Regulations Governing Human Subjects Research in the United States, Exams of Nursing

Download Regulations Governing Human Subjects Research in the United States and more Exams Nursing in PDF only on Docsity! CCRP Exam Prep (300 Questions and Answers) 2024 LATEST UPDATE BEST RATED A+ Who was tried in the Nuremburg Military Tribunals and why? - SOLUTION Doctors who committed war crimes against humanity including medical experiments on concentration camp inmates and other human subjects without consent What was the outcome of the Nuremburg Military Tribunals? - SOLUTION After 140 days of proceedings with testimony of 85 witnesses and submission of 1,500 documents, American judges convicted 16 doctors on 8/20/1947. Seven were sentenced to death and executed 6/2/1948. What historical document was born from the Nuremberg Military Tribunals? - SOLUTION The Nuremberg Code (1947) According to the Nuremberg Code (1947), all unnecessary physical and mental suffering and injury... - SOLUTION should be avoided According to the Nuremberg Code (1947), voluntary consent of the human subject is... - SOLUTION absolutely essential According to the Nuremberg Code (1947), the experiment must yield.... - SOLUTION generalizable knowledge that could not be obtained in any other way and is not random and unnecessary in nature According to the Nuremberg Code (1947), animal experimentation should... - SOLUTION precede human experimentation According to the Nuremberg Code (1947), no experiment should be conducted if there is reason to believe... - SOLUTION death of disabling injury will occur According to the Nuremberg Code (1947), the degree of risk to subject should... - SOLUTION never exceed the humanitarian importance of the problem According to the Nuremberg Code (1947), risk to subjects should be minimized through... - SOLUTION proper preparations According to the Nuremberg Code (1947), experiments should only be conducted by... - SOLUTION scientifically qualified investigators According to the Nuremberg Code (1947), subjects should always be at liberty to... - SOLUTION withdraw from experiments According to the Nuremberg Code (1947), investigators must be ready to end an experiment at any stage if... - SOLUTION there is cause to believe that continuing the experiment is likely to result in injury, disability, or death to the subject The Declaration of Helsinki (1964) emphasized what? - SOLUTION Brought about by the need for human research as opposed to human experimentation and better defined the criteria for consent What organization originally adopted the Declaration of Helsinki? - SOLUTION The World Medical Association General Assembly What did the Declaration of Helsinki (1964) provide recommendations for? - SOLUTION Recommendations guiding physicians in biomedical research involving human subjects The Declaration of Helsinki (1964) reiterated the basic ethical principles from what document? - SOLUTION The Nuremberg Code According to the Declaration of Helsinki (1964), informed consent must be obtained from who? - SOLUTION The subject or legal guardian According to the Declaration of Helsinki (1964), design and performance of experimental procedure must be... - SOLUTION formulated in a clear protocol According to the Declaration of Helsinki (1964), research protocols should be transmitted to... - SOLUTION a specially appointed independent committee for consideration, comment and guidance According to the Belmont Report (1979), justice means that selection of subjects for research should be based on... - SOLUTION reasons directly related to the problem being studied, not systematic selection of a class of individuals due to compromised position, manipulability, etc. What does the Belmont Report (1979) say about who should receive benefits of research? - SOLUTION Benefits should not be restricted to those who can afford it, and research should not involve persons from groups not likely to benefit from application of the research What did the Henry K Beecher Paper reveal - SOLUTION 22 published medical studies where patients had been experimented on with no expected benefit to them, showing that unethical studies were widespread and represented a systemic problem in medical research rather than exceptions Human Radiation Experiments (1945-1957) - SOLUTION The Atomic Energy Commission conducted secret and classified radiation experiments and releases on unknowning Americans to assess how the human body metabolizes radioactive material. What are the three foundations ethical research as outlined the Belmont Report (1979)? - SOLUTION 1. Respect for persons 2. Beneficence 3. Justice Wichita Jury Study (1953) - SOLUTION Social scientists covertly recorded discussions of 6 Wichita federal district court civil juries, without the consent of the jurors. Willowbrook Hepatitis Study (1955) - SOLUTION Gave children with mental retardation hepatitis in order to track the progression of the disease and to test treatments Milgram's Obedience Study (1963) - SOLUTION study of the phenomenon of obedience to an authority figure, examinfed the effects of punishment on learning (shock treatment for mistakes, 65% shocked dangerous amounts when ordered Jewish Hospital Cancer Study (1963) - SOLUTION Elderly hospitalized patients were injected with live cancer cells to study the mechanism of immune reaction without true informed consent. Tearoom Trade Study (1970) - SOLUTION Analysis of male-male sexual behavior in public toilets by Laud Humphreys. He observed acts masquerading as a voyeur rather than a researcher, tracked participants without their consent by using their license plate numbers, and interviewed them in disguise without disclosing his true intent (research) Stanford Prison Experiment (1970) - SOLUTION Volunteers in a mock prison took on the roles of guards and inmates. The experiment was discontinued due to ongoing physical and psychological abuse inflicted on many prisoners. San Antonio Contraceptive Study (1971) - SOLUTION Poor Mexican- American women given placebos instead of contraceptives without knowing they were subject to such research. There were high numbers of unplanned pregnancy in the placebo group University of Rochester Death of Healthy Subject (1996) - SOLUTION Student dies of heart attack after undergoing lung procedure (bronchoscopy) in study on smoking and air pollution Death in a Gene Transfer Trial (1999) - SOLUTION 18 year old volunteer was injected with adenoviral vector carrying a corrected gene to test the safety of the procedure and died four days later despite not being ill prior. PI on the study had a conflict of interest and animal data regarding risks given patient's underlying liver issues was not considered. IRB approved consent form was not used. Johns Hopkins Death of Healthy Subject in an Asthma Study (2001) - SOLUTION Inhaled hexamethonium, used to treat high BP in the 50s and 60s and designed to promote a mild asthma attack. Federal investigation found that IRB did not take proper precautions or follow federal regulations, leading to suspension of research. Also issues with pressure on employees to participate in research. What is ICH? - SOLUTION The International Conference on Harmonization of Technical Requirements for the registration of pharmaceuticals for human use What is the purpose of the International Conference on Harmonization (ICH)? - SOLUTION An attempt to streamline the process for developing and marketing new drugs internationally What is Good Clinical Practice (GCP)? - SOLUTION An international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects What does compliance with Good Clinical Practice (GCP) provide assurance of? - SOLUTION That the rights, safety, and well-being of trial subjects are protected consistent with the principles of the Declaration of Helsinki, and that clinical trial data are credible The ICH GCP guideline provides a unified standard for what countries and why? - SOLUTION For the European Union (EU), Japan, and the US to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions The guideline for Good Clinical Practice (GCP) was developed with consideration of the current good clinical practices of what countries? - SOLUTION The EU, Japan, US, as well as Australia, Canada, the Nordic countries, and the World Health Organization When generating clinical trial data that are intended to be submitted to regulatory authorities, what guideline should be followed? - SOLUTION The guideline for good clinical practice The principles established in GCP may also be applied to what? - SOLUTION Other clinical investigations that may have an impact on the safety and well-being of human subjects What are the categories of International Committee on Harmonization (ICH)? - SOLUTION Quality guidelines Efficacy guidelines Safety guidelines Multidisciplinary guidelines What does 45 CFR 46 outline? - SOLUTION Regulations set forth by the U.S. Department of Health and Human Services. HHS regulations apply to research involving human subjects conduced or funded in whole or in part by HHS 21 CFR 50 refers to what - SOLUTION Protection of Human Subjects, as set forth by the FDA 21 CFR 56 refers to what - SOLUTION Institutional Review Boards, as set forth by the FDA FDA regulations apply to all clinical investigations regulated by the FDA under sections... - SOLUTION 505(i) and 520(g) of the Federal Food, Drug, and Cosmetic Act, as well as clinical investigations that support applications for research or marketing permits for products regulated by the Food and Drug Administration, including floods, dietary supplements that bear a nutrient content claim or a health claim, infant formulas, food and color additives, drugs for human use, medical devices for human use, biological products for human use, and electronic products 45 CFR 46 Subpart A - SOLUTION Basic HHS Policy for Protection of Human Research Subjects, also called the Common Rule. Describes the required protections for all human subjects 45 CFR 46 Subpart B - SOLUTION Additional protections for pregnant women, human fetuses, and neonates involved in research 45 CFR 46 Subpart C - SOLUTION Additional protections pertaining to biomedical and behavioral research involving prisoners as subjects 45 CFR 46 Subpart D - SOLUTION Additional protections for children involved as subjects of research 45 CFR 46 Subpart E - SOLUTION Registration of Institutional Review Boards 21 CFR 50 - SOLUTION Protection of Human Subjects 21 CFR 50 Subpart A - SOLUTION General Provisions for the Protection of Human Subjects 21 CFR 50 Subpart B - SOLUTION Informed Consent of Human Subjects 21 CFR 50 Subpart C - SOLUTION Reserved 21 CFR 50 Subpart D - SOLUTION Additional Safeguards for Children in Clinical Investigations 21 CFR 56 - SOLUTION Institutional Review Boards 21 CFR 56 - SOLUTION IRB general provisions 21 CFR 56 Subpart B - SOLUTION IRB organization and personnel 21 CFR 56 Subpart C - SOLUTION IRB functions and operations 21 CFR 56 Subpart D - SOLUTION Records and Reports 21 CFR 56 Subpart E - SOLUTION Administrative Actions for Noncompliance Are there exemptions to 45 CFR 46.101? - SOLUTION Exemptions do not apply to research involving prisoners, subpart C. Exemption for research involving survey or interview procedures or observation of public behavior does not apply to research with children, subpart D, except for research involving observations of public behavior when the investigators do not participate in the activities being observed What are the exemptions from IRB requirement (21 CFR 56.104)? - SOLUTION Any investigation that commenced before July 27, 1981 Emergency use of a test article Taste and food quality evaluations and consumer acceptance studies Emergency use of a test article is exempt from 21 CFR 56.104 (IRB requirement) provided that.... - SOLUTION Such emergency use is reported to the IRB within 5 working days. Any subsequent use of the test article at the institution is subject to IRB review What is a legally authorized representative? - SOLUTION 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 procedure involved in the research What does minimal risk mean? - SOLUTION The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves that those ordinarily encountered in daily life or during the performance of routine physical or psychological exams or tests According to 45 CFR 46.102, research means... - SOLUTION a systemic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge According to 21 CFR 50.3c, clinical investigation means... - SOLUTION Any experiment that involves a test article and one or more human subjects and that their is subject to requirements for prior submission to the FDA under section 505(i) or 520(g) of the act, or is not subject to requirements for prior submission but the results of which are intended to be submitted later to, or held for inspection by, the FDA as part of an application for a research or marketing permit How does 45 CFR 46.102 define a human subject? - SOLUTION A living individual about whom an investigator (professional or student) conducting research obtains data through intervention or interaction with the individual or identifiable private information How does 21 CFR 50.3g define a human subject? - SOLUTION An individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be a healthy human or a patient How does 45 CFR 46.102 define an IRB? - SOLUTION An institutional review board established in accord with and for the purposes expressed in this policy How does 21 CFR 50.3i define an IRB? - SOLUTION Any board, committee, or other group formally designated by an institution to review biomedical research involving humans as subjects, to approve the initiation of and conduct periodic review of such research. The term has the same meaning as the phrase institutional review committee as used in section of 520(g) of the act. According to 45 CFR 46.107 and 21 CFR 56.107, who should be included in an IRB that regularly reviews research involving vulnerable subjects (children, prisoners, pregnant women, handicapped/mentally disabled persons)? - SOLUTION Individuals who are knowledgeable about and experience in working with these subjects According to 45 CFR 46.108 and 21 CFR 56.108, each IRB should follow... - SOLUTION written procedures According to 45 CFR 46.108 and 21 CFR 56.108, what conditions must be met at convened meetings - SOLUTION Majority of members are present, including at least one member whose primary concerns are in nonscientific areas. For research to be approved, it shall receive approval of a majority of those members present. The exception is when an expedited review procedure is used. According to 45 CFR 46.109 and 21 CFR 56.109, IRB shall review and have the authority to... - SOLUTION Approve, require modifications, or disapprove of research activities According to 45 CFR 46.109 and 21 CFR 56.109, the IRB shall require that information given to subjects as part of informed consent is in accordance with... - SOLUTION with 46.116 or 50.25 According to 45 CFR 46.109 and 21 CFR 56.109, the IRB may require that information in addition to that specifically mentioned in 46.116 or 50.25 be given to subjects when... - SOLUTION in the IRB's judgement the information would meaningfully add to the protection of the rights and welfare of subjects According to 45 CFR 46.109 and 21 CFR 56.109, IRBs should notify investigators and the institution... - SOLUTION in writing of its decision to approve, disapprove, or require modifications to the proposed research activity According to 45 CFR 46.109 and 21 CFR 56.109, continuing reviews should be conducted at intervals appropriate to... - SOLUTION the degree of risk of the research According to 45 CFR 46.110 and 21 CFR 56.110, the IRB may use an expedited