BACKGROUND:In 2023, the United States Food and Drug Administration revised its blood donor eligibility policy for men who have sex with men (MSM) from a 3-month deferral to individual assessment. Human Immunodeficiency Virus (HIV) pre-exposure prophylaxis (PrEP) use remains a reason for deferral, and nondisclosure is a concern. STUDY DESIGN AND METHODS:In a cross-sectional study of sexually active MSM from 8 U.S. cities who were interested in future blood donation, we assessed the performance of an enzyme-linked immunosorbent assay for detecting tenofovir (TFV) in whole blood (WB) and plasma and the correlation with self-reported PrEP use. RESULTS:Of 1548 individuals, 48% reported oral PrEP use. The WB assay identified 95% of PrEP users, while the plasma assay detected 88%. The WB assay performed well up to 14 days after the last reported dose. Receiver operating characteristics curve analysis showed an area under the curve of 0.96 (95% confidence interval [CI]: 0.95-0.97) using WB and 0.88 (95% CI: 0.86-0.90) using plasma. Specificity was 80% for WB and 66% for plasma. Detection rates for TFV disoproxil fumarate/emtricitabine (FTC) formulations were 99% in WB and 98% in plasma, compared to 93% and 86% for the TFV alafenamide/FTC formulation. DISCUSSION:High concordance between self-reported oral PrEP use and TFV detection was observed among PrEP users, suggesting the potential utility of WB as a biomatrix for TFV detection to support screening strategies. Given the expanded eligibility for MSM, who may be PrEP users, to donate blood, further examination of undisclosed PrEP use is important.

As of December 31, 2023, the FDA had become aware of 22 cases of T-cell cancers that occurred after treatment with CAR-T products. For now, such cancers appear to be relatively rare adverse events.

This Viewpoint discusses declining vaccination rates in the US, specifically against COVID-19, and the ways in which clinicians and the Food and Drug Administration can counter the current large volume of vaccine misinformation.

Background Functional limitations and physical disabilities associated with aging and chronic disease are major concerns for human societies and expeditious development of function-promoting therapies is a public health priority. Methods Expert panel discussion. Results The remarkable success of Operation Warp Speed for the rapid development of COVID-19 vaccines, COVID-19 therapeutics, and of oncology drug development programs over the past decade have taught us that complex public health problems such as the development of function-promoting therapies will require collaboration among many stakeholders, including academic investigators, the National Institutes of Health, professional societies, patients and patient advocacy organizations, the pharmaceutical and biotechnology industry, and the U.S. Food and Drug Administration. Conclusions There was agreement that the success of well designed, adequately powered clinical trials will require careful definitions of indication/s, study population, and patient-important endpoints that can be reliably measured using validated instruments, commensurate resource allocation, and versatile organizational structures such as those used in Operation Warp Speed.

While the coronavirus disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those insights to inform policy and approaches to prepare for the next pandemic. In May 2022, the Duke Clinical Research Institute convened a think tank with thought leaders from academia, clinical practice, the pharmaceutical industry, patient advocacy, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Disease Control and Prevention to share, firsthand, expert knowledge of the insights gained from the COVID-19 pandemic and how this acquired knowledge can help inform the next pandemic response. The think tank focused on pandemic preparedness, therapeutics, vaccines, and challenges related to clinical trial design and scale-up during the early phase of a pandemic. Based on the multi-faceted discussions, we outline 10 key steps to an improved and equitable pandemic response. The coronavirus disease 2019 pandemic showcased collaborative successes of academia, federal agencies, and industry but also mistakes and deficiencies. We highlight critical lessons and necessary steps toward a more effective response to ensure the United States and the world are prepared for the next pandemic.

Interview with Dr. Peter Marks on the FDA's experience with emergency use authorizations during the Covid-19 pandemic. (06:13)Download Despite the planned ending of the Covid-19 public health emergency in the United States, medical products approved under emergency use authorizations will remain available for the foreseeable future.

