Patient-reported Outcome Tools Research Articles

A study demonstrating users' preference for the adapted-REQUITE patient-reported outcome questionnaire over PRO-CTCAE® in patients with lung cancer.

The use of patient-reported outcomes (PROs) has been shown to enhance the accuracy of symptom collection and improve overall survival and quality of life. This is the first study comparing concordance and patient preference for two PRO tools: Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) and the adapted-REQUITE Lung Questionnaire. Patients with lung cancer were recruited to the study while attending outpatient clinics at a tertiary cancer centre. Clinician-reported outcomes were generated through initial patient assessment with CTCAE v4.03. Participants then completed the PRO-CTCAE® and adapted-REQUITE questionnaires. Concordance between the 2 questionnaires was assessed by calculating Pearson correlation coefficient. PRO-CTCAE® and CTCAE concordance was demonstrated by calculating Pearson correlation coefficient from the linear predictors of an ordinal logistic regression. P-values were also calculated. Out of 74 patients approached, 65 provided written informed consent to participate in the study. 63 (96.9%) patients completed both PRO-CTCAE® and adapted-REQUITE questionnaires. Pearson correlation coefficient between PRO tools was 0.8-0.83 (p <.001). Correlation between CTCAE and PRO-CTCAE® ranged between 0.66-0.82 (p <.001). Adapted-REQUITE and CTCAE correlation was higher for all symptoms ranging between 0.79-0.91 (p <.001). Acceptable discrepancies within one grade were present in 96.8%-100% of symptom domains for REQUITE and in 92.1%-96.8% for all domains in the PRO-CTCAE®. 54% of the total participant cohort favored the adapted-REQUITE questionnaire due to reduced subjectivity in the questions and ease of use. The adapted-REQUITE questionnaire has shown a superior correlation to clinician-reported outcomes and higher patient preference than the PRO-CTCAE®. The results of this study suggest the use of the REQUITE questionnaire for patients with lung cancer in routine clinical practice.

Are measures and related symptoms of cachexia recorded as outcomes in gastrointestinal cancer chemotherapy clinical trials?

Cachexia is prevalent in gastrointestinal cancers and worsens patient outcomes and chemotherapy compliance. We examined to what extent registered gastrointestinal cancer chemotherapy clinical trials record measures and related symptoms of cachexia as outcomes, and whether these were associated with trial characteristics. Four public trial registries (2012-2022) were accessed for Phase II and/or III randomized controlled pancreatic, gastric, and colorectal cancer chemotherapy trial protocols. Trial outcome measures of overall survival and toxicity/side effects, and those related to cachexia [physical activity, weight/body mass index (BMI), dietary limitations, caloric intake, lean muscle mass] and symptoms (appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, and oral mucositis) were extracted, along with the number and types of performance status and patient-reported outcomes (PROs) tools. Data were summarized descriptively. Chi-square tests examined associations between outcomes and trial characteristics (cancer type, trial location, funding source, PROs tools, and commencement year). Statistical significance was set at P<0.05. We included 540 trial protocols (pancreatic (35.2%), colorectal (33.3%) and gastric (31.5%)), with most trials from Europe (44.1%). Trial lead investigator was from academia (28.3%), industry (27.6%) and government (26.3%). Allied health professional involvement (26.9%) occurred at eligibility. Adjuvant therapy in trials was mainly treatment-related (68.1%). Additional medication included anti-nausea (2.2%) and analgesia (0.9%). Trial protocols mostly recorded overall survival (90.4%) and toxicity (78.9%), and the symptoms appetite loss (26.1%) and diarrhoea (19.1%), with the other symptoms recorded in <10% of the trials. Reporting of physical activity (P=0.001), dietary limitations (P=0.002), lean muscle mass (P=0.027), appetite loss (P<0.001), pain (P=0.001), nausea (P=0.012), and oral mucositis (P=0.049) varied depending cancer type. Toxicity/side effects (P=0.022), physical activity (P<0.001), appetite loss, nausea, and vomiting (all P<0.001), diarrhoea (P=0.010), pain (P=0.001), fatigue/insomnia (P=0.001) varied depending on the trial location. Trial funding was predominantly from private/industry (34.3%) and influenced the reporting of overall survival (P=0.049), weight/BMI (P=0.005), caloric intake (P=0.015), and pain (P=0.031). Performance status and PROs tools were mentioned in 91.2% and 46.3% of the trials, respectively. Trials that incorporated PROs tools were more likely to report cachexia related outcomes, except for overall survival, lean muscle mass, and oral mucositis. The proportion of trials measuring weight/BMI increased with trial commencement year (P=0.04). Cachexia-related outcomes were under-recorded in gastrointestinal cancer chemotherapy trials. As trial patients experience a high symptom burden, cachexia-relevant measures and symptoms should be assessed throughout the trial, and integrated with primary endpoints to support their progress.

Effectiveness of asfotase alfa for treatment of adults with hypophosphatasia: results from a global registry

BackgroundHypophosphatasia (HPP) is a rare inherited disease caused by deficient activity of tissue-nonspecific alkaline phosphatase. Many adults with HPP have a high burden of disease, experiencing chronic pain, fatigue, limited mobility, and dental issues, contributing to decreased health-related quality of life (HRQoL). HPP may be treated with the enzyme replacement therapy asfotase alfa though real-world data in adults are limited. This analysis was conducted to assess the clinical effectiveness of asfotase alfa among adults in the Global HPP Registry.MethodsThe Global HPP Registry is an observational, prospective, multinational study. Adults ≥ 18 years of age were included in this analysis if they had serum alkaline phosphatase (ALP) activity below the age- and sex-adjusted reference ranges, and/or ALPL variant(s), and received asfotase alfa for ≥ 6 months. Mobility was assessed with the 6-Minute Walk Test (6MWT), and patient-reported outcomes tools were used to assess pain (Brief Pain Inventory-Short Form), quality of life (36-item Short Form Health Survey, version 2 [SF-36v2]), and disability (Health Assessment Questionnaire-Disability Index) at multiple time points from baseline through Month 36. Data were collected as per usual standard of care; patients may not have contributed data at all time points.ResultsA total of 190 patients met the inclusion criteria. For patients with ≥ 1 follow-up measurement, the mean distance achieved on 6MWT increased from 404 m (range 60–632 m) at baseline (n = 31) to 484 m at Month 12 (range 240–739 m; n = 18) and remained above baseline through Month 36 (n = 7). Improvements in mean self-reported pain severity scores ranged from − 0.72 (95% CI: − 1.23, − 0.21; n = 38) to − 1.13 (95% CI: − 1.76, − 0.51; n = 26) and were observed at all time points. Improvements in the Physical Component Summary score of SF-36v2 were achieved by Month 6 and sustained throughout follow-up. There was a trend toward improvement in the Mental Component Summary score of SF-36v2 at most time points, with considerable fluctuations from Months 12 (n = 28) through 36 (n = 21). The most frequent adverse events were injection site reactions.ConclusionsAdults with HPP who received asfotase alfa for ≥ 6 months experienced improvements in mobility, physical function, and HRQoL, which were maintained over 3 years of follow-up.Registration: NCT02306720; EUPAS13514.

