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By David Tuller, DrPH

BMJ seems to be in a state of paralysis over what to do about the Lightning Process study. The fact that this study was cited positively last month in a major review of pediatric CFS/ME (as the review called the illness) raises the stakes all around. The other day I sent the following letter to Dr Terry Segal, a pediatrician at London’s University College Hospital and the senior author of the review, which appeared in the journal Current Opinion in Pediatrics.

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Dear Dr Segal—

You recently co-authored a major review in Current Opinion in Pediatrics called “Child and adolescent chronic fatigue syndrome/myalgic encephalomyelitis: where are we now?” This review cites the Lightning Process as having been shown to be “effective” in treating children with the illness. The basis of this claim is a 2017 paper published in Archives of Disease in Childhood, a BMJ journal, called “Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial.” Yet the Lightning Process trial and paper are rife with serious methodological and ethical lapses that cast doubt on the validity and reliability of its reported findings.

By way of introduction, I am a senior fellow in public health and journalism at UC Berkeley’s Center for Global Public Health, which is part of the School of Public Health. I have been a journalist for decades and more recently received a public health doctorate from Berkeley. For the last few years, I have examined–and critiqued harshly–some of the research in the ME/CFS field, including the PACE trial.

I have chronicled my findings in more than 150 posts and articles on the site Virology Blog, hosted by Professor Vincent Racaniello, a microbiologist at Columbia University. I have also written about the issue for The New York Times, the health policy journal Health Affairs, and elsewhere. My investigation of ME/CFS research has been mentioned in Science, Nature, The Wall Street Journal, The Guardian, and Slate, among other publications.

In December of 2017, I documented on Virology Blog that the investigators of the Lightning Process study recruited more than half the participants before trial registration, swapped primary and secondary outcomes based on the early results, and then failed to mention these details in the published paper. The following month, I alerted Archives of Disease in Childhood to these issues in an open letter signed by more than 20 experts from Columbia, Berkeley, Harvard, University College London, Queen Mary University of London, Stanford and elsewhere.

Last June, Archives posted an editor’s note about the study, which essentially confirmed the concerns I had raised. The note also informed readers that the investigators had provided the journal with “clarifications” and that the matter was now under “editorial consideration.” It is unclear why this period of “editorial consideration” has now lasted 11 months, since it takes no more than ten minutes to verify the details from the relevant trial documentation. You and your co-authors likely did not notice this editor’s note, since it is not linked directly to the paper itself and has been placed on a separate page in the editorial equivalent of Siberia. (The publisher has not explained why the editor’s note is so obscurely located that readers of the paper are unlikely to see it.)

I have been vigorously urging BMJ to resolve the matter, so far to no avail. It is important to note that all the major medical publishers agreed more than a decade ago, as part of efforts to ensure research integrity, not to consider any trials in which participants were recruited before registration. Fiona Godlee, BMJ’s editorial director, reaffirmed her commitment to this key principle in parliamentary testimony several years ago. BMJ’s apparent unwillingness to adequately deal with this present situation raises some questions about the depth of that commitment. It also suggests that the publisher is more concerned about avoiding reputational damage than protecting the health and well-being of children. It does not make me happy to draw that conclusion, but I see no other way of reading the available facts.

Under the circumstances, it goes without saying that the Lightning Process trial cannot be appropriately cited as an authoritative source for any claims that this pseudo-scientific intervention is “effective.” I think it is especially important to highlight this point now because the National Institute for Health and Care Excellence is currently developing new guidance for the illness, which it calls ME/CFS. Your review, or future publications unwittingly promoting the Lightning Process as a credible piece of scientific research, could easily influence the opinions of those involved with the NICE process. I am therefore urging you to immediately revise your review in a way that adequately addresses the problems with the Lightning Process paper, as documented at length on Virology Blog and acknowledged more briefly in the editor’s note posted by Archives of Disease in Childhood.

