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Purpose The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core Questionnaire (QLQ-C30) is a widely used generic self-report measure of health-related quality of life (HRQOL) for cancer patients. However, no validated voice script for interviewer-led telephone administration was previously available. The aim of this study was to develop a voice script for interviewer administration via telephone. Methods Following guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) PRO Mixed Modes Good Research Practices Task Force, a randomised cross-over equivalence study, including cognitive debriefing, was conducted to assess equivalence between paper and telephone administration modes. Assuming an expected intraclass correlation coefficient (ICC) of 0.70 and a minimally acceptable level of 0.50, a sample size of 63 was required. Results Cognitive interviews with five cancer patients found the voice script to be clear and understandable. Due to a protocol deviation in the first wave of testing, only 26 patients were available for analyses. A second wave of recruitment was conducted, adding 37 patients (n = 63; mean age 55.48; 65.1% female). Total ICCs for mode comparison ranged from 0.72 (nausea and vomiting, 95% CI 0.48–0.86) to 0.90 (global health status/QoL, 95% CI 0.80–0.95; pain, 95% CI 0.79–0.95; constipation, 95% CI 0.80–0.95). For paper first administration, all ICCs were above 0.70, except nausea and vomiting (ICC 0.55; 95% CI 0.24–0.76) and financial difficulties (ICC 0.60; 95% CI 0.31–0.79). For phone first administration, all ICCs were above 0.70. Conclusions The equivalence testing results support the voice script’s validity for administration of the QLQ-C30 via telephone.

Objectives In the CheckMate 141 trial (NCT02105636), nivolumab demonstrated survival, health-related quality of life, and healthcare resource utilization benefits vs single-agent therapy of investigator’s choice (IC) (methotrexate, docetaxel or cetuximab) in patients with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We assessed between-treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). Methods Survival data from CheckMate 141 (nivolumab, n = 240; IC, n = 121) was partitioned into toxicity (TOX), time without symptoms or toxicity (TWiST), and relapse (REL). TOX was defined as time spent with all-cause grade 3–4 adverse events after randomization, before disease progression. TWiST was defined as time not in TOX or REL. REL was defined as time between disease progression and death. Utility values derived from three-level EuroQol five-dimensional questionnaire data from CheckMate 141 were used to calculate Q-TWiST as the utility-weighted sum of the mean duration in each health state. Results The between-group difference in Q-TWiST score was 1.23 months (95% confidence interval 1.17–1.29) favoring nivolumab (p 10%) in quality-adjusted survival vs standard of care in patients with R/M SCCHN.

Objectives The introduction of innovative, high-cost oncology treatments, coupled with mounting budgetary pressures, necessitates value trade-offs across cancer types. Defining value is critical to informing decision-making. A cost-value analysis tool was used to assess relative clinical value from a US perspective using multiple outcome metrics for a variety of metastatic cancers. Methods Literature published (January 1, 2000-August 31, 2016) was reviewed to identify outcome metrics for approved treatments for metastatic cancers. Data were extracted or derived for median and mean overall survival (OS), landmark survival rates, and other survival metrics, and compared across treatments vs their respective trial comparators, with and without considering costs. Results Reported survival metrics varied by agent within cancer type. For treatment of prostate cancer, abiraterone yielded the highest improvement in 1-year survival rate (13.7%, previously treated), whereas enzalutamide yielded the highest median OS improvement (4.8 months, previously treated) and sipuleucel-T, the highest mean OS improvement (3.6 months, previously untreated) vs their respective trial comparators. For treatment of non-small cell lung cancer vs their respective trial comparators, nivolumab yielded the highest improvement in mean OS (11.9 months) and 3-year survival rate (12.6%), each in previously treated squamous disease, whereas afatinib yielded the highest median OS improvement (4.1 months, previously untreated EGFR del19 and L858R mutants). Cost-value analysis results varied with the applied survival metric. Conclusions Although median OS is the traditional gold standard oncology efficacy metric, it fails to capture long-term survival benefits-the ultimate goal of cancer treatment-offered by new treatment modalities. Diverse metrics are needed for comprehensive value assessments of cancer therapies.

Purpose The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core Questionnaire (QLQ-C30) is a widely used generic self-report measure of health-related quality of life (HRQOL) for cancer patients. However, no validated voice script for interviewer-led telephone administration was previously developed that could be used as an alternative to self-completion. The aim of this study was to develop a voice script for interviewer administration via telephone. Methods Following guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) PRO Mixed Modes Good Research Practices Task Force, a randomised cross-over equivalence study, including cognitive debriefing, was conducted to assess equivalence between paper and telephone administration modes. Assuming an expected intraclass correlation coefficient (ICC) of 0.70 and a minimally acceptable level of 0.50, a sample size of 63 was required. Results Cognitive interviews with five cancer patients found the voice script to be clear and understandable. Due to a protocol deviation in the first wave of testing, only 26 patients were available for analyses. A second wave of recruitment was conducted, adding 37 patients (n=63; mean age 55.48; 65.1% female). ICCs for mode comparison ranged from 0.72 (nausea and vomiting, 95% CI 0.48-0.86) to 0.90 (global health status/QoL, 95% CI 0.80-0.95; pain, 95% CI 0.79-0.95; constipation, 95% CI 0.80-0.95). For paper versus phone, all ICCs were above 0.70, except nausea and vomiting (95% CI 0.55). For phone versus paper, all ICCs were above 0.70. Conclusions The equivalence testing results support the voice script’s validity for administration of the QLQ-C30 via telephone.

