by Keith Syverson

This month, The Lancet retracted a 1998 study conducted by Andrew Wakefield that demonstrated a connection between the MMR vaccine and autism.  The Lancet made the retraction in response to the findings of a UK General Medical Council’s Fitness to Practice Panel, which found that Wakefield falsely claimed that the study participants were referred by routine methods and that the investigations were approved by local ethics committees.  The Lancet retraction reignited the debate over whether vaccines cause autism and invites a brief history of the Wakefield paper and a discussion on the more recent debate over the connection between mitochondrial disorders, autism, and vaccines.

In 2004, The Lancet published results of its own investigation of Wakefield's alleged professional misconduct concerning the 1998 study.  The editors reviewed all available documentary evidence and interviewed the study's authors to determine the validity of six claims of misconduct: (1)that the study falsely claimed it received ethics approval; (2)that the study was completed under the ethics approval of an entirely different study; (3) that the children involved were invited to participate directly by Wakefield and his co-authors, rather than through outside referrals; (4) the children from the study were also part of a Legal Aid Board funded project led by Dr. Wakefield with the goals to investigate the "grounds for pursuing a multi-party legal action on behalf of parents allegedly vaccine-damaged children;" (5) that the results of the study were passed to lawyers to justify the legal action; and (6) that Wakefield received £55,000 from the Legal Aid Board to conduct the study and that, "since there was a substantial overlap of children in both the Legal Aid Board funded pilot project and the Lancet paper, this was a financial conflict of interest that should have been declared to the editors and was not."

The editors of The Lancet found that the evidence presented to them did not support allegations 1, 2, or 3.  However, they found that the information in allegations 4-6 "would have been material to [their] decision-making about the paper’s suitability, credibility, and validity for publication."  Although at that time the editors did not suggest that the paper should be retracted, they repeatedly referred to the conflict of interests as regrettable.  The information regarding the funding and the possibility of pending legal action "would have provided important information to editors and peer reviewers about the context in which this work was taking place–a context that would have been vital in making a final decision about publication."  Although disclosure would have been proper, the editors argued that all research papers published in peer reviewed journals must be concise and as a result, they often leave out aspects of the protocol.  As a result, the editors found that there was not "any intention to conceal information or deceive editors, reviewers, or readers about the ethical justification for this work and the nature of patient referral."

On January 28, 2010, the General Medical Counsel, a European professional conduct review board, published its findings regarding the alleged unprofessional conduct of Wakefield and his co-authors.  The Fitness to Practice hearing heard evidence for 148 days over the course of two and a half years and deliberated for approximately 45 days.  The panel made several factual determinations in a quasi-legal setting where it found a fact or allegation proved only "if it is sure there is other corroborating evidence."  The GMC found that on several occasions Wakefield intentionally misrepresented the recruitment methods used to obtain the study participants.  Wakefield repeatedly said that the participants had come through referrals by "the standard route."  The board found these statements "dishonest and irresponsible" because Wakefield omitted necessary and relevant information.  Moreover, the referrals were not made via the standard route because several of the referrals were made "for investigation of the role played by the measles vaccination or the MMR vaccination into their developmental disorders" not for research on gastrointestinal symptoms as disclosed in the Lancet paper and to the ethics review board.

Ultimately, the GMC concluded a majority of the participants in the study were there without ethics committee approval and that Wakefield repeatedly made misrepresentations about study protocol study.   In addition to problems with recruiting the patients, the panel also reprimanded Wakefield for paying children at his son’s birthday party to donate blood used in the study.  The panel found that Wakefield "showed a callous disregard for the distress and pain that … the children involved might suffer" and that he "abused [his] position of trust as a medical practitioner."  Each of the more than 30 proved charges against Wakefield could potentially result in his losing the ability to practice medicine.  A hearing in April will determine whether "serious professional misconduct" was committed and what punishment Wakefield will receive.

Despite all the controversy and accusations of misconduct, Wakefield continues to maintain a devout following.  Audience members at the hearing burst out "Those doctors are not guilty of anything other than saving our children."  Moreover, parents of 8 of the 12 children in the study have expressed their support for Wakefield, stating that "we are appalled that these doctors have been the subject of this protracted enquiry in the absence of any complaint from any parent about any of the children who were reported in the Lancet paper."  Nonetheless, the allegations against Wakefield are serious. The findings that Wakefield intentionally misrepresented several aspects of the recruitment methods and continued outside the bounds of ethics committee approval justify retracting his paper.  Although parents of 8 of the 12 study participants indicated that they were not hurt or offended in any way by Wakefield's conduct, sanctioning the operation of research outside the bounds of ethics committee approval could have dangerous implications for future research.  This is particularly true because of a doctor's position of power over his patients.  Wakefield's misrepresentation of participant referrals and Wakefield's preexisting partnership with a legal community investigating connecting autism with vaccination raise serious questions about any bias of ulterior motives Wakefield may have had. 

