How Mercury Was Absolved: Creativity, Collusion and Censorship
Thimerosal and the Occurrence of Autism, Negative Ecological Evidence from Danish Population-Based Data” by Madsen et al. was recommended by the CDC, published in the September 2003 issue of PEDIATRICS and considered a "well-designed epidemiological study" by the IOM Vaccine Safety Review Committee in February, 2004.
The study appears to be a foul purport of scientific labor because of changes in participant selection methods, mid-study expansion of cohort populations and changes in diagnostic grouping.
These concerns were formulated in a letter to the editor of PEDIATRICS. They were not addressed and the letter was never published.
The 5/18/04 published findings from the Institute of Medicine (IOM) Vaccine Safety Review (VSR) Committee report on “Autism and Vaccinations” concludes, in part, with the following:
Given the IOM’s conclusions, my concerns are two-fold. First, there are at least three points that, if left without clarification, invalidate the Danish, Madsen et al. 2003 study, “Thimerosal and the Occurrence of Autism, Negative Ecological Evidence from Danish Population-Based Data” which was published in the September 2003 issue of Pediatrics . This is of primary concern because the Madsen et al. study is one of the works that the IOM Vaccine Safety Review (VSR) Committee has deemed “well-designed.” My concern related to the Madsen et al. publication is not that the study may be disconfirmatory evidence central to the thimerosal-autism controversy, but that it is a foul purport of scientific labor. This is demonstrated among at least three points: changes in participant selection methods, expansion of cohort populations completed mid-study, and changes in diagnostic grouping markedly skewed findings.
of inpatient treatment data since 1971 was polluted by adding outpatient
activities post 1994 (Figure 1, below). Madsen et al. attempts to reconcile
this disparity by writing: “In additional analyses we examined data using
inpatients only…to elucidate the contribution of the outpatient registration
to the change in incidence. The same trend with an increase in the incidence
rates from 1990 until the end of the study period was seen (data not shown)
.” This is an incredible claim in light of their previous declarations.
First, within the same study, Madsen et al. claim that “The proportion of
outpatient to inpatient activities was about 4 to 6 times as many outpatients
as inpatients…” Perhaps more importantly, in an earlier publication,
Madsen et al. use the same data to purport: “In our cohort, 93.1 percent of
the children were treated only as outpatients…” This creates a huge
disparity between the study published in Pediatrics and the previous
one published in The New England Journal of Medicine which reportedly
used the same data. The former study claims “4 to 6 times as many outpatients
as inpatients”, yet the latter study maintains that 93.1% of all cohorts were
outpatients and 6.9% were inpatients, yielding a proportion in excess of
13.5:1. Despite the authors’ remarks claiming that the outpatient
registration did not substantively change the incidence in autism, we may
easily see, by making an adjustment for the more valid claim of 13.5:1 (Figure
2), that the original assertion of a statistically valid upward trend is due
only to the difference in accounting of cohorts before and after 1995.
1 - Uncorrected data from Madsen et al. 2003 
Two additional corrections need be made in order to accurately reflect the autism incidence rates in Denmark thus contributing to our Figure 3. First, it is necessary to address Madsen’s changes in diagnostic grouping. According to the authors: “The date of onset was defined as the first day of the first admission leading to a diagnosis of psychosis proto-infantilis (International Classification of Diseases, Eighth Revision [ICD-8]: 299.00) or psychosis infantilis posterior (ICD-8: 299.01) or from 1994 onward, infantile autism (International Classification of Diseases, 10th Revision [ICD-10]: F84.0) or atypical autism (ICD-10: F84.1) .” One might wonder why the authors feel comfortable changing the diagnostic grouping. Although the authors do not fully address the effect of this change, data presented in Figure 1 of the Madsen et al. 2003 study show that the autism incidence prior to 1994 is on average approximately 6/10000 patients (derived by summing the incidence data for each of the three age groups presented and dividing that sum by the inpatient to total patient ratio). In contrast, the earlier Madsen et al. 2002 publication reports autism incidence from anywhere between 1.2/10000 (DSM IV criteria) to 30.8/10000 (ICD-10 criteria). The earliest available study on the incidence of autism in Denmark  reports an intermediate value of 4/10000. Thus, using the pre-1992 ICD-8 psychosis infantilis incidence derived from the 2003 Madsen study (6/10000), the ICD-10/ICD-8 diagnosis ratio is at least 5:1 (i.e.,30.8 divided by 6) and may be as high as 25:1 (30.8 divided by 1.2). To remain conservative in the analysis, a correction factor of 5:1 is applied to the data in Figure 3.
last correction needs be made in order to accurately reflect the autism
incidence rates in Denmark thus resulting in our Figure 3. In an article
published in the American Journal of Preventive Medicine, Stehr-Green et al.
write: “Prior to 1992, the data in the [Danish] national register did not
include cases diagnosed in one large clinic in Copenhagen (which accounts for
approximately 20% of cases occurring nationwide).”
This presumably means that all data points up to 1992 should be multiplied by
1.2 to correct for this discrepancy.
