MMR vaccine and autism: Difference between revisions

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A controversy surrounding the combined measles, mumps, and rubella (MMR) vaccine started with the 1998 publication of a fraudulent research paper in The Lancet linking the vaccine to colitis and autism spectrum disorders.^[1] The claims in the paper were widely reported,^[2] leading to a sharp drop in vaccination rates in the UK and Ireland and increases in the incidence of measles and mumps, resulting in deaths and serious permanent injuries.^[3][4] Following the initial claims in 1998, multiple large epidemiological studies were undertaken. Reviews of the evidence by the Centers for Disease Control and Prevention,^[5] the American Academy of Pediatrics, the Institute of Medicine of the US National Academy of Sciences,^[6] the UK National Health Service,^[7] and the Cochrane Library^[8] all found no link between the MMR vaccine and autism.

An investigation by journalist Brian Deer found that Andrew Wakefield, the author of the original research paper linking the vaccine to autism, had multiple undeclared conflicts of interest,^[9][10] had manipulated evidence,^[11] and had broken other ethical codes. The Lancet paper was partially retracted in 2004 and fully retracted in 2010, when Lancet's editor-in-chief Richard Horton described it as "utterly false" and said that the journal had been deceived.^[12] Wakefield was found guilty by the General Medical Council of serious professional misconduct in May 2010 and was struck off the Medical Register, meaning he could no longer practise as a doctor in the UK.^[13] In 2011, Deer provided further information on Wakefield's improper research practices to the British Medical Journal, which in a signed editorial described the original paper as fraudulent.^[14][15] The scientific consensus is that there is no link between the MMR vaccine and autism and that the vaccine's benefits greatly outweigh its risks.

Wakefield's paper was described as "perhaps, the most damaging medical hoax of the last 100 years".^[16] Physicians, medical journals, and editors^{[17][18][19][20][21]} have described Wakefield's actions as fraudulent and tied them to epidemics and deaths.^[22][23]

Before the autism-related controversy started in 1998, some concern had already arisen about the safety of the MMR vaccine due to side effects associated with the Urabe mumps strain, including rare adverse events of aseptic meningitis, a transient mild form of viral meningitis.^[24][25] A late-1980s trial in Britain of a form of the MMR vaccine containing the Urabe mumps strain produced three cases of probably associated febrile convulsions per 1,000 vaccinations. Concerns about adverse reactions to the vaccine were raised by American and Canadian authorities based on reports from Japan linking Urabe MMR with meningoencephalitis. Canadian authorities withdrew a Urabe-based vaccine in the late 1980s.^[26]

The UK National Health Service introduced an MMR vaccine using the Urabe mumps strain in 1988, replacing it entirely with the Jeryl Lynn strain in September 1992 following the identification of an unacceptable risk of aseptic meningitis 15–35 days after vaccination.^[27] With no such risk seen in vaccines using the Jeryl Lynn mumps strain,^[27][28] the UK NHS withdrew two of the three MMR vaccines then available (Immravax, made by Merieux UK, and Pluserix, made by SmithKline Beecham) in favor of Merck Sharp and Dohme's MMR II brand, based on the Jeryl Lynn strain.^[28] Although MMR administration did continue with MMR II, the MMR vaccination rate first began to fall after 1996, following claims by Wakefield that it was linked to Crohn's disease.^[29]

The Urabe strain remains in use in a number of countries; MMR with the Urabe strain is much cheaper to manufacture than with the Jeryl Lynn strain,^[30] and a strain with higher efficacy along with a somewhat higher rate of mild side effects may still have the advantage of reduced incidence of overall illness.^[28]

In the wake of the measles outbreaks, which occurred in England in 1992, and on the basis of analyses of seroepidemiological data combined with mathematical modeling, British Health authorities predicted a major resurgence of measles in school-age children. Two strategies were then examined: either to target vaccination at all children without a history of prior measles vaccination or to immunize all children irrespective of vaccination history.^[31] In November 1994, the latter option was chosen and a national measles and rubella vaccination campaign, described as "one of the most ambitious vaccination initiatives that Britain has undertaken" was commenced:^[32] within one month, 92% of the 7.1 million schoolchildren in England aged 5–16 years received measles and rubella (MR) vaccine.^[33]

In April 1994, Richard Barr,^[34] a solicitor, succeeded in winning legal aid for the pursuit of a class action lawsuit against the manufacturers of MMR vaccines under the UK Consumer Protection Act 1987. The class action case was aimed at Aventis Pasteur, SmithKline Beecham, and Merck, manufacturers respectively of Immravax, Pluserix-MMR and MMR II.^[35] This suit, based on a claim that MMR is a defective product and should not have been used, was the first big class action lawsuit funded by the Legal Aid Board (which became the Legal Services Commission, which in turn was replaced by the Legal Aid Agency) after its formation in 1988. Noticing two publications from Andrew Wakefield that explored the role of measles virus in Crohn's disease and inflammatory bowel disease,^[36][37] Barr contacted Wakefield for his expertise. According to Wakefield supporters, the two men first met on 6 January 1996.^[38] The Legal Services Commission halted proceedings in September 2003, citing a high probability of failure based on the medical evidence, bringing an end to the first case of research funding by the LSC.^[39]

In February 1998, a group led by Andrew Wakefield published a fraudulent paper in the respected British medical journal The Lancet, supported by a press conference at the Royal Free Hospital in London.^[40][41] This paper reported on twelve children with developmental disorders referred to the Royal Free Hospital. The parents or physicians of eight of these children were said to have linked the start of behavioral symptoms to MMR vaccination. The paper described a collection of bowel symptoms, endoscopy findings and biopsy findings that were said to be evidence of a possible novel syndrome that Wakefield would later call autistic enterocolitis, and recommended further study into the possible link between the condition and the MMR vaccine. The paper suggested that the connection between autism and the gastrointestinal pathologies was real, but said it did not prove an association between the MMR vaccine and autism.^[1]

At the press conference before the paper's publication, later criticized as "science by press conference",^[40] Wakefield said that he thought it prudent to use single vaccines instead of the MMR triple vaccine until this could be ruled out as an environmental trigger; parents of eight of the twelve children studied were said to have blamed the MMR vaccine, saying that symptoms of autism had set in within days of vaccination at approximately 14 months. Wakefield said, "I can't support the continued use of these three vaccines given in combination until this issue has been resolved."^[42] In a video news release issued by the hospital to broadcasters in advance of the press conference, he called for MMR to be "suspended in favour of the single vaccines".^[43] In a BBC interview Wakefield's mentor Roy Pounder, who was not a coauthor, "admitted the study was controversial". He added: "In hindsight it may be a better solution to give the vaccinations separately,... When the vaccinations were given individually there was no problem."^[44] These suggestions were not supported by Wakefield's coauthors nor by any scientific evidence.^[45]

The initial press coverage of the story was limited. The Guardian and the Independent reported it on their front pages, while the Daily Mail only gave the story a minor mention in the middle of the paper, and the Sun did not cover it.^[2]

The controversy began to gain momentum in 2001 and 2002, after Wakefield published papers suggesting that the immunisation programme was not safe. These were a review paper with no new evidence, published in a minor journal, and two papers on laboratory work that he said showed that measles virus had been found in tissue samples taken from children who had autism and bowel problems. There was wide media coverage including distressing anecdotal evidence from parents, and political coverage attacking the health service and government peaked with unmet demands that Prime minister Tony Blair reveal whether his infant son, Leo, had been given the vaccine. It was the biggest science story of 2002, with 1257 articles mostly written by non-expert commentators. In the period January to September 2002, 32% of the stories written about MMR mentioned Leo Blair, as opposed to only 25% that mentioned Wakefield. Less than a third of the stories mentioned the overwhelming evidence that MMR is safe.^[2] The paper, press conference and video sparked a major health scare in the United Kingdom. As a result of the scare, full confidence in MMR fell from 59% to 41% after publication of the Wakefield research. In 2001, 26% of family doctors felt the government had failed to prove there was no link between MMR and autism and bowel disease.^[46] In his book Bad Science, Ben Goldacre describes the MMR vaccine scare as one of the "three all-time classic bogus science stories" by the British newspapers (the other two are the Arpad Pusztai affair about genetically modified crops, and Chris Malyszewicz and the MRSA hoax).^[47]

Confidence in the MMR vaccine increased as it became clearer that Wakefield's claims were unsupported by scientific evidence. A 2003 survey of 366 family doctors in the UK reported that 77% of them would advise giving the MMR vaccine to a child with a close family history of autism, and that 3% of them thought that autism could sometimes be caused by the MMR vaccine.^[48] A similar survey in 2004 found that these percentages changed to 82% and at most 2%, respectively, and that confidence in MMR had been increasing over the previous two years.^[49]