review procedure to review... - SOLUTION -research found by the reviewers to involve no more than minimal risk AND/OR -minor changes in previously approved research According to 45 CFR 46.110 and 21 CFR 56.110, expedited review may be carried out by... - SOLUTION The IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB. Reviewers may exercise all of the authorities of the IRB except that they may not disapprove the research According to 45 CFR 46.111 and 21 CFR 56.111, the IRB must determine that all of the following requirements are satisfied: - SOLUTION -Risks to subjects are minimized -Risks are reasonable in relation to anticipated benefits -Selection of subjects is equitable -Informed consent is sought from each subject or the subject's legally authorized representative -Informed consent is appropriately documented -When appropriate data collected is monitored to ensure subject safety -When appropriate provisions are in place to protect the privacy and confidentiality of subjects -There are additional safeguards for vulnerable populations According to 45 CRF 46.112 and 21 CFR 56.112, research approved by the IRB may be subject to further appropriate review and approval or disapproval by... - SOLUTION Officials of the institution According to 45 CFR 46.112 and 21 CFR 56.112, institution officials may not approve research if... - SOLUTION it has not been approved by an IRB According to 45 CFR 46.113 and 21 CFR 56, IRB has the authority to suspend or terminate approval of research that... - SOLUTION is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects According to 45 CFR 46.113 and 21 CFR 56, any suspension or termination of approval shall... - SOLUTION include a statement of the reasons for the IRB's action and shall be reported promptly to the investigator, appropriate institutional officials, and the department or agency head 45 CFR 46.116 and 21 CFR 50.25 - SOLUTION General requirements for informed consent According to 45 CFR 46.116 and 21 CFR 50.25, what are the general elements for informed consent? - SOLUTION -a concise and focused presentation of key information -a statement that the study involves research -purposes of the research -expected duration -procedures -what's considered experimental -risks -benefits -alternatives -confidentiality -who to contact with pertinent questions/injury -how to contact someone independent of the research team -voluntary -no loss of benefits -can discontinue at any time -use in future research -compensation (greater than min risk) -FDA may review -unforeseeable risks as applicable -repro risk -when participation may be terminated -costs -new info may be shared with subject if affecting research -approx number of participants -commercial profit sharing -whether results are disclosed to subject -whether whole genome sequencing possible What do research subjects need to be told about ClinicalTrials.gov according to 21 CFR 50.25? - SOLUTION Clinical trial information has or will be submitted for inclusion in the clinical trial registry databank under paragraph j of section 402 of the Public Health Service Act saying that a According to the principles of ICH GCP, the available nonclinical and clinical information on an investigational product should be... - SOLUTION adequate to support the proposed clinical trial According to the principles of ICH GCP, clinical trials should be scientifically sound and described in... - SOLUTION a clear, detailed protocol According to the principles of ICH GCP, a trial should be conducted in compliance with the protocol that has received... - SOLUTION prior IRB/ independent ethics committee (IEC) approval/favorable opinion According to the principles of ICH GCP, the medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of... - SOLUTION a qualified physician or, when appropriate, a qualified dentist According to the principles of ICH GCP, each individual involved in conducting a trial should be qualified by... - SOLUTION education, training, and experience to perform his or her respective tasks According to the principles of ICH GCP, freely given informed consent... - SOLUTION Should be obtained from every subject prior to clinical trial participation According to the principles of ICH GCP, all clinical trial information should be recorded, handled, and stored in a way that allows for... - SOLUTION accurate reporting, interpretation, and verification According to the principles of ICH GCP, the confidentiality of records that could identify subjects should... - SOLUTION be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements According to the principles of ICH GCP, investigational products should be manufactured, handled, and stored in accordance with... - SOLUTION applicable good manufacturing practice, and used in accordance with the approved protocol According to the principles of ICH GCP, systems with procedures that assure that assure the quality of every aspect of the trial... - SOLUTION should be implemented According to the principles of ICH GCP, the IRB/IEC should obtain what documents? - SOLUTION Protocols, amendments, written ICFs, proposed updates, recruitment procedures, written info provided to subjects, IBs, safety info, info about payment and compensation, CVs for