1. Human Subject Research Ethics
Colleen M. Gallagher, PhD, FACHE
Chief & Executive Director, Section of Integrated Ethics
Associate Professor, Department of Critical Care

2. Definition of Research
Research is designated as an activity that permits conclusions to be drawn, and develops or contributes to generalizable knowledge.

3. Research: Code of Federal Regulation(CFR)Definition
Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.
Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

4. Human Subjects
Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains
(1) Data through intervention or interaction with the individual, or (2) Identifiable private information.

5. Clinical Care and Clinical Research
Clinical care based on individual patient well being and “best interests”
Clinical research based on developing new knowledge not individual patient well being and “best interests”

6. Human Subject Research Ethical Guidelines
1947 Nuremburg Code
1964 Declaration of Helsinki (amended most recently 2004)
1979 The Belmont Report
-Respect for persons,
beneficence, non-maleficence,
justice
1982 International Guidelines-International Organization of Medical Sciences (amended 2004)

7. Belmont Report Principles
Three basic principles
1.Respect for Persons (Autonomy):
This principle acknowledges the dignity and freedom of every person.
It requires obtaining informed consent from research subjects (or their legally authorized representatives)

8. Belmont Report Principles
Beneficence and Nonmaleficence: This principle requires that researchers maximize benefits and minimize harms associated with research. Research-related risks must be reasonable in light of expected benefits.

9. Belmont Report Principles
Non-Maleficence
One ought not to inflict evil or harm
Generally the “do nots”
Do not kill
Do not injure
Do not violate
Do not cause pain and suffering
Do not cause offense

10. Belmont Report Principles
Justice:
This principle requires equitable selection, recruitment and fair treatment of research subjects.

11. What makes clinical research ethical?
Social or scientific value
Scientific validity
Fair subject selection
Favorable risk - benefit ratio
Independent review has been conducted
Informed consent process
Respect for potential and enrolled subjects

12. Investigators Responsibilities
Follow the protocol
Submit research to the IRB and have approval prior to initiation of research
Comply with IRB policies, decisions, conditions, and requirements
Obtain and document informed consent
Provide a copy of the IRB approved consent form to each subject

13. Investigators Responsibilities
Ensure that assent is obtained from research participants who are minors (18 years of age and under)
Report progress of approved research annually
Submit any modifications to a protocol or consent form
Maintain a protocol file

14. Special Considerations Vulnerability
“When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged person, additional safeguards have been included in the study to protect the rights and welfare of these subjects”
(45 CFR b)

15. Types of Vulnerability
Incapacitational
Juridic
Deferential
Social
Situational
Medical
Allocational

16. Incapacitational
Lacks the capacity to deliberate about and decide whether to participate in the study.
Pediatric patients
Mentally/cognitively impaired

17. Juridic
Liability to the authority of others who may have an independent interest in participation in the study.
Minor – parent
Adult child – parent in some cultures
Wife – husband in some cultures
Elderly parent – adult child

18. Deferential
Given to patterns of deferential behavior that may mask an underlying unwillingness to participate.
Child to parent
Female to males
Young to elders
Deference to all doctors

19. Social
Belongs to a group whose rights and interests have been socially disvalued.
Racial/ethnic minority
Women
Disabled

20. Situational
In a situation in which medical exigency prevents the education and deliberation needed to decide whether to participate.
A number cancer patients – especially leukmias and CNS tumors

21. Medical
Selected, in part, because of the presence of a serious health-related condition for which there is no satisfactory remedies.
Many relapsed/refractory cancer patients

22. Allocational
Lacking in subjectively important social goods that will be provided as a consequence of participation in research.

23. Additional Research Risks
Pregnant women and fetuses
Research carries additional or special risks
Gestating women’s bodies may have special needs or respond differently.
Potential conflict between woman’s health needs and the fetus – what is a risk or benefit for one may not be for the other

24. Additional Research Risks
Subpart B
Require more preliminary studies (higher burden to do research) (46.204a)
Any risk is the least possible for achieving objectives of the research (46.204c)
Greater than minimal risk to fetus has to be justified by prospect of direct benefit to pregnant woman or fetus, and by the fact that there is no other means to obtain that knowledge. (46.204d)

25. Targeting for Wrong Reasons
Being asked to take participate in research because it is expedient (cheaper, more convenient, less administratively burdensome) and not for scientific reasons (condition being studied affects this group more often)
Think about Havasupai situation as an example.
Subject Selection Fairness (45 CFR a.3)

26. Targeting for Wrong Reasons
Subpart C (prisoners)
Research has to be about one of the following:
Causes, effects, etc, of criminal behavior
Prison structures
Conditions particularly affect prisoners as a class
Practices that have intent of improving health or well-being of prisoners (46.306a)

27. IRB and Vulnerability Recognize different types of vulnerability
Use different strategies to address different vulnerabilities.
Research protocol design
Empowering subjects in the research process

28. Questions Ask for Research Ethics Consultation 713-792-8775
contact one of the ethicists using the paging system