Validated Patient-reported Outcomes Instruments Research Articles

#1151 The prevalence and disease burden of CKD associated pruritus in Danish dialysis patients and current treatment practices—preliminary results

Abstract Background and Aims Chronic kidney disease associated pruritus (CKD-aP) is rarely assessed by health care providers and potentially under-reported by patients despite the potential negative impact on health-related quality of life (HRQoL). Our aim was to investigate the prevalence of CKD-aP in a large cohort of Danish dialysis patients based on validated patient-reported outcome (PRO) instruments. A secondary aim was to investigate CKD-aP awareness among renal physicians including current treatment practices. Method The study was designed as a non-interventional, cross-sectional multicentre study. Chronic dialysis patients from four different regions in Denmark were invited to participate. CKD-aP was assessed with a one-page questionnaire containing Danish versions of two validated PRO instruments. The worst itch numeric rating scale (WI-NRS) was used for itch severity within the previous 24 hours (ranging from 0-10 with CKD-aP defined as WI-NRS score >4 which equals moderate to severe CKD-aP). The 5-D itch scale was used as a multidimensional measure of itching and HRQoL. The five dimensions of the 5-D itch scale (degree, duration, direction, disability, and distribution) were summed together to obtain total score ranging from 5 (no pruritus) to 25 (most severe). CKD-aP awareness and treatment practices among doctors and nurses were investigated with a simple self-invented questionnaire. Results We recruited 500 chronic dialysis patients of which 87% were treated with in-center haemodialysis (HD), 10% with peritoneal dialysis (PD) and 3% with home HD (HHD). Mean age ± SD was 65 ± 14 years and 64% were males. Fig. 1 shows WI-NRS and total 5-D itch score distribution according to dialysis modality. CKD-aP prevalence (based on WI-NRS score >4) was 19% (all patients regardless of dialysis modality) but tended to be higher among PD patients (29%) in comparison with HD (18%) and HHD (23%) as shown in Fig. 1. Odds ratio (OR) with logistic regression for CKD-aP based on WI-NRS score as a binary dependent variable (≤4 or >4) and dialysis modality yielded: OR (PD vs. HD): 1.83 (0.96-3.49) and OR (HHD vs. HD): 1.35 (0.36-5.03). No pruritus (WI-NRS score = 0) was found in 61% of patients and 20% had mild pruritus (WI-NRS score ≤4). WI-NRS score correlated significantly with total 5-D itch score (Spearman's rank correlation coefficient (all patients): ρ = 0.80; P < .001). Median total 5-D itch score (IQR) was 5 (5-10) based on all patients regardless of dialysis modality. Itch intensity over the past 2 weeks was rated moderate to unbearable by 23% and not present in 54% of patients. Itch duration was less than 6 hours in 91% of patients and 29% of patients had no change in itching over the past 2 weeks. Overall, the impact of CKD-aP on daily activities (leisure/social, housework/errands and work/school) was minimal in most patients but sleep disability (score >1) was found in 18%. Sleep disability was significantly associated with higher WI-NRS score. Perceived CKD-aP prevalence (based on 28 questionnaires) was 20-40% according to most physicians (54%), 25% estimated it to be lower and 21% expected it to be higher. Topical therapy with fatty cream was the preferred treatment by most physicians followed by increased dialysis and non-sedating antihistamines. Conclusion Roughly one out of five patients on chronic dialysis treatment suffers from moderate to severe CKD-aP. HRQoL is negatively affected by CKD-aP primarily manifested as sleep disturbance. Most physicians tend to overestimate CKD-aP prevalence and prescribe fatty cream as their preferred treatment.

Postnasal Drip

Postnasal drip (PND) is a common symptom encountered when evaluating subjects with sinonasal disease; it may be present without sinonasal disease or as a symptom of laryngopharyngeal reflux (LPR). It is postulated that PND stems from dysfunction of normal mucus clearance mechanisms, however, there is no definitive evidence elucidating an exact pathophysiology. Compounding the uncertainties surrounding PND is the lack of an objective assessment tool. Instead, treating physicians must rely on subjective complaints and investigators utilize validated patient reported outcome instruments, such as the sino-nasal outcome test (SNOT), to determine treatment efficacy. This review seeks to discuss the current understanding of PND and evidence regarding effective treatment strategies.

Burden of Hidradenitis Suppurativa: A Systematic Literature Review of Patient Reported Outcomes.

Hidradenitis suppurativa (HS) has a profound negative impact on patients' health-related quality of life (HRQoL). Here we summarize the evidence on HRQoL and Patient Reported Outcomes (PROs) in patients with HS in real-world settings by conducting a systematic literature review (SLR) of observational studies. Data sources included MEDLINE, Embase & PsycINFO between January1, 2010 and August29, 2021, and conference proceedings between 2019 and 2021. Identified abstracts were reviewed and screened independently by two reviewers. Eligibility criteria included patients with HS of any severity, sample size ≥ 100, reporting PROs including HRQoL measures. Included studies were critically appraised. Fifty-eight observational studies matched inclusion criteria. Dermatology Life Quality Index (DLQI) was the most commonly utilized instrument: 57% of included studies reported mean baseline DLQI scores, ranging between 8.4 and 16.9, indicating a very large impact on the patients' HRQoL. Higher scores were reported with increasing disease severity and among female patients. Pain was assessed mostly by an 11-point (0-10) numeric rating scale (NRS) with a mean baseline score ranging from 3.6 to 7.7 indicating moderate to high pain levels. There was a negative impact of HS on patients' psychological well-being, based on PRO scores related to depression and anxiety. A high proportion of sexual dysfunction was reported, with a larger impact on women than men. Work productivity and leisure activity were consistently found to be impaired in patients with HS. All included studies reported a negative impact of HS on patients' lives. A diverse set of disease- and non-disease-specific PRO instruments were utilized highlighting the need for more consistent use of HS-specific validated PRO instruments to assess the impact of HS on the different aspects of patients' HRQoL to allow for data to be more meaningfully interpreted and compared in real-world settings. Patients with HS need better disease management approaches that address the observed low quality of life.

