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Scientific Advocacy and Biases of the Ideological and Industry Kinds

 

 

I think the main thing I learned – very painfully – in 20 years as a health consumer advocate, is that zealots always, always end up hurting patients. Because whatever it is that they are against, is not the same as being for patients, and it will, inevitably, betray us.

I tweeted that thought in a conversation about recent events in the Cochrane Collaboration. Why have I been using words like zealotry and extremism, even though they are emotive? Let’s dig into this. It’s a central issue of our polarized times generally, and for much of science. And it’s definitely critical in health sciences, and for the Collaboration right now.

Political scientist, Joel Olson, published a terrific essay in 2007 called “The freshness of fanaticism: the abolitionist defense of zealotry”. This articulates the case for the kind of zealotry from people who want to bring about social change, in a noble cause. Olson showed the critical role it played in the movement to abolish slavery in the US, and wrote:

Zealotry is an activity practiced not so much by disturbed temperaments as by collectivities working to transform relations of power by creating an “us” in struggle against a “them,” and by pressuring those in between to choose sides. Accordingly, zealotry is political activity, driven by an ardent devotion to a cause, which seeks to draw clear lines along a friends/enemies dichotomy in order to mobilize friends and moderates in the service of that cause…

If the essence of zealotry as political activity is a vigor to draw lines between friends and enemies, then its antithesis is not reason but moderation, for moderation denies that us/them distinctions are the defining characteristic of politics…[Z]ealotry as a political strategy typically implies a three-corner fight among friends, enemies, and the moderate middle…

Resource mobilization scholarship finds that disruptive tactics and the extremist wing of social movements can add new energy to a movement and spur bargaining between elites and moderate elements of the movement. This suggests that zealotry may emerge when a movement is deadlocked with elites.

Movements of critics of industry have mobilized to attack, and/or fight for the soul of, the Cochrane Collaboration, as one of their heroes faces expulsion from the organization from which he derived so much authority (Peter Gøtzsche).

The final straw for the organization, the board said, was “repeated, seriously bad behaviour”, including to staff. But Gøtzsche put it down to various causes which he champions – one of which is opposing industry influence: [PDF]

There is stronger and stronger resistance to say anything that could bother pharmaceutical industry interests…There has also been great resistance and stalling on the part of the central executive team to improving Cochrane’s conflict of interest policy. A year ago, I proposed that there should be no authors of Cochrane reviews to have financial conflicts of interests with companies related to the products considered in the reviews. This proposal was supported by other members of the Board, but the proposal has not progressed at all…

The collaborative aspect, social commitment, our independence from commercial interests and our mutual generosity are what people in Cochrane have always appreciated the most and have been our most cherished added-value…

As most people know, much of my work is not very favourable to the financial interests of the pharmaceutical industry. Because of this Cochrane has faced pressure, criticism and complaints. My expulsion is one of the results of these campaigns. What is at stake is the ability of producing credible and trustworthy medical evidence that our society values and needs.

Posts in parts of the movement for independence in drug evaluation and policy, like No Gracias and David Healy’s blog, suggest, I think, mutual importance of the relationship between at least part of the movement, and Gøtzsche/Cochrane – from whom they, too, have derived authority, and/or vested with high hopes.

Some are asking: how close to industry is too close for the Cochrane Collaboration? An important question. But there’s another that’s more relevant to the current situation: how close to industry-bashing and fear mongering about drugs and vaccines is too close? I think the resistance Gøtzsche experienced could be resistance to anti-industry bias and extremism, not support for pharmaceutical interests.

 

Cartoon about conflict of interest declaration

 

The problem that critics of industry influence seek to address is a serious one. Industry influence on health researchclinical practice guidelines, clinical practice, and patient information is pervasive, and acting in these interests is inimical to patient and public health. Industry bias can lead to unreliable research results. Yet, although I don’t think anyone has studied it, the reverse – anti-industry bias – could also render research unreliable, by the same mechanisms: spin and selectivity in questions, methods, and reporting, for example. Neither would be in patients’ interests.

In this post, I’ll use the terms pro- and anti-industry bias as shorthand for opposing ends of a complex and variegated spectrum, with what antagonists call “industry shills” at one end, and “industry-bashing” at the other. Both pro- and anti-industry bias lead to problems like motivated reasoning and fear mongering. Motivated reasoning, according to Lewandowsky, “refers to the discounting of information or evidence that challenges one’s prior beliefs accompanied by uncritical acceptance of anything that is attitude-consonant.” (Motivated reasoning was described by Ziva Kunda in 1990 [PDF].) Fear mongering is recognizable by frequent repetition of dangers (for the one side, of disease, for the other, of treatment), casting isolated incidents as trends, and misdirection.

There are differences of course, too: commercially motivated actions might tend to be more deliberate. Whereas ideology and solidarity to comrades blind you to your own errors of judgment, bias, and the harm you’re doing – I speak here from painful personal experience. Those differences, though, are irrelevant for patients when harm is being done.

Extremes of anti-industry bias can be harmful in other ways, too. For one, by casting a cloud of doubt around research results that challenge the ideology, or are favorable to a drug or vaccine that is a current punching bag. For another, it could make research so unfeasible, or so untrusted, that we’re stuck forever in the situation the Cochrane Collaboration sought to tackle in the first place. This is Iain Chalmers and Adrian Grant nailing it back in 1996 [PDF]:

For 70 years, the proponents of various drugs and drug cocktails have hurled disdainful abuse at each other from separate mountain tops, secure in the knowledge that no strong evidence existed that could undermine any one of their multitude of conflicting opinions.

 

Cartoon of an audience member thinking "He would say that, wouldn't he?"

 

This cartoon is from my reader’s guide to conflicts of interest in biomedicine. In it, I talk about non-financial conflicts of interest. A few months later, Lisa Bero and Quinn Grundy published a paper called, “Why having a (nonfinancial) interest is not a conflict”. First up, a disclosure: Bero is a friend. Conflict of interest (COI) has been a major area of scholarship and action for her. One of her claims to fame is being a co-author of The Cigarette Papers. Another is being chair of the Collaboration – at the time the current COI policy was finalized. Years of discussion and deliberation went into formulating Cochrane’s current policy, and its funding arbiter system.

I think bias from non-financial interests is a big deal. But Bero and Grundy convinced me that if you go past clearly justified and objective commercial interests as the only conflict, you open up a door where anything goes, everyone can be dismissed as being conflicted, and no one is trusted. We’re seeing that happen with the Cochrane HPV vaccine review (for example, in this string here).

We have a long way to go, though, to be able to recognize and reduce biases well – our own, first of all. Some forms of ideological bias are fairly easy to defend ourselves from. It’s the more sophisticated kind that can take us in – where there is so much that is reasonable and rigorous-sounding and true, that the omissions, spin, and other untrustworthy parts mixed in with them just slide past.

We have to increase our skills at detecting bias, error, and the signs of fear mongering – and remember that it’s dangerously easy to be led astray by someone else’s passionately held conviction.

 

 

Arthur Miller quote: "Nothing is as visionary or as blinding as moral indignation"
From Timebends: A Life

