Glossary of clinical research

A

Activities of daily living

Adverse drug reaction

Adverse effect

Adverse event

An unexpected medical problem that happens during treatment with a drug or other therapy. Adverse events do not have to be caused by the drug or therapy, and they may be mild, moderate, or severe. (NCI)

An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product (see the ICH guidance for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). (ICH E6)

Adverse reaction

Advocacy and support groups

Animal model

Animal study

Applicable regulatory requirement

Approval (in relation to institutional review boards (IRBs))

Approved drugs

Arm

Audit

Audit certificate

Audit report

Audit trail

B

Baseline

1. Information gathered at the beginning of a study from which variations found in the study are measured. 2. A known value or quantity with which an unknown is compared when measured or assessed. 3. The initial time point in a clinical trial, just before a participant starts to receive the experimental treatment which is being tested. At this reference point, measurable values such as CD4 count are recorded. Safety and efficacy of a drug are often determined by monitoring changes from the baseline values. (NLM)

An initial measurement that is taken at an early time point to represent a beginning condition, and is used for comparison over time to look for changes. For example, the size of a tumor will be measured before treatment (baseline) and then afterwards to see if the treatment had an effect. (NCI)

Bayesian approaches

Best practice

Bias

In a scientific research study or clinical trial, a flaw in the study design or the method of collecting or interpreting information. Biases can lead to incorrect conclusions about what the study or clinical trial showed. (NCI)

When a point of view prevents impartial judgment on issues relating to the subject of that point of view. In clinical studies, bias is controlled by blinding and randomization (NLM)

The systematic tendency of any factors associated with the design, conduct, analysis and evaluation of the results of a clinical trial to make the estimate of a treatment effect deviate from its true value. Bias introduced through deviations in conduct is referred to as 'operational' bias. The other sources of bias listed above are referred to as 'statistical'. (ICH E9)

Bioavailable

Bioinformatics

Biological drug

Biometrics

Biometry

Biostatistics

Blind

A randomized trial is "Blind" if the participant is not told which arm of the trial he is on. A clinical trial is "Blind" if participants are unaware on whether they are in the experimental or control arm of the study; also called masked. (NLM)

A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single blinding usually refers to the subject(s) being unaware, and double blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s). (ICH E6)

Blind review

Blinded study

C

Case report

Case report form

Case series

Case-control study

Clinical

Clinical investigation

Clinical investigator

Clinical practice guidelines

Clinical researcher

Clinical series

Clinical study or Clinical trial

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical trial. (NCI)

A clinical trial is a research study to answer specific questions about vaccines or new therapies or new ways of using known treatments. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people. Trials are in four phases: Phase I tests a new drug or treatment in a small group; Phase II expands the study to a larger group of people; Phase III expands the study to an even larger group of people; and Phase IV takes place after the drug or treatment has been licensed and marketed. (NLM)

Any investigation in human subjects intended to discover or verify the clinical, pharmacological, and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous. (ICH E6)

Clinical Trial/Study Report

Clinician

Cohort (statistics)

A group of individuals who share a common trait, such as birth year. In medicine, a cohort is a group that is part of a clinical trial or study and is observed over a period of time. (NCI)

In epidemiology, a group of individuals with some characteristics in common. (NLM)

Cohort study

Community-based clinical trial (CBCT)

Comparator

Compassionate use

Compassionate use trial

Complementary and alternative therapy

Compliance

Confidentiality regarding trial participants

Refers to maintaining the confidentiality of trial participants including their personal identity and all personal medical information. The trial participants' consent to the use of records for data verification purposes should be obtained prior to the trial and assurance must be given that confidentiality will be maintained. (NLM)

Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity. (ICH E6)

Consecutive case series

Content validity

Contract

Contract Research Organization

Contraindication

Control

Control animal

Control group

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. (NCI)

The standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo (NLM)

Controlled clinical trial

A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. (NCI)

An experiment or clinical trial that includes a comparison (control) group. (NCI)

Controlled trials

Coordinating Committee

Coordinating Investigator

D

Data and Safety Monitoring Board or Independent Data Monitoring Committee

DSMB. An impartial group that oversees a clinical trial and reviews the results to see if they are acceptable. This group determines if the trial should be changed or closed. Also called DSMB. (NCI)

An independent committee, composed of community representatives and clinical research experts, that reviews data while a clinical trial is in progress to ensure that participants are not exposed to undue risk. A DSMB may recommend that a trial be stopped if there are safety concerns or if the trial objectives have been achieved. (NLM)

An independent data monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial. (ICH E6 and ICH E9)

Diagnostic trials

Direct Access

Documentation

Dose

Dose-dependent

Dose-limiting

Dose-ranging study

Dose-rate

Double-blind study

A clinical trial design in which neither the participating individuals nor the study staff knows which participants are receiving the experimental drug and which are receiving a placebo (or another therapy). Double-blind trials are thought to produce objective results, since the expectations of the doctor and the participant about the experimental drug do not affect the outcome; also called double-masked study. (NLM)

A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. (NCI)

Double-dummy

Dropout

Drug

Drug-drug interaction

E

Efficacy

The maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed. In the procedure mandated by the FDA, Phase II clinical trials gauge efficacy, and Phase III trials confirm it (NLM)

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect. (NCI)

Eligibility criteria

In clinical trials, requirements that must be met for an individual to be included in a study. These requirements help make sure that patients in a trial are similar to each other in terms of specific factors such as age, general health, and previous treatment. When all participants meet the same eligibility criteria, it gives researchers greater confidence that results of the study are caused by the intervention being tested and not by other factors. (NCI)

Summary criteria for participant selection; includes Inclusion and Exclusion criteria. (NLM)

Empirical

Endpoint

In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor. (NCI)

Overall outcome that the protocol is designed to evaluate. Common endpoints are severe toxicity, disease progression, or death. (NLM)

Enrolling

Epidemiology

The branch of medical science that deals with the study of incidence and distribution and control of a disease in a population. (NLM)

The study of the patterns, causes, and control of disease in groups of people. (NCI)

Equivalence trial

Essential Documents

Evaluable disease

Evaluable patients

Expanded access

Expanded access trial

Experimental

Experimental drug

A drug that is not FDA licensed for use in humans, or as a treatment for a particular condition (NLM)

A substance that has been tested in a laboratory and has gotten approval from the U.S. Food and Drug Administration (FDA) to be tested in people. A drug may be approved by the FDA for use in one disease or condition but be considered experimental or investigational in other diseases or conditions. Also called investigational drug. (NCI)

F

Follow-up

Food and Drug Administration (FDA)

Frequentist methods

Full analysis set

G

Generalisability, Generalisation

Global assessment variable

Good clinical practice

H

Healthy control

Historic cohort study

Historical control subject

Human subject

Hypothesis

I

Impartial Witness

In vitro

In vivo

Incidence

Inclusion/exclusion criteria

Independent Ethics Committee

Indication

Informed consent

A process in which a person is given important facts about a medical procedure or treatment, a clinical trial, or genetic testing before deciding whether or not to participate. It also includes informing the patient when there is new information that may affect his or her decision to continue. Informed consent includes information about the possible risks, benefits, and limits of the procedure, treatment, trial, or genetic testing. (NCI)

The process of learning the key facts about a clinical trial before deciding whether or not to participate. It is also a continuing process throughout the study to provide information for participants. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study. (NLM)

A process by which a subject 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 subject's decision to participate. Informed consent is documented by means of a written, signed, and dated informed consent form. (ICH E6)

Informed consent document

Inspection

Institution

Any public or private entity or agency or medical or dental facility where clinical trials are conducted. (ICH E6)

Any public or private entity or agency (including Federal, State, and other agencies). (21CFR50.3)

Institutional Review Board (IRB)

1. A committee of physicians, statisticians, researchers, community advocates, and others that ensures that a clinical trial is ethical and that the rights of study participants are protected. All clinical trials in the U.S. must be approved by an IRB before they begin. 2. Every institution that conducts or supports biomedical or behavioral research involving human participants must, by federal regulation, have an IRB that initially approves and periodically reviews the research in order to protect the rights of human participants. (NLM)

