, Fatigue, Mobility, Upper Extremity, Pain Interference, Cognitive Function, and Emotional Support ( www.nihpromis.org ). PROMIS forms are standardized on a T-Scale with a mean of 50 and a standard deviation of 10. Pain intensity was assessed from 0 (no pain) to 10 (worst pain imaginable) using the Numeric Rating Scale for Pain (NRS) (Wolters, 2013). The Pain Interference Index (PII) was used to assess the impact of pain on daily functioning on a 7-point Likert scale (Martin et al., 2015). Results: A total of 49 out of 85 patients provided completed PROs: 47 NET and 2 NEC. Mean (M) age was 58.8 years and 61.2% of the sample was female. Amongst NET patients (n = 47), primary tumor locations were the small bowel (45.7%), pancreas (21.7%), and lungs (13.0%). Other primary sites (19.6%) included the appendix, rectum, thyroid, kidney, and prostate. 46.8% had metastatic disease. Fatigue was the primary symptom complaint; 34% of NET patients reported fatigue in the moderate to severe range (Mean: 54.1; Standard Deviation: 11.2). Self-perceived mobility (M:47.4; SD: 9.1) and pain interference (M: 51.8; SD: 9.0) were a moderate concern for 19.1% and 17.0% of patients, respectively. At follow-up, 24 patients have returned PROs to date. Fatigue and mobility remained prevalent concerns; 29.1% of patients reported moderate to severe fatigue and 25% reported moderate concerns with mobility. Challenges with upper extremity mobility were endorsed by 20.8% of the sample. Conclusions: Our prospective and comprehensive PRO assessment confirms previously reported fatigue as the most prevalent symptom in patients with NET. Assessment of PROs over time will inform the development of clinical interventions and assessment of their impact on patient quality of life and functioning.

Common Patient-Reported Outcomes Within the Food and Drug Administration Voice of the Patient Reports

ObjectivesProponents of disease-specific patient-reported outcome measurements (PROMs) often argue disease-agnostic measures do not adequately capture their patient population’s experience. Patient-Reported Outcomes Measurement Information System (PROMIS) provides a disease-agnostic domain set that may adequately cover many diseases. This study seeks to investigate whether PROMIS’s quality of life domain coverage can span patient-reported outcomes (PROs) elicited from patients across unrelated diseases. MethodsThe Food and Drug Administration Voice of the Patient reports were an initiative to elevate patient voices regarding their condition and associated treatments. Two reviewers extracted patient-reported health-related (quality of life) domains from the reports and categorized them into PROMIS domains or non-PROMIS domains. Domain coverage was summarized for each report. Any extracted PROs not covered by PROMIS domains were placed in an “other” category and analyzed for common themes. ResultsAcross 26 reports, PROMIS covered 216 of 374 (70%) of the reports’ PRO domains. The heritable bleeding disorders report had the highest coverage (82%). Human immunodeficiency virus had the lowest coverage (50%). The most common PROMIS domain, “ability to participate in social roles,” appeared in 25 reports (96%). The most common domains not included in PROMIS were stigma, sensitivities, and sensory deficits as evident in 19 (73%), 18 (69%), and 18 reports (69%), respectively. If the top 3 unincluded domains were amended into PROMIS, the total domain coverage would increase to 84%. ConclusionsPRO domains elicited in the Food and Drug Administration Voice of the Patient reports were widely captured by PROMIS, suggesting domains patients experience contain enough overlap to be recorded by appropriate PROMIS domains. PROMIS could increase its coverage by adding domains.

An evaluation of patient-reported outcomes in sickle cell disease within a conceptual model

PurposeTo examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 – 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains.MethodsParticipants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare.ResultsHigher pain frequency was associated with higher odds of worse outcomes in all PRO domains, controlling for age, gender and site (OR range 1.02–1.10, 95% CI range [1.004–1.12]). Reported history of treatment for depression was associated with 5 of 7 PRO measures (OR range 1.58–3.28 95% CI range [1.18–4.32]). Fewer individual barriers to care and fewer SCD complications were associated with better outcomes in the emotion domain (OR range 0.46–0.64, 95% CI range [0.34–0.86]).ConclusionsStudy results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes.