citi

Per 45 CFR 46, the following activies are deemed not to be reseach

1. Public health surveillance activities 2. Scholarly and journalistic activities 3. Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes 4. Authorized operational activities in support of intelligence, homeland security, defense, or other national security missions

An investigator has received IRB approval for a clinical trial. During the course of the study, the investigator decides to make some changes to the study procedures to make management of the study easier for him and his study team. The investigator must do the following:

Contact the IRB office to determine the appropriate course of review. Once IRB approval is obtained, the investigator may proceed with the changes.

A investigator decides to conduct a survey of adult learners to understand the barriers to adult education. The investigator has obtained permission from the adult education program to explain his study to these adult students and ask if they would be interested in participating. The investigator plans to pass out surveys to everyone in the class. Anyone who cares to complete it may do so. All surveys will be returned to the instructor who will place them in an envelope provided by the investigator. The envelope will then be sealed and mailed to the investigator for analysis. The investigator believes this study meets the definitions of minimal risk and the criteria for exemption from IRB review. What are his next steps?

Contact the local IRB office to determine whether or not the study must be submitted for review. federal guidance indicates that researchers themselves should not determine whether their project or activity is exempt. Therefore, many institutions have established procedures to certify a project's exemption. The researcher should inquire with the IRB office regarding the institution's procedures for determining exemption status. Note the determination must be made in advance of the activity; it cannot be made retroactively.

Respect for Persons

treating persons as autonomous agents and protecting those with diminished autonomy subjects who enter into the research are provided with sufficient information to understand the choice to participate and voluntarily make decisions that are accepted by the research team not every human being is capable of self-determination

HHS regulations at 45 CFR 46, Subpart A (the Common Rule) provide guidance on

what human subjects research requires IRB review and approval.

U.S. Department of Health and Human Services (HHS) guidelines provide information about

what research requires Institutional Review Board (IRB) review and approval

Justice

"fairness in distribution" or "what is deserved no group should be unfairly burdened with the risks without the potential of benefit while another group potentially benefits without being burdened by the risks the selection of research subjects needs to be scrutinized in order to determine whether some groups (for example, welfare patients, particular racial and ethnic minorities, or persons confined to institutions) are being systematically selected simply because of their easy availability, their compromised position, or their manipulability, rather than for reasons directly related to the problem being studied or the setting of the research

The framework for informed consent can be found at

45 CFR 46.116(a) and 21 CFR 50.25(a).

Limited IRB Review

A limited IRB review is a requirement for certain exempt research categories. An IRB may use the expedited review procedure for limited IRB review (Protection of Human Subjects 2017). Limited IRB review determines if the defined criteria are met for the exemption category.

45 CFR 46.116[c]

A statement that the procedure may involve unforeseeable risks. When appropriate, include a statement that the research could involve unforeseeable risks to the embryo or fetus or to the subject if the subject is or becomes pregnant. A description of circumstances under which the subject's participation may be terminated by the investigator without the subject's consent. A description of any additional costs to the subject that may result from participation in the research. A clear statement of the consequences of a subject's decision to withdraw from the research, and, if so, how to withdraw safely. A statement that significant new findings developed during research which may relate to the subject's willingness to continue will be provided to the subject. Also describe the process whereby subjects will be notified of significant new findings. A description of the approximate number of subjects that will be involved in the study. A statement that the subject's biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit. A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions. For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (that is, sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).

Which of the following research scenarios would present likelihood of harm to the subjects?

A survey about sexual attitudes, beliefs, and practices, mailed by an HIV/AIDS prevention study to people randomly selected from a commercial mailing list.

Which of the following research scenarios would present a likelihood of harm to the participants?

A survey about sexual attitudes, beliefs, and practices, mailed by an HIV/AIDS prevention study to people selected from a targeted mailing list.

