Learn definitions, explanations, and acronyms commonly used on the research enterprise website and through daily activities related to clinical research and associated regulations, processes and practices.

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Adverse Event: Any untoward or unfavorable medical occurrence in a human research study participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, clinical event, or disease, that occurs during the subject’s participation in the research, whether or not it is considered related to the subject’s participation in the research. Adverse events encompass clinical, physical and psychological harms. Adverse events occur most commonly in the context of biomedical research, although on occasion, they can occur in the context of social and behavioral research. Adverse Events must be reported to the IRB as part of ongoing study management.

Amendment: Per the requirements of 45 CFR 46.103(b)(4) and 21 CFR 56.108(a)(3)(4), changes to approved research may not be initiated without prior IRB review and approval, unless necessary to eliminate apparent immediate hazards to the subject or provide important information germane to informed consent. An amendment includes any planned modification to the research study, such as:

  • Change in research procedures
  • Change in subject eligibility criteria
  • Addition of a research site
  • Change in funding source
  • Change of study personnel
  • Revision of protocol or consent documents
  • Addition of data points/variables
  • Increase in enrollment numbers
  • Change in subject reimbursement etc.

Arm: Group or subgroup of participants in a clinical trial that receives specific interventions, or no intervention, according to the study protocol. This is decided before the trial begins.

Arm Type: General description of the clinical study arm. It identifies the role of the intervention that participants will receive. Types of arms include experimental , active comparatorplacebo comparatorsham comparator and no intervention.

Assent: A child’s affirmative agreement to participate in the research/clinical investigation. Mere failure to object or absent affirmative agreement should not be construed as assent. The assent form (including the assent script) is also the document used to inform and verify the child’s agreement to participate in research.

Associate (Seton): All persons who are employed by Ascension Seton or its direct or indirect subsidiary organizations.  Also refers to persons who are not employees of Ascension Seton but who are associated with Ascension Seton by contractual arrangement.

The Belmont Report: A statement of basic ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of research with human subjects.

Blinding (masking): A clinical trial design strategy in which one or more parties involved in the trial, such as the investigator or participants, do not know which participants have been assigned which interventions. Types of masking include open labelsingle blind masking and double blind masking.

Clinical Trial: A “clinical trial” generally includes interventional studies (with one or more arms) of drugs, biological products, or devices that are subject to FDA regulation, meaning that the trial has one or more sites in the U.S, involves a drug, biologic or device that is manufactured in the U.S. (or its territories), or is conducted under an investigational new drug application (IND). To add to this definition, the ICMJE defines a clinical trial as any research project that prospectively assigns human subjects to intervention or concurrent comparison or control groups to study the cause-and-effect relationship between a medical intervention and a health outcome. Health-related interventions include any intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions and process-of-care changes). Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events. PRS and U.S. Public Law 110-85.

Clinicaltrials.Gov Identifier (NCT Number): A unique identification code is given to each clinical study registered on ClinicalTrials.gov. Because the format is “NCT” followed by an 8-digit number (for example, NCT00000419), this identifier is also known as the NCT Number.

Clinical Research Associate (CRA): Person employed by a sponsor, or by a contract research organization acting on a sponsor’s behalf, who monitors the progress of investigator sites participating in a clinical study.

Clinical Research Coordinator (CRC): Person who handles most of the administrative responsibilities of a clinical trial on behalf of a site investigator, acts as liaison between investigative site and sponsor, and reviews all data and records before a monitor’s visit. (Synonyms: trial coordinator, study coordinator, research coordinator, clinical coordinator, research nurse, protocol nurse.)

ClinCard: An electronic patient payment software system used to deliver research participant stipends.

Cognitively Impaired/Mentally Disabled: 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. Others, including persons under the influence of or dependent on drugs or alcohol, those suffering from degenerative diseases affecting the brain, terminally ill patients and persons with severely disabling physical handicaps may also be compromised in their ability to make decisions in their best interests.

Collaborative Institutional Training Initiative (CITI): Training modules required by the Research Enterprise for affiliated personnel associated with conducting research at Seton.

Collaborator: an organization other than the Sponsor that provides support for a clinical study. This support may include funding, design, implementation, data analysis or reporting. (See also: collaborators data element on ClinicalTrials.gov.)

Comparative Study: One in which the investigative drug is compared against another product, either active drug or placebo.

