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Objectives To examine whether the case fatality rate (CFR) of coronavirus disease 2019 (Covid-19) decreased overtime, and whether the Covid-19 testing rate is a driving factor for the changes if the CFR decreased. Methods Analyzing Covid-19 cases, deaths, and tests in Ontario, Canada, we compared the CFR between the first wave and the second wave across 26 Public Health Units in Ontario. We also explored whether a high testing rate was associated with a large CFR decrease. Results The first wave CFR ranged from 0.004 to 0.146; whereas the second wave CFR ranged from 0.003 to 0.034. The pooled RR estimate of the second wave Covid-19 case fatality, compared to first wave, was 0.24 (95% CI: 0.19-0.32). Additionally, Covid-19 testing percentages were not associated with the estimated RR (p-value = 0.246). Conclusions The Covid-19 CFR decreased profoundly in Ontario during the second wave, and Covid-19 testing was not a driving factor for this decrease.

Background Given the growth in dense breast notification (DBN) legislation in the United States, we examined the association between different types of DBN laws and supplemental screening behaviors among women. Methods We surveyed in March–April 2018 a nationally representative sample of women aged 40‐59 years who received a routine screening mammogram in the past 18 months. Survey items included the following topics regarding supplemental screening: discussing risks or benefits with a provider, knowledge about the risk of false positives, and utilization. We grouped women by state DBN into non‐DBN, generic DBN (mentions breast density but not supplemental screening), DBN that mentions supplemental screening (DBN‐SS), and DBN with mandated insurance coverage for supplemental screening (DBN‐coverage), and estimated adjusted predicted probabilities for supplemental screening behaviors. Results Of 1641 women surveyed, 21.3% resided in non‐DBN, 41.2% in generic DBN, 25.8% in DBN‐SS, and 12.5% in DBN‐coverage states. Overall, 23.0% of respondents had discussed supplemental screening with a provider, 11.3% of whom discussed the risks, and 49.5% discussed the benefits. In adjusted analysis, women living in DBN‐coverage states were more likely to discuss supplemental screening (27.5%) than women in non‐DBN states (13.6%); pairwise contrast 13.8% (95% CI, 2.1% to 25.6%; P = .01). They were also more likely to have received supplemental screening for increased breast density (19.3%) compared to women living in non‐DBN (9.9%); contrast 9.4% (95% CI, 1.6% to 17.3%; P = .01), Generic DBN (7.3%); difference 12.0% (95% CI, 4.6% to 19.4%; P =, In a nationally representative survey, women living in states with dense breast notification laws requiring insurance coverage for supplemental screening in the context of increased breast density were more likely to have discussed supplemental screening with a provider, and to have received supplemental screening. There was a limited knowledge of risks associated with supplemental screening, which underscores the need for increased awareness of risks and benefits, as well as the need to generate additional evidence regarding effectiveness of supplemental screening for women with increased breast density.

Importance Immune checkpoint inhibitors (ICIs) are part of standard of care for patients with many advanced solid tumors. Patients with poor performance status or organ dysfunction are traditionally ineligible to partake in pivotal randomized clinical trials of ICIs. Objective To assess ICI use and survival outcomes among patients with advanced cancers who are traditionally trial ineligible based on poor performance status or organ dysfunction. Design, Setting, and Participants This retrospective cohort study was conducted in 280 predominantly community oncology practices in the US and included 34 131 patients (9318 [27.3%] trial ineligible) who initiated first-line systemic therapy from January 2014 through December 2019 for newly diagnosed metastatic or recurrent nontargetable non–small cell lung, urothelial cell, renal cell, or hepatocellular carcinoma. Data analysis was performed from December 1, 2019, to June 1, 2021. Exposures Trial ineligibility (Eastern Cooperative Oncology Group performance status ≥2 or the presence of kidney or liver dysfunction); first-line systemic therapy. Main Outcomes and Measures The association between trial ineligibility and ICI monotherapy uptake was assessed using inverse probability–weighted (IPW) logistic regressions. The comparative survival outcomes following ICI and non-ICI therapy among trial-ineligible patients were assessed using treatment IPW survival analyses. Because we observed nonproportional hazards, we reported 12-month and 36-month restricted mean survival times (RMSTs) and time-varying hazard ratios (HRs) of less than 6 months and 6 months or greater. Results Among the overall cohort (n = 34 131), the median (IQR) age was 70 (62-77) years; 23 586 (69%) were White individuals, and 14 478 (42%) were women. Over the study period, the proportion of patients receiving ICI monotherapy increased from 0% to 30.2% among trial-ineligible patients and 0.1% to 19.4% among trial-eligible patients. Trial ineligibility was associated with increased ICI monotherapy use (IPW-adjusted odds ratio compared with non-ICI therapy, 1.8; 95% CI, 1.7-1.9). Among trial-ineligible patients, there were no overall survival differences between ICI monotherapy, ICI combination therapy, and non-ICI therapy at 12 months (RMST, 7.8 vs 7.7 vs 8.1 months) or 36 months (RMST, 15.0 vs 13.9 vs 14.4 months). Compared with non-ICI therapy, ICI monotherapy showed evidence of early harm (IPW-adjusted HR within 6 months, 1.2; 95% CI, 1.1-1.2) but late benefit (adjusted HR among patients who survived 6 months, 0.8; 95% CI, 0.7-0.8). Conclusions and Relevance In this cohort study, compared with trial-eligible patients, trial-ineligible patients with advanced cancers preferentially received first-line ICI therapy. A survival difference was not detected between ICI and non-ICI therapies among trial-ineligible patients. Positive results for ICI in phase 3 trials may not translate to this vulnerable population.

