Evaluating biologics and their biosimilars using a distributed research network to demonstrate real-world outcomes.

BACKGROUND: The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) was initiated in anticipation of biosimilars entering the U.S. market. OBJECTIVE: To present descriptive and comparative analyses of innovator compounds and biosimilars to address patient and physician concerns and potentially facilitate greater acceptance and adoption of biosimilars. METHODS: The BBCIC leverages Sentinel\u27s distributed research network (DRN) and the collaboration includes 18 founding member organizations from managed care integrated delivery networks, pharmacy benefit managers, and industry sponsors. Initial descriptive analysis (DA) studies were conducted to characterize the DRN data. Primary outcome measures included: (1) febrile neutropenia hospitalizations among first cycle granulocyte-colony stimulating factor (G-CSF) prophylaxis for breast and lung cancer (2) adverse events following erythropoietin stimulating agent (ESA) use in hemodialysis; (3) major adverse cardiac and hypoglycemia events following long-acting insulin (LAI) use in Types 1 and 2 diabetes and; (4) hospitalizations for serious infections following anti-inflammatory (AI) use for rheumatoid arthritis, psoriatic and gastrointestinal conditions. RESULTS: (1) G-CSF prophylaxis can be discerned from treatment and rare safety events were identified; (2) DRN ESA data lack granularity and future studies will be conducted using the Medicare ESRD data set; (3) major adverse cardiac and hypoglycemia events associated with LAIs are comparable to other observational trials; and (4) serious infection outcomes are comparable to other AI observational trials. In addition, it was identified that methods workgroups are needed to define best practices for switching patterns in comparative effectiveness research (CER) studies, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CD) to ICD-10-CM mapping will be needed, and monitoring of data partner capture of National Drug Code and Healthcare Common Procedure Coding System codes is necessary. CONCLUSIONS: Outcomes comparable to those in the published literature were demonstrated for G-CSFs, LAIs, and AIs. ESA data do not contain needed granularity and future research will use alternative data sources. Following sufficient biosimilar exposures, CER studies will be initiated to assess the safety and effectiveness of biosimilars compared with innovators. In preparation for the planned CER studies, workgroups are identifying best practices to be implemented

Prospective influenza vaccine safety surveillance using fresh data in the Sentinel System†

Abstract Purpose To develop the infrastructure to conduct timely active surveillance for safety of influenza vaccines and other medical countermeasures in the Sentinel System (formerly the Mini‐Sentinel Pilot), a Food and Drug Administration‐sponsored national surveillance system that typically relies on data that are mature, settled, and updated quarterly. Methods: Three Data Partners provided their earliest available (“fresh”) cumulative claims data on influenza vaccination and health outcomes 3–4 times on a staggered basis during the 2013–2014 influenza season, collectively producing 10 data updates. We monitored anaphylaxis in the entire population using a cohort design and seizures in children ≤4 years of age using both a self‐controlled risk interval design (primary) and a cohort design (secondary). After each data update, we conducted sequential analysis for inactivated (IIV) and live (LAIV) influenza vaccines using the Maximized Sequential Probability Ratio Test, adjusting for data‐lag. Results: Most of the 10 sequential analyses were conducted within 6 weeks of the last care‐date in the cumulative dataset. A total of 6 682 336 doses of IIV and 782 125 doses of LAIV were captured. The primary analyses did not identify any statistical signals following IIV or LAIV. In secondary analysis, the risk of seizures was higher following concomitant IIV and PCV13 than historically after IIV in 6‐ to 23‐month‐olds (relative risk = 2.7), which requires further investigation. Conclusions: The Sentinel System can implement a sequential analysis system that uses fresh data for medical product safety surveillance. Active surveillance using sequential analysis of fresh data holds promise for detecting clinically significant health risks early. Limitations of employing fresh data for surveillance include cost and the need for careful scrutiny of signals. © 2015 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd

Risk of Guillain-Barre syndrome after meningococcal conjugate vaccination

Item does not contain fulltextPURPOSE: A new meningococcal conjugate vaccine (MCV4) was introduced in 2005. Shortly after, case reports of Guillain-Barre syndrome (GBS), a serious demyelinating disease, began to be reported to the Vaccine Adverse Event Reporting System. In 2006, the Centers for Disease Control and Prevention and the Food and Drug Administration requested the evaluation of GBS risk after MCV4 vaccination. We conducted a study to assess the risk of GBS after MCV4 vaccination using health plan administrative and claims data together with the review of primary medical records of potential cases. METHODS: Retrospective cohort study among 12.6 million 11- to 21-year-old members of five US health plans with a total membership of 50 million. Automated enrollment and medical claims data from March 2005 through August 2008 were used to identify the population, the vaccinations administered, and the medical services associated with possible GBS. Medical records were reviewed and adjudicated by a neurologist panel to confirm cases of GBS. The study used distributed data analysis methods that minimized sharing of protected health information. RESULTS: We confirmed 99 GBS cases during 18,322,800 person-years (5.4/1,000,000 person-years). More than 1.4 million MCV4 vaccinations were observed. No confirmed cases of GBS occurred within 6 weeks after vaccination. The upper 95% CI for the attributable risk of GBS associated with MCV4 is estimated as 1.5 cases per 1,000,000 doses. CONCLUSIONS: Among members of five US health plans, MCV4 vaccination was not associated with increased GBS risk. Copyright (c) 2012 John Wiley & Sons, Ltd

Factors associated with anxiety during the first two years of the COVID-19 pandemic in the United States: An analysis of the COVID-19 Citizen Science study.

COVID-19 increased the prevalence of clinically significant anxiety in the United States. To investigate contributing factors we analyzed anxiety, reported online via monthly Generalized Anxiety Disorders-7 (GAD-7) surveys between April 2020 and May 2022, in association with self-reported worry about the health effects of COVID-19, economic difficulty, personal COVID-19 experience, and subjective social status. 333,292 anxiety surveys from 50,172 participants (82% non-Hispanic white; 73% female; median age 55, IQR 42-66) showed high levels of anxiety, especially early in the pandemic. Anxiety scores showed strong independent associations with worry about the health effects of COVID-19 for oneself or family members (GAD-7 score +3.28 for highest vs. lowest category; 95% confidence interval: 3.24, 3.33; p<0.0001 for trend) and with difficulty paying for basic living expenses (+2.06; 1.97, 2.15, p<0.0001) in multivariable regression models after adjusting for demographic characteristics, COVID-19 case rates and death rates, and personal COVID-19 experience. High levels of COVID-19 health worry and economic stress were each more common among participants reporting lower subjective social status, and median anxiety scores for those experiencing both were in the range considered indicative of moderate to severe clinical anxiety disorders. In summary, health worry and economic difficulty both contributed to high rates of anxiety during the first two years of the COVID-19 pandemic in the US, especially in disadvantaged socioeconomic groups. Programs to address both health concerns and economic insecurity in vulnerable populations could help mitigate pandemic impacts on anxiety and mental health

Factors associated with anxiety during the first two years of the COVID-19 pandemic in the United States: An analysis of the COVID-19 Citizen Science study.

COVID-19 increased the prevalence of clinically significant anxiety in the United States. To investigate contributing factors we analyzed anxiety, reported online via monthly Generalized Anxiety Disorders-7 (GAD-7) surveys between April 2020 and May 2022, in association with self-reported worry about the health effects of COVID-19, economic difficulty, personal COVID-19 experience, and subjective social status. 333,292 anxiety surveys from 50,172 participants (82% non-Hispanic white; 73% female; median age 55, IQR 42-66) showed high levels of anxiety, especially early in the pandemic. Anxiety scores showed strong independent associations with worry about the health effects of COVID-19 for oneself or family members (GAD-7 score +3.28 for highest vs. lowest category; 95% confidence interval: 3.24, 3.33; p&lt;0.0001 for trend) and with difficulty paying for basic living expenses (+2.06; 1.97, 2.15, p&lt;0.0001) in multivariable regression models after adjusting for demographic characteristics, COVID-19 case rates and death rates, and personal COVID-19 experience. High levels of COVID-19 health worry and economic stress were each more common among participants reporting lower subjective social status, and median anxiety scores for those experiencing both were in the range considered indicative of moderate to severe clinical anxiety disorders. In summary, health worry and economic difficulty both contributed to high rates of anxiety during the first two years of the COVID-19 pandemic in the US, especially in disadvantaged socioeconomic groups. Programs to address both health concerns and economic insecurity in vulnerable populations could help mitigate pandemic impacts on anxiety and mental health

The U.S. COVID-19 County Policy Database: a novel resource to support pandemic-related research

BackgroundIt is increasingly recognized that policies have played a role in both alleviating and exacerbating the health and economic consequences of the COVID-19 pandemic. There has been limited systematic evaluation of variation in U.S. local COVID-19-related policies. This study introduces the U.S. COVID-19 County Policy (UCCP) Database, whose objective is to systematically gather, characterize, and assess variation in U.S. county-level COVID-19-related policies.MethodsIn January-March 2021, we collected an initial wave of&nbsp;cross-sectional data from government and media websites for 171 counties in 7 states on 22 county-level COVID-19-related policies within 3 policy domains that are likely to affect health: (1) containment/closure, (2) economic support, and (3) public health. We characterized the presence and comprehensiveness of policies using univariate analyses. We also examined the correlation of policies with one another using bivariate Spearman's correlations. Finally, we examined geographical variation in policies across and within states.ResultsThere was substantial variation in the presence and comprehensiveness of county policies during January-March 2021. For containment and closure policies, the percent of counties with no restrictions ranged from 0% (for public events) to more than half for public transportation (67.8%), hair salons (52.6%), and religious gatherings (52.0%). For economic policies, 76.6% of counties had housing support, while 64.9% had utility relief. For public health policies, most were comprehensive, with 70.8% of counties having coordinated public information campaigns, and 66.7% requiring masks outside the home at all times. Correlations between containment and closure policies tended to be positive and moderate (i.e., coefficients 0.4-0.59). There was variation within and across states in the number and comprehensiveness of policies.ConclusionsThis study introduces the UCCP Database, presenting granular data on local governments' responses to the COVID-19 pandemic. We documented substantial variation within and across states on a wide range of policies at a single point in time. By making these data publicly available, this study supports future research that can leverage this database to examine how policies contributed to and continue to influence pandemic-related health and socioeconomic outcomes and disparities. The UCCP database is available online and will include additional time points for 2020-2021 and additional counties nationwide

Effectiveness of BNT162b2 COVID-19 primary series vaccination in children aged 5–17 years in the United States: a cohort study

Abstract Background COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study’s objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children. Methods This cohort study identified children aged 5–17 years vaccinated with BNT162b2 matched with unvaccinated children. Participants and BNT162b2 vaccinations were identified in Optum and CVS Health insurance administrative claims databases linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. Results There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person-years; CVS Health, 44.1 per 10,000 person-years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36–40%]) and hospital/ED–diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56–65%]). VE estimates were lowest among children 5–11 years and during the Omicron-variant era. Conclusions Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED–diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era. Registration The study protocol was publicly posted on the BEST Initiative website ( https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf )