Pathology records are at the centre of a new disagreement over disgraced medic Andrew Wakefield.
It is one of the most serious allegations that could be made about a doctor: manipulating patients' histories to make money. So it is no wonder that the charges, levied by editors of the British Medical Journal (BMJ) in January against medical researcher Andrew Wakefield, are still getting close scrutiny. Now an American whistleblower advocacy group has joined the fray over Wakefield, who in 1998 hypothesized a link, now scientifically disproven, between the measles, mumps and rubella vaccine (MMR) and autism.
On 9 November, David Lewis of the National Whistleblower's Center in
Washington DC published a letter in the BMJ (http://bmj.com) arguing
that Wakefield did not commit research fraud. Lewis told Nature that he
thinks the combination of public charges and a slow, secretive
investigation has left the public not knowing whom to believe and is
unfair to the accused researcher. "[The system] throws people like Andy
into a no-man's-land," Lewis says.
Wakefield was the lead author of a 1998 paper in The Lancet (A. J.
Wakefield et al. Lancet 351, 637–641; 1998) reporting on the case
histories of 12 children who had received the MMR vaccine and developed
symptoms of autism or inflammatory bowel disease.
The paper inflamed public fears about vaccines, but it was retracted in
2010 after the UK General Medical Council (GMC) concluded that Wakefield
had a charge of serious professional misconduct to answer, in part
because it found that his team did not have proper ethical approval for
tests performed on the children. Later in the year, the GMC found him
guilty of the misconduct charge and revoked his licence to practice as a
doctor. By then, more than 12 large-scale epidemiological studies had
failed to find evidence of the hypothesized link (J. S. Gerber and P. A.
Offit Clin. Infect. Dis. 48, 456–461; 2009) and the MMR vaccine is
today regarded as safe.
But was the paper merely mistaken, or a deliberate fraud? Articles by
medical journalist Brian Deer published in the BMJ in 2010 and 2011
accused Wakefield of reporting histories for the children that were not
consistent with their records and their parents' recollections, at a
time when Wakefield was also being paid by lawyers intending to sue MMR
manufacturers. Deer's articles themselves did not allege fraud, but on
their basis a BMJ editorial in January 2011 called the paper fraudulent.
Wakefield has always denied allegations of manipulating data or having a
financial motive in the Lancet paper, but no institution has yet ruled
on the matter. In March, University College London (UCL), which took
over divisions of the Royal Free Hospital where Wakefield worked, said
it had launched an investigation.
In the meantime, Lewis, a microbiologist and former whistleblower who
says he was falsely accused of misconduct after alleging links between
human illness and the spreading of sewage sludge, asked Wakefield for
the chance to review his files. His claims are not likely to challenge
the conclusion based on much other evidence that the vaccine does not
trigger autism. But they could complicate the debates about Wakefield's
integrity and the UCL investigation.
The documents that Lewis reviewed include confidential forms describing
biopsies from the guts of children. The forms were filled out by
pathologists Andrew Anthony and Paul Dhillon, who worked with Wakefield
at the Royal Free. These documents, Lewis says, are relevant to Deer's
charge that records he obtained do not support Wakefield's claims in the
Lancet paper that the children had nonspecific colitis, a supposed
element of an MMR-induced syndrome. On sheets for three of the children
graded by Anthony, the handwritten word "colitis" appears, and Dhillon
checked a box labelled "non-specific" on 10 forms. Anthony's sheets are
dated after the Lancet publication, whereas Dhillon's are dated before.
Lewis believes that the sheets show that Anthony and Dhillon were making
good-faith diagnoses of colitis. Anthony, who has left UCL, could not
be reached by Nature, and Dhillon indicated that UCL had told him not to
comment. (Neither has been accused of manipulating data.)
Before publishing Lewis's letter, the BMJ asked Ingvar Bjarnason, a
gastroenterologist at King's College Hospital, London, to review the
materials. Bjarnason says he doesn't believe they are sufficient to
support claims in the Lancet paper of a new disease process. He also
questions whether "non-specific" on the grading sheets refers to
colitis, saying it could refer to any kind of gut changes. But he says
that the forms don't clearly support charges that Wakefield deliberately
misinterpreted the records. "The data are subjective. It's different to
say it's deliberate falsification," he says.
Deer notes that he never accused Wakefield of fraud over his
interpretation of pathology records. But he says that records read to
him from the Royal Free pathology service clearly stated that the
children's gut biopsies were within normal limits, even though they were
reported in the Lancet paper as having enterocolitis.
Fiona Godlee, the editor of the BMJ, says that the journal's conclusion
of fraud was not based on the pathology but on a number of discrepancies
between the children's records and the claims in the Lancet paper. She
says she will be calling for a public inquiry into the matter, noting
that it has been more than a year since she first informed UCL about
concerns over Wakefield's work.
Wakefield denies charges of data manipulation. He says that UCL has yet
to officially request his response to any charges and he isn't convinced
that the inquiry will give him a fair hearing. A UCL spokesman says
that the investigation will be "thorough, fair and wide-ranging". But
eight months after announcing its inquiry, the university is still
looking for a suitable external chairman.
By:
Eugenie Samuel Reich
Nature
November 9, 2011
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