NIH Course

As such, the relationship between investigators and human subjects is critical and should be based on ___, ___, and ___.
honesty, trust, and respect

Nazi Medical War Crimes (1939-1945) “Medical experiments” were performed on thousands of concentration camp prisoners and included deadly studies and tortures such as _____
injecting people with gasoline and live viruses
immersing people in ice water
forcing people to ingest poisons

The Nuremberg Military Tribunals found that the defendants had:
1. Corrupted the ethics of the medical and scientific professions
2. Repeatedly and deliberately violated the rights of the subjects

In the August 1947 verdict, the judges included a section called Permissible Medical Experiments. This section became known as the ____ and was the first international code of research ethics.
Nuremberg Code

The Code provides ten Directives for Human Experimentation
1. need voluntary consent
2. The experiment must yield generalizable knowledge that could not be obtained in any other way and is not random and unnecessary in nature
3. try animals first
4. All unnecessary physical and mental suffering and injury should be avoided
5. No experiment should be conducted if there is reason to believe that death or disabling injury will occur
6. The degree of risk to subjects should never exceed the humanitarian importance of the problem
7. Risks to the subjects should be minimized through proper preparations
8. Experiments should only be conducted by scientifically qualified investigators
9. Subjects should always be at liberty to withdraw from experiments
10. Investigators must be ready to end the experiment at any stage if there is cause to believe that continuing the experiment is likely to result in injury, disability or death to the subject

The Syphilis Study at Tuskegee- who performed this
conducted by the United States Public Health Service in Tuskegee, Alabama

This study of the natural history of untreated syphilis was initiated in the 1930s and continued until ___

The Syphilis Study at Tuskegee involved approximately ___ African-American men:
400- with syphilis
200 controls

did they get consent for this

they found PCN to tx it in 1940- but didnt
instead they let the study continue

Outcomes of the Syphilis Study at Tuskegee
1. National Research Act of 1974
2. Basic HHS Policy for Protection of Human Research Subjects
3. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

Following the public outrage over the Syphilis Study at Tuskegee, Congress established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in 1974. The National Commission was charged with:
1. Identifying the ethical principles to guide all research involving human subjects
2. Developing guidelines for the conduct of ethical research involving human subjects

In 1979, the National Commission drafted ____- Ethical Principles and Guidelines for the Protection of Human Subjects of Research.
the belmont report

The Belmont Report identified three principles essential to the ethical conduct of research with humans:
Respect for persons

The principle of respect for persons can be broken down into two basic ideas:
1. Individuals should be treated as autonomous agents
2. Persons with diminished autonomy are entitled to additional protections

Two general rules have been articulated as complementary expressions of beneficent actions:
Do no harm
Maximize possible benefits and minimize possible harms

The challenge inherent in applying the Belmont principle of beneficence is how to determine
when potential benefits outweigh considerations of risks and vice versa.

The challenge of applying the Belmont principle of justice is how to decide
which criteria should be used to ensure that harms and benefits of research are equitably distributed to individuals and populations. (The principle of justice may arise in decisions about inclusion and exclusion criteria for participation in research )

say which principle

the individuals should be able to make their own desicions
respect fo rpersons

the burdens and benefits of research should be fairly distributed among individuals, groups, and societites

The ethical principles for research involving human subjects described in the Belmont Report are codified in the _______
code of federal regulations

The NIH follows all Subparts of the HHS regulations: subpart A
Basic HHS Policy for Protection of Human Research Subjects

Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research



Registration of Institutional Review Boards (effective July 14, 2009)

Subpart A, also called “_____”, describes the required protections for all human subjects.
the common rule

Subpart A defines a human subject as
“a living individual about whom an investigator…conducting research obtains:Data through intervention or interaction with the individual, or Identifiable private information.”

Subpart A defines research as “a systematic investigation…designed to develop or contribute to generalizable knowledge.”

