Health-related Quality Of Life Burden Research Articles

#3034 PHASE 3 TRIAL OF TOLVAPTAN IN PEDIATRIC AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD): TWO YEARS OF DATA FROM AN OPEN-LABEL EXTENSION

Abstract Background and Aims The 1-year, randomized, placebo-controlled phase (Phase A) of a 2-part trial of tolvaptan in children/adolescents with ADPKD (NCT02964273) demonstrated acceptable safety/tolerability and evidence of vasopressin V2 receptor antagonism. A 2-year, open-label extension (Phase B) evaluated longer-term outcomes. Method By entry criteria, participants at Phase A baseline were aged 4-17 years, had a diagnosis of ADPKD, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, and body weight ≥20 kg. Participants in the tolvaptan and placebo arms who completed Phase A could enter Phase B to receive open-label tolvaptan for 24 months. Dosing was based on body weight and tolerability, with tolvaptan re-initiated in participants who had received tolvaptan in Phase A to preserve the blind until Phase A completion. Phase B post-baseline study visits occurred at Week 1, Months 1, 6, 12, 18, and 24. Laboratory assessments to monitor safety were performed monthly, with more frequent liver function testing if any indication of liver injury was detected. eGFR and height-adjusted total kidney volume (htTKV) were calculated using the mixed model repeated measures method with model terms treatment, visit, treatment by visit, and baseline by visit interaction. To exclude the acute hemodynamic effect of tolvaptan, change in eGFR after week 1 of treatment is shown. Results Of 83 Phase A completers, 81 (42 prior tolvaptan, 39 prior placebo) enrolled in Phase B; 33/42 (78.6%) prior tolvaptan and 30/39 (76.9%) prior placebo participants completed the Phase B Month 24 visit on tolvaptan. The average daily tolvaptan dose was 41.1 mg in the prior tolvaptan group (mean [SD] age 14.3 [3.2] years) and 38.0 mg in the prior placebo group (13.9 [2.9] years). Adherence determined by returned drug was ≥90% in 32/42 (76.2%) participants in the prior tolvaptan group and 28/39 (71.8%) in prior placebo. In Phase A, eGFR increased in the tolvaptan group and decreased in the placebo group (significant difference at Month 6), with significant benefit maintained at most assessment visits in Phase B for the prior tolvaptan group compared to the prior placebo group (Figure 1A). Growth in htTKV on MRI (participants ages 12-17) was slowest during the first year of tolvaptan treatment, as shown by the slope of htTKV during Phase A in the tolvaptan group and during year 1 of Phase B in the prior placebo group (Figure 1B), with growth rates higher thereafter, although sample sizes did not permit meaningful statistical comparison of the changes. Scores on pediatric health-related quality of life assessment instruments, including the PedsQL Generic Core Scale and the PedsQL Multidimensional Fatigue Scale, remained stable during both phases and indicated low health-related quality of life burden and high functioning. The most common adverse events in Phase B (>15% participants overall; prior tolvaptan and prior placebo, respectively) were headache (36%, 44%), nasopharyngitis (26%, 33%), rhinitis (26%, 10%), oropharyngeal pain (21%, 18%), pyrexia (19%, 18%), cough (17%, 21%), abdominal pain (12%, 31%), polyuria (5%, 33%). Eleven participants overall experienced elevated liver enzymes by investigator report (no prespecified enzyme levels were required to report an event): 6 recovered without intervention, treatment was interrupted in 4, and in 1 tolvaptan was withdrawn for a reason other than the hepatic event. No participant met predefined laboratory criteria for serious drug-induced liver injury in either phase. There were no notable differences between prior tolvaptan and prior placebo in Tanner staging progression or change from baseline in growth percentile in Phase B. Conclusion Consistent with adult data in the TEMPO 3:4 and TEMPO 4:4 trials, children and adolescents who received tolvaptan during a randomized trial exhibited eGFR benefit relative to those who received placebo, a difference that was preserved during a 2-year, open-label extension. As in adults, kidney volume growth was higher after 1 year of treatment. Tolvaptan exhibited acceptable safety and good tolerability, with few discontinuations and a low quality of life burden.

#4018 CHARACTERISATION OF THE CLINICAL, HUMANISTIC AND ECONOMIC BURDEN OF ANAEMIA IN CHRONIC KIDNEY DISEASE: A SYSTEMATIC LITERATURE REVIEW

Abstract Background and Aims Chronic kidney disease (CKD) is defined as structural kidney damage and/or decreased kidney function (glomerular filtration rate <60mL/min/1.73 m2) persisting for ≥3 months [1]. Anaemia is a frequent CKD comorbidity associated with increased cardiovascular (CV) morbidity, mortality, reduced health-related quality of life (HRQoL) and greater healthcare resource utilisation (HRU) [2]. Our systematic literature review provided an overview of the clinical, humanistic and economic burden of anaemia of CKD. Method A search was performed in MEDLINE, EMBASE, MEDLINE IN-PROCESS, Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews from database inception to 10 April 2022, using predefined criteria to identify cohort, cross-sectional, observational and cost studies, economic evaluations, conceptual model studies, systematic and literature reviews (complemented by grey literature and congress abstract searches and back-referencing relevant review papers [2016–2021]). Full-text selected citations were examined by two independent reviewers. Clinical burden parameters included CKD progression, differences in progression between patients with/without CKD anaemia, time to blood transfusion and association of CKD stage/progression with CV outcomes or mortality. Humanistic burden included HRQoL and caregiver burden. Economic burden was determined by HRU and direct/indirect costs. Results Data were extracted from 115 studies (12,109 database records, 79 supplementary items; Figure 1), including patients: pre- or non-dialysis (n = 61), on dialysis (n = 21), mixed non-/on dialysis (n = 19) and unknown dialysis status (n = 14). Incidence of advanced CKD was significantly higher in adult non-dialysis dependent (NDD) patients with anaemia of CKD vs those without (incidence per 1000 person-years: 15 to ∼85 vs 3 to ∼25). Patients with CKD anaemia had a higher risk of disease progression than those without anaemia (n = 21), e.g. non-dialysis stage 1–5 adults with CKD anaemia had ∼double the risk of developing end-stage CKD (hazard ratio [95% confidence interval [CI]] = 2.08 [1.50–2.89]). Median time to dialysis initiation was significantly lower in adult NDD stage 1–5 patients with anaemia of CKD vs those without anaemia (45.1 vs 68.3 months p<0.01). A higher proportion of stage 3 adult NDD patients with anaemia of CKD progressed to stage 4 or 5 over follow-up periods of 1, 2 and 3 years vs those without anaemia (40% vs 20%; 60% vs 25%; 75% vs 30%, respectively). Available data from the 43 studies reporting humanistic burden suggested significantly worse HRQoL in patients with vs without CKD anaemia; e.g. non-dialysis adults with CKD anaemia had worse 36-item kidney disease and QoL scores for symptoms/problems, effect- and burden-of CKD. Comparative caregiver burden data in patients with/without CKD anaemia were limited. Limited available evidence from an economic perspective suggested higher HRU in patients with anaemia of CKD vs those without. Patients with anaemia of CKD has ∼2 times greater risk of hospitalisation due to heart failure vs those without (crude incidence rate ratio [95% CI] = 1.9 [1.6–2.1]). Similarly, patients with anaemia of CKD has significantly higher risk of hospitalisations (adjusted relative risk [ARR] [95% CI] = 1.33 [1.31–1.34]) and emergency department visits (ARR [95% CI] = 1.14 [1.12–1.15]) in a multivariate logistic regressions model. No data were available on change in economic parameters over time or on inter-relationships between humanistic/economic burden parameters. There were no published disease models in CKD anaemia; Figure 2 illustrates identified relationships between clinical, humanistic and economic burden parameters. Conclusion Based on limited moderate-to-good quality data, we found that patients with CKD anaemia face greater clinical, humanistic and economic burdens than those without anaemia, with significantly worse HRQoL and greater HRU. CKD anaemia was also associated with a higher risk of CKD progression.

