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Background: There are no established methods for pancreatic cancer (PAC) screening, but the NCI and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in patients with new-onset diabetes (NOD), a group with elevated PAC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) risk model validation study, we assessed the potential value of CT screening for PAC in those determined to be at elevated risk, as is being done in a planned PanCAN Early Detection Initiative trial. Methods: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of PAC screening in patients aged ≥50 years with NOD using CT imaging versus no screening. PAC prevalence, sensitivity, and specificity were derived from the END-PAC validation study. PAC stage distribution in the no-screening strategy and PAC survival were derived from the SEER program. Background mortality for patients with diabetes, screening and cancer care expenditure, and health state utilities were derived from the literature. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2020 US dollars, and we took a limited US healthcare perspective. Results: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $293 in additional expenditures for a cost per QALY gained of $65,076. In probabilistic analyses, screening resulted in a cost per QALY gained of 25% of screen-detected PAC cases needed to be resectable for the cost per QALY gained with screening to be Conclusions: We found that risk-based PAC screening in patients with NOD is likely to be cost-effective in the United States if even a modest fraction (>25%) of screen-detected patients with PAC are resectable. Future studies should reassess the value of this intervention once clinical trial data become available.

PURPOSE: Biomarker-driven master protocols represent a new paradigm in oncology clinical trials, but their complex designs and wide-ranging genomic results returned can be difficult to communicate to participants. The objective of this pilot study was to evaluate patient knowledge and expectations related to return of genomic results in the Lung Cancer Master Protocol (Lung-MAP). METHODS: Eligible participants with previously treated advanced non–small-cell lung cancer were recruited from patients enrolled in Lung-MAP. Participants completed a 38-item telephone survey ≤ 30 days from Lung-MAP consent. The survey assessed understanding about the benefits and risks of Lung-MAP participation and knowledge of the potential uses of somatic testing results returned. Descriptive statistics and odds ratios for associations between demographic factors and correct responses to survey items were assessed. RESULTS: From August 1, 2017, to June 30, 2019, we recruited 207 participants with a median age of 67, 57.3% male, and 94.2% White. Most participants “strongly/somewhat agreed” with statements that they “received enough information to understand” Lung-MAP benefits (82.6%) and risks (69.5%). In items asking about potential uses of Lung-MAP genomic results, 87.0% correctly indicated that the results help to select cancer treatment, but < 20% correctly indicated that the results are not used to confirm cancer diagnosis, would not reveal risk of developing diseases besides cancer, and would not indicate if family members had increased cancer risk. There were no associations between sociodemographic factors and proportions providing correct responses. CONCLUSION: In a large National Clinical Trials Network biomarker-driven master protocol, most participants demonstrated incorrect knowledge and expectations about the uses of genomic results provided in the study despite most indicating that they had enough information to understand benefits and risks.

Novel interventions for sickle cell disease (SCD) bring hope to patients, yet concern about the associated economic costs exists. Cost-effectiveness analysis (CEA) uses standardized methods, with robust underpinnings in health economics, to estimate the value of these interventions compared with usual care. However, because of the complexity and lifetime trajectory of SCD, CEAs are challenging to conduct. The objectives of this rapid review were to summarize the main characteristics, components, and results of published CEAs of existing interventions for SCD, identify research gaps, and provide directions for future analyses. We identified records through searches of bibliographic databases, from reference lists of relevant review articles, and through consultation with experts. A total of 13 CEAs met our inclusion criteria and were qualitatively synthesized. These evaluated blood transfusions (n = 2), hematopoietic stem cell transplantation (n = 1), pharmaceuticals (n = 2), hypothetical cell or genetic therapy (n = 1), screening programs (n = 4), and interventions for SCD treatment complications (n = 3). A limited number of potential SCD and treatment complications were evaluated. No study adopted a societal perspective in the base case, six studies examined lifetime cost-effectiveness, seven studies employed a Markov or discrete-event simulation model, and eight studies used an outcome metric that captured both quality and length of life. To better compare the value of emerging and current therapies, future CEAs should adopt a societal perspective incorporating both medical and nonmedical costs, comprehensively model SCD complexity using robust health economic simulation models over the patient’s entire lifespan, and capture the intervention’s effect on both survival and quality of life.

