CITI Training
Which member of a study team acts as the liaison between a sponsor and site, ensuring that reported data are verifiable to source documentation?
The Clinical Research Associate
The regulatory agency that oversees export controls related to military items is:
The Directorate of Defense Trade Controls (DDTC)
Regarding subject receipt of a signed and dated copy of the consent forms, which is true about FDA regulations?
The FDA regulations allow subjects or the legally acceptable representatives (LARs) to receive either a signed or unsigned copy.
Every member of a study team must define quality the same way in order to produce a high quality database.
False
Which is an example of a situation where deferential vulnerability might be a factor?
A physician recruiting patients to be subjects
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
Which is true of inducements in research?
Inducements constitute an "undue influence" if they alter a potential subject's decision-making processes, such that they do not appropriately weigh the risk-benefit relationship of the research.
Which of the following best describes the principle of Respect for Persons as described in the Belmont Report?
Information, comprehension, voluntariness.
A federally funded research study involving children 8 to 12 years old involves collecting a single voided urine sample to assess the frequency of asymptomatic proteinuria (higher amounts of protein in the urine without any signs or symptoms of illness or infection). According to 45 CFR 46, an IRB's risk assessment would likely conclude that this study involves:
No more than minimal risk to the child.
Can research subject to Subpart B and that includes pregnant women as subjects be exempt from the regulations, per 45 CFR 46, if all of the conditions of the exemption are met?
Yes, each of the exemptions in 45 CFR 46.104 may be applied to research subject to Subpart B.
Which of the following is included in the Nuremberg Code:
Voluntary consent
The sponsor must submit an IND Safety Report to the FDA if an adverse event is (1) serious; (2) unexpected; and:
there is a reasonable possibility that the drug caused the event.
The Data Manager should review the study protocol:
to understand primary and secondary endpoints
Subjects with a serious illness may be at risk for exploitation because they may be desperate for a possible cure. This is an example of:
Medical vulnerability
A primary purpose of the ICH is to:
Minimize the need for redundant research.
Typical study conduct activities performed by the data manager include all of the following EXCEPT:
defining edit checks
In order for a quality process to work, study team members must understand all of the following EXCEPT:
how to perform the other team members' jobs
Development of most new drugs, from discovery to marketing approval, usually takes:
9 years or more
According to ICH E6, an "audit" is defined as:
A systematic and independent examination of trial-related activities and documents.
The Fundamental Research Exclusion (FRE) can be applied:
As long as the research does not constitute "development" as defined by the regulations
A double-blinded trial for a new indication is conducted under an IND comparing two (2) marketed drugs, at twice the approved prescribed doses. On Day 2, subject 603 had difficulty breathing. Although it was life-threatening initially, subject 603 was treated and discharged directly from the emergency department after complete recovery. On Day 5, subject 20 had a headache, which led to hospitalization and required blood pressure lowering medications. These episodes cannot be explained on the basis of the pharmacological property of either drug or the subjects' medical histories. The investigator would submit an SAE report for:
Both of the subjects
An application for an export license:
Can be a lengthy process.
Penalties for violating export control laws and regulations:
Can be up to $1,000,000 USD in fines per violation and/or up to 20 years in prison.
Investigational product dispensing or administration information for the sponsor is recorded on the:
Case report form
ICH E6 has broader requirements than FDA or HHS concerning confidentiality of medical records and access by third parties. If investigators are complying with ICH E6 guideline, they must:
Clearly disclose to subjects in the informed consent form that the monitor, auditor, IRB/IEC, and the regulatory authorities may have access to the subject's medical records
As of January 2015, the NIH expects investigators to obtain the informed (valid) consent of research participants in NIH -funded genetic research for broad research use of data and data sharing, even if the cell lines or specimens are:
De-Identified
Which of the following brought increased public attention to the problems with the IRB system?
Death of Research Subject (Jesse Gelsinger)
Which of the following is an example of how the principle of beneficence can be applied to a study employing human subjects?
