Human Subject Research EthicsColleen M. Gallagher, PhD, FACHEChief & Executive Director, Section of Integrated EthicsAssociate Professor, Department of Critical Care

Definition of Research

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

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.

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.

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”

Human Subject ResearchEthical 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)

Belmont Report Principles

Three basic principles1.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)

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.

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

Belmont Report Principles

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

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

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

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

Special ConsiderationsVulnerability• “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 46 111b)

Types of Vulnerability

1. Incapacitational 2. Juridic3. Deferential4. Social5. Situational6. Medical7. Allocational

Incapacitational

•Lacks the capacity to deliberate about and decide whether to participate in the study.

• Pediatric patients • Mentally/cognitively impaired

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

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

Social

•Belongs to a group whose rights and interests have been socially disvalued.

• Racial/ethnic minority• Women• Disabled

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

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

Allocational

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

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

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)

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 46.111a.3)

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)

IRB and Vulnerability

• Recognize different types of vulnerability

• Use different strategies to address different vulnerabilities.

• Research protocol design• Empowering subjects in

the research process

Questions

• Ask for Research Ethics Consultation

• 713-792-8775 • contact one of the ethicists using the

paging system 404-2863