After Wakefield: the real questions that need addressing
BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c2829 (Published 26 May 2010) Cite this as: BMJ 2010;340:c2829All rapid responses
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Dr Evan Harris and the chairperson of COPE, Elizabeth Watson, raise
important issues regarding how journals should handle possible misconduct
or allegations of misconduct.
COPE chairperson Elizabeth Watson describes COPE's position as
follows:
"We remain convinced that journals should not set themselves up as
judge and jury, but do have a responsibility to inform readers about
publications that may be unsound or unreliable."
This position sounds very understandable. However, just trusting the
instution's judgement has problems, some of which have already been stated
in the discussion - the institution has an interest to protect
the institution's reputation. Just contacting the institution and relying
on the judgement of the institution does not always give satisfactory
results.
I would like to suggest that whenever a reliable third-party
judgement is available, such a judgement would be used and aired, made
public, even if the instution's position is there is no problem.
I would like to describe a specific case to illustrate the issue.
In 2006, the Parliamentary Ombudsman of Finland gave out a decision
concerning medical research on newborns carried out. The research was
related to type 1 diabetes, IDDM and infant formula, and funded by an
infant formula manufacturer, with the leader of the trial having an
undisclosed competing interest of also being a possible beneficiary in a
patent on the research formula. The research was carried out by the by the
National Public Health Institute of Finland, currently known as
National Institute for Health and Welfare. The decision is described as
follows in the Parliamentary Ombudsman's Annual Report:
"In her decision on a complaint concerning medical research that had
involved babies in a maternity hospital, the Ombudsman took the view that,
in light of deficiencies identified in the consent form, the parents
participating in the research programme had not been able to give their
informed consent to the conduct of the research in the manner required by
law." [1]
In 2007, a study was published in the journal Immunology [2] which
possibly included data gathered from the trial which, according to the
Parliamentary Ombudsman's decision, was gathered so that the parents had
not been able to give informed consent.
The Parliamentary Ombudsman is the highest oversight official in
Finland. The Ombudsman's decision was made known to the editor of the
journal. The essence of the journal's editor's response is (quoted):
"I have now had a chance to review all the information we have
received on this issue. On consideration, I feel that despite my utmost
interest and respect for your proper concerns, there is no formal issue
here on which either the journal or the publishers absolutely need to step
in with any additional clarification, in light of the information we
received from Mr Juhani Eskola, Deputy Director General of the National
Public Health Institute (NPHI), amongst which was stated:
"The NPHI has no doubts that the FINDIA study led by Professor Outi
Vaarala was conducted in accordance with the Helsinki Declaration, Finnish
law and the institutional guidelines (Good Research Practice at the NPHI)
e.g. as regard to the informed consent given by the parents for the FINDIA
study."" [3]
Surely the reader can appreciate the strong opposition between the
views presented in Parliamentary Ombudsman's annual report and Dr Juhani
Eskola's reply.
Two issues raised here:
(1) When a journal has conflicting information on whether a
misconduct has happened or not, should the journal just take the word of
the institution and disregard the word of an oversight official as the
journal in the above example has done?
(2) When a journal has conflicting claims on whether a misconduct has
happened or not, should the journal inform the readers of the possible
issue, or should it just keep quiet unless it is judged the journal
"absolutely needs to step in with any additional clarification"?
[1] Summary of the Annual Report 2006 of the Parliamentary Ombudsman
of Finland
Available online at
http://www.oikeusasiamies.fi/dman/Document.phx/eoa/english/annualreports...
[2] 2007: Luopajärvi Kristiina; Skarsvik Susanne; Ilonen Jorma;
Akerblom Hans K; Vaarala Outi
Reduced CCR4, interleukin-13 and GATA-3 up-regulation in response to type
2 cytokines of cord blood T lymphocytes in infants at genetic risk of type
1 diabetes.
Immunology 2007;121(2):189-96.
