Ethical Regulations for Human Subjects Research: An Overview of US Policies and Guidelines, Exams of Nursing

Download Ethical Regulations for Human Subjects Research: An Overview of US Policies and Guidelines and more Exams Nursing in PDF only on Docsity! SOCRA - CCRP (high level) SOCRA - Certified Clinical Research Professional (high level) Containing 173 Questions with Solutions 2024. Nuremberg Code (1947) - Answer: A research ethics code that arose in response to the Nazis' inhumane experimentation (Nuremberg trials) - holocaust, racial hygiene / eugenics / master race. The Nuremberg Code - 10 points - Answer: 1. voluntary 2. necessary for results 3. logical design and results SOCRA - CCRP (high level) 4. avoid unnecessary harm 5. cannot result in death or disablement 6. risk assessment 7. protect subjects against harm 8. qualified investigators 9. right to withdrawal 10. right to end trial if needed Belmont Report (1979) - Answer: Three core principles are identified: respect for persons, beneficence, and justice. Arose in response to Tuskegee Syphilis Study - studying untreated syphilis on African-American men unaware of their true condition and tx plan. Belmont Report - definitions of core - Answer: 1. Respect for persons: informed consent + no deception 2. Beneficence: maximize benefits and minimize risk 3: Justice: fair procedures considering risk analysis. Belmont Report - current role - Answer: Serves as a historical document and provides the moral framework for understanding regulations in the United States on the use of humans in experimental methods. Belmont Report - review of 7 items for research trials - Answer: 1. IRB approved 2. Obtain informed consent SOCRA - CCRP (high level) 50 - protection human subjects 56 - IRB that oversee trials 312 - drug trial requirements 812 - controlled substances Title 21 CFR Part 11 - Answer: 1. Controls - audits, validators, audit trails, e-sigs, documentation for software + systems processing e-data. 2. E-records cannot be illegible, inaccessible, or corrupted 3. "Hard copies" are authoritative documents for regulatory purposes Title 21 CFR P art 50 - Answer: The National Research Act of 1974 - Answer: Established the National Commission. Issued in 1974, 45 CFR 46 raised to regulatory status: - Answer: US Public Health Service Policy Henry K. Beecher Article (1966) - Answer: Detailed 22 published medical studies presenting risk to subjects without their knowledge or approval. Beecher's article clearly demonstrated that unethical research was not confined to Nazi atrocities. SOCRA - CCRP (high level) U.S. Public Health Service (PHS) Study of Untreated Syphilis / Tuskegee Syphilis Study (1932-1972) - Answer: Examined the natural course of untreated syphilis in Black American men. All were impoverished sharecroppers from Macon County, Alabama, were unknowing subjects in the study; they were not told that they had syphilis, nor were they offered effective treatment when it became available in the late 1940s with the availability of penicillin. Willow brook studies (1956-1970) - Answer: Children with intellectual disabilities were deliberately infected with the hepatitis virus Jewish Chronic Disease Hospital study (1963) - Answer: Live cancer cells were injected into 22 cognitively impaired patients. National Research Act (1974) - Answer: Congress passed this act in response to the concern on prior studies (PHS Syphilis, prisoner research, willowbrook etc) - est. National Commission to identify basic ethical principles + guidelines - required IRBs at organizations receiving funding SOCRA - CCRP (high level) The National Commission (1975-1978) - Answer: Created recommendations for regulating human subject research - vulnerable populations, psychosurgery, IRBs, etc. Final report published 1979 - Ethical Principles and Guidelines for the Protection of Human Subjects of Research -> Belmont Report The Belmont Report - Answer: Based on National Commission deliberations. 1. Respect for Persons 2. Beneficence 3. Justice Analytical framework guiding the resolution of problems arising from human subject research. Belmont: Respect for Persons - Answer: Subjects are autonomous agents - informed consent If diminished autonomy, need additional protection. - Condition (age, health, cognition) - Circumstances (poverty, lack of education, social status) Also respect person's right to privacy (not directly addressed in Belmont). SOCRA - CCRP (high level) 1964 - World Medical Assembly meeting in Helsinki Finland adopted "Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects." Has been revised multiple times (1975, 1983, 1989, 1996, 2000, 2008, and 2013). CIOMS guidelines - Answer: International codes + standard in response to Nuremberg Trials 1982 - Council for International Organizations of Medical Sciences adopted "International Ethical Guidelines for Biomedical Research Involving Human Subjects". Revised in 1993, 2002, and 2016. WHO guidelines - Answer: International codes + standard in response to Nuremberg Trials 2001 - World Health Organization (WHO) adopted "Standards and Operational Guidance for Ethics Review of Health-Related Research with Human Participants." Designed to serve as international guidelines for the review + conduct