Clinical Research Study Investigator's Toolbox
NIA Glossary of Clinical Research Terms
Adverse Event (AE) – Any untoward or unfavorable medical occurrence in a clinical research study participant, including any abnormal sign (e.g. abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participants’ involvement in the research, whether or not considered related to participation in the research.
Baseline – The initial time point in a clinical trial that provides a basis for assessing changes in subsequent assessments or observations. At this reference point, measurable values such as physical exam, laboratory tests, and outcome assessments are recorded.
Bias – A point of view or preference which prevents impartial judgment in the way in which a measurement, assessment, procedure, or analysis is carried out or reported.
Case Report Form (CRF) – A printed, optical, or electronic (eCRF) document designed to capture all protocol-required information for a study.
Coordinating Center (CC) – A group organized to coordinate the planning and operational aspects of a multi-center clinical trial. CCs may also be referred to as Data Coordinating Centers (DCCs) or Data Management Centers (DMCs).
Clinical Research or Study Coordinator (CRC) – An individual that handles the administrative and day-to-day responsibilities of a clinical trial and acts as a liaison for the clinical site. This person may collect the data or review it before it is entered into a study database.
Clinical Research – NIH defines clinical research as:
- Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, or (d) development of new technologies.
- Epidemiologic and behavioral studies.
- Outcomes research and health.
Clinical Trial – The NIH defines a clinical trial as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, nutritional supplements, surgical intervention, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective. Behavioral clinical trials involving an intervention to modify behavior (diet, physical activity, cognitive therapy, etc.) fit this definition of a clinical trial.
Concomitant Medication – Prescription and over-the-counter drugs and supplements a study participant has taken along with the study intervention. This information may be collected as a history item as well as during the study. Some studies may collect only those medications that may interact with the study or intervention or that may exclude an individual from participating in a study.
Conflict of Interest – A conflict of interest occurs when individuals involved with the conduct, reporting, oversight, or review of research also have financial or other interests, from which they can benefit, depending on the results of the research.
Control Group – The group of individuals in a clinical trial assigned to a comparison intervention.
Controlled Clinical Trial – A clinical trial in which at least one group of participants is given a test intervention, while at least one other group concurrently receives a control intervention.
Data Management – The processes of handling the data collected during a clinical trial from development of the study forms/CRFs through the database locking process and transmission to statistician for final analysis.
Data Management Plan (DMP) – A plan that documents the processes for handling the flow of data from collection through analysis. Software and hardware systems along with quality control and validation of these systems, as relevant are described.
Data and Safety Monitoring Board (DSMB) –A group of individuals independent of the study investigators that is appointed by the NIA to monitor participant safety, data quality and to assess clinical trial progress.
Efficacy – Indication that the clinical trial intervention produces a desired therapeutic effect on the disease or condition under investigation.
Eligibility Criteria – List of criteria guiding enrollment of participants into a study. The criteria describe both inclusionary and exclusionary factors, (e.g. inclusion criterion - participants must be between 55 and 85 years old; exclusion criterion – must not take drug X three month prior to the study).
Food and Drug Administration (FDA)– An agency within the U.S. Department of Health and Human Services (DHHS) responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, nation’s food supply, cosmetics, and products that emit radiation.
Good Clinical Practice – 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 participants are protected.
Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule – The first comprehensive Federal protection for the privacy of personal health information. The Privacy Rule regulates the way certain health care groups, organizations, or businesses, called covered entities under the Rule, handle the individually identifiable health information known as protected health information (PHI).
Human Subject – A patient or healthy individual who is or becomes a participant in research, either as a recipient of the intervention or as a control.
Informed Consent – A process by which a participant or legal guardian voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the participant’s decision to take part in the clinical trial. Informed consent is usually documented by means of a written, signed, and dated informed consent form, which has been approved by an IRB/IEC.
Informed Consent Form – A document that describes the rights of a study participant and provides details about the study, such as its purpose, duration, required procedures, and key contacts. Risks and potential benefits are explained in the informed consent document.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) – An independent body constituted of medical, scientific, and nonscientific members whose responsibility it is to ensure the protection of the rights, safety, and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trials, protocols and amendments, and of the methods and material to be used to obtaining and documenting informed consent of the trial participant.
Intervention – A procedure or treatment such as a drug, nutritional supplement, gene transfer, vaccine, behavior or device modification that is performed for clinical research purposes (45 CFR 46.102(f)).
Investigational New Drug Application (IND) – An IND is a request for authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans. Such authorization must be secured prior to interstate shipment and administration of any new drug or biological product that is not the subject of an approved New Drug Application or Biologics/Product License Application (21 CFR 312).
Masking/Blinding – A procedure in which the investigator administering the assessments and intervention as well as the participants in a clinical trial are kept unaware of the treatment assignment(s). Single blinding usually refers to the study participant(s) being unaware, and double blinding usually refers to the study participant(s) and any of the following being unaware of the treatment assignment(s): investigator(s), monitor, and data analyst(s).
Manual of Procedures (MOP) – A set of procedures describing study conduct. A MOP is developed to facilitate consistency in protocol implementation and data collection across study participants and clinical sites.
