The Lancet Says It Never Claimed the Study Proved a Link Between the Vaccine and Autism

By Deborah Brauser in Medscape Medical News

January 20, 2011 — The medical establishment “closed ranks” to protect Andrew Wakefield, the researcher whose 1998 study linked the measles-mumps-rubella (MMR) vaccine to autism, according to a third and final article of a special investigative series published online January 18 in the BMJ.

UK journalist Brian Deer alleges that when he approached The Lancet editor Richard Horton in 2004 with concerns about potential issues of research fraud, conflicts of interest, and unethical treatment of children discovered while researching an article about the study for the Sunday Times, The Lancet failed to ensure that a formal, independent investigation was conducted.

In his most recent BMJ article, Mr. Deer writes that failure to conduct such an investigation and the series of denials issued by Mr. Wakefield, his coauthors, and the Royal Free Hospital led to the public being “misled for 6 years” about the credibility of the article before The Lancet finally retracted it in February 2010.

“That’s really the nubbin of this story — the failing of The Lancet and the Royal Free to investigate adequately when questions were raised back in 2004,” Fiona Godlee, MD, BMJ editor-in-chief, told Medscape Medical News.

“Although it was discredited in some ways, this damaging article still sat in the literature for 6 years. And the GMC [General Medical Council] went through this incredibly lengthy and expensive investigation, which potentially might have been avoided to some extent,” added Dr. Godlee.

The Lancet Responds

Although it was discredited in some ways, this damaging article still sat in the literature for 6 years. And the GMC went through this incredibly lengthy and expensive investigation, which potentially might have been avoided to some extent.

In a statement, The Lancet disputes Mr. Deer’s “portrayal of events” in 2004. “We strongly disagree with his assessment and firmly stand by our actions and decisions,” they write.

The Lancet also notes that the original 1998 article did not assert that MMR caused autism and that it was at a separate press conference where Mr. Wakefield suggested this association.

“It is the role of medical journals to foster debate, even disagreeable debate, and we took this role seriously and responsibly,” says The Lancet release.

What none of us knew at the time, including many of his coauthors, was the extraordinary part that Andrew Wakefield had been playing in this affair and the part that he was about to play. At no point did we actively defend [his] public statements about the link between MMR and autism.”

What none of us knew at the time, including many of his co-authors, was the extraordinary part that Andrew Wakefield had been playing in this affair and the part that he was about to play. At no point did we actively defend [his] public statements about the link between MMR and autism.

No matter how the events unfolded, Dr. Godlee writes in her Editor’s Choice editorial this week that a new process is needed in the United Kingdom to ensure research integrity. Although the UK Research Integrity Office was established in 2006, it lacks mandatory powers and is running out of funding.

“Other countries have models we could adapt, [such as] the US Office of Research Integrity, which has a mandate to oversee institutional investigations of publicly funded research,” she writes.

“In America, you’ve got a process set up that could possibly be improved, but in Britain we haven’t got a good set-up at all. I think this case should be used as a springboard for really improving and raising our game on that score,” she added.

In the first article in the BMJ series, as reported by Medscape Medical News, Mr. Deer wrote that the investigators altered and falsified medical records of the 12 children involved.

In the second article, reported last week, Mr. Deer “followed the money.” He found that while the first study patient was still in the hospital, Mr. Wakefield met with managers from the Royal Free Medical School to discuss forming a joint business.

In this last piece, Mr. Deer writes that he first approached The Lancet in assumed confidence on advice from his editor at the Sunday Times for comment and “to be sure we were getting it right.”

False Reassurance

We were falsely reassured. We were told by authoritative sources…that an investigation had been done and cleared Wakefield of most charges. But as shown by documents obtained under the Freedom of Information Act, there was no proper investigation, merely a 48-hour ‘scramble’ to protect reputations and discredit the story.

According to the BMJ article, within 48 hours of this meeting, an editor from The Lancet met with the study’s 3 senior authors and the journal published “a 5000-word avalanche of denials in statements unretracted to this day.”

Further statements reported that an investigation was undertaken by the Royal Free Hospital that “cleared Wakefield of wrongdoing.”

However, according to documents obtained under the Freedom of Information Act, the investigation was actually conducted internally by the coauthors themselves. Both the Royal Free Hospital and Medical School have now confirmed that no formal investigation was performed, no physicians were ever interviewed, and no documents generated.

