Methods for addressing “innocent bystanders” when evaluating safety of concomitant vaccines

Wang, Shirley; Abdurrob, Abdurrahman; Spoendlin, Julia; Lewis, Edwin; Newcomer, Sophia R.; Fireman, Bruce; Daley, Matthew F.; Glanz, Jason M.; Duffy, Jonathan; Weintraub, Eric; Kulldorff, Martin

doi:10.1002/pds.4399

Cited by 5 publications

(4 citation statements)

References 21 publications

(52 reference statements)

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“…A self-controlled risk interval study using data from an integrated electronic health record system evaluated the degree to which measles, mumps, rubella (MMR) vaccines increased risk for febrile seizures in children aged 11 to 23 months (47). (Appendix Figure 3).…”

Section: An Exposure-indexed Self-controlled Design (Self-controlled ...mentioning

confidence: 99%

Graphical Depiction of Longitudinal Study Designs in Health Care Databases

et al. 2019

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Pharmacoepidemiologic and pharmacoeconomic analysis of health care databases has become a vital source of evidence to support health care decision making and efficient management of health care organizations. However, decision makers often consider studies done in nonrandomized health care databases more difficult to review than randomized trials because many design choices need to be considered. This is perceived as an important barrier to decision making about the effectiveness and safety of medical products. Design flaws in longitudinal database studies are avoidable but can be unintentionally obscured in the convoluted prose of methods sections, which often lack specificity. We propose a simple framework of graphical representation that visualizes study design implementations in a comprehensive, unambiguous, and intuitive way; contains a level of detail that enables reproduction of key study design variables; and uses standardized structure and terminology to simplify review and communication to a broad audience of decision makers. Visualization of design details will make database studies more reproducible, quicker to review, and easier to communicate to a broad audience of decision makers.

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Section: An Exposure-indexed Self-controlled Design (Self-controlled ...mentioning

confidence: 99%

Graphical Depiction of Longitudinal Study Designs in Health Care Databases

et al. 2019

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“…Administration of multiple vaccines at the same time is convenient as it reduces the number of clinical visits, thus saving time and resources, and provides protection against multiple pathogens in a shorter time-span when an individual may be vulnerable to infection. In addition, most reports deem concomitant vaccinations safe and effective [ 25 , 29 , 66 , 67 ]. In this respect, the guidelines of the US Food and Drug Administration (FDA) regarding the YFV vaccine YF-Vax (Sanofi Pasteur) state that it can be administered with the that measles vaccine, diphtheria and tetanus toxoid and whole cell pertussis vaccine (DTP), Hepatitis A and B vaccines, meningococcal vaccine, and typhoid vaccine ( www.fda.gov ).…”

Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity following co-administration of Yellow fever vaccine with Tick-borne encephalitis or Japanese encephalitis vaccines: Results from an open label, non-randomized clinical trial

Sandberg

Löfling²,

Varnaitė³

et al. 2023

PLoS Negl Trop Dis

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Background Flavivirus infections pose a significant global health burden underscoring the need for the development of safe and effective vaccination strategies. Available flavivirus vaccines are from time to time concomitantly delivered to individuals. Co-administration of different vaccines saves time and visits to health care units and vaccine clinics. It serves to provide protection against multiple pathogens in a shorter time-span; e.g., for individuals travelling to different endemic areas. However, safety and immunogenicity-related responses have not been appropriately evaluated upon concomitant delivery of these vaccines. Therefore, we performed an open label, non-randomized clinical trial studying the safety and immunogenicity following concomitant delivery of the yellow fever virus (YFV) vaccine with tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus (JE) virus vaccines. Methods and findings Following screening, healthy study participants were enrolled into different cohorts receiving either TBEV and YFV vaccines, JEV and YFV vaccines, or in control groups receiving only the TBEV, JEV, or YFV vaccine. Concomitant delivery was given in the same or different upper arms for comparison in the co-vaccination cohorts. Adverse effects were recorded throughout the study period and blood samples were taken before and at multiple time-points following vaccination to evaluate immunological responses to the vaccines. Adverse events were predominantly mild in the study groups. Four serious adverse events (SAE) were reported, none of them deemed related to vaccination. The development of neutralizing antibodies (nAbs) against TBEV, JEV, or YFV was not affected by the concomitant vaccination strategy. Concomitant vaccination in the same or different upper arms did not significantly affect safety or immunogenicity-related outcomes. Exploratory studies on immunological effects were additionally performed and included studies of lymphocyte activation, correlates associated with germinal center activation, and plasmablast expansion. Conclusions Inactivated TBEV or JEV vaccines can be co-administered with the live attenuated YFV vaccine without an increased risk of adverse events and without reduced development of nAbs to the respective viruses. The vaccines can be delivered in the same upper arm without negative outcome. In a broader perspective, the results add valuable information for simultaneous administration of live and inactivated flavivirus vaccines in general. Trial registration Eudra CT 2017-002137-32.

