Any serious adverse effect on health or safety, any life-threatening problem or death caused by or associated with a device, or any other serious problem associated with a device that relates to the rights, safety, or welfare of research participants.
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:
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, letters, emails, notices, posters, radio/TV spots, newspaper ads, signs, brochures, internet postings that are used to invite potential participants into research studies.
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.
Any change that does not materially increase the risks, nor materially decrease the benefits of the study, nor materially decrease scientific merit. 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.
Any change that materially increases risks, or materially decreases benefits or scientific merit of the study. Substantive changes are those that may increase participant risk or decrease research benefits, and are not among the list of research activities eligible for expedited review. Examples of substantive amendments include changes to subject population, consent processes, or study design; or addition of new instruments.
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).
A virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), used for the prevention, treatment, or cure of a disease or condition of human beings. Biological products include bacterial vaccines, allergenic extracts, gene therapy products, growth factors, cytokines, monoclonal antibodies, and recombinant DNA. Biological products may be considered drugs.
Broad consent involves asking participants for permission to store identifiable data and/or biospecimens for future research on a specific disease or condition, but where the nature of the future research is not yet known.
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.
Research sponsored by a Federal government entity that involves restrictions imposed, by agreement or otherwise, on the distribution or publication of the research findings, or results for a specified period or for an indefinite duration following completion of the research.
For studies subject to FDA regulations, any experiment (an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice) 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.
Replacement of identifiable private information with a number, letter, symbol, or combination thereof (i.e., identification code) when a key to decipher the code is maintained thus linking the identification code (and coded data or specimen) to private information.
Clinical trial means a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.
The act of using force or threats, whether actual, implied, perceived or indirect, to encourage an individual to participate in a research study.
Having either a 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. May include persons under the influence of drugs or alcohol or who suffer from degenerative diseases affecting the brain, and those with severely disabling physical handicaps or who are terminally ill.
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.
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.)
Denotes capacity to act on 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.
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.
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.
Conflict of Interests for IRB Members/Consultants
Any financial or non-financial interest specified above, or which is subject to University or institutional disclosure requirements (for IRB members/consultants who are University employees or representatives of an University Affiliate, respectively); and the following additional considerations for all IRB members/consultants:
Financial Interests include anything of monetary value the member/consultant believes may influence his/her objectivity in reviewing the research (e.g., financial support/reimbursement from the company sponsoring the research; potential for monetary gain based on study outcome).
Non-financial interests include professional or personal interests the member/consultant believes may influence his/her objectivity in reviewing the research (e.g., thesis/dissertation committee member; project advisor/consultant; substantial alignment or conflict between own research interests and the proposed research; or unpaid consultant for the company sponsoring the research).
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 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 the provider and the intended recipient of research data set that establishes the ways in which the information may be used and how it will be protected.
Investigators give participants false information or intentionally mislead participants about a key aspect of the research.
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.
Any individual captured by, or transferred to the custody or control of, DoD personnel pursuant to the law of war. This does not include persons being held solely for law enforcement purposes, except where the United States is the occupying power. Detainees who are U.S. citizens or U.S. resident aliens will continue to enjoy all applicable rights and privileges under U.S. law and DoD regulations (from DoD Directive 2310.01E).
An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is
recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them;
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
intended to affect the structure or any function of the body of man or other animals and which does not achieve its primary intended purposes through chemical action or metabolism within or on the body.
A product meant for ingestion that contains a "dietary ingredient" intended to add further nutritional value to (supplement) the diet. A "dietary ingredient" may be one, or any combination, of the following substances:
herb or other botanical,
dietary substance for use by people to supplement the diet by increasing the total dietary intake
concentrate, metabolite, constituent, or extract
NOTE: A food, dietary ingredient, or dietary supplement for which a truthful and not misleading statement is made in accordance with Dietary Supplement Health and Education Act it is not a drug solely because the label or the labeling contains such a statement.
The release, transfer, provision of access to or divulgence in any other manner of PHI outside the entity holding the information.
Any article (other than food)
recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them;
intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals;
intended to affect the structure or any function of the body of man or other animals; or
intended for use as a component of any article as specified above.
Curriculum-related interventions or classroom activities. For Special Education these include activities that correspond to the Individualized Educational Program for a student with an identified disability.
An environment in which students learn. Educational settings include preschool, elementary, secondary, and higher educational facilities and programs; and alternative settings where educational services or activities are provided such as home instruction, electronic or web-based courses and schools, and after-school programs when these involve tutoring or homework help.
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, biological product, or device 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 information or biospecimens through intervention or interaction with the individual, and use, study, or analyze the information or biospecimens;
Obtain, use, study, analyze, or generate identifiable private information or identifiable biospecimens; or
Obtain 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 information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens;
Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens; or
Obtains the informed consent of human subjects for the research.
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.
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.
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)]
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 obtained from projects or investigations that are designed to draw general conclusions, to transfer or extrapolate results to a broader population or situation than those from which the information was initially derived, or to establish or enhance scientific evidence about a topic of interest.
The process of converting text-based postal address data into digital geographic coordinates, generally for the purpose of mapping information.
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.
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.
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.
The scientific discipline concerned with the understanding of interactions among humans and other elements of a system.
A human subject is a living individual about whom an investigator conducting research:
obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or
Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.
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.
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.
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 living individual for the primary purpose of obtaining data regarding the effect of the intervention or interaction. Research involving a human being as an experimental subject is a subset of research involving human participants. 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 not more than 8,000 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.
Definitions I through P
An identifiable biospecimen is a biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen. [45 CFR 46.102(e)(6)]
Identifiable private information is private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information. [45 CFR 46.102(e)(5)]
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.
Anticipated Results that are outside the original purpose for which a test or procedure was conducted, but that are known to be associated with the test or procedure: Study is designed to discover A, but learns B, a result known to be associated with the test or procedure in use. B is an anticipated incidental finding. Example: Researchers use the Patient Health Questionnaire (PHQ) assess for depression and learn a participant is having suicidal thoughts.
Unanticipated Results that are outside the original purpose for which a test or procedure was conducted and that could not have been anticipated given the current state of scientific knowledge: Study is designed to discover A, but learns C, a unexpected result. C is an unanticipated incidental finding. Example: Genetic testing identifies a health risk based on a newly discovered genetic association (not known at the time the study was designed).
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.
Investigators withhold information from participants related to the specific purpose, nature, or other key aspect of the research.
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.
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.
Information which either is labelled by name or other personal identifiers; or by virtue of sample size or other factors, be reasonably interpreted as referring to a particular private person.
Institution means any public or private entity, or department 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 45 CFR 46 and 21 CFR 56 that 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.
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.
An interaction may be communication or interpersonal contact between the investigator (or research team) and the living individual. Examples include interviews, questionnaires, surveys, observations, manipulations of subject behavior, diet, or environment, physical measurements, specimen collection (e.g. blood tissue), and administration of experimental drugs or devices. Projects which collect information about policies, practices or procedures - even if the person who provided that information is identified - do not constitute human subject research.
Intervention includes both physical procedures by which information or biospecimens are gather and manipulations of the subject of the subject's environment that are performed for research purposes.
Permits the lawful shipment of a device for the purpose of conducting investigations of that device when the device would otherwise be required to comply with a performance standard or have premarket approval to be shipped lawfully.
A new drug or biological agent 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.
Three additional IND types 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.
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 Institutional Review Board (IRB) designated as the Reviewing IRB for human subject research as specified in an IRB Authorization Agreement, Cooperative Agreement, Memorandum of Understanding, or other contract between the University and an external institution. The IRB of Record assumes all of the IRB responsibilities for human research activities subject to the agreement.
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.
Protected Health Information (PHI) that excludes the following direct identifiers of the individual or of relatives, employers, or household members of the individual:
Postal address information, except town or city, State, and zip code
Social Security Numbers
Medical record numbers
Health plan beneficiary numbers
Certificate/ license numbers
Vehicle identifiers and serial number, including license plate numbers
Biometric identifiers, including finger and voice prints and
Full face photographic images and any comparable images
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 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.
Research that involves closely watching or noting facts about people in public places (e.g., observing shopping or eating habits) or in a natural setting.
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.
Any individual, partnership, corporation, association, public or private organization or governmental entity, or combination thereof.
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.