A factor in the controversy is that only the combined vaccine is available through the UK National Health Service. As of 2010 there are no single vaccines for measles, mumps and rubella licensed for use in the UK.^[50] Prime minister Tony Blair gave support to the programme, arguing that the vaccine was safe enough for his own son, Leo,^[51] but refusing on privacy grounds to state whether Leo had received the vaccine; in contrast, the subsequent Prime Minister, Gordon Brown, explicitly confirmed that his son has been immunised.^[52] Cherie Blair confirmed that Leo had been given the MMR vaccination when promoting her autobiography.^[2][53]

Administration of the combined vaccine instead of separate vaccines decreases the risk of children catching the disease while waiting for full immunisation coverage.^[54] The combined vaccine's two injections results in less pain and distress to the child than the six injections required by separate vaccines, and the extra clinic visits required by separate vaccinations increases the likelihood of some being delayed or missed altogether;^[54][55] vaccination uptake significantly increased in the UK when MMR was introduced in 1988.^[54] Health professionals have heavily criticized media coverage of the controversy for triggering a decline in vaccination rates.^[56] There is no scientific basis for preferring separate vaccines, or for using any particular interval between separate vaccines.^[57]

John Walker-Smith, a coauthor of Wakefield's report and a supporter of the MMR vaccine, wrote in 2002 that epidemiology has shown that MMR is safe in most children, but observed that epidemiology is a blunt tool and studies can miss at-risk groups that have a real link between MMR and autism.^[58] However, if a rare subtype of autism were reliably identified by clinical or pathological characteristics, epidemiological research could address the question whether MMR causes that autism subtype.^[59] There is no scientific evidence that MMR causes damage to the infant immune system, and there is much evidence to the contrary.^[57]

In 2001, Berelowitz, one of the co-authors of the paper, said "I am certainly not aware of any convincing evidence for the hypothesis of a link between MMR and autism".^[60] The Canadian Paediatric Society,^[61] the Centers for Disease Control and Prevention,^[5] the Institute of Medicine of the National Academy of Sciences, ^[6] and the UK National Health Service^[7] have all concluded that there is no evidence of a link between the MMR vaccine and autism, and a 2011 journal article described the vaccine–autism connection as "the most damaging medical hoax of the last 100 years".^[16]

In February 2004, after a four-month investigation, reporter Brian Deer wrote in The Sunday Times of London that, prior to submitting his paper to The Lancet, Wakefield had received £55,000 from Legal Aid Board solicitors seeking evidence to use against vaccine manufacturers, that several of the parents quoted as saying that MMR had damaged their children were also litigants, and that Wakefield did not inform colleagues or medical authorities of the conflict of interest. When the editors of The Lancet learned about this, they said that based on Deer's evidence, Wakefield's paper should have never been published because its findings were "entirely flawed".^[9] Although Wakefield maintained that the legal aid funding was for a separate, unpublished study^[62] (a position later rejected by a panel of the UK General Medical Council), the editors of The Lancet judged that the funding source should have been disclosed to them.^[63] Richard Horton, the editor-in-chief, wrote, "It seems obvious now that had we appreciated the full context in which the work reported in the 1998 Lancet paper by Wakefield and colleagues was done, publication would not have taken place in the way that it did."^[64] Several of Wakefield's co-researchers also strongly criticized the lack of disclosure.^[9]

Deer continued his reporting in a Channel 4 Dispatches television documentary, MMR: What They Didn't Tell You, broadcast on 18 November 2004. This documentary alleged that Wakefield had applied for patents on a vaccine that was a rival of the MMR vaccine, and that he knew of test results from his own laboratory at the Royal Free Hospital that contradicted his own claims.^[10] Wakefield's patent application was also noted in Paul Offit's 2008 book, Autism's False Prophets.

In January 2005, Wakefield sued Channel 4, 20/20 Productions, and the investigative reporter Brian Deer, who presented the Dispatches programme. However, after two years of litigation, and the revelation of more than £400,000 in undisclosed payments by lawyers to Wakefield, he discontinued his action and paid all the defendants' costs.

