For the Eye’s benefit, the Madsen study is compromised by a multitude of factors, notably that the co-author who liaised between the US Centers for Disease Control and Aarhus University, Poul Thorsen, is now under indictment for 13 counts of financial fraud and 9 of money laundering  relating to his work for the CDC. The pivotal role of Thorsen in the commissioning of the study is evident from this internal CDC email of 2000:

'As we discussed on Friday, we have become aware through Poul Thorsen of an exciting opportunity to study the role of MMR vaccine and autism using several registries/existing studies and the repository of biologic specimens and laboratory capabilities in Denmark. Attached below is a proposal for such a study. Poul will be leaving on Thursday to travel to Denmark where he will be meeting with the PIs for the proposed study on June 6th. We would like to be able to have Poul say whether it is likely that CDC (NIP) can fund the study, if NIP is interested. The proposed budget is included; there may be additional sources of funding (in addition to NIP) but we are not certain at this time. Unfortunately, the DD Branch does not have much (if any) $$ to fund the study, but we do have the expertise that we have developed due to the autism surveillance in Atlanta and the MMR/autism casecontrol study. I will be out of the office tomorrow, but you may contact Diana or Poul if you have questions. Thank you so much for considering this proposal.’

It is very hard to determine the good faith an article conceived under such circumstances, and there are unresolved problems about the complicity of Dr Thorsen’s colleagues in his financial activities. Additionally, the Cochrane Review of MMR was much more trenchant about the inadequacy of this study than indicated by Hammond, stating:

"The follow up of diagnostic records ends one year (31 Dec 1999) after the last day of admission to the cohort. Because of the length of time from birth to diagnosis, it becomes increasingly unlikely that those born later in the cohort could have a diagnosis"

And:

“The interpretation of the study by Madsen was made difficult by the unequal length of follow up for younger cohort members as well as the use of date of diagnosis rather than onset of symptoms for autism.”

Review of the data in the Journal of American Physicians and Surgeons also suggested the under-estimation of autism cases in the vaccinated cohort. Notably, Prof Suissa, an epidemiologist from McGill University made available to Dr Wakefield a letter he had written to New England Journal of Medicine (for which publication had been blocked) in which his recalculation of the raw data suggested that autism incidence should be 45% higher in the vaccinated group, rather than 8% lower according to Madsen’s figures. The Madsen team have never been prepared to enter into correspondence over possible anomalies in their study. When the paper was criticised in JP and S it was a leading pharmaceutical industry ghostwriter, Adam Jacobs, who attempted to answer.

Cochrane also suggested selection bias in the controls of the study by Smeeth  favoured by Hammond:

““In the GPRD - based studies (Black 2003; Smeeth 2004) the precise nature of controlled unexposed to MMR and their generalisability was impossible to determine…The study (Smeeth 2004) appeared carefully conducted and well reported, however, GPRD-based MMR studies had no unexposed (to MMR)representative controls. In this study the approximately 4% to 13% seemed to be unexposed controls regarded by the authors as representative. Such a small number may indicate some bias in the selection of controls.” (Re: Smeeth 2004)”

There were numerous other problems, collated by John Heptonstall  which Smeeth et al would not be drawn on.  One problem with GPRD studies was that ascertainment of autism cases appeared to an order of magnitude smaller than the officially reported numbers in the child population, so most of the autism cases would have been in the non-autistic control group.  But it is typical of the arrogance of government epidemiologists that they will not answer awkward questions.

A further problem lay with Cochrane itself: that the rubric of “no evidence for” masked the reality that there was also “no evidence against”: in short behind the weasel terminology the science had not be done, and after sifting 5000 related studies Cochrane could not find 31 epidemiological articles for review which were any good. Moving beyond the plainly misleading “plain language summary” the abstract was rather more candid:

"The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate.”

Nor, was the situation any better with the six autism related studies, none of which was rated of low risk of bias. Cochrane reported well of a CDC funded and executed gut related study but this was compromised by the fact that the data was buried after completion. It was outrageous that the media and the public were told that MMR was safe, when the scientific answer was that we did not know, and the institutional answer that we were being betrayed by scientists en masse not conducting proper science.

