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Report of the MMR Expert Group

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Report of the MMR Expert Group

Executive Summary

1. The Expert Group established by the Scottish Executive was asked:

"to consider the matters raised by the Health and Community Care Committee (HCCC) relating to immunisation against measles, mumps and rubella, with particular reference to:

a) describing the consequences of pursuing an alternative vaccination policy to MMR;
b) reviewing evidence on the apparent rise in the incidence of autism, taking account of the current work of the Medical Research Council;
c) describing the process of vaccine testing and the monitoring of adverse effects; and
d) in all its work, having regard to the role and remit of the Joint Committee on Vaccination and Immunisation, the Committee on Safety of Medicines and the Medicines Control Agency".

2. It is important to recognise that the remit of the Expert Group acknowledges both that other bodies advise Ministers on medicines, and immunisation policy, and that the Expert Group should consider those matters, to some degree, in the course of its work. The Expert Group gratefully acknowledges the support and assistance of all those individuals and organisations who contributed to that work, particularly the Parents' Reference Group. Full details are available on http://www.show.scot.nhs.uk/mmrexpertgroup /.

Autistic Spectrum Disorders

3. "Autism" is one of a spectrum of neurodevelopmental disorders which impair a person's capacity to communicate and interact with others. Thus, autistic spectrum disorder (ASD) is a complex, debilitating and lifelong set of conditions which manifests itself in many different ways.

4. The Medical Research Council (MRC) Review of Autism Research published on 13 December 2001 represents the most up-to-date expert assessment of the range and relative merit of current research evidence. The Expert Group endorses the conclusions reached by the MRC:

  • ASD is considerably more common than has previously been recognised, with as many as 60 in 10,000 children affected;

  • Methodological differences between studies, changes in diagnostic practice and public and professional awareness are likely causes of increases in prevalence. Whether these factors are sufficient to account for increased numbers of identified individuals, or whether there has been a rise in actual numbers affected, is as yet unclear.

  • Current research evidence indicates that ASD has a variety of possible genetic and environmental risk factors which, acting together, may cause the disorder. As such, key issues for future research include case-definition, the roles and interplay between genetic and environmental risk factors, causal pathways and mechanisms, and new approaches to treatment.

5. The Expert Group acknowledges, like the HCCC, the MRC and others, that the current scientific evidence does not support the hypothesised link between the MMR vaccine and autism.

6. The Expert Group also considered the range and quality of services required for, and provided to, such families, and how these might be improved, supported by the Public Health Institute of Scotland (PHIS) Needs Assessment Report on Autistic Spectrum Disorders. The Expert Group strongly endorses that report's findings and conclusions and looks to the Scottish Executive for action.

7. ASD is diagnosed on the basis of qualitative abnormalities in social, communicative and imaginative behaviours, and the presence of repetitive and stereotyped patterns of interests and activities. Diagnosis is therefore an involved and complicated matter. Evidence presented to the Expert Group supports the conclusion that diagnosis remains, for many, time-consuming and traumatic, and that, generally, health, social care and education professionals who do not specialise in ASD need up-to-date information and knowledge, and consistent national and local structures, in order to deliver improved, effective and integrated services that meet the varied needs of individuals with autism and their families.

Crohn's Disease

8. Crohn's disease is a form of inflammatory bowel disease (sometimes referred to as IBD). The most recent estimate of the prevalence of Crohn's disease in children aged less than 16 years is 1.37 cases per 10,000 population in Scotland.

9. We do not know what causes Crohn's disease. Epidemiological data have emphasised the importance of both environmental and genetic factors. Which precise environmental factors trigger the onset of Crohn's disease are not known. The measles virus is one of the possible environmental triggers suggested as causing Crohn's disease, and some researchers have suggested a possible connection between MMR vaccine, bowel disease and autism. All relevant research has been reviewed by a number of expert groups, and, while there may be abnormalities of the bowel in some children with ASD, the current scientific evidence does not support the suggestion that they are either a feature of, or involved in, the pathogenesis of ASD.

Vaccine Testing and Monitoring

10. The Committee on Safety of Medicines (CSM) is an independent advisory committee which advises Health Ministers on the quality, efficacy and safety of medicines in order to ensure that appropriate public health standards are met and maintained.

11. The UK Medicines Control Agency (MCA) is an Executive Agency of the Department of Health (in England). Its primary objective is to safeguard public health by ensuring that all medicines on the UK market meet appropriate standards of safety, quality and efficacy.

12. Medicines, which meet standards of safety, quality and efficacy, are granted a marketing authorisation, which is necessary before they can be prescribed or sold. The MCA carries out pre-marketing assessment of the medicine's safety, quality and efficacy, examining all the research and test results in detail, before a decision is made on whether the product should be granted a marketing authorisation.

13. Before a product is marketed, experience of its safety and efficacy is limited to its use in clinical trials. The conditions under which patients are studied, pre-marketing, do not necessarily reflect the way the medicine will be used in hospital or in general practice once it is marketed. Consequently, there is a continued need for vigilance to detect adverse effects that become apparent when the medicine is more widely used.

14. The MCA is responsible for the UK's spontaneous adverse drug reaction reporting scheme (called the "Yellow Card" reporting scheme) to which doctors report suspected adverse drug reactions. The scheme provides an important early warning of suspected adverse reactions to medicines. The work of the MCA in pharmacovigilance is conducted in a world-wide context, with close links and increasing information transfer with other regulatory authorities, for example the Food and Drug Administration (FDA) in the USA.

15. The submissions presented to the Expert Group fully support the conclusion that MMR was appropriately and rigorously tested before introduction, consistent with standards and science relevant at the time. The Expert Group also recognises that the MCA continually monitors the safety of MMR vaccines in clinical practice and, if necessary, updates the marketing authorisation and product information if and when new data become available.

16. The Medicines Act 1968 contains an exemption which allows the supply of unlicensed relevant medicinal products for human use (commonly known as "specials") in response to a genuine unsolicited order, formulated in accordance with the specification of a doctor or dentist, and for use by his individual patients on the doctor's or dentist's direct personal responsibility. Responsibility for deciding whether an individual patient has "special needs" which the licensed product cannot meet is a matter for the doctor responsible for the patient's care. There are single component measles, mumps and rubella vaccines licensed in the UK, but the licensed single measles and mumps vaccines are not currently marketed by their licence holders in the UK. The MCA has confirmed that the importation of unlicensed monocomponent vaccines is not uncommon.

The Consequences of Alternative Vaccination Policies

18. The Expert Group was asked by the Executive to describe the consequences of pursuing an alternative vaccination policy to MMR and, as such, recognised that it was not expected or required to review MMR policy or the current immunisation programme.

19. The success of immunisation against measles, mumps and rubella has led to a decline in the incidence of these diseases. As such, the associated risks may not be fully appreciated:

Complications of measles

Complications of mumps

Complications of rubella

  • ear infection (1 in 20)

  • pneumonia/bronchitis (1 in 25)

  • convulsions (1 in 200)

  • diarrhoea (1 in 6)

  • meningitis/encephalitis (1 in 1000)

  • conditions affecting blood clotting (1 in 6000)

  • late onset subacute sclerosing panencephalitis (SSPE) (1 in 8000 children under 2 years)

  • deaths (1-2 deaths in 1000 reported cases in recent years)

  • viral meningitis (1 in 20)

  • encephalitis (1 in 1000)

  • permanent hearing loss (1 in 20,000)

  • inflammation of testicles (4 in 10 adult males)

  • inflammation of ovaries

  • encephalitis (1 in 6000)

  • birth defects (90% chance baby will have birth defects if mother catches rubella early in pregnancy). Birth defects include blindness, deafness, learning difficulties and heart disease

  • conditions affecting blood clotting (1 in 3000)

20. Serious complications have been reported for one in 15 notified cases of measles, but are more common and severe in chronically ill children. In recent years, one to two people in every 1000 with reported measles infection have died from it. Death from measles is highest in children under 1 year - a group of children who do not receive MMR vaccine - and in those who are immunosuppressed, due to disease (e.g. leukaemia) or treatment (e.g. organ transplantation) and cannot receive MMR vaccine (or indeed single vaccines). Mumps can have serious complications, with neurological involvement in 10-20% of cases. Pre-immunisation, it was one of the main causes of acquired sensorineural deafness in childhood. Rubella is generally a mild illness, which, if acquired by mothers in early pregnancy, nevertheless can have devastating effects on unborn children.