This definition includes:

research development

The use of healthy hearts from cadavers does not constitute human subjects research

Each IRB that is designated by an institution under an assurance of compliance approved for federalwide use by the ________ (OHRP)
office of human research protections

A study proposes to observe the challenges for former prisoners returning to office jobs. Researchers will recruit individuals who have spent over ten years in prison, have completed their sentences, and are now interviewing for office jobs.- does the study need addition protection under B, C or D
nope- not prisoners anymore

A study proposes to examine the effectiveness of a medical treatment and prevention program for adolescents in a location where the legal age for consent to such treatment is 12. The adolescents involved range from ages 12 to 17.- need protection from D?
nope- old enough to consent

The HHS regulations (45 CFR 46.120) require that Federal Departments and Agencies that conduct or support human subjects research must evaluate all applications for research using the following criteria:
1. risks to the subjects
2. Adequacy of protection against these risks
3. Potential benefits of the research to the subjects and others
4. Importance of the knowledge gained or to be gained

In a Federal Register Notice on July 7, 2006, HHS clarified that the requirements of the HHS regulations (45 CFR 46) must be satisfied for all HHS-conducted or -supported research covered by the _____, regardless of whether the research is conducted domestically or internationally
Federalwide Assurance,

Each institution that is engaged in NIH-funded human subjects research must:
1. Obtain or hold a current Federalwide Assurance (FWA), assuring that an institution will comply with HHS regulatory requirements for the protection of human subjects
2. Certify to NIH that grant applications and contract proposals describing research involving human subjects has been reviewed and approved by an Institutional Review Board (IRB) designated in the FWA, and will be subject to continuing review by an IRB.

IRBs are committees that consist of __ or more members with varying expertise and diversity that are responsible for reviewing and approving human subjects research activities on behalf of institutions.

Identify the most influential event that led to the HHS Policy for Protection of Human Research Subjects:
Syphilis Study at Tuskegee

Which entity has regulatory authority for the protection of human subjects for PHS-funded research?

A study proposing to involve pregnant adolescents who are detained in a juvenile detention center would only be allowed if:
The requirements of Subparts A, B, C, and D are met.

Which of the following should be eliminated or minimized in the research design?
Research Risks
Repeated recruitment of research participants for new protocols

The Belmont principle of respect for persons is primarily applied by requiring that all human subjects research participants provide voluntary ____ to participate in research.
informed consent

The three fundamental aspects of informed consent are:
disclosure (purpose of study, risks, benefits, alternatives, confidentiality, compensation in case of injury, contact info for questions, The conditions of participation, including right to refuse or withdraw without penalty)

This disclosure must be made in such a way that it provides a ____ the information she or he would need in order to make an informed decision.
reasonable person

who says you must obtain informed consent
HHS regulations

In order for participation in research to be voluntary, the potential for ____ and ____ must be minimized.
undue influence

The HHS regulations allow institutional review boards (IRBs) to waive or alter some or all of the required elements of informed consent if all of the following conditions are met:
“The research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; (iv) possible changes in methods or levels of payments for benefits or services under those programs, and
The research could not practicably be carried out without the waiver or alteration.”

The HHS regulations also allow IRBs to waive or alter some or all of the required elements of informed consent if all of the following conditions are met:
1. research involves no more than minimal ris
2. The waiver or alteration will not adversely affect the rights and welfare of the subjects
3. The research could not practicably be carried out without the waiver or alteration
4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation”

Decisions about waivers of informed consent often concern the issue of _____.

