Glossary of Human Research Terms

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A
Accrual

The process of seeking eligible participants and obtaining their consent to participate in the research. Accrual generally starts with recruitment, leading to screening for eligibility, and consent to enroll in the study. Also see Enrollment.

Acknowledged

The Office of the IRB uses the term "Acknowledged" when a document or memo is sent to the IRB that does not, according to applicable regulations or policy, require IRB approval. In this way the Investigator and sponsor are administratively notified that the document or memo was received by the OIRB and reviewed by the OIRB staff to ensure any regulatory issues are addressed and placed in the protocol record.

Administrative Change

A modification to an approved IRB application which does not require IRB approval.  Administrative changes should be submitted to the OIRB for review and acceptance.

 

Examples include (but are not limited to):

  • Correction of typos
  • Translations of approved consent forms and recruitment material,
  • Verification of media advertisements based on IRB approved scripts,
  • Minor changes to contact information,
  • Removal of a study sites,
  • Changes requested by affiliated institutions,
  • Changes that correct administrative errors made during previous IRB review. 
Administrative Hold (VA definition)

An administrative hold is a voluntary interruption of research enrollments and ongoing research activities by an appropriate VA facility official, researcher, or Sponsor (including the ORD when ORD is the sponsor). The term “administrative hold” does not apply to interruptions of VA research related to concerns regarding the safety, rights, or welfare of human research participants, research investigators, research staff, or others. An administrative hold must not be used to avoid reporting deficiencies or circumstances that otherwise require reporting by federal agencies.

Adverse Event

In general AE is used very broadly and encompasses physical and psychological harms and includes:

Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject's participation in the Research, whether or not it is considered related to the subject's participation in the research.

Adverse Event That Suggests That The Research Places Subjects or Others At A Greater Risk of Harm

Is an Adverse Event that:

  • is a Serious Adverse Event
  • or
  • Suggests that the research places subjects or others at a greater risk of physical or psychological harm than was previously known or recognized.

Note: The IRB recognizes this definition is very broad. Keep in mind that AE suggesting greater risk routinely warrants consideration of substantive changes in the research protocol or informed consent process/document or other corrective actions in order to protect the safety, welfare, or rights of subjects or others.

Affiliated Institution

Is any institution that relies on the HSC IRB.

A signed agreement between the relying institution and the HSC IRB is required to establish the affiliation. There are three general categories of institutional agreements: 1) a blanket agreement indicates that any study from the relying institution can be reviewed by the HSC IRB (e.g., South Texas Veterans Health Care System or University Health System), 2) a limited agreement applies to a defined category or group of studies (more than one study) (e.g., , and 3) a single study agreement applies to a single-study. Single-study agreements may be covered under an IRB Authorization Agreement (IAA) without a Memorandum of Understanding or Agreement (MOU/MOA). However, blanket and limited agreements generally require both an IAA and an MOU/MOA.

Agent

Used to indicate when an individual is working on behalf of the institution (i.e., performing HSC designated activities or exercising HSC delegated authority or responsibility) in relation to research. An agent can be an employee of the institution (e.g., faculty or staff) or a non-employee who is authorized by the institution to act on behalf of the institution (e.g., student, affiliated faculty, emeritus professors).

An institution is considered Engaged In Research_Individuals when an Employee or agent of the institution conducts human research activities.

It is possible for a HSC employee to conduct research and not be considered an agent of the university if the research is conducted during non-official duty time, is not in connection with her/his HSC responsibilities, is not being conducted at a HSC facility and the research is not supported by a direct HHS award to the HSC (review the HSC Handbook of Operating Procedures (HOP) on Conflict of Commitment). The institution however generally reserves the right to determine for themselves whether their employee (in whole or in part) is performing institutionally designated activities and acting on behalf of the institution or exercising institutional authority or responsibility in regard to that research and the IRB will generally consider this in determining whether the institution in question is engaged in research.

Allegation Of Noncompliance

An unproven assertion of Noncompliance.

Amendment

Any changes to previously approved research.

Investigators may not initiate any changes in research procedures or consent form(s) without prior IRB review and approval, except where necessary to eliminate apparent immediate hazards to the subject (Note: IRB approval of the actions taken in this circumstance must still be sought after the fact). Also see Major Change Or Modification

Appropriate Institutional Officials

Officials determined by each organization to be points of contact for research. This may include an individual, an office or a committee. (This term should not be confused with another similar but distinctly different DHHS term Authorized Institutional Official).

Assent

Affirmative agreement by an individual not Competence to give legally valid informed consent (e.g., child or person with limited mental capacity) to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent.

Assurance Of Compliance

An assurance of compliance is a written document submitted by an institution (not an Institutional Review Board) that is Engaged In Research_Individuals in non-exempt human subjects research conducted or supported by a specific federal agency. Through the assurance, an institution commits to the governing agency that it will comply with the requirements set forth in the regulations for the protection of human subjects. For research supported or funded by DHHS, the Federalwide Assurance is the only type of assurance accepted and approved by OHRP. The VA does not have an equivalent assurance program.

Or Assurance

Assured Institution
An institution holding an approved assurance from the applicable federal agency.
Attend
When the term is used in reference to attending an IRB meeting the term is meant to encompass both physical attendance and attendance via teleconference so long as all members are connected simultaneously.
Authorization

As outlined in 45 CFR 160 and 164 (HIPAA): An individual's written permission to allow a covered entity to use or disclose specified PHI for a particular purpose. 

Authorized Institutional Official
Within the institution, there must be a point of responsibility for the oversight of research and IRB functions. This point should be an official of the institution who has the legal authority to act and speak for the institution, and should be someone who can ensure that the institution will effectively fulfill its research oversight function. The authority can be delegated.
Authorized Representatives

HIPAA 45 CFR - 164.502(g) defines authorized personal representatives as persons who have the authority under applicable law to make health care decisions on behalf of adults or emancipated minors, as well as parents, guardians or other persons acting in loco parentis who have the authority under applicable law to make health care decisions on behalf of unemancipated minors.

Persons who are authorized under Texas state law to make health care decisions on behalf of other individuals will also be personal representatives under HIPAA.

B
Belmont Report
Ethical Principles and Guidelines for the protection of human subjects of research. On July 12, 1974, the National Research Act (Pub. L. 93-348) was signed into law, there-by creating the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. One of the charges to the Commission was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles. In carrying out the above, the Commission was directed to consider: (i) the boundaries between biomedical and behavioral research and the accepted and routine practice of medicine, (ii) the role of assessment of risk-benefit criteria in the determination of the appropriateness of research involving human subjects, (iii) appropriate guidelines for the selection of human subjects for participation in such research, and (iv) the nature and definition of informed consent in various research settings.
Benefit

Something that promotes or protects well-being; an advantage. Compensation cannot be considered a benefit. Just as there are a range of harms: physical, social, economic, psychological, and legal, there can also be a range of benefits: physical benefit is clinically beneficial - as with standard-of-care procedures known to be helpful in guiding the subject's care when plans include using them as such (experimental procedures or procedures that must be verified by an approved device might not result in this benefit), notwithstanding that the subjects could have received the benefit without being in the study (this information comes to light in the alternatives description); psychological benefit of educational, informational, counseling or other resources provided in the study or empowerment. These can be directed at the individual (direct benefit, secondary benefit, monitoring benefit), the community or a general knowledge gained benefit (philanthropic on behalf of the individual). Only certain anticipated benefits may be considered appropriate for consideration to weigh against the probability of harm in certain populations and circumstances.

Bonus Payment
Compensation tied to the rate or timing of recruitment or performance or other aspects of a clinical study. Examples of bonus payments include the following:
  • the sponsor announces that the highest enrolling site in the nation will receive a $10,000 bonus;
  • the sponsor offers to pay an additional $10,000 beyond the budgeted study costs to any site that enrolls five participants within a week;
  • the sponsor offers to pay an additional $10,000 beyond the budgeted study costs to any site that fulfills its recruitment target by the end of the month;
  • the sponsor offers to pay an additional $1,000 beyond the budgeted study costs for any subject who agrees to enroll within one day of initial contact.

This does not include compensation for services rendered which include screening and referral activity unrelated to whether the participant ultimately enrolls in or completes the research study.

C
Capacity

The ability based on reasonable medical judgment to understand and appreciate the nature and consequences of a treatment decision, including the significant benefits and harms of and reasonable alternatives to any proposed treatment decisions. Also see Incapacitated and Impaired Decision-Making Capacity. Subjects who are incapacitated are not capable of giving informed consent for research but may be capable of providing assent.

(Texas)

Case Report Form

Sometimes referred to as Data Collection Tool (DCT), is a printed, optical or electronic document designed to record all of the protocol information to be reported on each study participant. CRFs and DCTs are designed by the sponsor or investigator and maintained at the investigative site. Information captured in a CRF must be supported by a Source Document (unless the CRF is the source document).

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Example Source Documents

Original Study Documents – Completed Informed Consent Forms (ICF) and Case Report Forms (CRF)

Records from study execution or supporting documents on medical history including the following:

  • Medical records
  • Hospital, clinic, & office charts
  • Progress notes, patient visit notes, physician’s notes/orders
  • Records:  laboratory, radiology, cardiology, medico-technical departments
  • Pharmacy dispensing records
  • X-Rays, Scans (bone, brain, MRI)
  • Video (angiography, endoscopy)
  • Instrumentation print-out: EKG, ECG, Spirometry, etc.
  • Memos to record concerning the study
  • Subjects’ diaries, evaluation checklists, or Quality of Life questionnaires
  • Recorded data from automated instruments
  • Certified transcription of recorded results including dictation (i.e., verified as accurate and complete)
  • Photographs, negatives, microfilm or magnetic media
Certificate of Confidentiality
A Certificate of Confidentiality helps researchers protect the privacy of human research participants enrolled in biomedical, behavioral, clinical and other forms of sensitive research. Certificates protect against compulsory legal demands, such as court orders and subpoenas, for identifying information or identifying characteristics of a research participant. Researchers may apply for a Certificate through the NIH or Center funding the research, Contact information is available on the NIH website at: http://grants2.nih.gov/grants/policy/coc/index.htm
Certification
The official notification by the institution to the DHHS that a research project or activity involving human subjects has been reviewed and approved by the IRB in accordance with the approved assurance on file at DHHS. In order for a proposal involving human subjects to be eligible for federal funding, it must first be approved by the IRB and certified by the institutional representative.
CFR-Code of Federal Regulations
Rules published in the Federal Register by the executive departments and agencies of the Federal Government. It is divided into 50 titles that represent broad areas subject to Federal regulation. Each volume of the CFR is updated once each calendar year and is issued on a quarterly basis.
Child
See Minor.
Class Project
Academic projects or student assignments involving collection of data from human subjects, when the data is used solely for the purpose of teaching course content and not intended to be used to develop or contribute to generalizable knowledge.
Classified Research

In the interest of national security, federally funded research can be 'classified' in terms of limited access to data, information, and facilities (inputs) that may be required to carry out the research or in terms of the limited distribution of the results of the research (outputs).

Current UTHSCSA policy does expressly allow the University to accept, a classified contract. If it can be accommodated without compromising the University's pursuit of its educational mission and if its purpose is clearly in the public interest it may be possible with the approval of the Vice President for Research.

Interested parties should contact the involved institution's Security Officer for further information regarding security clearances, classified document control, foreign visitor information, security inspections, and so forth.

Clinical Equipoise
A genuine uncertainty on the part of the expert medical community about the comparative therapeutic merits of each arm of a clinical trial. When the relative benefits and risks of the proposed intervention, as compared to standard therapy, are unknown, or thought to be equivalent or better, there is clinical equipoise between the historic intervention and the proposed test intervention.
Clinical Investigation

Involves the use of a Test Article (i.e., drug, device, food substance or biologic) and one or more human subjects. This applies to test articles that require prior submission to the FDA and those that do not if the results of the investigation are intended to be part of an application to the FDA for a research or marketing permit. It does not include the use of FDA approved devices or drugs in routine medical practice. (21 CFR 50.3(c), 21 CFR 56.102(c))

Co-Principal Investigator
The Local PI may designate a Co-Principal Investigator (Co-PI) to assist with local PI responsibilities (e.g., report unanticipated problems, authorize modifications or progress reports). The primary authority and accountability for the conduct of the research may not be assigned or delegated to the Co-PI although they are considered to share equal responsibility for all aspects of the study and are both allowed to submit any IRB required reports/requests.
Coded
(1) Identifying information (such as name or social security number) 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 (i.e., the code); and (2) a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.
Coercion
This occurs when an overt threat of harm is intentionally presented by one person in order to obtain compliance Belmont Report. To be coercive, a subject who refuses must be made worse off than if he or she would have been, if never asked even if the harm is only perceived. Coercion occurs, for example, in cases where retribution is conceivable or perceived by the subject. Examples of coercion include situations where it is implied that continued services are dependent upon participation in the research; or where refusal may affect some future care or outcome. (Inducements (including payment) are not considered coercion for the purposes of UTHSCSA IRB applications of policy. See Undue Influence concerning when judgment may be compromised by financial incentives especially when the subject is not the recipient of the financial incentive).

The IRB must eliminate all sources of coercion.

Cognitively Impaired

While having either a psychiatric disorder (e.g., psychosis, neurosis, personality, or behavior disorder), a developmental disorder (e.g., mental retardation), or a neurological disorder that affects cognitive or emotional functions to the extent that capacity for judgment is significantly diminished may be considered to have a Diminished Autonomous Decision-Making Capacity (DADMC), cognitively impaired should not be automatically considered to be unable to provide valid consent or assent. Additionally, other individuals may be also be considered by the PI or the IRB to be cognitively-impaired or have a Diminished Autonomous Decision-Making Capacity (DADMC) or have limited decision-making ability because they are under the influence of drugs or alcohol, suffering from degenerative diseases affecting the brain, are terminally ill, or have disabling physical handicaps, depending on the circumstances.(Also see Mentally Disabled, Diminished Autonomous Decision-Making Capacity (DADMC), Handicapped)

Collaborating Individual Investigator

This term is limited to collaborative research between an institution with a Federal wide Assurance and an outside researcher. The local implementation of these type agreements is as follows. The research covered by this agreement must be conducted under the direction and supervision of a Health Science Center Principal Investigator or a PI from an HSC-IRB Affiliated institution and the collaborating individual investigator may not be an employee or agent of a HSC-IRB Affiliated Institution and must be conducting the collaborative research activities outside the facilities of the affiliated institution(s). There are two types of collaborating individual investigators:

  1. A collaborating independent investigator is not acting as an employee of any institution with respect to his or her involvement in the research being conducted by the assured institution(s).
  2. A collaborating institutional investigator is acting as an employee or agent of a non-assured institution with respect to his or her involvement in the research being conducted by the assured institution and the non-assured institution that does not routinely conduct human subjects research.
Collector Of Data/Specimens

Anyone who obtains data/specimens from the source and provides it to the Management Center/Repository, see Repository, for storage. A collector (sometimes referred to as collector-investigator) can be from an organization covered by the UTHSCSA IRB or from an organization not covered by the UTHSCSA IRB. The source is where the data/specimens originated (e.g., hospital pathology department, electronic record system, or a research study).

