Estimation of health utility values for alopecia areata.

PURPOSE: Alopecia areata (AA) is an autoimmune-mediated inflammatory dermatological disease characterised by non-scarring hair loss affecting the scalp and sometimes other hair-bearing sites. This study aimed to elicit health state utility values (HSUVs) from the UK general population for AA using time trade off (TTO) interviews. METHODS: Vignette descriptions of health states defined by the extent of hair loss were developed (as well as one describing caregiver burden). These were developed using data from standardised patient reported outcome (PRO) measures, a literature review and qualitative interviews. Health states were defined based on the severity of alopecia tool (SALT), which assesses extensiveness of scalp hair loss. HSUVs were then elicited for each health state in TTO interviews with the UK public. RESULTS: One caregiver and five patient health states were developed based on the literature review findings, clinical trial PRO (Hospital Anxiety and Depression Scale and Alopecia Areata Patient Priority Outcomes Questionnaire) data and qualitative interviews with patients (N = 11), clinical experts (N = 4) and caregivers of adolescents with AA (N = 10). These data showed a more severe impact among patients with more extensive hair loss. One hundred and twenty participants evaluated the vignettes in TTO interviews. Patient HSUVs ranged from 0.502 for the most extensive hair loss health state (SALT 50-100 + eyebrow and eyelash loss) to 0.919 (SALT 0-10) for the mildest health state. The caregiver HSUV was 0.882. CONCLUSION: Quantitative and qualitative data sources were used to develop and validate vignettes describing different AA health states. Patient and caregiver HSUVs demonstrate a large impact associated with AA, especially for states defined by more extensive hair loss.

Treatment preferences of adults and adolescents with alopecia areata: A discrete choice experiment.

PRODUCTS with janus kinase (JAK) inhibition have been shown to promote hair regrowth in patients with alopecia areata (AA). To guide drug-approval and treatment decisions, it is important to understand patients' willingness to accept the potential risks of JAK inhibition in exchange for potential benefits. We quantified the treatment preferences of adult (≥18 years) and adolescent patients (12-17 years) with AA in the US and Europe to determine the trade-offs they are willing to make between benefits and risks. Preferences for oral AA treatment attributes were elicited using a discrete choice experiment consisting of 12 tasks in which patients chose between two hypothetical treatment alternatives and no treatment. Benefits included the probability of 80%-100% scalp hair regrowth (Severity of Alopecia Tool score ≤ 20) and achieving moderate-to-normal eyebrow and eyelash hair. Treatment-related risks included 3-year probabilities of serious infection, cancer, and blood clots. Preference estimates were used to calculate the maximum level of each risk that patients were willing to accept for increases in treatment benefits. The most important attribute to both adults (n = 201) and adolescents (n = 120) was a 50% probability of achieving hair regrowth on most or all the scalp; however, adolescents placed greater relative importance on this attribute than did adults. Adults were averse to the risks of serious infection, cancer, and blood clots, whereas adolescents were averse to the risk of cancer. For a 20% increase in the probability of 80%-100% scalp hair regrowth, adults were willing to accept a mean (95% confidence interval) 3-year risk of serious infection, cancer, and blood clots of 7.4% (5.5-9.3), 2.5% (1.9-3.1), and 9.3% (6.4-12.2). Adolescents were willing to accept a 3-year risk of cancer of 3.3% (2.4-4.2). Patients with AA in the US and Europe are willing to accept substantial risks to obtain an effective treatment.

Patient-reported outcomes in high-risk HR+ /HER2- early breast cancer patients treated with endocrine therapy with or without palbociclib within the randomized PENELOPEB study.