 

~~~~

 

I’m tracking key events and sources in the Cochrane situation at my personal website, hildabastian.net.

 

Disclosures: I led the development of a fact sheet and evaluation of evidence on HPV vaccine for consumers in 2009 for Germany’s national evidence agency, the Institute for Quality and Efficiency in Healthcare (IQWiG), where I was the head of the health information department. We based our advice on this 2007 systematic review including 6 trials with 40,323 women, and an assessment of those trials. The findings were similar to those of the 2018 Cochrane review. I have no financial or other professional conflicts of interest in relation to the HPV vaccine. My personal interest in understanding the evidence about the HPV vaccine is as a grandmother (of a boy and a girl).

I am one of the members of the founding group of the Cochrane Collaboration and was the coordinating editor of a Cochrane review group for 7 years, and coordinator of its Consumer Network for many years. I am no longer a member, although I occasionally contribute peer review on methods. I often butt heads with the Cochrane Collaboration (most recently as a co-signatory to this letter in the BMJ). I have butted heads on the subject of bias with authors of the Copenhagen critique.

26 September: In light of developments, some further disclosures which I did not realize may relate to this controversy and the theories around it, when I first started writing about the Cochrane HPV vaccine review. I was invited to speak at Evidence Live, and my participation was supported by the organizers, a partnership between the BMJ and the Centre for Evidence-Based Medicine (CEBM) at the University of Oxford’s Nuffield Department of Primary Care Health Sciences – the director of the CEBM is the editor of BMJ EBM. Between 2011 and 2018, I worked on PubMed projects at the National Center of Biotechnology Information (NCBI), which is part of the US National Institutes of Health. I am currently working towards a PhD on some factors affecting the validity of systematic reviews.

[Updates 26 September 2018]: As well as expanding my disclosures as the scope and criticisms related this controversy have widened, I added an explanation abut using the terms pro- and anti-industry bias that reads:

In this post, I’ll use the terms pro- and anti-industry bias as shorthand for opposing ends of a complex and variegated spectrum, with what antagonists call “industry shills” at one end, and “industry-bashing” at the other.

Rather than relying solely on the links in the original, I added these expansions on the terms motivated reasoning and fear mongering:

Motivated reasoning, according to Lewandowsky, “refers to the discounting of information or evidence that challenges one’s prior beliefs accompanied by uncritical acceptance of anything that is attitude-consonant.” (Motivated reasoning was described by Ziva Kunda in 1990 [PDF].) Fear mongering is recognizable by frequent repetition of dangers (for the one side, of disease, for the other, of treatment), casting isolated incidents as trends, and misdirection.

To make it more precise, I edited a sentence which originally read:

The final straw for the organization, the board said, was “repeated, seriously bad behaviour” to staff.

I shortened “Some of them are asking” to “Some are asking”.

I edited and added a link to an example in a sentence that originally read:

But Bero and Grundy convinced me that if you go past clearly justified and objective commercial interests, you open up a door where anything goes, everyone can be dismissed as having a conflict, and no one is trusted. We’re seeing that happen with the Cochrane HPV vaccine review.

[Update 28 September] I added links to an example of going to an extreme about who can be trusted in relation to scientific assessment of evidence of the HPV vaccine.

 

The cartoons are my own (CC BY-NC-ND license). (More cartoons at Statistically Funny and on Tumblr.)

 

Discussion
  1. I think non financial conflicts should be taken just a seriously as financial ones. The damage already done to ME patients by the PACE trial acknowledged to be scandalously poor science due to reputational and ideological interests is tragic. Yet Cochrane has given it a clean bill of health despite an unprecedented level of criticism. Just because it’s not a drug doesn’t mean patients can’t be seriously harmed by a treatment which powerful academics have built their careers on.

  2. Everything we see is a shadow cast by that which we do not see.

    The Cochrane logo itself has a long shadow cast over it by publication bias. Something we do not see. And another shadow cast by our locality bias – something less sinister but no less destructive.

    The issues of industry bias, corruption, and conflicts of interest cast long shadows over all of medicine, including Cochrane. Peter Gotzsche is trying to root out the shadows. Those who are responsible for the shadows do not want people looking for them.

    Our lives begin to end the day we become silent about things that matter.

    Of course, you are not responsible for the shadows. No, your position is much worse. That of the enabler. The enablers sat idly and watched injustice occur before their eyes – or closed their eyes to it. Or claimed to agree with the protestors, but not their methods. Without the enablers, the fire hoses would have had no water, the batons no force behind them.

    On the issue of industry takeover of healthcare, people like you are not the enemy. No, you are something worse. You are the friend who does nothing in the face of corruption. The one who complains about it and decides the remedy is to walk away, only to return to criticize those who stayed behind to fight. “If only you were not so confrontational!” they said to the freedom riders. “If only you were not so confrontational!” you say to Gotzsche.

    Your constant labeling of Gotzsche as “anti-industry” is an indictment of yourself, not him. You cast yourself as the neutral party, the fair arbiter in the whole ordeal. When you are really just an enabler. Gotzsche does not work from labels. He works from evidence. Sure, he calls researchers corrupt. And he calls them biased. But he does so based on evidence. His arguments do not rest on his assertions that people are biased or corrupt. Those assertions are merely explanations for why the research is biased. People do like to have human explanations. When research shows that non-blinded observers exaggerate effects by 37% on average, it seems entirely appropriate to explain the cause of this result: that the researchers are biased. When researchers are taking millions of dollars from companies and lying about it, while cranking out a new journal article every two weeks for years – to the benefit of those companies, only an enabler would refuse to call that corruption.

    Gotzsche has good reason for calling others biased and corrupt. What is your reason for calling him “anti-industry”? Blind faith based on disagreement. You have no reason. The only reasons you could give are tautologies. The label is slanderous and beneath a scientist. In contrast to Gotzsche, it is made to avoid engaging arguments.

    The link to your “painful personal experience” is a further indictment. Since that experience is admittedly personal, then it is not surprising you would fall for one of the most human of fallacies – the belief that everyone else must have the same shortcomings as yourself. That you were misguided in your activisim is not at all evidence that others are misguided in theirs. Though your mind may desperately want it to be so – such are the needs of the ego. And to use your foolishness as a tool against your ideological adversaries is quite a trick indeed. “I was foolish, and I realized it, causing me to switch my view. So they must be foolish, too!” That is itself foolish logic, on the same level as your “painful personal experience”. I guess you really cannot teach an old dog new tricks.

    Your discussion of non-financial conflicts of interest is an illogical, confused mess. You first quote Chalmers with a quote that is fine by itself, but seems to say nothing about this situation (A better, more recent quote might be this one: “Should the Cochrane logo be accompanied by a health warning?”). Gotzsche himself might hang your chosen quote on his wall. After all, he has spent a lifetime studying evidence quality. You say that Bero convinced you we cannot go beyond financial conflicts of interest because it never ends. That is a good point. But another issue is that many conflicts of interest are only useful at the beginning of an argument. When a researcher has financial conflicts and publishes a biased study, we can make an easy link to the conflict. But when a researcher like Gotzsche takes a position critical of the Cochrane HPV vaccine review, what is his conflict and how did it motivate his stance? Are you really going to argue he is “anti-industry” and therefore picked this one issue out of everything out there and chose to be critical because he dislikes industry? That is an odd claim to make – and insulting against a fellow scientist without a lot of evidence to the contrary. Of course, once he takes a stance, it is fair to say he has some bias in protecting his reputation when he defends his stance. Though that does not get you very far because at that point everyone on all sides shares the same potential bias. Are we going to argue that Gotzsche picked psychiatry because it is an easy target for his “anti-industry” crusade? That road leads to crazy town.

    Toward the end of this section you say:

    “But Bero and Grundy convinced me that if you go past clearly justified and objective commercial interests, you open up a door where anything goes, everyone can be dismissed as having a conflict, and no one is trusted. We’re seeing that happen with the Cochrane HPV vaccine review.”

    Do you realize that YOU are the one who is making that second sentence true? Gotzsche et al have pointed out the conflicts of the Cochrane reviewers, not to dismiss them, but to acknowledge the potential for bias and ask why Cochrane could not find non-conflicted reviewers. Having conflicted reviewers diminishes the quality and trust in the review. Surely, Cochrane can find someone else? On such an important review? And surely anyone who is not an enabler would agree those conflicts are problematic. So while Gotzsche et al are following the logic you claim to have accepted from Bero and Grundy, you are not. You are calling Gotzsche “anti-industry” and dismissing his arguments as biased. You are the one saying we cannot trust either side. You are practicing the very problem you claim to lament.

    In the end, we will remember not the words of our enemies, but the silence of our friends.

    If only it were just silence! Instead, we get active defenses of industry, posing as neutral observations. When those who would root out the insidious effects of industry are attacked as “anti-industry” and their silencing is applauded by self-styled “neutral” observers, corruption is enabled. If Gotzsche is gone, who will look for the corruption? You? From what I can see, you prefer to spend your time drawing cartoons. Your response to Cochrane’s drift seems to be to quit. Gotzsche’s response was to join the board and fight the drift. According to our best (admittedly sparse) evidence, psychiatric drugs kill more than 500,000 people over 65 each year in the US and Europe. While we would love to have more data so we can make a firmer claim (who is to blame for the lack of study?), it is clear these drugs kill an enormous number of people based on the quality data we do have and an examination of how these people die. One of the most frequent responses I hear to this data is that people cannot believe it because the scale is too large to be true. Indeed! We have reached a point where the medical harm is so great that people are unable to accept it can be happening. This is a disaster. The kind of disaster that Cochrane is supposed to prevent. And while you draw cartoons, Peter Gotzsche is trying to put an end to this madness. Gotzsche is helping people come off the drugs that are killing them. He is advocating for changes to policies that are forcing horrific “treatment” on people.