It is important that patient-reported outcome (PRO) measures used to assess cancer therapies adequately capture the benefits and risks experienced by patients, particularly when adverse event profiles differ across therapies. This study explores the case for augmenting preference-based utility measures to capture the impact of cancer treatment-related symptoms. Additional cancer treatment-related items could be specific (e.g., rash) or global. While specific items are easier to describe and understand, their use may miss rarer symptoms and those that are currently unknown but will arise from future medical advancements. The appropriate number of additional items, the independence of those items, and their impact on the psychometric properties of the core instrument require consideration. Alternatively, a global item could encompass all potential treatment-related symptoms, of any treatments for any disease. However, such an item may not be well understood by general public respondents in valuation exercises. Further challenges include the decision about whether to generate de novo value sets for the modified instrument or to map to existing tariffs. The fluctuating and transient nature of treatment-related symptoms may be inconsistent with the methods used in conventional valuation exercises. Fluctuating symptoms could be missed by sub-optimal measure administration timing. The addition of items also poses double-counting risks. In summary, the addition of treatment-related symptom items could increase the sensitivity of existing utility measures to capture known and unknown treatment effects in oncology, while retaining the core domains. However, more research is needed to investigate the challenges, particularly regarding valuation.

Aim: To assess the cost-effectiveness of nivolumab monotherapy for recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) in the US. Methods: We constructed a cohort-based partitioned survival model for three health states (progression-free, progressed disease, and death). Using overall survival and progression-free survival data from the nivolumab and investigator’s choice (IC) arms of the CheckMate 141 study, the proportion of patients in each health state was estimated by parametric modeling over a 25-year period. Cost, utility, adverse event, and disease management data inputs were obtained from relevant literature and applied to patients in each health state. A scenario analysis was conducted assuming increased uptake of subsequent immunotherapies. A one-way deterministic sensitivity analysis assessed the impact of variation in multiple parameters. A probabilistic sensitivity analysis in which probabilistic distributions were applied to each input during 1,000 model iterations was also conducted. Results: Total costs incurred were higher with nivolumab ($101,552) than with IC ($38,067). Nivolumab was associated with a higher number of life-years (LY; 1.21) and quality-adjusted life-years (QALYs; 0.89), compared with IC (0.68 and 0.42, respectively). The incremental cost-effectiveness ratio for nivolumab compared with IC was $134,438 per QALY, and this remained qualitatively similar when increased uptake of subsequent immunotherapies was assumed ($129,603 per QALY). Sensitivity analyses supported these findings. Conclusions: These results suggest that, at a willingness-to-pay threshold of $150,000 per QALY, nivolumab is a cost-effective option for therapy of SCCHN in the US.

Background Incorporating patient reporting of symptomatic adverse events (AEs) is important in evaluating safety and tolerability in cancer clinical trials. The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to assess the frequency, severity, and/or interference of patient-reported symptomatic AEs. The objective of this study was to identify, based on oncologist and patient interviews, a relevant subset of symptomatic AEs from the PRO-CTCAE that can be used to optimize patient reporting of symptomatic AEs in hepatocellular carcinoma (HCC) clinical trials. Methods Qualitative and quantitative data on HCC diagnosis, treatment, symptoms, and side effects were collected from patients. Using a numerical rating scale, medical oncologists specializing in HCC rated the importance of (1) 34 symptomatic AEs (Grade ≥2) identified in past sponsor HCC clinical trials, (2) each PRO-CTCAE symptomatic AE item to the patient, and (3) each PRO-CTCAE symptomatic AE item with respect to patient safety or tolerability. Patients completed the PRO-CTCAE items and were debriefed on the importance of each PRO-CTCAE symptomatic AE to them. Results Five medical oncologists from the United States, Spain, Taiwan, Korea, and Hong Kong with 14 to 30 years of experience, and 17 patients with HCC and Child-Pugh class A or B cirrhosis status completed interviews. Medical oncologists rated the following symptomatic AEs from prior trials as being highly important to patients (mean rating of ≥7 on a scale from 0 to 10): hand-foot syndrome, diarrhea, fatigue, decreased appetite, rash, vomiting, and weight loss. PRO-CTCAE symptomatic AEs rated by medical oncologists as being highly important to patients included diarrhea, vomiting, shivering or shaking chills, hand-foot syndrome, rash, fatigue, difficulty swallowing, decreased appetite, and loss of control of bowel movements. Patients rated the following PRO-CTCAE symptomatic AEs as being highly important: loss of appetite/lack of interest in food, pain/tenderness at injection/insertion site, fatigue/lack of energy/tiredness, nausea, and hair loss. Conclusions This study identified a preliminary list of clinically relevant symptomatic AEs from interviews with both medical oncologists and patients that can be used to support assessments of treatment safety and tolerability in HCC clinical trials.

