11. Commissioned Cochrane MMR Reviews

  1. Commissioned Cochrane Collaboration MMR reviews: 2003, 2005, 2012:
    Commissioned Cochrane Collaboration MMR reviewsBoth the UK and US governments played a pivotal role in the effort to discredit the Wakefield Lancet study.
    One approach was to commission MMR reviews, by the reputable Cochrane Collaboration, whose policy on financial conflicts of interest, concentrates on direct funding from industry, not government (as if governments that set public health policies, don’t have a conflict of interest in protecting those policies). This heavy dependence on government support leaves the Cochrane open to undue political influence.[91]

In reality, the Cochrane is not wholly independent of either commercial or government funding. In addition to funds obtained from the UK government, for each of the three commissioned Cochrane MMR reviews, funds were also obtained from the European Union Programme for Improved Vaccine Safety Surveillance (EUSAFEVAC); their funds derive from the Brighton Collaboration, which is in turn is funded in large part by the US CDC. [Appendix 9 details the interconnected consortiums that control vaccine safety assessments.]

An important caveat to bear in mind “absence of evidence is not evidence of absence.”[92]

Cochrane reviewers can only assess the results of studies that have been conducted and published; they cannot comment on studies that haven’t been done – nor can they assess studies that have been done, but remain unpublished, because the negative results conflict with an established health policy, or the commercial interests of the sponsor. Such study findings are concealed and the studies either remain unpublished, or the inclusion /exclusion criteria for data is altered and manipulated to achieve the desired results.

The opening sentence of the Cochrane “Systematic Review[93] of unintended events following immunization with MMR (commissioned by EUSAFEVAC) and published in the journal, Vaccine (2003, whose deputy editor is CDC’s Robert Chen) suggests that the primary objective of the review was to assuage public concern about the safety of the MMR:

Public debate over the safety of the trivalent measles, mumps and rubella (MMR) vaccine and the drop in vaccination rates in several countries persists, despite its almost universal use and accepted effectiveness.”

  • Universal use and accepted effectiveness” is not evidence of either safety of effectiveness.

In the 2003 review, Dr. Tom Jefferson and colleagues identified 4,500 articles, screened 120, but only 22 MMR studies were said to have met the criteria for the review. However, even these studies failed to meet scientific standards – as noted by the reviewers:

“We found limited evidence of safety of MMR compared to its single-component vaccines…external validity of included studies was also low. In addition, inadequate and inconsistent descriptions of reported outcomes (a well-known problem), limited observation periods (maximum 42 days), and selective reporting of results…As MMR vaccine is universally recommended, recent studies are constrained by the lack of a non-exposed control group…

We were unable to include a majority of the retrieved studies because a comparable, clearly defined control group or risk period was not available. The exclusion may be a limitation of our review or may reflect a more fundamental methodological dilemma: how to carry out meaningful studies in the absence of a representative population not exposed to a vaccine universally used in public health programs. Whichever view is chosen, we believe that meaningful inferences from individual studies lacking a non-exposed control group are difficult to make.”93

In 2005 the Cochrane reviewers analyzed 31 MMR studies.[94] Again, the stated objective was to assess the MMR effectiveness and safety in light of the “public debate over the safety of the trivalent MMR vaccine…” Alas, the evidence again failed to meet that objective:

We could not identify studies assessing the effectiveness of MMR that fulfilled our inclusion criteria.” The reviewers further acknowledged: “A lack of clarity in reporting and systematic bias made comparability across studies and quantitative synthesis of data impossible.

They acknowledged that the evidence for the MMR safety was:

largely inadequate… incomplete… [and suffered from] high risk bias. We found only limited evidence of the safety of MMR compared to its single component vaccines from studies that had a low risk bias…”

Lacking credible evidence, the Cochrane reviewers claimed that the safety and effectiveness of the MMR is demonstrated by “the impact of mass immunization”.