Health-related quality of life in patients with hematologic malignancies treated with chimeric antigen receptor T-cell therapy: review and current progress.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the care of patients with relapsed/refractory B-cell derived hematologic malignancies. To date, six CAR T-cell therapies, targeting either CD19 or B-cell maturation antigen, have received regulatory approval. Along with the promising survival benefit, CAR T-cell therapy is associated with potentially lifethreatening adverse events (AE), including cytokine release syndrome and immune effector cellassociated neurotoxicity syndrome. While clinical trials evaluating CAR T-cell therapy consistently report the incidence of these AE, most trials do not collect health-related quality of life (HRQoL) data. As such, the impact of CAR T-cell therapy process and related AE on the physical and psychological well-being of patients remains uncertain. HRQoL and other patientreported outcome (PRO) assessments in patients with relapsed or refractory hematologic malignancies are of utmost importance, as individuals may have unmet needs and a high demand for tolerable therapy if a cure is not obtained. In addition, it is important to standardize methods of data collection to better assess the impact of CAR T-cell therapy on quality of life, optimize patient care and costs, and enable comparison between different studies. We conducted a literature search up to June 2023 to identify the HRQoL tools used in clinical trials and in realworld studies investigating CAR T-cell therapy in patients with lymphomas or leukemias. In the present comprehensive review, we summarize the most commonly used CAR T-cell specific and non-specific HRQoL tools and discuss how the use of HRQoL and other PRO tools may be optimized.

Test-retest reliability of a mobile application of the patient reported outcomes burdens and experiences (PROBE) study.

The Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaire is a patient-reported outcome tool that assesses quality of life and disease burden in people with haemophilia (PWH). To assesses the test-retest reliability of PROBE when completed using the mobile phone application. We recruited PWH, including carriers, and individuals with no bleeding disorders who attended haemophilia-related workshops or via social media. Participants completed PROBE three times (twice on the app: T1 and T2, and once on the web, T3). Test-retest reliability was analysed for T1 versus T2 (app to app, time period one) and T2 versus T3 (app to web, time period two). We enrolled 48 participants (median age=56 [range 27-78] years). Eighteen participants (37.5%) were PWH and seven (14.6%) were carriers. On general health domain questions, we found almost perfect agreement, except for a question on the frequency of use of pain medication in the last 12 months [Kappa coefficient (κ).72 and.37 for time period one and two, respectively] and any use of pain medications (κ.75) for time period two. For haemophilia-related questions, we found substantial to perfect agreement, except for the questions on the number of joint bleeds in the previous 6 months for time period one (κ.49) and the number of bleeds in the previous two weeks for time period two (κ.34). The results demonstrate the reliability of the PROBE app. The app can be used interchangeably with the paper and web platforms for PROBE administration.

A conceptual model for chronic hepatitis B and content validity of the Hepatitis B Quality of Life (HBQOL) instrument

BackgroundThere is increased emphasis on incorporating patient perspectives and patient-relevant endpoints in drug development. We developed a conceptual model of the impact of chronic hepatitis B (CHB) on patients’ lives and evaluated the content validity of the Hepatitis B Quality of Life (HBQOL) instrument, a patient-reported outcome tool for use in clinical studies, as a patient-relevant endpoint to measure health-related quality of life in patients with CHB.MethodsA literature review of qualitative studies of patient experience with CHB and concept elicitation telephone interviews with patients with CHB in the United Kingdom were used to develop a conceptual model of the experience and impact of living with CHB. The content validity of the HBQOL was evaluated using cognitive debriefing techniques.ResultsThe qualitative literature review (N = 43 publications) showed that patients with CHB experience emotional/psychological impacts. During concept elicitation interviews (N = 24), fatigue was the most commonly reported symptom, and most participants were worried/anxious about virus transmission and disease progression/death. A conceptual model of patients’ experiences with CHB was developed. The conceptual relevance and comprehensibility of the HBQOL were supported, though limitations, including the lack of a self-stigma item and recall period, were noted for future improvement.ConclusionsThe conceptual model shows that patients with CHB experience emotional/psychological impacts that affect their lifestyles, relationships, and work/schooling. The cognitive debriefing interviews support the content validity of the HBQOL as a conceptually relevant patient-reported outcome measure of health-related quality of life.

Real-world use and clinical impact of an electronic patient-reported outcome tool in patients with solid tumors treated with immuno-oncology therapy

