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A novel approach to evaluating the UK childhood immunisation schedule: estimating the effective coverage vector across the entire vaccine programme
© Crowe et al. 2015
Received: 7 September 2015
Accepted: 30 November 2015
Published: 29 December 2015
The availability of new vaccines can prompt policy makers to consider changes to the routine childhood immunisation programme in the UK. Alterations to one aspect of the schedule may have implications for other areas of the programme (e.g. adding more injections could reduce uptake of vaccines featuring later in the schedule). Colleagues at the Department of Health (DH) in the UK therefore wanted to know whether assessing the impact across the entire programme of a proposed change to the UK schedule could lead to different decisions than those made on the current case-by-case basis. This work is a first step towards addressing this question.
A novel framework for estimating the effective coverage against all of the diseases within a vaccination programme was developed. The framework was applied to the current (August 2015) UK childhood immunisation programme, plausible extensions to it in the foreseeable future (introducing vaccination against Meningitis B and/or Hepatitis B) and a “what-if” scenario regarding a Hepatitis B vaccine scare that was developed in close collaboration with DH.
Our applications of the framework demonstrate that a programme-view of hypothetical changes to the schedule is important. For example, we show how introducing Hepatitis B vaccination could negatively impact aspects of the current programme by reducing uptake of vaccines featuring later in the schedule, and illustrate that the potential benefits of introducing any new vaccine are susceptible to behaviour changes affecting uptake (e.g. a vaccine scare). We show how it may be useful to consider the potential benefits and scheduling needs of all vaccinations on the horizon of interest rather than those of an individual vaccine in isolation, e.g. how introducing Meningitis B vaccination could saturate the early (2-month) visit, thereby potentially restricting scheduling options for Hepatitis B immunisation should it be introduced to the programme in the future.
Our results demonstrate the potential benefit of considering the programme-wide impact of changes to an immunisation schedule, and our framework is an important step in the development of a means for systematically doing so.
KeywordsChildhood immunisation programme Modelling framework Effective coverage
Decisions to change the immunisation programme are currently made on a case-by-case basis, informed primarily by cost-effectiveness analysis specific to the vaccine change being considered [1–5]. Typical changes might involve introducing a new vaccine to protect against a disease not previously covered, or changing the vaccine product used to protect against a disease already in the programme.
However, alterations to one aspect of the schedule, whether to the timing of existing vaccinations or the introduction of a new vaccine product, may have implications for other areas of the programme. For example, there are potential mechanisms whereby adding more injections to the schedule could reduce the uptake of vaccines that feature later in the schedule [6–12]. For instance, the likelihood that a parent brings their child to a particular visit may depend on the number of visits they have already attended (visit fatigue) and/or whether any of these visits involved a “bad experience”, as well as the perceived importance and safety of each vaccine scheduled for that visit. This introduces the scope for changes to the programme having less overall benefit than anticipated - or even causing net harm.
Given this, it is important to consider whether assessing the overall programme-level impact of a proposed change to the schedule could lead to different decisions than those made on a case-by-case basis. However, at present, decision-makers do not have a systematic way to do this. For example, there is no framework for exploring the impact that a particular change to the immunisation schedule might have on the coverage achieved for other diseases that occur later in the programme and thus the potential consequences on the overall burden of vaccine preventable disease on the population. Authors from the UK Department of Health (DH) (GW and PG) asked the other authors to explore collaboratively the feasibility of developing such a framework that could be used for future UK immunisation planning.
Within the context of the US immunisation schedule, previous work has considered the optimal formulation of combination vaccines using integer programming, incorporating schedule-relevant constraints and capturing the associated costs [13–17]. Jacobson et al.  developed a web-based tool that enables decision-makers to use economic factors beyond vaccine purchase price to design childhood vaccine formularies within a given context, including the value of existing and new combination vaccines. In contrast to this previous work, we do not consider costs in this paper and instead focus our study on developing a framework to estimate how changes to the vaccine programme could impact the effective coverage against each disease in order to inform decision making, given the current schedule. With the intent of illustrating how a programme-view of vaccine procurement could be beneficial, we apply the framework to the current UK childhood immunisation programme (August 2015) and explore a selection of feasible future changes to the schedule. The parameter space and set of constraints we consider is thus smaller than in Jacobson et al.’s work. The development and application of our framework is an important first step towards evaluating the programme-level impact of changes in a given childhood immunisation programme.
