human subject protection committee on the use of human subjects in research harvard university * a...

Human Subject Protection

Committee on the Use of Human Subjects in Research

Harvard University *

A program designed for faculty, staff, and students involved in research using human subjects.

*Modified by the Kennedy School of Government December2001

Welcome to the HumanSubject Protection Training Program

This program should take less than one hour to complete. At the end of the program you will be asked to send an email message confirming your completion of the tutorial to your PAC/SYP Seminar Leader and to Julie Wilson, Chair of the KSG human subjects advisory committee.

This on-line exercise presents a survey of important issues relating to the conduct of research involving human subjects.

The following topics will be addressed:• Definitions of research involving human

subjects• History• Ethical principles• University and federal rules regarding the

use of human subjects• Roles and responsibilities• Informed consent• Special categories of research and research subjects

At the end of the course is a bibliography and a list of useful web sites where further information is available.

Definitions

Research is a systematic investigation designed to develop or to contribute to generalizable knowledge. A research investigator may be faculty, student, or staff. The intent of the project need not be to generate results for publication.

Definitions

Research may involve direct interactions, such as obtaining data by taking medical histories, or other interview procedures, or administering psychological tests, ordrawing blood samples or collecting saliva samples, or conducting other diagnostic procedures.

Definitions

Research may also involve indirect interactions, such as the analysis ofspecimens or data already obtained from people (either by you or by others).

Definitions

A human subject is a living individual from or about whom an investigator conducting research obtains data through intervention or interaction,or identifiable private information.

Definitions

Intervention includes both physical procedures for data gathering (venipuncture, EEG recordings, etc.)and manipulations of the subject or the subject’s environment that are performed for research purposes.

Definitions

Interaction includes communication or interpersonal contact between investigator and subject.

Definitions

information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place.

Definitions

Private information includes

Private information also includes information that has been provided for specific purposes by an individual, and which the individual can

Definitions

Smith, John

reasonably expect will not be made public (for example, a school or medical record or a loan application).

Note that private information must be individually identifiable — that is, the identity of the subject is or may readily be ascertained by the investigator, orassociated with the information — in order for obtaining the information to constitute research involving human subjects.

Subject #2

John Smith

Brfnrfl anf

flibr snosmf

wacihod ….

Definitions

Would the following activities be considered research involving human subjects ?

A telephone survey of middle school teachers in the Greater Boston area to learn about television watching habits

Definitions

Yes, because it is a systematic investigation with interaction between the investigator and the subjects

Would the following activities be considered research involving human subjects ?

A telephone survey of middle school teachers in the Greater Boston area to learn about television watching habits

Definitions

Review of patients’ emergency room records to determine the relationship between age and type of traumatic injury

Research involving human subjects?

Definitions

Review of patients’ emergency room records to determine the relationship between age and type of traumatic injury

Yes, because it is a systematic investigation in which the investigator is obtaining identifiable private information (from the subjects’ medical records)


Definitions

Videotaping a Memorial Day Parade to determine later which groups provoked the most enthusiastic spectator response.


Definitions

Videotaping a Memorial Day Parade to determine later which groups provoked the most enthusiastic spectator response.

Probably not. Some subjects’ images may be identifiable, but there is no interaction between the investigator and the subject, and the activity occurs in a public place.


Definitions

Collection of blood samples from needle exchange program participants to determine HIV status


Definitions

Collection of blood samples from needle exchange program participants to determine HIV status

Yes, because there is interaction with subjects and an intervention (drawing blood)


Definitions

Interviewing Bruce Springsteen about the songs he played on his recent concert tour


Definitions

Interviewing Bruce Springsteen about the songs he played on his recent concert tour

Probably not. There is interaction, and the subject may be clearly identifiable, but the activity is not designed to yield generalizable knowledge.


Definitions

An Institutional Review Board (IRB) is a federally-mandated committee established to review and approve research involving the use of human subjects.

There are three IRBs at Harvard, each a standing committee of the faculty.

