research ethics focusing on research involving human subjects

Research Ethics

Focusing on research involving human subjects

Research & Planning2004

Session Objectives

Overview research ethics. History of research involving human

subjects. Ethical guidelines for research. Integrity in research and scholarship.


Why is human research ethics review necessary?

Protects research subjects AND

Protects researchers.Tri-Council Policy Statement (1998)

Memorandum of Understanding (2002)

“… to promote the ethical conduct of research involving human subjects.”

“. . .will consider funding (or continued funding) only to individuals and institutions which certify compliance

with this policy.”

Source: Tri-Council Policy Statement


What do we mean by “ethics?”

Ethic “A body of moral principles or values”

Ethical “of or pertaining to ethics” “in accordance with professional or moral standards

for right conduct or practice”

Ethics “a system of moral principles” “the right and wrong of certain actions and the good

and bad of such actions often embedded in a code”


What is research?

… a systematic investigation to establish facts, principles or generalizable knowledge.



What is meant by human research?

A systematic investigation to establish facts, principles or generalizable knowledge in which humans take part as research subjects. refers to any project that involves the collection of

specimens, data or information from persons, through intervention or otherwise.

included are procedures that have a low degree of invasiveness (e.g. surveys, interviews, naturalistic observations, exercise or psychometric testing, examination of patient records), as well as more invasive procedures (e.g. blood sampling, administration of a substance).



Why conduct human research?

Research involving humans is premised on a fundamental moral commitment to advancing human welfare, knowledge, and understanding, and to examining cultural dynamics.

Tri-Council p. i.4



Why research ethics? Correct past and prevent new problems and

abuses. Human subjects have not always been well

protected. Research is big business with enormous amounts

of money involved. The future impact of such issues as genetic

engineering, cloning, gene therapy, etc. is not known.

Privacy issues for individuals is a growing societal concern.

Encourage high quality research accompanied by high standards of research ethics.


MilestonesNuremberg Code 1947.

War Trials by the Allies in Nuremberg

Declaration of Helsinki 1964. World Medical Association

Belmont Report 1979. U.S. National Commission for the Protection of

Human Subjects of Biomedical and Behavioral Research

TCPS 1998 NSERC, SSHRC, CIHR


Nuremburg Code

The formal elaboration of ethical guidelines for the conduct of research involving humans began in the late 1940's.

In 1946, Nazi physicians were tried at Nuremberg because of research atrocities performed on prisoners of war.

Subsequently, in 1947, the Nazi War Crimes Tribunal issued the Nuremberg Code, which was the first internationally recognized code of research ethics.


The Nuremberg Code Voluntary consent of the participant. Results need to benefit society in some way. Human experimentation should be based on

animal research results as well as knowledge of the natural course of events.

All unnecessary mental or physical harm should be avoided.

Researchers should serve as subjects if there is reason to believe that death or injury may occur.

[from Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Nuremberg, October 1946–April 1949. Washington, D.C.: U.S. G.P.O, 1949–1953.]


The Nuremberg Code Risk should never exceed the benefits. Every precaution should be taken to protect

subjects from harm. Only qualified personnel should be allowed to

conduct experiments. Subjects must be able to withdraw from a study

at any time. The researcher must be ready to terminate the

experiment if it appears that the subjects are being harmed.

[from Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Nuremberg, October 1946–April 1949. Washington, D.C.: U.S. G.P.O, 1949–1953.]


Continuing research problems

Abuses of research subjects came to public attention in the U.S. between 1953 and 1972.

This led some people to conclude that researchers could not be trusted to conduct studies involving humans.


Infamous research studies

Tuskegee Syphilis Study (1932-72) Harvard Radiation Tests (1946 -56) Willowbrook Study (1963-1966) Jewish Chronic Disease Hospital

Study - 1963


Tuskegee Syphilis Study (1932-72)

Nearly 400 black men in Macon County, AL in 1932.

Originally a treatment/study (mercury rubs). Subjects not informed when treatment stopped. Became a “Study in Nature’ - Observe natural

history of disease. Penicillin available as treatment in 1943. Provisions were taken to prevent Tuskegee

subjects from getting penicillin. The study was exposed in 1972, the subjects

given treatment by 1973 and the treatment was extended to the families of the subjects in 1975.

