Impact case study database

Meningococcal disease is a leading infectious cause of death in young children in the UK. The disease progresses rapidly even with appropriate treatment and can leave survivors with severe disabling after-effects, including amputation, skin scarring and neurological damage. At the time of initial model development for this work, a broadly effective vaccine against group B meningococcal disease was not available, though several candidate ‘MenB’ vaccines were in late stage clinical trials.

Impact on vaccination policy in the UK

In January 2013, once the first broadly effective vaccine against MenB disease (Bexsero) was granted an EU license, policy makers needed to urgently consider if and how to utilise it. In the UK, the requirement for the JCVI to only recommend vaccines that are cost-effective means that mathematical models are used as a key tool to inform policy making, as they can explore multiple different scenarios.

The underpinning research by UoB had indicated which introductory vaccine strategy would have the greatest impact in terms of meningococcal case reduction and estimated the cost-effectiveness of the programme [1]. As a result of submitting evidence on UoB’s research results to a JCVI call for evidence on issues relating to meningococcal vaccination in 2011, Dr Christensen was invited to present the findings of the ongoing model development at closed JCVI meetings in February, April, June 2013, and February 2014 [A].

In March 2014, the JCVI recommended the introduction of Bexsero in the UK with a schedule from UoB’s model that offered the greatest direct protection at reduced cost [2], subject to a cost-effective vaccine price [B]. JCVI’s position statement on the use of Bexsero explained that a “key component” in JCVI’s assessment of the drug was “a study on the impact and cost-effectiveness of different vaccination strategies using Bexsero® conducted by the University of Bristol and London School of Hygiene and Tropical Medicine” [Bi p.2]. UoB’s research is discussed at length (pp.2-3) and cited on five occasions in the statement [Bi]. The vaccine has been offered free on the NHS to babies at 2, 4 and 12 months of age since September 2015 and forms part of the ongoing national programme [B].

Public Health impact in the UK

Bexsero vaccine uptake has been high. In 2019/20, 92.5% of 12 month olds had been vaccinated [C]. The programme has been effective at reducing cases of meningococcal disease [D] and the associated morbidity and mortality. Cases in vaccine-eligible infants halved in the first 10 months of the programme, irrespective of the infants’ vaccination status, and subsequent data have shown a sustained reduction in MenB cases compared with pre-vaccine levels in those targeted for vaccination (Figure 1). By the third year of the programme there was a 75% reduction in MenB cases in children who were fully eligible for vaccination [E]. Due to the vaccine’s composition, it also offers some protection against other capsular groups and, whilst case numbers are small, there is evidence that the vaccine has also reduced MenW disease in infants [D].

Economic impacts for the NHS

UoB’s models suggested vaccination would only be cost-effective at a low vaccine price [2]. The JCVI can only recommend introducing a vaccine if it is deemed cost-effective, thus UoB’s models were critical to their decision to recommend the vaccine and at what price.

These were the only independent models considered by JCVI [B]. The list price for the Bexsero vaccine in the UK was GBP 75 per vaccine dose; however, UoB’s final model results suggesting ≤GBP 7 per dose [2] were used to inform the procurement process, thus leveraging a considerable saving to the NHS. As for all vaccines procured for the NHS, the final price paid for the vaccine is confidential. Notwithstanding, if the negotiated price of the vaccine was close to that suggested by UoB’s final model, it can be assumed that the research could currently save the Department of Health approximately GBP 136 million annually on delivering the programme (difference between GBP 75 and GBP 7 for a 3-dose vaccine given to a birth cohort annually of 722,881 UK infants with 92.5% uptake).

Impact on international vaccination policy

The models developed for the UK have been adapted by the UoB-led group in collaboration with international researchers to inform Bexsero policy decisions in Belgium (2014) [G] and Germany (December 2013) [H]. Our group was approached by researchers at the Robert Koch Institute and the Belgian Healthcare Knowledge Centre and commissioned to undertake the work. Models for these countries [3] indicated that whilst vaccination could reduce case numbers, immunisation would be beyond that normally considered cost-effective; consequently, these countries have not recommended widespread introduction of the vaccine [G, H].

Figure 1: MenB cases in children under 5 years of age during 2013/2014–2018/2019 surveillance years (September–August following year) in England (solid line) compared with MenB cases predicted by trends among unvaccinated childhood cohorts (dashed line) over the same period. The arrow indicates the start of the MenB infant immunisation programme. Only around half of the birth cohorts in children under 5 in this figure were eligible for the Bexsero vaccine, thus underestimating the true impact of the vaccine in those who actually received it [F]. In children who were fully eligible for vaccination there was a 75% reduction in MenB cases by the third year of the programme [E].