Determining that the study has a maximization of benefits and a minimization of risks.
Which of the following is an example of how the Principle of Beneficence can be applied to a study employing human subjects?
Determining that the study has maximized benefits and minimized risks.
Where is information on storage requirements for the investigational product usually found?
In the study protocol
What is the status of ICH in U.S.?
It is a FDA guidance.
An item that is used all over the world:
May still be controlled.
A research study will compare a new combined behavioral and pharmacologic treatment with the standard behavioral treatment alone for individuals with severe seasonal affected disorder (SAD). The researcher wants to include pregnant women in the study. However, the pharmacologic treatment has not been previously studied in non-pregnant women, nor have preclinical studies on pregnant animals been conducted. Is this research permitted under Subpart B?
No - this research is not permitted with pregnant women.
At which study visits can the site expect the sponsor to review subjects' signed informed consent forms?
Periodic and termination site visits
Pharmacokinetics and pharmacodynamics of a new formulation of an investigational drug most likely refers to which clinical phase of a study in humans?
Phase I
The ICH GCP guidelines:
Set standards for the design, conduct, monitoring and reporting of clinical research.
OHRP is an oversight body primarily concerned with:
Protection of human research subjects
Which of the following was the result of the Beecher article?
Realization that ethical abuses are not limited to the Nazi regime
When the FDA conducts an inspection, the inspectors will:
Review regulatory records.
Evaluation of Unanticipated Adverse Device Effects (UADEs) must be reported to the FDA by the:
Sponsor
The investigator must report adverse events to the:
Sponsor
Some of the items that should be included in a study budget are:
Study staff costs, pharmacy costs, IRB fees, and items and services promised free in the informed consent
At what point should a Data Manager get involved with the database development?
At study startup
Which member of a study team is ultimately responsible for the conduct of the study at a site?
The Investigator
Which of the following is required at a prestudy site visit?
Evaluation of the site's capacity to conduct the study
Issued in 1974, 45 CFR 46 raised to regulatory status:
US Public Health Service Policy
Prior to locking a database, a data manager should ensure all data have been entered and all queries are resolved.
True
When an export-controlled item or activity is released to a foreign person in the U.S., it is known as:
A deemed export
An investigator conducting a study of a medical device under an IDE is required to complete and sign which of the following?
An investigator's agreement
According to ICH E6, an inspection is defined as:
An official review of documents, facilities, records, and any other resources related to a clinical trial.
An investigator proposes a study to determine the clinical relevance of a new assay technique to measure minimal residual disease (MRD) in adolescent (age 14-16) cancer patients undergoing chemotherapy. The study requires that two additional bone marrow aspirates be performed during the course of chemotherapy. The subject's chemotherapy will not be altered based on the results of the assay technique measures. However, future patients with cancer would benefit from improved interventions based on study findings. The IRB determined that the activity was a minor increase over minimal risk. Which of the following statements best describes the IRB approval requirements for involving adolescent cancer patients in the research study?
Assent of the child and permission of both parents are required.
The FDA requires retention of investigational drug study records for:
At least two (2) years after the investigational drug's approval by the FDA
The packaging of investigational drugs should ideally:
Be designed to help with subject compliance
The National Research Act of 1974
Established the National Commission.
The NBAC looks at characteristics individuals might have that would prevent them from being able to provide voluntary informed consent. The traits may be thought of as falling into six broad areas: cognitive or communicative, institutional, deferential, medical, economic, and social. Prospective research subjects who are not able to comprehend information, deliberate, and make decisions about participation in a proposed research study have a:
Cognitive or communicative vulnerability
In completing Form FDA 1572, Statement of Investigator, the investigator agrees to
Conduct or supervise the investigation personally
A 46-year-old man is currently enrolled in a Phase III study of a drug for severe diabetic neuropathy. While the study is ongoing, a new drug becomes commercially available that may have equal or greater benefit to the subject. The investigator should do which of the following?