Comparator (product): An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial. [ICH E6 Glossary] (See also: control.)

Competence: Technically, a legal term, used to denote capacity to act in one’s own behalf; the ability to understand information present, to appreciate the consequences of action (or not action) on that information and to make a choice.

Conflict of Interest (CoI): A conflict of interest exists when two or more contradictory interests relate to an activity by an individual or an institution. The conflict lies in the situation, not in any behavior or lack of behavior of the individual. That means that a conflict of interest is not intrinsically a bad thing.  Examples include a conflict between financial gain and meticulous completion and reporting of a research study or between responsibilities as an investigator and as a treating physician for the same trial participant. Institutional examples include the unbalancing of the institutional mission by acceding to the space requests of a large donor for an idiosyncratic program. (DHHS Office of Research Integrity)

Continuing Review: 
IRB review of previously approved research, which includes (but is not limited to) current subject enrollment, study activity in the previous year and any significant new findings, problems and/or updates that may affect the risks/benefits ratio of the study or the willingness of subjects to continue to participate in the study. Per federal regulation 45 CFR 46.109(e), all open protocols must complete a Continuing Review at least once every 365 days as determined by the IRB.

Contract Research Organization (CRO). A person or an organization (commercial, academic or other) contracted by the sponsor to perform one or more of a sponsor’s trial-related duties and functions. [ICH E6 Glossary]

Contract: A written, dated and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract. [ICH E6 Glossary]

Control Group: The group of subjects in a controlled study that receives no treatment, a standard treatment or a placebo. [21 CFR 314.126] (See also: controls.)

Control(s): 1. Comparator against which the study treatment is evaluated [e.g., concurrent (placebo, no treatment, dose-response, active) and external (historical, published literature)] ICH E10. 2. Computer: processes or operations intended to ensure authenticity, integrity and confidentiality of electronic records 21 CFR Part 11; CSUCT. NOTE: The protocol incorporates scientific rationale for selection of comparator and describes how the comparator serves as a reference point for the evaluation.

Controlled Trial: A type of clinical trial in which observations made during the trial are compared to a standard, called the control. The control may be observations of a group of participants in the same trial or observations from outside the trial (for example, from an earlier trial, which is called a historical control).

Cross-Over Design: Describes a clinical trial in which groups of participants receive two or more interventions in a particular order. For example, a two-by-two cross-over design involves two groups of participants. One group receives drug A during the initial phase of the trial, followed by drug B during a later phase. The other group receives drug B during the initial phase, followed by drug A. So during the trial, participants “cross over” to the other drug. All participants receive drug A and drug B at some point during the trial but in a different order, depending on the group to which they are assigned. One type of intervention model (design).

CR# (Seton): Unique tracking number assigned to each study by Research Administration and used to identify an approved study through the life of the study.

Curriculum Vitae (CV): Document that outlines a person’s educational and professional history.

Data Monitoring Committee (DMC): A group of independent scientists who monitor the safety and scientific integrity of a clinical trial. The group can recommend to the study sponsor that the study be stopped if it is not effective, is harming participants or is unlikely to serve its scientific purpose. Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also referred to as a data safety and monitoring board (DSMB).

Declaration of Helsinki. A set of recommendations or basic principles that guide medical doctors in the conduct of biomedical research involving human subjects. It was originally adopted by the 18th World Medical Assembly (Helsinki, Finland, 1964) and recently revised (52nd WMA General Assembly, Edinburgh, Scotland, October 2000).

Double Blind Masking: A type of masking in which two or more parties involved in the clinical trial do not know which participants have been assigned which interventions. Typically, the parties include the investigator and participants.

Economically Disadvantaged: Defined as those persons placed at an increased risk due to their socioeconomic background. This includes those persons who may struggle to provide basic necessities for themselves and/or their families. Therefore, the use of financial incentives for research participation is a special issue with economically disadvantaged persons. Medical care, remedial education and financial remuneration are common incentives in research. To a person who is economically disadvantaged, seemingly nominal inducements may be powerfully coercive. Incentives cannot be so strong that they take away a person’s voluntary choice to participate in research.

Educationally Disadvantaged: Defined as those persons placed at an increased risk due to their educational background. Educationally disadvantaged persons may have educational deficits, learning disabilities or cultural backgrounds that limit communication with a researcher. It is the responsibility of the researcher to ensure that a subject is fully informed. This includes presenting material at an appropriate level, in an appropriate language and via an appropriate medium (e.g., verbal or visual).

Eligibility Criteria: The key standards that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria include both inclusion criteria and exclusion criteria. For example, a study might only accept participants who are above or below certain ages.

Ethical Religious Directives: Often called ERDs or the Directives, Ethical Religious Directives is a document issued by the United States Conference of Catholic Bishops that offers moral guidance for healthcare delivery based upon theological teachings of the Catholic Church. A copy of the directives can be found here.

Exclusion Criteria: The factors or reasons that preclude a person from participating in a clinical study. (See also: Inclusion Criteria)

Expanded Access: A process regulated by the Food and Drug Administration (FDA) that allows manufacturers to provide investigational new drugs to patients with serious diseases or conditions who cannot participate in a clinical trial. One of several study types. For more information on expanded access programs, visit the Expanded Access: Information for Patients page on the FDA Web site.

Experimental Arm: A group of participants that receives the intervention that is the focus of the study. One of several arm types.

Emergent Use (Emergency Use): Use of an investigational drug, device or biologic that meets all of the following conditions:

  • The patient has a life-threatening situation or severely debilitating disease or condition;
  • There are no standard or generally recognized alternative treatment options with an equal or greater likelihood of treating the patient’s condition; AND
  • The patient’s condition requires immediate intervention before review at a convened meeting of the IRB is possible to avoid major irreversible morbidity or death.

Exempt: Some studies may be considered “exempt” from the regulations. At Ascension Seton the determination of exempt Status must be made by the SIRB prior to initiation and cannot be made by the investigator. Federal regulations identify specific categories of research activities that are exempt from certain federal regulations on the protection of human subjects in research (exempt categories can be found here: 45 CFR 46.101(b)). It is important to note that while a project may be exempt from the regulations, the ethical principles of conducting research with human subjects still apply and, per Ascension Seton IRB policy, IRB review is still required. The investigator may not make the determination of exempt status.

Expedited: Research activities that (1) present no more than minimal risk to human subjects, and (2) involve only procedures listed in one or more of the predetermined expedited categories. Research that includes activities in the list is not necessarily deemed to be of minimal risk simply because the activities are included on this list. Standard requirements for informed consent (or its waiver, alteration or exception) apply regardless of the type of review — expedited or full board — utilized by the IRB.

External IRB: An Institutional Review Board other than the IRB of record for the institution at which the study will take place.

Fabrication: Making up data or results and recording or reporting them. (DHHS Office of Research Integrity)

Falsification: Manipulating research materials, equipment, or processes or changing or omitting data or results such that the research is not accurately represented in the research record. (DHHS Office of Research Integrity)

Final Study Closure (IRB): Closure of a research study where the research is permanently closed to the enrollment of subjects, all subjects have completed all research-related interventions/activities and collection and analysis of private identifiable information is completed and there are no plans to collect any additional data. Studies that have completed a final study closure are no longer subject to continuing review requirements.

Food And Drug Administration (FDA): An agency within the U.S. Department of Health and Human Services. FDA is responsible for protecting the public health by making sure that human and veterinary drugs, vaccines and other biological products, medical devices, the Nation’s food supply, cosmetics, dietary supplements and products that give off radiation are safe, effective and secure.

Full Board: Research activities that are more than minimal risk or do not qualify under the criteria for expedited review. These studies are reviewed at a fully convened meeting of the IRB with quorum present.

Funder Type: Describes the organization that provides funding or support for a clinical study. Support may include providing facilities, expertise or financial resources. Organizations listed as sponsors and collaborators for a study are considered the funders of the study. There are four types of funders:

  • National Institutes of Health
  • Other U.S. Federal agencies (for example, the Food and Drug Administration, Centers for Disease Control and Prevention, U.S. Department of Veterans Affairs)
  • Industry (pharmaceutical and device companies)
  • All others (including individuals, universities and community-based organizations)

Generalizability: The extent to which the findings of a clinical trial can be reliably extrapolated from the subjects who participated in the trial to a broader patient population and a broader range of clinical settings. [ICH E9]

Good Clinical Practice (GCP): A standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality of trial subjects are protected. NOTE: For Guidance on Good Clinical Practice see COMP/ICH/135/95; Declaration of Helsinki; 21 CFR 50, 21 CFR 54, 21 CFR 56, and 21 CFR 312. [ICH]

HIPAA Authorization: In regards to a research study, HIPAA Authorization is the written permission from a prospective subject for the researcher to access the subject’s protected health information (PHI) for research purposes. At Ascension Seton, the HIPAA Authorization Form is reviewed and approved by the CROR.