Community-Based Participatory Research

A collaborative research approach that is designed to ensure and establish structures for participation by communities affected by the issue being studied, representatives of organizations, and researchers in all aspects of the research process to improve health and well-being through taking action, including social change (From AHRQ - Agency for Healthcare Research and Quality)

Compassionate Use (Expanded Access)

While the phrase "compassionate use" is commonly used to describe some of the ways of making unapproved products available to patients, the technical term for this is Expanded Access (to investigational drugs or devices for treatment). The use of an investigational drug or device when the primary purpose is to diagnose, monitor, or treat a patient's disease or condition. The distinction between expanded access and the use of an investigational drug (or device) in the usual studies covered under an IND (IDE) is that expanded access uses are not primarily intended to obtain information about the safety or effectiveness of a test article. Although not considered research, the FDA requires IRB approval prior to non-emergency use. (IRB approval required).

Compensation
Compensation is payment for participation in research and should be the same for each subject as opposed to reimbursement which may be different for each subject if for example reimbursement is based on verification of travel expenses, etc.

Note: Compensation could also be considered payment or medical care for study-related injury in certain circumstances.

Compensation For Services Rendered
Compensation for recruitment and screening related activities that are unrelated to whether the participant ultimately enrolls in or completes the research study (such as advertising, administrative and personnel costs) or compensation for the costs of services provided to those individuals who do ultimately enroll. Investigators should be sure to determine a reasonable budget amount that is directly related to the value of the services provided to the study, and to document how that amount was determined.

Examples include the following:

  • the budget might include a portion of the salary of individuals that is related to the time spent recruiting and screening potential research participants (regardless of whether they are successful in recruiting those participants),
  • time spent for subsequent study visits,
  • survey administration, and so forth.

Staff may not be paid a fee for every successful recruitment (e.g., $10 for every participant who signs the consent document to participate in the study). Further, any payments to University for personnel must be reflected in the study budget and in the written agreement that is reviewed by Office of Sponsored Programs (OSP).

Competence

Technically a legal term, used to denote Capacity to act in one's own behalf; the ability to understand information presented, to appreciate the consequences of acting (or not acting) on that information, and to make a choice.

(Also see Mentally Disabled, Diminished Autonomous Decision-Making Capacity (DADMC), Handicapped, Incompetent, Capacity)

.

Competitive Enrollment
Indicates that the local site may enroll more subjects than originally planned by the study sponsor. In this situation, the total number of subjects enrolled study-wide does not change.
Concurrent Control
A concurrent or prospective control is a subject who is not given the treatment or intervention under the study and who is compared with subjects given the treatment under the study. There are three types of concurrent controls: a concurrent control may be given a placebo (concurrent placebo control) or no treatment (a non-treatment concurrent control), or an active drug (a concurrent active control).
Confidential Disclosure Agreement (CDA)

Sometimes called a 'Confidentiality Agreement' or 'Non-Disclosure Agreement', is a legal document which ensures the confidentiality or 'secrecy' of information that one party discloses to another party.

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 in ways that are inconsistent with the understanding of the original disclosure, without permission.
Conflict of Interest

The same threshold is used to evaluate conflicts of interest for investigators, IRB members, and IRB consultants. Examples of conflict of interest include: the member or consultant or an immediate family member is a PI or Sub-Investigator on the protocol and receives any compensation through fees or stock with the protocol sponsor when the value of the interest could be affected by the outcome of the research, non-financial compensation such as Board or Executive relationship related to the research, regardless of compensation, financial interest in the sponsor, product or service being tested, etc.

The general definition is maintained in HOP 10.1.6.

Consent

Consent is a person's voluntary agreement to participate in research or to undergo a diagnostic therapeutic or preventive procedure in contrast to the term Informed Consent which is making this decision with a knowledge and understanding of the relevant information and Legally Effective Informed Consent of the subject or the subject's legally authorized representative as outlined in 45 CFR 46 (Common Rule). Also see Mentally Disabled, Diminished Autonomous Decision-Making Capacity (DADMC), and Handicapped. Also Informed Consent or Legally Effective Informed Consent.

Consultant
A consultant may be defined from multiple perspectives in research. A consultant to the IRB may be a member of the institution or of another institution from whom an IRB may request a written opinion of a protocol submitted to the IRB for review and approval. A consultant may also be defined from the investigators perspective as an individual not on the research team from whom expert assistance is requested allowing the investigator to design, perform or analyze the results of research. The latter is restricted by virtue of not being an official member of the research team (e.g., therefore not being authorized to interact or intervene with human subjects for purposes of collecting research data) and not being authorized access to PHI under HIPAA rules.
Continuing Noncompliance

A pattern of recurring (in one or more protocols simultaneously or over a period of time) or ongoing instances of actions or omissions (Noncompliance) which indicate:

  1. an underlying deficiency in knowledge of the regulations and IRB requirements or;
  2. a possible inability or unwillingness to comply with them. Instances may or may not constitute Serious Noncompliance.
Continuing Review Of Research
Designates the review of requests to re-approve a study for continuation at any time after initial approval is granted.
Controlled Study

Before a new drug or biologic can be marketed, its sponsor must show, through adequate and well-controlled clinical studies, that it is effective. A well-controlled study permits a comparison of subjects treated with the new agent with a suitable control population, so that the effect of the new agent can be determined and distinguished from other influences, such as spontaneous change, "placebo" effects, concomitant therapy, or observer expectations. FDA regulation 21 CFR 314.126 cites five different kinds of controls that can be useful in particular circumstances:

  1. placebo concurrent control
  2. dose-comparison concurrent control
  3. No-Treatment Control, also No-Treatment Concurrent Control.
  4. active-treatment concurrent control, and
  5. historical control

. No general preference is expressed by the FDA for any one type, but the study design chosen must be adequate to the task.

Cooperative Research

In cooperative research, the HSC investigators (employees/agents) are engaged in research or the HSC will receive a direct federal (DHHS) award to conduct human subjects research, even where all activities involving human subjects are carried out by a non-HSC entity (e.g., subcontractor or collaborator).

The HSC PI may be: 1) the Lead PI for the entire collaborative study (e.g., coordinates or directs the research at all study locations), 2) a collaborating investigator under the direction of a Lead PI from another institution, or 3) a collaborating investigator equally sharing the Lead PI responsibility with a local PI.

The Off-Site Research study site may be either: 1) an institution that regularly relies on the HSC IRB for review and continuing oversight of research  Affiliated Institution, or 2) an institution that is not normally affiliated with the HSC IRB. The employees of an off-site location that is part of the cooperative research may or may not be Engaged In Research_Individuals. An off-site institution or facility may be domestic or international and may or may not have its own IRB. Also see Off-Site Research.

Covered Entity

Federal: Health plans, health care clearinghouses and health care providers who transmit any health information in electronic form in connection with a transaction that is subject to federal HIPAA requirements, as those terms are defined and used in the HIPAA regulations 45 CFR Parts 160 and 164.

Texas State: Texas Health and Safety Code, Chapter 181, Medical Records Privacy: (2) "Covered entity" means any person who: (A) for commercial, financial, or professional gain, monetary fees, or dues, or on a cooperative, nonprofit, or pro bono basis, engages, in whole or in part, and with real or constructive knowledge, in the practice of assembling, collecting, analyzing, using, evaluating, storing, or transmitting protected health information. The term includes a business associate, health care payer, governmental unit, information or computer management entity, school, health researcher, health care facility, clinic, health care provider, or person who maintains an Internet site; (B) comes into possession of  PHI: Protected Health Information; (C) obtains or stores protected health information under this chapter; or (D) is an Employee, Agent, or contractor of a person described by Paragraph (A), (B), or (C) insofar as the employee, agent, or contractor creates, receives, obtains, maintains, uses, or transmits PHI: Protected Health Information.

Therefore in Texas, all healthcare providers must comply with the provisions relating to notice of privacy practices and access, amendment and uses and disclosures of protected health information, even if they do not engage in electronic transactions.

Custom Device

A custom device means a device that:

 (1) Necessarily deviates from devices generally available or from an applicable performance standard or pre-market approval requirement in order to comply with the order of an individual physician or dentist;

(2) Is not generally available to, or generally used by, other physicians or dentists;

(3) Is not generally available in finished form for purchase or for dispensing upon prescription;

(4) Is not offered for commercial distribution through labeling or advertising; and

(5) Is intended for use by an individual patient named in the order of a physician or dentist, and is to be made in a specific form for that patient, or is intended to meet the special needs of the physician or dentist in the course of professional practice.

A custom device may be exempt from the requirement for prior submission to the FDA for an IDE unless the device is being used to determine safety or effectiveness for commercial distribution.  Note in some cases where not exempt, a custom device may still qualify for abbreviated requirements, in which case prior submission to the FDA for an IDE may not be required prior to IRB approval.

 

Customer Satisfaction Survey

This refers to surveys of program users to obtain feedback for use by program managers. This is similar to program evaluation.

D
Data Management Centers

Facilities that collect, store, and distribute human data for research purposes.  Data management activities involve three components: (i) the collectors of data; (ii) the data storage and management center; and (iii) the recipient investigators.  Data management centers may be combined with human Repository.

Debriefing

Giving subjects previously undisclosed information about the research project following completion of their participation in the Research.

Deception

The intentional misleading of subjects or the withholding of full information about the nature of the experiment. Misleading or omitted information might include the purpose of the research, the role of the researcher, or what procedures in the study are actually experimental. Deception increases ethical concerns, because it interferes with the ability of the subject to give informed consent. However, deception is arguably necessary for certain types of behavioral research. Because humans act differently depending on circumstances, full knowledge by the subject might bias the results.

Some research can only be conducted without the full knowledge of the research subjects. Yet the use of deception in research raises special problems that the IRB will review closely. One consideration is whether the deception is necessary. Present federal rules prohibit the use of deceptive techniques which place subjects at more than minimal risk.

Debriefing - IRBs expect investigators to debrief subjects who have been deceived during participation in research activities. The debriefing should include a detailed description of the ways in which deception was used. The investigator is responsible for ensuring that the subject leaves the research setting with an accurate understanding of the deception. The debriefing process, including any written materials, should be explained to the IRB as a part of submitted protocols. 

Declaration of Helsinki

An international ethical code first issued in 1964 by the 18th World Medical Assembly in Helsinki, Finland. The Declaration contains 12 basic principles, which are similar to the Nuremberg Code, but represent an expansion of what constitutes acceptable Research and the ethical responsibilities of investigators. Unlike the Nuremberg Code, the Declaration of Helsinki addresses the need for peer review (i.e., IRB review). It is interesting to note that the FDA will not accept foreign data unless the studies in which such data are generated are conducted in compliance with the Declaration of Helsinki (21 CFR 312.20, 46 Fed Reg 8953; Tuesday, January 17, 1981).

Belmont Report: A report consisting of ethical principles and guidelines for protection of human subjects in Research. It was issued April 18, 1979, by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.

Department or Agency Head

(See Department or Agency Heads, http://www.usa.gov/directory/federal/index.shtml) 

If an institution engaged in research is subject to an assurance to said department or agency, federal reporting requirements include reports to said department or agency heads.  Reports are made generally to OHRP when the department is DHHS, but if not DHHS, then reports shall also be made to OHRP in addition to said department or agency head.

Designated Reviewer

One or more experienced reviewers designated by the Chair from among the members of the IRB.  Experience is determined by review of CV and interview with IRB Chair or IRB Director/Associate Director and includes previous experience on IRBs (or other research review committees), or research regulatory/ethical education.

Deviation

A departure from the approved study protocol without prior IRB approval that:

  1. is generally noted or recognized after it occurs, or
  2. if identified before it occurs  cannot be prevented by the investigator (not an intentional deviation); and
  3. has no potential substantive effect on the risks to research participants, and
  4. has no potential substantive effect on the scientific integrity of the research plan or the value of the data collected, and
  5. did not result from willful or knowing misconduct on the part of the investigator(s). 

Examples when the deviation is recognized after it occurs include an investigator’s accidental failure to perform a protocol-required physical, a subject’s failure to self-administer or incorrectly administer the test agent, or a coordinator’s accidental failure to perform a protocol-required blood test on subjects.  An example when the deviation is identified before it occurs but it cannot be prevented includes a research subject who is on a business trip and calls the investigator to announce that she is stuck in a snow storm and cannot be at a study visit scheduled for the next day. The investigator knows in advance that the deviation will occur, but it is not under the investigator’s control, and it is not the investigator’s intent to deviate from the protocol.

Device

A device per the FDA is: "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: 1) recognized in the United States Pharmacopeia–National Formulary (USP–NF http://www.usp.org/USPNF/), or any supplement to them,  2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or  3) intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes."

See also Medical Device

DHHS

The Department of Health and Human Services, under the Secretary of Health and Human Services, is responsible for “Improving the health and well-being of America”.  The National Institutes of Health (NIH), Center for Disease Control (CDC), Health Resources and Services Administration (HRSA) and the Substance Abuse and Mental Health Services Administration are examples of DHHS agencies.  

Also HHS.

Dietary Supplement

Congress defined the term "dietary supplement" in the Dietary Supplement Health and Education Act (DSHEA) of 1994. A dietary supplement is a product taken by mouth that contains a "dietary ingredient" intended to supplement the diet. The "dietary ingredients" in these products may include: vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites. Dietary supplements can also be extracts or concentrates, and may be found in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders. They can also be in other forms, such as a bar, but if they are, information on their label must not represent the product as a conventional food or a sole item of a meal or diet. Whatever their form may be, DSHEA places dietary supplements in a special category under the general umbrella of "foods," not drugs, and requires that every supplement be labeled a dietary supplement.  If a research study is intended to show a certain health benefit, the supplement may be subject to regulation as a drug in that the study is considered to be designed to make a Drug Claim.

