IRB Membership and Informed Consent Regulations in Human Subject Research, Exams of Nursing

Download IRB Membership and Informed Consent Regulations in Human Subject Research and more Exams Nursing in PDF only on Docsity! MEGA SOCRA CCRP EXAM CONTENT MEGA SOCRA CCRP EXAM CONTENT CONTAINING 790 QUESTIONS WITH CERTIFIED ANSWERS 2024 (Combination of multiple sets from other sources including some ACRP Content) The minimum number of IRB members - Answer: 5 MEGA SOCRA CCRP EXAM CONTENT In a non-emergency situation, under which of the following conditions, if any, may subjects be enrolled into a study prior to IRB/IEC approval? - Answer: Subjects cannot be enrolled until IRB/IEC approval has been obtained The responsibility for ensuring that the investigator understands a clinical trial lies with: - Answer: The Sponsor This subject should undergo all study procedures as outlined in the protocol - Answer: A subject has been enrolled on a study and was randomized to the non- treatment arm. The protocol outlines study procedures for all subjects to be performed within one week of enrollment. Which of the following statements about this case is correct? a. Intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject. b. Purported or represented to be for a use in supporting or sustaining human life and presents a potential risk to the health, safety, or welfare of a subject. c. For a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject. - Answer: A significant risk device is defined as an investigational device that is: MEGA SOCRA CCRP EXAM CONTENT with the outcome of death. Per the ICH E2A guideline, which are items that should be submitted to the Sponsor? 1. Report to the Sponsor per the protocol timelines for serious, unexpected events. 2. Report to the IRB/IEC per their event reporting requirements for serious, unexpected events. - Answer: Two weeks after starting an investigational therapy, a subject is rushed to the hospital after experiencing a heart attack. The subject is currently being treated in the Intensive Care Unit (ICU). The ICU doctor has noticed that the subject was enrolled in the trial and has contacted the trial Principal Investigator. Heart attack is not described in the Investigator's Brochure. What actions must be taken by the Principal Investigator? As soon as possible, but no later than seven calendar days after first knowledge of the event - Answer: What is the timeframe for "expedited" reporting of serious, fatal or life-threatening, unexpected adverse drug reactions to regulatory authorities? Your third subject in a Phase III drug trial calls to report that she has developed a rash on her chest 12 hours after taking her second dose of the investigational study drug. She states that it itches and is slightly uncomfortable. She tells you that she has never had a rash and this is totally unexpected. You know from the Investigator Drug Brochure that only 12% of the patients get a rash from this drug. Which of the following options best describes this situation? - Answer: Adverse Drug Reaction (ADR) Example MEGA SOCRA CCRP EXAM CONTENT Safeguard the rights, safety, and well-being of all trial subjects - Answer: What is the purpose of the IRB/IEC? Sponsor - Answer: Who is responsible for designing the clinical trial protocol? The process by which a subject voluntarily confirms his or her willingness to participate in a clinical trial is best described as which of the following options? - Answer: Informed Consent Process Who is ultimately responsible for Source Data Verification or SDV? - Answer: The Monitor The IRB/IEC should consist of a reasonable number of members, who collectively have the qualifications and experience to review and evaluate the science, medical aspects, and ethics of the proposed trial. It is recommended that the IRB/IEC should include which of the following options? - Answer: A. At least five members B. At least one member whose primary interest is non-scientific C. At least one member who is independent from the Institution/trial site A listing of all site personnel who will be involved in the research - Answer: Which of the following is NOT one of the required elements of an informed consent form? MEGA SOCRA CCRP EXAM CONTENT 1. The purpose of the research 2. A description of benefits that may be reasonably expected from the research 3. A contact person for questions about the research - Answer: Name 3 of several required elements of an informed consent form The person who conducted the informed consent discussion The subject or the subject's legally acceptable representative - Answer: According to ICH E6, who must sign the Informed Consent Form or ICF? Members of the armed forces Patients with incurable diseases Persons in nursing homes - Answer: As per ICH E6 GCP, which groups of potential subjects could be defined as "vulnerable subjects"? False - Answer: As per ICH E6 GCP, patients with heart conditions alone are defined as "vulnerable subjects"? Document that the subject has forgotten to return her medication in the source document and ask her to bring the medication back to the clinic as soon as possible or during her next visit. - Answer: A subject, who has been 100% compliant thus far, has forgotten to bring her medication back to the clinic for her regular visit. She reports that she has not missed any doses and has been fully compliant with the protocol. What is the most appropriate action for the investigator or clinical research coordinator to take? MEGA SOCRA CCRP EXAM CONTENT When the subject and the Investigator and sponsor staff who are involved in the treatment or clinical evaluation of the subjects are unaware of the treatment assignments - Answer: The study subject asks you why the study is called a double blind study. You explain double blind as what? Data Safety Monitoring Board - Answer: What does "DSMB" stand for? True - Answer: True or False? The Data and Safety Monitoring Board (DSMB) is a separate entity from an Institutional Review Board (IRB) or an Independent Ethics Committee (IEC)? To assess the progress of a clinical trial, the safety data, and the critical efficacy endpoints - Answer: What is the purpose of the "Data and Safety Monitoring Board (DSMB)?" A design in which subjects are randomized to one of two or more arms, each arm being allocated a different treatment - Answer: Parallel Group Design Introduces a deliberate element of chance into the assignment of treatments to subjects in a clinical trial - Answer: Randomization a study in which there are two or more independent variables, or factors - Answer: factorial design the sponsor should continue the trial MEGA SOCRA CCRP EXAM CONTENT the sponsor should modify the trial the sponsor should stop the trial - Answer: Data and Safety Monitoring Boards or DSMBs, have the power to recommend which of the following? Which variable in a study should be used to determine the sample size? - Answer: Primary Variable What do you call the clinical trial design in which each subject is randomized to a sequence of two or more treatments and hence acts as his or her own control for treatment comparisons. - Answer: crossover design The target population - Answer: When writing an early phase clinical study plan, which of the following do you want to pay attention to, if you wish to maximize the chance of observing specific clinical effects of interest? You are designing a cross-over study. Cross-over designs have a number of problems that can invalidate their results. The chief difficulty concerns __________, that is, the residual influence of treatments in subsequent treatment periods. - Answer: Carryover effect Guidance pertains to the Pediatric Population - Answer: ICH E11 False - Answer: True or False? Due to low blood volumes researchers should not do pharmacokinetic studies in the pediatric population. MEGA SOCRA CCRP EXAM CONTENT when a child is given information about a trial and asked if he or she wishes to participate? - Answer: example of assent True - Answer: True or False? Medicinal products may affect physical and cognitive growth and development, and the adverse event profile may differ in pediatric patients. 