Background: Graft placement is a modifiable and often discussed surgical factor in anterior cruciate ligament (ACL) reconstruction (ACLR). However, the sensitivity of functional knee mechanics to variability in graft placement is not well understood. Purpose: To (1) investigate the relationship of ACL graft tunnel location and graft angle with tibiofemoral kinematics in patients with ACLR, (2) compare experimentally measured relationships with those observed with a computational model to assess the predictive capabilities of the model, and (3) use the computational model to determine the effect of varying ACL graft tunnel placement on tibiofemoral joint mechanics during walking. Study Design: Controlled laboratory study. Methods: Eighteen participants who had undergone ACLR were tested. Bilateral ACL footprint location and graft angle were assessed using magnetic resonance imaging (MRI). Bilateral knee laxity was assessed at the completion of rehabilitation. Dynamic MRI was used to measure tibiofemoral kinematics and cartilage contact during active knee flexion-extension. Additionally, a total of 500 virtual ACLR models were created from a nominal computational knee model by varying ACL footprint locations, graft stiffness, and initial tension. Laxity tests, active knee extension, and walking were simulated with each virtual ACLR model. Linear regressions were performed between internal knee mechanics and ACL graft tunnel locations and angles for the patients with ACLR and the virtual ACLR models. Results: Static and dynamic MRI revealed that a more vertical graft in the sagittal plane was significantly related ( P < .05) to a greater laxity compliance index ( R2 = 0.40) and greater anterior tibial translation and internal tibial rotation during active knee extension ( R2 = 0.22 and 0.23, respectively). Similarly, knee extension simulations with the virtual ACLR models revealed that a more vertical graft led to greater laxity compliance index, anterior translation, and internal rotation ( R2 = 0.56, 0.26, and 0.13). These effects extended to simulations of walking, with a more vertical ACL graft inducing greater anterior tibial translation, ACL loading, and posterior migration of contact on the tibial plateaus. Conclusion: This study provides clinical evidence from patients who underwent ACLR and from complementary modeling that functional postoperative knee mechanics are sensitive to graft tunnel locations and graft angle. Of the factors studied, the sagittal angle of the ACL was particularly influential on knee mechanics. Clinical Relevance: Early-onset osteoarthritis from altered cartilage loading after ACLR is common. This study shows that postoperative cartilage loading is sensitive to graft angle. Therefore, variability in graft tunnel placement resulting in small deviations from the anatomic ACL angle might contribute to the elevated risk of osteoarthritis after ACLR.

BACKGROUND: Larotrectinib and entrectinib are FDA-approved therapies for patients with non-small cell lung cancer (NSCLC) with neurotrophic receptor tyrosine kinase gene fusion (TRK fusion-positive...

Aims Evidence is sparse on the long-term outcomes of continent cutaneous ileocecocystoplasty (CCIC). We hypothesized that obesity, laparoscopic/robotic approach, and concomitant surgeries would affect morbidity after CCIC and aimed to evaluate the outcomes of CCIC in adults in a multicenter contemporary study. Methods We retrospectively reviewed the charts of adult patients from sites in the Neurogenic Bladder Research Group undergoing CCIC (2007-2017) who had at least 6 months of follow-up. We evaluated patient demographics, surgical details, 90-day complications, and follow-up surgeries. the Mann-Whitney U test was used to compare continuous variables and χ² and Fisher's Exact tests were used to compare categorical variables. Results We included 114 patients with a median age of 41 years. The median postoperative length of stay was 8 days. At 3 months postoperatively, major complications occurred in 18 (15.8%), and 24 patients (21.1%) were readmitted. During a median follow-up of 40 months, 48 patients (42.1%) underwent 80 additional related surgeries. Twenty-three patients (20.2%) underwent at least one channel revision, most often due to obstruction (15, 13.2%) or incontinence (4, 3.5%). Of the channel revisions, 10 (8.8%) were major and 14 (12.3%) were minor. Eleven patients (9.6%) abandoned the catheterizable channel during the follow-up period. Obesity and laparoscopic/robotic surgical approach did not affect outcomes, though concomitant surgery was associated with a higher rate of follow-up surgeries. Conclusions In this contemporary multicenter series evaluating CCIC, we found that the short-term major complication rate was low, but many patients require follow-up surgeries, mostly related to the catheterizable channel.

In the United States the increasing number of Food and Drug Administration (FDA)-approved, innovative, and potentially effective commercial cancer therapies pose a significant financial burden on public and private payers. Chimeric antigen receptor (CAR) T cells are prototypical of this challenge. In 2017 and 2018, tisagenlecleucel (Kymriah, Novartis) and axicabtagene ciloleucel (Yescarta, Kite) were approved by the FDA for use after showing groundbreaking results in relapsed/refractory B-cell malignancies. In 2020 and 2021, four further submissions to the FDA are expected for CAR T-cell therapies for indolent and aggressive B-cell malignancies and plasma cell myeloma. Yet, with marketed prices of over $350,000 per infusion for the two FDA-approved therapies and similar price tags expected for the coming products, serious concerns are raised over value and affordability. In this review we summarize recent, peer-reviewed cost-effectiveness studies of tisagenlecleucel and axicabtagene ciloleucel in the United States; discuss key issues concerning the health plan budget impact of CAR T-cell therapy; and review policy, payment and scientific approaches that may improve the value and affordability of CAR T-cell therapy.

Cross-sectional survey of the Neurogenic Bladder Research Group (NBRG) registry; a multicenter prospective observation study. To assess how patient-reported urinary tract infections (PRUTIs) in spinal cord injury (SCI) affect quality of life (QOL). Multiple United States hospitals. 1479 participants with SCI were asked about neurogenic bladder-related QOL. Eligibility: age ≥ 18 years with acquired SCI. PRUTI frequency over the last year was classified as 0, 1–3, 4–6, or >6. Four UTI QOL domains were assessed: (1) UTIs limited daily activities, (2) UTIs caused increased muscle spasms, (3) UTIs would not go away, and (4) UTIs made me avoid going out. Multivariable regression identified variables associated with poor QOL. PRUTI frequency was 0 in 388 patients (26%), 1–3 in 677 (46%), 4–6 in 223 (15%), and more than 6 in 190 (13%). Increasing PRUTI rate was independently associated with worse QOL for all four questions. Compared with those with 0 PRUTIs, participants reporting >6 were more likely to limit daily activities (OR 9.0 [95% CI 8.1–21.2] p

