Use of Vulnerable Populations in US Medical Research- 1950's to Present

Ethical considerations:

• Prisoners were not told what substances were being orally or dermally administered to them
• Would not directly benefit any of the prisoners actually involved
• "Greater good"
• Coerced by monetary incentives

If those with money/power/respect can do whatever they want, do you think anything has really changed today?

Reflection

Based on information we have learned from this course is it is clear there are still many research studies that do not meet ethical standards, why is this?

Consider the following current IRB criteria: Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be reasonably expected to result

Due to many different researchers views about what ends justify the means do you think faults exist in current ethical standards that allow leeway for researchers and give way to unethical studies?

The Use of Vulnerable Populations in US Medical Research

Institutionalized Children: The Tudor Study also known as the monster study 1939

Patients at The Chronic Disease Hospital

Who was the vulnerable population?

The Iowa Soldier's Orphan Home , exposed to a lot of research studies one of the children was quoted saying, "Every week somebody else from the University would come and start testing us for God knows what" (Johnson, 2006)

Mary Korlaske, an orphan that was in the experimental group wrote a letter to Mary Tudor in 2001 that said "you destroyed my life, I could have been a scientist, archaeologist or even president. Instead I became a pitiful stutterer. The kids made fun of me, my grades fell off, I felt stupid. Clear into my adulthood, I still want to avoid people to this day"

What happened in this study? Chester Southam wanted to see the affect diseases, other than cancer, had on cancer immunity. So he went to the Jewish Chronic Disease Hospital in New York where he found twenty-two patients to use as research subjects. He then proceeded to inject them with HeLa cells to observe the way their body would react to them.

What happened in the study?

The Tudor Study was designed to test if applying labels of stuttering to children with normal speech would cause them to produce a stutter. The experimental group consisted of children with normal speech who would be told they were stuttering and be asked to repeat words over and over again.

Were the subjects properly informed? And were they even competent enough to consent? These patients were not properly informed. When being told of the procedure for the study the word cancer was never used and the test was "described as a test to discover their resistance or immunity to a disease" (Langer, 1966). Also the State Attorney General at the time said that "a substantial number of the patients "had not sufficient mental or physical ability to comprehend what was being told to them or what was being done to them," and those patients with such capacity had been misled" (Lerner, 2004) therefore stating that most were not even competent enough to consent.

Inmates

What were the consequences?

As a result of the study, the children were exposed to "emotional distress and fraudulent misrepresentation" and many of them still have speech disfluencies that have greatly affected their daily lives (Reynolds, 2006).

Rules don't apply to geniuses.

Why did the director of the hospital, Mandel, allow Southam to use the patients at his hospital, which were a vulnerable population, as subjects and without receiving informed consent? In an article I found, it stated that Mandel "was alarmed by what seemed to him disastrously insufficient medical attention to the long-term ill patients" and that "the added attention would improve their care" (Langer, 1996).

After the affects of the study became known the graduate student conducting the experiment Mary Tudor, supervised by Wendell Johnson, was labeled a monster by journalist and the study became know as "the monster study"

Researcher:

Dr. Albert Kligman, MD, PhD

• researcher at the University of Pennsylvania

Specialty:

Dermatology with a focus on fungal infections

Subjects:

Inmates at the infamous Holmesburg prison in Pennsylvania

Study Period: 1950's and 60's

David Lacks: "I've always known this much: they is the doctor, and you got to go by what they say. I don't know as much as they do."

So was this experiment ethical?

William Hyman, the lawyer on the hospital's board of directors that ultimately helped end the study, said that "the issue here was whether these experimenters had the right to inject live cancer cells--harmless or not--into patients without the patients knowing that they were doing so; the ruling was that the experimenters did not have this right" (Hyman, 1966). Therefore saying this experiment was NOT ethical.