2 to 11 years - Answer: According to ICH E11, what would the suggested age categorization for children be if you were planning a study in "children"? Sparse sampling Population PK Use of indwelling catheters - Answer: What are the three ways to minimize the number of samples obtained from each pediatric patient? False - Answer: True or False? Pharmacokinetic Phase 1 studies in the pediatric population are generally conducted in healthy pediatric subjects. The current protocol for a study in pediatrics is asking for all new patients to have stages of pubertal development assessed. What is this assessment called? - Answer: Tanner staging Recruitment Consent and assent Minimizing risk MEGA SOCRA CCRP EXAM CONTENT False - Answer: The Confidentiality agreement is considered a regulatory document? Individual listed in the ICF - Answer: A subject is upset and wants to know whom she should contact regarding her rights as a research subject. The CRC should tell her to contact the: Correct errors on the CRFs as discovered - Answer: During the monitoring visit, a CRA discusses the following queries with the CRC: • Dates of the subject visits recorded as month/day/year instead of day/month/year • Subjects' identification numbers are missing lead-in zeros • Weights are recorded as pounds instead of kilograms • Discrepancies in the two subjects' visit dates between source data and CRF entries. Which of the following actions should the CRC take? Have the subject come to the site for an interim assessment - Answer: During a respiratory trial, a subject calls the CRC 1 week before his next scheduled trial visit and reports upper respiratory symptoms and a pea-sized lump in his neck. Which of the following should the CRC do FIRST? Confirm the subject's understanding of the ICF MEGA SOCRA CCRP EXAM CONTENT Have the subject sign the ICF - Answer: A potential subject for a trial has been mailed an ICF prior to his screening visit. When the subject arrives at the research department for his screening visit, he states he read the ICF and is ready to do the trial. He does not have the copy of the ICF that was mailed to his home with him. According to ICH Guidelines, which of the following are the BEST actions for the CRC to take initially? Episodes of vaginal bleeding - Answer: A clinical trial is being conducted for hormone replacement. The trial includes a diary. Which of the following would be considered an objective parameter? 102 mmHg - Answer: At a screening visit, a CRC takes the following sitting BPs: • 168/100 mmHg • 166/104 mmHg • 167/102 mmHg The patient's mean sitting diastolic BP is: 167 mmHg - Answer: At a screening visit, a CRC takes the following sitting BPs: • 168/100 mmHg • 166/104 mmHg • 167/102 mmHg The patient's mean sitting Systolic BP is: 2 and 4 only - Answer: Which of the following are responsibilities of an MEGA SOCRA CCRP EXAM CONTENT IDMC/DSMB? 1) Assess the financial aspects of a trial 2) Assess the progress of a trial 3) Recommend initiating a trial 4) Recommend stopping a trial 1 and 3 only - Answer: Which of the following are NOT responsibilities of an IDMC/DSMB? 1) Assess the financial aspects of a trial 2) Assess the progress of a trial 3) Recommend initiating a trial 4) Recommend stopping a trial 1 and 4 only - Answer: A CRC is screening subjects for an oral IP. All subjects must be stabilized on currently approved medication. Which of the following questions should be asked by the CRC? 1) When was the last time your medication dose changed? 2) Have you made any dietary changes in the last month? 3) When was your last chest x-ray? 4) Do you have any difficulty swallowing oral medications? MEGA SOCRA CCRP EXAM CONTENT 1) Infection following surgery prolonging hospital stay 2) Pregnancy resulting in normal delivery of twins 3) Boating accident with overnight hospitalization 4) Use of illicit drug during the trial 2 and 4 only - Answer: Which of the following scenarios are NOT considered SAEs? 1) Infection following surgery prolonging hospital stay 2) Pregnancy resulting in normal delivery of twins 3) Boating accident with overnight hospitalization 4) Use of illicit drug during the trial Phase 1 trial - Answer: A clinical trial is being conducted to determine the safety and tolerability of a new anti-emetic IP. The sponsor expects to enroll 20 subjects. This would be considered a: C. Washout from medication - Answer: Which of the following would require consent when screening a subject? A. Subject demographics B. Relevant medical history MEGA SOCRA CCRP EXAM CONTENT C. Washout from medication D. Routine diagnostic lab tests A. Subject demographics B. Relevant medical history D. Routine diagnostic lab tests - Answer: Which of the following Might NOT require consent when screening a subject? A. Subject demographics B. Relevant medical history C. Washout from medication D. Routine diagnostic lab tests Trial Schedule of Events - Answer: Which of the following is MOST useful for scheduling trial procedures? $125 - Answer: The CRC reviewed a new protocol to prepare the trial budget for submission to the sponsor. According to the protocol, each subject is required to return for follow-up visits at 30 days, 6 months and 1 year. • At 30 days, the protocol requires a physical exam, an electrocardiogram and a chest x-ray • At 6 months, the protocol requires a physical exam and an electrocardiogram MEGA SOCRA CCRP EXAM CONTENT • At 1 year, the protocol requires a physical exam, an electrocardiogram and a chest x-ray The hospital charges $75 for the physical exam, $50 for the electrocardiogram, and $100 for the chest x-ray. The 30 day and 1 year visits are considered standard of care for the subjects. How much should the CRC budget per subject for the non-standard of care visits? $575 - Answer: The CRC reviewed a new protocol to prepare the trial budget for submission to the sponsor. According to the protocol, each subject is required to return for follow-up visits at 30 days, 6 months and 1 year. • At 30 days, the protocol requires a physical exam, an electrocardiogram and a chest x-ray • At 6 months, the protocol requires a physical exam and an electrocardiogram • At 1 year, the protocol requires a physical exam, an electrocardiogram and a chest x-ray The hospital charges $75 for the physical exam, $50 for the electrocardiogram, and $100 for the chest x-ray. The 30 day and 1 year visits are NOT considered standard of care for the subjects. How much should the CRC budget per subject for the non-standard of care visits? MEGA SOCRA CCRP EXAM CONTENT be closing in 1 hour. Which of the following is the MOST appropriate action for the CRC? 3 and 4 only - Answer: At a trial site, CRCs perform quality assurance as needed throughout the progress of their trials. A CRC notes that five of the seven research nurses failed to document subject understanding of the trial. Which of the following actions should the CRC perform? 1) Inform the sponsor of this practice 2) Revise the delegation of responsibility 3) Ensure the subjects have been well informed of the trial 4) Review the informed consent process with the individual research nurses 1 and 2 only - Answer: At a trial site, CRCs perform quality assurance as needed throughout the progress of their trials. A CRC notes that five of the seven research nurses failed to document subject understanding of the trial. Which of the following 2 of 4 actions should the CRC perform last if necessary? 1) Inform the sponsor of this practice 2) Revise the delegation of responsibility 3) Ensure the subjects have been well informed of the trial 4) Review the informed consent process with the individual research nurses 1, 2 and 4 only - Answer: According to the Declaration of Helsinki, biomedical research involving MEGA SOCRA CCRP EXAM CONTENT human subjects: 1) Should be based on adequately performed laboratory and animal experimentation 2) Should be conducted by scientifically qualified persons and under the supervision of a clinically competent medical person 3) Must evaluate the potential benefits to society as opposed to the potential risk to individual subjects 4) Must be preceded by careful assessment of predictable risks in comparison with foreseeable benefits 3) Must evaluate the potential benefits to society as opposed to the potential risk to individual subjects - Answer: What is NOT part of Declaration of Helsinki, biomedical research involving human subjects: 1) Should be based on adequately performed laboratory and animal experimentation 2) Should be conducted by scientifically qualified persons and under the supervision of a clinically competent medical person 3) Must evaluate the potential benefits to society as opposed to the potential risk to individual subjects 4) Must be preceded by careful assessment of predictable risks in comparison with foreseeable benefits MEGA SOCRA CCRP EXAM CONTENT Add the initials of the person making the change, date the change, and, if necessary, a brief explanation of the change. - Answer: Which of the following is the proper way to make a correction to a CRF? Completely blacken the incorrect entry and then enter the correct information Back date the corrected entry with the date of the original entry - Answer: What is NOT the proper way to make a correction to a CRF? At least one member's primary area of interest is in a nonscientific area. - Answer: With respect to IRB/IEC membership, both the FDA and ICH require that... Be approved by the IRB/IEC prior to use. - Answer: Advertising for study subjects must... D. The protocol specifies how the clinical development of an investigational product will be conducted. - Answer: All of the following statements regarding the study protocol are true, except: A. The protocol describes the objectives, design, and MEGA SOCRA CCRP EXAM CONTENT A. The research nurse leaves and a new one is added to the study. B. New information arises which affects the safety of study participants. C. The CT scanner breaks and you to reschedule the study visit. D. It's been more than 30 days since consent was last obtained. IP accountability log - Answer: You've been informed that a batch of IP is being recalled and you've been asked to identify which subjects received medication from the recalled batch. Where will you find this information? A. The research nurse leaves and a new one is added to the study. C. The CT scanner breaks and you to reschedule the study visit. D. It's been more than 30 days since consent was last obtained. - Answer: In which of the following scenarios is re-consent NOT required? A. The research nurse leaves and a new one is added to the study. B. New information arises which affects the safety of study participants. C. The CT scanner breaks and you to reschedule the study visit. D. It's been more than 30 days since consent was last obtained. MEGA SOCRA CCRP EXAM CONTENT May not meet the definition of serious - Answer: An adverse event that is severe in intensity False - Answer: An adverse event that is severe in intensity is considered serious. True - Answer: An adverse event that is severe in intensity may not be considered serious. True or False? Falsification - Answer: An investigator intentionally removes data points on a graph in order to generate a deceptive conclusion. This is an example of: Defines the duties and responsibilities of the involved parties in cases of loss or injury linked to a clinical trial - Answer: What is indemnification? The subject's responsibilities Alternative treatments available to the subject Indemnification statement - Answer: A clinical trial protocol should include: A method of verifying an individual's identity based on measurement of the individual's physical features or repeatable actions where those features and or actions are both unique to that individual and measurable. (21 CFR, Sec. 11.3) - Answer: Biometrics MEGA SOCRA CCRP EXAM CONTENT An environment in which system access is controlled by persons who are responsible for the content of electronic records that are on the system. (21 CFR, Sec. 11.3) - Answer: Closed System An electronic signature based upon cryptographic methods of originator authentication, computed by using a set of rules and a set of parameters such that the identity of the signer and the integrity of the data can be verified. (21 CFR, Sec. 11.3) - Answer: Digital Signature Any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved or distributed by a computer system. (21 CFR, Sec. 11.3) - Answer: Electronic Record A computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be legally binding equivalent of the handwritten signature. (21 CFR, Sec. 11.3) - Answer: Electronic Signature An environment in which system access is not controlled by persons who are responsible for the content of the electronic records that are on the system. (21 CFR, Sec. 11.3) - Answer: Open system Any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or is not subject to MEGA SOCRA CCRP EXAM CONTENT Means that the probability and magnitude of harm or discomfort anticipated in the research are no greater in an of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (21 CFR, sec. 50.3) - Answer: Minimal Risk 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. (21 CFR, sec. 50.3) - Answer: Legally Authorized Representative Any one of the following legally competent persons: spouse; parents; children (including adopted children); brothers, sisters and spouses of brothers and sisters; and any individual related by blood or affinity whose close association with the subject is equivalent of a family relationship. (21 CFR, sec. 50.3) - Answer: Family Member A child's affirmative agreement to participate in a clinical investigation. Mere failure to object may not, absent affirmative agreement, be construed as assent. (21 CFR, sec. 50.3) - Answer: Assent Persons who have not attained the legal age for consent to treatment or procedures involved in clinical investigations, under the applicable law of the jurisdiction in which the clinical investigation will be conducted. (21 CFR, sec. 50.3) - Answer: Children MEGA SOCRA CCRP EXAM CONTENT A child's biological or adoptive parent. (21 CFR, sec. 50.3) - Answer: Parent A child who is placed in legal custody of the State or other agency, institution, or entity, consistent with applicable Federal, State or Local law. (21 CFR, sec. 50.3) - Answer: Ward The agreement of the parent(s) or guardian to the participation of their child or ward in a clinical investigation. Permission must be obtained in compliance with part 50 subpart B and must include all the elements of the informed consent. (21 CFR, sec. 50.3) - Answer: Permission An individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care when general medical care includes research. (21 CFR, sec. 50.3) - Answer: Guardian The use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and in which there is no sufficient time to obtain IRB approval. (21 CFR, sec. 56.102) - Answer: Emergency Use The determination of the IRB that the clinical investigation has been reviewed and may be conducted at an institution within the constraints set forth by the IRB and by other institutional and federal Requirements. (21 CFR, sec. 56.102) - Answer: IRB Approval MEGA SOCRA CCRP EXAM CONTENT A person that assumes, as an independent contractor with the sponsor, one or more of the obligations of a sponsor, e.g., design of a protocol, selection or monitoring of investigations, evaluation of reports, and preparation of materials to be submitted to the FDA. (21 CFR, sec. 312.3) - Answer: Contract Research Organization An investigational new drug application. Is synonymous with "Notice of Claimed Investigational Exemption for a New Drug". (21 CFR, sec. 312.3) - Answer: IND A review panel the is responsible for ensuring the protection of the rights, safety, and well-being of human subjects involved in a clinical investigation and is adequately constituted to provide assurance of that protection. An IRB is one type of IEC. (21 CFR, sec. 312.3) - Answer: Independent Ethics Committee (IEC) A device that 1) necessarily deviates from devices generally available 2) is not generally available to Physicians/dentists 3) not generally available in finished form for purchase or dispensing 4) is not offered for commercial distribution through labeling/advertising 5) is intended for use by an individual patient named in the order of the physician or dentist and is made to be in a specific form for that patient. (21 CFR, sec. 812.3) - Answer: Custom Device A device that is placed into a surgically or naturally formed cavity of the human body if it is intended to remain there for a period of 30 days or more. (21 CFR, sec. 812.3) - Answer: Implant MEGA SOCRA CCRP EXAM CONTENT The official notification by the institution to the supporting department or agency, in accordance with the requirements of this policy, that a research project or activity involving human subjects has been reviewed and approved by an IRB in accordance with an approved assurance. (45 CFR, sec. 46.102) - Answer: Certification All noxious and unintended responses to a medicinal product related to any dose. (ICH GCP E6 1.1) - Answer: Adverse Drug Reaction (ADR) 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) - Answer: Adverse Event (AE) Any laws and regulations addressing the conduct of clinical trials of investigational products (ICH GCP E6 1.4) - Answer: Applicable Regulatory Requirements A 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, sponsors SOPs, GCP and the applicable regulatory requirements. (ICH GCP E6 1.6) - Answer: Audit A declaration of the confirmation by the auditor that an audit has taken place. (ICH GCP E6 1.7) - Answer: Audit Certificate MEGA SOCRA CCRP EXAM CONTENT A written evaluation by the sponsor's auditor of the results of the audit. (ICH GCP E6 1.8) - Answer: Audit Report Documentation that allow reconstruction of the course of events. (ICH GCP E6 1.9) - Answer: Audit Trail A procedure in which one or more parties to the trial are kept unaware of the treatment assignment. (ICH GCP E6 1.10) - Answer: Blinding/Masking 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. (ICH GCP E6 1.11) - Answer: Case Report Form (CRF) A written description of a trial/study of any therapeutic, prophylactic or diagnostic agent conducted in human subjects, in which the clinical and statistical description, presentations, and analysis are fully integrated into a single report. (ICH GCP E6 1.13) - Answer: Clinical Trial/Study Report An investigational or marketed product (i.e. active control). or placebo, used as a reference in a clinical trial. (ICH GCP E6 1.14) - Answer: Comparator (Product) Adherence to all the trial related requirements, GCP requirements and the applicable regulatory requirements. (ICH GCP E6 1.15) - Answer: Compliance MEGA SOCRA CCRP EXAM CONTENT Prevention or disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity. (ICH GCP E6 1.16) - Answer: Confidentiality A written, dated and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and if appropriate on financial matters. (ICH GCP E6 1.17) - Answer: Contract A committee that a sponsor may organize to coordinate the conduct of a multicentre trial. (ICH GCP E6 1.18) - Answer: Coordinating Committee An investigator assigned the responsibility for the coordination of investogators at different centres participating in a multicentre trial. (ICH GCP E6 1.19) - Answer: Coordinating Investigator A person or an organization (commercial academic or otherwise) contracted by the sponsor to perform one or more of a sponsor's trial-related duties and functions. (ICH GCP E6 1.20) - Answer: Contract Research Organization (CRO) Permission to examine, analyze, verify, and reproduce any records and reports that are important to the evaluation of a clinical trial. (ICH GCP E6 1.21) - Answer: Direct Access MEGA SOCRA CCRP EXAM CONTENT for an unapproved indication, or when used to gain further information about an approved use. (ICH GCP E6 1.33) - Answer: Investigational Product 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) - Answer: Investigator's Brochure An individual or juridicial or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subjects participation in the clinical trial. (ICH GCP E6 1.37) - Answer: Legally Acceptable Representative A written report from the monitor or sponsor after each site visit and/or other trial-related communication according to the sponsor's SOPs. (ICH GCP E6 1.39) - Answer: Monitoring Report A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator. (ICH GCP E6 1.40) - Answer: Multicentre Trial Biomedical studies not performed on human subjects. (ICH GCP E6 1.41) - Answer: Nonclinical Study A written description of changes to or formal clarification of a protocol. (ICH GCP E6 1.45) - Answer: Protocol Amendment MEGA SOCRA CCRP EXAM CONTENT All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented, and reported in compliance with Good Clinical Practices and the applicable regulatory requirements. (ICH GCP E6 1.46) - Answer: Quality Assurance (QA) The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled. (ICH GCP E6 1.47) - Answer: Quality Control (QC) The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias. (ICH GCP E6 1.48) - Answer: Randomization Bodies having the power to regulate. In the ICH GCP guideline that guidelines the expression Regulatory Authorities includes the authorities that review submitted clinical data. - Answer: Regulatory Authorities Statement of investigator for IND - Answer: Form 1572 Cover sheet for an IND application - Answer: Form 1571 - information about behavior which occurs in a context in which an individual can reasonably expect that no observation or recording is taking place MEGA SOCRA CCRP EXAM CONTENT - information which has been provided for a specified purpose by an individual and which the individual can reasonably expect will not be made public (e.g. medical record) - Answer: Private Information - minimum of 5 members - IRB must be qualified through experience, expertise, diversity - diversity with respect to race, gender, cultural background - cannot consist of members of one profession - at least one member must have a primary concern in a scientific area and one in a non-scientific area - at least one member not affiliated with the institution - Answer: IRB membership requirements according to 45 CFR 46 - subject has had sufficient opportunity to consider whether to participate - the possibility of coercion or undue influence is minimized - Answer: Circumstances/conditions required for informed consent - explanation of purpose of research - duration of participation - description of procedures to be followed - identification of any procedures which are experimental - any foreseeable risks or discomfort - statement about potential benefits to subjects - statement if no reasonable alternative procedures or treatments are available to subjects MEGA SOCRA CCRP EXAM CONTENT Certification of financial interest and arrangements of clinical investigators - Answer: Form 3454 Notice of inspection - Answer: Form 482 Inspectional observations - Answer: Form 483 Voluntary safety reporting of adverse events and product problems - Answer: Form 3500 Mandatory safety reporting by user facilities, distributors, and manufacturers - Answer: Form 3500A Disclosure of financial interest and arrangements of clinical investigators - Answer: Form 3455 IND - Answer: 21 CFR 312 IDE - Answer: 21 CFR 812 the IRB - Answer: Who is responsible for the safety and well-being of all trial subjects? MEGA SOCRA CCRP EXAM CONTENT When it fits all SAE criteria but is not life-threatening and does not result in death. - Answer: When does an SAE have to be reported to the FDA within 15 calendar days? Protection of Human Subjets/Informed Consent - Answer: 21 CFR 50 Electronic Records/Signatures - Answer: 21 CFR 11 US Code of Federal Regulations - Answer: Where would you look to find official government information regarding GCP? at least 5 - Answer: According to ICH guidelines, how many members should an IRB have? 7 calendar days - Answer: How many calendar days does a sponsor have to report a fatal or life-threatening unexpected adverse drug reaction? 3 years - Answer: According to ICH guidelines, IRB must retain records for... Small trials with healthy subjects, purpose is to determine pharmacokinetics and maximum tolerated dose - Answer: Phase I Clinical Trial IRB - Answer: 21 CFR 56 The Common Rule - Answer: 45 CFR MEGA SOCRA CCRP EXAM CONTENT Pregnant Women and Fetuses - Answer: 45 CFR Part B Prisoners - Answer: 45 CFR Part C Children - Answer: 45 CFR Part D IRBs - Answer: 45 CFR Part E Initial demonstration of efficacy in patients, short-term safety information - Answer: Phase II Clinical Trial Use in large numbers of patients, long-term safety - Answer: Phase III Clinical Trial Post-marketing, continue assessing therapeutic value and monitor less common adverse events - Answer: Phase IV Clinical Trial Yes - Answer: Are devices intended solely for veterinary use exempt form IDE regulations? Yes - Answer: According to GCP guidelines, does the term vulnerable subject also include employees under direct supervision of clinical investigator? 