Historical Origins of
Institutional Review Boards and
Human Research Protections
Susan M. Loess-Perez, MS, CIP, CCRC, Director of
Research Compliance
Office of Research Services
DePaul University
Graduate Thesis and Dissertation Conference
February 6, 2016
Outline
Historical cases/examples
 Reactions/results

◦ The Belmont Report
◦ The Regulations
Current perspective
 What is instore for the future

Timeline of Events
1979
Belmont
Report
1962
KefauverHarris
Amendments
1947
Nuremberg
Code
1950-60s
Thalidomide
1963-66
Willowbrook
1944-1974
US Radiation Experiments
Stanford
Prison Study
1971
1972
Syphilis Study
exposed-1973
stopped
2000
1966
Beecher
1990
1963
Milgram
Study
1980
1970
1946-1948
Guatemala
Syphilis
Study
1991
Common
Rule
1974
NRA
1960
1950
1940
1930
1946-47
Nuremberg
Doctors
trial
1932
Syphilis
Study
begins
1964
Declaration
of Helsinki
1981
DHHS and
FDA
regulations
1999
Jesse
Gelsinger
Un. Penn.
2001
John
Hopkins
Nazi War Crimes

Nazi medical experiments
◦
◦
◦
◦
Prison camp internees
No voluntary consent
Vacuum chambers to simulate high altitudes
Immersing in ice water or sub-freezing for 12 to 14
hours
◦ Wound, burns, amputation,
◦ Chemical or biological agents
◦ Mortality rates 25-40%

Nazi Doctors Trial (1946-1947)

Nuremberg Code (1947)
The Milgram Study-Yale (1963)
 Obedience
and response to
authority
 Asked questions - shocked if wrong
 60% of subjects were persuaded to
give shocks up to the highest level
 Deception
 Social psychological risks- extreme
psychological stress on subjects
Thalidomide Drug Use and Birth
Defects (1950-1960s)
 Approved
European sedative -1950s
 Not FDA approved in US
 No damage to mother…, but fetus…
◦ First trimester
 Led to FDA Drug Amendments
◦ Kefauver-Harris Amendments -1962
U.S. Public Health Service Syphilis
Study (Tuskeegee) (1932)
 200-300 black males age 25 or older
 Effects of the untreated disease
 In 1943 penicillin discovered
 By 1951 penicillin was widely
available
 Exposé by Jean Heller 1972
 Study not stopped until March 1973
Willowbrook Hepatitis Study (19631966)
 Willowbrook
was a State School for
Mentally retarded children.
 Children injected with live hepatitis virus
 Parents told - vaccination
 Example of coercion
◦ Enrolled children moved up the list to
be eligible for the school
 Also a vulnerable population
Jewish Chronic Disease Hospital
(1963)
Cancer-free, severely debilitated patients
 Injected with live human cancer cells
 Studying human transplant rejection
 Oral consent, but patients were not
informed
 Science not understood
◦ Doctors thought the cells would be
rejected
 A vulnerable population

Tearoom Trade Study (Mid-1960s)
Studied men who had sex in public
restrooms
 Researcher volunteered as look-out
 Traced license plate numbers
 Pretended to be a healthcare worker and
visited their homes
 Issues related to privacy, deception, and
consent

Henry Beecher New England
Journal of Medicine Article (1966)
 Summarized
22 research studies that
involved questionable ethics
 Included Willowbrook study, Jewish
Chronic Disease Study,
Transplantation of melanoma from
mother to daughter, and a trial with
placebo versus penicillin for strep
throat (penicillin was standard of
care)
Stanford Prison Study (1971)

PI Phillip Zimbardo

Studied psychological effects of becoming a prisoner or prison guard

Of interest to US Navy and Marines to understand conflict between
military guards and prisoners

Guards enforced authoritarian measures and psychologically tortured
prisoners, prisoners accepted the abuse and ultimately harassed other
prisoners, and the PI (the jail superintendent) allowed abuse to continue

Original theory was inherent personality traits were the cause of abusive
behavior, but the actual results showed that the situation rather than the
personality cause the issues.

PI argued results similar to Milgram study in that normal ordinary people
went through these changes, especially since the subjects were chosen as
the most psychologically stable and healthy

Prisoners not allowed to leave even though told research was voluntary

Suggested need for immediate debriefing process
Human Radiation Experiments


During Clinton administration (1993)
Clinton requested an investigation
◦ Hospital patients, children, and soldiers,
◦ Often without consent or permission
◦ 1944-1974



Congressional report noted 13 more cases
Government funding at major universities
Created Advisory Committee on Human
Radiation Experiments (ACHRE) report
◦ Led to National Bioethics Advisory Commission
(NBAC)-Replaced by Secretary's Advisory
Committee on Human Research Protections
(SACHRP)
Guatemala Syphilis Experiments
(1946-1948)
In 2005 a professor at Wellesley College found
documentation of the Guatemalan experiments
 US Public Health service led experiments with
about 1500 soldiers, prostitutes, and prisoners,
and mental patients infecting them with syphilis
and other sexually transmitted diseases. Infected
prostitutes paid to have sex with prisoners.
 In 2010, the US government formally apologized
 In 2011 Presidential Commission found, “the
experiments involved unconscionable basic
violations of ethics as judged against the
researchers’ own recognition of medical ethics of
the day.”

