CITI GCP Training Questions and Answers Graded A+

CITI GCP Training Questions and Answers Graded A+ 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. ICH (2016) E6 Section 4.8.10(n) states that the informed consent should indicate that "the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) will be granted direct 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 or the subject's legally acceptable representative is authorizing such access." The FDA regulations at 21 CFR 50.25(a)(5) (Protection of Human Subjects 2016) state only that in seeking informed consent, the following information shall be provided to each subject:. . . (5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records. While it is true that data sent out of the U.S. loses certain federal protections, this statement is not required. The possibility of hacking data is a risk that should be addressed in the study design and conduct. Non-disclosure forms are not required for communications with primary care providers. What is the status of ICH in U.S.? It is a FDA guidance. After the ICH E6 guideline was finalized, several countries adopted it as law. In the United States, however, the FDA adopted the ICH E6 only as guidance. Therefore, the ICH E6 guideline does not have the force of law in the United States and is not a regulation. In the Federal Register notice, FDA stated that the ICH E6 guideline "does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes, regulations, or both" (HHS and FDA 1997, 25692). Therefore, compliance is voluntary, but as with any published FDA guidance, compliance is considered part of good clinical practice. 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. The FDA regulations allow subjects to receive either a signed or unsigned copy. ICH E6 Section 4.8.11 requires that the subject or the legally acceptable representative (LAR) receive a copy of the signed and dated written informed consent form. The FDA (1998) regulations allow subjects to receive either a signed or unsigned copy. To be in compliance with ICH E6 guideline, the investigator should include a statement in the consent form that the subject will receive a signed and dated copy of the consent form. Persons obtaining consent must then ensure that this procedure is followed. 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. ICH (2016) E6 Section 5.0.4 states that the sponsor should decide which risks to reduce and/or which risks to accept. The approach used to reduce risk to an acceptable level should be proportionate to the significance of the risk. Risk reduction activities may be incorporated in protocol design and implementation, monitoring plans, and agreements. Routine scheduled audits of study documentation whether on-site or remote are not considered fully responsive to the need for continuous monitoring of data under a proactive risk-based approach. While data from Case Report Forms may be selected for ongoing monitoring, there is no ICH template and a “one-size-fits-all” approach is not appropriate for study-specific monitoring. The use of any specific method of analysis quality improvement is not required and routine annual review may not be sufficient for monitoring the study-specific risks that have been identified. 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. ICH (2016) E6 Section 4.8.10(c) states that “Both the informed consent discussion and the written informed consent form and any other written information to be provided to subjects should include the probability for random assignment to each treatment;" however, it does not specify how the information should be presented. The FDA has no such requirement about including probability for random assignment to each treatment, but does require an identification of any procedures which are experimental. This difference can be addressed by including a description of each arm of the study in the consent form, and including a statement about the likelihood of receiving each of the study arms. Form FDA 1571 Investigational New Drug Application. By signing the 1571, the sponsor-investigator agrees to the following: Not to begin clinical investigations until thirty (30) days after FDA's receipt of the IND, unless the investigator receives earlier notification from the FDA Not to begin or continue investigations covered by the IND if those studies are placed on clinical hold That an IRB/IEC that complies with 21 CFR 56 will be responsible for initial and continuing review and approval of each of the studies in the proposed clinical investigations To conduct the investigation in accordance with all other applicable regulatory requirements Form FDA 1572 Statement of Investigator Investigator's Brochure A compilation of the clinical and nonclinical data on the investigational products which is relevant to the study of the investigational products in human subjects. (ICH GCP E6 1.36) Letters of Cross-Reference In some instances, the manufacturer of an IND might already have an active IND for the drug being studied by a sponsor-investigator. In these instances, the manufacturer may agree to provide a letter of cross-reference that enables the sponsor-investigator to reference the following technical information from the manufacturer's IND in the sponsor-investigator IND: Chemistry, manufacturing, and controls (CMC) information Pharmacology and toxicology information Previous human experience with the drug This cross-referencing between INDs prevents the unnecessary submission of duplicate information to the FDA and lessens the burden on the sponsor-investigator. However, if the drug product or process is different from that of the drug information being cross-referenced from the manufacturer's IND, a CMC section detailing those different processes must be included in the sponsor-investigator IND. 21 CFR 56 Institutional Review Boards 21 CFR 312.50 General Responsibilities of Sponsors. Sponsors are responsible for selecting qualified investigators, providing them with the information they need to conduct an investigation properly, ensuring proper monitoring of the investigation(s), ensuring that the investigation(s) is conducted in accordance with the general investigational plan and protocols contained in the IND, maintaining an effective IND with respect to the investigations, and ensuring that FDA and all participating investigators are promptly informed of significant new adverse effects or risks with respect to the drug. Additional specific responsibilities of sponsors are described elsewhere in this part. 21 CFR 312.60 An investigator is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safety, and welfare of subjects under the investigator's care; and for the control of drugs under investigation. An investigator shall, in accordance with the provisions of part 50 of this chapter, obtain the informed consent of each human subject to whom the drug is administered, except as provided in 50.23 or 50.24 of this chapter. Additional specific responsibilities of clinical investigators are set forth in this part and in parts 50 and 56 of this chapter. An investigator is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safety, and welfare of subjects under the investigator's care; and for the control of drugs under investigation. An investigator shall, in accordance with the provisions of part 50 of this chapter, obtain the informed consent of each human subject to whom the drug is administered, except as provided in 50.23 or 50.24 of this chapter. Additional specific responsibilities of clinical investigators are set forth in this part and in parts 50 and 56 of this chapter. 