Discuss the pros and cons of both the investigational drug and the commercially available drug and then allow the subject to decide whether to withdraw from the research to take the new drug.
Which of the following is an important component of drug accountability?
Drug shipping and disposition records
When must the investigator update the IRB about the progress of a trial?
During the conduct of the study and at termination
When conducting research that involves collecting biological specimens for genetic testing, which of the following issues is the most important for the IRB to consider?
Effects of findings on other family members
The overall goal of monitoring, audits, and inspection activities is to:
Ensure the protection of human research subjects and data integrity.
Accurate reporting of adverse events is most important for:
Ensuring subject safety.
Identify which types of discrimination the Genetic Information Non-Discrimination Act (GINA) protects individuals from:
Health insurance and employment discrimination
A federally funded research study involving children 8 to 12 years old involves collecting a single voided urine sample to assess the frequency of asymptomatic proteinuria (higher amounts of protein in the urine without any signs or symptoms of illness or infection). Your IRB has determined that assent of children age 8 and older is required for the study. A 10-year-old firmly declined to participate in the study described above. Which of the following procedures best describes the action to be taken by the investigator?
Honor the child's decision.
Which of the following statements in a consent form is an example of exculpatory language?
I waive any possibility of compensation for injuries that I may receive as a result of participation in this research.
In terms of explaining the probability of assignment to trial arms in consent forms, which is true?
ICH notes that it should be included, but does not specify how the information should be presented.
When the sponsor-investigator holds the IND for an investigational drug he or she is responsible for annual reporting of which one of the following to FDA?
IND report
The new ICH E6(R2) integrated addendum requires sponsors to implement systems to manage quality throughout all stages of the trial process. The system should use a risk-based approach including which of the following?
Identification of study risks to determine which may safely be omitted from continual monitoring.
Who is ultimately responsible for product accountability at the study site?
Investigator
ICH E6 describes standards that apply to:
Investigators, sponsors, and IRBs
A Foreign Person is an individual who:
Is only a citizen of a country other than the U.S.
The Belmont Report's principle of respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that:
Persons with diminished autonomy are entitled to protection.
Adults with more than a twelve (12)-month history of migraines were assigned randomly in a double-blinded study to receive treatment with experimental drug X (10 or 20 mg/day) or placebo. The primary efficacy measure was the reduction in severity of the migraine attacks. Enrollment was twelve-hundred (1200) subjects. Which of the following best describes the clinical phase of this study?
Phase III
Long-term toxicology of an experimental drug in animals most likely refers to which part of drug development?
Preclinical
For a Phase I new drug study in humans, what is the primary source of the data included in the initial Investigator's Brochure?
Preclinical data
A subject presents to the emergency department (ED) with complaints of chest pain and shortness of breath. Blood studies are positive for a heart attack and the subject is hospitalized. The subject has a history of coronary artery disease. The subject reports to the ED nurse that he is currently enrolled in a Phase I study of a new lipid lowering agent. Which individual should determine causality of the serious adverse event?
Principal Investigator
An investigator obtains consent and HIPAA authorization from subjects to review their medical records and HIV status. She plans to go back to the medical record, so the HIV status information is stored along with subject identifiers in a database that she keeps on her laptop computer. What are some safeguards she could use to protect subject privacy and data confidentiality?
Privacy is about people and their expectations. Privacy risk pertains primarily to the methods used to obtain information about subjects. Confidentiality pertains to the actual treatment of the personal information once it is obtained. In other words, now that the researcher has obtained private information, how will it be used, stored, and reported. Clearly, this event represents a breach of confidentiality.
A subject of a research study is a passenger in a car involved in a motor vehicle crash. The subject sustained a broken wrist and mild concussion. The subject was treated and released from the emergency department. What should the investigator do when learning of the crash?
Report adverse events of both a broken wrist and a mild concussion.
