http://youtu.be/z_XFfdkJXnM

There were very disturbing  cases of human subjects abuse which had been  conducted by in Imperial Japan and the Nazis during World War II and known research involving prisoners which eventually came to light at the Nuremberg Doctor’s trial.  So today there are strict policies that exist when a human being is the subject of an experiment.   Human subject research includes experiments (formally known as interventional studies) and observational studies. Human subjects are commonly participants in research on basic biology, clinical medicine, nursing, psychology, and all other social sciences.   The discussion over the ethical concerns about the use of human subjects lead to the document the Nuremberg Code which delineates what is considered ethical conduct for human subjects research.   In recent years because of advances in science and the growing effect of corporate financial and other influences there have been increasing concerns about what constitutes informed consent and other aspects research conduct.   

There have been numerous human experiments performed in the United States, which have been considered unethical, and were often performed illegally, without the knowledge, consent, or informed consent of the test subjects.

Unfortunately human beings have been used in many types of experiments including the deliberately infecting people with deadly or debilitating diseases, exposing people to biological and chemical weapons, human radiation experiments, injecting people with toxic and radioactive chemicals, surgical experiments, interrogation/torture experiments, tests involving mind-altering substances, and a wide variety of others.  Children, mentally disabled persons and prisoners were particularly singled out for this kind of abuse.  In addition persons who are vulnerable – suffering already from disease or injury, financially disadvantaged, immigrants, or from a racial minority population were targeted for use by researchers.  Research can be disguised as “treatment” but instead actually be a harmful or deadly experiment done without the patient’s knowledge or informed consent to treatment.

Although there was public outcry when these abuses were discovered and many official inquires and even congressional investigations and hearings, there have not been successful prosecutions and not even notice given to the persons who were harmed. ( For example: the Church Committee, Rockefeller Commission, and Advisory Committee on Human Radiation Experiments).  In the USA there is a code of regulations that specify ethical research conduct in the use of human subjects.  Title 45 Code of Federal Regulations, Part 46 (45 CFR 46) is the primary set of Federal regulations regarding the protection of human subjects in research and is often referred to as the common rule. It defines the laws, criteria for exemption, as well as definition and formulation of institutional review boards, though some agencies have established their own implementation of this code that supersedes portions or all of 45 CFR 46. The Department of Defense uses CFR 46 but has different exemption criteria. The Food and Drug Administration also applies a modified code that is associated with research into development of any food, drug, or medical devices.

The code establishes what is required to be considered research activities, and for participants to be considered human subjects of research. The definitions are written as such to include situations where the human is the subject of the experiment, their environment is manipulated by the researchers, and data regarding their responses are collected. If the project does not meet these definitions (or there is minimal risk to participants) then the project is exempt from IRB review and the requirements of informed consent. Generally this decision is made and documented by an IRB.

In clinical studies patients are at risk of adverse side effects, discomfort and even at risk of serious pain and death.   Those in the field of bioethics and governmental regulation discuss and decide what degree of risk is acceptable in clinical studies and how those risks should be presented to subjects and the way those risks should be balanced against the potential benefits a subject might receive.  It is assumed that the research is being conducted to produce scientific knowledge but this may not be the case, recent studies have been done to position drugs in the market place – to create slogans used in advertising.  The CAFÉ study was designed to allow AstraZeneca to claim that Seroquel was as good as the other drugs and use that in advertising.

The director of the clinical study, Dr. Olson and his co-investigator Dr. Charles Schulz got significant remuneration for their involvement in the AstraZeneca clinical study.  Dr. Olson was a paid member of the AstraZeneca "speaker's bureau," giving paid talks for the company. He had similar arrangements with Eli Lilly and Janssen, the makers of the other atypicals being tested in the CAFE study, as well as Bristol-Myers Squibb and Pfizer. Olson according to the Minnesota pharmacy board,  received a total of $240,045 from the pharmaceutical industry between 2002 and 2008, with $149,344 coming from AstraZeneca. Dr. Charles Schulz, his co-investigator and department chair, received an even greater sum: more than $571,000 from the industry, with $112,020 coming from AstraZeneca.

The Nuremberg Code is the foundation of medical ethics for doctors.  The Nuremberg Code, which was instituted following Nazi experiments on concentration camp victims. The Nuremberg Code stipulates that an "experiment should be such as to yield fruitful results for the good of society," and "the degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment."

In a recent clinical study where a patient Dan committed suicide begs the question does the Nuremberg Code and protections for human subjects apply in Minnesota.  Dan who was a human subject in a pharmaceutical clinical trial committed suicide while taking an “atypical” antipsychotic drug.  

The purpose of the clinical study was to compare the effectiveness of three "atypical" antipsychotic drugs, each of which had already been approved by the FDA: Seroquel (quetiapine), Zyprexa (olanzapine), and Risperdal (risperidone.) The study was designed and funded by AstraZeneca, the manufacturer of Seroquel, and it called for 400 subjects experiencing their first psychotic episode to take one of the three drugs for a year. AstraZeneca called it the "CAFE" study, which stood for "Comparison of Atypicals in First Episode."  In this study patients were not allowed to be taken off their assigned drug and were also not allowed to be switched to another drug if their assigned drug was not working; and it also restricted the number of additional drugs subjects could be given to manage side effects and symptoms such as depression, anxiety, or agitation. Like many clinical trials, the study was also randomized and double-blinded: Subjects were assigned a drug randomly by a computer, and neither the subjects nor the researchers knew which drug it was. Thus the patients could not give informed consent to take a particular drug.

Dan as a patient enrolled in the study  had fewer therapeutic options than they would have had outside the study.  Most studies of antipsychotic drugs specifically bar researchers from recruiting patients at risk of violence or suicide, for fear that they might kill themselves or someone else during the study.  But in this study Dan, who was mentally incapable of consenting to antipsychotic medication and who had threatened to slit his mother’s throat was a legitimate target for recruitment. During his treatment Dan stabbed himself to death in the bathtub with a box cutter, ripping open his abdomen and nearly decapitating himself.  Later, when the blind on the study was broken, researchers found that Dan was being treated with Seroquel, a drug manufactured by the study sponsor, AstraZeneca. 

AstraZeneca agreed to pay $520 million to settle two federal investigations and two whistleblower lawsuits alleging that it had marketed Seroquel illegally and concealed its health risks.  AstraZeneca faces more than 25,000 civil suits. 

The first drug used to relieve symptoms of schizophrenia, Thorazine (chlorpromazine), was developed in 1950. But it was soon found that such relief came with serious consequences and thus it was reserved only for the most serious cases of mental illness.  But today pharmaceutical companies have found lucrative ways to market these drugs while suppressing unfavorable clinical research data from human subjects and the public. For example pharmaceutical sales representatives told doctors that Seroquel doesn't cause diabetes, even though the company knew about the link to diabetes as early as 1997.   In recent litigation Eli Lilly, the manufacturer of Zyprexa settled a claim for $1.4 billion for illegal marketing and allegedly hiding the risks of that drug. Not only do antipsychotics often make patients feel sedated and sluggish  just like tranquilizers do,  but they can also cause akathisia, which is severe agitation that can be excruciating.  In addition these drugs cause irreversible "extrapyramidal" symptoms because they permanently damage areas of the brain and this causes symptoms such as the shuffling gait, rigid muscles, and involuntary lip-smacking sometimes seen in patients who have been taking the drugs for years. The antipsychotics can also cause akathisia, a type of driven, agitated restlessness that ranges from unpleasant to excruciating. Until recently, psychiatrists reserved the drugs for patients with very severe mental illnesses, but marketing efforts now have created sales that make antipsychotics were the most lucrative class of drugs in America. Seroquel alone had nearly $4 billion in sales, making it the country's fifth most profitable drug. In a recent study quoted by the New York Times (2006) it was found that nearly one in five children who visited a psychiatrist came away with a prescription for an antipsychotic drug, despite early reports of alarming side effects.  It became pharmaceutical industry practice to simply not to publish potentially damaging trials.  Most pharmaceutical clinical trials are funded by the pharmaceutical companies themselves, thus allowing them to control what is published and what is not published in medical journals. Documents unsealed in related civil suits suggest an alarming pattern of deception.  

For more on this study:

Elliot, Carl, “The Deadly Corruption of Clinical Trials” Mother Jones Magazine September/October 2010,  http://motherjones.com/environment/2010/09/dan-markingson-drug-trial-astrazeneca  Carl Elliott is a bioethics professor at the University of Minnesota.

Stefan Kruszewski, a psychiatrist sued the AstraZeneca  company for misrepresenting Seroquel’s risks and benefits.  Dr. Stefan Kruszewski was originally hired by  AstraZeneca to discuss Seroquel with other doctors for up to $1,500 per appearance.  But he found he was required to use a prepackaged slide show that contained “false and misleading information” about the drug’s efficacy.  In addition he accused the company of promoting the drug for unapproved uses and misleading the FDA, doctors and the public about the safety of the drug and its superiority to other medicines.   As a practicing psychiatrist he said that pharmaceutical sales people encouraged him to write off-label prescriptions for his patients.  Kruszewski testified many times in court against drug companies – including cases over Pfizer’s epilepsy drug Neurontin, Johnson & Johnson’s antipsychotic Risperdal, Lilly’s Zyprexa and Purdue Pharma LP’s OxyContin painkiller.

Dr. Stefan Kruszewski blew the whistle on the drug manufacturers and won  the rights to split a $45 million award after AstraZeneca Plc settled claims of illegally marketing a schizophrenia drug. James Wetta, a former company sales representative, claimed that AstraZeneca marketed Seroquel to children, prisoners and the elderly for uses not approved by regulators.   Under the False Claims Act and with the help of the U.S. Department of Justice they won their cases.  The False Claims Act lets private citizens sue on behalf of the government and share in any recovery. The U.S. government rejects about 80 percent of the federal cases, leaving it to whistleblowers to continue on their own or drop the suit. Government participation leads to settlements 98 percent of the time.  So it would help protect the public if the US Department of Justice would more actively pursue whistleblower cases.  Both these men had blown the whistle on Big Pharma before.  Kruszewski earlier sued Pfizer Inc. and would be getting  $14.5 million from a settlement last year in which Pfizer agreed to pay $2.3 billion. Wetta marketed the antipsychotic Zyprexa at Eli Lilly & Co. before joining AstraZeneca. He was in a group of whistleblowers who split about $100 million when Eli Lilly paid $1.42 billion last year to settle state and federal claims.  

References:

Voreacos, David and Cronin Fisk, Margaret, http://www.bloomberg.com/news/2010-05-12/astrazeneca-s-520-million-u-s-settlement-rewards-repeat-whistleblowers.html  AstraZeneca Case Rewards Repeat Whistleblowers With $45 Million - May 12, 2010 11:01 PM CT

The ten points of the Nuremberg Code, (all from United States National Institutes of Health)

1.  The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him/her to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonable to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.

2.  The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.

3.  The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.

4.  The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.

5.  No experiment should be conducted where there is a prior reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.

6.  The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.

7.  Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.

8.  The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.

9.  During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible.

1. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.

Reprinted from Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, Vol. 2, pp. 181–182. Washington, D.C.: U.S. Government Printing Office, 1949. Note that complete electronic copies of the Trials of War Criminals Before the Nuernberg [Nuremberg] Military Tribunals Under Control Council Law No. 10] are available online, as are most of the other proceedings from the Nuremberg Trials.