Developing a modelling framework to estimate the effective coverage against all diseases within a schedule
Assumptions regarding vaccine uptake
Estimated percentage of parents refusing a vaccine for each vaccine considered
% children whose parents refuse vaccine
Pediacel (primary and booster); Repevax; Infanrix Hexa (primary and booster); Infanrix Penta (primary and booster); Bexsero
Meningitec (primary and booster); Menitorix (primary and booster); M-M-RVAXPRO (courses 1 and 2); HBVaxPro; Rotarix
Prevenar 13 (courses 1 and 2)
Model inputs for the probability of attendance
Probability of attendance (no bad experience)
Probability of attendance (after bad experience)
Inputs for the modelling framework
Diseases covered and vaccine products available
Within our framework we first identified the set of diseases/causative agents that are either already covered as part of the UK childhood immunisation programme (Diphtheria, Pertussis, Tetanus, Polio, Neisseria Meningitides Group C, Haemophilus influenzae B, Measles, Mumps, Rubella, Pneumococcal disease), or that were considered by DH authors to be possible candidates for inclusion in the programme within the foreseeable future (Hepatitis B and Meningitides Group B). We note that at the time of conducting the work, the recent decision to introduce Meningitis B vaccination to the programme had not been made and a procurement contract was agreed (as of end March 2015) just before submission of this work. Hepatitis A and Varicella were not included on the basis that, on cost-effectiveness grounds, they were less likely to be included in the schedule in the medium term. We compiled a list of available vaccine products relevant to these diseases [19–21].
The current immunisation schedule (GP visits)
At the time of writing (August 2015), the current childhood immunisation programme in the UK comprises five scheduled General Practitioner (GP) visits, at 2, 3, 4, 12–13 months and 40–60 months old with immunisation against 11 diseases (see Table 1).
Establishing plausible alternative immunisation schedules (GP visits)
Assuming it nonviable to withdraw vaccination against any disease currently targeted, we firstly manually explored alternative schedules for delivering vaccination against the diseases targeted by the current programme. We then extended this by allowing the possible addition of vaccination against Hepatitis B, Meningitis B, or both Hepatitis B and Meningitis B. In each case we constructed feasible vaccine schedules and attendant product combinations under five simplifying assumptions. Firstly, we assumed that additional vaccinations in the programme would, where possible, fit into existing scheduled GP visits, which would remain in the scheduled visits of the current programme (unless removed entirely), and where this was not possible we minimised the number of additional visits. Secondly, we assumed that no more than 3 injections would be given in any one GP visit within infancy (up to 1 year of age) but that after 1 year, a child can receive 4 injections in any one visit [DH, private communication]. We note that the Joint Committee on Vaccination and Immunisation (JCVI) have recommended the introduction of the Men B vaccine at months 2, 4 and 12 [22, 23], which would require four injections in the visit at month 12, so we explicitly allow for this option. Thirdly, we assumed that a disease cannot be vaccinated against more than once within the same visit (i.e. a disease can only be vaccinated by one product at any one time). Fourthly, we ignored vaccination against diseases not explicitly included in the programme (e.g. as a by-product of a combination vaccine). Finally, if two or more vaccine products provide protection against the same diseases under the same schedule then they were considered within the same option. We used the Electronic Medicines Compendium  to determine possible vaccine schedules where needed.