45 CFR 46 subpart D

Additional Protections for Children Involved as Subjects in Research

An investigator proposes a study to determine the clinical relevance of a new technique to quantitate minimal residual disease (MRD) during therapy for acute lymphoblastic leukemia in adolescents. The study requires that two additional bone marrow aspirates be performed during the course of treatment. The subject's treatment will not be altered based in the results of the assay, but if the presence of minimal residual disease is found to predict for higher risk of relapse, future patients with this disease would benefit from improved treatment. This study is approvable only if:' he IRB determines that the two additional bone marrow aspirates constitute only a minor increase over minimal risk. The investigators will obtain assent from the child to participate in the research. All of the above

All of the above The research as described presents greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition. It is therefore potentially approvable under 45.406, provided: (1) the risk represents a minor increase over minimal risk; (2) the intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations; (3) the intervention or procedure is likely to yield generalizable knowledge about the subjects' disorder or condition which is of vital importance for the understanding or amelioration of the subjects' disorder or condition; and (4) adequate provisions are made for soliciting assent of the children and permission of their parents or guardians. Therefore, the IRB must determine that two additional bone marrows only constitute a minor increase over minimal risk.

45 CFR 46

Also known as the Common Rule, this legislation established the role of institutional review boards (IRBs) for research on human rights.

Which of the following would be true regarding a randomized trial comparing efficacy and toxicity of two FDA-approved medications for hypertension to support a change in advertising?

An IND would be required for the study. IRB approval of a clinical investigation is required unless exempt under 21 CFR 56.104, or waived under 56.105. Route of administration, dosage level, or subject population are irrelevant for determining need for IRB approval. An IND is only required if the data will be used to support a new indication, new labeling, or change in advertising, or if the research involves a route of administration, dosage level, or subject population that significantly increases the risks of the drug. This is true even if the drugs are FDA-approved.

Based on the definition of "prisoner" in the text, which of the following would not be considered a prisoner?

An adult person on parole. The word "prisoner" as defined in 45 CFR 46.303(c), are people who are being held in a jail, prison, or treatment facility or who have been convicted or are awaiting arraignment, trial, or sentencing. This includes those who are in hospitals, alcohol, and drug treatment facilities under court order, or under court ordered house arrest. It does not include persons on parole.

A research study is designed to assess the rate of lung maturation of preterm infants with Down syndrome, by measuring the Lecithin to Sphingomyelin ratio (L/S ratio) in amniotic fluid, as a surrogate of adequate surfactant production. Weekly amniocentesis are performed during the last trimester of pregnancy. The rate of miscarriage due to amniocentesis is estimated at one in 200 procedures. The IRB determines that this procedure carries a greater than minimal risk to the fetus and that there is no direct benefit to the mother or to the fetus. Which of the following is true?

As described, the research is not approvable under subpart B. Research that is not intended to meet the health needs of the mother or the fetus is only approvable under subpart B if the risk to the fetus is minimal. Consent of one or both of the parents in this case is irrelevant. For greater than minimal risk research, under subpart B, benefit to society does not outweigh risk to the fetus.

An investigator would like to initiate a study to determine if the epidemiology of HIV infection is different in prisoner populations from that in non-prisoner populations. Which category might this research fall under?

Category 3. Research on conditions particularly affecting prisoners as a class.

A routine pre-natal ultrasound detects a life-threatening heart defect in a fetus prior to delivery. Standard care, allowing the fetus to come to deliver and then repairing the defect, is associated with significant fetal and neonatal morbidity and mortality. There is an experimental in utero surgical procedure that may have less morbidity and mortality. Which of the following is true?

Consent must be obtained from the mother and the father of the fetus (if he is available). If the research has the prospect of direct benefit only to the fetus then consent of both the pregnant woman and the father of the fetus are required. The father's informed consent also need not be secured if his identity or whereabouts cannot reasonably be ascertained, he is not reasonably available, or the pregnancy resulted from rape.

A research project is designed to test a new treatment for eclampsia (a life-threatening condition in pregnant women). Which of the following conditions must be satisfied for the research to be potentially approvable under subpart B?

Consent must be sought and obtained from the pregnant woman. If the research has the prospect of direct benefit to the mother (or to the mother and the fetus) only the mother's consent is needed. Further, the research is potentially approvable under subpart B even if the risk to the fetus is greater than minimal. The risk to the fetus, however, must be minimized to the greatest extent possible.