[3] E-mail from Dr Danny Altmann, editor of Immunology, 3 September
2007
Competing interests:
(a) Chairman of Rokotusinfo ry, a Finnish pro-vaccine-choice, pro-information NGO founded June 1st, 2002. Rokotusinfo has contacted the World Health Organization, WHO, regarding Dr Juhani Eskola's omission to report a conflict of interest with regards to his SAGE membership (BMJ 2010;340:c201, doi:10.1136/bmj.c201)
(b) Member of the Breastfeeding Association of Finland which lodged the complaint to the Parliamentary Ombudsman of Finland resulting in the decision judging lack of informed consent described above; a volunteer in helping to write the complaint.
Competing interests: No competing interests
I beg to differ with Liz Wager, who recalls the Royal Free’s
assertion that serious misconduct had not occurred in the case of the
Royal Free Three. On the contrary, I think this begs the question of
whether the GMC’s judgment, was in fact correct, despite the fact that it
has taken so long to reach a verdict on the three eminent physicians in
the dock.
The GMC has got it wrong before.
Professor Sir Roy Meadow was struck off by the GMC in July 2005. He
contested his erasure and was reinstated after hearings in the High Court
and the Court of Appeal. Consultant Paediatrician, Professor David
Southall was erased from the register in December 2007, and in May this
year was finally reinstated by a decree of the High Court.
Paediatricians know that the GMC can make terrible mistakes. In fact,
in April 2008, British paediatricians debated a motion of no confidence in
the GMC. [1]
Perhaps recognising that such lengthy prosecutions are likely to
deter further research into childhood inflammatory bowel disease and some
of the other possible causes of autistic spectrum disorders, will
Britain’s paediatricians call for another vote of no confidence in the
GMC?
[1] News. Owen Dyer. Paediatricians debate a motion of no confidence
in General Medical Council. BMJ 2008; 336: 791.
http://www.bmj.com/cgi/content/full/336/7648/791
Competing interests:
None declared
Competing interests: No competing interests
Again Evan Harris sits on his high horse and lords over the affairs
of scientists at large, not just over Dr Wakefield and his two colleagues,
without regard for the views of parents and patients involved and without
regard for the role of science in a democratic society. At the base of
the Wakefield affair is the widening credibility gap between the public
interest and the interests of the medical profession. Harris is clearly
confident that the GMC has finally meted out true justice. But from a
public interest perspective this looks more like a case of 'doctor knows
best'.
Look at two of Harris' questions and consider the answers the doctors
gave to the GMC hearing.
1. Why did the ethical approval allow the Lancet 12 children to be
subjected to lumbar punctures and colonoscopies for research? Answer, they
were all patients with clinical needs that in the judgement of the senior
clinician, Professor Walker-Smith, required the use of the conventional
diagnostic interventions available to paediatric gastroenterology. Given
the inevitably tentative nature of diagnosis in the relatively unexplored
area of autism and bowel disease in the mid-1990s, it was hardly of
conclusive significance that the GMC's expert witness arrived, more than a
decade later, at a different judgement of clinical need based on an
examination of the historically available clinical records with no
patients at hand.
2. Why did the Royal Free allow research practices that the GMC
showed were unethical? Answer, the correct ethical approval, according to
the three doctors, was granted in 1995 and allowed additional gut samples
for research purposes to be taken from patients undergoing treatment.
However, the GMC insisted, for reasons that are not given in the hearing
summary, that the approval was granted in 1996, ie approval 172-96 (which
the doctors argued was the incorrect approval) and applied a range of
ethical requirements for a research project that was never done. The
doctors were bound by definition to break ethical requirements meant for a
different study. For example, the GMC argued that under 172-96 the
children were admitted for research and not treatment.
