Section 2: Definitions

2.1 Definitions Applicable to All Sections of this Manual

Adverse events are a subset of unanticipated problems involving risks to the subject or others and are related to untoward or unfavorable medically-related events, including any abnormal sign, symptom or disease temporarily associated with the subject’s participation in the research or clinical trial.

Agent of the Organization is a faculty member or non-faculty employee, who may also be a principal investigator of a research protocol or an Institutional Review Board member, or non-employees who perform institutionally designated activities or who exercise institutionally delegated authority or responsibility such as research or teaching activities. Examples would include community IRB members, University faculty who are conducting research at another institution, a faculty member performing research while on sabbatical or a University student conducting research at another institution as part of a course requirement.

Allegation of Noncompliance means an unproven assertion of noncompliance.

Anonymity means that the identity of a research subject cannot be readily ascertained by anyone, including the Principal Investigator, either directly or through the used of coded data.

Approved means a protocol is approved as written with no explicit conditions.

Approved Assurance means a document that fulfills the requirements of 45 CFR Part 46 and is approved by the Secretary of Department of Health and Human Services (HHS). The University of Texas at Austin has an approved Federalwide Assurance on file with HHS.

Approved with Explicit Conditions means the protocol is approved with explicit conditions for minor changes or simple concurrence of the Principal Investigator that will be identified to the Principal Investigator and must be completed and documented prior to beginning the research. In most instances, the Institutional Review Board (IRB) Program Coordinators will review and approve but explicit conditions deemed as significant or are directly relevant to regulatory criteria must go back to the convened IRB for review and approval.

Assent means an affirmative agreement to participate in research or clinical investigation. Mere failure to object an absence of affirmative agreement may not be construed as assent. This most often is applicable to children and decisionally impaired adults.

Authorized deception means that a Principal Investigator has intentionally not described certain aspects of a research study but subjects are informed that certain information will be withheld until the subject completes the study tasks.

Basic community partnership research is a project that involves a relationship with a community partner in which the researcher makes the key decisions in the project, but considers the needs and interests of the community in how the research is conducted and how the outcomes are disseminated.

Children are persons who have not attained the legal age for consent to treatments or procedures involved in research or clinical investigations. In Texas, where federal regulations and state law both apply, individuals under the age of 18 are considered to meet the definition of children. For research conducted outside Texas, children are defined under the applicable law of the jurisdiction in which the research or clinical investigations will occur. Some funding agencies may define children differently.

Close community partnership research is an ongoing collaborative project in which goals are co-defined in ways that balance benefit to the PI and utility of the findings for the community. There is some sharing of decision making between the Principal Investigator and the community, but the research methodology is primarily determined by the Principal Investigator.

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

Coercion is an overt or implicit threat of harm that is intentionally presented by one person to another in order to obtain compliance. For example, an investigator might tell a prospective subject that his or her grades might suffer if they do not participate in the research.

Collaborator is anyone who plays a part in the protocol and has access to study records.

Common rule refers to Department of Health & Human Services 45 CFR Part 46, Subpart A.

Community is a group that self-identifies by geography, age, ethnicity, gender, sexual orientation, disability, illness or health condition, common interest or cause, a sense of identification or shared emotional connection, shared values or norms, mutual influence, or commitment to meeting a shared need. Community need not be defined solely by geography. Defining “community” in a community-university partnership is more about the process of asking questions than about a strict definition of who “is” community or “represents” community: “Are those most affected by the problem at the table? Are community members at the table? Are those who have a stake in the issue being addressed at the table? Do they play decision making roles?” The purpose of the research partnership drives the definition - each project must define the community of interest.

Community-based research is research that takes place in or involves a community. The more precise definitions below reflect the degree of engagement of the community in the research, which can take place along a spectrum of engagement and shared governance.

Community-placed research is a researcher-initiated project involving a one time or short-term relationship between the PI and the community, with limited community involvement beyond being a venue for recruiting research subjects or for implementing research procedures.

Community-based participatory research (CBPR) is a project defined by co-creation of project ideas and procedures by Principal Investigator and a community, active and substantive participation by the community in all or nearly all stages of the research, and shared power and decision-making responsibilities. There is an expectation that findings will be used to change systems or solve community problems. CBPR sees research subjects as both individuals and as a community comprised of individuals. Issues of confidentiality in CBPR should be viewed differently than with individual subjects and decisions made as to what may or may not be appropriate.

Confidentiality pertains to the treatment of information that an individual has disclosed in a relationship of trust and with the expectation that it will not be divulged to others without permission.

Conflict of Interest is defined as any situation in which financial or personal obligations may compromise or present the appearance of compromising an individual or group’s professional judgment in conducting, reviewing, or reporting research. Members of the Institutional Review Board may not review, deliberate on or approve research if they have a conflict of interest related to the research.

Dead fetus means a fetus that does not exhibit heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, or pulsation of the umbilical cord.

Data and Safety Monitoring Plan (DSMP) is an individualized plan, written by the Principal Investigator (PI) responsible for the study. The DSMP sets forth mechanisms for reviewing and evaluating unanticipated problems and other study-relevant data. The rationale for requiring a DSMP is the need to enhance research subject safety by clearly defining safety related issues prior to subjects being enrolled in a study. These issues include:

1. Monitoring the safety of the environment including the safe handling of drugs, solutions, specimens, physical space, and equipment;
2. Monitoring and protecting the validity and integrity of the data collected for the study; and
3. Documenting, grading, attributing, and reporting unanticipated problems involving risks to subjects or others.

Deception (as applies to research) means intentionally giving research subjects false information in order to establish false beliefs during the course of a research study.

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

Designated Reviewers are experienced IRB members, defined in this policy as having been an IRB member for at least one year and having been trained on the expedited process by an IRB Chair or the ORS Director. The IRB Chair has designated the IRB Vice Chair, ORS Director and other IRB members as reviewers of protocols requesting and qualifying for expedited review.

Disapproved means the protocol describes a research activity that is deemed to have risks which outweigh potential benefits or the protocol is significantly deficient in several major areas. The protocol and/or other documents will need to be completely re-written and re-submitted as a new submission. Principal Investigators may request reconsideration of a determination for disapproval in writing and possibly be invited to attend an Institutional Review Board meeting and presenting reasons for reconsideration.

Engaged in human subject research as defined by the Department of Health and Human Services guidance document states that in general an institution is considered engaged in a particular 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.
3. Informed consent of human subjects for the research.

Food and Drug Administration (FDA) is an agency within the U.S. Department of Health and Human Services. FDA is responsible for protecting the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products, medical devices, our nation’s food supply, cosmetics, dietary supplements, and products that give off radiation.

Fetus means the product of conception from implantation until delivery.

Financial Interest in or related to the research means financial interest of any amount in the sponsor, product or service being provided, or a competitor of the sponsor. This can also be referred to as Financial Conflict of Interest.

Guardian means a person appointed by a court to have full authority to make decisions for and act on behalf of a child or decisionally impaired adult, except as otherwise provided for by law. For research conducted outside Texas, children are defined under the applicable law of the jurisdiction in which the research or clinical investigations will occur.

Human Embryonic Stem Cells are pluripotent cells that are derived from early stage of embryos, up to and including the blastocyst stage, are cable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.

Human Subject has two definitions depending on the federal agency overseeing the research.

1. Department of Health and Human Services regulations define human subject as a living individual* about whom the Principal investigator conducting research obtains:
   1. Data through intervention or interaction with the individual; or
   2. Identifiable private information.
      1. Intervention means both physical procedures by which data are gathered and manipulation of the subject or the subject’s environment for research purposes.
      2. Interaction includes communications or interpersonal contact between the investigator and the subject, i.e., obtaining informed consent.
      3. Private information includes information about behavior when the subject can reasonably expect that no observation is taking place and information that has been provided for specific purposes and which the subject can reasonably expect will not be made public (e.g., medical record). Private information is individually identifiable, i.e., the identity of the subject may be readily ascertained by the investigator.
   
   The definition provided in the Common Rule (See Section 1.4) is expanded to include investigators, technicians, and others assisting investigators, when they serve in a "subject” role by being observed, manipulated, or sampled. For the purposes of this manual, research involving human biological specimens (e.g., urine, blood, tissue, and other bodily fluids) will be considered human subject research.
   
   *Note: Research on autopsy materials or specimens from deceased individuals is not considered to be human subject research. However, some research, such as genetic studies providing private medical information about living relatives may need IRB review.
   
   
2. Food and Drug Administration definition is an individual who is or becomes a participant in research, either as a recipient of a test article (investigational drug, biologic or device) or as a control and may be either a healthy human or a patient. The definition also includes an individual on whose specimen a device is used.

Human Subject Research has reference to two definitions defined by federal agencies.

1. Department of Health and Human Services defines human subject research as systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge (45 CFR 46.102(d)) and includes a living individual about whom the investigator conducting research obtains:
   1. Data through intervention or interaction with the individual.
   2. Identifiable private information.
   3. Data about the subjects of the research through intervention or interaction with them.
   4. Identifiable private information about the subjects of the research.
   5. Informed consent of human subjects for the research.
2. Food and Drug Administration (FDA) defines human subject research as (21 CFR 56.102):
   1. A clinical investigation on one or more individuals who are or become participants in the investigation, either as recipients of a test article (drug, biologic, or device) or as controls and may be either patients or healthy non-patients.
   2. The data obtained from participants (and controls) will be submitted to, or held for inspection by, the FDA in support of a marketing or research application for an FDA-regulated product, or data obtained from the use of a device (in vitro diagnostic device) on tissue specimens will be submitted to, or held for inspection by, the FDA in support of a marketing or research application for an FDA-regulated product.

If the research does not meet either HHS or FDA definitions, it is not human subject research.

Neonate means a newborn.

Incidents of Noncompliance/ Protocol Violations means that principal investigators did not adhere to Federal Regulations and/or The University of Texas at Austin policies, procedures, requirements, or Institutional Review Board determinations for conducting research involving human subjects.

Incomplete disclosure means that the principal investigator withholds some information about the real purpose of the study or the nature of the research procedures.

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 procedure must include all essential elements listed later in this manual.

Institution means any public or private institution or agency (including federal, state, and local government agencies).

Institutional Official (IO) is the University official responsible for ensuring that the human research protection program has the resources and support necessary to comply with all federal regulations and guidelines that govern human subject research. The IO is legally authorized to represent the institution, is the signatory official for all Assurances, and assumes the obligations of the institution's Assurance. At The University of Texas at Austin, the Vice President for Research is the IO.

Investigator is considered to be an individual performing various tasks related to the conduct of human subject research activities such as:

1. Obtaining information about living individuals by intervening or interacting with them for research purposes.
2. Obtaining identifiable private information about living individuals for research purposes.
3. Obtaining voluntary informed consent of individuals to be subjects in research.
4. Studying, interpreting or analyzing identifiable private information or data for research purposes.

Key Personal includes (see section 3.17.1)

Lapse of approval means that, for whatever reason, the Institutional Review Board (IRB) has not received or reviewed required documentation for protocol continuation prior to the protocol’s expiration date and all research activities must cease. Continuing review of research activities by the IRB must occur at least annually and a request for continuation must be accompanied by a report and other pertinent documentation. By regulation, no grace period is allowed. The IRB notifies Principal Investigators of lapses in approval and the requirement to cease all research activities until approval for continuation is obtained (currently with a “Cessation” letter).

Legally authorized representative (LAR) means an individual, judicial or other entity authorized under applicable law to consent on behalf of a prospective subject to such subject's participation in the particular research activity or procedure. For research conducted in Texas where federal regulation and Texas law both apply, for healthcare related treatments and procedures and for non-healthcare procedures, individuals in the following order may serve as an LAR: a legal guardian, persons appointed as health care agents under Durable Power of Attorney for Health Care, a spouse, adult child, parent, or an adult sibling. For research conducted outside of Texas, individuals who meet the definition of a LAR are those who are described under the applicable law of the jurisdiction in which the research will be conducted. Legal counsel may be consulted by the Director of Office of Research Support and the Institutional Review Board Chair for assistance in applying laws to research involving human subjects.

Legally effective informed consent means that the Principal Investigator obtained consent to participate from a subject or the subject’s legally authorized representative (LAR) and documented it in a manner consistent with the human subject protection regulations and applicable laws of the jurisdiction in which the research is conducted. It is expected that the Principal Investigator will seek consent only under circumstances that provide the prospective subject or LAR sufficient opportunity to consider whether or not to participate and to minimize the possibility of coercion or undue influence. The information provided in the consent process should be understandable to the subject or subject’s LAR and may not include any exculpatory language.

Member includes an Institutional Review Board member or consultant and their immediate family members defined as spouse and dependent children and step-children.

Minimal Risk means that the risks of harm anticipated in the proposed research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. These are risks that reflect background risks that are familiar and part of the routine experience of life for an average person in the general population. For children, the definition means 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 a healthy child) or during the performance of routine physical or psychological examinations or tests. For Prisoners, minimal risk is 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 who are not prisoners.

Neonate means a newborn.

Noncompliance means that researchers or individuals other than researchers, such as research staff, Institutional Review Board (IRB) staff, or IRB members, did not adhere to Federal Regulations and/or The University of Texas at Austin policies, procedures, requirements, or IRB determinations for conducting research involving human subjects.

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

Office for Human Research Protections 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 pregnant if she exhibits any of the presumptive signs of pregnancy, particularly missed menses, until the results of pregnancy testing are negative or until delivery.

Principal Investigator means an individual under whose immediate direction research is conducted or in the event of research conducted by a team of individuals, is the responsible leader of that team.

When The University of Texas at Austin (University) accepts a grant or contract from an outside sponsoring agency, certain legal and ethical obligations are stated or implied in the document of agreement. The University becomes responsible for the proper performance of the stated work and for fiscal management of the funds received from the sponsor. Sponsors usually require an individual be named to oversee the project with the reasonable assurance that the agreed responsibilities will be discharged faithfully and prudently in the mutual interest of the sponsor and the University and over the full period of the award.

In order to implement these obligations, only individuals in the categories shown below are authorized to be PIs or project directors for sponsored projects. Only in rare instances will others be authorized, and then only with the written approval of the ORS Director.

1. Members of the faculty in the professorial ranks (assistant professor, associate professor and professor)
2. Directors (code 1000)
3. Research scientists/engineers (code 1000) and senior research scientists/engineers (code 1000)
4. Special research associates at the Applied Research Laboratory.
5. Students who list a full-time faculty member as a sponsor/mentor (or a part-time or adjunct faculty member when specifically requested by the department chair).
6. Adjunct faculty when Principal Investigator status is specifically requested

Prisoner means any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing. Individuals are prisoners if they are in any kind of penal institution, such as a prison, jail, or juvenile offender facility, and their ability to leave the institution is restricted. Some common examples of the definition are:

1. Individuals who are detained in a residential facility for court-ordered substance abuse treatment as a form of sentencing or alternative to incarceration.
2. Individuals with psychiatric illnesses who have been committed involuntarily to an institution as an alternative to criminal prosecution or incarceration.
3. Individuals who have been voluntarily admitted for treatment or who have been civilly committed to non-penal institutions for treatment because their illness makes them a danger to themselves or others are not prisoners.
4. Parolees who are detained in a treatment center as a condition of parole. Parolees living in the community, even with community-supervised monitoring, are not prisoners.
5. Probationers and individuals wearing monitoring devices are generally not considered to be prisoners. However, some situations of this kind may require analysis of circumstances and Office for Human Research Protections should be consulted when questions arise about research involving this population.

Prisoner Advocate is an individual representing the interests of incarcerated persons who may be approached and enrolled as research subjects.

Privacy means having control over the extent, timing and circumstances of sharing oneself (physically, behaviorally or intellectually) with others.

Privacy Board is a review body that may be established to act upon requests for waiver or alteration of the requirement for a signed “Authorization for Use or Disclosure of Protected Health Information (PHI)” under the HIPAA Privacy Rule for uses and disclosures of PHI for a particular research study. A Privacy Board may waive or alter all or part of the Authorization requirements for a specified research project or protocol. The IRB may act as a privacy board.

Private Information consists of the following:

1. Information that has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (e.g., medical record).
2. Information that can be readily identified with individuals, even if the information was not specifically collected for the study in question.
3. Information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place.

Protocol Deviation means a deviation from Institutional Review Board-approved activities related to a research study. This means that the principal investigator(s) has performed activities that are different than those described in the protocol, that procedures not previously described in the protocol were performed, or that procedures described in the protocol were not performed.

Quality Improvement (QI) projects are defined as those activities that are designed purely to evaluate and improve practice or to improve clinical care to better conform to established or accepted standards or are designed to bring clinical care in line with evidence or consensus-based standards. These types of activities are generally not subject to Institutional Review Board (IRB) review and approval. However, if data from the QI activity are used to draw general or widely applicable conclusions beyond evaluating a particular program or activity, the activity probably is research. The distinction is not always clear. The intent to publish, in and of itself, does not require that an activity be reviewed by the IRB. If the activities and data being reported are a result of QI assessment, then no IRB review is required for the activity or for its publication.

Quorum is defined as a majority of the voting members. In the case of the Institutional Review Board (IRB), a quorum will consist of at least 51% of the voting IRB members and must include at least one non-scientific member. All members present have equal voting power. At meetings of the IRB, a quorum must be established and maintained throughout the entire meeting. A member with a conflict of interest cannot contribute to a quorum. For Food and Drug Administration-regulated research, a licensed physician must be present during the review, deliberation and voting to satisfy the quorum requirement under Code of Federal Regulations Title 21 CFR 56.108(c).

Research by definition of Department of Health and Human Services means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge (45 CFR 46.102(d)) or, under Food and Drug Administration (FDA) regulations, an activity that involves a drug or drug, other than use of a market drug in the course of medical practice, or the use of a device to evaluate safety and effectiveness of that device, and data from the activity will be submitted to, or held for inspection by, the FDA in support of a marketing or research application for an FDA-regulated product. If the activity is designed to improve internal practices it is not research (See Definition: Quality Improvement).

Research Records are records consisting of both Institutional Review Board-related records and any data gathered for research purposes.

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

Sponsor means any person or entity that takes responsibility for, initiates or funds a study. The sponsor may be an individual, pharmaceutical company, device manufacturer, governmental agency, academic institution, private organization, or other organization.

Student means any individual who is enrolled as a student at The University of Texas at Austin.

Staff means all employees of The University of Texas at Austin.

Suspension means a temporary cessation of research activities, to include enrollment of new subjects, collection of data from enrolled subjects, and performance of any research activities described in the approved protocol. Suspensions can be administered by the Institutional Review Board (IRB), the IRB Chair, or the principal investigator in order to eliminate an immediate hazard to subjects. A suspended protocol requires continuing review.

Tabled means generally, the protocol or consent form has deficiencies that prevent accurate determination of risks and benefits or requires significant clarifications, modifications or conditions that, when met or addressed, require full Institutional Review Board (IRB) review and approval of the Principal Investigator’s (PI) responses and revisions. The deficiencies will be specified to the PI, and on occasion the PI is asked to attend the full board meeting in order to clarify the points in question. The PI must revise the protocol, consent forms, or other documents as specified by the IRB and re-submit.

Termination means a permanent discontinuance of research activities described in a research protocol due to withdrawal of Institutional Review Board (IRB) or regulatory agency approval. If subjects are currently enrolled, the IRB and Principal Investigator must implement actions for immediate care of and safe withdrawal of subjects from the research study. A terminated protocol does not require submission for continuing review.

Unanticipated problem involving risks to subjects and others means any problem, event, occurrence or new information related to the research project hat is unanticipated and indicates that subjects or others are at increased risk of harm.

Undue influence is an offer or implication, real or perceived, of an excessive or inappropriate reward or other overture in order to obtain compliance. For example, professors recruiting their students may lead to the perception of undue influence to participate.

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 the 45 CFR 46 Subpart B. If a neonate is viable then it is a child and the45 CFR 46 Subpart D may apply.

Ward is defined as a child who is placed in the legal custody of the state or other agency, institution or entity consistent with applicable federal, state or local law.