Health-related quality of life in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors: the role of combination treatment therapy.

While the addition of androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) results in better of overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC), information regarding health related quality of life (HR-QoL) is sparse. We aimed at summarizing current evidence on the impact of ARSIs on HR-QoL. We performed a systematic review of the published literature on PubMed/EMBASE, Web of Science, SCOPUS, and the Cochrane libraries between January 2011 and April 2022. We included only phase III randomized controlled trials (RCT), which were selected according to the PRISMA guidelines. We aimed at evaluating differences in HR-QoL, assessed by validated patient reported outcomes instruments. We analyzed global scores and sub-domains such as sexual functioning, urinary symptoms, bowel symptoms, pain/fatigue, emotional and social/family wellbeing. We reported data descriptively. Six RCTs were included: two used enzalutamide with ADT as intervention arms (ARCHES, ENZAMET); one used apalutamide with ADT (TITAN); two abiraterone acetate and prednisone (AAP) with ADT (STAMPEDE, LATITUDE); and one darolutamide with ADT (ARASENS). Enzalutamide or AAP with ADT increase overall HR-QoL in comparison with ADT alone, ADT with first generation nonsteroideal anti-androgens or ADT with docetaxel, whereas apalutamide and darolutamide with ADT maintain HR-QoL similarly to ADT alone or ADT with docetaxel, respectively. Time to first deterioration of pain was longer with combination therapy with enzalutamide, AAP or darolutamide, but not with apalutamide. No worsening of emotional wellbeing was reported from the addition of ARSIs to ADT than ADT alone. The addition of ARSIs to ADT in mHSPC tends to increase overall HR-QoL and prolong time to first deterioration of pain/fatigue compared with ADT alone, ADT with first generation nonsteroideal anti-androgens, and ADT with docetaxel. ARSIs show a complex interaction with remaining HR-QoL domains. We advocate a standardization of HR-QoL measurement and reporting to allow further comparisons.

Patient-Reported Quality of Life in Adolescents and Young Adults with Cancer before, during, and after Radiation Therapy

<h3>Purpose/Objective(s)</h3> Adolescents and young adults (AYAs, 15-39 yo) with cancer have unique vulnerabilities that affect quality-of-life (QOL) during treatment and in survivorship. Yet, few studies have assessed QOL in AYAs with cancer who received radiation therapy (RT). Therefore, we performed a cross-sectional study in AYAs with cancer who completed patient-reported outcomes (PROs) assessing QOL before, during, or after RT. <h3>Materials/Methods</h3> We identified 265 AYAs with cancer who were treated with RT and completed an AYA PRO survey from 2019-2022. The survey containing ten validated PRO instruments from the PROMIS inventory: Global Physical and Mental Health, Anxiety, Depression, Fatigue, Sleep Disturbance, Social Roles, Pain Interference, and Cognitive Function (score of 50 represents the mean from the reference U.S. general population; higher score represents more of the concept being measured). Patients were stratified into 3 cohorts based on the date of PRO completion: before RT, peri-RT (during RT or within 6 months of RT completion), or after RT (6+ months following RT completion). Mean (standard deviation [SD]) PRO scores were calculated. Patient characteristics were extracted from the medical record. Kruskal-Wallis analysis was used to compare scores between cohorts. ANOVA and t-test analyses were used to compare scores between co-variates. <h3>Results</h3> 87 (33%) patients completed PROs before RT, 84 (32%) peri-RT, and 94 (35%) after RT; median [IQR] age was 28 [21-33], 26 [20-32], and 22 [17-27], respectively. Cancer types varied; most had sarcoma (26%) or CNS cancer (23%). Compared to the before RT cohort, the peri-RT cohort had worse Global Physical and Mental Health PRO scores [SD] (48.7 [8.9] vs. 44.9 [9.8] (p=0.03) and 50.9 [8.6] vs. 46.2 [10.3] (p<0.01), respectively). These PRO scores were similar between the peri- and after RT cohorts (44.9 [9.8] vs. 45.5 [9.8] (p=0.68) and 46.2 [10.3] vs. 47.9 [9.6] (p=0.26), respectively). Compared to the before RT cohort, the peri- and after RT cohorts had better Anxiety PRO scores [SD] (55.2 [9] vs. 52.6 [10.4] and 51 [10], respectively, p=0.02). Remaining PRO scores were similar between cohorts (p>0.05). In the peri-RT cohort, patients with any acute RT toxicity had worse Pain Interference PRO scores [SD] vs. patients with none (50.8 [8.9] vs. 44.7 [5.7], p=0.03). In the after RT cohort, adolescents (15-18 yo) and young adults (26-39 yo) had worse Global Mental Health PRO scores [SD] vs. emerging adults (19-25 yo) (46.9 [9.1] and 47.9 [11.2], respectively, vs. 53.8 [9.2], p=0.04); patients with any late RT toxicity had worse Sleep Disturbance PRO scores [SD] vs. patients with none (58.4 [8] vs. 52.4 [9.2], p<0.001). <h3>Conclusion</h3> AYAs with cancer reported lower general physical and mental health QOL scores during RT, which persisted into survivorship. Developmental age, stage, and presence of RT toxicities may contribute to differing scores. Future longitudinal analyses are needed to improve QOL for AYAs receiving RT.

