History of Research Ethics Case studies Tuskegee and Guatemala Jeffrey D. Klausner, MD, MPH Professor of Medicine and Public Health Attending Physician.

History of Research EthicsCase studies

Tuskegee and Guatemala

Jeffrey D. Klausner, MD, MPHProfessor of Medicine and Public Health

Attending Physician Ronald Reagan Medical Center

Program in Global Health and Division of Infectious DiseasesDavid Geffen School of Medicine

Department of EpidemiologyKarin and Jonathan Fielding School of Public Health

August 2014

http://ph.ucla.edu/

Disclosures

Dr. Klausner is a faculty member of the University of California Los Angeles Dr. Klausner is a guest researcher with the US CDC Mycotics Diseases Branch Dr. Klausner is a member of the WHO STI advisory group Dr. Klausner is a board member of YTH.org

In the past 12 months, Dr. Klausner has received: Travel support for meeting attendance from Standard Diagnostics, Inc. His institution has received research grant funding, supplies or unrestricted gifts

from the NIH, CDC, California HIV Research Program, Hologic Inc., Alere Inc., Orasure, Inc., Cepheid, Healthvana, Inc.

[email protected]

Outline

• Quick review of ethical principles• Tuskegee syphilis experiment• Guatemala syphilis experiment• Small group discussion and report back

Research Ethical Principles

• Respect for Persons• Beneficience• Justice

http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html [1979]

Application of Research Ethical Principles

Principle Practice

Respect for Persons Informed consent

Beneficience Risks and benefits

Justice Selection of subjects

Tuskegee Study 1932-1972

• Macon County, Alabama, pop. 11,846

• To study the natural progression of untreated syphilis in rural African-American men

• US Public Health Services began the study in 1932

• Investigators enrolled in the study a total of 600 men:

• 399 who had previously contracted syphilis

• 201 without syphilis


• Research team included Tuskegee Institute, US Public Health Service doctors, Dr. Eugene Dibble and Nurse Eunice Rivers

• Men were given free medical care, meals and free burial insurance

• Study members were told they were being treated for "bad blood", a local term for various illnesses that included syphilis, anemia and fatigue


• In 1947, penicillin proven to be effective treatment for syphilis

• Study participants never specifically told they had syphilis, nor were they ever treated for it

• Researchers prevented men from being treated elsewhere

• Post-World War II research requirements changed but not the Tuskegee Study


• In 1966, Peter Buxton, a venereal-disease investigator in San Francisco, raised concerns about the study

• The CDC reconfirmed the study’s value along with

• National Medical Association• American Medical Association

• In 1972, Washington Star broke the story, followed by NY Times

• Investigation ensued and study terminated


• USG paid $9M to survivors and families• National Research Act 1974• Belmont Report (1979) included guidelines for ethics in medical

research

President Clinton ApologyMay 16th, 1997

• “…today America does remember the hundreds of men used in research without their knowledge and consent. Men who were poor and African American, without resources and with few alternatives, they believed they had found hope when they were offered free medical care by the United States Public Health Service. They were betrayed.”

• The United States government did something that was wrong—deeply, profoundly, morally wrong. It was an outrage to our commitment to integrity and equality for all our citizens... clearly racist.

Real Time with Bill Maher

March 6, 2007

Video

American J Public Health, 1991

The Tuskegee study of untreated syphilis in the Negro male is the longest non-therapeutic experiment on human beings in medical history.

The strategies used to recruit and retain participants were quite similar to those being advocated for HIV/AIDS prevention programs today. Almost 60 years after the study began, there remains a trail of distrust and suspicion that hampers HIV education efforts in Black communities. The AIDS epidemic has exposed the Tuskegee study as a historical marker for the legitimate discontent of Blacks with the public health system.

The belief that AIDS is a form of genocide is rooted in a social context in which Black Americans, faced with persistent inequality, believe in conspiracy theories about Whites against Blacks. These theories range from the belief that the government promotes drug abuse in Black communities to the belief that HIV is a manmade weapon of racial warfare. An open and honest discussion of the Tuskegee Syphilis Study can facilitate the process of rebuilding trust between the Black community and public health authorities. This dialogue can contribute to the development of HIV education programs that are scientifically sound, culturally sensitive, and ethnically acceptable.

Thomas SB, Quinn SC. The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community.Am J Public Health. 1991 Nov;81(11):1498-505.

Community Impact of Tuskegee Study

• What is the community impact?

• Distrust, conspiracy, fear• ? Lack of participation in research

and preventive health care

RV Katz et al. American Journal of Public Health June 2008; 98 (6): 1137–1142

Brandon DT J Natl Med Assoc. Jul 2005; 97(7): 951–956.