But readers should compare the terms of ethical approval and protocol
172-96, which focuses on specific pathological processes associated with
the malabsorption of vitamin B12, with the now well-known 1998 Lancet
paper which discusses general hypotheses on how bowel disease may be
implicated in autism - both available on http://briandeer.com For this
reader it seems clear that the 5-page Lancet paper is a small case series
that speculates broadly over a range of issues about the environmental
aetiology of autism and bowel disease. Approval 172-96 outlines a more
focused research programme following different aims and studying different
pathological processes from the subject matter described in the Lancet
paper. In looking for the deliverables from such a research programme one
wouldn't expect to find the Lancet paper among them. In terms of the
development of the research programme and the conceptualisation involved,
the Lancet paper appears to precede 172-96. Indeed the one mention of B12
malabsorption in the paper, far from being pivotally placed, is in a short
paragraph in the 'discussion' section at the end. Conceivably, the GMC
based its case against the doctors on the wrong ethical approval.
Harris undermines the role of science in a democratic society by
seeking to censure papers published in peer-reviewed journals without a
word to say on the evidence and argumentation they contain. At the end of
the day, the power of the argument in science should win over the
arguments for power that Harris proposes under the guise of 'scientific
ethics'.
Competing interests:
Father of child with autism and bowel disease
Competing interests: No competing interests
John Stone ignores the substance of Evan Harris's article and instead
concentrates on perceived competing interests.
Mr Stone states that Dr Harris "...failed to mention [the
unremunerated Industry and Parliament Trust Fellowship programme] when
introducing the House of Commons debate on this topic on 15 March 2004",
but as I understand it the parliamentary rules are such that an IPT
fellowship neither did at that time nor now does (even since rules were
tightened) need to be declared. Indeed, the categories of 'registrable
interests' do not seem to allow for such interests to be registered. [1]
Mr Stone seems to believe that it is clear that Dr Harris should have
declared his unregistrable interest. I beg to differ. In referring to
"contact with senior executives", Mr Stone appears to imply that merely
meeting someone would represent a conflict of interest. Again, I beg to
differ.
Dr Harris, according to Stone, "disclosed in the 2004 debate, but not
here, that his father (Frank Harris) was a recently retired professor of
paediatrics". It was necessary in neither case. Mr Stone further states
that Evan Harris "has not disclosed on either occasion that his father sat
on the Committee on Safety in Medicines". Stone, though, fails to explain
why Harris senior's work with the Committee on Safety in Medicines should
be listed as a competing interest by Harris junior. Did Evan Harris know
of his father's work with the CSM? Would knowledge of this work have any
bearing on the article written by Evan Harris? John Stone has given me no
reason to suspect that this is the case. I have no knowledge of the
competing interests of John Stone's father - should I be pressing Mr Stone
for full disclosure of his family's competing interests?
It is perhaps also worth noting that as "UK editor, Age of Autism",
and a member of the anti-vaccination lobby that has campaigned so
vociferously against MMR, John Stone might be said to have "a strong
antipathy to persons whose interests may be affected by publication [of
his response]". I would have thought that this would be as relevant a
competing interest as the fact that he has a relative with autism
("Competing interests: Autistic son") - yet Stone does not see fit to
refer to this as a competing interest.
The Age of Autism website has consistently published articles which
claim or imply that MMR causes autism, and has also published articles
that imply a conspiracy around MMR involving "improper relations between
government and industry" (the quote comes from this piece written by John
Stone: "Scandalous history of MMR in the UK" [2]).
The Age of Autism article I refer to above also contains the
information that the person who commissioned Deer's articles was the son
of somebody who sat on the Committee on Safety of Medicines. Mr Stone
seems overly interested in familial relationships, while paying
insufficient attention to major financial competing interests - for
example, Mr Andrew Wakefield's competing interest to the tune of £50,000
that was apparently not declared at the submission of the Lancet paper.
It seems that whether it is MMR or a competing interest that is the
subject of discussion, the anti-vaccination lobby highlight poor quality
evidence and tenuous links, while ignoring well-conducted research and
quite blatant conflicts of interest.
[1]
http://www.publications.parliament.uk/pa/cm200809/cmcode/735/735.pdf
[2] http://www.ageofautism.com/2010/01/the-scandalous-history-of-mmr-
in-the-uk.html
Competing interests:
I am a blogger who has been critical of the anti-vaccination lobby's campaign against MMR.
