15 Mar 2004 :
Column 128
MMR Vaccinations
and Autism
10.2 pm
Dr. Evan Harris
(Oxford, West and Abingdon) (LD):
I wish to discuss issues around
clinical ethics and research ethics
in the work done at the Royal Free
hospital by the inflammatory bowel
disease group since 1995. Before I
start, I would like to declare my
interests. I was a member of an
all-party group that recently visited
the American society of clinical
oncology conference for four days in
Chicago, which was organised and
funded by the pharmaceutical company
Aventis. I am a member of the British
Medical Association medical ethics
committee, although I am not speaking
for that body. I also spent a number
of years as a member of the central
Oxford research ethics committee,
which gave me direct experience of
many of the issues that I will deal
with tonight. I am a member of the
all-party group on autism, and my
father is a recently retired
professor of paediatrics.
Autism is a serious
condition, and all of us in the House
need to be aware of how distressing
it is to parents and other family
members and how challenging and
troubling autistic spectrum disorders
are to the children and their
families. The controversy surrounding
the work of the inflammatory bowel
disease group at the Royal Free
should not detract from the need to
improve the health and social care
provided to the children or the need
for more research into causation,
diagnosis and treatment of
developmental delay or regression in
children. None of the criticisms that
I make of the researchers, the
ethical regulators and the Legal
Services Commission should be taken
to extend to the parents who gave
their consent and co-operation to
those studies in good faith.
As we know, many of them
still support the individuals
involved and perhaps see no problem
in what they did. In the scandal over
Dr. Andrew Wakefield's failure to
declare financial and conflicts of
interest when his research group's
article was published in The Lancet
six years ago, the welfare of the
children who were his research
subjects seems to have been
forgotten. Documents revealed by the
investigative journalist Brian Deer
and by The Sunday Times raise major
doubts about a far more serious
matter than publication misconduct.
By that, I mean doubts and
allegations about whether children
were exposed to unacceptable risks
and unnecessary procedures.
I do not make those
allegations lightly, conscious as I
am of the need to avoid the abuse of
parliamentary privilege, but there is
very clear evidence pointing towards
unethical conduct by the
researchers—or by one or some of
them—and equally strong evidence
of failure and incompetence by the
research ethics committee. The papers
to which I refer are published on
Brian Deer's website:
www.briandeer.com
In 1996, and
subsequently, researchers in the
inflammatory bowel disease study
group subjected children to a battery
of invasive tests. Those included
upper GI endoscopy, which is passing
a flexible telescope down the throat
into the stomach and upper gut
through the mouth or nose;
ileo-colonoscopy, which is passing a
flexible telescope through the anus
and rectum right round the large
intestine and into the small bowel;
and spinal taps, which is passing a
needle into lower back to drain some
of the fluid that bathes the brain
and spinal cord. Those procedures are
not trivial on consenting adults, let
alone on autistic children, who must
be heavily sedated or even
anaesthetised. In addition to those
tests, the children underwent blood
tests, brain scans and monitoring of
electric currents in the brain.
Glenda Jackson
(Hampstead and Highgate) (Lab):
Will the hon. Gentleman give way?
Dr. Harris:
I shall certainly give way to the
constituency MP for the Royal Free
hospital.
Glenda Jackson:
I am delighted that the hon.
Gentleman remembers that the hospital
is in my constituency. Is he
disputing the fact that the
hospital's ethics committee was
concerned, particularly about the
fact that the project required
children to undergo, as he has just
pointed out, an intensive regime of
investigation? The hospital's ethics
committee put that point to the
senior clinical investigator,
Professor John Walker-Smith, who
replied: "I can confirm that the
children would have these
investigations even if there were no
trial."
Dr. Harris:
That is the key question, which I
shall deal with. If that were the
case, there would be less of a
problem, although there would not be
no problem at all. I do not believe
that that was right then or that it
is now.
