|
|
|
http://www.redflagsdaily.com/yazbak/2005_oct28.html
Alive and Well: The MMR-Autism Connection
Zero x 31 is still zero
and if it is not the MMR,
then what was it
that damaged our children?
By Red Flags Columnist, F. Edward Yazbak, MD, FAAP
(tlautstudy@aol.com)
Many parents believe that one or more of their children regressed
after receiving the measles, mumps and rubella (MMR) vaccine. No one
knows exactly the number of these children, but they probably
constitute 10 to15 percent of children with regressive autism. The
majority of children appear not to react unfavorably to the triple
vaccine. Obviously, for a couple whose only son is fascinated with
garage doors, or makes strange whirling noises all day, or hits his
head against the wall to keep entertained or answers by pointing to
pictures in a book, the percentage jumps to 100 percent.
The poor parents of affected children, particularly those living in
England, woke up on Oct. 18 to the news that yet another "definitive"
epidemiological study - the most thorough survey of MMR vaccination
data - had concluded that there is no credible evidence behind claims
of harm from the MMR vaccine. The news had been carefully leaked with
an impressive notice that it should be "strictly" embargoed until
00:01 hours (BST), Oct. 19, 2005. This was the most effective way to
guarantee that it would spread like a California wild fire on Tuesday
the 18th. After all, with everything happening around the world, from
earthquakes to hurricanes, wars, elections and bird flu, it was not
safe to take a chance that some new calamity would distract people on
Wednesday from appreciating the important findings of the study.
It was Tuesday when I received the embargoed press release. It
started, "There was no credible evidence behind claims of harm from
the MMR vaccination. This is the conclusion drawn by the Cochrane
Review Authors, an international team of researchers, after carefully
drawing together all of the evidence found in 31 high quality studies
from around the world."
The lead author of the study, Vittorio Demicheli, MD, of the Servizo
Sovrazonale di Epidemiologia, Alessandria, Italy, promptly tempered
the initial sweeping statement by adding, "In particular we conclude
that all the major unintended events, such as triggering Crohn's
disease or autism, were suspected on the basis of unreliable
evidence."
He then was quoted as saying, "Public health decisions need to be
based on sound evidence. If this principle had been applied in the
case of the MMR dispute, then we would have avoided all the fuss."
The fuss!
Is that what it was all about?
Is that what regressive autism is? A fuss!
Now Demicheli had my attention.
What was not mentioned in the widely circulated embargoed press
release was the actual first conclusion listed by the authors in their
abstract: "The design and reporting of safety outcomes in MMR vaccine
studies, both pre- and post-marketing, are largely inadequate."
I have to say in fairness that I have always admired the work done by
the Cochrane group. In fact, I quoted their excellent pediatric
influenza vaccination review in "Influenza vaccination of infants: A
useless risk" on Red Flags less than a month ago. (1) The lead author
for that review was Tom Jefferson, MD, who is a Cochrane researcher
based in England; Demicheli was one of the co-authors. Of the most
recent 15 reviews listed in MEDLINE, which they have co-authored with
others, Jefferson was the lead author in eight and Demicheli, the lead
author in four. Most studies were related to influenza vaccination.
It is well known that the Italians have never had much amore for the
MMR vaccination. In 2002, a measles epidemic was attributed to
"inadequate" vaccination coverage (Morbidity and Mortality Weekly
Report, Oct. 31, 2003). Actually "inadequate" was a charitable way to
describe a seven-percent vaccination rate in the area with the most
cases that year - 3,750 cases per 100,000 children under the age of
15. (2)
To see Demicheli listed as the lead author of this recent MMR review
(3) was, therefore, intriguing to say the least. The MMR-autism issue
had created much "fuss" - indeed, more of an obsession - in the United
Kingdom for years and Jefferson has been connected with it since 1999.
So, why was the apparent expert on the subject not the lead author,
while his Italian colleague was? We'll get to that later.
