Human Experimentation

Origins of the Nuremburg Code

• After World War II the people involved in the mutilation of thousands of jews,germans and french were put on trial at Nurmeburg. Twenty of which were physicians part of the nazi party. They were charged with murder, torture, and other atrocities.

• They performed many experiments on these captives causing majority of them to die. These all were used to test the limits of human beings and understand their structure and function which they used to better torture etc.

• On July 1947, all 23 defendants were found guilty, seven were sentenced to death. Four American Judges presiding made a 10 point code that described basic principles of ethical behavior in the conduct of human experimentation.

• Nuremburg made it clear that some members of the medical community had abandoned the Hippocratic Oath which is to benefit the individual patient.

Main Points of Nurmeburg Code

• Informed consent should be obtained without coersion• The experinebt should be useful and neccesary• Human experiments should be based on previous ones

with animals• Physical and mental suffering should be avoided• Death and disability should not be the expected outcomes• Subjects should be protected against even the remote

possibilities of harm• Only qualified scientists should conduct the experiments• Human subject should be free to end experiment at

anytime• Scientist involved should be prepared to end experiment

at any stage

Acts and laws passed in U.S

• In 1974, the US Congress passed the National Research Act which called for requirments of informed consent and review of research by IRBs.

• The latter act then led to the creation of the National Commission for the protection of Human Subjects of Biomedical and Behavioral Rresearch.

• The National Commission then issued the Belmont Report which serves at the backbone to the US department of health and human services (HSS) and the FDA regulations involving regulating IRBs.

• The 3 fundamental principles in this report are:

1) Respect for persons 2)Beneficence and 3) Justice

• Respect for persons implies “that individuals should be treated as autonomous agents and persons with diminished autonomy are entitled to protection.”

• Beneficence implies two main rules or obligations which are 1) Do no harm 2) maximize possible benefits and minimize possible harms

• Justice pertains to who ought to “who ought to receive the benefits of research and bear its burdens”

• However, as these principles are stated in the belmont report, there is no clear procedure on how these 3 standards should be carried out

• Instead, it states that IRBs are charged with weighting these principles and deciding on how they should be applied.

• Regardless of disease condition under investigation, no medical therapy is tested in a US clinical trial without the approval of NAFDAC which is the chief agency overseeing pharmaceutical and medical device research. Their main duty is to that of the human subject, or volunteers in the clinical trials.

• It is quite common for people to be used in Nigeria and other underdeveloped countries for these various clinical trials without following neccesary procedure of clinical trials, which is abuse of human rights and the main problem in this is the lack of proper knowledge to the subject on what he or she is being given.

• It should be imperative that all subjects be aware of their rights in respect to clinical trials

Consent Process

• Proper information must be given about the procedure

• Comprehension of the procedure must be attained by subject

• Subject must volunteer once the latter guidelines are met

• Assesment of possible risks and benefits must be reviewed such as psycholgical and physical

Doctors “Duty”

• A doctors duty is to do no harm, and to come upon treatment for a patient only by a clear scientific approach but there is a potential road block for the medical community to go forward with this scientific approach- Autonomy

• A fear is that with total respect to autonomy, no potential results can come about for risk that no one would want to go forward with an experimental procedure that could possible cure them or show results on how to cure others with a potential of harm unto themselves.

Case Studies:Tuskegee Syphilis study

• From 1932-1972 African American men were involuntarily put into a study to show the affects of untreated syphilis to a population. 400 men were chosen by lying to them and saying they were being treated for “bad blood” when they were in fact being given syphilis. Allan Brandt who recounts the study in his book stated that “deceit was integral to the study”.

• Other than not receiving informed consent, these researchers, largely from the U.S Public Health Services held back and present treatment for syphilis that was in use. The experiments were scientifically pointless, subjects were deceived, useless results other than “racism”, and subjects were taken from socially deprived groups. Of Course the Belmont report was made right after the revelation of this study.

• It was not until 1997 that president clinton apologized to the families who had already suffered through generations of children being afflicted with syphilis from generations before.

Children and the Disabled

• When it comes to human experimentation where does autonomy come to play when we deal with children, mentally ill, prisoners, and with the new age of technology, the human fetus and embryo?