Summary Background Patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options and poor prognosis. Nivolumab significantly improved survival of this patient population when compared with standard single-agent therapy of investigator's choice in Checkmate 141; here we report the effect of nivolumab on patient-reported outcomes (PROs). Methods CheckMate 141 was a randomised, open-label, phase 3 trial in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who progressed within 6 months after platinum-based chemotherapy. Patients were randomly assigned (2:1) to nivolumab 3 mg/kg every 2 weeks (n=240) or investigator's choice (n=121) of methotrexate (40–60 mg/m 2 of body surface area), docetaxel (30–40 mg/m 2 ), or cetuximab (250 mg/m 2 after a loading dose of 400 mg/m 2 ) until disease progression, intolerable toxicity, or withdrawal of consent. On Jan 26, 2016, the independent data monitoring committee reviewed the data at the planned interim analysis and declared overall survival superiority for nivolumab over investigator's choice therapy (primary endpoint; described previously). The protocol was amended to allow patients in the investigator's choice group to cross over to nivolumab. All patients not on active therapy are being followed for survival. As an exploratory endpoint, PROs were assessed at baseline, week 9, and every 6 weeks thereafter using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Core 30 (QLQ-C30), the EORTC head and neck cancer-specific module (EORTC QLQ-H&N35), and the three-level European Quality of Life–5 Dimensions (EQ-5D) questionnaire. Differences within and between treatment groups in PROs were analysed by ANCOVA among patients with baseline and at least one other assessment. All randomised patients were included in the time to clinically meaningful deterioration analyses. Median time to clinically meaningful deterioration was analysed by Kaplan-Meier methods. CheckMate 141 was registered with ClinicalTrials.org, number NCT02105636. Findings Patients were enrolled between May 29, 2014, and July 31, 2015, and subsequently 361 patients were randomly assigned to receive nivolumab (n=240) or investigator's choice (n=121). Among them, 129 patients (93 in the nivolumab group and 36 in the investigator's choice group) completed any of the PRO questionnaires at baseline and at least one other assessment. Treatment with nivolumab resulted in adjusted mean changes from baseline to week 15 ranging from −2·1 to 5·4 across functional and symptom domains measured by the EORTC QLQ-C30, with no domains indicating clinically meaningful deterioration. By contrast, eight (53%) of the 15 domains in the investigator's choice group showed clinically meaningful deterioration (10 points or more) at week 15 (change from baseline range, −24·5 to 2·4). Similarly, on the EORTC QLQ-H&N35, clinically meaningful worsening at week 15 was seen in no domains in the nivolumab group and eight (44%) of 18 domains in the investigator's choice group. Patients in the nivolumab group had a clinically meaningful improvement (according to a difference of 7 points or greater) in adjusted mean change from baseline to week 15 on the EQ-5D visual analogue scale, in contrast to a clinically meaningful deterioration in the investigator's choice group (7·3 vs −7·8). Differences between groups were significant and clinically meaningful at weeks 9 and 15 in favour of nivolumab for role functioning, social functioning, fatigue, dyspnoea, and appetite loss on the EORTC QLQ-C30 and pain and sensory problems on the EORTC QLQ-H&N35. Median time to deterioration was significantly longer with nivolumab versus investigator's choice for 13 (37%) of 35 domains assessed across the three questionnaires. Interpretation In this exploratory analysis of CheckMate 141, nivolumab stabilised symptoms and functioning from baseline to weeks 9 and 15, whereas investigator's choice led to clinically meaningful deterioration. Nivolumab delayed time to deterioration of patient-reported quality-of-life outcomes compared with single-agent therapy of investigator's choice in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck. In view of the major unmet need in this population and the importance of maintaining or improving quality of life for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, these data support nivolumab as a new standard-of-care option in this setting. Funding Bristol-Myers Squibb.

Aims: In 2016, nivolumab and pembrolizumab were approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) following progression after initial platinum-based therapy. We sou...

To compare self-rated health among the United States general population in 2002 and 2017. 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). 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. 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.

In the present study, we examined real-world treatment patterns for squamous cell carcinoma of the head and neck (scchn) in Canada, which are largely unknown. Oncologists across Canada provided data for disease history, characteristics, and treatment patterns during May&ndash, July 2016 for 6&ndash, 8 consecutive patients receiving first-line or second-line drug treatment for scchn (including locally advanced and recurrent or metastatic disease). Information from 16 physicians for 109 patients receiving drug treatment for scchn was provided, 1 patient was excluded from the treatment-pattern analysis. Median age in the cohort was 63 years [interquartile range (iqr): 57&ndash, 68 years], and 24% were current smokers, with a mean exposure of 26.2 &plusmn, 12.7 pack&ndash, years. The most common tumour site was the oropharynx (48%). Most patients (84%) received platinum-based regimens as first-line treatment (44% received cisplatin monotherapy). Use of cetuximab-based regimens as first-line treatment was limited (17%). Of 53 patients receiving second-line treatment, 87% received a first-line platinum-based regimen. Median time between first-line treatment with a platinum-based regimen and initiation of second-line treatment was 55 days (iqr: 20&ndash, 146 days). The most common second-line regimen was cetuximab monotherapy (43%), platinum-based regimens were markedly infrequent (13%). Our analysis provides real-world insight into scchn clinical practice patterns in Canada, which could inform reimbursement decision-making. High use of platinum-based regimens in first-line drug treatment was generally reflective of treatment guidelines, cetuximab use in the second-line was higher than anticipated. Additional real-world studies are needed to understand the effect of novel therapies such as immuno-oncology agents on clinical practice and outcomes, particularly for recurrent or metastatic scchn.

Patients with recurrent or metastatic cancer commonly suffer from debilitating toxicity associated with conventional treatment modalities, as well as disease-related symptoms, often with a concomitant negative impact on health-related quality of life (HRQoL). Patient-reported outcomes (PROs) provide important insights into the patient experience in clinical trials. Nivolumab is a programmed death-1 receptor inhibitor that extends survival in patients with recurrent or metastatic disease in multiple tumor types. In this review, we summarize published PRO analyses from eight phase II-IV clinical trials with nivolumab for the treatment of melanoma, non-small cell lung cancer, renal cell carcinoma (RCC), and squamous cell carcinoma of the head and neck (SCCHN). Symptom burden, physical functioning, and HRQoL were measured using generic, cancer-specific, and tumor type-specific validated PRO instruments. Nivolumab showed sustained stabilization across all tumor types and, in some cases, clinically meaningful improvement in HRQoL, whereas standard of care therapies often led to deteriorations. Exploratory analyses found a positive correlation between baseline HRQoL scores and overall survival in RCC, and between baseline HRQoL scores and healthcare resource utilization in SCCHN, suggesting that patient-reported symptoms at treatment initiation may have clinical value. In the era of value-based oncology care, stakeholders are increasingly interested in PRO findings to guide clinical, regulatory, and reimbursement decisions. However, missing data remain a significant challenge in PRO analyses, including in nivolumab trials. Future clinical trials in immuno-oncology should incorporate PRO data collection, including beyond treatment discontinuation or trial completion to assess the long-term effects of treatment on HRQoL.