Details of the Release
"Aware of the controversy surrounding the use of MMR, members of The
Cochrane Collaboration set out to review the evidence for
effectiveness of the vaccine and also to review evidence of adverse
events. In a process of 'systematic reviewing' researchers searched
international databases and found 139 articles about MMR use. Because
many of them referred to studies that had been conducted in a way that
could not rule out bias or error, the researchers discarded all but 31
of them. Using rigorously established methods, the researchers then
synthesized the findings from these pieces of higher-quality research
to create the most authoritative assessment yet available."
The above would suggest that 108 of 139 studies on MMR did not meet
the Cochrane criteria. In fact, the authors reviewed some 5,000 MMR-related
articles and found only 31 that could "possibly" fulfill their
inclusion criteria.
According to the embargoed information, the authors concluded that:
There is no credible link between the MMR vaccine and any long-term
disability, including Crohn's disease and autism.
MMR is an important vaccine, which has prevented diseases that still
carry a heavy burden of death and complications where the vaccine is
not used consistently.
The lack of confidence in MMR has caused great damage to public
health.
People arguing for or against the use of any therapy need to make sure
that they base their conclusions on carefully collected evidence, not
just on biased opinion, speculation or suspicion.
>From here on, my comments will be limited to regressive autism.
Conclusion 1
The fact that a review of the 31 studies suggested that no link exists
between the MMR vaccine and autism does not mean that, indeed, no link
exists. We have seen each one of those epidemiological studies make a
splash, get some applause and then fade away while the so-called study
of 12 by Wakefield, has endured. Indeed, if one of the adversarial
studies had been strong enough to stand on its merits, we would not
have needed another and another and another to follow. We would not
have needed 5,000 of them and we would not have needed the Cochrane
review.
In 2002, K. M. Madsen, MD, stated that preceding studies lacked
sufficient statistical power to detect an association and did not have
a population-based cohort design. In time, his own study was proved
deficient by G. S. Goldman, PhD, and myself. (4) The 2004 Smeeth study
only survived a few weeks and now the Cochrane reviewers suggest that
it, too, is lacking something.
In addition, the impartiality of some authors and the significance of
their findings came into question. The research group led by Heikki
Peltola, MD, received financial support from Merck. The U.K. Medicines
Control Agency (MCA) and Public Health Laboratory Service (PHLS)
commissioned the studies by Brent Taylor, PhD, and friends. Madsen's
study was funded by the Centers for Disease Control and Prevention,
MCA and PHLS. And those are only three of many.
Conclusion 2
The authors are expressing a personal MMR-favorable opinion although
they know or should know, as everyone else does, that measles
mortality had decreased drastically in the Western world before the
advent of vaccination because of improved hygiene and nutrition. In
Third World countries today, improved nutrition and hygiene are the
top priorities.
Conclusion 3
The lack of confidence in the MMR vaccine was the result of the
inability of its promoters to instill confidence and maintain it. The
so-called, and so-far theoretical, "damage to public health" would
have been nil if the U.K. Department of Health had not outlawed the
monovalent measles, mumps and rubella vaccines in 1999 - just to force
people to their knees. This should be remembered as the worst public
health decision ever: vaccination's Day of Infamy.
Conclusion 4
No one ever said that MMR vaccination should be withdrawn. In fact,
Wakefield's biggest troubles started when he warned the U.K. health
department to get ready and have some single vaccines available in
case there was a further drop in MMR vaccination rates - following the
publication of his article - as the rates had been falling since 1996.
(5)
***
MMR and Autism
The evidence supporting an MMR-autism link was carefully collected and
duplicated and is rock solid. It is certainly not "biased opinion,
speculation or suspicion."
In hundreds of children with post-MMR regressive autism, a specific
type of enterocolitis has been identified by many investigators in
several countries. Some of the affected children have evidence of
measles virus genomic RNA in the cerebrospinal fluid, some in the gut
wall and some in both sites. In many, the sequences obtained were
consistent with being vaccine strains and, in these children, there
was no history of exposure to wild measles.
Many affected children have specific patterns of urinary polypeptides,
high serum measles and MMR antibody titers and elevated myelin basic
protein auto-antibody levels.
In fact, it will be safe to say that it is impossible to find one
normal child who has evidence of both MMR antibody and myelin basic
protein auto-antibodies in his serum or his cerebrospinal fluid or one
child, who regressed after MMR vaccination, who does not have at least
one of the following: the typical enterocolitis of autism, a
suggestive pattern of urinary polypeptides, evidence of measles virus
genomic RNA, elevated serum measles virus antibody, MMR antibody or
myelin basic protein auto-antibodies..
These are not suspicions. These are facts - rock-solid facts.
In many children, two regressions have been clearly documented by
health-care providers, photographs and videos. The first regression
occurred shortly after the first MMR vaccination and the second, much
more severe, after the MMR booster at age 4 or 5, following a period
of relative improvement. This biphasic course, or challenge-dechallenge-rechallenge,
has been accepted as evidence of causation by the courts and by a
special committee of the Institute of Medicine.
In a May 2005 presentation to the American Gastroenterological
Association of a study titled "Autistic enterocolitis: confirmation of
a new inflammatory bowel disease in an Italian cohort of patients,"
Frederico Balzola, MD, of Turin, Italy, and associates described in
detail the many gastrointestinal (GI) findings in nine consecutive
patients with autism who had long-standing and serious GI
symptomatology including abdominal pain, bloating, constipation and/or
diarrhea.
The authors concluded, "These preliminary data are strongly consistent
with previous descriptions of autistic enterocolitis and supported a
not-coincidental occurrence. Moreover, they showed for the first time
a small intestinal involvement, suggesting a panenteric localization
of this new IBD. The treatment to gain clinical remission has still to
be tried and it will be extremely important to ameliorate the quality
of life of such patients who are likely to be overlooked because of
their long-life problems in the communication of symptoms."
Now this is the kind of study that Demicheli and his colleagues should
have looked at, instead of reviewing epidemiological studies of
dubious quality financed by the vaccine manufacturer or vaccine
agencies.
Conflict or Bias
A conflict of interest is a situation in which someone in a position
of trust has competing personal, professional and/or financial
interests.
Bias is an inclination that inhibits impartial judgment.
Jefferson, the real MMR expert of the Cochrane team, did disclose that
he had a "potential" conflict of interest: In 1999, he acted as an ad
hoc consultant for a legal team advising MMR manufacturers.
The Cochrane publication also carried the following acknowledgements:
"Drs Harald Heijbel, Carlo DiPietrantonj, Paddy Farrington, Ms Sally
Hopewell,
Melanie Rudin, Anne Lusher, Letizia Sampaolo and Valeria Wenzel. The
authors wish to thank the following for commenting on this review
draft: Bruce Arroll, Lize van der Merwe, Janet Wale and Leonard
Leibovici."
***
If the lawyers for the MMR manufacturer(s) in the U.K. hired Tom
Jefferson as a consultant in 1999, while they were preparing for the
looming MMR autism case, they must have been certain that he would be
ready to testify under oath that MMR did not and could not cause
autism - in anyone.
In June 2000, Jefferson wrote an editorial in the Journal of
Epidemiology and Community Health Online, titled"Real or perceived
adverse effects of vaccines and the media - a tale of our times." In
it, he stated, "Since the publication of the Wakefield study on 28
February 1998, public concern fueled by extensive media coverage
caused a steady decline in MMR coverage in parts of the United
Kingdom, with a subsequent risk of a decline in herd immunity and
resurgence in morbidity.
"A swift reaction by the U.K. government and the subsequent
publication of studies by the Committee on Safety of Medicines and by
Taylor et al, showing no evidence of a causal link, partly redressed
the balance. As usual with vaccine "scare stories," there was a delay
between publication of the initial case series and that of
population-based causal assessment study. During this time, declining
coverage took place." (6)
Jefferson acknowledged that he received help in the preparation of the
editorial from Robert Chen, Ulrich Heininger, Elisabeth Loupi and
Harald Heijbel.
Since 1998, and until a short while ago, Chen, an epidemiologist with
the National Immunization Program (NIP), had been the CDC's point man
for all MMR matters arising from the Wakefield publication. He wrote
frequent anti-Wakefield articles and gave many interviews. He was also
always in close contact with Elizabeth Miller of the U.K. Department
of Health, who co-authored the Taylor studies and who led the charge
against Wakefield in England.
Ulrich Heininger was the European editor of the Archives of Disease in
Childhood. In 2002, he wrote, "However, safety questions raised about
certain vaccines - whether true (intussusception associated with
rotavirus vaccine) or false (autism due to MMR) - have challenged
pediatricians." (7)
Elizabeth Loupi was senior director of Pharmacovigilance, Sanofi
Pasteur SA, Lyon, France. Sanofi Pasteur MSD is the only European
company dedicated exclusively to vaccines and was founded in 1994, as
a joint venture between Sanofi Pasteur and Merck & Co., Inc.
Lastly, Harald Heijbel was the coordinator, Immunization Registry
Project, Swedish Institute of Infectious Disease Control, Stockholm,
Sweden
Jefferson was obviously a big booster of MMR vaccination and a firm
believer in its safety - no matter what. He also had to be
anti-Wakefield.
Even if he only had a "potential" financial conflict of interest, he
certainly had a major personal conflict and bias and he should have
declared them. A father who regularly contributes comments on the
autism situation to the electronic British Medical Journal has always
added "father of an autistic child." And I certainly have always
declared that I had a grandson who regressed after MMR vaccination. I
thought it was only fair that readers know.
As stated earlier, the Cochrane researchers who designed the present
study, evaluated the 31 "chosen epidemiological works" and wrote the
present report received assistance and scientific support from Harald
Heijbel, Carlo DiPietrantonj, Paddy Farrington, Sally Hopewell,
Melanie Rudin, Anne Lusher, Letizia Sampaolo and Valeria Wenzel.
Information about Harald Heijbel was reported earlier.
Paddy Farrington co-authored Brent Taylor's and Elizabeth Miller's
first article "Autism and measles, mumps, and rubella vaccine: no
epidemiological evidence for a causal association" (The Lancet, June
12, 1999). Having him help review that study and others like it is
strange - to say the least.
Farrington's statistical contribution to the first Taylor study was
criticized by James H. Roger, PhD, at a meeting of the Royal
Statistical Society in London. In a letter to the editor of The Lancet
(July 8, 2000), Roger wrote, "Sir - Rather than clarify the measles,
MMR, and autism confusion with your editorial, you perpetuated the
myth that good scientific evidence rejects a link between MMR
vaccination and autism.
You quote Taylor and colleagues as publishing "epidemiological
evidence contradicting this alleged association." On March 28, 2000, I
presented a talk to the Royal Statistical Society, in which I showed
how the currently published data, including that from this study, are
consistent with an appreciable number of autism cases being triggered
by MMR vaccination. In short, Taylor and colleagues used the wrong
study design to detect an association between immunization and a
disease with chronic onset, such as autism."
Sally Hopewell, Melanie Rudin and Ann Lusher are employed at the U.K.
Cochrane Centre.
Scientists Valeria Wenzel and Letizia Sampaolo work at the Istituto
superiore di sanità in Rome, the main Italian Institute of
technical-scientific research, control and advice in public health.
Because the listing of personal bias is not required, Jefferson's past
association with the Brighton Collaboration was also not disclosed.
No wonder Vittorio Demicheli of the Servizo Sovrazonale di
Epidemiologia, Alessandria, Italy, became the lead author of the
Cochrane MMR review.
