CIP Exam Terms Flashcards
Any public or private entity or agency (including federal, state, and other agencies).
Institution
The head of a federal department or agency and any other officer or employee of any department or agency to whom authority has been delegated.
Department or agency head
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(s) involved in research.
Legally authorized representative
a systematic investigation, including research development, testing, and evaluation, designed to contribute to generalizable knowledge.
research
activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes.(ex: demonstration and service program may include research activities)
research
research activities for which a federal department or agency has specific responsibility for regulating as a research activity (for example IND requirements by the FSA). It does not include research activities which are incidentally regulated by a federal dept or agency solely as part of the dept’s or agency’s broader responsibility to regulate certain types of activities whether research or non-research in nature (for example: wage and hour requirements administered by DOL)
research subject to regulation
a living individual about whom and investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information.
human subject
includes both physical procedures by which data are gathered (ex: venipuncture) and manipulation of the subject or the subjects’ environment that are performed for research purposes.
intervention
includes communication or interpersonal contact between investigator and subject.
interaction
includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by and individual and which the individual can reasonably expect will not be made public (ex. medical record).
private information
must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving humans
private information
a board established in accord with and for the purposes expressed in this policy.
IRB
determination of the IRB that the research 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.
IRB approval
the probability and magnitude of hard or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
minimal risk
Pharmacological substances that have the potential for creating abusive dependency. Abuse-liable substances can include both illicit (heroine) drugs and licit (methamphetamines) drugs
abuse-liable
Alcohol, drug abuse, and mental health administration, reorganized in October 1992 as the Substance Abuse and Mental Health Services Admin (SAMHSA).
ADAMHA
Therapy provided to enhance the effect of an primary therapy; auxiliary therapy.
Adjuvant therapy
an undesirable and unintended, although not necessarily unexpected, result of therapy or other intervention
adverse effect
agreement by an individual not competent to give legally valid informed consent (child or cognitively impaired)
assent
formal written, binding commitment with federal agency which institution promises to comply with applicable regs governing research with humans & stipulates the proc which compliance will be achieved
assurance
an officer of institution with authority to speak for and commit the institution to adherence to requires of fed regs regarding HSR
authorized institutional official
personal capacity to consider alternatives, make choices, and act without undue influence or interference of others
autonomy
a statement of ethical principles governing research involving HS issued by Natl Commission for Protection of HS in 1978
Belmont Report
an ethical principle that entails an obligation to protect persons from harm.
Beneficence
Belmont principle expresses 2 gen rules: (1) do no harm; (2) protect from harm by max. benefits & min. risks
beneficience
a valued or desired outcome; an advantage
benefit
any therapeutic serum, toxin, ant-toxin, or analogous microbial product applicable to prevention, treatment, cure of diseases or injuries
biologic
a study comparing persons with a given condition/disease (case) & persons w/o (controls) with respect to antecedent factors
case-control study
x-ray technique for producing images of internal bodily structures through a computer
cat-scan
persons who have not attained the legal age for consent, as determined under the applicable law of the jurisdiction in which the research will be conducted
children
classification by FDA of medical devices according to potential risks or hazards
class I, II, and III devices
a controlled study involving HS, designed to evaluation prospectively the safety & effectiveness of new drugs or devices or beh. interventions
clinical trial
a group of subjects initially identified as having one or more characteristics in common who are followed over time
cohort
payment or medical care provided to subjects injured in research; does not refer to payment as incentive to participate
compensation
technically, a legal term, used to denote capacity to act on one’s own behalf; ability to understand info presented, consequences & making a choice
competence
pertains to the treatment of info disclosed in a relationship of trust w/the expectation it will not divulged w/o permission
confidentiality
an agreement that research activity will be performed at the request & under direction of agency providing funds. More closely controlled than a grant
contract
subjects who are not given a treatment under the study
control subjects
disadvantageous; a treatment that should not be used in certain individuals due to the risks
contraindicated
statistical index of the degree of relationship b/t two variables (0.00 - no relationship; -1.00 - 1.00 strong relationship)
correlation coefficient
type of clinical trial where the subject experiences both the experimental and control therapy at different times
cross-over design
a committee that collects and analyzes data during the course of a trial to monitor for adverse effects and trends that would warrant modification of termination
data safety monitoring board
an expelled or delivered fetus that as no heartbeat
dead fetus
giving subjects previously undisclosed info about the research project following completion of participation
debriefing
a code of ethics for clinical research approved by World Medical Assoc in 1964 and widely adopted by med assoc in various countries. Revised in 75 and 89
Declaration of Helsinki
the outcomes that are measured in an experiment. these are expected to change as a result of the manipulation of the IV
dependent variable
any study that is not truly experimental (quasi-experimental, correlational, records review, case histories, observational studies
descriptive study
Department of Health, Education and Welfare - now DHHS and DoEd (1980)
DHEW
tests used to identity a disorder or disease in a living person
diagnostic (procedure)
the probability of harm or injury (phys., psy., social, econ) occurring as a result of participation
risk
the probability and magnitude of harm or discomfort is not greater, in and of themselves, than those encountered in every day life
minimal risk
a study design in which neither the investigators nor the subjects know the treatment group assignments of individual subjects. Sometimes referred to as “double-blind”.