1947 - Answer: Nuremberg Code MEGA SOCRA CCRP EXAM CONTENT 2. Revision and change control procedures to maintain an audit trail that documents time-sequenced development and modification of systems documentation - Answer: Electronic records - Controls over systems documentation Procedures and controls must be used to ensure the authenticity, integrity and confidentiality of electronic records from the point of creation to the point of receipt. Examples: Encryption, Use of digital signatures - Answer: Electronic records - Open system Must contain information associated with the signing that clearly indicate all of the following: 1. Printed name of signer 2. Date and time when signature was executed 3. Meaning (such as review, approval, responsibility or authorship) associated with signature - Answer: Signed Electronic Records Before any organization establishes, assigns, certifies or otherwise sanctions an individual's electronic signature, the identity of the individual must be verified - Answer: Electronic Signature Verification Prior to using their electronic signature, one must certify to the agency that the electronic signatures in their system, used on or after 8/20/97, are intended to be the legally binding equivalent of traditional handwritten signatures MEGA SOCRA CCRP EXAM CONTENT 1. Certification must be submitted in paper form and signed with a traditional handwritten signature 2. Upon agency request, must provide additional certification or testimony that a specific electronic signature is the legally binding equivalent of the handwritten signature - Answer: Electronic Signature Certification 1. Employ at least 2 distinct identification components such as identification code and password a. During a series of signings over a continuous period of controlled system access, the first signing uses all electronic signature components while each subsequent signature uses at least 1 electronic signature component that is only executable by the individual 2. Be used by the genuine owners 3. Administered and executed to ensure that attempted use of an electronic signature by anyone other than its genuine owner requires the collaboration of 2 or more individuals - Answer: Electronic Signatures not based on biometrics Designed to ensure that they cannot be used by anyone other that their genuine owners - Answer: Electronic Signatures based on biometrics 1. Maintain uniqueness of each combined ID code and password (No 2 people have same combo) 2. ID code and password are periodically checked, recalled, revised (Prevent PW aging) MEGA SOCRA CCRP EXAM CONTENT 3. Loss management procedures to deauthorize lost, stolen, missing or otherwise compromised devices that generate ID code or PW information and issue replacements 4. Use of safeguards to prevent unauthorized use of PWs and/or ID codes and to detect and report any attempts at their unauthorized use 5. Initial and periodic testing of devices that generate ID or PW information to ensure they function properly - Answer: Security and Integrity of identification codes/passwords Must obtain legally effective informed consent Must allow for sufficient opportunity to consider whether or not to participate Minimize possibility of coercion or undue influence Must use language understandable by participant - Answer: General Requirements for informed consent Language may not include exculpatory language in which the subject is made to waive or appear to waive their legal rights or releases or appears to release the investigator, the sponsor or its agents from liability or negligence - Answer: Informed consent - Language may not Obtaining informed consent is deemed feasible unless both the investigator and a physician who is not not participating in clinical investigation certify in writing all of the following: 1. Subject is confronted by life-threatening situation necessitating the use of the test article MEGA SOCRA CCRP EXAM CONTENT Before using the device, the investigator must make the determination and it must be reviewed within 5 working days by uninvolved physician - Answer: Waiving informed consent for use of in-vitro diagnostic device and not sufficient time to obtain independent determination Determination for waiving consent must be submitted to the IRB for review within 5 working days - Answer: Waiving informed consent for in-vitro diagnostic device 1. Subject is in life-threatening situation, available treatments are unproved or unsatisfactory, and collection of scientific evidence is necessary to determine safety and effectiveness of intervention 2. Consent is not feasible because subject cannot consent due to their condition, intervention must be administered before consent can feasibly be attained, no reasonable way to prospectively ID eligible participants 3. Participation on the research holds the prospect of a direct benefit to the subject 4. Clinical investigation could not be carried out without waiver of informed consent 5. Potential therapeutic window is defined and efforts are made to contact LAR and obtain consent - Answer: Exception from informed consent for emergency research 1. Consultation with representative of the communities from which subjects will be drawn MEGA SOCRA CCRP EXAM CONTENT 2. Public disclosure to the communities where the clinical investigation will take place prior to study and include risks and benefits. Disclosure will also take place following conclusion of the study including demographic characteristics and resukts 3. Establish independent data monitoring comittee - Answer: Waiving informed consent for emergency research - Additional protections of the rights and welfare of subjects 1. A statement that the study involves research, purpose of the research, expected duration, description of procedures, ID of an experimental procedures 2. Description of risks or discomforts 3. Description of benefits 4. Disclosure of alternative procedures or courses of treatment 5. Statement describing extent to which confidentiality will be maintained and notes FDA may inspect records 6. For research involving more than minimal risk, statement explaining whether an compensation or medical treatments are available if injury occurs 7. Explanation of who to contact for answers to pertinent questions about the research 8. Statement that participation is voluntary and refusal to participate will involve no penalty - Answer: Elements of Informed consent - General requirements 1. Statement that treatment may involve risks to subject which are currently unforeseeable MEGA SOCRA CCRP EXAM CONTENT 2. Circumstances under which participation may be terminsted by investigator without participant's consent 3. Additional costs to subject 4. Consequences of subject's decision to withdraw from research 5. Statment that new findings which may relate to the subject's willingness to participate will be provided 6. Approximate number of subjects in study - Answer: Additional elements of informed consent - General requriements, when appropriate Related to their status as wards Conducted in schools, camps, hospitals, institutions or similar settings in which the majority of the children involved are not wards - Answer: Children who are wards of the state can be included in research if the research is: Related to their status as wards Conducted in schools, camps, hospitals, institutions or similar settings in which the majority of the children involved are not wards - Answer: Children who are wards of the state can be included in research if they are: 1. Advocate will serve in addition to any other individual acting on behalf of the child as guardian 2. One individual may serve as an advocate for more than one child 3. Advocate must be an individual who has the background and experience to act in, and agrees to act in, the best interest of the child for the duration of the child's participation in the clinical investigation MEGA SOCRA CCRP EXAM CONTENT 4. Copies of correspondence between IRB and investigators 5. List of IRB members 6. Written procedures for IRB as required by regulations 7. Statements of significant new findings provided to subjects - Answer: IRB Records - maintenance of documentation of IRB activities 1. Conduct initial and continuing review 2. Determine which projects require more than annual review 3. Ensuring prompt reporting to IRB 4. Ensure changes to approved research may not be initiated without IRB approval 5. Ensure prompt reporting of any unanticipated problems involving risks to human subjects, any instance of serious or continuous non-compliance, or any suspension/termination of IRB approval 6. Review proposed research - Answer: IRB Functions -Inspector will present an oral or written summary of observations to an appropriate representative of IRB -FDA may send a letter describing non-compliance -Agency will require IRB to respond to the letter within a time period specified by the FDA and describe corrective actions -FDA may schedule re-inspection based on response to confirm adequacy of corrective actions - Answer: Apparent non-compliance observed by FDA - Withhold approval of new studies -Direct no new subjects be added to ongoing studies MEGA SOCRA CCRP EXAM CONTENT -Terminate ongoing studies - Answer: Apparent non-compliance observed by FDA, the agency may require IRB to -If non-compliance creates a significant threat to rights/welfare of human subjects, FDA