In 2006, Deer reported in The Sunday Times that Wakefield had been paid £435,643, plus expenses, by British trial lawyers attempting to prove that the vaccine was dangerous, with the undisclosed payments beginning two years before the Lancet paper's publication.^[65] This funding came from the UK legal aid fund, a fund intended to provide legal services to the poor.^[42]

The Lancet and many other medical journals require papers to include the authors' conclusions about their research, known as the "interpretation". The summary of the 1998 Lancet paper ended as follows:

Interpretation We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.^[1]

In March 2004, immediately following the news of the conflict of interest allegations, ten of Wakefield's 12 coauthors retracted this interpretation,^[66] while insisting that the possibility of a distinctive gastrointestinal condition in children with autism merited further investigation.^[39] However, a separate study of children with gastrointestinal disturbances found no difference between those with autism spectrum disorders and those without, with respect to the presence of measles virus RNA in the bowel; it also found that gastrointestinal symptoms and the onset of autism were unrelated in time to the administration of MMR vaccine.^[67]

On 8 February 2009, Brian Deer reported in The Sunday Times that Wakefield had "fixed" results and "manipulated" patient data in his 1998 paper, creating the appearance of a link with autism.^[11] Wakefield denied these allegations,^[68] and even filed a complaint with the Press Complaints Commission (PCC)^[69] over this article on 13 March 2009. The complaint was expanded by a 20 March 2009 addendum by Wakefield's publicist.^[70] In July 2009, the PCC stated that it was staying any investigation regarding the Times article, pending the conclusion of the GMC investigation.^[71] In the event, Wakefield did not pursue his complaint, which Deer published with a statement that he and The Sunday Times rejected it as "false and disingenuous in all material respects", and that the action had been suspended by the PCC in February 2010.^[72]

The General Medical Council (GMC), which is responsible for licensing doctors and supervising medical ethics in the UK, investigated the affair.^[73] The GMC brought the case itself, not citing any specific complaints, claiming that an investigation was in the public interest. The then-secretary of state for health, John Reid, called for a GMC investigation, which Wakefield himself welcomed.^[74] During a debate in the House of Commons, on 15 Mar 2004, Dr. Evan Harris,^[75] a Liberal Democrat MP, called for a judicial inquiry into the ethical aspects of the case, even suggesting it might be conducted by the CPS.^[76] In June 2006 the GMC confirmed that they would hold a disciplinary hearing of Wakefield.

The GMC's Fitness to Practise Panel first met on 16 July 2007^[77] to consider the cases of Dr. Wakefield, Professor John Angus Walker-Smith, and Professor Simon Harry Murch.^[78] All faced charges of serious professional misconduct. The GMC examined, among other ethical points, whether Wakefield and his colleagues obtained the required approvals for the tests they performed on the children; the data-manipulation charges reported in the Times, which surfaced after the case was prepared, were not at question in the hearings.^[79] The GMC stressed that it would not be assessing the validity of competing scientific theories on MMR and autism. The General Medical Council alleged that the trio acted unethically and dishonestly in preparing the research into the MMR vaccine. They denied the allegations.^[80] The case proceeded in front of a GMC Fitness to Practise panel of three medical and two lay members.^[81]

On 28 January 2010, the GMC panel delivered its decision on the facts of the case: Wakefield was found to have acted "dishonestly and irresponsibly" and to have acted with "callous disregard" for the children involved in his study, conducting unnecessary and invasive tests.^[82][83] The panel found that the trial was improperly conducted without the approval of an independent ethics committee,^[84] and that Wakefield had multiple undeclared conflicts of interest.^[85]

In response to the GMC investigation and findings, the editors of The Lancet announced on 2 February 2010 that they "fully retract this paper from the published record".^[86]

The Hansard text for 16 March 2010 reported^[87] Lord McColl asking the Government whether it had plans to recover legal aid money paid to the experts in connection with the measles, mumps and rubella/measles and rubella vaccine litigation. Lord Bach, Ministry of Justice dismissed this possibility.

In an April 2010 report in The BMJ, Deer expanded on the laboratory aspects of his findings recounting how normal clinical histopathology results generated by the Royal Free Hospital were later changed in the medical school to abnormal results, published in The Lancet.^[88] Deer wrote an article in The BMJ casting doubt on the "autistic enterocolitis" that Wakefield claimed to have discovered.^[88] In the same edition, Deirdre Kelly, President of the European Society of Pediatric Gastroenterology and Nutrition and the Editor of the Journal of Pediatric Gastroenterology and Nutrition expressed some concern about The BMJ publishing this article while the GMC proceedings were underway.^[89]

On 24 May 2010, the GMC panel found Wakefield guilty of serious professional misconduct on four counts of dishonesty and 12 involving the abuse of developmentally challenged children, and ordered that he be struck off the medical register.^[90] John Walker-Smith was also found guilty of serious professional misconduct and struck off the medical register, but that decision was reversed on appeal to the High Court in 2012, because the GMC panel had failed to decide whether Walker-Smith actually thought he was doing research in the guise of clinical investigation and treatment. The High Court criticised "a number of" wrong conclusions by the disciplinary panel and its "inadequate and superficial reasoning".^[91] Simon Murch was found not guilty.^[90]

