Policy Manual Definitions
A through H
Not to vote either for or against a motion before the IRB. An IRB member may abstain from voting for any reason and need not reveal the reason for abstaining.
An Assent Form generally written for children 13-17 years of age in a format appropriate for their cognition and understanding. An Adolescent Assent Form differs from the Assent Form noted below in that it may use more sophisticated language and format than one written for younger children and may follow the format for adult consent forms.
Any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. (21 CFR 312.32(a))
The DHHS regulations at 45 CFR part 46 do not define or use the term "adverse event" but in the DHHS document "Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events, January 15, 2007" the term adverse event is used to reference any event meeting the following definition: 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 considered related to the subject's participation in the research.
A local or internal adverse event is one that occurs at the local investigator's site.
Life-Threatening Adverse Event or Life-Threatening Suspected Adverse Reaction
An adverse event or suspected adverse reaction is considered "life-threatening" if, in the view of either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a more severe form, might have caused death.
Serious Adverse Event
Any untoward physical or psychological occurrence in a human subject participating in research that results in any of the following outcomes:
- Life-threatening experience;
- Inpatient hospitalization or prolongation of existing hospitalization;
- Persistent or significant disability or incapacity, or congenital anomaly or birth defect;
- Or any other adverse event that, based upon appropriate medical judgment, may jeopardize the participant's health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction
An incident that is not listed in the investigator brochure or is not listed at the rate of occurrence or severity that has been observed; or if an investigator brochure is not required or available, is not consistent with the risk information described in the general investigational plan or elsewhere in the current application, as amended. (FDA)
Flyers, notices, posters, radio/TV spots, newspaper ads, signs, brochures, internet postings, etc. that are intended to attract potential participants into research studies.
An individual's affirmative agreement to participate in research. This should be sought in addition to the consent of a legally authorized representative or surrogate when the individual is sufficiently cognitively capable of understanding the nature of his or her participation in a research study. Mere failure to object should not, absent affirmative agreement, be construed as assent.
A child's affirmative agreement to participate in research. When the child is sufficiently cognitively capable of understanding the nature of her or his participation in a research study, assent should be sought in addition to parent permission or consent of a legally authorized representative or surrogate. Mere failure to object should not, absent affirmative agreement, be construed as assent.
A document written in language that is appropriate to the child subject's maturity and cognitive level and used as part of the assent process to:
- Describe the research study, including the research procedures, risks and benefits.
- Obtain the child's written agreement to participate in the study.
An institution with a Federalwide Assurance (FWA) that is approved by the DHHS Office for Human Research Protections (DHHS OHRP).
Authorization is defined under HIPAA as the granting of rights to access protected health information (defined below) (PHI). Authorization is required by HIPAA for disclosures or uses of PHI other than for treatment and related procedures and operations. Importantly, treatment cannot be conditioned on granting of an authorization. An authorization is a specific, detailed document requesting patient-subject permission for the use of covered PHI.
A summary of clinical data, including medical history and other relevant information, that was collected initially for the purposes of analyzing and diagnosing an individual's condition or for instructional purposes. Case reports do not ordinarily require IRB approval but must comply with HIPAA.
- Anything of monetary value including, but not limited to the following paid or given directly to research team members:
- salary, loans, gifts or royalties;
- other payments for services such as honoraria, speaking and lectureship fees, study completion or enrollment bonuses or study outcomes awards; or
- payments for consulting services and services on advisory committees;
- Intellectual property rights, including patents, patent applications, copyrights and royalties from such rights;
- Equity interests (e.g., owning or having the right or obligation to acquire stocks or stock options, partnership interests or other securities in a for-profit entity);
- Debt interests (e.g., owning or having the right or obligation to acquire bonds associated with the research); or
- A paid position as consultant, employee, director or manager of an entity for which the individual is conducting research.
The term "Financial Interest" does NOT include any of the following:
- Salary or other remuneration received from grants or contracts to the University or affiliates that directly support the conduct of a specific research endeavor;
- Stock owned through mutual funds;
- Intellectual property rights developed in the course of employment at a previous or current employer that remain the exclusive property of that entity or that may be widely published and for which the individual may be pursuing patent interests provided that the interest is not associated with ongoing research.
Note: Consistent with the DHHS rule involving individual financial conflict of interest, effective August 12, 2012, disclosure of ownership interest, stock options, or other financial interest related to the research is not required if the amount is less than $5,000. The University conflict of interest policy and reporting forms have been updated to reflect the new threshold.
Non-Financial Interest or Relationship
Any relationship, position or the promise of a position with sponsors, other external entities or persons that might influence or appear to influence the outcome of, or a decision related to, a research project. Such relationships include, but are not limited to
- An unpaid directorship or management position;
- A board membership;
- An unpaid consulting relationship; or
- A personal relationship.
When there is the promise of monetary reward for which the value is presently unknown or the personal gain, intellectual property rights, including patents, patent applications and copyrights constitute non-financial interests.
When evaluating non-financial interests or relationships, the IRB Chair, Vice Chair or qualified designee will seek to determine the ability of the parties to remain objective in light of the interests or relationships.
Significant Financial or Non-Financial Interest
A financial interest that exceeds $5,000 or a non-financial interest that is deemed significant by University Policy on Conflict of Interest and Conflict of Commitment. Generally speaking, investigators with significant financial or non-financial interests are prohibited from partaking in research pursuant to University policy, unless they can justify exceptional circumstances and rebut the presumption against the participation of conflicted researchers in a research project or the interest has been sufficiently mitigated.
