Adverse Drug Reaction (ADR) - An unintended reaction to a drug taken at doses normally used in man for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function. In clinical trials, an ADR would include any injuries by overdosing, abuse/dependence, and unintended interactions with other medicinal products.
Adverse Event (AE) - A negative experience encountered by an individual during the course of a clinical trial that is associated with the drug. An AE can include previously undetected symptoms, or the exacerbation of a pre-existing condition. When an AE has been determined to be related to the investigational product, it is considered an Adverse Drug Reaction.
Adverse Reaction - An unwanted effect caused by the administration of drugs. Onset may be sudden or develop over time.
Arm - Any of the treatment groups in a randomized trial. Most randomized trials have two "arms," but some have three "arms," or even more.
Assent - A child’s affirmative agreement to participate in a clinical investigation. Mere failure to object may not, absent affirmative agreement, be construed as assent.
Baseline - Information gathered at the beginning of a study from which variations found in the study are measured. A known value or quantity with which an unknown is compared when measured or assessed. The initial time point in a clinical trial, just before a participant starts to receive the experimental treatment which is being tested. Safety and efficacy of a drug are often determined by monitoring changes from the baseline values
Blinding - The process through which one or more parties to a clinical trial are unaware of the treatment assignments. In a single-blinded study, usually the subjects are unaware of the treatment assignments. In a double-blinded study, both the subjects and the investigators are unaware of the treatment assignments. Also, in a double-blinded study, the monitors and sometimes the data analysts are unaware. "Blinded" studies are conducted to prevent the unintentional biases that can affect subject data when treatment assignments are known.
Clinical Investigation - A systematic study designed to evaluate a product (drug, device, or biologic) using human subjects, in the treatment, prevention, or diagnosis of a disease or condition, as determined by the product's benefits relative to its risks. Clinical investigations can only be conducted with the approval of the Food and Drug Administration (FDA).
Clinical Research - Study of drug, biologic or device in human subjects with the intent to discover potential beneficial effects and/or determine its safety and efficacy. Also called clinical study and clinical investigation. Note that in this manual, this term is used in its narrow sense as used by the FDA. Thus, it does not encompass all the research that is carried out in the clinical setting (e.g., health services research).
Clinical Trial - Any investigation in human subjects intended to determine the clinical pharmacological, pharmacokinetic, and/or other pharmacodynamic effects of an investigational agent, and/or to identify any adverse reactions to an investigational agent to assess the agent's safety and efficacy.
Comparison – To learn more, researchers compare results from patients in the experimental groups with results from patients in the control groups.
Compassionate Use - A method of providing experimental therapeutics prior to final FDA approval for use in humans. This procedure is used with very sick individuals who have no other treatment options. Often, case-by-case approval must be obtained from the FDA for "compassionate use" of a drug or therapy.
Confidentiality regarding participants – This refers to the practice of maintaining as private all information related to clinical trial participants, including their personal identity and all personal medical information. Results from the study will usually be presented in terms of trends or overall findings and will not mention any specific participants.
Consent Form - A document explaining all relevant study information to assist the study volunteer in understanding the expectations and requirements of participation in a clinical trial. This document is presented to and signed by the study subject.
Control group – The group of participants that receives standard treatment or a placebo. The control group may also be made up of healthy volunteers. Researchers compare results from the control group with results from the experimental group to find and learn from any differences.
Demographic Data - Refers to the characteristics of study participants, including sex, age, family medical history, and other characteristics relevant to the study in which they are enrolled.
Device - An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part or accessory, which is intended for use in the diagnosis, cure, treatment or prevention of disease. A device does not achieve its intended purpose through chemical action in the body and is not dependent upon being metabolized to achieve its purpose.
Diagnostic Trials - Refers to trials that are conducted to find better tests or procedures for diagnosing a particular disease or condition. Diagnostic trials usually include people who have signs or symptoms of the disease or condition being studied.
Disease - Disorders (e.g., anxiety disorders, seizure disorders), conditions (e.g., obesity, menopause), syndromes, specific illnesses, and other medical problems that are an acquired morbid change in a tissue, organ, or organism. Synonyms are illness and sickness.
Documentation - All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records; and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.
Dosage Regimen - The number of doses per given time period (usually days), the time that elapses between doses (e.g., dose to be given every six hours) or the time that the doses are to be given (e.g., dose to be given at 8 a.m., noon, and 4 p.m. each day) or the quantity of a medicine (e.g., number of tablets, capsules, etc.) that are given at each specific time of dosing.
Dose-Ranging Study - A clinical trial in which two or more doses of an agent (such as a drug) are tested against each other to determine which dose works best and is least harmful.