BackgroundUtilization of electronic patient-reported outcome (ePRO) tools to monitor symptoms in patients undergoing cancer treatment has shown clinical benefits. Tennessee Oncology (TO) implemented an ePRO platform in 2019, allowing patients to report their health status online. We conducted a real-world, multicenter, observational, non-interventional cohort study to evaluate utilization of this platform in adults with solid tumors who initiated immuno-oncology (IO) therapy as monotherapy or in combination at TO clinics.MethodsPatients initiating IO therapy prior to platform implementation were included in a historical control (HC) cohort; those initiating treatment after implementation were included in the ePRO cohort, which was further divided into ePRO users (platform enrollment ≤ 45 days from IO initiation) and non-users. Data were extracted from electronic medical records; patients were followed for up to 6 months (no minimum follow up). Outcomes included patient characteristics, treatment patterns, duration of therapy (DoT), and overall survival (OS).ResultsData were collected for 538 patients in the HC and 1014 in the ePRO cohort; 319 in the ePRO cohort were ePRO users (uptake rate 31%). Baseline age was higher, more patients had stage IV disease at diagnosis, and more received monotherapy (82 vs 52%, respectively) in the HC vs the ePRO cohort. Median follow-up was 181.0 days (range 0.0–182.6) in the HC and 175.0 (0.0–184.0) in the ePRO cohort. Median DoT of index IO regimen was 5.1 months (95% confidence interval [CI], 4.4–NE) in the HC cohort vs not estimable (NE) in the ePRO cohort. Multivariable regression adjusting for baseline differences confirmed lower risk of treatment discontinuation in the ePRO vs HC cohort: hazard ratio (HR) 0.83 (95% CI, 0.71–0.97); p < 0.05. The estimated 6-month OS rate was 65.5% in the HC vs 72.4% in the ePRO cohort (p < 0 .01). Within the ePRO cohort, DoT of index IO regimen and OS did not differ between users and non-users. In ePRO users, patient platform use was durable over 6 months.ConclusionImprovements in DoT and OS were seen after ePRO platform implementation. Conclusions are limited by challenges in separating the impact of platform implementation from other changes affecting outcomes.

Abstract TP97: Feasibility and Reliability of Patient-Reported Scores to Assess Long-Term Functional Outcomes in Stroke: A Sub-Group Analysis of the MaRISS Trial

Obtaining delayed functional outcomes such as the modified Ranking score (mRS) after stroke is challenging in clinical practice, often resulting in missing data. Self-reported outcomes are an alternative to functional outcome collection, but their reliability and accuracy are not well-established Methods: In this subgroup analysis of the Mild and Rapidly Improving Stroke Study (MaRISS), we aimed to test the feasibility and reliability of the MaRISS Patient Reported Outcome (PRO) survey tool for obtaining delayed functional outcomes in low (0-5) National Institute of Health Stroke Scale ischemic stroke, particularly the modified Rankin Score (mRS), by assessing its inter-rater reliability with a score calculated by a clinician through a structured telephone interview. Other scores were compared as secondary outcomes. 125 surveys were distributed between January 2017 and July 2018. The tool consisted of an online survey aiming to collect information regarding the patient's functional status 90 days after stroke including the mRS (utilizing the mRS 9-Q version), Stroke Impact Scale-16 (SIS), Barthel Index (BI), European Quality of Life-5D-5L (EQ-Index). All participants also completed these scales administered by trained personnel through a structured telephone interview. Cohen's weighted kappa coefficients (κ) with 95% confidence intervals (CI) were calculated to assess the reliability of the PRO Tool Results: Of 125 surveys sent, 55/125 (46.4%) participants opened and started the survey but only 44/125 (36.8%) completed it entirely (mean age 62±12.5, 54.6% female, white 79.6%, NIHSS 2.3±1.8, ischemic stroke 84%, 16% TIA). 52 subjects completed both the online mRS 9-Q PRO and the telephone version (Table). The weighted kappa for the comparison of PRO mRS and the clinician-performed mRS was moderate [κ 0.53, SE 0.10; 95% CI (0.3-0.7)] as well as for the SIS (κ 0.43, SE 0.09) and EQ-Index (κ 0.40, SE 0.10) scores, whereas for BI was fair (κ 0.32, SE 0.15) Discussion: Engaging participants after hospital discharge remains difficult. Although participant completion rates for self-reported outcomes were low, the MaRISS PRO Tool showed moderate reliability. These findings should be confirmed in larger samples with a focus on improving participant engagement

Patient-reported outcomes in patients with gastrointestinal cancer on oral chemotherapy.

732 Background: Over the last several years, patient reported outcomes (PROs) have been demonstrated to address patient symptoms, improve outcomes, and reduce health care utilization. We aim to provide an electronic PRO (ePRO) tool for gastrointestinal (GI) oncology patients with the goals of improving adherence, reducing toxicity, and enhancing patient access to the clinical team. Methods: Patients are provided an ePRO tool consisting of a cellphone app integrated into the electronic health record with questions on adherence and 10 questions on symptoms adapted from the NCI PRO-CTCAE for local use. Emails are sent to the clinical team for nonadherence, new or worsening symptoms, or patient requested callback. Outcomes including time to first symptom assessment, emergency department (ED) visit and/or hospitalization at 30 and 90 days from enrollment will be compared with historical controls. Other outcomes including adherence and patient-reported access to the clinic will be assessed. Results: Six patients have been enrolled between May 1, 2023 and September 4, 2023. Five patients were newly starting oral chemotherapy agents and one patient had already been on therapy. Types of cancers included colon cancers (2), rectal cancer (1), pancreatic cancer (1), GIST (1), and cholangiocarcinoma (1). Types of oral chemotherapy included capecitabine (4), olaparib (1), and imatinib (1). Five patients have submitted a total of ten responses. Of the five who completed the ePROs, patients responded a median of one time (range 1-5). Reported symptoms were fatigue (4), pain (2), nausea (1), diarrhea (1), other symptoms (2) and a request callback (1). Seven (70%) responses have prompted emails alerts for clinical symptoms and one (10%) for adherence concerns. All alerts were resolved; average time to alert response 1.6 calendar days (range 1-3). Among historical controls, time to first symptom assessment after a new oral chemotherapy prescription was seven days, 30-day rate for ED and/or hospitalizations was 12%, and 90-day rate of ED visits and/or hospitalizations was 28%. Conclusions: Early data suggests a new process to manage ePROs can provide timely responses to email alerts. Of the responses thus far, 70% prompted email alerts due to clinical symptoms and 10% reported nonadherence, suggesting a high need for ongoing ePRO tools. Results are forthcoming on outcomes including time to symptom assessment/clinical action, ED visit/hospitalization and access.

Goals and benefits in topical treatment for psoriasis: development and pilot validation of a patient-reported outcomes tool, the Patient Benefit Index for Topical Treatment (PBI-TOP).

