Selection Effects and COVID-19 Mortality Risk after Pfizer vs. Moderna Vaccination: Evidence from Linked Mortality and Vaccination Records.

Prior research generally finds that the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA1273) COVID-19 vaccines provide similar protection against mortality, sometimes with a Moderna advantage due to slower waning. However, most comparisons do not address selection effects for those who are vaccinated and with which vaccine. We report evidence on large selection effects, and use a novel method to control for these effects. Instead of directly studying COVID-19 mortality, we study the COVID-19 excess mortality percentage (CEMP), defined as the COVID-19 deaths divided by non-COVID-19 natural deaths for the same population, converted to a percentage. The CEMP measure uses non-COVID-19 natural deaths to proxy for population health and control for selection effects. We report the relative mortality risk (RMR) for each vaccine relative to the unvaccinated population and to the other vaccine, using linked mortality and vaccination records for all adults in Milwaukee County, Wisconsin, from 1 April 2021 through 30 June 2022. For two-dose vaccinees aged 60+, RMRs for Pfizer vaccinees were consistently over twice those for Moderna, and averaged 248% of Moderna (95% CI = 175%,353%). In the Omicron period, Pfizer RMR was 57% versus 23% for Moderna. Both vaccines demonstrated waning of two-dose effectiveness over time, especially for ages 60+. For booster recipients, the Pfizer-Moderna gap is much smaller and statistically insignificant. A possible explanation for the Moderna advantage for older persons is the higher Moderna dose of 100 µg, versus 30 µg for Pfizer. Younger persons (aged 18-59) were well-protected against death by two doses of either vaccine, and highly protected by three doses (no deaths among over 100,000 vaccinees). These results support the importance of a booster dose for ages 60+, especially for Pfizer recipients. They suggest, but do not prove, that a larger vaccine dose may be appropriate for older persons than for younger persons.

Understanding COVID-19 Vaccine Effectiveness against Death Using a Novel Measure: COVID Excess Mortality Percentage.

COVID-19 vaccines have saved millions of lives; however, understanding the long-term effectiveness of these vaccines is imperative to developing recommendations for booster doses and other precautions. Comparisons of mortality rates between more and less vaccinated groups may be misleading due to selection bias, as these groups may differ in underlying health status. We studied all adult deaths during the period of 1 April 2021-30 June 2022 in Milwaukee County, Wisconsin, linked to vaccination records, and we used mortality from other natural causes to proxy for underlying health. We report relative COVID-19 mortality risk (RMR) for those vaccinated with two and three doses versus the unvaccinated, using a novel outcome measure that controls for selection effects. This measure, COVID Excess Mortality Percentage (CEMP), uses the non-COVID natural mortality rate (Non-COVID-NMR) as a measure of population risk of COVID mortality without vaccination. We validate this measure during the pre-vaccine period (Pearson correlation coefficient = 0.97) and demonstrate that selection effects are large, with non-COVID-NMRs for two-dose vaccinees often less than half those for the unvaccinated, and non-COVID NMRs often still lower for three-dose (booster) recipients. Progressive waning of two-dose effectiveness is observed, with an RMR of 10.6% for two-dose vaccinees aged 60+ versus the unvaccinated during April-June 2021, rising steadily to 36.2% during the Omicron period (January-June, 2022). A booster dose reduced RMR to 9.5% and 10.8% for ages 60+ during the two periods when boosters were available (October-December, 2021; January-June, 2022). Boosters thus provide important additional protection against mortality.

The Effect of the COVID-19 Pandemic on the Elderly: Population Fatality Rates, COVID Mortality Percentage, and Life Expectancy Loss