OBJECTIVE Children with JIA have long-term morbidity and require extensive parental assistance. This study aimed to evaluate the impact of having a child with JIA on parents' missed work time, which can lead to decreased work productivity. METHODS The Truven Health MarketScan Commercial Database (2000-9) was accessed to identify a cohort of parents having a child with newly diagnosed JIA. For comparison, a cohort of parents having no children with JIA was identified and matched with the preceding cohort. Parents' work absences were analysed using descriptive statistics and multivariable regression. Estimates were weighted to be generalizable to the US employer-sponsored insurance population. RESULTS The study identified 108 parents having a child with newly diagnosed JIA (mean age 42.5 years), representing an estimated 3335 (weighted) parents nationally. Most of them were from the South (45%), male (71%) and employed in the transportation and utilities industry (58%). The demographic characteristics of the control cohort of parents were generally similar. Children with JIA (mean age 10.6 years) represented an estimated 3528 cases nationally. The mean number of reported missed work-time hours was 281.81 (s.e. 40.50) in a 9 year period for parents having a child with JIA compared with other parents 183.36 (28.55). Work-time loss was significantly related to having a child with JIA, sex and geographical region of residence. Parents having a child with JIA were 2.78 times more likely to report work-time loss [odds ratio (OR) 2.78 (95% CI 1.47, 5.26)] than those having no children with JIA. CONCLUSION Parents having a child with JIA report significant work-time loss compared with parents with no children having JIA, particularly during the year following the child's diagnosis.

Objective: To assess the QoL reported by GBM patients and their caregivers METHODOLOGY: Real-world data were collected through a cross-sectional survey administered to physicians, patients, and caregivers in France, Germany, and the UK between May and July 2016. Physicians confirmed diagnosis and assessed patients as having progressed, being stable, or responding to treatment. Patient-reported outcomes (PROs) were measured using the 3-level EQ-5D as well as the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and brain cancer-specific module (QLQ-BN20). For patients who could not complete the EQ-5D, proxy assessments were obtained from caregivers. Summary statistics were reported and differences were assessed using pairwise t tests. Results: A total of 313 GBM patients completed the PRO measures, while 203 caregivers provided a proxy EQ-5D assessment. Patient QoL was poor as indicated by a mean (SD) EQ-5D index score of 0.51 (0.38). Significant differences were observed among patient groups defined according to progression. Those whose disease had progressed had a mean (SD) index score of 0.26 (0.38) compared with 0.53 (0.37 p

OBJECTIVE To assess the impact of rheumatoid arthritis (RA) on absence time, absence payments, and other health benefit costs from the perspective of US employers. METHODS Retrospective regression-controlled analysis of a database containing US employees' administrative health care and payroll data for those who were enrolled for at least 1 year in an employer-sponsored health insurance plan. RESULTS Employees with RA (N = 2705) had $4687 greater average annual medical and prescription drug costs (P < 0.0001) and $525 greater (P < 0.05) indirect costs (because of sick leave, short- and long-term disability, and workers' compensation absences) than controls (N = 338,035). Compared with controls, the employees with RA used an additional 3.58 annual absence days, including 1.2 more sick leave and 1.91 more short-term disability days (both P < 0.0001). CONCLUSION Employees with RA have greater costs across all benefits than employees without RA.

Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition.In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life.The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group.Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636 .).

Objectives. We examined the effects of 2 worksite health-promotion interventions (compared with a health-education control) on older workers’ healthy behaviors and health outcomes. Methods. We conducted a prospective, randomized controlled trial with 423 participants aged 40 years and older. Participants were categorized into 3 study arms: the COACH intervention combined Web-based risk assessments with personal coaching support, the RealAge intervention used a Web-based risk assessment and behavior-specific modules, and a control group received printed health-promotion materials. Participants were assessed at baseline, 6 months, and 12 months. Random-effects modeling controlled for baseline stage of change for all behaviors of interest in all groups. Results. At 6 and 12 months, COACH participants showed significantly increased fruit and vegetable consumption (P = .026; P < .001) and participation in physical activity (P = .05; P = .013), and at 12 months they showed decreased percentage of energy from fat (P = .027). RealAge participants showed significantly decreased waist circumference at 6 and 12 months (P = .05; P = .018). Conclusions. COACH participants were twice as likely to use the COACH intervention as RealAge participants were to use the RealAge intervention. COACH participants experienced twice the number of positive outcomes that control participants experienced.

Introduction Although the Sexual Encounter Profile (SEP) and International Index of Erectile Function (IIEF) are frequently used to measure erectile dysfunction (ED) treatment outcomes, stopwatch-assessed duration of erection is a new, objective, and potentially useful endpoint of ED treatment effect. Aims To assess the validity and reliability of stopwatch-assessed erection duration against responses to SEP items 2 (SEP-2) and 3 (SEP-3) and IIEF scale scores. Methods Data were taken from a multi-center trial of vardenafil for the treatment of ED. Patients were randomized to vardenafil 10 mg or placebo for 4 weeks. After a 1-week washout period, patients received the alternate therapy for an additional 4 weeks. An electronic diary was used to record information about sexual attempts. The duration of erection was measured using a stopwatch and transcribed into the diary. The SEP was completed following each sexual attempt, and the IIEF was completed at the end of each treatment period. Main Outcome Measures Mean and median values of erection duration, mean SEP-2 and SEP-3 success rates, and scores for each of the 5 IIEF scales were calculated. Results At baseline, correlations of median erection duration with the 5 IIEF scale scores ranged from 0.06 to 0.53, while correlations with mean SEP-2 and SEP-3 success rates were 0.66 and 0.49, respectively. Compared with the other measures, mean and median values of erection duration were less sensitive to differences between placebo- and vardenafil-treated patients and less responsive to clinical change associated with treatment crossover. However, mean erection duration exhibited a good level of reliability (intraclass correlation coefficient=0.72, P Conclusions This study provides evidence for the validity and reliability of stopwatch-assessed duration of erection. Our findings suggest that erection duration is suitable for use as a unique endpoint in ED treatment-efficacy trials conducted for phosphodiesterase type 5 inhibitors.