Healthy Volunteer: Subject (not a patient) in a clinical trial. NOTE: Usually healthy volunteers serve as subjects in Phase 1 trials.

Human Subject: 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. (45 CFR 46.102)

Humanitarian Use Device (HUD): A medical device that is intended for use in patients with conditions that affect less than 4,000 people in the United States. Since the number of patients is relatively small, the Food and Drug Administration (FDA) allows the use of HUDs for treatment of patients without having to complete the same amount of safety and effectiveness testing which other investigational devices are required to complete. Use of an HUD does not necessarily constitute research; however, a HUD may be used in a research study.

Incapacity: When referring to a person’s mental status, incapacity means inability to understand information presented, to appreciate the consequences of action (or not acting) on that information and to make a choice. Often used as a synonym for incompetence.

Inclusion Criteria: The factors, or reasons, that allow a person to participate in a clinical study. (See also: Exclusion Criteria)

Industry-Sponsored: A clinical research study is industry sponsored when a commercial entity contributes to the design or conduct of the study; coordinates the study as a multi-center trial; reimburses the institution for costs associated with conducting the clinical trial; or will have access to, or publish or present data gained from conducting the trial.

Informed Consent: A process used by researchers to communicate with potential and enrolled participants about a clinical study. As part of the informed consent process, researchers:

  • Provide all the important information about the study, so potential participants can decide whether to enroll or, if they are already enrolled, whether to continue to participate
  • Make sure that potential participants understand the risks and potential benefits of participating in the study and the alternatives to the research being conducted
  • Stress that enrolling in, and staying in, a clinical study is completely voluntary. Because giving consent to participate in research is nota contract, participants may leave a study at any time.

The goal of the informed consent process is to protect participants. It begins when a potential participant first asks for information about a study and continues throughout the study until the study ends. The researcher and potential participant have discussions that include answering the participant’s questions about the research. All the important information about the study must also be given to the potential participant in a written document that is clear and easy to understand. The informed consent document is reviewed and approved by the human subjects review board before the document is given to potential participants. Generally, a person must sign an informed consent document to enroll in a clinical study.

Informed Consent Form (ICF): The document used to provide the information necessary for a prospective subject to understand the nature of the research and knowledgeably and voluntarily decide whether or not to participate. Unless waived or altered, the ICF documents the subject’s voluntary agreement to participate in research or to undergo a diagnostic therapeutic or preventative procedure.

Institutional Official (IO): The Institutional Official is responsible for the administration and oversight of research ethics at the institution engaged in research, which includes the appointment of IRB members. At Ascension Seton, the IO is the President, External Affairs.

Institutional Review Board (IRB): IRB means an institutional review board established in accord with and for the purposes expressed in the HHS.gov Protection of Human Subjects Policy.

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. (45 CFR 46.102)

Investigational New Drug (IND): A drug or biological product that is used in a clinical trial but has not been approved by the Food and Drug Administration (FDA) (the drug is either not available for a doctor to prescribe or is available but has not been approved by FDA for the use being studied).

Investigational Product: A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication or when used to gain further information about an approved use.

Investigational Treatment: An intervention under investigation in a clinical study.

Investigator: An individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team. [21 CFR 50.3] (See also: sponsor-investigator, site investigator.)

Investigator’s Brochure (IB): A compilation of the clinical and nonclinical data on the investigational product(s) that is relevant to the study of the investigational product(s) in human subjects.

IRB Approval: IRB approval means the determination of the IRB that the research has been reviewed and may be conducted at an institution within the constraints set forth by the IRB and by other institutional and federal requirements. (HHS.gov Definition for IRB Approval)

Legally Authorized Representative (LAR): 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 procedure(s) involved in the research. (45 CFR 46.102)

Minimal Risk: The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (45 CFR 46.102)

Minimal Risk (in research involving prisoners)*: Research in which the probability and magnitude of physical or psychological harm in the research are not greater in and of themselves than those normally encountered in the daily lives, or in the routine medical, dental or psychological examination of healthy persons.

