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CITI training Exam with complete
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What must you file before conducting human clinical trials with an experimental drug? - ANSWER IND application (Form FDA 1571) During the clinical development phase of the IND process, what must sponsors do? - ANSWER Maintain current IND application by amending IND with new Form FDA 1571 and providing FDA with: safety updates copies of new protocols FDA 1572 Annual Progress reports this document notifies FDA of relevant changes in investigators conducting clinical trials under the IND. - ANSWER Form FDA 1572 What is the timeline of drug development? - ANSWER Preclinical trials, IND Submission, Clinical Development (Phase I-III), NDA submission, Marketing (Phase IV) When does a sponsor submit the IND? - ANSWER Prior to clinical development phases (human trials). *30 day process. What is the NDA? - ANSWER New Drug Application, submitted prior to Phase IV marketing phase. How long does the NDA submission take? - ANSWER 6 months - 2 years. What is determined for a drug in the preclinical phase - ANSWER Pharmacokinetics and bioavailability Outcome shows promise of safety and efficacy warranting additional studying. How long does FDA have to review IND submission? - ANSWER 30 days How long is the clinical development phase (Phase 1-III) in process for IND? - ANSWER 6-7 years. Determine the trial phase:
- Assess toxicity
- Determine drug's PK and PD profiles
- Determine doses resulting in sufficient biological level of drug - ANSWER Phase I
Determine the trial phase:
- Determine drug's effectiveness (primary goal)
- Determine long-term drug safety
- Confirm findings - ANSWER Phase III Determine the trial phase:
- Determine drug's short-term risk (safety) (primary goal)
- Examine preliminary effectiveness of drug - ANSWER Phase II Determine the trial phase from the subject population: Controlled studies enrolling limited numbers of patients - ANSWER Phase II Determine the trial phase from the subject population: Controlled and uncontrolled studies (but typically placebo-controlled and double- blinded) enrolling larger patient numbers. - ANSWER Phase III 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. - ANSWER Phase I If an IND application is submitted and the FDA has not contacted the physician within 30 days after acknowledging receipt, can the trial start? - ANSWER Yes, one of two conditions must be met.
- 30 days elapsed since FDA received IND application and no hold as been placed.
- Correspondence has ben received from FDA allowing the trial to start. What must be provided to investigators before they beginning conducting trials at their site? - ANSWER Protocol and Investigator's Brochure What regulation must a PI comply with in order to use an edc system for a clinical trial?
- ANSWER 21 CFR Part 11 21 CFR 56.115(b) - ANSWER 21 CFR 312.57 - ANSWER 21 CFR 312.62 - ANSWER 21 CFR 812.140 - ANSWER What happened because of the concern and confusion regarding interpretation of Part 11in 2003. - ANSWER FDA withdrew all the guidance documents related to Part 11, while re-examining. They then issued: Guidance for Industry: Part 11, Electronic Records; Electronic Signatures-Scope and Application (2003) and Guidance for Industry: Computerized
- US Food and Drug Administration (FDA)
- Pharmaceutical Research and Manufacturing of America (PhRMA) How do the World Health Organization (WHO) and the European Free Trade Association (EFTA) [represented by Swissmedic, and Health Canada participate with ICH? - ANSWER As observers. How is the ICH governed? - ANSWER a Steering Committee Who supports the ICH? - ANSWER the ICH Secretariat Who provides the ICH secretariat? - ANSWER The International Federation of Pharmaceutical Manufacturers Association (IFPMA) How many seats on the Committee does each of the 6 working groups of ICH have? - ANSWER 2 who nominates other nonvoting participants to attend ICH steering Committee meetings? - ANSWER The observer groups (WHO, Health Canada, and EFTA) Is the ICH GCP regulation or guideline? - ANSWER Depends, several countries adopted it as law, but the U.S FDA adopted it only as guidance. (Federal Register, Vol. 62, MAY 9, 1997) What are the four main categories covered by ICH guidelines? - ANSWER Q: Quality topics (chemical and pharmaceutical assurance) S: Safety topics: in vitro and in vivo preclinical research E: Efficacy topics: relating to research in human subjects M: Multidisciplinary topics: those that do not fit uniquely into one of the above categories. (QSEM) What are the expert working groups responsible for? - ANSWER developing specific guidelines.
- The ICH then provides an efficient process and format to standardize the new requirements across agencies and countries. ICH E6 guideline pertains specifically to what - ANSWER the conduct of clinical research to support marketing applications for drugs. Provides a unified standard for designing, conducting, recording, and reporting research involving human subjects. - ANSWER ICH E6 guideline for good clinical practice. What are the two important goals of the ICH E6 standard? - ANSWER To assure that 1: The rights, well-being, and confidentiality of trial subjects are protected. 2: Trial data are credible.