A group of scientists, doctors, clergy, and consumers that reviews and approves the action plan for every clinical trial. There is an Institutional Review Board at every health care facility that does clinical research. Institutional Review Boards are designed to protect the people who take part in a clinical trial. Institutional Review Boards check to see that the trial is well designed, legal, ethical, does not involve unnecessary risks, and includes safeguards for patients. Also called IRB. (NCI)

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, of protocols and amendments, and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects. (ICH E6)

Any board, committee, or other group formally designated by an institution to review biomedical research involving humans as subjects, to approve the initiation of and conduct periodic review of such research. (21CFR50.3)

Intent to treat

Analysis of clinical trial results that includes all data from participants in the groups to which they were randomized even if they never received the treatment. (NLM)

The principle that asserts that the effect of a treatment policy can be best assessed by evaluating on the basis of the intention to treat a subject (i.e. the planned treatment regimen) rather than the actual treatment given. It has the consequence that subjects allocated to a treatment group should be followed up, assessed and analysed as members of that group irrespective of their compliance to the planned course of treatment. (ICH E9)

Interaction (Qualitative & Quantitative)

Inter-rater reliability

Interim analysis

Interim Clinical Trial/Study Report

Intervention

In medicine, a treatment or action taken to prevent or treat disease, or improve health in other ways. (NCI)

Primary interventions being studied: types of interventions are Drug, Gene Transfer, Vaccine, Behavior, Device, or Procedure. (NLM)

Intervention group

Intervention name

Intra-rater reliability

Investigational

Investigational drug

A substance that has been tested in a laboratory and has gotten approval from the U.S. Food and Drug Administration (FDA) to be tested in people. A drug may be approved by the FDA for use in one disease or condition but be considered investigational in other diseases or conditions. Also called experimental drug. (NCI)

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. (ICH E6)

Investigational New Drug

Investigator

A researcher in a clinical trial or clinical study. (NCI)

A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator. (ICH E6)

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. (21CFR50.3)

Investigator's Brochure

L

Legally Acceptable Representative

Levels of evidence

M

Masked

Maximum tolerated dose

Medication

Medicine

Meta-analysis

Monitoring Report

Monitoring

Multicenter study

A clinical trial that is carried out at more than one medical institution. (NCI)

A clinical trial conducted according to a single protocol but at more than one site, and, therefore, carried out by more than one investigator. (ICH E6 and ICH E9)

Multidisciplinary opinion

Multiplicity

N

National Institutes of Health

Natural history study

A study that follows a group of people over time who have, or are at risk of developing, a specific medical condition or disease. A natural history study collects health information in order to understand how the medical condition or disease develops and how to treat it. (NCI)

Study of the natural development of something (such as an organism or a disease) over a period of time. (NLM)

New Drug Application (NDA)

Nonblinded

Nonclinical Study

Nonconsecutive case series

Non-inferiority trial

Nonrandomized clinical trial

O

Objective improvement

Objective response

Observation

Observational study

Off-label

Describes the legal use of a prescription drug to treat a disease or condition for which the drug has not been approved by the U.S. Food and Drug Administration. (NCI)

A drug prescribed for conditions other than those approved by the FDA. (NLM)

Open label study

A type of study in which both the health providers and the patients are aware of the drug or treatment being given. (NCI)

A clinical trial in which doctors and participants know which drug or vaccine is being administered. (NLM)

Orphan drugs

Outcome

Outpatient

Over-the-counter drug

P

Patient advocate

Peer review

Per protocol set (Valid Cases, Efficacy Sample, Evaluable Subjects Sample)

Pharmacokinetics

Phase I trial

The first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection) and the best dose. The dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments. (NCI)

Initial studies to determine the metabolism and pharmacologic actions of drugs in humans, the side effects associated with increasing doses, and to gain early evidence of effectiveness; may include healthy participants and/or patients. (NLM)

Phase 1 includes 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. 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. (21CFR312)

Phase I/II trial

Phase II trial

A study to test whether a new treatment has an effect (NCI)

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. (NLM)

Phase 2 includes the 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. 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. (21CFR312)

Phase II/III trial

Phase III trial

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people. (NCI)

Expanded controlled and uncontrolled trials after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide and adequate basis for physician labeling. (NLM)

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 evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling. Phase 3 studies usually include from several hundred to several thousand subjects. (21CFR312)