Introduction The aim of this study was to survey pediatric urology fellowship directors (PFD) and adult reconstruction fellowship directors (AFD) to assess who they believe has sufficient training to care for adults with congenital urologic conditions (ACUC). Material and methods An online survey was created to assess attitudes towards specific training to care for ACUC. The survey was administered to 27 PFD and 26 AFD [16 from genitourinary reconstructive surgery (GURS) and 10 from female pelvic medicine and reconstructive surgery (FPMRS)]. Both groups were asked if specific training is warranted, and if general urologists, pediatric urologists or adult reconstructive urologists were sufficiently trained to care for ACUC. Results A total of 26 (96%) PFD and 10 (39%) AFD completed the survey. All PFD were fellowship trained in pediatrics. Of the AFD, 5 were GURS trained, 4 were FPMRS trained and 1 was not fellowship trained. The majority (65% PFD, 90% AFD) believed specific training is warranted. Few believed general urologists have sufficient training (8% PFD, 20% AFD). Most PFD believed pediatric urologists have sufficient training (85%), but a minority believed those with adult reconstructive training do (40%). Conversely, a minority of AFD believed that pediatric urologists have sufficient training (40%), while those with adult reconstructive training do (FPMRS: 67%, GURS: 60%). Conclusions Both pediatric and adult reconstructive urologists believe specific training to care for adults with congenital urologic conditions is warranted. Neither group considers the other to be ideally suited to care for this complex patient group. This suggests both groups may have something to learn from each other.

BACKGROUND: There remains debate over the best invasive diagnostic modality for mediastinal nodal evaluation. Prior studies have limited generalizability and insufficient power to detect differences in rare adverse events. We compared the risks and costs of endobronchial ultrasound (EBUS)-guided nodal aspiration and mediastinoscopy performed for any indication in a large national cohort. METHODS: We conducted a retrospective study (2007-2015) with MarketScan, a claims database of individuals with employer-provided insurance in the United States. Patients who underwent multimodality mediastinal evaluation (n = 1,396) or same-day pulmonary resection (n = 2,130) were excluded. Regression models were used to evaluate associations between diagnostic modalities and risks and costs while adjusting for patient characteristics, year, concomitant bronchoscopic procedures, and lung cancer diagnosis. RESULTS: Among 30,570 patients, 49% underwent EBUS. Severe adverse events—pneumothorax, hemothorax, airway/vascular injuries, or death—were rare and invariant between EBUS and mediastinoscopy (0.3% vs 0.4%; P = .189). The rate of vocal cord paralysis was lower for EBUS (1.4% vs 2.2%; P < .001). EBUS was associated with a lower adjusted risk of severe adverse events (OR, 0.42; 95% CI, 0.32-0.55) and vocal cord paralysis (OR, 0.57; 95% CI, 0.54-0.60). The mean cost of EBUS was $2,211 less than mediastinoscopy ($6,816 vs $9,023; P < .001). After adjustment this difference decreased to $1,650 (95% CI, $1,525-$1,776). CONCLUSIONS: When performed as isolated procedures, EBUS is associated with lower risks and costs compared with mediastinoscopy. Future studies comparing the effectiveness of EBUS vs mediastinoscopy in the community at large will help determine which procedure is superior or if trade-offs exist.

Background Spina bifida (SB) may differentially impact adults’ participation in solo and partnered sexual behaviors, but little research investigates this topic. Aim Describe solo and partnered sexual behaviors among an international sample of adult men and women with SB. Main Outcome Measures Ever participated (no/yes) and recent participation (>1 year ago/within last year) in solo masturbation, cuddled with a partner, held hands with a partner, kissed a partner, touched a partner's genital, had genitals touched by a partner, gave a partner oral sex, received oral sex from a partner, vaginal sex, anal sex, and sex toy use. Methods Data were drawn from a larger cross-sectional, internet-based survey assessing the sexual behaviors of an international sample of men and women with SB. We used logistic regression to examine the impact of background (gender, age, independent living, and relationship status) and health (shunt status, ambulation, and genital sensation) factors on each outcome. Results The sample consisted of 345 respondents aged 18–73 years from 26 nations. Very few ( Clinical Implications Despite impairment, adults with spina bifida do participate in solo and partnered sexual behaviors. Medical personnel who work with this population should include discussions about sexuality as part of routine care. Strengths & Limitations Although this research measured solo and partnered sexual behavior in large international sample of adults with spina bifida, it is limited by its cross-sectional retrospective design and non-clinical convenience sample. Conclusion Despite disability, many adults with SB participate in solo and partnered sexual behavior. Medical and psychosocial supports are needed to help adults in this population enjoy sexuality in a healthy and safe manner.