Diminished Autonomous Decision-Making Capacity (DADMC)

Refers to a person with limits in either mental capacity or voluntariness.  Mental capacity is the ability to understand and process information.  Voluntariness is the freedom from the control or undue influence of others.  A person has full autonomy when he/she has the capacity to understand and process information, and the freedom to volunteer for research without coercion or undue influence from others.

Subjects with diminished autonomous decision-making capacity who have not been determined to have Impaired Decision-Making Capacity,  Incapacitated or Incompetent, are capable of giving informed consent for research.

Dissent

Behaviors that would indicate an individual does not want to participate (Where seeking assent, dissent behaviors may be interpreted in certain studies as simply moving away, certain facial expressions, head movements, etc.)

Drug

A drug is defined as:

  • A substance recognized by an official pharmacopoeia or formulary.
  • A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.
  • A substance (other than food) intended to affect the structure or any function of the body.
  • A substance intended for use as a component of a medicine but not a Device or a component, part or accessory of a Device.
  • Biological products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical process versus biological process).
Drug Claim

Is that the product is useful in diagnosing, mitigating, treating or curing a specific disease or class of diseases. Nutrient content claims characterize the level of a nutrient in a food (e.g., "high in fiber"). Health claims describe the role of a food substance in reducing the risk of a disease (e.g., "Adequate folate in healthful diets may reduce a woman's risk of having a child with a brain or spinal cord birth defect. "). If a research study is intended to show a certain health benefit, care should be taken to consider whether the research is intended to claim that a Dietary Supplement is useful in diagnosing, mitigating, treating or curing a specific disease or class of diseases, as these are drug claims, not health claims   Dietary supplements that bear such disease claims are subject to regulation as Drug.


The Investigation / Investigational use of approved, marketed Drug products to develop information about the product's safety or efficacy differs from the situation for food products or Nutritional Supplement used in scientific studies to develop information to support a “health claim”. "Investigational use" of an approved drug product suggests the use in the context of a clinical study protocol, see 21 CFR 312.3(b). When the principal intent of the investigational use of a drug or device test article is to develop information about the product's safety or efficacy, submission of an IND or IDE may be required unless certain criteria are met. Under the Dietary Supplement Health and Education Act of 1994 (DSHEA), the dietary supplement manufacturer is responsible for ensuring that a dietary supplement is safe before it is marketed. FDA is responsible for taking action against any unsafe dietary supplement product after it reaches the market as well as reviewing safety information in 75-day premarket notifications for new dietary ingredients, to ensure that such products are reasonably expected to be safe (21 CFR 190.6).  As of August 24, 2007, manufacturers of dietary supplements are required to follow current good manufacturing practices (cGMPs) for dietary supplements, known as the Final Rule cGMPS For Dietary Supplements

E
Elements of Informed Consent

No investigator may involve a human being as a subject in research covered by UTHSCSA policy unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence. The information that is given to the subject or the representative shall be in language understandable to the subject or the representative. No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability for negligence.

 

(a) Basic required elements of informed consent. Except when waiver or alteration is sought and approved by the IRB, in seeking informed consent, the following information is required to be provided to each subject:

(1) A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental;

(2) A description of any reasonably foreseeable risks or discomforts to the subject;

(3) A description of any benefits to the subject or to others which may reasonably be expected from the research;

(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;

(5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;

(6) For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;

(7) An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and

(8) A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

 

(b) Additional elements of informed consent.

When appropriate (in part based on risk and complexity of the study), one or more of the following elements of information are required (NOTE: “required by the IRB when appropriate” means that after approval, they are considered part of the list of required elements that must be considered in the discussion of consent form changes that would not constitute a minor change) to be provided to each subject:

(1) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;

(2) Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent;

(3) Any additional costs to the subject that may result from participation in the research;

(4) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;

(5) A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and

(6) The approximate number of subjects involved in the study.  

Embryo

Early stages of a developing organism, broadly used to refer to stages immediately following fertilization of an egg through implantation and very early pregnancy (i.e., from conception to the eighth week of pregnancy).

Emergency Use

Emergency Use of an unapproved drug (i.e., Emergency IND or Emergency Protocol) or device (Emergency Use)

When an unapproved drug or device was used to treat a patient emergency situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval.  The FDA definition of an emergency is similar but slightly different for drugs and devices.

Drug – either Life-threatening or Severely Debilitating

  • Life threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
  • Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke.
  • For drugs, FDA authorization must be obtained (either telephone or written submission) prior to use of a drug. 

Device – either life-threatening or serious disease or condition that needs immediate treatment

  • For devices, the FDA must be notified within five days.  The FDA recognizes that typically there will not be time to obtain prior IRB approval - must be reported within five (5) working days of initiation of treatment.

 

Emergency Violation

A departure from the approved study protocol without prior IRB approval that occurs in an emergency situation, such as when a departure from the protocol is required to eliminate apparent immediate hazard to the subject. 

  • Examples include withholding study drug in response to a serious adverse event (actual harm) or to avoid a serious harm (risk of harm).
  • Emergency violations are considered Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs) and require prompt reporting to the IRB
Employee

Used as a term within the definition of whether an institution is Engaged In Research_Individuals (in combination “employee or Agent”).  An employee is a person who is hired for a wage, salary, fee or payment to perform work for an employer.  Employees are individuals performing institutionally designated activities and acting on behalf of the institution or exercising institutional authority or responsibility.

Therefore, the critical issue in determining whether an institution is engaged in research is whether the facts indicate that someone is working on the institution’s behalf, on their own behalf, or someone else's behalf, when they are performing the research activities in question.  In certain cases, even though the individual may be employed in whole or in part by an institution, where the individual is performing research activities outside the institution, outside their affiliation with the institution in question, there exists the possibility that he/she may not be considered an employee or agent of the institution in question where the research activity is concerned since they are not “performing institutionally designated activities and acting on behalf of the institution or exercising institutional authority or responsibility” in that regard.  It is possible for a HSC employee to conduct research and not be considered an agent of the university if the research is conducted during non-official duty time, is not in connection with her/his HSC responsibilities, is not being conducted at a HSC facility and the research is not supported by a direct HHS award to the HSC.

The institution however generally reserves the right to determine for themselves whether their employee (in whole or in part) is “performing institutionally designated activities and acting on behalf of the institution or exercising institutional authority or responsibility” in regard to that research and the IRB will generally consider this in determining whether the institution in question is engaged in research.

Employee Of A Covered Entity

A covered entity is responsible for civil monetary penalties resulting from HIPAA violations committed by its agents, including employees, independent contractors, and other members of its workforce, therefore where the word employee is used in research policies where HIPAA may be applied, this definition will include such individuals.  Note that although a covered entity will not be responsible for violations committed by its business associates, the covered entity must have complied with the HIPAA business associate contractual provisions and must not have known of the pattern of activity or practice of the business associate that resulted in the violation, or if aware of such pattern or practice, must have made a good faith effort to take appropriate corrective action. 

Engaged In Research - Institutions

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) the informed consent of human subjects for the research; 4) whenever the institution receives a direct HHS award to support such research, even if all of the human subjects activities will be performed by agents or employees of another institution 45 CFR 46.102(d),(f).

Institutions that are engaged in non-exempt human subjects research that is conducted or supported by any HHS agency must be covered by an Office for Human Research Protections-approved Assurance Of Compliance.  An institution holding an OHRP-approved Federal wide Assurance is referred to as an Assured Institution.

Federally-supported is defined throughout the FWA and the Terms of Assurance as the U.S. Government providing any funding or other support.

An institution may extend its FWA to cover a collaborating individual investigator from a Non-Assured Institutions under certain conditions using the OHRP sample Individual Investigator Agreement (IIA) or a comparable agreement developed by the institution.

For detailed description of when an institution is engaged in research see the OHRP Website, https://www.hhs.gov/ohrp/regulations-and-policy/guidance/guidance-on-engagement-of-institutions/index.html

Engaged In Research_Individuals

The UTHSCSA IRB has defined when an individual is engaged in research based on the OHRP policy guidance of when institutions are engaged.

In general, individuals are considered engaged in a non-exempt human research project (and therefore would need IRB approval) when their involvement in the human subjects research includes any of the following activities:

  • The individual receives an award through a grant, contract, or cooperative agreement directly from HHS for the non-exempt human subjects research (i.e., awardee), even where all activities involving human subjects are carried out by individuals of another institution.
  • The individual intervenes (see Intervention) for research purposes with any human subjects of the research by performing Invasive or Noninvasive procedures (e.g., drawing blood; collecting buccal mucosa cells using a cotton swab; administering individual or group psychotherapy; administering Drug or other treatments; surgically implanting medical Device; utilizing physical sensors; and utilizing other measurement procedures).
  • Individual intervenes for research purposes with any human subject of the research by manipulating the environment (e.g., controlling environmental light, sound, or temperature; presenting sensory stimuli; and/or orchestrating environmental events or social interactions).
  • The individual interacts (see Interaction) for research purposes with any human subject of the research. (e.g., engaging in protocol-dictated communication or interpersonal contact; asking someone to provide a specimen by voiding or spitting into a specimen container; and conducting research interviews or administering questionnaires).
  • The individual obtains the informed consent of human subjects for the research.
  • Individual obtains for research purposes, Identifiable private information or identifiable biological specimens from any source for the research. Obtaining includes, but is not limited to: (a) observing and/or recording private behavior; (b) using, studying, or analyzing for research purposes, identifiable private information or identifiable specimens provided by another institution, and (3) using, studying, or analyzing for research purposes identifiable private information or identifiable specimens already in the possession of the investigators. **Private information or specimens are considered to be individually identifiable when they can be linked to specific individuals by the investigator either directly or indirectly through coding systems.

Examples of when individuals are NOT “Engaged” in non-exempt human research:

- an appropriately qualified laboratory technician from UHS performs routine serum chemistry analyses of blood samples for investigators as part of a commercial service.

- a CTRC employee who obtains blood through a blood draw or collects urine and provides such specimens to investigators as a service.

- a radiology technician from the Dental School performs bite-wing x-rays and sends the results to investigators as a service.

- an individual who only function is to: (a) inform prospective subjects about the availability of the research; (b) provide prospective subjects with information about the research (which may include a copy of the relevant informed consent document)

Enrolled Subject

See Subject Status: Enrolled

Enrollment

The process of seeking eligible participants and obtaining their consent to participate in the research.  Enrollment generally starts with recruitment, leading to screening for eligibility, and consent to enroll in the study.  

See Accrual.

Equitable

Fair or just; used in the context of selection of subjects, to indicate that the benefits and burdens of research are fairly distributed.

Ethical Codes and Statements Of Ethical Principles

There are three major ethical codes that provide general ethical guidelines for the responsible conduct of Research in the United States and which provide the basis for the HHS/FDA regulations on the protection of human Research subjects. It should be noted that HHS/FDA regulations are not intended to serve as an ethical code. In fact, 45 CFR 46.103 requires each institution’s Assurance of Compliance to include a statement of principles for ethical conduct of research which may be based upon “an appropriate existing code, declaration or statement of ethical principles.”

Most institutions use the Belmont Report, Declaration of Helsinki and the Nuremberg Code.

Ex-Officio

Member by virtue of the office held.

Exception

A one-time, intentional action that departs from the IRB approved protocol for a single subject. An exception is identified before it occurs and is under the control of the investigator.

Single subject exceptions may not be initiated without prior IRB review and approval, except where necessary to eliminate apparent immediate hazards to the subject.

Examples include (but are not limited to): enrollment of a single subject who does not meet all eligibility criteria for a study, but the investigator and sponsor have agreed this subject should be enrolled. 

Existing Data/Specimen

Data/specimen in the records or on the shelf prior to IRB review and was created for a reason other than the proposed research. All data included in the request to analyze existing data must exist at the time the research is proposed.

Expedited Research

Non-exempt human research that is eligible for Expedited Review Of Research.

Expedited Review Of Research

Initial Review Of Research or Continuing Review Of Research or review of Modification Of Research, also, modification of amendments, to previously approved research may be conducted by a designated reviewer(s) under the authority of the IRB. 

Modifications to previously approved research are eligible for expedited review if the changes are Minor.

Experimental

Term often used to denote a therapy (Drug, Device, procedure, etc.) that is unproven or scientifically yet to be validated with respect to safety and efficacy. Often used to denote FDA approval has not yet been obtained.  A procedure may be considered “experimental” without necessarily being part of a formal study (research) to evaluate its usefulness.

Exploitation

When one has unfair advantage over another.  Often raised as a concern when paying (offering Inducements to) vulnerable populations (e.g., economically disadvantaged or institutionalized individuals).  Paying economically disadvantaged individuals the same amount as would be paid to others who are not disadvantaged may be seen as unduly influential.  However, paying these individuals less to reduce Undue Influence may be seen as exploitative.

External

As it relates to adverse events and unanticipated problems, external refers to those events or problems experienced by subjects enrolled by investigator(s) approved by IRBs other than the UTHSCSA IRB, to perform research at their respective institutions.  These reports might be received as part of a multicenter clinical trial, because a local site/institution has obtained UTHSCA IRB approval, or even if not part of the same trial if the external event involves an FDA-regulated item under investigation at a local site/institution that has obtained UTHSCA IRB approval.

F
FDA

US Food and Drug Administration, an agency of the Federal government, established by Congress in 1912 and presently part of the Department of Health and Human Services (HHS).

FDA Approved

Approved or cleared by the FDA is a general term in which FDA regulated articles which have been submitted to the FDA have been reviewed and resulted in any of the following:.

Drugs, Biologics: FDA Approved or cleared refers to FDA having issued premarketing approval (PMA)

Devices: FDA Approved or cleared refers to FDA having issued a pre-market approval (PMA); cleared the device for marketing via a Premarket Notification 510(k); considered the device exempt under 510(k) (807.85). 

FDA Regulatory Paths To Market Devices

Three regulatory paths to the market for devices are via Premarket Approval (PMA), Premarket Notification (510(k)), and HDE (see a brief description below).

