CCRC Exam Preparation questions with complete solutions

What is an Adverse Event (AE) ? Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. (ICH GCP E6 1.2) What is an Adverse Drug Reaction (ADR)? All noxious and unintended responses to a medicinal product related to any dose. (ICH GCP E6 1.1) What is the definition of Severity? intensity What are the criteria for a Serious Adverse Event? Any event that: (1) results in death; (2) is life-threatening; (3) results in inpatient hospitalization or prolongation of existing hospitalization; (4) results in a persistent or significant disability/incapacity (5) results in a congenital anomaly/birth defect; or (6) based upon appropriate medical judgment, may jeopardize the subject's health and may require medical or surgical intervention to prevent one of the other outcomes listed above. What is CRF characterized by? A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject What are the different types of Comparators? An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial. Type I Error Rejecting null hypothesis when it is true Type II error Failing to reject a false null hypothesis. composite variables If a single primary variable cannot be selected from multiple measurements associated with the primary objective, another useful strategy is to integrate or combine the multiple measurements into a single or composite variable, using a pre-defined algorithm. Role of IRB (Institutional Review Board) safeguard the rights, safety, and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects Phase I Initial clinical safety studies in humans. May be as few as 10 subjects, often healthy volunteers, includes PK, ADME and dose escalation studies. Usually open label. Phase II The study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety. Phase III Clinical Trial Testing of drug on patients to assess efficacy, effectiveness and safety (usually multi-center trials on a much larger patient groups). The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. Phase IV Clinical Trial Post-marketing, continue assessing therapeutic value and monitor less common adverse events Nonclinical Study Biomedical studies not performed on human subjects. (ICH GCP E6 1.41) double-dummy technique -a technique used to maintain blinding under conditions in which treatments differ, such as by route of administration -it consists of preparing both treatment and placebo (or an alternative treatment) in such a manner that such cues do not identify the treatment Confirmatory Trial Phase 3 trial during which the previously revealed actions of a therapeutic intervention are confirmed GCP Good Clinical Practice, a standard for the conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected. ICH International Council on Harmonization Declaration of Helsinki The World Medical Association's international ethical guidelines for medical professionals researching human subjects ICH GCP E2a Expedited reporting IB 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) What is an IDMC? Independent Data Monitoring Committee, established by the sponsor to assess at intervals the progress, the safety data, and the critical efficacy endpoints of a clinical trial. IRB composition (a) At least five members. (b) At least one member whose primary area of interest is in a nonscientific area. (c) At least one member who is independent of the institution/trial site. Only those IRB/IEC members who are independent of the investigator and the sponsor of the trial should vote/provide opinion on a trial-related matter. A list of IRB/IEC members and their qualifications should be maintained. Record retention IRB All relevant records (e.g., written procedures, membership lists, lists of occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for a period of at least 3 years after completion of the trial and make them available upon request from the regulatory authorities. Can a PI notify a patient's primary care provider regarding participation in clinical trial? It is recommended that the investigator inform the subject's primary physician about the subject's participation in the trial if the subject has a primary physician and if the subject agrees to the primary physician being informed What requirements must be met before an investigator can implement protocol changes? The investigator should not implement any deviation from, or changes of, the protocol without agreement by the sponsor and prior review and documented approval/favorable opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s)). What an investigator must do in the event of accidental unblinding The investigator should follow the trial's randomization procedures, if any, and should ensure that the code is broken only in accordance with the protocol. If the trial is blinded, the investigator should promptly document and explain to the sponsor any premature unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the investigational product(s) Protocol language cannot.... Contain any language that causes the subject or the subject's legally acceptable representative to waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence. When can an investigator deviate from the protocol? The investigator may implement a deviation from, or a change in, the protocol to eliminate an immediate hazard(s) to trial subjects without prior IRB/IEC approval/favorable opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be submitted: (a) To the IRB/IEC for review and approval/favorable opinion; (b) To the sponsor for agreement and, if required; (c) To the regulatory authority(ies). How much time does a potential subject have to sign a consent form? Provide the subject or the subject's legally acceptable representative ample time and opportunity to inquire about details of the trial and to decide whether or not to participate in the trial. All questions about the trial should be answered to the satisfaction of the subject or the subject's legally acceptable representative. 4.8.8 Prior to a subject's p Category of SAE: Intensive treatment in ER or at home for an allergic bronchospasm Important medical event (not immediately life threatening)