Meningitis B vaccinationresearchbriefings.files.parliament.uk/documents/CBP-7569/CBP-7569.pdf ·...

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www.parliament.uk/commons-library | intranet.parliament.uk/commons-library | [email protected] | @commonslibrary BRIEFING PAPER Number 7569, 22 April 2016 Meningitis B vaccination By Sarah Barber Inside: 1. Meningitis and septicaemia 2. The meningitis B vaccination petition 3. The JCVI and decision-making 4. Introduction of the meningitis B vaccination 5. Raising awareness

Transcript of Meningitis B vaccinationresearchbriefings.files.parliament.uk/documents/CBP-7569/CBP-7569.pdf ·...

www.parliament.uk/commons-library | intranet.parliament.uk/commons-library | [email protected] | @commonslibrary

BRIEFING PAPER

Number 7569, 22 April 2016

Meningitis B vaccination By Sarah Barber

Inside: 1. Meningitis and septicaemia 2. The meningitis B vaccination

petition 3. The JCVI and decision-making 4. Introduction of the meningitis

B vaccination 5. Raising awareness

Number 7569, 22 April 2016 2

Contents Summary 3

1. Meningitis and septicaemia 5 1.1 Vaccinations 6

2. The meningitis B vaccination petition 8 2.1 Government response 9 2.2 Petitions Committee 11

Evidence sessions 11

3. The JCVI and decision-making 13 3.1 The JCVI 13 3.2 How the JCVI make decisions on vaccinations 13

Cost-effectiveness 15

4. Introduction of the meningitis B vaccination 18 Petitions committee and Health committee evidence 21

4.1 Vaccine shortage 22

5. Raising awareness 24

Cover page image copyright: CRI-8021 by UK Parliament/Mark Crick image. Licensed under CC BY 2.0 / image cropped.

3 Meningitis B vaccination

Summary A petition to call on the Government to extend the programme of Meningitis B vaccination to all children has received over 820,000 signatures, the highest number of signatures since the launch of the Parliament and Government Petitions website.

Meningitis can affect anyone of any age, but it is more common in children under five and teenagers aged 15-19. Invasive meningococcal disease (including meningitis and/or septicaemia) caused by meningococcal B is three times as likely to affect babies under the age of 1 year as any other age group. It is also more common in 1-4 year olds than other age groups.1

The Joint Committee on Vaccinations and Immunisations (JCVI) is the independent advisory body that is responsible for providing advice to the Secretary of State for Health on vaccinations. It has conducted an assessment of the evidence on the Meningococcal B vaccination (MenB) (Bexsero) and published its final position statement in March 2014. The JCVI recommended that the introduction of an infant programme at 2, 4 and 12 months of age would be cost effective if the vaccine could be procured at a lower than list price.

The JCVI highlighted that infants under one year are those most at risk from meningococcal disease and an infant programme would provide direct protection for this group.

Following the recommendations from the JCVI, the Department of Health entered into negotiations with the vaccine manufacturer. It was reported in March 2015 that an agreement had been reached regarding the price of the vaccine. The MenB immunisation programme started in September 2015 across the UK, in line with the recommendations from the JCVI.

The UK is the first country in the world to introduce the MenB vaccine to its routine childhood vaccination programme. In response to a Parliamentary Question in December 2015, the Under-Secretary of State for Health reported that cost effectiveness analysis models estimated that the meningitis B vaccination schedule would prevent 325 cases, 66 severe cases and 6 deaths a year in England.2

A petition that calls for all children, at least up to the age of 11 years, to be given the MenB vaccine was created on the Parliament and Government petitions website in September 2015. The petition received increased attention in February 2016 following the publication of pictures of Faye Burdett, a two year old girl who died of meningitis B on 14 February 2016. Her parents are in support of an extension of the vaccination to all children.3

The Petitions Committee considered the petition on extending the meningitis B vaccination on 23 February 2016 and agreed to schedule a debate. However, they said that they would like the House of Commons to hear from medical experts and families affected by meningitis B prior to the debate.

1 PHE, Invasive meningococcal B infections laboratory reports in England by age group & epidemiological

year, 1998/99-2014/15, October 2015 2 HC Written Question, Meningitis: vaccination, 2 December 2015 3 Meningitis Now, Faye’s story, 16 February 2016

Number 7569, 22 April 2016 4

The Department of Health have responded to the petition. They have said that the programme introduced protects those most at risk from meningococcal B disease, and is in line with the recommendations from the JCVI.

The Petitions Committee and the Health Select Committee have held two joint sessions on the petition. One of these was a roundtable event with families affected by meningococcal disease, and a second heard evidence from charities, healthcare professionals and representatives from the JCVI and Public Health England.

A number of issues were raised during the sessions, these included consideration of extending the vaccine to older children, a review of the cost-effectiveness analysis used by the JCVI, raising awareness of meningococcal disease amongst families and health professionals and the progress with the study into adolescent meningococcal B carriage. Professor Pollard, the Chair of the JCVI reported that the Public Health Minister had requested that the JCVI reconsider the MenB vaccination in the 1-2 year age group and that they would be looking at this in the near future.

The meningitis charities (Meningitis Now and the Meningitis Research Foundation) have also recently announced a ten point meningitis MenB action plan. This includes calling for the Government to fund research into how peace of mind health benefits can be included in cost-effectiveness analysis and that a catch up campaign for under 5s to be reconsidered by the JCVI in light of a new fairer cost effectiveness framework and emerging data on vaccine effectiveness

A debate on this petition has been tabled in Westminster hall on 25 April 2016, and will be led by Ben Howlett MP.

5 Meningitis B vaccination

1. Meningitis and septicaemia Meningococcal bacteria can cause both meningitis (an infection of the meninges, the layer of tissue over the brain and spinal cord) and septicaemia (blood poisoning). Both of these conditions can be life threatening, and lead to serious complications.