Key Points Question Is adoption of prostate magnetic resonance imaging (MRI) and genomic testing associated with increased use of observation rather than active treatment for prostate cancer? Findings In this cohort study of 65 530 commercially insured patients with prostate cancer, uptake of prostate MRI and genomic testing was associated with increased use of observation vs active treatment as initial management. Although prostate MRI, genomic testing, and observation increased overall, use was highly varied across hospital referral regions. Meaning The findings of this study suggest that adoption of technologies designed to improve decision-making may lead to perceivable reductions in overtreatment of prostate cancer, Importance The clinical decisions that arise from prostate magnetic resonance imaging (MRI) and genomic testing in patients with prostate cancer are not well understood. Objective To evaluate the association between regional uptake of prostate MRI and genomic testing and observation vs treatment for prostate cancer. Design, Setting, and Participants This retrospective cohort study of commercial insurance claims for prostate MRI and genomic testing included 65 530 patients 40 to 89 years of age newly diagnosed with prostate cancer from July 1, 2012, through June 30, 2019. Exposures Patient- and regional-level use of prostate MRI and genomic testing. Main Outcomes and Measures Observation vs definitive treatment for prostate cancer. Patient-level analyses examined the association between receipt of testing or residing in a hospital referral region (HRR) that adopted testing and observation. In regional-level analyses, the dependent variable was the change in the proportion of patients observed for prostate cancer at the HRR level between 2 periods: July 1, 2012, to June 30, 2014, and July 1, 2017, to June 20, 2019. The independent study variables included HRR-level changes in the proportion of men undergoing prostate MRI and genomic testing between these periods, and the models were adjusted for contextual factors associated with prostate cancer care and socioeconomic status. Results This study identified 65 530 patients, including 27 679 in the early period (mean [SD] age, 58.0 [5.9] years) and 37 851 in the late period (mean [SD] age, 59.0 [5.7] years). Use of prostate MRI increased significantly from 7.2% (95% CI, 6.9%-7.5%) to 16.7% (95% CI, 16.3%-17.1%) from the early to late period. Use of genomic testing increased significantly from 1.3% (95% CI, 1.1%-1.4%) to 12.7% (95% CI, 12.3%-13.0%) from the early to late period. Compared with the lowest, the highest HRR quartiles of prostate MRI and genomic testing uptake were associated with an adjusted 4.1% (SE, 1.1%; P, This cohort study assesses the association between the use of prostate magnetic resonance imaging and genomic testing and the initial management of prostate cancer.

Background/Aims: Over the past decade, numerous data sharing platforms have been launched, providing access to de-identified individual patient-level data and supporting documentation. We evaluated the characteristics of prominent clinical data sharing platforms, including types of studies listed as available for request, data requests received, and rates of dissemination of research findings from data requests. Methods: We reviewed publicly available information listed on the websites of six prominent clinical data sharing platforms: Biological Specimen and Data Repository Information Coordinating Center, ClinicalStudyDataRequest.com , Project Data Sphere, Supporting Open Access to Researchers–Bristol Myers Squibb, Vivli, and the Yale Open Data Access Project. We recorded key platform characteristics, including listed studies and available supporting documentation, information on the number and status of data requests, and rates of dissemination of research findings from data requests (i.e. publications in a peer-reviewed journals, preprints, conference abstracts, or results reported on the platform’s website). Results: The number of clinical studies listed as available for request varied among five data sharing platforms: Biological Specimen and Data Repository Information Coordinating Center (n = 219), ClinicalStudyDataRequest.com (n = 2,897), Project Data Sphere (n = 154), Vivli (n = 5426), and the Yale Open Data Access Project (n = 395); Supporting Open Access to Researchers did not provide a list of Bristol Myers Squibb studies available for request. Individual patient-level data were nearly always reported as being available for request, as opposed to only Clinical Study Reports (Biological Specimen and Data Repository Information Coordinating Center = 211/219 (96.3%); ClinicalStudyDataRequest.com = 2884/2897 (99.6%); Project Data Sphere = 154/154 (100.0%); and the Yale Open Data Access Project = 355/395 (89.9%)); Vivli did not provide downloadable study metadata. Of 1201 data requests listed on ClinicalStudyDataRequest.com , Supporting Open Access to Researchers–Bristol Myers Squibb, Vivli, and the Yale Open Data Access Project platforms, 586 requests (48.8%) were approved (i.e. data access granted). The majority were for secondary analyses and/or developing/validating methods ( ClinicalStudyDataRequest.com = 262/313 (83.7%); Supporting Open Access to Researchers–Bristol Myers Squibb = 22/30 (73.3%); Vivli = 63/84 (75.0%); the Yale Open Data Access Project = 111/159 (69.8%)); four were for re-analyses or corroborations of previous research findings ( ClinicalStudyDataRequest.com = 3/313 (1.0%) and the Yale Open Data Access Project = 1/159 (0.6%)). Ninety-five (16.1%) approved data requests had results disseminated via peer-reviewed publications ( ClinicalStudyDataRequest.com = 61/313 (19.5%); Supporting Open Access to Researchers–Bristol Myers Squibb = 3/30 (10.0%); Vivli = 4/84 (4.8%); the Yale Open Data Access Project = 27/159 (17.0%)). Forty-two (6.8%) additional requests reported results through preprints, conference abstracts, or on the platform’s website ( ClinicalStudyDataRequest.com = 12/313 (3.8%); Supporting Open Access to Researchers–Bristol Myers Squibb = 3/30 (10.0%); Vivli = 2/84 (2.4%); Yale Open Data Access Project = 25/159 (15.7%)). Conclusion: Across six prominent clinical data sharing platforms, information on studies and request metrics varied in availability and format. Most data requests focused on secondary analyses and approximately one-quarter of all approved requests publicly disseminated their results. To further promote the use of shared clinical data, platforms should increase transparency, consistently clarify the availability of the listed studies and supporting documentation, and ensure that research findings from data requests are disseminated.

