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Background: Comparative‐effectiveness studies using real‐world data (RWD) can be susceptible to surveillance bias. In solid tumor oncology studies, analyses of endpoints such as progression‐free survival (PFS) are based on progression events detected by imaging assessments. This study aimed to evaluate the potential bias introduced by differential imaging assessment frequency when using electronic health record (EHR)‐derived data to investigate the comparative effectiveness of cancer therapies. Methods: Using a nationwide de‐identified EHR‐derived database, we first analyzed imaging assessment frequency patterns in patients diagnosed with advanced non‐small cell lung cancer (aNSCLC). We used those RWD inputs to develop a discrete event simulation model of two treatments where disease progression was the outcome and PFS was the endpoint. Using this model, we induced bias with differential imaging assessment timing and quantified its effect on observed versus true treatment effectiveness. We assessed percent bias in the estimated hazard ratio (HR). Results: The frequency of assessments differed by cancer treatment types. In simulated comparative‐effectiveness studies, PFS HRs estimated using real‐world imaging assessment frequencies differed from the true HR by less than 10% in all scenarios (range: 0.4% to −9.6%). The greatest risk of biased effect estimates was found comparing treatments with widely different imaging frequencies, most exaggerated in disease settings where time to progression is very short. Conclusions: This study provided evidence that the frequency of imaging assessments to detect disease progression can differ by treatment type in real‐world patients with cancer and may induce some bias in comparative‐effectiveness studies in some situations. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Racial disparities in cancer care and outcomes remain a societal challenge. Medicaid expansion through the Affordable Care Act was intended to improve health care access and equity. This study aimed to assess whether state Medicaid expansions were associated with a reduction in racial disparities in timely treatment among patients diagnosed with advanced cancer. STUDY DESIGN: This difference-in-differences study analyzed deidentified electronic health record--derived data. Patients aged 18 to 64 years with advanced or metastatic cancers diagnosed between January 1, 2011, and January 31, 2019, and receiving systemic therapy were included. METHODS: The primary end point was receipt of timely treatment, defined as first-line systemic therapy starting within 30 days after diagnosis of advanced or metastatic disease. Racial disparity was defined as adjusted percentage-point (PP) difference for Black vs White patients, adjusted for age, sex, practice setting, cancer type, stage, insurance marketplace, and area unemployment rate, with time and state fixed effects. RESULTS: The study included 30,310 patients (12.3% Black race). Without Medicaid expansion, Black patients were less likely to receive timely treatment than White patients (43.7% vs 48.4%; adjusted difference, -4.8 PP; P < .001). With Medicaid expansion, this disparity was diminished and lost significance (49.7% vs 50.5%; adjusted difference, -0.8 PP; P = .605). The adjusted difference-in-differences estimate was a 3.9 PP reduction in racial disparity (95% CI, 0.1-7.7 PP; P = .045). CONCLUSIONS: Medicaid expansion was associated with reduced Black-White racial disparities in receipt of timely systemic treatment for patients with advanced or metastatic cancers. [ABSTRACT FROM AUTHOR]

The NBA, the WNBA, and the NHL have shown how detailedprotocolsandtestingmandatescankeepgroupssafe and enable them to function at a high level when complementedbycontacttracingandtheisolationofpositivecases from the start. Downloaded from http://journals.lww.com/jbjsjournal by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60EtgtdlLYrLzSPu+hUapVK5dvms8 on 02/09/2021 Downloaded from http://journals.lww.com/jbjsjournal by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60EtgtdlLYrLzSPu+hUapVK5dvms8 on 02/09/2021 the Orthopaedic forum What's Important: Reopening Lessons from the Big Leagues' Experiences with COVID-19 Robby Sikka, MD, Andrew E. Lincoln, ScD, MS, Blythe J.S. Adamson, PhD, MPH,Jonathan A. Epstein, MD, and Harlan M. Krumholz, MD, SM, on behalf of the COVID-19 Sports and Society Working Group As Major League Baseball (MLB), the National Basketball Association (NBA), the National Hockey League (NHL), and the Women's National Basketball Association (WNBA) bring their seasons to a close 1, there remains no consensus ontheperfectwaytoplaysportsduringapandemic. [Extracted from the article]

This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines in development by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for the assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standardHIVprevention, daily oral PrEP,HIVvaccine, and their combination. We constructed aMarkov model based on clinical trial data and the published literature.We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices, PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER = $463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. The results suggest that boosting potential may be key to HIV vaccine value. [ABSTRACT FROM AUTHOR]

Background: Limited data compare first-line carboplatin-based chemotherapy and immune checkpoint blockade in cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. The primary evidence guiding treatment decisions was a recent Food and Drug Administration/European Medicines Agency safety alert based on emerging data from two ongoing phase III trials, reporting shorter survival in programmed death-ligand 1 (PD-L1)-negative patients receiving immunotherapy. Final results from these trials are unknown., Objective: To compare survival in cisplatin-ineligible mUC patients receiving first-line immunotherapy versus those receiving carboplatin-based chemotherapy., Design, Setting, and Participants: We conducted a retrospective cohort study of 2017 mUC patients receiving first-line carboplatin-based chemotherapy (n = 1530) or immunotherapy (n = 487) from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record-derived database., Outcome Measurements and Statistical Analysis: The primary outcomes were overall survival (OS), comparing 12- and 36-mo OS, and hazard ratios before and after 12 mo. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression model estimates of comparative effectiveness., Results and Limitations: IPTW-adjusted OS rates in the immunotherapy group were lower at 12 mo (39.6% [95% confidence interval {CI} 34.0-45.3%] vs 46.1% [95% CI 43.4-48.8%]) but higher at 36 mo (28.3% [95% CI 21.8-34.7%] vs 13.3% [95% CI 11.1-15.5%]) relative to the chemotherapy group. Immunotherapy treatment demonstrated inferior OS during the first 12 mo relative to carboplatin-based chemotherapy (IPTW-adjusted hazard ratio [HR] 1.37, 95% CI 1.15-1.62), but superior OS beyond 12 mo (IPTW-adjusted HR 0.50, 95% CI 0.30-0.85). Limitations include retrospective design and potential unmeasured confounding., Conclusions: In the setting of mUC, clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy., Patient Summary: To determine the optimal first-line therapy for metastatic bladder cancer patients who are unfit for cisplatin, we compared carboplatin-based chemotherapy versus immunotherapy using real-world data. Survival in the 1st year of treatment was lower with immunotherapy relative to chemotherapy, but for patients surviving beyond the 1st year, immunotherapy was superior., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Several immune checkpoint inhibitor therapies (CPIs) have been approved to treat metastatic urothelial cell carcinoma (mUC). Because of the favorable toxicity profile of CPI compared with chemotherapy, oncologists may have a low threshold to prescribe CPI to patients near the end of life. We evaluated trends in initiation of end-of-life systemic therapy in 1,637 individuals in the Flatiron Health Database who were diagnosed with mUC between 2015 and 2017 and who died. Rates of systemic therapy initiation in the last 30 and 60 days of life were 17.0% and 29.8%, respectively. The quarterly proportion of patients who initiated CPI within 60 days of death increased from 1.0% to 23% during the study period ( p trend < .001). After CPI approval, end-of-life CPI initiation significantly increased among patients with poor performance status ( p trend = .020) and did not significantly change among individuals with good performance status. The quarterly proportion of patients who initiated any systemic therapy at the end of life doubled (17.4% to 34.8%) during the study period, largely explained by increased CPI use. These findings suggest a dramatic rise in CPI use at the end of life in patients with mUC, a finding that may have important guideline and policy implications., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Background: RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective., Methods: Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions., Results: Our analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750)., Conclusions: While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Engagement of early stage investigators (ESIs) in the search for a safe and effective vaccine is critical to the success of this highly challenging endeavor. In the wake of disappointing results from a large-scale efficacy trial, the HIV Vaccine Trials Network (HVTN) and Center for HIV/AIDS Vaccine Immunology (CHAVI) developed a novel mentored research program focused on the translation of findings from nonhuman primate studies to human trials of experimental vaccines. From 2008 to 2011, 14 ESI Scholars were selected from 42 complete applications. Post program surveys and tracked outcomes suggest that the combination of flexible funding, transdisciplinary mentorship, and structured training and networking promoted the scientific contributions and career development of promising ESIs. Embedding a multicomponent research program within collaborative clinical trial networks and research consortia is a promising strategy to attract and retain early career investigators and catalyze important translational science., (© 2014 Wiley Periodicals, Inc.)