Vaccines considered, the diseases they vaccinate against and the efficacies used in the modelling
Diseases vaccinated (efficacy used for modelling)
Menjugate or NeisVac Primary (<1 year old)
Men C (0.994)
Menjugate or NeisVac Booster (>1 year old)
Men C (1)
Menitorix Primary (<1 year old)
Men C (0.993), Hib (1)
Menitorix Booster (>1 year old)
Men C (0.98 different primary, 1 otherwise), Hib (1)
MMR VAXPRO/Priorix after one dose (>1 year old)
Measles (0.90), Mumps (0.64), Rubella (0.99)
MMR VAXPRO/Prioirix after two dosesa (>1 year old)
Measles (0.99), Mumps (0.87), Rubella (0.999)
Pediacel (<1 year old)
Tetanus (1), Polio (1), Diphtheria (0.992), Pertussis (0.987), Hib (0.91)
Pediacel (>1 year old)
Tetanus (1), Polio (1), Diphtheria (0.991), Pertussis (0.967), Hib (0.991)
Prevenar 13 (both doses)
Repevax or Infanrix IPV (>3 years old)
Tetanus (1), Polio (1), Diphtheria (1), Pertussis (0.995)
Rotarix (<1 year old)
HBVaxPRO (both doses)
Hep B (0.96)
Infanrix Hexa (<1 year old)
Tetanus (1), Polio (1), Diphtheria (1), Pertussis (1), Hib (0.964), Hep B (0.995)
European medicines agency
Infanrix Hexa (>1 year old)
Tetanus (0.999), Polio (0.999), Diphtheria (0.999), Pertussis (0.999), Hib (0.997), Hep B (0.984)
European medicines agency
Men B (0.836)
Application of the framework to different vaccine scenarios
To demonstrate how the framework could be used, we applied it to the current UK childhood vaccination schedule and each of the plausible schedules that had been established in order to compare the vectors of effective coverage. We then developed some illustrative examples, each involving the introduction of Hep B vaccination, to demonstrate how the programme-view of vaccine procurement could potentially lead to different decisions than the case-by-case approach. In Example 1, we introduce vaccination against Hep B to the current schedule using HBVaxPro, resulting in an extra GP visit at 10 months. In Example 2 , vaccination against Hep B is introduced to the current schedule by replacing the DtaP primary course (Pediacel) and booster (Repevax or Infanrix IPV) with Infranix Hexa and switching the Men C booster from Menitorix to NeisVac (or Menjugate Kit). In Example 3 we used the framework to examine a ‘what-if’ scenario of interest to policy makers around the possible impact of a negative media reporting that might impact on parents’ willingness to partake in aspects of the programme. This is a scenario of particular interest following the impact of the MMR scare in the UK, which reduced the coverage for MMR vaccines from 92 % in 1996 to 80 % in 2003 [24, 25]. This Hep B scenario is also relevant given the public concern and relatively low uptake of the flu vaccine in the UK  and reported parental concern and low uptake of the Hepatitis B vaccine in France [26, 27]. In this hypothetical scenario, we assumed that there was negative media reporting surrounding the introduction of the Infanrix Hexa vaccine for Hepatitis B that increased parental refusal of this vaccine (see for instance these 2009 UK media articles worrying about such an introduction [28, 29]). To model this, we use Option 5 (Table 6) but assume a higher proportion (5 % rather than 0.5 %) of parents refusing to attend for visits where Infanrix Hexa is administered. In addition to its impact on the coverage of all diseases targeted by the combination vaccine this would also affect the Men C, Rotavirus, Pneumococcal and MMR vaccinations. Our intention was to illustrate how strategies for targeting efforts to improve the vaccination programme could be informed by scenario analysis such as this, alongside considerations of feasibility and cost.