investigators According to the principles of ICH GCP, when a non-therapeutic trial is to be carried out with consent of a subjects LAR, the IRB/IEC should... - SOLUTION determine that the proposed protocol and/or other documents adequately address relevant ethical concerns and meets applicable regulatory requirements for such trials According to the principles of ICH GCP, the IRB should ensure info regarding payments to subjects is provided in the ICF, including... - SOLUTION methods, amounts, and schedule According to the principles of ICH GCP, the language used in consent forms should be... - SOLUTION non-technical as is practical and understandable to the subject, LAR, and witness as applicable According to the principles of ICH GCP, the ICF should be signed and dated by - SOLUTION The subject/LAR and the person who conducted the informed consent discussion According to the principles of ICH GCP, if a subject or LAR is unable to read... - SOLUTION An impartial witness should be present during the entire informed consent discussion to sign the consent form attesting that information was accurately explained and understood, and consent was freely given According to the principles of ICH GCP, a non therapeutic trial is... - SOLUTION a trial in which there is no anticipated direct clinical benefit to the subject According to the principles of ICH GCP, when a clinical trial includes subjects who can only be enrolled in the trial with the consent of the subjects LAR, the subject... - SOLUTION should be informed about the trial to the extent compatible with the subjects understanding and, if capable, the subject should sign and personally date the written informed consent According to the principles of ICH GCP, non-therapeutic trials may be conducted in subjects with consent of a LAR provided that... - SOLUTION - the trial cannot be conducted in subjects who can give consent personally -foreseeable risks are low -negative impact on well-being is minimized and low -the trial is not illegal -IRB approval on inclusion of these subjects What does 21 CFR 11 cover? - SOLUTION Electronic records and signatures. It sets for the criteria under which the agency considers electronic records, signatures, and handwritten signatures executed to electronic records to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper According to 21 CFR 11.3, biometrics are... - SOLUTION a method of verifying an individual's identity based on measurement of the individual's feature(s) or repeatable action(s) where those features and or actions are both unique to that individual and measurable According to 21 CFR 11.3, a closed system is... - SOLUTION An environment in which system access is controlled by persons who are responsible for the content of electronic records that are on the system According to 21 CFR 11.3, electronic records are - SOLUTION any combination of text, graphics, data, audio, pictorial, or other information represented in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system According to 21 CFR 11.3, an open system is... - SOLUTION an environment in which system access is not controlled by persons who are responsible for the content of electronic records According to 21 CFR 11.3, digital signatures are... - SOLUTION an electronic signature based on cryptographic methods of originator authentication, computed by using a set of rules and parameters such that the identity of the signed and the integrity of the data can be verified According to 21 CFR 56, a sponsor of the covered clinical study means... - SOLUTION the party supporting a particular study at the time it was carried out According to 21 CFR 56, a clinical investigator means... - SOLUTION only a listed or identified investigator of subinvestigator who is directly involved in the treatment or evaluation of research subjects. The term also includes the spouse and each dependent child of the investigator According to 21 CFR 56, compensation affected by the outcome of clinical studies includes... - SOLUTION compensation that could be higher for a favorable outcome than for an unfavorable outcome, such that compensation that is explicitly greater for a favorable result or compensation to the investigator in the form of an equity interest in the sponsor of a covered study or in the form of compensation tied to sales of the product, such as a royalty interest According to 21 CFR 56, significant equity interest in the sponsor of a covered study means... - SOLUTION any ownership interest, stock options, or other financial interest whose value cannot be readily determined through reference to public prices (generally, interest in a nonpublicly traded company), or any equity interest in a publicly traded corporation that exceeds $50,000 during the time the clinical investigator is carrying out the study and for 1 year following the completion of the study According to 21 CFR 56, significant payments of other sorts include... - SOLUTION payments made by the sponsor of a covered study to the investigator or the institution to support activities of the investigator that have a monetary value of more that $25,000, exclusive of the costs of conducting the clinical study or other clinical studies (e.g., a grant to fund ongoing research, compensation