BACKGROUND: The PENELOPEB trial investigating efficacy and safety of additional 1-year post-neoadjuvant palbociclib to standard endocrine therapy (ET) high-risk hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer patients failed to improve invasive disease-free survival (iDFS). This analysis compared patient-reported outcomes (PROs) between treatment groups. PATIENTS AND METHODS: Patients received 13 cycles of palbociclib 125 mg/day (n = 631) or placebo (n = 619) orally for 3 out of 4 weeks + ET. European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30), its breast cancer (BR23) and fatigue (FA13) modules, mood questionnaire GAD7 and European Quality of Life 5 Dimensions (EQ-5D) instruments were used for the assessment of quality of life (QoL). Repeated-measures mixed-effects models were used to evaluate differences in PRO, changes of PRO over time, and treatment-by-time interactions. RESULTS: 924 of 1250 patients (73.9%) completed baseline and at least one post-baseline questionnaire of all PRO instruments. General health status (GHS)/QoL based on EORTC QLQ-C30 was high in both arms (mean [SD]: palbociclib 70.1 [19.3], placebo 71.4 [18.8]) and was slightly higher in the placebo arm (LeastSquare mean difference: 0.82, p < 0.001). Higher fatigue was reported in the palbociclib arm (mean [SD]: 30.3 [23.8] vs. placebo 28.3 [22.7]; p < 0.001). No statistically significant differences were observed among FA13 physical, cognitive, and emotional fatigue subscales. CONCLUSION: Patient-reported global QoL and fatigue did not substantially change in both treatment arms. Slight differences in GHS, physical functioning, and fatigue favored the placebo arm statistically without achieving clinically meaningful thresholds.

Hair Loss Profiles and Ritlecitinib Efficacy in Patients with Alopecia Areata: Post Hoc Analysis of the ALLEGRO Phase 2b/3 Study.

INTRODUCTION: Ritlecitinib demonstrated efficacy in patients with alopecia areata (AA) in the ALLEGRO phase 2b/3 study (NCT03732807). However, hair loss presentation may vary based on location (e.g., scalp, eyebrow/eyelash, body). Here, we sought to identify distinct hair loss profiles at baseline and evaluate whether they affected the efficacy of ritlecitinib. METHODS: Patients with AA aged ≥ 12 years with ≥ 50% scalp hair loss were randomized to daily ritlecitinib 10 mg (assessed for dose ranging only), 30 or 50 mg (± 4-week, 200-mg loading dose), or placebo for 24 weeks. Latent class analysis (LCA) identified hair loss profiles based on four baseline measurements: clinician-reported extent of scalp (Severity of Alopecia Tool score), eyebrow hair loss, eyelash hair loss, and patient-reported body hair loss. Logistic regression evaluated ritlecitinib (50 and 30 mg) efficacy vs placebo using Patient Global Impression of Change (PGI-C) and Patient Satisfaction with Hair Growth (P-Sat; amount, quality, and overall satisfaction) responses at Week 24, adjusting for key covariates, including latent class membership. RESULTS: LCA identified five latent classes: (1) primarily non-alopecia totalis (AT; complete loss of scalp hair); (2) non-AT with moderate non-scalp involvement; (3) extensive scalp, eyebrow, and eyelash involvement; (4) AT with moderate non-scalp involvement; and (5) primarily alopecia universalis (complete scalp, face, and body hair loss). Adjusting for latent class membership, patients receiving ritlecitinib 30 or 50 mg were significantly more likely to achieve PGI-C response (30 mg: odds ratio, 8.62 [95% confidence interval, 4.42-18.08]; 50 mg: 12.29 [6.29-25.85]) and P-Sat quality of hair regrowth (30 mg: 6.71 [3.53-13.51]; 50 mg: 8.17 [4.30-16.46]) vs placebo at Week 24. Results were similar for P-Sat overall satisfaction and amount of hair regrowth. CONCLUSION: Distinct and clinically relevant hair loss profiles were identified in ALLEGRO-2b/3 participants. Ritlecitinib was efficacious compared with placebo, independent of hair loss profile at baseline. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03732807.

Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: This subgroup analysis of the ALLEGRO phase 2b/3 trial (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, for the treatment of alopecia areata (AA) in patients aged 12-17 years. METHODS: In ALLEGRO-2b/3, patients aged ≥12 years with AA and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (±4-week 200-mg loading dose) or 10 mg or placebo for 24 weeks. In a subsequent 24-week extension period, ritlecitinib groups continued their doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily. Clinician- and patient-reported hair regrowth outcomes and safety were assessed. RESULTS: In total, 105 adolescents were randomized. At Week 24, 17%-28% of adolescents achieved a Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp without hair) in the ritlecitinib 30 mg and higher treatment groups versus 0% for placebo. At Week 48, 25%-50% of patients had a SALT score ≤20 across ritlecitinib treatment groups (30 mg and higher). Adolescents reporting that their AA "moderately" or "greatly" improved were 45%-61% in the ritlecitinib groups (30 mg and higher) (vs. 10%-22% for placebo) at Week 24 and 44%-80% at Week 48. The most common adverse events in adolescents were headache, acne, and nasopharyngitis. No deaths, major adverse cardiovascular events, malignancies, pulmonary embolisms, opportunistic infections, or herpes zoster infections were reported. CONCLUSION: Ritlecitinib treatment demonstrated clinician-reported efficacy, patient-reported improvement, and an acceptable safety profile through Week 48 in adolescents with AA with ≥50% scalp hair loss.