Use of Pro in Evaluating TAA and its Indications

Category: Ankle Introduction/Purpose: The indications for total ankle arthroplasty (TAA) have greatly expanded over the past decade. This rapid growth has been made possible with evidence-based medicine. Patient-reported outcomes (PROs) have been the primary outcome measure in many of these studies. To evaluate the quality of the evidence underlying expanded indications for TAA, we must first understand what PROs have been used in the evaluation of outcomes of TAA. Methods: The goal of this study was to conduct a systematic review of the literature from 2010 to 2021 capturing all studies of TAA to determine what PRO instruments were used, and what facets of TAA practice were studied. Studies reporting on outcomes and PROs following a TAA procedure were selected to review from the PubMed database between January 2010 and July 2021. Results from one hundred sixty-three studies were reviewed and pooled for analysis for this study. Results: After the evaluation of one hundred sixty-three studies, twenty-four separate PRO measures were identified in the literature. The PROs that were most reported in the literature from 2010 to 2021 were American Orthopedic Foot and Ankle Score (AOFAS) (49.1%), 36-Item Short Form Survey (SF-36) (40.5%), visual analog scale - pain (VAS) (35.6%), Ankle Osteoarthritis Scale (AOS) Questionnaire (17.8%), and Short Musculoskeletal Function Assessment (SMFA) (14.7%). The independent variables in these studies included a wide range of modifiable and unmodifiable patient factors such as age (27 studies), BMI (23 studies), smoking (8 studies), and preoperative coronal plane deformity (5 studies). A significant portion of the studies (41%) advocating for expanded indications did so based on the failure to find a difference in groups. Conclusion: The most commonly used PROs for TAA were AOFAS, SF-36, and VAS. The AOFAS score which had been the most commonly used PRO in 2009, is still today despite the determination in 2011 that it is not valid and there is a substantial risk for bias. Newer, validated PRO instruments, such as PROMIS, have not yet attained significant implementation in studies of TAA. The vast majority of the evidence supporting the expanded indications for TAA has come from studies with negative results. Caution should be exercised in interpreting these results and their study implications.

S211: CLINICAL AND PATIENT-REPORTED OUTCOMES IN A PHASE 3 STUDY OF AXICABTAGENE CILOLEUCEL (AXI-CEL) VS STANDARD-OF-CARE IN ELDERLY PATIENTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (ZUMA-7)

Background: The median age at large B-cell lymphoma (LBCL) diagnosis is 66 years, and older patients with relapsed/refractory (R/R) LBCL are at risk of inferior outcomes, increased toxicity, and inability to tolerate second-line standard-of-care (SOC) treatment (Di M, et al. Oncologist. 2021). Further, second-line SOC treatment is often associated with poor health-related quality of life (Lin V, et al. J Clin Oncol. 2020;38:e20070). In the global Phase 3, randomized ZUMA-7 study, axi-cel, an autologous anti-CD19 CAR T-cell therapy, significantly improved event-free survival (EFS; hazard ratio [HR], 0.398, P<0.0001; median 8.3 vs 2 months, respectively) compared with second-line SOC in R/R LBCL (Locke FL, et al. N Engl J Med. 2022;386:640-654). Aims: Here we report results of a planned subgroup analysis of the ZUMA-7 study assessing outcomes, including patient-reported outcomes (PROs), of second-line axi-cel vs SOC in patients aged ≥65 years. Methods: Patients with ECOG performance status 0-1 and R/R LBCL ≤12 months after first-line chemoimmunotherapy were randomized 1:1 to axi-cel or SOC (2-3 cycles of platinum-based chemoimmunotherapy; patients with partial or complete response [CR] proceeded to high-dose therapy with autologous stem cell transplantation). PRO instruments, including the EORTC QLQ-C30 (Global Health and Physical Functioning) and the EQ-5D-5L visual analog scale (VAS), were administered at baseline (prior to treatment), Day 50, Day 100, Day 150, and Month 9, then every 3 months up to 24 months or time of EFS event, whichever occurred first. The quality-of-life analysis set included all patients who had a baseline PRO and ≥1 completed measure at Day 50, 100, or 150. A clinically meaningful change was defined as 10 points for each EORTC QLQ-C30 score and 7 points for EQ-5D-5L VAS score. Results: The data cutoff for this analysis was March 18, 2021 and included 51 axi-cel and 58 SOC patients with median ages of 70 years (range, 65-80) and 69 years (range, 65-81), respectively. At baseline, more axi-cel vs SOC patients had high-risk features, including second-line age-adjusted International Prognostic Index 2-3 (53% vs 31%) and elevated lactate dehydrogenase (61% vs 41%). EFS was superior with axi-cel vs SOC (HR, 0.276, P<0.0001), with higher CR rates (75% vs 33%). Grade ≥3 treatment-emergent adverse events (AEs) occurred in 94% and 82% of axi-cel and SOC patients, respectively, and Grade 5 treatment-related AEs occurred in 0 and 1 patient. In the quality-of-life analysis set comprising 46 axi-cel and 42 SOC patients, there were statistically significant and clinically meaningful differences in mean change of scores from baseline at Day 100 favoring axi-cel for EORTC QLQ-C30 Global Health (P<0.0001) and Physical Functioning (P=0.0019) and EQ-5D-5L VAS (P<0.0001). For all 3 domains, scores also favored (P<0.05) axi-cel over SOC at Day 150. The mean estimated scores numerically returned to or exceeded baseline scores earlier in the axi-cel arm (by Day 150) but never equaled or exceeded baseline scores by Month 15 in the SOC arm. Summary/Conclusion: Axi-cel demonstrated superiority over second-line SOC in patients ≥65 years with significantly improved EFS and a manageable safety profile. Axi-cel also showed meaningful improvement in quality of life over SOC, measured by multiple validated PRO instruments, with suggested faster recovery to pretreatment quality of life. The superior clinical outcomes and patient experience with axi-cel over SOC should help inform treatment choices in second-line R/R LBCL for patients ≥65 years.

Racial and ethnic disparities in adherence and reported symptoms during routine collection of patient-reported outcomes (PROs).