of human subject research. SOCRA - CCRP (high level) ICH guidelines - Answer: International codes + standard in response to Nuremberg Trials 1996 - International Conference on Harmonisation (ICH) brings together drug regulatory authorities and pharmaceutical industry of Europe, Japan, and the U.S. They adopted standards on Good Clinical Practice (ICH E6). ICH E6 details the responsibilities and expectations of all individuals - including researchers, monitors, sponsors, and IRBs. ICH E6 standards, while not part of any country's regulations, provide international standards for transnational pharmaceutical research. ICH renamed itself "International Council for Harmonisation" in 2015, added members, and in 2016 released a revised E6(R2) guideline. The FDA adopted the revised E6(R2) guideline as guidance. Presidential Commission report - Answer: 1983 - Response on to further concerns regarding human subject research despite new regulations. Report raised concerns on adequacy of IRB review process. Office for the Protection from Research Risks (OPRR) (the predecessor to OHRP) at the National Institutes of Health (NIH) conducted multiple investigations of allegations of non-compliance with the regulations. SOCRA - CCRP (high level) Independent Reviews - General Accounting Office (GAO) & HHS Inspector General - Answer: March 1996 and June 1998 respectfully GAO - IRBs overworks, competing demands, limited funds for inspections, complex research + large volumes HHS - reviewed too much too quickly with little expertise, minimal CR of approved research, little training. Are IRBs effective? Response to IRB concerns - Answer: increased vigilance. OPRR began for cause and not for cause investigations. Did enact change, however then human subject Jesse Gelsinger died -> public outcry. Human Research Protections Program (HRPP) - Answer: Response to issues with IRBs to further protect human subjects. Objective to assist in meeting ethical principles and regulatory requirements. Resulted in - Higher IRB standrads SOCRA - CCRP (high level) -IB + protocols (for FDA-regulated research) Type of IRB Review - Answer: 1. Convened Committee Review - standard approach, for all new and greater than minimal risk research 2. Expedited Review - minimal changes to an approved study, no more than minimal risk & - IND / IDE not required - only collecting blood by sticks or venipuncture - noninvasive specimen collection - noninvasive procedures commonly done in clinical practice (no anesthesia or sedation, only FDA approved medical devices being used as marketed) - data collection / voice-video etc - individual group characteristic/behavior research -CR where enrollment is permanently closed with all subjected completed and is only in long-term follow-up -CR where no subjects enrolled with no additional risks -CR where study is only doing data analysis 3. Limited IRB Review of Select Exempt Categories - research education instructional strategies, techniques, curricula, or classroom management methods, which is not likely to adversely impact the student. - interactions for educational tests, surveys, interviews, or observations of public behavior & (1 or more) + privacy is kept with no identifiers + no liability to the subjects SOCRA - CCRP (high level) + identity can be ascertained by the investigator if needed. - Benign behavior interventions w/ data collection & (1 or more) + see above. Examples: board games, puzzles with various noises, etc. - Secondary research using private info / identifiable biospecimens & (1 or more) +knowledge is publicly available - Internal federal employee studies, contract/consulting arrangements, cooperative agreements, grants to better the public programs. - Consumer taste / food quality study - Broad consent to store / maintain identifiable private info / biospecimens for potential secondary research - Broad consent to use data/specimens for secondary research NOT Exempt: subjects prisoners, children, or observation of children w PI Recordkeeping - Answer: PIs must keep signed consent documents, IRB correspondence, and research records for at least 3 years post trial. - sponsor/IRB may require longer. HHS Regulations - Answer: 45 CFR 46 (Protection of Human Subjects 2018) applies to all human research submitted to or funded by HHS. Subpart A: Basic HHS Policy for the Protection of Human Subjects Subpart B: Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research SOCRA - CCRP (high level) Subpart C: Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects Subpart D: Additional Protections for Children Involved as Subjects in Research Subpart E: Registration of Institutional Review Boards NIH Regulations - Answer: sIRBs be used for multi-site trials. All Phase III randomized clinical trials are to have DSMB/DSMCs Site FWA - Answer: Federalwide Assurance (FWA) = compliance assurance is a written document submitted by an organization (not an IRB) that is engaged in non-exempt human subjects research conducted or supported by HHS. Site in non-exempt research + Subject to Common Rule Each IRB that is designated by an organization under an assurance of compliance approved for federal wide use by OHRP under 45 CFR 46.103(a) and that reviews research involving human subjects