In 1996, just as now,
there were tough rules to protect
children from being exposed to risk
for research purposes. We are not
judging this case by the standards of
today but by the standards of 1996,
when four separate sets of guidelines
applied. The guidelines were
published and circulated by the
Department of Health in 1991, the
British Paediatric
Association—now the Royal
College of Paediatrics and Child
Health—in 1992, the General
Medical Council in 1994 and the Royal
College of Physicians in 1996. The
guidelines made it clear that
children should not be exposed to
anything more invasive or risky than
a blood test unless certain
conditions—likely specific
clinical benefit to the
child—were met; that proper
approval be sought in advance from a
research ethics committee; that the
advice and instructions of the
research ethics committee be followed
to the letter; that changes to the
agreed arrangements be agreed in
advance by the research ethics
committee; and that patients or their
parents be given all the necessary
information about risks for them to
able to give adequate and adequately
informed consent.
The research ethics
committee was bound by the same
guidelines to refuse permission for
any tests or procedures that were
more than minimal risk if they were
not in the best interests of the
individual child. That means that
so-called non-therapeutic
research—as it was called at
that time—where there was no
likely clinical benefit to the child
in terms of therapy, was not allowed
to involve anything worse than a
blood test.
I shall quote some of
the guidance that existed around that
time. The BPA guidelines 1992 state:
"Children are unique as a
research group for many reasons. They
are the only people, in British law,
on whose behalf other individuals may
consent to medical procedures. Many
children are vulnerable, easily
bewildered and frightened, and unable
to express their needs or defend
their interests . . . The physical
integrity of children, as of all
other people, is protected by law.
Unless they, or their parents or
guardians acting on their behalf,
agree to it, nothing can be done
lawfully that involves touching them
. . . Parental consent will probably
not be valid if it is given against
the child's interests. This means
that parents can consent to research
procedures which are intended
directly to benefit the child, but
that research that does not come into
this category can only be validly
consented to if the risks are
sufficiently small to mean that the
research can be reasonably said not
to go against the child's
interests."
The Department of Health
guidelines 1991 are similarly clear:
"Where the proposal is for
non-therapeutic research, all of the
above applies"— criteria
for other patients— "but in
addition the child must be subject to
no more than minimal risk as a result
of his/her participation." The
local research ethics committee
"should note that those acting
for the child can only legally give
their consent provided that the
intervention is for the benefit of
the child."
The BPA was very clear
about what sort of procedures were
considered minimal risk, low risk and
high risk: "High risk procedures
. . . should be carried out only when
research is combined with diagnosis
or treatment intended to benefit the
child concerned. It would be
unethical to submit child subjects to
more than minimal risk when the
procedure offers no benefit to them,
or only a slight or very uncertain
one."
Glenda Jackson:
Is the hon. Gentleman disputing what
Professor Humphrey Hodgson, the
vice-dean and campus director at the
Royal Free and University college
medical school, said in a statement
issued on behalf of the school and
the Royal Free Hampstead NHS trust:
"The committee, after clarifying
a number of issues . . . and having
taken expert advice, approved the
protocol submitted. The clinical
management and the investigation of
these children was performed at the
Free by a dedicated team of
consultant paediatric
gastroenterologists, in full
consultation with and agreement of
the parents of the affected
children."
Dr. Harris:
I disagree with the Royal Free when
it says that the protocol was subject
to rigorous ethical analysis, and I
shall say why I do not think that the
necessary requirements were met.
Glenda Jackson:
Will the hon. Gentleman give way
again?
Dr. Harris:
I wish to make some progress, if I
may. According to papers released to
The Sunday Times by the strategic
health authority, the research ethics
committee did not appear to ask an
independent outside expert—that
is, someone who is independent and
outside and expert—whether the
battery of tests could be considered
of therapeutic value to the children.
In fact, after publication of the
paper, the research ethics committee
tried to claim that it was not even
its job to make a judgment about
whether procedures were in the
children's best interests. That in
itself is a shocking admission of
incompetence, so the Department of
Health should investigate every
ethics approval that the committee
has ever given for research on
children, to see whether anything
else was allowed through—in
effect, on the nod.
The published paper
stated that the investigations had
been granted clinical ethical
approval by the ethical practices
committee of the Royal Free, but the
research ethics committee says, in a
letter from the chairman to the dean,
dated 24 July 1998: "On 9th July
you wrote to me for my comment on the
letter of Professor David Hull. In
his letter Professor Hull states: 'I
see that the investigations were
approved by the Ethical Practices
Committee of the Royal Free Hospital
NHS Trust.' This is, of course,
incorrect. We did not approve the
investigations."
However, the paper says
clearly that the investigations were
approved by the ethical practices
committee of the Royal Free hospital.