in the form of equipment or retainers for ongoing consultation or honoraria) during the time the clinical investigator is carrying out the study and for 1 year following the completion of the study According to 21 CFR 56, what are sponsor responsibilities related to financial disclosure? - SOLUTION -Collect financial disclosure information from investigators; perform due diligence -Submit summary forms to FDA in marketing applications (3454 and 3455) -Store clinical investigators' financial disclosure info for 2 years after the date of application approval According to 21 CFR 56, what does the sponsor's certification of Form FDA 3454 represent? - SOLUTION Attestation to the absence of financial interests and arrangements According to 21 CFR 56, what does the sponsor's disclosure on Form FDA 3454 include? - SOLUTION -Any financial arrangement between the sponsor and the clinical investigator where the value of the compensation to the clinical investigator for conducting the study could be influenced by the outcome of the study -any significant payments of other sorts from the sponsor, such as a grant to fund ongoing research, compensation in the form of equipment, retainer for ongoing consultation, or honoraria -Any proprietary interest in the tested product held by any clinical investigator -any significant equity interest in the sponsor held by any clinical investigator -any steps taken to minimize potential bias resulting from any of the disclosed arrangements, interests, or payments According to 21 CFR 56, what responsibility does the clinical investigator have? - SOLUTION Clinical investigators subject to investigational new drug or investigational device exemption regulations must provide the sponsor of the study with sufficient accurate information needed to allow subsequent disclosure or certification. They must promptly update this information if any relevant changes occur in the course of the investigation or for 1 year following the completion of the study. What is Form FDA 1572? - SOLUTION The statement of investigator What does the investigator commit to by signing Form FDA 1572? - SOLUTION -to conduct the study in accordance with the relevant current protocols, and only make changes after notifying the sponsor except when necessary to protect the safety, rights, or welfare of subjects -to personally conduct or supervise the investigation -to inform any patients that drugs are investigational -to ensure the requirements related to informed consent in 321 CFR Par 50 and IRB approval in 21 CFR 56 are met -to report AEs in accordance with 21 CFR 312.64 and understand the IB risks and side effects -to ensure all people involved in study contact are informed on their obligations in meeting the above commitments -to maintain adequate an accurate records in accordance with 31 CFR 312.62 and make those available for inspection in accordance with 21 CFR 312.68 -to ensure IRB complies with 21 CFR 56, initial and continuing review, to promptly report to IRB changes and UPIRTSOs, and not make changes without IRB approval except to eliminate immediate hazards to subjects -comply with all other requirements regarding the obligations of clinical investigators and all other pertinent requirements in 21 CFR 312 According to ICH GCP E6.7, what are investigator brochures? - SOLUTION A compilation of clinical and nonclinical data on the investigational product According to ICH GCP E6.7, what purpose does the IB serve to investigators? - SOLUTION To provide information that facilitates their understanding of the rationale and compliance with key features of the protocol (dosing, administration, safety monitoring). To provide insight to support clinical management of study subjects. According to ICH GCP E6.7, how must IBs be updated? - SOLUTION IBs should be reviewed at least annually, revised in compliance with sponsor's written procedures, and relevant new information should be communicated to investigators, IRBs, and regulatory authorities prior to revision. Sponsors should ensure investigators have the current IB, and investigators are responsible for submission to the IRB. According to ICH GCP E6.8, essential documents should... - SOLUTION - Individually and collectively permit the evaluation of the trial conduct and data quality -demonstrate compliance of the investigator, sponsor, and monitor with standards of GCP and regulatory requirements -assist in successful management of the trial -be audited by the sponsor and inspected by regulatory agencies According to ICH GCP E6.8, essential documents should be grouped by... - SOLUTION Stage of the trial -before clinical phase -during clinical conduct It must not bear any statement that is false or misleading, particularly that the new drug is safe or effective for the purposes for which it is being investigated According to 21 CRF 312.7, what regulations are there about the promotion of investigational drugs? - SOLUTION A sponsor or investigator shall not represent in a promotional context that the drug is safe or effective to preclude commercialization before approval. According to 21 CRF 312.7, can a sponsor commercially distribute or test market investigational new drugs? - SOLUTION No According to 21 CRF 312.7, a sponsor