Competing interests: No competing interests
BMJ Editors and Mr. Harris,
An issue identified in a timeline
(http://www.timesonline.co.uk/tol/life_and_style/health/article5683642.ece
) published in February 2009 in association with the Brian Deer series in
the ToL--but given little attention thereafter--was existence of one or
more patent application(s) for competing vaccines filed by or on behalf of
Andrew Wakefield in June 1997 and in advance of his 28 February, 1998,
Lancet "Early Report" article.
Presuming even the normal submission-to-publication delays, there is
no question that some--if not all--of the the patent-application-
preparation process coincided with the article-draft-submission process.
With this history in view, clearly Wakefield failed to disclose his
pursuit of these intellectual property interests and, therefore, his
conflict of interest with regard to the patent application(s) that ante-
dated his Lancet article by some seven (7) months.
In September 2001, Lancet published the statement by a gaggle of
journal editors, including its own, entitled "Commentary: Sponsorship,
authorship, and accountability," setting forth the respective duties of
journals and authors. And in January 2003, Lancet set forth it's own
express requirements for disclosure in "The Lancet's policy on conflicts
of interest."
At the very latest, the February 2009 publication by ToL of the
Wakefield timeline placed Lancet on notice of the conflict. Yet Lancet
apparently then failed to inquire of Wakefield and so obtain from him a
letter of disclosure. Moreover, it was almost a year-to-the-day before
Lancet finally withdrew Wakefield's long-discredited 1998 article.
Thus the questions: What, if anything, were the Lancet editors
thinking--and when, if ever, were they thinking it?
Competing interests:
None declared
Competing interests: No competing interests
Our advice to authors (http://resources.bmj.com/bmj/authors/types-of-article/research) explains that we will not send an RCT paper for external review without its protocol; that we also ask authors to send in protocols (if available) for other study types for consideration during peer review; and that we invite authors to send us, among other supplementary information, copies of patient information sheets used to obtain informed consent for the study.
And, most importantly, BMJ editors try to consider the following questions when appraising submitted research (see http://resources.bmj.com/bmj/authors/editorial-policies/guidelines):
How much does this deviate from current normal (accepted, local) clinical practice?
What is the (additional) burden imposed on the patients (or others)?
What (additional) risks are posed to the patients (or others)?
What benefit might accrue to the patients (or others)?
What are the potential benefits to society (future patients)?
Even when a study has been approved by a research ethics committee or institutional review board, editors may be worried about the ethics of the work. Editors may then ask authors for more detailed information and ask them how they justified the ethical and moral basis of the work. Editors may also ask authors to provide the contact details of the research ethics committee that reviewed the work, so that the journal can request further information and justification from that committee. For studies that have not been reviewed by research ethics committees or institutional review boards editors may ask authors to explain what ethical issues they considered and how they justified their work.
Lastly, if any such issues arise we consult the BMJ's ethics committee and the Committee on Publication Ethics (COPE).
Competing interests:
I'm the BMJ's senior research editor and a member of the council of COPE
Competing interests: No competing interests
Evan Harris asks whether COPE will be investigating the Lancet's
handling of the Wakefield case, and what we are doing to prevent future
problems. COPE advises editors that they should generally not try to
investigate misconduct cases themselves since they are not properly set up
or resourced to do this. The difficulties of such an investigation are
perhaps reflected by the fact that it has taken the GMC so long to reach a
verdict. In the meantime, the Lancet took the course that would normally
be recommended, i.e. by contacting the institution and waiting for its
verdict. Given the Royal Free's assertion that serious misconduct had not
occurred, it would have been unusual for a journal to immediately retract
a publication. However, as Dr Harris points out, this begs the question of
whether the institution's judgement was, in fact correct. Sadly, journal
editors often have to act on partial evidence, and COPE is aware of cases
where lack of a proper investigation by an institution has made it almost
impossible for journals to know what they should do.