Background. The complexity of decision science models may prevent their use to assist in decision making. User-centered design (UCD) principles provide an opportunity to engage end users in model development and refinement, potentially reducing complexity and increasing model utilization in a practical setting. We report our experiences with UCD to develop a modeling tool for cancer control planners evaluating cancer survivorship interventions. Design. Using UCD principles (described in the article), we developed a dynamic cohort model of cancer survivorship for individuals with female breast, colorectal, lung, and prostate cancer over 10 y. Parameters were obtained from the National Program of Cancer Registries and peer-reviewed literature, with model outcomes captured in quality-adjusted life-years and net monetary benefit. Prototyping and iteration were conducted with structured focus groups involving state cancer control planners and staff from the Centers for Disease Control and Prevention and the American Public Health Association. Results. Initial feedback highlighted model complexity and unclear purpose as barriers to end user uptake. Revisions addressed complexity by simplifying model input requirements, providing clear examples of input types, and reducing complex language. Wording was added to the results page to explain the interpretation of results. After these updates, feedback demonstrated that end users more clearly understood how to use and apply the model for cancer survivorship resource allocation tasks. Conclusions. A UCD approach identified challenges faced by end users in integrating a decision aid into their workflow. This approach created collaboration between modelers and end users, tailoring revisions to meet the needs of the users. Future models developed for individuals without a decision science background could leverage UCD to ensure the model meets the needs of the intended audience. Highlights Model complexity and unclear purpose are 2 barriers that prevent lay users from integrating decision science tools into their workflow. Modelers could integrate the user-centered design framework when developing a model for lay users to reduce complexity and ensure the model meets the needs of the users.

This study aims to assess differences in costs and benefits of treatment strategies for high-risk human epidermal growth factor receptor 2 positive (HER2+) early-stage breast cancer (ESBC).We used a hybrid decision-tree/Markov model to simulate costs and outcomes across six health states: Invasive disease-free, non-metastatic recurrence, remission, first-line and second-line metastatic cancer, and death. We considered several strategies, defined by four attributes: (1) Neoadjuvant targeted therapy (infused pertuzumab and trastuzumab (PH) versus subcutaneous fixed-dose combination (FDC) of pertuzumab and trastuzumab versus trastuzumab alone (H)); (2) adjuvant targeted therapy if pathological complete response (pCR) is achieved (PH, FDC, or H); (3) adjuvant targeted therapy (T-DM1 or H) in the case of residual disease (RD); and (4) use of branded or biosimilar H. Transition probabilities were derived from relevant clinical trials. We included drug costs and costs associated with adverse events and administration. Health state utilities were obtained from clinical trials and the literature.Strategies not containing T-DM1 were dominated (worse outcomes and greater costs) by strategies containing T-DM1. Among strategies with pertuzumab continuation in the case of pCR and T-DM1 in the case of RD, use of FDC was dominant (equivalent outcomes and lower costs), relative to strategies using infused therapies, regardless of biosimilar versus branded trastuzumab. Adjuvant continuation of FDC was also cost-effective (better outcomes at reasonable cost increases) relative to strategies which discontinued pertuzumab following pCR.Dual targeted therapy via FDC (with transition to T-DM1 in the case of RD) is a cost-effective treatment strategy in high-risk HER2+ ESBC.

PURPOSE: Delays in adjuvant breast cancer (BC) therapy have been shown to worsen outcomes. However, thus far studies have only evaluated delays to initial treatment, or a particular modality, such as chemotherapy, leaving uncertainty about the role of delay to subsequent therapy and the effects of cumulative delay, on outcomes. We investigated the associations of delays across treatment modalities with survival. METHODS: We included 3368 women with incident stage I-III BC in the Women’s Health Initiative (WHI) enrolled in fee-for-service Medicare who underwent definitive surgery. This prospective analysis characterized treatment delays by linking WHI study records to Medicare claims. Delays were defined as >8 weeks to surgery, chemotherapy, and radiation from diagnosis or prior treatment. We used Cox proportional hazards models to estimate BC-specific mortality (BCSM) and all-cause mortality (ACM) in relation to treatment delays. RESULTS: We found 21.8% of women experienced delay to at least one therapy modality. In adjusted analysis, delay to chemotherapy was associated with a higher risk of BCSM (HR=1.71; 95% CI: 1.07–2.75) and ACM (HR=1.39; 95% CI: 1.02–1.90); delay in radiation increased BCSM risk (HR=1.49; 95% CI: 1.00–2.21) but not ACM risk (HR=1.19; 95% CI: 0.99–1.42). Delays across multiple treatment modalities increased BCSM risk 3-fold (95% CI: 1.51–6.12) and ACM risk 2.3-fold (95% CI: 1.50–3.50). CONCLUSIONS: A delay to a single treatment modality, and to a greater extent an accumulation of delays were associated with higher BCSM and ACM after BC. Timely care throughout the continuum of breast cancer treatment is important for optimal outcomes.