In some situations, a waiver of informed consent may be appropriate for a
medical record review
using existing data
specimens that can be linked to identifiable individual

Specific decisions regarding practicability are made by

Now, based on new hypotheses, the investigator plans to conduct new analyses to fulfill purposes different from those described in the informed consent document, the NIH grant application and the IRB-approved protocol. He knows that he needs to obtain approval for the new research from his IRB and his NIH Program Official. Does he also need to get another informed consetn
The investigator does not need to obtain new informed consent as long as the IRB has approved a waiver of informed consent. (if there is no waiver- still need informed consent)

An individual’s autonomy can be affected by several factors including
cog impairment

An individual’s capacity to consent to a particular study should be assessed based on:
the persons level of capacity
The complexity and risks of the study

The HHS regulations `require that legally authorized representatives provide voluntary informed consent for individuals with diminished capacity to participate in research
should still obtain consent from the participants to the extent possible

Preclinical studies be completed prior to the involvement of pregnant women

The HHS regulations prohibit:3
1. inducements of any kind to terminate a pregnancy
2. Investigators from taking part in decisions about terminating a pregnancy
3. Investigators from determining the viability of a neonate

Because children cannot provide informed consent, children provide ____ to participate in research
assent (to the extent that they are able)- and then the parents give permission

The ages, maturity and psychological states of the children involved in the research should be taken into account when determining whether children have the capacity to assent. This determination is made by
the IRB

The requirements specific to informed consent for prisoners are:
1. “Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired”
2. clearly informed in advance that participation in the research will have no effect on his or her parole

One example of a situation in which community consent is required is
emergency research in life-threatening situations where obtaining informed consent is not feasible

Waivers of informed consent can be granted by which of the following:
JUST the IRB- no the dep of justice, or the NIH

Communities may grant emergency waivers of informed consent for research involving pregnant women in the community who are in active labor and call Emergency Medical Services.
FALSE emergency waivers do not apply to children, pregnant, or prisoners

When might human subjects research require investigators to obtain informed consent?
Investigators must obtain informed consent if the study involves interactions with research participants.
Investigators must obtain informed consent if the study involves interventions with research participants.
Investigators must obtain informed consent if the study involves collection of private information from or about research participants.

For research involving pregnant women, participation requires:
Consideration of risks and potential benefits for the fetus and the pregnant woman.

Most risks encountered by participants in research fall into the following categories:
1. physical
2. psychological
3. social= jeopardizing the individual’s reputation and social standing, to placing the individual at-risk of political or social reprisals.
4. legal
5. economic= could make it difficult for a research participant to retain a job or to find a job, or if insurance premiums increase or loss of insurance is a result of the disclosure of research data.

all research involes some risk

“that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”
minimal risk

how can you protect against psych risks
remininding patients of their right to withdraw if they become uncomfortable

how can you protect against social risks
keep data confidential- same thing for legal

investigators can apply for ______, which are intended to prevent investigators from being forced to disclose data that can be linked to identifiable research participants in legal proceedings.
certificats of confidentiality

say which category the following risks fall into



disclosure of illegal drug use

loss of job

the certificate of confidentiality can help with

when should you explain if there will be compensation
during informed consent

Compensation is not a benefit of the research.
just to reimburse participants for their time

the level and kind of compensation must take into consideration the vulnerabilities of the research population to minimize the possibility of undue inducement.

the tendency for research participants to:

“… downplay or ignore the risks posed to their own well-being by participation … [due to] the participants’ deeply held and nearly unshakeable conviction that every aspect of their participation in research has been designed for their own individual benefit.

therapeutic misconception

Substantial scientific uncertainty about which treatments will benefit subjects most, or a lack of consensus in the field that one intervention is superior to another.
eqipoise- researchers must consider this due to beneficence
A state of “equipoise” is required for conducting research that may pose risks to research participants.

if there is a definite understanding of the best treatment (meaning no equipoise) then no research would need to be done

There are two standard treatments for autistic children who display a specific set of characteristics. One treatment is a cognitive behavioral intervention, and the other is a dietary and biomedical intervention. Both treatments have equally strong clinical evidence supporting their efficacy. A researcher proposes a comparison of the two interventions to determine which is preferable. The children will be randomized to one of two groups: half of the children will receive the cognitive behavioral intervention and the other half of the children will receive the dietary and biomedical intervention.
this study is in eqipoise