    In a Birmingham jail, a great man once wrote to critics who called his actions “unwise and untimely”. Just as that man determined the great moderates were the real stumbling block to freedom, I can see the supposed “neutral” observers in this fight against the corruption of medicine are the real block to truly evidence based medicine. Those neutral observers who prefer congeniality over truth, much like those who preferred order over justice. “I agree with you in the goal you seek, but I can’t agree with your methods” they say. History does not look kindly on the meek and silent in times of crisis. We remember those who fought against powerful forces. We remember the freedom riders. We remember Thomas Paine. With any luck, we will remember Peter Gotzsche as one of those willing to go against the grain and fight for truth in medical science.

  3. as Peter C Gøtzsche said in the press release (14 September 2018) :

    The Cochrane executive leadership almost always uses the commercial terms of “brand”, “products”
    and “business” […]

    the bill & melinda gates foundation gave more than 1 m$ (USD), the Cochrane company (I don’t write “collaboration” as it seems to be outdated), the Cochrane company made an annual revenue of 6,669,000 £ in 2017. Who are the customers ?

    Don’t bite the hand that feeds you.

    enough said.

  4. A problem with this pro/anti industry argument is that it forgets that Gøtzsche and others reached their so-called “anti-industry” viewpoint AFTER they have reviewed the available data and in the process realise that there is a great deal of data hidden from public purvue.

    The author refers to an early 2007 Cochrane Review as helping her inform her advice for consumers in 2009 for Germany’s national evidence agency, the Institute for Quality and Efficiency in Healthcare (IQWiG).

    That Cochrane review contains a number or errors of both facet and fact. For simple examples, it refers to the use of ‘placebos’ in the studies when that is not the case. The so-called placebos contained the adjuvant used in the vaccines meaning that the studies were not assessing the vaccine, but were only assessing a component (antigen) of the vaccine. If the adjuvant itself was problematic then the fact that it was in both arms of the trial means that these studies can not be used to assess its safety.

    Secondly, it is claimed in the Cochrane Reviews that there is 225ug of amorphous hydroxyphosphate sulphate [AAHS] in the [gardasil] vaccine when there is about 2,000ug of the adjuvant present in Gardasil 4, and 4,350ug in Gardasil 9.

    The fact that aluminium is a common element present in the general environment including food is irrelevant to the scientific process. Hydrogen, carbon and nitrogen are all common elements widely present in the environment and deemed safe, including in food. When combined together they have been used in compounds such as Zyklon B with devastating effect.

    AAHS is manufactured by Merck using proprietary methodology which was recently modified. AAHS is non-stoichiometric, meaning its exact composition is unknown and varies depending on things like pH, temperature, concentration of various salts used in manufacture, etc.

    No safety studies of AAHS are in the public domain. Requests to various regulators for such safety studies were refused on the grounds that such studies do not exist.

    Gøtzsche and others have identified a major flaw in the assessment of safety in certain medicines.

    When novel ingredients are included in both arms of so-called safety studies of new medicines and those studies are then used by gold-standard institutions, such as Cochrane, to claim that those products are safe, then objective science is thrown out the window. The only benefactors are the purveyors of the products mostly paid for by the State.

    It’s sad that scientists who expose such flaws in the system are then deem anti-industry or even anti-vaccine, when all they are doing is championing objective and transparent science.

  5. I have sent an email to your University of Copenhagen address listed on your profile there. Let me know if that does not work.

    To others on here: this is not about being “anti-vaccine”. This is about Scientific McCarthyism. “Are you now or have you ever been a member of the anti-vaccine movement?” This is the question scientists fear now. I am appalled when I go on supposedly science based websites, some of them maintained by people who have written books on logical fallacies, only to find articles on this subject built on ad hominem attack after ad hominem attack. The authors play games of six degrees of separation with anyone who says anything negative about a vaccine. If you have ever had any connection or even spoken to someone who has been put on the list in Mr. McCarthy’s back pocket, you can and will be ignored.

    This is pursued to silence criticism. If you control mainstream sources of information, then critics have no choice but to seek out any alternative voice that will allow them to speak. Those alternative sources threaten control of information, so attempts to use those sources are branded as outside the bounds of acceptability and will get you put on Uncle Joe’s list. And from another perspective, what kind of scientist sees people who are misinformed and decides the best way to handle them is to avoid engaging them? I will return to that in a bit.

    I read someone recently who said Tom Jefferson should not have appeared on someone’s radio show (someone on Uncle Joe’s list). A response noted that mainstream outlets are unwilling or afraid to air Jefferson’s views. The response to that was that Jefferson is a member of Cochrane and has enough of a platform to speak. For one thing, Cochrane is an inadequate platform, as what they do is very limited. They are not a platform for expressing opinions or anything remotely similar. They are not an advocacy group. But the biggest irony is that Dr. Gotzsche’s Cochrane position has been under attack for years, trying to deprive him of that platform. And so has Tom Jefferson’s. So on one side you have someone saying they should not use certain outlets to convey information, because they have Cochrane, and on the other side you have people attacking their position at Cochrane. The purpose here is clearly censorship and silencing dissent.

    In a recent opinion piece in the NY Times, Melinda Wenner Moyer documents that self-censorship in vaccine research is already widespread among independent scientists. This distorts the research base. And who can blame them? Most scientists are either not as brave or not in a position to stick their necks out like Dr. Gotzsche. They do not have his career, his history, his position of authority. They cannot afford to sacrifice their career for something that will get them nothing in the end. No one wants to be on Joe McCarthy’s list. And at the end of the day, even Dr. Gotzsche has now been removed from Cochrane. If he is not immune from the hysteria, who is? The question answers itself: no one. And that is the point of the attacks on Dr. Gotzsche. The message being sent out is loud and clear: criticism is a red line and if you cross it we will destroy you. A striking thing about the tone of Moyer’s piece is how it blames anti-vaccination activists for the self-censorship. Sure, they share some of the blame, but what about the figurative Un-Scientific Activities Committees who are directly causing this fear? The problem with McCarthyism was the McCarthyites.

    The perversity of this all is that a large reason the anti-vaccination movement is so strong is that trust in medical science and the government agencies that regulate it is basically zero with many people. And they are not wrong. No matter their claims, the underlying motivation of people who are anti-vaccination is nearly universally mistrust of medical scientists and the government. And on that score, they are more informed than many scientists. Not everyone can be a scientist and understand sophisticated arguments, but the average person has a good understanding of bias and conflicts of interest. In contrast to the medical sciences, where it appears having no understanding of these things is a prerequisite for entry into the club. There are some detailed reasons why medical scientists are blind to conflicts and bias, but that is outside the scope of what I will say here.

    So, given that trust is so low, and that got us where we are today, do we think it is a good idea to suppress information and create a climate of fear around vaccine research? Is this a good strategy going forward? Is this likely to convince the public vaccines are safe and effective? Do we think it was a wise decision to greenlight pandemrix with no information about its safety? Or to ignore the safety information that was available to agencies like EMA? Do you think someone who developed narcolepsy as a result of that vaccine or was otherwise injured is going to be in favor of future flu vaccinations? Is it a good idea to still keep that information quiet and/or deny it? We may be on the cusp of a breakthrough in flu vaccinations. What happens if those vaccines arrive and almost no one is willing to get them? If we keep following the current path, apparently the answer is to insult people and refuse to engage them. It is working great so far! I object to that path. The only thing it gives us is a feeling of self-righteousness. My ego is not that fragile.

    A final irony in this whole fiasco is how it contrasts with climate science. In climate science, the scientific “consensus” is built around the work of independent scientists, and the bad science of industry funded scientists is rejected. But in medical science, the opposite is true. The “consensus” is built around conflicted scientists connected to industry who produce bad science, while independent scientists are ridiculed and called “anti-industry”. The difference here is clear: in medicine, among other reasons, industry needs research to market its products. So they co-opted a large number of researchers. And it is surprisingly easy to co-opt an entire field. If you gain control of the leaders in the field (or ensure those you control are promoted to leaders), then everyone below tends to fall in line, even without explicit control. The paradigms are set by the leaders and those looking to advance their careers know the best way to do so is to work within those paradigms. One thing I find striking that almost no one discusses is what avenues of research are not pursued because they do not fit within the financial interests of those who set the paradigms. Shadows cast by that which we do not see.

    Sadly, climate science probably suffers from some amount of loss of trust due to loss of trust in other sciences, like medical science. And when the sea levels rise and we are all riding around in a boat with Kevin Costner looking for dry land, perhaps we will look back and realize that sowing distrust in science was not a good idea. More likely, the boating industry and whoever is profiting from the absence of dry land will make sure that information is suppressed.

    There will always be people who believe in Goop. If people were not so suggestible, marketing would not be so effective. The role of scientists is to help people sort out the facts. Scientists are authority figures, and people naturally believe authority figures. That is why appeals to authority are so widespread. But when trust breaks down, people no longer see scientists as authority figures. When there are no authority figures, more people are likely to believe in the power of Goop. When authority figures on vaccination are not trustworthy, people are open to suggestion by anyone. You cannot convince everyone, but the response to the loss of authority is surely not to continue the behavior that burned that authority.

    And I do not want to get too political, but our current political situation, not just in the United States, but to varying degrees in Europe, is largely a result of the breakdown of trust in authorities. When financial institutions are allowed to steal trillions of dollars and leave a trail of destruction in their path, then not only get bailed out by the authority figures when it inevitably goes sour, but avoid any prosecution for their crimes, trust in authority breaks down. And people are likely to believe any charlatan that comes along when they no longer have any faith in institutions of authority. They are likely to follow the person who validates their lack of trust and encourages them to burn everything to the ground.