(Headache 2010;50:63-70) Objective.— To assess the characteristics of patients receiving botulinum toxin type A (BoNTA; BOTOX®) in the treatment of headache (HA) disorders. Methods.— The following observational epidemiologic data and baseline patient characteristics were prospectively collected from eligible patients treated with BoNTA at 10 US HA specialty centers: demographics; HA diagnoses and characteristics (frequency, severity, and disability); prior and current HA treatments and response; clinical response to BoNTA; Migraine Disability Assessment (MIDAS) questionnaire; and adverse events. Patients maintained a daily HA diary and were evaluated at each follow-up visit. Results.— Of 703 patients enrolled (mean age 43.1 years, 78.5% females, 95.4% white), nearly 66% had a diagnosis of chronic migraine (CM), with or without medication overuse. Approximately 75% had severe disability (MIDAS grade IV), and the mean pain rating was 6.5 (where 0 = no pain, 10 = pain as bad as it can be). More than 90% of patients had ≥1 prophylactic HA treatment failure; median number of failures was 4. Significant association was observed between HA frequency and MIDAS grade (P

Objective We examined differences in preferences for the EQ-5D health states among blacks, Hispanics, and others living in the United States. Study Design and Setting A multi-stage probability sample was selected from the adult U.S. population. Each respondent valued a subset of the 243 EQ-5D health states. Regression analysis was used to analyze differences in mean valuations for 13 health states among the racial/ethnic groups. First, we compared unadjusted mean valuations among the three groups. Second, we evaluated differences in mean valuations among the groups after adjusting for other sociodemographic characteristics. Third, we evaluated the impact of race/ethnicity on estimates derived from the U.S. health state valuation (i.e., D1) model. Results Valuations differed among the groups for seven of the 13 health states, and these differences persisted after adjusting for other sociodemographic factors. Blacks appeared to perceive extreme health problems to be associated with less disutility than did members of the other two groups. Conclusion Within the United States, there exist racial/ethnic differences in the perceived desirability of the EQ-5D health states that cannot be readily explained by socioeconomic disparities.

≥Ying Zhang,1 Trong Kim Le,1 James W Shaw,2 Srividya Kotapati31Center for Observational Research and Data Sciences, Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Hopewell, NJ, USA; 2Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Princeton, NJ, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Wallingford Center, CT, USABackground: This study examines real-world drug utilization patterns, health care resource use, and costs among patients receiving adjuvant treatment with IFN versus patients receiving no treatment ("observation") for malignant melanoma following surgery.Methods: A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan®) to identify all adjuvant melanoma patients (aged ≥18 years) diagnosed between June 2007 and June 2011 who had a lymph node dissection (ie, index surgery) and were treated with IFN or subsequently observed. Health care resource use and costs of services were converted to 2012 US dollars and were evaluated and compared using multivariable regression.Results: Of 1,999 eligible subjects with melanoma surgery claims, 179 (9.0%) were treated with IFN and 1,820 (91.0%) were observed. The median duration (days) and number of doses of IFN therapy were 73 and 36, respectively. Among IFN-treated patients, only 10.6% completed ≥80% of maintenance therapy. The total average cost for patients treated with IFN was US$60,755±$3,972 (n=179); significantly higher than for patients undergoing observation ($31,641±$2,471; P

1. IntroductionThis study is concerned with understanding the determinants of life expectancy in developed countries. The level (and variability) of life expectancy has important implications for individual and aggregate human behavior; it affects fertility behavior, economic growth, human capital investment, intergenerational transfers, and incentives for pension benefit claims (Zhang, Zhang, and Lee 2001; Coile et al. 2002). From the social planners perspective, it has implications for public finance. For example, Gradstein and Kaganovich (2004) conclude that increasing longevity results in increasing public funding of education and economic growth. Cremer, Lozachmeur, and Pestieau (2004, p. 2260) argue that early retirement "puts pressure on the financing of healthcare and pension schemes [and this pressure] is made worse by growing longevity." While typically assumed strictly exogenous for the purpose of policy analysis, it has been argued that life expectancy (or more broadly "health") is predetermined by behavioral and policy variables in what can be loosely described as a production function for health. Estimating this function is the goal of this study.Auster, Leveson, and Sarachek (1969) were the first economists to study a population production function for health: a regression of state-level mortality rates on medical care and environmental variables. Today their research motivations and questions remain compelling. Indeed, given the size and rapid growth of health care-related industries and recent public interest in containing medical and insurance costs, it could be argued that understanding the socioeconomic determinants of societal health is more important today than ever. Moreover, issues concerning the government's role in sponsoring basic medical and pharmaceutical research; in regulating drug, alcohol, and tobacco consumption; and in promoting healthy lifestyles are all particularly newsworthy. The research questions related to public health are obvious. If societal health can be measured as life expectancy or mortality rates, what are the various socioeconomic factors that increase or decrease it? Can the marginal effects of these factors be disentangled? If so, which of these factors produces the largest health benefits (or costs) to society? These questions are as important now as when first posed by Auster, Leveson, and Sarachek in 1969.Since Auster, Leveson, and Sarachek, several economic studies have attempted to answer these questions using data from the United States or multiple countries.1 Many of these have used aggregate data from the member countries of the OECD to explain cross-country mortality rates or life expectancies.2 While the empirical results are mixed, the general consensus is that population life expectancy (or mortality) is a function of environmental measures (e.g., wealth, education, safety regulation, infrastructure), lifestyle measures (e.g., tobacco or alcohol consumption), and health care consumption measures (e.g., medical or pharmaceutical expenditures). However, the appropriate econometric methodology for disentangling these effects and its meaning for the relative importance (statistical or economic) of the estimated effects is more contentious.These methodological issues are most vividly illustrated in the few studies that have focused on pharmaceutical expenditures as a separate input to life expectancy. These include Peltzman (1987), Babazono and Hillman (1994), Lichtenberg (1996, 1998), Frech and Miller (1999), and Miller and Frech (2000). For example, Peltzman (1987) examined the effects of wealth and prescription drug laws on infectious disease mortality and on poisoning mortality across middle-income countries in a generalized least squares (GLS) framework. He found that wealth variables significantly decreased both disease and poisoning mortality rates, while prescription drug laws had a significant and positive effect on poisoning mortality only. …