6510 Background: Routine collection of PROs for patients with cancer is an evidence-based practice and critical component of high-quality cancer care, but real-world adherence and reporting patterns are poorly understood. We examined differences in PRO adherence and reported symptoms by race and ethnicity. Methods: We conducted a retrospective cross-sectional study using de-identified electronic health record data from a National Cancer Institute Comprehensive Cancer Center. Participants included adults seen in follow-up at one of two medical oncology practices (1 academic, 1 community) from June 2019 to February 2020, during which two validated PRO instruments (NCI PRO-CTCAE and PROMIS Global v1.2) were routinely administered electronically via portal or tablet at return visits. Adherence was defined for each participant as the proportion of visits in which a PRO questionnaire was completed within 30 days. Using ordinary least squares regression, we modeled patient adherence as a function of race/ethnicity and adjusted for age, sex, insurance, median area income, ECOG performance status, cancer type, cancer stage, visit site, and number of visits during the study. Among study participants completing at least one PRO questionnaire, we modeled reported symptoms from the first questionnaire using a similar approach. Results: From June 2019 to February 2020, there were 29,726 patients (mean [SD] age 60.8 [15.1] years; 18,045 [60.7%] female) seen across 111,262 medical oncology visits. Of these patients, 19,971 (67.2%) completed at least one PRO questionnaire. Adjusted mean PRO adherence and reported symptoms varied by race/ethnicity, with Black and Hispanic patients reporting significantly higher symptom burden than White patients (Table). Conclusions: In this large cohort reflecting real-world PRO collection patterns, Black and Hispanic patients were less likely than White patients to complete PRO questionnaires, but more likely to report more severe symptoms. There is urgent need to ensure equitable PRO access and implementation and to address greater reported symptom burden among minority patients. [Table: see text]

Patient-Reported Outcomes in a Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard of Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma (ZUMA-7)

Patient-Reported Outcomes in a Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard of Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma (ZUMA-7)

Long-Term Patient-Reported Quality of Life and Functional Outcomes After Chemoradiation Using Intensity Modulated Radiotherapy for Anal Cancer

Few studies have long-term follow-up assessing patient-reported outcomes (PROs) after intensity-modulated radiation therapy (IMRT)-based chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). There is poor agreement between physician-graded toxicity and PROs regarding quality of life (QOL) in patients with SCCA. Therefore, we surveyed SCCA survivors ≥ 2 years out from CRT with validated PRO instruments assessing bowel, bladder, and sexual function.We identified 248 patients with SCCA treated with definitive IMRT-based CRT at a large tertiary cancer center from 2010-2018, who were alive and without recurrence. Patients were asked to complete five PRO instruments: Fecal Incontinence QOL Scale (FIQOL), Low Anterior Resection Syndrome Score (LARS), International Consultation on Incontinence Questionnaire (ICIQ), male and female lower urinary tract symptoms (MLUTS and FLUTS, respectively), International Index of Erectile Function (IIEF), and Female Sexual Function Index (FSFI). FIQOL, LARS, IIEF, and FSFI scores were dichotomized and logistic regression used to identify predictors of QOL scores.One hundred eight (44%) patients completed the PROs. Respondents' median [interquartile range, (IQR)] age was 66 [59-72] years, 80% were female, and 95% were white. Median [IQR] gross tumor volume (GTV) was 45 [27-71] cc; dose to GTV was 50 Gray (Gy), 54 Gy and 58 Gy in 25%, 53%, and 22%, respectively. Median [IQR] time from CRT was 51 [37-84] months. Median [IQR] FIQOL score was 14.3/20 [11.2-16.1]; higher is better. Larger GTV size (OR 0.99; P = 0.03) was associated with lower FIQOL score. Sixty-one (56%) patients met major LARS criteria. There was a trend towards a higher incidence of major LARS with GTV dose ≥ 54 Gy (OR 2.39; P = 0.08). Men had median [IQR] ICIQ MLUTS voiding and incontinence scores of 5/20 [2-6] and 1/24 [1-3], respectively. Women had median [IQR] ICIQ FLUTS voiding and incontinence scores of 1/12 [1-3] and 5/20 [3-8], respectively; higher is worse. Fifty-nine (55%) patients reported being sexually active in the last month. Men had a median [IQR] IIEF score of 14/25 [6-19]; higher is better. Only age (OR 1.17; P = 0.04) was significantly associated with IIEF ≤ 11 (moderate or severe ED). Women had a median [IQR] FSFI score of 20.2/26 [13.6-24.9]; higher is better. Age < 65 was associated with sexual dysfunction, defined as FSFI < 26.55 (OR, 5.5; P = 0.04). Forty (37%) patients disagreed or strongly disagreed that they were prepared for long-term side effects. Seventy (65%) patients agreed or strongly agreed that educational materials would have been helpful.SCCA survivors experience significant long-term bowel and sexual toxicities from modern CRT. Larger tumors and higher RT doses may be associated with worse function. Interventions to reduce toxicities and improve patient education are needed.

A Systematic Literature Review of Patient-Reported Outcome Instruments Used in Sickle Cell Disease