double-masked design
any chemical compound that may be used on or administered to humans as an aid in the diagnosis, treatment, cure, mitigation, or prevention of disease or other abnormal conditions.
drug
a legal status conferred upon persons who have not yet attained the age of legal competency as defined by state law (for such purposes as consenting to medical care), but who are entitle to treatment as if they had by virtue of assuming adult responsibilities such as being self-supporting and not living at home, marriage, or procreation.
emancipated minor
early stages of developing organism, broadly used to refer to states immediately following fertilization of an egg through implantation and very early pregnancy (i.e. from conception to the eighth week of pregnancy.
embryo
a scientific disciple that studies the factors determining the causes, frequency, and distribution of diseases in a community or given population.
epidemiology
fair or just; used in the context of selection of subjects to indicate that the benefits and burdens of research are fairly distributed
equitable
an interdisciplinary group that advises the Secretary, HHS, on general policy matters and on research proposals (or classes of proposals) that pose ethical problems
ethics advisory board
the study of people and their culture. also called fieldwork, involves observation of and interaction with the persons or group being studied in the group’s own environment, often for long periods of time.
ethnographic research
policy and procedure that permits individuals who have serious or life-threatening diseases for which there are no alternative therapies to have access to investigational drugs and devices that may be beneficial to them. examples include: treatment INDs, parallel track, and open study protocols
expanded availability
review of proposed research by the IRB chair or a designated voting member or group of voting members rather than by the entire IRB. Federal rules permit review for certain kinds of research involving no more than minimal risk and for minor changes in approved research.
expedite review
term often used to denote a therapy (drug, device, procedure) that is unproven or not yet scientifically validated with respect to safety and efficacy.
experimental
a study in which subjects are randomly assigned to groups that experience carefully controlled interventions manipulated by the experimenter according to a strict logic allowing causal inference about the effects of the interventions under investigation
experimental study
when a test wrongly shows an effect or condition to be absent
false negative
when a test wrongly shows an effect or condition to be present
false positive
an agency establish by Congress in 1912 and presently part of DHHS
FDA
provides regulations for the involvement of human subjects in research. applies to all research involving human subjects conducted, supported, or otherwise subject to regulation by any federal dept or agency that takes appropriate administrative action to make the policy applicable to such research. AKA Common Rule
The Federal Policy
the placenta, amniotic fluid, fetal membranes, and umbilical cord
fetal material
the product of conception from the time of implantation until delivery.
fetus
behavioral, social, or anthropological research involving the study of persons or groups in their own environment and without manipulation for research purposes
fieldwork
a medical device that is considered substantially equivalent to a device that was or is being legally marketed. A sponsor is planning to market such a device must submit notification to the FDA 90 days in advance of placing the device on the market. If the FDA concurs with the sponsor, the device may be marketed.