Meningitis can also be caused by viral infection, this can make people very unwell but is rarely life threatening and most people will make a full recovery.

There are several types of meningococcal bacteria (A, B, C, W, Y and Z) and most cases of meningococcal disease in the UK are caused by the B strains, especially in young children. Meningitis and septicaemia can also be caused by other types of bacteria.

Meningococcal disease can affect anyone of any age, but it is more common in children under five and teenagers aged 15-19. Invasive meningococcal disease caused by meningococcal B is three times as likely to affect babies under the age of 1 as any other age group. It is also more common in 1-4 year olds.4

The table below provides information on the prevalence of invasive meningococcal B infections in different age groups:

Source: Public Health England and ONS mid-year population estimates.

With early diagnosis and antibiotic treatment most people with meningococcal disease will make a full recovery but it is estimated that about a quarter of those with meningococcal disease will have complications that may be temporary or permanent and will vary in severity. These may include hearing loss, cerebral palsy and epilepsy. It is estimated that meningococcal disease results in about 1 death in every 10 cases.5

For more information on the causes, symptoms and management of meningitis and septicaemia, the following sources are useful:

4 PHE, Invasive meningococcal B infections laboratory reports in England by age group

& epidemiological year, 1998/99-2014/15, October 2015 5 NHS Choices, Meningitis

Number 7569, 22 April 2016 6

• NHS Choices, Meningitis • Meningitis Now, Meningitis explained • Meningitis Research Foundation, Meningitis

1.1 Vaccinations Immunisation gives protection against serious infectious diseases. It enables our bodies to fight those diseases better if we come into contact with them.

Vaccines are given primarily to protect the individual who receives them, but they can also prevent the vaccinated person spreading the infection on to unvaccinated individuals. This leads to a population (or herd) immunity. This herd immunity protects those who cannot be immunised, and if enough people are immunised, this can lead to the eradication of a disease, such as smallpox. No vaccine offers 100% protection, a small number of people will become infected despite vaccination.

More information about immunity and how vaccines work is provided in chapter one of the Department of Health Green Book. This publication provides information, aimed at healthcare professionals, on immunisations and infectious diseases.6

A number of vaccines have been introduced to the childhood immunisation programme that will help prevent cases of meningitis. These include:

• Meningococcal C vaccine • 5 in 1 vaccine (diptheria, tetanus, pertussis, polio, Haemophilus

Influenza type B (Hib)) • Pneumococcal vaccine The meningococcal B immunisation programme was introduced for infants in September 2015, more information on this is provided in section 4 of this briefing paper.

A good overview of the childhood immunisation programme is provide in a September 2015 POSTbrief.

The introduction of vaccinations to tackle meningococcal disease has had a significant effect on the number of infections. An example of this success has been the meningococcal C vaccination that was introduced into the UK routine immunisation programme along with a catch-up campaign for older children, adolescents and young adults up to 18 years in November 1999. In January 2002, the campaign was extended to include adults under 25 years of age.

Following this, the reported cases of invasive meningococcal disease due to meningococcal C fell by over 90% in the age groups immunised. Reported cases also dropped by around two thirds in all age groups as a result of reduced carriage rates and reduced exposure- this indirect

6 Department of Health, Green Book, 2013

7 Meningitis B vaccination

(herd) immunity contributed to the reduction in cases.7 The number of cases has remained low since this time.

7 Public Health England, The Green Book, Chapter 22: Meningococcal, September

2015

Number 7569, 22 April 2016 8

2. The meningitis B vaccination petition

A petition that called for all children up to the age of 11 to be given the MenB vaccine was created on the Parliament and Government petitions website in September 2015. This is now closed and has over 820,000 signatures, the highest number of any petition since the launch of the website.

The petition received increased attention following the publication of pictures of Faye Burdett, a two year old girl who died of meningitis B in February. Her parents are in support of an extension of the vaccination to all children.8

A petition on the website will receive a response from the Government once it receives 10,000 signatures and will be considered by the House of Commons Petitions Select Committee once it reaches 100,000 signatures.

The charity, Meningitis Now, supported the petition and encouraged people to sign the petition. It said it would continue to campaign to get the meningitis B vaccine extended:

“Our heartfelt sympathies go out to Faye’s family and friends – they know we are here to support them in any way we can."

“The response to Faye’s petition has been overwhelming, with signatures reaching over 250,000 in a matter of days. We are using our voice to support the petition to raise the profile of meningitis, keeping it high on the political agenda and increasing awareness among the public to prevent more lives being lost to this devastating disease."

“Although the introduction of the Men B vaccine on the childhood immunisation scheme for young babies was a momentous achievement, saving thousands of lives, there are still so many, like Faye, left unprotected."

“Moving forward, we continue to campaign to see the Men B vaccine rolled out, particularly to at risk groups to ensure a future where no one in the UK loses their life to meningitis.”

The Meningitis Research Foundation (MRF) responded to the petition. They said that to see the end of meningitis in the UK, there needs to be the widest protection. This may mean extending the current MenB vaccination programme, but more evidence is needed in order to look at this and make the case.