This cross-sectional study examines the proportion of US nonprofit hospitals with community health needs assessments and implementation strategies as required by the Patient Protection and Affordable Care Act.

ObjectivesTo examine company characteristics associated with better transparency and to apply a tool used to measure and improve clinical trial transparency among large companies and drugs, to smaller companies and biologics.DesignCross-sectional descriptive analysis.Setting and participantsNovel drugs and biologics Food and Drug Administration (FDA) approved in 2016 and 2017 and their company sponsors.Main outcome measuresUsing established Good Pharma Scorecard (GPS) measures, companies and products were evaluated on their clinical trial registration, results dissemination and FDA Amendments Act (FDAAA) implementation; companies were ranked using these measures and a multicomponent data sharing measure. Associations between company transparency scores with company size (large vs non-large), location (US vs non-US) and sponsored product type (drug vs biologic) were also examined.Results26% of products (16/62) had publicly available results for all clinical trials supporting their FDA approval and 67% (39/58) had public results for trials in patients by 6 months after their FDA approval; 58% (32/55) were FDAAA compliant. Large companies were significantly more transparent than non-large companies (overall median transparency score of 95% (IQR 91–100) vs 59% (IQR 41–70), pConclusionsIt was feasible to apply the GPS transparency measures and ranking tool to non-large companies and biologics. Large companies are significantly more transparent than non-large companies, driven by better data sharing procedures and implementation of FDAAA trial reporting requirements. Greater research transparency is needed, particularly among non-large companies, to maximise the benefits of research for patient care and scientific innovation.

Background Current reporting of Covid-19 mortality data by race and ethnicity across the United States could bias our understanding of population-mortality disparities. Moreover, stark differences in age distribution by race and ethnicity groups are seldom accounted for in analyses. Methods To address these gaps, we conducted a cross-sectional study using publicly-reported Covid-19 mortality data to assess the quality of race and ethnicity data (Black, Latinx, white), and estimated age-adjusted disparities using a random effects meta-analytic approach. Results We found only 28 states, and NYC, reported race and ethnicity-stratified Covid-19 mortality along with large variation in the percent of missing race and ethnicity data by state. Aggregated relative risk of death estimates for Black compared to the white population was 3.57 (95% CI: 2.84-4.48). Similarly, Latinx population displayed 1.88 (95% CI: 1.61-2.19) times higher risk of death than white patients. Discussion In states providing race and ethnicity data, we identified significant population-level Covid-19 mortality disparities. We demonstrated the importance of adjusting for age differences across population groups to prevent underestimating disparities in younger population groups. The availability of high-quality and comprehensive race and ethnicity data is necessary to address factors contributing to inequity in Covid-19 mortality.

This study examines price availability and variation for thyroid cancer care at National Cancer Institute (NCI)–Designated Cancer Centers following a 2021 CMS policy reform requiring hospitals to disclose commercial payer-specific negotiated prices for all items and services.

PURPOSE: Hospitalizations during cancer treatment are costly, can impair quality of life, and negatively affect therapy completion. Our objective was to identify risk factors for unplanned hospitalization among older adults receiving chemotherapy. METHODS: This is a secondary analysis of a multisite cohort study (N = 750) of patients ≥ 65 years of age evaluated with a geriatric assessment (GA) to predict chemotherapy toxicity. The primary outcome of this analysis was unplanned hospitalizations during treatment; the secondary outcome was length of stay (LOS) of the first hospitalization. Independent variables included pretreatment GA measures, laboratory values, cancer type and stage, and treatment intensity characteristics. We used logistic regression to estimate the odds of hospitalization and generalized linear models for LOS in multivariable analyses. RESULTS: The sample median age was 72 years (range, 65-94 years); 59% had stage IV disease. At least one unplanned hospitalization occurred in 193 patients (25.7%) during receipt of chemotherapy. In multivariable analyses controlling for cancer type, the following baseline characteristics were significantly associated with increased odds of hospitalization: needing help bathing or dressing (odds ratio [OR], 1.8; 95% CI, 1.0 to 3.1), polypharmacy (≥ 5 meds) (OR, 1.6; 95% CI, 1.1 to 2.4), more comorbid conditions (OR, 1.1; 95% CI, 1.0 to 1.3), availability of someone to take them to the doctor (OR, 2.0; 95% CI, 1.0 to 4.1), CrCl < 60 mL/min (OR, 1.7; 95% CI, 1.1 to 2.4), and albumin < 3.5 g/dL (OR, 1.8; 95% CI, 1.2 to 2.8). In multivariable analyses, older age, self-reported presence of liver or kidney disease, living alone and depressive symptoms were associated with longer LOS. CONCLUSION: Readily available GA variables and laboratory data, but not age, were associated with unplanned hospitalizations among older adults receiving chemotherapy. If validated, these data can inform prediction models and the design of interventions to decrease unplanned hospitalizations.