A device with an approved PMA is approved for marketing based on valid scientific evidence and reasonable assurance that the device is safe and effective for its intended use.  Once approved, it can be marketed and sold within its approved labeling.  There are no restrictions on the price, and it can be used by anyone qualified to use the device.

A 510(k) device is cleared for marketing when the agency finds that it is at least as safe and effective, that is, substantially equivalent, to a legally marketed device that is not required to have a PMA. Using valid scientific evidence, submitters compare their device to one or more similar legally marketed devices, comparing the indications for use and technological characteristics.

A device with an approved HDE is approved for marketing, but the approval is based on evidence of safety and probable benefit. The Act and implementing regulations exempt HUDs from the requirement to establish a reasonable assurance of effectiveness. The HUD is intended for use in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 individuals in the US per year.

FDA-Regulated Human Research

Human research will be considered FDA-regulated and therefore may be subject to FDA regulations (including but not limited to those specific to:

  1. informed consent
  2. IRB review and
  3. drugs, biologics or devices as appropriate) when the human research activity is Human Research according to FDA Regulations.

Human research is considered FDA regulated when the activity involves an FDA-regulated test article and the activity involves human participants.   

An activity involves an FDA regulated test article when one or more of the following is true:

  • The activity involves the use of a Drug, or other than the use of a marketed drug in the course of medical practice; or
  • The activity involves the use of a Device to evaluate safety or effectiveness of that device; or
  • 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.

An activity involves human participants when one or more of the following is true:

  • The test article will be used on one or more humans; or
  • Data obtained from 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 use of a 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.
FDA-Regulated Product

Used in human research involves any product (e.g., food including dietary supplements that bear a nutrient content claim or a health claim, infant formulas, food and color additives, drugs for human use, biological products for human use, medical device for human use or electronic products, ) used in or being developed for use in man. The FDA is responsible for determining whether sufficient evidence exists for such products to be claimed as safe and effective.  For the purposes of human research, the term is often used to clarify when human research, in addition to being subject to other federal regulations, also falls under the FDA research regulations.

Federal Wide Assurance (FWA)

The Federalwide Assurance (FWA) is the only type of new Assurance Of Compliance accepted and approved by OHRP for institutions engaged in non-exempt human subjects research conducted or supported by HHS (DHHS).  Under an FWA, an institution commits to HHS that it will comply with the requirements set forth in 45 CFR part 46, as well as the Terms of Assurance.

Fetus

The developing human organism from the time of implantation until delivery; generally refers to later phases of development.

Final Rule cGMPS For Dietary Supplements

The U.S. Food and Drug Administration issued the final rule establishing regulations to require current good manufacturing practices (CGMPs) for dietary supplements. The final CGMP is effective August 24, 2007. To limit any disruption for Dietary Supplement produced by small businesses, the rule has a three-year phase-in for small businesses. Companies with more than 500 employees have until June 2008 to comply, companies with less than 500 employees have until June 2009 to comply, and companies with fewer than 20 employees have until June 2010 to comply with the regulations.  If a research study is intended to show a certain health benefit the a dietary supplement may be subject to regulation as a Drug in that the study is considered to be designed to make a Drug Claim.

Financial Records

Specified financial information is maintained to support accurate billing of clinical services associated with a research study, including:

  1. Coverage Analysis (Billing Grid and Qualifying Clinical Trial form if applicable); CMS (Centers for Medicare and Medicaid Services) requires the use of specific HCPCS modifier codes for billing in clinical trials.
  2. Internal Budget prepared in the Research Activity Billing Trigger template (RABT)
  3. Feasibility Assessment – a document outlining the scientific value and feasibility of performance of the protocol, its procedures and services.

Also Study Financial Records.

Financial Sponsor

The agency, organization, company, or person that pays for the trial.

Finder's Fee

Compensation of any type (e.g. cash, cash equivalents, office or medical supplies, educational stipends, gift certificates, travel cost in excess of normal reimbursement costs, or anything else of value) to an individual made in exchange for referral or recruitment of a participant to a research study.  Such payments, generally, are made to study team members who are in a position to identify potential participants who might qualify for enrollment into a study.  The finder's fee is paid to the study team member for each participant they recruit who actually enrolls in the study.  It is not permissible to pay or accept "finder's fees" at UTHSCSA.  Additionally, it is not permissible for UTHSCSA employees or students to accept personal payments from sponsors or others in exchange for accelerated recruitment or referrals of patients. This does not include compensation for services rendered which include screening and referral activity unrelated to whether the participant ultimately enrolls in or completes the research study.

Finding Of Noncompliance

Noncompliance that is supported by a preponderance of evidence.  A finding of noncompliance may exist because there is clear evidence, an admission supported by evidence, or an investigation into an allegation has determined the allegation to be supported by a preponderance of evidence.

G
Generalizable Knowledge

Knowledge that is universally or widely applicable. 

Guardian

An individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care when general medical care includes participation in research. [21 CFR §50.3(s)]

A guardian also means an individual who is authorized to consent on behalf of a child to participate in research. [21 CFR§50.3(s)]

Guardian means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care. [45 CFR §46.402(e)]

H
Halt

(to research) is a cessation of some or all research activities voluntarily initiated by the Principal Investigator or sponsor (for example temporarily stopping enrollment or other research procedures, placing the study “on hold”).  This does not constitute IRB Suspension Of Research or Termination. 

Handicapped

Handicapped person means any person who has a Physical Or Mental Impairment that substantially limits one or more major life activities, has a record of such an impairment, or is regarded as having such an impairment by criteria (for evaluating the subject during the screening process or scheduled evaluations during a research study) established in the research protocol that represent a need for additional safeguards for vulnerable populations described by the PI in the research protocol or as determined by the IRB (possibly including Diminished Autonomous Decision-Making Capacity (DADMC) if the physical or mental impairment leads to a decreased capacity to make their wishes known).

As used in this research definition of handicapped, the phrase:

  1. Physical or mental impairment includes as described below impairment that represent a need for additional safeguards for vulnerable populations described by the PI in the research protocol or as determined by the IRB (possibly including Diminished Autonomous Decision-Making Capacity if the physical or mental impairment leads to a decreased capacity to make their wishes known)-
    • Any physiological disorder or condition, cosmetic disfigurement, or anatomical loss affecting one or more of the following body systems: Neurological; musculoskeletal; special sense organs; respiratory, including speech organs; cardiovascular; reproductive; digestive; genitourinary; hemic and lymphatic; skin; and endocrine; that represent a need for additional safeguards for vulnerable populations 
    • Any mental or psychological disorder, such as mental retardation, organic brain syndrome, emotional or mental illness, and specific learning disabilities. The term "physical or mental impairment" includes, but is not limited to, such diseases and conditions as orthopedic, visual, speech, and hearing impairments, cerebral palsy, epilepsy, muscular dystrophy, multiple sclerosis, cancer, heart disease, diabetes, mental retardation, emotional illness, and drug addiction and alcoholism that represent a need for additional safeguards for vulnerable 
       
  2.  Major Life Activities includes functions such as caring for one's self, performing manual tasks, walking, seeing, hearing, speaking, breathing, learning, and working.
Health Information

Any information, whether oral or recorded in any form or medium, that (1) is created or received by a health care provider, health plan, public health authority, employer, life insurer, school or university, or health care clearinghouse; and (2) relates to the past, present, or future physical or mental health or condition of an individual; the provision of health care to an individual; or the past, present, or future payment for the provision of health care to an individual. This constitutes a larger set of information which may be broken down into that health information which is not identifiable and that which is Identifiable Health Information. See Individually Identifiable Health Information.

Health Science Center (HSC)

Is the abbreviation of The University of Texas Health Science Center at San Antonio

Health Surveillance

Is an ongoing part of the medical care and public health care functions closely integrated with timely dissemination of these data to those responsible for preventing and controlling disease or injury (may include emergent or urgently identified or suspected imminent health threats to the population to document the existence and magnitude).  Generally not considered a research activity.

HHS (DHHS)

Health and Human Services (HHS) or the Department of Health and Human Services DHHS, under the Secretary of Health and Human Services is responsible for “Improving the health and well-being of America”.  The National Institutes of Health (NIH), Center for Disease Control (CDC), Health Resources and Services Administration (HRSA) and the Substance Abuse and Mental Health Services Administration are examples of HHS agencies.

HUD Clinical Investigation

Once a HDE is granted, and if a clinical investigator or the HDE holder wants to conduct a clinical investigation (i.e., research study) using the HUD.

An HDE holder may collect safety and effectiveness data for the HDE-approved indication(s) without an IDE.  While this is a clinical investigation, FDA considers the study exempt from the requirement of 21 CFR Part 812 as long as the HUD is being studied in accordance with the approved indication(s) described in labeling, because the HUD as such is legally marketed and can be lawfully shipped without an IDE. See 21 CFR 812.1. IRB approval (21 CFR Part 56) and informed consent (21 CFR Part 50) are still required for these studies, however, because they are FDA-regulated clinical investigations.

 

Human Subject

“An individual who is or becomes a participant in Research, either as a recipient of the Test Article or as a control. A subject may be either a healthy individual or a patient.” (21 CFR 56.102(e)) For research involving a Medical Device, a human subject means “A human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control. A subject may be in normal health or may have a medical condition or disease.” (21 CFR 812.3(p)) 

Human Subject Research

Research involving Human Subject.

Humanitarian Device Exemption (HDE)

Is an application to the FDA that is similar to a premarket approval (PMA) application, but is exempt from the effectiveness requirements of sections 514 and 515 of the Food, Drug, and Cosmetic Act (the Act).  FDA approval of an HDE authorizes an applicant to market a Humanitarian Use Device Humanitarian Use Device (HUD), subject to certain profit and use restrictions set forth in section 520(m) of the Act (i.e., HUDs cannot be sold for profit except in narrow circumstances and they can only be used in a facility after an IRB has approved their use in that facility, except in certain emergencies).  An HDE approval is based on safety and probable benefit.  HDEs are exempt from the requirement to provide a reasonable assurance of effectiveness as required in Investigational Device Exemption (IDE) applications.  The person who obtains the Humanitarian Device Exemption (HDE) from FDA is the HDE holder. 

The FDA will consider an HDE application for any of the following:

  • no comparable device is available to treat or diagnose the disease or condition; or
  • a comparable device is available under another approved HDE application; or
  • a comparable device is being studied under an approved Investigational Device Exemption (IDE) (21 CFR 814.104(b)(2)).

If a comparable device with the same indications for use is marketed through either the premarket approval (PMA) process or the premarket notification (510(k)) process, a new HDE for a HUD device cannot be granted by the FDA.

Humanitarian Use Device (HUD)

Is a Medical Device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year.  

I
Identifiable

Identifies the individual; or with respect to which there is a reasonable basis to believe the information can be used to identify the individual.  Not all identifiable information is necessarily Identifiable Health Information. Individually Identifiable Health Information.  This would only be the case if it was actually associated with Health Information.

Identifiable Data/specimens are generally identifiable health information and are either:

Coded samples – sometimes termed “linked” or “identifiable”, are those from identified materials with a code rather than a name or any other personal identifier such as a patient number, where the source retains information linking the code to particular human materials or where the extent of the clinical or demographic information provided with the sample is sufficient that the investigator, the repository, or a third party could link the biological information derived from the Research with material from a particular person or a very small group of identifiable persons.  If the key is destroyed or not accessible by the investigator or repository then it is possible that these samples would then be considered de-identified coded samples but they would be identifiable health information until this occurred.

or

Identified samples - are those samples supplied from identified materials with a personal identifier sufficient to allow the biological information derived from the research to be linked directly, with the particular person from whom the material was obtained.

Identified Prospective Subject

See Subject Status.

Immediately Life-Threatening Disease

Means a stage of a disease in which there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment.

Impaired Decision-Making Capacity

A person lacking the ability based on reasonable medical judgment to understand and appreciate the nature and consequences of a treatment decision, including the significant benefits and harms of and reasonable alternatives to any proposed treatment decisions.  Also see Incapacitated.  Subjects who have impaired decision-making capacity are not capable of giving informed consent for research but may be capable of providing assent. 

For VA Research, the determination that a person has impaired decision-making capacity must be made by the practitioner (a psychiatrist or licensed psychologist if based on mental illness diagnosis), in consultation with the chief of service after appropriate medical evaluation indicates the participant lacks capacity and is unlikely to regain it within a reasonable period of time.  This determination must be documented in the person’s medical record in a signed and dated progress note.

In Vitro

Literally, “in glass” or “test tube” – used to refer to processes that are carried out outside the living body, usually in the laboratory, as distinguished from in vivo.

In Vivo

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.

Incapacitated

A person lacking the ability based on reasonable medical judgment to understand and appreciate the nature and consequences of a treatment decision, including the significant benefits and harms of and reasonable alternatives to any proposed treatment decisions.  Also see Impaired Decision-Making Capacity.   Subjects who are incapacitated are not capable of giving informed consent for research but may be capable of providing assent. 

For VA Research, the determination that a person is incapacitated must be made by the practitioner (a psychiatrist or licensed psychologist if based on mental illness diagnosis), in consultation with the chief of service after appropriate medical evaluation indicates the participant lacks capacity and is unlikely to regain it within a reasonable period of time.  This determination must be documented in the person’s medical record in a signed and dated progress note.

Incidents, Experiences OR Outcomes

Are general sources of information that may indicate an actual harm has occurred or that there is an increased risk of harm

Information of actual harm can be:

  • an Adverse Event (encompassing both physical and psychological harms); or
  • a problem or event not considered an adverse event** (encompassing social or economic harms)

Information indicating an increased risk of harm is:

  • a problem or event not considered an adverse event** that place subjects or others at increased Risk of harm than was previously known or recognized, but no harm occurred.

[** referred to as “non-AE incidents, experiences or outcomes”]

Incompetent

Referring to a person who is not able to manage his/her affairs due to mental deficiency (low IQ, deterioration, illness or psychosis) or sometimes physical disability and who has been appointed a guardian or conservator by a legal determination. 

Persons determined to be legally incompetent are unable to provide Informed Consent or Legally Effective Informed Consent.   They may be able to provide assent.

[Incompetent is legal term removed from Texas Probate Code in 1993 but still used in various federal regulations (e.g., 38 CFR concerning guardian).  Texas state law now uses the term “Incapacitated.”]

Individual Investigator Agreement (IIA)

An agreement between an Assured Institution and a Collaborating_Individual_Investigator or Collaborating Institutional Investigator that permits the assured institution to extend its Federalwide Assurance to cover the investigator.