shall not unduly prolong an investigation after finding that the results... - SOLUTION appear to establish sufficient data to support a marketing application According to 21 CRF 312.8, under what circumstances can a sponsor charge for an investigational drug? - SOLUTION Not without prior written authorization from FDA, and they may only recover the direct costs of making the investigational drug available According to 21 CFR 312.20, what should a sponsor do if they want to conduct a clinical investigation with an investigational new drug? - SOLUTION -a sponsor shall submit an IND to FDA and wait to begin clinical investigation until the IND is in effect According to 21 CFR 312.20, a sponsor should submit a separate IND for any clinical investigation involving an exception from... - SOLUTION informed consent under 21 CFR 20.54 According to 21 CRF 312.30, new protocols may be submitted and changes in previously submitted protocols may be made if... - SOLUTION - there is a new protocol -changes in a protocol (phase 1- significantly affects safety, phase 2-3- significantly affects safety, scope of investigation, or scientific quality) -new investigator According to 21 CFR 312.31, what essential information on the IND requiring amendments is not within the scope of the protocol amendment, IND safety reports, or annual reports? - SOLUTION -New toxicology, chemistry, or other technical information -Discontinuance of a clinical investigation According to 21 CFR 312.33, how long does a sponsor have to submit a brief annual report on the progress of the investigation? - SOLUTION 60 days According to 31 CFR 312.38, the withdrawal of an IND requires... - SOLUTION FDA notification, all clinical investigations conducted under the IND ended, all current investigators notified, and all stocks of the drug returned to the sponsor or otherwise disposed of According to 21 CFR 312.40, an IND goes into effect... - SOLUTION 30 days after the FDA receives the IND, unless the FDA notifies the sponsor that investigations are subject to a clinical hold. The FDA may notify the sponsor earlier that clinical investigations may commence. According to 21 CFR 312.50, what are the general responsibilities of the sponsor? - SOLUTION -to select qualified investigators -provide investigators with information needed to conduct the investigation properly -ensure proper monitoring of the investigation -ensure investigation is conducted in accordance with protocol -maintain an effective IND -ensure FDA and all participating investigators are promptly informed of significant new AEs, risks According to 21 CFR 312.60, what are the general responsibilities of investigators? - SOLUTION -ensure the investigation is conducted according to the signed investigator statement, investigational plan, and applicable regulations -protecting the rights, safety, and welfare of subjects -control of drugs under investigation -obtain informed consent of each subject -assure that an IRB that complies with 21 CFR 56 is responsible for initial and continuing review According to 21 CFR 312.21, what phase represents the introduction of an investigational new drug into humans? - SOLUTION Phase 1 According to 21 CFR 312.21, what kind of research subjects are used in Phase 1 trials? - SOLUTION Normal volunteers or patients According to 21 CFR 312.21, what is the goal of Phase 1 trials? - SOLUTION To determine metabolism and pharmacologic actions in humans, side effects with increasing doses, and early evidence of effectiveness According to 21 CFR 312.21, what phase of study is often conducted inpatient and why? - SOLUTION Phase 1, to allow to close monitoring According to 21 CFR 312.21, how many subjects are involved in Phase 1 studies? - SOLUTION A small number (20-80) According to 21 CFR 312.21, what is the goal of a Phase II trial? - SOLUTION A well controlled clinical study to evaluate the effectiveness of a drug for a particular indication and determine short-term side effects and risks According to 21 CFR 312.21, how many subjects are involved in a phase II trial? - SOLUTION A relatively small number, usually no more than several hundred According to 21 CFR 312.21, what is the purpose of phase III trials? - SOLUTION Expanded controlled and uncontrolled studies intended to gather additional information about effectiveness and safety. They evaluate the overall risk-benefit relationship and provide adequate basis for physician labeling. According to 21 CFR 312.21, how many subjects are involved in phase III trials? - SOLUTION Several hundred to several thousand According to 21 CFR 312.21, what is the timing and rationale for phase IV studies? - SOLUTION Post-marketing assessment of ongoing safety, effectiveness, and overall therapeutic value. They address FDA requirements for additional info not in the New Drug Application andsurveil for less common AEs and involve a large number of subjects (thousands). How does 21 CFR 812.3 define a transitional device? - SOLUTION A device that FDA considered to be a new drug or an antibiotic drug before May 28, 1976 How does 21 CFR 812.3 define a custom device? - SOLUTION A device intending for use by an individual patient named in the order of a physician or dentist, and is to be made in specific form