Real-world Treatment Patterns and Clinical Outcomes Associated With Palbociclib Combination Therapy: A Multinational, Pooled Analysis From the Ibrance Real World Insights Study.

PURPOSE: Palbociclib was the first cyclin-dependent kinase 4/6 inhibitor approved by the US Food and Drug Administration for use in combination with aromatase inhibitors (AIs) as initial endocrine-based therapy or with fulvestrant in postmenopausal women who previously received endocrine therapy based on data from randomized clinical trials. Real-world studies examining the effectiveness of palbociclib in large, diverse patient populations in routine clinical practice were needed. PATIENTS AND METHODS: Ibrance Real World Insights (IRIS) was a retrospective medical record review study of women with confirmed hormone receptor-positive, HER2-negative advanced/metastatic breast cancer treated with palbociclib plus an AI or with palbociclib plus fulvestrant according to approved indications. Participating physicians reviewed medical records of up to 16 sequentially presenting patients, collecting demographic and clinical data. Outcomes included objective response rates, progression-free rates, and survival rates overall and in patients stratified according to age, race and ethnicity, Eastern Cooperative Oncology Group (ECOG) performance status (PS), disease-free interval, visceral disease, liver metastases, bone-only metastases, and previous lines of therapy. FINDINGS: Data were abstracted by 417 physicians for 2954 patients in 13 countries; 1415 patients (47.9%) were ≥65 years of age, 369 patients (12.5%) had an ECOG PS ≥2 at initiation, and 835 patients (28.3%) were races other than White. The 12-month progression-free rate was 88% for palbociclib plus an AI and 79% for palbociclib plus fulvestrant; the 12-month survival rate was 96% in both groups. The objective response rates were 80% for palbociclib plus an AI and 75% for palbociclib plus fulvestrant. Palbociclib was similarly effective in most subgroups examined. IMPLICATIONS: Data from IRIS provide in-depth, real-world evidence for the use of palbociclib in a range of breast cancer populations in multiple countries. These data support the findings of the randomized PALOMA-2 and PALOMA-3 studies.

Health-related Quality of Life in Hormone Receptor-Positive Early Breast Cancer: Analyses From the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey.

This study describes health-related quality of life (HRQoL) among older Medicare beneficiaries with hormone receptor-positive (HR+) early breast cancer (eBC). Women aged ≥65 years diagnosed with stage I-III HR+ eBC between 1997 and 2014 using the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey Data Resource were included. HRQoL was measured using the Short Form Health Survey including physical/mental component summary (PCS/MCS) scores and subscales. Patient surveys ≤ 24 months post-diagnosis were matched to non-cancer controls. Mean differences in HRQoL were compared using analysis of covariance. Among 1880 HR+ eBC patients versus 5640 matched non-cancer controls, eBC patients surveyed ≤ 6 months post-diagnosis (n = 530) scored lower on component scores (PCS mean difference = 1.6 [95%CI: 0.6-2.6]; MCS mean difference = 2.0 [95%CI: 1.0-3.0]) and multiple subscales. Among women surveyed 19 to 24 months post-diagnosis (n = 402), mean differences in HRQoL were modest (PCS: 1.2 [95%CI: 0.1-2.4]; MCS: -1.5 [95%CI: -2.7 to -0.3]). Most differences in HRQoL following diagnosis of eBC did not indicate statistical significance or minimally important difference, emphasizing that preservation of HRQoL is an important and realistic goal among patients with eBC.

Time-Specific Differences in Stated Preferences for Health in the United States.

