Trial By Error: Calls for Retraction of the LP Study

By David Tuller, DrPH

Last week, when I sent Dr Fiona Godlee an open letter about the untenable decision by Archives of Disease in Childhood to republish the originally reported findings from the Lighnting Process trial, I cc’d many of the 55 signatories. Now three of them–Professor Ola Saugstad from the University of Oslo, Professor Racaniello from Columbia University (and host of Virology Blog), and Professor Elisa Oltra* of Universidad Católica de Valencia San Vicente Martir–have sent their own forceful comments to Dr Godlee and the others cc’d on the original letter.

All three strongly support the case against the paper. Professor Saugstad and Professor Racaniello explicitly call for retraction. Professor Oltra* questions why such a trial was even conducted, given the paucity of information available about the Lightning Process, and calls the published report “unsustainable.”

I am reposting their comments here.

*I corrected the spelling of Professor Oltra’s name from “Ultra” in both places a few hours after posting this.

**********

Dear Dr. Godlee,

I recently signed the letter to you regarding the pediatric study of the Lightning Process conducted by investigators from the University of Bristol. The study, published in Archives of Disease in Childhood, was titled: “Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial.” [ref]

I am Professor of Pediatrics at University of Oslo and was until my retirement last year Director of Norway’s largest research institute of Pediatrics. For more than 25 years I have followed the field of ME/Chronic Fatigue Syndrome closely and visited in their homes numerous of the bed ridden ME/CSF patients in my country, those who are too sick to come to hospital.

In my opinion, the above-mentioned article must be retracted. Its reported findings have the potential to cause severe damage to young ME patients. I am surprised that a study breaking so many fundamental rules was accepted for publication, and that the journal has now decided to republish it.

I have been and still am editor and member of several editorial boards of international pediatric/neonatal/perinatal journals, including: J Pediatrics, Pediatric Research, Acta Paediatrica, Neonatology, J Perinatal Medicine, and J Perinatology. I know how important it is to not accept any manuscripts based on a study that began enrolling patients before the trial itself was registered. To change primary and secondary outcome measures during the study period is of course absolutely not acceptable. The investigators conducted the research in ways that are known to increase the chances of bias rather than reduce it. And then they did not mention in the article itself what they had actually done.

Much more could be said about this article’s other major weaknesses. In my opinion, this publication has done much damage to vulnerable ME patients and illustrates that low-quality research can be worse than no research at all. Republishing it, even with the long correction, is a serious mistake.

Sincerely yours

Ola Didrik Saugstad, MD, PhD, FRCPE
Professor of Pediatrics
Director (em) Department of Pediatric Research
Oslo University Hospital
University of Oslo
Norway

Ref
Crawley E, Gaunt D, Garfield K, et al. Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial. Archives of Disease in Childhood; 2018; 103:155-164

**********

Dear Dr. Godlee,

I have signed a letter which was sent to you on 27 August about the pediatric study of the Lightning Process entitled “Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial.”

I notice that Dr. Ola Saugstad has written you individually to express his dismay about this paper…I would like to add my voice in this follow up.

It is my opinion that this study should be retracted from publication. It breaks a number of rules that are fundamental to the conduct of clinical trials. I am concerned that the application of such findings to young ME patients might cause serious physical damage.

I am a Professor of Microbiology and Immunology at Columbia University and have followed the CFS/ME field since it was thought to be associated with a retrovirus (I am a virologist). Since then I have opened my virology blog to David Tuller who has published extensively on the topic.

The main problem with the study is that patients cannot be enrolled in a trial before the trial itself is registered. Furthermore, the primary and secondary outcome measures were changed during the trial. Even more astounding is that the authors failed to mention these incorrect clinical trial practices in the article. They are utterly unacceptable, yet you have allowed the study to remain in the literature.

As you are aware, many other scientists of repute have signed on to the original letter to you. I am sure we could have hundreds more. How many do you need before you are convinced that the work should be retracted? How much longer do you wish to risk harm to young patients? I cannot understand why you choose to leave this publication in the literature.
______________________________
Vincent Racaniello, Ph.D. | Higgins Professor
Department of Microbiology & Immunology
Columbia University, New York

**********

Dear Dr. Godlee,

I signed a letter which was sent to you on 27 August about the pediatric study of the Lightning Process entitled “Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial.”

