Jay D. Amsterdam: The Paroxetine 352 Bipolar Study Ethical Conduct
Edward Tobe’s comment
New comments have been submitted about misconduct in scientific research. Before the Jay Amsterdam Leemon McHenry 2020 article exposed scientific misconduct in the Paroxetine 352 Bipolar Study and provoked an outpouring of disquiet, Barry Blackwell spoke to corporate corruption in 2016.
My prior comments addressing the Amsterdam and Leemon post include: “The Iceberg of Improbity” posted to INHN Controversies on April 23, 2020; and a comment on Barry Blackwell’s comment on Jay Amsterdam and Leemon McHenry’s reply to his comment on Barry Blackwell’s comment on Jay Amsterdam and Leemon McHenry’s reply to his comment posted to the same INHN section on July 1, 2021. I also commented on Blackwell’s 2016 post on October 8, 2020, with the tagline: “Then sometime, with great luck, he will succeed.”
I was particularly moved by Mark Kramer’s 2021 comment on Samuel Gershon’s 2021 comment on Amsterdam’s collated document:
“Why isn't there an outcry from every quarter? Why aren't those who perpetrated these crimes against academia, industry and big publishing, outcast – made to pay in some way?”
I would ask why would there be an outcry? We live our lives with various illusions that offer hope, comfort, and in a group setting, camaraderie. Why forfeit the illusion?
It is a comfortable idea that big corporations and government search for avenues to help promote health and safety. Democratic governments are elected by the people and represent the people. The last sentence of the United States Declaration of Independence offers a very high standard of human behavior: “…we mutually pledge to each other our Lives, our Fortunes, and our sacred Honor.”
But there is a different standard. “Business as usual” means doing what you want as long as you can get away with it. “Business” represents a goal to achieve; “as usual” means to achieve the goal in an expedient manner without sanctions. This is especially a successful formula when the offended are not valued by themselves and by others.
From the legal correspondence of Dr. Amsterdam’s attorney, Mr. Esfandiari, we observe a bold acceptance of “business as usual”:
“On April 3, 2001, Dr. Rickels sent Dr. Amsterdam a letter discussing what he had learned during his investigation. (Attachment K.) In that letter, Dr. Rickels noted, among other things, the following information:
(1) Dr. Amsterdam was co-investigator of the trial;
(2) Dr. Amsterdam had enrolled more patients in the trial than Dr.Gyulai;
(3) The ghostwriting firm, STI, had chosen Dr. Gyulai as the paper's first author;
(4) GSK had decided to replace Dr. Gyulai as first author with Dr.Charles Nemeroff; and
(5) Academic investigators in the trial never reviewed or even saw the submitted manuscript.”
The University of Pennsylvania’s Department of Psychiatry knew about ethical violations in scholarly representation of science, yet the department wanted a vanilla “resolution” with no apparent consequence for those breaching ethical standards.
In attachment X, Bijan Esfandiari, Esq. provides information suggesting ghost writing benefitted an employee of NIH:
“According to documents, Sally Laden of STI ghostwrote the 2003 editorial for Biological Psychiatry for Dr. Dwight L. Evans and Dr. Dennis Charney. Dr. Charney was then an employee at the NIH Intramural Program and he is now Dean of Research at the Mt. Sinai School of Medicine in New-York.
“In an email to a GSK employee, Ms. Laden wrote, ‘Is there a problem with my invoice for writing Dwight Evans' editorial for the [Depression and Bipolar Support Alliance], s comorbidity issue to Biological Psychiatry?’ [See Attachment W] When the editorial was published, Drs. Evans and Charney ‘acknowledge[d] Sally K. Laden for editorial support.’ (Attachment X.)"
Authority coupled with large corporate interests is not likely to face significant consequence. Government may use its authority, often without risk, to advance the peculiar interests of some.
Between 1932 and 1972 the "Tuskegee Study of Untreated Syphilis in the Negro Male” studied 399 black men living in Tuskegee, Alabama, infected by Treponema palladium, the spirochete that causes syphilis. The researchers lied to the infected men stating that the men were being treated for health problems caused by “bad blood.” The main purpose of the study was to collect postmortem data about syphilis, and the men were considered laboratory animals. There was no effort to treat the men or to warn their families of the potential dangers of the disease. There was no informed consent. When penicillin emerged as the treatment of choice for syphilis in 1940s, none of the subjects were offered penicillin.
The consequences to the families included 40 wives became infected with the syphilis spirochete and 19 children were born with congenital syphilis. The study involved John A. Andrew Memorial Hospital located in Tuskegee, Alabama, the Tuskegee Institute, the Alabama State Board of Health, the Macon County Health Unit, United States Public Health Service (USPHS), Centers for Disease Control and Prevention (CDCP) and the United States National Institute of Health. There were no legal consequences for those conducting the 40-year study (Tobe 2017).
Fraud is easier and more acceptable when performed on something less valued. What is not valued is usually not as well documented. In the Tuskegee experiment, the subjects of the study were not valued; those conducting the study were associated with national and state government, large corporations and universities. Protection is assumed.