#3990 PACE-CKD: HEALTH-RELATED QUALITY OF LIFE OF PATIENTS WITH CKD AND CAREGIVERS: RESULTS FROM A US SURVEY

Abstract Background and Aims The substantial mortality and morbidity burden of chronic kidney disease (CKD) is well described, with the highest burden associated with progression to end-stage kidney disease (ESKD), where kidney replacement therapy (dialysis or kidney transplantation) is indicated. CKD is known to have a detrimental effect on patient health-related quality of life (HRQoL). However, there is a lack of data comparing the impact of CKD on patient and caregiver HRQoL versus the general population. This study aimed to administer validated HRQoL instruments using a quantitative online survey to estimate the HRQoL of patients with CKD and their caregivers compared to the general population. Method A non-interventional survey enrolled adult patients with CKD and caregivers. Patients with a diagnosis of CKD for at least 3 months were included. ESKD was defined as patients with CKD stage 5 or receiving dialysis or a kidney transplant. Caregivers were required not to receive formal payment and must have cared for a CKD patient for a minimum of 1 hour a week in the previous 4 weeks. A general population cohort was also enrolled, matching key patient and caregiver demographic characteristics (e.g. age, sex, and area of residence). Patient and caregiver HRQoL were assessed using the EQ-5D-5L instrument. Caregiver HRQoL was also measured by the CarerQoL-7D carer-specific instrument. Results This analysis is based on 199 patients with CKD and 113 caregivers in the United States who were enrolled between June and July 2022. Patient and caregiver median age was 58 years and 38 years, respectively. There were 32.2% patients who were on dialysis, while 81.4% caregivers were caring for a patient on dialysis. Most dialysis patients (79.7%) were receiving treatment in a clinic or hospital, with 20.4% of patients receiving it at home. Caregivers typically cared for their parent (45.1%) or partner (25.7%) and their duties would most commonly include driving to/from medical appointments (89.4%). When comparing mean [SD] EQ-5D-5L index scores for patients with CKD with the general population, patients had 33.7% lower utility (0.63 [0.27] vs 0.95 [0.08]) and caregivers had 13.8% lower utility (0.81 [0.22]) vs 0.94 [0.11]) versus the general population. EQ-5D-5L index scores were lower in dialysis-dependent patients (0.59 [0.27]) versus non dialysis-dependent patients (0.65 [0.27]). Patients and caregivers reported problems across all EQ-5D domains (anxiety and depression, mobility, pain/discomfort, selfcare and usual activities) when compared to the general population, with anxiety and depression domains scoring highest. According to the CarerQoL-7D index, caregivers for patients with CKD had worse HRQoL than caregivers for other major illnesses, including hip fractures, breast cancer and dementia, according to published estimates [1–3]. Results for patients and caregivers in other countries (United Kingdom, Germany and Mexico) will also be presented at the congress. Conclusion This survey provides new evidence on the HRQoL burden of CKD, both for patients and their caregivers, compared to the general population. Patients with CKD and caregivers incurred substantial detriment to their HRQoL, which was driven by all EQ-5D-5L domains, particularly anxiety and depression. Evidence based policy interventions should aim to slow CKD progression to reduce the large societal burden to patients and their caregivers. Funding: This study was supported by AstraZeneca.

#4026 ECONOMIC EVALUATION OF ANAEMIA OF CHRONIC KIDNEY DISEASE (CKD): A SYSTEMATIC LITERATURE REVIEW AND MODEL CONCEPTUALISATION