Your IRB has determined that the age of assent is 8 years. A 10-year-old does not assent to participate in the study described above. However, since it is "minimal risk," his dissent can be overruled provided one parent gives permission.

False The assent of minors to participate in research is required, unless the "capability of some or all of the children is so limited that they cannot reasonably be consulted or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well being of the children and is available only in the context of the research" (45 CFR 46.408). The fact that the study is minimal risk does not affect the need for child assent, and assent is required from this child to participate in this research project.

Exempt Reviews

Federal regulations specify eight categories of research involving human subjects that are exempt from the other provisions of the regulations

Genetic privacy and confidentiality are sometimes thought to be more important than privacy and confidentiality in other kinds of research for a number of reasons, including:

Genetic information is shared among "blood" relatives, including the subject's parents, siblings, and children.

45 CFR 160 & 164

HIPAA

21 CFR 56

Institutional Review Boards

Consider this scenario. Employees of a pharmaceutical sponsor are provided the opportunity on a regular basis to provide blood samples for in-house research protocols. Subjects will be paid $10 dollars for each blood draw. Clinically relevant results will be reported to the company employee health service for follow up with the employee. Supervisors are not provided with lists of subordinate employees who participate, but this information is not considered confidential and there is no prohibition on supervisors inquiring about subordinate employee participation in research. The employee subjects fit best into which of the following categories of vulnerability? Cognitive Vulnerability Communicative Vulnerability Institutional Vulnerability Medical Vulnerability

Institutional Vulnerability The best answer is "Institutional Vulnerability." This type of vulnerability increases the risk that one's decision will not be truly voluntary as the subordinate status of the individual could be exploited.

21 CFR 312

Investigational New Drug Application

The IRB may send IRB members to audit the consent process in order to:

Observe the process and confirm for themselves that subjects are engaged in an appropriate consent process.

Risks associated with genetics research are best described as:

Physical, social and psychological risks

Additional information associated with genetics research that should be disclosed to subjects during the consent process includes:

Plans and options for re-contacting the subjects with results. It is important for researchers to discuss any plans or options for re-contacting the subjects with genetic results. The IRB may also require a description of whether the samples are linked or anonymous, how they will be stored and who will have access to them or the information they contain, and whether the research will be used to develop proprietary products or assays along with any plans for sharing financial rewards from the project.

An investigator planning to study behavioral changes during alcohol intoxication will pay subjects $600 for 6 hours of testing that includes drinking a moderate level of alcohol and completing several written questionnaires. He plans to recruit college students taking his courses, as well as economically disadvantaged and homeless people. Which of the following is the most important for the investigator to address before submitting the protocol to the IRB? Forms of advertising for subject recruitment. Literacy of homeless subjects. Potential coercion or undue influence. Method of payment to subjects.

Potential coercion or undue influence.

Respect for the incapacitated may require:

Protecting them while they are incapacitated Although maximizing benefits is something that applies to all human subjects, respect for persons would require that incapacitated persons be provided extra protections while they are incapacitated.

Category 5

Research and demonstration projects that are conducted or supported by a federal department or agency, or otherwise subject to the approval of department or agency heads (of the approval of the heads of bureaus or other subordinate agencies that have been delegated authority to conduct the research and demonstration projects), and that are designed to study, evaluate, improve, or otherwise examine public benefit or service programs, including: procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs. Such projects include, but are not limited to, internal studies by federal employees, and studies under contracts or consulting arrangements, cooperative agreements, or grants. Exempt projects also include waivers of otherwise mandatory requirements using authorities (such as, sections 1115 and 1115A of the Social Security Act [as amended]).

Category 1

Research conducted in established or commonly accepted educational settings, involving normal educational practices, that are not likely to adversely affect students' opportunity to learn required educational content or the assessment of educators who provide instruction. This includes research on regular and special education instructional strategies, and research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

Category 3

Research involving benign behavioral interventions in conjunction with the collection of information from adult subjects through verbal or written responses (including data entry) or audiovisual recording if the subjects prospectively agree to the intervention and information collection and at least one of the following criteria is met: The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects. Any disclosure of the human subjects' responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement, or reputation. The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by 46.111(a)(7).