Authorizations to withhold the names or other identifying characteristics of individuals participating in research from any person or authority not connected with the conduct of such research including any Federal, State or local civil, criminal, administrative, legislative, or other proceedings. These authorizations may be granted by agencies within the Department of Health and Human Services (DHHS) such as the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), or the National Institutes of Health (NIH) This protection is afforded by the Public Health Service Act 301(d), 42 USC 241(d). It does not protect against voluntary disclosures by the researcher, and as such anticipated disclosures must be specified in the informed consent and HIPAA Authorization forms. A researcher may not rely on the Certificate of Confidentiality to withhold data if the participant consents in writing to the disclosure.
A person under the age of 18 years (NRS 432B.040). Investigators working in locations outside of Nevada should confirm the local age of majority to determine at what age an individual is considered to be an adult.
For studies subject to FDA regulations, any experiment that involves a test article and one or more human participants and that either:
- Is subject to requirements for prior submission to the FDA under section 505(i) (Abbreviated New Drug Applications) or 520(g) (device exemptions) of the Food Drug and Cosmetic Act or
- Is not subject to the requirements for prior submission but the results of the experiment are intended to be submitted later to, or held for inspection by, the FDA as part of an application for a research or marketing permit.
The act of using force or threats, whether actual, implied, perceived or indirect, to encourage an individual to participate in a research study.
Having psychiatric disorder (e.g., psychosis, neurosis, personality or behavior disorders), an organic impairment (e.g., dementia) or a developmental disorder (e.g., mental retardation) that affects cognitive or emotional functions to the extent that capacity for judgment and reasoning is significantly diminished. Others, including persons under the influence of or dependent on drugs or alcohol, those suffering from degenerative diseases affecting the brain, terminally ill patients, and persons with severely disabling physical handicaps, may also be compromised in their ability to make decisions in their best interests.
An individual who is not otherwise an employee or agent of an assured institution and who is conducting collaborative research activities with a University or affiliate investigator. Collaborating investigators may be either:
- "Collaborating Institutional Investigators" who are acting as an employee or agent of a non-assured institution that does not routinely conduct human subjects research or
- "Collaborating Independent Investigators" who are not acting as an agent or employee of any institution.
A formal written request for the University to extend the applicability of its FWA and/or IRB oversight to cover a collaborating investigator and the collaborating investigator agrees to abide by the terms of the University's FWA and policies and procedures relating to the conduct of human research.
Providing the opportunity for discussion with, and soliciting opinions from, the communities in which the study will take place and from which the study subjects will be drawn. These communities may not always be the same; when they are not the same, all affected communities should be consulted.
For purposes of this policy, compassionate use refers to the use of an investigational device as the only option available for a patient faced with a serious, albeit not life-threatening condition. (The term "compassionate use" is not recognized by the FDA when referring to investigational drugs.)
The use of an HUD in a situation that is not an emergency, but one for which a clinician determines there is no alternative device to treat the patient's condition. The FDA recommends that clinicians first obtain FDA approval for compassionate use.
The maintenance of information in keeping with the investigator's agreement with the research participant regarding how the participant's involvement in research and their identifiable private information will be handled, managed, disseminated and protected from release or access by others. Confidentiality becomes part of the agreement between the researcher and the research participant, and is described in the consent documents and is detailed during the consent process.
Data which is collected and maintained in such a way that research participants may be identified but which will be protected from further release by the investigator in accordance with an IRB-approved protocol.
A conflict of interest in human research exists when an individual, member of her or his immediate family, or both; or an institution has an external interest that affects or may provide an incentive to affect actions or decisions related to the conduct, review or approval of research. A conflict of interest may be financial or non-financial in nature.
Convenience sampling selects a particular group of people based on aspects of the potential participants' situation which renders them more easily accessed by the investigator or more likely to complete research participation without regard for the representativeness of the sample. Convenience sampling does not come close to sampling all of a population or a representative sample of a population. Convenience sampling may unfairly expose a population to research related risks.
Under HIPAA, a covered entity is defined as any organization or individual that constitutes one or more of the following:
- Health care provider that conducts certain transactions in electronic form;
- Health care clearinghouse or
- Health plan.
Health Care Provider
Providers such as doctors, clinics, psychologists, dentists, chiropractors, nursing homes and pharmacies if they transmit any information in an electronic form in connection with a transaction for which HHS has adopted a standard.
Health insurance companies, HMOs, company health plans, government programs that pay for health care, such as Medicare, Medicaid, and the military and veterans' health care programs.
Health Care Clearinghouse
Entities that process nonstandard health information they receive from another entity into a standard (i.e., standard electronic format or data content), or vice versa.
