The next MMR could we do better

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The next MMR could we do better?

• Fiona Godlee
• Head of BMJ Knowledge

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Chronology

• 1988/9 MMR introduced
• 1990 new MMR introduced
• 1994 National immunization campaign, beginnings
  of link between MMR and autism
• 1995 BSE crisis unfolds
• 1997 MMR linked to Crohns disease
• 1998 Wakefield paper and press conference
  linking MMR to autism
• 2002 Wakefield et al report measles vaccine in
  gut in children with autism and IBD
• 2004 Partial retraction of 1998 paper

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Result

• Fall in uptake
• Localised measles and mumps outbreaks
• Further loss of trust in government science
• GPs cast as enforcers/added stress and workload
• Parents confused and anxious
• Problems for future vaccination efforts

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Anatomy of a crisis

• Vaccination policy
• Drug regulation/surveillance
• Editorial decisions
• Managing the press
• Government and public health response
• Personal versus political
• The role of the journals
• Public perception and understanding

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Vaccination policy

• Avoid compulsion/sense of compulsion
• Avoid hitches in vaccine delivery and
  acceptability
• 1988/9 inadequate supply of MMR vaccine
• 1990 Urabe mumps vaccine too immunogenic/reactog
  enic, 1/4000 children developed mumps meningitis
• Avoid national campaigns
• They tend to encourage public hysteria
• Link between MMR and autism grew out of 1994 MMR
  catch up campaign
• Hep B for school age children in France, linked
  to multiple sclerosis

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Drug regulation/surveillance

• Gather good data to call on when claims are made
• Should have had prospective follow up of a sample
  of vaccinated children since 1989 and 1994
• Vaccine companies wont do long term follow up
• Drug regulators (MHRA) - too close to industry
• Establish an independent agency, like the FSA
• Library of evidence Jefferson et al
• Put much more resource into assessing harms of
  interventions

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Why were flaws not spotted by Lancet editors?

• Is the topic area important and relevant to the
  Lancets readership?
• Was the study original?
• Was the research hypothesis clearly stated?
• What was the study design?
• Was this design an appropriate way to test the
  research hypothesis?
• Were the studies conclusions supported by the
  data?
• If the answer to (5) is no, would a more robust
  design have been practical to test the studys
  main hypothesis?

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Why were flaws not spotted by Lancet editors?

• Is the topic area important and relevant to the
  Lancets readership? Yes
• Was the study original? Yes
• Was the research hypothesis clearly stated? No
• What was the study design? Descriptive report
• Was this design an appropriate way to test the
  research hypothesis? No
• Were the studies conclusions supported by the
  data? No
• If the answer to (5) is no, would a more robust
  design have been practical to test the studys
  main hypothesis? Yes

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Why was the design not appropriate?

• Highly selected sample
• Extremely small sample
• No control group
• Link with MMR based on parental recall
• Short follow up
• Investigators not blinded

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Appropriate design Bradford Hill criteria for
proving causation

• Evidence from experiments in humans
• Association strong
• Association consistent from study to study
• Temporal relationship
• Dose response gradient
• Association makes epidemiological sense
• Association makes biological sense
• Association specific
• Association analogous to a previously proven
  causal association

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Some well designed studies

• Patja et al, 2000
• Taylor et al, 1999
• Davis et al, 2001

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Editorial decisions/peer review

• Improved standards of research and reporting of
  research
• COPE code of conduct for editors
• WAME statistical training for editors
• Training of peer reviewers

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Managing the press

• Press response initially balanced
• Increasingly unbalanced equal weight to two
  sides
• Evangelist/maverick versus the rest
• Personal stories create impact Hear the Silence
  docudrama
• Limited reporting of subsequent negative studies

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Managing the press

• Press conference
• Training for journalists in risk and causality
• Make all information available
• Dont give up/lose heart
• Keep the message constant and clear

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Government/public health response

• CMO letter 2 weeks late and unconvincing
• CMO letter to parents patronising
• Forced GPs into role of enforcers
• Docu-drama Hear the silence no one
  fielded/lost heart
• Negative message rather than positive
• Talked about risk rather than harm
• 2002 intensive media campaign/MMR website

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The personal versus the political

• Gummer and the Hamburger
• Blair delayed MMR for Leo
• Livingstone supports single vaccine

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The journals

• Publish commentaries
• Publish subsequent negative studies
• Educate readers about risk
• Journals are in the uncertainty business
  debate rather than pronouncement

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Do journals have a competing interest?

• Yes, collegiate and personal links between
  editors risk creating a pseudo-monopoly of ideas
• Joint editorials
• Joint initiatives
• Mentoring
• Socialising Lancet/BMJ annual softball match

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Dealing with anecdotes

• Listen to what patients and clinicians say
• SSRI/Paroxitine shows the need for this
• Find ways to capture and analyse anecdotal
  reports
• Standardised reporting of adverse effects

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Public perception and understanding
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The next MMR?

• Autism and DTP

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A story of conflicts of interest

• At every level
• We know about the Wakefield conflict is that
  the most important?
• What about the journal -
• Other medical journals
• The medical profession GPs
• The public health community
• The government
• The drug regulators

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Conclusions

• Better data on adverse effects
• Balance between benefits and harms
• Surveillance and follow up by an independent body
• High standards of editorial judgement and
  accountability
• Awareness of competing interest at all levels
• More distance between journals
• Greater public understanding of risk
• Two way conversation as part of healthy democracy

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• Thank you
• fgodlee_at_bmjgroup.com