*(Please note that this definition is different from “minimal risk” not involving prisoners.)

Multicenter Study: Clinical trial conducted according to a single protocol but at more than one site, and, therefore, carried out by more than one investigator.

New Drug Application (NDA): An application to FDA for a license to market a new drug in the United States.

Non-compliance: Failure to comply with applicable regulations or policies related to the conduct or oversight of human subjects research; or failure to comply with the requirements or determinations of the IRB.

Non-disclosure Agreement: A legal contract between at least two parties that outlines confidential material, knowledge or information that the parties wish to share with one another for certain purposes, but wish to restrict access to or by third parties.

Nuremberg Code: Code of ethics, set forth in 1947, for conducting human medical research.

Open-label Study: A trial in which subjects and investigators know which product each subject is receiving; opposite of a blinded or double-blind study. (See blinding.)

Open to Enrollment. The status of a study such that a subject can be enrolled into that study. NOTE: Registry terminology in common use is “open to recruitment”; however, recruitment can begin upon IRB approval of the site; whereas enrollment requires availability of study supplies, subject informed consent, etc., to allow participation of eligible subjects.

Participant: A person or entity with a role in healthcare or a clinical study. NOTE: Participants in a clinical trial may include subjects and study personnel. A subject participates as part of the group of people who are administered the therapeutic intervention or control. (See also: subject, patient.)

Patient: A person under a physician’s care for a particular disease or condition. NOTE: A subject in a clinical trial is not necessarily a patient, but a patient in a clinical trial is a subject. Although often used interchangeably as a synonym for subject, a healthy volunteer is not a patient. (See also: subject, trial subject, healthy volunteer.)

Pharmacodynamics: Branch of pharmacology that studies reactions between drugs and living structures, including the physiological responses to pharmacological, biochemical, physiological and therapeutic agents.

Pharmacoeconomics: Branch of economics that applies cost-benefit, cost-utility, cost-minimization and cost-effectiveness analyses to assess the utility of different pharmaceutical products or to compare drug therapy to other treatments.

Pharmacogenetic test: An assay intended to study inter-individual variations in DNA sequence related to drug absorption and disposition or drug action. (Compare to pharmacogenomic test.)

Pharmacogenetics: Study of the way drugs interact with genetic makeup or the study of genetic response to a drug.

Pharmacogenomic Test: An assay intended to study inter-individual variations in whole genome or candidate gene maps, biomarkers and alterations in gene expression or inactivation that may be correlated with pharmacological function and therapeutic response. Compare to pharmacogenetic test.

Pharmacogenomics: Science that examines inherited variations in genes that dictate drug response and explores the ways such variations can be used to predict whether a person will respond favorably, adversely or not at all to an investigational product.

Pharmacokinetics: Study of the processes of bodily absorption, distribution, metabolism and excretion (ADME) of medicinal products.

Pharmacology: Science that deals with the characteristics, effects and uses of drugs and their interactions with living organisms.

Pharmacovigilance: Term used for adverse event monitoring and reporting

Phase: One in a set of successive stages in a progression or sequence such as:

  1. A step in the progression of a therapy from initial experimental use in humans to postmarket evaluation.
  2. A stage in the conduct of a clinical trial.

NOTE: Clinical trials are generally categorized into four (sometimes five) phases. A therapeutic intervention may be evaluated in two or more phases simultaneously in different trials, and some trials may overlap two different phases. (For meaning 1, see Phase 0–5. For meaning 2, see epoch.)

Phase 0. First-in-human trials, in a small number of subjects, that are conducted before Phase 1 trials and are intended to assess new candidate therapeutic and imaging agents. The study agent is administered at a low dose for a limited time, and there is no therapeutic or diagnostic intent. NOTE: FDA Guidance for Industry, Investigators and Reviewers: Exploratory IND Studies, January 2006 classifies such studies as Phase 1. [Improving the Quality of Cancer Clinical Trials: Workshop Summary – Proceedings of the National Cancer Policy Forum Workshop, Improving the Quality of Cancer Clinical Trials (Washington, DC – Oct 2007)]