Topical agents are an essential component of psoriasis therapy. To develop a new version of the patient-reported Patient Benefit Index assessing the importance and achievement of treatment goals in topical psoriasis therapy in adult patients (PBI-TOP). Through semi-structured interviews, focus groups and free-text questionnaires, patients reported their needs in topical treatment. Based on qualitative content analysis, items were developed by a consensus group and were refined in cognitive debriefing interviews. A pilot validation assessed the PBI-TOP and convergent criteria [Dermatology Life Quality Index (DLQI); Psoriasis Area and Severity Index (PASI); affected Body Surface Area (BSA)]. Thirty patients (26-72 years, mean 47; 60% male) reported various treatment goals relating to the themes 'effectiveness' and 'characteristics of the preparation'. Twenty patients took part in cognitive debriefings (22-84 years, mean 50.6, 50% male). There were 154 patients who participated in the pilot validation (18-85 years, mean 46.9, 63.6% male). An importance-weighted total score on overall effectiveness and three subscales based on exploratory factor analysis were defined: effectiveness on symptoms, effectiveness on quality of life (QoL), and characteristics of the preparation. All scores showed excellent internal consistency (α > 0.9). The global effectiveness score correlated significantly with DLQI (r = -0.41), PASI (r = -0.32) and BSA (r = -0.22). The effectiveness subscales (symptoms; QoL) correlated significantly with DLQI (r = -0.41; -0.32) and PASI (r = -0.27; -0.33). The score on characteristics of the preparation correlated significantly with the DLQI (r = -0.34). The PBI-TOP showed good feasibility and favourable psychometric characteristics in this pilot validation.

Stroke self-efficacy questionnaire (SSEQ), a reliable measure of disease burden: psychometric validation of the Romanian version

Self-efficacy is a relevant outcome measure of functional status in stroke research. It can be measured with various patient-reported outcome (PRO) tools, which can be generic or disease (stroke) related. However, in Romania, there is a limited availability of such measures. The Stroke Self-Efficacy Questionnaire(SSEQ) is a specific PRO scale that measures the impact of stroke on self-management and on performance of daily activities. We conducted a two-stage study: (1) translation and cross-cultural adaptation of the SSEQ-Romanian version (SSEQ-RO) and (2) a prospective cohort clinical study designed for psychometric validation of the SSEQ-RO. For the enrolled stroke patients, Barthel index, quality of life and indexes of disease severity, such as NIHSS, MRC and mRS, were measured at baseline and ten days. For psychometric validation we assessed construct validity, reliability and repeatability. In a sample of fifty stroke patients, SSEQ-RO was found to have an excellent construct validity, excellent reliability (Cronbach's alpha = 0.92), and repeatability (ICC = 0.91). SSEQ-RO was also a good measure of disease burden in mild versus moderate to severe stroke as assessed with NIHSS (p = 0.002). In conclusion, for stroke patients, SSEQ-RO is a reliable PRO able to assess the impact of stroke on the ability to perform daily activities and, therefore can reliably be used to monitor functional status dynamics during the disease course.

The electronic Person Specific Outcome Measure (ePSOM) development program in the US: A survey to understand what matters to individuals most about their brain health

AbstractBackgroundIt is essential both drug and lifestyle‐based interventions aimed to delay the onset of advanced cognitive decline deliver a meaningful outcome for the patient. In the early stages of Alzheimer’s disease and related dementias (ADRDs), patient‐reported outcome (PRO) measures should be used in parallel with biological investigations of ADRDs to provide a complementary endpoint offering further proof of intervention’s effectiveness from the patients’ point of view. The aim of the electronic Person‐Specific Outcome Measure (ePSOM) programme is to develop a scalable, easily accessible and efficient PRO tool for monitoring personally meaningful outcomes in early ADRD.MethodWe designed and ran an online nation‐wide study to understand what matters to people about their brain health in the US. The ePSOM US survey started in Jan 2023 and collects primarily free‐text responses along with sociodemographic information and self‐reported neurodegenerative disease diagnosis. Respondents are presented with five domains and asked to describe in their own words their brain‐health priorities. Free‐text data will be analysed using Natural Language Processing (NLP) techniques to identify the most common brain‐health priorities by key sociodemographic groups. We will also compare these results with previously published UK results to look for any notable differences between the US and UK respondents’ priorities.ResultThe survey aims to recruit n = 6,000 respondents. Data collection started early 2023 and is planned to be complete by Spring/Summer 2023. The previously published ePSOM UK study (Saunders et al., 2021) with n = 5,808 respondents resulted in over 80,000 free‐text responses and 184 unique priority themes about brain health. We will present the preliminary results of the US study at AAIC and contextualising the results in light of new pharmacological treatments approved for AD.ConclusionThis large‐scale population‐based study will offer an evidence base for what outcomes constitute a meaningful impact of new treatments. Previous work from our group suggests that brain health priorities shift along the preclinical, prodromal and dementia continuum. The ultimate aim of the ePSOM programme is to design an electronic outcomes app which would allow an individual to define the most important outcomes against which we should measure treatment success across a range of severities.

Patient-Reported Outcomes (PROs) in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Treated with Crovalimab and Eculizumab: Results from the Phase III Randomized COMMODORE 2 and COMMODORE 1 Trials

Introduction COMMODORE 2 (NCT04434092) and COMMODORE 1 (NCT04432584) are global, randomized, open-label, multicenter Phase III trials evaluating crovalimab (crova) vs eculizumab (ecu) in patients (pts) with PNH. COMMODORE 2 tested the non-inferiority of crova vs ecu in C5i-naive pts and demonstrated that crova was non-inferior to ecu for hemolysis control, transfusion avoidance, breakthrough hemolysis, and hemoglobin stabilization (Röth EHA 2023; #S181). In both studies, crova was well tolerated for both C5i-naive and C5i-experienced pts (Röth EHA 2023; #S181, Scheinberg EHA 2023; #S183). To investigate the efficacy of crova vs ecu from a pt perspective, PRO tools were used to assess fatigue, PNH-related symptoms, functioning, and global health status/quality of life (GHS/QoL) among COMMODORE 2 and COMMODORE 1 pts. Methods In COMMODORE 2, C5i-naive pts were randomized 2:1 to receive crova or ecu during a 24-week primary treatment period. In COMMODORE 1, C5i-experienced pts receiving ecu at study start were randomized 1:1 to receive crova or ecu during a 24-week primary treatment period. Pts received crova as a weight-based tiered regimen (Liu ASH 2022; #293) that included loading doses followed by maintenance doses via subcutaneous injection every 4 weeks, or ecu via intravenous infusion every 2 weeks (900 mg per label). After completing 24 weeks of treatment, COMMODORE 1 and 2 pts randomized to crova continued crova, and those randomized to ecu switched to crova if continuing in the extension period. Paper PRO questionnaires were completed by adult pts at baseline (BL) and at Weeks 2, 5, 9, 17, and 25 during the primary treatment period (up to Week 25) and during the crova extension period (from Week 25 onwards). Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (higher scores indicate lower fatigue severity). Additional PNH symptoms (dyspnea, dysphagia, headaches, abdominal pain, chest pain, and erectile dysfunction) were assessed using relevant questions selected from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library (EORTC IL-40; higher scores indicate worse symptoms). Physical function, role function, and GHS/QoL were assessed with the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30; higher scores indicate better functioning/quality of life). Results For the primary analysis, COMMODORE 1 randomized 45 pts to crova and 44 to ecu, and enrolled 38 pts in the descriptive arm; COMMODORE 2 randomized 135 pts to crova and 69 to ecu. In COMMODORE 2, C5i-naive pts in both arms showed rapid and sustained improvement across all PRO measures during the primary treatment period. Clinically meaningful improvement (≥5 points; Cella ASH 2021; #1952) in mean FACIT-Fatigue scores from BL occurred in both arms, with numerically higher improvement with crova (crova: 7.8, 95% CI: 6.5, 9.1; ecu: 5.2, 95% CI: 3.4, 6.9; Table 1). Mean fatigue levels of pts treated with crova improved by Week 2 and were similar to normative population values by Week 25. Analysis of the individual FACIT-Fatigue items was also conducted. Additionally, improvements were observed for both treatment arms in all EORTC IL-40 symptoms and in the functioning and GHS/QoL scales of the EORTC QLQ-C30, with numerically greater improvement with crova for most scales (Table 2). The improvements with crova treatment were maintained during the crova extension period. In COMMODORE 1, C5i-experienced pts randomized to receive crova or ecu maintained BL levels of fatigue, PNH symptoms, functioning, and GHS/QoL scores throughout the primary treatment period (Tables 1 and 2) and with crova treatment during the extension period. There was no meaningful change in the mean values of any PRO scores after pts switched from ecu to crova at Week 25. Conclusions C5i-naive pts inCOMMODORE 2 experienced rapid and sustained improvements from BL in fatigue, PNH symptoms, functioning, and GHS/QoL scores while on treatment with crova and ecu, with numerically greater improvement in fatigue and most GHS/QoL scales in the crova arm. C5i-experienced pts in COMMODORE 1 maintained BL levels during the first 24 weeks of treatment with crova or ecu. These trends were maintained after pts were switched from ecu to crova. These data provide supportive evidence for the treatment benefit of crovalimab for self-reported fatigue and quality of life.

Patient Recorded Outcomes from a Randomized, Controlled Phase 2 Trial of E-Selectin Inhibition with Uproleselan Vs Placebo to Reduce GI Toxicity during Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Background: The use of high-dose melphalan conditioning followed by autologous hematopoietic cell transplant (AHCT) continues to be a key component in the treatment of patients with multiple myeloma (MM). However, high-dose melphalan is associated with a high rate of GI toxicity (&amp;gt;90%), which adversely impacts clinical outcomes and negatively influences patient quality of life (QoL). Indeed, it has been reported that AHCT leads to short-term deterioration of health-related QoL in patients with MM, and QoL typically improves by 2-3 months post-AHCT. Pre-clinical and clinical data suggest that E-selectin inhibition may play a role in reducing immune-mediated GI epithelial injury following cytotoxic chemotherapy. We hypothesized that uproleselan (upro), a synthetic, competitive E-selectin antagonist, may improve health-related QoL by reducing risk of chemotherapy-induced diarrhea in patients undergoing AHCT. Methods: We conducted a Phase 2, single-center, randomized, double-blind, placebo-controlled trial in patients with MM receiving high-dose melphalan (200 mg/m2) as conditioning for AHCT for MM. Patients were randomized 1:1 to receive prophylactic upro+standard of care (SoC) vs placebo+SoC. Uproleselan was given in 6 doses of 800 mg IV starting on day-3 through day 0. The primary endpoint was diarrhea severity as assessed by CTCAE v5.0 (secondary endpoint - Bristol Stool Scale). In addition, a key secondary endpoint was patient reported outcomes (PRO) of GI-related QoL using the National Cancer Institute (NCI) PRO-CTCAE Measurement System, a validated PRO tool developed to evaluate symptomatic toxicities in patients with cancer in clinical trials. Significance level of p&amp;lt;0.2 was pre-specified for all endpoints, per protocol. Patients were surveyed during the peri-transplant period at day-3 (baseline), day+8, and day+14 or day of discharge (DoD). Responses were graded on a scale of 1-5, with 1 indicating absence of symptoms or zero interference with daily activities and 5 indicating very severe symptoms or very significant interference with daily activities. GI-specific domains assessed included swallowing, mouth sores, appetite, nausea, vomiting, heartburn, bloating, abdominal pain, flatulence, and incontinence. Results: Fifty adult patients with MM were enrolled from 5/2021-10/2022. Baseline PRO symptoms were similar between the upro+SoC and placebo+SoC arms at baseline (day-3). By day+8 post-AHCT patients in the upro+SoC arm reported a significant improvement in severity of GI-related symptoms across 30% (6/20) of domains surveyed vs placebo+SoC (p=0.07-0.14). Furthermore, improvement in mouth sore-related symptoms continued to day+14 post-AHCT in the upro+SoC arm vs placebo+SoC (p=0.17). The remaining GI-related symptoms returned to baseline by D+14 or DoD (p&amp;gt;0.20). Also of note, a numerically lower mean diarrhea severity score and lower incidence of Grade 3 diarrhea (by CTCAE v5.0) was observed favoring upro+SOC which did not meet the pre-specified significance threshold (p=0.34, p=0.26, respectively). However, a significant reduction in severe diarrhea (by Bristol Stool Scale) was observed favoring upro+SoC (p=0.10) vs placebo+SoC, with improvement in the upro+SoC arm to mild diarrhea (p=0.02). Conclusions: Upro+SoC resulted in a clinically significant improvement in GI-toxicity related symptoms as assessed via PRO-CTCAE in patients with MM undergoing melphalan-conditioned AHCT, when compared to placebo+SoC. These improvements in patient reported outcomes are further supported by data from the primary and additional secondary endpoints of the study. Taken together, these results suggest prophylactic E-selectin inhibition may represent a promising strategy to mitigate chemotherapy-associated GI-toxicity. Further studies are needed to verify these findings and to further define the optimal dosing of upro in the peri-AHCT period.