They have called on the Government, to conduct research on the vaccination of the teenage population. The Joint Committee on Vaccination and Immunisation (JCVI) recommended this research, which the MRF say could show if vaccinating teenagers will protect the whole population, including children aged 2-11 which are the subject of the petition:

8 Meningitis Now, Faye’s story, 16 February 2016

9 Meningitis B vaccination

Vinny Smith, CEO of MRF says “In the light of the unprecedented levels of public interest brought about by the MenB petition we call on the government to urgently examine this vital issue. This petition has done a wonderful job of highlighting the importance of increasing access to the vaccine for children at risk. We know the key to unlocking this is showing whether vaccinating teenagers will stop them acquiring and spreading the disease. Our best hope of eradicating this dreadful disease is by using vaccines to stop the infection from spreading and we need the government to listen and deliver the plan to show the best way to do that.”9

The Meningitis charities (Meningitis Now and the Meningitis Research Foundation) have also recently (March 2016) announced a ten point meningitis MenB action plan. This includes calling for the Government to fund research into how peace of mind health benefits can be included in cost-effectiveness analysis and that a catch up campaign for under 5s to be reconsidered by the JCVI in light of a fairer cost effectiveness framework and emerging data on vaccine effectiveness. More information on this campaign can be found on the Meningitis Research Foundation website,10 and in written evidence submitted to the Petitions and Health Select Committees.11

There has been widespread media coverage of the petition. This has included a number of articles describing the support for the petition12 but also some articles by health professionals and others that have highlighted the complexities involved in funding NHS treatments, and that decisions on vaccines and treatments have to consider cost-effectiveness.13

The Science Media Centre (an organisation that aims to provide accurate and evidence based information to the media and the public) have also collated a number of expert responses to the petition:

Expert reaction to MenB vaccine for meningitis B, following the public petition calling for all children in the UK to be given the vaccine, 16 February 2016

2.1 Government response The Department of Health have responded to the petition. They have said that the programme introduced in 2015 offers protection to those at the highest risk:

MenB vaccine is offered to infants, free on the NHS, at 2 months with further doses at 4 and 12 months. The programme, as advised by independent experts, offers protection to those at highest risk.

As the UK, we are proud to have been the first– and to date the only - country in the world to introduce a national, publicly-

9 MRF, MRF calls for effective protection for everyone from MenB, 23 February 2016 10 MRF, Charities announce 10-Point Meningitis Men B Action Plan, 21 March 2016 11 Petitions Committee, Written evidence: Meningitis research Foundation, 19 April

2016 12 The Independent, Meningitis B: Petition calling for vaccine breaks Government

website record, 19 February 2016 13 Dr David Elliman and Helen Bedford, For a cash-strapped NHS, extending the

meningitis B vaccine isn’t cost-effective, The Guardian, 24 February 2016

Number 7569, 22 April 2016 10

funded MenB immunisation programme for infants using the Bexsero vaccine. We are leading the world in offering children protection from this devastating disease.

National immunisation programmes are introduced on the advice of the Joint Committee on Vaccination and Immunisation (JCVI), the independent expert body that advises the Government on all immunisation matters. https://www.gov.uk/government/groups/joint-committee-on-vaccination-and-immunisation

JCVI reviewed all available evidence before it advised on eligibility for the Bexsero vaccine. It recommended that MenB immunisation should be routinely offered to the group of children at the highest risk - infants at two months of age with a further dose at four months and a booster at 12 months, provided that the vaccine could be procured at a cost-effective price. There is a duty on the Secretary of State for Health to ensure, so far as is reasonably practicable, that the recommendations of the JCVI, are implemented.

The programme started on 1st September 2015 for those babies due to receive their primary immunisations starting at 2 months of age on or after 1 September 2015 (i.e. those born on or after 1 July 2015). A one off catch-up programme was recommended by JCVI for infants born from 1 May 2015 to 30 June 2015 (aged 3 or 4 months of age when the programme launched) when they attended for their primary immunisation appointments. This ensured that those infants were offered the vaccine before the winter peak of the disease. By May 2017, all children under the age of two years will have been offered the vaccine. The vaccine is also available for a small number of older children and adults who are at increased risk of infection, such as those with no spleen. Early indications are that the vaccine has been very well accepted by parents and coverage is likely to be high.

With this programme, our priority is to protect those children most at risk of MenB, in line with JCVI’s recommendation. The NHS budget is a finite resource. It is therefore essential that JCVI’s recommendations are underpinned by evidence of cost-effectiveness. Offering the vaccine outside of JCVI’s advice would not be cost effective, and would not therefore represent a good use of NHS resources which should be used to benefit the health and care of the most people possible.

When any new immunisation programme is introduced, there has to be a cut-off date to determine eligibility. While this is extremely difficult for parents whose children aren’t eligible there is no other way of establishing new programmes to target those at highest risk without introducing inequalities. This approach is supported by the best evidence and by independent recommendations. JCVI considered older age groups (1-4 year olds) but did not advise a catch-up programme in view of the marginal cost-effectiveness of even the infant programme. JCVI considered that the priority should be the implementation of the primary immunisation programme for infants. They also considered a programme for adolescents but advised that further research was needed Preparatory research has been commissioned and is underway.

There are many bacterial, viral and other causes of meningitis (inflammation of the lining of the brain and surrounding tissues) and septicaemia (blood poisoning). Successful vaccination programmes have already reduced the risk of these serious diseases. Current rates of group B meningococcal disease are low.

11 Meningitis B vaccination

In the early 2000s there were more than 1,600 cases in England, compared to around 400 cases in 2014.

The vaccine should provide direct protection against MenB for infants and those who are at increased risk of meningococcal disease. However, not all strains of the group B meningococcal bacteria are covered by this vaccine and cases can still occur in vaccinated infants and children. There are also other strains of meningococcal disease for which there is currently no vaccine. It therefore remains important for parents to be alert to the symptoms of meningococcal disease such as fever, blotchy skin, refusal to feed, irritability, cold hands and feet, rash, muscle pain, and a stiff body with jerky movements or else floppy and lifeless. They should trust their instincts and seek urgent medical attention if they have concerns.14

2.2 Petitions Committee The Petitions Committee considered the petition on 23 February 2016 and agreed to schedule a debate. However, they said that they would like the House of Commons to hear from medical experts and families affected by meningitis B prior to the debate:

The Petitions Committee has agreed to schedule a debate on this petition.

Before setting a date for the debate, the Committee would like the House of Commons to have the chance to hear from some of the families who have been affected by meningitis B as well as from relevant medical experts. This will help to inform MPs taking part in the House of Commons debate.

