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MMR tutorial 2002.

Reason for tutorial.
Recent controversy regarding MMR, identified this as a Hot Topic.

Fran Machado 13/02/2002 

Points to discuss.

• MMR vaccine safety
• Patients perspective
• Public health issues and government policy
• Ethical issues
• GP practice issues

The controversy regarding MMR.

The suggestion of a link between measles vaccine and/or vaccines containing measles (such as MMR) and inflammatory bowel disease or autism have largely come from one source, a team at the Royal Free Hospital, London, led by Dr Andrew Wakefield.

The evidence regarding MMR and it’s safety was summarised in a document produced by the government which can be accessed at http://www.doh.gov.uk/mmr.htm

The document includes the following:

• In March 1998 the UK’s Medical Research Council called together a meeting of over 30 experts in all relevant fields. They reviewed all the evidence and heard full presentations from the team at the Royal Free Hospital. They concluded: "There is no evidence to indicate any link between MMR vaccination and bowel disease or autism".

• In June 1999 an independent expert Working Party of the Committee on Safety of Medicines made a detailed evaluation of over 100 children’s records referred to them by a firm of solicitors where the parents believed their autism or bowel disease was due to MMR. The Working Party concluded that: "The information available did not support the suggested causal associations or give cause for concern about the safety of MMR or MR [measles, rubella] vaccines".

• In June 1999 a study was published in the medical journal, the Lancet, reviewing the cases of nearly 500 children born in north London between 1979 and 1994 who had been diagnosed as having autism and examining possible associations between their condition and MMR vaccine (which was introduced in 1988). The study found:

- No increase in autism associated with the introduction of MMR in 1988.

- No difference in age of diagnosis between MMR immunised and unimmunised children.

- No difference in MMR immunisation rates between children with autism and the rest of the population.

- No link between the timing of MMR and the onset of autism.

• In April 2000 a further independent expert group was brought together by the Medical Research Council, which had met regularly since 1998 and considered all available evidence including further presentations from the Royal Free team. Again, the group concluded that there was no evidence of a link between MMR vaccination and autism or bowel disease.

• In February 2001 a study by Kaye et al was published in the British Medical Journal showing more evidence of no link between MMR vaccine and autism. The study reported:

- That there was a notable rise from 1988 to 1999 in the diagnosis of autism recorded by UK general practitioners in their records.

- That over the same period, there was no change in the proportion of children who had been vaccinated with MMR which remained at over 95% for the age groups and children in this study.

- The study therefore provides good evidence that MMR has not caused the large increase in diagnoses of autism that has taken place since 1988.

The study authors conclude that: "These data provide evidence against a causal association between MMR vaccination and the risk of autism".

• In March 2001 a paper by Dales et al in the Journal of the American Medical Association compared time trends in autism and in MMR immunisation coverage in California. The paper concludes: "These data do not suggest an association between MMR immunization among young children and an increase in autism occurrence"

• In March 2001, the British Journal of General Practice published a paper by De Wilde et al. The authors looked at whether children who go on to be diagnosed as autistic are more likely to see their GP in the six months after MMR than other non-autistic children. If MMR were causing the sudden loss of skills reported by the Royal Free Hospital research team, then such a study should pick up an increase in GP consultations in the months after MMR. The authors concluded: "there is no change in consultation behaviour in autistic children and matched controls in the six months after MMR".

• In April 2001 a major review of the evidence relating MMR and autism was conducted under the auspices of the American Academy of Pediatrics (AAP) (published in ‘Pediatrics’). The review concluded that "the available evidence does not support the hypothesis that MMR vaccine causes autism or associated disorders or inflammatory bowel disease". It also concluded that "separate administration of measles, mumps and rubella vaccines to children provides no benefit over administration of the combined MMR vaccine and would result in delayed or missed immunisations". In arriving at their conclusion, the writers of the report reviewed over 200 references and heard oral evidence presented by researchers at a two-day scientific meeting.

• The AAP review followed closely on the publication of the United States Institute of Medicine Safety Review of MMR that reached similar conclusions about the postulated causal relationship between MMR vaccine and autism and the importance of continuing with the current MMR programme. Their main conclusion was that "the evidence favors rejection of a causal relationship at the population level between MMR vaccine and autistic spectrum disorders."

• A report published in Vaccine (2001) found "further evidence against a causal association between MMR vaccination and autism". The report is of a reanalysis of the data collected for a study of those diagnosed as autistic who were born over a 15 year period in the North Thames region (Lancet, June 1999, above). This latest study concluded "the results presented here, combined with those we obtained earlier, provide powerful evidence against the hypothesis that MMR vaccine, or indeed any measles-containing vaccine, causes autism at any time after vaccination."