A principal investigator (PI) is a qualified individual who directs a research project or research program. The PI oversees scientific, technical, and day-to-day management of the research. In the event of research conducted by a team of individuals, the PI is the responsible leader of the research team.
Any individual involuntarily confined or detained in a penal institution including prisons, jails, juvenile offender facilities, and residential facilities for court-ordered substance abuse treatment or a mental institution when required through sentencing or as an alternative to incarceration. 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.
An individual's right to control access to his or her body and personal information; to be free from unauthorized intrusion into one's affairs and individual records.
Any individual (including those acting as in individual in her/his official capacity), partnership, corporation, association, public or private organization or governmental entity, or combination thereof, other than an agency, or department of Federal, State, or local government, or any component or combination thereof.
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 that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public.
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.
Closely watching or noting facts about people exposed to the general view (i.e., in a public place).
Definitions 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).
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 evaluation, designed to develop or contribute to generalizable knowledge [45 CFR 46.102(l)]. The following activities are deemed not to be research:
Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information, that focus directly on the specific individuals about whom the information is collected.
Public health surveillance activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in diseases, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters).
Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes.
Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.
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.
A subset of non-exempt research involving human subjects in which an activity conducted for research purposes consists of intervention or interaction with a living individual for the primary purpose of obtaining data regarding the effect of the intervention or interaction.
Changes requested by the IRB following review by expedited procedures or at convened meetings.
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.
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.
An assessment of whether or not a study represents good science. For example a study with scientific merit addresses an area of importance to the discipline, utilizes established scientific principles, exhibits alignment within the study, offers congruence among research questions and study design, and is likely to contribute to scientific knowledge.
Result that is not the primary target of the test or procedure but is an additional result actively sought by the researcher: Study is designed to discover A; due to relevant associations or per expert recommendation, researchers also actively seek D. D would be a secondary finding. Example: Researchers use standard, discrete tests (e.g., urinary and blood) to assess renal function to categorize participants. Results identify participants with normal or with reduced kidney function. Researchers also assess for iron status and identify participants with anemia.
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.
See Adverse Event
A disease or condition associated with persistent or recurrent morbidity that has substantial impact on day-to-day functioning. Generally the definition does not include short-lived and self-limiting morbidity. The morbidity needn't be irreversible to constitute a serious disease or condition. 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.
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.
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.)
A determination by the IRB Chair, a designated IRB member, or the convened IRB to temporarily interrupt some or all previously-approved research activities. The suspended activities could include, but not be limited to, recruiting and enrolling new subjects. Suspended studies remain open and require continuing review.
NOTE: Suspensions of IRB approval apply to interruptions in research activities due to concerns about the safety, rights, or welfare of human research subjects or others. They do not include interruptions in human research resulting solely from the expiration of the IRB approval period.
Systematic Investigation is typically a predetermined method for studying a specific topic, answering a specific question(s), testing a specific hypothesis(es), or developing theory. Systematic investigations include observational studies, interview or survey studies, group comparison studies, test development, and interventional research.
A determination by the convened IRB to permanently halt some or all previously approved research activities including, but not limited to, enrollment of new subjects.
NOTE: Terminations of IRB approval apply to a cessation of research projects or activities due to concerns about the safety, rights, or welfare of human research subjects or others. They do not include interruptions in human research resulting solely from the expiration of the IRB approval period.
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.
Tiered consent involves offering a number of options to participants for permission to store identifiable or de-identified data and/or biospecimens for future research on a specific disease or condition. The participant opts in or out of the various choices offered.
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.
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
A VA investigator is any individual who conducts research approved by the VA R&D Committee and the IRB while acting under a VA appointment on VA time, including full and part-time compensated employees, trainees, without compensation (WOC) employees, and individuals appointed or detailed to VA under the Intergovernmental Personnel Act (IPA) of 1970. NOTE: Contractors cannot be VA Investigators.
Research that is approved by the R&D Committee and conducted by VA Investigators including PIs, Co-PIs, and Site Investigators on VA time (serving on compensated, WOC, or IPA appointments), utilizing VA resources (e.g., equipment), or on VA property including space leased to, and used by VA. The research may be funded by VA, by other sponsors, or be unfunded.
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.