Individually Identifiable Health Information

Information that is a subset of Health Information, see Private Information including demographic information collected from an individual, and (1) is created or received by a health care provider, health plan, employer, or health care clearinghouse; and (2) relates to the past, present, or future physical or mental health or condition of an individual; the provision of health care to an individual; or the past, present, or future payment for the provision of health care to an individual; and (a) that identifies the individual; or (b) with respect to which there is a reasonable basis to believe the information can be used to identify the individual.

Individually Identifiable Private Information

Private Information or Specimens are individually identifiable when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems. 

 

Private information or specimens are not individually identifiable when they cannot be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems. For example, if the following conditions are both met:

  1. the private information or specimens were not collected specifically for the currently proposed research project through an interaction or intervention with living individuals; and
  2. the investigator(s) cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain because, for example:
    • the key to decipher the code is destroyed before the research begins;
    • the investigators and the holder of the key enter into an agreement prohibiting the release of the key to the investigators under any circumstances, until the individuals are deceased (note that the HHS regulations do not require the IRB to review and approve this agreement);
    • there are IRB-approved written policies and operating procedures for a repository or data management center that prohibit the release of the key to the investigators under any circumstances, until the individuals are deceased; or
    • there are other legal requirements prohibiting the release of the key to the investigators, until the individuals are deceased.
Inducements

Are offers that get people to do things they may not otherwise do.  Inducements or incentives, rewards or payments may be acceptable depending on the population, level and type but they may also be considered Undue Influence if the reward/payment is so large as to persuade the person to take undue risks or volunteer against their better judgment. Another concern about undue influence (unacceptable inducements) is they can result in a subject lying or concealing information that may otherwise exclude them from the research.  As a result, if the study involves no risk or minimal risk, the concern over undue influence is reduced.  The IRB should consider ways to reduce the influence of payments or rewards that undermine a person’s capacity to exercise free choice and could invalidate consent.  The IRB should balance the need to reduce undue influence with the need to avoid Exploitation of populations.

 

Or, Potential For Undue Influence.

Informed Consent

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 preventive procedure. For the purposes of contrast, “Consent,” is voluntary agreement without mention of whether full knowledge was imparted or understanding took place and “Legally Effective Informed Consent” is obtained when a subject or a subject's legally authorized representative as outlined in 45 CFR 46 (Common Rule) agrees to participate. Informed Consent (often used as a variation of “consent” or “legally effective informed consent”) is obtained only after the prospective subject is provided sufficient opportunity to consider whether or not to participate.  Neither, informed consent nor legally effective informed consent can be obtained from a subject with  Diminished Autonomous Decision-Making Capacity (DADMC) for research purposes (Surrogate Consent or Legally Authorized Representative (LAR) is obtained in such a case). 

Initial Review Of Research

The review of new, not previously approved research including new studies tabled/deferred at previous meetings.  

Also Initial Review.

Innovative Therapy

Innovative therapy represents a deviation from standard medical practice.  Physicians are free to innovate if the innovative procedure is applied solely to enhance the well-being of their patient.  However, when innovative therapy differs significantly from routine practice it should be viewed and treated as experimental, with appropriate safeguards in place to protect the rights and welfare of the patients (subjects) (e.g., RSRB review, informed consent, etc.).  In order to validate innovative therapy, the innovative procedure should be subjected early on to an evaluation via a formal  Research protocol.

Institution

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

Institutional Review Board (IRB)

The institutional review board is a federally mandated, institution-designated regulatory body empowered to oversee Human Subject Research.

  • Internal IRB – for the HSC, the HSC IRB’s
  • External IRB – for the HSC, any IRB managed by another organization
Institutionalized

Confined, either voluntarily or involuntarily, in a facility for the care of the mentally or otherwise disabled (e.g., a psychiatric hospital, home or school for the retarded).

Also, Mentally Disabled.

Interaction

Includes communication or interpersonal contact between investigator and subject.

Internal

As it relates to adverse events and unanticipated problems internal refers to those events or problems experienced by subjects enrolled by the investigator(s) approved by the UTHSCSA IRB to perform research at their respective institutions.

Also, AE's or UPIRSOs.

Intervention

Includes both physical procedures by which data are gathered (for example, venipuncture) and manipulation of the subject or the subject’s environment that are performed for research purposes.

Interventional Study

A clinical study in which participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. The assignments are determined by the study protocol. Participants may receive diagnostic, therapeutic, or other types of interventions.

Also, Clinical Trial; Study Type.

Interventional Study Phase

The phase of investigation including:

 

Phase 0: exploratory trials, involving very limited human exposure, with no therapeutic or diagnostic intent (e.g., screening studies, microdose studies). See FDA guidance on exploratory IND studies for more information.

Phase 1: includes initial studies to determine the metabolism and pharmacologic actions of drugs in humans, the side effects associated with increasing doses, and to gain early evidence of effectiveness; may include healthy participants and/or patients

Phase 1/Phase 2: for trials that are a combination of phases 1 and 2

Phase 2: includes controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks

Phase 2/Phase 3: for trials that are a combination of phases 2 and 3

Phase 3: includes expanded controlled and uncontrolled trials after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide an adequate basis for physician labeling

Phase 4: studies of FDA-approved drugs to delineate additional information including the drug's risks, benefits, and optimal use

 

Interventional Study Purpose

The reason for the protocol. 

  • Treatment: protocol designed to evaluate one or more interventions for treating a disease, syndrome or condition
  • Prevention: protocol designed to assess one or more interventions aimed at preventing the development of a specific disease or health condition
  • Diagnostic: protocol designed to evaluate one or more interventions aimed at identifying a disease or health condition
  • Supportive Care: protocol designed to evaluate one or more interventions where the primary intent is to maximize comfort, minimize side effects or mitigate against a decline in the subject's health or function. In general, supportive care interventions are not intended to cure a disease.
  • Screening: protocol designed to assess or examine methods of identifying a condition (or risk factors for a condition) in people who are not yet known to have the condition (or risk factor).
  • Health Services Research: protocol designed to evaluate the delivery, processes, management, organization or financing of health care.
  • Basic Science: protocol designed to examine the basic mechanism of action (e.g., physiology, biomechanics) of an intervention.
Invasive

Invasive is considered to be entering the body via puncture or incision or requiring numbing or sedative medication for insertion into the body. 

Note: Noninvasive does not always constitute minimal risk. 

Examples of invasive procedures are those that:  1) penetrate or pierce the skin (except for simple venipuncture) or mucous membranes of the body, the ocular cavity, or the urethra, or (2) enter the ear beyond the external auditory canal, the nose beyond the nares, the mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina beyond the cervical os.

Clarification: For procedures already being performed for standard care purposes: It is possible to consider a procedure to be noninvasive if performed in addition to the usual activities performed during a standard care invasive procedure so long as the additional activity does not require further puncture or incision or require additional numbing or sedative medication for further insertion into the body. This does not mean the procedure qualifies as minimal risk simply by meeting the definition of noninvasive as extending the standard care procedure time or investigational nature of a device used in that activity might add risk to the standard procedure. Risk determination is a separate criterion for the purposes of Expedited Review for example or for the purposes of determining whether a Diagnostic device is exempt from submission to the FDA for an IDE. 

Investigation / Investigational

Investigation is a term used by the FDA concerning activities subject to FDA regulations and means a Clinical Investigation (any experiment that involves a Test Article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the FFD&C Act, or is not subject to requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be submitted later to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit) or Research involving one or more subjects to determine the safety or effectiveness of a drug, biologic or device.  The terms research, clinical research, clinical study, study, and Clinical Investigation are deemed to be synonymous for purposes of the FDA.

Investigational Device

Includes unapproved devices and some approved devices: 

A Device not yet approved for marketing by the FDA when used in research, see Clinical Investigation, involving one or more subjects to determine the safety or effectiveness of a device is an investigational device. 

Also, any medical device, including approved devices or transitional devices (devices previously approved as a drug (before 1976)), are  Investigation / Investigational devices if they are the object of a Clinical Investigation (abridged: research involving one or more subjects to determine the safety or effectiveness of a device).  They may then be considered exempt from certain FDA regulations (e.g. 21 CFR 812) in certain circumstances but they remain investigational devices if they are the object of the study and the study in most cases remains subject to other FDA regulations (e.g., 21 CFR 50 and 56).

Investigational Device Exemption (IDE)

An IDE is like an IND for a new drug. It allows an unapproved medical Device to be shipped for use for Investigation / Investigational purposes. It is also required when an FDA approved or FDA cleared device is used in a Clinical Investigation for the purposes of testing safety or effectiveness (unless exempt from prior submission for the IDE or where abbreviated requirements may be allowed) where the intent is for the data to be included in a submission to the FDA or may later be held for inspection by the FDA.  FDA has 30 days to review the IDE request and notify the sponsor if approval is withheld. The requirements for an IDE are similar to an IND and are designed to ensure that the sponsor conducts adequate preclinical testing, selects appropriate subjects for clinical Research, obtains IRB approval, obtains adequate informed consent, uses qualified investigators, monitors the investigation, and collects data promptly. In deciding whether to approve an IDE, the FDA focuses on how the investigation will be conducted rather than on a precise risk-benefit analysis. The IDE regulation is 21 CFR 812 (45 Fed Reg 3751, January 19, 1980).

Under abbreviated requirements when medical Device are classified as non-significant risk (NSR) by the sponsor and the IRB agrees, the investigation may begin without prior submission of an IDE.  Under the abbreviated IDE requirements the device is considered to have an approved IDE issued by the IRB.  If, however, the IRB determines the Device to be a significant risk (SR) device, an IDE must be submitted and approved before the study can be initiated.  In this circumstance, it does not matter if the sponsor has classified the device as NSR.

 

Investigational Drug

Includes those substances in any of the clinical stages of evaluation which have not been released by the FDA for general use or cleared for sale in interstate commerce. An investigational drug may also be defined by one of the following:

  1. A drug in any of the clinical stages of evaluation (Phase I, II, III) which has not been released by the FDA for general use or cleared for sale in interstate commerce.
  2. Any commercially available drug proposed for a new use.
  3. A new dosage form or method of administration.
  4. A commercially available drug which contains a new component such as an excipient, coating or menstruum.
  5. A new combination of two or more commercially available drugs.
  6. A combination of commercially available drugs in new proportions.

 

Investigational New Drug - Exemption (IND)

An IND (Form FDA 1571) is an application filed (usually by the sponsor) with the FDA that includes a detailed description of the planned investigation including Phase I, II and III studies. The application must also contain names and addresses of the investigators and identification of the IRB responsible for initial and continuing review and approval of the proposed study. The FDA has 30 days to review the IND and notify the sponsor if approval is withheld. The applicable FDA regulation for INDs is 21 CFR 312.1. Each investigator who will participate in the study must provide the sponsor with a completed Statement of Investigator (Form FDA 1572) as required by 21 CFR 312.53(c). This form addresses investigator training and experience as well as investigator commitments.

Investigational New Drug Application

Once the clinical evaluation of a drug is completed, an NDA must be submitted to FDA to obtain approval to market the drug. The NDA regulations are 21 CFR 314. In an NDA review there is a much closer scrutiny of the data by FDA to ensure safety and efficacy. In contrast, the IND review requires only enough evidence of effectiveness to justify a clinical trial.

Investigator-Initiated INDs/IDEs

See Sponsor-Investigator.

IRB Authorization Agreement (IAA)

An agreement between two institutions where one institution agrees to rely on the IRB from the other institution for the review and continuing oversight of its human research.  The agreement can cover all human research conducted by the institution, all human research conducted under the institution’s Federalwide Assurance (FWA), a subset of research studies, or a single study.  A copy of the IAA is filed with Office of Human Research Protections (OHRP) for Assured Institution.

IRB of Record

Denotes the IRB responsible for approval of a specific research study at a given institution.  An institution may rely on any number of IRBs within or outside the institution.  If an institution relies on an external IRB, an IRB Authorization Agreement must be in effect.

IRB Project Type

Given the various regulatory responsibilities, there are different types of projects that require IRB approval (not just research) including:

Human Subjects Research – research involving living individuals whenever the investigator obtains private identifiable private information or interacts/intervenes for research purposes.  (IRB approval required)

Human Subjects Data or Specimen Repository – a special category of human subjects research where data and/or specimens are stored in a bank or repository for use in future research studies.  (IRB approval required)

Non-Regulated Research determination – activities that do not meet the regulatory definition of research and do not require IRB approval.  Examples include quality improvement, health surveillance, and program evaluation.  This application should be submitted if you would like an official determination letter from the IRB Office.

Research Not Involving Humans – research that does not involve “human subjects” as defined by the IRB regulations and does not require IRB approval.  Examples include research using leftover, de-identified specimens, cell lines and de-identified materials from a repository.  This application should be submitted if you would like an official determination letter from the IRB Office.

Exempt Determination – certain minimal risk human subject research is exempt from the IRB regulations.  Examples include retrospective chart review if not recording identifying information, survey of adults, and research comparing educational methods. This application should be submitted if you would like an official determination from the IRB Office.

Treatment Use of a Humanitarian Device – humanitarian devices receive a specific FDA approval (HDE) for treating rare conditions.  Although not considered research, the FDA requires IRB approval prior to non-emergency use. (IRB approval required)

Expanded Access to Investigational Drugs or Devices for Treatment – refers to use of an investigational drug or device when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition.  The distinction between expanded access and the use of an investigational drug (or device) in the usual studies covered under an IND (IDE) is that expanded access uses are not primarily intended to obtain information about the safety or effectiveness of a test article.  Although not considered research, the FDA requires IRB approval prior to non-emergency use. (IRB approval required).

Emergency Use of an unapproved drug (Emergency IND or Emergency Protocol) or device (Emergency Use)

  • This application should be submitted to notify the IRB that an unapproved drug or device was used to treat a patient emergency situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval.  The FDA definition of an emergency is similar but slightly different for drugs and devices.
  • Drug – either life threatening or severely debilitating
    • Life threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
    • Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke.
    • For drugs, FDA authorization must be obtained (either telephone or written submission) prior to use of a drug.    
  • Device – either life-threatening or serious disease or condition that needs immediate treatment
    • For devices, the FDA must be notified within five days.  The FDA recognizes that typically there will not be time to obtain prior IRB approval - must be reported within five (5) working days of initiation of treatment.  
K
Key Personnel

Term used in federal grant applications to indicate individuals subject to additional conflict of interest rules and reporting.  In general, key personnel includes any individual responsible for the design, conduct, and reporting of research for a given study.  Key personnel may or may not include the following: study staff, investigators, individuals engaged in human research and individuals not engaged in human research.

L
Legally Authorized Representative (LAR)

A person authorized either by statute or by court appointment to make health care decisions on behalf of another person who is Incapacitated,  Incompetent, or has Impaired Decision-Making Capacity.  It is not always required that Informed Consent to participate in research be given by the legally authorized representative if another form of Surrogate Consent is available such as family member consent depending on applicable state law and institutional policy.  Consent by a legally authorized representative should involve all the same considerations that informed consent from a competent subject involves. 

See the IRB “Informed Consent Policy and Procedure” document for specific information on who may serve as a legally authorized representative or surrogate.

Legally Effective Informed Consent

Is consent of a subject, or if the subject is incapacitated, incompetent, or has impaired decision-making capacity, then the consent of the subject's  Legally Authorized Representative (LAR) or surrogate as outlined in 45 CFR 46 (Common Rule). “Consent” is often used as a short version of “Informed Consent” or “Legally Effective Informed Consent”. It is not always required that Informed Consent to participate in research be given by the legally authorized representative if another form of Surrogate Consent is available such as family member consent depending on applicable state law, institutional policy and the determination of the IRB. Someone who is Incapacitated, Incompetent, or has Impaired Decision-Making Capacity cannot give legally effective informed consent for research purposes (a Surrogate Consent or Legally Authorized Representative (LAR) is obtained in such a case).

 

Life-threatening

Diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the recipients must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.

M
Major Change Or Modification

(to previously approved research)

Any change that does not meet the definition of a minor change or modification to previously approved research, and/or 

A modification which in the judgment of the reviewer fundamentally alters the judgments relied upon to make determinations on any of the criteria for IRB approval under 45CFR 46.111 and/or involves modifications which would not be eligible for expedited review (considering risk and expedited review categories 1-9) 

Major, Non-Emergency Deviations

See Deviation

Mature Minor

Someone who has not reached adulthood (as defined by state law), but who may be treated as an adult for certain purposes (e.g., consenting to certain types of medical care).

Medical Device

The Food and Drug Administration (FDA) defines a medical Device as:

An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is

º    recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them

º    intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals. 

º     intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes.

 

Before 1976, medical devices could be marketed without review by the FDA. However, in 1976 the medical device amendments of 1976 to the Federal Food, Drug and Cosmetic Act were passes in order to ensure that new devices were safe and effective before they were marketed. The FDA regulations which govern medical devices are 21 CFR 812, 814, 860, 861.

Mental Capacity

See Capacity.

Mentally Disabled

Having either a psychiatric disorder (e.g., psychosis, neurosis, personality, or behavior disorder), a developmental disorder (e.g., mental retardation), or a neurological disorder that affects cognitive or emotional functions to the extent that it results in a Diminished Autonomous Decision-Making Capacity (DADMC).  Neither, informed consent nor legally effective informed consent can be obtained from a subject with  Diminished Autonomous Decision-Making Capacity (DADMC) for research purposes (Surrogate Consent or Legally Authorized Representative (LAR) is obtained in such a case).

See Cognitively Impaired, Diminished Autonomous Decision-Making Capacity (DADMC), Handicapped.

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.” For VA studies the determination includes tangible or intangible risk.

Examples of research activities that may well be determined by the Board to involve no more than minimal risk include collection of blood samples from healthy, non-pregnant adults by venipuncture in amounts not exceeding 450 ml in an eight-week period and no more often than two times per week; electrocardiography; electroencephalography; and moderate exercise by healthy subjects.(Examples are not automatically deemed to be of minimal risk simply because they are included on this list).

While the harms and discomforts ordinarily encountered differ widely among individuals and individual populations, an ethically meaningful notion of "harms and discomforts ordinarily encountered" should reflect "background risks" that are familiar and part of the routine experience of life for "the average person" in the "general population." It should not be based on those ordinarily encountered in the daily lives of the proposed subjects of the research or any specific population.

Minimizing Risk

Federal regulations describe minimizing risks to subjects (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.  Therefore using the least number of procedures possible to answer the research question is a method of minimizing risk when additional procedures are required.  Addressing whether you have minimized risk requires addressing all three aspects of this definition.

Minor

A person who has not attained the legal age of majority under the applicable law of the jurisdiction in which the Research will be conducted (18 years in the state of Texas), and therefore as a general rule cannot consent to treatment or procedures involved in research. However, “Mature Minor” can consent for certain types of treatment.  For the purposes of research performed under DHHS regulations Viable Neonates are considered children, whereas neonates of uncertain viability and Nonviable Neonates require additional protections under section B of 45 CFR 46. See the IRB “Informed Consent Policy and Procedure” document for specific information on minors and if/when they can give consent to participate in research.

Minor Change or Modification

(to previously approved research)

A modification which in the judgment of the reviewer does not fundamentally alter the judgments relied upon to make determinations on any of the criteria for IRB approval under 45CFR 46.111 does not adversely impact the overall risk-benefit relationship for the subjects of the research (based on new or modified risk information).

For studies originally approved by expedited review, a minor change is a modification that does not change the study’s eligibility for expedited review (considering risk and expedited review categories 1-9).

Minor Or Administrative Protocol Deviations

See Deviation

Modification Of Research

See Amendment.

Multi-Site Research

Research conducted at more than one location and under the jurisdiction of only one IRB.

Multicenter Research

Research conducted at more than one location and under the jurisdiction of more than one IRB.

N
National Commission

In July 1974, in response to widespread publicity concerning unethical human experimentation in the U.S. (e.g., Tuskegee Syphilis Study, Jewish Chronic Diseases Hospital Study, Willowbrook Study, San Antonio Contraceptive Study), Congress passed the National Research Act (Public Law 93-348), which established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The charge of the Commission was to conduct a comprehensive investigation and study to identify the basic ethical principles which should underlie the conduct of biomedical and behavioral Research involving human subjects. Although both FDA and HHS had regulations for the protection of human subjects, they were obviously inadequate in light of the many human subject abuses that occurred in medical and behavioral research conducted in the U.S.

From 1975 through 1978 the Commission published eight reports on various aspects of research involving human beings. These reports formed the basis for the development of the 1981 DHHS and FDA regulations. Undoubtedly, the most ethically fundamental report produced by the Commission was the Belmont Report. The other reports produced by the National Commission are: Research on the Fetus (1975), Research  Involving Prisoners (1976), Research Involving Children (1977), Research Involving Those Institutionalized as Mentally Infirm (1978), Institutional Review Boards (1978), Ethical Guidelines for the Delivery of Health Services by DHEW (1978). The National Commission disbanded in 1978.

Neonates

Neonates are newborns who are 30 days old or younger. For the purposes of DHHS regulations viable neonates are considered children and only require the protections under sections A and D of 45 CFR 46 whereas neonates of uncertain viability and nonviable neonates require additional protections under section B of 45 CFR 46.

No-Treatment Control

Placebo Control, No-Treatment Control (suitable where objective measurements are felt to make blinding unnecessary), and dose-comparison control studies are all study designs in which a difference is intended to be shown between the test article and some control. The alternative study design generally proposed to these kinds of studies is an active-treatment concurrent control in which a finding of no difference between the test article and the recognized effective agent (active-control) would be considered evidence of effectiveness of the new agent. There are circumstances in which this is a fully valid design.

Non-Assured Institutions

An institution that does not hold an OHRP-approved Federalwide Assurance is referred to as a non-assured institution.  HSC researchers who conducted Cooperative Research with investigators from non-assured institutions provide additional information to define the responsibilities of each institution.  In some cases, an investigator from a non-assured institution may request the HSC extend its FWA to cover his/her research activities by signing an Individual Investigator Agreement (IIA).

Non-Therapeutic Research

Research that has no likelihood of intent of producing a diagnostic, preventive, or therapeutic benefit to the current subjects, although it may benefit subjects with a similar condition in the future.

Noncompliance

Conducting research in a manner that disregards or violates federal regulations, failure to follow the requirements and determinations of the IRB, or institutional policies and procedures applicable to human research (in the case of VA research it includes noncompliance with the requirements of the VA Handbook 1200.5 as applicable) which can be characterized by severity of the event and the pattern of like or similar events.  Noncompliance with IRB and/or federal requirements may involve a range of issues from relatively minor or technical Deviations which result from inadvertent errors, inattention to detail, or inadequate training and supervision of research staff to Violations, which pose risk to subjects or others and/or violations of their rights and welfare.   Noncompliance does not generally include individual protocol deviations.  However, protocol deviations should be tracked and assessed by the investigator because they may collectively be considered noncompliance.

Nonsignificant Risk Device

A Nonsignificant Risk device is one that does not meet the definition for a significant risk device. 

Note: A nonsignificant risk device does not require prior submission to the FDA for an Investigational Device Exemption (IDE) in order to be approved by the IRB so long as the IRB agrees and approves the device under FDA Abbreviated Requirements.

Nonviable Neonates

The inability of a baby, in the first 28 days of live birth, to survive outside the womb.  In research federal regulations require, after delivery, there must be a determination as to whether the neonate is viable (viable means being able to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration.  Additionally, there are limitations on determining viability of neonates - individuals engaged in the research may not have any part in determining the viability of a neonate being considered for inclusion in a study. In addition, after delivery, nonviable neonate may not be involved in research unless there is scientific justification for their inclusion, legally effective informed consent of both parents (exceptions apply, see Form U, http://research.uthscsa.edu/irb/Forms/Form U.doc,  Research Involving Pregnant Women, Human Fetuses And/Or Neonates) and all of the following additional conditions are met:

(1) Vital functions of the neonate will not be artificially maintained;

(2) The research will not terminate the heartbeat or respiration of the neonate;

(3) There will be no added risk to the neonate resulting from the research;

(4) The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means; and

(5) The legally effective informed consent of both parents of the neonate is obtained (waiver or alteration of consent is not allowed). However, there are some exceptions. 

Nuremberg Code

An international ethical code published in 1947 which established standards for the conduct of Research involving human beings. It arose out of the Nuremberg War Crimes Trial, where 23 Nazis were charged with crimes against humanity that involved murderous pseudomedical experimentation. Twenty of the individuals charged were physicians.

Nutritional Supplement

See Dietary Supplement.

O
Observational Study

Studies in human beings in which biomedical and/or health outcomes are assessed in pre-defined groups of individuals.  Subjects in the study may receive diagnostic, therapeutic, or other interventions, but the investigator does not assign specific interventions to the subjects of the study.

Also, Study Type.

Observational Study Model

Primary strategy for subject identification and follow-up.

  • Cohort: group of individuals, initially defined and composed, with common characteristics (e.g., condition, birth year), who are examined or traced over a given time period
  • Case-control: group of individuals with specific characteristics (e.g., conditions or exposures) compared to group(s) with different characteristics, but otherwise similar
  • Case-only: single group of individuals with specific characteristics
  • Case-crossover: characteristics of case immediately prior to disease onset (sometimes called the hazard period) compared to characteristics of same case at a prior time (i.e., control period)
  • Ecologic or community studies: geographically defined populations, such as countries or regions within a country, compared on a variety of environmental (e.g., air pollution intensity, hours of sunlight) and/or global measures not reducible to individual level characteristics (e.g., health care system, laws or policies median income, average fat intake, disease rate)
  • Family-based: studies conducted among family members, such as genetic studies within families or twin studies and studies of family environment
Observational Study Time Perspective

Temporal relationship of observation period to time of subject enrollment.

  • Prospective: look forward using periodic observations collected predominantly following subject enrollment
  • Retrospective: look back using observations collected predominantly prior to subject selection and enrollment
  • Cross-sectional: observations or measurements made at a single point in time, usually at subject enrollment
Obtaining Identifiable Private Information Or Specimens

Means receiving or accessing identifiable private information or identifiable specimens for research purposes.  Obtaining includes an investigator’s use, study, or analysis for research purposes of identifiable private information or identifiable specimens already in the possession of the investigator.

Off-Site Research

Designates research conducted at study sites that are not part of the UT Health Science Center San Antonio.  Off-site locations may make arrangements to allow the HSC IRB to act as the reviewing IRB for research conducted at that location or the research may be reviewed by another IRB.  Some institutions rely on the HSC IRB to review all research covered by the institution’s Federalwide Assurance.  These Affiliated Institution  are covered by an IRB Authorization Agreement (IAA) and a Memorandum of Understanding or Agreement (MOU/MOA) with the HSC.

Other off-site research may involve researchers from other (non-affiliated) institutions that may or may not already have an FWA/IRB or may involve individual investigators who either are not employed by an institution (Collaborating Individual Investigator) or is employed by an institution that does not routinely conduct research and does not have an FWA/IRB (Collaborating Institutional Investigator).

Office of Human Research Protections (OHRP)

Is responsible for implementing HHS regulations governing Research with human subjects.  DHHS elevated the Office for Protection from Research Risks (OPRR) to become the Office of Human Research Protections (OHRP) within OPHS, DHHS.

OIRB

Office of the IRB

Open-Label Study

In an open label study subjects are assigned to one treatment only. In an open label study two doses of a drug are often compared.

Operator Of Data Center/Repository

Individuals responsible for the operation of the repository and /or data management center.  Generally, one individual has overall authority and responsibility for the repository (Principal Investigator).  Depending on the structure and use of the repository, a data manager or specimen repository manager is appointed to oversee the operations of the repository.  The manager is often the only member of the repository team who has access to the identifying information linked to the data/specimens (all other team members have access only to coded data/specimens).

OPRR

Historically, the Office for the Protection from Research Risks was at NIH and responsible for implementing HHS regulations governing Research  with human subjects.  DHHS has elevated the Office for Protection from Research Risks (OPRR) to become the Office of Human Research Protections (OHRP) within OPHS, DHHS.

P
Participation Complete

See Subject Status.

Permission

Is defined as the agreement of parent(s) or guardian to the participation of their child or ward in research or clinical investigation and includes the elements of consent set forth in federal regulations and outlined in the informed consent template included in the IRB expedited and full review applications.

