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Chemically Induced Psychosis Experiments: An Inhumane Paradigm in Psychiatric Research Print E-mail
Wednesday, 02 February 2000

Congressional Testimony submitted by Vera Sharav *

Statement For the Record Submitted to
The U.S. Senate Sub-Committee: Public Health & Safety
of the Senate Health, Education, Labor & Pensions Committee Hearing

Our efforts helped bring to public attention major medical ethics violations in Federally-funded research in which uninformed, vulnerable American citizens are put at high risks without justification. As a result, such individuals have often suffered severe consequences - some have lost their lives unnecessarily. Based on the evidence - including testimonies by families and patients - we believe five factors contribute to unethical human experiments:

  1. Federal regulations are silent about the limits of permissible risk in human experimentation;
  2. Failure of Institutional Review Boards (IRBs) to protect human subjects. The entire human research approval process is entrusted to researchers and their colleagues on the IRB. The inherent and documented conflicts of interest preclude the ability of IRB members to serve the interests of human subjects;
  3. The absence of a single Federal authority to guide IRBs and to ensure that human subjects are protected from preventable harm and exploitation;
  4. The absence of independent oversight and lack of enforcement mechanisms to ensure compliance with Federal regulations;
  5. The absence of accountability when Federal regulatory safeguards are violated - such as, full disclosure of the risks prior to obtaining informed consent - even when harm results.

Current safeguards do not prevent unethical, or scientifically questionable experiments from being conducted: Those at highest risk are vulnerable individuals who are ignorant about the actual risks involved or incapable of protecting themselves. Current regulatory safeguards are insufficient. In the absence of independent monitoring and oversight, or mandatory reporting of serious adverse incidents, no authorized agency maintains a record of human casualties of research. This lacuna has given rise to a culture that contradicts medical ethics: it has led some biomedical researchers to put the search for scientific knowledge above the health and welfare of vulnerable, trusting patients, requiring them to assume ever greater risks and potential long-term harm. Jesse Gelsinger was a victim of that culture - and neither the FDA, nor the special NIH Recombitant DNA Advisory Committee (RAC), nor Federal law protected him from this dangerous experiment. Given the risks - such as toxicity and animal deaths in prior experiments - this experiment should not have been approved by the IRB. Even well-meaning researchers need to have limits imposed on the level of risk human subjects are exposed to - they should not be granted rubber stamp approval. Neither Jesse nor other patients like him should have been exposed to unjustifiable high risks.

Evidence indicates that this fatal gene experiment is not unique and may be the tip of an iceberg. Its value is that the FDA's unusually thorough investigation - after Jesse's death - provides Congress and the public with disturbing, but valuable information ordinarily kept secret. The experiment sheds light on the pitfalls of inadequately regulated human research, demonstrating how the absence of an enforcement mechanism - no advisory committee, under the auspices of NIH (such as RAC), has adequate authority to protect unsuspecting, patients from experiments that cause them needless harm. This experiment clearly demonstrates why we need a National Human Subject Protection Act - with enforcement mechanisms such as are provided under the Animal Welfare Act of 1966. Now more than ever, unsuspecting citizens need to be protected from some overly aggressive researchers whose eyes are on the prize, instead of on the welfare of their human subjects.

Gene therapy experiments are not the only field in which vulnerable patients are exposed to high risks of harm, in speculative experiments with unlikely therapeutic benefits. In a May 4, 1999 letter to the President of the U.S., the National Bioethics Advisory Commission reported:

"NBAC finds that the absence of Federal jurisdiction over much privately funded research means that the U.S. government cannot know how many Americans currently are subjects in experiments, cannot influence how they have been recruited, cannot ensure that research subjects know and understand the risks they are undertaking, and cannot ascertain whether they have been harmed."

Financial conflicts of interest are rampant and recent findings by the Office of Protection from Research Risks corroborate widespread, outright lawless disregard for medical ethics standards - including Federal informed consent requirements. The Director of the Office from Research Risks acknowledges informed consent violations occur in more than 90% of cases investigated by the agency. Researchers at prestigious academic institutions, the Veterans Affairs Administration, and even at the National Institute of Mental Health fail to comply with Federal regulations, ignoring the safety of vulnerable, often disabled human subjects. Some patients, such as 18 year old Jesse Gelsinger, are not even eligible to participate according to the approved research study protocol, others are dependent mentally disabled and cannot possibly comprehend the consequences of experiments for which they are recruited.

Human subjects' lives are in jeopardy because their lives and safety depends upon oversight by local Institutional Review Boards (IRB). But IRBs operate without public scrutiny. They are compromised by major conflicts of interest. Although their mandate under Federal regulations is to protect the welfare of human research subjects, financial interests lead IRBs to circumvent ethical requirements that are meant to protect human subjects from harm. IRBs routinely approve research protocols that put patients at risk of serious, often irreversible harm. The absence of a single Federal authority to provide oversight and ensure enforcement of Federal standards, has resulted in harmful consequences.

In the field of psychiatric research, we have found evidence demonstrating that researchers are increasing the suffering of disabled patients who are being put at high risk of relapse and suicide in wholly nontherapeutic provocation experiments, known as chemical "challenge" or "probe" studies. These symptom-provocation experiments are designed to induce psychosis and "flash-back" in severely disabled patients - many of whom are recruited in an incoherent, psychotic state in hospital emergency rooms. First, patients in these experiments are subjected to abrupt withdrawal of their prescribed antipsychotic medications ("washout") - thereby causing as many as 40% to 67% to relapse. Then, rather than treating them, researchers further exacerbate their patients' excruciating symptoms with psychosis-inducing controlled substances - chemical "probes" such as: amphetamine, L-dopa, methylphenidate and the PCP-derivative, ketamine, fenfluramine, among others. Other provocation experiments expose detoxified veterans to addictive controlled drugs such as amphetamine and cocaine.

None of these experiments offer any possible benefit for the subjects, indeed such experiments clearly undermine the welfare of severely disabled patients - including veterans - who seek treatment from doctors whom they perceive as "healers."

1995: A Yale University experiment conducted at the West Haven VA is described by researchers [Laruelle, et al] as follows: Eighteen stable schizophrenia patients who were living in the community were recruited into an amphetamine experiment . Their medications were abruptly withdrawn ("washout") for at least 21 days - causing three patients to drop out "because of clinical deterioration." The report does not indicate anything about these subjects' welfare. Fifteen remaining patients were then intravenously injected with amphetamine and with radioactive substances.. The risks: "Acute exposure to amphetamine induces emergence or worsening of positive symptoms in schizophrenic patients at doses that do not produce psychotic symptoms in healthy subjects." The experiment "Induced the emergence oor worsening of positive psychotic symptoms" measured by A photo-imaging technique.

1995: A report about a ketamine experiment at the University of Maryland [Tamminga, et al] describes how nine patients responded to the intravenously administered drug, ketamine: " These data suggest that PCP ketamine-induced psychosis closely resembled the patient's own psychotic symptoms... Moreover, these psychotic symptoms were not blocked or reduced by concurrent haloperidol treatment." Furthermore, "several subjects evidenced delayed or prolonged (8 - 24 hours) psychotomimetic effects such as worsening of psychosis with visual hallucinations...." The informed consent document falsely refers to ketamine as "a medication" for schizophrenia.

The human subjects of these inhumane experiments lack the capacity to evaluate risks and potential consequences. They are especially vulnerable, since their severe mental disability prevents them from functioning independently, limiting their free choice. Therefore, such individuals need added protections for they cannot volunteer freely, or give informed consent for research - as is their human right since the Nuremberg Code. Researchers claim "chemical challenge" experiments are a means for studying the underlying pathophysiology of severe mental illness, such as schizophrenia, and that it will lead to improved treatments. In fact, these "fishing expeditions" are often done merely to give researchers an opportunity to use photo-imaging techniques to record brain receptors in action. Are experiments that undermine the welfare of human subjects morally acceptable?