    I will conclude with more remarks from a moral giant.

    “The question is not whether we will be extremists, but what kind of extremists we will be.”

    AND

    “The hope of a secure and livable world lies with disciplined nonconformists, who are dedicated to justice, peace, and brotherhood. The trailblazers in human, academic, scientific, and religious freedom have always been nonconformists. In any cause that concerns the progress of mankind, put your faith in the nonconformist!”

  6. I agree that non-financial interests can do as much harm as financial ones. It’s just that it’s so hard to even get agreement on the parameters of what constitutes the boundaries of financial conflict – and that can be objective. I think it could be that as time goes on, ways to do all of this better become clearer. I hope so.

  7. I disagree. I think that point was well and truly reached in 2015 at this point:

    There weren’t as many who thought he was a champion when he called in the BMJ for a stop to longterm use of almost all psychotropic drugs, based in large part on his then soon-to-be-published book, Deadly Medicines and Organised Crime: How Big Pharma has Corrupted Healthcare.

    I haven’t read it: here’s a book review on PLOS Blogs with Tom Yates talking about some strengths, but also concern about hyperbole, offensive rhetoric, selective use of evidence, and unsupported claims (like “bipolar disorder … is mainly iatrogenic, caused by SSRIs and ADHD drugs”).

    About the 2007 review: it wasn’t a Cochrane review – it was in the CMAJ. There wasn’t a Cochrane review on the HPV vaccine till this year. Its inclusion criteria allowed for placebo or “no HPV vaccine” controls, and when it was an adjuvant, the table clearly marked it as such. I agree, though, that it didn’t take the lack of inactive controls into account. There were quite a few issues with that review, so we did analyses ourselves based on the 2 key trials that accounted for almost all of the weight of its findings.

    No, I don’t believe objective science is thrown out the window: the Cochrane HPV vaccine review clearly describes this as a reason to be cautious about their conclusion on safety. Another team is working on a Cochrane review on specially this question.

    If it were true “that scientists who expose such flaws in the system are then deem[ed] anti-industry or even anti-vaccine, when all they are doing is championing objective and transparent science”, I agree that would be sad. But it’s not true, is it? No one is calling the authors of the HPV vaccine review that, even though they point out this flaw. Nor are the authors of the Cochrane protocol on adjuvants, who are specifically addressing this question, being called out. I think the critiques here are showing major bias and error, and I’ve pointed those out in the two posts (here and here) – for specific and objective reasons, not because I don’t like their conclusions. That included a lack of transparency as well as a lack of objectivity, and several key errors were acknowledged by the authors in the later response (although they introduced new errors, too).

  8. It’s too late for ME patients though. And despite the very obvious conflicts of the PACE triallists and obvious methodological flaws in their trial and all the other included studies Cochrane has failed patients by completely ignoring patient and methodological concerns before the review was published and then ignoring them afterwards too. More than failing. It’s betrayal. You can’t even complain officially because the conflict of interest policy doesn’t cover non-financial conflicts however objectively obvious they are.

  9. I’d like to expand on some of the above concerns, and provide some links for those interested in checking the details for themselves.

    One way of mitigating the harm done by ideological conflicts of interest is by genuinely committing to post-publication review, and ensuring that concerns raised about Cochrane reviews are taken seriously. In this area, Cochrane has failed.

    A patient identified a number of problems with Cochrane’s review of exercise therapy for CFS (the PACE trial was the largest trial included in this review), and submitted his careful and clear comments explaining these problems from 16th April 2016. His comments, and the replies from Lillibeth Larun, can be found from p123 of the re-published review: https://www.dropbox.com/s/koehut6iw2bm9v5/Larun_et_al-2017-The_Cochrane_Library.pdf?dl=0

    Larun’s responses should never have been considered acceptable by Cochrane, and I question whether anyone who has taken the time to read them believes that they can be defended. While Robert Courtney passed away earlier this year, and so will not be able to receive the apology that he deserves, Cochrane as an institution should still apologise to the patients affected by their failure to adequately supervise Larun’s work.

    Cochrane’s work has played an important role in slowing progress with debates about the quality of research into potential treatments for CFS, a matter where intellectual and financial COIs can be important. Cochrane has also played a role in leading to patients concerned about the quality of evidence supporting claims about the efficacy of CBT and GET being treated unfairly by researchers, doctors and disability assessors. The now quite widely known PACE trial is a useful example of this.

    In addition to their widely known ideological biases in favour of the treatments that they developed, all three of the PACE trial’s principal investigators also declared COI’s involving the insurance industry. Despite claiming that PACE was conducted in accordance with the declaration of Helsinki, their COIs were not declared to potential trial participants, violating the declaration of Helsinki: http://www.virology.ws/2015/11/17/trial-by-error-continued-pace-teams-work-for-insurance-companies-not-related-to-pace-really/ Should this matter?

    Regardless of the many problems with PACE that have now been recognised (and which led to an entire special edition of the Journal of Health Psychology), Cochrane allowed itself to be used by the PACE trial researchers to fight against access to trial data and evade important questions about the problems with their work.

    QMUL university refused an FOI request to release results for the outcomes pre-specified in the PACE trial’s published protocol, claiming that this would be too expensive to do as “there is no longer a statistician employed by the PACE trial, one would need to be recruited for this operation and trained.” https://www.whatdotheyknow.com/request/pace_trial_recovery_rates_and_po_2#incoming-463991

    They then spent £250k on lawyers fees to fight against a request for the anonymised data required to calculate these prespecified outcomes: https://johnthejack.com/2016/06/29/using-public-money-to-keep-publicly-funded-data-from-the-public/

    Cochrane provided them important cover during their fight. A statement from QMUL claimed that:

    “We have supplied requested, anonymised data to independent scientists, as part of normal research collaboration. Among others, these include a Cochrane review group who have independently validated the trial findings on the primary outcomes, and who are now undertaking an individual patient data meta-analysis using these data.”
    https://www.qmul.ac.uk/media/news/items/smd/168729.html

    When a PACE trial PI was questioned in court about whether this sharing with ‘independent scientists’ showed that the requested data could be released, she then argued that: “disclosure to the Cochrane review does not count as disclosure to independent scientists as all three of the PACE principal investigators sat on the review panel.”
    http://informationrights.decisions.tribunals.gov.uk//DBFiles/Decision/i1854/Queen%20Mary%20University%20of%20London%20EA-2015-0269%20(12-8-16).PDF

    Indeed, a PACE trial PI’s academic fund paid for one of the meetings for developing the protocol for a planned Cochrane IPD review, and the PACE researchers stated that an outcome of their trail was: “We have provided individual patient data for this Cochrane group meta-analysis, as well as our active involvement in design and writing.” https://gtr.ukri.org/projects?ref=G0200434

    Fortunately the Information Tribunal did not fall for the claims used to attempt to justify the refusal to release PACE trial data, and when the released data was analysed it served to further illustrate how justified the concerns about this work were. Two papers have now been published which used the analyses pre-specifed in the trial’s protocol and found that:

    1) “The claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading to clinicians and patients considering these treatments.” https://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1259724?journalCode=rftg20&

    2) “These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.”
    https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-018-0218-3

    Given the clear problems with PACE, and many of the other trials included in Cochrane’s review, it is doubtful that these researchers would have agreed to share data with those who did not share their own ideological biases. It is worrying that Cochrane appears to have allowed themselves to be used for this selective form of data sharing and ‘validation’.

    While the problems with Larun’s work are illustrated by her earlier Cochrane review, and her responses to Courtney, I also wish to note that the final author of the IPD protocol appears to suffer from his own ideological distortions. Paul Glasziou has long claimed that there was good evidence exercise therapy was useful for CFS, and was the co-author of a book which argued that CFS was a ‘self-perpetuating disease’ where the self-perpetuating process “creates fatigue, lack of physical activity and leads to an ongoing sense of fatigue”. It is not made clear what evidence is thought to justify this claim. When David Tuller’s investigation into the PACE trial attracted wider concern from within academia Glasziou attempted to dismiss his work as ‘ad hominem’ (although provided no reason for this claim): https://twitter.com/PaulGlasziou/status/658488688091922432 Even after data from the PACE trial showed how the researchers had spun their ‘recovery’ results, Glasziou has gone on promoting articles which use their misleading recovery figures on social media, eg: https://twitter.com/PaulGlasziou/status/700078726826971136 I can see why the PACE researchers would be happy to have him providing an ‘independent’ review of their research, just as I can see why others would see him as unfit to do such work.

    Important institutions whose reputations are tied to the PACE trial continue to try to use Cochrane’s work as an excuse for not addressing criticisms made of the trial’s design, execution and analysis, eg:
    https://mrc.ukri.org/news/browse/criticism-of-the-pace-trial/ When Cochrane fails to take post-publication peer review seriously, leaving the misleading claims of Cochrane authors uncorrected, there is good reason to be concerned about any potential distortions of thought that review authors may suffer from.

    While the BMJ has a history of misrepresenting the controversy surrounding the PACE trial, they appear to be starting to cover the issue more fairly. In their most recent piece on this scandal they drew attention to Simon McGrath’s concern that concerns about problems with PACE only started to e taken seriously once academics started to speak out on behalf of patients: “for many years, researchers and the medical establishment would not engage with patients who made the same criticisms — simply because, it seems, they were patients.” https://www.bmj.com/content/362/bmj.k3621.short?rss=1

    Larun’s exercise review claims to have found a “positive effect” on physical functioning from exercise therapy at follow-up, yet their own analysis (1.6) showed that there was not a significant difference between the exercise group and the passive control group. This ‘physical functioning’ outcome was based on mere questionnaire results from non-blinded trials, and during these trail participants were being told that exercise therapy had been found to be effective. Concerned patients have long attempted to draw attention to the potential problem of bias distorting subjective self-report outcomes, and the fact that more objective outcomes show less positive results: https://www.bmj.com/content/350/bmj.h227/rr-10