Double-blind research design – A study in which neither the participant nor the researcher knows whether the participant is in the treatment or control group.
Double-blind, randomized, controlled clinical trial – This is a clinical trial in which the researchers evenly divide study participants into a group receiving the experimental intervention and a group receiving standard or no treatment. Neither group knows how it has been assigned. This practice reduces the chance for a “placebo effect,” in which a treatment with no active ingredient produces results expected from a treatment with an active ingredient.
Drug - As defined by the Food, Drug and Cosmetic Act, drugs are "articles (other than food) intended for the use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals, or to affect the structure or any function of the body of man or other animals."
Drug-Drug Interaction - A modification of the effect of a drug when administered with another drug. The effect may be an increase or a decrease in the action of either substance, or it may be an adverse effect that is not normally associated with either drug.
Effective Dose - A product's ability to produce beneficial effects on the duration or course of a disease. Efficacy is measured by evaluating the clinical and statistical results of clinical tests.
Efficacy - A product's ability to produce beneficial effects on the duration or course of a disease. Efficacy is measured by evaluating the clinical and statistical results of clinical tests.
Endpoint - Overall outcome that the protocol is designed to evaluate. Common endpoints are severe toxicity, disease progression, or death.
Enrolling - The act of signing up participants into a study. Generally this process involves evaluating a participant with respect to the eligibility criteria of the study and going through the informed consent process.
Epidemiology - The branch of medical science that deals with the study of incidence and distribution and control of a disease in a population.
Ethics Committee - An independent group of both medical and non-medical professionals who are responsible for verifying the integrity of a study and ensuring the safety, integrity, and human rights of the study participants.
Exclusion Criteria - Refers to the characteristics that would prevent a subject from participating in a clinical trial, as outlined in the study protocol.
Expanded Access - Refers to any of the FDA procedures, such as compassionate use, parallel track, and treatment IND that distribute experimental drugs to participants who are failing on currently available treatments for their condition and also are unable to participate in ongoing clinical trials.
Experiment – A study done to answer a question. Other words to describe an experiment are “research,” “study,” and “protocol.”
Experimental Drug - A drug that is not FDA licensed for use in humans, or as a treatment for a particular condition.
Experimental group – The group of participants in a study that receive the experimental or study intervention (such as medication or psychotherapy).
Food and Drug Administration (FDA) - Within the Department of Health and Human Services. Enforces Food, Drug and Cosmetics Act and related federal public health laws. Grants IND, IDE, PMA and NDA approvals.
Food Drug and Cosmetic Act (FD & C Act ) - States only drugs, biologics and devices proven safe and effective can be marketed.
Formulation - The mixture of chemicals and/or biological substances and excipients used to prepare dosage forms.
Generic Drug - A medicinal product with the same active ingredient, but not necessarily the same inactive ingredients as a brand-name drug. A generic drug may only be marketed after the original drug's patent has expired.
Good Clinical Practice (GCP) - International ethical and scientific quality standard for designing, conducting, monitoring, recording, auditing, analyzing and reporting studies. Insures that the data reported is credible and accurate, and that subject's rights and confidentiality are protected.
Healthy volunteer – In a clinical study, a person who does not have the disorder or disease being studied. Results from healthy controls are compared to results from the group being studied.
In vitro – In glass, as in a test tube. An in vitro test is one that is done in glass or plastic vessels in the laboratory. In vitro is the opposite of in vivo.
In vivo – In the living organism. For example, an experiment that is done in vivo is done in the body of a living organism. In vivo is the opposite of in vitro.
Inclusion/exclusion criteria – Inclusion criteria are the factors that allow someone to participate in a clinical trial. Exclusion criteria are the factors that prevent someone from participating in the trial. These factors may include a person’s illness, health history, past treatment, age, sex, or where he or she lives.
Informed consent – When a participant provides informed consent, it means that he or she has learned the key facts about a research study and agrees to take part in it. For more detailed information, see the “What is informed consent?” section in this guide.
Inpatient – A person who is hospitalized for at least one night to receive treatment or participate in a study.
Institutional Review Board - any board, committee, or other group formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of, biomedical research involving human subjects. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects. The term has the same meaning as the phrase institutional review committee
Legally Acceptable Representative - An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject's participation in the clinical trial.
Longitudinal Study - A study conducted over a long period of time.
Molecular compound – A molecular compound may be a solid, liquid or gas that has electrically neutral atoms held together by covalent chemical bonds.
National Institutes of Health (NIH) – Part of the U.S. Department of Health and Human Services, NIH is the primary Federal agency for conducting and supporting medical research. NIH scientists investigate ways to prevent disease as well as the causes, treatments, and even cures for common and rare diseases. Composed of 27 Institutes and Centers, NIH provides leadership and financial support to researchers in every state and throughout the world.
