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Pressure mounts for inquiry into MMR furore

BMJ 2004; 328 doi: https://doi.org/10.1136/bmj.328.7438.483-a (Published 26 February 2004) Cite this as: BMJ 2004;328:483

Not Really

Please allow me to comment on certain statements in Ms. Clare Dyer’s
piece:

Statement I: “Andrew Wakefield's study of 12 children, published in
the Lancet (1998;351: 637) …provoked a huge media controversy that was
followed by a substantial fall-off in the percentage of children given the
triple vaccine.”

Comment: Not Really. The fact is that Andrew Wakefield never
suggested that vaccination against measles, mumps and rubella be stopped.
On the contrary, his recommendation to have the monovalent vaccines
available, alongside the MMR, would have improved vaccination rates in the
United Kingdom, because all parents, including those concerned about the
safety of the triple vaccine, would have rushed to have their children
vaccinated. Furthermore, MMR uptake in the United Kingdom had already
decreased substantially before the February 1998 article by Dr. Wakefield.

The source of the following information is a document entitled “NHS
Immunisation Statistics, England: 1997-1998”
[www.doh.gov.uk/pub/docs/doh/imstat98pdf]. If it cannot be accessed
online, the document is available from the UK Department of Health.

Between 1994 and 1998, MMR (first dose) vaccination rates decreased
at a faster rate (16.1%) than all other vaccines.

In 1993-94, 588,000 children received three doses of pertussis
vaccine and 640,000 received the first dose of MMR. In 1997-98, 589,000
children received the pertussis vaccine series of three injections and
only 563,000 received one dose of MMR. Put in perspective, British parents
were more likely in 1997 to bring their children back THREE times to
receive the pertussis vaccine, a vaccine that has historically been a
concern in the United Kingdom, than once for the MMR vaccine.
The authors’ comment was: “In the case of pertussis, coverage rates have
regained the ground lost in the mid-1970’s due to public anxiety about the
safety and efficacy of the vaccine. The recent fall in MMR coverage may be
the result of similar concern over the vaccine”.

Examining the vaccination rates in the year of second birthday, 93.7%
of eligible UK children received 3 doses of pertussis and 91.9% received
their first MMR in 1995-96 compared to 94.2% for 3 doses of pertussis
vaccine and 90.8% for MMR in 1997-98.

When one looks at coverage rates, at age 24 months, by health
district in England, only 4 of the 100 health authorities reported a
coverage rate of less than 90% for diphtheria, tetanus and polio in 1997-
98 and 72 reported rates of 95% or over. For MMR, 28 health authorities
reported coverage rates of less than 90% including 9 with rates below 85%
and only 6 reported rates of 95% or over.

The United Kingdom district range vaccination coverage at age 2 years
in 1997-98 was a low of 82.6% and a high of 97.6% for three doses of
pertussis vaccine compared to a low of 75.2% and a high of 95.9% for one
MMR.

Statement II: “The chief medical officer for England, Professor Liam
Donaldson, told BBC radio's Today programme that Dr Wakefield's research
had led to a loss of confidence in a vaccine that had saved millions of
children's lives”.

Comment: Not Really. I respectfully submit that measles deaths had
decreased precipitously before the introduction of the measles vaccine
because of better nutrition and hygiene. The following can be checked with
the DOH. In 1901, there were 9,019 deaths attributed to measles in a
population of 32,612,1000 in England and Wales, giving a mortality rate of
276.5 per million.
In 1960, there were 80 deaths and the population was 45,775,000. The
measles mortality rate in England and Wales was therefore 1.75 per million
in 1960. In other words, the mortality rate from measles had decreased by
99.12% before the introduction of the measles vaccine. If Professor
Donaldson were talking about measles control (and not deaths) then indeed
vaccination would be most helpful. He offers two options: MMR or
“nothing”. Dr. Wakefield offers two other options: MMR or single vaccines.
I submit that single vaccines are immensely better than “nothing”.
Unfortunately, for many English parents, it has been “nothing” for years
before Dr. Wakefield’s article.

Statement III: Professor Donaldson added: "We have always thought
that Dr Wakefield's original study was poor science, but it is not just us
that thought that. Individual experts and individual medical bodies around
the world criticised it,"

Comment: Not Really. Six years after the study in question, there is
ample evidence by several independent investigators, from respectable
scientific centers, in support of Wakefield’s research. Identical
endoscopic findings have been described, measles virus persistence in
diseased tissues has been documented and abnormal measles immunity, in a
specific subset of children with regressive autism, has been repeatedly
detected.

Many of the individual experts and medical bodies who criticized
Wakefield had ties with the health authorities, the immunization programs
or the vaccine manufacturer. In adition, most of the epidemiological
studies they quoted had serious flaws and were funded by the CDC or the
vaccine manufacturer. (1)

Two of those anti-Wakefield studies actually reported increases in
autism after the introduction of the MMR vaccine in the UK and in one, a
regression after MMR vaccination was also documented.

In the first by Taylor and Associates, (2) the authors stated: “We
looked for evidence of a change in trend in incidence or age at diagnosis
associated with the introduction of MMR vaccination to the UK in 1988…
There was a steady increase in cases by year of birth… No significant
temporal clustering for age at onset of parental concern was seen for
cases of core autism or atypical autism with the exception of a single
interval within 6 months of MMR vaccination.”
Two co-authors of this study are employees of the Immunisation Division,
Public Health Laboratory Service Communicable Disease Surveillance Centre,
London. In addition, Dr. Taylor’s inter-personal conflict with Dr.
Wakefield should have been declared.