21. Very rarely, in common with any medical intervention, MMR can cause serious adverse effects. Such adverse effects are significantly more common following the natural disease.

Conditions

Rate after natural disease

Rate after first dose of MMR

Febrile convulsions (temperature fits)

1 in 200

1 in 1000

Meningitis/encephalitis

1 in 1000 (measles, mumps encephalitis)
1 in 20 (mumps meningitis)
1 in 6000 (rubella encephalitis)

less than 1 in 1,000,000

Conditions affecting blood clotting (ITP)

1 in 3000 (rubella)
1 in 6000 (measles)

1 in 22,000

Severe allergic response (anaphylaxis)

-

1 in 100,000

SSPE (a delayed complication of measles that causes brain damage and death)

1 in 8000 (children under 2)

0

Deaths

1 in 2500 to 1 in 5000 (measles; higher in children under 1)
1-2 in 1000 for measles in recent years

0

22. There are of course some children who should not have MMR, at all, or at a particular time. For example, children with untreated cancer or diseases of the immune system, those receiving immunosuppressive therapy or high dose steroids cannot be given MMR (or the corresponding single vaccines). In such circumstances, children depend upon the population immunity that is a product of high immunisation uptake. In contrast, if a child is suffering from an acute illness, immunisation would be postponed until recovery has occurred.

23. The Expert Group accepted and endorsed without reservation the high-level strategic objectives of immunisation: prevention of diseases at the individual level; control of disease at the population level; and elimination or eradication of disease. The Expert Group developed a framework of principles to guide its thinking, and consider that future debate could be informed and facilitated by a Joint Committee on Vaccination and Immunisation (JCVI) framework of principles for immunisation policy.

24. The Expert Group considered five immunisation policies, which might be considered as an alternative to the current policy:

  • no immunisation;

  • compulsory immunisation;

  • deferral of MMR;

  • a choice between either MMR or single vaccines;

  • single vaccines.

Before addressing these options it is important to recognise a very practical consideration, which is that, although single antigen measles and mumps vaccine were previously available in the UK, they are not currently manufactured to UK licence specifications.

25. None of the submissions presented to the Expert Group question the merit of immunisation against measles, mumps and rubella, more generally. There is therefore
a clear and overwhelming consensus that a "no immunisation" policy is not tenable. Similarly, none of the submissions presented to the Expert Group supported compulsion or the option of single vaccines replacing MMR in the childhood vaccination programme.

26. The Expert Group recognises that deferring MMR immunisation is in effect an option. However, the Expert Group concluded such a policy is not consistent with key elements of its framework of principles for immunisation policy. It is not supported by current scientific evidence, and it leaves children unprotected and at greater risk of infection for longer than is necessary.

27. The Expert Group recognises that some parents express a wish to be given the capacity to select either MMR or single vaccines for their children. The case for making single vaccines available by popular choice, as opposed to the clinical judgement of a health professional (as at present), cannot however be sustained on the basis of the available scientific evidence. There is no proven scientific link between the MMR vaccine and autism or Crohn's disease. Another important factor is that even if there were substantive scientific evidence to support the original hypothesised link between autism and measles virus, there is no evidence that the single vaccine option would actually be any safer. Similarly, the scientific evidence supports the conclusion that the MMR component viruses do not interfere with each other. The efficacy of MMR and single vaccines is the same, subject to issues of manufacture and quality control, but the comparative effectiveness of single vaccines is more open to question. It is clear that, if single vaccines were made available in this way, protection at individual and population level would depend on:

i) the extent to which this would result in increased vaccine uptake by those who refuse to accept the safety of MMR and leave their children, and others, unprotected;
ii) the extent to which this would change the vaccine uptake decisions taken by those who currently accept MMR;
iii) the extent to which multiple visits would result in increased default; and
iv) the extent to which leaving a space between vaccines rather than using concurrent administration would open up a window within which temporarily unvaccinated children would be at significantly elevated vulnerability to infection.

