Cochrane Board Expels Critic of Group's HPV Vaccine Review

Zosia Chustecka

September 17, 2018

The director of the Nordic Cochrane Centre at the Rigshospitalet, Copenhagen, Denmark, has been expelled from membership of the Governing Board of the Cochrane Collaboration, a position to which he was elected in early 2017.

The move comes weeks after Peter Gøtzsche, MD, DrMedSci, MSc, and colleagues harshly criticized a Cochrane review of the human papillomavirus (HPV) vaccine, describing it as incomplete and biased.

After his expulsion, four other members of the governing board resigned — Gerald Gartlehner, David Hammerstein Mintz, Joerg Meerpohl, and Nancy Santesso — the Cochrane Collaboration Governing Board announced on September 15.

The shake-up comes at a rather awkward moment, as the announcement was made just as a large international meeting of the organization was unfolding. The 25th Cochrane Colloquium is taking place September 16-18 in Edinburgh, Scotland, with 1300 participants from 57 countries.  

Gøtzsche has been described as "one of the founding fathers" of Cochrane, back in 1993, and has appeared as an author on 17 Cochrane reviews. He was elected to the Governing Board of the Cochrane Collaboration in early 2017.  

Accused of Causing "Disrepute"

"No clear reasoned justification has been given for my expulsion aside from accusing me of causing 'disrepute' for the organization," Gøtzsche writes in a letter dated September 14.

"In just 24 hours the Cochrane Governing Board of thirteen members has lost five of its members, four of which are centre directors and key members of the organization in different countries," he writes.

The Cochrane Collaboration has entered an unchartered territory of crisis. Dr Peter Gøtzsche

"As a result, the Cochrane Collaboration has entered an unchartered territory of crisis and lack of strategic direction."

In the three-page letter, Gøtzsche gives his version of what led to his expulsion.

The Cochrane Collaboration is "a scientific, grass-roots organization whose survival depends entirely on unpaid contributions from tens of thousands of volunteers and substantial governmental support throughout the world," he explains.

"We make a substantial contribution to people's understanding and interpretation of scientific evidence on the benefits and harms of medical interventions, devices and procedures that impact the population," he writes.

"Our work informs government legislation globally, it influences medical guidelines and drug approval agencies. Therefore, the integrity of the Cochrane Collaboration is paramount. We pride ourselves on being global providers of 'trusted evidence' on a foundation of values such as openness, transparency and collaboration.

"However, in recent years Cochrane has significantly shifted more to a business — a profit-driven approach," he writes. "Even though it is a not-for-profit charity, our 'brand' and 'product' strategies are taking priority over getting out independent, ethical and socially responsible scientific results.

"Despite our clear policies to the contrary, my centre, and others, have been confronted with attempts at scientific censorship, rather than the promotion of pluralistic, open scientific debate about the merits of concrete Cochrane reviews of the benefits and harms of health care interventions," he writes.

"This is not a personal question," Gøtzsche writes. "It is a highly political, scientific and moral issue about the future of Cochrane.

"What is at stake is the ability of producing credible and trustworthy medical evidence that our society values and needs," he comments.

"As most people know, much of my work is not very favorable to the financial interests of the pharmaceutical industry. Because of this Cochrane has faced pressure, criticism and complaints," he writes. "My expulsion is one of the results of these campaigns."

Recent Cochrane Review of HPV Vaccine

Gøtzsche has in the past been an outspoken critic of mammography screening for breast cancer, arguing that the benefits are oversold and that potential harms are underplayed.

He has also argued against the widespread use of psychotropic drugs, saying that they are immensely harmful in the long term and provide little benefit.

In recent years, however, he has spoken out against scientific reviews of the HPV vaccine.

In 2016, his center filed a complaint against the European Medicines Agency (EMA) over its handling of safety issues concerning HPV vaccines.

The EMA had looked at the safety issue last year after a request from Denmark, where physicians had documented in the medical literature case reports of chronic symptoms in girls who had received HPV vaccines. After conducting a review of HPV vaccine safety, the EMA concluded that "evidence does not support that vaccines cause" the chronic symptoms. However, several European researchers questioned the review process, and the Nordic Cochrane group, headed by Gøtzsche, lodged an official  complaint, arguing that the official EMA report is flawed.

More recently, Gøtzsche was coauthor of an article that harshly criticized a Cochrane review of HPV vaccines.

That Cochrane review, published online on May 9, 2018, concluded: "There is high‐certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and women who are vaccinated between 15 and 26 years of age. The protection is lower when a part of the population is already infected with HPV. Longer‐term follow‐up is needed to assess the impact on cervical cancer."

The authors also stated that HPV vaccines "do not increase the risk of serious adverse events, miscarriage or pregnancy termination. There are limited data from trials on the effect of vaccines on deaths, stillbirth and babies born with malformations."

Gøtzsche and two coauthors argue that this Cochrane review was "incomplete and ignored important evidence of bias" in an article published online July 27 in BMJ Evidence Medicine.

His coauthors, Lars Jørgensen and Tom Jefferson, are colleagues from the Nordic Cochrane Center in Copenhagen. They also both work at the Center for Evidence Based Medicine, University of Oxford, United Kingdom.

The review "missed nearly half of the eligible trials...[and] was influenced by reporting bias and biased trial designs," they write.