Background: Potential discordance in estrogen receptor (ER) status between primary and metastatic breast cancer (mBC) site mandates the need for accurate diagnosis. Biopsy is not performed routinely due to inaccessible sites. Additionally, interpretation is limited by specimen processing and a likelihood that the tumor is persistently ER+, leading to variations in diagnosis and therapy selection. Flouroestradiol (FES) is an estrogen PET analogue imaging tracer which measures ER expression at multiple tumor sites simultaneously. FES can potentially be applied to ascertain ER status across multiple sites, thereby providing a more clinically feasible and accurate means to guide therapy selection. To inform the high-value translation of this technology, we used data from the literature to evaluate the potential cost-effectiveness of FES vs. biopsy to determine ER status in mBC. Methods: We created a decision model to evaluate clinical and economic outcomes in a hypothetical cohort of 60-year-old patients with suspected mBC to assess the value of FES vs biopsy to establish ER status. Patients received appropriate/inappropriate therapy based on the accuracy of the test for determining ER status. We obtained test sensitivity, test specificity, costs, and utility inputs from the peer-reviewed literature. The model assessed outcomes with endocrine and non-endocrine treatment regimens to reflect the range of current practice and associated variation in costs and outcomes. The base case evaluated therapy with aromatase inhibitor (AI) for endocrine therapy or capecitabine for non-endocrine therapy. Model outcomes included life years (LYs), quality adjusted-life-years (QALYs), and cost. Probabilistic analyses were conducted to assess uncertainty in model outcomes. We took a payer perspective, evaluated a lifetime horizon, and outcomes were discounted at 3% per year. Results: In the base case, appropriate therapy was provided for 93.1% of patients receiving FES and 80.1% of patients receiving biopsy. FES resulted in appropriate endocrine therapy selection for 63.7% vs 51.5% of patients with biopsy strategy in our model. Table 1 shows outcomes for all strategies. In the base case, FES was expected to increase QALYs by 0.23 and reduce cost by $11,254 per patient—thereby dominating the biopsy strategy. FES resulted in more QALYs than the biopsy strategy (range: 2.5 to 3.2 QALYs) in all alternative scenarios, and FES resulted in higher costs in scenarios applying CDK4/6 therapies (range: $591,843 to $620,631). In probabilistic analyses of FES vs. biopsy, FES increased QALYs in 94% of simulations, decreased cost in 94% of simulations, and was cost-effective ( Citation Format: Poorni Manohar, Hannah Linden, Joshua Roth. Potential cost effectiveness of 18-Flouroestradiol (FES)-PET in metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-13-03.

Many Japanese workers in lower-paying positions were drawn to the growing trucking sector in the 1950s and 1960s, characterized by contingency and the thrill of risk and reward, in contrast to the stasis of lifetime employment guarantees emerging in other sectors of the economy. The gamified reward structure in trucking, however, led to a spike in traffic accidents and a backlash against “kamikaze trucks.” Only after regulations and enforcement limited the most dangerous kinds of incentives did meaningful forms of play emerge at work from the bottom up, rather than the stultified forms imposed by businesses from the top down.

Disease-free survival (DFS) in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer is significantly greater with the addition of neratinib after adjuvant trastuzumab versus no additional therapy. However, it remains uncertain whether these survival gains represent good value for the money, given the substantial cost of neratinib.To evaluate clinical and economic implications of adding neratinib after adjuvant trastuzumab based on results from the phase III ExteNET trial.A 3-state Markov model was developed to estimate the cost-effectiveness of neratinib for women with early-stage (I-III) HER2-positive breast cancer. Five-year recurrence rates were derived from the ExteNET trial. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Outcomes included life-years, quality-adjusted life-years (QALYs), and direct medical expenditures. The analysis was performed from a payer perspective over a lifetime horizon. One-way sensitivity and probabilistic analyses were conducted to evaluate uncertainty.Total cost of neratinib following adjuvant trastuzumab was $317,619 versus $152,812 for adjuvant trastuzumab alone. A gain of 0.4 QALYs (15.7 vs. 15.3) and 0.1 years of projected life expectancy (18.3 vs. 18.2) favored neratinib after trastuzumab versus trastuzumab alone. The neratinib cost per QALY gained was $416,106. At standard willingness-to-pay thresholds of $50,000, $100,000, and $200,000 per QALY gained, neratinib has a probability of 2.8%, 16.7%, and 33.9% of cost-effectiveness, respectively. The cost per QALY gained in a scenario analysis only including patients with hormone-receptor positive disease was $275,311.Based on 5-year data from ExteNET, neratinib following adjuvant trastuzumab is not projected to be cost-effective, even among those patients shown to derive the greatest clinical benefit. Future analyses should reassess the cost-effectiveness associated with neratinib treatment as trial data mature.No outside funding supported this study. Roth reports consulting fees from Genentech. Steuten reports grants from AstraZeneca, EMD Serono, and Genomic Health, along with personal fees from Agendia, unrelated to this study. The other authors have no conflicts of interest in connection with this study.

Purpose The purpose of this paper is to analyze the Supreme Court’s decision in Lucia v. Securities and Exchange Commission, 138 S.Ct. 2044 (June 21, 2018). Design/methodology/approach The approach of this paper is to discuss the Securities and Exchange Commission’s (“SEC”) use of Administrative Law Judges (“ALJs”), and the litigation challenging the appointment of those ALJs, culminating in the Supreme Court’s decision in Lucia. Findings In Lucia, the Court held that SEC ALJs are “officers of the United States,” and thus subject to the Constitution’s Appointments Clause, which limits the power to appoint “officers” to the President, “Courts of Law” or “Heads of Departments.” Because the ALJ who presided over Lucia’s administrative proceeding was not appointed by the SEC itself, the Court held that the ALJ’s appointment was unconstitutional and ordered the SEC to provide Lucia with a new hearing in front of a new (constitutionally appointed) ALJ. Practical implications The Supreme Court’s decision in Lucia provides defense counsel with new ammunition to challenge SEC administrative proceedings. It will likely have a significant effect on many pending and already-concluded SEC administrative proceedings but also leaves open a number of important questions for further litigation. Originality/value This paper provides expert analysis and guidance from experienced securities litigators.