On the basis of that assumption, they declared:

(a) “No credible evidence of an involvement of MMR with either autism or Crohn’s disease was found.”
(b) “the impact of mass immunisation on the elimination of the diseases has been largely demonstrated.” (c) “…lack of confidence in MMR has caused great damage to public health

Dr. Vittorio Demicheli

Dr. Vittorio Demicheli

However, declaration (a) is refuted by the principle, “absence of evidence is not evidence of absence”; declaration (b) is disputed by those who argue that most of the infectious diseases for which children are being vaccinated have been eliminated in the developed world, largely due to improved standards of living, clean water, hygiene, and medical care. [See Appendix 5] Declaration (c) is refuted by statistical evidence documented by the UK Office of National Statistics data demonstrating that NO evidence of “great damage to public health” is due to low vaccination coverage. [See Appendix 2: Historical record]

In widely disseminated promotional public statements, [95] the lead author, Dr. Vittorio Demicheli, and the co-chair of the Cochrane Collaboration Steering Group, Mark Davies touted the quality of the MMR review as providing “sound evidence” on which to base public decision:

“If this principle had been applied in the case or the MMR dispute, then we would have avoided all the fuss.” (Dr. Domicheli)

This review exemplifies what Cochrane reviews are all about – for the first time all the evidence that is available on the efficacy and safety of MMR vaccine has been gathered together into one report.” (Dr. Davies)

Unfortunately, the Cochrane reviewers’ conclusions are not supported by the reviewers’ own careful assessment of the six studies in its review that related to autism:

  1. “Autism and Measles, Mumps, and Rubella Vaccine: No Epidemiological Evidence for a Causal Association”. Taylor B et al. The Lancet, 1999

The study demonstrates the difficulties of drawing inferences in the absence of a non-exposed population or a clearly defined causal hypothesis”.

  1. “Pervasive Developmental Disorders In Preschool Children”.Fombonne E.et al JAMA, 2001

“The retrospective cohort study by Fombonne et al tested several causal hypotheses and mechanisms of association between exposure to MMR and pervasive development disorders

(PDD). The number and possible impact of biases in this study was so high that interpretation of the results is impossible”.

  1. “Neurologic Disorders After Measles-Mumps-Rubella Vaccination”. Mäkelä A, Nuorti JP, Peltola H. Pediatrics, 2002

“The retrospective person-time cohort study by Makela assessed the association between exposure to MMR and encephalitis (EN), aseptic meningitis (AM) and autism (AU) in a cohort of 535,544 Finnish children…They concluded that there was no evidence of association. The study was weakened by the loss of 14% of the original birth cohort and the effects of the rather long time frame of follow up. What the impact of either of these factors was in terms of confounder is open to debate, however the long follow up for autism was due to the lack of a properly constructed causal hypothesis …” [Between 11% and 20% of adverse event data was missing.]

  1. “A Population-Based Study of Measles, Mumps, And Rubella Vaccination And Autism”. Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P, Olsen J, Melbye M. The New England Journal of Medicine, 2002

“The study by Madsen reported no increased risk of autism or other autistic spectrum disorders between vaccinated and unvaccinated children. 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.

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 i.e. there was extensive under-counting of autism cases in the MMR group”. [Between 11% and 20% of adverse event data was missing in the study.]

Dr. Poul Thorsen

Poul Thorsen

This was one of six pivotal CDC-commissioned and co-authored Danish epidemiological studies; the principal investigator was Dr. Poul Thorsen, a criminally indicted fugitive from justice. A recent report by the World Mercury Project (WMP, August 2017)[96] utilizes its newly obtained internal CDC documents, pertaining to the Danish studies, to update the saga of “Poul Thorsen Furgitive Researcher”. CDC documents reveal that the study published by the New England Journal of Medicine violated US and Danish mandatory ethics review:

“Not only was this paper fatally flawed in design, but it was conducted illegally. Madsen, Thorsen and their team did not have the legally required ethical clearances to access the data they used in this study.”(p. 10)

“when CDC officials including Coleen Boyle, Marshalyn Yeargin-Allsopp, Joanne Wojcik, and Diana Schendel became aware, in 2009, that Poul Thorsen failed to obtain legally required ethics permissions for the autism bio and genetic data projects, CDC employees participated in a cover-up with the Danish grantees. These CDC officials knew that the psychiatric registry records were reviewed without required permissions and they covered it up.”