The treaty between the Canadian government and the First Nations included a provision that after 1920 there was mandatory education of the First Nations children presumably on the Reserves. But residential schools for education were established distant from home, not on the reserve, with mandatory attendance. The schools aimed for a complete cultural transformation of the child. The conditions of some schools were compromised. About an estimated 150,000 First Nations, Métis and Inuit children who were taken from their home and attended Indian Residential Schools. Many parents did not know their child died. Deaths were not regularly documented. There are estimates of 4,100 child deaths at the Indian Residential Schools; however, recently discovered mass grave sites raise more questions.
Recently, after almost 100 years, Canada has attempted to address the explosion of information. Over many years there was no public outcry because the First Nations people were not valued. Famous athletes were followed, but not the fate of dehumanized people (Eshet 2915; Hill-MacDonald 2017; Honderich 2021).
Pertinence of remarks to fraud in psychiatric research
The vulnerability for fraud includes people or subjects that are disparaged, dehumanized. The subject of the fraud is not valued and documentation is either obscure and easily manipulated.
Mental illness has historically been perceived as shameful, poor behavior, volitional or a minacious ghost to chain to the wall. It was fear of the lunatics that led to the founding of Pennsylvania Hospital. Although there was hope that good care would relieve some madness, lunatics were confined to barred cells in the basement of the building. In 1828, William Malin, a clerk and librarian at Pennsylvania Hospital noted the morbid curiosity of the public to see mad people (Gamwell and Tomes 1995).
The fear of madness, like all fears, is handled in a limited number of ways. When dealing with the very mentally ill, fear also includes helplessness and hopelessness. Devaluation of what is feared is a common method of responding to fear. Observing madness from a safe distance provided an opportunity to scoff at what was once intimidating.
The science of mental illness lacks replicable biological markers for many psychiatric disorders. Published pharmacological studies or reviews of the literature about mood disorder are based upon a phenomenological presentation of patient history and some observations. The rating scales in mood disorder assume merit not established by biological marker. Expressed concern exists about the alliance between the United States Food and Drug Administration, the American Psychiatric Association and the pharmaceutical industry. Although the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders is influential in clinical practice, there are those who raise another diagnosis “Conflict-of-Interest Disorder” (Cosgrove 2010; Cosgrove, Bursztajn and Krimsky 2009; Frances 2012). There are members on the panels creating the DSM with ties to pharmaceutical industry. These members do not recuse themselves when discussion or decision is made that might be relevant to their economic allegiances. The diagnostic system shows significant overlap in signs and symptoms and responses to psychotropics. Perhaps a preferable concept would be a Modulation System Disorder (Tobe 2000).
The extraordinary incidence of placebo speaks negatively to the merit of drug studies in the scientific investigation of mood disorder. The very methodology of studies creates an opportunity to economically advantage a very unsophisticated system. Many studies struggle to show superiority of drug over placebo in achieving a 50% response on a rating scale. This is different from response to antibiotics or antihypertensives.
Joseph Schildkraut recognized “the significant effects which social and interpersonal factors have on the clinical response to antidepressant drugs” (Schildkraut 1965).
My assertion that psychiatry is not currently well regarded is demonstrated by the pervasive presence and acceptance of a procedure called a medication check. Thousands of psychiatrists perform and bill for this procedure. This procedure is now a standard of care whether declared not. The “med check” is performed by the psychiatrist perhaps every few weeks or months.
The med check restricts the thoroughness and importance of determining emotional stability of the patient, examination for blood pressure, extrapyramidal signs, weight changes, appropriate laboratory studies, interim personal family and work history, interim medical history, and current medication evaluation. The patient is prescribed a drug that affects their central nervous system. How serious could mental illness possibly be! Commonly, the patient is sent to a counsellor for therapy, to reveal their lives and ask for help. The counsellor is often perceived as the real doctor and why not!
Doctor in Latin means “a teacher” from docere, “to teach” (Webster's 1975). As a contrast to the med check, allow one possible translation of Hippocrates’s Epidemics, Book I, Section XI, which reads “Declare the past, diagnose the present, foretell the future; practice these acts. As to diseases, make a habit of two things – to help, or at least to do no harm.”
To summarize, the lack of outcry about fraud in psychopharmacological research reflects a vulnerable area of science where forces of powerful economic interests may advantage without consequence. There continues to be a devaluation of the mentally ill.
Psychiatrists and organized psychiatric associations have allowed pharmaceutical companies and insurance companies to guide them adding further to the denigration of the science of psychiatry.
Mark Kramer’s success was to follow a path of dignity possessing both scientific and musical talent. To be able to not only hear but to listen to the music of life as we travel through this voyage is an accomplishment.
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Tobe E. Comment (Barry Blackwell: Corporate Corruption in the Psychopharmaceutical Industry). inhn.org.controversies. October 8, 2020.
Tobe E. Comment on Barry Blackwell’s comment on Jay Amsterdam and Leemon McHenry’s reply to his comment (Jay D. Amsterdam and Leemon B. McHenry: The Paroxetine 352 Bipolar Study Revisited: Deconstruction of Corporate and Academic Misconduct). inhn.org.controversies. July 1, 2021.
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May 5, 2022