In a recent post Infection Super-Spreaders, I outlined the disturbing publication of an article by Andrea Cipriani and colleagues that gives a green light to prescribing antidepressants to children. Prescribing antidepressants to children could even be part of Precision Psychiatry – a new Oxford University brand to complement Evidence Based Medicine.
Concerned about developments, Jim Gottstein and I wrote to the Bosses of Frontiers – normally we would have written to an editor about something like this but editing is outsourced in the Frontiers business model.
Kamila and Miriam
Kamila Markram C.E.O.
Mirjam Eckert Publishing Director
Frontiers Media SA
Avenue du Tribunal Fédéral 34
September 24th 2020
Dear Drs Markram and Eckert
On September 2nd you published an article by Andrea Cipriani and colleagues:
K Boaden, A Tomlinson, S Cortese, A Cipriani. Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment. Frontiers in Psychiatry, doi: 10.3389/fpsyt.2020.00717
For the reputation of Frontiers journals in general, a matter that will be of concern for you, for the safety of anyone taking antidepressants, children in particular, as well as the integrity of the legal system, we think this article should be retracted.
Andrea Cipriani is known personally to one of us and is a very charming man concerned we believe to do his job well. The problem we are raising here is somewhat novel in that we are not criticising the technical methods used in his study – although it can be argued these methods cannot support the conclusions he draws. But there is a more important point.
The general wisdom is that it is a bad idea to introduce a Holocaust comparison into arguments, but we are drawing here on the work of the Jewish sociologist of the Holocaust, Zygmunt Baumann, who was also a leading analyst of technique in general. Applying his insights on technical matters to this instance, we might get the following:
A Frontiers journal could conceivably publish an article on the technical specifications for a sealed rail carriage that allowing for the elimination of defecation and micturition could be used to transport animals several hundred miles ensuring that most if not all of them got there alive – without paying any heed to the fact that the animals to be transported are human.
Dr Cipriani’s article was accepted because some of your reviewers thought the technical specifications were reasonable but the material to which his techniques are applied are a set of ghost-written articles reporting the results of clinical trials to whose data there is no access. Without any consideration of the moral issue of the likely effects on people of publishing his results, the lack of access to data breaches the canons of empirical method,
The consequences of a breach of this kind, which is relatively widespread across medicine, become very clear in the case of trials done with antidepressants in children, where the entire literature has been essentially ghost or company written and where there is no access to the raw data from the relevant trials. In some cases, the data has been destroyed. In one case the mismatch between published articles claiming the trials showed the drugs worked well and are free of problems led New York State to take legal action for fraud against GlaxoSmithKline over paroxetine. In two other cases the US Department of Justice took action against companies for illegal off-label marketing where scientific evidence for their support was lacking, resulting in criminal and civil fines of $3 Billion against GlaxoSmithKline for paroxetine (at the time the largest corporate settlement with the US Dept. of Justice), and $313 million against Forest Laboratories for citalopram in 2012.
It would be a mistake to think that these actions mean the system has managed to spot the bad apples in the barrel – the articles that led to legal actions were not outliers. These trials and articles in fact were likely more ethical than many of the trials done since on which Dr Cipriani and colleagues have depended.
The upshot in the case of antidepressants used for children who are diagnosed with depression is that in fact as one of us has published, there have been 30 trials done, all negative – the greatest concentration of negative trials for any indication ever in human history – yet because of ghost-written publications and articles like Dr Cipriani’s which works from those ghost-written publications, antidepressants may now be the second most commonly taken drugs by teenage girls. The science should make this impossible – it is the ghost-written reporting on this science that has enabled it. Dr Cipriani’s attention was drawn to this, but he chose to ignore the point making him complicit in turning the science inside out, and in so doing he has made Frontiers complicit in this also.
The editor it appears thought there was no room in the Frontiers process for him to draw attention to the issues
There will be deaths as a direct result of this article. In addition to antidepressant scripts escalating rapidly in teenage girls, their suicide rate in the UK has doubled over the past 5 years.
A further concern is the knock-on effect this article will have on legal processes. One of us is a lawyer who has represented people who do not want to take medicines, most often neuroleptics, recommended to them by doctors. These doctors, operating on the basis of a ghost-written literature in which the supposed results of clinical trials are reported which hype the benefit of treatments and hide their harms, have a power they exercise routinely to deprive people of their liberty and force them to take medicines. It turns out that when the real data comes to light, the lack of benefit and the harms such people complain about correspond with what the actual data shows – and the ghost-written literature denies. This situation almost certainly contributes to the widely reported 20-25 year reduction in life expectancy for people diagnosed with serious mental illness.