510(k) device
review of proposed research at a convened meeting at which a majority of the membership of the IRB are present, including at least one member whose primary concerns are in nonscientific areas. For the research to be approved, it must receive the approval of a majority of those members present at the meeting
full board review
the treatment of genetic disease accomplished by altering the genetic structure of either somatic (nonreproductive) or germline (reproductive) cells
gene therapy
obsolete term, previously used to denote an institutional assurance covering multiple research projects
general assurance
certain FDA statutory provisions designed to control the safety of marketed drugs and devices. The general controls include provisions on adulteration, misbranding, banned devices, good manufacturing practices, notification and record keeping, and other sections of the Medical Device Amendments to the FDA Act.
general controls
tests to identify persons who have an inherited predisposition to a certain phenotype or who are at risk or producing offspring with inherited diseases or disorders
genetic screening
the genetic constitution of an individual
geotype
financial support provided for research study designed and proposed by the PI. The granting agency exercises no direct control over the conduct of the approved research supported
grant
an individual who is authorized under applicable state or local law to give permission on behalf of a child to general medical care
guardian
Control subjects (followed at some time in the past or for whom data are available through records) who are used for comparison with subjects being treated concurrently. The study is considered historically controlled when the present condition of subjects is compared with their own condition on a prior regimen or treatment.
historical controls
any fertilization involving human sperm and ova that occurs outside the human body
human in vitro fertilization
refers to a person’s mental status and means inability to understand information presented, to appreciate the consequences of acting (or not acting) on that information, and to make a choice.
incapacity
investigational new drug
IND
a legal term meaning inability to manage one’s own affairs.
incompetence
the conditions of an experiment that are systematically manipulated by the investigator
independent variables
a person’s voluntary agreement, based upon adequate knowledge and understanding of relevant information, to participate in research or to undergo a diagnostic, therapeutic, or preventative procedure.
informed consent
subjects may not waive or appear to waive any of their legal rights, or release or appear to release the investigator, sponsor, the institution or agents thereof from liability for negligence
informed consent (46.116; 21 CFR 50.20 and 21 CFR 50.25)
a specially constituted review body established or designated by an entity to protect the welfare of human subjects recruited to participate in biomedical or behavioral research.
institutional review board
a residential facility that provides food, shelter, and professional services (including treatment, skilled nursing, intermediate or long-term care, and custodial or residential care).
institution
confined, either voluntarily or involuntarily
institutionalized
persons who are confined, either voluntarily or involuntarily, in a facility for the care of the mentally or otherwise disabled
institutionalized cognitively impaired
exemptions from certain regulations found in the medical device amendments that allow shipment of unapproved devices for use in clinical investigations
investigational device exemptions (IDE)
a drug or device permitted by FDA to be tested in humans but not yet determined to be safe and effective for a particular use in the general populations and not yet licensed for marketing
investigational new drug or device
in clinical trials, an individual who actually conducts an investigation.
investigator
literally, “in glass” or “in test tube”; used to refer to processes that are carried out outside the living body, usually in a laboratory, as distinguished in vivo.
in vitro
literally, “in the living body”; processes, such as the absorption of a drug by the human body, carried out in the living body rather than in a laboratory (in vitro)
in vivo
an ethical principle discussed in the Belmont Report requiring fairness in distribution of burdens and benefits; often expressed in terms of treating persons of similar circumstances or characteristics similarly
justice
the period of time during which a woman is providing her breast milt to an infant or child
lactation
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 in research
legally authorized representative
an expression of the probability that a gene and a marker are linked
LOD score
a study designed to follow subjects forward through time
longitudinal study
study designs comparing two or more interventions in which either the investigators, the subjects, or some combination thereof do not know the treatment group assignments of individual subjects.
masked study designs
someone who has not reached adulthood (as defined by state law) but who may be treated as an adult for certain purposes.
mature minor
a diagnostic or therapeutic article that does not achieve any of its principal intended purpose through chemical action within or on the body.