Abstract Background and Aims Anaemia is a common complication of chronic kidney disease (CKD), affecting up to 53.4% of patients with Stage 5 CKD compared to 8.4% of patients with Stage 1 CKD [1]. Anaemia of CKD is associated with increased risk of cardiovascular events and death, increased healthcare resource utilisation (HRU), and reduced health-related quality of life (HRQoL) [2]. Established treatments for anaemia of CKD include erythropoiesis-stimulating agents (ESAs) [1,2]; however, hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), targeting both erythropoietin production and iron metabolism (the two key mechanisms of anaemia of CKD), are an emerging class of agents in this indication [3]. The cost and HRQoL burden associated with anaemia of CKD treatment is not well characterised.1 Thus, we conducted a systematic literature review (SLR) to evaluate published economic models (including the cost inputs, time horizon, subgroups, and clinical assumptions used) and HRU data in patients with anaemia of CKD. Findings of the SLR will help guide future economic model development and inform economic evaluation strategies as part of health technology assessment submissions to support daprodustat, an HIF-PHI under development for use in both dialysis-dependent and non-dialysis-dependent patients. Method Relevant publications were identified using structured searching of MEDLINE, Embase, MEDLINE In-Process, Cochrane Controlled Trials Register, and the Cochrane Database of Systematic Reviews from database inception to 10 April 2022 using disease- (e.g. CKD, chronic kidney failure, anaemia) and economic-associated (e.g. economics, economic evaluation, quality-adjusted life-years, model structure) search terms. Additional supplemental searches (conference proceedings [2016–2021], grey literature, and bibliographies) were conducted. Studies were assessed for inclusion or exclusion by two independent reviewers, with any discrepancies resolved by a third reviewer. Objectives were to determine the structure of any published economic models and the availability of health utility data in patients with anaemia and additional complications of CKD, and to examine what cost inputs, time horizons, subgroups, and clinical assumptions are used to inform economic modelling. Results From 1397 citations identified in the searches, 40 primary studies were included in the final analysis. Review of the data revealed an established approach for modelling the ESA cost-effectiveness (i.e. a Markov model with health states defined according to CKD treatment received or anaemia status): most studies were conducted from a North American or European perspective, time horizons varied, and reporting of cycle length was poor. Only one economic evaluation included an HIF-PHI model: given the different mechanisms of action of ESAs and newer treatments, a modelling strategy focused mainly on a Markov approach may not be the most optimal way of assessing cost-effectiveness in anaemia of CKD where HIF-PHIs are used. Considerations of modelling factors that could influence cost-effectiveness of HIF-PHIs are shown in Fig. 1. While existing models typically only stratified patient populations according to age (<65 vs >65 years), for appropriate modelling of treatment effectiveness, the impact of prior treatments (including response to prior ESAs) was also considered. As in every model, comorbidities may also have a role in effect modification and this impact will need to be considered in economic models of anaemia of CKD treatment. Due to the natural history of anaemia in CKD, innovative modelling techniques that retain the Markov approach and which account for respective haemoglobin levels, CKD stage, and potential kidney transplantation should be incorporated into the economic evaluation (Fig. 2). Conclusion Adjustment of existing models using the approaches described may provide more reliable estimates of treatment efficacy in a highly heterogenous population of patients with anaemia of CKD.

PCR73 Health-Related Quality of Life and Economic Burden in Chinese Patients with Cutaneous T-Cell Lymphoma (CTCL) – Results from Interim Analysis

Little is known about health-related quality of life (HRQoL) and economic burden in Chinese patients with cutaneous T-cell lymphoma (CTCL). This study aimed to measure the overall HRQoL and economic burden of CTCL patients with mycosis fungoides (MF) and Sezary syndrome (SS) subtypes in China.

EPH66 Epidemiological Population Study of Sars-Cov-2 in Lake County, Illinois: Contact: Health-Related Quality of Life Assessment

The prospective, longitudinal, community-based CONTACT study aimed to improve our understanding of COVID-19 immunity, and other characteristics related to SARS-CoV-2 long-term, including the assessment of health-related quality of life (HRQoL) at baseline and over time by infection status. Participants living or working in Lake County, IL were recruited between November 2020 and January 2021. At baseline and follow up visits (3-, 6-, and 9-Months-M-), participants self-reported their occupational exposure, COVID-19 vaccination status and provided nasal and blood serum specimens for molecular (RT-PCR) and serologic (IgG) testing to detect current or previous SARS-CoV-2 infection. HRQoL questionnaires EQ-5D-5L were completed online approximately within two weeks post-testing (at 0.5, 3.5, 6.5, and 9.5 months) after results were communicated. EQ-5D-5L information was described and stratified by COVID-19 status at baseline, 3M, 6M and 9M – software: SAS®-v9.4. Data from 1008 participants were analyzed. Participants testing positive to COVID-19 were 56/952, 48/751, 40/693, and 19/654, respectively, at baseline, 3M, 6M, and 9M. Of the five domains of EQ-5D-5L, a higher percentage of participants who tested positive for COVID-19 reported having no anxiety or depression versus those who tested negative: at baseline (55.4% [31/56] vs 50.5% [481/952]); 3M (68.8% [33/48] vs. 56.3% [423/751]); 6M (67.5% [27/40] vs. 56.3% [390/693]); and 9M (73.7% [14/19] vs. 60.4% [395/654]). Median Visual Analogue Scale (VAS) score was at least 2 points higher at all time- points for participants who tested positive except at last visit (baseline: 89.0 vs. 87.0; 3M: 88.0 vs. 86.0; 6M: 87.5 vs. 85.0; 9M: 85.0 vs. 87.0) This analysis provides insight into participant HRQoL burden at enrollment and over time when a positive test to COVID-19 was communicated. At all time-points, anxiety or depression was experienced by more participants who tested negative versus those who didn´t.

Estimation of Health Utility Scores for Glycogen Storage Disease Type Ia.

Glycogen Storage Disease Type Ia (GSDIa) is a rare genetic metabolic disorder characterized by hypoglycemia, hepatomegaly, growth failure, and possible seizures/death. Patients frequently consume cornstarch to maintain blood glucose. Evidence demonstrating the impact of GSDIa on health-related quality of life (HRQoL) is lacking. This study aims to understand the burden of GSDIa by obtaining utility values for economic appraisals. A targeted literature review and interviews with experts (n=4) and caregivers (n=4) informed the development of health state vignettes describing different GSDIa severities by age and level of hypothetical treatment (i.e., gene therapy) response. Health states reflecting caregivers' experiences were also developed. A convenience sample of the UK general public completed a time trade-off (TTO) exercise. Scores conceptually varied from 0 (dead) to 1 (full health). States were also rated using a visual analog scale (VAS) and the EQ-5D-5L. Data were descriptively summarized. One hundred participants completed the exercise (male: 48%; mean age: 42 years). Scores were lowest for the adolescent pre-treatment state (TTO=0.38). Large increments in HRQoL were observed for the response (adult: TTO=0.86; child: TTO=0.84) and complete response (adult and child: TTO=0.94) hypothetical treatment response states. Caregiver values were lowest for the pre-treatment state (TTO=0.57) and highest for the complete response state (TTO=0.95). VAS and EQ-5D-5L scores followed a similar pattern. This study found an HRQoL burden on GSDIa patients and caregivers, with potential large improvement from a hypothetical treatment. These findings may be useful for families, clinicians, regulatory agencies, and in therapy economic evaluations.