may alert state and federal regulatory agencies - Answer: Apparent non-compliance creates significant threat IRB has refused or repeatedly failed to comply with any regulations and non- compliance affects the rights and welfare of human subjects in a clinical investigation - Answer: Commissioner may disqualify an IRB or parent institution if he determines that: Commissioner must determine: IRB explains corrective action and the has provided adecuate assurance that it will operate in compliance - Answer: Reinstatement of IRB/institution -Sponsor must submit IND to FDA if they intend to conduct a clinical investigation -Sponsor may not begin clinical investigation until the investigation is subjects to an IND -Sponsor must submit a separate IND for any clinical investigation involving an exception from informed consent - Answer: Requirements for an IND -Typically conducted in patients or normal volunteer subjecys -Determine metabolism and pharmacologic action of the drug, side effects associated with increasing doses, and gain early evidence of effectiveness MEGA SOCRA CCRP EXAM CONTENT -Sufficient information about pharmokinetics and pharmological effects should be obtained -Total number of subjects: generally 20-80 -Studies of drug metabolism, structure-activity relationships and mechanism of action in humans -Studies investigation drugs as used as research tools to explore biological phenomena or disease process - Answer: Phases of an investigation: Phase 1 -Evaluate effectiveness of the drug for a particular indication in patients with the disease -Determine common short-term side effects and risks associated with the drug -Total number of subjects usually no more than several hundred - Answer: Phases of investigation: phase 2 -Performed after preliminary evidence suggesting effectiveness has been obtained -Intended to gather additional information about effectiveness and safety -Evaluate overall benefit-risk relationship of drug -Total number of subjects: several hundred to several thousand - Answer: Phases of investigation: Phase 3 IND Cover sheet - Answer: Form FDA - 1571 1. Cover sheet 2. Table of contents 3. Intro statement and general investigation plan MEGA SOCRA CCRP EXAM CONTENT Acceptable limits and analytical methods to assure the identity- stregnth, quality an purity of drug product Info to assure product's stability - Answer: IND - Drug product Info about pharmacological and toxicological studies of the drug involving animal studies and in vitro studies - Answer: IND - Pharmacology and toxicology information A separate IND must be submitted - Answer: Conducting a clinical investigation with an exception for informed consent for emergency research Sponsor must notify FDA of new investigator within 30 days of being added Sponsor must submit protocol amendment when a new investigator is added to carry out a previously submitted protocol - Answer: Protocol Amendment -New Investigator Sponsor must notify FDA of new investigator within 30 days of being added Sponsor must submit protocol amendment when a new investigator is added to carry out a previously submitted protocol - Answer: Protocol Amendment -New Investigator .Essential information now within the scope of a protocol amendment, IND safety report or annual report. Examples: 1. New toxicology, chemistry or other technical info 2. Report regarding discontinuance of investigation MEGA SOCRA CCRP EXAM CONTENT Information amendments should not be submitted more than every 30 days - Answer: Information Amendment - IND Sponsor must notify FDA and all investigators of potential serious risks no later than 15 calendar days after the sponsor determines that the info qualifies for reporting - Answer: IND safety reports Serious and unexpected suspected adverse reaction Findings from other studies Findings from animal or in vitro testing Increased rate of occurence of serious suspected adverse reactions - Answer: IND Safety Reports - What to report Sponsor must notify FDA of Unexpected fatal or life-threatening suspected adverse reactions ASAP but no later that 7 calendar days after sponsor's initial receipt of info - Answer: Unexpected fatal or life-threatening suspected adverse reaction reports Sponsor must submit a brief report of the progress of the investigation within 60 days of the anniversary date - Answer: IND - Annual reports 1. Individual study information - Brief summary of the status of each study in progress and each study completed the previous year MEGA SOCRA CCRP EXAM CONTENT 2. Summary Information - Info obtained during the previous year's clinical and non-clinical investigations 3. Description of general investigational plan for the coming year 4. If IB was revised, a description of revision and copy of new brochure 5. Description of any significant Phase 1 protocol modifications made during the previous year and not previously reported to IND in protocol amendment 6. Brief summary of foreign marketing developments 7. If desired, log of outstanding business wrt IND for which the sponsor requests a reply, comment or meeting - Answer: IND annual report includes IF FDA proposes to terminate an IND, they will notify the sponsor in writing and invite correction or explanation within a period of 30 days (Sponsor must reply within 30 days) If FDA does not accept response, sponsor may request regulatory hearing within 10 ays of sponsor's recepit of non-acceptance - Answer: Termination of IND No subjects enrolled for a period of 2 or more years or if investigations remain on hold for 1 year or more Sponsor is not required to submit annual reports to an inactive IND To resume clinical investigations under an inactive IND, sponsor must submit a protocol amendment containing proposed general investigational plan IND that remains on inactive status for 5 years will be terminated - Answer: Inactive Status - IND Notice of inspection - Answer: FDA Form 482 MEGA SOCRA CCRP EXAM CONTENT Risk/benefit relationship Maximize benefit and minimize risk - Answer: Belmont Report - Benefecience Who ought to receive the benefits of research and bear its burdens? Equals out to be treated equally Formulations of just ways to distribute benefits and burdens 1. To each person an equal share 2. To each person according to individual need 3. To each person according to individual merit 4. To each person according to societal contribution 5. To each person according to merit Example of injustice: Burden of smedical research fallin on poor wards while benefits to improved medical care primarily flowed to private patients Tuskegee syphilis study - Answer: Belmont Report - Justice Respect for persons requires that subjects be given the opportunity to choose what shall or shall not happen to them - Answer: Belmont report - informed consent Information Comprehension Voluntariness - Answer: Belmont report - elements of informed consent MEGA SOCRA CCRP EXAM CONTENT Research procedure, their purposes, risks and anticipated benefits; alternative procedures, and a statement offering the subject the opportunity to ask questions and to withdraw at any time from research Extent and nature of infomration should be such that people can decide whether they wish to participate in the furthering of knowledge Subject should clearly understand risk and voluntary nature of participating - Answer: Belmont report - Informed consent- information 1. Incomplete disclosure is truly necessary to accomplish the goals of research 2. There are no undisclosed risks to subjects that are more than minimal 3. There is an adequate plan for debriefing subjects and for dissemination of research results to them - Answer: Belmont Report - Informed consent - Incomplete disclosure of infomration Manner and context in which information is conveyed is as important as the info itself It is necessary to adapt the presentation of the information to the subject's capacities - Answer: Belmont Report - Compresension The Investigator - Answer: Who is responsible for ascertatining that the subject has comprehended information - Belmont Report - Comprehension This element of informed consent requires conditions free of coercion and undue influence - Answer: Belmont Report - Voluntariness MEGA SOCRA CCRP EXAM CONTENT Overt threat of harm is intentionally presented by one person to another in order to obtain compliance - Answer: Belmont Report - Voluntariness - Coercion An offer of excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance - Answer: Belmont Report - Voluntariness - Undue Influence Examining whether the proposed research is