medical device
amendments to the FDA act passed in 1976 to regulate the distribution of medical devices and diagnostic products
medical device amendments (MDA)
the manner in which a drug is acted upon (taken up, converted to other substances, and excreted) by various organs of the body
metabolism (of a drug)
the collection and analysis of data as the project progresses to assure the appropriateness of the research, its design and subject protections
monitoring
an interdisciplinary advisory body, established by congressional legislation in 1974, which was in existence until 1978, and which issued a series of reports and recommendations on ethical issues in research and medicine, many of which are now embodied in federal regulations
National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research
new drug application
NDA
request for FDA approval to market a new drug
new drug application
National Institute on Alcohol Abuse and Alcoholism; and institute in NIH
NIAAA
a federal agency within the Public Health Service, DHHA, comprising 21 institutes and centers. it is responsible for carrying out and supporting biomedical and behavioral research
NIH
NIMH
National Institute of Mental Health
member of an IRB who has no ties to the parent institution, its staff, or faculty. this individual is usually from the local community.
nonaffiliated member
an investigational medical device that does not present significant risk to the patient
nonsignificant risk device
research that has no likelihood or intent of producing a diagnostic, preventive, or therapeutic benefits to the current subjects, although it may benefit subjects under a similar condition in the future
nontherapeutic research
an expelled or delivered fetus which, although living, cannot possibly survive to the point of sustaining life independently, even with the support of available medical therapy
nonviable fetus
volunteer subjects used to study normal physiology and behavior or who do not have the condition under study in a particular protocol, used as comparison with subjects who do have the condition.
normal volunteers
the proposition, to be tested statistically, that the experimental intervention has “no effect”, meaning that the treatment and control groups will not differ as a result of the intervention.
null hypothesis
a code of research ethics developed during the trials of Nazi war criminals following WWII and widely adopted as a standard during the 50’s and 60’s for protecting human subjects
Nuremberg Code
an experimental design in which both the investigators and the subjects know the treatment group(s) to which subjects are assigned
open design
making decisions for others against or apart from their wishes with the intent of doing them good
paternalism
the agreement of parent(s) or guardian to the participation of their child or ward in research
permission
the scientific discipline that studies the action of drugs on living systems
pharmacology
HHS regulations at 45 CFR part 46 stipulate substantive and procedural requirements for investigators and institutions engaged in HHS-supported or -conducted research.
human research issues addressed in 45CFR46
which specific regulation addresses assuring compliance with the regulations
45CFR46.103
which specific regulation addresses IRB membership
46.107
which specific regulation addresses IRB functions and operations
46.108
which specific regulation addresses expedited review procedures for certain kinds of research involving no more than minimal risk, and for minor changes in approved research
46.110
which specific regulation addresses criteria for IRB approval of research, including minimizing risk, ensuring confidentiality, and protecting vulnerable populations
46.111
which specific regulation addresses review by institution
46.112
which specific regulation addresses suspension or termination of IRB approval of research
46.113
which specific regulation addresses cooperative research
46.114
which specific regulation addresses IRB records
46.115
which specific regulation addresses general requirements for informed consent
46.116
which specific regulation addresses documentation of informed consent
46.117
which specific regulation addresses application and proposals lacking definite plans for involvement of human subjects
46.118
which specific regulation addresses research undertaken without the intention of involving human subjects
46.119
which specific regulation addresses evaluation and disposition of applications and proposals for research to be conducted or supported by a federal department or agency
46.120
which specific regulation addresses use of federal funds
46.122
which specific regulation addresses early termination of research support: evaluation of applications and proposals
46.123
which specific regulation addresses conditions
46.124
additional protections for pregnant women, human fetuses and neonates are in subpart
B
additional protections pertaining to biomedical and behavioral research involving prisoners as subjects are in subpart
C
additional protections for children involved as subjects in research are in subpart
D
46.103(a) requires that each insitution engaged in HSR that is supported or conducted by HHS provide OHRP with an assurance of compliance to comply with the regulations, unless the research is exempt under 46.101(b). The assurance identifies policies and procedures for the institution and describes the activities to which the regulations apply.
How can I find out if 45CFR46 regulations apply to my research.
IRB registration and assurance, HHS regulations require institutions to commit to compliance with 45CFR46 before initiating participation in HHS-conducted or -supported research involving humans. On behalf of the Secretary, OHRP approves the terms of these written assurances, which constitute binding commitments.
How does HHS ensure that regulatory requirements for human research are met.
OHRP’s division of Compliance Oversight monitors compliance through no-for-cause compliance oversight surveillance activities and for-cause compliance oversight evaluations of allegations or indications of noncompliance with regulations.
How HHS ensures regulatory requirements are met.
Whenever non-U.S. institutions are engaged in non-exempt HHS-supported or -conducted HSR.
Do the human subject regulations apply to non-U.S. institutions?
The current US system of protections for HRS is heavily influenced by the Belmont Report which outlines the basic ethical principles in research involving human subjects. In 1981, HHS and FDA revised, as much as possible their respective statutory authorities, to be compatible with 45CFR46.
How does 45 CFR 46 relate to the Common Rule and human subjects regulations used by non-HHS agencies?
The Common Rule was published in 1991 and codified in separate regulations by 15 federal department and agencies. Each agency includes section numbers and language that are identical to those of the subpart A. For all participating departments and agencies the Common Rule outlines the basic provisions for IRB’s, informed consent, and Assurances of Compliance.
How does 45CFR46 relate to the Common Rule and human subjects regulations used by non-HHS agencies?
Subparts B (women), C (prisoners), and D (children) are regulations that supplement subpart A. Investigators conducting HHS-supported research in these populations must comply with all of the requirements of subpart A as well as the requirements of the relevant subpart. Institutions may further choose to apply subparts B-D to all research regardless of whether it is HHS-supported.
How do subparts B,C, and D relate to subpart A?
The Code captures many of what are now taken to be the basic principles governing the ethical conduct of research involving human subjects.
Nuremberg Code, 1947
Nuremberg Code, 1947 Declaration of Helsinki, 1964 National Research Act,1974 Belmont Report, 1978 45 CFR 46, subparts A-D, revised late 70's early 80's
The historical basis for the current human research regulations.
Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects. Similar to basic principles governing the ethical conduct of research involving human subjects
Declaration of Helsinki, 1964
A series of highly publicized abuses in research led to the enactment of PL 93-348. Charged with task of identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research and to develop guidelines to assure that such research is conducted in accordance with those principles.
National Research Act and National Commission for the Protection of HS of Biomedical and Behavioral Research, 1974
Identifies three fundamental ethical principles for all HSR.
Belmont Report
Regulations based in large part on the Belmont Report. Informally known as the Common Rule. In 1995 the CIA was required by Executive Order to comply with all subparts of these regulations.
45 CFR 46
FDA field investigators interview institutional officials and examine the IRB records to determine compliance with FDA regulations.
What happens during and FDA inspection of an IRB?
Does a treatment IND/IDE require prior IRB approval?
Test articles given to HS under a treatment IND/IDE require IRB approval with two exceptions. If a life-threatening emergency exists or a waiver of the IRB requirements is granted to the sponsor/investigator.
The FDA regulations exempt an emergency use of a test article from prospective IRB review, however, “…any subsequent use of the test article at the institution is subject to IRB review.” What does the phrase “subsequent use” mean?
FDA regulations allow for one emergency use of a test article in an institution without prospective IRB review, provided that such emergency use is reported to the IRB with 5 working days after such use. An emergency use is defined as a single use (or single course of treatment) with one subject. Subsequent use would be a second use with that subject or the use with another subject.
Are sponsors allowed access to IRB written procedures, minutes, and membership rosters?
FDA regulations do not require public or sponsor access to IRB records. However, FDA does not prohibit the sponsor from requesting IRB records. The IRB and the institution may establish a policy on whether minutes or a pertinent portion of the minutes are provided to sponsors. State and local laws regarding access to IRB records should be followed.
Must an investigator’s brochure be included in the documentation when an IRB reviews an investigational drug study?
For IND applications, the brochure is usually required by the FDA. There is no specific regulatory requirements for the brochure, the IRB may establish written procedures which require its submission. The brochure may be part of the investigational plan that the IRB reviews when reviewing medical device studies.
To what extent is the IRB expected to actively audit and monitor the performance of the investigator with respect to human subject protection issues?
FDA does not expect IRBs to routinely observe consent interviews, observe the conduct of the study or review study records. However, the IRB as the authority to observe, or have a third party observe, the consent process and the research.
How can a sponsor know whether an IRB has been inspected b FDA, and the results of the inspection?
The Division of Scientific investigations maintains an inventory of the IRB’s that have been inspected. The information is available through the Freedom of Information Act procedures.
If an IRB disapproves a study submitted to it, and it is subsequently sent to another IRB for review, should the second IRB be told of the disapproval?
Yes. It the study is submitted to a second IRB the written statement of the reasons for disapproval should be included in the study documentation so an informed decision can be made.
Could an IRB lose its quorum when members with a conflict of interest leave the room for deliberation and voting on a study?
Yes. The quorum is the count of the number of members present. IF the number present falls below a majority, the quorum fails.
Does the FDA prohibit direct communication between sponsors and IRBs?
It is important that a formal line of communication be established between the investigator and the IRB. Investigators should report adverse events directly to the responsible IRB, and should send progress reports directly to the IRB. However, FDA does not prohibit direct communication between the sponsor and the IRB.
Does the FDA prohibit direct communication between sponsors and IRBs?
FDA does require direct communication between the sponsors and the IRB for certain studies of medical devices and when informed consent waiver has been invoked.
May informed consent be obtained by telephone from a legally authorized representative?
A verbal approval does not satisfy the FDA requirement for a signed consent document. However, it is acceptable to send the IC to the LAR by fax and conduct the consent interview by telephone when the LAR can read the consent. If the LAR agrees, the IC can be signed and sent back.
FDA requires that a copy of the IC be given to the person signing the form. Does this copy have to be a photocopy with the signature affixed?
No, although it is encouraged.
The IC regulations require the consent document to include a statement that notes the possibility that FDA may inspect the records. Is this statement a waiver of the subject’s legal right to privacy?
No. FDA does not require any subject to “waive” a legal right. Rather, FDA requires that the subjects be informed that complete privacy does not apply in the context of research involving FDA regulated products.
Is the sponsor required to review the consent form approved by the IRB to make sure all FDA requirements are met?
For investigational devices, the IRC is a required part of the IDE submission. It is therefore, approved by FDA as part of the IDE application. When the IRb makes substantive changes in the document, FDA reapproval is required and the sponsor is necessarily involved in this process.
Does a physician, in private practice, conducting research with an FDA regulated product, need to obtain IRB approval?
Yes. The FDA regulation require IRB review and approval of regulation clinical investigations, whether or not the study involves institutionalized subjects. An investigator should be able to obtain IRB review by submitting the research proposal to a community hospital, independent IRB, or other organizations.
Does a clinical investigation involving a marketed product require IRB review and approval?
Yes. IF the investigation is governed by FDA regulations.
What is a medical device?
A medical device is any instrument, apparatus, or other similar or related article, including component, part, or accessory which is (a) recognized in the official National Formulary, or the US Pharmacopeia, or any supplement to them; (b) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in humans or other animals; OR (c) intended to affect the structure or any function of the human body or in animals AND does not achieve any of its principal intended purposes through chemical action within or on the human body or in animals and is not dependent upon being metabolized for the achievement of its principal intended purposes.
Are in vitro diagnostic products medical devices?
Yes. The definition of a “device” includes in vitro diagnostic products.
Must a manufacturer comply with 21 CFR 50 and 56 when conducting trials within its own facility using employees as subjects?
Yes. The situation represents a prime example of a vulnerable subject population.
Do Radioactive Drug Research Committees (RDRCs) have authority to approve initial clinical studies in lieu of an IND?
No. An IND is required when the purpose of the study is to determine safety and efficacy of the drug or for immediate therapeutic, diagnostic or similar purposes.
Does FDA approve RDRCs?
Yes. An RDRC must obtain and maintain approval by the FDA.
The Council for International Organizations of Medical Sciences (CIOMS) is an international nongovernmental organization established jointly by WHO and UNESCO in 1949.
serves the scientific interests of the international biomedical community in general and has been active in promulgating guidelines for the ethical conduct of research, among other activities. CIOMS promulgated guidelines in 1993 entitled International Ethical Guidelines for Biomedical Research Involving Human Subjects. These 15 guidelines address issues including informed consent, standards for external review, recruitment of participants, and more. The Guidelines are general instructions and principles of ethical biomedical research.
Who is responsible for the initial assessment of significant vs. non-significant risk
sponsor
applies to programs receiving federal money; give certain rights to parents with regard to survey research
Protection of Pupil Rights (PPRA)
Do state laws supersede federal laws?
No. As long as they add additional protections.
Who do Certificates of Confidentiality protect?
NIH issues to protect identifiable information from forced disclosure (protects the researcher and institution from having to disclose).
Can uncertain viable neonates be used in research?
can’t be used until viability is determined
Does the Common Rule mention privacy and maintenance of confidentiality?
yes. It is mention in 46.111
after animal testing, this is done to determine human use safety
Phase I IND
Different dosages are tested to determine the appropriate dosage.
Phase II IND
Controlled trials are performed.
Phase III - IND
Post approval trials
Phase IV - IND
The ICH Guidelines require that the subject be given a copy of their signed consent form. HHS and FDA regulations do not.
True
When DSMBs are in use, who is the line of communication between?
IRB and investigator. The IRB is not to speak directly to program Officer or the DSMB
identifiable information held by a covered entity that cannot be disclosed without subject’s authorization
Privately Held Information (PHI)
How long are HIPPA records to be retained.
HIPPA - 6 years. The Privacy Rule does not include rention
Who is a covered entity?
Health plan, health care provider etc who transmits information in an electronic format
when a genuine uncertainty in the expert medical community exists over whether a treatment will work is called…
clinical equipoise
45 CFR 46 Subpart A is known as
The Common Rule
Are 45 CFR 46 subparts B-E part of the Common Rule
No.
Do the federal regulations require that the names of those board members abstaining be included in the minutes?
NO. Guidance on Written Procedures and 45 CFR 46.115(2) state numbers.
non-exempt human subjects research project when its employees or agents for the purposes of the research project obtain: (1) data about the subjects of the research through intervention or interaction with them; (2) identifiable private information about the subjects of the research; or (3) the informed consent of human subjects for the research.
engaged in research
majority of the members of the IRB are present, including at least one member whose primary concerns are in nonscientific areas. In order to be approved, it shall receive approval of a majority of those members present at the meeting.
quorum requirements
research involves no more than minimal risk to subjects; the waiver or alteration will not adversely affect the rights and welfare of the subjects; the research could not practicably be carried out without waiver or alteration; and whenever appropriate, the subjects will be provided with additional pertinent information after participation.
conditions for alteration or waiver of the consent process
only linking record of subject to research; and study presents no more than minimal risk of harm
conditions for waiving requirement for signed consent
means the use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is avail-able, and in which there is not suffi-cient time to obtain IRB approval
emergency use
means any drug for human use, biological product for human use, medical device for human use, human food additive, color addi-tive, electronic product, or any other article subject to regulation
test article
provided that such emergency use is re-ported to the IRB within 5 working days. Any subsequent use of the test article at the institution is subject to IRB review.
FDA emergency use of a test article is exempt. DHHS is not exempt
any pro-tocol for which an IRB conducted an initial review or a continuing review at a convened meeting or under an expe-dited review procedure during the pre-ceding 12 months;
active protocol
risks are minimized and reasonable in relation to anticipated benefits; selection of subjects is equitable; informed consent is sought and documented; when appropriate a research plan makes provisions for data monitoring; and contains adequate provisions to protect the privacy of subjects and to maintain confidentiality of data.
criteria for approval
when a protocol is subject to review under more than one agency, do the requirements of each regulation need to be met?
yes
what role does an advocate play in the review of research involving children who are wards of the state?
an advocate for a child who is a ward of the state has a fiduciary relationship (one of trust and confidence) to the child. In other words, the advocate must act with the child’s interest as the primary consideration.
why must foreign sites abide by DHHS regulations when the Declaration of Helsinki or another international code is available?