They cannot both be right. I suspect
that both are wrong, in some ways,
but one at least is wrong. As it
happens, the researchers had
submitted their application in a form
to which approval might have been
given, even if the research ethics
committee had looked at it properly.
The researchers asked for permission
to carry out the tests on 25 children
with a condition known as
disintegrative disorder, which is
also known as disintegrative
psychosis or Heller's disease. DD is
a much worse form of developmental
disorder than autism, and the
researchers stressed in their
application that it is separate from
autism. They said, in paragraph 5,
"Scientific background",
that "disintegrative disorder
differs from autism in the loss of
motor and self-help skills and
usually, too, in the lack of more
complex stereotype behavioral
patterns".
The researchers were
clear on that point, and it is still
the accepted view today. DD is of
later onset and involves significant
loss of acquired skills. DD is rare
and, in a few cases, can be caused by
a metabolic disorder that can be
detected by high lactate levels in
the cerebrospinal fluid. It could be
argued that doing spinal taps on such
children would allow doctors to
diagnose a metabolic disorder, or to
rule it out. Since such diseases are
not treatable, generally speaking,
the benefit is limited, but at least
a benefit can be argued. However, no
major group of doctors in the UK
argued at the time, or argues now,
that spinal taps be performed on
children with autism for any clinical
benefit, and certainly not as an
excuse to obtain cerebrospinal fluid
for private research contracts.
Despite getting research
ethics approval to perform the tests
only on children with disintegrative
disorder and despite the researchers
stating that the tests were
clinically necessary to benefit the
children, the published research
shows that not one of the 12 children
had DD. One was diagnosed
"Autism? DD?", but not one
had DD. Most had autism. In another
paper published later in 1998—an
abstract in Gut—the authors
admit to carrying out the tests on 30
children, only two of whom had DD. By
2000, some 60 children had been
subjected to endoscopies, according
to an article in The American Journal
of Gastroenterology, of whom only two
had DD. When the research ethics
committee gave approval for the
application it saw, it made it clear
that any changes to the proposed
tests or the group of children should
be cleared with it in advance. That
is standard, and it is written in the
letter of approval. The research
ethics committee received no such
request to change the protocol, so up
to 30 children were experimented on
with no proper ethical approval and
with no likelihood of individual
clinical benefit.
Glenda Jackson:
Is it not the case that, in the
initial request, the criteria for
investigation were that children
"should have disintegrative
disorder; have symptoms and signs of
intestinal dysfunction, and there was
a parental request for investigation
to be undertaken"? Is it not
also the case that disintegrative
disorder is a syndrome that is part
of the autistic spectrum?
Dr. Harris:
The selection criteria at paragraph 7
of the protocol application include
"presence of disintegrative
disorder"; the applicants state
that the syndrome is separate, and it
is established in their argument that
it could be caused by something that
would make a CSF test worth doing,
but not by autism. Autism was not
mentioned in the scientific
background; had it been, I suspect
that the procedure would rightly not
have been permitted. When CSF tests
on autistic children were required
for Legal Services Commission
purposes, no hospital in the UK gave
ethics approval and children had to
be taken to America for the tests. I
hope that the hon. Lady understands
the point that I
making—[Interruption.] I want to
continue. It turns out that Dr.
Wakefield was receiving undisclosed
funding for at least four of the
children from the Legal Aid Board for
some of the results. A central
component of the deal was genetic
analysis of fluid collected from
those spinal taps, with further
undisclosed payments for genetic
analysis of biopsy samples from the
bowels, following endoscopy. The
evidence strongly suggests that, from
start to finish of his research, Dr.
Wakefield withheld the information
about his legal aid board funding
interest from the REC.
The question in the
protocol application under paragraph
10 was, "How are the substances
for the study being provided, and how
is the study being funded?" The
reply was "Clinical research at
the Royal Free Hospital (ECR)".
There was no mention of any Legal Aid
Board funding. The failure to
disclose that information suggests
that even the approval Dr. Wakefield
received for 25 children with DD may
be invalid. It also seems clear that
he had no ethical approval to carry
out those procedures on any child who
did not have DD.
Without ethical
approval, the consent that the
doctors obtained from the parents may
not be valid. Without a valid
consent, doctors could face action
for assault. I do not dispute that
the parents gave consent in good
faith, knowing that there was REC
approval for the study—albeit
apparently for a different study from
the one that was carried out—but
even valid parental consent does not
make it lawful to conduct high-risk
research procedures on children with
no likely clinical benefit.
Glenda Jackson:
Will the hon. Gentleman give way?
Dr. Harris:
I must conclude, so that the Minister
has time to reply. The whole affair
seems dubious. It is not just that
there was non-declaration of
interest, nor that up to 30 children
were exposed to invasive procedures
under those tests, but that many more
may have been thus exposed in tests
agreed and funded by the Legal
Services Commission with no ethical
oversight at all. The
GMC—currently the Government's
favoured path—cannot investigate
or judge the LSC. It cannot look into
the actions of non-medically
qualified management. It cannot make
recommendations to prevent any such
practices from happening again, nor
can it look for similar acts. That is
why an independent inquiry is
needed—not a hospital inquiry.
The accused cannot investigate
themselves, especially because, as
the letter read out by the hon.
Member for Hampstead and Highgate
(Glenda Jackson) shows, they have
already declared themselves not
guilty.
An independent inquiry
is needed and the Government must
order one. After all, such activities
could still be going on at the Royal
Free or elsewhere. Children need
protection from that sort of research
behaviour. If the Government cannot
guarantee that it is no longer
happening at the Royal Free or
anywhere else, they have no choice
but to order an independent inquiry.
The
Parliamentary Under-Secretary of
State for Health (Miss Melanie
Johnson): I congratulate the
hon. Member for Oxford, West and
Abingdon (Dr. Harris) on securing a
debate on this important subject.
Like all Members, I care greatly
about the health and safety of
children and I am reassured that some
of the infectious diseases that used
to be devastating in childhood are
now seen only rarely, if at all in
some cases. It is easy to forget the
impact that some of those diseases
had. Nowadays, parents in the UK
never see their children crippled by
polio. Diphtheria and tetanus are
exceptionally rare in children. Since
the meningitis C vaccine was
introduced in the UK in the 1990s, it
has cut the rate of that terrible
disease by 95 per cent.
Immunisation in the UK
has been greatly successful at
protecting children against
preventable diseases, and all those
achievements have happened because of
effective vaccination programmes. In
particular, measles cases fell from
more than 70,000 a year in
1987—before MMR was
introduced—to fewer than 100 per
year in 1999. Before MMR, there were
between 15 and 20 deaths each year,
but no child has died of acute
measles for a decade.
One of the greatest
achievements was the prevention of
congenital rubella syndrome and the
avoidance of rubella-associated
terminations of pregnancy. In 2001,
there was not one single case of
congenital rubella syndrome in
England and Wales in which a woman
acquired the infection in this
country. Let us not forget mumps.
Before MMR, it was the commonest
cause of viral meningitis and lead to
around 1,200 hospital admissions a
year. The MMR vaccine has dealt a
hammer blow to these three serious
diseases of childhood and has
released children from the risk of
death and disability as a
consequence, which is something with
which I know that the hon. Gentleman
and my hon. Friend the Member for
Hampstead and Highgate (Glenda
Jackson) agree.
The hon. Gentleman
indicated that he is well aware of
the significant media interest in MMR
following the findings of an
investigative journalist, Mr. Brian
Deer, from The Sunday Times. Mr. Deer
raised several concerns about the
research carried out at the Royal
Free hospital that first claimed a
link between MMR and autism. The
first concern was an alleged conflict
of interest, and the editor of The
Lancet has made it clear that the
information now makes the original
Lancet paper "fatally
flawed". The second concern is
about ethics approval for the
research carried out at the Royal
Free hospital, and I shall address
that matter next.
As the hon. Gentleman
emphasised, ethical approval,
especially regarding children, is an
essential part of medical research,
and such medical research involving
children is a matter of increasing
concern. It can be an important means
of promoting child health and
well-being, but as the Royal College
of Paediatrics and Child Health
clearly recognises in its
"Guidelines for the ethical
conduct of medical research involving
children",
"Children are
unique as a research group for many
reasons. They are the only people, in
British law, on whose behalf other
individuals may consent to medical
procedures. Many children are
vulnerable, easily bewildered and
frightened, and unable to express
their needs or defend their
interests."