The COVID-19 pandemic has disproportionately affected the elderly. This Article provides a detailed analysis of those effects, drawing primarily on individual-level mortality data covering almost three million persons aged 65+ in three Midwest states (Indiana, Illinois, and Wisconsin). We report sometimes surprising findings on population fatality rates (“PFR”), the ratio of COVID to non-COVID deaths, reported as a percentage, which we call the “Covid Mortality Percentage,” and mean life expectancy loss (“LEL”). We examine how these COVID-19 outcomes vary with age, gender, race/ethnicity, socio-economic status, and time period during the pandemic. For all persons in the three Midwest areas, COVID PFR through year-end 2021 was 0.22%, mean years of life lost (“YLL“) was 13.0 years, the COVID Mortality Percentage was 12.4%, and LEL was 0.028 years (eleven days). In contrast, for the elderly, PFR was 1.03%;YLL was 8.8 years, the COVID Mortality Percentage was 13.2%, and LEL was 0.091 years (thirty-four days). Controlling for gender, PFR and LEL were substantially higher for Blacks and Hispanics than for Whites at all ages. Racial/ethnic disparities for the elderly were large early in the pandemic but diminished later. Although COVID-19 mortality was much higher for the elderly, the COVID Mortality Percentage over the full pandemic period was only modestly higher for the elderly, at 13.2%, than for non-elderly adults aged 25–64, at 11.1%. Indeed, in 2021, this ratio was lower for the elderly than for the middle-aged, reflecting higher elderly vaccination rates.

Engaging veteran stakeholders to identify patient-centred research priorities for optimizing implementation of lung cancer screening.

BACKGROUND: Patient engagement in research agenda setting is increasingly being seen as a strategy to improve the responsiveness of healthcare to patient priorities. Implementation of low-dose computed tomography (LDCT) screening for lung cancer is suboptimal, suggesting that research is needed. OBJECTIVES: This study aimed to describe an approach by which a Veteran patient group worked with other stakeholders to develop a research agenda for LDCT screening and to describe the research questions that they prioritized. METHODS: We worked with Veterans organizations to identify 12 Veterans or family members at risk for or having experience with lung cancer to form a Patient Advisory Council (PAC). The PAC met repeatedly from June 2018 to December 2020, both independently and jointly, with stakeholders representing clinicians, health administrators and researchers to identify relevant research topics. The PAC prioritized these topics and then identified questions within these areas where research was needed using an iterative process. Finally, they ranked the importance of obtaining answers to these questions. RESULTS: PAC members valued the co-learning generated by interactions with stakeholders, but emphasized the importance of facilitation to avoid stakeholders dominating the discussion. The PAC prioritized three broad research areas-(1) the impact of insurance on uptake of LDCT; (2) how best to inform Veterans about LDCT; and (3) follow-up and impact of screening results. Using these areas as guides, PAC members identified 20 specific questions, ranking as most important (1) innovative outreach methods, (2) the impact of screening on psychological health, and (3) the impact of outsourcing scans from VA to non-VA providers on completion of recommended follow-up of screening results. The latter two were not identified as high priority by the stakeholder group. CONCLUSIONS: We present an approach that facilitates co-learning between Veteran patients and providers, researchers and health system administrators to increase patient confidence in their ability to contribute important information to a research agenda. The research questions prioritized by the Veterans who participated in this project illustrate that for this new screening technology, patients are concerned about the practical details of implementation (e.g., follow-up) and the technology's impact on quality of life. PATIENT OR PUBLIC CONTRIBUTION: Veterans and Veteran advocates contributed to our research team throughout the entire research process, including conceiving and co-authoring this manuscript.

Adapting the design of a Web-based decision support clinical trial during the COVID-19 pandemic.

BACKGROUND: The public health crises that emerged in the COVID-19 pandemic significantly impacted the provision of medical care and placed sudden restrictions on ongoing clinical research. Patient-facing clinical research confronted unique challenges in which recruitment and study protocols were halted and then adapted to meet safety procedures during the pandemic. Our study protocol included the use of a Lung Cancer Screening Decision Tool (LCSDecTool) in the context of a primary care visit and was considerably impacted by the pandemic. We describe our experience adapting a multi-site clinical trial of the LCSDecTool within the Department of Veterans Affairs Health Care System. We conducted a randomized controlled trial (RCT) comparing the LCSDecTool to a control intervention. Outcomes included lung cancer screening (LCS) knowledge, shared decision-making, and uptake and adherence to LCS protocol. We identified three strategies that led to the successful adaptation of the study design during the pandemic: (1) multi-level coordination and communication across the organization and study sites, (2) flexibility and adaptability in research during a time of uncertainty and changes in regulation, and (3) leveraging technology to deliver the intervention and conduct study visits, which raised issues concerning equity and internal and external validity. CONCLUSION: Our experience highlights strategies successfully employed to adapt an intervention and behavioral research study protocol during the COVID-19 pandemic. This experience will inform clinical research moving forward both during and subsequent to the constraints placed on research and clinical care during the COVID-19 pandemic.