Background Digital breast tomosynthesis (DBT) may have a higher cancer detection rate and lower recall compared with 2-dimensional (2 D) mammography for breast cancer screening. The goal of this study was to evaluate screening outcomes with DBT in a real-world cohort and to characterize the population health impact of DBT as it is widely adopted. Methods This observational study evaluated breast cancer screening outcomes among women screened with 2 D mammography vs DBT. We used deidentified administrative data from a large private health insurer and included women aged 40-64 years screened between January 2015 and December 2017. Outcomes included recall, biopsy, and incident cancers detected. We used 2 complementary techniques: a patient-level analysis using multivariable logistic regression and an area-level analysis evaluating the relationship between population-level adoption of DBT use and outcomes. All statistical tests were 2-sided. Results Our sample included 7 602 869 mammograms in 4 580 698 women, 27.5% of whom received DBT. DBT was associated with modestly lower recall compared with 2 D mammography (113.6 recalls per 1000 screens, 99% confidence interval [CI] = 113.0 to 114.2 vs 115.4, 99% CI = 115.0 to 115.8, P Conclusions In a large population of privately insured women, DBT was associated with a slightly lower recall rate than 2 D mammography and a higher cancer detection rate. Whether this increased cancer detection improves clinical outcomes remains unknown.

This cross-sectional study investigates demographic data reporting and demographic representation by sex, age, and race/ethnicity in premarketing and postmarketing studies of novel cancer therapeutics., Key Points Question Are the demographic characteristics of patients enrolled in premarketing and postmarketing studies used by the US Food and Drug Administration (FDA) to evaluate the safety and efficacy of novel cancer therapeutics clearly reported and representative of the US cancer population? Findings In this cross-sectional study of 77 premarketing studies and 56 postmarketing studies for FDA-approved cancer therapeutics, there was inconsistent reporting of demographic data and underrepresentation of older adults and Black patients in premarketing and postmarketing studies of cancer therapeutics. Meaning Premarketing and postmarketing studies used by the FDA to evaluate novel cancer therapeutics may not adequately represent the US cancer population., Importance Adequate representation of demographic subgroups in premarketing and postmarketing clinical studies is necessary for understanding the safety and efficacy associated with novel cancer therapeutics. Objective To characterize and compare the reporting of demographic data and the representation of individuals by sex, age, and race in premarketing and postmarketing studies used by the Food and Drug Administration (FDA) to evaluate novel cancer therapeutics. Design, Setting, and Participants In this cross-sectional study, premarketing and postmarketing studies for novel cancer therapeutics approved by the FDA from 2012 through 2016 were identified. Study demographic information was abstracted from publicly available sources, and US cancer population demographic data was abstracted from US Cancer Statistics. Analyses were conducted from February 25 through September 21, 2020. Main Outcomes and Measures The percentages of trials reporting sex, age, and race/ethnicity were calculated, and participation to prevalence ratios (PPRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the US cancer population in each group. PPRs were constructed for premarketing and postmarketing studies and by cancer type. Underrepresentation was defined as PPR less than 0.8. Results From 2012 through 2016, the FDA approved 45 cancer therapeutics. The study sample included 77 premarketing studies and 56 postmarketing studies. Postmarketing studies, compared with premarketing studies, were less likely to report patient sex (42 studies reporting [75.0%] vs 77 studies reporting [100%]; P

Context Among adults with cancer, measures for high quality end-of-life care (EOLC) include avoidance of hospitalizations near end of life. For children with cancer, no measures exist to evaluate or improve EOLC, and adult quality measures may not apply. Objective We engaged key stakeholders to explore EOLC priorities for children with cancer and their families, and to examine relevance of existing adult EOLC quality measures for children with cancer. Methods In a multicenter qualitative study, we conducted interviews and focus groups with: adolescents and young adults (AYAs) with advanced cancer, parents of children with advanced cancer, bereaved parents, and interdisciplinary healthcare professionals. We transcribed, coded, and employed thematic analysis to summarize findings. Results We enrolled 54 stakeholders (25 parents [including 12 bereaved parents], 10 AYAs, and 19 healthcare professionals). Participants uniformly prioritized direct communication with children about preferences and prognosis, interdisciplinary care, symptom management, and honoring family preference for location of death. Many participants valued access to the emergency department or hospital for symptom management or supportive care, which diverges from measures for high quality EOLC in adults. Most wished to avoid mechanical ventilation and cardiopulmonary resuscitation. Notably, participants generally valued hospice; however, few understood hospice care or had utilized its services. Conclusion Childhood cancer stakeholders define high quality EOLC primarily through person-centered measures, characterizing half of existing adult-focused measures as limited in relevance to children. Future research should focus on developing techniques for person-centered quality measurement to capture attributes of greatest importance to children with cancer and their families.

Key Points Question Is there an association between sexual orientation and burnout among US medical students, and is this association mediated by experiences of mistreatment? Findings Cross-sectional surveys of 2016 and 2017 graduating US medical students showed significantly higher rates of perceived mistreatment and burnout symptoms among lesbian, gay, or bisexual (LGB) medical students compared with heterosexual students. Perceived experiences of mistreatment mediated the association between LGB sexual orientation and burnout but did not completely account for excess burnout reported by LGB students. Meaning The findings of this study suggest that medical students in sexual minority groups report increased symptoms of burnout regardless of their perceived experiences of mistreatment., Importance Medical trainee burnout is associated with poor quality care and attrition. Medical students in sexual minority groups report fear of discrimination and increased mistreatment, but the association between sexual orientation, burnout, and mistreatment is unknown. Objective To evaluate whether medical student burnout differs by sexual orientation and whether this association is mediated by experiences of mistreatment. Design, Setting, and Participants This cross-sectional study surveyed US medical students graduating from Association of American Medical Colleges (AAMC)–accredited US allopathic medical schools who responded to the AAMC graduation questionnaire in 2016 and 2017. Statistical analyses were performed from March 15, 2019, to July 2, 2020, and from November 20 to December 9, 2020. Main Outcomes and Measures Burnout was measured using the Oldenburg Burnout Inventory for Medical Students, and sexual orientation was categorized as either heterosexual or lesbian, gay, or bisexual (LGB). Logistic regression models were constructed to evaluate the association between sexual orientation and experiencing burnout (defined as being in the top quartile of exhaustion and disengagement burnout dimensions) and to test the mediating association of mistreatment. Results From 2016 to 2017, 30 651 students completed the AAMC Graduation Questionnaire, and 26 123 responses were analyzed. Most respondents were younger than 30 years (82.9%) and White (60.3%). A total of 13 470 respondents (51.6%) were male, and 5.4% identified as LGB. Compared with heterosexual students, a greater proportion of LGB students reported experiencing mistreatment in all categories, including humiliation (27.0% LGB students vs 20.7% heterosexual students; P, This cross-sectional study evaluates whether medical student burnout differs by sexual orientation and whether this association is mediated by experiences of mistreatment.

Background: Aggressive care at the end of life (EOL) is a persistent issue for patients with stage IV nonsmall cell lung cancer (NSCLC). We evaluated the use of concurrent care (CC) with hospice care and cancer-directed treatment simultaneously within the Veteran's Health Administration (VHA) and aggressive care at the EOL. Objective: To determine whether VHA facility-level CC is associated with changes in aggressive care at the EOL. Design/Setting: Veterans with stage IV NSCLC who died between 2006 and 2012 and received lung cancer care within the VHA. Measurements: The primary outcome was aggressive care at EOL (i.e., hospital admissions, chemotherapy, and intensive care unit) within the last month of life. To compare aggressive care across VHA facilities, we used a random intercept multilevel logistic regression model to examine the association between facility-level CC within each study year (

This cohort study evaluates the association between programmed cell death ligand 1 testing and first-line immune checkpoint inhibitor use in patients with advanced non–small cell lung cancer., Key Points Question How was programmed cell death ligand 1 (PD-L1) testing used to select immune checkpoint inhibitor treatment for patients with advanced non–small cell lung cancer (NSCLC)? Findings In this cohort study of 45 631 patients with advanced NSCLC, substantial increases occurred in the use of first-line immune checkpoint inhibitor treatment among patients with low or negative PD-L1 expression and those without documented PD-L1 testing. These increases were consistent with the dissemination of new evidence supporting benefit in these groups. Meaning The findings suggest that use and interpretation of the PD-L1 biomarker to guide first-line treatment for advanced NSCLC was rapidly responsive to new clinical evidence., Importance Initial approval for immune checkpoint inhibitors (ICIs) for treatment of advanced non–small cell lung cancer (NSCLC) was limited to patients with high levels of programmed cell death ligand 1 (PD-L1) expression. However, in the period after approval, it is not known how new evidence supporting efficacy of these treatments in patients with low or negative PD-L1 expression was incorporated into real-world practice. Objective To evaluate the association between PD-L1 testing and first-line ICI use. Design, Setting, and Participants This retrospective cohort study (January 1, 2011, to December 31, 2018) used a deidentified nationwide electronic health record–derived database reflecting real-world care at more than 280 US community and academic cancer clinics (approximately 800 sites of care). Patients included those with advanced NSCLC without other identifiable variations diagnosed in the period after the US Food and Drug Administration’s initial first-line approval of ICIs for patients with high PD-L1 expression (≥50%). Exposure First-line ICI treatment. Main Outcomes and Measures Patterns of PD-L1 testing and first-line ICI treatment among all patients and patients stratified by tumor histologic type (squamous vs nonsquamous). Results A total of 45 631 patients (mean [SD] age, 68.4 [9.6] years; 21 614 [47.4%] female) with advanced NSCLC were included in the study. PD-L1 testing increased from 468 (7.2%) in 2015 to 4202 (73.2%) in 2018. Within a subset of 7785 patients receiving first-line treatment in the period after first-line approval of pembrolizumab, those who received PD-L1 testing had a greater odds of receiving an ICI (odds ratio, 2.11; 95% CI, 1.89-2.36). Among patients with high PD-L1 expression (≥50%), 1541 (83.5%) received first-line ICI treatment; 776 patients (40.3%) with low PD-L1 expression (1%-49%) and 348 (32.3%) with negative PD-L1 expression (0%) also received ICIs. In addition, 755 untested patients (32.8%) were treated with a first-line ICI. The proportion of patients who received ICIs without PD-L1 testing increased during the study period (59 [17%] in quarter 4 of 2016 to 141 [53.8%] in quarter 4 of 2018). Conclusions and Relevance In this study, use of first-line ICI treatment increased among patients with advanced NSCLC with negative, low, or untested PD-L1 expression status in 2016 through 2018. These findings suggest that national practice was rapidly responsive to new clinical evidence rather than adhering to regulatory guidance in place at the time.