Phase 1: The initial introduction of an investigational new drug into humans. Phase 1 studies are typically closely monitored and may be conducted in patients or normal volunteer subjects. NOTE: These studies are designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses and, if possible, to gain early evidence on effectiveness. During Phase 1, sufficient information about the drug’s pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase 2 studies. The total number of subjects and patients included in Phase 1 studies varies with the drug, but is generally in the range of 20 to 80. Phase 1 studies also include studies of drug metabolism, structure–activity relationships, and mechanism of action in humans, as well as studies in which investigational drugs are used as research tools to explore biological phenomena or disease processes. [After FDA CDER Handbook, ICH E8]

Phase 2: Controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks associated with the drug. NOTE: Phase 2 studies are typically well controlled, closely monitored and conducted in a relatively small number of patients, usually involving no more than several hundred subjects. [After FDA CDER Handbook, ICH E8]

Phase 2A: Controlled clinical studies that occur after the completion of Phase 1 studies and the first set of exposure-response studies in patients, and before beginning Phase 2B (i.e., patient dose-ranging trial) and Phase 3 clinical efficacy-safety studies. [FDA draft Guidance for Industry End of Phase 2A meetings, 9/08].

Phase 3: Studies are expanded controlled and uncontrolled trials. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather the additional information about effectiveness and safety that is needed to confirm efficacy and evaluate the overall benefit–risk relationship of the drug and to provide an adequate basis for physician labeling. NOTE: Phase 3 studies usually include from several hundred to several thousand subjects. [After FDA CDER Handbook, ICH E8]

Phase 3B: A subcategory of Phase 3 trials done near the time of approval to elicit additional findings. NOTE: Dossier review may continue while associated Phase 3B trials are conducted. These trials may be required as a condition of regulatory authority approval.

Phase 4: Postmarketing (Phase 4) studies to delineate additional information about the drug’s risks, benefits, and optimal use that may be requested by regulatory authorities in conjunction with marketing approval. NOTE: These studies could include, but would not be limited to, studying different doses or schedules of administration than were used in Phase 2 studies, use of the drug in other patient populations or other stages of the disease, or use of the drug over a longer period of time. [After FDA CDER Handbook, ICH E8]

Phase 5: Postmarketing surveillance is sometimes referred to as Phase 5. (See also: outcomes research.)

Placebo: A substance that does not contain active ingredients and is made to be physically indistinguishable (that is, it looks and tastes identical) from the actual drug being studied.

Placebo Comparator Arm: A group of participants that receives a placebo during a clinical study; one of several arm types.

Plagiarism: The appropriation of another person’s ideas, processes, results or words without giving appropriate credit. (DHHS Office of Research Integrity)

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. (45 CFR 46.102)

Prospective: In regards to a chart review study, “prospective” means all of the clinical data that is going to be reviewed for research purposes may not yet be existing at the time of submission of the application to the IRB and will be collected for research purposes as the data are collected for clinical purposes.

Protected Health Information (PHI): Any information in the medical record or designated record set that can be used to identify an individual and that was created, used or disclosed in the course of providing a health care service such as diagnosis or treatment. The Privacy Rule outlines 18 “HIPAA Identifiers” and the Ascension Seton IRB uses these as a standard for determining what is considered “identifiable” information.

Protocol: The written description of a clinical study. It includes the study’s objectives, design and methods. It may also include relevant scientific background and statistical information.

Protocol Amendment(s). A written description of a change(s) to or formal clarification of a protocol [ICH E3].

Protocol Deviation: A variation from processes or procedures defined in a protocol. Deviations usually do not preclude the overall evaluability of subject data for either efficacy or safety and are often acknowledged and accepted in advance by the sponsor. NOTE: Good clinical practice recommends that deviations be summarized by site and by category as part of the report of study results so that the possible importance of the deviations to the findings of the study can be assessed. (Compare to protocol violation.) [See ICH E3]

Protocol Violation: A significant departure from processes or procedures that were required by the protocol. Violations often result in data that are not deemed evaluable for a per-protocol analysis and may require that the subject(s) who violate the protocol be discontinued from the study. (Compare to protocol deviation.)

Quality of Life: A broad ranging concept that incorporates an individual’s physical health, psychological state, level of independence, social relationships, personal beliefs and their relationships to salient features of the environment. NOTE: Quality of life is one way to measure the benefits or negative impacts of an “improvement” measured in terms of a physiological or psychological symptom. QOL research seeks to quantify what an intervention means to a patient’s sense that their life has changed. [WHO Group, 1994]

Query: A request for clarification on a data item collected for a clinical trial; specifically a request from a sponsor or sponsor’s representative to an investigator to resolve an error or inconsistency discovered during data review.

