Assessing the Role of Infant and Toddler MenACWY Immunisation in the UK: Does the Adolescent MenACWY Programme Provide Sufficient Protection?

A combined Haemophilus influenzae type b (Hib)/meningococcal serogroup C (MenC) vaccine will soon be unavailable in the UK immunisation schedule due to discontinuation by the manufacturer. An interim statement by the Joint Committee on Vaccination and Immunisation (JCVI) advises stopping MenC immunisation at 12 months of age when this occurs. We undertook an analysis of the public health impact of various potential meningococcal vaccination strategies in the UK in the absence of the Hib/MenC vaccine. A static population-cohort model was developed evaluating the burden of IMD (using 2005-2015 epidemiological data) and related health outcomes (e.g., cases, cases with long-term sequelae, deaths), which allows for the comparison of any two meningococcal immunisation strategies. We compared potential strategies that included different combinations of infant and/or toddler MenACWY immunisations with the anticipated future situation in which a 12-month MenC vaccine is not used, but the MenACWY vaccine is routinely given in adolescents. The most effective strategy is combining MenACWY immunisation at 2, 4, and 12 months of age with the incumbent adolescent MenACWY immunisation programme, resulting in the prevention of an additional 269 IMD cases and 13 fatalities over the modelling period; of these cases, 87 would be associated with long-term sequelae. Among the different vaccination strategies, it was observed that those with multiple doses and earlier doses provided the greatest protection. Our study provides evidence suggesting that the removal of the MenC toddler immunisation from the UK schedule would potentially increase the risk of unnecessary IMD cases and have a detrimental public health impact if not replaced by an alternate infant and/or toddler programme. This analysis supports that infant and toddler MenACWY immunisation can provide maximal protection while complementing both infant/toddler MenB and adolescent MenACWY immunisation programmes in the UK.

Impact of pandemics and disruptions to vaccination on infectious diseases epidemiology past and present.

Infectious diseases are a leading cause of morbidity and mortality worldwide with vaccines playing a critical role in preventing deaths. To better understand the impact of low vaccination rates and previous epidemics on infectious disease rates, and how these may help to understand the potential impacts of the current coronavirus disease 2019 (COVID-19) pandemic, a targeted literature review was conducted. Globally, studies suggest past suboptimal vaccine coverage has contributed to infectious disease outbreaks in vulnerable populations. Disruptions caused by the COVID-19 pandemic have contributed to a decline in vaccination uptake and a reduced incidence in several infectious diseases; however, these rates have increased following the lifting of COVID-19 restrictions with modeling studies suggesting a risk of increased morbidity and mortality from several vaccine-preventable diseases. This suggests a window of opportunity to review vaccination and infectious disease control measures before we see further disease resurgence in populations and age-groups currently unaffected.

An Insurance Value Modeling Approach That Captures the Wider Value of a Novel Antimicrobial to Health Systems, Patients, and the Population.

Background: Traditional health economic evaluations of antimicrobials currently underestimate their value to wider society. They can be supplemented by additional value elements including insurance value, which captures the value of an antimicrobial in preventing or mitigating impacts of adverse risk events. Despite being commonplace in other sectors, constituents of the impacts and approaches for estimating insurance value have not been investigated. Objectives: This study assessed the insurance value of a novel gram-negative antimicrobial from operational healthcare, wider population health, productivity, and informal care perspectives. Methods: A novel mixed-methods approach was used to model insurance value in the United Kingdom: (1) literature review and multidisciplinary expert workshops to identify risk events for 4 relevant scenarios: ward closures, unavoidable shortage of conventional antimicrobials, viral respiratory pandemics, and catastrophic antimicrobial resistance (AMR); (2) parameterizing mitigable costs and frequencies of risk events across perspectives and scenarios; (3) estimating insurance value through a Monte Carlo simulation model for extreme events and a dynamic disease transmission model. Results: The mean insurance value across all scenarios and perspectives over 10 years in the UK was £718 million, should AMR remain unchanged, where only £134 million related to operational healthcare costs. It would be 50%-70% higher if AMR steadily increased or if a more risk-averse view (1-in-10 year downside) of future events is taken. Discussion: The overall insurance value if AMR remains at current levels (a conservative projection), is over 5 times greater than insurance value from just the operational healthcare costs perspective, traditionally the sole perspective used in health budgeting. Insurance value was generally larger for nationwide or universal (catastrophic AMR, pandemic, and conventional antimicrobial shortages) rather than localized (ward closure) scenarios, across perspectives. Components of this insurance value match previously published estimates of operational costs and mortality impacts. Conclusions: Insurance value of novel antimicrobials can be systematically modeled and substantially augments their traditional health economic value in normal circumstances. These approaches are generalizable to similar health interventions and form a framework for health systems and governments to capture broader value in health technology assessments, improve healthcare access, and increase resilience by planning for adverse scenarios.

Persistence with daily growth hormone among children and adolescents with growth hormone deficiency in the UK.

Background: Children with growth hormone deficiency (GHD) are treated with daily somatropin injections; however, poor treatment persistence and adherence have been recognized previously and have been shown to negatively impact growth outcomes. A recent real-world study of a US pediatric GHD population found that a substantial proportion of children discontinued somatropin therapy, but similar data for a real-world UK population are lacking. Objectives: To describe the discontinuation of, and persistence with, daily somatropin treatment among children with GHD in the UK. Methods: This was a retrospective cohort study of children (≥3 and <16 years old) with ≥1 medication prescription for daily injectable somatropin from 1 July 2000 to 31 December 2020 in the IQVIA Medical Research DATA (IMRD) database. Early persistence was defined as the proportion of children prescribed ≥1 somatropin refill (≥2 prescriptions). Discontinuation was defined as the first date at which a medication gap for somatropin (of >60 or >90 days between prescriptions) occurred. Kaplan-Meier methods were used to evaluate persistence (non-discontinuation) over time to assess time to first discontinuation event. Cox proportional hazards models were used to evaluate the relationship between patient characteristics and time to medication discontinuation. Results: Among the cohort identified in this study (n = 117), the majority (n = 84, 71.8%) had 48 months of available follow-up; 56.4% were boys and the mean (median) age was 8.6 (8.0) years. About 98% exhibited early persistence, but persistence over the follow-up period decreased with follow-up duration. Using the conservative 90-day gap definition of persistence, an estimated 72.4%, 52.8%, and 43.3% were persistent at 12, 36, and 48 months. Lower persistence rates were observed using the 60-day definition. No significant patient predictors of time to discontinuation were identified. Conclusions: Despite high early persistence with somatropin, a high percentage of children with GHD were increasingly non-persistent over time. More than 1 in 4 were non-persistent at 12 months and more than 1 in 2 were non-persistent at 48 months of follow-up. These results suggest that strategies to support improved medication-taking behavior among children with GHD in the UK are warranted.