Citi Training GCP and Refresher
Approximately how many subjects generally participate in phase I studies?
20-80
As the amount of adaptive study designs and multiple-arm protocols increases, researchers are now adding small cohorts of a diseased population to phase I studies to assess the initial safety and effectiveness in the drug's targeted population. This approach allows researchers to gather preliminary efficacy data in the diseased population. An example of this would be:
A first-in-human protocol testing of a new drug being developed for the treatment of diabetes, including a group of subjects with diabetes.
What do sponsor audits, monitoring visits, and regulatory inspections have in common?
Ensure human subject protection, data integrity, and product accountability.
Which of the following are common deficiencies noted during FDA inspections?
Failure to follow the protocol, protocol deviations, and inadequate recordkeeping.
The ICH E6 guideline should be followed when:
Generating clinical trial data that are intended to be submitted to regulatory authorities
Which of the following criteria could lead to a site regulatory inspection/audit?
High enrollment numbers
Which of the following statements in a consent form is an example of language that appears to waive a subject's rights?
I waive any possibility of compensation for injuries that I may receive as a result of participation in this research.
Which of the following is the current international GCP standard for medical devices?
ISO 14155:2011
Many phase I studies will compensate subjects for their time and participation in the research. The FDA (1998) includes the following statement in their Information Sheet on Payment to Research Subjects: "Financial incentives are often used when health benefits to subjects are remote or non-existent." While payment to subjects is considered a recruitment incentive and not a benefit, it is common in phase I research to:
Include a compensation stipend.
Which of the following is part of a clinical site inspection?
Interview with study staff
According to ICH E6, who should explain the correct use of the investigational product(s) to each study subject and check, throughout the study, to see if each subject is following the instructions properly?
Investigator or person designated by the investigator
ICH E6 describes standards that apply to:
Investigators, sponsors, and Institutional Review Boards (IRBs) / Independent Ethics Committees (IECs) / Research Ethics Boards (REBs).
A primary purpose of the ICH E6 guideline is to:
Minimize the need for redundant research.
Many phase I studies now include adaptive study designs which allow changes to the design of the trial as new information is discovered; as is often the case with phase I studies. According to the author, adaptive trial designs have many benefits, including:
More efficient and thorough late phase multicenter research related to dose selection, subject selection, and safety monitoring.
You are a sponsor-investigator and submitted an IDE to the FDA thirty (30) days ago. You just received a telephone call from an FDA reviewer stating that they completed their review and the investigational device exemption (IDE) is not approved. However, they will require 1-2 additional days to provide you with written feedback about deficiencies. Would you begin the clinical investigation?
No, you received a phone call at the end of the thirty (30)-day IDE review period notifying you that the IDE is not approved.
Which of the following is addressed in both the ISO 14155:2011 GCP standard and the FDA regulations?
Overseeing the use of an investigational device
Which of the following defines phase I research as it relates to non-clinical and other phases of research:
Phase I research is the first phase of research after animal testing and helps define future phase II and III studies.
When should informed consent be obtained?
Prior to initiating any requirements of the study protocol.
What is a regulatory challenge of taking on the "sponsor" role in investigator-initiated studies for a sponsor-investigator that is not the regulatory responsibility of an investigator?
Providing study monitoring
Who has the ultimate responsibility for the administration/dispensation of an investigational product at the clinical site?
Qualified/Principal Investigator
Who has ultimate responsibility for an investigational product at the study site?
Qualified/Principal Investigator
A monitor visits a site conducting a Phase III study for an investigational drug to treat depression. The monitor is surprised to see so many improperly completed case report forms (CRFs) by the study personnel. The monitor would likely take the following action:
Retrain, if necessary, the study coordinators on CRF filling procedures as outlined in the protocol.
You are an investigator conducting a pivotal IDE clinical investigation in the European Union (EU) jurisdiction. A FDA investigator arrives at your busy outpatient clinic unannounced, asks for you by name, and shows identification and states your study will be audited. What should you do?