BACKGROUND: Changes over time in health state values from a societal perspective may be an important reason to consider updating societal value sets for preference-based measures of health. OBJECTIVE: The aim was to examine whether stated health preferences are different between 2002 and 2017, controlling for demographic changes in the United States. METHODS: Data from 2002 and 2017 US EQ-5D-3L valuation studies were combined. The primary analysis compared valuations of better-than-dead (BTD) states only, as both studies used the same time trade-off (TTO) method for these states. For worse-than-dead (WTD) states, the 2017 study used the lead-time TTO and the 2002 study used the conventional TTO, which necessitated transformation. Regression models were fitted to BTD values to estimate time-specific differences, adjusting for respondent characteristics. Secondary analyses examined models that fitted WTD values (using linear and nonlinear transformations of the 2002 data) and all values. RESULTS: The adjusted BTD-only model showed mean values were higher for 2017 compared with 2002 (ßY2017=0.05, P<0.001). WTD-only models showed negative changes over time but that were dependent on the transformation method (linear ßY2017=-0.72; nonlinear ßY2017=-0.35; both P<0.001). Using all values, 2017 mean valuations were lower using a linear transformation (ßY2017=-0.11; P<0.001) but did not differ with the nonlinear transformation. CONCLUSIONS: Individuals in 2017 are generally less willing to trade quantity for quality of life compared with 2002. This study provides evidence of time-specific differences in a society's preferences, suggesting that the era in which values were elicited may be an important reason to consider updating societal value sets.

Impact of time to distant recurrence on breast cancer-specific mortality in hormone receptor-positive breast cancer.

Women with hormone receptor (HR)-positive early-stage breast cancer (BC) have five-year survival rates of > 90% but remain at serious risk for developing distant metastases beyond five years from diagnosis. This retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) registries to examine associations between distant recurrence-free interval (DRFI) and risk of BC-specific mortality following distant relapse. The analysis includes 1,057 women with second primary stage IV BC who were initially diagnosed with AJCC stages I-III HR-positive BC between1990 and 2016. Overall, 65% of women had a preceding DRFI of ≥ 5 years. Five-year BC-specific survival following development of distant recurrence was 52% for women with DRFI ≥ 5 years compared to 31% in women with DRFI of < 5 years. In multivariable analyses, risks of cancer-specific mortality following distant recurrence were lower in women with DRFI of 5 years or more (subdistribution hazard ratio = 0.72, 95% CI 0.58-0.89, p = 0.002). The results of this study may inform patient-clinician discussions surrounding prognosis and treatment selection among HR-positive patients who develop a distant recurrence of disease.

Palbociclib versus abemaciclib in HR+/HER2- advanced breast cancer: an indirect comparison of patient-reported end points.

Aim: To assess the relative impact of palbociclib plus fulvestrant (PAL + FUL) and abemaciclib plus fulvestrant (ABEM + FUL) on patient-reported outcomes in patients with hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer. Patients & methods: Anchored matching-adjusted indirect comparisons were conducted using individual patient data from PALOMA-3 (PAL + FUL) and summary-level data from MONARCH-2 (ABEM + FUL). Outcomes included the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30) and its breast cancer-specific module (QLQ-BR23). Results: Significantly different changes from baseline favoring PAL + FUL compared with ABEM + FUL were observed in global quality of life (6.95 [95% CI: 2.19-11.71]; p = 0.004) and several functional/symptom scales, including emotional functioning, nausea/vomiting, appetite loss, diarrhea and systemic therapy side effects. Conclusion: PAL + FUL was associated with more favorable patient-reported outcomes than ABEM + FUL in patients with HR+/HER2- advanced breast cancer.

Voice Analysis of Cancer Experiences Among Patients With Breast Cancer: VOICE-BC.

Patient experience literature in early-stage breast cancer (eBC) is limited. This study used a mixed-methods approach to examine patient conversations from public online forums to identify and evaluate eBC-related themes. Among 60,000 eBC-related posts published September 2014-2019, text from a random subset of 15,000 posts was extracted and grouped into linguistically similar, mutually exclusive clusters using an advanced natural language processing (NLP) algorithm. Clusters were characterized using four quantitative metrics: betweenness centrality (linguistic similarity to other areas of the cluster network), sentiment (general attitude toward a topic), recency (average date of posts), and volume (total number of posts). This analysis represented 3906 unique users (67% and 33% obtained from cancer-specific and general health/nonhealth forums, respectively). Of the 27 clusters identified, most important were "discussing recurrence & progression," "understanding diagnosis & prognosis," and "understanding cancer, biomarkers, and treatments." Several major themes related to recurrence risk, diagnosis, monitoring, and treatment were identified. Additional emphasis on communicating the disease recurrence risk and shared decision-making could strengthen patient-clinician partnerships.