• A leading article and commentary in Archives of Disease in Childhood (September 2001) – the journal of the Royal College of Paediatrics and Child Health - provides further support for the vaccine. It reviews the evidence on MMR safety and identifies the arguments why separate vaccines are not an alternative to MMR. The authors conclude: "There is no good scientific evidence to support a link between MMR vaccine and autism or inflammatory bowel disease; indeed there is mounting evidence that shows no link. There is considerable evidence of the effectiveness and safety of MMR vaccine. Using separate vaccines is an untried and untested policy and, as far as protecting children from infectious disease is concerned, a backward step. While the final decision rests with the parents, the evidence of the safety and efficacy of MMR vaccine is so overwhelmingly conclusive that health professionals should have no hesitation in recommending its use".

• A study which looked at the postulated link between MMR and a form of autism that is a combination of developmental regression and gastrointestinal symptoms that occur shortly after immunization (ie. as suggested by Dr Wakefield) (Pediatrics, October 2001), concludes: "No evidence was found to support a distinct syndrome of MMR-induced autism or of "autistic enterocolitis." These results add to the recent accumulation of large-scale epidemiological studies that all failed to support an association between MMR and autism at population level. When combined, the current findings do not argue for changes in current immunization programs and recommendations." The study compared groups of children with developmental disorders who had had MMR; with autism who had had MMR; and with autism had not had MMR.

8. In short, no independent groups – including those independent of Government and those independent of Dr Wakefield and his colleagues – have been able to confirm Dr Wakefield’s clinical research findings and all have concluded that there is no link between MMR and autism or inflammatory bowel disease.

9. All this evidence has led :-

• The World Health Organisation (WHO) to conclude: "WHO strongly supports the use of MMR vaccine on the grounds of its convincing record of safety and efficacy" (January 2001).

• The All Party Parliamentary Group on Primary Care and Public Health to conclude that: "MMR is safe and … concerns about alleged links with various conditions such as inflammatory bowel disease and autism were unfounded" (August 2000).

• The major UK health organisations - including the British Medical Association, Royal College of General Practitioners, Royal College of Nursing, Faculty of Public Health Medicine, United Kingdom Public Health Association, Royal College of Midwives, Community Practitioners and Health Visitors Association, Unison, Sense, Royal Pharmaceutical Society, Public Health Laboratory Service and Medicines Control Agency - to issue the following statement following a meeting with the Government’s Chief Medical Officer: "MMR is a very effective vaccine with an excellent safety record … All of the major health organisations in the UK support the MMR programme … MMR is scientifically proven to be the safest and most effective way to protect children from disease … We strongly recommend that children are protected with MMR and not left at risk". (January 2001)

• The Committee on Safety of Medicine to conclude - when suggestions were made by Dr Wakefield that MMR vaccine had been licensed prematurely - "MMR is very safe. There is no question mark whatever over its licensing". The JCVI reported the same conclusion and said: "If there is a question mark, it is over the advice to have single vaccines". (January 2001)

• The Scottish Parliament’s Health and Community Care Committee, which had considered the issue of MMR, to conclude in its report: "On the basis of currently available evidence, there is no proven scientific link between the MMR vaccine and autism or Crohn’s disease. The Committee does not recommend any change in the current immunisation programme at this time." (March 2001)

• The Irish Parliament’s Joint Committee on Health and Children – which reviewed all the evidence, including hearing a presentation from Dr Wakefield – to conclude "that there is no evidence of a proven link between MMR and autism; there is no evidence to show that the separate vaccines are any safer than the combined MMR vaccine; …giving separate measles, mumps and rubella vaccines would leave children unnecessarily exposed and vulnerable". (September 2001)

Despite this evidence there are still concerns raised by parents and by health professionals. These concerns were discussed in an ethical debate in the BMJ 2001.

Vaccination against mumps, measles, and rubella: is there a case for deepening the debate?

BMJ 2001;323:838–40

The views of a GP included the following:

• Concern about the safety of the MMR and whether he would give the MMR to his children
• Disbelief of the evidence presented by the government regarding MMR and a feeling that the evidence presented is one sided.
• Current climate of involving patients in decisions regarding their health appear to have been ignored when the MMR is being discussed with respect to autism
• There is considerable financial pressure on GPs to endorse the vaccine due to fiancial pressures to meet target payments. Possible conflict of interest ?
• Confusion amongst health professional regarding the need for a second dose of MMR
• Questionnig authority can result in abuse of individuals who do so!

An epidemiologist raises the following points.  

·         The basic that needs to be answered is “Is the MMR unsafe?”