conducted or supported by the HHS must be registered with HHS. sIRB - Answer: Single IRBs for multi-site trials. SOCRA - CCRP (high level) - cannot be carried out w/o waiver - cannot be carried out w/o private info (if applicable) - will not adversely affect rights + welfare - subjects provided with pertinent info after participation (whenever appropriate) 3. Screening, recruiting, or determining eligibility ICF Exceptions - Answer: - emergency research requirements are met - life-threatening with requirements for an exception met + documentation of (a). researcher + physician agree the situation calls for test article (b). subject/LAR unable to communicate (c). insufficient time to obtain consent (d). no alternative exists providing equal or better chance of survival Waiver of Signed Consent / Oral Consent - Answer: FDA - minimal risk, no procedures HHS - + only identifiable link of subject to research would be the consent and principal risk would be breach of confidentiality. Subjects will be asked if they want consent to be documented. + minimal risk, no procedures + subject part of group/community where signing forms is not the norm, minimal risk, appropriate alternative mechanism to documents ICF obtained. SOCRA - CCRP (high level) LAR verbal telephone consent - Answer: FDA - Fax ICF to LAR, review on phone, LAR returns faxed ICF to researcher HHS - does allow the exchange of consent information to take place face-to-face or by mail, telephone, fax, or video. An electronic format for the consent signature is also allowed. Electronic informed consent (eIC) - Answer: video to demonstrate a study procedure, use of a tablet instead of a paper-based consent form, and use of electronic signatures HHS regulations also require that a written copy be given to the person signing the informed consent form. The copy could be in paper or an electronic format (Protection of Human Subjects 2018). SBR - Answer: Social and Behavioral Research (SBR) Refers broadly to research that deals with human attitudes, beliefs, and behaviors. Biomedical and clinical researchers sometimes incorporate SBR questions and methodologies into their physiological research. SBR Methods - Answer: Questionnaires Opinion data and other oral data SOCRA - CCRP (high level) Direct observation Data already collected for other purposes (such as records from education, healthcare, social service programs, employment, and insurance coverage) Non-invasive physiological measurement (such as skin impedance and pupil dilation as reflection of emotional arousal or attention). SBR Risks + Benefits - Answer: Psychosocial stress + discomfort Physiological harms that are less predictable, more subjective, variable, and less remediable. Socio-cultural factors (i.e. collecting demographics of undocumented immigrants v citizens) Main risk tends to be breaches of confidentiality involving sensitive data SBR Data Management - Answer: Code data, secure master list, secure environment, de-linking data from identifiers SBR Debriefing - Answer: Distress or deception experiment design includes debriefing about information withheld at the end of their participation. SOCRA - CCRP (high level) 3. Research information for purpose of "health care operation" or "research" 45 CFR 164.501 - or "public health activities and purposes" - 45 CFR 164.512[b] 4. Federal dept/agency using gov't information for non-research activities 5. Identifiable private information used for secondary research in which broad consent was obtained + documented; waiver of consent obtained; IRB does limited IRB review to determine secondary research is within scope of broad consent + does not include returning individual research results to subjects unless legally required Expedited review? - Answer: If the records review activity constitutes human subjects research, and does not qualify for exemption, it will then be subject to federal regulations. - no more than minimal risk - in expedited review category 5 (prospective / retrospective research using materials) limited data set - Answer: If most, but not all, mandated identifiers are removed Family Educational Rights and Privacy Act (FERPA) - Answer: Includes public kindergarten through twelfth grade (K-12) schools and postsecondary institutions SOCRA - CCRP (high level) Genomics v Genetics - Answer: Genomics - DNA sequence in cell to biological function Genetics - inherited differences in DNA sequence between individuals + the effect of the difference in biological function if any Genetic & Genomic Research Risks - Answer: - reveal predispositions to future disease, making information psychologically powerful + raising concerns of stigma/discrimination - Gene sequences shared by relatives, one person's genetic info provides information on their relatives who did not necessarily consent - Reveal ancestry conflicting with family / social / religious histories & beliefs - Genetic concepts + info have historically been misused to affect social/political ends Genetic Determinism - Answer: controlling influence on human health, behavior, and disease. GWAS studies with WGS or WES - Answer: GWAS = genome-wide association studies WGS = whole genome sequencing WES = only parts of genome coding for proteins (1% of