2. Madsen et al. 2003 data corrected for inpatient to outpatient
reflects the aforementioned correction factors which are applied to the Madsen
et al. 2003 data (previously revised for a correct inpatient to outpatient
ratio, as in Figure 2). In contrast to Madsen’s published claim, our
correction for the disparity between the two studies (i.e., Madsen et al. 2002
versus Madsen et al. 2003), which purport to utilize the same data, reveals a
dramatic decrease in autism incidence after 1993—particularly among the 2-4
Reproduced with permission from PEDIATRICS Vol. 112 No. 3 September 2003, pp. 604-606 by the AAP
examining the 2-4 year-old cohort, it is apparent that if the discrepancy in
the diagnosis codes before and after 1993 is not corrected for, the Madsen et
al. 2003 study is essentially statistically indeterminate. This is
demonstrated in Figure 4 which shows P-values and Odds Ratios (OR) for average
autism incidence calculated before and after 1993 for the 2-4 year-old cohort
when applying corrections for diagnosis code differences before and after 1993
of between 0.5 and 25. At a correction of 1.0 (i.e., no factor applied),
autism incidence is nearly identical before and after the removal of
thimerosal at an OR of 1.17 (P=0.39). In fact, a statistically significant
increase in autism incidence after the removal of thimerosal is seen only if
the correction is lowered to 0.6 (OR=1.95, P<0.05). Conversely if a
modest upward correction of 2.0 is applied, a statistically significant
decrease in autism incidence for this cohort is seen (OR=0.59, P<0.05). At a
correction of 5.0 used to calculate autism incidence in Figure 3, the odds
ratio becomes 0.23 (P<0.0005). Thus, at most (i.e., at a correction of 1.0),
the Madsen et al. 2003 study is indeterminate. When the data are treated
properly, however (at a correction of 2.0 or great), it is easily shown that
autism incidence decreased in the 2-4 year-old cohort as a direct consequence
of the removal of thimerosal.
Madsen attempted to publish the study in two respected journals and was turned down. This is when his supporters at the Centers for Disease Control and Prevention sprang into action.
On December 10, 2002, Assistant Surgeon General Jose F. Cordero MD, MPH, Director of the National Center on Birth Defects and Developmental Disabilities sent a “personal” letter to Jerold F. Lucey, MD, the editor of Pediatrics that started:
The letter ended:
By so stating, Cordero not only validated the study’s contents but indeed anointed them strong and reliable enough to rule out a causal link between Thimerosal and regressive autism.
On February 9, 2004 the study was pronounced a "well-designed epidemiological study “ by the Vaccine Safety Review Committee of the Institute of Medicine. The committee rejected outright the “hypothesis” that thimerosal could trigger autism because it was theoretical and lacked supporting evidence. The committee also opinioned that further research to find the cause of autism should be directed toward other lines of inquiry “that are supported by current knowledge and evidence and offer more promise for providing an answer.”
Another disturbing remnant related to the Madsen study is the absence of concern for nullifying arguments in frontline publications. That is, when confronted with evidence that invalidates an already published study, the medical community has ignored substantive criticism by appealing to the IOM’s findings. On 4/13/04, my concerns regarding the Madsen et al. 2003 publication, previously detailed herein, were submitted as a letter to the editor of the journal, Pediatrics. This letter was in fact solicited by one editor who noted that the rebuttal would be most appropriately submitted as a letter to the editor rather than as a Post-publication Peer Review (P3R) submission. Soon after the submittal of this letter, the authors of the Madsen et al. 2003 publication, “Thimerosal and the Occurrence of Autism, Negative Ecological Evidence from Danish Population-Based Data,” were notified of the letter and given a chance to reply to the issues elucidated therein. These researchers chose NOT to reply, and on June 9, 2004, the editor of Pediatrics, Dr. Jerold F. Lucey, rejected the submitted letter without addressing the substance of my concerns.
The journal Pediatrics, like the members of the Institute of Medicine Vaccine Safety Review Committee, chose politics over science, thus squelching true debate over the issues surrounding vaccine safety. It is all too often misunderstood that conventional publications do not customarily circulate studies and censure subsequent, substantive materials which challenge the validity of such works. The previous example demonstrates a perhaps desired effect of the IOM VSR’s May 18th conclusions. Additionally, it is completely clear that these findings were based upon profoundly flawed science, in contrast to what most professionals expect from solid, “well-designed” epidemiological studies.
concern detailing three criticisms of the Madsen et al. findings invalidates
the Danish study. The three criticisms together implicate a greater
mischievousness occurring than simple carelessness. The Madsen et al.
publication takes on the form of a study, but leaves the aftertaste of
propaganda through the apparent use of incongruent language, suspicious data
collection, and data omission all of which are mechanisms of confusion rather
than clarity. Indeed, such mechanisms suggest that this team of researchers
was trying to create truth; in contrast, science seeks to discover it. In
light of their declared outcome, one might be left wondering why they did not
recommend a continued use of thimerosal as an autism preventative. Given the
authors’ trivializations, omissions, inconsistent data interpretations between
studies, and complete lack of self criticism, it seems prudent to reflect on
Madsen’s conclusions with extreme skepticism.
I wish to thank the friends who have helped with the preparation of this manuscript and its mathematical calculations.
I have no financial conflicts of interest. I am the
father of two children with medical diagnoses of autism.
 Lewis, C.S. 1961. The Screwtape Letters. New York: Macmillan Publishing Company
 Institute of Medicine of the National Academies. Immunization Safety Review: Vaccines and Autism. Washington, DC: National Academy Press
 Madsen et al. 2003. Pediatrics 112(3):604-6
 Madsen et al. 2002. New England Journal of Medicine 347(19):1477-82
 Brask, 1972. A prevalence investigation of childhood psychoses. In Nordic Symposium on the Comprehensive Care of the Psychotic Children, 1972:145-153, Oslo: Barnpsykiatrist Forening
 Stehr-Green et al. 2003. Autism and Thimerosal-Containing Vaccines: Lack of Consistent Evidence for an Association. Am J Prev Med 25(2):101-106