At the moment, Pontius Pilate-like, the courts and inquests have washed their hands of this issue, but it only takes one judge to put some journal and publication in the firing line.
For the above reasons, we would encourage Frontiers to engage with our concerns about your publication of the Cipriani article.
David Healy MD James B. (Jim) Gottstein, Esq.
Professor of Psychiatry Pres. Law Project for Psychiatric Rights
McMaster University, Canada Alaska, USA.
As we composed this letter, the Lancet changed its retraction policy having been shamed by their publication of an article on hydroxychloroquine – see article from Guardian below. The drugs and conditions differ but the key issue the Lancet identified – access to the raw data – is the issue that concerns us and hopefully you.
The Lancet changes editorial policy after hydroxychloroquine Covid study retraction
Tue 22 Sep 2020 05.08 BST
One of the world’s leading medical journals, the Lancet, has reformed its editorial policies following a shocking case of apparent research misconduct involving the study of hydroxychloroquine as a treatment for Covid-19.
In May, the Lancet published a peer-reviewed study about the controversial drug hydroxychloroquine, which concluded Covid-19 patients who received the drug were dying at higher rates and experiencing more heart-related complications than other virus patients.
The large observational study analysed data purported to be from nearly 15,000 patients with Covid-19 who received the drug alone or in combination with antibiotics, comparing this data with 81,000 controls who did not receive the drug.
This data was recorded by hospitals around the world in a database by a US data analytics company known as “Surgisphere”, the Lancet paper said. The findings prompted the World Health Organization to halt its clinical trials of the drug, given the paper’s findings that it was linked with deaths and complications.
But days after the paper was published, Guardian Australia revealed issues with the Australian data in the study. Figures on the number of Covid-19 deaths and patients in hospital cited by the authors did not match up with official government and health department data. Senior clinicians involved in Covid-19 research told Guardian Australia they had never heard of the Surgisphere database.
Researchers from other countries identified similar issues with the data from their hospitals, and a further Guardian Australia investigation revealed doubts over whether the database used by the study authors even existed. Sapan Desai was a co-author of the paper and founder of the Surgisphere database. Following the revelations, information about Surgisphere was deleted from the internet.
It was also revealed that none of the co-authors of the paper had seen the Surgisphere data for themselves, and they said that Desai did not give them access to it even after questions about the paper were raised by Guardian Australia and the research community. The paper’s co-authors, which included a highly respected vascular surgeon, supported the retraction of the paper and distanced themselves from the data.
While the latest available data shows hydroxychloroquine does not reduce deaths among severely unwell patients in hospital with Covid-19, or reduce illness in those with moderate disease, the higher death rates among those given the drug outlined in the Surgisphere study have never been replicated.
The publication of the Surgisphere study by the Lancet meant well-controlled studies to definitely determine the drug’s efficacy in preventing or treating the virus were stopped prematurely. Given the drug has been highly politicised by figures such as US president Donald Trump, who has made numerous false claims about its usefulness against Covid-19, rigorous studies into the drug remain important.
World Health Organization studies into hydroxychloroquine resumed following Guardian Australia’s Surgisphere investigation, and the Lancet retracted the Surgipshere paper and vowed to review its publication policy. Such rapid retractions are rare, and followed pressure from the international research community who questioned how the study passed quality control processes.
The new policy, published three months after the study was retracted, requires that more than one author on a paper must directly access and verify the data reported in the manuscript.
“For research articles that are the result of an academic and commercial partnership, one of the authors named as having accessed and verified data must be from the academic team,” the policy states. “In addition, all authors will be asked to sign the author statements form to confirm they had full access to the data reported in their article and accept responsibility for submitting the article for publication.”
One of the questions raised by the publication of the Surgisphere paper was how the paper passed the peer-review process.
The Lancet has updated its peer-review policy, stating: “Editors will ensure that at least one peer reviewer is knowledgable about the details of the dataset being reported and can understand and comment on its strengths and limitations in relation to the research question being addressed.”
For studies that use very large datasets, such as the Surgisphere dataset, editors will ensure that in addition to statistical peer review, a review from an expert in data science is obtained.
“Finally, we will explicitly ask reviewers if they have concerns about research integrity or publication ethics regarding the manuscript they are reviewing,” the new policy states. The new policy is effective immediately.