Hammond also failed to understand the point that actually even relatively well conducted epidemiological studies could not show for certain that this damage was not occurring in sub-groups, as the late former National Institutes of Health director Bernardine Healy pointed out on CBS News. Healy recommended the clinical study of sub-groups for vaccine damage, which is of course what Wakefield was doing. The work could not be invalidated by epidemiological studies. Hammond mentions also four studies co-authored by Wakefield which were not included for review by Cochrane but of course these were anyhow not epidemiological studies which could have fitted into a meta-analysis of epidemiological studies.

But for Hammond the clincher was the weasel worded and designed study by Hornig and Lipkin "Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study". But “lack of association” is not “no association” and Hammond carefully states:

“The children were selected because their gut symptoms were sufficiently grave that a biopsy was indicated for clinical reasons, which allowed the researchers to obtain tissue samples for the current study and try to replicate the Wakefield research, which found measles virus RNA in bowel tissue of 77 percent of children who had both autism and gut disorders, but not in children in a non-autistic control group.

“However, the Lipkin research found no difference between the two groups, with evidence of measles viral RNA found in only one case and one control, depsite using three labs and the best molecular detection methods available. Neither did the timing support a link between the vaccine and either autism or gut disorders. Only 13 of the 25 children with autism had the vaccine before the onset of autism, and in only 16 had the gut symptoms preceded the autism.”

It is nevertheless hard to see how ethically you get to the position from this where persistent measles virus in the gut is not worth investigating or treating. As the study itself admits in the discussion section, referring to the earlier Wakefield co-authored study :

“Our results differ with reports noting MV RNA in ileal biopsies of 75% of ASD vs. 6% of control children…Discrepancies are unlikely to represent differences in experimental technique because similar primer and probe sequences, cycling conditions and instruments were employed in this and earlier reports; furthermore, one of the three laboratories participating in this study performed the assays described in earlier reports. Other factors to consider include differences in patient age, sex, origin (Europe vs. North America), GI disease, recency of MMR vaccine administration at time of biopsy, and methods for confirming neuropsychiatric status in cases and controls.”

Two excellent commentaries show the Hornig study could have been designed not to find an association. Dr Hammond, it would seem, proposes that children with inflammatory problems and persistent measles virus should not be investigated or treated because it is not politically acceptable, even though they certainly exist. This looks like the medical profession protecting itself, not children.

Paul Foot wrote in the  Guardian December 2003 :

“Last week's Channel Five programme Hear the Silence about the MMR controversy was one of the best dramas I have seen. It was not just a moving true story, beautifully acted. It was also a shocking indictment of the medical establishment. A group of parents were confronted with the fear that their children had become autistic after having the triple vaccine for measles, mumps and rubella. A responsible authority should surely take such fears seriously and deploy the full extent of scientific research to testing the fears, if only to allay them. The reaction of the authorities was exactly the opposite.

"The one senior doctor who took the parents seriously, Andrew Wakefield, had his research stopped and was effectively banished to the US. Despite his record as an often published scientist, he was widely smeared. Legal aid for the parents to sue the government was cut off.

"On the programme, the two sides confronted each other. On the parents' side there was anguished concern, backed by sober science from Wakefield. On the other was outraged impatience, led by two slightly fanatical GPs, including Evan Harris, the Liberal Democrat MP for Oxford West. He insisted there was no link between autism and MMR, and loudly failed to prove that this was so. Instead, he went some way to proving the time-honoured medical principle that doctors know everything, and patients nothing."

When Foot died a few months later Private Eye and the Guardian set up a prize for investigative journalism, but when they closed ranks with the British establishment over MMR they did not honour his memory. The only thing they have not done so far is award it to Brian Deer (and here), although who knows what the 2011 awards to be announced next month will bring.

John Stone is UK Editor for Age of Autism.