Query Management: Ongoing process of data review, discrepancy generation and resolving errors and inconsistencies that arise in the entry and transcription of clinical trial data.

Query Resolution: The closure of a query usually based on information contained in a data clarification.

Random Sample: Members of a population selected by a method designed to ensure that each person in the target group has an equal chance of selection.

Randomization: The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias. NOTE: Unequal randomization is used to allocate subjects into groups at a differential rate; for example, three subjects may be assigned to a treatment group for every one assigned to the control group. [ICH E6 1.48] (See also: balanced study.)

Raw Data: Data as originally collected. Distinct from derived. Raw data includes records of original observations, measurements and activities (such as laboratory notes, evaluations, data recorded by automated instruments) without conclusions or interpretations. Researcher’s records of subjects/patients, such as patient medical charts, hospital records, X-rays and attending physician’s notes. NOTE: These records may or may not accompany an application to a Regulatory Authority, but must be kept in the researcher’s file. (See also: eSource, source data, source documents)

Recruitment (investigators): Process used by sponsors to identify, select and arrange for investigators to serve in a clinical study.

Recruitment (subjects): Process used by investigators to find and enroll appropriate subjects (those selected on the basis of the protocol’s inclusion and exclusion criteria) into a clinical study.

Recruitment Period: Time period during which subjects are or are planned to be enrolled in a clinical trial.

Recruitment Target: Number of subjects that must be recruited as candidates for enrollment into a study to meet the requirements of the protocol. In multicenter studies, each investigator has a recruitment target.

Registry: A databank of information on clinical trials for drugs for serious or life-threatening diseases and conditions. NOTE: The registry should contain basic information about each trial sufficient to inform interested subjects (and their healthcare practitioners) how to enroll in the trial. [FDAMA 113]

Regulatory Authorities: Bodies having the power to regulate. NOTE: In the ICH GCP guideline the term includes the authorities that review submitted clinical data and those that conduct inspections. These bodies are sometimes referred to as competent authorities. [ICH] Synonym: regulatory agencies.

Regulatory Body: An agency, group, organization held responsible by the government for setting standards, rules, guidelines and ensuring adherence to them for a specific industry. A few examples of regulatory bodies include:

  • Centers for Medicare & Medicaid Services
  • Health and Human Services
  • Health Insurance Portability and Accountability Act
  • Office of the National Coordinator for Health Information Technology
  • Joint Commission
  • Office for Civil Rights
  • Food and Drug Administration

Research: 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. (45 CFR 46.102)

Research Misconduct: The fabrication, falsification, or plagiarism in proposing, performing or reviewing research, or in reporting research results; does not include honest error or differences of opinion. (DHHS Office of Research Integrity)

Retrospective: In regards to a chart review study, “retrospective” means all of the clinical data that is going to be reviewed for research purposes already exists at the time of submission of the application to the IRB.

Risk: In clinical trials, the probability of harm or discomfort for subjects. NOTE: Acceptable risk differs depending on the condition for which a product is being tested. A product for sore throat, for example, will be expected to have a low incidence of troubling side effects. However, the possibility of unpleasant side effects may be an acceptable risk when testing a promising treatment for a life-threatening illness.

Sample Size: 1. A subset of a larger population, selected for investigation to draw conclusions or make estimates about the larger population. 2. The number of subjects in a clinical trial. 3. Number of subjects required for primary analysis.

Sample Size Adjustment: An interim check conducted on blinded data to validate the sample size calculations or re-evaluate the sample size.

Schedule of Activities: A standardized representation of planned clinical trial activities including interventions (e.g. administering drug, surgery) and study administrative activities (e.g, obtaining informed consent, distributing clinical trial material and diaries, randomization) as well as assessments.   (See also: schedule of assessments.)

Screen Failure: Potential subject who did not meet one or more criteria required for participation in a trial. (See also: screening of subjects.)

Screening (of sites): Determining the suitability of an investigative site and personnel to participate in a clinical trial.

Screening (of subjects): A process of active consideration of potential subjects for enrollment in a trial. (See also: screen failure.)

