Developing Product Label Information to Support Evidence-Informed Use of Vaccines in Pregnancy

Background: Product labelling information describing the use of vaccines in pregnancy continues to contain cautionary language even after clinical and epidemiological evidence of safety becomes available. This language raises safety concerns among healthcare providers who may hesitate to recommend vaccines during pregnancy. Purpose: To develop clear evidence-based language about vaccine safety and effectiveness in pregnancy for inclusion in vaccine product labels. Methods: We conducted a three-stage consensus-methods project with stakeholders, including: healthcare providers, vaccine regulators, industry representatives, and experts in public health, communication, law, ethics, and social sciences. Using qualitative and quantitative methods, we held a nominal group technique (NGT) meeting, followed by a Delphi survey, and then a consensus workshop with a subset of Delphi participants. We developed a methodological tool to analyse data for consensus. Principal results: Stakeholders (N = 14) at the NGT meeting drafted product label statements for evaluation in the Delphi survey. Survey participants (N = 41) provided feedback on statements for five hypothetical vaccines. Workshop participants (N = 27) initiated discussions that demonstrated a lack of awareness that the regulatory purpose of product labels is to provide a scientific summary of product-specific preclinical and clinical trial data. Each stage of this project built on earlier stages until we achieved strong consensus on the language, structure, and types of data that stakeholders wanted to include in inactivated influenza vaccine (IIV) and tetanus-diphtheria-acellular pertussis (Tdap) vaccine product labels in Canada. Conclusions: The revised statements for IIV and Tdap aligned with workshop participants’ goals that the product label be evidence-based, with a consistent structure and language that is easily understood by healthcare providers. Emergent methods uncovered stakeholder concerns about the regulatory purpose, content, and evidence used in product labels. Involving healthcare providers in the development and regular updating of product information could prevent interpretations of that information that contribute to vaccine hesitancy

Neonatal infections: Case definition and guidelines for data collection, analysis, and presentation of immunisation safety data.

Maternal vaccination is an important area of research and requires appropriate and internationally comparable definitions and safety standards. The GAIA group, part of the Brighton Collaboration was created with the mandate of proposing standardised definitions applicable to maternal vaccine research. This study proposes international definitions for neonatal infections. The neonatal infections GAIA working group performed a literature review using Medline, EMBASE and the Cochrane collaboration and collected definitions in use in neonatal and public health networks. The common criteria derived from the extensive search formed the basis for a consensus process that resulted in three separate definitions for neonatal blood stream infections (BSI), meningitis and lower respiratory tract infections (LRTI). For each definition three levels of evidence are proposed to ensure the applicability of the definitions to different settings. Recommendations about data collection, analysis and presentation are presented and harmonized with the Brighton Collaboration and GAIA format and other existing international standards for study reporting

Risk of seizures after immunization in children with epilepsy: a risk interval analysis

Abstract Background In children with epilepsy, fever and infection can trigger seizures. Immunization can also induce inflammation and fever, which could theoretically trigger a seizure. The risk of seizure after immunization in children with pre-existing epilepsy is not known. The study objective was to determine the risk of medically attended seizure after immunization in children with epilepsy < 7 years of age. Methods We conducted a retrospective study of children < 7 years of age with epilepsy in Nova Scotia, Canada from 2010 to 2014. Hospitalizations, emergency visits, unscheduled clinic visits, and telephone calls for seizures were extracted from medical records. Immunization records were obtained from family physicians and Public Health with informed consent. We conducted a risk interval analysis to estimate the relative risk (RR) of seizure during risk periods 0–14, 0–2, and 5–14 days post-immunization versus a control period 21–83 days post-immunization. Results There were 302 children with epilepsy who were eligible for the study. Immunization records were retrieved on 147 patients (49%), of whom 80 (54%) had one or more immunizations between the epilepsy diagnosis date and age 7 years. These 80 children had 161 immunization visits and 197 medically attended seizures. Children with immunizations had more seizures than either those with no immunizations or those with no records (mean 2.5 versus 0.7 versus 0.9, p < 0.001). The risk of medically attended seizure was not increased 0–14 days after any vaccine (RR = 1.1, 95% confidence interval (CI): 0.5–2.8) or 0–2 days after inactivated vaccines (RR = 0.9, 95% CI: 0.1–7.1) versus 21–83 days post-immunization. No seizure events occurred 5–14 days after live vaccines. Conclusions Children with epilepsy do not appear to be at increased risk of medically attended seizure following immunization. These findings suggest that immunization is safe in children with epilepsy, with benefits outweighing risks

Vaccine regulation should require and enforce the inclusion of pregnant and breastfeeding women in prelicensure clinical trials