What is COPE doing
about this? We already have detailed guidance on retraction (see
www.publicationethics.org), since we know this is a difficult area, and we
are working on guidance about journal's relations with institutions. We
remain convinced that journals should not set themselves up as judge and
jury, but do have a responsibility to inform readers about publications
that may be unsound or unreliable. We don't have all the answers, and
these will remain tough decisions, but COPE is trying to help editors
faced with such cases.
Competing interests:
Chairperson, COPE
Competing interests: No competing interests
Sadly, I don't recognise substantive elements of Dr Evan Harris's
"Observations" article concerning my MMR investigation, which this week
led to Dr Andrew Wakefield and Professor John Walker-Smith - both formerly
of the Royal Free medical school, London - to be ordered by a GMC fitness
to practise panel to be erased from the medical register.
Most importantly, it's misleading for Dr Harris to say that he
"assisted" that investigation. For me, Dr Harris was a routine
journalistic contact who supplied a number of quotes for stories, and one
document - a letter sent to him by Wakefield's lawyers. At his own
initiative, Dr Harris observed a meeting between myself and the senior
editors of the Lancet, in February 2004, but he misspeaks when he claims
that "we" explained to the editor Dr Richard Horton what "lay behind" the
now-retracted Wakefield paper of February 1998. Although unexpected, Dr
Harris's presence at the meeting was welcome to me, since, as an
investigative journalist dealing in matters of reputation, I like to have
independent witnesses to my conduct and demeanour. However, the material
presented was entirely my own.
Dr Harris hasn't been pivotally involved in the MMR story over the
past six years, as I've been, and so perhaps his memory of these events
has dimmed. However, as I recall it, Dr Harris made no material
contribution at that meeting until a brief exchange of opinions following
my five-hour presentation.
Likewise, all the ethical issues pursued by the GMC in its longest-
ever fitness to practise hearing were raised in my investigation.
Although it's true that Dr Harris initiated a brief parliamentary exchange
with Glenda Jackson, following my first reports, it wouldn't be right to
suggest that those ethical issues eluded, or needed to be explained to,
me. Indeed, I raised them with Wakefield paper authors before I met Dr
Harris, and I personally travelled around London to gather together the
many professional statements and official guidance documents on research
ethics and, particularly, on the protection of child and mentally-
challenged patients.
It's a shame that I must make these comments. However, it has been a
feature of a number of interventions in this area by what one might call
"pro-MMR" campaigning doctors, both in the UK and the United States, that,
after a namecheck to me and perhaps some brief acknowledgement in their
writings of my investigation, they then procede to hold out my findings as
if they were their own. This is no small point, as investigative
journalism needs to be sustained in times of historic difficulty for both
newspapers and current affairs broadcasters.
More importantly, Dr Harris gives the impression that he and I are
somehow in it together. This isn't right. Dr Harris is a politician and
longstanding campaigner over vaccine safety, often turning up for media
appearance opportunities that have arisen as a result of my investigation.
I've never involved myself in campaigning over MMR, and, throughout my
inquiries, I've acted towards contacts such as Dr Harris with proper
professional distance. Indeed, there has been no collaboration, or, say,
discussions about what stories I might write, between myself and any other
person, apart from media professionals working with me to publish or
broadcast my findings.
I disagree with Dr Harris's opinion that "it is time to forget about
Andrew Wakefield". I think this is wrong on the facts, unprofessionally
collusive, and disrespectful to my work. Much remains to be said about the
research which initiated and sustained what has become a global health
crisis, frightening young parents, exposing children to infectious
diseases, and causing many parents of autistic children to be wracked with
unwarranted guilt. Similarly, I disagree with several other doctors, who
I associate with Dr Harris, who have suggested that Wakefield's research
was misrepresented by the media, or that the GMC proceedings were a
"witchhunt".