Spina bifida (SB) patients are at increased risk for hydronephrosis, bladder storage and emptying problems, and renal failure that may require multiple bladder surgeries. We retrospectively reviewed patients born with SB 2005–2009, presenting to our institution within 1 year of birth. Outcomes at 8–11 years old included final renal/bladder ultrasound (RBUS) results, clean intermittent catheterization (CIC) use, anticholinergic use, surgical interventions, and final renal function. We excluded those without follow-up past age 8 and/or no RBUS or fluoroscopic urodynamic images (FUI) within the first year of life. Imaging was independently reviewed by four pediatric urologists blinded to radiologists’ interpretation and initial findings compared with final outcomes. Of 98 children, 62 met inclusion criteria (48% male, 76% shunted). Median age at last follow-up was 9.6 years. Upon initial imaging, 74% had hydronephrosis (≥ SFU grade 1), decreasing to 5% at 10 years (p

Hundreds of gene therapies are undergoing clinical testing and are likely to be priced more than $1 million per course of treatment. The association that high prices will have with insurance coverage of gene therapy remains unclear. Gene therapy for sickle cell disease has shown early success and would be one of the first gene therapies available for a relatively large population.To estimate the budget impact and affordability of a gene therapy for severe sickle cell disease from the perspective of US Medicaid programs with the highest prevalence of sickle cell disease while exploring the impact of an annuity payment model.A budget impact analysis was performed from January 1 to May 31, 2020, for a sickle cell disease gene therapy from the perspective of 10 state Medicaid plans with a 5-year time horizon, using state-level disease prevalence data from 2012. Disease prevalence, Medicaid enrollment, and expenditures were derived from the available literature. The eligible population was based on modified clinical trial inclusion criteria including individuals aged 13 to 45 years with severe disease.The gene therapy was assumed to be administered to 7% of the eligible population annually and was curative (no subsequent disease-related expenditures). The gene therapy price was $1.85 million in the base case, and baseline disease-related expenditures were $42 200 per year.The main outcomes were total budget impact and budget impact per member per month in years 1 through 5. One-way sensitivity analysis was used to evaluate uncertainty of market diffusion, size of eligible population, price of therapy, and cost of routine care.An estimated 5464 Medicaid enrollees would be eligible for the gene therapy nationally, with 2315 individuals in the 10 Medicaid programs of interest (16 per 100 000 enrollees). The model projected a mean 1-year budget impact of $29.96 million per state Medicaid program in the sample ($1.91 per member per month). A 5-year annuity payment reduced the short-term budget impact.This study suggests that a gene therapy for severe sickle cell disease is likely to produce a considerable budget impact for many Medicaid plans while potentially offering substantial benefit to patients. Payers may need to take steps to ensure affordability and access. Gene therapy for sickle cell disease is likely to provide an early demonstration of the unique financial challenges associated with this emerging drug class.

Objectives Sickle cell disease (SCD) is a complex, chronic condition that impairs health-related quality of life of affected individuals and their caregivers. As curative therapies emerge, comprehensive cost-effectiveness models will inform their value. These models will require descriptions of health states and their corresponding utility values that accurately reflect health-related quality of life over the disease trajectory. The objectives of this systematic review were to develop a catalog of health state utility (HSU) values for SCD, identify research gaps, and provide future directions for preference elicitation. Methods Records were identified through searches of PubMed and Embase, Tufts Medical Center Cost-Effectiveness Analysis Registry, reference lists of relevant articles, and consultation with SCD experts (2008-2020). We removed duplicate records and excluded ineligible studies. For included studies, we summarized the study characteristics, methods used for eliciting HSUs, and HSU values. Results Five studies empirically elicited utilities using indirect methods (EQ-5D) (n = 3) and Short Form-6 Dimension (n = 2); these represent health states associated with general SCD (n = 1), SCD complications (n = 2), and SCD treatments (n = 3). Additionally, we extracted HSUs from 7 quality-adjusted life-years-based outcome research studies. The HSU among patients with general SCD without specifying complications ranged from 0.64 to 0.887. Only 36% of the HSUs used in the quality-adjusted life-year-based outcomes research studies were derived from individuals with SCD. No study estimated HSUs in caregivers. Conclusions There is a dearth of literature of HSUs for use in SCD models. Future empirical studies should elicit a comprehensive set of HSUs from individuals with SCD and their caregivers.

Importance Hundreds of gene therapies are undergoing clinical testing and are likely to be priced more than $1 million per course of treatment. The association that high prices will have with insurance coverage of gene therapy remains unclear. Gene therapy for sickle cell disease has shown early success and would be one of the first gene therapies available for a relatively large population. Objectives To estimate the budget impact and affordability of a gene therapy for severe sickle cell disease from the perspective of US Medicaid programs with the highest prevalence of sickle cell disease while exploring the impact of an annuity payment model. Design, Setting, and Participants A budget impact analysis was performed from January 1 to May 31, 2020, for a sickle cell disease gene therapy from the perspective of 10 state Medicaid plans with a 5-year time horizon, using state-level disease prevalence data from 2012. Disease prevalence, Medicaid enrollment, and expenditures were derived from the available literature. The eligible population was based on modified clinical trial inclusion criteria including individuals aged 13 to 45 years with severe disease. Exposures The gene therapy was assumed to be administered to 7% of the eligible population annually and was curative (no subsequent disease-related expenditures). The gene therapy price was $1.85 million in the base case, and baseline disease-related expenditures were $42 200 per year. Main Outcomes and Measures The main outcomes were total budget impact and budget impact per member per month in years 1 through 5. One-way sensitivity analysis was used to evaluate uncertainty of market diffusion, size of eligible population, price of therapy, and cost of routine care. Results An estimated 5464 Medicaid enrollees would be eligible for the gene therapy nationally, with 2315 individuals in the 10 Medicaid programs of interest (16 per 100 000 enrollees). The model projected a mean 1-year budget impact of $29.96 million per state Medicaid program in the sample ($1.91 per member per month). A 5-year annuity payment reduced the short-term budget impact. Conclusions and Relevance This study suggests that a gene therapy for severe sickle cell disease is likely to produce a considerable budget impact for many Medicaid plans while potentially offering substantial benefit to patients. Payers may need to take steps to ensure affordability and access. Gene therapy for sickle cell disease is likely to provide an early demonstration of the unique financial challenges associated with this emerging drug class.