Decreased prostate-specific antigen screening since 2008 has generated much concern, including report of recent increase in metastatic prostate cancer incidence among older men. Although increased metastatic disease was temporally proceeded by decreased screening and decreased localized prostate cancer at diagnosis, it is unclear whether the 2 trends are geographically connected. We therefore used the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database to assess geographic-specific associations between changes in localized (2008-2011) and later changes in metastatic prostate cancer incidence (2012-2015). We examined trends from 200 health-care service areas (HSAs) within SEER 18 registries. While on average for each HSA, localized incidence decreased by 27.4 and metastatic incidence increased by 2.3 per 100 000 men per year, individual HSA-level changes in localized incidence did not correlate with later changes in metastatic disease. Decreased detection of localized disease may not fully explain the recent increase in metastatic disease at diagnosis.

Purpose To examine the associations between sentinel lymph node biopsy (SLNB) and complications among older patients who underwent breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Methods We identified women from the Surveillance, Epidemiology, and End Results–Medicare dataset aged 67–94 years diagnosed during 1998–2011 with DCIS who underwent BCS as initial treatment. We assessed incidence of complications, including lymphedema, wound infection, seroma, or pain, within 9 months of diagnosis. We used Mahalanobis matching and generalized linear models to estimate the associations between SLNB and complications. Results Our sample consisted of 15,515 beneficiaries, 2409 (15.5%) of whom received SLNB. Overall, 16.8% of women who received SLNB had complications, compared with 11.3% of women who did not receive SLNB (p

This study uses administrative claims from an insurance database to examine adoption of digital breast tomosynthesis for cancer screening and describe regional patterns and sociodemographic characteristics associated with its use.

Objectives. To evaluate the association of state dense breast notification (DBN) laws with use of supplemental tests and cancer diagnosis after screening mammography. Methods. We examined screening mammograms (n = 1 441 544) performed in 2014 and 2015 among privately insured women aged 40 to 59 years living in 9 US states that enacted DBN laws in 2014 to 2015 and 25 US states with no DBN law in effect. DBN status at screening mammography was categorized as no DBN, generic DBN, and DBN that mandates notification of possible benefits of supplemental screening (DBN+SS). We used logistic regression to examine the change in rate of supplemental ultrasound, magnetic resonance imaging, breast biopsy, and breast cancer detection. Results. DBN+SS laws were associated with 10.5 more ultrasounds per 1000 mammograms (95% CI = 3.0, 17.6 per 1000; P = .006) and 0.37 more breast cancers detected per 1000 mammograms (95% CI = 0.05, 0.69 per 1000; P = .02) compared with no DBN law. No significant differences were found for generic DBN laws in either ultrasound or cancer detection. Conclusions. DBN legislation is associated with increased use of ultrasound and cancer detection after implementation only when notification of the possible benefits of supplemental screening is required.

This study examines the change in matriculant sex, race, and ethnicity in US medical schools after the 2009 implementation of diversity standards from the Liaison Committee on Medical Education (LCME) meant to broaden diversity among qualified applicants.

The Yale University Open Data Access (YODA) Project has facilitated access to clinical trial data since 2013. The purpose of this article is to provide an overview of the Project, describe key decisions that were made when establishing data sharing policies, and suggest how our experience and the experiences of our first two data generator partners, Medtronic, Inc. and Johnson & Johnson, can be used to enhance other ongoing or future initiatives.

Purpose In a recent randomized, open-label trial (ECHELON-1), brentuximab vedotin (BV) combined with doxorubicin, vinblastine, and dacarbazine (AVD+BV) decreased the risk of progression in adults diagnosed with stage III or IV Hodgkin lymphoma (HL) compared with standard bleomycin-containing chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]). However, the cost effectiveness of incorporating BV (US$6,970 per 50-mg vial) into the first-line setting is unknown. Patients and Methods We constructed a Markov decision-analytic model to measure the costs and clinical outcomes for AVD+BV compared with ABVD as first-line therapy in a cohort of patients with stage III or IV HL. Transition probabilities were estimated from ECHELON-1 by fitting parametric survival distributions. Lifetime direct health care costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for AVD+BV compared with ABVD from a US payer perspective. Our model was also used to estimate BV price reductions that would achieve more favorable cost effectiveness under indication-specific pricing. Results AVD+BV was associated with an improvement of 0.56 QALYs compared with treatment with standard ABVD. However, incorporating BV into first-line therapy led to significantly higher lifetime health care costs ($361,137 v $184,291), causing the ICER for AVD+BV to be $317,254 per QALY. If indication-specific pricing were implemented, acquisition costs for BV used in the first-line setting would need to be reduced by 56% to 73% for ICERs of $150,000 to $100,000 per QALY, respectively. Conclusion Substituting BV for bleomycin during first-line therapy for stage III or IV HL is unlikely to be cost effective under current drug pricing. Should indication-specific pricing be implemented, significant price reductions for BV used in the first-line setting would be needed to reduce ICERs to more widely acceptable values.

Amid growing excitement for immune checkpoint inhibitors of programmed death protein 1 (anti-PD1 agents), little is known about whether race- or sex-based disparities exist in their use. In this observational study, we constructed a large and mostly community-based cohort of patients with advanced stage cancers, including melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma, to compare the odds of receiving systemic treatment with or without anti-PD1 agents by race and by sex. In multivariable models that adjusted for age, stage, and number of prior anticancer therapies, we found no significant race-based disparities in anti-PD1 treatment. However, among patients with NSCLC, males had significantly higher odds of receiving anti-PD1 treatment compared with females (odds ratio 1.13, 95% confidence interval 1.02–1.24, p = .02). This finding suggests that as anti-PD1 agents enter the market to transform patient care, it will be critical to monitor for disparities in the use of these drugs.

IMPORTANCE: The US Food and Drug Administration (FDA) is increasing its pace of approvals for novel cancer therapeutics, including for immune checkpoint inhibitors of programmed cell death 1 protein (anti–PD-1 agents). However, little is known about how quickly anti–PD-1 agents agents reach eligible patients in practice or whether such patients differ from those studied in clinical trials that lead to FDA approval (pivotal clinical trials). OBJECTIVES: To assess the speed with which anti–PD-1 agents agents reached eligible patients in practice and to compare the ages of patients treated in clinical practice with the ages of those treated in pivotal clinical trials. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study, performed from January 1, 2011, through August 31, 2016, included patients from the Flatiron Health Network who were eligible for anti–PD-1 agents treatment of selected cancer types, which included melanoma, non–small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). MAIN OUTCOMES AND MEASURES: Cumulative proportions of eligible patients receiving anti–PD-1 agents treatment and their age distributions. RESULTS: The study identified 3089 patients who were eligible for anti–PD-1 agents treatment (median age, 66 [interquartile range, 56-75] years for patients with melanoma, 66 [interquartile range, 58-72] years for patients with RCC, and 67 [interquartile range, 59-74] years for patients with NSCLC; 1742 male [56.4%] and 1347 [43.6%] female; 2066 [66.9%] white). Of these patients, 2123 (68.7%) received anti–PD-1 agents treatment, including 439 eligible patients with melanoma (79.1%), 1417 eligible patients with NSCLC (65.6%), and 267 eligible patients with RCC (71.2%). Within 4 months after FDA approval, greater than 60% of eligible patients in each cohort had received anti–PD-1 agents treatment. Overall, similar proportions of older and younger patients received anti–PD-1 agents treatment during the first 9 months after FDA approval. However, there were significant differences in age between clinical trial participants and patients receiving anti–PD-1 agents treatment in clinical practice, with more patients being older than 65 years in clinical practice (range, 327 of 1365 [60.6%] to 46 of 72 [63.9%]) than in pivotal clinical trials (range, 38 of 120 [31.7%] to 223 of 544 [41.0%]; all P

Purpose Prior studies examining cost effectiveness of the 21-gene assay (Oncotype DX [ODX]) for women with hormone receptor–positive, early-stage breast cancer have yielded disparate results. We aimed to explore why these analyses may have yielded different conclusions. Methods We conducted a systematic literature review of cost-effectiveness analyses (CEAs) of ODX. We examined the extent to which the structure of CEA modeling, the assumptions of the models, and the selection of input parameters influenced cost-effectiveness estimates. We also explored the prevalence of industry funding and whether industry funding was associated with study designs favoring ODX. Results We identified 27 analyses, 15 of which received industry funding. In 18 studies, the clinical characteristics (eg, tumor size and grade) commonly used to make chemotherapy decisions were not incorporated into simulation modeling; thus, these studies would favor ODX being cost effective and might not reflect clinical practice. Most studies ignored the heterogeneous effect of ODX on chemotherapy use; only five studies assumed that ODX would increase chemotherapy use for clinically low-risk patients but decrease chemotherapy use for clinically high-risk patients. No study used population-based joint distributions of ODX recurrence score and tumor characteristics, and 12 studies inappropriately assumed that chemotherapy would increase distant recurrence for the low recurrence score group; both approaches overestimated the benefits of ODX. Industry-funded studies tended to favor ODX; all five studies that reported ODX as being cost saving were industry funded. In contrast, two studies that reported an incremental cost-effectiveness ratio > $50,000 per quality-adjusted life-year were not funded by industry. Conclusion Although a majority of published analyses indicated that ODX is cost effective, they incorporated study designs that can increase the risk of bias.

Introduction Although prior research has demonstrated lower lung cancer survival in England than in the United States, more detailed comparisons are needed. We conducted a population-based analysis to compare diagnostic, treatment, and survival patterns. Methods Data from cancer registries and administrative databases were linked for older patients with a diagnosis of NSCLC in England and the United States (2008–2012). We compared patient and clinical characteristics, as well as the distribution of age-standardized receipt of treatment by stage. We compared relative survival overall by stage and treatment. Finally, we assessed the degree to which stage distribution and stage-specific survival contributed to survival differences. Results Among patients age 66 years or older with a diagnosis of NSCLC in England (n = 86,978) and the United States (n = 84,415), the rate of pathological confirmation was 63% in England compared with 85% in the United States (a 22.2% difference [99% confidence interval: 22.8%–21.7%]). The rate of receipt of active treatment was lower in England than in the United States (46% versus 60%, for a difference of 14.0% [99% confidence interval: 13.3%–14.7%]). In England, we identified 98 excess deaths per 1000 patients with pathologically confirmed NSCLC; these additional deaths could be partially mitigated by adjusting stage at diagnosis (reduction to 54 excess deaths) or stage-specific survival (reduction to 36 excess deaths). Conclusions Compared with patients with NSCLC in the United States, patients with NSCLC in England are less likely to present with early-stage disease and receive treatment and are more likely to die. Future work should explore whether the intensity of resources directed to diagnostic and therapeutic activity may help mitigate disparities in outcomes.