    If such poor quality research had been misleadingly presented to justify a claim that vaccines were dangerous, I do not believe complaints about this would have been ignored. Yet when misleading claims serve the interests of well connected researchers many seem happy to dismiss concerns raised by patients like Courtney.

    Why have Robert Courtney’s carefully stated concerns been left unanswered (aside from an “agree to disagree” non-reply from Larun) for two years, while Gøtzsche’s concerns were treated as urgent? If Cochrane fails to engage seriously with those who are attempting to play by their rules, including a patient devoting their limited health to trying to help ensure their fellow patients are not misled by poor quality work from Cochrane, how can Cochrane’s board then complain about others who stretch (or break) the rules? If Gøtzsche is to be expelled for his unreasonable behaviour in criticising work at Cochrane, should those at the Common Mental Disorder Group be expelled for their unreasonable behaviour in failing to adequately respond to criticism? Has their behaviour really been any better than Gøtzsche’s? Are high standards only insisted upon when behaviour troubles researchers rather than patients?

    David Tuller writes that those at Cochrane are aware of the problems with their CFS work, and are slowly considering their next step: http://www.virology.ws/2018/09/03/trial-by-error-the-cochrane-controversy/ But this should have been considered a matter of urgency when concerns were first raised. The Larun exercise review was not fit to be published, and the slow recognition of this illustrates serious problems at Cochrane. Indefensible work should be withdrawn, not left to go on distorting public debates, and clinical decisions about patients’ health-care or eligibility for insurance and welfare payments.

  10. I haven’t kept up with the controversy around PACE and the Cochrane review, so I can’t comment on that. I agree it’s important, though, and I should. However, just to point out: Gøtzsche wasn’t expelled for criticizing a Cochrane review. The process had started long before he criticized the HPV vaccine review. (Disclosure: Paul Glasziou is a friend, and my PhD supervisor, but I’m not familiar with the case you’re discussing.)

  11. I still say Cochrane Collaboration, because it still exists (see its articles of association) – even if there has been a strategic decision not to use that name in its “branding”. The revenue you’re reporting here is mostly from royalties for the Cochrane Library. I’m not going to defend that, and I’m no more of a fan of the “branding” direction than you are: I have long been on the record opposing this direction for the organization. But I don’t believe this current dispute is at all about funding.

  12. Sorry – I meant to say “while criticising work at Cochrane”, not “in criticising work at Cochrane”. It does seem that whatever behaviour of Gøtzsche’s Cochrane found unacceptable, it took place while Gøtzsche was criticising Cochrane.

    It is difficult for outsiders to know exactly what behaviour of Gøtzsche’s was seen as unacceptable as I do not believe this has yet been detailed. The board’s statement said: “The Governing Board’s decision was based on an ongoing, consistent pattern of disruptive and inappropriate behaviours by Professor Gøtzsche, taking place over a number of years, which undermined this culture and were detrimental to the charity’s work, reputation and members.” To me it seems that there are important parts of the culture at Cochrane which need to be undermined.

    I would certainly encourage you to look at the PACE trial and the problems with Cochrane’s CFS work, particularly given your interest in consumer engagement. While a growing number of independent researchers are now speaking out about the problems here, those who are already in positions of authority in this area tend to be those with a vested interest in maintaining the status quo. As it seems that achieving real change in medicine can be more dependent on politics than evidence or arguments, making progress here is likely to require that many more independent researchers take the time to get involved.

  13. I don’t consider myself “the friend who does nothing in the face of corruption”: I am neither the friend of this kind of activism, nor someone who does nothing. Raising the issue of me having left the Cochrane Collaboration and having limited engagement with it, is meant to indict me somehow here. But I think it raises different critically important points.

    When I first stopped being an active participant in the Collaboration, I had pushed for the causes which concerned me as far as I could: I was no longer going to be effective. And to me, that is the point: effecting change, not fighting. Fighting can become purely destructive, too, with no benefit to the public whatsoever, for all some people cheer it and see it as somehow heroic. Fighting ineffectively can even set back the causes in which believe. (As I mentioned in my “boilover” post, I expanded on this in the international Cochrane newsletter in May 2002: valorizing fighting a “holy war” is antithetical to collaboration.)

    I was actually far more effective advancing the cause of open access in Cochrane, for example, from outside the organization than I had been in it. The final parting of the ways came because I had done as much good as I felt I could do even from outside at that point, and I believed I could do more good elsewhere.

    Why am I going into this? It’s to highlight the issue of being effective. Gøtzsche had to do very little in order to stay within the Collaboration: refrain from harassing staff, abide by the trustees’ code of conduct as long as he was a trustee of the board, and not use his Cochrane leadership affiliation for his activism on issues that aren’t directly Cochrane-related or policy areas where this is outside Cochrane policy. Those aren’t onerous or repressive requirements.

    The Cochrane Collaboration isn’t a university: it’s culturally, societally, and legally different. Not using a formal leadership title, and making it clear when your views are your own and not the organization you work for, is not a heavy burden. Nor does it require the slightest bit of loss of integrity. He chose to burn the bridge he was standing on, for no noble cause at all. Certainly, harassing staff when you’re a board member is the opposite of a noble cause, and to object to that isn’t a debate over tone: it’s to take a stand against abuse of power.

    I don’t cast myself as “the neutral party, the fair arbiter in the whole ordeal”: I disclosed a range of my interests, and expressed strong personal opinions. I’m not neutral at all, and I don’t pretend to be. What I try to do is identify and understand my biases as much as I can, work to assess situations as objectively I can, learn from scholarship and evidence, and communicate about ideas effectively.

    You asked what is my reason for placing Gøtzsche towards the “anti-industry” and extreme end of the spectrum. I added some explanation of my use of the terms “pro-” and “anti-industry” in this post, and some key points in Gøtzsche’s journey to substantiate my judgement in this one. And it, as well as this one shows, in my opinion, how the values of rigorous and open science, and principles of collaboration, weren’t all that evident in the critique of the HPV vaccine review.

    To this point:

    Are you really going to argue he is “anti-industry” and therefore picked this one issue out of everything out there and chose to be critical because he dislikes industry? That is an odd claim to make – and insulting against a fellow scientist without a lot of evidence to the contrary. Of course, once he takes a stance, it is fair to say he has some bias in protecting his reputation when he defends his stance. Though that does not get you very far because at that point everyone on all sides shares the same potential bias. Are we going to argue that Gotzsche picked psychiatry because it is an easy target for his “anti-industry” crusade? That road leads to crazy town.

    I think our interests do have a lot to do with why we pick up some issues and not others. I don’t think it is crazy town to think that Gøtzsche invests a lot of time in high profile issues that go to fighting for, and increasing awareness of, causes he believes in so strongly – the perniciousness of “pro-industry” interests, and harmful effects of medications. He wasn’t obligated to do these things: this is a discretionary agenda.

    To this point:

    When those who would root out the insidious effects of industry are attacked as “anti-industry” and their silencing is applauded by self-styled “neutral” observers, corruption is enabled. If Gotzsche is gone, who will look for the corruption? You? From what I can see, you prefer to spend your time drawing cartoons.

    I think there are many, many people committing enormous effort to these issues – and most of them aren’t extremists. I think Gøtzsche will continue to pursue these issues from outside the Cochrane Collaboration. And industry influence is a critical issue to many, many people in the Cochrane Collaboration, and they will continue to work hard on these issues. It seems likely that Gøtzsche’s expulsion will increase those efforts, not stifle them.

    I absolutely do not “prefer congeniality over truth, much like those who preferred order over justice”. I spoke above about ideological warfare being antithetical to collaboration. It’s also a problem when it comes to finding the truth, as is any severe bias. Wars of all kinds aren’t famous for being conducive to truth-telling and truth-finding either.

    Finally, people who protest over the influence of commercial interests in health are not analogous to people who fought and fight for civil rights in the US: they don’t face life-threatening terrorism, batons, or fire hoses, and appropriating this isn’t just hyperbole – it is disrespectful, to say the least.

  14. I agree that throwing around “anti-vaccine” etc too liberally can have a chilling effect on discussion and deter some people from studying safety issues and raising concerns about them. However, people scare-mongering about vaccines is a real problem too. And attacking and labeling people expressing serious concerns is also a way of trying to discredit people with whom someone disagrees.

    I think the Cochrane Collaboration is a key place where these issues can be studied objectively and without fear or favor. Apropos of the discussion about the HPV vaccine evidence, there are 2 protocols for Cochrane reviews-in-progress on safety issues and adjuvants (here and here). And as far as I’m aware, no one is concerned this is “anti-vaccine”: it’s Cochrane business as usual.

    I disagree strongly, though, with this argument defending people mobilizing destructive movements, in order to get their message out:

    If you control mainstream sources of information, then critics have no choice but to seek out any alternative voice that will allow them to speak.

    Gøtzsche and Jefferson have a great deal of access to leading medical journals, and get quite a lot of mass media attention, too. Probably not as much as they might want, but more than most researchers would dream of. So I don’t buy that justification in this particular case. I think there are important reasons to avoid doing this. Firstly and most importantly, there are anti-social social movements, that do a great deal of harm: encouraging/legitimizing them could mean you increase the harm the do. And the association damages your reputation, and therefore your ability to be effective. Mobilizing people from extremely damaging movements can also rain down trolling etc on others, which is inherently problematic, and counter-productive.

    I agree with the point you’re making here:

    And from another perspective, what kind of scientist sees people who are misinformed and decides the best way to handle them is to avoid engaging them?

    But feeding prejudices doesn’t change this situation. The problem in the kinds of venues we’re talking about here is extreme bias and disinformation campaigning. Yes, there are forms of engagement that could be constructive, but that’s not seeking a platform to air views so biased and extreme, they can’t get airtime elsewhere. (I haven’t seen the specific one with Tom Jefferson you’re referring to, so I’m not commenting on that.)

    To this point:

    Most scientists are either not as brave or not in a position to stick their necks out like Dr. Gotzsche. They do not have his career, his history, his position of authority. They cannot afford to sacrifice their career for something that will get them nothing in the end….The message being sent out is loud and clear: criticism is a red line and if you cross it we will destroy you.

    As I argued in reply to your previous comment, Gøtzsche chose to squander that position of authority, and I don’t think what he did was brave; and it wasn’t because he criticized evidence or corruption. It’s inconvenient to heroic myth-making, but there it is: the truth can be inconvenient.

    (If anyone is interested in my take on these movements, this post is a good starting point. And I’d welcome suggestions for better ways to characterize the spectrum I labeled “pro-“/”anti-industry”.)

  15. Yes, I see what you mean. You have to spend a lot of time following all the threads to see what this was about in detail. And I have more background on the past, as I had a front-row seat on some of that history – including the Cochrane AGM a few years ago where they got close to the point they reached this year. (I was no longer a part of the organization, but was an invited speaker at the conference.) Some of the confidential material is being leaked, but I’m not passing it in because I believe some of it really does involve as serious a breach of a (non-Cochrane) person’s privacy and so on.

    There are nearly always parts of any organization that could do with a good jolt, but I don’t think that’s what we’re talking about here. I think the key issue is what I said here:

    By the AGM on the 17th, though, the Board had a prepared statement. They emphasized the right of people to a work environment free of attack and harassment.

    It’s hard for people to understand the import of this, if they’ve never borne the brunt of something like this, or seen it happen to someone else. When your boss, or a board member with power over your job, or someone in whose line of fire you’re trapped because of your job, frequently engages in bullying behavior, life can be miserable. It’s a huge stress, and it impairs your ability to get all your work done – which adds to the stress. And it’s an abuse of power. There has to be zero tolerance to it.

    In this post, I detail some of the bushfires that have been created when Gøtzsche used his Cochrane leadership title in activism that wasn’t Cochrane-related, instead of his university affiliation alone, or just his own name. As you know for sure, these things can engulf people too, and again they diverted from their workload etc. I can see why people focus on the criticism – but the Cochrane Collaboration membership is just riddled with critical people, including many of us forever barking on about our pet issues and bugbears. So the tolerance level for that is high. It’s just hard, I think, for people to realize that a respected person goes rogue, in ways that aren’t visible from the outside.

    Yes, I should look at the issues you raise. Thanks for reminding me I should.

  16. I do not want to get into a tit for tat that goes nowhere, but I feel the need to respond to a few things.

    First, working from outside can be effective, but I do not see that from you, nor do I see that it would have been more effective for Dr. Gotzsche. Many people wanted him removed from Cochrane precisely because they think it would make him less effective.

    refrain from harassing staff

    Why do you trust the board’s clearly slanderous language here? Everyone can now read the report from the lawyer the board hired. There was no harassment. There was disagreement the board decided to publicize as harassment as a pretext for its decision. Your trusting that information and then repeating as if it is true says a lot about your character and judgment. Board members do not resign in protest over just anything. They resign because other board members are acting inappropriately, or at least they feel that way. Ignoring this and putting your trust in the remaining board is a serious mistake – particularly when they make vague statements and refuse to elaborate, providing excuses that are transparently bogus.

    Everything else you say in that paragraph is also false. As anyone who reads the report can see, the lawyer found no evidence the spokesperson policy was violated. He said it cannot be argued that Gotzsche misrepresented himself. While bending over backwards to please the board, the only assertion in the board’s favor was that Gotzsche might have technically violated the Collaboration Agreement. But he then goes on to note that any punishment for this would be inappropriate because, for one thing, the Collaboration Agreement is so bare that basic functions of the Centres would also violate that agreement (this is not explicitly stated, but is implied by what he says). “It may be said that the “Functions of Centres” document is not exhaustive of function. My respectful view is that the issues raised by this review require the Governing Board ultimately to come to a conclusion about what are those limits and set them out clearly in a policy.” Basically, the document is vague and open to interpretation and specifies little of what the Centres actually do.

    Further, this whole arguing over very technical rules is nonsense. The spokesperson policy and the collaboration agreement were put in place to muzzle Dr. Gotzsche. They were intended as a pretext for his later dismissal. And the board could not even get that right. These issues arise due to exactly what Dr. Gotzsche is complaining about – the centralization of power at Cochrane and change from a collaborative structure to a corporate one. The Cochrane Collaboration is a loosely structured group of Centres of research. The Centres act with autonomy, doing what they think is best. Under the new corporate Cochrane, the central leadership wishes to strip the Centres of their autonomy. And label actions that were previously normal as misconduct. And even worse, all this new structure and new rules were clearly not evenly applied. They were largely being applied to Dr. Gotzsche, while others were free to do as they please.

    Certainly, harassing staff when you’re a board member is the opposite of a noble cause, and to object to that isn’t a debate over tone: it’s to take a stand against abuse of power.

    Again, this is an absolutely slanderous statement with no evidence. It is alarming that you make it with such confidence.

    I don’t cast myself as “the neutral party, the fair arbiter in the whole ordeal”: I disclosed a range of my interests

    I think this is dishonest. Your article is headed by a cartoon portraying “pro-industry”, “anti-industry”, and “anti-both of those”, which is clearly meant to be how you want others to see you. That is absolutely calling yourself a neutral observer. And I also found your disclosures lacking. Given the personal history you have with Dr. Gotzsche (that I was not aware of until doing a bit of research), particularly over mammography, I think you could have disclosed that to readers as well.

    Gøtzsche and Jefferson have a great deal of access to leading medical journals, and get quite a lot of mass media attention, too.

    Medical journals are not read by most of the public. When I first started researching psychiatry, it took about one year before I even became aware of Dr. Gotzsche’s work. And then it was only because he published his book. When reading medical journals and other scientific articles, there is almost a total blackout of Dr. Gotzsche’s research. You can read hundreds of studies and papers on antidepressants and never find references to Dr. Gotzsche’s work. It is kept very well hidden in my experience. And “mass media” attention is insufficient. First of all, they actually get very little attention from what I have seen. Any time they speak in a mainstream outlet, there is serious McCarthyism directed at those outlets in an attempt to pressure them to avoid allowing them to speak in the future. And who knows what behind the scenes pressure is applied by advertisers. Aside from this, I will just agree to totally disagree that engaging “anti-social movements” encourages them. It is very pleasing to write people off and pretend they are not your responsiblity, rather than engaging. But not very helpful. Perhaps you could read some of Dr. King’s writing and understand how wrong you are on this point. Dr. King did not win over his adversaries by failing to engage.

    “Here is the true meaning and value of compassion and nonviolence, when it helps us to see the enemy’s point of view, to hear his questions, to know his assessment of ourselves. For from his view we may indeed see the basic weaknesses of our own condition, and if we are mature, we may learn and grow and profit from the wisdom of the brothers who are called the opposition.”

    If only some people in the “pro-vaccine” space would listen to anti-vaxxers and understand their point of view. Forget what they say. Why do they say it? They have no trust in authorities. They have no trust in you. No one wants to ask this question because the answer is uncomfortable, and it implies that those on the pro side have done something wrong and might need to change.

    “There’s another reason why you should love your enemies, and that is because hate distorts the personality of the hater. We usually think of what hate does for the individual hated or the individuals hated or the groups hated. But it is even more tragic, it is even more ruinous and injurious to the individual who hates. […] For the person who hates, the true becomes false and the false becomes true. That’s what hate does.”

    Oh, is this ever true! Though hate is not the right word here, the analogy is the same. Replace “love” with engage and hate with “ignore/insult”. The point is not just associated with “hate” but is about the effect of holding onto beliefs based on emotion and not rationality. For “pro-vaccine” advocates, little white lies, dishonesty, ad hominem attacks, and suppression of information have become essential parts of the reportoire. ‘We cannot speak this truth because it will be used by them against us. We cannot do this research because its results might harm my cause. We cannot talk to them because they have bad intentions.’ I am sorry, but the ends do not justify the means. When you are telling half-truths and suppressing research, you can no longer say what you are doing is based on facts. The moral high ground has been lost.

    As a final point I would like to really draw the issues here in black and white. One of the recent “complaints” made against Dr. Gotzsche is that he sent a request to Fuller Torrey asking about a trial of antipsychotics where children died. I have not seen the full text of the letter, only what was excerpted in the lawyer’s report. But the excerpt indicates that Dr. Gotzsche is seeking information about the deaths and also urging Fuller Torrey to publish either the results of the trial and/or details of the deaths. And Dr. Torrey’s response to this serious inquiry was to make a complaint about Gotzsche’s supposed lack of independence. And Cochrane leaders became obsessed about Gotzsche using Nordic Cochrane letterhead to send this request. And a very large number of people seem to agree with the board’s obsession. I will use all caps to emphasize the point: JESUS CHRIST, WHAT IS WRONG WITH YOU PEOPLE. A researcher is making inquiries about the suppression of information regarding children who died in a clinical trial and everyone is worried about what letterhead it is written on? If that is not an indictment of what is going on here, I do not know what is. And why is it not the business of Cochrane to ask about dead children? What could possibly be MORE important than that? Even worse, it is clear the outrage over use of Cochrane letterhead is feigned outrage, as this was a private letter, sent to Fuller Torrey. Was Fuller Torrey confused about whether the letter represented Cochrane’s views? Apparently not, as the lawyer’s report does not describe that. Instead, Torrey argued that Gotzsche was not “objective” and this damaged Cochrane’s reputation – something totally different. So the target of this letter was not even confused about it. He just wants Gotzsche removed from Cochrane. And of course he was not confused because everyone knows who Peter Gotzsche is and that many of his views are not official Cochrane views. That has been broadcast fairly wide by now. Let’s not pretend otherwise. It is insulting. So, Cochrane leadership’s use of this complaint in its case was misleading. The complaint is about one thing, and they used it as evidence of another (false allegation). That is how kangaroo courts operate.