“We were falsely reassured,” writes Dr. Godlee. “We were told by authoritative sources…that an investigation had been done and cleared Wakefield of most charges. But as shown by documents obtained under the Freedom of Information Act, there was no proper investigation, merely a 48-hour ‘scramble’ to protect reputations and discredit the story.”

The Lancet statement also says that it followed the guidelines by the Committee on Publication Ethics when speaking to the study authors after Mr. Deer brought his concerns to them in 2004 and published a partial retraction by 10 of the study’s coauthors soon after.

Major Flaws in Peer Review Process

According to the BMJ article, the GMC became involved soon after the allegations were made, but it took the panel 6 years to substantiate the allegations.

“Were it not for the GMC case, which cost a rumored 6 million pounds, the fraud by which Wakefield concocted fear of MMR would forever have been denied and covered up,” writes Mr. Deer.

“It is hard to escape the conclusion that this represents institutional and editorial misconduct, and its impact has been substantial. The international damage might have been lessened by earlier definitive action,” adds Dr. Godlee.

“This case reveals major flaws in pre- and postpublication peer review,” said Dr. Godlee in a release. “Allegations of research misconduct must be independently investigated in the public interest. But it’s still too easy for institutions to avoid external scrutiny, and editors can fail to adequately distance themselves from work they have published and then defended.”

She noted that “this is where coauthors become crucially important. If coauthors are going to sign their names to a paper, I think they need to have real knowledge and understanding of the entire study.”

Dr. Godlee added that “it was interesting” that the Wakefield study had case reports on just 12 children but had 13 authors. “One would think it would be difficult to be fraudulent with so many coauthors, but he’s obviously a person who is very compelling and persuasive and managed to achieve this without them being alerted to it.”

Need for Healthy Skepticism

In an accompanying article, clinicians from Seattle, Washington, write that there is an urgent need to fix a research system that failed to protect its subjects and the public from the consequences of fraudulent science.

”So much has been written about Wakefield himself, but we felt that, especially in light of Deer’s articles, there were a lot of unindicted coconspirators here,” Douglas J. Opel, MD, MPH, acting assistant professor at the Treuman Katz Center for Pediatric Bioethics at Seattle Children’s Research Institute, Washington, told Medscape Medical News.

“I think it’s important…to look into and investigate why these existing safeguards that are meant to protect research subjects didn’t do their job. Wakefield was able to circumvent them and conduct unethical and fraudulent research. We need to understand what those defects are, fix them, and prevent situations like this from happening again,” added Dr. Opel.

The editorialists offer several suggestions for preventing future “research adverse events” including the following:

• Empower everyone in research to raise questions throughout the process;
• Train research leaders to manage inquiries once raised;
• Not allow journal editors to “take the word” of researchers after allegations are made against them; and
• Train research leaders to recognize that they may have conflicts of interest in looking into allegations.

“We perhaps need a paradigm shift in the research world. We need to look to what we’re doing in the clinical world with respect to quality improvement and patient safety and determine whether some of those can be applied to the research realm to protect human subjects,” said Dr. Opel.

“We…need to rethink and reform our customs and culture. The disastrous impact that Wakefield’s study has had on vaccine coverage, recrudescence of disease, public trust, and, most of all, science requires that we do so in haste,” write the editorial authors.

Dr. Godlee added that when it comes to medical journals, clinicians should also maintain a healthy skepticism.

“We work hard to make sure that what we publish is accurate, and I’m sure the same is true with The Lancet. One is aware that clinicians are going to be reading this and using the information to treat and advise their patients. Yes, there can be inaccuracies, and we know that there will be fraud. But how often that happens is almost impossible to judge,” she said.

“So physicians need to, one hopes, not be cynical but absolutely question. The whole scientific enterprise is organized skepticism, where we all are meant to look at what’s put in front of us and submit it to a process of questioning internally in terms of whether this is valid and relevant,” she concluded.

Mr. Deer’s original investigation was funded by the Sunday Times of London and the Channel 4 television network. The current articles were funded by the BMJ. He reported receiving no other funding except for legal costs from the Medical Protection Society on behalf of Mr. Wakefield. The editorial authors have disclosed no relevant financial relationships.

BMJ. Article and editorial published online January 18, 2011.

BMJ. Editor’s Choice published online January 19, 2011.