This is a matter of current public health and medical concern involving members of a highly vulnerable population–children with a debilitating and stigmatizing illness. For maximum transparency, I am therefore cc-ing this letter to several people: Professor Philip Pizzo, the editor of Current Opinion in Pediatrics; Dr Godlee, BMJ’s editorial director; Professor Alan Montgomery, the senior author of the Lightning Process paper; four physicians involved in the process of developing the NICE guidance for ME/CFS; and Sue Paterson, director of legal services at Bristol University. I also plan to post this letter on Facebook and on Virology Blog.

Thank you for your quick attention to this matter.

Best–David

David Tuller, DrPH
Senior Fellow in Public Health and Journalism
Center for Global Public Health
School of Public Health
University of California, Berkeley

By David Tuller, DrPH

Two weeks ago, I exchanged e-mails with Professor Roger Jones, editor of the British Journal of General Practice. I asked him to correct a false statement in an editorial about the cost of so-called medically unexplained symptoms to the National Health Service.

In response, he invited me to send in “one or two short sentences” that the journal would consider publishing. I declined this invitation and suggested it was his and the authors’ job to fix their own mistakes. I haven’t heard back.

Although the journal published the editorial two years ago, Professor Jones rightly pointed out in his e-mail to me that the data being mis-cited were ten years old. He appeared to suggest it was therefore a waste of time to bother correcting them–although I must have been mistaken because no editor of a prominent medical journal would make such a ridiculous suggestion.

But perhaps Professor Jones has more pressing matters on his mind than dealing with dated data. As it turns out, he is a current candidate for president of the Royal College of General Practitioners.

Hey, and voting takes place this month! Here is some information about what this position entails: “The RCGP President is the ceremonial head of the College, but without executive powers, whereas our Chair…leads on strategic direction and policy at the organisation.”

I guess being RCGP president is like being the queen. Maybe you get to tilt your head and wave politely at affairs of state. I wish Professor Jones the best of luck in his electoral campaign!

In any event, I sent him the following on Sunday. I cc-d those I had previously cc-d–three members of Parliament, four doctors involved in the NICE guidance development process, the lead author of the cited paper, the lead author of the journal editorial.

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Dear Professor Jones—

I have not heard back from you about when you and/or Professor Chew-Graham intend to correct the claim that medically unexplained symptoms (MUS) among the working-age population in England account for 11% of all National Health Service expenditures. As I documented, this statement–from a 2017 editorial published in the British Journal of General Practice–is a misrepresentation of a 2010 study by Bermingham et al. That study reported that the NHS costs associated with treating working-age people in England identified as having MUS accounted for about 10% of all expenditures on that age group–a very different statistic than the one quoted by Professor Chew-Graham and her co-authors in their editorial.

As you know, I declined your invitation to send in “one or two short sentences” to be considered for publication. Publishing a letter from me would be appropriate if there were a point of dispute. There is no dispute here. The figure cited in the British Journal of General Practice is wrong. It does not conform to what was reported in the referenced article, and it needs to be corrected.

It is the responsibility of editors and authors to correct their own errors. According to its website, the British Journal of General Practice is a member of the Committee on Publication Ethics and “subscribes to the principles and guidelines” of the International Committee of Medical Journal Editors. Failure to safeguard the accuracy of the medical literature surely violates the principles and guidelines of both of these organizations. Do I really need to cite specific phrases from authoritative publishing ethics codes to make this point?

So I am asking again: When do you and/or Professor Chew-Graham plan to replace the misquotation of Bermingham et al in the 2017 editorial with an accurate description of the study’s findings? Or do you plan to leave this mistake uncorrected and ensure that future readers of the British Journal of General Practice will be misinformed about a major public health policy issue?

Best–David

David Tuller, DrPH
Senior Fellow in Public Health and Journalism
Center for Global Public Health
School of Public Health
University of California, Berkeley

Vincent travels to the European Congress of Virology in Rotterdam and with local co-host Marion Koopmans speak with Martin Beer, Stephan Gunther, and Vera Ross about their careers and their work on Lassa virus, Borna virus, and insect viruses.

