Benefit-risk assessment of Covid-19 vaccine, MRNA (MRNA-1273) for males age 18–64 years

Since the authorization of the Moderna mRNA COVID-19 vaccine, real-world evidence has indicated its effectiveness in preventing COVID-19 cases. However, increased cases of mRNA vaccine-associated myocarditis/pericarditis have been reported, predominantly in young adults and adolescents. The Food and Drug Administration conducted a benefit-risk assessment to inform the review of the Biologics License Application for use of the Moderna vaccine among individuals ages 18 and older. We modeled the benefit-risk per million individuals who receive two complete doses of the vaccine. Benefit endpoints were vaccine-preventable COVID-19 cases, hospitalizations, intensive care unit (ICU) admissions, and deaths. The risk endpoints were vaccine-related myocarditis/pericarditis cases, hospitalizations, ICU admissions, and deaths. The analysis was conducted on the age-stratified male population due to data signals and previous work showing males to be the main risk group. We constructed six scenarios to evaluate the impact of uncertainty associated with pandemic dynamics, vaccine effectiveness (VE) against novel variants, and rates of vaccine-associated myocarditis/pericarditis cases on the model results. For our most likely scenario, we assumed the US COVID-19 incidence was for the week of December 25, 2021, with a VE of 30% against cases and 72% against hospitalization with the Omicron-dominant strain. Our source for estimating vaccine-attributable myocarditis/pericarditis rates was FDA’s CBER Biologics Effectiveness and Safety (BEST) System databases. Overall, our results supported the conclusion that the benefits of the vaccine outweigh its risks. Remarkably, we predicted vaccinating one million 18–25 year-old males would prevent 82,484 cases, 4,766 hospitalizations, 1,144 ICU admissions, and 51 deaths due to COVID-19, comparing to 128 vaccine-attributable myocarditis/pericarditis cases, 110 hospitalizations, zero ICU admissions, and zero deaths. Uncertainties in the pandemic trajectory, effectiveness of vaccine against novel variants, and vaccine-attributable myocarditis/pericarditis rate are important limitations of our analysis. Also, the model does not evaluate potential long-term adverse effects due to either COVID-19 or vaccine-attributable myocarditis/pericarditis

Modeling the potential impact on the US blood supply of transfusing critically ill patients with fresher stored red blood cells

<div><p>Background</p><p>Although some studies have suggested that transfusion recipients may have better medical outcomes if transfused with red blood cell units stored for a short time, the overall body of evidence shows mixed results. It is important to understand how using fresher stored red blood cell units for certain patient groups may affect blood availability.</p><p>Methods</p><p>Based on the Stock-and-Flow simulation model of the US blood supply developed by Simonetti et al. 2014, we evaluated a newly implemented allocation method of preferentially transfusing fresher stored red blood cell units to a subset of high-risk group of critically ill patients and its potential impact on supply.</p><p>Results</p><p>Simulation results showed that, depending on the scenario, the US blood total supply might be reduced between 2-42%, when compared to the standard of care in transfusion medicine practice. Among our simulated scenarios, we observed that the number of expired red blood cell units modulated the supply levels. The age threshold of the required red blood cell units was inversely correlated with both the supply levels and the number of transfused units that failed to meet that age threshold.</p><p>Conclusion</p><p>To our knowledge, this study represents the first attempt to develop a comprehensive framework to evaluate the impact of preferentially transfusing fresher stored red blood cells to the higher-risk critically ill patients on supply. Model results show the difficulties to identify an optimal scenario.</p></div

Patterns of seasonal influenza activity in U.S. core-based statistical areas, described using prescriptions of oseltamivir in Medicare claims data

Using Medicare claims data on prescriptions of oseltamivir dispensed to people 65 years old and older, we present a descriptive analysis of patterns of influenza activity in the United States for 579 core-based statistical areas (CBSAs) from the 2010–2011 through the 2015–2016 influenza seasons. During this time, 1,010,819 beneficiaries received a prescription of oseltamivir, ranging from 45,888 in 2011–2012 to 380,745 in 2014–2015. For each season, the peak weekly number of prescriptions correlated with the total number of prescriptions (Pearson’s r ≥ 0.88). The variance in peak timing decreased with increasing severity (p < 0.0001). Among these 579 CBSAs, neither peak timing, nor relative timing, nor severity of influenza seasons showed evidence of spatial autocorrelation (0.02 ≤ Moran’s I ≤ 0.23). After aggregating data to the state level, agreement between the seasonal severity at the CBSA level and the state level was fair (median Cohen’s weighted κ = 0.32, interquartile range = 0.26–0.39). Based on seasonal severity, relative timing, and geographic place, we used hierarchical agglomerative clustering to join CBSAs into influenza zones for each season. Seasonal maps of influenza zones showed no obvious patterns that might assist in predicting influenza zones for future seasons. Because of the large number of prescriptions, these data may be especially useful for characterizing influenza activity and geographic distribution during low severity seasons, when other data sources measuring influenza activity are likely to be sparse. Keywords: Antivirals, Influenza, Medicar

Percentage of total RBC units transfused and reported by the CMS database for the period 2007-2012 by type of scenario.

<p>Scenario illustration (Venn diagrams), group description, and allocation method used for each scenario are also presented.</p

Average percent of total RBC units transfused for each of the mutually exclusive, one or more, of the High Risk Groups (HRGs) from CMS during 2007-2012.

<p>Average percent of total RBC units transfused for each of the mutually exclusive, one or more, of the High Risk Groups (HRGs) from CMS during 2007-2012.</p

The annual average daily (AAD) age of transfused blood units for each simulated scenario listed in Table 2.

<p>We provide a description of each element of the half-pie chart from the inner to the outer layer, as follows: 1) percentage of total RBC units transfused among elderly for the overall HRGs (blue) versus BBRs (tan); 2) percentage of total RBC units transfused partitioned by HRGs (purple, orange and pink); 3) allocation method used foreach recipient group (HRGs – different shades of light blue; BBRs in teal); 4) AAD age of the blood transfused to each recipient group and the percentage of ‘met’ (green) and ‘unmet’ (red) RBC units by age forHRGs only (in parenthesis); and 5) AAD age of the overall transfused blood given to HRGs (bold red).</p