    Wars of all kinds aren’t famous for being conducive to truth-telling and truth-finding either.

    Who said this was a war? Dr. Gotzsche rejects the use of war language because it is used to ignore arguments. Even if people use the war analogy in passing, this is totally irrelevant. War is not conducive to truth-telling/finding because it produces fear. Who is afraid of Dr. Gotzsche? Do pharmarceutical companies live in fear? Are those Dr. Gotzsche criticizes living in fear? If anyone is fearful here, it would surely be Dr. Gotzsche. What is your argument here by bringing up war? Harry Frankfurt wrote a book about arguments like this one. You can find it on Amazon.

    Finally, people who protest over the influence of commercial interests in health are not analogous to people who fought and fight for civil rights in the US: they don’t face life-threatening terrorism, batons, or fire hoses, and appropriating this isn’t just hyperbole – it is disrespectful, to say the least.

    Ah, more feigned outrage. Or maybe the outrage is real and you just understand nothing about Dr. King. Of course, no two situations are exactly alike. We call this ‘analogy’. But your argument is ridiculous on its face. In your argument, Dr. Gotzsche cannot be oppressed unless he is facing fire hoses and batons. That is not how it works. This is why Dr. King spoke out against Vietnam and against poverty. He was fighting all oppression and all injustice. And many of his allies were highly critical of this. His response was that injustice anywhere is a threat to justic everywhere. We cannot close our eyes to injustice just because it is not our own. Dr. King was leading a Civil Rights movement, but he was not isolated to just this one cause. Dr. King would advocate for the fighting of injustice anywhere it occurs. And industry takeover of medicine is a grave injustice that is ongoing. People are dying. People are being seriously harmed. It is not hyperbole to analogize to the Civil Rights movement. You want it to be hyperbole because when the analogy is laid out for everyone to see and they realize it holds true, it makes your position look untenable. And it is not disrespectful to make this comparison. What is disrespectful is marshalling outrage at the comparison while rejecting everything Dr. King stood for. Just as Dr. King felt Vietnam and poverty were the same struggles as Civil Rights, he would look at industry takeover of medicine today and say “This is my cause.”

  17. Thank you ES for a great summary of the problems with the Cochrane reviews of exercise for ME. I know of someone with ME who raised concerns before the first review was published. He offered to review it, and was turned down because of lack of time. This was many months before the first version of the review was published without any input from patients (in 2013). He has been in contact with Cochrane for FIVE years on this issue, and only now is Cochrane getting round to investigating Robert Courtney’s concerns? Hilda, I know you can’t yet comment because you haven’t kept up with it. But please could you get up to speed (probably reading David Tuller’s posts on http://www.virology.ws would be the best place to start) and then comment?

  18. To these points:

    First, working from outside can be effective, but I do not see that from you, nor do I see that it would have been more effective for Dr. Gotzsche. Many people wanted him removed from Cochrane precisely because they think it would make him less effective.

    Just because you can’t see it, doesn’t mean something doesn’t exist. I agree many outside wanted Gøtzsche not to have the weight of Cochrane credibility on his side. But the discussion point originally had been about influencing Cochrane itself.

    To this:

    “refrain from harassing staff”: Why do you trust the board’s clearly slanderous language here? Everyone can now read the report from the lawyer the board hired. There was no harassment. There was disagreement the board decided to publicize as harassment as a pretext for its decision. Your trusting that information and then repeating as if it is true says a lot about your character and judgment. Board members do not resign in protest over just anything. They resign because other board members are acting inappropriately, or at least they feel that way. Ignoring this and putting your trust in the remaining board is a serious mistake – particularly when they make vague statements and refuse to elaborate, providing excuses that are transparently bogus.

    As one of the Cochrane center directors said in the discussion at the AGM, I’ve seen the kind of bad behaviors of which they spoke. As they said, this went back years: I was on the board till 2001, and it was already happening then. These are other people’s stories to tell, though: although I’ve felt the brunt of his anger, I’ve never been in a position where he had that kind of power over me. I’ve witnessed it, though.

    Although I don’t know who you are, I doubt you’re in a position to speak for the board members. According to the board statement, 11 of 12 voted that he had breached the trustees’ code of conduct. So you’re skating on thin ice here. No, board members don’t only resign because they believe other board members have behaved inappropriately.

    To this:

    Everything else you say in that paragraph is also false. As anyone who reads the report can see, the lawyer found no evidence the spokesperson policy was violated. He said it cannot be argued that Gotzsche misrepresented himself.

    I haven’t seen the full lawyer’s report – just selected parts that serve some arguments Gøtzsche is making. The leaked parts I’ve seen were consistent with the board’s statements. I’ll look for it.

    To this argument:

    Further, this whole arguing over very technical rules is nonsense. The spokesperson policy and the collaboration agreement were put in place to muzzle Dr. Gotzsche. They were intended as a pretext for his later dismissal.

    The board spoke of many attempts in the past to resolve the problem. Developing policies and procedures where they are lacking is clearly one of the ways you would go about that: in the same paragraph, you’re quoting a call to develop more detailed writing on what’s expected of centers. I think, given that this has been going on through so many different board and staff cohorts over the years, that we’ve seen multiple good faith attempts to resolve this situation, from fresh blood through more fresh blood. The spokesperson policy was not intended to “muzzle” people, nor could it have: it had nothing to do with what he could do or say under his pwn name or his university affiliation or any other – just not on Cochrane letterhead, and with his formal Cochrane title/affiliation. This is normal for NGOs and many other sectors. He could say what he wanted: but he chose to continue doing it in Cochrane’s name.

    To this point:

    The Centres act with autonomy, doing what they think is best. Under the new corporate Cochrane, the central leadership wishes to strip the Centres of their autonomy. And label actions that were previously normal as misconduct.

    I think the first part of this is true – centers had more autonomy in the past. That’s why I wrote that it was consequential that all but one of the resignees were from centers. I don’t accept it was necessarily a good thing. (Disclosure: I employed (up to half-time) by a Cochrane center for many years.) Indeed, many people long argued there shouldn’t even be Cochrane centers, and many had problems with them. I don’t know if that’s still the case. I think having so many Cochrane center people on the board, when they are such a minority of Cochrane’s membership, was neither representative nor healthy.

    To this:

    I also found your disclosures lacking. Given the personal history you have with Dr. Gotzsche (that I was not aware of until doing a bit of research), particularly over mammography, I think you could have disclosed that to readers as well.

    You didn’t have to do much research: I raised it myself. From day 1, the disclosures said I had gone rounds with authors (plural) of the HPV critique. (Should it become relevant, the other is Tom jefferson. I don’t think I have ever encountered the third author: if I have, I don’t remember him.) The first post I wrote when the Gøtzsche issue exploded, I linked to my 2002 writing on aggression in the mammography issue.

    The cartoon doesn’t depict neutrality: it depicts active anti-extremism.

    To this point:

    Aside from this, I will just agree to totally disagree that engaging “anti-social movements” encourages them. It is very pleasing to write people off and pretend they are not your responsiblity, rather than engaging. But not very helpful. Perhaps you could read some of Dr. King’s writing and understand how wrong you are on this point. Dr. King did not win over his adversaries by failing to engage.

    That’s not what I said. If you or anyone else is interested in my positon here, please read what I wrote, and the link I included that goes into my views on this.

    I share the sentiments about trying hard to be respectful in discussing people with whom you vehemently disagree, and avoiding ad hominem attacks. Have you thought about re-reading your own comments here, to see if you think you’ve met that standard yourself, in relation to me?

    I don’t know who you are, as you are effectively anonymous both here and on Twitter. But you’ve had more than a fair run of ad hominem remarks here, mixed in with a diminishing amount of valuable addition to this debate. I moderate this blog, and as I’ve said from the day it started, am interested in dialogue, but not in hosting yet another unpleasant pocket on the internet. So before you invest time in more of this, please take into consideration that I might not publish it. Thank you, though, for the important issues you have raised so far.

  19. I will keep it short, no tit for tat. Hopefully you will publish.

    1) I do not believe I have made ad hominem attacks against you. If I did, I would apologize for that. Certainly I have attacked you, but always intending to attack you based on your arguments and positions. I specifically spoke of your character in the last post, but based on what you have done and said. As an example (not aimed at you at all), it is not ad hominem to call someone a liar if you have in fact just pointed out a lie. It is ad hominem to call them a liar and refuse to engage their arguments because you do not debate with liars.

    I have certainly characterized your positions and statements quite a bit – my view of the meaning behind your statements. I believe that is fair, though I am sure unappreciated on your end.

    2) I appreciate that you have been gracious enough to approve my comments – even though they included a lot of criticism of you and your positions.

    3) The full lawyer’s report was posted by Dr. Gotzsche on his website, along with a lot of other documents. He was not selectively quoting from it, he was waiting until he spoke to a lawyer about posting it. I have read the whole thing. Despite being clearly written in a biased manner in favor of the board, it is damning for the board.

    Even the new claim that 11 of 12 voted that he violated the trustees code is yet another misleading claim. The trustees code can be violated simply by not having a working relationship with a staff member. And we already know that is the case. It doesn’t even have to be your fault. So that vote is misleading and irrelevant, which is probably why the board did not mention it in its first statement. I would say some other trustees clearly breached the code as well, yet no vote was taken on them.