Which of the following activities is more than minimal risk and would not qualify for expedited review? Research that requires no additional intervention or interaction with a subject other than obtaining consent to use, for research purposes, a portion of his/her information being obtained during clinical care. Request to change the room in which a non-invasive research procedure will be conducted. Quality of life questionnaire in which the subject reveals answers about how they interpret their health during receipt of clinical care. Research involving the implantation of an investigational pacemaker.

Research involving the implantation of an investigational pacemaker.

A researcher wants to explore how children are affected by domestic violence against the mother by testing the effectiveness of children participating in a multi-week discussion group. Children will be enrolled and randomized into one of two groups: A discussion group or wait-list control playgroup. The mothers will fill out a mailed or emailed questionnaire about their child's behavior and emotional state at baseline, and after the last meeting for each group. Which is the best statement regarding research risks of harm?

Research risks of harm exist for both the mothers and children; the type of potential harm is different for each group.

Category 2

Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording), if at least one of the following criteria is met: Information obtained is recorded in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects. Any disclosure of the human subjects' responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation. Information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by 46.111(a)(

three basic ethical principles of the Belmont report

Respect for persons, justice, beneficence

Category 8

Secondary research for which broad consent is required: Research involving the use of identifiable private information or identifiable biospecimens for secondary research use, if the following criteria are met: Broad consent for the storage, maintenance, and secondary research use of the identifiable private information or identifiable biospecimens was obtained in accordance with 46.116(a)(1) through (4), (a)(6), and (d); Documentation of informed consent or waiver of documentation of consent was obtained in accordance with 46.117; An IRB conducts a limited IRB review and makes the determination required by 46.111(a)(8) and makes the determination that the research to be conducted is within the scope of the broad consent referenced in paragraph (d)(8)(i) of this section; and The investigator does not include returning individual research results to subjects as part of the study plan. This provision does not prevent an investigator from abiding by any legal requirements to return individual research results.

Category 4

Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met: secondary research use means "re-using identifiable information and identifiable biospecimens that are collected for some other 'primary' or 'initial' activity.

Category 7

Storage or maintenance for secondary research for which broad consent is required: Storage or maintenance of identifiable private information or identifiable biospecimens for potential secondary research use if an IRB conducts a limited IRB review and makes the determinations required by 46.111(a)(8).

Category 6

Taste and food quality evaluation and consumer acceptance studies, public benefit or service programs. If wholesome foods without additives are consumed. If a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the U.S. Food and Drug Administration (FDA) or approved by the Environmental Protection Agency (EPA) or the Food Safety and Inspection Service of the U.S. Department of Agriculture (USDA).

Expedited Reviews

The Common Rule grants an IRB the authority to review certain types of research involving no more than minimal risk using expedited procedures. The IRB chairperson, an experienced reviewer, or a group of experienced reviewers from the IRB designated by the chairperson can initiate an expedited review without requiring review at a convened IRB meeting.

A researcher wants to conduct a secondary analysis using a Centers for Disease Control (CDC) database of prostate cancer patients that was collected by the agency. The researcher was not part of the original database creation and the database was originally created to monitor public health and not for research purposes. The database is publicly available. The database does not include any identifiers. Consent from the patients is not required because:

The database is publicly available.

If the FDA determines that an IND is not required in a drug study, then which of the following is true?

The investigator should prepare and submit a protocol and consent document to the IRB. These materials should include the fact that the FDA advised that an IND is not required.

An investigator wishes to utilize an FDA-unapproved drug to treat a patient for whom there is no standard acceptable treatment. There is no IRB-approved protocol available for use of this drug. Which of the following is true?

The patient must be in a life-threatening or severely debilitating situation which necessitates the use of the investigational drug.

In order to grant a waiver or alteration of the requirements of informed consent, an IRB must find which of the following:

The research could not practicably be carried out without the waiver of consent. In order for an IRB to grant a waiver of consent, it must ensure the following federal criteria at 45 CFR 46.116 (Protection of Human Subjects 2017) are met: he research involves no more than minimal risk. The research could not practicably be carried out without the waiver of consent. If the research involves using identifiable private information, the research could not practicably be carried out without using such information in an identifiable format. The waiver will not affect the rights and welfare of the subjects. Whenever appropriate, the subjects (or legally authorized representatives) will be provided with pertinent information after participation.