Off Label - The use of a drug for a purpose other than that approved of by the FDA.
Open-Label Study - A study in which all parties, (patient, physician and study coordinator) are informed of the drug and dose being administered. In an open-label study, none of the participants are given placebos. These are usually conducted with Phase I & II studies
Orphan Drug - A designation of the FDA to indicate a therapy developed to treat a rare disease (one which afflicts a U.S. population of less than 200,000 people).
Outpatient – A person who receives treatment or participates in a study but is not hospitalized overnight.
Pharmacodynamic (PD) Study - A study of a pharmacological or clinical effect of the medicine in individuals to describe the relation of the effect to dose or drug concentration. A pharmacodynamic effect can be a potentially adverse effect (anticholinergic effect with a tricyclic), a measure of activity thought related to clinical benefit (various measures of beta-blockade, effect on ECG intervals, inhibition of ACE or of angiotensin I or II response), a short term desired effect, often a surrogate endpoint (blood pressure, cholesterol), or the ultimate intended clinical benefit (effects on pain, depression, sudden death).
Pharmacokinetics - The processes (in a living organism) of absorption, distribution, metabolism, and excretion of a drug or vaccine.
Pharmacology/Toxicology - The science of drugs and poisonous materials (respectively) and their effects on the body. Studies in these areas include: diet and nutrition; overdoses; and vitamin deficiencies.
Phase I Study - The first of four phases of clinical trials, Phase I studies are designed to establish the effects of a new drug in humans. These studies are usually conducted on small populations of healthy humans to specifically determine a drug's toxicity, absorption, distribution and metabolism.
Phase II Study - After the successful completion of phase I trials, a drug is then tested for safety and efficacy in a slightly larger population of individuals who are afflicted with the disease or condition for which the drug was developed.
Phase IIa Study - Pilot clinical trials to evaluate efficacy (and safety) in selected populations of subjects with the disease or condition to be treated, diagnosed, or prevented. Objectives may focus on dose-response, type of subject, frequency of dosing, or numerous other characteristics of safety and efficacy.
Phase IIb Study - Well-controlled trials to evaluate efficacy (and safety) in subjects with the disease or condition to be treated, diagnosed, or prevented. These clinical trials usually represent the most rigorous demonstration of a medicine’s efficacy.
Phase III Study - The third and last pre-approval round of testing of a drug is conducted on large populations of afflicted patients. Phase III studies usually test the new drug in comparison with the standard therapy currently being used for the disease in question. The results of these trials usually provide the information that is included in the package insert and labeling.
Phase IIIa - Trials conducted after efficacy of the medicine is demonstrated, but prior to regulatory submission of a New Drug/product Application (NDA) or other dossier. These clinical trials are conducted in subjects’ populations for which the medicine is eventually intended. Phase IIIa clinical trials generate additional data on both safety and efficacy in relatively large numbers of subjects in both controlled and uncontrolled trials. Clinical trials are also conducted in special groups of subjects (e.g. renal failure subjects), or under special conditions dictated by the nature of the medicine and disease. These trials often provide much of the information needed for the package insert and labeling of the medicine.
Phase IIIb Study - Clinical trials conducted after regulatory submission of an NDA or other dossier, but prior to the medicine’s approval and launch. These trials may supplement earlier trials, complete earlier trials, or may be directed towards new types of trials (e.g., quality of life, marketing) or phase IV evaluations. This is the period between submission and approval of a regulatory dossier for marketing authorization.
Phase IV Study - After a drug has been approved by the FDA, phase IV studies are conducted to compare the drug to a competitor, explore additional patient populations, or to further study any adverse events.
Pilot Study - A pilot trial is used to obtain information, and work out the logistics and management, deemed necessary for further clinical trials. Although pilot trials are often unblind and use open-label medicines, they may also be single or double blind and may include tight control on all appropriate variables. The term “pilot” refers to the purpose of the trial (2).
Pivotal Study - Usually a phase III study which presents the data that the FDA uses to decide whether or not to approve a drug. A pivotal study will generally be well-controlled, randomized, of adequate size, and whenever possible, double-blind.
Placebo – An inactive pill. This is sometimes called a “sugar pill.” In some studies, participants may be assigned to take a placebo rather than the study medication. Ask the researcher if this is a possibility for the study that interests you.
Placebo effect – Sometimes people taking a study medication receive benefits that are not from the chemicals in the medicine. This is called a “placebo effect.” For example, if a participant feels hopeful about a treatment, he or she may be more likely to notice positive changes than negatives ones. A researcher’s hope may also sway a participant’s response. Double-blind research design helps minimize the placebo effect.
