CITI training – Flashcards

What must you file before conducting human clinical trials with an experimental drug?

During the clinical development phase of the IND process, what must sponsors do?

this document notifies FDA of relevant changes in investigators conducting clinical trials under the IND.

What is the timeline of drug development?

When does a sponsor submit the IND?

What is the NDA?

How long does the NDA submission take?

What is determined for a drug in the preclinical phase

How long does FDA have to review IND submission?

How long is the clinical development phase (Phase 1-III) in process for IND?

Determine the trial phase: - Assess toxicity - Determine drug's PK and PD profiles - Determine doses resulting in sufficient biological level of drug

Determine the trial phase: - Determine drug's effectiveness (primary goal) - Determine long-term drug safety - Confirm findings

Determine the trial phase: - Determine drug's short-term risk (safety) (primary goal) - Examine preliminary effectiveness of drug

Determine the trial phase from the subject population: Controlled studies enrolling limited numbers of patients

Determine the trial phase from the subject population: Controlled and uncontrolled studies (but typically placebo-controlled and double-blinded) enrolling larger patient numbers.

Determine the trial phase from the subject population: Normal healthy volunteers unless toxicity prevents exposure (e.g, cancer drugs). In this, case patients with end-stage disease might be enrolled.

If an IND application is submitted and the FDA has not contacted the physician within 30 days after acknowledging receipt, can the trial start?

What must be provided to investigators before they beginning conducting trials at their site?

What regulation must a PI comply with in order to use an edc system for a clinical trial?

What happened because of the concern and confusion regarding interpretation of Part 11in 2003.

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

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

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?

Long-term toxicology of an experimental drug in animals most likely refers to which part of drug development?

Pharmacokinetics and pharmacodynamics of a new formulation of an investigational drug most likely refers to which clinical phase of a study in humans?

For a Phase 1 new drug study in humans, what is the primary source of the data included in the initial Investigator's Brochure?

What is ICH's more specific name?

what is the goal of the ICH?

Define the term: an individual, or judicial or other body, authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedures involved in the research

an unplanned excursion from the requirements of the protocol that is not implemented or intended as a systematic change.

What are the 6 regulatory and pharmaceutical industry groups that have representatives working for ICH?

How do the World Health Organization (WHO) and the European Free Trade Association (EFTA) [represented by Swissmedic, and Health Canada participate with ICH?

How is the ICH governed?

Who supports the ICH?

Who provides the ICH secretariat?

How many seats on the Committee does each of the 6 working groups of ICH have?

who nominates other nonvoting participants to attend ICH steering Committee meetings?

Is the ICH GCP regulation or guideline?

What are the four main categories covered by ICH guidelines?

What are the expert working groups responsible for?

ICH E6 guideline pertains specifically to what

Provides a unified standard for designing, conducting, recording, and reporting research involving human subjects.

What are the two important goals of the ICH E6 standard?

Where do the ethical principles followed by ICH GCP guidelines originate from?

What ethical principles stem from the Declaration of Helsinki?

If planning to market drugs outside the US, what guidance must a PI follow while conducting the clinical trial?

Can an employee at the research site be witness to a patient's consent?

What must a witness do before the consent process starts?

If following ICH guidelines who all should sign the consent form between the subject, witness, and person obtaining consent.

Define: Oversee research involving human subjects to assure the protection of their rights, safety, and welfare.

FDA or ICH: requires the consent form to include a statement that "monitors, auditors, the IRB/IEC, and the regulatory authorities will be granted access to the subject's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the subject is authorizing such access

FDA or ICH: Treatment alternatives only need to be listed in the consent form

FDA or ICH: requires that the potential benefits and risks of the alternatives should also be included in the consent form.

What does the ICH E6 guidelines require in a consent form for treatment arms.

Does FDA require description in consent if research provides no expected benefit?

What does ICH require in terms of benefits in the ICF?

Is assent required for both FDA and ICH?

Define Assent

FDA vs. ICH when enrolling an adult who is unable to consent for him or herself.