Definitions

• Human Subjects Committee (serving the School of Public Health)

• HMS/HSDM Committee on Human Studies (serving the Medical School and the School of Dental Medicine)

• Committee on the Use of Human Subjects in Research (serving the Faculty of Arts and Sciences, Graduate School of Education, Kennedy School of Government, and all other non-medical professional schools and institutes)

Definitions

Background

At least three parties have legitimate interests in any research venture involving human subjects: the investigator who initiates it, the society that provides the conditions for it, and the subjects who participate in it.

Background

Ultimately, if the study is important, their interests do not conflict, but in the short range they can and often do. Sad experience has demonstrated that able and conscientious scholars sometimes fail to give proper weight to considerations that are salient to the interests of either the public or the subjects. To leave all the decisions solely in the hands of one of the parties involved is not wise.

Background

For this reason, the Faculty of Arts and Sciences established its review system almost forty years ago. Review is administered by a standing committee of the Faculty, the Committee on the Use of Human Subjects in Research. The policies and procedures under which the Committee operates were voted by the President and Fellows of Harvard College (most recently in 1981) and can be found at:

www.fas.harvard.edu/~research/greybook/humsubs.html

Background

http://www.fas.harvard.edu/~research/greybook/humsubs.html











For similar reasons, most federal agencies that sponsor research involving human subjects have mandated similar review systems for grantees.

Harvard’s IRB system meets both the University’s requirements and the federal requirements for prior review of research involving human subjects.

Background

No one has illusions that the committee system — or any other set of institutionalized procedures — is a substitute for ethically-alert scientists who are sensitive to the well-being of their subjects.

That is the sine qua non of meaningful protection and no system relieves the investigator of the primary responsibility for securing subject's rights and welfare. The committees serve only to remind all concerned of the network of interdependence that exists and to interpose a disinterested judgment where necessary.

Background

History

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

In 1946, twenty-three Nazi defendants, twenty of them physicians, were tried for war crimes and crimes against humanity. Sixteen of the defendants were found guilty. Seven were hanged and nine were sentenced to prison terms ranging from ten years to life.

The world was shocked at the revelations of experiments these doctors conducted, including studying the effects of extreme cold, high altitude, exposure to noxious substances, poisons, infection with all manner of disease, and list of other dreadful procedures.

History

Out of this experience grew a set of principles known as the Nuremberg Code, which have remained remarkably durable. Although they were intended to apply primarily to medical research, they serve as useful guidelines for the conduct of other types of research, including research typically conducted by behavioral and social science investigators at Harvard.

History

Principles Taken from the Nuremberg Code

• Researchers are responsible for obtaining voluntary informed consent from their subjects. They should not delegate this responsibility to others.

• Experiments should be designed to benefit society, and not be random or unnecessary.

• Precede human research with animal experiments and studies on the natural history of disease whenever this is possible, so that the anticipated results will justify the performance of the experiment.

Jane Calhoun:

Jane Calhoun:Jane

Calhoun:

Jane Calhoun:Jane CalhouJane Calhou

Jane Calhoun:

Jane Calhoun:Jane Jane

Jane Calhoun:

Jane Calhoun:

History

Nuremberg Code (continued)

• Research should involve no unnecessary physical or mental suffering or exposure to harm. In particular, the experiment should not be conducted if there is reason to believe it may lead to death or disabling injury of a subject, "except, perhaps, in those experiments where the experimental physicians also serve as subjects.”

• Risks should be reasonable based on the possible benefits of the research, which should take into account the humanitarian importance of the problem being studied.

Jane Calhoun:

Jane Calhoun:Jane

Calhoun:

Jane Calhoun:Jane CalhouJane Calhou

Jane Calhoun:

Jane Calhoun:Jane Jane

Jane Calhoun:

Jane Calhoun:

History

Nuremberg Code (continued)

• Researchers must be scientifically qualified and should perform professionally at every stage of the experiment.

• Subjects must be at liberty to withdraw at any time of their own free will.