The Brighton Collaboration
On its Web site (8), The Brighton Collaboration reports:
"[It] was founded by Robert Chen, Harald Heijbel, Tom Jefferson,
Ulrich Heininger, and Elisabeth Loupi in 1999 at a meeting in
Brighton, England. It was officially launched in autumn 2000. The
Collaboration consists of volunteers from patient care, public health,
scientific, pharmaceutical, regulatory and professional organizations
coming from developed and developing countries. They are experienced
and knowledgeable in the field of immunization safety and
corresponding medical specialties."
It says its objectives are:
"A. Global Collaboration
To establish a global collaboration of professionals and organizations
concerned with immunization safety.
B. Development
To develop a single standardized case definition per AEFI and
guidelines for data collection, analysis, and presentation for global
use.
C. Evaluation
To develop and implement study protocols for evaluation of case
definitions and guidelines in clinical trials and surveillance
systems.
D. Implementation
To raise global awareness of the availability, educate about the
benefit of use, facilitate access to and monitor worldwide use of
standardized case definitions and guidelines for data collection,
analysis, and presentation."
It reports the following about its sources of support:
"The work of the Brighton Collaboration is based on a large number of
volunteers worldwide. It obtained its first funding in 1999. The
Brighton Collaboration is presently supported by the Centers for
Disease Control and Prevention (CDC) and the World Health Organization
(WHO). From 2000 until 2003, the Collaboration also received funding
through the European Research Program for Improved Vaccine Safety
Surveillance (EUSAFEVAC).
"In December 2003, the Brighton Collaboration Foundation was
established by the University Children's Hospital Basel, Switzerland.
The purpose of the Foundation is to protect and preserve public health
by promoting immunization safety. The Foundation promotes the
development and availability of globally accepted, high quality
scientific standards for research on and communication of immunization
safety. The Foundation may also conduct immunization safety research
itself or support such research projects."
It is well known that U.S. Congressman Dave Weldon, MD, of Florida has
been watching health matters carefully as a member of the committee on
government reform of the House of Representatives.
In one particular address to the House of Representatives in 2004,
Weldon discussed autism, MMR research and the Brighton Collaboration
among other things. The address (9) is now part of the Congressional
Record, June 18, 2004, beginning on page H4564 and can be seen in its
entirety at
http://weldon.house.gov/UploadedFiles/RepWeldonMDonIOM.pdf
The following segment is relevant to this discussion:
"Mr. Speaker, I want to touch on one more additional issue, and that
is something called the Brighton Collaboration. I am very concerned
about the development of the Brighton Collaboration, which began in
the year 2000. This is an international group comprised of public
health officials from the CDC, Europe, and world health agencies like
WHO and vaccine manufacturers.
The first task of the Brighton Collaboration, created several years
ago, was to define what constitutes an adverse reaction to a vaccine.
They have established committees to work on various adverse reactions
to vaccines. Particularly troubling to me is the fact that serving on
these panels defining what constitutes an adverse reaction to a
vaccine are the vaccine manufacturers. What is even worse is the fact
that some of these committees are chaired by vaccine manufacturers.
It is inappropriate for a manufacturer of vaccines to be put in the
position of determining what is and what is not, an adverse reaction
to its product. Do we allow GM, Ford and Chrysler to define the safety
of their automobiles? Do we let airlines set the safety standards for
their airlines and determine the cause of an airline accident? Do we
allow food processors to determine whether or not their food is
contaminated or causing harm? Then, I ask, why we are allowing vaccine
manufacturers to define what constitutes an adverse reaction to a
vaccine?
This collaboration is fraught with pitfalls, and merges regulators and
the regulated into an indistinguishable group. It is critical that the
American public look at what is going on here and how this entity may
further erode the ability for us to fully understand the true
relationship between various vaccines and some adverse reactions in
some subsets of our population. I plan to devote additional attention
to this effort in the future.
Mr. Speaker, I look forward to working with you and others in this
body to address the problem that we face today.
As I stated at the outset of my comments this afternoon, autism was
once in America a rare and infrequently seen condition. I went through
four years of medical school, internship, residency, and years of
private practice and practice within the military and had not seen one
single case. I have seen case after case in my Congressional District
over the last seven years, a disease that I had never seen before.