Background: Responses in patients (pts) treated with immune checkpoint inhibitors may occur after initial evidence of radiological disease progression. In CheckMate 141, a randomized phase 3 study of nivolumab (nivo) vs investigator’s choice (IC) of standard single-agent therapy in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN), nivo demonstrated prolonged OS compared with IC therapy, hazard ratio = 0.70 (97.73% confidence interval [CI]: 0.51, 0.96). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 13.1% of nivo-treated pts and 35.1% of IC-treated pts. Patient-reported quality of life was stable with nivo and worsened with IC therapy. Here we assessed safety and efficacy in pts treated beyond progression (TBP) with nivo in CheckMate 141. Methods: Treatment beyond investigator-assessed RECIST 1.1-defined progression was permitted in pts in the nivo arm if all criteria prespecified in the protocol were met. Otherwise, pts were not treated beyond progression and discontinued treatment after first progression. Pts without progression, or those who died or discontinued without a tumor assessment to determine progression, were excluded from this analysis. Results: Of the 240 pts randomized to nivo, 139 (58%) experienced RECIST-defined disease progression. Among these pts, 57 (41%) received ≥1 subsequent dose of nivo after progression (TBP group), and 82 (59%) were not treated beyond progression (NTBP group). The mean duration of treatment beyond progression was 2.0 months (range: 0, 9). Median OS was 12.7 months (95% CI: 9.7, not reached) in the TBP group and 6.1 months (95% CI: 4.8, 7.8) in the NTBP group. The objective response rate from randomization to initial progression was 12.3% and 4.9% for the TBP and NTBP groups, respectively; 31.6% and 19.5% of pts, respectively, had stable disease. After initial progression, 13 pts (23%) in the TBP group had tumor burden reduction, with >30% reduction in 2 pts. Of these 13 pts, 7 were HPV+, 3 were PD-L1+, and 4 had ≥20% tumor size increase at first progression. In the TBP and NTBP groups, select TRAEs were similar, with a higher frequency of skin/subcutaneous tissue disorders in the TBP group (29.8% and 11.0%; none were grade 3-4). Select endocrine TRAEs occurred in 10.5% (TBP) and 8.5% (NTBP) of pts; none were grade 3-4. Grade 3-4 TRAEs occurred in 12.3% and 13.4% of pts in the TBP and NTBP groups, respectively. Patient-reported quality of life from randomization through week 21 was generally stable in the TBP group, consistent with trends observed in the overall nivo-treated population. Additional analyses to further characterize TBP and NTBP pts will be presented. Conclusions: These results suggest that nivo treatment beyond RECIST-defined disease progression was tolerable in R/M SCCHN, with some pts experiencing tumor reduction after initial progression. Citation Format: Robert Haddad, Robert L. Ferris, George Blumenschein, Jerome Fayette, Joel Guigay, Alexander D. Colevas, Lisa Licitra, Stefan Kasper, Everett E. Vokes, Francis Worden, Nabil F. Saba, Makoto Tahara, Manish Monga, Mark Lynch, Jin Zhu, James W. Shaw, Maura L. Gillison, Kevin Harrington. Treatment beyond progression with nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck in the phase 3 Checkmate 141 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT157. doi:10.1158/1538-7445.AM2017-CT157

Background: There is an existing unmet need in glioblastoma multiforme (GBM) due lack of effective treatment options. To understand the treatment landscape as newer agents are in development, it was the objective of this study to gain a better understanding of the current treatment of second line (2L) GBM therapy with related outcomes in a “real-world” setting in Canada, France and Germany. Methods: A retrospective, chart-review study was conducted in each country; 72 oncologists were recruited to contribute patients ≥18 years of age, newly diagnosed with GBM between January 1, 2013 - June 30, 2015 with a minimum of 12 months follow-up or until death. Excluded were those treated with investigational agents. Patients were followed through August 2016. Enrollment was in 2 cohorts, Cohort 1 comprising a random selection of 337 patients irrespective of line of the therapy (LOT). Cohort 2 included 136 patients who received more than one LOT for a total N = 473 (146 each in France and Germany, and 181 in Canada). Demographics and treatment data were analyzed descriptively. Survival was determined using Kaplan-Meier analysis censoring for date of chart abstraction in surviving patients. Results: Patients were 61% male with mean (SD) age of 61.4 (12.0) years at initial diagnosis. Overall, most patients (92%) were treated 1L with temozolomide (TMZ) monotherap and 88% received radiation. In the 337 patient random sample, 97 (29%) received 2L treatment. A total of 233 patients in both cohorts were analyzed for 2L treatment and outcomes. Of all 2L-treated patients the majority were Eastern Cooperative Oncology Group (ECOG) performance grade 1 (38%) or 2 (49%) at the time of 2L start. In 2L, 27% were retreated with TMZ monotherapy, 7% received TMZ in combination with other agents, 40% received bevacizumab either as monotherapy 22%, or combination therapy (18%). In all patients receiving a 2L therapy, complete response following 2L was achieved by 5%, 23% partial response and 29%, stable disease. Median overall survival from start of 2L was 7.5 months (95% CI 6.5 – 8.5) in all patients, (7.0 [95% CI 6–8.1] in France; 6.0 [95% CI 4.5–7.4] in Germany; 10.5 [95% CI 8.6–12.5] in Canada). Conclusions: Most GBM patients received TMZ during 1L and bevacizumab monotherapy or combination therapy during 2L treatment with some regional differences. Survival following initiation of 2L treatment was poor. Prognosis remains grim under current treatment paradigms.