NIMH bears the major responsibility for current ethical violations in psychiatric research:

As the authorized federal agency approving federal mental health grant proposals involving mentally disabled human subjects and children, NIMH is also entrusted to ensure that government support is provided only if "the rights and safety of participants of clinical research" are protected. But NIMH has been violating its public mandate and contradicting public policy: NIMH has been supporting, conducting, and funding experiments in which human rights are violated, and the welfare of disabled subjects endangered.

The agency's failure to protect "the rights and safety" of disabled research subjects, as is its public responsibility, arises from a fundamental, though undisclosed conflict of interest: NIMH's leading researchers and administrators are members of American College of Neuropsychopharmacology (ACNP), some actually serving on its governing Council. NIMH researchers have formulated lobbying strategies against federal regulatory safeguards. This conflict of interest is reflected in NIMH's January 30, 1998 response to our Freedom of Information requests for Informed Consent documents involving symptom-provoking experiments conducted at, or funded by NIMH: "NIMH is not a repository for informed consent documents; grantee institutions are not routinely required to submit copies of these records in clinical research studies."

Who then, ensures that ethical and legal safeguards are followed and that Informed Consent forms fully disclose the risks involved to comprehending subjects?

We Recommend:

I. A moratorium on non-therapeutic experiments that put patients at high risk of harm - such as abrupt drug "washout" and "provocation"experiments that have induced psychotic relapses in patients suffering from incapacitating illness. A moratorium on experiments that expose vulnerable persons to addictive drugs which may, with repeated exposure, lead to addiction and / or cause brain damage. Such experiments are being conducted on vulnerable, underprivileged persons, including children, who are unable to exercise their rights.

II. A no-fault personal injury insurance be required for every human subject of research to cover the duration of the research and one-year following completion. A $250,000 policy per subject (premiums to be paid by the sponsor/ research team/ institutions) would be an incentive to reduce unnecessary risks and would compensate individuals / family for undue harm. It would also reduce the taxpayers' burden for uninsured persons who may require costly after-care as a result of experimental adverse consequences.

III. Reconstituting Institutional Review Boards: at least 51% of IRB members should be independent scientists and community representatives not affiliated with the institution. Qualifications for members should include prior training & education in medical ethics and issues related to human subject protections.

IV Enact A National Human Subject Protection Act to provide safeguards for all human subjects in experimental research to provide regulatory safeguards for vulnerable human beings - at least equal to those currently provided to laboratory animals under the National Animal Welfare Act of 1966. Investigators must be held accountable for the conduct of the research and the well-being of the human subjects.

V. Establish an independent Federal Review Board to provide guidance and oversight for research involving vulnerable human subjects - regardless of funding source. The Board should include at least 33% non-scientists to ensure that our public policy and community values are upheld.

VI. Establish a national data bank for human subject research in order to facilitate the flow of information and progress, and to avoid unnecessary duplication of efforts, thereby minimizing the use of human subjects in experiments involving more than minimal risks. All physician- researchers should be required to report adverse incidents to this independent oversight board or to the FDA's Physician's Hotline, indicating what preventive measures have been taken to prevent other such incidents.

VII. Require an independent physician - not connected with the project - to monitor vulnerable patient-subjects in experimental research to ensure the subject's well-being, and that continued participation in the research is in the patient's interest. Medical follow-up after-care services should be described, and nature of compensation to those harmed should be stated. NBAC has adopted this position.

Bibliography submitted with testimony: Federally Funded Relapse Producing Experiments in Psychiatry: Drug Washout / Chemical Provocation - A Partial Bibliograhpy (January, 2000)

* This (slightly edited) testimony was written by Vera Hassner Sharav and originally submitted under the corporate name CIRCARE. The bibliography has been updated, and an addendum added.

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