e18588 Background: Real-world studies comparing racial differences in overall survival (OS) outcomes between African American (AA) and White (W) patients (pts) with TNBC have yielded mixed findings. This exploratory study assessed differences between national and county-level OS estimates-comparing AA vs. W pts, and identifying counties with greater racial disparities for future research. Methods: This retrospective cohort study used the Surveillance Epidemiology and End Result (SEER) cancer registry to assess county-level OS among non-hispanic AA and W pts ≥18 years of age who were diagnosed with TNBC 2011-2016. Counties with low levels of racial diversity (< 30 AA or W TNBC pts) were excluded. Five-year OS was evaluated using Kaplan-Meier and multilevel parametric OS models with a Weibull distribution. By county, OS differences between AA and W pts were tested using linear hypothesis tests after model estimation. OS models were adjusted for age at diagnosis, year of diagnosis, marital status, insurance type, surgery type, stage, grade and metastasis at brain, bone, liver and lung. Results: Among 46,125 TNBC pts in SEER, 15,723 pts (33.4% AA, 66.6% W) residing in 8 States and 47 Counties met inclusion criteria. W pts were older (mean 60; ∓14 vs 57∓13 for AA) and more likely to be married (57% vs 33%), insured (49% vs 45%) and diagnosed at an earlier stage (stage I 37% vs 29%). Controlling for potential confounders, AA pts were more likely to experience 5-year mortality compared to W pts (Hazard Ratio [HR] = 1.16; 95%CI = 1.07, 1.26). Among 47 included counties, only 4 counties demonstrated a statistically significant 5-year OS racial disparities after adjusting for confounders. The difference in HRs between AA and W pts in these 4 counties ranged from 1.49 to 2.26 as depicted in the result table (p value < 0.05). Removing these 4 counties (n = 2,929) from the final analytic cohort yielded statistically non-significant estimates (HR = 1.06; 0.97,1.16). Conclusions: There is clinically meaningful OS variation between AA and W pts with TNBC across U.S. counties included in SEER. Measuring disparities at the national or state level may mask important OS disparities at the county level. Using a county-level analytic approach, we were able to identify localities that disproportionately contribute to OS disparities at the national level. Our findings will facilitate better targeting of local interventions to address TNBC racial disparities. Future analyses should also assess counties excluded (n = 13,032) for small population sizes and/or low levels of racial diversity, as well as states not represented in SEER.[Table: see text]

6591 Background: BMT CTN 1101 was a Phase III randomized controlled trial evaluating the comparative effectiveness of unrelated umbilical cord blood (UCB) versus HLA-haploidentical related donor bone marrow (haplo-BM) cell sources for hematopoietic cell transplantation (HCT) in patients with high-risk hematologic malignancies (leukemias, lymphomas). We report results of an economic evaluation conducted as part of the clinical trial. Methods: 368 patients (90% of planned accrual) enrolled from 33 centers in the U.S. were randomly assigned to unrelated UCB (n=186) or haplo-BM (n=182) transplant. Healthcare utilization and costs were estimated using propensity-score matched cohorts of BMT patients in the OptumLabs Data Warehouse for trial participants

Metabolic Syndrome (MetS) has detrimental effects on the bladder, including detrusor underactivity. The progression and mechanism of disease are poorly understood. A swine model for diabetic bladder dysfunction (DBD) was established because of the pig's human-sized bladder and its ability to develop MetS by dietary modification alone. The hypothesis of this study is that this swine model will demonstrate oxidative stress associated with MetS, which contributes to both bladder fibrosis and detrusor underactivity (DU). Ossabaw pigs underwent dietary modification consisting of a hypercaloric, atherogenic diet for 10 mo to induce MetS, and were compared with a group of control (lean) pigs. Urodynamic studies were performed in both groups to confirm DU. Thiobarbituric acid reactive substances (TBARS) detected in the urine were used to measure oxidative stress activity in the urinary tract, and urinary IL17a was used to detect profibrotic activity. MetS was confirmed by assessing body weight, blood pressure, glucose tolerance, total cholesterol, and triglycerides. The MetS group exhibited an increase in the relative levels of urinary TBARS and IL17a. Bladder pressures at capacity were lower in the MetS group, suggesting DU. Histologic analysis of a cohort of control (lean) and MetS pigs revealed that as compared with the control pigs, the MetS pigs had significantly more collagen in the muscularis layer, but not in the submucosa or mucosa layer. In conclusion, the Ossabaw pig model for diet-induced MetS is associated with oxidative stress and profibrotic activity in the bladder, which results in DU. This has previously been shown in mice and rats, but never in pigs. This novel model will better represent human MetS and DBD because the mechanism and size of the pig bladder more closely resemble that of a human, resulting in a more valid model and facilitating further study into the signaling mechanisms responsible for this impairment.