properly designed - Answer: Assessments of Benefits and risks - Belmont report - Investigator responsibility Method for determining whether the risks that will be presented to the subjects are justified - Answer: Assessment of risks and benefits - Belmont Report - Review comittee Protect against risk of harm to subjects and also be concerned about the loss of substantial benefits that might be gained from research - Answer: Beneficience - Risk/benefit assessment - Belmont Report Idea of systematic, nonarbitrary analysis of risks and benefits should be emulated insofar as possible First a determination of the validity of the presuppositions of the research, then the nature of probability and magnitude of risk should be distinguished with as much clarity as possible MEGA SOCRA CCRP EXAM CONTENT 4. Ensuring that the investigation is conducted in accordance with the general investigational plan and protocols contained in the IND 5. Maintaining an effective IND wrt investigations 6. Ensuring that FDA and all participating investigators are promptly informed of significant new adverse effects or risks - Answer: Responsibilities for Sponsors A sponsor may transfer responsibility for any or all of the obligations to a CRO - Answer: Transfer of obligation to CRO 1. Signed investigator statement (FDA from 1572) 2. CV 3. Clinical protocol: Phase 1: general outline of planned investigations, duration of the study and max number of subjects; Phase 2/3: Outline of protocol, approx. number of subjects including number to be controls, clinical uses to be investigated, demographics of subjects, kind of clinical observations and lab tests to be conducted, duration of the study, copies or descriptions of CRFs to be used 4. Financial disclosure information - Answer: Before permitting an investigator to begin participation in an investigation, the sponsor shall obtain the following Name and address of investigator Name and code number of the protocol in the IND identifying study to be conducted by investigator Name and address of any medical school, hosptial or other research facility where clinical investigations will be conducted Name and address of clinical labs used in study MEGA SOCRA CCRP EXAM CONTENT Name and address of responsible IRB Commitment by investigator - Answer: FDA form 1572 contains Will conduct studies in accordance to current protocol and will only make changes after notifying the sponsor except when necessary to protect the safety, rights or welfare of subjects Will comply with all requirements regarding the obligations of clinical investigators Will personally conduct or supervise the investigations Will inform any potential subjects that the drugs are being used for an investigational purposes and will ensure that requirements relating to informed consent are met and IRB review and approval are met Will report AEs to sponsor Has read and understood the info in the IB including potential risks and side effects Ensures that associates, colleagues and employees assisting in the study are informed about their obligations Commitment that an IRB complies with requirements for the initial review and CR and will promptly report all changes in research activity and unanticipated problems involving - Answer: FDA form 1572: Commitments by investigator Sponsor must maintain adequate records showing the receipt, shipment or other disposition of the drug Must include name of investigator to whom the drug is shipped, the date, quantity and batch or code mark of each shipment - Answer: Sponsor record keeping - investigational drug MEGA SOCRA CCRP EXAM CONTENT Sponsor must maintain records for 2 years after a marketing application is approved for the drug If an application is not approved records must be kept until 2 years after shipment and delivery of investigational drug is discontinued - Answer: Sponsor record keeping - duration 1. Ensure investigation is conducted according to signed investigator statement, investigational plan and applicable regulations 2. Protect the rights, safety and welfare of subjects under their care 3. Control of drugs under investigation 4. Investigator must obtain informed consent 5. Investigator must assure that the IRB complies with applicable federal requirements and will be responsible for initial and continuring review and approval of the study 6. Investigator must promptly report all changes in research activity, unanticipated problems involving human risk, and that he will not make changes in the research without IRB approval except when necessary to eliminate apparent immediate hazard - Answer: Investigator Responsibilities Has primary responsibilities for protecting the rights and welfare of human research subjects Conducts all research according to IRB approved protocol Ensures each potential subject understands the nature of research Provides a copy of the IRB approved consent document to each subject MEGA SOCRA CCRP EXAM CONTENT CAUTION: Contains a biological product for investigational in vitro diagnostic tests only - Answer: A person may ship a biological product for investigational in vitro disgnostic use if it is labeled as follows Maintain adequate records including name and address of whom the product is shipped to and the date shipped, quantity, batch or code mark of each shipment and delivery Records are to be maintained for 2 years after the shipment - Answer: Record keeping for shipping drug/biologics for use in lab animals/in vitro research 1. Patient(s) have a serious/immediately life-threatening condition and there is no comparable satisfactory alternative therapy to diagnose, monitor or treat it 2. Potential benefit justifies the potential risks of the treatment and those potential risks are not unreasonable in the context of the condition - Answer: Requirements for all expanded access use: FDA must determine that An expanded access submission is required for each type of expanded access. Submission may be a new IND or a protocol amendment to an existing IND. Information required for a submission may be supplied by referring to pertinent infomration contained in an existing IND if the sponsor of the existing IND grants a right to reference the IND - Answer: Requirements for all expanded access use: Submission Look to Manual for more details 1. Form 1572 MEGA SOCRA CCRP EXAM CONTENT 2. Rationale for intended use of the drug, including a list of available therapeutic options that would ordinarily be tried before resorting to the investigational drug or an explanation of why the use of the investigational drug is preferable to the use of available therapeutic options 3. The criteria for patient selection or, for an individual patient, a descriptions of the patient's condition, including recent medical history and previous treatments of the condition Expanded access submission and mailing cover must be clearly marked "EXPANDED ACCESS SUBMISSION" - Answer: Requirements for all expanded access use: Submission must include 1. Reporting AEs to the sponsor 2. Ensuring that informed consent requirements are met 3. Ensuring that IRB review of the expanded acesss use is obtained 4. Maintaining accurate case histories and drug disposition records and retaining records - Answer: Responsibilities of Investigators- expanded access 1. Submitting IND safety reports and annual reports to the FDA 2. Ensuring that lisenced physicians are qualified to administer the drug for expanded access use 3. Providing licensed physicians with the information needed to minimize risk and maximize benefits 4. Maintain an effective IND for expanded access use MEGA SOCRA CCRP EXAM CONTENT 5. Maintain adequate drug disposition records and retain records - Answer: Responsibilities of Sponsors - Expanded access Use 30 days after FDA received the IND or on earlier notification by the FDA - Answer: Expanded Access IND goes into effect All criteria must be met for all expanded access use in addition to: 1. Physician must determine that the probable risk to the person from the drug is not greater than the probable risk from the disease or condition 2. FDA must determine that the patient cannot obtain the drug under another IND or protocol - Answer: Expanded access use - Individual patients: Criteria 1. Treatment is generally limited to a single course of therapy for a specified duration unless FDA expressly authorized multiple courses of therapy 2. At the conclusion of treatment, the licensed physician or sponsor must provide the FDA with a written summary of results of the expanded access use, including AEs 3. FDA may require