PHI: Protected Health Information

Federal Definition: PHI is Individually Identifiable Health Information transmitted by electronic media, maintained in electronic media, or transmitted or maintained in any other form or medium. PHI excludes education records covered by the Family Educational Rights and Privacy Act, as amended, 20 U.S.C. 1232g, records described at 20 U.S.C. 1232g(a)(4)(B)(iv), and employment records held by a covered entity in its role as employer.

The HIPAA definition of Protected Health Information is not meant to include all identifiable information or necessarily to protect identifiers.  There is often the misconception that identifiers are removed to protect them from release when in fact they are removed from the health information to protect the individual from anyone knowing the health information that is released is theirs.  Many of the actual identifiers are often public domain.  The most practical definition is, “any identifiable information (including demographic information) collected from an individual, that is created or received by a health care provider, health plan, employer or health care clearing house, and relates to (a) the past, present, or future physical or mental health or condition of an individual; (b) the provision of health care to the individual and identifies the individual or there is a reasonable basis to believe can be used to identify the individual.”

Note that the identifiable information is further divided into the identifiable information created or received by a health care entity and that identifiable information that is not, plus the requirement that it relate to the health of the patient versus identifiable information that is in no way associated with their health information.  Therefore the collection of health information that is recorded in a manner such that even if someone had the identifiable information they could not tell whose belonged to whom then this may not be considered PHI.  An example would be collecting the name and identification number of potential subjects so the research can go into other electronic or paper files and write down (in a physically separate document/media) the health information (without identifiers) but since they do not need to go back later and confirm or check the information there is no need to maintain a link to the identifiers.  They are only using the identifiers initially but not recording them with health information.

Alternately it could include identifiable information is further limited to the identifiable information created or received by a health care entity plus the requirement that it relates to the information about who, where, how and when the patient was cared for in the institution which can actually be traced back to the individual. 

The concept that this would not be PHI if there was not a reasonable basis for identification can be established if anyone knowledgeable in statistical procedures were to certify that in their opinion subjects could not be identified with the information collected.

Privacy Rule “Safe-Harbor” Identifiers:

(The categories of information below are considered identifiers under the privacy rule.  Health information accompanied by any of these identifiers is consider PHI and subject to the Privacy Rule.

Data that are stripped of these 18 identifiers (the “safe-harbor” method) are regarded as de-identified, is not PHI and not subject to the Privacy Rule, unless the covered entity has actual knowledge that it would be possible to use the remaining information alone or in combination with other information to identify the subject)

  • Names; Address; Dates except year; Ages over 89 (can be grouped as age 90 or older); Phone numbers; Fax numbers; E-mail addresses; Social security numbers; Medical record numbers; Account numbers; Certificate/license numbers; Health plan beneficiary numbers; Vehicle identifiers and serial numbers, or license plate numbers; Device identifiers and serial numbers; Web Universal Resource Locators (URLs); Internet Protocol (IP) address numbers; Biometric Identifiers, including finger and voice prints; Full face photographic images and any comparable images; Any other unique identifying number, characteristic, or code
Pregnancy

Encompasses the time from confirmation of implantation (through any of the presumptive signs of pregnancy, such as missed menses, or by a medically acceptable pregnancy test), until expulsion or extraction of the fetus.

Principal Investigator (PI)

The individual with primary responsibility for the design and conduct of a research project.  In multi-center Research, the Study PI is the individual with primary responsibility for the entire project and the Local PI is the individual with primary responsibility for the research activities under the purview of the HSC IRB. 

 

The Local PI may be a UT Health Science Center employee, student, or agent (e.g., affiliated faculty) or the PI may be an employee or agent of any institution affiliated with the HSC IRB through a current IRB Authorization Agreement or Memorandum of Understanding/Agreement (Affiliated Institution). 

 

The Local PI may designate a Co-Principal Investigator (Co-Principal Investigator) to assist with local PI responsibilities (e.g., report unanticipated problems, authorize modifications or progress reports).  The primary responsibility for the conduct of the research may not be assigned to the Co-PI.

 

For FDA regulated research filling a Form FDA 1572, Statement of Investigator, the local PI is the individual listed in Section 1 (investigator).

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.

Privacy

Control over the extent, timing and circumstances of sharing oneself (physically, behaviorally, or intellectually) with others.

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 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 human subjects (bolding added for emphasis).

Procedure or Care

A procedure or activity performed solely for the study.

Program Evaluation

Refers to assessments of the success of established programs in achieving objectives when the assessments are for the use of program managers, for example, a survey to determine if program beneficiaries are aware of the availability of program services or benefits. Not generally considered a research activity as long as the evaluation is designed to assess or improve the program or service rather than to generate knowledge about a disease or condition.

Protocol

The formal design or plan of an experiment or Research activity; specifically, the plan submitted to an IRB for review and to an agency for research support.  In some institutions this takes the form of a special template created by the institution.  In other institutions who may accept a sponsor’s protocol as partial completion of the requirements for a full protocol additional description of local parameters may be required in the form of addendums or additional forms/subforms.  In all cases the protocol must contain not only information concerning the larger scale multicenter trial but also address the local context.

Protocol Directed

Includes all procedures, therapies, interventions or interactions that are required by the protocol.  Even procedures that are considered to be standard practice are still protocol directed if the protocol requires it.

 

Public Service Announcement

A public service announcement is generally a non-profit organization or government broadcast on radio or television, ostensibly for the public good.  Public service announcements are intended to modify public attitudes by raising awareness about specific issues. Although technically it would be difficult to convince a newspaper, radio or television station that information concerning a research study constitutes raising public awareness or was intended for the public good, recruitment advertising activities that must be review by the IRB prior to use include posted notices, paid and unpaid newspaper solicitations or magazine advertisements (which may include public service announcements), websites, radio or television advertisements (which may include public service announcements).

Q
Quality Assurance

Refers to activities particular to an institution’s QA program, such as those activities protected from disclosure by the Department of Veterans Affairs as part of its confidential medical quality-assurance program or other equivalent programs. (e.g., see VHA Directives or equivalent university or institutional policy)

Quality Improvement

Routine Quality Improvement (QI) means systematic, data-guided activities designed to bring about immediate, positive changes in the delivery of health care in particular settings. QI involves deliberate actions to improve care, guided by data reflecting the effects (e.g., types of practical problem solving; an evidence-based management style; the application of science of how to bring about system change; review of aggregate data at the patient/provider/unit/ organizational level to identify a clinical or management change that can be expected to improve care).  QI is generally not considered research – however, QI activities can be research if they are also intended to contribute to generalizable knowledge.

Quorum

The minimal number of members of IRB who must be present at a convened meeting for valid transaction of business.

R
Recipient Of Data/Specimens

Anyone who receives the data/specimens from the data center/repository.  Recipient (sometimes referred to as recipient-investigator) can be from an organization covered by the UTHSCSA IRB or can be from an organization not affiliated UTHSCSA IRB.

Recorded

Regarding exempt research, “recorded” refers to information (data) that is “collected” or “documented” during the process of a research investigation.  The information may be written, typed, copied, audio or video recorded, etc

Recruitment

A “pre-enrollment” activity used to find potential subjects. 

Recruitment activities include:

  • advertisements or solicitations that are intended to be seen or heard by prospective subjects to solicit their participation in a study;
  • encounters to discuss the availability of studies and the possibility of entry into a study with a prospective subject;
  • dear doctor letters, etc.
  • obtaining the results of procedures performed as part of the practice of medicine for the purpose of determining study eligibility (if the IRB approves a waiver of consent and HIPAA waiver). 

Once potential subjects are Identified, see Subject Status-Identified/referred, an assessment of eligibility (Screening) follows.

Regulatory Binder (Essential Documents)

Essential documents are those which individually and collectively permit evaluation of the conduct of a research study and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor, and monitor with the regulatory requirements of various federal, state and local agencies.

 

Regulatory Specialist

Individual who serves as the subject matter expert on institutional policies and federal regulations regarding human subjects protections. 

Regulatory Sponsor

The agency, organization, company or person primarily responsible for initiating and overseeing the research and ensuring the study complies with federal regulations

  • For clinical trials (studies involving drugs or biologics) this is typically the IND holder, for device studies, this is the IDE holder
  • For industry-sponsored trials, typically the pharmaceutical/ device/biotechnology company is the regulatory sponsor
  • For non-industry sponsored trials, the regulatory sponsor is typically the PI
Reimbursement

Reimbursement is for expenses and generally requires justification/verification of the expense and should be available to all but may be different for each subject in contrast to Compensation which is usually required to be the same for each subject as payment for participation in Research.

Related Adverse Event Or Possibly Related Adverse Event

Means that there is at least a reasonable possibility that the Unexpected Adverse Event may have been caused by the procedures involved in the research.  Possibly related should be considered more likely than not, e.g., > 50% chance that it is at least partially related should be the threshold since the alternative would not be considered a reasonable possibility)

Repository

Data management centers (data centers) and human specimen repositories (sometimes called registries, banks, or libraries) are used to store data and/or specimens for future use.  When the use is for Research purposes, the data centers/repositories must be approved by the Institutional Review Board (IRB).  Human Specimen Repositories collect, store, and distribute human tissue/specimen materials for research purposes. Repository activities involve three components: (i) the collectors of tissue samples; (ii) the repository storage and data management center; and (iii) the recipient investigators.  Human repository repositories may be combined with data management centers.

Links to Additional Definitions Specific to Repositories:

Affiliated Institution, Data Management Centers, Collector Of Data/Specimens ,Specimen Repository Manager, Operator Of Data Center/Repository, Recipient Of Data/Specimens, Unidentifiable Data/Specimens , Identifiable Data/Specimens.  

Research

a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.” [5CFR 46.102(d)]

The Belmont Report provides addition clarification:

“…the term "research' designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships).  Research is usually described in a formal protocol that sets forth an objective and a set of procedures designed to reach that objective."

Activities which meet this definition constitute research, 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.  Some research development or testing and evaluation may also meet this definition.

Also see Clinical Investigation for FDA’s definition of research.

Research Only

A procedure or activity performed solely for the study.

Retrospective Research

The research study involves data or specimens that already exist in their entirety at the time of IRB submission. 

Risk

A potential harm.  Generally in research, risks of research that a reasonable person, in what the investigator knows or should know to be the subject’s position, would be likely to consider significant in deciding whether or not to participate in the Research should be disclosed to the potential subject.

Risks may be physical, social, legal, economic or psychological in nature, and may relate to employability or insurability. In addition, risks may apply to the individual subject or may apply to a broader segment of the society

Risk is usually discussed in terms of two factors probability (chance) and magnitude (severity). In order to minimize the risk, the researcher and the IRB need to assess the chances the risk will occur and how severe that risk can be, then look at the mechanism or methods built into the research for decreasing both the chance and severity.

For example, risk that a metal object may become a projectile during an MRI procedure. The severity could be high, but if precautions are taken the probability is low.

Additionally in certain circumstances additional parameters of risk such as permanence and immediacy should be included in the description of risk in research.  For example it may improve a potential subjects understanding of the risk and assist them in deciding whether or not to participate, if for some risks they were told whether the effect might be permanent rather than self limiting or at least treatable and for some risks the subject should be informed whether they should only expect this effect immediately or whether it might occur after the have left the care of the researcher in which case might they need emergency care.

S
Screen Failure

See Subject Status.

Screened Participant

Individuals who are screened to determine eligibility. 

Screening

See Subject Status: Screening

Screening

See Subject Status: Screening

Serious Adverse Event

Is any Adverse Event that:

1. results in death;

2. is life-threatening (places the subject at immediate risk of death from the event as it occurred);

3. results in inpatient hospitalization or prolongation of existing hospitalization;

4. results in a persistent or significant disability/incapacity;

5. results in a congenital anomaly/birth defect; or

6. based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (examples of such events include allergic bronchospasm requiring intensive treatment in the 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).

(based on OHRP definition)

Serious Disease Or Condition

Means 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 Noncompliance

Noncompliance that may: adversely affect subject safety or the safety of others; increase risks to subjects; violate the rights and welfare of participants (any of which may also be an unanticipated problem). Serious noncompliance may affect the subject’s willingness to participate in research or may affect the integrity of the data (which may also be scientific misconduct). The unfounded classification of a serious adverse event as “anticipated” constitutes serious non-compliance.  

Severely Debilitating

diseases or conditions causing major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke.

Significant Risk Device

A Significant Risk device is defined [21 CFR 812.3(m)] as a device that presents a potential for serious risk to the health, safety, or welfare of a subject and (1) is intended as an implant; or (2) is used in supporting or sustaining human life; or (3) is of substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise prevents impairment of human health; or (4) otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

Note: A significant risk device requires submission to the FDA for an Investigational Device Exemption (IDE) in contrast to a nonsignificant risk device which may be approved by the IRB under FDA Abbreviated Requirements.

The IRB does not make a SR/NSR device determination when considering requests to approve the use of a Humanitarian Use Device  Humanitarian Use Device (HUD) under an FDA approved Humanitarian Device Exemption (HDE).

 

Single Masked Design

In a single masked design, the subject does not know the treatment assignment but the investigator does.

Source Document

Sometimes referred to as source data, all information in original records of clinical findings, observations, or other activities in a study necessary for the reconstruction and support of the progress and adjudication of outcomes described in the research design.  Source data are the first recording of subject-related information.  In a drug study, for example, an investigator is required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual.  Source documents must be complete, accurate, and valid.

Sponsor

Sponsors are the agencies, institutions, companies, organizations, foundations, or individual grantors responsible for the initiation, management, or financing of a research study.  The term sponsor is understood to include any intermediaries, such as contract research organizations or coordinating centers, acting as agents of the sponsor in carrying out the responsibilities above.  All research falling under these types of agreements is considered sponsored research. 

 

In FDA regulated research, the Sponsor is the entity who takes responsibility for and initiates a clinical investigation.  The sponsor can be any legal entity, including a company, an academic organization, or an individual.  The intent of the sponsor’s IND/IDE is to allow testing for marketing approval of the drug or device. These are generally considered commercial or corporate IND/IDEs.

Note: the sponsor is often but not always the entity that funds the clinical research – i.e., Financial Sponsor

 

Sponsor-Investigator

A sponsor-investigator is an individual who both initiates and conducts a clinical investigation and under whose immediate direction the investigational drug/device is being administered, used or dispensed.  For administrative reasons, only one individual should be designated as the sponsor.