entire DNA sequence) SOCRA - CCRP (high level) Large genomic studies by NIH requirements - Answer: de-identify upload to central databases Maximizes use of information generated since studies are complex, difficult, and expensive Clinical v Research Information - Answer: Many organizations do not segregate clinical and research information in electronic medical records. Is DNA truly able to anonymized? - Answer: Yes In order to re-identify DNA sequence information, those attempting the re- identification must have a reference sequence that includes individual identifiers. That is, the DNA sequence is not intrinsically identifiable. While the risk of re-identification currently is low, it may increase with time due to technological developments. Therefore, research subjects should be told that there is a small risk of future re-identification of de-identified information or biospecimens. As with all research involving informational risks, researchers cannot guarantee complete confidentiality. To date, there are no instances of re-identification of data or specimens for illicit motives. SOCRA - CCRP (high level) 45 CFR 46.404 - Answer: Research on children must present no more than minimal risk to the subject. (blood work, urine, CXR, psychological tests, observation) Direct benefit is not required. Requires consent from >=1 parent 45 CFR 46.405 - Answer: Research that presents greater than minimal risk to the subject may be approvable under 45 CFR 46.405 if it holds the potential for direct personal benefit to the child. Requires consent from >=1 parent 45 CFR 46.406 - Answer: Research involving greater than minimal risk and no prospect for direct benefit to the child subject. - Risk is no more than minor increase (catheter, biopsy, MRI, sensitive survey) - Risks must be commensurate with those risks inherent in the subject's actual medical situation, assent if possible. (additional bone marrow biopsy in) - Research must be likely to yield knowledge of vital importance about the child's disease or condition. Requires consent from >=2 parent SOCRA - CCRP (high level) 45 CFR 46.407 - Answer: Presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health and welfare of children. -Review by HHS by panel of experts Requires consent from >=2 parent 45 CFR 46.409 - Answer: Ward research not permitted if not necessary to include them. Advocate needs to be appointed to act in best interest of the child. Assent - Answer: The child's assent is not a necessary condition for proceeding with the research if the IRB determines that: - capability of some or all of the children is so limited that they cannot reasonably be consulted - intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the child (45 CFR 46.405) and is available only in the context of the research NIH Guidelines - research on children - Answer: March 1998, the NIH published Guidelines on the Inclusion of Children as Participants in Research Involving Human Subject SOCRA - CCRP (high level) -Children must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific or ethical reasons not to include them Exclusion reasons: -irrelevant to children -study results are known in children or from another study ongoing -separate age-specific study is warranted + preferable -insufficient data in adults to determine potential risks in children 21 CFR 50, Subpart D - Answer: Additional Protections for Children in Clinical Investigations in response to Children's Health Act of 2000 -does not allow waiver of consent except in emergency research keeping with 21 CFR 50.23 & 50.24 -FDA will not object when IRBs approve waiver/alteration of consent in research with minimal risk if other criteria are met + documented Best Pharmaceuticals for Children Act (2002) - Answer: extends marketing exclusivity for pharmaceutical companies who test new drugs in children Pediatric Research Equity Act (2004) - Answer: enables FDA to require testing of drugs for pediatric use SOCRA - CCRP (high level) Research Involving Dead Fetus, Fetal Material, or the Placenta - Answer: In most states, the use of tissue from dead fetuses for research purposes would fall under the Uniform Anatomical Gift Act (UAGA), which requires consent of both parents. However, some states specifically ban research that involves aborted fetuses, their organs, tissues, or remains. Research involving fetal material for transplantation and utilizing embryos produced by in vitro fertilization for the generation of human embryonic stem cell lines has been subject to additional restrictions. 