Source: http://darkwing.uoregon.edu/~pmwhite/1


Harvard Radiation Tests

From 1946 to 1956, 19 boys who thought they were participating in a science club were fed radioactive milk by researchers who wanted to learn about the digestive system.

The experiments were performed at the Fernald State School in Massachusetts. Researchers from Harvard University and MIT fed radioactive forms of iron and calcium to the boys, sometimes in their breakfast milk, to study the body's ability to digest minerals.



Willowbrook Study - 1963-1966 State School for mentally challenged persons in

New York. Study natural history of infectious hepatitis. Subjects were all children who were deliberately

infected. Defended by saying that the vast majority of

them acquired the infection anyway and it was better for them to be infected under controlled research conditions.

School closed to new residents - but study took new patients - parents only able to place children there if they participated in study.



Jewish Chronic Disease Hospital Study - 1963

Injection of live cancer cells into chronically ill patients to develop information on the nature of the human transplant rejection process.

Researchers said consent was given orally but not documented because it was customary to undertake much more dangerous procedures without consent forms.

Patients weren’t told they would receive cancer cells because it would frighten the patients unnecessarily.



Declaration of Helsinki

Ethical Principles for Medical Research Involving Human Subjects.

Medical research is subject to ethical standards that promote respect for all human beings and protect their health and rights.

Every patient – including those of a control group, if any – should be assured of the best proven diagnostic and therapeutic method.


Belmont Report

RESPECT FOR PERSONS: This principle acknowledges the dignity and freedom of every person. It requires obtaining informed consent from all potential research subjects (or their legally authorized representatives).

BENEFICENCE: This principle requires that researchers maximize benefits and minimize harms associated with research. Research-related risks must be reasonable in light of expected benefits.

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

Source: http://www.rgs.uci.edu/ora/rp/hrpp/1


TCPS

Tri-Council Policy Statement

The joint policy expresses the continuing commitment of the three Councils to the people of Canada, to promote the ethical conduct of research involving human subjects.

TCPS i.1



Tri-Council Policy StatementAct of Parliament Creates Councils

1985Medical Research Council (MRC), now

CIHRNatural Sciences and Engineering

(NSERC)Social Sciences and Humanities (SSHRC)

Start of Joint Initiative 1994First Tri-Council Draft 1998


Why Protect Research Subjects?

… it is they who bear the risks of the research …


What are the guiding ethical principles?

Human DignityFree and Informed ConsentVulnerable PersonsPrivacy and ConfidentialityJustice and InclusivenessBalancing Harms and BenefitsMinimizing HarmMaximizing Benefits



A Moral ImperativeRespect for Human Dignity

It is unacceptable to treat persons solely as means (mere objects or things), because doing so fails to respect their intrinsic dignity and thus impoverishes all of humanity.

Tri-Council i.5


Research & Planning2004Source: Seattle Times


“Uniformed Consent”“PATIENTS DIED PREMATURELY in two failed clinical trials atSeattle's Fred Hutchinson Cancer Research Center — experiments in which the Center and its doctors had a financial interest. The patients and their families were never told about those connections, nor were they fully and properly informed about the risks of the experiments, an investigation by The Seattle Times has found. The patients in these trials were ill with cancers that, left untreated, would almost certainly have killed them. But many stood a good chance of survival or at least prolonged life with traditional care. Instead, many actually died from the experiments — sooner than they would have with no treatment at all. “

http://seattletimes.nwsource.com/uninformed_consent/


Free & informed consent

Free and informed consent derives from respect we owe to human dignity, for respecting persons means respecting their capacity and right to make free and informed choices.

It is also a continuing dialogical process: it starts when prospective subjects are first approached and ends when their actual involvement is over.