• When the Nurmeburg code came to play is regarded no experimentation on those who were not mentally competant and children but the Declaration of Helsinki of 1964 eliminated this exclusion is stating that consent from a legal guardian must be obtained.

• The National Commision in the 1970s was asked to review this and enact a Childrens report which stated that as long as minimal risk to the child was present, it was ok to proceed after the consent of a guardian

• But who is to say the guardian has the best intentions for the child, especially when that guardian is a doctor in a psychiatric ward who has full authority over their patients for the purpose of “treatment”?

Paul Rhamsey

• “Any Human being is more than patient or experimental subject; he is a personal subject—everybit as much a man as the physician-investigator”

• “to attempt to consent for a child to be made an experimental subject is to treat a child as not a child”

• Parents duty is to safeguard their children, but how do they define therapeutic as opposed to not?

Willowbrook Hepatitis Study

• Researchers Fed live viruses to children in this hospital• “The line of treatment and experimentation seemed to

vanish”• They injected gama globulin with the hep A and B virus to

see if their bodies would make natural antibodies varying the dosages of gama globulin which is used to induce antibodies

• Consent forms were sent out but written in such a way that would encourage parents that they were helping

• The end results did in fact show that there were two types and distinctions between Hepatitis A (MS-1) and B(MS-2), Hep B could be transmitted through intimate contact, and preventative measures in Hepatitis B

IRB’s

• IRBs can have positive and negative advantages• When it comes to research on children where it depends

upon the consent of a legal guardian, the IRB’s are there to filter out any type of research program where harm may actually come to the child/patient

• Yet, how can we fully trust these IRBs into the concept of autonomy when they try to enact rules of what they believe

• Is best for the child or any subject and how to assess minimal harm.

Randomized Clinical trials

• Taxol causes tempory regressions of tumors in 20-30% of subjects

• A doctor decides, for example, that even though this drug is still experimental and there are other non-experimental drugs that have showed positive signs, is it ethical for the doctor to put a women with ovarian cancer on this RCT?

• Is the doctor acting our of pure beneficence for the patient, or under another influence to see if this new treatment can actually work and use this data to help many other cancer patients?

• If there are possible treatments for sickness but there is a potential for a better one, under what conditions do we use the potentially better one?

AZT studies

• Many african countries could not afford AZT which helps prevent HIV transmission to children so they did a study of a less expensive version of the drug on people in Africa

• The study didn’t use control groups comparing less expensive AZT and More expensive, but rather one group had inexpensive AZT while the other had none at all?

• Is it ethical to give one group nothing when in fact you know there is a treatment that does in fact work?

Extreme Measures

• Dr. Lawrence Myrick: People die everyday. And for what? For nothing. What do we do? What do *you* do? You take care of the ones you think you can save. Good doctors do the correct thing. Great doctors have the guts to do the right thing. Your father had those guts. Dr. Guy Luthan: Those men upstairs, maybe there isn't much point to their lives. Maybe they are doing a great thing for the world. Maybe they are heroes. But they didn't choose to be. You chose for them. And you can't do that, because you're a doctor, and you took an oath. I don't care if you find a cure for every disease on the planet! You tortured and murdered those men upstairs, and that makes you a disgrace to your profession!

• http://www.imdb.com/title/tt0116259/trailers

Women

• In 1993, FDA broadened the inclusion criteria by allowing women to be involved in experimental procedures by consent

• The FDA’s reasoning was that the potential benefits of assessing the outcomes of drug effects on opposing sexes which could in turn help doctors give better information before consensus comes from either male or female about the potential side effects.

• It would potentially lower the risk of surprise deaths or side effects to women (pregnant or not)

International Issues

• The Belmont report is derived largely from the Nuremburg Codes. It is well recognized in the United States, however it has come to slow acceptance among foreign countries.

• This is due to the fact that the under lining principles of this report are the emphasis on the rights of the individual which are distinctly Western culture ideals.

• One argument for its International application is the diversity that the U.S brings with a population originally from a variety of cultures and backrounds.

Ethical Issues

• Are RCTs ethical if the subject doesn’t know there is no benefit and the researcher does?

• Can we rely on the legal guardian to make the choice of the child or mentally-ill?

• How well informed are IRBs?• How much should we rely on autonomy when making these

decisions?• Is the life of the few worth the life of the many? And who is

to decide this?