45 CFR 46, Subpart B - Exempt from IRB - Answer: Same exemption conditions outlined in 45 CFR 46.104 FDA Review - Answer: The FDA bases its approval decision upon bioresearch data generated and reported to the FDA by the sponsor to support the product's marketing approval. These data are collected by the sponsor during clinical research conducted under an IND application or an Investigational Device Exemption (IDE). Investigational New Drug (IND) Application - Answer: Research involving a drug or biologic that has not yet reached the marketplace or that studies a new use of the marketed product requires an IND application per 21 CFR 312. IND Application Approval - Answer: This determination is based upon: SOCRA - CCRP (high level) - Data from prior animal or human testing - Methods of manufacturing - Plans for testing and reporting significant toxicities - A well-developed clinical research plan that minimizes risks to the subjects Clinical investigation of a marketed drug does not require an IND if all of the following conditions are met: - Answer: -Not for a new indication, new labeling, or significant change in advertising. -Does not involve change to the route of administration or dosage level, subject population usage, or other factors that significantly increases the drug product's risks of harm (or decreases the acceptability of the risks). - In compliance with IRB review in 21 CFR 56 and informed consent requirements in 21 CFR 50. - In compliance with requirements for promotion and sale at 21 CFR 312.7. Form FDA 1572 - Answer: Agreement between the researcher and the sponsor assuring compliance with FDA regulations *Not used for devices Off Label" Use of Drugs, Devices, and Biologics - Answer: Use of a marketed product in this manner, when the intent is the practice of medicine, does not require the submission of an IND per 21 CFR 312.2(d) or IDE per 21 CFR 812.2. SOCRA - CCRP (high level) Definition of a Medical Device - Answer: Healthcare product that does not achieve its primary intended purpose by a chemical interaction or by being metabolized. Ex: laser, sutures, pacemakers, diagnostic aids (reagents + test kits for in vitro diagnosis) Medical Device Amendments of 1976 + Safe Medical Devices Act of 1990 - Answer: Provide the regulatory framework for medical device development, testing, approval, and marketing. Premarket approval process - Answer: If the device is not exempt, the FDA at 21 CFR 807.81(a)(1) determines whether the device is substantially equivalent to similar devices marketed before the 1976 amendment. These devices are often referred to as 510(k) devices and require a summary to be submitted to the FDA to determine substantial equivalence (21 CFR 807.92). If the new medical device is not substantially equivalent, the company may need to demonstrate safety and efficacy in a premarket approval application, which could include clinical trials. Investigational Device Exemption (IDE) - Answer: The IDE regulations at 21 CFR 812 specify how to conduct these clinical trials. Classify as: SOCRA - CCRP (high level) 21 CFR 50.23 Exception from General Requirements - use of test article - Answer: The IRB must be notified within a maximum of five days if a test article was used in an emergency situation for one individual. 21 CFR 50.24 Exception from Informed Consent Requirements for Emergency Research - Answer: Unlike the exception noted in 21 CFR 50.23, the activities described in 21 CFR 50.24 are associated with an IRB-approved research study that involves research in emergencies. Requires -urgent intervention necessary with available tx unproven/unsatisfactory -subjects cannot consent b/c of condition -subject prospect of direct benefit -IP administered before consent can be obtained via pt or LAR -unreasonable to identify prospective individuals for eligibility in advance Waive / Alt Consent - No more than minimal risk - Answer: Will not object if an IRB approves a waiver or alteration of consent for a no more than minimal risk clinical investigation if the IRB determines: 1. no more than minimal risk 2. The waiver / alteration will not adversely affect the rights and welfare of the subjects 3. research could not practicably be carried out without the waiver or alteration SOCRA - CCRP (high level) 4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation. When FDA and HHS Regulations Differ - Answer: FDA (2018) guidance says that the regulation that offers the greater protection to human subjects should be followed. For example, the revised Common Rule has a "key information" requirement for consent, and the FDA regulations do not. However, this key information requirement offers additional protections to subjects and it is not in conflict with any FDA regulations. However, research that is no longer subject to continuing review under the revised Common Rule would still require continuing review under FDA regulations pursuant to 21 CFR 56.109(f). Verbal Consent - Answer: 21 CFR 56.109(c)(1), the FDA allows the IRB to waive the requirement for the subject (or the subject's LAR) to sign the consent if two conditions are met: 1. no more than minimal risk 2. no procedures requiring written documentation outside of participation in the study IRB may require the researcher to provide the subject with written materials about the research per 21 CFR 56.109. SOCRA - CCRP (high level) IND/IDE Requirements for Emergency Use (FDA/Sponsor) - Answer: Options if patient does not fit trial needs or no active trial 1. Contact manufacturer and determine if the drug can be made available for an "emergency use" under the company's IND. 2. FDA per 21 CFR 312.36 may authorize the manufacturer to allow the drug to be used in advance of an IND submission 3. If the company agrees to provide the product, the physician can contact FDA, explain the situation, and obtain an emergency IND to permit the drug's shipment. 