New Drug Application (NDA) – An application submitted by the manufacturer of a drug to the FDA, after the clinical trial has been completed, for a license to market the drug for a specified indication.
Office for Human Research Protection (OHRP) – A federal government agency within the Department of Health and Human Services (DHHS) charged with the protection of human subjects participating in government funded research. It issues assurances and oversees compliance of regulatory guidelines by research institutions.
Open-Label Trial – A clinical trial in which investigators and participants know which intervention is being administered.
Pharmacokinetics – The process (in a living organism) of absorption, distribution, metabolism, and excretion of a drug or vaccine.
Phase I – clinical trials to test a new biomedical intervention in a small group of people (e.g., 20-80) for the first time to evaluate safety (e.g., to determine a safe dosage range and to identify side effects). It can include healthy participants or patients.
Phase II – clinical trials to study the biomedical or behavioral intervention in a larger group of people (several hundred) to determine efficacy and to further evaluate its safety. It is conducted in participants with the condition or disease under study and will determine common short-term side effects and risks.
Phase III – studies to investigate the efficacy of the biomedical or behavioral intervention in large groups of human subjects (from several hundred to several thousand) by comparing the intervention to other standard or experimental interventions as well as to monitor adverse effects, and to collect information that will allow the intervention to be used safely.
An NIH-defined Phase III clinical trial is a broadly based prospective Phase III clinical investigation, usually involving several hundred or more human subjects, for the purpose of evaluating an experimental intervention in comparison with a standard or controlled intervention or comparing two or more existing treatments. Often the aim of such investigation is to provide evidence leading to a scientific basis for consideration of a change in health policy or standard of care. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included.
Phase IV – studies conducted after the intervention has been marketed. These studies are designed to monitor effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use.
Placebo – A placebo is an inactive pill, liquid, powder, or other intervention that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment's effectiveness.
– A method of investigation in which an inactive substance/treatment (the placebo) is given to one group of participants, while the test article is given to another group. The results obtained in the two groups are then compared to see if the investigational treatment is more effective in treating the condition.
Protocol – A document that describes the objective(s), design, methodology, statistical consideration, and organization of a trial.
Protocol Amendments – A written description of a change(s) to or formal clarification of a protocol.
Protocol Deviations – Failure to conduct a study as described in the protocol. The failure may be accidental or due to negligence and in either case, the protocol deviation should be documented. This also includes failure to comply with federal laws and regulations, the institution's commitments and policies, and standards of professional conduct and practice. Examples of noncompliance include:
- failure to obtain/maintain approval for research,
- failure to obtain informed consent when required,
- failure to file adverse event reports,
- performance of an unapproved study procedure,
- performance of research at an unapproved site,
- failure to file protocol modifications and
- failure to adhere to an approved protocol.
Protocol Deviations Report – Internal document created as part of the ongoing quality control process summarizing compliance with the protocol and listing protocol deviations and/or violations.
Quality Assurance (QA) – Systematic approach to ensure that the data are generated, documented (recorded), and reported in compliance with the protocol and good clinical practice (GCP) standards.
Quality Control (QC) – The internal operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of trial related activities have been fulfilled (e.g., data and form checks, monitoring by study staff, routine reports, correction actions, etc.).
Randomization – The process of assigning clinical trial participants to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.
Recruitment Plan – The plan that outlines how individuals will be recruited for the study and how the study will reach the recruitment goal.
Retention Plan – The plan that details the methods in which the study will use in order to retain study participation in the clinical trial.
Safety Monitoring Plan – A plan that outlines the oversight of a clinical trial.
Screening Log – An essential document that records all individuals who entered the screening process. The screening log demonstrates the investigator’s attempt to enroll a representative sample of participants.
Screening Process – A process designed to determine individual’s eligibility for participation in a clinical research study.
Serious Adverse Event (SAE) – Any adverse event that:
- Results in death
- Is life threatening, or places the participant at immediate risk of death from the event as it occurred
- Requires or prolongs hospitalization
- Causes persistent or significant disability or incapacity
- Results in congenital anomalies or birth defects
- Is another condition which investigators judge to represent significant hazards
Source Document – Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, participant diaries, recorded data from automated instruments, x-rays, etc.) that are used in a clinical trial.
Standard Operating Procedure (SOPs) – Detailed written instructions to achieve uniformity of the performance of a specific function across studies and patients at an individual site.
Stopping Rules –Established safety criteria that would either pause or halt a study due to reasons including but not limited to futility or risk(s) to the participants.
Stratification – Separation of a study cohort into subgroups or strata according to specific characteristics such as age, gender, etc., so that factors which might affect the outcome of the study, can be taken into account.
Unmasking/Unblinding – A procedure in which one or more parties to the trial are made aware of the treatment assignment(s).
NINDS Glossary of Clinical Research Terms
CenterWatch, Inc. Patient Resources: Glossary.
Friedman LM, Furberg CD, DeMets DL. Fundamentals of Clinical Trials (3 ed.). Missouri: Mosby-Year Book Inc., 1996.
Meinert CL. Clinical Trials: Design, Conduct, and Analysis. New York: Oxford University Press, Inc., 1986.