Objective:

To find the appropriate dosage of retinoic acid designed to clear acne and reduce the appearance of wrinkles on skin

Results:

• chemically-induced rough patches, then applied more than recommended doses of retinoic acid frequently on backs and faces of prisoners -> burns
• marketing and tremendous success of Retin-A a prescription-strength anti-aging cream in widespread use to this day
• civil lawsuits against Dr. Kligman for violating patent rights

• lawsuits against Ortho pharmaceuticals for unlawfully marketing directly to consumers before applying for approval by the FDA

A Discussion of Research Ethics

Four Phases of Ethical Evaluation:

Phase 1: During the 19th Century, the ethical standards, along with research designs were left almost entirely to individual researchers

Phase 2: During World War II and through the 1970's abuses came to public attention, consciousness was raised, and international ethical standards were published

Phase 3: During the 1980's-1990's new standards were put in place

Phase 4: Last five years of the 20th century procedures and concerns are at their most intricate, intense stage

Nuremberg Code of Ethics 1947

National Research Act (Required Institutional Review Boards) 1979

Nicholas Johnson stated that in vulnerable populations, such as schizophrenics, where "it is impossible to truly obtain consent, if the concern for their best interests is genuine is that served by prohibiting additional research?". In his interview he added to this comment by stating that "inability to do research could cause more human harm than allowing it"

"Inasmuch as prisoners may be under constraints because of their incarceration which could affect their ability to make a truly voluntary and uncoerced decision whether or not to participate as subjects in research, it is the purpose of this subpart to provide additional safeguards for the protection of prisoners involved in activities to which this subpart is applicable."

When asked if Southam had ever injected himself with the cancerous HeLa cells his response was "there are relatively few skilled cancer researchers and it seemed stupid to take even a little risk" (Hyman, 1966.

What has changed today in regards to ethical guidelines?

Him saying this was almost a partial admission to the fact that his experiments were unethical. If he would not inject himself with the cancer cells than why is it alright to do it to his research subjects, and even injecting some without their informed consent. No matter if there were standards at the time or no, it still seemed to me that these experimenters knew their studies were unethical and still chose to go through with them.

Office for Human Research Protections, May 2003

Nicholas Johnson

Office for Human Resource Protections (OHRP)

• If using prisoners, must be declared at the beginning of the study.
• Permitted research:
• no more than minimal risk and inconvenience to subjects
• objectives pertaining specifically to study of prisons or prisoners

as a class

• on "practices both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the subject"

What do some individuals believe to be weaknesses of new ethical guidelines?

Was research on these vulnerable populations in accordance with the ethical standards of the time?

• According to the son of Wendell Johnson it is important for critics of the Tudor study to remember that it took place 60 years ago when no ethical guidelines were in place. He states that it would be wrong to criticize the study in relation to today's standards.

University of Iowa Requirements

CITI training

• all investigators, IRB members, working with studies involving prisoners, even if unaffiliated with U of I
• online tutorial for certification in "human subject protections"

Professor of Philosophy, Richard Fumerton's Opinion on Southam's Cancer Research Studies:

Utilitarian point of view versus a Deontologist point of view: Utilitarian point of view believes that, in the big picture of things, doing experiments on what some may consider a vulnerable population is worth it in the end because what is learned can save many more people than it can hurt. Richard Fumerton told me that he views himself more as a utilitarian. A deontologist point of view is the belief that you cannot define right or wrong with good or bad consequences. This view would believe that experimenting on anyone, vulnerable population or not and with informed consent or not, is wrong and unethical.

Mary Tudor

Trolley example: What defines right or wrong? Fumerton went on to explain the trolley example to me. If a trolley was out of control and the driver had the option to pull a lever switching onto a different track that had only one person on it instead of staying on the same track, which had a group of people on it, what would be the right thing to do? Most people would chose to pull the lever switching tracks so that only one person is killed instead of multiple people, and this is the utilitarian view point. Fumerton said he believes that if the stakes are high enough a deontologist will give in to the utilitarian point of view.

• In an article published in June 2001 by Jim Dyer 84 year old Mary Tudor is quoted saying, "that was the most pitiful part- that I got them to trust me and then I did this horrible thing to them"

So in his opinion are these research studies ethical? Yes he believes that these experiments were ethical and that using a few people to save the lives of many people is worth it.

Value Assumption that the advancement in cancer research is more important than the lives of the vulnerable populations being put at risk

• It is clear from this statement that Tudor believed what she was doing was unethical.