More details about this will be announced in due course. We will keep you informed about what is happening and how you can get involved.15

The Committee announced on 1 March that it would hold two evidence sessions on 15 and 22 March.16

Evidence sessions On 15 March, the Petitions Committee and the Health Select Committee jointly heard from the creator of the petition, Lee Booth, and family members who have been affected by meningococcal disease. Beyond the issue of extending the MenB vaccination to older children, concerns raised by family members during the session included a perceived lack of awareness of meningitis and septicaemia, a need for better education for families and healthcare professionals on this issue, and whether the cost-effectiveness analysis of the JCVI should be changed.

On 22 March the two Committees took evidence from meningitis charities, health professionals, and representatives from the JCVI and Public Health England. Issues raised during this session included the cost effectiveness analysis of vaccine, the efficacy of the MenB vaccine

14 Government and Parliament petitions, Give the Meningitis B vaccine to ALL children,

not just newborn babies [accessed 1 March 2016] 15 UK Government and Parliament petitions, Give the Meningitis B vaccine to ALL

children, not just newborn babies [accessed 23 February 2016] 16 Petitions Committee, Decisions of the Petitions Committee Tuesday 1 March

Number 7569, 22 April 2016 12

and clinical guidance for health professionals regarding meningococcal disease.

More information about the evidence given in these sessions is provided in the sections below. The videos and transcripts of these sessions can be found on the Petitions Committee website.

13 Meningitis B vaccination

3. The JCVI and decision-making

3.1 The JCVI The Joint Committee on Vaccination and Immunisation (JCVI) provides advice and recommendations on vaccinations to the UK Health departments. It is an independent departmental expert committee. Its terms of reference, as agreed by the UK health departments, are:

“To advise UK health departments on immunisations for the prevention of infections and/or disease following due consideration of the evidence on the burden of disease, on vaccine safety and efficacy and on the impact and cost effectiveness of immunisation strategies. To consider and identify factors for the successful and effective implementation of immunisation strategies. To identify important knowledge gaps relating to immunisations or immunisation programmes where further research and/or surveillance should be considered.”17

The JCVI is responsible for providing advice and recommendations based on consideration of scientific and other evidence, to be used by the Government to inform policy.

Since 2009, there has been a statutory duty placed on the Secretary of State for Health to ensure that the recommendations of the JCVI are implemented, where those recommendations:

a) relate to new provision for vaccination under a national vaccination programme or to changes to existing provision under such a programme and

b) are made by JCVI (and not therefore a Sub-committee of JCVI) and

c) are in response to a question referred to the JCVI by the Secretary of State and

d) are based on an assessment which demonstrates cost-effectiveness and

e) do not relate to vaccination in respect of travel or occupational health.18

This statutory duty does not extend to advice provided for Ministers in Scotland or Northern Ireland. However, those health departments may accept the recommendations of the JCVI.

3.2 How the JCVI make decisions on vaccinations

The JCVI provides detailed information on how it develops its advice and recommendations within its Code of Practice.

Topics are identified for consideration by Public Health England, the UK health departments, the members of the JCVI or the public. Advice and recommendations are developed based on appraisal of the best scientific and other evidence.

17 JCVI, Code of Practice, 2013 18 JCVI, Code of Practice, 2013

Number 7569, 22 April 2016 14

The Code of Practice explains that the process “involves a robust, transparent, and comprehensive appraisal of the available evidence from a wide range of sources…” The evidence may include relevant published and unpublished studies and data, expert opinion, advice from relevant national and international bodies and JCVI commissioned research.

In response to questions from the Petitions Committee, the Chair of the JCVI, Professor Andrew Pollard, provided an overview of the decision-making process used by the JCVI, with specific reference to the decision regarding the Meningococcal B vaccine:

The process that we go through is first to look at how many cases there are and to look at the burden of disease for the families as well as for the health system. Then, with the information that there is about the vaccine, we look at its likely effectiveness.

You heard that very nicely described in the previous session. We have that uncertainty with this vaccine because we could not do trials to look at impact before the vaccine could be recommended, so we had to use data from the laboratory to try to define that, which leaves us with some uncertainty. Clearly, we look very carefully at the safety of the vaccine. We are fortunate that the regulators do a lot of that work before it ever comes to the committee to look at.

The final bit of the process is that we look at the cost-effectiveness, because of the terms of reference of the JCVI. The cost-effectiveness uses the health technology assessment methodology from NICE because that is what our terms of reference say.

We have to fit into that framework as required by the Department of Health, which is the final arbiter.

The modelling to work out the cost-effectiveness is done by a combination of health economists and modellers at Public Health England and, as in this case, at the London School of Hygiene and Tropical Medicine. They have independently looked at this to assess the likely cost-effectiveness of this particular vaccine fitting in with those rules.

That process involves a lot of work to try to understand the likely impact of the vaccine and how this particular infection is transmitted to work out the framework for the model in order to look at the likely effect of the vaccine.

All those costs—the current burden of disease on the health system and the quality of life issues—need to be factored into the model, as well as the cost of the vaccine and the current burden on the NHS. That is all put together with evidence that already exists in the literature and experts’ opinions. My colleague Andrew Riordan has, for a number of years, chaired the sub-committee on meningococcal disease. They were responsible for trying to assess which parameters were the most plausible to put into the model based on what was published and, where there was no information, by taking the best available evidence. That group worked extremely hard over a number of years.

It is important to remember, in the context of where we are with cost-effectiveness and this question over which age groups could be vaccinated, that, over that period of time, we have seen very borderline cost-effectiveness. At one point, the model really

15 Meningitis B vaccination

looked like it was not cost-effective to use the vaccine even for infants, where the highest rates of disease occur.

As we have been through the iterations of the model, and taken advice from stakeholders, including the charities, to try to improve it, we went from the point of it being considered not cost-effective to it being just cost-effective, which is where the model ended up when we came to the final decision. It was just cost-effective for infants. Really, in the other age groups, with the data we have at the moment, it does not meet the criteria set through the HTA methodology.19

Cost-effectiveness The JCVI Code of practice (2013) explains that its assessment of cost-effectiveness uses the methodology and criteria of the National Institute of Health and Care Excellence (NICE), but also takes account of the advice and recommendations of the working group on Uncertainty in Vaccine Evaluation and Procurement:

In order to assess whether a national NHS-provided vaccination programme can be considered cost effective (or not), JCVI uses the methodology and criteria of the National Institute for Health and Clinical Excellence (NICE). Using the NICE approach, a vaccination programme can be considered to be cost effective if the health benefits (both the direct health benefits to those vaccinated and the indirect health benefits to the unvaccinated population) are greater than the opportunity costs measured in terms of the health benefits associated with programmes that may be displaced to fund the new vaccination programme. In other words, the general consequences for the wider group of patients in the NHS are considered alongside the effects for those patients who may directly benefit from the vaccination programme of interest. The Committee also takes account of the advice and recommendations of the Working Group on Uncertainty in Vaccine Evaluation and Procurement when assessing cost effectiveness.20

Reassessing cost-effectiveness

A Department of Health working group on cost-effectiveness has been established to look at the way JCVI conducts its assessment on vaccines.

The minutes of a February 2014 meeting of the JCVI report that the working group will look at whether the current system used by the JCVI is still appropriate, particularly when considering vaccination against diseases such as invasive meningococcal disease that disproportionately affect children.21

In a letter to the Chair of the Commons Health Select Committee, Dr Sarah Wollaston, the Chair of the JCVI confirmed that a Department of Health coordinated committee has been meeting over the last year to

19 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

(p 28) 20 JCVI, Code of practice, 2013 (p 7) 21 JCVI, Meeting minutes, February 2014

Number 7569, 22 April 2016 16

look at the methodology of cost-effectiveness for vaccines. This group is in the process of drafting a report.22

The assessment of cost-effectiveness used by the JCVI was raised a number of times during the Petitions Committee evidence session. Linda Glennie, from the charity Meningitis Research Foundation highlighted a study the charity had conducted called ‘Counting the cost’ that looked at the lifelong costs of people with severe disabilities associated with meningococcal disease. She said that the JCVI had done what it could within the parameters it has but that the framework used by the JCVI was not fair, focusing on the discount rate used23:

We have done a study on this, actually. We did a “counting the cost” study, where we looked at the lifelong costs of people with severe disabilities. One of the things that it showed was what it was like for someone with very severe disabilities, who has had—let’s say—multiple amputations and throughout childhood has to have revisions to their stumps and new sockets and new prosthetics fitted, and physiotherapy; the various things that are involved in rehabilitating them and making them able to work and take part in life. That ends up costing upwards of £3 million.

One thing we are trying to draw attention to, though, is the fact that these costs are discounted at 3.5%. That ends up meaning just over £1 million. We are trying to draw attention to the fact that the costs that we are looking at just are not measured properly. The JCVI has done the most it can with the numbers and parameters that it has got, but the framework is just not fair, because discounting should not be 1.5% in health. In public health interventions considered by NICE, the discount rate used is 1.5%, for everything else it is 3.5%, and that just is not fair.24

Vinnie Smith, also from the Meningitis Research Foundation, said that the current cost-effectiveness model was unfair on a number of levels. He highlighted that it did not take into account peace of mind benefits and that a public preference for prevention, and for targeting children over adults is not considered.25

Professor John Cairns, the Chair of the cost-effectiveness working group provided an overview of the work of the group in evidence to the Petitions Committee:

Let me explain briefly what the working group is trying to do.

We are asking a very basic question: are the methods that are deemed appropriate in evaluating health technologies by NICE appropriate for vaccination and immunisation, or are there specific characteristics of the vaccination and immunisation programme that suggest we need to adapt our methods? That is the basic question we are trying to address.

While I do not feel I can give the detail of our report, because it has not been finalised yet, we have identified some areas in which

22 Letter to Chair of Commons Health Select Committee from JCVI Chair, Re: Meningococcal B vaccination in the UK, 23 February 2016 23 A discount rate is a method used to convert future costs into a value for the current

period. 24 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

(p 7) 25 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

(p 8)

17 Meningitis B vaccination

you can make an argument that immunisation is somewhat different. But overwhelmingly, we are moving in the direction that most of the methods that are appropriate for other health technologies are also appropriate for vaccination.26

Dr Riordan, chair of the JCVI Meningococcal sub-committee stated that in consideration of the MenB vaccine, the sub-committee had tried within the rules to make the assessment as good as it could have been. Dr Ramsey, Consultant Epidemiologist and Head, Immunisation, Hepatitis and Blood Safety Department at Public Health England, reported that some of the considerations the charities mentioned, such as social costs, are currently not allowed to be considered as part of the vaccine assessment.

Professor Cairns reported that the report of the working group was being finalised. He said he anticipated it would be made public but this would be a decision for the Department of Health.

26 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

(p 28)

Number 7569, 22 April 2016 18

4. Introduction of the meningitis B vaccination

In March 2014, the JCVI recommended the implementation of a programme for the use of serogroup B meningococcal (MenB) vaccine (Bexsero) within the NHS immunisation schedule at 2, 4 and 12 months of age, those most at risk from the disease. This followed a lengthy and detailed consideration of the evidence on the Bexsero vaccine. An initial interim statement on the MenB vaccine had concluded that a routine immunisation programme for any age group was unlikely to be cost effective at any price.27

At the time of the publication of the final position statement, the Chair of the JCVI, Professor Andrew Pollard said that the introduction of the new vaccine could reduce cases of meningococcal meningitis and septicaemia and lead to a reduction in the deaths and complications due to the disease:

MenB disproportionately affects babies and young children and can be devastating. After very careful consideration, JCVI concluded that use of the new vaccine could reduce cases of meningococcal meningitis and septicaemia and lead to a reduction in deaths, limb amputations and brain injury caused by the disease. Today the JCVI published its recommendation to the UK health departments that if the new vaccine can be purchased at a low price and is therefore cost effective for the NHS, it should be used in the routine immunisation programme for babies in the UK to prevent disease.