The trio had harsh criticism on many issues: all of the trials that were included in the review were sponsored by industry; the trials used composite surrogate outcomes for cervical cancer; and none of the trials used a placebo as a comparator. (They used active comparators, which "probably increased the occurrence of harms in the comparator groups and thereby masked harms caused by the HPV vaccine," they comment.) In addition, the review "incompletely assessed serious and systemic adverse events" and "did not assess HPV vaccine-related safety signals."

In their conclusion, the three authors point out that "part of the Cochrane Collaboration's motto is 'Trusted evidence.'

"We do not find the Cochrane HPV vaccine review to be 'Trusted evidence,' as it was influenced by reporting bias and biased trial designs," they write. "We believe that the Cochrane review does not meet the standards for Cochrane reviews or the needs of the citizens or healthcare providers that consult Cochrane reviews to make 'Informed decisions,' which also is part of Cochrane's motto."

Began As a " Simmering Personality Clash"

More insight into what happened comes from a blog post entitled "Cochrane — A Sinking Ship?" that was published online September 16 in BMJ Evidence Medicine.

It was written by Maryanne Demasi, PhD, a researcher working with Gøtzsche at the Nordic Cochrane Center, who says she "was present in Edinburgh at the time of the meeting, but not present in the discussion room."

What began as "a simmering personality clash...[has] boiled over into a spectacular war of words, where the underlying issues of Cochrane have bubbled to the surface, with many insiders predicting the beginning of the end of Cochrane," Demasi comments.

The initial clash was between Gøtzsche and Mark Wilson, chief executive officer of the Cochrane Collaboration.

The original dispute was over the fact that Gøtzsche had used the Cochrane letterhead when he filed the official complaint to the EMA about its safety review of the HPV vaccine.

But it was the recent paper with its harsh criticism of the Cochrane review of HPV vaccines that really added fuel to the flames.

Demasi writes that the Cochrane leadership accused Gøtzsche's team of "causing reputational damage to the organization, fueling anti-vaxxers, and risking 'the lives of millions of women worldwide by affecting vaccine uptake rates,' " according to a complaint by the editor of the Cochrane group that published the HPV review.

Gøtzsche stood by his group's paper, sparking an urgent internal review at Cochrane, she writes. 

Then on September 3, Cochrane's editor in chief, David Tovey, and his deputy, Karla Soares-Weiser, issued a  statement claiming  that the criticisms of the HPV vaccine review had been "substantially overstated" and "inaccurate and sensationalized."

In reaction, Gøtzsche said, "People all over the world have interpreted the Cochrane editors' criticism of us as being the 'final word'...the editors did not even address our most important concern that the harms of the HPV vaccine had been greatly under-reported and that much of the clinical data is not included in the review."

Shock at Expulsion

Several board members were shocked over Gøtzsche's expulsion from the board, Demasi writes. The decision was made at the September 13 board meeting, after he was asked to leave the room; the remaining 12 board members voted: six members for him to be removed, five for him to remain, and one abstained.

The four board members who resigned the next day in protest outline their position in another blog post published online September 15 in BMJ Evidence Medicine. "We consider the Board's use of its authority to expel Peter from Cochrane to be disproportionate," they write.

"The general public, consumers, students, and researchers involved in Cochrane value the plurality of opinions, views, and perspectives Cochrane has worked hard to give voice to since its foundation," they continue. "We believe that the expulsion of inconvenient members from the Collaboration goes against Cochrane ethos and neither reflects its founding spirit nor promotes the Collaboration's best interests. We are concerned that these actions might cause great damage to the reputation of the Collaboration."

"Extraordinary Times"

"These are extraordinary times and we find ourselves in an extraordinary situation," the Cochrane Governing Board comments in a statement released on September 17.

"This is about the behavior of one individual," it states, without actually naming the individual, but adding that there was "repeated bad behavior over many years."

It goes on to note that the meeting on September 13 divided the Board.

"Subsequently, four Board members chose to resign and have actively disseminated an incomplete and misleading account of events. At the same time, others contributed to a public and media campaign of misinformation," it states.

"We now want to put before you as much evidence as we can, so you know what is going on," the Board says in the statement, which is addressed to Cochrane members.

Using bold type for emphasis, it states that: "This Board decision is not about freedom of speech. It is not about scientific debate. It is not about tolerance of dissent. It is not about someone being unable to criticize a Cochrane Review."

"It is about a long-term pattern of behavior that we say is totally, and utterly, at variance with the principles and governance of the Cochrane Collaboration," it explains.  

The Board had received several complaints about the individual, the most recent received in March, but the earliest of which dates back to 2003.

Many of these complaints have "been dealt with over the years," the Board writes. "Many disputes have arisen. Formal letters have been exchanged. Promises have been made. And broken. Some disputes have been resolved, some have not."

"It was clear to the co-chairs that the Board had to reach a decision about these most recent complaints. The individual then made serious allegations against one of the Senior Management Team and shared those with the Board."

An independent review conducted by a senior independent lawyer (QC) "completely exonerated the member of the Senior Management Team but did not exonerate the other individual."

In the meantime, while this review was ongoing, the individual co-authored a paper in BMJ Evidence Medicine, which "has proved controversial" and sparked "a number of letters of complaint to the Board."

The statement emphasizes the timing of these events. "In order to avoid any misunderstanding, the Board want you to be clear that this was a matter that arrived very late in this whole process."

The result of this process was the vote at the September 13 board meeting to terminate the membership of the Cochrane collaboration for the individual in question. 

The individual has been invited to make a written response within 7 days.

"At this point in time, this person remains a member of the Cochrane Collaboration. We are waiting for the process to be completed," the Board notes.

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