Usually, the intent of the sponsor-investigator IND/IDE is to gain scientific knowledge without seeking market approval for the drug or device.  These are considered 'Investigator-Initiated' or sponsor-investigator IND/IDEs.

Sponsor-Investigator INDs/IDEs

There a three general categories of sponsor-investigator INDs/IDEs: 

1) new drug/device developed by the investigator,

2) new uses, new routes of administration, new dosages, or new patient populations for currently approved drugs, or

3) new use of a significant risk device that has either been cleared under 510 (k) or approved under a Premarket Approval (PMA).

 

Also known as Investigator Initiated.

Standard Care or Practice

Care or procedures that are routinely or typically provided absent a research study.

(or generally accepted practice, routine or conventional care)

Study Operations Center

Most multi-center studies designate an operations center (generally the lead Principal Investigator (PI)'s location).  Study operations centers are designed to assist the study PI in meeting the oversight responsibility of the entire project.  Examples of operation center responsibilities include: collection of data and specimens from satellite sites, monitoring safety data, communicating study-wide amendments, regulatory oversight, etc. 

In order to meet these responsibilities, most operations centers obtain private, identifiable information from the satellite sites.  This action alone constitutes human research requiring IRB approval.

Sub-Investigator

Any investigator who is not the Principal Investigator.

Also, Sub-I.

 

Subject Status

Used to track the various states (milestones) in a subject's trajectory through a specific research study. The HSC's Clinical Trial Management System (CTMS) developed the following statuses for use in all types of clinical research (not just clinical trials):

  • Identified/Referred -during recruitment, and individual is identified as a prospective subject: 1) by obtaining the results of procedures performed as part of the practice of medicine (reviewing medical records with an IRB waiver), 2) by responding to recruitment activities, or referred by a provider
  • Did Not Consent- an identified subject who initially declines participation in research
  • Consent Signed- identified subjects who have been appropriately consented and are awaiting screening to begin
  • Pre-Screen -a consented subject who undergoes minimal procedures or gives authorization to obtain additional health records prior to a complete screening activity. The information obtained in prescreening is used to determine if a subject meets the minimum requirements to proceed to be screened. Consented subjects that are pre-screened are either eligible or ineligible. Eligible participants that pre-screen continue on to screening. Ineligible participants are considered a pre-screen failure.
  • Pre-Screen Failure-a pre-screened participant determined to be ineligible to proceed to screening as the subject does not meet the minimum eligibility requirements for the study.
  • Screening/Eligibility-A 'pre-enrollment' activity used to determine eligibility. Screening procedures are necessary solely for the purpose of determining eligibility (including fasting, withdrawal of medication), as a result informed consent must be obtained in some form (i.e., verbal, abbreviated or full informed consent). Prospective subjects that are screened are considered Screened Participant. Screened participants either: eligible or ineligible. Eligible subjects that consent to continue are considered enrolled. Ineligible subjects are considered Screen Failure.
  • Screen Failure- A screened participant determined to be ineligible for enrollment because they do not meet the eligibility criteria, or whatever other requirements must be met for research participation.
  • Re-screening- A subject that has previously completed screening and either did not complete the screening process or was determined to be ineligible. If previously arranged (by sponsor or PI) and approved (by IRB), subject can be reentered into the screening process a second time. The Re-Screening status is appropriate if the sponsor (or PI) wants the re-screening recorded under the same subject ID. If a new subject ID is assigned, the original subject ID status is changed to Screen Failure. Re-Screened participants are either: eligible or ineligible. Eligible subjects that consent to continue are considered Enrolled. Ineligible subjects are considered Screen Failure.
  • Enrolled - Screened participants are enrolled if eligibility is verified (meet all inclusion criteria and none of the exclusion) and they consent to continue in the study.
  • Active Observations - Applicable to non-interventional studies (e.g., Observational Study, indicates subject is actively involved with study  Intervention(s) or Interaction(s).
  • Run In/Wash Out - Applicable to Interventional Study, indicates a pre-intervention step commonly involving a run-in or wash out of study interventions.
  • Active Treatment (intervention) - Applicable to Interventional Study, indicates subject is actively involved with study Intervention(s) (Including the intervention of being tested or evaluated) and other study intervention.
  • Follow-Up As Planned - Applicable to Interventional Study, indicates the subject has completed the intervention being tested or evaluated as planned and is continuing with non-interventional procedures or other study Interaction(s).
  • Intervention Stopped Early - following -applicable to Interventional Study indicates the intervention being tested or evaluated was stopped pre-maturely and the subject is continuing with non-interventional procedures or other study Interaction.
  • Intervention Stopped Early - following-up complete- applicable to Interventional Study indicates intervention being tested or evaluated was stopped prematurely, the follow-up procedures have been completed.
  • Withdrawn - (prior to active, during active, during follow-up) - an early end to all participation for an enrolled subject (even if the subject did not start the treatment).
  • Completed - indicates that all study procedures (including Intervention), research related Interaction with the subject, and acquiring the subject's Private Identifiable Information were completed as planned. The subject is no longer participating in the research.
Substantive Changes Or Clarifications

Any change or request for additional information required by the IRB to an application (initial, progress report or amendment) that are directly relevant to the determinations required by the IRB under HHS regulations at 45 CFR 46.111. 

Supplement

See Dietary Supplement.

Surrogate Consent

When Informed Consent is obtained from someone other than the participant such as with family member consent (parental consent for a minor, immediate family consent during an emergency, etc.) or Legally Authorized Representative (LAR) consent.  It is not always required that Informed Consent to participate in research be given by the Legally Authorized Representative (LAR) if another form of surrogate consent is available depending on applicable state law, institutional policy and the determination of the IRB. 

See the IRB “Informed Consent Policy and Procedure” document for specific information on who may serve as a legally authorized representative or surrogate.

Survey

Whenever you gather information from your constituents or the general public, you need to give some thought to why you are collecting the information and how you plan to use it. 

Suspension Of Research

A suspension of IRB approved research that is required by the IRB, IRB Director, IRB Chair or designee, or Institutional Official results in a temporary cessation of some or all of the research activities.  Research may be suspended: 1) if it is not being conducted in accordance with the IRB approval; 2) when the continuation of the research may adversely affect the rights and welfare of research subjects; or 3) when continuation may represent an immediate threat of harm to the subjects.

Note: a Cessation of some or all research activities Halt voluntarily initiated by the Principal Investigator or sponsor is not considered suspension of research.

Systematic Investigation

Use of a clear plan, system or method to conduct a detailed examination or inquiry for facts.

T
Termination Of Research

A termination of IRB approval required by the IRB that results in a permanent cessation of all research activity.  Research may be terminated: 1) if it is not being conducted in accordance with the IRB approval; 2) when the continuation of the research may adversely affect the rights and welfare of research subjects; or 3) when continuation may represent an immediate threat of harm to the subjects.

Note: Cessation of all research activities resulting from the PI’s decision to inactivate the study is not considered termination of research.  Withdrawal of institutional support for research that results in cessation of all research activities is not considered termination of research.

Test Article

A general term that encompasses Drug, Device, food additives, etc. that are regulated by the FDA.

Therapeutic Research

Refers to interventions that are designed to determine the efficacy and safety of a therapeutic or diagnostic method.  The interventions are not applied solely to enhance the well-being of the individual subject who is sick (note use of the term “subject” as opposed to “patient”). Achievement of maximum possible therapeutic benefit cannot, therefore, be presumed, since the intervention is still being evaluated. The objective of therapeutic  Research is to increase generalized knowledge (i.e., test a hypothesis and draw conclusion), and at the same time provide the subject with a needed health benefit. Accordingly, the responsibilities of a physician who is also an investigator must take into consideration the fact that the patient is also a research subject.

Therapy

Refers to interventions that are applied solely to enhance the well-being of an individual patient who is sick.  The interventions are procedures commonly accepted by the medical community and represent standard care.

Treatment Team

Refers to healthcare providers (e.g., physicians, nurses, aides, technicians, and administrative assistants that are normally involved with the delivery of routine medical care.  

U
Unanticipated Adverse Device Effect (UADE)

Is defined by the FDA (21 CFR 812.3(s))

1. any:

  • serious adverse effect on health or safety; or
  • any life-threatening problemor
  • 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

2. any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

Unanticipated Problem Involving Risk to Subjects or Others

See UPIRSO.

Unapproved Device

An unapproved medical device is defined as a device that is used for a purpose or condition 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. 360(e)}. An unapproved device may be used in human subjects only if it is approved for clinical testing under an approved application for an Investigational Device Exemption (IDE) under section 520(g) of the Act {21 U.S.C. 360(j)(g)} and 21 CFR part 812. Medical devices that have not received marketing clearance under section 510(k) of the FD&C Act are also considered unapproved devices which require an IDE. http://www.fda.gov/oc/ohrt/IRBS/devices.html

Undue Influence

Belmont Report states that undue influence occurs “through the offer of Inducements excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance” (National Commission, 1978, p.8).  It also argues that “unjustifiable pressures” occur when “persons in positions of authority … urge a course of action for a subject.” This includes manipulating a prospective subject’s choice by utilizing the “influence of a close relative.”  Lastly issues may be raised as potential undue influence when judgment may be compromised by financial incentives especially when the subject is not the recipient of the financial incentive.  Undue influence needs to be distinguished from coercion for the purposes of UTHSCSA IRB applications of policy. Coercion is considered the use of a threat of harm or punishment to influence behavior; e.g., in general, payments do not constitute coercion per se.  There are also less apparent examples of vulnerability to undue influence such as Institutional vulnerability and Deferential vulnerability to undue influence.  Institutional is when an individual is subject to the formal authority of others which could influence the subject’s participation.  Examples- prisoners, military personnel, students, employees.  Deferential is similar to institutional but arises from informal relationships characterized by inequities in social status (gender, race, class) power or knowledge (doctor-patient relationship), or cognitive ability (elderly person defer to adult kids).  Heightened concern that subject’s decision re: participation not truly voluntary.  Deferential vulnerability can be very subtle- investigators must be especially sensitive to potential for subjects to believe refusing to participate will negative impact their future treatment.  Investigators need to be sensitive to such deference and assess whether subject is truly exercising his/her autonomy and adjust the informed consent accordingly (a suggested addition to the usual consent process might include discussing participation in absence of the individual to whom the potential subject ordinarily defers-additional because the PI or investigator with the relationship may be the best person to discuss the study and answer questions and it would not be appropriate to bypass them all together). Deferential may be misconstrued to include therapeutic misconception but it is generally a separate concept though still requiring consideration in the consent process.  Where potential subjects may be drawn to research because of lack of effective standard treatments and desire to find treatment they may be prone to misunderstand the risks and potential benefits and have unreasonable expectations about potential benefits.  Pay special attention to ensuring potential benefits of participation are properly characterized.  Where investigator is also treating physician, in addition to the issue of deference, there exists a higher risk of therapeutic misconception.  Again you may want to consider having impartial third party obtain consent or finalize the consent process in the absence of the individual to whom the potential subject ordinarily defers.

 

Unexpected Adverse Event

Is any adverse event, the nature, severity, or frequency of which is not consistent with either:

(1) the known or foreseeable risk of adverse events associated with the procedures involved in the research that are described in (a) the protocol related documents, such as the IRB-approved research protocol, any applicable investigator brochure, and the current IRB-approved informed consent document, and (b) other relevant sources of information, such as product labeling and package inserts;

or

(2) the expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse event

Unidentifiable

are either:

• Unidentifiable – sometimes referred to as “anonymous”, are an unidentified collection of human biological materials or data.

or

• Unlinked – sometimes referred to as “anonymized”, originate from identified human biological materials or data but have been stripped by the source (not the researcher) of all identifiers (including the 18 HIPAA identifiers – refer to the University Handbook of Operations for the complete list) or codes such that the ability to identify particular individuals via clinical or demographic information supplied with the sample, or information derived from the Research would be impossible for the investigator, the repository, or a third party.

 

UPIRSO

UPIRSO: An acronym for the regulatory phrase “Unanticipated Problem Involving Risk To Subjects Or Others”. 

 

Unanticipated problem involving risk to subjects or others includes any incident, experience or outcome that meets all of the following criteria:

  1. 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 subject population being studied (note: the unfounded classification of a serious adverse event as “anticipated” constitutes serious non-compliance);
  2. definitely related or probably related to participation in the research; and
  3. suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized. 

 

For VA Research all determinations of a UPIRSO would met the definition of a Serious Adverse Event [an untoward occurrence in human research that results in death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly, or birth defect, or that requires medical, surgical, behavioral, social, or other intervention to prevent such an outcome] or Serious Problem [Presenting a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research personnel, or others, including their rights to privacy and confidentiality of identifiable private information; or (2) Substantively compromising a facility’s HRPP or research information security program] as defined in VHA Handbook.

V
VA Research

A term used to define when a research study is subject to the VA regulations governing human research.  Similar to the DHHS term “engaged in research”.

 

VA research is any research that is:

  1. sponsored by the VA
  2. being conducted by or under the direction of any salaried or without compensation (WOC) employee of the STVHC during her/his official duty time or in connection with her/his STVHCS responsibilities
  3. being conducted at a STVHCS facility
  4. recruiting subjects at the STVHCS or using the STVHCS’s records (CPRS) to identify or contact subjects for research
  5. being funded or managed by the STVHCS or the Foundation for Advancing Veterans Health Research (formerly the Biomedical Research Foundation of South Texas)

 

Viable

As it pertains to the fetus, means being able, after either spontaneous or induced delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heart beat and respiration. Once a fetus is viable it is a premature infant.

Violation

A departure (generally intentional on the part of the investigator) from the approved study protocol, and occurs without prior IRB approval that:

  1. has the potential to cause harm or increase the risk of harm to one or more research participants or
  2. has the potential to damage the scientific integrity of the data collected for the study; or
  3. impacts a subject's safety, rights, or welfare

Examples include:

  • Failure to obtain informed consent, use of an invalid consent form, enrollment of a subject who was ineligible for the study, performing a research procedure not in the approved protocol, changing an approved study procedure such as increasing the infusion rate
  • Protocol violations require prompt reporting to the IRB and are summarized in the study progress report submitted during continuing review.
Voluntary

Free of coercion, duress or undue inducement; used in Research context to refer to a subject’s decision to participate (or to continue to participate) in a Research activity.

W
Withdrawn

See Subject Status: withdrawn