Exclusion of pregnant and breastfeeding women from the pivotal randomized controlled trials for COVID-19 vaccines that led to emergency regulatory approval created gaps in data needed for vaccine policy, healthcare provider recommendations, and women’s decisions about vaccination. We argue that such knowledge gaps increase potential for vaccine hesitancy and misinformation relating to the health of women and infants, and that these gaps in evidence are avoidable. Over several decades, ethical and scientific guidance, scholarship, and advocacy in favor of pregnant and breastfeeding women’s participation in clinical development of vaccines has accumulated. Guidance on how to include pregnant and breastfeeding women in vaccine trials ethically and safely predates the COVID-19 pandemic but has yet to be routinely incorporated in vaccine development. We highlight the important role regulatory authorities could play in requiring that pregnant and breastfeeding women be eligible as volunteer participants in prelicensure vaccine trials for products that are expected to be used in this population. Inclusion of pregnant and breastfeeding populations in clinical trials leading to market approval or emergency use authorization should be undertaken early or concurrently at the time of trials in the general population

Physician vaccination practices in mild to moderate inborn errors of immunity and retrospective review of vaccine completeness in IEI: results from the Canadian Immunization Research Network

Background and objectives Safety and effectiveness concerns may preclude physicians from recommending vaccination in mild/moderate inborn errors of immunity (IEI). This study describes attitudes and practices regarding vaccination among physicians who care for patients with mild/moderate B cell or mild/moderate combined immunodeficiencies (CID) and vaccination completeness among patients diagnosed with IEIs. Methods Canadian physicians caring for children with IEI were surveyed about attitudes and practices regarding vaccination in mild/moderate IEI. Following informed consent, immunization records of pediatric patients with IEI evaluated before 7 years of age were reviewed. Vaccine completeness was defined at age 2 years as 4 doses of diphtheria-tetanus-pertussis (DTaP), 3 doses pneumococcal conjugate (PCV), and 1 dose measles-mumps-rubella (MMR) vaccines. At 7 years 5 doses of DTP and 2 doses MMR were required. Results Forty-five physicians from 8 provinces completed the survey. Most recommended inactivated vaccines for B cell deficiency: (84% (38/45) and CID (73% (33/45). Fewer recommended live attenuated vaccines (B cell: 53% (24/45), CID 31% (14/45)). Of 96 patients with IEI recruited across 7 centers, vaccination completeness at age 2 was 25/43 (58%) for predominantly antibody, 3/13 (23%) for CID, 7/35 (20%) for CID with syndromic features, and 4/4 (100%) for innate/phagocyte defects. Completeness at age 7 was 15%, 17%, 5%, and 33%, respectively. Conclusion Most physicians surveyed recommended inactivated vaccines in children with mild to moderate IEI. Vaccine completeness for all IEI was low, particularly at age 7. Further studies should address the reasons for low vaccine uptake among children with IEI and whether those with mild-moderate IEI, where vaccination is recommended, eventually receive all indicated vaccines.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche

Kawasaki disease following immunization reported to the Canadian Immunization Monitoring Program ACTive (IMPACT) from 2013 to 2018

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting children younger than 5 y of age that has been reported as an adverse event following immunization (AEFI). The Canadian Immunization Monitoring Program ACTive (IMPACT) conducts active surveillance for KD following immunization across Canada. We characterized KD cases reported to IMPACT between 2013 and 2018. Cases admitted to an IMPACT hospital with a physician diagnosis of complete or incomplete KD with onset 0–42 d following vaccination were reviewed. Cases meeting the Brighton Collaboration case definition (BCCD) levels of diagnostic certainty levels 1 a/b, 2a/b or 3a-e were defined as KD cases. Demographic and vaccination characteristics were compared between KD cases and non-cases. Of 84 cases reviewed, 58 met the BCCD: 47 (81%) cases met level 1a (Complete KD), 8 (14%) met level 1b (Incomplete KD), 2 (3%) met level 2a, and 1 (2%) met level 2c (Probable KD). Median age at admission was 13 months (interquartile range 7–26 months). A median of 9.5 cases were reported per year (range 4–14). Thirty-one (53%) KD cases were temporally associated with diphtheria-tetanus acellular pertussis containing vaccinations, followed by 21 (36%) cases with pneumococcal conjugate vaccines. Symptom onset was 0–14 d after vaccination in 32 (55%) cases. Echocardiogram results were available for 43 (74%) cases with 22 reported as abnormal. Age, sex, interval to symptom onset, and vaccines received were similar between KD cases and non-cases. No safety signals were detected in these data