ABSTRACTSince 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 benefit-risk assessment to inform review of the Biologics License Application for use of the Moderna vaccine among individuals ages 18 years and older. We modeled 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, and 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.

Importance Blood donor selection policies should be evidence-based. Individual risk assessment allows potential donors to be evaluated based on their own behaviors.Objective The Assessing Donor Variability and New Concepts in Eligibility (ADVANCE) study examined behavioral and biomarkers of HIV risk in sexually active men who have sex with men (MSM) to estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors and might be eligible to donate.Design A cross-sectional assessment of sexually active MSM interested in blood donation. Setting: An 8-city study of MSM aged 18 – 39 years assigned male sex at birth.Interventions or Exposures Participants completed surveys during 2 study visits to define eligibility, self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, 1 of the drugs in oral HIV pre-exposure prophylaxis (PrEP).Main Outcomes and Measures Associations between HIV infection status or HIV PrEP use and self-reported HIV risk behaviors, including number of male sex partners, new partners, and anal sex.Results Among 1788 screened MSM, 1593 were eligible and 1566 completed the visit 1 HIV risk questionnaire and blood draw. A median of 22 days later, 1197 completed the visit 2 follow-up questionnaire. Four individuals tested HIV positive (0.25%). Among HIV-negative participants, 789 (50.4%) reported no PrEP use in the past 3 months. The number of sex partners in the past 3 months was significantly higher among PrEP users versus non-users, as was the number reporting a new male sex partner in the same period. Among HIV-negative, non-PrEP using participants, 66.2% reported only 1 sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months.Conclusion and Relevance Among sexually active MSM, there are subgroups who self-report no new sexual partners and only 1 sexual partner within the past 3 months. These individuals are likely at lower risk of HIV infection than other MSM and would meet proposed individual risk assessment criteria for blood donation in the U.S.Question Can a set of blood donor screening questions based on individual behaviors identify a population of lower HIV risk men who have sex with men (MSM) who wish to donate blood?Findings In this cross-sectional study of 1566 enrolled MSM, among 1562 persons without HIV, 789 (50.4%) were not taking pre-exposure prophylaxis (PrEP). Of those not taking PrEP, 66.2% reported only 1 sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months.Meaning Potential blood donor history questions were able to identify sexually active MSM with lower-risk sexual behaviors who may be eligible to donate blood.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis study was funded by the U.S. Food and Drug Administration### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Advarra Institutional Review Board (Columbia, MD) gave ethical approval for this work under protocol number 00043278.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesData from this study are not openly available. Authors should be contacted to discuss data availability.

ABSTRACT During infectious disease emergencies, it may be necessary to deploy new therapies without conclusive evidence for their effectiveness. During the SARS-CoV-2 pandemic, several countries used registries to track the use of COVID-19 convalescent plasma (CCP). Those registries provided evidence that CCP was effective when used early and with high titer.

This Viewpoint argues that the development of a distinctly improved generation of SARS-CoV-2 vaccines is paramount to offering a greater breadth and depth of protection for a longer duration against COVID-19 disease.

Investment, collaboration, and coordination have been key

BACKGROUND:Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. STUDY DESIGN AND METHODS:Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. RESULTS:A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. CONCLUSION:The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.

Abstract While the coronavirus disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those insights to inform policy and approaches to prepare for the next pandemic. In May 2022, the Duke Clinical Research Institute convened a think tank with thought leaders from academia, clinical practice, the pharmaceutical industry, patient advocacy, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Disease Control and Prevention to share, firsthand, expert knowledge of the insights gained from the COVID-19 pandemic and how this acquired knowledge can help inform the next pandemic response. The think tank focused on pandemic preparedness, therapeutics, vaccines, and challenges related to clinical trial design and scale-up during the early phase of a pandemic. Based on the multi-faceted discussions, we outline 10 key steps to an improved and equitable pandemic response.

Adequate and well-controlled clinical trials remain critical tools for helping to bring benefit to patients in medical need.

Supplementary Data from Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy