Appendix A: Definitions

"Abstain" is when an IRB member does not vote upon a protocol under review.

"Agent" is a representative who acts on behalf of other persons or organizations.

"Assent" is the affirmative agreement by a child, or an adult who lacks full decision-making capacity to participate in a research or clinical investigation. Mere failure to object may not, absent affirmative agreement, be construed as assent. [45 CFR §46.402(b)] [21 CFR §50.3(n)]

"Assurance" is an agreement between an Organization and a federal agency that stipulates that the Organization will comply with the agency's regulatory requirements. [45 CFR §46.103]

"Children" are persons who have not attained the legal age for consent to treatments or procedures involved in research or clinical investigations, under the applicable law of the jurisdiction in which the research or clinical investigations will occur. In Texas, a minor can petition to be "emancipated", but must do so by filing a petition and meeting the statutory requirements. Only if a minor were "emancipated" as described above; or was adjudicated to be an adult for the purpose of criminal prosecution under the Juvenile Justice Code would the state of Texas consider the minor an "adult."

"Conflict of Interest" a PI or Co-PI is said to have a conflict of interest whenever that PI or IRB member, his or her spouse, or dependent child falls under any of the following conditions:

Is an investigator or sub-investigator on the protocol (IRB members only, not applicable to PIs);
If the IRB member, the member's spouse, or dependent children are involved in the conduct of research;
Has entered into a financial arrangement with the sponsor or agent of the sponsor, whereby the outcome of the study could influence the value of the economic interest;
Acts as an officer, director, or agent of the sponsor;
Has any equity interest in the sponsor that when aggregated for the investigator or member and the investigator's or member's spouse and dependent children is $10,000 or greater as determined through reference to public prices (e.g., NYSE or NASDAQ), any amount if the value cannot be determined through reference to public prices, or 5% or greater of the equity of the sponsor;
Has received payments or other incentives from any sponsor when aggregated for the investigator or member and the investigator's or member's spouse and dependent children that of $10,000 or greater;
Has identified him or herself for any other reason as having a conflicting interest.

"Consent/Permission" - The agreement of participant or the parent(s) of or guardian to the participation of their child or ward in the research/clinical investigation.

"Continuing Review" is the periodic review of a research study by an IRB to evaluate whether the study continues to meet organizational and regulatory requirements. Federal regulations stipulate that continuing review should be conducted at intervals appropriate to the level of risk involved in the study, and not less than once per year. [45 CFR §46.109 (e)] [21 CFR §56.109 (f)]

"Data and Safety Monitoring plan" (DSMP) is a process that reviews the integrity, safety and progress of a research protocol with the purpose of protecting participants during the course of study and makes decisions regarding continuance, modification, or stopping of the study for reasons of efficacy or safety. A DSMP may take a variety of forms, such as an investigator reviewing his or her own data, a review by another faculty member not otherwise involved in the conduct of the research, a committee of investigators, an independent committee, or an independent data and safety monitoring board. The type of safety monitoring that is adequate depends on the specifics of the research.

"Dead Fetus" means a fetus that exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord.

"Decision Making Capacity" is the ability to understand the choices presented, to appreciate the implications of choosing one alternative rather than another, and to make -- and communicate -- a choice.

"Delivery" means complete separation of the fetus from the woman by expulsion, or extraction, or any other means.

"Emancipated Minor" A minor can petition to be "emancipated", but must do so by filing a petition and meeting the statutory requirements of Sec. 31 of the Texas Family Code. Only if a minor were "emancipated" as described above; or was adjudicated to be an adult for the purpose of criminal prosecution under the Juvenile Justice Code would the state of Texas consider the minor an "adult."

"Engaged in Research" An institution becomes “engaged” in human subjects research when its employees or agents (all individuals performing institutionally designated activities or exercising institutionally delegated authority or responsibility) (i) intervene or interact with living individuals for research purposes; or (ii) obtain individually identifiable private information for research purposes [45 CFR 46.102(d),(f)]. Solicitation of consent by performance site staff would be considered engagement.

"FDA" means the Food and Drug Administration.

"Federal Wide Assurance" (FWA) means a document that fulfills the requirements of 45 CFR Part 46 and is approved by the Secretary of Health and Human services. The University of Texas at Austin has an approved FWA on file with DHHS. UT-Austin's FWA number is # 2030. The University will make available a copy of Federal Wide Assurance to any faculty, student or staff who requires said information.

"Fetus" means the product of conception from implantation until delivery.

"Guardian" Pursuant to Section 601 of the Texas Probate Code, a "guardian" means a person who is appointed guardian of the person and/or the estate of an incapacitated person under a court order issued pursuant to Section 693 of the Texas Probate Code.

"HIPAA" is the Health Insurance and Portability and Accountability Act of 1996 (HIPAA) that protects the privacy of a research participant's health information.

"Human Research Protection Program" (HRPP) is a system that includes all structural units, policies, and activities critical to protecting individuals studied in research and that is managed in accordance with these standards and with applicable federal, state, and local laws. Some components of the HRPP may be external to the Organization seeking accreditation; essential components of the HRPP are identifiable.

Human Subject Research: Human Subject Research is defined by the institution as any activity that either:

Meets the DHHS definition of “Research” and involves “Human Subjects” as defined by DHHS; or
Meets the FDA definition of “Research” and involves “Human Subjects” as defined by FDA;

Human Subject: A human subject is defined by DHHS as a living individual about whom a research investigator (whether a professional or a student) obtains data through intervention or interaction with the individual or from individually identifiable information.

“Intervention” as defined by DHHS regulations means both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject’s environment that are performed for research purposes. [45 CFR 46.102(f)]
“Interaction” as defined by DHHS regulations means communication or interpersonal contact between investigator and subject. [45 CFR 46.102(f)]
“Private information” as defined by DHHS regulations means 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). [45 CFR 46.102(f)]
“Identifiable information” as defined by DHHS means information that is individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information).

A human subject is defined by FDA is an individual who is or becomes a participant in research, either as a recipient of a test article or as a control who may be either a healthy human or a patient. [21 CFR 50.3(g), 21 CFR 56.102(e)]. A human subject according to FDA includes an individual on whose specimen a medical devise is used [21 CFR 812.3(p)].

"Informed Consent" means the agreement to participate in research that is made voluntarily by an individual with legal and mental competence and the requisite decision-making capacity, after disclosure of all material information about the research. Informed Consent means the knowing consent of an individual or his legally authorized representative, so situated as to be able to exercise free power of choice without undue inducement or any element of force, fraud, deceit, duress, or other form of constraint or coercion. Information conveyed in the informed consent/ authorization procedure must include all essential elements listed in Section 5 of this manual.

"Institution" means any public or private institution or agency (including Federal, State, and local Government agencies).

"Institutional Review Board" (IRB) is an independent committee comprised of scientific, non-scientific, and non-affiliated members established according to the requirements of federal regulations. Any board, committee, or other group formally designated by an organization to review research involving humans as participants, to approve the initiation of and conduct periodic review of such research. The term includes, but is not limited to Institutional Review Boards, Investigational Review Boards, Central Review Boards, Independent Review Boards, and Cooperative Research Boards. [45 CFR §46.402(g)] [21 CFR §50.3(i)]

"Investigational Device Exemption" (IDE) The exemption by which the FDA permits a device that otherwise would be required to comply with a performance standard or to have pre-market approval, to be shipped lawfully in interstate commerce for the purpose of conducting investigations of that device. (21 CFR part 812)

"Investigational New Drug" (IND) – An investigational drug or biologic application by which the FDA allows testing in human beings of a substance having an effect in the body. (21 CFR part 312, subpart B)

Investigator: An Investigator is each faculty member, principal investigator, or other researcher responsible for the design, conduct, or reporting of the research or other educational activity proposed for funding. In some cases, even graduate students and postdoctoral fellows may be responsible for the design, conduct, or reporting of research such that the graduate student or postdoctoral fellow is considered to be an Investigator under this policy and may be required to complete a financial disclosure statement. The principal investigator on each grant or contract should insure that all researchers on the project are aware of and comply with this policy.

"Key Personnel" are defined as the principal investigators, co-principal investigators, and others, specified within each project, as having decision-making power over the investigation.

"Legally Authorized Representative" means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective participant to that subject's participation in the procedures involved in the research. [45 CFR §46.402(c)] [21 CFR §50.3(l)]. The individuals authorized under Texas law to consent on behalf of a prospective participant to participation in the procedures involved in the research are the parent or legal guardian if the patient is a minor, a legal guardian if the individual has been adjudicated incapacitated to manage the individual's personal affairs, an agent of the individual authorized under a durable power of attorney for health care, an attorney ad litem appointed for the individual, a guardian ad litem appointed for the individual, or an attorney retained by the individual.

"Minimal Risk" means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in the participant's daily life or during the performance of routine physical or psychological examinations or tests. [45 CFR §46.102(i)] [21 CFR §50.3(k)] In research involving prisoners, minimal risk is also defined as the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons. [45 CFR §46.303(d))]

"Minimal Risk Research" is Research in which 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 (of normal subjects) or during the performance of routine physical or psychological examinations or tests. Clinical investigations are usually more than minimal risk.

"Monitoring" may refer either to data monitoring or monitoring the conduct of research. Data monitoring means the systematic tracking of data from a research study with the intent to evaluate the harms and benefits that accrue to participants. Monitoring the conduct of research mean the systematic tracking of the implementation of a research study with the intent to maintain compliance with the protocol and regulations, and maintain the integrity of the data.

"Neonate" means a newborn.

"Nonviable Neonate" means a neonate after delivery that, although living, is not viable.

"OHRP" means the Office for Human Research Protections. This is an office in the Office of the Secretary of Health and Human Services that is responsible for regulatory oversight of human subject research.

"Parent" means a child's biological or adoptive parent.

"Permission" means the agreement of parent(s) or guardian to the participation of the child in the research or clinical investigation.

"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 missed menses, until the results of pregnancy testing are negative or until delivery.

"Principal Investigator" (PI) is that individual with signatory power on all documents related to the research project. This person has final authority over the project is accountable for the overall conduct of a particular research protocol and is accountable for the overall conduct of a study. The principal investigator accepts responsibility for training all personnel associated with the study in compliance with the human subjects regulations of 45 CFR 46. "Co-principal investigator" is that individual who co-signs on documents related to the project or who may be designated as a co-principal investigator in grant-related documents. This person has decision-making power with regard to the conduct of the research. The co-principal investigator reports to the principal investigator who is ultimately responsible for the conduct of the research. Others with decision-making power may include such persons as project managers, directors, and trainers. These designations are not all-inclusive. Operationally, these individuals have some oversight responsibility for one or more portions of the project. Individuals in this category are determined uniquely for each project by the principal investigator.

"Protocol" is a formal plan that includes, at minimum, the objectives, rationale, design, methods and other conditions for the conduct of a research study. (ICH-GCP)

"Quality Improvement" (QI) Periodic examination of organizational activities, policies, procedures and performance to identify best practices and target areas in need of improvement; includes implementation of corrective actions or policy changes where needed. (Preserving Public Trust, 2001)

"Reporting Requirements" Section 261.004 of the Texas Family Code provides that a person having cause to believe that a child's physical or mental health or welfare has been adversely affected by abuse or neglect by any person shall immediately make a report. The second clause of the statute addresses the reporting obligation of professionals, i.e. those licensed or employed by the state who have direct contact with children. The third clause waives any confidentiality privilege of an attorney, member of the clergy, medical practitioner, social worker, mental health professional or an employee of a clinic or health care facility that provided reproductive services who becomes aware of abuse or neglect of a child.

"Research"

Research as defined by DHHS is a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.

Research as defined by FDA is means any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the Federal Food, Drug, and Cosmetic Act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the Federal Food, Drug, and Cosmetic Act, but the results of which are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The terms research, clinical research, clinical study, study, and clinical investigation are synonymous for purposes of FDA regulations. [21 CFR 50.3(c), 21 CFR 56.102(c)]

“Experiments that must meet the requirements for prior submission to the Food and Drug Administration under section 505(i) of the Federal Food, Drug, and Cosmetic Act” means any use of a drug other than the use of an approved drug in the course of medical practice. [21 CFR 312.3(b)]

“Experiments that must meet the requirements for prior submission to the Food and Drug Administration under section 520(g) of the Federal Food, Drug, and Cosmetic Act” means any activity that evaluates the safety or effectiveness of a device. [21 CFR 812.2(a)]

"Research Staff" are individuals who are delegated responsibility by the Investigator for specific research tasks.

"Secretary" means the Secretary of Health and Human Services and/or any other officer or employee of the Department of Health and Human Services to whom authority has been delegated.

"Serious Unanticipated problem" (SAE) -- Any event that results in death, a life-threatening situation, hospitalization or prolonged hospitalization, persistent or significant disability/incapacity or a congenital anomaly/birth defect or requires medical intervention to prevent one of the outcomes listed above. SAEs require prompt reporting to the Sponsor, the FDA and the IRB.

"Site" A site whose staff, facilities or private records of identifiable individuals are engaged in the conduct of research; or, a site that receives HHS funds. The performance site is the actual place where the research activity takes place (e.g., clinic or hospital). The performance site’s location may be different from the location where the IRB review takes place.

"Sponsor" is an entity who takes responsibility for and initiates research, but who may not conduct the investigation. A person other than an individual (e.g., corporation or agency) that uses one or more of its own employees to conduct research it has initiated is considered to be a sponsor, and the employees are considered to be investigators. [21 CFR §50.3(k)] [21 CFR §50.102(j)] [21 CFR §312.3]

"Sponsor Investigator" is an individual who both initiates and actually conducts, alone or with others, a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject. The term does not include any person other than an individual, e.g., it does not include a corporation or agency. (21 CFR 56.102 (k))

"Student" is any individual who is enrolled at The University of Texas at Austin.

"Staff" is all other employees of The University of Texas at Austin, including faculty.

"Unanticipated Problems" (UP) -- The University defines an unanticipated problem as any of the following:

An actual unforeseen harmful or unfavorable occurrence to participants or others that relates to the research protocol (injuries, side effects, deaths);
An unforeseen development that potentially increases the likelihood of harm to participants or others in the future.
A problem involving data collection, data storage, privacy, or confidentiality
A participant complaint about IRB approved research procedures
New information about a research study (e.g., a publication in the literature, interim findings, safety information released by the sponsor or regulatory agency, or safety monitoring report) that indicates a possible change in the risks of the research;
Changes in approved research initiated without IRB review and approval to eliminate apparent immediate hazards to the participant

"Unanticipated Problem Involving Risks to Participants or Others" is an event that was (1) unforeseen, (2) related to the research procedures, (3) either caused harm to participants or others, or placed them at increased risk of harm.

"Unexpected Unanticipated Problem" (UAE) -- Any unanticipated problem that was unanticipated or not previously observed (e.g., not included in the consent form or investigator brochure). This includes adverse effects that occur more frequently or with greater severity than anticipated. Events that are unexpected and serious require prompt reporting to the Sponsor, the FDA and the IRB.

“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 regulation under the Federal Food Drug and Cosmetic Act or under Sections 351 and 354-360F of the Public Health Services Act (42 USC 262 and 263b-263n).

"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.

"Vulnerable Subjects/Participants" mean individuals who lack the capacity to provide informed consent or whose willingness to participate in research may be subject to undue influenced or coercion. Vulnerable subjects include, for example, children, prisoners, individuals with emotional or cognitive disorders/impairments, and economically or educationally disadvantaged persons. [45 CFR §56.107] [45 CFR §56.111(a)(3)] [45 CFR §56.111(b)] [21 CFR §56.107] [21 CFR §56.111(a)(3)] [21 CFR §56.111(b)]