Development of a Patient Reported Outcome Daily Diary to Assess Symptom Burden in Sickle Cell Disease

Introduction Sickle cell disease (SCD) is a genetic vascular disease that causes pain, fatigue and multiple complications, ultimately affecting health-related quality of life of patients (Osunkwo et al. Am J Hematol 2021). The purpose of this study was to conduct qualitative interviews to inform the development of a patient reported outcome (PRO) daily diary to capture key symptoms and impacts of vaso-occlusive crisis (VOCs) experienced at home, based on methods consistent with US Food and Drug Administration (FDA) guidance for incorporating patient input and clinical outcome assessments into clinical research (FDA Fed Reg 2009, FDA PFDD Draft Guidance 3 2022). Methods This was a cross-sectional, non-interventional, qualitative study involving 16 concept elicitation (CE) interviews with adults (18-65 years), 15 cognitive interviews with adults (two rounds of n=12 and n=3), and 8 hybrid CE/cognitive interviews with adolescents (12-17 years). Up to 50% of adult participants were able to participate in both CE and cognitive interviews. Adult participants were recruited by clinical sites in the United States (US) and adolescent participants were recruited by a recruitment vendor. Patients were eligible to participate if they had a confirmed diagnosis of SCD, at least two VOCs in the past 12 months, a hemoglobin level of ≥4 gm/dL in past six months, and did not have a blood transfusion in the past three months. All interviews were conducted in English according to the approved study protocol and interview guide. Key symptoms and impacts were identified during CE interviews as those that were reported by at least 75% of sample and experienced daily by at least 50% of sample. The daily diary items were refined based on cognitive interviews to ensure patient understanding, medical expert input (n=1) and medical expert advisory board input (n=4) to ensure clinical relevance. Results Adult CE and cognitive interview participants (n=25 unique participants, with 6 participating in both CE and cognitive interviews) were mostly female (n=18; 72.0%), with a mean age of 38.0 ± 9.4 years (range 20 to 56 years). Among adolescent participants, nearly all were female (n=7, 87.5%), with a mean age of 14.6 ± 2.1 years (range 12 to 17 years). All adult and adolescent participants self-identified as African American. Twenty percent (n=5) of adult participants had a history of taking crizanlizumab-tmca, 16.0% (n=4) had a history of taking voxelotor, 8.0% (n=2) had a history of taking both, and 56.0% (n=14) had never taken crizanlizumab-tmca or voxelotor. Twelve and a half percent (n=1) of adolescent participants had a history of taking crizanlizumab-tmca, 50.0% (n=4) had a history of taking voxelotor, and 37.5% (n=3) had never taken crizanlizumab-tmca or voxelotor. Findings from CE interviews identified the following key concepts: pain severity, pain crisis, tiredness, stiffness, impact on daily activities, impact on work or school, and impact on sleep. Four items were included based on medical expert/advisory board input to address swelling, ability to keep up with peers (for adolescents only), ability to control pain, and overall SCD severity. The current draft PRO daily diary includes four symptoms, four SCD-related impacts, and overall SCD severity, which will undergo further qualitative testing. Conclusion Results from this qualitative study provides further insight into the daily experience of patients with SCD, including their experience with pain crises. Findings from this study were used to develop a daily diary PRO tool for use in future clinical trials. Future work includes additional CE/cognitive interview with adults and adolescents to refine the PRO as needed and establish content validity and psychometric validation.

Patient and Parent-Reported Outcomes Post-Treatment with Shmir-Based Lentiviral Gene Therapy for Sickle Cell Disease