Introduction: Patients with sickle cell disease (SCD) often have recurrent episodes of acute severe pain (vaso-occlusive crises, VOCs), which result in repeated hospital admissions and use of pharmacological treatments, and can negatively impact patients' health-related quality of life (HRQL). Most SCD randomized clinical trials (RCTs) are designed to evaluate efficacy in relation to changes in the number of VOCs and their impact on HRQL. We conducted a systematic literature review (SLR) to identify patient-reported outcome (PRO) and healthcare resource utilization (HCRU) instruments used in RCTs and real-world studies and to evaluate their psychometric properties with a view to provide recommendations of appropriate PRO endpoints for use in clinical trials for SCD treatments in the United States (US).Methods: An SLR was conducted to search, identify and summarize validated PRO instruments that have been used by patients with SCD in the US and their caregivers. MEDLINE and EMBASE were searched using terms synonymous with “sickle cell disease” and “psychometric properties” of PRO instruments for articles published in English between 1997 and March 2017 focusing on pediatric patients (5-17 years) and their caregivers, and adults (≥18 years). Studies were included if results were based on assessing psychometric properties of PRO instruments and if the studies were interventional or observational in design. Exclusion criteria included studies conducted in non-US populations, reporting on non-validated generic questionnaires or without any psychometric data. Conference abstracts, narrative reviews, letters to the editor, laboratory studies and case reports/series were excluded. The quality of PRO instruments in the included studies was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist, a well-established checklist to measure the methodological quality and performance of PRO instruments across a number of domains as reported in psychometric evaluation studies.Results: The SLR identified 504 references for title/abstract screening. Of these, 46 full-text articles were further assessed for inclusion and 19 articles were included. Two additional articles were identified from manual reference checks of relevant SLRs. Thus, a total of 21 US-based studies assessing 10 child and 15 adult PRO instruments in SCD were included in the review. No validated PRO instruments were found that measured caregiver burden in SCD and no validated HCRU instruments for any SCD population were identified. The review of pediatric studies identified the most commonly reported instrument to be the Pediatric Quality of Life Inventory (PedsQL), while most of the adult instruments (9 of 15) focused on evaluating self-efficacy/-esteem and pain in relation to SCD. Only one instrument, the Adult Sickle Cell Quality of Life Measurement (ASCQ-Me), was identified as evaluating HRQL in adults. Out of the 25 PRO instruments reviewed for both children and adults, only 3 out of 10 and 5 out of 15 instruments, respectively, were specifically developed for these age groups with SCD. There were little or no data on validation conducted in SCD development cohorts for most instruments. Additionally, the included studies did not assess minimally important differences in any of the instruments reviewed. In terms of instruments' psychometric properties, most instruments (9 of 15) identified for adult populations had strong internal reliability; however, there was often insufficient information to assess the content validity, construct validity, responsiveness and test-retest reliability of the instruments identified for both child and adult populations.Conclusions: Limited evidence on the psychometric properties of PRO instruments used in patients with SCD was identified. Furthermore, among the instruments reviewed, none was found to sufficiently capture all the PRO aspects of SCD and its complications on patients' HRQL for use as key trial endpoints. Further research should validate, or develop if no instrument is in existence, PRO instruments to assess HRQL of patients with SCD, PRO instruments for caregivers and HCRU instruments. DisclosuresSarri:Evidera: Employment. Bhor:Novartis: Employment, Equity Ownership, Research Funding. Abogunrin:Evidera: Consultancy; Novartis: Research Funding. Farmer:Evidera: Employment; Novartis: Research Funding. Nandal:Novartis: Employment, Equity Ownership, Research Funding. Revicki:Novartis: Consultancy, Research Funding.

Meniscal and Articular Cartilage Predictors of Outcome following Revision ACL Reconstruction: A 6-Year Follow-up Study

Objectives:Previous work has shown that having a lateral meniscectomy prior to revision ACL surgery, as well as grade 3-4 chondral damage to the trochlea at the time of revision ACL surgery results in poorer outcomes at 2 years. Alternatively, meniscal or articular cartilage (AC) pathology documented at the time of a revision surgery were not found to be significant risk factors for 2-year activity levels. The purpose of this study was to follow this cohort for a longer time period, to determine if either meniscal and/or articular cartilage pathology noted at the time of revision ACL surgery significantly affects a patient’s activity level, sports function, and OA symptoms at 6-year follow-up.Methods:Revision ACL reconstruction patients were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline demographics, surgical technique and pathology, and a series of validated patient reported outcome instruments (IKDC, KOOS, WOMAC, and Marx activity rating score). Patients were followed up for 6 years and asked to complete the identical set of outcome instruments.Regression analysis was used to control for age, gender, BMI, smoking status, activity level, baseline outcome scores, revision number, time since their last ACL reconstruction, graft choice, and previous and current meniscal and articular cartilage pathology, in order to assess the meniscal and AC pathology risk factors for clinical outcomes 6 years after revision ACL reconstruction.Results:1234 patients met the inclusion criteria and were successfully enrolled, with 716 (58%) males and a median cohort age of 26 years. The median time since their last ACL reconstruction was 3.4 years. Surgeons noted previous pathology in the medial meniscus (39%), lateral meniscus (20%), and articular surfaces (12%) at the time of revision surgery. Surgeons reported current pathology at the time of revision surgery in the medial meniscus (45%), lateral meniscus (36%), medial femoral condyle (MFC; 43%), lateral femoral condyle (LFC; 29%), medial tibial plateau (MTP; 11%), lateral tibial plateau (LTP; 17%), patella (30%), and trochlea (21%). At 6 years, follow-up was obtained on 77% (949/1234). Previous and current meniscal pathology (both medial and lateral), as well as current AC pathology (in the MFC, LTP, trochlea, and patella) were found to be significant drivers of poorer outcomes at 6 years. The most consistent cartilage-related factors driving outcome in revision patients were either a previous or current repair or excision of the medial meniscus and patellofemoral AC pathology. Six-year Marx activity levels were negatively impacted by having either a repair or an excision of the medial meniscus (odds ratio range =0.58-66; 95% CI=0.38-0.91; p=0.01) or having grade 3-4 patellar chondrosis (OR=0.57; 95% CI= 0.35-0.95; p=0.03). Conversely, 6-year activity levels significantly improved by having either a lateral meniscus repair or excision (OR=1.49-2.22; 95% CI=1.07-4.04; p=0.005). Previous medial or lateral meniscal pathology negatively affected all KOOS subscales except for sports/recreation (p<0.05). Articular pathology significantly impaired KOOS symptoms, sports/recreation and the quality of life subscales (p<0.05). The KOOS sports/recreation subscale was significantly affected by articular cartilage pathology (LTP, patella, trochlea; p<0.03). Lower baseline outcome scores, lower baseline activity level, and being a smoker all significantly increased the odds of reporting poorer clinical outcomes at 6 years.Conclusion:Meniscal and articular cartilage pathology was found to have a larger impact at 6 years following revision ACL surgery, as compared to 2-year follow-up. In contrast to 2-year follow-up, incidence of medial meniscal and AC pathology at the time of a patient’s revision surgery were found to significantly diminish a patient’s activity level at 6 years, whereas the incidence of lateral meniscal repair or excision was found to improve a patient’s activity level. Having a previous medial meniscal repair or excision or exhibiting grade 2-4 chondral damage noted at the time of ACL revision reconstruction results in poorer IKDC and KOOS scores and worse WOMAC pain and ADL scores at 6 years following revision surgery.

Patient-reported outcomes (PRO) from a phase I/II dose-escalation study of fractionated dose 177Lu-PSMA-617 for progressive metastatic castration-resistant prostate cancer (mCRPC).

45 Background: We performed the 1st dose-escalation study of PSMA-targeted radionuclide therapy with 177Lu-PSMA-617. Using dose-fractionation, we intended to deliver a dose-intense regimen designed to minimize radioresistance due to repopulation. Radionuclide therapy may be able to treat symptoms due to tumor and therefore may be associated with improvement in PRO. Methods: Inclusion: progressive mCRPC following potent AR-pathway inhibitor (ARPI, e.g. abi/enza) and taxane (or unfit/refuse chemo) without limit of # prior therapies, adequate organ function, ECOG performance status 0-2, without preselection for PSMA expression. Treatment was a single cycle of fractionated dose 177Lu-PSMA-617 on D1 and D15 (7.4 to 22 GBq in phase 1; 22.2 GBq in phase 2). PRO tools included FACT-P and BPI-SF at baseline and follow up. Results: 44 men with median age 69 (range 55-91), median PSA 182.97 (range 0.89-5541) were treated. 93% with bone, 45% nodal, 18% lung, 9% liver, 9% other visceral metastases. 55% with at least 1 prior chemo regimen, 52% &gt;2 prior ARPI, 27% with Ra223, 30% sip-T, 5% 177Lu-J591. 59.1% with &gt;50% PSA decline (66.7% at 22.2 GBq, n=21), median overall survival 16 months (95% CI 11-NR). High grade (Gr) toxicity was rare with 6.8% Gr 3 anemia and 2.3% Gr 3 platelets. Gr 1/2 treatment-emergent AE’s include 81.8% with pain flare, 61.4% xerostomia, 29.5% fatigue, 25% platelets, 25% anemia, 25% pain, 15.5% nausea. FACT-P scores tended to improve in all categories by D22 (1 week later), with overall FACT-P scores improving by mean of 8.9 points (p=0.07) at D22 and remaining improved at 12 wks. All BPI scores also improved, with BPI overall severity score improving by mean of 3.0 at D22 (p=0.008) and remained better than baseline at 12 wks. There was no clear association with any AE and PRO changes, but those with PSA decline tended to have improved pain scores (p=0.1). Conclusions: A single cycle of up to 22.2 GBq of 177Lu-PSMA-617 is safe with fractionated (D1 &amp; D15) dosing, with encouraging early efficacy signals in a population unselected for PSMA expression and improved quality of life and pain scores by validated PRO instruments. Clinical trial information: NCT03042468.

The atopic dermatitis itch scale: development of a new measure to assess pruritus in patients with atopic dermatitis

Introduction: Pruritus is the primary symptom of atopic dermatitis (AD). The objective of this study was to develop a patient-reported outcome (PRO) instrument for daily administration in clinical trials to measure AD-related itch in adolescents and adults that would meet the standards described in the US Food and Drug Administration’s (FDA’s) PRO Guidance.Materials and methods: Six focus groups were conducted with 49 patients with AD (32 adults; 17 adolescents). Three iterative rounds of cognitive debriefing interviews were conducted in 26 patients with AD (17 adults; 9 adolescents) to pretest and refine the instrument.Results: AD-related itching was considered the most bothersome AD symptom by nearly two-thirds of the focus group participants. The items in the initial version of the instrument, named the Atopic Dermatitis Itch Scale (ADIS), were developed to reflect concepts most relevant to the assessment of itching as described during the focus groups. Based on results of the cognitive debriefing interviews, an 8-item final version of the ADIS was created.Conclusion: The ADIS is a content valid PRO instrument addressing the concepts critical to the measurement of AD-related itching. To our knowledge, it is the first instrument developed to assess AD-related itch in patients as young as 12 years following the recommendations of the PRO Guidance.

Routes to diagnosis of Fabry disease according to patient age and geographic distribution

Health related quality of life is important in bladder cancer care and clinical decision making because patients must choose between diverse treatment modalities with unique morbidities. A patient reported outcome measure of overall health related quality of life for bladder cancer regardless of disease severity and treatment could benefit clinical care and research.Prospective questionnaire development was completed in 3 parts. In study 1 the BUSS (Bladder Utility Symptom Scale) questions were created by experts using a conceptual framework of bladder cancer health related quality of life generated through patient focus groups. In study 2 patients with bladder cancer, including those treated with surgery, radiation and chemotherapy, completed the BUSS and 5 health related quality of life instruments at baseline and 4 weeks to assess validity and test-retest reliability. External validity was then explored in study 3 by administering the BUSS to 578 patients online and at clinics. Construct validity was assessed by whole and subscale Spearman rank correlations, and by comparisons of BUSS scores across known groups.The BUSS had high whole scale correlation with the FACT-Bl (Functional Assessment of Cancer Therapy-Bladder) (rs = 0.82, p <0.0001) and substantial to high subscale correlations with the EQ-5D™-3L (EuroQol 5 Dimensions Questionnaire-3 Levels) (eg emotional well-being rs = 0.69, p <0.0001). BUSS scores were lower in patients with comorbidity and advanced disease. Cognitive debriefing and the 94% completion rate suggested good comprehensibility. There was excellent test-retest reliability (ICC = 0.79). Limitations included an extended time from diagnosis in many patients.The BUSS is a reliable and valid patient reported outcome instrument for health related quality of life in all patients with bladder cancer regardless of the treatment received or the stage of disease.

Predictors of Patient-Reported Outcomes at 2 Years After Revision Anterior Cruciate Ligament Reconstruction

Background: Patient-reported outcomes (PROs) are a valid measure of results after revision anterior cruciate ligament (ACL) reconstruction. Revision ACL reconstruction has been documented to have worse outcomes when compared with primary ACL reconstruction. Understanding positive and negative predictors of PROs will allow surgeons to modify and potentially improve outcome for patients. Purpose/Hypothesis: The purpose was to describe PROs after revision ACL reconstruction and test the hypothesis that patient- and technique-specific variables are associated with these outcomes. Study Design: Cohort study; Level of evidence, 2. Methods: Patients undergoing revision ACL reconstruction were identified and prospectively enrolled by 83 surgeons over 52 sites. Data included baseline demographics, surgical technique and pathology, and a series of validated PRO instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale. Patients were followed up at 2 years and asked to complete the identical set of outcome instruments. Multivariate regression models were used to control for a variety of demographic and surgical factors to determine the positive and negative predictors of PRO scores at 2 years after revision surgery. Results: A total of 1205 patients met the inclusion criteria and were successfully enrolled: 697 (58%) were male, with a median cohort age of 26 years. The median time since their most recent previous ACL reconstruction was 3.4 years. Two-year questionnaire follow-up was obtained from 989 patients (82%). The most significant positive predictors of 2-year IKDC scores were a high baseline IKDC score, high baseline Marx activity level, male sex, and having a longer time since the most recent previous ACL reconstruction, while negative predictors included having a lateral meniscectomy before the revision ACL reconstruction or having grade 3/4 chondrosis in either the trochlear groove or the medial tibial plateau at the time of the revision surgery. For KOOS, having a high baseline score and having a longer time between the most recent previous ACL reconstruction and revision surgery were significant positive predictors for having a better (ie, higher) 2-year KOOS, while having a lateral meniscectomy before the revision ACL reconstruction was a consistent predictor for having a significantly worse (ie, lower) 2-year KOOS. Statistically significant positive predictors for 2-year Marx activity levels included higher baseline Marx activity levels, younger age, male sex, and being a nonsmoker. Negative 2-year activity level predictors included having an allograft or a biologic enhancement at the time of revision surgery. Conclusion: PROs after revision ACL reconstruction are associated with a variety of patient- and surgeon-related variables. Understanding positive and negative predictors of PROs will allow surgeons to guide patient expectations as well as potentially improve outcomes.

Effect of Graft Choice on the 6 Year Outcome of Revision Anterior Cruciate Ligament Reconstruction in the Multicenter ACL Revision Study (MARS) Cohort

Objectives: Most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome. The purpose of this study was to determine if revision ACL graft choice predicts outcomes related to sports function, activity level, OA symptoms, graft re-rupture, and reoperation at six years following revision reconstruction. We hypothesized that autograft use would result in increased sports function, increased activity level, and decreased OA symptoms (as measured by validated patient reported outcome instruments). Additionally, we hypothesized that autograft use would result in decreased graft failure and reoperation rate 6 years following revision ACL reconstruction. Methods: Revision ACL reconstruction patients were identified and prospectively enrolled by 83 surgeons over 52 sites. Data collected included baseline demographics, surgical technique and pathology, and a series of validated patient reported outcome instruments (IKDC, KOOS, WOMAC, and Marx activity rating score). Patients were followed up for 6 years, and asked to complete the identical set of outcome instruments. Incidence of additional surgery and re-operation due to graft failure were also recorded. Multivariate regression models were used to determine the predictors (risk factors) of IKDC, KOOS, WOMAC, Marx scores, graft re-rupture, and re-operation rate at 6 years following revision surgery. Results: 1234 patients were successfully enrolled with 716 (58%) males. Median age was 26. In 87% this was their first revision. 367 (30%) were undergoing revision by the surgeon that had performed the previous reconstruction. 598 (48%) underwent revision reconstruction utilizing an autograft, 599 (49%) allograft, and 37 (3%) both autograft and allograft. Median time since their last ACL reconstruction was 3.4 years. Questionnaire follow-up was obtained on 810 subjects (65%), while phone follow-up was obtained on 949 subjects (76%). The IKDC, KOOS, and WOMAC scores (with the exception of the WOMAC stiffness subscale) all significantly improved at the 6-year follow-up time point (p&lt;0.001). Contrary to the IKDC, KOOS, and WOMAC scores, the 6-year MARX activity scale demonstrated a significant decrease from the initial score at enrollment (p&lt;0.001). Graft choice proved to be a significant predictor of 6-year Marx activity level scores (p=0.005). Specifically, the use of an autograft for revision reconstruction predicted improved activity levels [Odds Ratio (OR) = 1.54; 95% confidence intervals (CI) = 1.14, 2.04]. Graft choice proved to be a significant predictor of 6-year IKDC scores (p=0.018), in that soft tissue grafts predicted higher 6-year IKDC scores [OR = 1.62; 95% confidence intervals (CI) = 1.09, 2.414]. For the KOOS subscales, graft choice did not predict outcome score. Graft re-rupture was reported in 55/949 (5.8%) of patients by their 6-year follow-up: 37 allografts, 16 autografts, and 2 allograft + autograft. Use of an autograft for revision resulted in patients 6.04 times less likely to sustain a subsequent graft rupture than if an allograft was utilized (p=0.009; 95% CI=1.57, 23.2). Conclusion: Improved sports function and patient reported outcome measures are obtained when an autograft is utilized. Additionally, autograft type shows a decreased risk in graft re-rupture at six years follow-up. Surgeon education regarding the findings in this study can result in potentially improved revision ACLR results for our patients.

Performance of the PROMIS After Operative Interventions for Shoulder Instability.