• The experimenter should stop the study at any time if in his opinion subjects may be harmed by continuing to participate.

History

IncreasingPublic Awareness

History

Over the next twenty-five years, several studies widely reported in the press helped to focus the public's interest on research involving human subjects in this country and led many people — including many in Washington — to think that some kind of federal oversight of research might be necessary.

• The Wichita Jury Case• Immunological research at The Jewish Chronic Disease

Hospital• LSD and Psilocybin research by Timothy Leary and Richard

Alpert• Research on obedience to authority by Stanley Milgram• PHS-funded research on the natural course of untreated

syphilis in Tuskegee

History

The Wichita Jury Case

In 1953, University of Chicago researchers tape recorded the deliberations of juries in six civil cases, with the consent of the judge and counsel for both sides, but without the jurors’ knowledge. Theresearchers were investigating whether the comments of some lawyers might have inappropriately affected the deliberative process.

History

Wichita Jury Case (continued)

When word of the research leaked out (one of the tapes was played at a Bar Association conference), public outrage led to Senate hearings chaired by James O. Eastland.

Even though there was no evidence that the recordings had influenced the actions of the jury, it was felt that the possibility of further recordings being made might affect jurors’ statements or deliberations.

A federal law was passed in 1956 banning all recording of jury proceedings.

History

The Jewish Chronic Disease Hospital

In 1963, researchers from The Sloan-Kettering Institute began a study at Brooklyn’s Jewish Chronic Disease Hospital to investigate certain aspects of the body’s reaction to foreign tissue. The protocol involved injecting a culture of cancerous cells under the skin of elderly, disabled patients with compromised

immune systems. Many patients were incapable of giving informed consent and even those who were capable were told the doctors were conducting a “harmless skin test.”

History

Jewish Chronic Disease Hospital (continued)

Similar studies had been performed in healthy individuals and in cancer patients, and the researchers had no reason to believe that their actions would lead to the development of cancerous tumors in their subjects

Nevertheless, when members of the hospital’s board of directors learned of the study, they took the hospital to court to force disclosure of the study records. Subsequent headlines blared that “Live Cancer Cells” had been injected into helpless elderly patients, and led to the termination of the study. Two of the physicians responsible for the research were put on probation for a year. Three years later, despite these sanctions, one of the researchers was elected president of the American Association for Cancer Research.

History

Timothy Leary and Richard Alpert

These two Harvard faculty (Leary was Lecturer in Social Relations and Alpert was Assistant Professor at the Ed School) worked together in the early 1960s at the Center for Research in Personality. Hallucinogenic drugs were not then illegal and they had experimented with psilocybin and LSD obtained from Sandoz Pharmaceuticals, which they also dispensed to friends, associates, and students.

As time passed, the research became more and more free-wheeling and, in the opinion of many departmental colleagues, rapidly lost any semblance of academic rigor.

History

Timothy Leary and Richard Alpert (continued)

At this time the University Health Services was just formulating its policies regarding the use of human subjects. An agreement was reached with Alpert and Leary in the fall of 1961 that they would not include any undergraduates in their research.

In early 1962, the two separated their activities from the Center for Research in Personality and formed their own private organization, the International Federation for Internal Freedom (IFIF). Eventually, both were fired from the University; Alpert for having given psilocybin to an undergraduate in 1962, in violation of the UHS agreement, and Leary for failing to teach his scheduled classes in the spring of 1963.

History

Research on Obedience to Authority

At Yale University in the early 1960s, Stanley Milgram devised a series of experiments to examine the circumstances under which naïve individuals would follow instructions whose consequence was the apparent injury of another person.

His protocol involved a “teacher” (the subject) and a “learner” (actually a confederate of the experimenter). The teacher was to click one of a series of switches on a large and impressive device each time the learner gave a wrong answer in a word-pairing test. The teacher was told that each switch would administer a painful electric shock to the learner, of increasing intensity. Realistic cries of pain came from a separate room in which the learner was strapped to his chair--later, pounding on the wall, and, ultimately, at switches labeled up to “450 volts,” no response.