Subject 311 has had elevated white blood cell (WBC) counts for the past two (2) study visits, with no clinical signs or symptoms. "Increased WBC count" is not listed in the Investigator's Brochure (IB) as an adverse event. The investigator should:
Report the elevated WBC to the sponsor as an unexpected adverse event
Which of the following are the three principles discussed in the Belmont Report?
Respect for Persons, Beneficence, Justice
Which of the following are the three principles included in the Belmont Report?
Respect for Persons, Beneficence, Justice.
When should the sponsor-monitor conduct the most detailed review of the study protocol with the site's study staff?
Site initiation visit
In considering NBAC's analytic approach, an otherwise competent person who is acutely ill might be considered at especially high risk of harm for:
Situational cognitive vulnerability
Who is responsible for making the initial risk determination for a device being used in a study?
The sponsor-investigator.
During the course of administration of an investigational drug, the following events occurred: On Day 7, subject 603 had an unexpected stroke that requires hospitalization; On Day 15, subject 415 complained of nausea, vomiting, and headache relieved by aspirin; On Day 21, subject 20 has brief dizzy spells upon trying to stand. Which of these subject's events meets the FDA definition of "serious" and "unexpected" and would require the sponsor to file an IND Safety Report with the FDA?
Subject 603 only
Which of the following is an investigator's commitment to the sponsor?
Submit a new Form FDA 1572 to the sponsor as needed
All unused investigational agents are expected to be returned to the sponsor at the:
Termination site visit
An investigator is confronted with a life-threatening situation that necessitates using a test article in a human subject who is unable to provide informed consent and there is no time to obtain consent for the individual's legal representative. Under the FDA regulations, which of the following describes the best course of action for the investigator:
The investigator and another physician not part of the study team agree that the situation necessitates the use of the test article and the IRB will be notified later.
The research study is no greater than minimal risk for the pregnant woman and the fetus, and holds the prospect of direct benefit to both the pregnant woman and the fetus. Who needs to provide consent under Subpart B?
The mother
A researcher wants to conduct a secondary analysis using a Centers for Disease Control and Prevention (CDC) database that was collected by the agency solely for surveillance purposes from 1996-2006. The researcher did not participate in the initial collection of the data. The database is publicly available. The database does not include any identifiers. The IRB makes a determination that the individuals whose records will be reviewed do not meet the federal definition of human subjects. Which of the following considerations was relevant to the IRB's determination that this activity does not constitute research with human subjects?
The researcher will not be interacting/intervening with subjects and the data has no identifiers.
Identify which party is responsible for reporting directly to the FDA the investigator's financial interests with the sponsor:
The sponsor
Under which circumstance does the FDA allow verbal consent prior to participation in a research study?
The study is minimal risk.
Which of the following is an acceptable criterion for determining that a study of an approved drug does not require an IND?
The study is not intended to be reported to FDA to support a new indication or support a labeling change.
When evaluating the causality of an adverse event, which of the following should be a consideration?
The timing of the event in relation to administration of the investigational agent
Which choice best describes the purpose of most pharmacogenomic research?
To evaluate the association between individual genotypes and the safety and efficacy of a particular drug or class of drugs
Pregnant women, fetuses, and neonates are often considered vulnerable categories of subjects. Additional protections are provided through regulation, however, the protections are meant to be inclusive and not exclusive of pregnant women in research.
True
When designing a database and data collection instruments for a study, the Data Manager should:
Use standards to reduce the time required to set up the database and to increase the consistency of the data
In the United States, following the ICH E6 guideline is:
Voluntary for FDA-regulated drug studies.
A 510(k) Premarket Notification is submitted:
When the new device to be marketed is substantially similar (equivalent) to one already on the market
A researcher wants to collect data about fetuses that were exposed to high levels of lead during their mother's pregnancy. The researcher plans to review the medical records for a control group (not known to be exposed to high levels of lead) and an experimental group (exposed to high levels of lead) of fetuses from 12 weeks of gestation through delivery. Is this research permitted under Subpart B?
Yes - research with neonates of uncertain viability may be involved because there is no additional risk