Population-based recurrence rates among older women with HR-positive, HER2-negative early breast cancer: Clinical risk factors, frailty status, and differences by race.

BACKGROUND: Multiple independent risk factors are associated with the prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), the most common BC subtype. This study describes U.S. population-based recurrence rates among older, resected women with HR+/HER2- early BC. METHODS: We conducted a retrospective cohort study of older women diagnosed with incident, invasive stages I-III HR+/HER2- BC who underwent surgery to remove the primary tumor using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked Database (2007-2015). SEER records and administrative health claims data were used to ascertain patient and tumor-specific characteristics, treatment, and frailty status. Cumulative incidences of BC recurrence were estimated using a validated algorithm for administrative claims data. Multivariable Fine-Gray competing risk models estimated adjusted subdistribution hazards ratios and 95 % confidence intervals for associations with BC recurrence risk. RESULTS: Overall, 46,027 women age ≥65 years were included in our analysis. Over a median follow up of 7 years, 6531 women experienced BC recurrence with an estimated 3 and 5-year cumulative incidence rates of 10 % and 16 %, respectively. Higher 3- and 5-year cumulative incidences were observed in women with larger tumor size (5+ cm, 21 % and 28 %), lymph node involvement (4+ nodes, 27 % and 37 %), and with frail health status at diagnosis (13 % and 20 %). Independent of these clinical risk factors, Black, Hispanic and American Indian/Alaskan Native women had significantly increased BC recurrence risks. CONCLUSIONS: Rates of recurrence in HR+/HER2- early BC differs by several patient and clinical factors, including high-risk tumor characteristics. Racial differences in BC outcomes deserve continued attention from clinicians and policymakers.

Health-Related Quality of Life Among Patients With HR+/HER2- Early Breast Cancer.

PURPOSE: The goal of this study was to characterize health-related quality of life (HRQOL) among patients diagnosed with early-stage, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. METHODS: A multinational (United States, Japan, France, Germany, Italy, Spain, and United Kingdom) study of patients diagnosed with stage I to III HR+/HER2- breast cancer, either receiving adjuvant treatment or under postadjuvant surveillance, was conducted between June and October 2019. Patients were identified by their consulting physician and invited to complete the Functional Assessment of Cancer Therapy-Breast (FACT-B) and the EQ-5D-5L pen and paper questionnaires. EQ-5D-5L index scores were derived by using available country-specific health state value sets, where available, and numerically compared with general population scores derived from published normative and population data. Descriptive summary statistics were reported for FACT-B, Functional Assessment of Cancer Therapy-General (FACT-G) (total and specific subscales), the EQ-5D index scores, and the EQ-VAS scores for each country. Results were stratified according to disease-free treatment status (active adjuvant treatment or postadjuvant surveillance), age (25-44, 45-54, 55-64, or ≥65 years), stage (I, II, or III), and menopausal status at the time of questionnaire completion (pre-/peri-menopausal or postmenopausal). FINDINGS: Overall, 1110 patients completed the HRQOL questionnaires (mean age, 59 years; 79% active adjuvant treatment, and 21% under surveillance postadjuvant treatment at time of questionnaire administration; 31% stage I, 48% stage II, and 20% stage III at diagnosis). Of these, 1102 completed the FACT-B and 1083 completed the EQ-5D-5L questionnaires. The mean (SD) FACT-B total score was 99.0 (21.9). The mean FACT-G total score was 72.5 (17.8), which was comparable to the published normative score. The mean EQ-5D index and EQ-VAS scores for each country were similar to corresponding population means; EQ-5D index scores ranged from 0.842 (0.098) in Japan to 0.916 (0.109) in France, and EQ-VAS scores from 68.0 (18.4) in Germany to 78.6 (16.4) in the United States. In addition, mean scores were comparable between the active adjuvant treatment and postadjuvant surveillance groups for the FACT-B total (99.4 [22.5] and 97.7 [19.7], respectively), FACT-G total (72.8 [18.3] and 71.3 [16.0]), EQ-5D index score (0.868 [0.135] and 0.869 [0.142]), and EQ-VAS (74.9 [17.2] and 74.4 [16.1]). IMPLICATIONS: Patient-reported HRQOL among patients with HR+/HER2- early breast cancer who were disease-free was high, with reported scores comparable to normative scores. These results improve our understanding of HRQOL among patients with early disease and may facilitate future studies examining the potential impact of adjuvant treatment and disease recurrence, including metastasis.