Routine use of the MenB vaccine is expected to make an important contribution to the health of our population.28

Following Department of Health negotiations with the manufacturer of the vaccine, it was announced in March 2015 that an agreement on price had been reached and the vaccine would be added to the childhood immunisation programme in September 2015.

This section provides a brief overview of the JCVI decision and the implementation of the infant immunisation programme.

JCVI decision Following information that a meningococcal B vaccination was being developed in 2010, a sub-committee was convened to conduct an assessment of the evidence on a MenB immunisation programme.

In July 2013, following a request from the Secretary of State for Health to provide a recommendation on the introduction of a routine MenB immunisation programme, the JCVI published an interim position statement. This said that the Committee had concluded that on the basis of available evidence routine infant, toddler or adolescent routine immunisation was highly unlikely to be cost effective at any vaccine

27 JCVI, JCVI interim position statement on use of Bexsero® meningococcal B vaccine

in the UK, July 2013 28 PHE, PHE welcomes prospect of new Meningitis B vaccine, 21 march 2014

19 Meningitis B vaccination

price.29 However, the JCVI reported that due to the importance of the decision, and the sensitivity of the cost-effectiveness analyses to a number of factors, they decided to consult on the decision with those who had provided evidence to the committee.

Following detailed submissions, relating to new and recently published studies, the JCVI concluded that further analyses were required to consider the MenB immunisation programme fully.

A JCVI position statement in March 2014 recommended the implementation of a programme for the use of serogroup B meningococcal (MenB) vaccine (Bexsero) within the NHS immunisation schedule at 2, 4 and 12 months of age. It provided detailed information on its considerations of an infant and adolescent immunisation programme in its March 2014 position statement.30 This included a review of vaccine efficacy, safety, strain coverage and duration of protection in different groups.

The Committee noted the seriousness of meningococcal infection on infants and young children and the importance of exploring prevention through immunisation:

The rapid and severe nature of IMD, the burden of disease seen in infants and young children, and the value society places upon preventing disease in its youngest members were considered throughout the Committee’s deliberations on the use of bexsero MenB vaccine in the UK. The Committee reaffirmed its position that the burden and severity of IMD in the UK made the need to explore the potential for its prevention through immunisation of vital importance.31

The JCVI made the following conclusions regarding an immunisation programme for infants and adolescents.

Infant programme

The JCVI concluded that, if the vaccine could be procured at a low price, it was likely to be cost-effective in an infant programme:

JCVI concluded that with a low vaccine price, the vaccine was likely to be cost-effective in an infant programme even if the strain coverage was lower than expected. The cost-effective price of Bexsero® in an infant programme in the UK could be increased with a reduced dose schedule (2+1) and/or removal of an infant MenC dose from the current schedule. The vaccine was not cost-effective in any scenario at the list price for Bexsero®.

Given the concerns of JCVI regarding uncertainty, and of members regarding the impact that introducing a reactogenic vaccine such as Bexsero® could have on the currently very successful infant programme, the Committee agreed that any implementation of Bexsero® should closely monitor:

• changes in the molecular epidemiology of MenB in the UK;

• duration of protection of the vaccine in infants;

29 JCVI, JCVI interim position statement on use of Bexsero® meningococcal B vaccine

in the UK, July 2013 30 JCVI, Position Statement on the use of Bexsero meningococcal vaccine in the UK,

march 2014 31 JCVI, Minutes February 2014

Number 7569, 22 April 2016 20

• medically attended events following vaccination;

• coverage of other infant vaccines.32

The JCVI reported that the infant programme would provide direct protection against meningococcal disease. An infant programme would have a quicker impact on meningococcal disease rates in a population at high risk of the disease than an adolescent programme.33

The Committee said it would review the effects of the implementation of an infant programme.

Adolescent programme

The JCVI reported that uncertainty regarding the duration of protection provided by the MenB vaccine in adolescents could not be resolved quickly. However, the uncertainty regarding the impact of the vaccine on carriage (presence of the bacteria in the nose and throat) could be reduced by undertaking a study on this issue. The JCVI concluded that whilst a number of plausible scenarios relating to an adolescent programme demonstrated cost-effectiveness, the level of uncertainty meant that it could not make a recommendation on a programme in this group.

It explained that “there was a significant risk such a programme would result in a net loss of health in the population through displacement of other interventions within the health service.”34

The JCVI recommended that a carriage study be carried out to look at the effect of the MenB vaccine on this in adolescents.

Implementation of the vaccine Following the recommendation from the JCVI, the Government entered into negotiations with the manufacturer of Bexsero, and it announced that an agreement had been made and the vaccination would be rolled out from September 2015. The vaccine was introduced by health departments across the UK.35,36,37

Information for healthcare professionals and parents on the meningococcal vaccination programme is provided on the Public Health England website.

In response to a Parliamentary Question in December 2015, the Under-Secretary of State for Health reported that cost effectiveness analysis models estimated that the MenB vaccination schedule would prevent 325 cases, 66 severe cases and 6 deaths a year in England.38

32 JCVI, Position Statement on the use of Bexsero meningococcal vaccine in the UK,

March 2014 33 JCVI, Minutes February 2014 34 JCVI, Position Statement on the use of Bexsero meningococcal vaccine in the UK,

March 2014 35 Welsh Government, Meningitis B vaccine to be made available to all babies in Wales,

8 April 2015 36 Scottish Government, Meningitis B added to routine vaccinations, 21 June 2015 37 NIDirect, Meningococcal B (Men B) vaccination programme for babies 38 HC Written Question, Meningitis: vaccination, 2 December 2015

21 Meningitis B vaccination

Petitions committee and Health committee evidence The carriage study

The JCVI recommended carriage study in adolescents was a subject raised during the Petitions committee evidence session. Professor Moxon, Emeritus Professor of Paediatrics at the University of Oxford discussed the potential for assessing community (or herd) immunity. He said he didn’t know how quickly the effectiveness of the vaccine in inducing community immunity would be known, but outlined how this may work:

[…]I do know that the way we have to do this is by implementing the vaccine in a population that would allow us to measure carriage and, from that, to be able to estimate the drop in acquisition rates of the organism, which would translate into prevention of disease. The idea here is that you would cut down the spread, then people who would be vulnerable to the disease would not actually get the bug, so you have intervened.