Objectives: To understand real-world utilization of treatments for GBM. METHODOLOGY: Real-world data were collected through a cross-sectional survey administered to physicians in Canada, France, Germany, and the UK between May and July 2016. Physicians provided data for eight consecutive patients receiving treatment for GBM regarding disease history, characteristics, and treatment patterns. Summary statistics were reported and differences assessed using chi-square tests. Results: A total of 161 physicians (Canada, 29; France, 52; Germany, 50; and UK, 30) provided information for 1,235 GBM patients (Canada, 195; France, 400; Germany, 400; and UK, 240). Nearly half (45%) of all patients presented with stable disease, while 28% were classified as progressing and the remaining 28% as responding to treatment. Forty-five percent of patients had experienced a recurrence. Methylation status was evaluated in 70% of patients with 59% of these showing gene promoter methylation. Approximately two-thirds (67%) of patients had undergone surgery of whom 88% had been operated on prior to initiation of drug treatment. More than three-quarters of patients had received treatment with radiotherapy Ninety percent of patients received first-line treatment with temozolomide (TMZ), while the remainder were treated with bevacizumab (BEV) (5%); a procarbazine, lomustine, and vincristine (PCV) regimen (4%); or irinotecan (IRI) (1%). 613 patients received second-line therapy of whom 36% were treated with BEV (alone or in regimen), 22% with TMZ or PCV, and 13% with IRI. BEV use varied among countries with a prevalence of 49% in France, 38% in Germany, 35% in Canada, and 10% in the UK (p

155 Background: The Pt-Reported Outcomes Version of the Common Terminology Criteria for AE (PRO-CTCAE) was developed for pts to report on the frequency, severity, and interference of SymAE. A study was conducted to identify a hepatocellular carcinoma (HCC)-relevant subset of the PRO-CTCAE's 124 items to enhance evaluation of SymAE in HCC trials and long-term effects in survivorship. Methods: Qualitative and quantitative data were collected from medical oncologists specializing in HCC and pts diagnosed with HCC stratified by Child-Pugh class and treatment. Oncologists were asked about HCC diagnosis, treatment, and SymAE and provided ratings (ranging from 0 = unimportant to 10 = very important) of the following: 1) importance to pts of 34 prevalent SymAE from past HCC trials (all phases); 2) importance to pts of each PRO-CTCAE item; and 3) their own perceived importance of each PRO-CTCAE item with regard to tolerability. Pts were asked about their diagnosis, treatment, and experience of SymAE after which they completed the PRO-CTCAE and were debriefed on the importance of each item. Results: Four medical oncologists from Spain, Taiwan, Korea, and Hong Kong with ≥ 20 years of experience completed interviews. SymAE from prior trials rated highly important to pts (mean rating across oncologists ≥ 7) included hand-foot syndrome, diarrhea, fatigue, decreased appetite, rash, vomiting, and weight loss. PRO-CTCAE items rated highly important to pts included diarrhea, vomiting, shivering or shaking chills, hand-foot syndrome, rash, fatigue, difficulty swallowing, and loss of control of bowel movements. Items rated highly for tolerability included diarrhea, shivering or shaking chills, and hand-foot syndrome. Pt interviews (planned up to 24) are ongoing. Conclusions: Oncologists identified 10 clinically relevant items from sponsor SymAE data and the PRO-CTCAE for use in HCC trials. Findings from pt interviews will compare provider and pt perspectives about SymAE and strengthen the set of selected items. Combining clinician and pt ratings with clinical trial data may be a promising method for identifying cancer-specific PRO-CTCAE item sets for use throughout the cancer care continuum.

Background: In the last decade, a number of studies have documented the economic impact of migraine headaches on society. Although previous research has shown that patients with migraine headache consume a greater amount of health care resources than those without migraine, the economic impact of this condition on a Medicaid population has not been assessed. Objective: The purpose of this study was to compare the health care resource utilization of patients with and without migraine headache in the Idaho Medicaid population. Methods: Idaho Medicaid claims from 1998 were reviewed to identify cases and controls. Four controls, matched for age, sex, race, and residence, were obtained for each case. Physician services, hospital services, emergency room services, and prescription use were compared between the 2 groups. Multivariate analyses were performed to determine differences between the 2 groups after controlling for potential confounders. Results: Eighty percent of the cases were female, and 94% of the patients were white. Patients with migraine headache had statistically significantly higher health care resource consumption than matched controls (P < 0.05). Total log costs for prescription use, physician services, and hospital services were significantly higher (P < 0.001) in the migraine group even after controlling for migraine-associated comorbid conditions and demographic variables. Conclusions: Total health care costs for migraine patients were 1.6 times higher than for matched controls. The results of this study suggest that migraine is a significant economic burden to the Medicaid program.

OBJECTIVE: To evaluate the effect of a closed formulary on pharmaceutical utilization and expenditures in a noncontinuously eligible population. DESIGN: A pretest-posttest design was used to compare changes in pharmaceutical utilization and expenditures between the formulary and a nonformulary group in the nine months before formulary implementation and the nine months after. SETTING: Two government employer plans in the eastern United States. PARTICIPANTS: Noncontinuously eligible individual plan members were included in the study if they had been enrolled in their plan for at least one month in both the pre- and the post periods. MAIN OUTCOME MEASURES: Mean pharmaceutical utilization and expenditures per member per month (PM PM). RESULTS: Formulary cases (n=1,542) were matched on age and baseline pharmaceutical utilization with controls who were not in a formulary group plan. These cases had a higher generic fill rate, lower mean total claims PMPM, and lower mean brand claims PMPM in the post-period, co...