History

Research on Obedience to Authority (continued)

Teachers who objected to the process were told simply that they must go on-- “The experiment requires that you continue.”

The research was designed to explore at what point people would defy authority in the face of a clear moral imperative. To the surprise of many (including Milgram), 26 of 40 subjects went through the process to the end, clicking the switch to administer the maximum shock. (In reality, of course, the learner received no shocks and his responses were all on audiotape.)

Publication of the research, and a dramatic film of the study, generated much controversy among psychologists. Some argued that subjects had been harmed--if not through the stress of the experiment itself, then through the “inflicted insight” into their own personalities.

History

Research on Obedience to Authority (continued)

Followup interviews of the subjects indicated that only 1% reported feeling “sorry or very sorry” to have participated. However, that finding itself was questioned; some writers suggested that the subjects were only saying what Milgram wanted to hear, or were trying to justify their own participation and their failure to defy the experimenter’s authority.

Nevertheless, the relevance of the research to current events—including the trial of Adolph Eichmann, who maintained that he was just following orders as he signed papers condemning concentration camp victims to death—made the findings all the more compelling.

History

Public Health Service study on the natural progression of untreated syphilis (“Tuskegee Syphilis Study”)

This research began in 1932. 600 men, all poor and all black, were enrolled in a study ostensibly designed to monitor and record their health. Some were told they had “bad blood” but none, apparently, were told they had syphilis. They were given free medical attention, a hot meal each time they came to the

clinic, and a promise that the government would cover their burial expenses. Two-thirds of the subjects had evidence of tertiary syphilis when they were recruited; many of the control subjects acquired the disease during the course of the study.

History

Tuskegee Study (continued)

However, even after penicillin was discovered to be effective in treating syphilis, in 1943, it was not offered to the subjects as treatment.

The project ended in 1972 after details were reported in the press. Senator Edward Kennedy held hearings on the study, and a class action suit was later brought against the government (including the Department of Health, Education, and Welfare (DHEW) — now known as the Department of Health and Human Services — the Public Health Service, the Centers for Disease Control, and several other government agencies). The case was settled for $10 million in 1974, to be shared among the surviving subjects and the heirs of those no longer living.

In April, 1997, President Clinton formally apologized on behalf of the federal government to the survivors.

History

The Kennedy hearings were a galvanizing force within the government. Subsequent passage of the National Research Act of 1974 authorized the DHEW to issue completely redesigned regulations on the use of human subjects in federally-funded research.

History

Ethical Principles

Ethical Principles On July 12, 1974, when the National Research Act

was signed into law, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was created. A primary charge to the National Commission was to identify ethical principles to guide research involving humansubjects. The Commission’s Belmont Report (formally titled Ethical Principles and Guidelines for the Protection of Human Subjects of Research) was published in 1978.

Ethical Principles

Ethical Principles The Belmont Report enumerates three

basic principles for investigators conducting research with human subjects:

• Respect for persons

• Beneficence

• Justice

Ethical Principles

Belmont ReportEthical Principles

1. Respect for Persons

Individuals should be treated as autonomous agents, with the right to self-determination.

Autonomy refers to the individual’s right to choose whether to participate or not. Autonomy is protected by the consent process. Each prospective subject must be given ample information and time to decide whether to participate in a research study

Ethical Principles

Belmont ReportEthical Principles (continued)

In addition, persons with limited or diminished autonomy are entitled to special protections

Not all human beings are capable of self-determination; special precautions must be taken to protect members of potentially vulnerable populations. There are specific federal rules that must be followed when research activities involve fetuses, pregnant women, human in vitro fertilization, children, prisoners, or subjects who may have diminished capacity.

Ethical Principles


2. Beneficence

• Do no harm

• Maximize possible benefits and minimize possible harms for science, humanity, and the individual research subjects

Ethical Principles

This principle is the basis of risk/benefit assessment, in which investigators, institutions, and IRBs all seek to ensure that any risks are minimized, and not taken unless there is likely to be a benefit to theindividual subject. Types of risk include emotional, financial, psychological, social, and legal, as well as physical.

Ethical Principles


3. Justice

Justice requires that the burdens and the benefits of research be distributed equitably. This means that research procedures should be carefully chosen and administered, and that costs and benefits should be equitably distributed among persons and groups. Subject selection should not be based solely on convenience to the investigator. Ordinarily, those who bear the risks of research should be those who benefit from it.

Ethical Principles

Harvard University’s rules regarding the use of human

subjects in research

Ethical Principles

By vote of the President and Fellows on 7 December 1981, the Committee on the Use of Human Subjects in Research is “authorized to review and to approve or disapprove, or state conditions for, the conduct of any research involving a human subject or subjects, in accordance with the policies stated herein.” The wide discretion given the Committee (“any research. . . ”) is intended to make clear its authority to intervene as necessary to protect research subjects.

Ethical Principles


Federal rules regarding the use of human subjects in

research

Ethical Principles

Federal regulations for the protection of human subjects are codified at Chapter 45 of the Code of Federal Regulations, Part 46 (45 CFR 46). This document is referred to as "The Common Rule" because it has been adopted by most federal agencies that fund human subjects research.

All Harvard investigators conducting research that is supported (even in part) by federal funds must adhere to the provisions of 45 CFR 46, in addition to the requirements of the Vote of the President and Fellows.

Ethical Principles

http://www.fas.harvard.edu/~research/45CFR46.html

Any institution with an IRB that reviews and approves federally-funded research must file an agreement with the Department of Health and Human Services stating the methods by which the institution will protect the welfare of all research participants (regardless of the source of funding, if any, for the research).

This agreement serves as the IRB’s “license” to approve human subjects research, and is called a Multiple Project Assurance (MPA).

Ethical Principles

Harvard has negotiated three Multiple Project Assurances: one for the Faculty of Arts and Sciences (and the Cambridge campus in general), one for the Medical School, and one for the School of Public Health.

The MPA for the Faculty of Arts and Sciences can be found at www.fas.harvard.edu/~research/MPA.html

Ethical Principles

http://www.fas.harvard.edu/~research/MPA.html







Roles and Responsibilities

Roles and Responsibilities

Three parties involved in the research process have their own separate, but interrelated, responsibilities: • the Investigator (and other research staff)• the Institutional Review Board• the University

Roles & Responsibilities

Investigator

The Investigator bears primary responsibility for the protection of human subjects in the study


Investigator responsibilities

– In consultation with the IRB, determines whether research involving human subjects requires IRB approval

– Submits protocol to the IRB for approval before the research begins

– Obtains (and documents as required) informed consent from all subjects


Investigator responsibilities (continued)

– Ensures the confidentiality of subject data– Immediately suspends research if any

subject is injured, or if previously-unanticipated risks are identified; obtains IRB approval before proceeding

– Applies to the IRB for approval of changes to previously-approved protocols


Institutional Review Board

The IRB must understand and apply the University’s rules and federal, state, and local regulations on the use of human


subjects in research

IRB Responsibilities

• Reviews, and has the authority to approve, require modification of, or disapprove, all human subjects research activities, including proposed changes to previously-approved research.

• Works with investigators to develop ethically-sound protocols

• Provides training and education as needed and requested on the use of human subjects in research.


IRB Responsibilities (continued)

• Facilitates constructive communication among the research administrators, department heads, research investigators, clinical care staff, human subjects, and institutional officials as a means of maintaining a high level of awareness regarding the safeguarding of the rights and welfare of research subjects


IRB Responsibilities (continued)

• Forwards to the appropriate University officials any significant or material findings or actions regarding injuries or other unanticipated problems or risks to subjects; any serious or continuing noncompliance with University or federal regulations; and any suspension or termination of IRB approval


University Although primary responsibility for protection

of human subjects from risk of harm is borne by the principal investigator and is shared by all others involved in the conduct of theresearch, this does not relieve the institution of its own responsibility for the performance of research involving human subjects conducted by University investigators.