References:

1.  Mustafa Khidir Mustafa Elnimeiri MD,  Nuremberg Code: A landmark document on medical research ethics, http://www.sjph.net.sd/files/vol3i2p94-96.pdf  Sudanese Journal of Public Health: April 2008, Vol.3 (2),  Associate Professor and National Consultant of Preventive Medicine and Epidemiology, Department of Community Medicine, Faculty of Medicine, International Africa University, Khartoum, Sudan. Tel: +249912353275. e-mail: nimeiri@hotmail.com

2,  Hurren, Elizabeth (May 2002). "Patients' rights: from Alder Hey to the Nuremberg Code" (in English). History & Policy. United Kingdom: History & Policy.

3,  Trials of War Criminals Before the Nuernberg [Nuremberg] Military Tribunals Under Control Council Law No. 10

4,  Weindling, Paul: Nazi Medicine and the Nuremberg Trials (Palgrave, Basingstoke 2004)

5,  Schmidt, Ulf: Justice at Nuremberg. Leo Alexander and the Nazi Doctors' Trial (Palgrave, Basingstoke 2004)

6,  Schmidt, Ulf: Karl Brandt. The Nazi Doctor. Medicine and Power in the Third Reich (Continuum, London, 2007)

7,  Weindling, Paul (2001). "The Origins of Informed Consent: The International Scientific Commission on Medical War Crimes, and the Nuremberg Code". Bulletin of the History of Medicine 75 (1): 37–71. doi:10.1353/bhm.2001.0049. PMID 11420451. Archived from the original on 2009-10-26.

 "Quantum mechanics is very impressive. But an inner voice tells me that it is not the real thing. The theory produces a good deal but hardly brings one closer to the secrets of the Old One. I am at all events convinced that He does not play dice."

Albert Einstein

1) Code of Federal Regulation (CFR), Title 45 (Public
Welfare), Part 46-Protection of Human Subjects (45CFR46)
http://ohsr.od.nih.gov/guidelines/45cfr46.html

2) Dunn, C. M. and Chadwick, G. L., Protecting Study
Volunteers in Research: A Manual for Investigative Sites
(2002). Boston, MA: Thomson Centerwatch. ISBN 1-
930624-36-0.
Can be purchased from:
http://www.amazon.com
NIH tutorial also provides similar information:
http://www.cancer.gov/clinicaltrials/learning/page2

3) Penslar, R.L., Institutional Review Board (IRB) Guidebook, (1993). Washington, DC: ORRP-NIH
http://www.hhs.gov/ohrp/irb/irb_guidebook.htm

4) Belmont Report, April 18, 1979
http://ohsr.od.nih.gov/guidelines/belmont.html

5) Standards for Educational and Psychological Testing.
(1999). Washington, DC: AERA, APA, NCME.
To order call: (800) 628-4094. If outside US,
call (717) 632-3535, Ext. 8087
http://www.apa.org/science/standards.html

6) American Psychological Association
750 First Street, NE
Washington, DC 20002-4242
phone: 202-336-5500; 1-800-374-2721
http://www.apa.org
Information for students:
http://www.apa.org/science/infostu.html
Information regarding publications:
http://www.apa.org/publications/

7) Educational and Psychological Testing
Testing Office for the APA Science Directorate
phone: 202-336-6000
email: testing@apa.org
http://www.apa.org/science/testing.html
Many of the documents above are also available by
contacting:
Office for Human Research Protections
Department of Health and Human Services
The Tower Building
1101 Wootton Parkway, Suite 200
Rockville, MD 20852
phone: 240-453-6900; toll free in U.S.

866-447-4777
email: ohrp@osophs.dhhs.gov

"The liberty of men of goodwill, though limited in the sphere of action, is complete in that of conscience. For, having incorporated the rules into their own being, the prohibited possibilities no longer present themselves to the mind, and have not to be rejected."

Simone Weil

No nation state may suspend or violate, even in times of public emergency:

(a)    the right to life;

(b)   freedom from torture or cruel, inhuman or degrading treatment or punishment and from medical or scientific experimentation;

(c)    the right not to be held in slavery or involuntary servitude; and,

(d)   the right not to be subjected to retroactive criminal penalties as defined in the Covenant.

Customary international law prohibits in all circumstances the denial of such fundamental rights.