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. The number of subjects in a study is not a consideration for IND exemption. Any study that significantly increases risk to subjects or invokes an exception from informed consent for emergency research (21 CFR 50.24) does not meet one of the criterion for an IND exemption. Investigations that are not intended to be reported to FDA do qualify as meeting one of the six required conditions for an IND exemption. 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 sponsor-investigator is required to keep the FDA updated through IND Safety Reports, IND amendments, and annual IND reports. IND Safety Reports are filed throughout the study, not just annually. There is no requirement for an annual submission of an IND renewal application or marketing plan. Who is responsible for making the initial risk determination for a device being used in a study? The sponsor-investigator. The sponsor-investigator is responsible for making the initial risk determination and presenting it to the IRB. The FDA is available to help sponsor-investigators and IRBs in making the risk determination. The drug manufacturer is not involved in the risk determination for a sponsor-investigator study. Financial Disclosures According to 21 CFR 54, the following information must be reported by investigators to the company that submits the new drug application (NDA): Compensation made to the investigator in which the value of compensation could be affected by study outcome A proprietary interest in the tested product, including, but not limited to, a patent, trademark, copyright or licensing agreement Any equity interest in the sponsor of a covered study (that is, any ownership interest, stock options, or other financial interest whose value cannot be readily determined through reference to public prices) Any equity interest in a publicly held company that exceeds $50,000 in value. The sponsor is required to obtain financial disclosures before an investigator can participate in the trial and is required to receive updated information for one year following completion of the trial. Investigators are required to promptly update this information if any relevant changes occur during the course of the trial and for one (1) year following completion of the trial (or all trials of the same product) at a particular site. Which of the following is an investigator's commitment to the sponsor? Submit a new Form FDA 1572 to the sponsor as needed. The investigator must submit a new Form FDA 1572 to the sponsor when an investigator is participating in a new protocol that has been added to the IND or when a new investigator is added to the study. The IRB, not the sponsor, provides ongoing approval for study continuation at the site. The investigator submits the financial disclosure document to the sponsor and the sponsor submits financial disclosure information to FDA. Study record retention is two (2) years after drug approval, disapproval, or study termination. The investigator must report adverse events to the: Sponsor. The investigator initially reports all adverse events to the sponsor The sponsor transmits reports to the FDA. Local institutions may require additional reporting. Identify which party is responsible for reporting directly to the FDA the investigator's financial interests with the sponsor: Sponsor. The investigator provides the sponsor with a completed form for reporting financial interests to the FDA. The sponsor is responsible for providing the FDA with this information. This includes potential financial interests in the sponsor's company or financial interests that might be influenced positively or negatively by the outcome of the clinical investigation. In completing Form FDA 1572, Statement of Investigator, the investigator agrees to Conduct or supervise the investigation personally. All investigators agree to personally conduct or supervise the investigation when they sign the Form FDA 1572. They must report adverse events to the sponsor, not the FDA. Records must be retained for two (2) years after drug approval, disapproval, or study termination. Maintaining a contract is not a requirement. Form FDA 1572, Statement of Investigator, is legally binding between the investigator and the: FDA. The investigator signs the Form FDA 1572 and provides the signed form to the sponsor for filing with the FDA. By signing this form, the investigator agrees to conduct the study according to the protocol and FDA regulations. Biological Product (or Biologic) Any virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment or cure of diseases or injuries. Device Intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. Investigational Drug 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. Investigational New Drug (IND) 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. Investigational Product Any unapproved drug, medical device, or biologic undergoing clinical trials to provide evidence to regulatory authorities that the product is safe and efficacious. Which of the following is an important component of drug accountability? Drug shipping and disposition records. Drug accountability includes tracking of the receipt and return/destruction of the investigational product and dispensing/administration records showing subject usage of the product. Although environmental controls should also be documented, they are not considered part of accountability tracking. Compounding procedures and patent expiration dates are the responsibility of the sponsor. Who has ultimate responsibility for an investigational product? Investigator. The investigator agrees to this responsibility in signing Form FDA 1572. Investigators are responsible for every individual unit of product received. The investigator may delegate some responsibility for product accountability to qualified personnel, such as the pharmacist or study coordinator, but the investigator retains ultimate responsibility for product accountability. Investigational product dispensing or administration information for the sponsor is recorded on the: Case Report Form When a drug is dispensed or administered to a subject, it is necessary to record this information for the sponsor's use and analysis by completing the case report form. Form FDA 1572, insurance claim forms, and informed consent forms do not include this information. Where is information on storage requirements for the investigational product usually found? In the Study Protocol. Investigational products must be stored according to protocol specifications and the manufacturer's directions. Sponsor requirements for this are usually found in the study protocol. Humanitarian Device Exemption (HDE) An application that is similar to a premarket approval (PMA) application, but for which the manufacturer does not need to provide evidence of efficacy. HDEs are subject to restrictions on profitability and can only be used in a facility after an IRB/IEC has approved their use in that facility, except in certain emergencies. Humanitarian Use Device (HUD) A device that is intended to benefit patients in the treatment or diagnosis of a disease or condition affecting fewer than 8,000 individuals in the U.S. per year. Investigational Device Exemption (IDE) A submission that must be made to the FDA before conducting a clinical trial of certain types of devices. Non-Significant Risk (NSR) Device studies Those that involve a device that does not pose a significant risk to subjects. Examples of NSR devices include: most daily-wear contact lenses and lens solutions, ultrasonic dental scalers, and temporary urinary catheters.