Patient, Oncologist, and Payer Preferences for Adjuvant Endocrine Therapy and CDK4/6 Inhibitor Regimens in Early-Stage Breast Cancer: A Discrete Choice Experiment.

PURPOSE: Several adjuvant phase III trials are evaluating cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy (ET) in hormonal receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer (eBC). This study examines preferences for this combination regimen and ET alone among patients, oncologists, and payers in the United States. METHODS: A web-based questionnaire, including a discrete choice experiment (DCE), was administered to patients, practicing oncologists, and payers. In the DCE, respondents selected between hypothetical treatment profiles with attributes associated with ET monotherapy and CDK4/6i + ET regimens. Each treatment alternative was defined by the following attributes: 5-year invasive disease-free survival (iDFS), nausea, diarrhea, neutropenia, alopecia, dosing schedule, and electrocardiogram (ECG) monitoring. Payers had the additional attribute of annual per-patient treatment cost. Hierarchical Bayesian models were used to estimate relative preference weights for each attribute-level and relative attribute importance. RESULTS: For patients (n=300) and oncologists (n=200), iDFS was most important (2 to 3 times more important than the next most important attribute), followed by neutropenia and diarrhea risks for patients and oncologists, respectively. Patients and oncologists required an improvement in iDFS of 8.0 and 5.6 percentage-points, respectively, to accept an increase in diarrhea risk from 11% to 81%. Payers (n=60) viewed annual per-patient cost as most important for treatment access decision-making, closely followed by iDFS. Payers required an improvement in iDFS of 21.8 percentage-points to accept an increase in cost from $5,100 to $149,400. Across all stakeholder groups, dosing schedule, alopecia risk, and ECG monitoring were perceived as least important. CONCLUSION: Patients, oncologists, and payers expect a large absolute risk reduction in efficacy to offset the potential risks and costs of adding a CDK4/6i to current standard of care. An open discussion between all stakeholders is necessary to ensure that decision-making, whether at patient- or system-level, is informed by preferences for novel treatments, like CDK4/6is.

Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis.

BACKGROUND: A systematic review and meta-analysis was conducted to assess breast cancer (BC) outcomes among patients with early-stage hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) BC, receiving adjuvant endocrine therapy. METHODS: Randomized controlled trials (RCTs) and real-world evidence (RWE) studies were identified using Ovid MEDLINE®, Embase, and Evidence-Based Medicine Reviews. Clinical and methodological similarities including alignment of outcome definitions with standardized definitions for efficacy endpoints criteria were assessed to evaluate feasibility of conducting a meta-analysis. Where feasible, 5-year probabilities of BC recurrence or death were estimated using a Bayesian hierarchical arm-based model. RESULTS: Of 21 included studies, 8 RCTs and 4 RWE studies reported outcome data of interest. There was heterogeneity in outcome reporting, as well as variation in recurrence risk amongst studies with aligned reporting. Of the 12 studies, 10 were considered for inclusion in a meta-analysis of BC recurrence or death. Only a subgroup analysis of node-positive patients (3 studies; n = 7307) was deemed feasible. The 5-year probability of BC recurrence or death was 17.2% (95% credible interval: 14.6%-20.3%). CONCLUSION: Although studies reporting recurrence outcomes were limited, there remains a high risk of BC recurrence, especially among node-positive patients. Approximately 1 in 6 women with node-positive HR+/HER2- early-stage BC receiving endocrine therapy experience recurrence or death within 5-years of initiating treatment, suggesting a need for novel treatments for this population.

Parallel Valuation of the EQ-5D-3L and EQ-5D-5L by Time Trade-Off in Hungary.