Background: Patients (pts) with platinum-refractory R/M SCCHN have an extremely poor prognosis and no chemotherapy (CT) options to extend survival. Nivo, a fully human anti-programmed death-1 monoclonal antibody, is FDA-approved and improves survival in other tumor types. Methods: A randomized, open-label, phase 3 trial (NCT02105636) assigned pts (stratified by prior cetuximab) with SCCHN who progressed within 6 mo of platinum-based CT in a 2:1 ratio to nivo 3 mg/kg Q2W or weekly single-agent IC (methotrexate 40-60 mg/m2, docetaxel 30-40 mg/m2, or cetuximab 400-mg/m2 loading dose followed by 250 mg/m2 weekly). Pts must not have received systemic therapy subsequent to biopsy and prior to screening. Pts could receive nivo beyond disease progression if there was evidence of clinical benefit. The primary endpoint was OS. Secondary endpoints were PFS and objective response rate (ORR) by RECIST 1.1. Additional endpoints included safety and outcomes by PD-L1 and HPV (p16 IHC) status. An interim analysis (IA) was planned after at least 195 deaths. Results: Of 361 randomized pts, median age was 60.0 yr, 76.5% were current/former smokers, 54.8% had received ?2 prior lines of CT, 91.4% had prior radiotherapy, and 98.3% had ECOG score ?1. At IA, 133 of 240 pts (55.4%) on nivo and 85 of 121 pts (70.2%) on IC had died. Nivo-treated pts had a 30% reduction in risk of death (HR, 0.70; 97.73% CI, 0.51-0.96; P = 0.010); median OS was 7.5 mo (95% CI, 5.5-9.1) with nivo vs 5.1 mo (95% CI, 4.0-6.0) with IC. Tumor PD-L1 status was evaluable in 260 pts (72.0%). Median OS in pts with PD-L1 ?1% was 8.7 mo with nivo vs 4.6 mo with IC (HR, 0.55; 95% CI, 0.36-0.83) and, in pts with PD-L1 Conclusions: Nivo improved OS in pts with platinum-refractory R/M SCCHN compared to single-agent IC therapy. Pts with PD-L1 ?1% and HPV+ pts had significantly longer median OS with nivo than with IC, but nivo was effective regardless of PD-L1 or HPV status. As the first immunotherapy agent to increase survival in a randomized phase 3 study in R/M SCCHN, nivo is a new standard of care option for these pts. Citation Format: Maura L. Gillison, George Blumenschein, Jérôme Fayette, Joel Guigay, A. Dimitrios Colevas, Lisa Licitra, Kevin Harrington, Stefan Kasper, Everett E. Vokes, Caroline Even, Francis Worden, Nabil F. Saba, Lara Carmen Iglesias Docampo, Robert Haddad, Tamara Rordorf, Naomi Kiyota, Makoto Tahara, Manish Monga, Mark Lynch, William J. Geese, Mark Schactman, Justin Kopit, James W. Shaw, Robert L. Ferris. Nivolumab (nivo) vs investigator's choice (IC) for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): CheckMate-141. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT099.

TPS4147Background: HCC is the fifth most prevalent cancer globally and the second-leading cause of cancer-related deaths. The high mortality rate is typically due to the late stage of disease at di...

6009Background: Patients (pts) with R/M SCCHN have poor prognosis, and median OS for pts with platinum-refractory disease is ≤6 mo. We investigated if nivo, a fully human IgG4 anti-PD-1 mAb improve...

Alzheimer’s disease (AD) is the most common form of dementia among the elderly with women exhibiting a higher risk than men for the disease. Due to these gender differences, there is great interest in the role that estrogens play in cognitive impairment and the onset of the classic amyloid and tau lesions in AD. Human and rodent studies indicate a strong association between low brain aromatase, sex hormone levels, and beta amyloid deposition. Therefore, the effects of depleting both circulating and brain estrogen levels, through gonadectomy and/or treatment with the aromatase inhibitor, anastrozole, upon hippocampal AD-like pathology in male and female 3xTgAD mice were evaluated. Liquid chromatography-mass spectrometry revealed anastrozole serum levels of 10.19 ng/mL and for the first time brain levels were detected at 4.7 pg/mL. Densitometric analysis of the hippocampus revealed that anastrozole significantly increased Aβ1-40/42- but not APP/Aβ-immunoreactivity in intact 3xTgAD females compared to controls (p < 0.001). Moreover, anastrozole significantly increased the number of Aβ1-40/42- compared to APP/Aβ-positive hippocampal CA1 neurons in intact and gonadectomized female mice. Concurrently, anastrozole significantly reduced the APP/Aβ plaque load in 9 months old female 3xTgAD mice. These data suggest that anastrozole treatment differentially affects select amyloid species which in turn may play a role in the extraneuronal to intraneuronal deposition of this peptide.

Background Evaluation of acute rhinosinusitis treatment effectiveness is based on patient-reported relief of symptoms. This study was designed to develop a multiattribute utility scoring algorithm for the Major Symptom Score (MSS) and secondarily to evaluate the psychometric characteristics (i.e., validity and responsiveness) of the MSS Utility Index (MSSUI). Methods Adult patients with acute rhinosinusitis were recruited for this longitudinal observational study through primary care and specialist physician offices. One hundred ninety patients participated in a preference elicitation exercise for MSS health states. Resulting preference data were used to generate a utility scoring algorithm for the MSS. Participants completed the MSS and 20-Question Sino-Nasal Outcome Test (SNOT-20) at baseline and completed the MSS twice daily for 15 days via daily diary. On days 7 and 15, participants completed the MSS, SNOT-20, and Overall Treatment Effect scale and were evaluated by physicians via the Physician Global Improvement Scale (PGIS). Results At baseline, the mean ± SD. MSSUI score was 0.51 ± 0.17 and was negatively correlated with SNOT-20 scores (r = -0.58; p < 0.001). Days 2–8 average MSSUI scores were negatively correlated with day 7 SNOT-20 (r = -0.46; p < 0.001) and PGIS (r = -0.22; p < 0.001) scores; whereas days 9-15 average MSSUI scores were inversely related to day 15 SNOT-20 (r = -0.40; p < 0.001) and PGIS (r = -0.32, p < 0.001) scores. Mean MSSUI scores improved from baseline with effect sizes at days 7 and 15 of 0.82 and 1.20, respectively. Conclusion The MSSUI represents an acceptable and psychometrically sound patient-reported end point for clinical trials comparing treatments for acute rhinosinusitis.