The disease incidence was previously thought to be one in 10,000. It
is now thought to be as high as possibly one in 167, an almost
100-fold increase in the incidence.
We need to get answers to these questions. We need to restore public
confidence and safety in our vaccine program. Our vaccine program
saves millions of lives, it saves millions of kids from a life of
disability, and the best way for us to ensure public confidence and
make sure that all the kids get vaccinated properly is to get answers
to these questions. The way the CDC and the Institute of Medicine and
the industry is going about trying to answer these questions is highly
flawed.
Mr. Speaker, I encourage my colleagues to begin to look at this issue.
I know that many of them are coming to me saying they have parents
coming in their offices now with autistic kids, saying something needs
to be done. Something needs to be done."
Discussion:
Epidemiological and statistical studies - even the best - cannot prove
that the MMR vaccination does not cause regressive autism in a small
percentage of genetically predisposed children.
So far, we have not seen one unbiased, well-done and convincing
epidemiological study.
Hundreds of weak studies have come and gone after they made a little
noise.
The Wakefield study of 12 certainly seems to have endured.
Reliable histories with documentation have clearly shown regression
occurs following vaccination and specifically MMR vaccination.
Accurate clinical studies have revealed the presence of typical and
similar intestinal findings in children with post MMR regressive
autism.
Reproducible laboratory investigations have confirmed the relationship
of the findings with the measles component of the MMR.
Challenge-dechallenge-rechallenge has been documented repeatedly.
Diet and therapeutic management of the gastrointestinal component of
the disease has improved behavior and speech.
Though technically impressive, the recent MMR review by the Cochrane
group will please those who are already "on board" and convince only
those who know little about the subject.
For everyone else, the huge effort did fall short.
The hierarchy of the Cochrane Institution should examine the
impartiality of all involved.
For an institution of that caliber, even the appearance of bias is
unacceptable.
The authors of the Cochrane review revealed their partiality when they
endorsed the MMR vaccine without reservation and declared that it
could not cause harm. Multiple reports to VAERS and a review of the
vaccine compensation programs in the U.S., the U.K., Japan and other
countries show otherwise.
Something Is Not Right When:
Epidemiological studies about MMR and autism are financed by the CDC,
the U.K. Department of Health, the vaccine manufacturers or someone
supporting them.
Those studies - even the worst of them - are easily published in the
best medical journals, while their criticism is not.
The same studies are applauded after publication by the CDC, the U.K.
DOH and friends who made them happen.
The studies are then reviewed by friends.
And they are re-reviewed by sympathizers who minimize their problems
and attest that "there is no credible link," while not looking at all
the evidence contradicting them.
Something Is Certainly Not Right When:
All this is happening and the only one accused of conflict of interest
is Andy Wakefield because his hospital received a grant of £55,000 to
support GI research.
Conclusion:
The recent Cochrane Review of the MMR vaccine epidemiological research
is not convincing.
References:
Influenza vaccination of infants: A useless risk
http://www.redflagsdaily.com/yazbak/2005_sep30.php
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5243a4.htm
Review Paper: Demicheli et al: Vaccines for measles, mumps and rubella
in children. The Cochrane Database of Systematic Reviews 2005, Issue
4.
Goldman GS, Yazbak FE: An Investigation of the Association between MMR
Vaccination and Autism in Denmark. JAmPhysSurg 2004; 9(3):70-75
http://www.jpands.org/vol9no3/goldman.pdf
MMR Vaccination rates were down before Wakefield
http://www.redflagsweekly.com/conferences/autism/2003_dec22.html
http://jech.bmjjournals.com/cgi/content/full/54/6/402
http://adc.bmjjournals.com/cgi/content/extract/87/1/9
http://www.brightoncollaboration.org/internet/en/index/about.html
http://weldon.house.gov/UploadedFiles/RepWeldonMDonIOM.pdf
|
|