Review the FDA investigator's identification, request a copy of the inspection letter, and ask your research team to provide any required documents.
Delegation of study-related tasks by the qualified/principal investigator to other study team members (for example, completion of the Case Report Form [CRF]) is permitted, provided that:
The individual has been trained/experienced in the task and has signed the task delegation log.
Which of the following statements appears in ICH E6 Section 4.2 entitled "Adequate Resources?"
The investigator should ensure that all persons assisting with the trial are adequately informed about the protocol, the investigational product(s), and their trial-related duties and functions.
The two important goals of the ICH E6 standard are:
To assure that the rights, well-being, and confidentiality of trial subjects are protected; to assure that trial data are credible.
The following is an IRB consideration for review of phase I research:
Type of subjects enrolled
Which of the following is a report that sponsors must submit to regulatory authorities during the conduct of a clinical investigation?
Withdrawal of IRB approval
A study subject breaks his leg in a skating accident. Is this incident a Serious Adverse Event (SAE)?
Yes - if the subject stayed in hospital overnight or had serious complications.
An Institutional Review Board (IRB) in the U.S. is reviewing a clinical investigation targeting children ages 3-5 years old with Fragile X syndrome. There is a prospect of direct benefit to the children in the context of the investigation. Based on this information, may the IRB waive the requirements for assent?
Yes, when the children are incapable of understanding the research, there is a prospect of direct benefit to the children that is not available outside of the research or when the requirements for a waiver of consent under federal regulation 21 CFR 50.55 are satisfied.
The packaging of investigational drugs should ideally
Be designed to help with subject compliance
An "Audit" is defined by ICH E6 as:
A systematic and independent examination of trial-related activities and documents.
Which of the following is true when a sponsor's responsibilities are transferred to a Contract Research Organization (CRO)?
All transferred responsibilities need to be documented in writing.
In ICH E6, what is the difference between an adverse event (AE) and adverse drug reaction (ADR)?
An adverse drug reaction is a response to the investigational product and an adverse event may or may not be a response to the investigational product.
A healthy volunteer is considering participating in a research study testing a new vaccine for Ebola. He has left his glasses at home and he is unable to read the informed consent form. According to ICH E6, who must be present during the discussion of informed consent?
An impartial witness
The ISO 14155:2011 GCP standard applies to clinical investigations of:
An intravascular catheter used to diagnose ischemia (reduced blood flow)
According to ICH E6 Section 4.11.1, the investigator should notify the sponsor of serious adverse events (SAE):
As soon as possible after the investigator is aware of the SAE
According to ICH E6 the investigator should fulfill the following criteria: Meet all the qualifications specified by the applicable regulatory requirements. Provide evidence of qualification through a Curriculum Vitae and other documentation requested as applicable by the sponsor, the IRB/IEC/REB, regulatory authorities and institution. What is the additional requirement stated by ICH E6?
Be qualified by education, training and experience
The sponsor of a study has several responsibilities, including:
Designating appropriately qualified medical personnel to advise on trial-related medical questions or problems.
A 46-year-old man is currently enrolled in a Phase 3 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
According to ICH E6, if a research study is prematurely terminated or suspended for any reason, the investigator should notify the IRB/IEC/REB and applicable regulatory authorities, as well as which of the following?
Promptly inform the research subjects of the study termination or suspension and assure appropriate therapy and follow-up for the research subjects.
ICH topics and guidelines fall into four main categories:
Quality, Safety, Efficacy, Multidisciplinary
A regulatory authority (for example, Health Canada or the FDA) sends a representative to evaluate a trial in order to assure protection of research subjects, verify data, and assure compliance with regulations. This is an example of:
Regulatory Inspection
Which of the following are included with an investigational device exemption (IDE) submission to the U.S. Food and Drug Administration (FDA)?
Report of prior investigations, summary of the investigational plan, and copies of device labeling.
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 effect.