Where do the ethical principles followed by ICH GCP guidelines originate from? - ANSWER the Declaration of Helsinki What ethical principles stem from the Declaration of Helsinki? - ANSWER in notes.... If planning to market drugs outside the US, what guidance must a PI follow while conducting the clinical trial? - ANSWER ICH E-6 Good Clinical Practice. Can an employee at the research site be witness to a patient's consent? - ANSWER No, they are involved in the trial. Witness must be "a person who is independent of the trial, who cannot be unfairly influenced by people involved in the trial" What must a witness do before the consent process starts? - ANSWER Read the consent form and other written information provided to the participant. They must also determine whether the participant has any other questions and should sign the impartial witness signature block on the consent document. If following ICH guidelines who all should sign the consent form between the subject, witness, and person obtaining consent. - ANSWER All of them. Define: Oversee research involving human subjects to assure the protection of their rights, safety, and welfare. - ANSWER IRBs/IECs 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 - ANSWER ICH GCP FDA or ICH: Treatment alternatives only need to be listed in the consent form - ANSWER FDA FDA or ICH: requires that the potential benefits and risks of the alternatives should also be included in the consent form. - ANSWER ICH What does the ICH E6 guidelines require in a consent form for treatment arms. - ANSWER Description of each arm, the likelihood of being assigned to each of the study arms, and an explanation of " the subject's responsibilities" Does FDA require description in consent if research provides no expected benefit? - ANSWER No, only an explanation of expected benefits of the research?
- any other docs IRB/IEC may require to fulfill its responsibilities - ANSWER ICH E Guideline. FDA not clear in requirements for IRB/IEC review of documents. Per FDA requirements, what is required of the IRB/IEC? - ANSWER to review the consent form (21 CFR 56.109) and to keep "copies of all research proposals reviewed, scientific evaluations, if any, that accompany the proposals, approved sample consent documents. 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 - ANSWER 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. - ANSWER Set standards for the design, conduct, monitoring and reporting of clinical research. The ICH E6 GCP describes standards that apply to: -Investigators, sponsors, and IRBs.
- Research sponsors only
- Investigators only
- IRBs only - ANSWER Investigators, sponsors, and IRBs. 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. - ANSWER Voluntary for FDA-regulated 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. - ANSWER The code of federal regulations What is the legal status of ICH in the U.S.? - ANSWER It is a guideline Regarding subject signature on consent forms, which is true about dates? - ANSWER Both the FDA and ICH require
ICH requires a witness when enrolling illiterate subjects, true or false? - ANSWER True Regarding probability of assignment to trial arms in consent forms, which is true? - ANSWER Only ICH recommends. When is there "Sponsor-investigators" - ANSWER Investigator-initiated trials of investigational drugs. Who addresses the role of "Sponsor-investigators?" - ANSWER FDA means in addition to producing the drug, the company also supplies the investigator with the drug for use in the study - ANSWER Drug Supplier/Manufacturer 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. - ANSWER Sponsor 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. - ANSWER Sponsor-investigator Usually, the intent of the sponsor-investigator/investigator-initiated trial is to - ANSWER gain scientific knowledge without seeking market approval for the drug. the regulation stating: exception from informed consent for emergency research - ANSWER 21CFR 50 What can Investigators reference when unsure if an IND is required for a study of an approved drug? - ANSWER IND exemptions for studies of lawfully marketed drug or biological products for the treatment of cancer OR seek opinion from FDA. Form FDA ______: Statement of the Invesitgator - ANSWER 1572 Form FDA ____: Investigational New Drug Application, NDA - ANSWER 1571 detailed requirements for the content and format of an IND can be found in - ANSWER 21 CFR 312
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. - ANSWER C. The study is not intended to be reported to FDA to support a new indication or support a labeling change. 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 - ANSWER B. Addition of a new investigator. the tool used to record data collected during a clinical trial - ANSWER CRF, case report form 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. - ANSWER Informed Consent Document 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. - ANSWER IRB All info in original records and certified copies of original records of clinical findings ETc
- ANSWER source data. Initial documentation of data in a clinical study and includes recorded observations, laboratory reports, medical records, etc. - ANSWER Source Document. This agreement is a contract that defines both the terms of study conduct and the financial agreements - ANSWER CTA (Clinical Trial Agreement) When is it necessary for an investigator to complete and sign a new 1572? - ANSWER - when participating in a new protocol that has been added to the IND
- When a new investigator is added to the study. 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) - ANSWER investigator should document the changes in the clinical study records and inform the sponsor of the changes, so that the sponsor can appropriately updated the IND.
ICH or FDA, requires submission of up to date curriculum with changes? - ANSWER ICH 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. - ANSWER "covered clinical studies" 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). - ANSWER Investigator 21 CFR 54 - ANSWER Financial Disclosure by Clinical Investigators 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 - ANSWER 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 - ANSWER 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 - ANSWER C) FDA The investigator must report adverse events to the: A) Subject B) Sponsor C) FDA D) IRB only - ANSWER B) Sponsor 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 - ANSWER A) During the conduct of the study and at termination
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? - ANSWER 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 statements in a consent form is an example of language that appears to waive a subject's rights? - ANSWER I waive any possibility of compensation for injuries that I may receive as a result of participation in this research. 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: - ANSWER 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. Under which circumstance does the FDA allow verbal consent prior to participation in a research study? - ANSWER The study is minimal risk. Which of the following should take place during periodic site visits? - ANSWER Identification of protocol violations Which of the following best describes when the majority of CRF data are verified against source record information? - ANSWER Periodic site visits. When should the sponsor-monitor conduct the most detailed review of the study protocol with the site's study staff? - ANSWER Site initiation visit. The FDA requires retention of investigational drug study records for: - ANSWER At least 2 years after the investigational drug's approval by the FDA.