ICH or FDA: Only subjects who are able to consent for themselves are allowed to enroll in non-therapeutic research studies (a trial in which there is no anticipated direct clinical benefit to the subject.

When can ICH allow subjects to be enrolled that cannot consent for themselves? (Exceptions)

T/F: FDA requires Investigator to inform the subject's primary physician about the subject's participation in the trial if subject has a PCP and if the subject agrees to the primary physician being informed.

FDA or ICH requirement: IRB/IEC is required to review -written ICF and updates - trial protocols/amendments - subject recruitment procedures (advertisements) - written information to be provided to subjects - IBs Safety information Info about payments and compensation to subjects - CVs and qualifications - any other docs IRB/IEC may require to fulfill its responsibilities

Per FDA requirements, what is required of the IRB/IEC?

A primary purpose of the ICH is to: - require publication of negative trial results. - develop mandatory worldwide regulations for drug development. - require FDA registration of worldwide clinical trials. - minimize the need for redundant research

The ICH GCP guidelines: - set standards for the design, conduct, monitoring and reporting of clinical research. - guarantee that a submission in any ICH region will be approved for marketing. - require certification of clinical research sites and investigators - replace FDA regulations for internationally conducted studies of drugs that will be marketed in the U.S.

The ICH E6 GCP describes standards that apply to: -Investigators, sponsors, and IRBs. - Research sponsors only - Investigators only - IRBs only

In the United States, following the ICH E6 GCP is: - Voluntary for FDA-regulated drug studies. - Mandatory for studies conducted outside the United States. - Mandatory for investigational device studies. - Mandatory for drug studies.

The FDA will apply: - The ICH E6 GCP standards - The Code of Federal Regulations - Local IRB requirements - State law where the sponsor's headquarters are located.

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

Regarding subject signature on consent forms, which is true about dates?

ICH requires a witness when enrolling illiterate subjects, true or false?

Regarding probability of assignment to trial arms in consent forms, which is true?

When is there "Sponsor-investigators"

Who addresses the role of "Sponsor-investigators?"

means in addition to producing the drug, the company also supplies the investigator with the drug for use in the study

means the entity who takes responsibility for and initiates a clinical investigation. The sponsor can be any legal entity, including a company, an academic organization, or an individual. The intent of the sponsor's IND is to allow testing for marketing approval of the drug. These are generally considered commercial or corporate INDs. Note: the sponsor is often but not always the entity that funds the clinical research.

means an individual who both initiates and conducts the clinical investigation and under whose immediate direction the investigational drug is being administered, used, or dispensed. The sponsor-investigator assumes all of the responsibilities of the sponsor as well as all the responsibilities of an investigator as outlined in the Form FDA 1572 (see the module, Investigator Obligations in FDA-Regulated Research). Usually, the intent of the sponsor-investigator trial is to gain scientific knowledge without seeking market approval for the drug. These are considered investigator-initiated or sponsor-investigator trials.

Usually, the intent of the sponsor-investigator/investigator-initiated trial is to

the regulation stating: exception from informed consent for emergency research

What can Investigators reference when unsure if an IND is required for a study of an approved drug?

Form FDA ______: Statement of the Invesitgator

Form FDA ____: Investigational New Drug Application, NDA

detailed requirements for the content and format of an IND can be found in

what can be cross-referenced when the manufacturer of an IND already has an active IND for the drug being studied?

Form: contractual agreement between the sponsor and FDA.

21 CFR 56

The content for an IND for studies of marketed products is the same as the content for studies of new drugs, with the following exception:

what are the three types of protocol amendments?

submitted when new toxicology, chemistry, or other technical information is available. Study discontinuation is also submitted as this.

When do Annual Reports need to be submitted to the FDA?

The following are purposes of what: -The rights and well-being of human subjects are protected. -The reported trial data are accurate, complete and verifiable from source documents. -The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable regulatory requirements.

