CITI - GCP for Clinical Trials with Investigational Drugs and Biologics (ICH Focus)

Which of the following should take place during periodic site visits?

Identification of protocol violations

Form FDA 1572, Statement of Investigator, is legally binding between the Investigator and the:

FDA

Which of the following best describes the principle of informed consent as described in the Belmont Report?

Information, comprehension, voluntariness.

Monitoring

"the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), GCP, and the applicable regulatory requirement(s)" (ICH [2016] E6). Monitoring may be on-site, centralized (also known as remote), or a combination of both.

The sponsor must submit an IND safety report to the FDA if an adverse event is (1) serious; (2) unexpected; AND:

(3) there is a reasonable possibility that the drug caused the event.

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A primary purpose of the ICH is to:

Minimize the need for redundant research.

Module 7

Monitoring Clinical Trials of Drugs by Industry Sponsors

Investigator-oriented inspections

directed at the specific clinical investigator conducting the trial. Typically, these inspections occur when there are complaints of known or suspected misconduct, such as fraud, falsification, or data fabrication.

Study-oriented inspections

directed toward review of study data supporting a pending marketing application, such as: New drug applications (NDAs) Bioequivalence (for abbreviated NDAs)

Module 12

Detecting and Evaluating Adverse Events

Inspection

"act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor's and/or contract research organization's (CRO) facilities, or at other establishments deemed appropriate by the regulatory authority(ies)" (ICH [2016] E6 Section 1.29).

audit

"systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed, and accurately reported according to the protocol, sponsor's standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s)" (ICH [2016] E6 Section 1.6).

Which of the following is required at a prestudy site visit?

Evaluation of the site's capacity to conduct the study

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.

Module 11

ICH—Comparison Between ICH GCP E6 and U.S. FDA Regulations

The FDA will apply:

The Code of Federal Regulations.

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Module 10

Overview of ICH GCP

OHRP is an oversight body primarily concerned with

Protection of human research subjects

Development of most new drugs from discovery to marketing approval usually takes:

9 years or more

According to ICH E6 GCP, an "Audit" is defined as:

A systematic and independent examination of trial-related activities and documents.

Which of the following reports must be filed using an Form FDA 1572?

Addition of a new investigator

According to ICH E6 GCP, an inspection is defined as:

An official review of documents, facilities, records, and any other resources related to a clinical trial.

The FDA requires retention of investigational drug study records for:

At least two years after the investigational drug's approval by the FDA.

Module 8

Audits and Inspections of Clinical Trials of Drugs and Biologics

A double-blinded trial for a new indication is conducted under an IND comparing 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.

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

In completing Form FDA 1572, Statement of Investigator, the Investigator agrees to:

Conduct or supervise the investigation personally.

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.

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

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.

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 integrated addendum (R2) 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.

Where is information on storage requirements for the investigational product usually found?

In the study protocol

Who has ultimate responsibility for an investigational product?

Investigator

The ICH E6 GCP describes standards that apply to:

Investigators, sponsors, and IRBs.

What is the legal status of ICH in U.S.?

It is a FDA guidance

Module 9

Overview of New Drug Development

Which of the following best describes when the majority of case report form (CRF) data are verified against source record information?

Periodic 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 first randomized, controlled study of an experimental drug versus aspirin for postoperative pain control will enroll 55 subjects in each arm. Which of the following best describes the clinical phase of this study?

Phase II

Adults with more than a 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 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

Which monitoring visit would NOT include an inventory of investigational agents?

Prestudy site visit

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

A subject 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 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.

Module 13

Reporting Serious Adverse Events in Investigations of Drugs and Biologics

Which of the following lists the three principles included in the Belmont Report?

Respect for Persons, Beneficence, Justice

If the FDA Investigator issues a FDA Form 483 after an inspection, the clinical investigator should:

Respond in writing to the FDA within 15 business days

When the FDA conducts an inspection, the inspectors will:

Review regulatory records.

The ICH GCP Guidelines:

Set standards for the design, conduct, monitoring and reporting of clinical research.

When should the sponsor-monitor conduct the most detailed review of the study protocol with the site's study staff?

Site initiation visit

The investigator must report adverse events to the:

Sponsor.

During the course of administration of an investigational drug, the following events occur: On Day 7, subject 603 has an unexpected stroke that requires hospitalization. On Day 15, subject 415 complains of nausea, vomiting, and headache relieved by aspirin. On Day 21, subject 20 has brief dizzy spells upon trying to stand. An IND Safety Report is most likely filed by the sponsor with the FDA for the observations associated with:

Subject 603 only

Which of the following is an investigator's commitment to the sponsor?

Submit a new Form FDA 1572 to 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 from 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 who is not part of the study team agree that the situation necessitates the use of the test article and the IRB will be notified later.

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 a criterion for determining if a study of an approved drug is exempt from the require of 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

In the United States, following the ICH E6 GCP is:

Voluntary for FDA-regulated drug studies.

The packaging of investigational drugs should ideally

be designed to help with subject compliance