OBJECTIVES: The wording of the Hungarian EQ-5D-3L and EQ-5D-5L descriptive systems differ a great deal. This study aimed to (1) develop EQ-5D-3L and EQ-5D-5L value sets for Hungary from a common sample, and (2) compare how level wording affected valuations. METHODS: In 2018 to 2019, 1000 respondents, representative of the Hungarian general population, completed composite time trade-off tasks. Pooled heteroscedastic Tobit models were used to estimate value sets. Value set characteristics, single-level transition utilities from adjacent corner health states, and mean transition utilities for all possible health states were compared between the EQ-5D-3L and EQ-5D-5L. RESULTS: Health utilities ranged from -0.865 to 1 for the EQ-5D-3L and -0.848 to 1 for the EQ-5D-5L. The relative importance of the 5 EQ-5D-5L dimensions was as follows: mobility, pain/discomfort, self-care, anxiety/depression, and usual activities. A similar preference ranking was observed for the EQ-5D-3L with self-care being more important than pain/discomfort. The EQ-5D-5L demonstrated lower ceiling effects (range of utilities for the mildest states: 0.900-0.958 [3L] vs 0.955-0.965 [5L]) and better consistency of mean transition utilities across the range of scale. Changing "confined to bed" (3L) to "unable to walk" (5L) had a large positive impact on utilities. Smaller changes with more negative wording in the other dimensions (eg, "very much anxious/feeling down a lot" [3L] vs "extremely anxious/depressed" [5L]) had a modest negative impact on utilities. CONCLUSION: This study developed value sets of the EQ-5D-3L and EQ-5D-5L for Hungary. Our findings contribute to the understanding of how the wording of descriptive systems affects the estimates of utilities.

The Role of Personality in Treatment-Related Outcome Preferences Among Pharmacy Students.

Objective. To examine whether personality traits, particularly conscientiousness and agreeableness, were associated with systematic differences in health outcome preferences in cancer treatment scenarios among second-year Doctor of Pharmacy students. Methods. An online survey that quantified outcome preferences using profile best-worst scaling tasks was administered to pharmacy students (n=185). The Big Five personality inventory was used to categorize respondents into tertile-based levels of each trait. Treatment-related health outcomes were described using the EQ-5D-Y system and framed with hypothetical cancer treatment scenarios. Preferences were obtained using count analysis for each treatment-related outcome, and differences based on the level of trait were tested using analysis of variance. Logistic regression was used to test for significant associations between higher levels of a trait and choosing dead over a severe health state. Results. Higher conscientiousness was associated with students who had an approximately 20% more positive preference for "no problems" in the Usual Activities and Pain/Discomfort attributes, as well as a 19% more negative preference for "a lot of problems" in the Pain/Discomfort attribute. No differences in treatment preferences were observed across agreeableness tertiles. Higher levels of personality traits were not significantly associated with choosing death over being in moderate health. Conclusion. Conscientiousness appears to be a factor in treatment-related outcome preferences among pharmacy students. Individuals with higher levels of conscientiousness may be more likely to recommend treatments that are less likely to cause pain or discomfort and negatively impact a patient's usual activities.

United States Valuation of EQ-5D-5L Health States Using an International Protocol.

OBJECTIVE: To derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. METHODS: Respondents from the US adult population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. RESULTS: Of 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the preferred model to generate the value set. Values ranged from -0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). CONCLUSIONS: A societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.

A comparison of self-rated health using EQ-5D VAS in the United States in 2002 and 2017.

PURPOSE: To compare self-rated health among the United States general population in 2002 and 2017. METHODS: Secondary data were analyzed from two EQ-5D valuation studies conducted in 2002 and 2017. Both studies included the EQ-5D-3L self-classifier and visual analog scale (VAS), where health is rated from 0 (worst imaginable health) to 100 (best imaginable health). VAS scores were compared between time points using regression models, adjusting for sociodemographic factors (Model 1), plus illness (Model 2), and health problems according to the EQ-5D classifier (Model 3). RESULTS: Mean VAS scores in 2002 [84.4 (SD = 16.1)] were not different from 2017 [84.6 (SD = 14.5)] (p = 0.63), nor different after adjusting for demographics (Model 1) or illness (Model 2). However, 2017 VAS mean scores were significantly higher than 2002 [2.2 (95% CI 1.36-3.10)] upon adjusting for the presence of dimension-specific health problems. CONCLUSIONS: Self-rated health of the general US adult population in 2017 was similar to 2002, but after adjusting for health problems, scores were slightly higher in 2017. Sociodemographic shifts in age and education explain some of the differences in scores, and by removing health and sociodemographic factors, we found the VAS reveals self-rated health is slightly better in 2017 than 2002.