University Responsibilities

• Ensures that IRB and University policies are in compliance with evolving law and regulations

• Publicizes human subjects policies and requirements to the research community

• Establishes and maintains appropriately-qualified IRBs

• Provides support for the IRBs and their staff


Special Issues

• Informed Consent

• Privacy, Confidentiality, and Anonymity

Special Issues

Informed Consent

In the simplest terms, informed consent means that the investigator has shared enough information about the study with a prospective subject so that the subject knows what the experience and effects

of being in the study will be like and, with that knowledge, agrees to participate.

Special Issues

It is important not to confuse the informed consent process with the consent form.

The consent form is simply a written confirmation of the agreement between investigator and the subject concerning

xConsent FormIn this study,conducted by

Professor Jones,

you will visitthe laboratory

on three daysand …

X ________

the content and terms of the proposed activity. In some studies that present no risk, a written consent form may not be required.

Special Issues

Think for a moment about the things you would want to know before you volunteer to participate in a research study:

• That it is a research project• What the purpose of the project is• What the experience of participation is going

to be like• How long participation will take• What compensation you will receive

Special Issues

Things you would want to know (continued)

• What (if any) are the risks of injury or other distress, and what will happen if you are injured

• What else might happen to you – Embarrassment?– Unpleasant side effects?– Disruption of normal schedule or activities?

• How participation might benefit you• How your participation might benefit others

if the research is successful

Special Issues

You would also want to understand:

• That you don’t have to participate if you don’t want to--for whatever reason

• That refusal to be in the study will carry no penalty

• That if you start to participate and then change your mind, you can stop

• Whether there are any alternate procedures that might instead be used (if the study involves medical interventions or treatment)

Special Issues

You would also want to understand (continued):

• What will happen to your personal information or materials or tissue samples gathered in the study

• How your identity and privacy will be protected

Special Issues

Finally, you need to understand that you do not waive any legal rights by agreeing to participate in the study,

Special Issues

regardless of what a consent form may or may not say.

xConsent FormIn this study,conducted by

Professor Jones,

you will visitthe laboratory

on three daysand …

X ________

There are special rules and requirements for informed consent when the research is federally funded.

In some cases, consent must be written; in others, an oral exchange is sufficient. In some cases, certain elements of informed consent may be waived.

Special Issues

Waiver of Consent

The IRB may waive or alter the elements of Informed Consent if the following conditions are met:– The research involves no more than minimal risk– The waiver will not adversely affect the rights and

welfare of the subject– The research could not practicably be carried out

without the waiver or alteration– If possible, subjects will be provided with

additional pertinent information after participation

Special Issues

Information about the required elements for informed consent when federal funds are involved can be found in the federal human subjects regulations at 45CFR46, section 116.

If you have questions about whether written consent is needed in your study, or what the consent process should include, check with your IRB office.

Special Issues

http://www.fas.harvard.edu/~research/45CFR46.html#_46.116

Privacy,Confidentiality,and Anonymity

Privacy Privacy refers to a state of being free

of unsanctioned intrusion.

Special Issues

Ordinarily, individuals have a right to privacy; that is, control over the extent, timing, and circumstances of sharing themselves, or information about themselves, with others.

Confidentiality and Anonymity

Confidentiality and anonymity are relevant to the treatment of individuals’ private information, both within and outside the research context.

Special Issues

Confidentiality refers to an agreement with an individual regarding the treatment of information obtained from or about that individual.

Special Issues

Data are confidential if they will not be disclosed outside the context of the research project in a way that reveals or implies a subject’s identity.

Smith, John

Anonymity refers to the complete absence of names or other identifying information.

Special Issues

X

Data are anonymous if it is impossible for the investigator--or anyone else--to connect a subject with the data they've provided.