4. If there is no IDE, the physician may use the device and notify FDA of its use after the fact. The physician should obtain both an independent assessment from another physician and informed consent from the subject, before emergency use of the device occurs. IND/IDE Requirements for Emergency Use (IRB) - Answer: In an emergency use situation, the FDA at 21 CFR 56.104(c) permits an exemption from prior review and approval by an IRB Devices - concurrence of the IRB chair is required before the use takes place. SOCRA - CCRP (high level) - Research solely for activities preparatory to research (i.e protocol development, potential subject & not leave the covered entity) - Deceased individual's information is used - "Grandfathered" where legal permissions were in place prior to effect of HIPPA Data that do not identify individuals can be used for research without specific authorization if: - Answer: 1. Only fully de-identified data are used. 2. A "limited data set" is used, under an approved "data use agreement." HIPAA - ICF waiver/alterations - Answer: Only if research is no more than minimal risk and includes privacy protections: 1. Plan to protect data identifiers from improper use/disclosure 2. Plan to destroy data identifiers at earliest opportunity dependent on research 3. Assurances that PHI will not be reused/disclosed to anyone else except as required by law for oversight or research as permitted by HIPPA 4. Could not be conducted without access and use of PHI 5. Could not be conducted without waiver / alteration of authorization Permitted access under HIPAA without consent - process - Answer: Researcher must make a written or oral representation to the covered entity's designated officials that such access is necessary for the research purposes -- someone from SOCRA - CCRP (high level) the IRB, the Privacy Board, or a privacy officer / designee -- who would then determine the appropriateness of the request. De-identified Data - Answer: No longer PHI and likely not human research if direct/indirect identifiers were removed. Limited data set (LDS) Disclosure - Answer: Requires data user agreement to obtain the LDA with all direct identifiers removed Agreement must: -explain permitted uses/disclosure by the recipient consistent with the research - limit individuals who can receive the data - require recipient to agree not to re-identify the data or contact subjects Disclosure Accounting - Answer: Not required for: -internal sharing / use -disclosures as described in authorization -to the subjects -LDS subject to data user agreement -de-identified data =/= PHI While HIPAA may not require it, many organizations will require that researchers maintain logs of all disclosures from research data collections as a security measure, including transfers to other individuals within the covered entity. SOCRA - CCRP (high level) Electronic data storage will increasingly offer this capability cheaply and automatically; older collections will require manual logging. HIPAA Authorizations - Answer: - plain language - signed by subject/ LAR - specify PHI used/disclosed, to who, and for how long (end of study etc) Can be included in ICF, cannot be with privacy notice Conflicts of Interest in Human Subjects Research - Answer: COIs may arise in human subjects research when researchers and/or organizations have financial or personal relationships that may compromise or appear to compromise the integrity of the research, protection of human subjects, and/or reputation of the researchers or organizations. 42 CFR 50, Subpart F - Answer: 1995 PHS became the first division of the federal government to implement regulations requiring disclosure and management of individual research-related COIs Goal is to promote objectivity in research by ensuring that PHS-funded research is free from bias due to researcher COIs. Jesse Gelsinger, died as a result of the experimental therapy he received in the study - COI - Answer: Both the researcher responsible for the study's oversight and the university where the research was conducted had significant financial ties SOCRA - CCRP (high level) Management of COIs - Answer: Critical to ensuring research integrity, the public's trust in the organization, and the protection of human subjects' rights, safety, and welfare. Aimed at reducing the opportunity to bias the research May include COI committees and management plans, informed consent form disclosure language, as well as additional management controls (such as divesture and independent data review). Divestiture Strategy - Answer: If an individual researcher had a significant conflict that was deemed unmanageable by other means, divesting (or selling) interests might be advised as a means of eliminating the source of the conflict. ICOI Management - Answer: For example, many ICOI management plans require use of an external IRB when the organization has an equity interest in an entity related to human subjects research. 