5589252 SYSTEMATIC LITERATURE REVIEW OF HEALTH-RELATED QUALITY OF LIFE BURDEN IN PATIENTS ACROSS THE SPECTRUM OF THALASSEMIA

Background: Recent systematic literature reviews (SLRs) have highlighted the health-related quality of life (HRQoL) burden in transfusion-dependent thalassemia (TDT), particularly β-thalassemia (β-thal). However, less is known about HRQoL in non–transfusion-dependent thalassemia (NTDT) and alpha-thalassemia (α-thal). Aims: To conduct an SLR on the real-world HRQoL burden across the spectrum of thalassemia and report evidence gaps. Methods: Searches (Jan 2010 to Sep 2021) were conducted in MEDLINE, Embase, Cochrane Database of Systematic Reviews, Health Technology Assessment Database, NHS Economic Evaluation Database, and EconLit for real-world studies reporting on HRQoL and utilities in adult and pediatric patients with thalassemia. Conference abstracts from Jan 2017 to Sep 2021 were also searched. References were screened by two independent reviewers, and HRQoL data were extracted by one reviewer and validated by another. Results were grouped by genotype (β-thal/α-thal) and transfusion phenotype (TDT/NTDT). Results: A total of 2,548 records were screened at title/abstract and 448 at full text. 126 publications from 116 unique studies were included and data extracted. Most evidence was published since 2015 (95/126) and sample sizes of study populations ranged from 22 to 1240. Most TDT/NTDT studies were conducted in β-thal (84/126); 10 were in mixed α-thal and β-thal, of which 2 reported data separately for Hemoglobin H disease (HbH) pediatric patients; the remaining studies did not specify the thalassemia genotype. HRQoL was significantly poorer in TD β-thal adult or adult/pediatric patients compared with healthy controls across the majority of domains. Among TDT patients, HRQoL also tended to decrease with increasing age. The burden associated with pediatric TD β-thal also impacts caregivers, with one study reporting significantly reduced HRQoL compared with healthy controls (p<0.001). In NTD β-thal patients, 2 studies identified significantly worse PedsQL scores in nearly all domains compared with healthy controls. Across studies in adult or mixed adult/pediatric patients, HRQoL (as measured by SF-36) tended to be poorer among NTDT (β-thal intermedia) compared with TDT (β-thal major) patients. For example, a prospective study found significantly lower SF-36 mental component scores at baseline in adult NTDT vs. TDT (mean [standard deviation (SD)]: 47.4 [8.4] vs. 51.6 [7.2]; p=0.009). While in pediatric patients, there was a pattern for poorer HRQoL burden in TDT vs. NTDT. TD α-thal and β-thal pediatric patients had similar total and subdomains of PedsQL scores, except for physical functioning, whereby homozygous β-thal patients had the best HRQoL, followed by HbH patients, with β-thal/Hb E patients demonstrating the greatest HRQoL burden (mean [SD]: 76.52 [15.23] vs. 61.16 [18.39] vs. 56.88 [17.17], p=0.008). Another study did not find differences in any PedsQL subdomain between HbH, β-thal, and homozygous β-thal (TDT and NTDT, patients 5-18 years; N=315). Conclusion: This SLR highlights the negative impact on HRQoL across the spectrum of thalassemia. Adding to previous SLRs, it shows limited evidence is available for NTDT patients; however, studies suggest that HRQoL burden may be worse in NTDT than TDT adult patients. Characterizing the HRQoL burden of α-thal is a clear evidence gap. High-quality, real-world studies in NTDT and α-thal are needed to better understand the HRQoL burden and the potential impact of new treatments on HRQoL.

THE IMPACT OF A DIGITAL CANCER SURVIVORSHIP PATIENT ENGAGEMENT TOOLKIT ON OLDER CANCER SURVIVORS’ HEALTH OUTCOMES

Abstract Cancer is a disease that predominantly affects older adults. The median age at diagnosis is 66 years and 62% of the 15.5 million American cancer survivors are age ≥65 years. Provision of supportive care after treatment is critical to this group due to their complex care needs; however, limited resources are available to them. As increasing numbers of older survivors adopt technology, digital health programs have significant potential to help them improve their health and communicate with their providers. Previously, we developed/tested a digital Cancer Survivorship Patient Engagement Toolkit program for older adults, CaS-PET Silver. The aim was to examine the preliminary impact of CaS-PET Silver on older survivors’ health outcomes. This was a 2-armed RCT with two observations (baseline, 8 weeks) on a sample of 60 survivors age ≥65 years (mean age, 70.1±3.8), who were treated with curative intent within 12 months from enrollment (02/2020-01/2022, COVID-19 pandemic). Outcomes included health-related quality of life (HRQoL), self-efficacy for coping with cancer, symptom burden, health behaviors, and patient-provider communication. Data were analyzed using descriptive statistics, linear mixed models, and content analysis. The majority of participants were black (68.3%, n=41) and female (56.6%, n=34). At 8 weeks, CaS-PET Silver group showed significantly improved physical HRQoL (p &amp;lt; .001, ES=0.64) and symptom burden (p=.053, ES= -0.41). Self-efficacy (ES=0.56), mental HRQoL (ES=0.26), and communication (ES=0.40) showed a tendency to improve. Most participants reported benefits from the program on health management (mean, 19.41±2.6 [3–21]). Further research is needed with larger, diverse older cancer populations.

HSD108 Physician Perceptions on the Treatment and Health-Related Quality of Life Burden of Endogenous Cushing's Syndrome

Endogenous Cushing’s syndrome (CS) results from chronic hypercortisolism and is associated with symptoms and complications that adversely impact morbidity. Research indicates that a health-related quality of life (HRQoL) burden persists despite treatment. This study evaluated physician perceptions on treatments and their rationale behind treatment decisions.