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By David Tuller, DrPH

On Wednesday, I sent the following to Dr Fiona Godlee, editorial director of BMJ. The topic, once again, was the ethically and methodologically challenged Lightning Process study, which was published two years ago in Archives of Disease in Childhood, a BMJ journal. My letter was prompted by the recent appearance of a review paper that cited this Archives report and called the Lightning Process “effective.”

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Michael Rossmann, 88

Michael Rossmann, a leader in the use of X-ray crystallography and cry-electron microscopy to solve the structure of viruses, died on 14 May 2019 at the age of 88.

I met Michael many times but had the good fortune to interview him during the preparation of the fourth edition of Principles of Virology (ASM Press). In our conversation he told the story of his career, from his early years in Germany, then moving to England and later the United States, and how he became interested in structural biology.

I first met Michael in 1985 at a picornavirus meeting in Seillac, France. His group had just solved the three-dimensional structure of rhinovirus, which along with poliovirus (done by Jim Hogle and his group) was the first for an animal virus. I recall vividly his excitement while presenting the work, in particular that the structure of rhinovirus had similarities to that of a plant virus, southern bean mosaic virus! Michael had brought a wireframe model of the rhinovirus protomer (VP1, VP2, VP3, VP4) and he sat with me outside over lunch for an hour, pointing out residues that we had found (in poliovirus) to be important for infection of mice. That he was willing to spend so much time with a little known virologist speaks volumes about his passion for science.

In Davis, CA, at the annual meeting of the American Society for Virology, I was chairing a session in which Michael was talking. Backstage he said, with a smile, that he hoped I would not say anything bad about him in my introduction. This comment was a consequence of a small disagreement we had in previous years. I assured him that I would never do that in public!

I last corresponded with Michael a few years ago when we had interesting results with rhinovirus pertaining to their sensitivity to low pH. He said if we supplied virus, he would be happy to have someone solve the structure of the virus.

My one-sentence summary of Michael is that he was always intense, but also had a good sense of humor.

By David Tuller, DrPH

This wrap-up is almost two weeks late, but things keep cropping up! It goes without saying that I am extremely gratified by the support for my April crowdfunding on Berkeley’s in-house platform. The university received 1025 donations totally $103,283 for “Trial By Error.” Of those donations, the most–384–came from the UK. That was more than twice as many as the 184 donations from the US. Next came Norway and Sweden, with 107 and 104 donations, respectively, followed by Australia with 68 and–a tie!–both Canada and the Netherlands with 30.

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Vincent travels to the University at Albany to speak with Cara, Rachel, and Alex about their careers and their work on stress granules, epitranscriptomics, and arboviruses.

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By David Tuller, DrPH

Last month, I sent Sue Paterson, Bristol University’s director of legal services, a couple of e-mails seeking answers to several questions. Those e-mails can be read here and here. I cc-d a few other people.

On Friday, May 10, I received a response. This morning, I wrote back. I cc-d those I had previously cc-d, since they did not seem to have been cc-d on Bristol’s response to me. I have posted this recent exchange below.

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A risky vaccine

Dengvaxiaby Gertrud U. Rey

Dengue fever, caused by dengue virus (DENV), is of substantial public health significance in the tropics, where the virus is spread by Aedes mosquitoes. Last week the FDA announced its approval of a first vaccine for the prevention of dengue disease in endemic areas.

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By David Tuller, DrPH

Update: Not long after I posted this, I sent the following short follow-up note to Dr Jones and the others I’d cc-d:

Dear Dr Jones–

In re-reading my response to you, I noticed that I made an error in the third paragraph when I referred to the “Improving Access for Psychological Therapies” program. The proper name, of course, is “Improving Access to Psychological Therapies.” I apologize for the error. Although I doubt most people would have noticed this mistake, I felt I should be scrupulous in acknowledging and correcting it–especially since I am asking the British Journal of General Practice and Professor Chew-Graham to do the same.

Best–David

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