Background: Sickle cell disease (SCD) is among the most common monogenic disorders and causes lifelong complications, including vaso-occlusive events (VOEs) and decreased quality of life (QOL). Gene therapy (GT) has emerged as a potential curative therapy for SCD, but its impact on patients' QOL remains underexplored. We previously reported preliminary safety and efficacy data on 6 patients who received autologous CD34+ cells transduced with the BCH-BB694 lentiviral vector (Esrick et al., NEJM, 2021). Here, we report the first results of parent- and patient-reported outcomes (PROs) for 10 patients treated with BCH-BB694 up to 24 months post-infusion. Methods: We evaluated the QOL of 10 patients with severe SCD who received GT with BCH-BB694 as part of a single-center, open-label pilot study. Assessment occurred during patients' scheduled visits for safety and efficacy monitoring at baseline and months 3, 6, 12, and 24. QOL was measured using the Pediatric Quality of Life Inventory (PedsQL) self- and parent-reported questionnaires for children &amp;lt; 18-years old and the self-reported 36-Item Short Form Health Survey (SF-36) for adults ≥ 18-years old. Assessed domains included: physical functioning, pain, emotional functioning, social functioning, school functioning, and general health. The percent change from baseline to post-treatment score (last observation carried forward [LOCF]) was calculated with 95% confidence intervals (CI). Clinically significant improvement was defined as a score increase ≥5%. Other laboratory and clinical data collected at study timepoints included fetal hemoglobin (HbF) measured by high-performance liquid chromatography, VOEs (including vaso-occlusive pain, priapism, and acute chest syndrome), and transfusion frequency. Results: All patients demonstrated elevated HbF levels at LOCF (mean 26.9%, range 11.7-38.2%). Of 10 patients enrolled, 1 was missing baseline data and 9 had sufficient data for analysis. Patients (n=9) were aged 8-27 years at time of BCH-BB694 infusion. Baseline self-reported total scale scores (median 69.6, interquartile range [IQR] 50.1, 77.2) were consistent with baseline PedsQL scores for patients with SCD reported in the literature (median 67.4, IQR 50.0, 83.5) (Panepinto et al., J Pediatr Hematol Oncol, 2008). Average self-reported total scale scores increased at 3 months post-treatment (mean % change from baseline [95% CI]: 21% [3.3% to 38%]) and maintained at LOCF (13% [-10% to 36%]). For the 3 patient/parent pairs, parent-reported total scale scores appeared more variable, with a mean % change from baseline of -1% (95% CI: -40% to 38%) at 3 months and -17% (95% CI: -36% to 1%) at 24 months. Clinically significant self-reported improvement occurred in 8 patients (89%) for at least 1 domain and in 5 (56%) for overall QOL. The patient without baseline data reported a maximum total scale score of 100 at 24-months. Specific domains (mean % change from baseline [95% CI]) demonstrating significant improvement included: general health (7% [-11%, 25%]), physical functioning (30% [-15%, 76%]), and emotional functioning (15% [-9%, 39%]). Excluding 1 patient who had a low HbF induction associated with a low in vivo vector copy number and increase in VOEs from baseline, this cohort demonstrated decreased numbers and/or absence of VOEs post-GT (n=8), and all patients required significantly fewer transfusions. Conclusion: At most recent study visit up to 24 months post-treatment, SCD patients who had received GT with successful HbF induction (&amp;gt;20% in 8 patients) reported higher QOL than baseline on average. Excluding 1 patient, this cohort demonstrated improvement in at least 1 QOL domain following GT, suggesting a positive impact of GT on QOL in this group of patients with SCD. For patients &amp;lt;18-years, discrepancies between parent-reports and higher self-reports warrant future investigation. Few patients (n=3) did not demonstrate overall QOL total score improvement post-GT. Follow up studies may assess whether this reflects insufficient treatment response, treatment- or pre-existing disease-related morbidity, and/or need for more specific QOL assessments. An understanding of the relationship of change in QOL with VOE and/or transfusion rates will be enriched by more patients, longer follow-up, and PRO tools designed specifically for the SCD population. Larger studies are needed to fully elucidate the impact of GT on QOL in this population.

Cross-cultural adaptation, validation and psychometric evaluation of the International Hip Outcome Tool 12 (iHOT12) to Hebrew

BackgroundThe “International Hip Outcome Tool 12” (iHOT12) is a self-administered patient-reported outcome tool for measuring health-related quality of life and physical functioning in young and active patients with hip pathology. Since the iHOT12 has become widely used, we sought to translate and validate it for Hebrew-speaking populations. The aims of this study were: (1) To translate and culturally adapt the iHOT12 into Hebrew using established guidelines. (2) To test the new Hebrew version for validity, and (3) reliability.MethodsThe iHOT12 was translated and culturally adapted from English to Hebrew (iHOT12-H) according to the COSAMIN guidelines. For validity, the iHOT12-H and Western Ontario and McMaster universities osteoarthritis index (WOMAC) were completed by 200 patients with hip pathology. Exploratory factor analysis was used to assess structural validity. Subsequently, 51 patients repeated the iHOT12-H within a 2-week interval. Intraclass Correlation Coefficient (ICC), Cronbach alpha, and Standard Error of Measurement (SEM) were calculated to assess reliability.ResultsConstruct validity: iHOT12-H correlated strongly to the WOMAC scores (r = -0.82, P < 0.001, Spearman). Factor analysis revealed a two-factor structure. Cronbach’s alpha was 0.953 confirming internal consistency to be highly satisfactory. Test–retest correlation of the iHOT12-H was excellent with an ICC = 0.956 (95% CI 0.924–0.974). There was no floor or ceiling effect.ConclusionThe iHOT12 Hebrew version has excellent reliability, good construct validity and can be used as a measurement tool for physical functioning and quality of life in young, physically active patients with hip pathology. This study will serve Israeli researchers in evaluating treatment effectiveness for these patients. Moreover, it will also enable multinational cooperation in the study of hip pathology.

Psychometric Analysis of the Patient-Reported Hypoparathyroidism Symptom Diary Symptom Subscale Using Data from Two Clinical Trials.

The hypoparathyroidism symptom diary (HypoPT-SD) is a disease-specific patient-reported outcome (PRO) tool comprising a 7-item symptom subscale, a 4-item impact subscale and 1-item anxiety, and sadness or depression components. This analysis assessed the psychometric properties of the HypoPT-SD symptom subscale scores using data from two open-label, single arm, Phase 4 studies (Study 402 and Study 404). Eligible patients were aged 18 years or older with a confirmed diagnosis of hypoparathyroidism. All patients received recombinant human parathyroid hormone (1-84) during the analysis period. Scores were recorded at baseline, and at months 6, 30 and 36 (end of treatment [EOT]) in Study 402, and at baseline and week 52 (EOT) in Study 404. The structure of the HypoPT-SD Symptom subscale was analyzed by measuring correlations between pairs of item scores; internal consistency and reliability were evaluated using Cronbach's coefficient α; test-retest reliability was assessed using intraclass correlation; and construct validity was determined by performing correlational analyses between scores recorded using the HypoPT-SD and those for other conceptually similar PRO tools. A total of 60 patients were included in the analysis. Inter-item pairwise correlations were strong for all but 5 of the item pairs analysed. Cronbach's α values for the HypoPT-SD Symptom subscale were 0.88 using data from Study 402 and 0.92 using data from Study 404. In general, the HypoPT-SD Symptom subscale scores had moderate or strong correlations with scores recorded using PRO tools. Intraclass correlation coefficients exceeded 0.70 using test-retest data from all patients in Study 402 and from a subgroup of patients with stable disease from Study 404. This analysis demonstrated the test-retest reliability, internal consistency and construct validity of the HypoPT-SD using data from longitudinal prospective studies and supports the use of the HypoPT-SD in future clinical studies.

Evaluating Predictors of Patient Satisfaction With Facial Appearance After Mohs Micrographic Surgery Using the FACE-Q.