Recommendations

28. In the course of addressing its remit the Expert Group identified a range of possible and desirable changes to existing arrangements. The Group therefore recommends that:

a) The Scottish Executive and the Medical Research Council should work together to drive forward and fund, as appropriate, the full research agenda outlined in the final chapter of the MRC Review of Autism Research, which was informed by the concerns of parents and consumers. Parents and other representatives of those
with autism must continue to play a key role in developing research strategies (paragraph 2.40).

b) The Scottish Executive and the Medical Research Council should, in pursuing that research agenda, seek to maximise international collaboration (paragraph 2.41).

c) The Scottish Executive should consult widely, in order to publish a firm timetable for addressing all of the detailed recommendations set out in the PHIS Autistic Spectrum Disorders Needs Assessment Report (paragraphs 2.48 and 2.49), and in particular those relating to the:

  • development and implementation of improved evidence-based approaches to the diagnosis and management of ASD;

  • integrated joint planning, delivery and review of related health, education and social care services, for children, parents and adults, in which context people with autism, or parents and other representatives of those with autism, should have a role;

  • need for a more coherent and systematic approach to training health, education and social care professionals, better and in appropriate numbers;

  • development of a database of people with ASD in Scotland.

d) The Scottish Executive and the Medical Research Council should work together to drive forward and fund, as appropriate, further research into inflammatory bowel disorders in children (paragraph 3.16).

e) The Medicines Control Agency should continue to work closely with the European Union, and appropriate corresponding bodies in individual member states, to improve collaboration and monitoring of vaccine safety issues, and regularly review the operation, management and voluntary nature of the "Yellow Card" system in the light of such developments (paragraph 4.18).

f) The Scottish Executive should ensure that (paragraph 4.35):

  • vaccination records relating to individual patients should include details of the name and batch number of the vaccine administered;

  • a national lifelong vaccination record is developed, to allow identification of the immunisation status of an individual throughout the health service - irrespective of age group and independent of setting;

  • NHS Health Boards put in place adequate quality assurance mechanisms to ensure accuracy and completeness of recording of vaccination data.

g) The Committee on Safety of Medicines and the Joint Committee on Vaccination and Immunisation should, taking account of ongoing and future research into the causes of IBD and autism, continue to keep vaccination contraindications under review (paragraph 5.25).

h) The Joint Committee on Vaccination and Immunisation should (paragraph 5.29):

  • develop and publish core principles for immunisation policy in order to provide all interested parties with a clear framework against which future policy options might be assessed in an open and transparent manner; and

  • continue to publish the conclusion of its regular reviews of the scientific evidence relating to the safety and efficacy of MMR, and seek to improve upon existing arrangements for publicising that material.

i) Health Ministers (in the UK Government and devolved administrations) should urgently implement existing plans to extend arrangements for appointing members to the Joint Committee on Vaccination and Immunisation who are non-medical experts and/or members of the general public (paragraph 5.31).

j) The Scottish Executive should take steps to improve the level and quality of information available to parents whose children are due to be immunised against measles, mumps and rubella (paragraphs 5.21 and 5.32), by:

  • ensuring that all parents receive basic factual information about MMR (for example, contraindications, the risks posed by measles, mumps and rubella, and the risks of adverse reactions) with the invitation to bring their child for vaccination;

  • ensuring that all parents know that they can, and should, discuss any related questions with their GP or health visitor in order to make an informed choice about vaccination;

  • asking HEBS to evaluate and develop the MMR discussion pack, in order to maintain and enhance the currency and accuracy of the information, training and support provided to GPs and other health professionals, in relation to the medical science underpinning the immunisation programme;

  • requiring NHS Boards to put in place systematic arrangements for providing further advice to parents who, despite discussions with their GP or other health professional, have concerns and questions about MMR or the particular circumstances of their child.

k) The Scottish Executive should ensure that appropriate resources are provided to allow the Scottish Centre for Infection and Environmental Health to carry forward research, in collaboration with the University of Strathclyde, with the aim of developing mathematical models, which might help demonstrate the range of possible outcomes, for the population as a whole, arising out of immunisation decisions made by individual parents (paragraph 5.47).

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