In the following situations, the data should be kept confidential, but will usually not be anonymous

• The use of audiotapes to record interviews (voices may be recognized)

• Use of Social Security numbers to identify subjects (can easily be linked to identity)

• Use of ID numbers on subjects' data with a separate name/number list

Special Issues

• Studies of defined groups of subjects with distinctive characteristics, experiences, or information

– Use of narrow descriptive categories (“Asian male executive nurse in a healthcare organization”)

– Recording or reporting of unusual personal information (a small group of employees describing their experience with a new management system)

Confidential, but not anonymous:

Special Issues

Violations of subject privacy and confidentiality are potential risks in much human subjects research. Such violations may result in serious harm to subjects: damage to their reputation, loss of employment, or even criminal prosecution.

Investigators are required to minimize these risks by respecting the privacy of subjects at all times, and maintaining all research records in a secure manner.

Special Issues

It is nevertheless possible, and may be entirely proper, to conduct a study in which data will not be kept confidential (e.g., an oral history project where subjects give permission for their names to be published with their comments).

Regardless of the degree to which confidentiality will be maintained, investigators must explain to subjects any limits of confidentiality that reasonably can be anticipated.

Special Issues

Research data are ordinarily not privileged and may be subject to subpoena in the absence of special protection. When the issue under study requires subjects to reveal highly sensitive information, such as criminal behavior or information about their own drug dependency, investigators can apply to the U.S. Department of Health and Human Services for a Certificate of Confidentiality, which will protect the data from outside inquiry. Investigators should consult their IRB office for further information.

Special Issues

Special Categories of Research Subjects

• Vulnerable Populations

• Research Involving Children

• Research Involving Students

Special Categories of Subjects

Vulnerable Populations

Federal regulations require that IRBs give special consideration to protecting the welfare of potentially-vulnerable subjects, including children, prisoners, pregnant women, or cognitively impaired individuals.


Vulnerable Populations (continued)

Regulations at 45 CFR 46 identify specific provisions for federally-funded research involving • pregnant women and in vitro fertilization

(Subpart B)• prisoners (Subpart C) • children (Subpart D)

Research involving cognitively impaired individuals should include additional safeguards to ensure that their rights and welfare are protected, as noted at

45 CFR 46.111(b)


http://www.fas.harvard.edu/~research/45CFR46.html#Subpart%20B

http://www.fas.harvard.edu/~research/45CFR46.html#Subpart%20C

http://www.fas.harvard.edu/~research/45CFR46.html#Subpart%20D

http://www.fas.harvard.edu/~research/45CFR46.html#_46.111

Vulnerable Populations (continued)

Although some research involving human subjects is exempt from the federal regulations, the exemptions do not apply to subjects identified in Subparts B or C of 45 CFR 46, nor does the exemption at section 101(b)(2) (survey or interview research) apply to research involving children.

Investigators planning research with subjects identified in Subparts B and C, or with cognitively impaired individuals, should consult with the IRB office prior to submitting an application.


Research Involving Children

Definitions• Children are persons who have not

attained the legal age for consent to treatments or procedures involved in the research. (In Massachusetts, in most cases, this is age 18.)


Research Involving Children

Definitions• Assent means a child’s affirmative agreement

to participate. Mere failure to object, absent affirmative agreement, should not be construed as assent.

• Permission means the agreement of parent or guardian to the participation of their child or ward in a research project.


When children are involved as subjects of research, the researcher must ordinarily obtain both the assent

Research Involving Children (continued)

of the child and the permission of the parent.



Federal Regulations require IRBs to document in their discussion the risks and benefits of the research and to classify research involving children into one of four categories.


1) Research not involving greater than minimal risk (i.e., where the probability and magnitude of harm or discomfort anticipated in the proposed research are not greater than those ordinarily encountered in daily life or during routine physical or psychological tests.)

2) Research involving greater than minimal risk, but presenting the prospect of a direct benefit to the child.



3) Research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subjects’ disorder or condition. 4) Research not otherwise approvable that presents an opportunity to understand, prevent, or alleviate a serious health problem affecting the health or welfare of children.



Note that the fourth category must also be reviewed by the Secretary of DHHS, in consultation with a convened panel of experts, before being allowed to proceed.



Use of Studentsas Research Subjects

College students can be excellent participants in research. They are readily available and often in a position to understand research procedures and questions. Research participation may also be a valuable learningexperience. However, they are also in a dependent position in relationship to faculty and teaching staff, and thus potentially vulnerable.


Instructors and teaching fellows are discouraged from collecting research data from students in their own courses or sections because of the potential for

Smith, John

coercion, and the problems inherent in student revelation of private information.


Special Categories of Research


• Survey research

• Deception

Survey Research

Often, survey research is exempt from the requirements of IRB review. However, some survey research may involve vulnerable populations, or deal with sensitive topics. In some cases (research on bereavement or other personal loss, for instance) the survey process itself may be stressful or potentially harmful to subjects.


Survey research may require prior IRB review and approval when

subjects are minors, patients, or adults not competent to consent

research deals with sensitive topics identifiers are recorded or linked to

data Your IRB office can advise you on

whether your survey project will require IRB review.


Deception

In some research, particularly some research in social psychology, fully explaining the purpose of a study to subjects in advance may bias their actions or responses. For instance, telling subjects in advance that a study is about the effects of stereotypes on behavior may cause subjects not to act naturally.


"Deception" includes not only provision of false or misleading information to subjects prior to or during the research, but also the withholding of information that may be relevant to subjects' decision about participation or actions in the research context.


Withholding information from subjects during the informed consent process is ordinarily permissible only if the following four conditions are met:

1) The research presents no more than minimal risk to subjects

2) The withholding will not adversely affect subjects’ rights and would be unlikely to affect their decision about participation


3) Prior disclosure would harm the scientific validity of the study

4) Where appropriate, subjects will be provided with a complete explanation (“debriefing”) as soon as possible after the conclusion of the experiment

Note that prior explanation of risks cannot be withheld.


Nevertheless, investigators should be careful about using deception as a research tool. Subjects are, after all, volunteering to participate in research and they have a right to be treated with respect.

One useful litmus may be: after a subject has completed the study, and been fully debriefed, will he or she understand and accept the reason for the deception, and not leave the study embarrassed or disheartened or upset?


Example

The following example of a study in which subjects were deceived shows how deception -- where necessary -- can be properly managed:

Subjects were told that language ability was being studied, and asked to construct grammatically correct sentences from groups of words given to them. In one condition there were many words associated with old age, such as Florida, old, grey, lonely, forgetful, etc. The other condition had only words that were neutral.


Example (continued)

Subjects were thanked for their participation and dismissed. Unbeknownst to them, their walking speed was measured as they walked down the corridor leaving the lab. Those subjects who had been given words traditionally associated with old age took significantly longer to walk down the hall than those given neutral words.

Before the subjects left the building, the investigator caught up to each one and gave a complete oral debriefing and a written version.


Resources

Resources

A list of web sites relevant to human subjects research, including all the sites referenced in this tutorial, and a bibliography of useful books and articles, is available through your school’s IRB web site. You may find it useful to bookmark the location for easy reference.

Resources

Faculty of Arts and Sciences (and other non-medical schools): www.fas.harvard.edu/~research/hsbib.html

Medical School and School of Dental Medicine: www.hms.harvard.edu/orsp/hsbib.html

School of Public Health www.hsph.harvard.edu/hsc/hsbib.html

Resources

http://www.fas.harvard.edu/~research/hsbib.html









http://www.hms.harvard.edu/orsp/hsbib.html











http://www.hsph.harvard.edu/hsc/hsbib.html











Registration

Registration

Please confirm your completion of the human subjects tutorial, by sending an email message to Julie Wilson and to your PAC/SYP Seminar Leader.

Thank you.

human subject protection committee on the use of human subjects in research harvard university * a...

Documents

definitions slide

definitions of research

research subjects

research investigator

bibliography slide

research purposes

conduct of research

definitions smith