As someone said earlier, it is really important to know that the target here is not the kids who are most vulnerable to disease—the young—but the adolescents and young adults, who have a very high carriage rate. If you measure the carriage rate in infants—the people who are most likely to get the disease—it is very low. I know that is a paradox and confusing, but that is the way it is. So you protect others by going to where carriage is at its highest, which is among teenagers and young adults.39

Professor Kroll, Professor of Paediatrics at Imperial College London said it was important to draw a distinction between primary prevention and prevention of transmission. The immunisation of adolescents may have a theoretical effect through community immunity on younger children. However, the immunisation of young children will have a primary protective effect and if we wish to prevent the disease in small children, we should vaccinate small children:

I want to draw a clear distinction between primary prevention and prevention of transmission. The immunisation of adolescents will have the impact of primary prevention in adolescents, and may have a theoretical—devoutly to be wished for, but uncertain— effect through community immunity on very small children. The immunisation of very small children will have a primary protective effect on very small children. That is the issue that is central to our thinking at present. So if we want to prevent the disease in very small children, we should vaccinate very small children.

We could also achieve—perhaps achieve—the same and more by vaccinating teenagers, but that is an uncertainty. What is quite clear is that a vaccination programme involving the one to fives will have the same anticipated impact as it might have on the under-ones. If there are uncertainties about the efficacy of the vaccine in under-ones, you could apply that pari passu to the older children, but that is a primary prevention issue and I would not, personally, want to endorse a programme of protecting

39 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

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Number 7569, 22 April 2016 22

young children solely by embarking on a teenage programme to avoid transmission.40

The Committee asked about the progress that had been made with the carriage study that had been recommended by the JCVI. In 2014. Professor Pollard explained that the first stage of the work was to study the strains that are being carried at the moment and that this work was ongoing.41 Dr Ramsey reported that this work is likely to report early in 2017 and these results would allow the development of a larger study.

When questioned about the time required for the study and delays, Dr Ramsey and Professor Pollard reported that the precise nature and size of the study had to be considered. Once the preliminary study was completed, the Department of Health would put out a call for proposals and a lot of planning would be required. Dr Ramsey said this would take a minimum of 3 years. Professor Pollard explained that the study was not a small one to set up, plan and deliver:

Doing this evaluation is not something where you give a vaccine and you have got the result immediately. You have to give the vaccine and then look at the impact that that has either on disease or on carriage of the meningococci, and you cannot do that in a short timeframe. We are probably talking about vaccinating, in one approach, maybe 20,000 adolescents. It is not a small programme to set up and plan and deliver.42

A JCVI assessment of the vaccine in older children

Professor Pollard reported during the Petitions Committee evidence session that he had written to the Public Health Minister to ask whether she would like the JCVI to look at assessing the vaccine in the one to two year age group. He explained that most of the cases, and deaths in the one to four year age group were in this group. The Minister had responded and asked the JCVI to reconsider this age group so they would be looking at this in the near future.43

4.1 Vaccine shortage Following high demand for the MenB vaccine in 2015, the manufacturer GlaxoSmithKline (GSK) issued a statement regarding a shortage of the vaccine. They have said that the NHS childhood immunisation programme is prioritised and will not be affected but private clinics should not start new courses at present.

The Meningitis Research Foundation provides more detail on the shortage on its website:

GSK, the manufacturers of the vaccine have released the following statement: “Due to unexpected global demand for Bexsero during 2015, we are experiencing supply constraints

40 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

(p 15) 41 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

(p 30) 42 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

(p 35) 43 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

(p 38)

23 Meningitis B vaccination

during the first half of this year. Although vaccination through the NHS childhood programme has been prioritised and is unaffected, we have unfortunately had to ask private clinics temporarily to not start new courses of vaccination. Children who have already started their course of the vaccine privately should still be able receive their follow up doses. We know the unexpectedly high demand for the vaccine reflects the importance parents have placed on protecting their children from meningitis B, so we are working hard to increase supply, and expect to have increased stock by summer 2016.”44

A March 2016 Parliamentary Question response confirms that supply for the NHS MenB immunisation programme is secure. However, the manufacturer has supply constraints for the private market:

Current availability of the Meningococcal B vaccine for the national immunisation programme is adequate with a central buffer of stock being maintained (and monitored) to ensure security of supply. The vaccine continues to be delivered to eligible infants as part of the National Health Service childhood immunisation schedule. However, the manufacturers of Bexsero, GlaxoSmithKline, have confirmed that they have supply constraints for the private market due to unexpected Global demand.45

44 MRF, MenB (meningococcal B) vaccine [accessed 24 February 2016] 45 HC Meningitis: Vaccination:Written question – 28953, 3 March 2016

Number 7569, 22 April 2016 24

5. Raising awareness The extension of the MenB vaccination to older children and the JCVI cost-effectiveness analysis was a main focus of the evidence given at the Petitions Committee evidence sessions. However, the importance of raising awareness amongst both parents and healthcare professionals was also highlighted.