“free from unsanctioned intrusion.”

holding secret all information relating to an individual, unless the individual gives consent permitting disclosure.

who is responsible for privacy and confidentiality
the investigators

After the conclusion of a clinical trial in a small rural community, an investigator is anxious to publish findings. Understanding the NIH policies encouraging the reporting of demographic differences in intervention effect, and concerned about protecting the confidentiality of research participants, the investigator publishes only general demographic data such as sex, age, state, and county. Is this an appropriate and acceptable way to protect the confidentiality of research participants?
NO- you can not publish demographic data in a rural setting- only when the populaiton is large enough

maintaining confidentiality is a matter of following some established practices, for example:
Properly disposing of data sheets and other paper records
Limiting access to identified data; and/or
Storing research records in locked cabinets or secured databases

Research with coded private information or specimens does not involve human subjects if:
1. The private information or specimens were not collected specifically for the currently proposed research project through an interaction or intervention with living individuals; and
2. The investigator(s) cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain

You are an investigator proposing to use data from a colleague�s database to conduct secondary analyses. You want to examine the behavior and attitudes in male spouses of female business executives. Your colleague will provide coded data for your proposed studies, and you and he enter into an agreement by which he will keep the key to the code and will have no other involvement in the research. Therefore, your colleague is not an investigator in your research. Does this involve human subjects

Institutional Review Boards (IRBs) are specialized committees required by ___ regulations that safeguard the rights and welfare of human subjects

The major roles of IRBs in the oversight of research are:
1. Initial review and approval or disapproval of the proposed research activity
2. Ensuring that the proposed informed consent process meets all of the requirements of 45 CFR 46.116
3. Providing continuing oversight for progress reports and protocols for ongoing research studies

General Criteria for IRB Approval of Research
minimize risks
risks is reasonable when considering benefits
the selection of human subjects is equitable
will get informed consent
informed consent will be appropriately documented
When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of the human subjects, and when appropriate there are adequate provisions to protect the privacy of human subjects and to maintain the confidentiality of data

For “certain types of research involving no more than minimal risk and for minor changes to existing research,” an IRB may choose to use an _____ procedure
expedited review

explain this
just less people deciding
still as stringent tho
not necesarrily fast

The NIH requires that all clinical trials supported by NIH have a _______(DSM) plan.
data and safety monitoring

An investigator proposes to work with the community organization of a population where many of the residents are exposed to high levels of mercury through occupational exposure. A previous study indicated that the harms resulting from exposure to a similar heavy metal contaminant could be mitigated through the use of a behavioral intervention. The investigators propose testing the intervention to see if mercury exposure can be reduced in this population. The research design involves randomizing human subjects either to the experimental behavioral intervention in addition to conventional therapy, or to conventional therapy alone. Should the behavioral intervention be determined to be successful, participants who received only conventional therapy will be offered the behavioral intervention after the completion of the study. Research participants will know which intervention they receive because conventional therapy does not include a behavioral component.
Does this require a data and safety monitoring board
yes- bc it is a clinical trial

When are researchers specifically required by NIH policy to describe Data and Safety Monitoring?
for all clinical trials

What is an appropriate method for maintaining confidentiality of private information obtained from human subjects?
Keeping data in a password-protected database
Storing images in a secured cabinet
Coding data or specimens and keeping the key to the code in a separate, locked drawer

The definition of justice has two parts:
1. Fair procedures and outcomes are used to select research participants
2. There is a fair distribution of benefits and burdens to populations who participate in research

______justice requires that investigators “should not offer potentially beneficial research only to some patients who are in their favor or select only ‘undesirable’ persons for risky research.”

____ justice “requires that distinction be drawn between classes of subjects that ought, and ought not, to participate in any particular kind of research, based on the ability of members of that class to bear burdens and on the appropriateness of placing further burdens on already burdened persons.”

To treat “equitably” means to treat
To treat “equally” means to treat
exactly the same way.