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? A. IND renewal application B. Adverse Event Summary Report, but only from unblinded portions of studies ("open-label IND safety report") C. IND report D. Marketing plan (i.e. annual updated projection of sales and profits)

Which of the following is a criterion for determining if a study of an approved drug is exempt from the require of an IND? A. The study intends to invoke an exception from informed consent. B. The study involves a route of administration that significantly increases the risks to the patient. C. The study is not intended to be reported to FDA to support a new indication or support a labeling change. D. The study intends to involve more than 100 patients in a study.

Which of the following reports must be filed using an FDA Form 1572? A. Annual Reports B. Addition of a new investigator C. Protocol amendments

the tool used to record data collected during a clinical trial

document that includes information needed for potential subjects to have sufficient info to provide informed consent to participate in a clinical trial. The FDA regulations and ICH E6 describe the information that must be included in the consent form.

any board, committee, or other group formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of, biomedical research involving human subjects. " Assure the protection of the rights and welfare of the human subjects.

All info in original records and certified copies of original records of clinical findings ETc

Initial documentation of data in a clinical study and includes recorded observations, laboratory reports, medical records, etc.

This agreement is a contract that defines both the terms of study conduct and the financial agreements

When is it necessary for an investigator to complete and sign a new 1572?

What needs to be done when there are other changes to information contacted on a signed and dated 1572? (IRB/IEC address change, addition of a clinical research lab)

ICH or FDA, requires submission of up to date curriculum with changes?

clinical trials of drugs or devices from which the data will be submitted to the FDA to support a marketing application or relied upon by the FDA to establish effectiveness.

For purposes of financial disclosures, the term (blank) includes anyone who is directly involved in the treatment or evaluation of research subjects. The term also includes the spouse and each dependent child of the (blank).

21 CFR 54

The investigator's financial interests with the pharmaceutical company (sponsor) or to the outcome of the clinical investigation is reported directly to the FDA by: A) The investigator's institution B) The investigator C) The IRB D) The sponsor

In completing Form FDA 1572, Statement of Investigator, the Investigator agrees to: A) Maintain a contract with the sponsor B) Maintain records indefinitely C) Report to the FDA any adverse events that occur. D) Conduct or supervise the investigation personally

Form FDA 1572, Statement of Investigator, is legally binding between the Investigator and the: A) Subjects B) Sponsor C) FDA D) IRB

The investigator must report adverse events to the: A) Subject B) Sponsor C) FDA D) IRB only

When must the investigator update the IRB about the progress of a trial? A) During the conduct of the study and at termination B) During the conduct of the study only C) Never D) At study termination only

Which of the following is an investigator's commitment to the sponsor? A) Submit documents to sponsor for yearly approval to continue the study B) Retain study documents for 3 years after study completion at the site C) Provide the financial disclosure document directly to FDA D) Submit a new FDA form 1572 to sponsor as needed

"...any virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment or cure of diseases or injuries"

"...a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use" (ICH GCP E6 Section 1.33).

"...a new drug, antibiotic drug, or biological drug that is used in a clinical investigation. The term also includes a biological product that is used in vitro for diagnostic purposes" (21 CFR 312.3).

Which of the following is an important component of drug accountability? A) Environmental controls B) Drug shipping and disposition records C) Patent expiration date D) Manufacturer's compounding procedures

Who has ultimate responsibility for an investigational product?

Investigational product dispensing or administration info for the sponsor is recorded on the:

The packaging of investigational drugs should ideally A) look like a marketed product B) allow subjects to identify placebo pills C) be designed to help with subject compliance D) be attractive so the study coordinators will use it

Where is info on storage requirements for the investigational product usually found? A) on the product code-breaker label B) In the CRF directions C) In the drug accountability log D) In the study protocol

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?

Which of the following statements in a consent form is an example of language that appears to waive a subject's rights?

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:

Under which circumstance does the FDA allow verbal consent prior to participation in a research study?

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

Which of the following best describes when the majority of CRF data are verified against source record information?

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

The FDA requires retention of investigational drug study records for: