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APPENDIX B. Additional Definitions

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Clinical Investigation - Any experiment that involves a test article and one or more human participants and that is subject to the Food and Drug Administration regulations.

Test Article - Any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to FDA regulation.

Department or Agency Head - The head of any federal department or agency and any other officer or employee of any department or agency to whom authority has been delegated.

Institution - Any public or private entity or agency (including federal, state, and other agencies).

Legally Authorized Representative (also referred to as surrogate or proxy) - An individual or judicial or other body authorized under applicable law to consent on behalf of a prospective participant to the participant’s participation in the procedure(s) involved in the research.

Research - A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. 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. For example, some demonstration and service programs may include research activities.

Research Participant to Regulation and similar terms - intended to encompass those research activities for which a federal department or agency has specific responsibility for regulating as a research activity (for example, Investigational New Drug requirements administered by the FDA). It does not include research activities which are incidentally regulated by a federal department or agency solely as part of the department'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 the Department of Labor).

Human Participant - A living individual about whom an investigator (whether professional or student) conducting research obtains data through intervention or interaction with the individual or identifiable private information. Intervention includes both physical procedures by which data are gathered and manipulations of the participant or the participant's environment that are performed for research purposes. Interaction includes communication or interpersonal contact between investigator and participant. Private information 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 an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the participant is or may readily be ascertained by the investigator associated with the information) in order for obtaining the information to constitute research involving human research participants. NOTE: The Food and Drug Administration (FDA) defines a human participant as an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A participant may be either a healthy human or a patient.

IRB - An Institutional Review Board established in accord with and for the purposes expressed in this policy.

IRB Approval - The 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.

Minimal Risk - The probability and magnitude of harm 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

Certification - The official notification by the institution to the supporting Department or Agency, in accordance with the requirements of this policy, that a research project or activity involving human participants has been reviewed and approved by an IRB in accordance with an approved assurance.

Unanticipated Problems Involving Risks to Participants or Others (UPIRTSOs) - Any incident, experience, or outcome that meets all of the following criteria: unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the participant population being studied; related or possibly related to a participant’s participation in the research; and suggests that the research places participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) related to the research than was previously known or recognized.

Associated With the Use of the Study Product (Drug or Device) or Procedure - there is a reasonable possibility that the experience may have been caused by the drug (21 CFR 312.32(a)).

Adverse Event/Experience (AE) - An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product (ICH-GCP-E6).

Serious Adverse Drug Event/Experience (SAE) - Any adverse drug experience occurring at any dose that results in any of the following outcomes: death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of an existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon appropriate medical judgment, they may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse (21 CFR 312.32(a)).

Life-threatening Adverse Drug Event/Experience - Any adverse drug experience that places the patient or participant, in the view of the investigator, at immediate risk of death from the reaction as it occurred, i.e., it does not include a reaction that, had it occurred in a more severe form, might have caused death (21 CFR 312.32(a)).

Unexpected Adverse Drug Experience - Any adverse drug experience, the specificity or severity of which is not consistent with the current investigator brochure, or, if an investigator brochure is not required or available, the specificity or severity of which is not consistent with the risk information described in the general investigational plan or elsewhere in the current application, as amended (21 CFR 312.32(a)).

Unanticipated Adverse Device Effect - An unanticipated adverse device effect means any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of participants (21 CFR 812.3(s)).


Dead Fetus - A fetus that exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord (if still attached).

Delivery - Complete separation of the fetus from the woman by expulsion or extraction or any other means.

Fetus - The product of conception from implantation until delivery.

Human Fetal Tissue - Tissue or cells obtained from a dead human embryo or fetus after a spontaneous or induced abortion, or after a stillbirth.

Neonate - A newborn.

Nonviable Neonate - A neonate after delivery that, although living, is not viable.

Pregnancy - Encompasses the period of time from implantation until delivery. A woman shall be assumed to be pregnant if she exhibits any of the presumptive signs of pregnancy, such as a missed menses, until the results of a pregnancy test are negative or until delivery.

Viable - As it pertains to the neonate, means being able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration. The Secretary may from time to time, taking into account medical advances, publish in the Federal Register guidelines to assist in determining whether a neonate is viable for purposes of this subpart. If a neonate is viable then it may be included in research only to the extent permitted and in accordance with the requirements of subparts A and D of this part.


Assent - A child’s affirmative agreement to participate in research obtained in conjunction with permission from the individual’s parents or legally authorized representative. A failure of a participant to object should not be construed as assent, absent affirmative agreement.

Children/Minors - Persons who have not attained the legal age for consent to treatments or procedures involved in research, under the applicable law of the jurisdiction in which the research will be conducted.

Permission - The agreement of parent(s) or guardian(s) to the participation of their child or ward in research.


Advertising - A public announcement usually by a printed notice or voice or data broadcast that describes a research study including contact information. Typically this is used for recruitment purposes for a survey or research study.

Anonymous – Unidentified (i.e., personally identifiable information was not collected, or if collected, identifiers were not retained and cannot be retrieved); information or materials (e.g., data or specimens) that cannot be linked directly or indirectly by anyone to their source(s).

Assent - An individual’s affirmative agreement to participate in research obtained in conjunction with permission from the individual’s parents or legally authorized representative. A failure of a participant to object should not be construed as assent, absent affirmative agreement.

Authorization – Except as otherwise permitted, the Privacy Rule requires that a research participant “authorize” the use or disclosure of his/her PHI to be utilized in the research. This authorization is distinct from the participant’s consent to participate in research, which is required under the Common Rule and FDA regulations. Just as a valid consent under Common Rule and FDA regulations must meet certain requirements, a valid authorization must contain certain core elements (45 CFR 164.508(c)). Often, this authorization is to be incorporated into the consent form. The participant’s right to revoke authorization is limited. The investigator and the institution may continue to use and disclose PHI that was obtained before the participant revoked in order to maintain the integrity of the research (45 CFR
164.508(b)(5)(i)). While consent may be given verbally under the Common Rule and FDA regulations for minimal risk research activities, authorization under the Privacy Rule must be in writing (signed and dated). Therefore, if a verbal (or other non-written) consent process will be used in research and if that research involves PHI, a waiver request of all elements of HIPAA authorization should be submitted for IRB review and approval.

Cadaver - a deceased person or portion thereof. The term cadaver includes organs, tissue, eyes, bones, arteries or other portion of a deceased person. The term cadaver does not include portions of an individual, such as tissue or blood, that were removed from the individual for research purposes while the individual was still alive.

Coded Information - Identifying information that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol, or combination thereof and a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.

Note: A code is sometimes also referred to as a “key,” “link,” or “map.”

Cognitive Impairment - An inability to reason, think, perceive, or remember. Cognitive impairment may result from progressive disease, injury, medication, or experience. Tests of cognitive ability carried out by qualified professionals are used to identify cognitive impairment.

Continuing non-compliance - A pattern of repeated non-compliance actions which continues after initial discovery, including inadequate efforts to take corrective actions within a reasonable timeframe. suggest a likelihood that, without intervention, instances of noncompliance will recur, or that indicate an unwillingness to comply with, or a lack of knowledge of, federal regulations, policy, and law, or determinations or requirements of the IRB. Examples of continuing noncompliance may include, but are not limited to the following: repeated failures to provide or review progress reports resulting in lapses of IRB approval, inadequate oversight of ongoing research, or failure to respond to or resolve previous allegations or findings of noncompliance.

Covered Entities – Defined as health plans, health care clearinghouses or health care providers who transmit any health information electronically. Individual investigators must comply with the regulations if they are also health care providers who electronically transmit health information or if they are employees or members of a covered entity.

Decedent Research – The Common Rule defines a human research participant as a living individual. The Privacy Rule recognizes both living and deceased humans as individuals whose privacy must be protected. If an investigator wishes to conduct research project using PHI of one or more deceased individuals, prior IRB review is required. The IRB may request documentation of death (45 CFR 164.512(i)(1)(iii)).

De-identified – All direct personal identifiers are permanently removed (e.g., from data or specimens), no code or key exists to link the information or materials to their original source(s), and the remaining information cannot reasonably be used by anyone to identify the source(s). Note: For purposes of human research participant protection policy, protected health information (PHI) is de-identified when it does not contain any of the 18 identifiers specified by the Health Insurance Portability and Accountability Act (HIPAA) at 45 CFR Part 164, or has been determined to be de-identified by a statistician in accordance with the standards established by the Privacy Rule.

Dissent - An individual’s negative expressions, verbal or non-verbal, that they object to participation in the research or research activities.

e-Consent – an electronic version of a written informed consent document that can be electronically signed, stored, shared and printed.

External adverse event – An adverse event that occurs at a site external to the authority of the IRB and is reported to the principal investigator.

Guardian - Under federal law, "guardian" means an individual who is authorized under applicable state or local law to consent on behalf of a child to general medical care.

  • A child’s "guardian" may provide legally effective informed consent for participation in research. If a guardian provides consent, the court order or legal authorization to consent to general medical care should be copied and included in the research records with the consent document. It is important to note that physical custody and legal guardianship may not be the same for some children, and that courts may only grant partial or joint custody in some cases. Review of the court order or other legal documentation establishing the guardianship is necessary to determine who may provide consent for participation in research on behalf of the child;
  • Depending on state law, foster parents or Children and Youth Services cannot consent to general medical care on behalf of a child, unless a court order or the consent of the parent has been obtained. Therefore, such persons do not meet the federal definition of “guardian” and cannot provide consent for the participation of a foster child in a research study. Only the birth or adoptive parent(s) can provide the legally authorized consent to participation in research. In addition, a child who is in the custody of Children and Youth Services is considered a ward of the state, and the procedures set forth below for enrolling wards must be followed.

Health Care Agent - The health care agent is the individual named in a Durable Power of Attorney for Health Care order executed by the participant while the participant had decisionmaking capacity. The health care agent acts on the participant’s behalf to make health care decisions, including enrolling the participant in a research study, when the participant is unable to provide consent.

Health information – Information about one’s physical or mental health or condition, or one’s health care, or one’s payment for health care. Human Research Protection Program – A system of interdependent elements that come together to implement policies and practices that ensure the protection of research participants.

IDE - An approved investigational device exemption permits a device that otherwise would be required to comply with a performance standard or to have premarket approval to be shipped lawfully for the purpose of conducting investigations of that device.

Immediately life-threatening disease or condition – a stage of disease in which there is reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment.

Informed Consent - An individual’s voluntary agreement, based upon adequate knowledge and understanding of relevant information, to participate in research or to undergo a diagnostic, therapeutic, or preventive procedure.

Internal adverse event – An adverse event that occurs at a site that falls directly under the authority of the IRB.

IRB of Record - The IRB that assumes primary responsibility for review and oversight of a protocol.

Key Research Personnel - Persons listed on human research protocols who have direct contact with participants or their records/data/identifiable specimens.

Leftover/Remnant Specimen – Remaining portion of a specimen obtained for clinical purposes that is no longer needed for its original purpose and that would otherwise be discarded.

Legal Guardian or Conservator - A legal guardian or conservator is a person appointed by a court to make decisions for an individual who has been judicially determined to be incompetent.

Local IRB Review – Review conducted by the IRB of the institution where the research will be implemented.

Non-compliance – Failure on the part of the investigator or any member of the study team to follow the terms of the IRB approved protocol or to abide by applicable state laws or federal regulations, or IRB policies. This includes including the requirements of the approved investigational plan (i.e., protocol deviations) protocol deviations. The IRB will determine whether reports meet the definition of serious or continuing non-compliance. Incidents of noncompliance on the part of research participants which do not involve risk need not be reported to the IRB.

Non-serious or minor non-compliance: Non-compliance that does not increase risk to research participants, compromise participants’ rights or welfare, or affect the integrity of the research/data or the human research protection program. Examples of minor noncompliance may include, but are not limited to the following:

  • Lapses in continuing IRB approval;
  • Failure to obtain exempt determination before exempt research involving human research participants is conducted;
  • Minor changes in or deviations from an approved protocol; OR
  • Administrative errors.

Parent - A child’s biological or adoptive parent.

Possibly Related to the Research Intervention – In the opinion of the principal investigator, there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research.

Privacy Board – The Privacy Rule (45 CFR 164.512(i)(1)(i)(B)) describes a new board, constituted in a manner similar to an IRB, that has authority to implement the Rule as it relates to alteration of authorization or waiver of authorization.

Privacy Rule – Federal privacy regulations implemented as a result of HIPAA (45 CFR 160 & 164.

Prospective Research – Research using humans as participants or identifiable human specimens/data that will be collected after the research is approved by the IRB.

Protected Health Information – The Privacy Rule defines individually identifiable health information transmitted or maintained by a covered entity in any form (electronic, written or oral) as “protected health information” (PHI) and establishes the conditions under which investigators may access and use this information in the conduct of research. PHI is any information that relates to the past, present or future physical or mental health or condition of an individual who can be identified by any of eighteen specific identifiers (name, geographic location smaller than a State or the first three digits of a ZIP code, dates except year, telephone number, fax number, e-mail address, social security number, medical record number, health plan beneficiary numbers, account numbers, certificate or license numbers, vehicle identifiers and serial numbers, device identifiers and serial numbers, URLs, Internet protocol (IP) address numbers, biometric identifiers, full face photographs, any other unique identifying number, characteristic or code (45 CFR 164.514(b)(2)(i)). Per guidance from the federal government, a patient’s or participant’s initials are included in the category of any other unique identifying number, characteristic or code.

Quality Assurance (QA) – QA focuses on the quality of the processes contributing to the completion of a product or an activity. QA is a proactive effort with a goal to minimize the need for QC where quality is built into processes so that need to inspect afterward is minimized. It refers to every component, including personnel, of the institution that produces a particular product (e.g., a vaccine) or performs a given activity (e.g., performing IRB review or conducting informed consent process), meeting minimum (the "floor") requirements. In case of a clinical trial, QA refers to all those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented and reported in compliance with good clinical practice (GCP) and the applicable regulatory requirements.

Recruitment – Seeking individuals to enroll or participate in a research project.

Related to the Research Intervention – In the opinion of the principal investigator, the incident, experience or outcome more likely than not was caused by the procedures involved in the research.

Repository or bank – Collection of data and/or specimens obtained and stored for future research uses and/or distribution, including a collection not originally or primarily obtained for research purposes. The Privacy Rule recognizes the creation of a research database or a specimen repository to be a research activity if the data/specimens stored contain PHI and requires either written authorization or an IRB approved waiver.

Research Not Involving Human research participants – An activity that has been determined to meet the 32 CFR 219.102 definition of “research” but not meet the definition of “human participant.”

Retrospective Research – Research using identifiable human specimens/data that were previously collected (i.e., on the shelf) before the research was submitted to the ORP IRB Office for review.

Review Preparatory to Research – If an investigator wishes to review PHI to determine the feasibility of a research project, s/he may do so by notifying the IRB of a planned Review Preparatory to Research (45 CFR 164.512(i)(1)(ii)). By this notification the investigator declares that s/he will use the PHI solely to prepare a research protocol or for similar purposes preparatory to conducting research, that the PHI will not be recorded or disclosed, and that the PHI is necessary to develop the protocol.

Secondary Research – Study of existing information or materials (e.g., data or specimens) that have been previously collected for a purpose (including non-research purposes) other than the currently proposed activity.

Serious disease or condition – a disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible, provided it is persistent or recurrent. Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one.

Serious non-compliance: Noncompliance that increases risk to research participants, compromises participants’ rights or welfare, or affects the integrity of the research/data or the human research protection program. Examples of serious noncompliance may include, but are not limited to the following:

  • conducting or continuing non-exempt human research participants research without IRB approval;
  • lack of legally effective informed consent from research participants;
  • failure to report or review serious adverse events, unanticipated problems, or substantive changes in research;
  • or inappropriate oversight of the research to ensure the safety of human research participants and the integrity of the research/data.

Short Form Consent - A written informed consent document that summarizes the required elements of informed consent to be presented orally to the participant or his or her legally authorized representative.

Specimen or sample – Human biological material, including solid material (e.g., tissue, organs), body fluid (e.g., blood, urine, saliva, semen, cerebrospinal fluid), and cells.

Unanticipated Problems Involving Risks to Participants or Others (UPIRTSOs) - Any incident, experience, or outcome that meets all of the following criteria: unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the participant population being studied; related or possibly related to a participant’s participation in the research; and suggests that the research places participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) related to the research than was previously known or recognized.

Unapproved medical device is a device that is utilized for a purpose, condition, or use for which the device requires, but does not have, an approved application for premarket approval under section 515 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360e)(the act) or an approved IDE under section 520(g) of the act (21 U.S.C. 360j(g)).

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