The purpose of informed consent is:

To provide a potential subject with appropriate information in an appropriate manner and allow that person to make an informed decision about participation in research

A research study involving children 8 to 12 years old involves collecting a single voided urine sample to assess the frequency of protein in the urine. According to 45 CFR 46, such a study would be considered "minimal risk."

True 45 CFR 46.102(i) defines minimal risk as "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." Because the risk associated with collection of a single voided urine specimen is not greater than risks encountered in the course of a routine physical examination, this research constitutes "minimal risk.

A researcher proposes to conduct a study that includes a survey of adolescents visiting a family planning clinic. The survey addresses the association between age of first sexual encounter and behaviors that might increase the risk of contracting sexually transmitted diseases (STDs). Subjects identified at higher risk of contracting STDs would be provided additional education and counseling on modifying behaviors and preventing STDs. Your IRB determines that participation in this study presents greater than minimal risk to subjects, but that it has the potential for direct personal benefit to the subject (and is therefore potentially approvable under 45 CFR 46.405). To be approvable under this section, the IRB must further determine that the potential benefit to the child balances or outweighs the risk.

True According to 45 CFR 46.405, studies that involve more than minimal risk to children but holds out the prospect of direct benefit for the individual subject, is approvable if (a) the risk is justified by the anticipated benefit to the subjects; and (b) the relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative therapy.

Which of the following statements is accurate in determining subject risk involved in a genetic study:

Understanding the purpose and context of a specific study is critical in determining the risk involved

Human subject is defined as

a living individual about whom an investigator (whether professional or student) conducting research does not require direct contact with a subject but may include the systematic collection of private individually identifiable information about individuals.

Exemption for Vulnerable Populations

esearch involving prisoners cannot be exempted (except for research aimed at involving a broader subject population that only incidentally includes prisoners). In addition, research involving the interviewing or surveying of children may also not be exempted, and observations of public behavior of children when the researcher(s) participates in the activities being observed.

Research

is defined as the "systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.

45 CFR 46.116(b)

legally appropriate informed consent will include the elements Information that the study involves research A clear description of the risks or discomforts to the subject. A description of the benefits to the subject or to others. A disclosure of any alternative procedures or treatments that may be advantageous to the subject, thus giving the subject a full range of available options. When appropriate, a statement that supportive care with no additional disease specific treatment is an alternative. A description explaining how the institution/investigator will maintain confidentiality of records or research involving more than minimal risk, an explanation should describe: Whether there will be any compensation. Whether there will be any medical treatment offered and who will bear the financial responsibility for treatment if injury occurs, and, if so, how and to what extent. Where the subject may obtain further information. The specific office, name, and telephone number(s) of whom to contact for further information regarding the research subject's rights, the research study, or for research-related injury. A statement that participation is voluntary, that refusal to participate involves no penalty or loss of benefits to which the person is otherwise entitled, and that the subject may discontinue at any time. ne of the following statements if the research involves the collection of identifiable private information or identifiable biospecimens

45 CFR 46.104

lists the following categories of research as exempt

Assent

means a child's agreement to participate in research. Mere failure to object should not be construed as consent or assent. However, not all children are capable of assent. This may be because of their age, maturity, and/or psychological state. Institutional Review Boards (IRBs) are responsible for making the decision when assent is an absolute requirement and what that assent should look like.

Beneficence

means to do good (and in more general terms, to do no harm) understood as an obligation Research should be designed and performed in a manner that possible harms are minimized when allowed by the research methods and that possible harms to subjects are reasonable given the benefits of the research require that risks be minimized to the greatest extent possible

Belmont Report

provide an analytical framework that will guide the resolution of ethical problems arising from research involving human subjects" 1979, ethical principles and guidelines for the protection of human subjects of research. describes three basic ethical principles that are particularly relevant to the ethics of research involving human subjects