On 5 January 2011, The BMJ published the first of a series of articles by Brian Deer, detailing how Wakefield and his colleagues had faked some of the data behind the 1998 Lancet article. By looking at the records and interviewing the parents, Deer found that for all 12 children in the Wakefield study, diagnoses had been tweaked or dates changed to fit the article's conclusion.^[92] Continuing BMJ series on 11 January 2011,^[93] Deer said that based upon documents he obtained under Freedom of information legislation,^[94] Wakefield—in partnership with the father of one of the boys in the study—had planned to launch a venture on the back of an MMR vaccination scare that would profit from new medical tests and "litigation driven testing".^[95] The Washington Post reported that Deer said that Wakefield predicted he "could make more than $43 million a year from diagnostic kits" for the new condition, autistic enterocolitis.^[94] WebMD reported on Deer's BMJ report, saying that the $43 million predicted yearly profits would come from marketing kits for "diagnosing patients with autism" and "the initial market for the diagnostic will be litigation-driven testing of patients with AE [autistic enterocolitis, an unproven condition concocted by Wakefield] from both the UK and the USA".^[96] According to WebMD, the BMJ article also claimed that the venture would succeed in marketing products and developing a replacement vaccine if "public confidence in the MMR vaccine was damaged".^[96]

Observers have criticized the involvement of mass media in the controversy, what is known as 'science by press conference',^[40] alleging that the media provided Wakefield's study with more credibility than it deserved. A March 2007 paper in BMC Public Health by Shona Hilton, Mark Petticrew, and Kate Hunt postulated that media reports on Wakefield's study had "created the misleading impression that the evidence for the link with autism was as substantial as the evidence against".^[97] Earlier papers in Communication in Medicine and British Medical Journal concluded that media reports provided a misleading picture of the level of support for Wakefield's hypothesis.^{[98][99][100]}

A 2007 editorial in Australian Doctor complained that some journalists had continued to defend Wakefield's study even after The Lancet had published the retraction by 10 of the study's 12 original authors, but noted that it was an investigative journalist, Brian Deer, who had played a leading role in exposing weaknesses in the study.^[101] PRWeek noted that after Wakefield was removed from the general medical register for misconduct in May 2010, 62% of respondents to a poll regarding the MMR controversy stated they did not feel that the media conducted responsible reporting on health issues.^[102]

A New England Journal of Medicine article examining the history of antivaccinationists said that opposition to vaccines has existed since the 19th century, but "now the antivaccinationists' media of choice are typically television and the Internet, including its social media outlets, which are used to sway public opinion and distract attention from scientific evidence".^[22] The editorial characterized anti-vaccinationists as people who "tend toward complete mistrust of government and manufacturers, conspiratorial thinking, denialism, low cognitive complexity in thinking patterns, reasoning flaws, and a habit of substituting emotional anecdotes for data", including people who range from those "unable to understand and incorporate concepts of risk and probability into science-grounded decision making" and those "who use deliberate mistruths, intimidation, falsified data, and threats of violence".^[22]

In a January 2011 editorial in The American Spectator, Robert M. Goldberg contended that evidence from the scientific community of issues with Wakefield's research " ... were undermined because the media allowed Wakefield and his followers to discredit the findings just by saying so".^[103]

Seth Mnookin, author of The Panic Virus, also partly blames the media for presenting a false balance between scientific evidence and people's personal experiences: "Reporting fell into this 'on the one hand, on the other hand' fallacy, this notion that if you have two sides that are disagreeing, that means that you should present both of them with equal weight."^[104]

Fiona Godlee, editor of The BMJ, said in January 2011:

The original paper has received so much media attention, with such potential to damage public health, that it is hard to find a parallel in the history of medical science. Many other medical frauds have been exposed but usually more quickly after publication and on less important health issues.^[18]

Concerns have also been raised over the journal peer review system, which largely relies on trust among researchers,^[17] and the role of journalists reporting on scientific theories that they "are hardly in a position to question and comprehend".^[20] Neil Cameron, a historian who specializes in the history of science, writing for the Montreal Gazette, labeled the controversy a "failure of journalism" that resulted in unnecessary deaths, saying that: 1) The Lancet should not have published a study based on "statistically meaningless results" from only 12 cases; 2) the anti-vaccination crusade was continued by the satirical Private Eye magazine; and 3) a grapevine of worried parents and "nincompoop" celebrities fueled the widespread fears.^[105] The Gazette also reported that:

There is no guarantee that debunking the original study is going to sway all parents. Medical experts are going to have to work hard to try to undo the damage inflicted by what is apparently a rogue medical researcher whose work was inadequately vetted by a top-ranked international journal.^[106]

During the 1980s and 1990s, a number of lawsuits were brought against manufacturers of vaccines, alleging the vaccines had caused physical and mental disorders in children. While these lawsuits were unsuccessful, they did lead to a large jump in the costs of the MMR vaccine, and pharmaceutical companies sought legislative protections. In 1993, Merck KGaA became the only company willing to sell MMR vaccines in the United States and the United Kingdom.

