RSV Prefusion F Protein-Based Maternal Vaccine - Preterm Birth and Other Outcomes.

BACKGROUND: Vaccination against respiratory syncytial virus (RSV) during pregnancy may protect infants from RSV disease. Efficacy and safety data on a candidate RSV prefusion F protein-based maternal vaccine (RSVPreF3-Mat) are needed. METHODS: We conducted a phase 3 trial involving pregnant women 18 to 49 years of age to assess the efficacy and safety of RSVPreF3-Mat. The women were randomly assigned in a 2:1 ratio to receive RSVPreF3-Mat or placebo between 24 weeks 0 days and 34 weeks 0 days of gestation. The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract disease in infants from birth to 6 months of age and safety in infants from birth to 12 months of age. After the observation of a higher risk of preterm birth in the vaccine group than in the placebo group, enrollment and vaccination were stopped early, and exploratory analyses of the safety signal of preterm birth were performed. RESULTS: The analyses included 5328 pregnant women and 5233 infants; the target enrollment of approximately 10,000 pregnant women and their infants was not reached because enrollment was stopped early. A total of 3426 infants in the vaccine group and 1711 infants in the placebo group were followed from birth to 6 months of age; 16 and 24 infants, respectively, had any medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 65.5%; 95% credible interval, 37.5 to 82.0), and 8 and 14, respectively, had severe medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 69.0%; 95% credible interval, 33.0 to 87.6). Preterm birth occurred in 6.8% of the infants (237 of 3494) in the vaccine group and in 4.9% of those (86 of 1739) in the placebo group (relative risk, 1.37; 95% confidence interval [CI], 1.08 to 1.74; P = 0.01); neonatal death occurred in 0.4% (13 of 3494) and 0.2% (3 of 1739), respectively (relative risk, 2.16; 95% CI, 0.62 to 7.56; P = 0.23), an imbalance probably attributable to the greater percentage of preterm births in the vaccine group. No other safety signal was observed. CONCLUSIONS: The results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT04605159.).

Safety surveillance and challenges in accelerated COVID-19 vaccine development.

The COVID-19 pandemic, caused by a novel type of coronavirus, continues to infect people, increasing morbidity and mortality across the globe. Measures to slow the transmission of the virus have had limited impact, and people, businesses, and economies have suffered. The disease has disproportionally impacted elderly and individuals with certain pre-existing conditions and has highlighted health and social inequities in some racial and ethnic minority groups. The majority of those who contract the disease recover completely, but some experience long-lasting complications. Vaccines have the potential to end the pandemic, and through the intense collaboration of scientists in government and private sectors, more than 200 COVID-19 candidate vaccines have been or are being developed, using known platforms and previous experiences with severe acute respiratory syndrome (SARS), at unprecedented speed. The expectations for vaccine safety and quality in the setting of accelerated development are the same as during non-emergency times; however, challenges inherent with the circumstances of the pandemic situation provide opportunities to improve clinical trial conduct and strengthen pharmacovigilance systems. We have reviewed and analyzed existing PV guidelines and recommendations throughout the lifecycle of vaccine development with a focus on developing a global/worldwide effort for post-marketing vaccine safety surveillance. Plain Language Summary: The Important Role of Pharmacovigilance in Accelerated COVID-19 Vaccine Development This is an extensive review that intends to address important aspects of COVID-19 vaccines' accelerated development and safety surveillance. It is focused on regulatory requirements for long-term safety monitoring, practical applications, and current global efforts in developing robust pharmacovigilance systems for post-authorization surveillance.Notably, different perspectives of authors from industry, academic institutions, and contract research organizations involved in drug safety were incorporated to reflect on various regulatory requirements and new developments in vaccine safety. All co-authors are current members of International Society of Pharmacovigilance (ISoP).

Enhancing Pharmacovigilance from the US Experience: Current Practices and Future Opportunities.

This review is intended to present perspectives from the US experience in enhancing pharmacovigilance on current practices and future opportunities. Best practices concepts could be applied worldwide through the presentation of how three pillars of pharmacovigilance: (1) medical and scientific excellence, (2) operational and compliance excellence, and (3) knowledge sharing and experts development in the field could serve as a framework for the establishment of an efficient and successful global pharmacovigilance system.

Interaction of daptomycin with two recombinant thromboplastin reagents leads to falsely prolonged patient prothrombin time/International Normalized Ratio results.

A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0-200 microg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; alpha = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two recombinant thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug-laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin.

Standards for adult immunization practices.

Since the Standards for Adult Immunization Practices were first published in 1990, healthcare researchers and providers have learned important lessons on how to better achieve and maintain high vaccination rates in adults. The success rate of childhood immunization far exceeds the success rate of adult immunization. Thus, information and practices that will produce higher success rates for adult vaccination are crucial, resulting in overall societal cost savings and substantial reductions in hospitalizations and deaths. The Standards, which were developed to encourage the best immunization practices, represent the collective efforts of more than 100 people from more than 60 organizations. The revised Standards are more comprehensive than the 1990 Standards and focus on the accessibility and availability of vaccines, proper assessment of patient vaccination status, opportunities for patient education, correct procedures for administering vaccines, implementation of strategies to improve vaccination rates, and partnerships with the community to reach target patient populations. The revised Standards are recommended for use by all healthcare professionals and all public and private sector organizations that provide immunizations for adults. All who are involved in adult immunization should strive to follow the Standards in order to create the same level of success achieved by childhood vaccination programs and to meet the Healthy People 2010 goals.