Characterizing the Clinical, Health-Related Quality of Life and Economic Burden of Alpha-Thalassemia: A Systematic Literature Review and Evidence Gaps Assessment

Introduction: The burden of beta-thalassemia (β-thal) is well documented but, to our knowledge, there are no systematic literature reviews (SLRs) on the burden of alpha-thalassemia (α-thal). To fill this gap, we conducted an SLR to characterize the clinical (complications, treatment patterns, or mortality), health-related quality of life (HRQoL), and economic burden associated with α-thal and report on evidence gaps. Methods: An SLR was conducted for publications on clinical burden, HRQoL, HCRU/costs and economic evaluations in thalassemia. MEDLINE, Embase, EconLit and Evidence-Based Medicine Reviews and relevant conference websites (2019-2021) were searched. Real-world, observational studies and economic evaluations were selected that reported on α-thal and any outcome data of interest; for clinical burden, only studies in adults (≥18 years) were included. Results: Across 7,881 search hits in thalassemia, 9 studies reported relevant data on α-thal (see Table 1).1-9 No evidence was identified on economic evaluations. Only three studies were exclusively in α-thal patients (sample size 50-86) and were limited to deletional (DEL) HbH and/or non-deletional (non-DEL) HbH, including Constant Spring (CS).2, 4, 9 These studies found that among adults with DEL and/or non-DEL HbH, almost 1 in 3 had moderate-to-severe iron overload (31%),2 and 2 out of 3 had iron overload of unspecified severity (66%).9 Advanced liver fibrosis was present among 1 in 5 patients (20%); 9% with probable cirrhosis.2 Complications including moderate-to-severe liver iron overload (53% vs. 25%, P=0.03) and median liver iron concentration (median [range]: 7.8 [1.7-17.7] vs. 2.9 [0.1-15.0] mg/g dry weight, P=0.002) were significantly higher in non-DEL versus DEL HbH adult patients with non-transfusion dependent thalassemia (NTDT).2 In addition, among HbH/CS transfusion-dependent thalassemia (TDT) and NTDT adult patients, iron overload was further exacerbated among those who were splenectomized compared to those who were not (80% vs. 52%, P=0.037).9 The other studies reporting clinical data were from a mixed (α-thal and β-thal) population where data for α-thal was reported separately (6 studies with sample sizes ranging from 2 to 54 with α-thal).1, 3, 5-8 Across these, the data also demonstrated a high burden of clinical complications for HbH and/or HbH/CS including iron overload (52.2%, 1 study)3, cholelithiasis (27.7% to 52.2%, 3 studies3, 6, 8), abnormal liver function (27.7%, 1 study8), osteoporosis (0.0% to 20.4%, 3 studies3, 6, 8) and hyperuricemia (60.0%, 1 study).1 Complication rates among α-thal patients across studies can be seen in Figure 1. With regard to treatment patterns, among patients with DEL and/or non-DEL HbH, the majority had historical/occasional transfusion (46.7% to 87.0%, 3 studies)2, 3, 6, followed by iron chelation therapy (6.0% to 52.2%, 5 studies)2, 3, 6, 8, 9 and splenectomy (10.0% to 14.8%, 3 studies).2, 6, 8 A single study on HRQoL in TD HbH and β-thal (age range: 2 to 18 years) found that HRQoL total score, and subdomains, psychological, emotional, social, and school functioning (as measured by Pediatric Quality of Life Inventory) were similar between HbH and β-thal patients, except for physical functioning.7 For physical functioning, homozygous β-thal patients had the best HRQoL, followed by HbH patients, with β-thal/Hb E patients demonstrating the poorest HRQoL (mean [SD]: 76.52 [15.23] vs. 61.16 [18.39] vs. 56.88 [17.17], respectively, P=0.008).7 This study was limited by a small sample size (n=49) with only 5 HbH patients.7 Lastly, one study on HCRU among adult and pediatric patients with DEL HbH and HbH/CS, found that patients with HbH/CS had a significantly increased number annual clinic visits, by a factor of 1.7, and hospital admissions, by a factor of 3.9, versus those with HbH (P<0.001).4 Conclusions: To our knowledge, this was the first SLR investigating the clinical, HRQoL and economic burden of α-thal. Most of the evidence was in HbH and HbH/CS adult patients, and complications, with no data on economic evaluations, and limited data on HRQoL and HCRU/costs. Our SLR highlights the need for further research to fully characterize the burden of this disease. Where reported, DEL and/or non-DEL HbH adult patients experience clinical complications across a range of conditions and generally, children and adolescents with HbH experience similar HRQoL burden as those with β-thal. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Health-Related Quality of Life of CML Patients Under 2nd or 3rd Line Bosutinib Is Not Impaired Significantly By Gastrointestinal Toxicity (GI Tox) but Influenced By Sex - Results from a Subanalysis of the Bosutinib Dose Optimization (BODO) Study (CML-VII) Trial of the German CML Study Group