Other more recent cases

University of Pennsylvania Gene Transfer Experiment
(1999)
◦ Jesse Gelsinger, age 18, dies as result of gene transfer
study
◦ The PI and the institution
 Significant financial interests
◦ Conflict of interest now in the fore front

John Hopkins Healthy Subject Death (2001)
◦ Healthy female volunteer age 24 - Died
◦ No IND
 Approved as tablet - Approval withdrawn
 New use inhaled - never been used
◦ Inadequate risk disclosure
◦ Failure to report unanticipated problems
◦ Revisions to the protocol - no IRB approval
◦ Investigators failed to resolve problems with one subject before
enrolling and treating another
Wikipedia List of additional
unethical research in US history

https://en.wikipedia.org/wiki/Unethical_hu
man_experimentation_in_the_United_St
ates
Timeline of Events
1979
Belmont
Report
1962
KefauverHarris
Amendments
1947
Nuremberg
Code
1950-60s
Thalidomide
1963-66
Willowbrook
1944-1974
US Radiation Experiments
Stanford
Prison Study
1971
1972
Syphilis Study
exposed-1973
stopped
2000
1966
Beecher
1990
1963
Milgram
Study
1980
1970
1946-1948
Guatemala
Syphilis
Study
1991
Common
Rule
1974
NRA
1960
1950
1940
1930
1946-47
Nuremberg
Doctors
trial
1932
Syphilis
Study
begins
1964
Declaration
of Helsinki
1981
DHHS and
FDA
regulations
1999
Jesse
Gelsinger
Un. Penn.
2001
John
Hopkins
Nuremberg Code 1947
10 items in the Code
 Voluntary consent “essential”
 For good of society not possible by other
methods
 Based on animal studies or other evidence
 Designed: avoid unnecessary suffering/injury
 Do not conduct if death or disability may
occur
Nuremberg Code 1947
(cont)
 Degree of risk not to exceed importance
of problem
 Proper preparations and adequate
facilities to protect against injury, disability,
or death
 Scientifically qualified persons
 Subject should be able to stop
 Scientist should be prepared to stop
Declaration of Helsinki- 1964

Expands upon principles in Nuremberg Code
◦ But again, only medical research

Introduces ethical guidelines:
◦
◦
◦
◦
◦
◦
◦
Written protocol
Ethical review board review
Ongoing monitoring
Awareness of undue duress
LAR for mentally incapable or minor subjects
Relaxes consent requirement from Nuremberg Code
Minor assent
Belmont Report

1974 National Research Act
◦ regulations
◦ informed consent and review by IRBs

Established the National Commission for the
Protection of Human Subjects of Biomedical
and Behavioral Research
◦ 1979, Belmont Report.

1981: DHHS and FDA regulations
◦ Based upon Belmont Report

1991 The Common Rule
Belmont Report
◦ Respect for Persons
 Informed consent
◦ Beneficence
 Do not harm, maximize benefits,
minimize risks
◦ Justice
 Selection of subjects
Regulations

Code of Federal Regulations (CFR) 45,
Part 46
◦ http://www.hhs.gov/ohrp/humansubjects/guidance/45c
fr46.htm

FDA-CFR 21, Parts 50, 56
◦ http://www.fda.gov/oc/gcp/regulations.html
Parts of the Federal Regulations

Subpart A
◦ Exemptions, IRB membership and procedures, IRB
responsibilities, informed consent
Subpart B- Special protections for pregnant
women, human fetuses, and neonates
 Subpart C- Special protections for prisoners
 Subpart D-Special protections for children


Subpart F (New)- IRB registration
The Purpose of the IRB

A committee that has been formally
designated to approve, monitor, and
review biomedical and behavioral
research involving humans with the aim to
protect the rights and welfare of the
research subjects.
Current Perspective- Human
Subject Protection Program
Human Subjects
Protection Program
FWA Institution
Office of Research Services
Institutional Review Board
Researchers
Local Review
Boards/Departmental
Review
Support Offices
• ORS-Grants and Contracts
•Compliance
•Billing
•General Counsel
What is instore for the future?
Advanced Notice of Proposed Rule
Making (ANPRM)-July 26, 2011
 Notice of Proposed Rule MakingSeptember 8, 2015- deadline for
comments January 6, 2016

Contact Information
Office of Research Services
DePaul University
1 East Jackson Blvd.
Chicago, IL 60604
Office Location: 14 E. Jackson, Suite 1030
General Research Protections Email box:
ORP@depaul.edu
IRB Webpage: https://offices.depaul.edu/ors/researchprotections/irb/Pages/default.aspx
Susan Loess-Perez Phone: 312-362-7593
Email: sloesspe@depaul.edu
Q &A