In a Parliamentary Question response in March 2016, the Minister for Public Health, Jane Ellison, set out the Government’s actions on raising awareness on the symptoms of meningococcal disease and eligibility for the vaccination:

The introduction of meningitis B (MenB) immunisation in September 2015 was supported by a comprehensive media and communications campaign led by Public Health England (PHE) in association with health partners and meningitis charities. Key objectives of this campaign were two-fold: to promote vaccination to parents of eligible children and raise awareness of the disease among parents, and to emphasise that not all strains can be prevented by immunisation. This led to significant coverage of the disease and its symptoms across social media, national, local and parenting media. The coverage included practical advice on recognising the symptoms, and the need to act quickly, supported by interviews with families affected by the disease on major news channels. The introduction of the adolescent MenACWY campaign in August 2015 was supported by a similar campaign that provided further opportunities to raise awareness of meningococcal disease.

PHE also produces a range of leaflets for the public providing detailed information to help parents with young children identify the early signs of meningitis. The leaflets include links to the web sites of meningitis charities and NHS Choices for those parents wishing to access more extensive information about meningococcal disease. PHE also supports influential meningitis charities in the implementation of awareness campaigns. In addition, PHE undertakes detailed surveillance of the disease, publishing routine reports and taking appropriate action to alert the public to any increase in incidence or change in the pattern of the disease. Appropriate media and communications activities are implemented to coincide with these publications, often ahead of the winter, when cases of the disease peak.46

Public Health England provides information on meningococcal disease and vaccinations on its website. This includes guidance for healthcare professionals, epidemiological information and posters and leaflets on symptom awareness:

• Public Health England, Meningococcal disease: guidance, data and analysis

• Public Health England, Meningococcal B (MenB) vaccination programme

Charities such as Meningitis Now and Meningitis Research foundation are active in the area of awareness raising. Vinnie Smith highlighted the

46 HC Written Question, Meningitis: vaccination, 28757, 2 March 2016

25 Meningitis B vaccination

role of the charities in this area in evidence to the Petitions Committee and Health Committee:

Both charities have been awareness-raising for many years with health professionals and GPs. I am sure we will talk later about hospitals and schools and other groups that can be influential. It is essential that we carry on that work. We spoke to 1,000 hospitals last year and 9,000 GPs. We are regularly in touch and I think most GPs have access to the materials that we produce.

On top of that, it is important to say that no matter how much we raise awareness with health professionals, how much we do to improve diagnosis and treatment and how much we educate parents, this is a fiendishly difficult disease to detect. It often looks like flu. It has rapid onset that, no matter how quickly you respond, you might be able to do nothing about.

The most important thing to help ensure that we do not have the tragic stories that we had around the table last week, is to protect people up front, and the only way to do that is by vaccines.47

Sue Davie, the CEO of Meningitis Now reported that it was important that parents are informed about meningococcal disease very early on, but without scaring them. She said that they had managed to get some information into the red book (the personal child health record) and it would be good to get information into all of these. She also talked about the work the charity was doing in schools to raise awareness.

Raising awareness of the condition amongst health professionals, and improving quick diagnosis and treatment rates was also discussed during the committee sessions. It was noted by the medical practitioners on the panels that diagnosing meningococcal infection can be difficult, and that it can be difficult in the very early stages to distinguish between a viral infection and an invasive bacterial infection. Dr Nadel, Consultant in Paediatric intensive care at St Mary’s Hospital highlighted the difficulties, the use of safety netting by healthcare professionals and the more indicative signs and symptoms:

[…] as has been stated, it can be impossible very early on in the disease to tell the difference between a viral infection and an invasive bacterial infection, which is what meningococcal disease is.

As the disease progresses, it becomes easier to tell. One of the main things that doctors and health professionals are going to do, or should be doing, is what’s called safety netting, which is saying, you know, “I don’t think your child’s that ill. If their symptoms persist or get worse, come back or go to the emergency department”, or whatever. And as the disease progresses, there are specific signs that would tell you that this child is more likely to have something else rather than a trivial viral infection.

In the early stages it can be very difficult, but there are signs, such as heart rate, breathing rate, colour of the skin and general appearance of the baby, if we are talking about babies, that should alert a health care professional and, more importantly, the parent to say, “This is not what I’m used to in my child” or “This

47 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

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is not what I’m used to seeing when other children have similar diseases.” Those more specific aspects can be emphasised as being more indicative. There is no 100% certainty, but there are certainly symptoms and signs that are more indicative.48

The 2010 NICE guidance on the diagnosis and management of meningitis and meningococcal septicaemia was also discussed during the sessions.49 Following the Committee session, the Chair of the JCVI Meningococcal subcommittee, Dr Riordan, submitted written evidence on supporting health professionals diagnosing meningitis, and adherence to the NICE guidance recommendation regarding treatment without delay:

What can be done to support health professionals to diagnose meningitis quickly?

“Spotting the Sick Child” was an award winning, interactive tool commissioned by the Department of Health to support health professionals in the assessment of the acutely sick child, including meningitis and septicaemia (www.spottingthesickchild.com). The tool was taken over by the Royal College of Paediatric and Child Health in 2014-5.

Funding a revision of this interactive tool would be an excellent way to support health professionals to diagnose meningitis quickly.

Are children with suspected meningococcal disease treated “without delay” as recommended in the NICE Meningitis and Meningococcal disease Guideline (recommendation 1.4.3)?

Studies looking at “Door to needle” time for children with meningococcal disease show 76-100% who present with the typical rash are treated within an hour. The average time from admission to first dose of intravenous antibiotic is;

- 36 minutes [1]

- 60 minutes improved to 18 minutes after training for staff [2]

- 51 minutes [3]

1. J Accid Emerg Med. 1998;15:249-51 2. Emerg Med J. 2001;18:162-3 3. Pediatr 2015;135:635-42. 50

48 Oral evidence: Petition on the meningitis B vaccine, HC 900 Tuesday 22 March 2016

(p 22) 49 NICE, Meningitis (bacterial) and meningococcal septicaemia in under 16s:

recognition, diagnosis and management, 2010 50 Petitions committee, Written evidence, Dr Riordan, 12 April 2016

BRIEFING PAPER Number 7569, 22 April 2016

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