Research should strive for ______ distribution of the risks and potential benefits of the research.

A researcher seeks to improve treatment for severe migraines that are partially responsive to oral medication. He proposes to test whether acupuncture, in addition to a sufferer�s oral medication, is more effective treatment than oral medication alone. Because women are three times more likely to experience migraines than men, he proposes to enroll three times as many women as men. They will be recruited from racially and ethnically diverse communities. Does this study design fulfill the principle of justice?

children must be included in all NIH-supported human subjects research unless “… there are scientific and ethical reasons not to include them.”
If an investigator proposes to conduct clinical research that does not include children, the exclusion of children must be fully justified using one or more of the exceptions described in the Policy.

what are some of these exceptions (why would we not want to include children)
1. research topic is irrelevant to children
2. There are laws or regulations barring the inclusion of children in the research
3. The knowledge is already available for children or will be obtained from another on-going study, and an additional study will be redundant
4. A separate, age-specific study in children is warranted and preferable
5. Insufficient data are available in adults to judge potential risk in children
6. The study design is aimed at collecting additional data on pre-enrolled adult study participants
7. Other special cases justified by the investigator and found acceptable to the review group and Institute Director

HHS regulations at Subpart D “Additional Protections for Children Involved as Subjects in Research” defines children as:
people who have not attained the legal age for consent to tx or procedures involved in research

Thus for HHS regulatory requirements, the need for protections for “children” is defined by the
location the study will take place

NIH inlcusion policy- The NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects defines children as:
those under 21

Risks associated with the use of placebos in research are:
deception (misleading research participants about the research purpose or procedures)
therapeutic misconception (tendancy of research participants to ignore the risks due to the idea that the research is designed for their own individual benefit)

Unless justifications for a waiver are approved, the informed consent process must disclose sufficient information to ensure that potential research participants:
understand what placebos are
understand the likelihood that they will recieve a placebo
consent that they are willing to receieve the placebo

When there are no approved, effective treatments for the condition
use of placebo would we good

can researchers ever use incomplete disclosure and deception
yes but must consider some things

what must they consider before using incomplete disclosure and deception
1.Whether the scientific goals of the research can be achieved by methods that do not involve incomplete disclosure or deception
2. Whether participants would consider the information withheld during the informed consent process important to their decision to participate in the study
3. Whether it is possible to inform participants that they will only learn about all the goals of the research after the research study is over

HHS regulations allow informed consent to be waived only if:
1. poses minimal risk
2. The waiver must not adversely affect the rights and welfare of research participants
3. Incomplete disclosure or deception must be essential to the ability to carry out the research
4. Whenever appropriate, research participants will be given additional pertinent information after they have participated in such a study (debriefing)

_______of research participants after the study involves an explanation of the deception or incomplete disclosure of research goals to participants as well as a complete disclosure of the true goals of the research.

The HHS Office for Human Research Protections (OHRP) has set the expectation that the HHS regulations, as well as any additional ____ and ____ standards, will be followed in all research conducted or supported by HHS.
institutional and local standards

If you plan to engage in NIH-funded research in non-U.S. settings you must comply with the protections and standards set out in the HHS regulations Subpart A. Researchers may go beyond HHS regulations, however, to meet the ethical, legal, and social standards for the local setting.
Non-U.S. institutions engaged in HHS-conducted or -supported human subjects research must obtain an international (non-U.S.) Federalwide Assurance (FWA) from OHRP.

If community consent is the cultural norm, it may be appropriate to obtain community consent in advance of obtaining informed consent from individuals.
but Community consent cannot replace the informed consent from individuals

NIH has specific policies addressing:
inclusion of children
inclusion of women and minorities
Treatment for research subjects in HIV/AIDS antiretroviral studies following completing of trials in developing countries

Which of the following is TRUE regarding applications for NIH-funded research overseas?
Research conducted overseas is subject to HHS Human Subjects Regulations and local regulations and policies

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