for that patient How does 21 CFR 812.3 define an implant? - SOLUTION A device that is placed into a surgically or naturally formed cavity of the body if it is intended to remain there for a period of 30 days or more (shorter duration up to FDA discretion) How does 21 CFR 812.3 define noninvasive as applied to a diagnostic device or procedure? - SOLUTION 1. Does not penetrate or pierce the skin or mucous membranes of the body, ocular cavity, or the urethra 2. Does not enter the ear beyond the external auditory canal, the nose beyond the nares, the mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina beyond the cervical os What does 21 CFR 812.2 apply to? - SOLUTION All clinical investigations of devices to determine safety and effectiveness, including IDE- significant risk devices and abbreviated requirements for nonsignificant risk devices. It does not apply to exempted investigations. What kind of device requires FDA and IRB approval? - SOLUTION A significant risk device, which is is IDE What qualifies as a significant risk device that requires FDA and IRB approval- IDE? - SOLUTION 1. intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject 2. purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject -is 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 or -otherwise poses a potential for serious risk to the health, safety, or welfare of a subject What qualifies as a nonsignificant risk (NSR) device? - SOLUTION A device that does not meet the definition for a significant risk device Who makes the initial determination of significant risk or nonsignificant risk? - SOLUTION The sponsor, followed by the IRB. The FDA is available to help in making the risk determination. An investigation of a device other than a significant risk device is considered to have approved applications for IDE's, unless... - SOLUTION FDA has notified the sponsor that approval of an application is required, if the device is is not a banned device, and the sponsor -labels the device in accordance with 812.5 -obtains IRB approval of the investigation after presenting the reviewing IRB with a brief explanation of why the device is not a significant risk device and maintains such approval -ensures that each investigator participating in an investigation of the device obtains informed consent Abbreviated IDE requirements include that the sponsor - SOLUTION - complies with monitoring requirements -maintains required records -follows reporting requirements -ensures that participating investigators maintain the required records and follow reporting requirements -complies with the prohibitions against promotion and other practices What are the reporting requirements according to 21 CFR 812.150? - SOLUTION The sponsor reports significant risk device determinations. If an IRB determines that a device is a significant risk device and the sponsor has proposed that the IRB consider the device not to be a significant risk device, the sponsor shall submit to FDA a report of the IRB's determination within 5 working days According to 21 CFR 812.2 (c), what are exempted investigations? - SOLUTION 1. A device, other than a transitional device, in distribution before May 28, 1976, which used according to labeling 2. A device other than a transitional device in distribution after May 28, 1976 that the FDA has determined to be substantially equivalent to a device in commercial distribution before May 28, 1976, when used according to labeling 3. A diagnostic device, if the sponsor complies with applicable requirements 4. A device undergoing consumer preference testing, testing of a modification, or testing of a combination of two or more devices in commercial distribution if the testing is not for the purpose of determining safety or effectiveness and does not put the subject at risk 5. A device intended solely for veterinary use 6. A device shipped solely for research on or with lab animals and labeled accordingly 7. A custom device unless being used to determine safety or effectiveness for commercial distribution What are the applicable requirements for exempted diagnostic device investigations according to 21 CFR 812.2 (c)? - SOLUTION -noninvasive -does not require an invasive sampling procedure that presents significant risk -does not by design or intention introduce energy into a subject -is not used as a diagnostic procedure without confirmation by another medically established product or procedure What requirements for labeling of investigational devices are described in 21 CFR 812.5? - SOLUTION An investigational device or immediate package must bear a label with -name and place of business of manufacturer, packer, or distributer -quantity of contents -"caution-- investigational device. Limited by Federal or US law to investigational use." -description of relevant contraindications, hazards, adverse effects, interfering substances or devices, warnings, and precautions -no false or misleading info, including that the device is safe or effective for the purposes for which it is being investigated When is an application required according to 21 CFR 812.20? - SOLUTION A sponsor shall submit an application to FDA if they intend to use a significant risk device in an investigation, conduct an investigation that