Background:The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to capture patient-reported outcomes (PROs) in an efficient manner. Few studies have assessed this instrument postoperatively.Purpose:To compare the PROMIS Physical Function computer adaptive test (PROMIS PF CAT) and Upper Extremity (PROMIS UE) item bank to other previously validated PRO instruments and to evaluate ceiling and floor effects and construct validity responsiveness in patients who underwent operative interventions for shoulder instability.Study Design:Cohort study (diagnosis); Level of evidence, 2.Methods:A total of 72 patients who underwent operative interventions for shoulder instability completed the American Shoulder and Elbow Surgeons (ASES) assessment form, Marx shoulder activity scale (Marx), 36-Item Short Form Health Survey physical function (SF-36 PF) and general health (SF-36 GH), Western Ontario Shoulder Instability Index (WOSI), PROMIS PF CAT, and PROMIS UE before surgery and then at 6 weeks and 6 months postoperatively. Correlation coefficients were calculated among these tools. The effect size of change was also calculated for each tool at each time point. A total of 91 patients who had also undergone surgery for shoulder instability completed these PRO instruments 2 years postoperatively. The percentage of patients hitting the ceiling and floor effects of each of the PRO instruments was calculated at all time points.Results:The PROMIS PF CAT demonstrated excellent-good correlation with the SF-36 PF at all postoperative time points (0.61 at 6 weeks, 0.68 at 6 months, and 0.64 at 2 years; P < .01 for all). The PROMIS UE showed excellent correlation with the ASES at 6 weeks postoperatively (0.73, P < .01). Both the PROMIS PF CAT and PROMIS UE demonstrated the ability to detect change after surgical interventions with a medium to large effect size. The PROMIS UE demonstrated a ceiling effect at 6 months (68.1%) and 2 years (67.0%) postoperatively. The PROMIS PF CAT demonstrated no ceiling effect at any time point.Conclusion:The PROMIS PF CAT demonstrated good to excellent correlation with other previously validated PRO instruments that assess physical function in patients with shoulder instability postoperatively. The PROMIS UE demonstrated good correlation with other PRO tools but had a significant ceiling effect and is not recommended for this patient population. Both tools demonstrated an ability to detect change after surgical interventions with a good effect size.

The China Patient-centred Evaluative Assessment of Cardiac Events (PEACE) prospective heart failure study design

IntroductionChina faces the prospect of a large growth in the prevalence of heart failure (HF). However, there is limited knowledge about outcomes in patients after HF hospitalisations, including patient-reported outcomes...

P074 SUSTAINED IMPROVEMENTS IN FATIGUE AND QUALITY OF LIFE IN PATIENTS WITH IBD AND IRON DEFICIENCY ANEMIA FOLLOWING A SINGLE COURSE OF FERUMOXYTOL: RESULTS OF A 6-MONTH EXTENSION STUDY

Iron deficiency anemia (IDA), common in patients with inflammatory bowel disease (IBD) due to blood loss, inflammation and malabsorption, negatively impacts patients’ health-related quality of life (HRQOL). Oral iron is often first-line treatment, but many patients do not tolerate it, or do not adequately respond; many live with chronic anemia and its related negative effects. A Phase 3 double-blind, placebo-controlled trial (NCT01114139) previously found that patients unsuccessfully treated with oral iron, including those with IBD, had very poor baseline HRQOL scores associated with fatigue, and that IV iron treatment resulted in significant, clinically meaningful improvement. To explore the durability of this treatment effect, this subgroup analysis reports on the impact on patient-reported outcomes (PRO) of a single course of IV ferumoxytol, received during the double-blind trial, over the subsequent 6-month extension study (NCT01114217) in patients with IBD. Patients with persistent or recurrent IDA (Hgb <11.0 g/dL and TSAT <20%) at any time during the extension study received ferumoxytol (1 course = 2x510 mg IV, 3 to 8 days apart). The same validated PRO instruments were administered as in the preceding double-blind trial: Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue), and Linear Analogue Scale Assessment (LASA) -Energy, -Activities of Daily Living (ADL) and -HRQOL. This analysis reports on the subgroup of patients who did not receive any additional ferumoxytol during the entire 6-month extension study. Most patients who had received a dose of ferumoxytol in the double-blind trial did not require any further doses during the extension study (285/471; 61% Overall) including 61% (23/30) of those with IBD. Among this cohort, the IBD patients’ mean Hgb had increased from 8.9 ± 0.7 g/dL at Baseline to 12.0 ± 0.8 at Week 5 of the double-blind trial and remained above 12.0 throughout the 6-month extension study visits (Month 7 Hgb 12.1 ± 1.0) despite receiving no further ferumoxytol. At Baseline of the double-blind trial, their FACIT-Fatigue scores were lower (Overall 24.3 ± 12.3; IBD 18.7 ± 12.6) than general (non-anemic) US population norms (40.1-43.6), and comparable to the scores of anemic cancer patients receiving chemotherapy (23.9, Cella 2002). By Week 5, FACIT-Fatigue scores increased significantly (Overall 36.1 ± 11.2; IBD 31.9 ± 13.4), and the improvement was sustained over 6 months (Month 7 score Overall 38.8 ± 11.5; IBD 37.0 ± 13.7). Significant improvements in the LASA domains that were observed in the double-blind study were also maintained. This study found that for the majority of patients, significant improvements in fatigue and quality of life domains, greater than the previously reported Minimal Clinically Important Differences (MID), were achieved and sustained for 6 months following a single treatment of ferumoxytol. Tabled 1Change from Baseline PRO Measures in IBD PatientsPRO InstrumentPretreatment BaselineMean (SD)Month 4 Change Mean (95% CI)Month 7 Change Mean (95% CI)MIDLASA-Energy36.2 (24.15)24.6 (12.8, 36.3)14.7 (4.5, 24.9)9.61LASA-Activity44.4 (23.7)15.9 (5.4, 26.3)13.3 (2.9, 23.8)8.74LASA-QOL46.9 (25.3)18.6 (8.2, 29.1)13.6 (4.5, 22.6)9.81FACIT-Fatigue18.7 (12.6)15.9 (9.3, 22.5)14.2 (8.1, 20.3)3.0PRO = Patient-reported outcomes; CI = confidence interval; MID = Minimum Important Difference (Patrick et al, Euro J Cancer 2003; Norman et al, Med Care 2003; Cella et al, J Pain Symptom Management 2002). Open table in a new tab PRO = Patient-reported outcomes; CI = confidence interval; MID = Minimum Important Difference (Patrick et al, Euro J Cancer 2003; Norman et al, Med Care 2003; Cella et al, J Pain Symptom Management 2002).