Although patient satisfaction with reconstructive outcomes after facial skin cancer resection is an important consideration in Mohs surgery, there is limited information evaluating this concern using validated patient-reported outcome tools. To characterize predictors that may be associated with increased postoperative patient satisfaction with facial appearance after Mohs surgery using the FACE-Q/Skin Cancer survey, a patient-reported outcome tool that has been validated in various studies. A total of 202 patients who underwent Mohs surgery for facial skin cancer at the Brigham and Women's Faulkner Hospital between April 2017 and November 2021 were included after completing the postoperative Satisfaction with Facial Appearance scale (FACE-Q scale). Male patients were significantly more likely to have higher satisfaction scores compared with female patients (aOR 2.4, 95% CI 1.1-5.1). Increased preoperative facial satisfaction scores was directly correlated with increased postoperative facial satisfaction scores ( p < .01). Patients with tumors on the lower face/neck (aOR 3.88; 95% CI 1.4-10.7) had significantly greater satisfaction scores compared with those with tumors on their nose/nasolabial folds. Potential interventions and counseling methods can be tailored toward specific patient populations with lower satisfaction scores to increase their overall satisfaction with reconstructive outcomes.

OR01-01 Oral, Once-daily, Paltusotine (Non-peptide Selective Somatostatin Receptor Subtype 2 Agonist) Therapy In Patients With Acromegaly Is Associated With Long-term Biochemical And Symptom Control And Is Preferred Over Injectable Somatostatin-Receptor Ligands

Abstract Disclosure: M.R. Gadelha: Advisory Board Member; Self; Crinetics Pharmaceuticals, Ipsen, Novo Nordisk, and Recordati Rare Diseases. Research Investigator; Self; Crinetics Pharmaceuticals and Recordati Rare Diseases. Speaker; Self; Crinetics Pharmaceuticals, Ipsen, Novo Nordisk, and Recordati Rare Diseases. H.S. Randeva: None. M.B. Gordon: Consulting Fee; Self; Crinetics Pharmaceuticals, HRA Pharma, Novo Nordisk, and Recordati Rare Diseases. Grant Recipient; Self; Ascendis, Camurus, Chiasma, Corcept, Crinetics, Ipsen, Novartis, Novo Nordisk, Opko, Pfizer, and Strongbridge. M. Doknic: Advisory Board Member; Self; Pfizer in CEE region. Research Investigator; Self; Crinetics Pharmaceuticals, Pfizer, Camurus, Ascendis, Opko, Ipsen, and Teva. Speaker; Self; Pfizer, Novartis, Novo Nordisk, Sandoz, and Merck. E. Mezosi: Research Investigator; Self; Crinetics Pharmaceuticals. M. Toth: Consulting Fee; Self; Ipsen, Novartis, Pfizer, and Recordati Rare Diseases. Research Investigator; Self; Crinetics Pharmaceuticals. C.L. Boguszewski: Consulting Fee; Self; Novo Nordisk. Research Investigator; Self; Crinetics Pharmaceuticals and Recordati Rare Diseases. Speaker; Self; Ipsen and Recordati Rare Diseases. C.T. Ferrara-Cook: Employee; Self; Crinetics Pharmaceuticals. A. Casagrande: Employee; Self; Crinetics Pharmaceuticals. A. Krasner: Employee; Self; Crinetics Pharmaceuticals. Paltusotine is an investigational oral, once-daily, non-peptide, SST2 agonist in development for the treatment of acromegaly and neuroendocrine tumors. Interim analysis results from patients with acromegaly treated with paltusotine for up to 2 years in ACROBAT Advance (NCT04261712), an ongoing, 4-year, single-arm, open-label extension study, are reported here. Patients who completed ACROBAT Edge (NCT03789656) or Evolve (NCT03792555) phase 2 parent studies were eligible to enroll in Advance. In Edge, patients were either sub-optimally controlled on injectable somatostatin-receptor ligand (iSRL; octreotide or lanreotide) therapy alone or in combination with cabergoline; or required combination therapy or pasireotide to achieve normal IGF-I levels at baseline. Evolve enrolled patients who had normal IGF-I levels on iSRL monotherapy at baseline. In Advance, adjunctive medication with cabergoline or pegvisomant was allowed in patients who had not achieved normal IGF-1 levels on maximum dose of paltusotine (40 mg). Serum IGF-I levels were measured using Immunodiagnostic Systems iSYS immunoassay. Symptoms were assessed using the Acromegaly Symptom Diary (ASD; score range, 0-70; higher numbers indicate greater symptom burden), which was developed based on FDA recommendations for patient-reported outcome tools. Patient treatment preference was also evaluated. Forty-three patients were enrolled in Advance (Edge, n=32; Evolve, n=11; 88% of eligible patients). At baseline on iSRL, mean (SD) age was 53.0 (11.6) years, 56% were females, 86% had previous pituitary surgery, and none had radiotherapy. Median (IQR) IGF-I levels remained stable: baseline on iSRL, 1.15x ULN (0.84, 1.46; n=43); in Advance, Week 51 1.08x ULN (0.87, 1.26; n=37), Week 77 1.01x ULN (0.85, 1.28; n=27), and Week 103 1.10x ULN (0.96, 1.45; n=10). Among patients receiving adjunctive medication in Advance, 94% were from the Edge study. Acromegaly symptoms were stably controlled: median (IQR) ASD scores at baseline on iSRL, 8.57 (3.57, 20.14; n=21) and, in Advance at Week 77, 8.0 (5.0, 18.0; n=14). At Week 52, 32 (88.9%) of the 36 respondents preferred once-daily oral paltusotine, 2 (5.6%) preferred previous injections, and 2 (5.6%) had no preference. The most common treatment-emergent adverse events (TEAEs) reported were headache (30.2%), arthralgia (25.6%), and fatigue (18.6%). No serious drug-related TEAEs were reported. Of the 6 patients who discontinued the study, 1 (2.3%) was due to a TEAE (headache). Glycemic control, as measured by HbA1c, was stable during paltusotine treatment. In conclusion, with up to 2 years of follow-up in patients with acromegaly, once-daily oral paltusotine treatment was well-tolerated, associated with stable IGF-I and symptom control relative to that achieved by iSRLs, and was preferred over injected therapy. Support: Crinetics Pharmaceuticals. Presentation: Thursday, June 15, 2023