The investigation into the Wakefield study is, more than anything else, evidence of the way that the scientific investigation between vaccine and autism has been politicized.  In various studies, Tufts University professor Sheldon Krimsky has found that, for one-third of the articles in top medical journals, the authors have a conflict of interest.  Researchers paid by the company that makes the drug they are supposedly investigating, for example, tend to find that the drugs work beneficially.  Many doctors prescribe heart medications, cholesterol-lowering drugs and other treatments that could have dramatic effects on people based on studies undertaken with a conflict of interest.  Yet these potentially tainted studies have not been retracted.  Why go after Wakefield?

The reason is that the stakes are so high in the vaccine context.  On the one hand, there is concern for the public health if children don't get vaccinated.  On the other there are financial concerns – the money companies could make for selling vaccines and the money that families could collect from the federal vaccine compensation fund if the could prove their child's autism was related to a vaccination.  There are also substantial implications for the development of prevention techniques or new treatments for autism.

In 1988, Congress established the Vaccine Injury Compensation Program, administered by be the federal government, to provide an efficient mechanism for compensating people if they are injured as a result of a vaccination.  Individuals who have been injured by vaccines can file a claim against the Department of Health and Humans services in the U.S. Court of Federal Claims detailing which vaccine caused the injury.  The injured person's complete medical records must also be provided.  To be awarded compensation, a person must either demonstrate an injury listed in a government provided table or show that "(1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a showing of a proximate temporal relationship between vaccination and injury."

The VICP has consistently rejected claims that certain vaccines can generally cause autism. However, in 2008 the VICP awarded the parents of Hannah Poling compensation because of a potential connection between the vaccines she received and the onset of autism.  The court found that Poling had a preexisting mitochondrial condition that was aggravated by the vaccinations she received.  Although the Director of the Centers for Disease Co
ntrol and Prevention was quick to point out that "the government has made absolutely no statement indicating that vaccines are the cause of autism," other commentators have suggested that the decision opened the doors for further autism compensation.  A study published in the November 2008 edition of PloS, a peer reviewed scientific journal, highlights some of the difficulty in conclusively proving a link between autism and vaccination. 

A significant portion of children with autism experience "regression" which occurs when their condition substantially worsens and they develop new symptoms.  This often occurs around the same time that children receive multiple vaccinations.  The PloS study analyzed 25 children with autism who also have a specific mitochondrial disease.  The researchers, noting that as many as 7% of children with autism have some type of mitochondrial disorder, found that these children were slightly more likely to have regressive symptoms then average children with autism (40% vs. 33%).  Of the 40% who showed regressive symptoms, only one child (Hannah Poling) showed regressive symptoms that appeared to be as a result of vaccination.  The authors were careful to point out, however, that "[a]lthough there may have been a temporal relationship of the events in this case, such timing does not prove causation."  Moreover, "there may be no difference between the . . . stress of vaccinations and that of common childhood disease, which are known precipitants of mitochondrial regression."

The retraction of Wakefield's 1998 study brought the vaccine-autism debate back into the public eye.  Although it is impossible to know for certain if Wakefield's conflicts of interests altered the findings in his study, the GMC's findings cast considerable doubt on the motivations behind Wakefield's research.   Similar arguments can be made questioning the motivation of the GMC because of the prospect of immense profits from vaccinations.   Even the case of Hannah Poling, where the VICM compensated the Poling family because of the potential connection in her situation between autism and vaccination fails to provide conclusive evidence of a systematic link between autism and vaccination.   Subsequent studies like the PloS study discussed above have failed to provide conclusive evidence of a connection but instead remind the public that "timing does not prove causation."  Regardless of whether one chooses to believe the studies supporting a connection between autism and vaccination or other studies suggesting that there is not a link, the reader should always evaluate the results in the proper context.  Lastly, it is becoming increasingly clear that in order to make a definitive conclusion in either direction, large-population based studies are required.