Formal requirementsResearch may begin only if the following conditions have been met:

Subjects need a comprehensible statement of the research purpose, the identity of the researcher, the expected duration and nature of participation, and a description of research procedures

Subjects have to be given the assurance that their participation is totally voluntary and that they have the right not to participate if they so wish

free and informed consent has been given and maintained throughout the subjects’ participation in the research



Freedom of decision

Consent must be voluntary given, without manipulation, undue influence or coercion

no deprivation no exercise of control no authority over prospective subjects no extortion of information (acting as

informants for the authorities in place)



What is the principle of minimal risk? If potential subjects can reasonably be expected

to regard the probability and magnitude of possible harms implied by participation in the research to be no greater than those encountered by the subjects in those aspects of his or her everyday life that relate to the research,

then the research can be regarded as within the range of minimal risk.



Dependency relationships

REBs and researchers should be especially careful when the research is being conducted in a dependant relationship setting: doctor conducting research with his or her

patients professor conducting research with his or

her students



Basic information package

At the commencement of the free and informed consent process, the researcher must provide subjects, or authorized third parties, with a basic information package appropriate for the subjects’ cultural settings



Privacy & confidentiality

Dignity and autonomy of human subjects is the ethical basis of respect for the privacy of research subjects

Privacy is perceived to be an essential means of protecting and promoting human dignity



Concerns about obtaining identifiable personal information

The type of data to be collected;

The purpose for which the data will be used;

Limits on the use, disclosure and retention of the data;

Appropriate safeguards for security and confidentiality;

Any modes of observation;

Any anticipated secondary uses of identifiable data from research;

Any anticipated linkage of data gathered in the research with other data about subjects, whether those data are contained in public or personal records;

Provisions of confidentiality of data resulting from the research.



Released data Researchers should ensure that the data

released does not contain names, initials or other identifying information.

While it may be important to preserve certain types of identifiers (e.g. region of residence), these should be masked as much as possible using a standardized protocol before the data are released for research purposes.



Harms and benefits

Subjects have the right to be given a comprehensible description of reasonably foreseeable harms and benefits that may arise from research participation and should be informed about likely consequences of non-action

this is especially relevant in the case of therapeutic research, or research involving invasive methodologies or research potentially resulting in physical or psychological harm



Minimal risk, human & social sciences, & biomedical sciences

Special issues are raised in clinical research, especially clinical trials, in which patients suffering from disease participate in research on interventions undertaken for purposes of therapy.

This does not mean that human and social sciences research do not pose any threat to the safety and well-being of subjects.



Right to withdrawal

They also have to know that they can withdraw at any time without prejudice to pre-existing entitlements

A physician should ensure that continued clinical care is not linked to research participation

Teachers should not recruit subjects from their classes, or students under their supervision without REB approval



What requires ethics review?

All research that involves human subjects requires review and approval by a Research Ethics Board (REB).

All human research undertaken by members of, or conducted at, RRC require ethics review by the RRC REB.


What is a Research Ethics Board (REB)?

Ensures that the highest ethical standards in the conduct of research involving human participants are maintained.

Reviews all proposed research to ensure meets ethical standards.



What is the REB composition?

REB Composition Expertise in relevant sciences (2) Expertise in ethics (1) Interest in a non-scientific area (1) Community Member (1)

Ad hoc members Substitute members

Institutional Review Boards (IRBs) in U.S.


REB decisions Types

approved as submitted; approved with suggestions for minor changes; approved with conditions (that must be met

before final approval is granted); deferred, pending receipt of additional

information or major revisions; not approved.

Notice To researchers in writing.

Approvals are for one year only. Researchers right to ask for reconsideration. Appeals.


REB authority

The RRC REB has jurisdiction over all research involving human participants.

The REB has the authority to approve, reject, propose modifications to, or terminate any proposed or ongoing research involving human participants which is conducted within, or by members of, RRC.


What are some RRC REB review guidelines? - 1 Clear who is conducting the research. Risks are minimized. Whether the risks are reasonable (balanced) in

relation to the anticipated benefits to the subjects. Informed and freely volunteered consent, including

providing for withdrawal from the research. Adequate protection of the privacy of the subjects

and the confidentiality of the information /data being obtained.

Selection and recruitment of subjects is inclusive and appropriate in relation to the research.


What are some RRC REB review guidelines? - 2 Purpose of the study is fully outlined to subjects,

or if deception is necessary, there is appropriate debriefing.

Research design is appropriate for the nature of the research.

Clarify researcher(s) position of power with subjects.

Previous REB reviews must be declared & submitted.