·         The controversy arose as a result of the observation by 8 out of 12 parents with children who had developed autism and GI symptoms who equated the onset of these with their children receiving the MMR vaccine.

·         No evidence supports this hypothesis

·         No epidemiological data to support that the increase in autism is related to a change in MMR uptake

·         No epidemiological data to suggest a causal link

·         Patients personal anecdotes regarding illness shold result in a hypothesis that needs to be tested

·         All the evidence we have at present is based on anecdote and not supported by evidence

·         Even if MMR does “produce” autism then the risk to children through not immunising would be much greater than the number of cases of autism that would be prevented

·         In summary he feels that there is no evidence for MMR causing autism and that there is a lot suggesting it doesn’t!

A theologian then discusses how to deal with uncertainty.

• We have a complex view of reality that at times may appear “irrational and superstitious” with no evidence to supoort it.
• We cannot ignore an individual parents view regarding the MMR, by doing so will not make it go away
• There is a crisis of expert authrority re MMR
• We need to acknowledge fears and deal with them
• Most patients would not know about target payments and the conflicts this proeduces
• Are GPs implementing government policy or looking after the individual

Health Professionals attitudes about MMR, ? adding to confusion!!

BMJ 2001;322:82-85 ( 13 January )

Second dose of measles, mumps, and rubella vaccine: questionnaire survey of health professionals

Objective: To determine the knowledge, attitudes, and practices among health professionals regarding the measles, mumps, and rubella (MMR) vaccine, particularly the second dose.

Design: Self administered postal questionnaire survey.

Setting: North Wales Health Authority, 1998.

Participants: 148 health visitors, 239 practice nurses, and 206 general practitioners.

Main outcome measures: Respondents' views on MMR vaccination, including their views on the likelihood of an association with autism and Crohn's disease and on who is the best person to give advice to parents, whether they agree with the policy of a second dose of the vaccine, and how confident they are in explaining the rationale behind the second dose.

Results:

·         Concerning the second dose of the vaccine, 48% of the professionals (220/460) had reservations and 3% (15) disagreed with the policy of giving it.

·         Over half the professionals nominated health visitors as the best initial source of advice on the second vaccine.

·         61% of health visitors (86/140), compared with 46% of general practitioners (73/158), reported feeling very confident about explaining the rationale of a two dose schedule to a well informed parent, but only 20% (28/138) would unequivocally recommend the second dose to a wavering parent.

·         33% of the practice nurses (54/163) stated that the MMR vaccine was very likely or possibly associated with Crohn's disease and 27% (44/164) that it was associated with autism.

·         Nearly a fifth of general practitioners (27/158) reported that they had not read the MMR section in the "green book," and 29% (44/152) reported that they had not received the Health Education Authority's factsheet on MMR immunisation.

Conclusions: Knowledge and practice among health professionals regarding the second dose of the MMR vaccine vary widely. Many professionals are not aware of or do not use the good written resources that exist, though local educational initiatives could remedy this.

Doctors must understand reasons behind vaccination

Nigel Higson discussed the rational for two doses in a letter in the BMJ

·         Measles vaccine is roughly 80% efficient in leading to immunity after a single vaccination. Thus if 80% of a population is vaccinated only 64% (80% of 80%) will actually develop effective antibodies and 36% will still be at risk of measles.

·         If a second attempt at raising immunity is made then a further 80% of that 36% will develop immunity. This will result in a total immune population of 92%, which is approaching the level needed to prevent epidemics.

·         The second dose is not a booster dose. It would not be needed if we could see which child had developed immunity and which hadn't merely by looking at the child; this is not the case, and blood tests are required to ascertain immune response. Routine administration of a second dose at an appropriate time interval is therefore the most sensible way forward.

Nigel Higson, chairman, Primary Care Virology Group. 
 

Why not use single vaccines.

Governments response

·        There is no scientific evidence to support the safety or efficacy of giving MMR as three separate vaccines at defined intervals.

·        Separating vaccines puts children at risk whilst they wait unnecessarily between vaccines.

·        There is also evidence that using separate vaccines would lessen the take-up of vaccination and hence increase the risk that these diseases will return.

·        It also means that children are subject to unnecessary repeat injections and more risk of adverse reactions – even if mild – at the injection site.

·        At the moment, none of the single component vaccines for mumps or measles licensed in the UK are manufactured for, or marketed in the UK.

·        Unlicensed medicines should not be imported when a safe and effective licensed alternative (i.e. MMR vaccine) is available and meets the patient's clinical needs.

·        There is also concern that some unlicensed single mumps vaccines may be ineffective or less safe than MMR.

FM 2002