In June 2012, a local court in Rimini, Italy, ruled that the MMR vaccination had caused autism in a 15-month-old boy. The court relied heavily on the discredited Lancet paper and largely ignored the scientific evidence presented to it. The decision was appealed.^[107] On 13 February 2015, the decision was overturned by a Court of Appeals in Bologna.^[108]

The MMR scare caused a low percentage of mumps vaccination (less than 30%), which resulted in outbreaks in Japan.^[109] There were up to 2002 measles-caused deaths in Japan while there were none in the UK, but the extra deaths were attributed to Japan's application of the vaccine at a later age. A spokesman for the Ministry of Health said that the discontinuation had no effect in measles, but also mentioning that there were more deaths by measles while MMR was being used.^[110] In 1994 the government dropped the vaccination requirement for measles and rubella due to the 1993 MMR scare.^[111]: 2 Japan is nowadays the only developed country with large measles epidemics. It has been called a "measles exporter" by the US Centers for Disease Control and Prevention.^[111] As another consequence of the scare, in 2003, 7 million schoolchildren had not been vaccinated against rubella.^[112]

Autism rates continued to rise in Japan after the discontinuation of the MMR vaccine, which disproves any large-scale effect of vaccination,^[113] and means that the withdrawal of MMR in other countries is unlikely to cause a reduction in autism cases.^[114] The Japanese government does not recognize any link between MMR and autism.^[110] By 2003 it was still trying to find a combined vaccine to replace MMR.^[115]

It was later discovered that some of the vaccines were administered after their expiry date and that the MMR compulsory vaccination was only retracted after the death of three children and more than 2000 reports of adverse effects.^[112] By 1993 the Japanese government had paid $160,000 in compensation to the families of each of the three dead children.^[112] Other parents received no compensation because the government said that it was unproven that the MMR vaccine had been the cause; they decided to sue the manufacturer instead of the government.^[112] The Osaka district court ruled on 13 March 2003 that the death of two children (among numerous other serious conditions) had been indeed caused by Japan's strain of Urabe MMR.^[116][117] In 2006, the Osaka High Court stated in another ruling that the state was responsible for failing to properly supervise a manufacturer of the measles-mumps-rubella vaccine, which caused severe side effects in children.^[118]

Commenced before the Civil Procedure Rules were promulgated, the MMR Litigation had its status as group litigation achieved by the then Lord Chief Justice's practice direction of 8 July 1999. On 8 June 2007, the High Court judge, Justice Keith, put an end to the group litigation because the withdrawal of legal aid by the legal services commission had made the pursuit of most of the claimants impossible. He ruled that all but two claims against pharmaceutical companies must be discontinued.^[119] The judge stressed that his ruling did not amount to a rejection of any of the claims that MMR had seriously damaged the children concerned.^[120]

A pressure group called JABS (Justice, Awareness, Basic Support) was established to represent families with children who, their parents said, were "vaccine-damaged". £15 million in public legal aid funding was spent on the litigation, of which £9.7 million went to solicitors and barristers, and £4.3 million to expert witnesses.^[121]

The omnibus autism proceeding (OAP)^[122] is a coordinated proceeding before the Office of Special Masters of the U.S. Court of Federal Claims—commonly called the vaccine court. It is structured to facilitate the handling of nearly 5000 vaccine petitions involving claims that children who have received certain vaccinations have developed autism. The Petitioners' Steering Committee have claimed that MMR vaccines can cause autism, possibly in combination with thiomersal-containing vaccines.^[123] In 2007 three test cases were presented to test the claims about the combination; these cases failed. The vaccine court ruled against the plaintiffs in all three cases, stating that the evidence presented did not validate their claims that vaccinations caused autism in these specific patients or in general.^[124]

In some cases, the plaintiffs' attorneys opted out of the Omnibus Autism Proceedings, which were concerned solely with autism, and issues concerned with bowel disorders; they argued their cases in the regular vaccine court.