According to a definition used in ICH E6, an individual (not a corporation or agency) who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a research subject is a:
Sponsor-Investigator
Which of the following statements describes the informed consent requirements in the U.S.?
Subjects must be given sufficient time to decide whether or not to participate.
According to ICH E6, one purpose of effective study monitoring is to verify that:
The rights, safety, and well-being of all study subjects are being protected.
Which of the following is an important component of drug accountability?
Drug shipping and disposition records
According to the FDA, which of the following describes a significant risk (SR) device?
Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of the subject.
You are a new investigator planning your first medical device clinical investigation in Europe. At a minimum, you should:
Comply with ISO 14155:2011, along with any country-specific legal or regulatory requirements
In first-in-human research, researchers review the non-clinical data thoroughly to assess if there is sufficient information to support the initiation of human studies. The highest dose level tested in animal species that did not produce a significant increase in adverse effects compared to a control group should be identified. This is identified as the No Observed Adverse Effect Levels (NOAEL) and is:
Much lower than the expected therapeutic level.
Investigators involved in clinical investigations of medical devices are responsible for which of the following:
Overseeing the use of the investigational device
Humanitarian Use Devices (HUDs) are devices that are intended to benefit:
Patients in the treatment or diagnosis of a disease or condition affecting less than 8,000 individuals in the U.S. per year.
Identify the following type of study design that is generally used in first-in-human research study:
Single Ascending Dose (SAD)
Who is responsible for ensuring that investigators conducting clinical investigations of medical devices are qualified by education, training, and experience?
Sponsor
Which of the following is a safeguard that can be used to protect healthy research subjects involved in first-in-human research?
Start with a single ascending dose design to allow for small increments in the dose level.
An Institutional Review Board (IRB) conducts the initial review of a sponsor's proposed clinical investigation of a non-significant risk (NSR) medical device and determines that the device as used in the clinical investigation is significant risk (SR). What does this mean?
The medical device requires an IDE submission to the FDA.
According to ICH E6, for a clinical trial in which there are no expected benefits to subjects (that is, a non-therapeutic trial), which of the following must apply in regards to informed consent for subjects unable to give their consent personally and must use a legally acceptable representative (LAR)?
The objectives of the trial cannot be met by means of a trial in subjects who can give informed consent personally.
The federal regulations for the informed consent process and documentation are:
The same for all phases of research.
An investigator calls you to get your opinion on whether an investigational device may be used in an individual with a life-threatening condition. According to the investigator, an independent physician also agrees with the seriousness of the condition, and there is no alternative treatment that provides an equal or better chance of saving the individual's life. The subject is unable to give consent, and there is insufficient time to obtain consent from the subject's LAR. What would you tell the investigator?
The situation does meet the requirements in 21 CFR 50.23 and ISO 14155:2011, so the investigational device may be used.
Which of the following statements about the informed consent form is true according to ISO 14155:2011?
The subject (or the subject's LAR) must receive a signed and dated copy of the informed consent form.
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 product
A study subject reports that he has been having headaches for years but they seem to have become more frequent since starting the study. The investigator believes this is not related to the study medication. How would a clinical research coordinator document this event?
This event would be an adverse event because the complaint is more frequent headaches since starting the study.
An investigator is conducting a medical device clinical investigation in the European Union (EU) under ISO 14155:2011 and received money from the same device sponsor for consulting work related to a new investigation. How should the investigator report this?
To the sponsor and IRB, as required
Dr. Cardio is conducting an IDE clinical investigation involving a drug-eluting stent. She is about to insert the stent into the right coronary artery, per protocol, when she notices that the subject has a major blockage in the left main artery. She decides to deviate from the protocol for the safety of the subject, and places the investigational stent in the left main artery. How should Dr. Cardio report this?
To the sponsor and the reviewing IRB within five (5) working days
What should happen to unused investigational agents when the study is over?
Unused investigational agents should be shipped back to the sponsor or to an alternative that the sponsor has designated.