45 CFR 46 B - x C - y D - z - Answer: 45 CFR 46 B - Pregnant Women C - Prisoners SOCRA - CCRP (high level) D - Children According to the authors, there are four common abuses that historically are described as giving rise to vulnerability. Which response below contains the correct four? - Answer: There are four common abuses that historically are described as giving rise to vulnerability 1) physical control, 2) coercion, 3) undue influence, and 4) manipulation. These exist along a continuum of severity with physical control being the most severe and undue influence and manipulation being the least (Nelson and Merz 2002, V69-80). The other abuses- prejudice, neglect, and disrespect - should still be avoided in research. Which of the following was the result of the Beecher article? A. Realization that ethical abuses are not limited to the Nazi regime B. An identification of basic ethical principles C. Multiple Congressional hearings D. Additional FDA regulations - Answer: Answer: A. Realization that ethical abuses are not limited to the Nazi regime When required, the information provided to the data subject in a HIPAA disclosure accounting ... - Answer: must be more detailed for disclosures that involve fewer than 50 subject records. SOCRA - CCRP (high level) Where fewer than 50 subjects' records are involved, the listing must be more specific and detailed, commensurate with the requirements for other kinds of PHI disclosure accounting, including: specific date(s) of disclosures; names of entities to which PHI was disclosed; description of the PHI involved in the disclosure; and purpose of the disclosure. The FDA regulations governing disclosure of individual COIs require: - Answer: Applicants submitting marketing applications to disclose financial COIs of researchers who conducted clinical studies The FDA's regulation governing disclosure of individual COIs requires applicants submitting marketing applications for drugs, biologics, or devices to certify the absence of certain financial interests or to disclose financial interests of researchers who conducted clinical studies covered by the regulation. The regulation specifies that the FDA may refuse to file any marketing application that does not contain a disclosure of researchers' financial interests or a certification that the applicant acted with due diligence to obtain researchers' disclosures, but was unable to do so. FDA Form 482 - Answer: Notice of inspection FDA Form 483 - Answer: Inspectional Observations SOCRA - CCRP (high level) - monitoring plan tailor specific human subject population + data integrity risks. 6. Sponsor Record Retention -at least 2 years post approval marketing application and no pending / contemplated marketing applications - OR at least 2 years since formal discontinuation of clinical development - longer as required 6. ICF IND Contents - Answer: - Cover letter - Form FDA 1571 (Investigational New Drug Application [IND]) - Form FDA 1572 (Statement of Investigator) - Introductory statement and general investigational plan - Investigator's Brochure (or copy of the approved labeling (including the package insert) can be provided in lieu of the Investigator's Brochure (IB). if for approved drug seeking ZYX) - Protocol(s) - Chemistry, manufacturing, and controls information - Pharmacology and toxicology information - Previous human experience with drug - Additional information - Relevant information SOCRA - CCRP (high level) Letters of Cross-Reference - Answer: Might already have an active IND for the drug being studied by a sponsor-investigator. In these instances, the manufacturer may agree to provide a letter of cross- reference that enables the sponsor-investigator to reference the following technical information from the manufacturer's IND in the sponsor-investigator IND: - Chemistry, manufacturing, and controls (CMC) information - Pharmacology and toxicology information - Previous human experience with the drug Form FDA 1571 - Answer: Contractual agreement between the sponsor and FDA. Agrees to: - Not to begin clinical investigations until thirty (30) days after FDA's receipt of the IND, unless the investigator receives earlier notification from the FDA - Not to begin or continue investigations covered by the IND if those studies are placed on clinical hold - That an IRB/IEC that complies with 21 CFR 56 will be responsible for initial and continuing review and approval of each of the studies in the proposed clinical investigations - To conduct the investigation in accordance with all other applicable regulatory requirements Required Reports on active IND - Answer: - Protocol Amendments SOCRA - CCRP (high level) - Informational Amendments (new toxicology etc) - AE & IND Safety where: + investigators immediately report any SAEs. + Sponsor-investigators must notify authorities & participating investigators in writing on unexpected & serious AE ASAP and no later than 15 calendar days. + AE unexpected, fatal, or life threatening no later than 7 calendar days -Annual reports (IND Reports) within 60 days of anniversary date that IND went into effect -Final report shortly after trial, and accurate financial information IDE Content - Answer: An IDE submission includes: - Cover letter to the FDA - Cross-reference letter from device supplier* - Table of contents - Report of prior investigations* - Investigational plan - Manufacturing information* - Investigator information** - IRB information - Sales information - Device labeling - Informed consent materials - Any other relevant information that FDA requests for review of the IDE application