I must also take issue with words attributed to me by Dr Harris in
his article. He has conjured these, perhaps with an aim to heighten the
drama of his writing. However, particularly given that Dr Harris is well-
known to journalists as a politician who expects attributions to be
accurate (indeed often asking for them to be supplied to him in writing),
I'm surprised that he has made up dialogue from events six years ago.
Nevertheless, I'm grateful to Dr Harris for his quotes, and
particularly for the legal letter copy which I refer to above. I also
appreciate the kind things that, at least until now, I know he says about
me. However, the investigation which led to the GMC proceedings and to
the retraction of Wakefield's research from the Lancet came from outside
both medicine and politics.
It would be wrong for people, no matter how few in number, or how
distant from our lives, to be misled by those who might wish to suggest to
them that the fall of Andrew Wakefield involved anything more than a very
difficult, time-consuming journalistic investigation, which was taken up
by the GMC, as, in the circumstances, it was bound to be.
Competing interests:
BD's investigation for The Sunday Times and Channel 4 led to the GMC case against Wakefield and others, and to the retraction of the Lancet "MMR" paper.
Competing interests: No competing interests
As a member of the last Parliament, Evan Harris should easily be able
to answer question 2 for himself. Even with the most barn-door obvious
errors and wrongdoing in conduct, it is rare for an organisation to put
its hand up and admit mistakes. Royal Free saw no ethical wrongdoing
because even if there was any wrongdoing this was about the protection of
reputation; never apologise, never explain, never admit mistakes!
The Wakefield affair has been going on for years. Dr Harris had
plenty of opportunity during this time to use the Freedom of Information
Act to check on his concerns and theories about an alleged chronic failure
of ethical oversight at the Royal Free putting patients at risk. A few
requests for the sorts of information obtained by Brian Deer about
Wakefield’s research could have confirmed or allayed any concerns. How did
question 2 get past the BMJ’s libel lawyers? Is it responsible journalism
to suggest that patients in studies at the Royal Free have been put at
risk over the years because of chronic failures in ethical oversight when
such facts could have been checked prior to publication?
Dr Evans should be aware that parliamentary privilege no longer
applies and what he may have brought up in the House of Commons in 2004
does not have protection out here in the real world. [1]
[1] Harris E. After Wakefield: the real questions that need
addressing. BMJ 2010;340:c2829
Competing interests:
None declared
Competing interests: No competing interests
Vaccine Controversies : future opportunities
The recent GMC ruling on Dr Wakefield has again shone the spotlight
on the MMR controversy. There have been numerous controversies regarding
vaccines in the past and we explore two such controversies to identify
missed opportunities and lessons that could be learnt.
a) The diphtheria-pertusis-tetanus (DPT) vaccine was routinely used
in public health with an established safety record. In 1974, a case series
from Hospital for Sick Children at Great Ormond street, described 36
children who suffered severe neurological complications following their
DTP immunization.
The negative publicity resulted in a sharp decline in vaccine uptake
from 77% to 33%.There was uncertainty among the public and practitioners
with regards to its safety until the National Childhood Encephalopathy
Study (NCES) was published 7 years later.
b) The Measles-Mumps-Rubella (MMR) vaccine was introduced in the U.K
in 1988.It suffered a major setback following the study by Wakefield et al
in 1998 suggesting an association between MMR and autism. There were
several publications in the press in the following years, which conveyed
ambiguous messages with no clear scientific consensus on MMR safety. MMR
vaccine uptake dropped to 84% resulting in a mumps epidemic in 2005.
Currently, measles is declared to be endemic in the U.K.
The delay in robust defence of MMR vaccine until the Cochrane review
in 2005, contributed to undermining confidence in MMR safety.
Significant delay has occurred in the past in responding to such
public health controversies, resulting in increased morbidity and
mortality. In the future, strategies have to be developed within the
department of health (DOH), through existing agencies like NICE, to
promote early response and prompt development of scientific consensus to
guide health professionals and public in adopting evidence based practice.
Competing interests:
None declared
Competing interests: No competing interests