    4)

    just not on Cochrane letterhead, and with his formal Cochrane title/affiliation.

    Except, as the lawyer’s report makes clear, that’s not what the policy said. It said he could use the letterhead if it was Cochrane business. And as the head of a Cochrane Centre, he had a difference of opinion about what was Cochrane business. And as the lawyer says, there is nothing you can do about that except write a more stringent policy. The policy allowed him to do what he did.

    This is normal for NGOs and many other sectors.

    This is normal for most NGOs, but not one with Cochrane’s structure. If the Centres are to act autonomously, then they necessarily need to be able to use their letterhead for business they feel is part of their work. Most NGOs do not have a de-centralized structure like this. You seem to think Cochrane should not, but many scientists in Cochrane think the opposite – that restructuring around a centralized structure is a disaster for a collaboration of scientists.

    Under the logic currently being imposed, Gotzsche is supposed to send requests on non-Cochrane letterhead when the materials he gets back are likely to be used in future Cochrane work. That makes no sense. If he receives data on deaths in an antipsychotic trial, presumably he would be interested in making that part of a Cochrane review.

    And as I said, the whole thing is silly because no one thinks Peter Gotzsche speaks for Cochrane on these issues at this point.

  20. Thanks for this.

    I’ve read the report now, too. And there you go then: I don’t think it is at all damning of the board, and makes clear that allegations he leveled at them aren’t justified. I think “bad” is an understatement for much of the behavior shown there. I’m not quoting from it or linking to it, though, because so much of it was confidential, and affects individuals with a right to privacy who are completely unrelated to Cochrane.

    We’ll have to agree to disagree on whether there was ad hominem in these comments: we’re miles apart here on what’s appropriate behavior, as our different responses to the documents being posted underscores. I wouldn’t have allowed comments belittling someone to that degree, and likening them to enablers of violence against civil rights activists, &c &c, if it wasn’t myself.

    And to your specific question: no, I don’t think you should call people liars, if you can possibly avoid it. Name-calling is problematic; calling out behavior is not. Claiming you know people’s motivations and intentions is inherently problematic, too, if they are not ones they have declared themselves. It’s not just the nastiness of ad hominem attacks that is objectionable, and how much of a chilling effect they have: they are hallmarks of logical fallacy, too. It’s an all-round bad way to try to make a case.

  21. OK. If you are short of time start here with the review and read the feedback. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003200.pub7/full.

    The PACE triallists are now co-authors of the forthcoming review using individual patient data, https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011040/full. I was confused that Paul Glasziou had also appeared on the published protocol as last author. Now I have learnt about his ideological conflicts relating to ME, it all makes sense.

    And he is now supervising your PhD on some factors affecting the validity of systematic reviews. Ironic

  22. Curious that you can acknowledge the problem of non-disclosure of conflicts of interest in your PLOS Medicine May 2016 article, but maintain a blind spot on this in regards to the US CDC’s Lauri Markowitz’ involvement in the Cochrane HPV vaccine review, and her non-disclosure of conflicts of interest (as raised in my comments on your post ‘Boilover: The Cochrane HPV Vaccine Fire Isn’t Really About the Evidence – but it’s critical to Science’: https://blogs.plos.org/absolutely-maybe/2018/09/18/boilover-the-cochrane-hpv-vaccine-fire-isnt-really-about-the-evidence-but-its-critical-to-science/

  23. Hilda Bastian, you refer to the Cochrane review in process ‘Aluminium adjuvants used in vaccines versus placebo or no intervention’ (My comments on the protocol are accessible via this link: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012805/read-comments )

    What do you think about a prior review on aluminium-adjuvanted vaccines prepared by Cochrane authors, i.e. Jefferson T, Rudin M, Di Pietrantoni C. Adverse events after immunisation with aluminium-containing DTP vaccines: systematic review of the evidence. Lancet Infect Dis. 2004 Feb; 4(2):84-90: http://www.ncbi.nlm.nih.gov/pubmed/14871632

    In their systematic review, Cochrane authors Tom Jefferson, Melanie Rudin and Carlo Di Pietrantonj state: “We found no evidence that aluminium salts in vaccines cause any serious or long-lasting adverse events.” They also admit that: “Overall, the methodological quality of included studies was low”. Bizarrely, Jefferson et al conclude: “Despite a lack of good-quality evidence we do not recommend that any further research on this topic is undertaken.”

    Do you not think it odd to come to such a categorical conclusion based on data that overall was of low methodological quality?

  24. I don’t agree that a funder always drives an organization, although it certainly can, and organizations can self-censor etc in order to “not bite the hand that feeds them”. However, this dispute is about many more things than this. The Cochrane Collaboration puts a lot of effort into independence – more than average, in my opinion. Particularly independent-minded individuals are drawn to it, in partly as a result. So issues on these matters are vigorously acted on.

    In this dispute, Gøtzsche, and some/many of those who support his position, contends that Cochrane’s funding e.g. from the Gates Foundation creates such a conflict, that it compromises the organization’s ability to deal with him fairly, and with the HPV vaccine rigorously. However, Gøtzsche’s work is apparently largely funded by the Danish Ministry of Health – according to this report, with an allocation of more than US$2.8 million in the country’s 2019 budget. And the Danish Ministry of Health funds the nation’s HPV vaccination program. That in itself doesn’t make Gøtzsche incapable of an independent scientific assessment of the HPV vaccine, any more than their funding makes the Cochrane Collaboration’s teams incapable of it.

  25. I will read this, and when I can spare a few days, I will. Don’t expect it to be soon. I’ll be able to follow my own trail on this. I am not, in this, accepting any of the contentions you are making – I may or may not do so after I have looked at this thoroughly. In relation to my PhD, it’s methodological and it’s not about non-financial conflicts of interest. So it’s not actually relevant to any of this, and I think I’m really lucky to have Paul as PhD advisor.

  26. Great. I’m not expecting you to look at it soon but it would be good if you did at some point. Even more ironically i asked my friend with ME – who has been trying to get Cochrane to look at the problems with these reviews for five years – to contact Peter Gotzsche thinking he would be interested and supportive. My friend wrote a long explanation of the problems and Peter wrote a short disnissive response along the lines of “exercise is good for everything”. I was extremely disappointed and somewhat angry about Peter’s response. I think i might have also contacted you to ask if you could help…can’t quite remember now. You certainly weren’t that disnissive but you weren’t in a position to help as far as I can remember. I believe i am the only former Cochranite willing to raise it – might be wrong about that.. At least now David Tovey has started an investigation (not because of me, but because of patient and patient advocate pressure over many years).

  27. It’s terrific that Tovey (Cochrane’s editor-in-chief) is investigating, and I will try to get up to speed. Yes, you did contact me, I can’t remember when that was: it’s been on the back burner for me for ages – I think it was more than a year ago.

    Well, I would have been surprised if Gøtzsche had been interested: his pattern in recent years has been to pick up only on issues that involve being critical of industry. It’s what I meant in this post, by people who are anti-something not being pro-consumer.

    Yes, that bias about exercise is widespread, isn’t it? I think that’s partly personal socio-economic bias, and partly because exercise studies typically don’t consider adverse effects (like injury).

  28. No, I don’t think it’s odd: people come to that kind of conclusion for various reasons. The new Cochrane protocol isn’t restricted to a type of vaccine; the earlier one was. (Note: Tom Jefferson is one of the co-authors of the critique of the Cochrane review.)

  29. This has been discussed already with another of your comments – my response is here. She was neither an author of the review, nor do I believe it is established that she had a conflict of interest.

    This will be the 8th comment of yours on the subject of the HPV vaccine here at my blog. They are becoming repetitive or raising issues covered in my posts. Please note that I moderate this comment section, and may not continue to engage with you further.

    (Anyone interested in reading more of Elizabeth Hart’s opinions can do so at her blog, Over-Vaccination.)

  30. I will stop posting about this I promise. But I have to emphasise that Graded Exercise Therapy (GET) is not only largely ineffective for people with ME, it is often extremely harmful. I’m not talking about studies ignoring side-effects like injury, I am talking about people with ME being forced to take a useless therapy that may set them back and incapacitate them for months or years rather than help them recover. They are forced to take the therapy because it has been previously recommended by NICE and other users of Cochrane evidence. Policy makers who want to reduce the costs to the state of supporting people with ME force them to have GET because they have trusted the Cochrane review saying that GET is moderately effective and safe. The largest included study in the review in favour of GET is the PACE trial which is now being used in universities as an example of how not to do a randomised trial. When Peter Gotzsche shouted about the possible bias in the HPV review, Cochrane did an urgent investigation to exonerate themselves. Consumers and others have been questioning the CFS/ME reviews for FIVE years but largely because there was no shouty internal Cochranite like Peter Gotzsche, nothing has been done. Yes, it is great that finally David Tovey is taking it seriously. It is not Peter Gotzsche to blame for this because he only shouts about industry bias, (although that is extremely frustrating) it is Cochrane for wilfully ignoring any other form of bias.

  31. I wasn’t talking about GET when I said that: I was talking about the bias about exercise generally.

    I disagree that the HPV investigation was done to exonerate themselves: it was to check if a review in a volatile situation was ok to remain as it was. It’s not that unusual. I can’t speak to the situation with the CFS/ME one, but I’ll try to get a handle on it.

    I don’t agree that Cochrane wilfully ignores biases other than industry bias. For a start, there’s not much that’s uniform across all Cochrane groups: it’s a set of sub-cultures, each with their own approaches. It doesn’t ignore non-financial interests as a matter of policy – even though it’s financial/commercial interests that are regarded as conflicts. The Cochrane Handbook (Part 1, 4.5) states:

    Authors should report any present or past affiliations or other involvement in any organization or entity with an interest in the review that might lead to a real or perceived conflict of interest. Situations that might be perceived by others as being capable of influencing a review author’s judgements include personal, political, academic and other possible conflicts, as well as financial conflicts. Authors must state if they have been involved in a study included in the review.

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