Phase IV trial

After a treatment has been approved and is being marketed, it is studied in a phase IV trial to evaluate side effects that were not apparent in the phase III trial. Thousands of people are involved in a phase IV trial. (NCI)

Post-marketing studies to delineate additional information including the drug's risks, benefits, and optimal use. (NLM)

Pilot study

Placebo

A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment's effectiveness. (NLM)

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo. (NCI)

Placebo controlled study

A method of investigation of drugs in which an inactive substance (the placebo) is given to one group of participants, while the drug being tested 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. (NLM)

Refers to a clinical study in which the control patients receive a placebo. (NCI)

Placebo effect

Placebo therapy

Population study

Preclinical

Refers to the testing of experimental drugs in the test tube or in animals - the testing that occurs before trials in humans may be carried out. (NLM)

Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done. (NCI)

Predictive factor

Prevention

Prevention trials

Preventive

Primary endpoint

Prospective

Prospective cohort study

Clinical trial protocol

A study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment (NLM)

An action plan for a clinical trial. The plan states what the study will do, how, and why. It explains how many people will be in it, who is eligible to participate, what study agents or other interventions they will be given, what tests they will receive and how often, and what information will be gathered. (NCI)

A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents. Throughout the ICH GCP Guidance, the term protocol refers to protocol and protocol amendments. (ICH E6)

Protocol Amendment

Q

Quality Assurance

Quality Control

Quality of life trials (or supportive care trials)

R

Randomization

A method based on chance by which study participants are assigned to a treatment group. Randomization minimizes the differences among groups by equally distributing people with particular characteristics among all the trial arms. The researchers do not know which treatment is better. From what is known at the time, any one of the treatments chosen could be of benefit to the participant (NLM)

When referring to an experiment or clinical trial, the process by which animal or human subjects are assigned by chance to separate groups that compare different treatments or other interventions. Randomization gives each participant an equal chance of being assigned to any of the groups. (NCI)

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. (ICH E6)

Randomized clinical trial

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. (NCI)

A study in which participants are randomly (i.e., by chance) assigned to one of two or more treatment arms of a clinical trial. Occasionally placebos are utilized. (NLM)

Recruiting

Recruitment status

Regimen

Regulatory Authorities

Retrospective

Retrospective cohort study

Retrospective study

Risk-benefit ratio

S

Safety & tolerability

Screening trials

Selection bias

Serious Adverse Event

Sham therapy

Side effect

A problem that occurs when treatment affects healthy tissues or organs. (NCI)

Any undesired actions or effects of a drug or treatment. Negative or adverse effects may include headache, nausea, hair loss, skin irritation, or other physical problems. Experimental drugs must be evaluated for both immediate and long-term side effects (NLM)

Significant

Single blind study

A type of clinical trial in which only the doctor knows whether a patient is taking the standard treatment or the new treatment being tested. This helps prevent bias in treatment studies. (NCI)

A study in which one party, either the investigator or participant, is unaware of what medication the participant is taking; also called single-masked study. (NLM)

Source Data

Source Documents

Sponsor

An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial. (ICH E6)

A person who initiates a clinical investigation, but who does not actually conduct the investigation, i.e., the test article is administered or dispensed to or used involving, a subject under the immediate direction of another individual. A person other than an individual (e.g., corporation or agency) that uses one or more of its own employees to conduct a clinical investigation it has initiated is considered to be a sponsor (not a sponsor-investigator), and the employees are considered to be investigators. (21CFR50.3)

Sponsor-Investigator

An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator. (ICH E6)

An individual who both initiates and actually conducts, alone or with others, a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject. The term does not include any person other than an individual, e.g., corporation or agency. (21CFR50.3)

Standard treatment

Standards of care

Standard Operating Procedures

Statistical analysis plan

Statistical significance

Study endpoint

Study type

Subinvestigator

Subject Identification Code

Subject/Trial Subject

Superiority trial

Surrogate variable

T

Test article

Toxicity

Treatment effect

Treatment emergent

Treatment IND

Treatment trials

Trial Site

Trial statistician

t-test

U

Uncontrolled study

Unexpected Adverse Drug Reaction

V

Vulnerable Subjects

W

Well-being of the trial subjects