Structured Benefit-Risk Assessment of a New Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Individuals Ages 12 Months and Older.

INTRODUCTION: A favorable benefit-risk balance is required to support licensure of biologics, in keeping with regulatory agencies' evolving recommendations, including the United States Food and Drugs Administration. We present a structured semi-quantitative benefit-risk analysis of MenACYW-TT, a quadrivalent meningococcal conjugate vaccine against Neisseria meningitidis serogroups, A, C, W and Y versus licensed comparators in individuals aged ≥ 12 months. METHODS: We used data from six MenACYW-TT clinical trials, stratified by age group, versus licensed vaccines: toddlers (12-23 months; Nimenrix® [MCV4-TT]), children (2-9 years; Menveo® [MCV4-CRM]), adolescents (10-17 years; MCV4-CRM or Menactra® [MCV4-DT]), adults (18-55 years; MCV4-DT) and older adults (≥ 56 years; Menomune®-A/C/Y/W-135 [MPSV4]). Eight benefit (seroresponse and seroprotection for A, C, W and Y) and five risk outcomes (any and grade 3 solicited injection site and systemic reactions, and serious adverse events) were measured at Day 30 after initial vaccination. Analyses were conducted by baseline vaccination status (meningococcal vaccine-naïve or vaccine-primed). RESULTS: MenACYW-TT showed favorable seroresponse and seroprotection among vaccine-naïve participants aged ≥ 2 years, against all serogroups, compared with MCV4-CRM, MCV4-DT and MPSV4. In vaccine-naïve toddlers, there was a favorable effect for serogroup C, but no difference between MenACYW-TT and MCV4-TT for serogroups A, Y and W. A favorable effect for MenACYW-TT against serogroup C was observed in all vaccine-naïve and combined vaccine-naïve and MenC conjugate vaccine-primed groups. For all risk criteria, there were no differences between MenACYW-TT and MCV4s in toddlers, children, adolescents and adults. Results for solicited injection site and systemic reactions favored MPSV4 in older adults. CONCLUSIONS: The benefit-risk profile for MenACYW-TT showed favorable seroresponse and seroprotection in individuals aged ≥ 2 years and no difference in risk criteria between MenACYW-TT and MCV4s. MenACYW-TT may provide an alternative to the standard-of-care for meningococcal disease prevention in those aged ≥ 12 months.

A cross-sectional survey to evaluate prescribers' knowledge and understanding of safety messages following Dengvaxia® product information update.

PURPOSE: We evaluated the effectiveness of additional risk minimisation measures (aRMMs; i.e., educational materials) distributed to prescribers to ensure that only individuals with evidence of prior dengue infection (PDI, i.e., dengue seropositive) would be vaccinated with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia®). METHODS: A survey was conducted in 2020 among 300 CYD-TDV prescribers in Brazil and Thailand to ascertain three success criteria: prescribers' awareness of the materials (receiving and reading them); knowledge of the key messages; and whether their self-reported behaviour regarding practice-related scenarios was aligned with the updated guidance. RESULTS: The aRMMs were not generally effective as <80% of prescribers in both countries met two of the three predefined success criteria. In Brazil, 98.7% were aware of the aRMMs whereas in Thailand this criterion was fulfilled by 74.0%. Almost all prescribers knew that CYD-TDV was recommended only in individuals with PDI (98.7% and 96.7% in Brazil and Thailand, respectively). In Brazil, where vaccination was restricted to those with a documented history of PDI, 11.3% considered that confirmation should be done through a blood test. More than 75% in both countries considered additional signs of dengue, as early warning signs, and not only those regarded as such by the 2009 WHO guidelines. CONCLUSIONS: These results do not support that the aRMMs were effective as the predefined success criteria were not met. The use of reliable rapid diagnosis tests together with the revised prescribing information and educational materials will facilitate the implementation and compliance with pre-vaccination screening for CYD-TDV eligibility.

Quantitative benefit-risk assessment by MCDA of the quadrivalent HPV vaccine for preventing anal cancer in males.

OBJECTIVES: To quantify the benefit-risk (BR) balance of the quadrivalent human papillomavirus (qHPV) vaccine for use in males, including anal cancer prevention, by using the multicriteria decision analysis (MCDA). METHODS: Value tree and an effect table were compiled using relevant qHPV vaccine efficacy/safety data. An expert panel validated the final model inputs. RESULTS: On a scale of 0-100, the MCDA qHPV vaccine score (66) was superior to the no vaccination score (46), indicating a more favorable BR balance for the qHPV vaccine. Significant changes in weight of individual outcomes were needed to change BR balance in sensitivity analyses. The qHPV vaccine maintained a better BR profile in all alternative models. CONCLUSIONS: MCDA can be used to transparently evaluate BR balance of vaccines. The qHPV vaccine had a favorable BR balance in males. Including anal cancer as a new indication further improves the BR profile of the qHPV vaccine.

Estimation of background incidence rates of Guillain-Barré syndrome in Germany - a retrospective cohort study with electronic healthcare data.

BACKGROUND: The Guillain-Barré syndrome (GBS) occurs after infections and as an adverse reaction to vaccines. No detailed information on incidence rates (IRs) in Germany is available. METHODS: This retrospective cohort study estimated age- and sex-specific IRs of GBS in Germany in the years 2007-2009 based on electronic healthcare data from the German Pharmacoepidemiological Research Database (GePaRD). Two case definitions were applied. GBS cases had a main discharge diagnosis of GBS. GBS_PROCEDURE cases in addition had codes for relevant diagnostic procedures. Crude and standardized IRs (SIRs) with 95% confidence intervals were stratified by year, age group, sex, region and season. IR ratios (IRRs) for each stratification factor were calculated by multivariable Poisson regression. RESULTS: Among 13,297,678 persons, 889 (693) incident GBS (GBS_PROCEDURE) cases were identified. Overall SIRs per 100,000 person years were 2.4 (2.2-2.5) for GBS and 1.8 (1.7-2.0) for GBS_PROCEDURE. (S)IRs increased with age, peaking in the age group 70-79 years (IR GBS: 5.5 (4.7-6.5)) and were higher in males than in females (e.g., IR GBS: IRR = 1.5 (1.3-1.7)) and in February-April, as compared to the rest of the year. No regional pattern was observed. CONCLUSION: (S)IRs of GBS in Germany differed by age, sex and season and were comparable to those found in other studies. RESULTS might be used as a comparator in vaccine safety monitoring.

Epidemiology and burden of rotavirus diarrhea in day care centers in Lyon, France.

This study gives, for the first time, an estimate of the incidence and the cost of rotavirus infection in day care centers in Lyon, France.