A device that
- In order to comply with the order of an individual physician or dentist, deviates from devices generally available, or from an applicable performance standard or premarket approval requirement;
- Is not generally available to, or generally used by, other physicians or dentists;
- Is not generally available in finished form for purchase or for dispensing upon prescription;
- Is not offered for commercial distribution through labeling or advertising; and
- 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 group charged by the investigator, sponsor, or steering committee to protect subject safety by examining the accruing data for indications of benefit or harm. The Data Safety Monitoring Board (DSMB) or Data Safety Monitoring Committee (DSMC) assesses the research findings to determine whether the study should continue, or should be suspended or terminated. For multi-center trials, the DSMB or DSMC usually looks at global data, as investigators forward all serious adverse event reports and safety data to a data-coordinating center, which compiles the data for the DSMB or DSMC to review at predefined intervals. These global data allow DSMBs or DSMCs to identify trends in increased frequency or severity of anticipated and unanticipated events or problems. Data presented to the DSMB or DSMC are unblinded or categorized by treatment arm thus allowing the DSMB or DSMC to determine whether a clear effect exists in one arm of the study versus other arms.
A plan, tailored to a particular protocol, that describes who has the responsibility to monitor study data and the frequency at which study data is monitored to ensure the safety of human subjects and integrity of study data.
An agreement between a HIPAA-defined covered entity and the intended recipient of a limited data set that establishes the ways in which the information in the limited data set may be used and how it will be protected.
Health information from which a covered entity has removed all 18 HIPAA identifiers as long as the covered entity has no actual knowledge that the remaining information could be used alone or in combination with other information to identify the individual to whom the information applies.
Implementation of a method, technology, policy or idea to assess feasibility prior to full implementation. For example, proof of concept studies or the initiation of a benefit or service program or modification of such program for the purpose of assessing its ability to improve the provision of government programs.
FDA will place all IDEs it approves into one of two categories:
Category A - Experimental
The IDE involves innovative devices in which "absolute risk" has not been established (i.e., initial questions of safety and effectiveness have not been resolved, thus FDA is unsure whether the device type can be safe and effective).
Category B - Investigational; Non-experimental
The clinical investigation involves device types believed to be in FDA classes I or II or device types believed to be in FDA class III where incremental risk is the primary risk in question (i.e., underlying questions of safety and effectiveness of that device type have been resolved). This category includes device types that can be safe and effective because, for example, other manufacturers have obtained FDA approval for that device type. Nonsignificant risk studies may also be included in this category. (Investigators who are uncertain of the classification of a medical device may wish to review the Device Classification pages of the FDA website.)
The release, transfer, provision of access to or divulgence in any other manner of PHI outside the entity holding the information.
A minor who is at least 16 years of age, who is married or living apart from his or her parents or legal guardian, and who is a resident of the county, and has petitioned the court of that county for a decree of emancipation; and the court determines that the petition should be granted and enters a decree of emancipation for the petitioner.
The use of an investigational drug or biological product with a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval. This "emergency use provision" in the FDA regulations allows for an exemption from requirements to for prior IRB review and approval before a test article is used (for details see the University policy for emergency use, or 21 CFR 56.102(d) and 104(c)).
For purposes of this policy, employee refers to a person employed by the University.
An institution is considered engaged in a particular human subjects research project when its employees or agents for the purposes of a non-exempt research project obtain:
- Data about the subjects of the research through intervention or interaction with them;
- Identifiable private information about the subjects of the research; or
- The informed consent of human subjects for the research.
An institution is also considered engaged when the institution receives a direct federal award to conduct human subject research, even when all activities involving human subjects are carried out by a subcontractor.
An individual is considered engaged in human research when he/she for the purposes of the non-exempt research project, obtains:
- Data about the subjects of the research through intervention or interaction with them
- Identifiable private information about the subjects of the research; or
- The informed consent of human subjects for the research.
Language that waives or appears to waive any of an individual's legal rights or which releases or appears to release the investigator, sponsor, the institution or its agents from liability for negligence.
For purposes of this policy, any one of the following legally competent persons: spouse; parents; grandparents; children (including adopted children); brothers, sisters, and spouses of brothers and sisters; and any individual related by blood or affinity whose close association with the subject is the equivalent of a family relationship. [21 CFE 50.3(m)]
A formal written, binding attestation in which an institution assures to DHHS that it will comply with applicable regulations governing research with human subjects.
A formal written, binding agreement in which an institution assures DHHS that it will comply with applicable U.S. federal regulations governing research with human participants.
Family Educational Rights and Privacy Act. A Federal law that protects the privacy of education records of students. The law applies to all schools that receive funds under an applicable program of the U.S. Department of Education.
The product of conception from the time of implantation until delivery.
Information that investigations designed to draw general conclusions (i.e., knowledge gained from a study may be applied to populations outside of the specific study population), inform policy, or apply findings to other populations or settings. It may be justifiably transferred or extrapolated to a broader population or situation than from which it was initially derived.
Any person appointed as guardian of the person, of the estate, or of the person and estate for any other person, and includes an organization under NRS 662.245 and joint appointees. The term includes, without limitation, a special guardian or, if the context so requires, a person appointed in another state who serves in the same capacity as a guardian in this State.
Any person appointed under this chapter as guardian of the person, of the estate, or of the person and estate for any other person. The term includes, without limitation, a special guardian or, if the context so requires, a person appointed in another state who serves in the same capacity as a guardian in this State.
An individual, appointed by the court to make decisions on behalf of the person under her or his guardianship (i.e., ward).
Note: In Nevada, Court approval is required before a guardian may consent to certain treatment of or experiment on a ward (per NRS 159.0805).
Any person appointed as guardian of the person, of the estate, or of the person and estate for any other person. The term includes, without limitation, a special guardian or, if the context so requires, a person appointed in another state who serves in the same capacity as a guardian in this State.
A person considered to be engaged in the patient's medical care.
The Health Insurance Portability and Accountability Act of 1996 (HIPAA) provides federal protections for personal health information (PHI) held by covered entities and gives patients an array of rights with respect to that information. The Privacy Rule is balanced so that it permits the disclosure of personal health information needed for patient care and other important purposes.
A human subject is a living individual:
- About whom an investigator (whether professional or student) conducting research obtains either
- data through intervention or interaction with the individual;
- identifiable private information; or
- Who is or becomes a participant in research involving drugs or devices, either as a recipient of a test article or as a control
The phrases "human subject" and "human participant" are used interchangeably in IRB policies and procedures. The term "participant" conveys the voluntary nature of an individual's agreement to participate in a research study and may convey a sense of partnership that is not reflected in all types of research. The term "subject" may imply that the research volunteer is acted upon as opposed to being in partnership with the researchers and may be more appropriate for some research.
A living individual about whom an investigator (whether professional or student) conducting research obtains either (a) data through intervention or interaction with the individual; or (b) identifiable private information.
Communication or interpersonal contact between investigator and subject.
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.
An individual who is or becomes a participant in research, either as a recipient of a test article or as a control. A subject may be either a healthy individual or a patient (21 CFR 50.3(g) and 21 CFR 56.102(e)). For clinical investigations involving medical devices, the results of which are intended to be submitted later to, or held for inspection, by the FDA as part of an application for a research or marketing permit, human subject also 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.
Note that the Office of Human Research (OHRP) policies and procedures use both human "subject" and human "participant" are. While the term participant conveys the voluntary nature of an individual's agreement to participate in the research, it may convey a sense of partnership that is not reflected in all types of research. In some research, the volunteer is the recipient of specific acts and any sense of partnership is absent, in which case the term subject may be more appropriate.
A subject may be either a healthy human or a patient. Specifically in regard to investigational device studies, 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.
Experimental Subject and Research Involving a Human Being as an Experimental Subject (Department of Defense-sponsored Research)
An activity, for research purposes, where there is an intervention or interaction with a human being for the primary purpose of obtaining data regarding the effect of the intervention or interaction (32 CFR 219. 102(f), reference(c)). Examples of interventions or interactions include, but are not limited to, a physical procedure, a drug, a manipulation of the subject or subject's environment, and the withholding of an intervention that would have been undertaken if not for the research purpose.
Projects that meet the definitions of both "research" and "human subject."
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. HUDs can only be used in a facility after an IRB has approved their use in that facility, except in certain emergencies.
FDA approval of a Humanitarian Device Exemption (HDE) application is necessary in order to allow the marketed use of a Humanitarian Use Device (HUD). The HDE is similar to a Pre-Market Approval (PMA), but because a HUD is exempt from the effectiveness requirements of a PMA, an HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose. The HDE must contain sufficient information for FDA to determine that the probable benefit to health outweighs the risk of injury or illness, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.
I through P
Spouse, domestic partner or dependent children.
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.
A person's mental status and means inability to understand information presented, to appreciate the consequences of acting (or not acting) on that information, and to make a choice. Often used as a synonym for incompetence.
A finding concerning an individual research participant that has potential safety, health, psychiatric or reproductive importance that is discovered in the course of research but is beyond the aims of the study. Incidental findings may or may not be anticipated for a portion of the research participants.
Inability to manage one's own affairs. Often used as a synonym for incapacity.
An adult person who, by reason of mental illness, mental deficiency, disease, weakness of mind or any other cause, is unable, without assistance, properly to manage and take care of himself or herself or his or her property, or both. The term includes a person who is mentally incapacitated.
Sponsor notifications to FDA and all participating investigators (i.e., all investigators to whom the sponsor is providing a drug under its or investigators' INDs) which may include:
- Serious and unexpected suspected adverse reaction;
- A single occurrence of an event that is uncommon and known to be strongly associated with drug exposure;
- One or more occurrences of an event that is not commonly associated with drug exposure, but is otherwise uncommon in the population exposed to the drug;
- An aggregate analysis of specific events observed in a clinical trial that indicates those events occur more frequently in the drug treatment group than in a concurrent or historical control group;
- Findings from other studies that suggest a significant risk in humans exposed to the drug;
- Findings from animal or in vitro testing that suggest a significant risk in humans exposed to the drug; or
- A clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.
An independent group of experts without University affiliation, established by the sponsor of a research protocol to periodically assess the progress of a study by evaluating the safety data and the critical efficacy endpoints (also known as a Data Safety Monitoring Committee). The committee makes recommendations to the sponsor whether to continue, modify or stop a trial. In some instances, the IRB may permit people with University affiliations to be members of a Data Monitoring committee so long as the majority of the membership is not affiliated with the University. However, no committee members may be affiliated with the research study.
A data monitoring committee, sometimes called a data and safety monitoring board (DSMB), that is an independent group of experts, established by the sponsor of a research protocol to assess periodically the progress of a clinical trial (the safety data and the critical efficacy endpoints), and to recommend to the sponsor whether to continue, modify or stop a trial.
A specially constituted review body whose responsibility is to ensure the protection of the rights, welfare and safety of research participants. An IEC shares the same general composition and operations as an Institutional Review Board.
The identity of the research participant is or may readily be, ascertained by the investigator or associated with the information.
Any information created, used, or received by a health care provider that 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 with respect to which there is a reasonable basis to believe the information can be used to identify the individual.
Note: The collection of individually-identifiable health information for research constitutes human subjects research.
Any public or private entity or agency (including federal, state, and other agencies).
Situations in which the University's beneficial relationship with corporate entities may place it in conflict with its responsibilities as a public institution of higher education. The conflict may involve equity interest in companies, receipt of significant financial donations from external entities, certain licensing situations and Board and other leadership positions held by University faculty or administrators.
A senior official named in the FWA who has the authority to commit the entire organization, as well as all of the components listed in the FWA, to a legally binding agreement. The Institutional Official (IO) also has the authority to assure compliance of the organization and all of its components to the Terms of the FWA. At the University, the IO is the Vice President of Research.
A group of University faculty and graduate students; VA representatives; OHRP Director and Program Managers; and community members who are qualified through training and education and who are responsible for review and oversight of biomedical or social behavioral human subjects research.
The University IRB is established in accordance with 45CFR46 and 21 CFR 56 which is designated by the University to ensure the ethical and equitable treatment of research volunteers and to protect the rights and welfare of those who participate in research. The IRB has the authority to approve, require modification or disapprove research projects involving human research participants or deem certain projects exempt from, or not requiring, IRB review and oversight.
A group of University faculty and graduate students; VA representatives; OHRP Director and Program Managers; and community members who are qualified through training and education and who are responsible for review and oversight of biomedical or social behavioral human subjects research.
Documented permission for outside institutions or agencies that serve as sources for subjects, records, or information; or on whose facilities human subjects research will be conducted; required for IRB review. Permission must come from an executive director, chief executive officer, board president or other individual with authority to commit the institution's resources. The documentation must acknowledge the proposed research activity; grant permission for the engagement of their employee (or students) and facilities (if applicable) in that activity; and include the title of the study, typewritten name and the title of the person signing, and signature or official email address of the individual with the authority to grant such permission. (The IRB may waive requirement for written documentation.)
- Act on behalf of the institution.
- Exercise institutional authority or responsibility.
- Perform institutionally designated activities. "Employees and agents" can include staff, students, contractors, and volunteers, among others, regardless of whether the individual is receiving compensation.
A new drug or biological drug that is used in a clinical investigation. The term also includes a biological product that is used in vitro for diagnostic purposes. The terms "investigational drug" and "investigational new drug" are deemed to be synonymous.
Exempts an investigational new drug from FDA premarketing approval requirements that are otherwise applicable thus allowing the drug to be shipped lawfully for the purpose of conducting clinical investigations of that drug. Because a sponsor will usually ship the investigational drug to clinical investigators in many states, it must seek an exemption from that legal requirement. The IND refers to the application and is the means through which the sponsor obtains this exemption from the FDA.
Three additional IND types and two IND categories are defined below.
Investigator IND (Sponsor-Investigator)
An Investigator IND is submitted to the FDA by an investigator who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. An investigator might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population.
A treatment IND is submitted to the FDA to make promising new drugs available to desperately ill patients as early in the drug development process as possible. FDA will permit an investigational drug to be used under a treatment IND if there is preliminary evidence of drug efficacy and the drug is intended to treat a serious or life-threatening disease in its later stage of development or if there is no alternative drug or therapy available to treat that stage of the disease in the intended individuals.
Emergency Use IND
The Emergency Use IND allows the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND in accordance with the regulations. It is also used for patients who do not meet the criteria of an existing study protocol, or if an approved study protocol does not exist. Emergency and Treatment INDs are sometimes referred to as "Compassionate Use" INDs, but the term "Compassionate Use" is not in the IND regulations.
Applications submitted primarily by companies whose ultimate goal is to obtain marketing approval for a new product.
Applications submitted for non-commercial use.
A formal, written, binding agreement in which the University agrees to serve as the IRB for another institution or vice versa. The IAA sets out terms and conditions for the institutions.
An individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedures involved in the research. (See definitions of guardian, and guardian and surrogate consent, above.)
Note: Per Chapter 159 of the Nevada Revised Statutes, court approval is required before a guardian may give consent for a ward to participate in research.
The subject or the subject's legally authorized representative agree to the participation in the research as described and this agreement is documented in a manner that is consistent with the DHHS protection of human subjects regulations and with applicable laws of the jurisdiction in which the research is conducted.
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.
A person who is able to make independently some but not all of the decisions necessary for the person's own care and the management of the person's property; and the person is not a minor.
PHI that is released for research purposes with certain identifiers removed and with a data use agreement between the researcher and the covered entity. Limited data sets may include the following: city, state, ZIP code, date of birth, date of death and dates of service.
Knowledge of the non-U.S. institution(s), local cultural norms, community environment, and applicable law in which human research will be conducted.
The least information reasonably necessary to accomplish the intended purpose of the use, disclosure or request of PHI.
The probability and magnitude of harm or discomfort anticipated in the research is not greater in and of itself than that ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
NOTE: This includes risk of criminal or civil liability, risks that could damage participants' financial standing, employability, insurability, reputation; or risks that could be stigmatizing.
Minimal risk, in regard to prisoners, is defined as: the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.
Note: "Harms," when referring to prisoners, are specifically described as physical or psychological and that the standard minimal risk for prisoners who are research subjects is not based on the daily life of a healthy prisoner, but refers to a healthy person as an absolute standard based on the daily lives of healthy non-incarcerated individuals.
Any person who is 18 years of age; or less than 19 years of age if guardianship is continued until the person reaches the age of 19 years pursuant to NRS 159.191.
Any change to a protocol from what was previously approved during the period for which approval was given. Changes in research procedures, the informed consent process, and/or the consent/assent document cannot be initiated by the investigator without IRB review and approval, except where necessary to eliminate apparent immediate hazards to the subject. Protocol changes made without prior IRB approval to eliminate apparent hazards to the subject(s), require the PI to immediately submit a memorandum to the IRB addressing the nature of the change, why it was necessary, and the outcome.
- Minor Modification
Any change that does not materially affect an assessment of the risks and benefits of the study or substantially change the specific aims or design of the study. Minor modifications include changes that are editorial or administrative, do not affect criteria for IRB approval, and fall within the list of categories of research eligible for expedited review.
- Substantive Modification
Any change that materially affects an assessment of the risks and benefits of the study or significantly alters the specific aims or design of the study. Substantive changes may increase participant risk or decrease research benefits, and are not among the list of research activities eligible for expedited review. Examples of substantive modifications include changes to subject population, consent processes, or study design; or addition of new instruments.
Any action or activity associated with the conduct or oversight of research involving human subjects that fails to comply with the research plan as approved by a designated IRB, or federal regulations or institutional policies governing such research. Noncompliance may range from minor to serious, be unintentional or willful, and may occur once or several times.
Noncompliance includes deviations to the protocol made in the interest of a single participant such as to coordinate study visits. Noncompliance may result from the action of a participant, investigator or staff and may or may not impact the rights and welfare of research participants or others, or the integrity of the study. Complaints or reports of noncompliance from someone other than the research investigator are handled as allegations of noncompliance until such time that the allegation is validated or found to be invalid and dismissed.
Any behavior, action or omission in the conduct or oversight of research involving human subjects that deviates from the approved research plan, federal regulations or institutional policies but because of its nature, the research project or the subject population,
- Does not place, or have the potential to place, participants and others at greater risk than previously anticipated;
- Does not have a substantive effect on the value of the data collected; and
- Does not result from willful or knowing misconduct on the part of investigators or study staff.
Examples of minor noncompliance may include, when such noncompliance does not create additional risks to subjects:
- Changing study personnel without notifying the IRB;
- Shortening the duration between planned study visits;
- Implementing minor wording changes in study questionnaires without first obtaining IRB approval; or
- Routine lab missed at scheduled visit and re-drawn later.
Any behavior, action or omission in the conduct or oversight of human research that has been determined to:
- Affect the rights and welfare of participants and others;
- Increase risks to participants and others, decrease potential benefits or otherwise unfavorably alter the risk/benefit ratio;
- Compromise the integrity or validity of the research; or
- Result from the willful or knowing misconduct on the part of investigators or study staff.
Examples include, but are not limited to the following:
- Failing to obtain Informed consent before enrolling a participant in a research study;
- Conducting non-exempt research that requires direct interaction or interventions with human subjects without first obtaining IRB approval;
- Enrolling subjects who fail to meet the inclusion or exclusion criteria in a protocol that involves greater than minimal risk and that in the opinion of the IRB Chair, designee, or convened Committee, places the participant(s) at greater risk; or
- Failing to report adverse events, unanticipated problems, or substantive changes to the proposed protocol to the IRB in accordance with IRB policy.
A pattern of noncompliance that, in the judgment of the IRB Chair, designee or convened Board,
- Indicates a lack of understanding or disregard for the regulations or institutional requirements that protect the rights and welfare of participants and others,
- Compromises the scientific integrity of a study such that important conclusions can no longer be reached,
- Suggests a likelihood that noncompliance will continue without intervention, or
- Involves repeated or frequent instances of minor noncompliance.
Continuing noncompliance may also include failure to respond to a request from the IRB to resolve an episode of noncompliance or a pattern of minor noncompliance
A neonate after delivery that, although living, is not viable.
A natural or adoptive parent whose parental rights over the child have not been terminated by the Courts.
A document used to obtain the written permission of a child subject's parent allowing that child to participate in research. The parental permission form must be written in a language understandable by the parent and must contain all elements of informed consent.
The agreement of parents to the participation of their child in research.
The FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices (See http://www.fda.gov/cdrh/devadvice/3132.html#class_3 for Class III device information).
For purposes of this policy, the period of time from implantation until delivery.
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. In addition, any individual who satisfies the above definition and who is receiving care in a medical treatment setting will be considered a prisoner for purposes of this policy. For purposes of this policy, the definition of prisoner does not include individuals on probation or parole, or supervised by electronic monitoring devices.
An individual's right to control access to personal information about him or herself.
In the context of research, privacy refers to an individual's right to control access to personal information about him or herself.
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.
Individually identifiable data:
- About behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, or
- Which has been provided for a specific purpose by an individual and which the individual can reasonably expect will not be made public or accessed for research purposes.
A student shall not be mandated to enroll in University research as a participant as part of a course requirement, without having other, equivalent, non-research opportunities to meet the requirement.
An employee shall not be required to enroll in employer-initiated research as a condition of employment.
Note: When the definitions in the Nevada Revised Statutes (NRS) differ from those found in OHRP regulations or guidance, the chapter and section of the NRS is provided.
Individually identifiable health information that is covered under HIPAA consisting of the following:
- Geographic subdivisions smaller than a state;
- All elements of dates except year (including birth, admission and discharge dates; date of death; and individuals over 89 years old);
- The following categories of numbers: telephone and fax, social security, medical record, health plan beneficiary, account, certificate and license numbers;
- Electronic mail (e-mail) and internet protocol (IP) addresses;
- Internet universal resource locators (URLs);
- Vehicle and device identifiers and serial numbers;
- Biometric identifiers (e.g., finger and voice prints);
- Full-face photographic or comparable images; and
- Any other unique identifying number, characteristic or code.
A federal, state, or local government initiated or endorsed program to deliver financial or medical benefits such as those provided under the Social Security Act or services to improve public welfare such as social, supportive, or nutrition services.
- Before a planned emergency research protocol begins, the dissemination of information in the communities in which the study will take place and from which the subjects will be drawn sufficient to allow a reasonable assumption that the communities are aware that the study will be conducted, and its risks and benefits; and
- After the study has been conducted, the dissemination of information to the communities in which the study was conducted and to scientific researchers sufficient to describe the study's demographic characteristics and the study's results.
Q through Z
A record is any information preserved in a fixed medium, whether on paper, electronically or otherwise.
IRB protocol records include protocol submissions, approved protocol documents (e.g., protocol application, recruitment materials, assessment instruments, and consent forms); all relevant correspondence between the IRB and investigators; and documentation of IRB review (e.g., reviewer checklists, file notes).
To disqualify oneself from discussion and vote on a protocol by leaving the IRB meeting. Recusals are generally initiated by the IRB member because of a real or perceived conflict of interest in the research under discussion. Recusals remove the member from the total number of members present and thus impact quorum.
These are events that are possibly, probably, or definitely caused by the research procedures or related to research participation.
A clinical investigation or a systematic investigation, including research and development, testing and evaluation, designed to develop or contribute to generalizable knowledge.
An institution with whom the University has entered into an IRB Authorization Agreement (IAA), allowing the institution to designate a University IRB as IRB of record on the institution's FWA or vice versa.
A systematic investigation, including research development, testing and evaluations, designed to develop or contribute to generalizable knowledge [45 CFR 46.102(d)].
Any experiment that involves a test article and one or more human subjects and that is either subject to requirements for prior submission to the FDA under section 505(i) or 520(g) of the Act, or is not subject to requirements for prior submission to the FDA under these sections of the Act, but the results of which are intended to be submitted later to, or held for inspection by, the FDA as part of an application for research or marketing permit. The terms "research," "clinical research," "clinical study," "study," and "clinical investigations" are deemed to be synonymous for purposes of this part (21 CFR 50.3(c) and 21 CFR 56.102(c)
Data used in research that would be personally identifiable but not considered PHI and is therefore not subject to the HIPAA privacy and security rules. Use of such information must comply with other state and federal laws for privacy and confidentiality of research health information. Research health information is not associated with or derived from a healthcare service event such as the provision of or payment for care. Examples of research health information not subject to HIPAA include aggregate data, the results of diagnostic tests that do not go into the medical record because they are part of a basic research study and the results will not be disclosed to the subject, and testing done without the PHI identifiers.
Changes requested by the IRB following review by expedited procedures or at convened meetings.
- Minor Revisions
Changes requested by the IRB that are editorial or proscriptive (i.e., investigators are given specific text or parameters for addressing the changes); or confirm IRB assumptions. Minor revisions may be re-reviewed by expedited procedures.
- Substantive Revisions
Changes requested by a convened IRB that relate directly to the criteria for IRB approval and require clarification or explanation from the researcher. Substantive revisions must be re-reviewed at a convened IRB meeting.
Any information which could be of interest to the court in civil, criminal or other judicial proceedings. Most commonly this includes the use of alcohol, illegal drugs or addictive products and illegal behavior. Other examples which may in some instances be of interest to the court include information regarding HIV, AIDS, and other STDs; sexual practices or preferences; the participant's psychological state or mental health; information that can be linked to a participant's financial standing, employability or reputation within the community or that might lead to social disgrace or prejudice; genetic information or identifiable biological samples and corresponding data that may be used to demonstrate predisposition to disease or disputes in paternity; or information regarding behavioral interventions.
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.
A device that presents a potential for serious risk to the health, safety, or welfare of a subject and:
- Is intended as an implant, or
- Is used in supporting or sustaining human life, or
- Is of substantial importance in diagnosing, curing, mitigating or treating a disease, or otherwise prevents impairment of human health, or
- Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.
See Institutional Support Letter
A guardian of a person of limited capacity, including, without limitation, such a guardian who is appointed because a person of limited capacity has voluntarily petitioned for the appointment and the court has determined that the person has the requisite capacity to make such a petition.
Sponsor-investigator is an individual who both initiates and actually conducts, alone or with others, a clinical investigation: in individual under whose immediate direction the investigational drug or device is administered, dispensed or used. The term does not include a corporation or agency. The obligations of a sponsor-investigator include those of an investigator and those of a sponsor.
For purposes of this policy, student refers to a person with whom the University or affiliate investigator has an academic instructional or mentoring relationship.
Research originated and conducted by a University student investigator to fulfill academic requirements for a class project, thesis or dissertation.
Consent for an individual to participate in research given by an appropriate surrogate (e.g., next of kin including spouse, parent, child, sibling) when an individual is assessed as not capable of providing fully informed and legally effective consent.