The importance of
evaluating the possible benefit, harm
and cost of research on human beings,
and the possible ways of carrying out
that research, are key issues. The
benefits of research can be great,
especially if the condition being
investigated is common or if the
research has a high chance of
success. Possible harm must be
assessed with equal care, and
possible considerations of harm
include questions of how invasive the
type of intervention is, how severe
the risks associated with the
research procedures are, and how
likely damage is to occur. These are
common-sense issues that are
difficult to question. Any parent
would expect that research carried
out on their children should have
addressed those issues thoroughly and
carefully, but balancing the pros and
cons of research is often complex, as
I know that the hon. Gentleman
appreciates.
Research ethics
committees play a vital role in
considering the issues and advising
on what is acceptable and what is
not. Ethics committees are faced with
the paradox of trying to be both
stringent assessors and an
approachable forum to help
researchers to resolve problems.
They have to compromise
between aiming for the perfect
protocol in advance and encouraging
researchers to respond to families'
unpredictable responses, which might
require changes to research design
later on. Questions have been raised
about whether the lumbar punctures
and colonoscopies that were carried
out on children at the Royal Free
were justified. Both interventions
are invasive and are not undertaken
lightly. Lumbar puncture—during
which cerebrospinal fluid is
extracted from the spinal cord for
examination—is undoubtedly
unpleasant and is not risk-free.
Colonoscopies are unpleasant and
distressing to the patient, and carry
the risk of complications, such as
perforation of the bowel. Should
children at the Royal Free have
undergone such investigations?
Professor Sir David Hull and
Professor Brent Taylor raised
concerns in 1998. The research team
believes that the investigations
werejustified, but I cannot say what
was clinically justified for each of
the children in the study. However,
that shows why the approval of
research proposals by ethics
committees is so important.
Glenda Jackson:
Is it not also the case that the
independent ethical committee raised
those very issues in 1996, before
permission was given for the
investigations to proceed?
Miss Johnson:
I am not an expert on all the details
of the arrangements and I would not
want to disagree with what my hon.
Friend suggests, but we need to be
certain that the right processes are
being carried out. Ethics is about
good practice. As the Royal College
of Paediatrics and Child Health
recommends, each research ethics
committee that considers a project
involving children should be advised
by people with a close practical
knowledge of babies and children. The
ethics committee also needs to have,
or to have access to, the appropriate
expertise to cover the breadth of
issues dealt with by the research
proposal. That is demanding because
of the complexity of much of the
research undertaken. Input from
independent experts is a means of
ensuring that the committee can cover
all the issues.
The hon. Gentleman made
an important point about the
management of research at the Royal
Free. I am sure that the hospital and
my hon. Friend, as the local MP, will
take careful note of his points and
that the hospital will consider his
concerns in the light of the
statements it has made.
The General Medical
Council is considering serious
matters of research and ethical
conduct. We must await its
deliberations and its indication of
how it intends to take them forward
in using its statutory powers. I
assure the House that should aspects
of the case require further scrutiny
or investigation at that point, we
will give them the most serious
consideration and act appropriately.
I assure the hon. Gentleman that we
are waiting for the outcome of the
GMC's deliberations and will give
them careful consideration. I trust
that the Royal Free will also look at
what he said and think about the
appropriate response.
Dr. Evan Harris:
I am grateful to the Minister for her
considered response. I raised my
concerns with her some days ago. Does
she accept that the GMC cannot
consider the conduct of, and the
procedures that were funded by, the
Legal Services Commission because
that is not part of the inquiry? Does
she also accept that there may be
other practices elsewhere of which
she and the Department of Health may
wish to take note? Are there not
grounds for considering a wider
inquiry, because there may be another
form of investigation—by the
Crown Prosecution Service—for
which the GMC would want to wait?
Miss Johnson:
It is conceivable, although perhaps
not likely—it is not for me to
comment on the likelihood either
way—that the case has not been
brought to a final conclusion. The
LSC has refused to grant further
financial support for the litigants'
case and it appears that it will not
continue. However, notwithstanding
the privileges that the House enjoys,
it would not be appropriate for us to
comment on something on which
theoretically, if not practically,
legal proceedings were still pending.
I take the hon. Gentleman's point
about the ethics committees. I am
sure that the Royal Free has listened
carefully to what he said.
