Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program
ABSTRACT The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by many parents as a factor that contributed to their intention to forgo vaccination (see www.hsph.harvard.edu/news/press-releases/2009-releases/survey-40-adults-absolutely-certain-h1n1-vaccine.html and www.med.umich.edu/mott/npch/reports/h1n1.htm). The safety profiles of 2009 H1N1 monovalent influenza vaccines were anticipated to be (and have been) similar to those of seasonal influenza vaccines, for which an excellent safety profile has been demonstrated. Here we describe steps taken by the US government to (1) assess the key federal systems in place before 2009 for monitoring the safety of vaccines and (2) integrate and upgrade those systems for optimal vaccine-safety monitoring during the 2009 H1N1 monovalent influenza vaccination program. These efforts improved monitoring of 2009 H1N1 vaccine safety, hold promise for enhancing future national monitoring of vaccine safety, and may ultimately help improve public confidence in vaccines.
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ABSTRACT: Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system. We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1) expected vaccination benefit from averted influenza; 2) expected vaccination risk from vaccine-associated febrile seizures; 3) expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4) expected change in vaccine-seeking behavior in future influenza seasons. Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3∶1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior. The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior.PLoS ONE 12/2014; 9(12):e115553. DOI:10.1371/journal.pone.0115553 · 3.53 Impact Factor
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ABSTRACT: To assess risks for acute adverse events and pregnancy complications in pregnant women following monovalent 2009 H1N1 inactivated influenza (MIV) vaccination.Vaccine 07/2014; DOI:10.1016/j.vaccine.2014.07.017 · 3.49 Impact Factor
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ABSTRACT: The Updating Sequential Probability Ratio Test (USPRT) developed by MaCurdy et al.. (2009, Updating sequential probability ratio test for real-time surveillance of vaccine safety, unpublished working paper) has been used by the U.S. Food and Drug Administration for near real-time surveillance of the safety of the flu vaccine since 2008. This procedure was the first method developed to account for data delay in pharmacovigilance studies. However, the current implementation is based on the strong assumption that the clinical and reporting delays do not vary from previous years. When this assumption does not hold, size distortion of the USPRT procedure might result. The goal of this article is to numerically investigate the robustness of the detection probabilities of the USPRT method with respect to possible misspecification of the clinical and reporting delay distributions through extensive simulations. We find that if the delay distribution used in calibrating the critical bound is lengthier than the delay distribution in the data generating process, then there is a higher rate of false signaling and vice versa. This is an inherent property of a real-time testing procedure. However, the distortion created by misspecifying the reporting delay distribution appears to be insignificant when compared to the overall power generated by an elevation of the adverse event rate. The size distortion is unevenly distributed across the interim tests, so the effect of misspecification of the delay distributions is more prominent in the median time-to-signal. In summary, although a misspecified delay distribution induces size distortion, we find that it does not erode the overall power.Statistical Analysis and Data Mining 10/2014; 7(5). DOI:10.1002/sam.11234