Definitions | Human Research Protection Program

Benefit

Children

Child: “Persons who have not attained the legal age for consent to treatments or procedures involved in the research [clinical investigations], under the applicable law of the jurisdiction in which the research [clinical investigation] will be conducted.” 21 CFR 50.3(o), 45 CFR 46.402(a) [FDA]

HRPP Manual Section 6-8-C, Special Categories of Research Subjects: Children:

In Michigan, a child is a person who has not:

1. Yet reached the age of 18; and

2. Been emancipated by court order; and

3. Been emancipated by operation of law under any of the following circumstances:

a. Marriage

b. Active duty with the armed forces of the United States

Michigan law states that an emancipated minor has the rights and responsibilities of an adult (with certain exceptions), including the right to authorize his or her own preventive healthcare. Although it is a reasonable inference, Michigan law does not explicitly state that emancipated minors may consent to participation in research. Thus, the IRB, with input from the MSU Office of the General Counsel, may choose not to approve research that relies solely on the consent of an emancipated minor.

Emancipated: A legal status conferred upon persons who have reached the age of 18 or who have not yet attained the legal age of competence as defined by state law (for such purposes as consenting to medical care), but who are entitled to treatment as if they had, by virtue of assuming adult responsibilities, such as marriage or serving on active duty in the military, or by virtue of a court order.

HRPP Manual Section 6-8-C, Special Categories of Research Subjects: Children

Clinical Investigation (FDA)

U.S. Food and Drug Administration

Clinical investigation means any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the Food and Drug Administration under section 505(i), 507(d), or 520(g) of the act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that must meet the provisions of part 58, regarding nonclinical laboratory studies. The terms research, clinical research, clinical study, study, and clinical investigation are deemed to be synonymous for purposes of this part.

U.S. Food and Drug Administration, 21 CFR 56.102(c)

For an activity involving drugs: Clinical investigation means any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For the purposes of this part, an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice.

U.S. Food and Drug Administration, 21 CFR 312.3(b)

For an activity involving devices: Investigation means a clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device.

U.S. Food and Drug Administration, 21 CFR 812.3(h)

Test article means any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 and 354-360F of the Public Health Service Act. (42 U.S.C. 262 and 263b-263n).

U.S. Food and Drug Administration, 21 CFR 50.3(j)

Clinical Research Billing Compliance Key Terms

Color additive

“Color additive”

(1) means a material which—

(A) is a dye, pigment, or other substance made by a process of synthesis or similar artifice, or extracted, isolated, or otherwise derived, with or without intermediate or final change of identity, from a vegetable, animal, mineral, or other source, and

(B) when added or applied to a food, drug, or cosmetic, or to the human body or any part thereof, is capable (alone or through reaction with other substance) of imparting color thereto;

except that such term does not include any material which the Secretary, by regulation, determines is used (or intended to be used) solely for a purpose or purposes other than coloring.

(2) The term “color” includes black, white, and intermediate grays.

(3) Nothing in subparagraph (1) of this paragraph shall be construed to apply to any pesticide chemical, soil or plant nutrient, or other agricultural chemical solely because of its effect in aiding, retarding, or otherwise affecting, directly or indirectly, the growth or other natural physiological processes of produce of the soil and thereby affecting its color, whether before or after harvest.

Federal Food Drug and Cosmetic Act, 21 U.S.C. 321(t)

Covered Entity (HIPAA)

Device (medical device)

Device (except when used in paragraph (n) of this section and in sections 331(i), 343(f), 352(c), and 362(c) of this title) means:

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

(1) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,

(2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or

(3) intended to affect the structure or any function of the body of man or other animals, and

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

Federal Food Drug and Cosmetic Act, 21 U.S.C. 321(h)

Dietary Supplement

Dietary supplement—

(1) means a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients:

(A) a vitamin;

(B) a mineral;

(C) an herb or other botanical;

(D) an amino acid;

(E) a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or

(F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), (D), or (E);

(2) means a product that—

(A)(i) is intended for ingestion in a form described in section 350(c)(1)(B)(i) of this title; or (ii) complies with section 350(c)(1)(B)(ii) of this title;

(B) is not represented for use as a conventional food or as a sole item of a meal or the diet; and

(C) is labeled as a dietary supplement; and

(3) does—

(A) include an article that is approved as a new drug under section 355 of this title or licensed as a biologic under section 262 of title 42 and was, prior to such approval, certification, or license, marketed as a dietary supplement or as a food unless the Secretary has issued a regulation, after notice and comment, finding that the article, when used as or in a dietary supplement under the conditions of use and dosages set forth in the labeling for such dietary supplement, is unlawful under section 342(f) of this title; and

(B) not include—

(i) an article that is approved as a new drug under section 355 of this title, certified as an antibiotic under section 357 of this title, or licensed as a biologic under section 262 of title 42, or

(ii) an article authorized for investigation as a new drug, antibiotic, or biological for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public,

which was not before such approval, certification, licensing, or authorization marketed as a dietary supplement or as a food unless the Secretary, in the Secretary's discretion, has issued a regulation, after notice and comment, finding that the article would be lawful under this chapter.²

Except for purposes of paragraph (g) and section 350f of this title, a dietary supplement shall be deemed to be a food within the meaning of this chapter.

Federal Food Drug and Cosmetic Act, 21 U.S.C. 321 (ff)

Directed

Disclosure (HIPAA)

Drug

Drug means:

(A) articles 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; and

(B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and

(C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and

(D) articles intended for use as a component of any article specified in clause (A), (B), or (C).

A food or dietary supplement for which a claim, subject to sections 343(r)(1)(B) and 343(r)(3) of this title or sections 343(r)(1)(B) and 343(r)(5)(D) of this title, is made in accordance with the requirements of section 343(r) of this title is not a drug solely because the label or the labeling contains such a claim.

A food, dietary ingredient, or dietary supplement for which a truthful and not misleading statement is made in accordance with section 343(r)(6) of this title is not a drug under clause (C) solely because the label or the labeling contains such a statement.

Federal Food Drug and Cosmetic Act 21 U.S.C. §321(g)

Food Additive

Food additive means any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food (including any substance intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food; and including any source of radiation intended for any such use), if such substance is not generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures (or, in the case of a substance used in food prior to January 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use; except that such term does not include—

(1) a pesticide chemical residue in or on a raw agricultural commodity or processed food; or

(2) a pesticide chemical; or

(3) a color additive; or

(4) any substance used in accordance with a sanction or approval granted prior to September 6, 1958, pursuant to this chapter, the Poultry Products Inspection Act [21 U.S.C. 451 et seq.] or the Meat Inspection Act of March 4, 1907, as amended and extended [21 U.S.C. 601 et seq.];

(5) a new animal drug; or

(6) an ingredient described in paragraph (ff) in, or intended for use in, a dietary supplement.

Federal Food Drug and Cosmetic Act, 21 U.S.C. 321(s)

Generalizable Knowledge

Generalizable Knowledge: To be considered "generalizable knowledge," the activity would include the following concepts:

Knowledge contributes to a theoretical framework of an established body of knowledge
Results are expected to be generalized to a larger population beyond the site of data collection or population studied
Results are intended to be replicated in other settings

MSU HRPP Manual 4-3, Determination of Human Subject Research

Health Information (HIPAA)

Health information means any information, including genetic information, whether oral or recorded in any form or medium, that is created or received by a health care provider, health plan, public health authority, employer, life insurer, school or university, or health care clearinghouse; and 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.

Health Insurance Portability and Accountability Act (HIPAA), 45 CFR 46.160.103

Human Subject (HHS)

Revised Common Rule (2018 Requirements)
(1) Human subject means a living individual about whom an investigator (whether professional or student) conducting research:

(i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or

(ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.

(2) Intervention includes both physical procedures by which information or biospecimens are gathered (e.g., venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes.

(3) Interaction includes communication or interpersonal contact between investigator and subject.

(4) 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 (e.g., a medical record).

(5) 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.

(6) 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.

Common Rule, 45 CFR 46.102(e)(2018 Requirements)

Pre-2018 Common Rule
Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains

(1) Data through intervention or interaction with the individual, or
(2) Identifiable private information.

Intervention includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. Interaction includes communication or interpersonal contact between investigator and subject. Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.

Common Rule, 45 CFR 46.102(f)(Pre-2018 Requirements)

Human subject (FDA)

U.S. Food and Drug Administration

Human subject means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient.

U.S. Food and Drug Administration, 21 CFR 50.3(g)

For a clinical investigation involving drugs: Subject means a human who participates in an investigation, either as a recipient of the investigational new drug or as a control. A subject may be a healthy human or a patient with a disease.

U.S. Food and Drug Administration, 21 CFR 312(b)

For a clinical investigation involving devices: 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.

U.S. Food and Drug Administration, 21 CFR 812.3(p)

Identifiable Biospecimen

Identifiable Private Information

Individually Identifiable Health Information

Individually identifiable health information is information that is a subset of health information, including demographic information collected from an individual, and Individually identifiable health information is information that is a subset of health information, including demographic information collected from an individual, and: employer, or health care clearinghouse; and (2) Relates to the past, present, or future physical or mental health or condition of an individual; the provision of health care to an individual; or the past, present, or future payment for the provision of health care to an individual; and (i) That identifies the individual; or ii) With respect to which there is a reasonable basis to believe the information can be used to identify the individual.

Health Insurance Portability and Accountability Act (HIPAA), 45 CFR 46.160.103

Infant Formula

Interaction

Revised Common Rule (2018 Requirement)

Interaction includes communication or interpersonal contact between investigator and subject.

Common Rule, 45 CFR 46.102(e)(3)(2018 Requirements)

Pre-2018 Common Rule

Interaction includes communication or interpersonal contact between investigator and subject.

Common Rule, 45 CFR 46.102(f)(Pre-2018 Requirements)

Intervention

Revised Common Rule (2018 Requirements)

Intervention includes both physical procedures by which information or biospecimens are gathered (e.g., venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes.

Common Rule, 45 CFR 46.102(e)(2)(2018 Requirements)

Pre-2018 Common Rule

Intervention includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes.