Note: Nevada State law requires court approval before a guardian may give consent for a ward to participate in research. (See I1D GD2 Applicable Nevada State Laws for information about State laws governing guardianships.)
Permission for an individual to participate in research given by an appropriate surrogate (e.g., next of kin such as spouse, parent, child, sibling) when an individual is assessed as not capable of providing fully informed and legally effective consent. See Guidance I1D GD2 for Chapters 159 and 162A for Nevada laws related to LARs and surrogate consent in research.
A determination made or endorsed by the IRB for a temporary cessation of one or more aspects of an IRB-approved study while the research is considered active. The activities to be suspended are determined by the specific concerns raised and the potential risks to subjects of continuing or not continuing study procedures. Suspensions may be initiated by the principal investigator, the Sponsor, University monitoring authorities, or the IRB. Suspensions may apply to some protocol related activities (e.g., stopping further enrollment of new subjects) or all protocol activities (e.g., stopping the research).
An activity that involves a prospective plan which incorporates data collection, either quantitative or qualitative, and data analysis to answer a question.
Withdrawal of IRB approval for a study. Following a determination to terminate a study, no study procedures may occur other than those identified by the IRB as necessary for the orderly closing of the study.
Any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under or under sections 351 and 354-360F of the Public Health Service Act (42 USC 262 and 263b-263n).
Potential research participants who are also patients believe that a clinical trial proposed by their health care provider will provide a therapeutic benefit to them, even after being told that there is no assured benefit.
The time period, based on available scientific evidence, during which the intervention under investigation in the planned emergency research might reasonably produce a demonstrable clinical effect.
For purposes of this policy, trainee refers to a person who is in the process of being formally trained by a research mentor, typically senior University faculty.
Transitional device: a device subject to section 520(l) of the FD&C Act and which FDA previously regulated as a new drug or an antibiotic drug before May 28, 1976.
Problems, risks or events that occur during the conduct of the research, but were not expected and therefore are not cited in the written protocol, the consent form(s) or the Investigator's Brochure. Unanticipated events also include problems, risks or adverse events that were expected but occur with greater severity or frequency than originally anticipated.
The phrase "unanticipated problems involving risks to subjects or others" is found but not defined in the DHHS regulations at 45 CFR part 46. DHHS OHRP considers Unanticipated Problems, in general, to include any incident, experience, or outcome that meets all three of the following criteria:
- Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
- Related or possibly related to participation in the research (in this guidance document, possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
- 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.
Other problems that must be reported include:
- Changes made to approved research without prior IRB approval to eliminate apparent immediate harm to subjects or others and
- Other unanticipated information that is related to the research and indicates that participants or others might be at increased risk of harm.
See IRB Policy II2F Reporting Adverse Events and Unanticipated Problems.
The inappropriate use of prestige, wealth, ability or position to directly or indirectly affect the potential participants' decision to participate.
Limits the scope of the University's Federalwide Assurance (FWA) to research receiving or supported by federal funds. This policy allows the University to apply protections that are equivalent to the regulations at 45 CFR 46 Subpart A, and Subparts B, C, and D to minimal risk research when no part of the research receives funding from a federal agency. The IRB-Flex policy allows for protections to be commensurate with risk as determined by the IRB. Specifically, the IRB-Flex policy adds exempt categories 7 and 8; and allows for flexibility in requirements for the protection of vulnerable populations, informed consent, and approval periods.
Mandatory Exclusions to the IRB-Flex Policy
· Research that is funded or supported by a federal agency such as VA, NIH, NSF, CDC, FDA, USDA, or DofEduc
· Studies that involve greater than minimal risk
· No-cost extensions for federally-funded research
· Research study where a student is paid/supported from a federal training grant or otherwise paid/supported directly from the Faculty Advisor's federal funds
· When study personnel receive federal funding, even if the funding is not specifically intended to support research activities (e.g., federal training grants, scholarships, fellowships)
· Studies with FDA-regulated components
· Studies involving use of data repositories when the data are to be used to support applications to the FDA
· Studies with clinical interventions
· Studies involving intervention or interaction with prisoners
· Studies seeking or obtaining Certificates of Confidentiality
· Studies with contractual obligations or restrictions that preclude eligibility in this policy
Records which are created or received in the course of conducting human subjects research, including subject responses to questionnaires, information obtained from subjects' medical or educational records, and biological specimens and associated data.
Records created or received by a University faculty member, staff member, student or trainee in her or his role as a University employee, or by a University student or trainee in the course of providing a service to the University or to others as part of her or his education or training, except the following:
- intellectual property which by University policy is owned, licensed, or otherwise legally controlled by a Record User; and
- records created or received by faculty members while participating in the peer review of any of the following:
- a manuscript,
- a sponsored research application, or
- the qualifications of a person seeking employment at another institution.
Pertaining to neonates and for purposes of this policy, the ability, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration. If a neonate is viable, it may be included in research only to the extent permitted and in accordance with the requirements of Subparts A (Basic DHHS Policy for Protection of Human Research Subjects) and D (Additional Protections for Children Involved as Subjects in Research) of 45 CFR 46.
Any person for whom a guardian has been appointed. For example, children under the protection of a court, child protective services, or under the care of a non-parental relative would be considered to be wards.
Any person for whom a guardian has been appointed.