Guatemala 1946-1948

• US Public Health Service conducted syphilis experiments in Guatemala from 1946 to 1948.

• Doctors infected soldiers, prisoners, and mental patients with syphilis without the informed consent of the subjects, and then treated them with antibiotics.

• In October 2010, the U.S. formally apologized to Guatemala for conducting these experiments

Special thanks to Prof. Jonathan Zenilman, Johns Hopkins University

What Was Known? What were the Questions?

By the end of World War II, the efficacy of Penicillin for Syphilis and Gonorrhea was being determined

There was tremendous interest in preventive treatment of contacts STDs had tremendous impact on military deployability Standard medical texts of the day (eg Stokes, 1944) did not address

preventive treatment

Slide courtesy of J. Zenilman


Syphilis rates per 1000, US, 1940


The Guatemala Study Questions

Can a preventive treatment regimen be evaluated in a model where humans are infected under controlled conditions?

Comparison groups—Orvus-Mapharsen (arsenical); Penicillin (at various doses), Controls

Studies done in syphilis, gonorrhea, chancroid Sources of infected material—ground up solutions of syphilis

organisms from rabbits; or transfer of human material (TP, GC, HD) Grant approved by the Syphilis Study Section, USPHS,

February 1946


Initial Approach--Develop the Model

“Natural” infection

Commercial Sex Workers Recruited

Experimentally infected with T. pallidum

Intercourse with Prison inmates or soldiers

Evaluated immediately post coital and serially

FINDING- Infection rate low—not useful for prevention experiments


Direct Infection Model--Syphilis Subject Population-Asylum, Prisoners Infection experiments:

Evaluate pedigree T pallidum strains Swab transfer Pledgets Direct Inoculation Differences in dose, organism pedigree, swab

placement time, “adjuvants” Followed by clinical exam, multiple RPR tests, subset

lumbar punctures



NY TimesApril 27, 1947


7 months earlier…

Guatemala Discovery Timeline

2003—Dr Susan Reverby discovers Cutler records at University of Pittsburgh

May 2010—Reverby notifies the former director of the CDC—Dr David Sencer

Summer 2010—US recovers Cutler documents and starts formal review

October 2010—Formal apology to Guatemala

November 2010—President Obama directs the Presidential Commission on Bioethical Issues to investigate

August 2011—Public Hearing December 2011—Full report

Susan M. Reverby, a Wellesley College Professor


Guatemala ApologyOctober 2010

Secretary of State Hillary Rodham Clinton and Health and Human Services Secretary Kathleen Sebelius apologized to the government ofGuatemala and the survivors and descendants of those infected.

They called the experiments “clearly unethical.”

“Although these events occurred more than 64 years ago, we are outraged that such reprehensibleresearch could have occurred under the guise of public health,” the secretaries said in a statement.

“We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices.”

www.bioethics.govSlide courtesy of J. Zenilman

Discussion

• Were those syphilis studies unethical? Why?• In what situation could such studies be ethical, if ever?

• What ethical principles were violated? What procedures exist to uphold those principles?

• Tuskegee—Respect for Persons• Guatemala—Beneficience

• How did the US respond to the study findings?• How do those experiences and common history relate to

HIV/AIDS?

Discussion• Agree or disagree and why?

“The Tuskegee study of untreated syphilis in the Negro male is the longest non-therapeutic experiment on human beings in medical history. The strategies used to recruit and retain participants were quite similar to those being advocated for HIV/AIDS prevention programs today. Almost 60 years after the study began, there remains a trail of distrust and suspicion that hampers HIV education efforts in Black communities. The AIDS epidemic has exposed the Tuskegee study as a historical marker for the legitimate discontent of Blacks with the public health system. The belief that AIDS is a form of genocide is rooted in a social context in which Black Americans, faced with persistent inequality, believe in conspiracy theories about Whites against Blacks. These theories range from the belief that the government promotes drug abuse in Black communities to the belief that HIV is a manmade weapon of racial warfare. An open and honest discussion of the Tuskegee Syphilis Study can facilitate the process of rebuilding trust between the Black community and public health authorities. This dialogue can contribute to the development of HIV education programs that are scientifically sound, culturally sensitive, and ethnically acceptable.”

S B Thomas and S C Quinn. The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community. American Journal of Public Health November 1991: Vol. 81, No. 11, pp. 1498-1505.

History of Research Ethics Case studies Tuskegee and Guatemala Jeffrey D. Klausner, MD, MPH Professor of Medicine and Public Health Attending Physician.

Documents

History of Research Ethics Case studies Tuskegee and Guatemala Jeffrey D. Klausner, MD, MPH Professor of Medicine and Public Health Attending Physician.