Following the e-mails of Dr Ola Didrik Saugstad, MD, PhD, FRCPE, Professor of Pediatrics from the University of Oslo and Vincent Racaniello, Ph.D. from the Department of Microbiology & Immunology, Columbia University, New York, I would like to add some concerns to the serious flaws they already presented, which make your report unsustainable:

1. No cite is provided to reference the mainly evaluated intervention (Lightening Process or LP) in your article. The description of the intervention in the methods section is vague. A scientific protocol should be described with enough detail as for other researcher to be able to reproduce it. This requirement is not met in your paper. Moreover, I have been unable to find in Pubmed, a rigorous description, neither scientific evidence supporting the effectiveness of the “mysterious” LP method to treat any health problem. Trained as a molecular biologist, I hesitate to consider as scientific activities performed using “undefined protocols”. Therefore, I do not understand how BMJ has ended publishing this work.

2. Outcomes only included subjective instruments, therefore providing limited evidence, plus 30% of participation for questionnaire completion at three time points seems rather low for an “improving” cohort plus compromising the validity of the results. This means that 70% of the participants missed to complete questionnaires at least at one of the three time points recorded.

3. What would the reason to evaluate the cost-effectiveness of an “undefined method” with no scientifically proven effect for any health problem be? Cost-effective to who or for what? Is this science or a sales campaign of a “mysterious product”?

I would really like to find answers to all these caveats to be able to understand the reasons behind exposing children suffering ME/CFS to additional stress and the families to unfounded hopes and additional economic costs.

Sincerely,

Elisa Oltra, PhD
Professor in Cell and Molecular Biology
Universidad Católica de Valencia San Vicente Mártir
Valencia (Spain)

Comments on this entry are closed.

  • jimells 3 September 2019, 1:14 pm

    Universities could easily put a stop to all this publishing nonsense, if they could make a decision to do so, a difficult task I’m sure. If university libraries quit paying the outrageous subscription fees, the publishers would immediately shape up or go out of business. Personally I favor the latter.

    I vaguely recall that a few years ago Dr Tuller attempted to contact Richard Horton, editor of The Lancet. I also recall that Horton was reported to be away on vacation. Did he ever come back?

  • Couch Turnip 3 September 2019, 3:34 pm

    A big thank you to the 3 professors for writing these letters. I was particularly struck by point 2 in Professor Oltra’s letter because I believe it reflects that the LP researchers contacted kids who hadn’t returned their forms by phoning them in their own homes and getting them to respond to a reduced selection of questionnaires over the phone. This meant that many of the kids reported on in the study hadn’t returned all the questionnaires.

  • Graham McPhee 3 September 2019, 3:57 pm

    Thank you. It means a lot to us patients for experts to pitch in with serious, scientific objections to these abysmal studies.

  • Alicia Butcher Ehrhardt 3 September 2019, 7:51 pm

    The scientific misconduct is appalling.

  • Lady Shambles 4 September 2019, 4:57 am

    I haven’t got anything more to say wrt to detail.. I think the three correspondents covered everything. But I do think it’s more than appropriate to thank each one of them for the taking the time to do this. When academics individually make such a stand on an issue, and this one is long overdue to be retracted, it really starts to turn up the heat on those transgressing in this arena. So ‘thank you’, ‘thank you’, ‘thank you’ to each author. As a very long term patient whose ME began at puberty many years ago, I know how important it is for minors to be protected from the sort of skewed, but dangerous,nonsense Crawley et al have spewed forth.

  • Margaret Laverick 4 September 2019, 7:18 am

    I would like to say thank you to each of you for taking the time to stand up for patients against unscientific studies and those who profit from them. It’s unbelievable to me how this can continue.

  • Anil van der Zee 5 September 2019, 1:33 pm

    Absolutely fantastic letters. Thank you so much!!

  • JL 6 September 2019, 4:56 am

    Thank you, thank you, thank you.