Evidence of Misconduct Danish-CDC Collaboration:[97]

The internal CDC emails document how CDC officials colluded with the Danish scientists in efforts to cover-up the illegality of the study. They attempted to maneuver “retrospective” IRB approval for the already published NEJM (2002) report and another that was in the process of publication; “Validity of Childhood Autism in the Danish Psychiatric Central Register” was published by the Journal of Autism and Developmental Disorders (2010). Both studies “were conducted and the results published without legally required ethics clearances.”

“These are serious ethical violations….CDC cannot retrospectively apply this policy. In fact, the CDC specifically told Dr. Schendel [that] annual IRB certification from the Danes would be required at the outset of funding. Furthermore when the money went missing, and Poul resigned, he confirmed via emails he had applied for and obtained ethical clearances (which turned out to be a lie) the new principal investigators were sure they needed ethical clearance (IRB approval).”

A letter to the editor in chief of the NEJM, co-signed by all 8 co-authors of this “Definitive Madsen MMR Study”, emphasized the political value of their study, which (they claimed) “refuted Wakefield and provided strong support for the MMR vaccine program”. [Read details Appendix 9]

  1. Age at First Measles-Mumps-Rubella Vaccination In Children With Autism And School-Matched Control Subjects: A Population-Based Study In Metropolitan Atlanta. DeStefano F, Bhasin TK, Thompson WW, Yeargin-Allsopp M, Boyle C. Pediatrics, 2004

“The design of the [sic] study assessing the association between MMR vaccine and the onset of autism [sic] compared the distribution of ages at first MMR vaccination in children with autism (cases) and controls. DeStefano provided inadequate explanations for missing data…excluded more than a third of cases”.

Dr. William Thompson

The explanation for the “excluded more than a third of cases” was provided by Dr. William Thompson, a senior CDC scientist and a co-author of the Pediatric 2004 study, who broke his silence in 2013, and disclosed how the data went missing. He provided documented evidence of CDC fraud and malfeasance.

In taped conversation over a 10 month period with Dr. Brian Hooker (a biochemical engineer, and a father of an injured child) Dr. William Thompson, senior CDC scientist and co-author of the Pediatrics (2003) study, described in detail how the findings reported in Pediatric were crafted. He stated that when he and his CDC co-authors, found a statistically significant 3.6 increased relative risk, of a causal relationship between MMR and autism, in African American boys, who were administered the vaccine prior to 24 months and prior to 36 months, they sought ways to eliminate that 360% increased risk.

Dr. Thompson stated that the published analysis in Pediatrics omitted 260 African American boys from the dataset. He further stated that CDC scientists destroyed the original data. [Read the details, including the publication saga of the re-analysis of the complete CDC dataset by Dr. Hooker in Appendix 9]

  1. “MMR Vaccination and Pervasive Developmental Disorders: A Case-Control Study”. Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG, Hall AJ. The Lancet, 2004

“The study assessed the association between exposure to MMR and the onset of autism and other PDD [sic] based on data from the UK’s General Practice Research Databased (GPRD) studies (Black 2003; Smeeth 2004) the precise nature of controlled unexposed to MMR and their generalisability was impossible to determine…

The [Smeeth] study 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.”

Numerous UK authors have relied on the GPRD data – most notably, epidemiologist, Dr. Elizabeth Miller , a WHO consultant, who was head of the UK Immunisation Department for 15 years – to support the claim that there is “no evidence of an association between thimerosal and autism”. However, senior CDC epidemiologist expressed serious doubts about the reliability of the UK GPRD.

Shortly before he left CDC to head the epidemiology department at GSK, Dr. Tom Verstraeten sent an email to Dr. Robert Chen, Chief of CDC’s Vaccine Safety for National Immunization Program (NIP) in which he raised serious doubts about the reliability of the UK GPRD database:

“I think two issues are important in assessing the potential strength of the GPRD study:.
1. Maximum exposure and 2. Unbiased controls. I’m not sure if the GPRD is that reliable that you can be sure that low exposure is really low exposure and not underascertainment in the database.” 
(June 26, 2001)

[Read about the permutations Dr. Verstraeten’s CDC Vaccine Safety Datalink study findings underwent in Appendix 9]

  • The Cochrane reviewers noted these studies’ bias, the lack of controls, the missing data, and, they even stated that “generalizability was impossible”. How then, could they justify the widely publicized conclusion, “No credible evidence of an involvement of MMR with either autism, or Crohn’s Disease”?

The widely circulated Cochrane press release was sheer propaganda; its headline declared:

Cochrane Library Publishes the Most thorough Survey of MMR Vaccination Data”. It was disseminated by the American Association for the Advancement of Science (AAAS EurekAlert, which touts itself as “The Global Source for Science News”). The news alert invoked the two institutions’ “authoritative” status. Cochrane delivered the findings that the UK government had commissioned, but without scientifically valid evidence to support the widely broadcast claim:

“There was no credible evidence behind claims of harm from the MMR vaccination. This is the conclusion drawn by the Cochrane Review Authors, an international team of researchers, after carefully drawing together all of the evidence found in 31 high quality studies from around the world.”

  • To repeat, studies not designed to detect evidence of MMR involvement in autism, are not likely to report such evidence. However, this does not mean that no evidence exists. (Absence of Evidence is Not Evidence of Absence, 2016) An accepted concept in computer science, applies equally to meta-analyses in medicine, “garbage in, garbage out.”

Incisive, detailed analyses of the studies followed on the heels of the widely publicized Cochrane “findings”.
Several critics noted that the Cochrane reviewers lent authority to studies of dubious quality which they admitted were deficient and compromised by:

“bias in the selection of controls”; “lack of a properly constructed causal hypothesis”; “extensive under-counting of autism cases in the MMR group”; “missing adverse event data”; and in one study, “more than a third cases were excluded”.

A detailed analytic dissection by Edward Yazbak, MD,[98] critiqued the fact that the Cochrane reviewers’ conclusions were based on 31 sub-standard epidemiological studies. He highlighted empirical evidence – real world evidence – that rendered the reviewers’ conclusions untenable:

Edward Yazbak, MD

Edward Yazbak, MD

“Many affected children have specific patterns of urinary polypeptides, high serum measles and MMR antibody titers and elevated myelin basic protein auto-antibody levels. In fact, it will be safe to say that it is impossible to find one normal child who has evidence of both MMR antibody and myelin basic protein auto-antibodies in his serum or his cerebrospinal fluid or one child, who regressed after MMR vaccination, who does not have at least one of the following: the typical enterocolitis of autism, a suggestive pattern of urinary polypeptides, evidence of measles virus genomic RNA, elevated serum measles virus antibody, MMR antibody or myelin basic protein auto-antibodies.

These are not suspicions. These are facts – rock-solid facts. In many children, two regressions have been clearly documented by health-care providers, photographs and videos. The first regression occurred shortly after the first MMR vaccination and the second, much more severe, after the MMR booster at age 4 or 5, following a period of relative improvement. This biphasic course, or challenge-dechallenge-rechallenge, has been accepted as evidence of causation by the courts and by a special committee of the Institute of Medicine.”98

The stated objective of the 2012 Cochrane Collaboration MMR Safety Review[99] remained:

to review existing evidence on the absolute effectiveness of the MMR vaccine in children” and “to assess the worldwide occurrence of adverse events, including those that are common, rare, short-term and long-term, following exposure to the MMR.

In this review 33 new trials were added, and a total of 64 MMR studies were assessed, after rejecting 4,889. The reviewers acknowledged that the problems with the evidence base remained the same as it was in 2003 and 2005; namely, the studies failed to meet valid scientific standards:

“There was a lack of adequate description of exposure (vaccine content and schedules) in all cohort studies. Another recurring problem was the failure of any study to provide descriptions of all outcomes monitored. A lack of clarity in reporting and systematic bias made comparability across studies and quantitative synthesis of data impossible.”

“The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate… The methodological quality of many of the included studies made it difficult to generalize their results.”

The Cochrane reviewers determined that the measles component is 95% effective after one dose. That determination is challenged by extensive reviews by scientists at the Mayo Clinic that focused on the immunogenicity and effectiveness of the MMR vaccine in preventing measles (2007, 2015, 2017).[100]

The Mayo Clinic researchers note that population-based studies have revealed 2-10% measles vaccine failure even after two vaccine doses.

“…in countries with high measles vaccine coverage, outbreaks have revealed measles vaccine failure among individuals previously vaccinated with two doses of measles-containing vaccine… It was anticipated that a two-dose MMR vaccination program would lead to substantial reductions in measles morbidity and measles elimination; however, various studies have approximated that 2–10% of individuals vaccinated with two MMR doses may not develop or sustain protective measles humoral immunity, allowing a gradual accumulation of individuals susceptible to infection and subsequently, the occurrence of viral outbreaks.”

The Mayo Clinic researchers also note that:

“current technological advances may indeed serve to better identify specific biomarkers of vaccine immunogenicity, and/or any potential adverse reactions presented in response to one or several group(s) of vaccines.” (Variability in Humoral Immunity to Measles Vaccine: New Developments, 2015)

The Cochrane review assessed the mumps component of the MMR as only (69% — 81%) effective using the Jeryl Lynn mumps strain, and only (70% –75%) effective in the Urabe strain.

“The highest risk of association with aseptic meningitis was observed within the third week after immunisation with Urabe-containing MMRwhereas administration of the vaccine containing Moraten, Jeryl Lynn, Wistar RA, RIT 4385 strains is associated with [a significant risk of] febrile convulsion in children aged below five years.”

Given the serious nature of the acknowledged adverse effects associated with the mumps component in the MMR – i.e., meningitis and convulsions – coupled with the vaccine’s low level of effectiveness, and the poor quality – “largely inadequate”—studies reviewed, the Cochrane reviewers’ “conclusion” is unsupported by the evidence in their review.

Cochrane reviewers are not free of competing interests. While Dr. Jefferson’s role as “a consultant for a legal team advising MMR manufacturers” is duly disclosed, and his copious consulting work on behalf of numerous pharma companies is elsewhere disclosed,[101] nevertheless, it raises the issue of the uneven and unfair playing field, if only because (I strongly suspect that) a consultant to the legal team representing litigants against MMR producers would ipso facto be unacceptable as a reviewer by the Cochrane.

In 2016, the BMJ feature, “Head to Head” posed the question: Is the Timing of Recommended Childhood Vaccines Evidence-Based? [102] Prominent Cochrane Collaboration reviewers, Dr. Jefferson and Dr. Demicheli, who have examined the quality of vaccine safety / efficacy data responded as follows:

the answer to the question is a simple NO. No field trials have compared the effectiveness and harms of all vaccines used according to various schedules listed in the recent BMJ infographic… The full evidence base to make such complex decisions as the timing of each vaccination, in conjunction with developmental issues and the effect each vaccine has on the response to the others, is seldom fully available when vaccination schedules are devised.”

because detailed reports for most clinical trials of vaccines are not available, and have not been independently reviewed, we cannot be certain of vaccines’ harms profiles. [emphasis added]

The evidence base used in designing schedules is incomplete… We should start by carrying out a more accurate assessment of the magnitude of disease threats. Those vaccines not targeting impending or credible threats should then be phased out or delayed.”