Current and plausible future vaccination schedules
Vaccination options for the current UK childhood immunisation programme and plausible extensions to it in the foreseeable future
Number of visits
Current programme: Diphtheria, Pertussis, Tetanus, Polio, Neisseria Men C, Hib, Pneumococcal disease, Measles, Mumps, Rubella and Rotavirus
Pediacel; Repevax (or Infanrix IPV); NeisVac (or Menjugate Kit); Menitorix; Prevenar 13; MMR-VAXPRO (or Priorix); Rotarix
Pediacel; NeisVac (or Menjugate Kit); Prevenar 13; MMR-VAXPRO (or Priorix); Rotarix
As in current programme + Hepatitis B
Pediacel; Repevax (or Infanrix IPV); NeisVac (or Menjugate Kit); Menitorix; Prevenar 13; MMR-VAXPRO (or Priorix); Rotarix; HBVaxPro
Pediacel; NeisVac (or Menjugate Kit); Prevenar 13; MMR-VAXPRO (or Priorix); Rotarix; HBVaxPro
Infanrix Hexa; NeisVac (or Menjugate Kit); Prevenar 13; MMR-VAXPRO (or Priorix); Rotarix
As in current programme + Men B
Pediacel; Repevax (or Infanrix IPV); NeisVac (or Menjugate Kit); Menitorix; Prevenar 13; MMR-VAXPRO (or Priorix); Rotarix; Bexsero
Pediacel; NeisVac (or Menjugate Kit); Prevenar 13; MMR-VAXPRO (or Priorix); Rotarix; Bexsero
As in current programme + Hepatitis B + Men B
Infanrix Hexa; NeisVac (or Menjugate Kit); Prevenar 13; MMR-VAXPRO (or Priorix); Rotarix; Bexsero
From Fig. 5 we see that introducing Hep B by replacing the DtaP/IPV/Hib primary course and booster with Infranix Hexa and switching the Men C booster (Example 2) has benefits over and above the impact of Hep B by improving Pertussis, Hib, Men C protection (higher efficacy for all three), as well as MMR protection (higher coverage). This is a marked contrast to the generally worse effective coverage seen across the programme from Example 1 (Option 7, discussed above). Finally, through Example 3, where we compare the impact of introducing a combination vaccine to the current schedule with and without a vaccine scare, Fig. 5 illustrates how the potential benefits of introducing a new vaccine are susceptible to behaviour changes that affect uptake and so its introduction could potentially result in an overall worsening of the programme instead of an improvement.
We have developed a novel framework for estimating the effective coverage that would be achieved against each disease included in a given childhood immunisation schedule and applied this within the context of the UK vaccination programme.
Firstly, we showed in our analysis that, under certain assumed constraints, there is only one plausible alternative vaccine schedule to the current one, an interesting finding that had not been explicitly recognised by colleagues at DH prior to this work.
Secondly, when we applied the framework to plausible extensions of the current (August 2015) immunisation schedule in the foreseeable future (introducing vaccination against Men B and/or Hep B) and an additional scenario exploring the impact of negative media coverage of a new vaccine, we illustrated how it might be useful to evaluate the programme-wide impact of a particular change to an immunisation schedule in contrast to the case-by-case approach used at present. For instance, introducing a single Hepatitis B vaccination is shown in one of our examples (Example 1) to impact negatively on many parts of the existing programme because it reduces the overall uptake of vaccines featuring later in the schedule (by increasing visit fatigue and the chances of a bad experience), but introducing Hep B as part of a combination vaccination benefits the rest of the programme since the combination vaccine also has higher efficacy against already covered diseases. Interestingly, however, negative media coverage surrounding the introduction of Hepatitis B, could potentially result in an overall worsening of the programme benefit of introducing Hepatitis B to the current schedule even in the most beneficial schedule option (Example 3). In this illustrative example, a higher than normal proportion of parents refuse to attend for visits where the Infanrix Hexa vaccine is administered, which affects the uptake of the Meningitis C, Rotavirus, Pneumococcal and MMR vaccinations as well as Hepatitis B and the other diseases covered by the combination vaccine, with knock-on negative impact on programme benefit as a whole.