Serious Adverse Event (SAE): Serious adverse events must be reported to the IRB as part of ongoing study management. An adverse event (see definition above) that may or may not be related to the research and meets one of the below criteria:

  • Results in death
  • Is life-threatening (places the subject at immediate risk of death from the event as it occurred)
  • Results in inpatient hospitalization or prolongation of existing hospitalization
  • Results in a persistent or significant disability/incapacity
  • Results in a congenital anomaly/birth defect, or
  • Based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

Services: In the context of service marks, a service (1) must be a real activity; (2) must be performed to the order of, or for the benefit of, someone other than the applicant; and (3) the activity performed must be qualitatively different from anything necessarily done in connection with the sale of the applicant’s goods or the performance of another service.

Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, X-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medicotechnical departments involved in the clinical trial).

Special Populations: Subsets of study populations of particular interest included in clinical trials to ensure that their specific characteristics are considered in interpretation of data (e.g. geriatric). [FDA]

Sponsor: 1. An individual, company, institution or organization that takes responsibility for the initiation and management of a clinical trial, although may or may not be the main funding organization. If there is also a secondary sponsor, this entity would be considered the primary sponsor. [ICH E6] 2. A corporation or agency whose employees conduct the investigation is considered a sponsor and the employees are considered investigators. [21 CFR 50.3 (e)]

Stopping Rules: A statistical criterion that, when met by the accumulating data, indicates that the trial can or should be stopped early to avoid putting participants at risk unnecessarily or because the intervention effect is so great that further data collection is unnecessary.

Study Design: Plan for the precise procedure to be followed in a clinical trial, including planned and actual timing of events, choice of control group, method of allocating treatments, blinding methods; assigns a subject to pass through one or more epochs in the course of a trial. Specific design elements, e.g. crossover, parallel; dose-escalation [Modified from Pocock, Clinical Trials: A Practical Approach] (See Trial Design Model. See also, arm, epoch, and visit.)

Subject:  An individual who participates in a clinical trial, either as recipient of the investigational product(s) or as a control. [ICH] (See also: healthy volunteer, human subject)

Target Enrollment: The number of subjects in a class or group (including the total for the entire trial) intended to be enrolled in a trial to reach the planned sample size. Target enrollments are set so that statistical and scientific objectives of a trial will have a likelihood of being met as determined by agreement, algorithm or other specified process.

Target Study Population: Demographic and health condition of the population to be included in a clinical study.

TOPAZ (Seton): The online submission system used by the Ascension Seton IRB and Conflict of Interest program to accept and review IRB applications and financial disclosure submissions, respectively.

Unanticipated Problem: This term is found, but not defined, in the federal regulations (45 CFR 46) and FDA regulations (21 CFR 56). Guidance from the regulatory agencies considers unanticipated problems to include any incident, experience or outcome that meets ALL of the following criteria:

  • Unexpected or unforeseen; and
  • Related or possibly related to participation 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.

Unblinding: Identification of the treatment code of a subject or grouped results in studies where the treatment assignment is unknown to the subject and investigators.

Volunteer: Person volunteering to participate as a subject in a clinical trial, often a healthy person agreeing to participate in a Phase 1 trial. (See also: Phase 1)

Vulnerable subjects: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure, such as:

  • Medical, pharmacy, dental and nursing students
  • Subordinate hospital and laboratory personnel
  • Employees of the pharmaceutical industry
  • Members of the armed forces
  • Persons kept in detention

Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors and those incapable of giving consent. [ICH]

Warning Letter: Written communication from FDA notifying an individual or firm that the agency considers one or more products, practices, processes or other activities to be in violation of the Federal FD&C Act, or other acts, and that failure of the responsible party to take appropriate and prompt action to correct and prevent any future repeat of the violation may result in administrative and/or regulatory enforcement action without further notice. [FDA]

Washout Period: Period in a clinical study during which subjects receive no treatment for the indication under study and the effects of a previous treatment are eliminated (or assumed to be eliminated).

Withdrawal: The subject-initiated act of discontinuing participation in a clinical study.  NOTE:  Withdrawal can range from the subject’s complete withdrawal from study procedures and follow-up activities, to the subject’s withdrawal from study-related interventions while the subject permits continued access to his/her medical records or identifiable information. Note that according to FDA regulations, when a subject withdraws from a study, the data collected on the subject to the point of withdrawal remain part of the study database and may not be removed.