The second study by Kaye and Associates (3) is based on information
from the UK general practice research database (GPRD). The authors
reported that: “The incidence of newly diagnosed autism increased
sevenfold, from 0.3 per 10 000 person years in 1988 to 2.1 per 10 000
person years in 1999.”
Dr. Kaye is employed at the Boston Collaborative Drug Surveillance
Program. He disclosed the following:
Funding: No specific funding. Competing interests: The Boston
Collaborative Drug Surveillance Program is supported in part by grants
from AstraZeneca, Berlex Laboratories, BoehringerIngelheim
Pharmaceuticals, Boots Healthcare International,Bristol-Myers Squibb
Pharmaceutical Research Institute, GlaxoWellcome,Hoffmann-La Roche,
Janssen Pharmaceutica Products, R W JohnsonPharmaceutical Research
Institute; McNeil Consumer Products, andNovartis Farmaceutica.
Dr. Kaye did not perceive that he had a conflict because GlaxoSmithKline
was a defendant in the MMR litigation in the UK.

Statement IV: “The furore was sparked by a Sunday Times investigation
(22 February, pp 1, 12, 13) which also cast doubt on whether research
ethics approval had been properly granted for the study”

Comment: Not Really. Statements by the Editor of the Lancet also
sparked much of the furor. Now that the dust has settled, here are the
facts. A class action suit brought by hundred of parents, who believed
that the MMR vaccination was responsible for their children’s regressive
autism, was getting to Court at last, when suddenly legal aid funds were
cut. Simultaneously, the researcher, who dared to suggest that there was a
link between the triple vaccine and autism, was attacked and vilified. His
pioneer research was also deemed flawed because he did not disclose to the
Lancet that a minority of the 12 children in his original study was
included in a separate study that was partly funded by the Legal Aid
Board. According to the editor of The Lancet, such a disclosure should
have been made, because of the potential perception of a conflict of
interest.

From Andrew Wakefield’s point of view, there was neither a real nor a
perceived financial conflict. Funds from the Legal Aid Board were never
used for any part of the study that was published in The Lancet, in
February 1998. In addition, Dr. Wakefield did not personally receive any
portion of the much-publicized Legal Aid Board grant of £55,000 to the
Royal Free Hospital Special Trustees. In a letter published in the Lancet
in May 1998, Dr. Wakefield reported that he was undertaking a pilot study
on behalf of the Legal Aid Board to examine the merits of parental claims
of an association between their child’s exposure to the MMR vaccine and
subsequent autistic regression and intestinal symptoms.

It is evident that the editor of The Lancet did not perceive, for six
long years, that any conflict of interest existed because neither did he
question the principal investigator nor did he disavow the research. He
only made his recent accusations just before the Sunday Times report of
February 22, 2004 for reasons that we can only conjecture.

The fact is that the first 12 children reported in the Lancet study
were properly referred to the Royal Free specialized unit solely because
of their intestinal symptoms. The physicians, who examined and
investigated them and later reported their findings, had no interest in,
and probably no knowledge of, any future litigation.

The February 1998 Lancet article (4) consisted of a summary of each
child’s history as reported by the parents and the relevant clinical and
laboratory findings. The authors, including Andrew Wakefield, did not
claim that a causal association with MMR vaccination existed and only
suggested further research and investigation of the findings. When most of
Wakefield’s co-authors simply repeated that fact recently, the Press and
the vaccine lobby and its puppets hailed their statement as an earth-
shattering event.

The clearly orchestrated efforts by numerous parties to halt the MMR-
Autism litigation in the UK had to target the man who appeared to have
some answers. Being unable to refute his findings by clinical studies,
Wakefield’s enemies targeted him personally and attacked his integrity and
his character. Such attack will not change the beliefs of many parents who
are seeing their legal cases stalled and the UK Government investing over
£3 million to promote the MMR vaccine and not a penny to-date towards
autism research.

So is the Government going to convince parents that the MMR vaccine
has never caused autism in a small percentage of predisposed children? Not
Really.

Is Andrew Wakefield going to just go away? Not Really.

Will the truth ever come out? Absolutely.

References

1. Regressive Autism and MMR Vaccination
F. Edward Yazbak, MD, FAAP, TL Autism Research.
http://www.redflagsweekly.com/yazbak/2003_nov01_1.html

2. Taylor B, Miller E, Farrington, Cetropoulos M, P, Favout-Mayaud,
JL, Waight P, Autism and measles, mumps, and rubella vaccine: no
epidemiological evidence for a causal association. Lancet 1999; 353: 2026-
29.

3. Kaye JA, del Mar Melero-Montes M. Mumps, measles, and rubella
vaccine and the incidence of autism recorded by general practitioners: a
time trend analysis. BMJ 2001; 322: 460-463 (24 February.)

4. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular
hyperplasia, non-specific colitis, and pervasive developmental disorder
in children. Lancet 1998; 351: 637-41.

Competing interests:
Grandfather of a boy with two documented regressions, autistic enterocolitis and evidence of measles genomic RNA in the gut wall.

Competing interests: No competing interests

20 March 2004
F. Edward Yazbak
Pediatrician, Director
TL Autism Research, Falmouth, Massachusetts 02540