DHHS wants to ensure that all DHHS-supported or -conducted research involving HS provide protections that at least equivalent to those afforded by DHHS regulations. Many international guidelines provide general principles but do not describe the specific procedures.
FDA will consider waiting local IRB review for treatment INDs. Do DHHS regulations require local IRB review for Treatment INDs, even when FDA does not?
If both FDA and DHHS have jurisdiction over research activities, IRBs must meet the requirements of both. DHHS regulations would still require local review if (1) the institution has agreed to follow the regs for all research; or (2) the research is supported by a DHHS component.
Even if FDA grants a waiver of local IRB review, the local IRBs retain the right to review the research if they choose.
True
can a masked or double masked study qualify for exemptions 46.101(b).
No. In masked studies, the participant does not know if he/she is receiving the intervention. In double masked studies, neither the participant or the researcher know.
do exemptions apply to subparts B &C?
No.
the provision of investigational drugs outside of an ongoing clinical trial to a limited number of patients who are desperately ill and for whom no standard alternative therapies are available.
compassionate use
a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval.
emergency use
a treatment protocol that is added to an existing IND, which allows physicians to treat qualifying patients according to the protocol, and which provides additional data on the drug’s safety and effectiveness.
treatment IND
allows a physician to obtain access to an IND for the treatment of a single patient, usually in a desperate situation, and unresponsive to other therapies, or in a situation where no approved or generally recognized treatment is available.
Access may be gained either through the sponsor or the FDA.
single patient use
makes available promising investigational agents as quickly as possible to persons with AIDS and other HIV-related disease while generating data on safety and effectiveness of the drug.
Parallel Track mechanism
a physician may, without IRB approval, treat the patient/subject using a test article (if the situation meets FDA standards), the subject may not be considered a research subject; data collected for the use of the test article may not be used in the study.
DHHS-supported or -conducted research
IRB membership changes; serious or continuing noncompliance; unanticipated problems involving risks; or suspension or termination of IRB approval for a project
Must be reported to DHHS.
The FDA regulates but does not, for the most part, support of conduct research.
True
This agency does not permit modification or waivers of informed consent requirements, except for emergency use of test articles, which are exempt from prior IRB review.
FDA
life-threatening situations necessitating use of the test article; where the subject is unable to provide effective consent; there is insufficient time in which to obtain consent from the LAR; and there is no available alternative method of approved or generally recognized therapy of equal or greater likelihood of saving the subject’s life
emergencies qualifying for exemption from the informed consent requirement
Parallel track mechanisms are an attempt to move drugs from late Phase 1 to Phase 2 and is available only for AIDS and other HIV-related diseases.
True
a covered entity may always use or disclose for research purposes health information which has been de-identified without regard to the privacy rule
true
covered entities are permitted to use and disclose protected health information for research with individual authorization, or without individual authorization under limited circumstances.
Privacy Rule
documented IRB or Privacy Board approval; preparatory to research and will not be removed from CE; research on PHI of decedents; limited data sets with a data use agreement
covered entities must obtain one of these in order to conduct research use/disclosure without authorization
establish the uses and disclosures of the limited data; limit who can use or receive the data; require receipt to agree to not use or disclose information other than as permitted, report any use not provided for by the agreement, anyone involved must agree, not to identify or contact the individual
a data use agreement must contain
when individual authorizes
research use/disclosure with individual authorization
authorization does not expire; may be combined with consent
components of research authorizations
if the authorization is combined with the consent then it would require IRB review of the combined document.
true
IRB’s do not approve authorizations.
true, unless required by IRB written procedures
DHHS regulations apply to research involving humans that is conducted or supported by DHHS; FDA regulations apply to regulated products that involve one or more HS; Privacy Rule applies to “covered entities” who electronically transmit any health information in connection with transactions from which DHHS has adopted standards.
Differences between DHHS, FDA and Privacy Rule regulations
DHHS - private information must be identifiable and the identity is or may be readily ascertained by the investigator; Privacy Rule - information that identifies or there is reasonable basis to believe the information can be used to identify
difference between individually identifiable information in DHHS regs and Privacy Rule
in general, ICH Good Clinical Practice guidelines are recommendations, not legal requirements.
True