It is uncertain whether the replication of systematic reviews, particularly those with the same objectives and resources, would employ similar methods and/or arrive at identical findings. We compared the results and conclusions of two concurrent systematic reviews undertaken by two independent research teams provided with the same objectives, resources, and individual participant-level data. Two centers in the USA and UK were each provided with participant-level data on 17 multi-site clinical trials of recombinant human bone morphogenetic protein-2 (rhBMP-2). The teams were blinded to each other’s methods and findings until after publication. We conducted a retrospective structured comparison of the results of the two systematic reviews. The main outcome measures included (1) trial inclusion criteria; (2) statistical methods; (3) summary efficacy and risk estimates; and (4) conclusions. The two research teams’ meta-analyses inclusion criteria were broadly similar but differed slightly in trial inclusion and research methodology. They obtained similar results in summary estimates of most clinical outcomes and adverse events. Center A incorporated all trials into summary estimates of efficacy and harms, while Center B concentrated on analyses stratified by surgical approach. Center A found a statistically significant, but small, benefit whereas Center B reported no advantage. In the analysis of harms, neither showed an increased cancer risk at 48 months, although Center B reported a significant increase at 24 months. Conclusions reflected these differences in summary estimates of benefit balanced with small but potentially important risk of harm. Two independent groups given the same research objectives, data, resources, funding, and time produced broad general agreement but differed in several areas. These differences, the importance of which is debatable, indicate the value of the availability of data to allow for more than a single approach and a single interpretation of the data. PROSPERO CRD42012002040 and CRD42012001907 .

Purpose To identify the information older women with early-stage breast cancer need when making radiation therapy decisions, and who patients identify as the main decision maker. Methods and Materials We surveyed (through face-to-face interview, telephone, or mail) women aged ≥65 years who received lumpectomy and were considering or receiving adjuvant radiation therapy for early-stage breast cancer. The survey instrument was constructed with input from patient and professional advisory committees, including breast cancer survivors, advocates of breast cancer care and aging, clinicians, and researchers. Participants rated the importance (on a 4-point scale) of 24 statements describing the benefits, side effects, impact on daily life, and other issues of radiation therapy in relation to radiation therapy decision making. Participants also designated who was considered the key decision maker. Results The response rate was 56.4% (93 of 165). Mean age was 72.5 years, ranging from 65 to 93 years. More than 96% of participants indicated they were the main decision maker on receiving radiation therapy. There was wide variation in information needs regarding radiation therapy decision making. Participants rated a mean of 18 (range, 3-24) items as "essential." Participants rated items related to benefits highest, followed by side effects. Participants who were older than 75 years rated 13.9 questions as essential, whereas participants aged ≤74 years rated 18.7 as essential ( P =.018). Conclusions Older women desire information and have more agency and input in the decision-making process than prior literature would suggest. The variation in information needs indicates that future decision support tools should provide options to select what information would be of interest to the participants.

The aim of the study was to compare costs associated with excision of routine cavity shave margins (CSM) versus standard partial mastectomy (PM) in patients with breast cancer.Excision of CSM reduces re-excision rates by more than 50%. The economic implications of this is, however, unclear.Between October 21, 2011 and November 25, 2013, 235 women undergoing PM for Stage 0-III breast cancer were randomized to undergo either standard PM ("no shave", n = 116) or have additional CSM taken ("shave", n = 119). Costs from both a payer and a hospital perspective were measured for index surgery and breast cancer surgery-related care through subsequent 90 days.The 2 groups were well-matched in terms of baseline characteristics. Those in the "shave" group had a longer operative time at the initial surgery (median 76 vs 66 min, P0.01), but a lower re-excision rate for positive margins (13/119 = 10.9% vs 32/116 = 27.6%, P0.01). Actual direct hospital costs associated with operating room time ($1315 vs. $1137, P = 0.03) and pathology costs ($1195 vs $795, P0.01) were greater for the initial surgery in patients in the "shave" group. Taking into account the index surgery and the subsequent 90 days, there was no significant difference in cost from either the payer ($10,476 vs $11,219, P = 0.40) or hospital perspective ($5090 vs $5116, P = 0.37) between the "shave" and "no shave" groups.Overall costs were not significantly different between the "shave" and "no shave" groups due to significantly fewer reoperative surgeries in the former.

Objective To characterise experiences using clinical research data shared through the National Institutes of Health (NIH)9s Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) clinical research data repository, along with data recipients’ perceptions of the value, importance and challenges with using BioLINCC data. Design and setting Cross-sectional web-based survey. Participants All investigators who requested and received access to clinical research data from BioLINCC between 2007 and 2014. Main outcome measures Reasons for BioLINCC data request, research project plans, interactions with original study investigators, BioLINCC experience and other project details. Results There were 536 investigators who requested and received access to clinical research data from BioLINCC between 2007 and 2014. Of 441 potential respondents, 195 completed the survey (response rate=44%); 89% (n=174) requested data for an independent study, 17% (n=33) for pilot/preliminary analysis. Commonly cited reasons for requesting data through BioLINCC were feasibility of collecting data of similar size and scope (n=122) and insufficient financial resources for primary data collection (n=76). For 95% of respondents (n=186), a primary research objective was to complete new research, as opposed to replicate prior analyses. Prior to requesting data from BioLINCC, 18% (n=36) of respondents had contacted the original study investigators to obtain data, whereas 24% (n=47) had done so to request collaboration. Nearly all (n=176; 90%) respondents found the data to be suitable for their proposed project; among those who found the data unsuitable (n=19; 10%), cited reasons were data too complicated to use (n=5) and data poorly organised (n=5). Half (n=98) of respondents had completed their proposed projects, of which 67% (n=66) have been published. Conclusions Investigators were primarily using clinical research data from BioLINCC for independent research, making use of data that would otherwise have not been feasible to collect.