The Jewish Chronic Disease

Hospital Study

Ethics in Clinical Research

Presented By

Linda Burak Paula Fasano-Piectrazak Phylis Rusinko Janice Titano

Ethics in Clinical Research

• The Study In 1963, studies were undertaken at New York City’s Jewish Chronic Disease Hospital to develop information on the nature of the human transplant rejection process.

• The studies involved the injection of live cancer cells into patients who were hospitalized with various chronic debilitating diseases.

Ethics in Clinical Research

• Indigent elderly patients were not told they would receive cancer cells because, in the view of the investigators, this would frighten the patients.

• Allegations of fraud and deceit were demonstrated by the investigators , Drs. Southam and Mandel, upon the group of 22 patients and their families involved based upon: (a) Inadequate consents having been obtained, and (b) The assumption the injections were harmful and may produce cancer.

What Happened in the Research World?

Cumulative Affect prior to The Jewish Chronic Disease Hospital Nuremberg Doctor’s TrialNuremberg CodeDeclaration of HelsinkiInternational Ethical Guidelines for Biomedical Research Involving Human SubjectsResearchers found guilty of fraud, deceit, and unprofessional conductResignationsProbations

What Followed the Jewish Chronic Disease Study?

Establishment of the current U.S. regulatory standardsNational Research Act of 1974National Commission for the Protection of Human Subjects of Biomedical and Behavioral ResearchBelmont Report of 1979Department of Health and Human Services in 1981Food and Drug Administration and the IRB

Prior to the research study:

-- Nuremberg Code –1947

•Voluntary consent

•Benefits outweigh risks

•Ability to withdraw

Safeguards

Safeguards

• Post research study:

– Declaration of Helsinki – 1964

•Concern for the interest of the participant must prevail

– National Research Act - 1974

•Regulatory protection for human subjects

•Creation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

Safeguards

•Belmont Report – 1979– Ethical concepts of respect for

persons, beneficence and justice

Safeguards

•1980 - Food and Drug Administration –established regulations for clinical research

•Code of Federal Regulations, Title 21,

Part 50

Safeguards • 1981 - Department of Health and Human

Services (DHHS) and Food and Drug Administration (FDA) regulations

– Main Elements•Compliance with regulations•Obtaining and documenting informed consent from

all study participants• IRB membership, function, operations, and review of

research•Record keeping•Subparts that provide protection for vulnerable

subjects

Safeguards

• 1982 - Council for International Organization of Medical Research (CIOMS)

• Published “International Ethics Guidelines for Biomedical Research Involving Human Subjects”

• Designed to guide researchers from more technologically advanced countries in conduction research in developing countries

Safeguards

• 1989 - Office of Scientific Integrity (OSI) –established within the National Institute of Health

• Purpose – investigate charges of scientific misconduct and determine instances of honest errors versus actual misconduct

Safeguards•1991 – The Common Rule

•Protection of human rights

•Covered research supported by the Depts. of Agriculture, Energy, Commerce, HUD, Justice, Defense, Education, VA, Transportation, EPA, NASA, SSA, CIA, plus more

Safeguards

• 1994 – Advisory committee on human radiation experiments

• Examined cases where radiation was released into the environment for experimental purposes

Safeguards

• 1995 – National Bioethics Advisory Commission (NBAC) – is established

• 2000 – Office of Human Research Protections (OHRP) is established

How are safeguards monitored?

• Institutional Review Board (IRB)– Requires the researcher to include clear, detailed

information that addresses the regulatory requirements

– Before starting a research study – review and approval by the IRB is required (unless there is minimal risk and fits one of the defined categories).

IRB approval needed?

Common Rule - DHHS

• Definition of Human Subject:

– a living individual about whom an investigator obtains data through intervention or interaction or obtains identifiable private information, and research as a systematic investigation designed to develop or contribute to generalizable knowledge

DHHS Regulations• Human research?

Focuses on:

– Type of information collected

– Manner in which it is collected

– Procedures that guide the collection of information

– How the information will be shared

FDA Regulations• Definition of Human Subject:

– An individual, either healthy or a patient, who or becomes a participant in research, either as a recipient of the test article or as a control

• Uses “clinical investigation” rather than research– Any experiment that involves a test article and

one or more human subjects, and that either must meet the requirements for prior submission to the FDA.

Exemptions from IRB

• Observation of public behavior

• Evaluation of teaching methods

• Collection of anonymous surveys of no vulnerable individuals in which the information is not sensitive

Institutional Review Board

• Integral to ensure regulatory compliance and ethical conduct of research involving human subjects

Preparing Materials for IRB Submission

• Institution –specific submission form

• Research protocol

• Full grant application (if one is available)

• Informed consent

• All subject recruitment materials

Consequences of Scientific Misconduct

• Public retraction

• Harder to get funding in the future

• Harder to get future articles published

• Adverse media attention

• Possible license suspension

Progression of the Research

• Research not hindered

• New York Board of Regents placed Southam & Mandel on probation only, citing lack of informed consent unacceptable (1966)

• Soon after, Southam elected president of the American Association for Cancer Research

Beneficence…

Freedom from harm

Freedom from exploitation

Risks VS Benefits

Beneficence…

Respect for Human Dignity

The Right to Self-Determination

Respect for Human Dignity

Providing False Information or Withholding Information

Respect for Human Dignity

The Right to Full Disclosure

The Right to Privacy

The Principle of Justice

The Participant Can Review the Information and Agree to the Accuracy of the Content

The Principle of Justice

The Right to Privacy

All Persons Involved in Research Must Maintain Confidentiality

Informed Consent for a Research Study…

ESSENTIAL ELEMENTS

• Presence of a written document

• The purpose of the research

• Expectations from the participant including time commitment

• The known and the unknown about the research

• Risks

• Benefits

• Contact information for questions

• Other treatment options

• States that participant may choose to leave and receive standard treatments

• Protection of privacy

CONCLUSION

Integrity Starts With The Individual