Post-marketing studies – Studies done after a treatment, medication or device is approved for use by the FDA. These studies gather additional information about a product’s safety, effectiveness, or best use.
Pre-Clinical Testing - Before a drug may be tested on humans, pre-clinical studies must be conducted either in vitro but usually in vivo on animals to determine that the drug is safe.
Prevention Trials - Refers to trials to find better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vaccines, vitamins, minerals, or lifestyle changes.
Protocol – A study done to answer a question. Other words to describe a protocol are “research,” “study,” and “experiment.” “Protocol” also refers to the plan that details what researchers will do during the study.
Quality of Life Trials (or Supportive Care Trials) - Refers to trials that explore ways to improve comfort and quality of life for individuals with a chronic illness.
Randomization/random assignment – This is the process in which researchers evenly assign study participants into a group receiving the experimental treatment being studied, and others into a group receiving standard or no treatment. Participants are assigned to a group based on chance, not choice. You have the same chance to be placed in any of the test groups.
Recruitment - Act of enrolling subjects with the proper inclusion criteria.
Recruitment Period - Time allowed to recruit all subjects for a study.
Regulatory Agency – is a public authority or government agency responsible for exercising autonomous authority over some area of human activity in a regulatory or supervisory capacity. An independent regulatory agency is a regulatory agency that is independent from other branches or arms of the government. Regulatory agencies deal in the area of administrative law—regulation or rulemaking (codifying and enforcing rules and regulations and imposing supervision or oversight for the benefit of the public at large).
Research – A study done to answer a question. Scientists do research when they’re not sure what will work best to help people with an illness. Other words to describe clinical research are “clinical trial,” “protocol,” “study,” and “experiment.”
Risk - A measure of the probability of occurrence of harm to human health or the severity of harm that may occur. Such a measure includes the judgment of the acceptability of risk. Assessment of safety involves judgment, and there are numerous perspectives (e.g., subjects, physicians, company, regulatory authorities) used for judging it.
Risk-Benefit Ratio - Risk to individual subject vs. potential benefits. Also called Risk-Benefit Analysis.
Screening Trials - Refers to trials which test the best way to detect certain diseases or health conditions.
Serious Adverse Event (SAE) - Any adverse event (AE) that is fatal, life-threatening, permanently disabling, or which results in hospitalization, initial or prolonged.
Side Effects - 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.
Single-blind research design – A study in which one party, either the investigator or participant, is unaware of what medication or intervention the participant is taking; also called single-masked study.
Sponsors – Clinical trials are sponsored or funded by various organizations or individuals, including physicians, foundations, medical institutions, voluntary groups, and pharmaceutical companies, as well as Federal agencies such as NIH, FDA, the Department of Defense, and the Department of Veterans Affairs.
Standards of Care - Treatment regimen or medical management based on state of the art participant care
Standard treatment – The treatment that medical professionals consider at the time of the study to be the most prevalent and best available treatment.
Standardized procedures – These are study rules that researchers must follow exactly for every participant, regardless of what each participant is used to. For example, if you normally take a medicine by injection but the experiment is testing the same medicine in pill form, the researcher must prescribe pills to you. The researcher cannot use a different method for you.
Statistical Significance - The probability that an event or difference occurred by chance alone. In clinical trials, the level of statistical significance depends on the number of participants studied and the observations made, as well as the magnitude of differences observed.
Study – Conducted by a principal investigator who is often a doctor. Members of the research team regularly monitor the participant’s health to determine the study’s safety and effectiveness. Other words to describe a study are “clinical trial,” “protocol,” “experiment,” and “research.”
Study Endpoint - A primary or secondary outcome used to judge the effectiveness of a treatment.
Study Type - The primary investigative techniques used in an observational protocol; types are Purpose, Duration, Selection, and Timing.
Sub-investigator - Helps design and conduct investigation at a study site.
Therapeutic Window - This term is applied to the difference between the minimum and maximum doses that may be given subjects to obtain an adequate clinical response and avoid intolerable toxic effects. The greater the value calculated for the therapeutic window, the greater a medicine’s margin of safety. Synonyms are therapeutic ratio and therapeutic index.
Toxicity - An adverse effect produced by a drug that is detrimental to the participant's health. The level of toxicity associated with a drug will vary depending on the condition which the drug is used to treat.
Treatment Trials - Refers to trials which test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
Unexpected Adverse Drug Reaction - A reaction that is not consistent in nature or severity with study application.
Vulnerable Subjects - Group/individual that cannot give informed consent because of limited autonomy (e.g., children, mentally ill and prisoners). Also refers to subjects who may be unduly influenced to participate (e.g., students, subordinates and patients).
Well-being - Subject's physical and mental soundness.