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“…Administration of multiple vaccines at the same time is convenient as it reduces the number of clinical visits, thus saving time and resources, and provides protection against multiple pathogens in a shorter time-span when an individual may be vulnerable to infection. In addition, most reports deem concomitant vaccinations safe and effective [25,29,64,65]. In this respect, the guidelines of the US Food and Drug Administration (FDA) regarding the YFV vaccine YF-Vax (Sanofi Pasteur) state that it can be administered with the that measles vaccine, diphtheria and tetanus toxoid and whole cell pertussis vaccine (DTP), Hepatitis A and B vaccines, meningococcal vaccine, and typhoid vaccine (www.fda.gov).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity following co-administration of Yellow fever vaccine with Tick-borne encephalitis or Japanese encephalitis vaccines: Results from an open label, non-randomized clinical trial

Sandberg

Löfling

Varnaitė

et al. 2022

Preprint

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Background Flavivirus infections pose a significant global health burden underscoring the need for the development of safe and efficient vaccination strategies. Available flavivirus vaccines are from time to time concomitantly delivered to individuals in need. Co-administration of different vaccines saves time and visits to health care units and vaccine clinics. It serves to provide protection against multiple pathogens in a shorter time-span, both for individuals living in, or travelling to, endemic areas. However, safety and immunogenicity-related responses have not been appropriately evaluated upon concomitant delivery of these vaccines. Therefore, we performed an open label, non-randomized clinical trial studying the safety and immunogenicity following concomitant delivery of the Yellow fever virus (YFV) vaccine with Tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus (JE) virus vaccines. Methods and findings Following screening, healthy study subjects were enrolled into different cohorts receiving either TBEV and YFV vaccines, JEV and YFV vaccines, or in control groups receiving only the TBEV, JEV, or YFV vaccine. Concomitant delivery was given in the same or different upper arms for comparison in the co-vaccination cohorts. Adverse effects were recorded throughout the study period and blood samples were taken before and at multiple time-points following vaccination to evaluate immunological responses to the vaccines. Adverse events were predominantly mild in the study groups. Four serious adverse events (SAE) were reported throughout the trial, none of them deemed related to vaccination. The development of neutralizing antibodies (nAbs) against TBEV, JEV, or YFV was not affected by the concomitant vaccination strategy. Concomitant vaccination in the same or different upper arms did not significantly affect safety or immunogenicity-related outcomes. Exploratory studies on immunological effects were additionally performed and included studies of lymphocyte activation, correlates associated with germinal center activation, and plasmablast expansion. Conclusions Inactivated TBEV or JEV vaccines can be co-administered with the live attenuated YFV vaccine without an increased risk of adverse events and without reduced development of nAbs to the respective viruses. The vaccines can be delivered in the same upper arm without negative outcome.

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Methods for addressing “innocent bystanders” when evaluating safety of concomitant vaccines

Cited by 5 publications

References 21 publications

Graphical Depiction of Longitudinal Study Designs in Health Care Databases

Graphical Depiction of Longitudinal Study Designs in Health Care Databases

Safety and immunogenicity following co-administration of Yellow fever vaccine with Tick-borne encephalitis or Japanese encephalitis vaccines: Results from an open label, non-randomized clinical trial

Safety and immunogenicity following co-administration of Yellow fever vaccine with Tick-borne encephalitis or Japanese encephalitis vaccines: Results from an open label, non-randomized clinical trial

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