sponsors to monitor an individual patient expanded access use if the use is for an extended duration 4. When a significant number of similar individual patient expanded access requests have been submitted, the FDA may ask the sponsor to submit an IND or protocol for use of the drug in the population - Answer: Expanded access use - Individual patients: Safeguards MEGA SOCRA CCRP EXAM CONTENT 4. If expanded access use is for immediately life-threatening condition, the available scientific evidence provides a reasonable basis to conclude that the investigational drug may be effective for the expanded access use and would not expose patients to unrea - Answer: Expanded Access Use - Treatment IND or treatment protocol: Criteria Sponsor is responsible for monitoring the treatment protocol to ensure that licensed physicians comply with the protocol and the regulations applicable to investigators - Answer: Expanded Access Use - Treatment IND or treatment protocol: Safeguard 1. A device, other than a transitional device, in commercial distribution before May 28, 1976, when used or investigated in accordance with the indications in labeling in effect at the time 2. (510K Pathway) A device, other than a transitional device, introduced into commercial distribution on or after May 28, 1976, the the FA has determined to be substantially equivalent to a device in commercial distribution immediately before May 28, 1976 and that is used or investigated in accordance with the indications in the labeling FDA reviewed in determining substantial equivalence 3. A diagnostic device if the testing: is noninvasice, does not require an invasive sampling procedure that presents significant risk, does not by design or intention introduce energy into a subject and is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure 4. - Answer: Investigation Device Exemptions -Exempted investigations MEGA SOCRA CCRP EXAM CONTENT Name and place of business of the manufacturer, packer, or distributer, the quantity of contents and the following statement "CAUTION- Investigational device. Limited by Federal law to investigational use." Label shall describe all relevant contraindications, hazards, adverse effects, interfering substances or devices, warnings and precautions Label (Animal research) - "CAUTION - Device for investigational use in lab animals or other tests that do not involve subjects." - Answer: Label - Investigational device 1. Name and address of the sponsor 2. Complete report of prior investigations of the device and an accurate summary of the investigational plan or the complete plan 3. Description of methods, facilities, and controls used for manufacture, processing, packing, storage and (if appropriate), installation of the device 4. Example of agreements to be entered into by all investigators to comply with investigator obligations and a list of names and addresses of all investigators who have signed the agreement 5. A certification that all investigators have signed the agreement 6. A list of name, address and chairperson of each IRB that has been or will be asked to review investigation and a certification of the action concerning the investigation taken by each IRB member 7. Names/address of any institution at which a part of the investigation may be conducted MEGA SOCRA CCRP EXAM CONTENT 8. If the device is to be sold, the amount to be charged and an ex - Answer: Investigational device exemption application contents 1. Purpose 2. Protocol 3. Risk Analysis 4. Description of the device 5. Monitoring procedures 6. Labeling 7. Consent materials 8. IRB infomration 9. Other institutions 10. Additional records and reports - Answer: Investigational device exemption - Investigational plan FDA will notify the sponsor in writing of the date it receives the application. FDA may approve an investigation as proposed, approve it with modifications or disapprove it. - Answer: Investigational Device Exemption - FDA action on applications 1. 30D after FDA received the application unless the FDA notifies the sponsor that the investigation may not begin 2. The FDA approved and IDE for the investigation - Answer: Investigational Device Exemption - FDA action on applications - Investigation may not begin until MEGA SOCRA CCRP EXAM CONTENT (a) General. A device that is not approved for marketing may be under clinical investigation for a serious or immediately life-threatening disease or condition in patients for whom no comparable or satisfactory alternative device or other therapy is available. During the clinical trial or prior to final action on the marketing application, it may be appropriate to use the device in the treatment of patients not in the trial under the provisions of a treatment investigational device exemption (IDE). The purpose of this section is to facilitate the availability of promising new devices to desperately ill patients as early in the device development process as possible, before general marketing begins, and to obtain additional data on the device's safety and effectiveness. In the case of a serious disease, a device ordinarily may be made available for treatment use under this section after all clinical trials have been c - Answer: Treatment use of an investigational device under a treatment investigation device exemption Treatment may begin 30 days after the FDA receives the treatment IDE submission unless the FDA notifies the sponsor in writing earlier than the 30 that the treatment use may or may not begin FDA may approve treatment use as proposed or approve it with modifications - Answer: FDA Actions on treatment IDE applications - Approval See Manual for more details 1. The device is intended for a serious disease or condition and there is insufficient evidence of safety and effectiveness to support such use MEGA SOCRA CCRP EXAM CONTENT 2. The device is intended for an immediately life threatening condition and the available scientific evidence fails to provide a reasonable basis for concluding that the device: may be effective for its intended use in the population, or would not expose patients to an unreasonable and significant additional risk of illness or injury 3. There is reasonable evidence that treatment use is impeding enrollment in, or otherwise interfering with the conduct or completion of, a controlled investigation of the same or another investigational device 4. The device has receive marketing approval/clearance or a comparable device or therapy becomes available to treat or diagnose the same condition in the same population 5. The sponsor is not pursuing marketing - Answer: FDA Actions on treatment IDE applications - Disapproval The sponsor must submit semi-annual reports to all reviewing IRBs and FDA until the filing of a market application. Includes: 1. The number of patients treated 2. Names of investigators 3. Brief description of the sponsor's efforts to pursue marketing approval/clearance Upon filing of a marketing application, progress reports must be submitted annually - Answer: Reporting requirements - Treatment use of IDE 1. Name, address and phone number of sponsor MEGA SOCRA CCRP EXAM CONTENT 2. Intended use of the device, criteria for patient selection and written protocol describing treatment use 3. Explanation of rationale for use of the device including (as appropriate) a list of available regiment that ordinarily should be tries before the investigational device o an explanation of why use of the investigational device is preferable to the use of marketed treatments 4. Descriptions of clinical procedures, laboratory tests or other measures used to evaluate effect of device and minimize risk 5. Written procedures for monitoring the treatment use and name/address of the monitor 6. Instructions for the device and all other labeling 7. Info related to safety and effectiveness of the device 8. Statement of sponsor's committment to meet all applicable responsibilities and to ensure compliance of all participating investigators with informed consent requirements - Answer: Application for treatment use of IDE A sponsor, investigator or any person acting on their behalf may not: 1. Promote or test market an investigation device until the FDA has approved the device for commercial distribution 2. Commercialize and investigational device by charging the subjects or investigators for a device a price larger than that necessary to recover costs of manufacture, research, development and handling 3. Unduly prolong an investigation - Sponsor must terminate investigation if they determine device cannot be approved