Introduction: Mechanical balloon dilation and direct visualization internal urethrotomy (DVIU) are the most widely used treatments for urethral stricture disease in the U.S., but recurrence rates are high, especially after re-treatment. This study investigates the safety and efficacy of the Optilume™ paclitaxel-coated balloon for the treatment of recurrent strictures. Methods: Men with recurrent bulbar strictures ≤2 cm with 1–4 prior endoscopic treatments were treated with the Optilume™ drug-coated balloon. Patients were evaluated within 14 days, three, six, 12, and 24 months post-treatment. The primary safety endpoint was serious urinary adverse events. The primary efficacy endpoint was ≥50% improvement in International Prostate Symptom Score (IPSS) at 24 months. Secondary outcomes included quality of life, erectile function, flow rate, and post-void residual urine volume. Results: A total of 53 subjects were enrolled and treated; 46 completed the 24-month followup. Forty-three percent of men had undergone >1 previous dilations, with a mean of 1.7 prior dilations. There were no serious adverse events related to treatment at two years. Success was achieved in 32/46 (70%), and baseline IPSS improved from a mean of 25.2 to 6.9 at 24 months (p

As the advances in medicine continue to emerge, more children with congenital or pediatric-onset chronic urologic conditions are surviving well into adulthood. This imposes an ever rising there is a need for adequate transition of these patients from pediatric to adult care. Despite position statements from multiple heath care organizations and several models proposed in literature, different issues and gaps in urologic transition continue to exist. Major barriers in this transition are adolescence, a challenging time that is characterized by impulsive behavior and risk taking, and the longstanding relation between both patients and paediatric providers. Both pediatric and adult care providers need to be aware of the special needs of maturing youth with chronic care problems related to education, self-management, legal issues and psychological support during care transition. Furthermore, they need to understand and address the currently existing obstacles for adequate transition. There is need for active communication with each other and the patient to develop sustainable relationships that can support the transitioning process. It is therefore in the greatest interest of the care provider to make this transition as smooth as possible. This paper aims to point out the currently perceived barriers in care transition within the urological context, reflect on previous implemented models for care transition and present proposals for improvement.

Objectives The Women's Health Initiative (WHI) randomized trial identified age differences in the benefit-risk profile of estrogen-alone (ET) use. The impact of WHI trial on disease-associated medical expenditures attributable to subsequent decreased ET utilization has, however, not been measured. Therefore, the objective of this analysis was to quantify the age-specific disease-associated medical expenditures attributable to reduced ET utilization after the WHI Hormone Therapy (HT) trials. Methods Population-level disease counts and associated expenditures between 2003 and 2015 were compared between an observed ET-user population versus a hypothetical ET-user population assuming absence of the WHI HT trials, constructed by extrapolating ET utilization rates from 1996 to 2002 assuming pre-WHI HT rates would have continued without publication of the WHI HT trial data (2002-2004). Analyses were stratified by age (50-59, 60-69, and 70-79 years). Input data were extracted from Medical Expenditure Panel Survey and the literature. The primary outcomes were: ET utilization, chronic diseases (breast cancer, stroke, coronary heart disease, colorectal cancer, pulmonary embolism, and hip fracture) and disease-associated direct medical expenditures. Results Over 13 years, the decline in ET utilization was associated with $4.1 billion expenditure for excess chronic diseases (37,549 excess events) among women in their 50s, compared to savings of $1.5 billion and $4.4 billion for diseases averted by lower ET utilization among women in their 60s (13,495 fewer events) and 70s (40,792 fewer events), respectively. Conclusion The decline in ET utilization had differential disease and expenditure consequences by age groups in the United States. These results are limited by the lack of inclusion of vasomotor symptom benefit and costs of alternative medications for these symptoms in the analysis.

One biomechanical goal of kinematically aligned total knee arthroplasty (KA TKA) is to achieve knee laxities and neutral positions that are not different from those of the native knee without soft tissue release. However, replacing the articular surfaces and menisci with implants of discrete sizes and average shapes and resecting the anterior cruciate ligament (ACL) might prevent KA TKA from achieving this goal in the tibiofemoral joint. Accordingly, the objective was to determine whether either or both surgically induced changes cause differences in laxities and/or neutral positions from native using a cruciate retaining implant. Eight laxities and four neutral positions were measured from 0° to 120° flexion in 30° increments in 13 human cadaveric knees in three knee conditions: native, ACL-deficient, and KA TKA. After KA TKA, 5 of the 40 laxity measures (8 laxities × 5 flexion angles) and 6 of the 20 neutral position measures (4 neutral positions × 5 flexion angles) were statistically different from those of the native knee. The greatest differences in laxities from native after KA TKA occurred at 30° flexion in anterior translation (1.6 ± 2.1 mm increase, p < 0.0001); this difference was 1.7 ± 2.1 mm less than that in the ACL-d knee (p < 0.0001). The greatest difference in neutral positions from native after KA TKA occurred in anterior-posterior translation at 0° flexion (3.8 ± 1.9 mm anterior, p < 0.0001); this difference was 2.6 ± 1.9 mm greater than that in the ACL-d knee (p = 0.0002). Clinical Significance: These results indicate that the biomechanical goal of KA TKA is largely realized despite the two surgically induced changes. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:358-369, 2019.