Methods of dissemination should be disclosed. Conflict of interest are disclosed and mechanisms

for handling outlined.


The opinion of the REB should be sought whether:

the research is conducted by faculty, students or staff, or external researchers;

the research is conducted in person or remotely (e.g., by mail, electronic mail, fax or telephone);

the information is collected directly from subjects or from existing records not in the public domain.

TCPS, Appendix 1.



The opinion of the REB should be sought whether:

the research is funded or not;the funding is internal or external;the subjects are from inside or outside

the institution;the subjects are paid or unpaid;the research is conducted inside or

outside the institution.

TCPS, Appendix 1.



The REB should be sought whether:

the research is observational, experimental, correlational or descriptive;

a similar project has been approved elsewhere or not;

the research is a pilot study or a fully developed project.

TCPS, Appendix 1.



Specific inclusion criteria

Information collected through intervention or interaction with a living individual(s);

Identifiable private information about individuals;

Information collected through naturalistic observation of humans,

Human organs, remains, tissues and body fluids, cadavers, embryos or fetuses; and/or

Written or recorded information derived from individually identifiable human subjects.



Exclusions

Use of a public database with aggregated data and /or information already in the public domain (e.g. autobiographies, biographies or public archives).

Naturalistic observation of participants in, for example, political rallies, demonstrations or public meetings where it can be expected that participants are seeking public visibility.

Preliminary, informal interviews or casual conversations that are carried out to help clarify the design of a research project.

Information gathering procedures in support of the general administration of the College.



More exclusions

Quality assurances studies, performance reviews or testing within normal educational requirements. To diagnose problems, identify appropriate

solutions, provide advice for operation management, or assess performance.

To collect data primarily designed to affect the operations of the College through affirming satisfaction with the status quo or leading to quality improvements.

Student in-class research exercises.



However . . .

All research involving human subjects must adhere to recognized ethical standards even if REB review is not required!


What is a code of ethics for Researchers?

Traditionally, codes can be cast in positive or negative language.

Expressed in RRC Integrity Policy.

Example: Research & Planning Code of Ethics at www.rrc.mb.ca/researchplan


A Positive View

Do the right thing. Tell the truth about what your work. Share your work. Be critical of your own work and the

work of others.

Source: http://www.lij.edu/education_and_research/research2001/1


Another approach: Do not lie, cheat, or steal

A code of ethics can also be formulated by forbidding certain actions. Collectively, these actions can be grouped under Scientific Misconduct.



Why have an integrity in research & scholarship policy?

To promote and advance a high standard of integrity in research and scholarship involving: careful supervision of research, including that

conducted by students; competent use of methods; adherence to ethical standards of discipline;

and the refusal to engage in or to condone instances

of fraud or misconduct. Required by external funding agencies. Define misconduct.


What is scientific misconduct?

"...fabrication, falsification, plagiarism, or other practices that seriously deviate from those that are commonly accepted in the scientific community for proposing, conducting or reporting research."



Definitions

fabrication: "making up data or results,"

falsification: "changing data or results,"

plagiarism: "using the ideas or words of another person without giving appropriate credit."



What is misconduct in research? - 2

Failure to acknowledge or recognize the contribution of others.

Use of material in violation of the Copyright Act.

Abuse of supervisory power Financial misconduct Failure to comply with policies for the

protection of researchers, human participants, or the health and safety of the public, or for the welfare of laboratory animals.

Failure to reveal any material conflict of interest,.


Role of REB

REBs take into account national and, when appropriate, international ethical standards of research on a protocol-by-protocol basis.

Protecting human research subjects is their primary responsibility.

Protection of the rights and welfare of research subjects is a high priority worldwide.


Conclusion- balance of ethics and science

Balance interest in advancing scientific knowledge with a mandate to protect the rights and welfare of people.

Ethics protects research subjects and researchers.

Sound ethics and good science are compatible.


If you want to know more …

Tri-Council Policy Statement Tutorial is

available at:

http://www.pre.ethics.gc.ca

research ethics focusing on research involving human subjects

Documents

research planning

research subjects

human research ethics

research atrocities

history of research

ethical conduct of research

high quality research

behavioral research