Within the context of the enormous progress over the last 60 years in protecting children against diseases such as Polio and Diphtheria, which are now virtually eliminated in the UK, the current immunisation programme arguably has greatest room for improvement in better protecting against: Pertussis (due to the high incidence  and relatively low efficacy of primary vaccine); Pneumococcal (for which there are many complications and some long term sequelae ) and; Rotavirus (which affects a lot of small children [2, 31]). Of the plausible extensions to the current programme, the introduction of Meningitis B vaccine may be particularly beneficial since it is serious disease that kills 1 in 10 people affected and leaves a further third with long lasting effects, some as serious as amputations, brain damage and hearing loss [1, 32]. Indeed, since conducting this work, the decision has been made to introduce Meningitis B vaccination into the childhood immunisation programme  and, as of March 2015, the UK government have negotiated a procurement contract to enable vaccination to start later in 2015 or early in 2016  (its routine use is not yet included in the Meningococcal chapter of the Government’s Green Book ). This decision was based largely on considerations of its cost effectiveness and uncertainty around estimates of cost-effectiveness . Within this context, our work provides a timely illustration of why it might also be useful to take a programme-view that considers the potential benefits and scheduling needs of all vaccinations on the horizon of interest rather than those of an individual vaccine in isolation. For instance, introducing Meningitis B immunisation into the current vaccination schedule would require an additional injection in the early (2 month) GP visit. Within our framework, this saturates that 2 month visit with the maximum number of injectable vaccines, which reduces flexibility for later introductions of other vaccines to the immunisation programme. For example, if immunisation against Hepatitis B was subsequently introduced to the programme (in addition to Meningitis B), this would only be achievable by switching certain other vaccine products (see schedule Option 8) or introducing another GP visit to the schedule. On the other hand, adding both Men B and Hep B to the schedule potentially provides greater overall gain to the immunisation programme (even excluding any benefit from preventing Hep B) than adding only Men B because the combination vaccine that includes Hep B offers better protection for Pertussis. This demonstrates how our framework can usefully augment existing cost-effectiveness analyses and why it may be important to take a more strategic view of procurement decisions.
This work was conducted in direct response to a specific request from DH to examine the potential usefulness of a programme-view in evaluating changes to the immunisation schedule. Thus one of the strengths of the work is that we collaborated with the DH to ensure that our work was informed by the nature of the potential decisions faced in this area. Aspects of the model development, parameterisation and analysis therefore focused on features of the current UK immunisation programme. However, we note that our framework is flexible in terms of input parameters and constraints and can therefore readily be applied to any vaccination programme and can easily accommodate possible alterations to incorporate future vaccination programme changes.
This work has successfully illustrated why it may be important to take a more strategic view of procurement decisions. We note, however, that a programme-wide evaluation of a schedule cannot include the level of detail incorporated in individual vaccine cost benefit analyses such as those currently performed when considering, for example, whether to introduce a particular vaccine. We therefore stress that this framework is not proposed as a replacement to cost-effectiveness analyses, but rather to sit alongside them in informing the difficult decisions that need to be made regarding vaccine procurement and options for improving the vaccination programme. We believe that the strategic view demonstrated using our framework offers a complementary approach to the current case-by-case one. However, whilst informative, the effective coverage vector does not provide an easy means for comparison across different diseases within a schedule or for the evaluation and comparison of different schedules at a programme level since it does not take into account disease burden (i.e. weighting the importance of effective coverage by severity and prevalence of the disease). Thus, the framework presented here represents an important starting point of what could be a larger-scale definitive framework able to inform national immunisation policy. For example, a natural extension of the framework would be to develop a platform for quantifying disease burden from the vector of effective coverage by incorporating disease-specific epidemiological models and, where necessary, developing models to project the number of disease cases under different vaccine scenarios.
We have developed a novel framework for estimating the vector of effective coverage across all of the diseases in a given vaccination programme and applied it within the UK context. This is an important step towards providing decision-makers with a means for systematically exploring the programme-wide impact of a particular change to an immunisation schedule and assessing scope for further reducing the burden of vaccine preventable disease across a programme. Our analyses using the framework highlight illustrative circumstances in which taking such a programme view may be beneficial.
We would like to thank Dr Mark Jit and Dr Joanna White (Public Health England, formerly the Health Protection Agency), Mr Tom Barlow (Department of Health, Immunisations) Dr Helen Bedford (Institute of Child Health, University College London) and Prof John Edmunds (London School of Hygiene and Tropical Medicine) for helpful discussions related to this work. The Clinical Operational Research Unit receives funding from the Department of Health’s Policy Research Programme.
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