On 30 July 2007, the family of Bailey Banks, a child with pervasive developmental delay, won its case versus the Department of Health and Human Services.^[125] In a case listed as relating to 'non-autistic developmental delay', Special Master Richard B. Abell ruled that the Banks had successfully demonstrated, "the MMR vaccine at issue actually caused the conditions from which Bailey suffered and continues to suffer." In his conclusion, he ruled that he was satisfied that MMR had caused a brain inflammation called acute disseminated encephalomyelitis (ADEM). He reached this conclusion because of two vaccine cases in 1994 and 2001, which had concluded, "ADEM can be caused by natural measles, mumps, and rubella infections, as well as by measles, mumps, and rubella vaccines."^[126]

In other cases, attorneys did not claim that vaccines caused autism; they sought compensation for encephalopathy, encephalitis, or seizure disorders.^[127]

The number of reported cases of autism increased dramatically in the 1990s and early 2000s. This increase is largely attributable to changes in diagnostic practices; it is not known how much, if any, growth came from real changes in autism's prevalence, and no causal connection to the MMR vaccine has been demonstrated.^[128]

In 2004, a meta review financed by the European Union assessed the evidence given in 120 other studies and considered unintended effects of the MMR vaccine, concluding that although the vaccine is associated with positive and negative side effects, a connection between MMR and autism was "unlikely".^[129] Also in 2004, a review article was published that concluded, "The evidence now is convincing that the measles–mumps–rubella vaccine does not cause autism or any particular subtypes of autistic spectrum disorder."^[130] A 2006 review of the literature regarding vaccines and autism found "[t]he bulk of the evidence suggests no causal relationship between the MMR vaccine and autism."^[131] A 2007 case study used the figure in Wakefield's 1999 letter to The Lancet alleging a temporal association between MMR vaccination and autism^[132] to illustrate how a graph can misrepresent its data, and gave advice to authors and publishers to avoid similar misrepresentations in the future.^[133] A 2007 review of independent studies performed after the publication of Wakefield et al.'s original report found that the studies provided compelling evidence against the hypothesis that MMR is associated with autism.^[134] A review of the work conducted in 2004 for UK court proceedings but not revealed until 2007 found that the polymerase chain reaction analysis essential to the Wakefield et al. results was fatally flawed due to contamination, and that it could not have possibly detected the measles that it was supposed to have detected.^[121] A 2009 review of studies on links between vaccines and autism discussed the MMR vaccine controversy as one of three main hypotheses that epidemiological and biological studies failed to support.^[135]

In 2012, the Cochrane Library published a review of dozens of scientific studies involving about 14,700,000 children, which found no credible evidence of an involvement of MMR with either autism or Crohn's disease. The authors stated "the design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate".^[8] A June 2014 meta-analysis involving more than 1.25 million children found "vaccinations are not associated with the development of autism or autism spectrum disorder. Furthermore, the components of the vaccines (thimerosal or mercury) or multiple vaccines (MMR) are not associated with the development of autism or autism spectrum disorder."^[136] In July 2014, a systematic review found "strong evidence that MMR vaccine is not associated with autism".^[137]

In spite of these assurances, other studies have supported a link between the MMR vaccine and autism, implicating brain autoimmunity^[138] and the presence of human fetal DNA fragments in the vaccine itself as responsible.^[139][140]

After the controversy began, the MMR vaccination compliance dropped sharply in the United Kingdom, from 92% in 1996 to 84% in 2002. In some parts of London, it was as low as 61% in 2003, far below the rate needed to avoid an epidemic of measles.^[141] By 2006 coverage for MMR in the UK at 24 months was 85%, lower than the about 94% coverage for other vaccines.^[3]

After vaccination rates dropped, the incidence of two of the three diseases increased greatly in the UK. In 1998 there were 56 confirmed cases of measles in the UK; in 2006 there were 449 in the first five months of the year, with the first death since 1992; cases occurred in inadequately vaccinated children.^[142] Mumps cases began rising in 1999 after years of very few cases, and by 2005 the United Kingdom was in a mumps epidemic with almost 5000 notifications in the first month of 2005 alone.^[143] The age group affected was too old to have received the routine MMR immunisations around the time the paper by Wakefield et al. was published, and too young to have contracted natural mumps as a child, and thus to achieve a herd immunity effect. With the decline in mumps that followed the introduction of the MMR vaccine, these individuals had not been exposed to the disease, but still had no immunity, either natural or vaccine induced. Therefore, as immunisation rates declined following the controversy and the disease re-emerged, they were susceptible to infection.^[144][145] Measles and mumps cases continued in 2006, at incidence rates 13 and 37 times greater than respective 1998 levels.^[146] Two children were severely and permanently injured by measles encephalitis despite undergoing kidney transplantation in London.^[4]

Disease outbreaks also caused casualties in nearby countries. Three deaths and 1,500 cases were reported in the Irish outbreak of 2000, which occurred as a direct result of decreased vaccination rates following the MMR scare.^[4]

In 2008, for the first time in 14 years, measles was declared endemic in the UK, meaning that the disease was sustained within the population; this was caused by the preceding decade's low MMR vaccination rates, which created a population of susceptible children who could spread the disease.^[147] MMR vaccination rates for English children were unchanged in 2007–08 from the year before, at too low a level to prevent serious measles outbreaks.^[148] In May 2008, a British 17-year-old with an underlying immunodeficiency died of measles. In 2008 Europe also faced a measles epidemic, including large outbreaks in Austria, Italy, and Switzerland.^[147]

Following the January 2011 BMJ statements about Wakefield's fraud, Paul Offit, a pediatrician at Children's Hospital of Philadelphia and a "long-time critic of the dangers of the anti-vaccine movement", said, "that paper killed children",^{[149][150][151]} and Michael Smith of the University of Louisville, an "infectious diseases expert who has studied the autism controversy's effect on immunization rates", said "clearly, the results of this (Wakefield) study have had repercussions."^[152][153] In 2014, Laurie Garrett, senior fellow at the Council on Foreign Relations, blamed "Wakefieldism" for an increase in the number of unvaccinated children in countries such as Australia and New Zealand, saying, "Our data suggests that where Wakefield's message has caught on, measles follows."^[154]

The New England Journal of Medicine said that antivaccinationist activities resulted in a high cost to society, "including damage to individual and community well-being from outbreaks of previously controlled diseases, withdrawal of vaccine manufacturers from the market, compromising of national security (in the case of anthrax and smallpox vaccines), and lost productivity".^[22]

Costs to society from declining vaccination rates (in US dollars) were estimated by AOL's Daily Finance in 2011:^[155]

• A 2002–2003 outbreak of measles in Italy, "which led to the hospitalizations of more than 5,000 people, had a combined estimated cost between 17.6 million euros and 22.0 million euros".
• A 2004 outbreak of measles from "an unvaccinated student return[ing] from India in 2004 to Iowa was $142,452".
• A 2006 outbreak of mumps in Chicago, "caused by poorly immunized employees, cost the institution $262,788, or $29,199 per mumps case".
• A 2007 outbreak of mumps in Nova Scotia cost $3,511 per case.
• A 2008 outbreak of measles in San Diego, California cost $177,000, or $10,376 per case.

In the United States, Jenny McCarthy blamed vaccinations for her son Evan's disorders and leveraged her celebrity status to warn parents of a link between vaccines and autism. Evan's disorder began with seizures and his improvement occurred after the seizures were treated, symptoms experts have noted are more consistent with Landau–Kleffner syndrome, often misdiagnosed as autism.^[156] After the Lancet article was discredited, McCarthy continued to defend Wakefield.^[157] An article in Salon.com called McCarthy "a menace" for her continued position that vaccines are dangerous.^[158]

Bill Gates has reacted strongly to Wakefield and the work of anti-vaccination groups:

Dr. [Andrew] Wakefield has been shown to have used absolutely fraudulent data. He had a financial interest in some lawsuits, he created a fake paper, the journal allowed it to run. All the other studies were done, showed no connection whatsoever again and again and again. So it’s an absolute lie that has killed thousands of kids. Because the mothers who heard that lie, many of them didn’t have their kids take either pertussis or measles vaccine, and their children are dead today. And so the people who go and engage in those anti-vaccine efforts — you know, they, they kill children. It’s a very sad thing, because these vaccines are important.^[159]

• Folk epidemiology of autism
• History of science portal
• Medicine portal
• Viruses portal

• "The Vaccine War". Frontline. PBS. 27 April 2010. Retrieved 28 December 2013.
• Willingham, Emily; Helft, Laura (5 September 2014). "The Autism-Vaccine Myth with Timeline". PBS NOVA.
• DeNoon, Daniel J (6 January 2011). "Autism/MMR Vaccine Study Faked: FAQ". WebMD Health News. Retrieved 27 December 2013.
• "MMR research timeline". BBC News. 4 February 2008. Retrieved 27 December 2013.