Common Rule, 45 CFR 46.102(f)(Pre-2018 Requirements)

Involve risk

Minimal Risk

Minimal Risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

Common Rule, 45 CFR 46.102(i)(Pre-2018 Requirements, 2018 Requirements)

U.S. Food and Drug Administration, 21 CFR 50.3(k)

Prisoner

Prisoner means any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing.

Common Rule, 45 CFR46.303(c)

Private Information

Revised Common Rule (2018 Requirements)

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 (e.g., a medical record).

Common Rule, 45 CFR 46.102(e)(4)(2018 Requirements)

Pre-2018 Common Rule

Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).

Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.

Common Rule, 45 CFR 46.102(f)(Pre-2018 Requirements)

Protected Health Information (HIPAA)

Protected health information means individually identifiable health information: (1) Except as provided in paragraph (2) of this definition, that is: (i) Transmitted by electronic media; (ii) Maintained in electronic media; or (iii) Transmitted or maintained in any other form or medium. (2) Protected health information excludes individually identifiable health information: (i) In education records covered by the Family Educational Rights and Privacy Act, as amended, 20 U.S.C. 1232g; (ii) In records described at 20 U.S.C. 1232g(a)(4)(B)(iv); (iii) In employment records held by a covered entity in its role as employer; and (iv) Regarding a person who has been deceased for more than 50 years.

Health Insurance Portability and Accountability Act (HIPAA), 45 CFR 46.160.103

Protocol Deviation

Protocol deviation: any change, divergence, or departure from the study design or procedures of a research protocol that is under the investigator control that has not been approved by the IRB and does not impact subject safety, compromise the integrity of study data and/or affect subject willingness to participate in the study.

MSU HRPP Manual Section 9-8, Protocol Deviations or Violations

Protocol Violation

Related to the Research

Research

Revised Common Rule (2018 Requirements)

Research means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Activities that meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program that is considered research for other purposes. For example, some demonstration and service programs may include research activities. For purposes of this part, the following activities are deemed not to be research:

(1) 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.

(2) 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).

(3) 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.

(4) Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.

Common Rule, 45 CFR 46.102(l)(2018 Requirements)

Pre-2018 Common Rule

Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

Common Rule, 45 CFR 46.102 (d)(Pre-2018 Requirements)

Significant Financial Interest

Significant Financial Interest: Significant financial interests are defined under the Faculty / Academic Staff Conflict of Interest Policy and must be reported.

A significant financial interest includes, but is not limited to, a financial interest in the sponsor, product, or service being tested, or in a competitor of the sponsor or product or service being tested.

The following are deemed to create a “significant financial interest”:

Income or receipt of payments of any kind totaling more than $5,000 over the last calendar year from a single entity;
Ownership interests in a single entity of greater than one percent (1%) or of an amount exceeding $5,000;
Intellectual property rights or licenses with an established fair market value exceeding $5,000 or which generate income of any value from other than MSU (including royalties from other domestic universities);
Unvalued stock options or other options for ownership in a privately held company of any value;
Paid or unpaid service on a governing or advisory board, or in a fiduciary or managerial role, for, or as a general partner of, an entity;
Serving as a trustee for a trust or estate, or having a beneficial interest in a trust or estate, whose value exceeds $5,000;
Indebtedness to or from a single entity in an amount exceeding $5,000;
receipt of gifts of goods, property, or services, like transportation, resort or hotel accommodations, or other recreational or personal amenities;
Other opportunity for tangible personal benefit.

The following financial interests are excluded from consideration and do not need to be reported:

MSU salary, remuneration by MSU, or other payments at MSU’s behest (including from an MSU-approved practice plan);
Income from seminars, lectures, teaching engagements, or service on advisory committees or review panels paid by:
- Federal, state, or local U.S. government agencies;
- U.S. institutions of higher education;
- U.S. academic teaching hospitals and medical centers;
- U.S. research institutes affiliated with an institution of higher education;
Financial interest arising solely by means of investment in a mutual, pension, or other institutional investment fund over whose management and investments neither the individual nor any immediate family member has control;
Indebtedness from a bank, credit union, or other commercial lender.

MSU HRPP Manual 10-1, Conflict of Interest

Systematic Investigation

Systematic Investigation: To be considered a "systematic investigation," the concept of a research study must:

Attempt to answer research questions (in some research, this would be a hypothesis)
Is methodologically driven, i.e., it collects data or information in an organized and consistent way
Data or information is analyzed in some way, be it quantitative or qualitative data analysis
Conclusions are drawn from the results

MSU HRPP Manual 4-3, Determination of Human Subject Research

Unanticipated Problems Involving Risks to Subjects or Others

Unexpected

Unexpected: the problems are unexpected in terms of nature, severity or frequency given the research procedures that are described in the protocol-related documents, such as the Institutional Review Board (IRB) approved research protocol and informed consent document and the characteristics of the subject population being studied.

MSU HRPP Manual 9-1, Unanticipated Problems Involving Risks to Subjects or Others

Use (HIPAA)

Written, or In Writing