Introduction: Patient-reported outcome measures (PROMs) are an important tool to assess the impact of disease and their treatments on daily living and thereby on Health-related quality of life (HrQoL). Impact of side effects and gender-specific differences have been partly been addressed in Chronic myeloid leukemia (CML) in the past. The "Bosutinib Dose Optimization (BODO) Study" is a multicenter, open-label single arm phase II study testing tolerability and efficacy of 2nd&3rd line bosutinib step-in dosing (i.e. starting with 300 mg QD) in chronic phase CML patients (pts) intolerant and/or refractory to previous imatinib, and/or nilotinib, and/or dasatinib therapy with the ultimate goal to decrease GI toxicity rates. PROMs were assessed via the EORTC-QLQ-C30 and EORTC-CML24 questionnaires to correlate HrQoL changes with the rate and severity of GI toxicity and gender. Methods: The BODO Study (NCT02577926) had to be terminated prematurely after 57 of 127 projected pts due to delayed recruitment but included detailed analysis of PROMs reported here. Summary statistics of the HrQoL questionnaires were calculated at baseline (BL), month 3, and month 6. Depending on the observed distribution of differences of a score (component), comparisons between groups (e.g., males vs. females) were performed using methods based on the normal distribution assumption (t test) or a non-parametric test (Mann-Whitney U test or Wilcoxon signed rank test). Results: 57 pts with a median age of 51 years (median duration of pretreatment: 19.8 months) were included in the BODO trial. Even though 74%, 53% and 26% of pts suffered from any grade of GI-toxicity (e.g., diarrhea, nausea and vomiting) during the study, GI toxicity triggered treatment discontinuation in only one patient. Median duration of GI toxicity was 15 days (range: 1-1281) and was self-limiting in most pts. Median time to first onset of diarrhea was 23 days, and the median duration of any grade diarrhea was 14 days (range: 1-960). HrQoL-results were available for 51, 44 and 35 pts at baseline, end of month 3 and end of months 6 visits, respectively (for median scores over time see figure 1A-C). PROM results were analyzed according to occurrence of GI toxicity: The only symptom reported to be aggravated in the 15 pts without vs. the 42 with diarrhea during the first 6 months was the insomnia symptom scale (52 vs. 23, p=0.02). Nausea and vomiting did not significantly impact symptom burden. As most of the AEs have an early onset, the 3 month visit was assessed. Again, no significant differences in HrQoL could be detected between pts with or without GI toxicity at 3 months. At baseline, women seemed to be more affected by necessity of treatment change than males: there were statistically significant differences in physical (87 vs. 72, p=0.0055) and role functioning (82 vs. 60, p=0.0043). Higher functional scores were reported in male pts. Regarding symptoms, statistically significant differences were found for fatigue (31 vs. 51, p=0.01) and insomnia (24 vs. 42, p=0.04). Female pts reported higher symptom burden. In addition, the impact on daily life was found to be lower in male pts than in females (24 vs. 34, p=0.04). At 3 months, emotional (79 vs. 57, p=0.003) and cognitive functioning (88 vs. 68, p=0.008), insomnia (17 vs. 39, p<0.05) and symptom burden (19 vs. 26, p=0.03) differed. Male pts reported higher functional scores and lower symptom burden than female pts. At 6 months, male pts reported statistically significantly higher scores in emotional functioning (75 vs. 56, p=0.04) than female pts. Regarding the CML-24 questionnaire, symptom burden showed a statistically significant increase from BL to month 6 (25 vs. 26, p=0.02) with no statistically significant difference in any scale between month 3 and 6. Conclusion: Although the analysis is limited by relatively small number of pts in the respective subgroups and by the pre-selected time points of PROM assessment, the data suggests that HrQoL from pts with chronic phase CML treated with bosutinib within the BODO trial is not significantly impaired by the presence of GI toxicity and that there are significant differences in HrQoL and symptom burden between male and female pts which should be addressed in future trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Mental health in myasthenia gravis patients and its impact on caregiver burden

Psychiatric comorbidities are relevant in patients with Myasthenia gravis (MG). Also, MG patients experience a reduced health-related quality of life (HRQoL). We aimed to quantify the impact of depression as well as self-perceived MG severity on HRQoL and caregivers' burden. In this cross-sectional study, we used a survey encompassing demographic, disease-related information, and standardized questionnaires to assess symptoms of depression, anxiety, HRQoL (MG Quality of Life scale; MG-QoL15), and caregiver burden (Burden Scale for Family Caregivers; BSFC). Data from 1399 participating patients (96%) and 1042 caregivers (65%) were eligible for further analysis. Symptoms of depression and anxiety disorder were indicated by 31% and 36% of patients. Self-reported MG severity (MG severity) and MG-QoL15 scores were strongly associated (estimated marginal means for severe versus mild MG severity = 18 95% CI [16; 21]; p ≤ 0.001). Adjusting for symptoms of depression decreased the estimated strength of this association (estimated marginal means for severe versus mild MG severity = 15 [13; 17]; p ≤ 0.001). Caregiver burden was associated to MG disease severity (estimated marginal means for severe vs. mild MG severity = 0.16 [0.13; 0,19); p ≤ 0.001) and also negatively influenced by symptoms of depression (estimated marginal means = 0.12 [0.09; 0.15]). Symptoms of depression and anxiety disorder in MG are frequent. Beyond MG severity, symptoms of depression have negative effects on HRQoL as well as on caregivers’ burden. Diagnosis and treatment of psychiatric comorbidities should be considered an important element in MG care. Screening tools for mental health conditions should be implemented at least in specialized MG centers.

A multisite randomized controlled trial of an early palliative care intervention in children with advanced cancer: The PediQUEST Response Study Protocol

The Pediatric Quality of Life and Evaluation of Symptoms Technology Response to Pediatric Oncology Symptom Experience (PQ-Response) intervention aims to integrate specialized pediatric palliative care into the routine care of children, adolescents, and young adults (AYAs) with advanced cancer. To evaluate whether PQ-Response, compared to usual care, improves patient's health related quality of life (HRQoL) and symptom burden (aim 1), parent psychological distress and symptom-related stress (aim 2), and family and symptom treatment activation (aim 3). Multisite, randomized (1:1), controlled, un-blinded, effectiveness trial comparing PediQUEST Response (intervention) vs usual cancer care (control). Five US large, tertiary level pediatric cancer centers. Children (≥2 years old)/AYAs who receive care at any of the participating sites because of advanced cancer or any progressive/recurrent solid or brain tumor and are palliative care "naïve." Target: 200 enrolled patient-parent dyads (minimum goal: 136 dyads randomized, N = 68/arm). PediQUEST Response: combines patient-mediated activation (weekly feedback of patient- and parent-reported symptoms and HRQoL to families and providers using the PediQUEST web system) with integration of the palliative care team. Usual Cancer Care: participants receive usual care, which can include palliative care consultation, and use PediQUEST web to answer surveys, with no feedback. Following enrollment, patients (if ≥5 years) and one parent receive weekly PediQUEST-Surveys assessing HRQoL (Pediatric Quality of Life Inventory 4.0) and symptom burden (PediQUEST-Memorial Symptom Assessment Scale). After a 2-week run-in period, dyads who answer ≥2 PediQUEST surveys per participant (responders), are randomized (concealed allocation) and followed up for 16-weeks. Parents answer six additional surveys (parent outcomes). Primary: mean patient HRQoL score over 16-weeks as reported by a) the parent; and b) the patient if ≥5 years-old. Secondary: patient's symptom burden; parent's anxiety, depressive symptoms, symptom-related stress; family activation; and symptom treatment activation. ClinicalTrials.gov (NCT03408314) 1/24/18. https://clinicaltrials.gov/ct2/show/NCT03408314.

Health-related quality of life in long-term Caribbean prostate cancer survivors: comparisons with prostate cancer-free men.

Prostate cancer (PCa) and its treatment can impact health-related quality of life (HRQoL). There are few studies of HRQoL in long-term PCa survivors of African ancestry from low- and middle-income countries. We examined the effect of PCa treatment on HRQoL of Jamaican PCa survivors compared with cancer-free controls and explored the effect of demographic and clinical factors on these outcomes. PCa survivors (n = 64) treated with and without ADT along with PCa-free controls (n = 88) from a case-control study of 10years post enrolment. HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30). Effects of demographic and clinical variables on HRQoL on PCa and type of therapy were evaluated in multivariable linear regression models. HRQoL of PCa survivors (overall and by treatment group) indicated a high quality of life, comparable to PCa-free men. However, ADT-treated survivors had lower physical functioning that was of small clinical relevance compared with those not on ADT. Symptom burden scores of PCa survivors and controls were similar excluding fatigue and dyspnoea which were highest in men on ADT and controls. In multivariable models, PCa was not an important determinant of overall HRQoL, functioning or symptom burdens. Underlying medical conditions and marital status were the main contributors to HRQoL in PCa survivors. PCa cancer status was not an independent determinant of long-term HRQoL in Jamaican men. Interventions addressing social factors and comorbid illnesses could improve HRQOL in long-term PCa survivors.

SA37 Economic and Health-Related Quality of Life Burden in Endogenous Cushing's Syndrome: A Systematic Literature Review

Endogenous Cushing’s syndrome (CS) is a rare endocrine disorder characterized by chronic cortisol overproduction. Our objective was to summarize the economic and health-related (HR) quality of life (QoL) burden of CS and evaluate post-treatment burden.

PB2233: SYSTEMATIC LITERATURE REVIEW OF HEALTH-RELATED QUALITY OF LIFE BURDEN IN PATIENTS ACROSS THE SPECTRUM OF THALASSEMIA

Background: Recent systematic literature reviews (SLRs) have highlighted the health-related quality of life (HRQoL) burden in transfusion-dependent thalassemia (TDT), particularly β-thalassemia (β-thal). However, less is known about HRQoL in non–transfusion-dependent thalassemia (NTDT) and alpha-thalassemia (α-thal). Aims: To conduct an SLR on the real-world HRQoL burden across the entire spectrum of thalassemia and report evidence gaps. Methods: Searches (2010 to September 2021) were conducted in MEDLINE, Embase, Cochrane Database of Systematic Reviews, Health Technology Assessment Database, NHS Economic Evaluation Database, and EconLit for real-world studies reporting on HRQoL, utilities, and patient-reported outcomes in adult and pediatric patients with thalassemia. Conference abstracts from 2017 to September 2021 were also searched. References were screened at title/abstract and then full text by two independent reviewers. Data extraction was undertaken by one reviewer and validated by a second independent reviewer. Results were grouped by genotype (β-thal/α-thal) and transfusion phenotype (TDT/NTDT) to support comparisons. Results: A total of 2,541 records were screened at title/abstract, 441 at full-text and 7 references were identified through other sources. A total of 126 publications reporting on 116 study populations were included. Most evidence was published since 2015 (n=95) and sample sizes ranged from 22 to 1240. The number of publications by transfusion phenotype (TDT/NTDT) and thalassemia genotype (β-thal/α-thal) is shown in Table 1. Overall, most TDT/NTDT studies were conducted in β-thal or did not report genotype. Four studies included patients with α-thal but did not report HRQoL results separately for this subgroup. Across 52 studies reporting on TD β-thal, most showed that both adult and pediatric patients have reduced HRQoL. One study found EQ-VAS utility values to be poorer in adults than in children with TDT (mean [SD]: 75.04 [17.86] for >18 years vs. 84.97 [15.16] for ≤18 years; P<0.001). Four studies in pediatric patients noted the negative impact of TDT on caregivers’ HRQoL. Very few studies assessed HRQoL for NTDT patients vs healthy controls, and none were in adult population. One pediatric study found NTDT patients had worse total and domain PedsQOL scores (all P<=0.05) than healthy controls. Several studies compared NTDT and TDT patients. Using the SF-36, one study found significantly poorer HRQoL in NTDT than in TDT adults (mean total score [SD]: 66.5 [16.1] vs. 75.8 [18.8]; P=0.021). A prospective, non-interventional study found significantly lower SF-36 mental component scores at baseline in NTDT compared to TDT adults (mean [SD]: 47.4 [8.4] vs. 51.6 [7.2]; P <0.01), and NTDT patients had worse HRQoL change from baseline at 24 weeks than TDT patients. In pediatric patients, one study found poorer HRQoL in TDT compared to NTDT (mean PedsQL total score [SD]: 42.25 [20.61] vs. 67.76 [18.31]; P=0.0001). However, both NTDT and TDT patients had poorer HRQoL than healthy controls (83.45 [15.6]); P<0.0001). Image:Summary/Conclusion: This SLR highlights the negative impact of thalassemia on HRQoL. Adding to previously published SLRs, it shows limited evidence is available for NTDT patients; however, studies suggest that HRQoL burden may be worse in NTDT than TDT patients, particularly in adults. Characterizing the HRQoL burden of α-thal is a clear evidence gap. High-quality, real-world studies in NTDT and α-thal are needed to better understand the HRQoL burden and the potential impact of new treatments on HRQoL.

P1741: EXAMINING THE BURDEN OF ILLNESS ASSOCIATED WITH TRANSFUSION-DEPENDENT ΒETA-THALASSEMIA FROM THE PATIENT’S PERSPECTIVE

Background: β-thalassemia is a rare genetic blood disorder affecting approximately 1 in 100,000 people globally. Typically diagnosed in childhood, β-thalassemia is marked by the inability to produce hemoglobin, which results in chronic anemia. Transfusion-dependent β-thalassemia (TDβT) is the most severe form of this disorder, with treatment requiring frequent red blood cell transfusions (RBCTs). Recognized complications of the frequent RBCTs include alloimmunization, iron overload, resultant cardiac and liver disease, and reported poor health-related quality of life (HRQoL). Aims: To examine the burden of illness and HRQoL in patients diagnosed with TDβT. Methods: Potential study participants were recruited with the assistance of the Cooley’s Anemia Foundation. Participants were ≥18 years of age, had a self-reported physician diagnosis of β-thalassemia, and had received ≥1 RBCT in the past 6 months. After providing informed consent, patients completed an institutional review board-approved 30-minute online survey that included both validated patient-reported outcome instruments, and other questions written expressly for the purpose of this study. Data were collected in May 2021. Patients who completed the survey earned an incentive payment of 75 US dollars. Results: A total of 100 patients completed the survey; mean age was 36.0 years (standard deviation [SD] 10.4) and 35% of patients were male. Patients had been diagnosed with TDβT for a mean of 34.4 years (SD 10.3) and experienced a mean of 9.6 (SD 4.3) RBCT events in the past 6 months. As an indication of severity, 66% of patients reported requiring >1 RBCT per month, 31% each month, and 3% every other month. Side effects of RBCT included iron overload (in 81% of patients), rashes/hives (74%), fatigue (61%), and pain/bruising at injection site (52%). Mean time required for an RBCT was 7.4 hours (SD 11.3), including transfusion preparation time. Travel and wait times were an additional 7.1 hours. Among all patients, 70% reported a “moderate” to “extremely high” burden of RBCT. On HRQoL, 71% of patients reported “wondering what life would be like without β-thalassemia,” 86% reported “feeling fatigued” leading up to RBCT, and 42% reported “not being as social with friends/family due to the time needed for RBCT.” On validated psychological instruments, 52% of patients reported mild-to-severe depression (Patient Health Questionnaire [PHQ-9]) and 53% reported mild-to-severe anxiety (Generalized Anxiety Disorder Questionnaire [GAD-7]), over the previous 2 weeks. Summary/Conclusion: The survey results suggest there is a substantial time, side-effect, and HRQoL burden associated with treatment by RBCTs in patients diagnosed with TDβT. This includes considerable time devoted to preparing for and receiving transfusions, transfusion-related side effects, and increases in depression and anxiety. These findings contribute to the understanding of the humanistic and psychological burden of RBCT dependency in patients with β-thalassemia. New treatment options that can improve outcomes in this population are needed.

The burden of non-alcoholic steatohepatitis: A systematic review of health-related quality of life and patient-reported outcomes

Background & AimsNon-alcoholic steatohepatitis (NASH) is associated with increased mortality and a high clinical burden. NASH adversely impacts patients’ health-related quality of life (HRQoL), but published data on the humanistic burden of disease are limited. This review aimed to summarise and critically evaluate studies reporting HRQoL or patient-reported outcomes (PROs) in populations with NASH and identify key gaps for further research.MethodsMedline, EMBASE, the Cochrane Library and PsycINFO were searched for English-language publications published from 2010 to 2021 that reported HRQoL/PRO outcomes of a population or subpopulation with NASH.ResultsTwenty-five publications covering 23 unique studies were identified. Overall, the data showed a substantial impact of NASH on HRQoL, particularly in terms of physical functioning and fatigue, with deterioration of physical and mental health as NASH progresses. Prevalent symptoms, including fatigue, abdominal pain, anxiety/depression, cognition problems, and poor sleep quality, adversely impact patients’ ability to work and perform activities of daily living and the quality of relationships. However, some patients fail to attribute symptoms to their disease because of a lack of patient awareness and education. NASH is associated with high rates of comorbidities such as obesity and type 2 diabetes, which contribute to reduced HRQoL. Studies were heterogeneous in terms of diagnostic methods, population, outcomes, follow-up time, and measures of HRQoL/utility. Most studies were rated ‘moderate’ at quality assessment, and all evaluable studies had inadequate control of confounders.ConclusionsNASH is associated with a significant HRQoL burden that begins early in the disease course and increases with disease progression. More robust studies are needed to better understand the humanistic burden of NASH, with adequate adjustment for confounders that could influence outcomes.Lay summaryNon-alcoholic steatohepatitis (NASH) has a significant impact on quality of life, with individuals experiencing worse physical and mental health compared with the general population. NASH and its symptoms, which include tiredness, stomach pain, anxiety, depression, poor focus and memory, and impaired sleep, affect individuals’ relationships and ability to work and perform day-to-day tasks. However, not all patients are aware that their symptoms may be related to NASH. Patients would benefit from more education on their disease, and the importance of good social networks for patient health and well-being should be reinforced. More studies are needed to better understand the patient burden of NASH.

Disease Burden of Huntington's Disease (HD) on People Living with HD and Care Partners in Canada.

Background:Huntington’s disease (HD) has been shown to reduce health-related quality of life (HRQoL) and affect healthcare resource utilization (HRU) among patients and care partners internationally but has not been studied specifically in the Canadian context.Objective:To characterize the burden of HD on individuals with HD and care partners of individuals with HD in Canada.Methods:An online survey was distributed (September 14–November 23, 2020) through patient organizations to collect data on demographic and clinical characteristics, as well as: HRQoL, measured using the 36-Item Short-Form Health Survey (SF-36v1); HRU, measured using the Client Service Receipt Inventory (CSRI); and care partner burden, measured using the Caregiver Strain Index (CSI) and Huntington’s Disease Quality of Life Battery for Carers (HDQoL-C). Descriptive statistics were used to report data and compare subgroups.Results:A total of 62 adult individuals with HD (or their proxies) and 48 care partners met defined eligibility criteria. The mean [standard deviation] age was 51.2 [13.8] and 58.1 [13.9] years for individuals with HD and care partner respondents, respectively. For individuals with HD, the greatest HRQoL burden (i.e., lowest score) was for the SF-36v1 Role –Physical scale (46.8 [42.9]). HRU was higher for some services (e.g., general practitioner visits) for respondents who had experienced motor onset transition. Among care partners, 55.3% experienced high strain, as indicated by the CSI. The HDQoL-C showed the greatest HRQoL burden in feelings about life (45.1 [17.9]).Conclusion:This study quantified the substantial burden on individuals with HD and care partners in Canada, addressing a critical knowledge gap that can affect the availability of and access to healthcare services.