Glossary of Clinical Trial Terms

ADVERSE REACTION: (Adverse Event):

Also known as side effects, adverse

reactions include any undesired actions or effects of the experimental drug or treatment.

Experimental treatments must be evaluated for both immediate and long-term side

effects.

APPROVAL:

A drug, device or biologic must be approved by a country’s regulatory

agency before it can be marketed. The approval process involves several steps

including pre-clinical (animal) studies, clinical trials for safety and efficacy, filing of a New

Drug Application (NDA) in the United States or Marketing Authorization Application

(MAA) in Europe by the manufacturer, regulatory agency review of the application, and

agency approval/rejection of application.

ARM:

Any of the treatment groups in a clinical trial. Most randomized trials have two

“arms,” but some have three “arms,” or even more.

BASELINE:

Baseline information is gathered at the beginning of a study from which

variations found in the study are measured. Baseline can also be described as a known

value or quantity with which an unknown is compared when measured or assessed.

Safety and efficacy of a drug are often determined by monitoring changes from the

baseline values.

BIAS:

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.

BLIND, BLINDED or BLINDING:

A clinical trial is “blinded” if the participants are

unaware on whether they are in the experiment

al or control arm of the study. Blinding

may also be extended to the investigators so that their patient observations are less

likely to be biased by their awareness of the treatment the patient is receiving.

CASE CONTROL STUDY:

A scientific study that compares a group of people with a

disease (such as leukemia) to a similar gr

oup of people without that disease. This type

of study compares the levels of exposure (for example, radiation or chemical) each

group had before appearance of the disease.

CLINICAL:

Pertaining to or founded on observation and treatment of human participants

or patients, as distinguished from theoretical or basic science.

CLINICAL INVESTIGATOR:

A medical researcher in charge of carrying out a clinical

trial's protocol.

CLINICAL RESEARCH ASSOCIATE (CRA):

Person employed by the study sponsor or

clinical research coordinator to monitor a clinical trial at one or more participating sites.

The CRA is responsible for ensuring all clinical studies are conducted according to study

protocol, within regulations and ICH guidelines.

CLINICAL RESEARCH COORDINATOR (CRC):

Site administrator for the clinical trial

who is responsible for coordinate administrative activities between field and home offices

staff, such as the collection of essential documents, distribution of supplies and site

selection. Also called research, study or health care coordinator, data manager,

research nurse or protocol nurse.

CLINICAL TRIAL:

Clinical trials, also known as clinical studies, test potential treatments

in human volunteers or patients to see whether they should be further investigated or

approved for wider use in the general population. A treatment could be a drug, medical

device, or biologic, such as a vaccine, blood product, or gene therapy. Potential

treatments, however, must first be studied in laboratory models or animals to determine

its safety before they can be tried in people. Treatments having acceptable safety

profiles for the disease or condition and showing the most promise are then moved into

clinical trials. Clinical trials are an integral part of new product discovery and

development, and are required by all regulatory agencies (e.g., the Food and Drug

Administration (FDA) in the United States), before a new product can be brought to the

market.

COMMUNITY-BASED CLINICAL TRIAL (CBCT):

A clinical trial conducted primarily

through primary care physicians rather than researchers at academic facilities.

COMPASSIONATE USE:

A method of providing experimental therapeutics prior to final

regulatory agency 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 by the patient’s physician from the regulatory agency for “compassionate use”

of an experimental drug or therapy.

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 must be obtained prior to the trial. The Informed Consent

Document will explain how personal health information and study data will be used in

accordance with pertinent data protection laws and regulations.

CONTRACT RESEARCH ORGANIZATION (CRO):

A commercial organization

contracted by a research and development organization to perform one or more

research-related functions.

CONTRAINDICATION:

A specific circumstance in whic

h the use of certain treatments

are not allowed usually because they could be harmful or fatal.

CONTROL GROUP:

A control is the standard by which experimental observations are

evaluated. In many clinical trials, one gr

oup 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.

CONTROLLED TRIALS:

A control is a standard against which experimental

observations may be evaluated. In a controlled clinical trial, one group of participants is

given an experimental drug, while another group (i.e., the control group) is given either a

standard treatment for the disease or a placebo.

CROSSOVER TRIAL:

A clinical trial in which all participants receive both treatments,

but at different times. At a predetermined point in the study, one group is switched from

the experimental treatment to the control treatment (standard treatment), and the other

group is switched from the control to the experimental treatment.

DATA SAFETY MONITORING BOARD (DSMB):

A committee, independent of the

sponsor, composed of clinical research experts that reviews trial 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 and further continuing the study would not benefit the patients.

DATA SAFETY MONITORING PLAN (DSMP):

This plan is meant to assure that each

clinical trial has a system for appropriate oversight and monitoring of the conduct of the

trial. This oversight ensures the safety of the participants and the validity and integrity of

the data.

DECLARATION OF HELSINKI

: A series of guidelines adopted by the 18th World

Medical Assembly in Helsinki, Finland in 1964. The Declaration addresses ethical issues

for physicians conducting biomedical research involving humans. Recommendations

include the procedures required to ensure subject safety in clinical trials, including

informed consent and Ethics Committee reviews.

DEMOGRAPHIC DATA:

The characteristics of participant group or populations. This

could include data on race, age, sex and medical history, all of which can be relevant to

the clinical trial study findings.

DEVICE:

An instrument, apparatus, implement, machine, contrivance, implant, in vitro

reagent, or other similar or related article, including any component, part or accessory,

that is used to diagnose, cure, treat, or prevent disease. A device does not achieve its

intended purpose through chemical action or metabolism in the body.

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.

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 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 knowledge, expectations and biases of

the doctor and the participant about the experimental drug or treatment do not affect the

outcome.

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.

EFFECTIVENESS:

Whether a drug achieves its desired effect in the real world.

EFFICACY:

(Of a drug or treatment) the ability of a drug or treatment to produce a

beneficial result. A drug demonstrates efficacy if it is effective at the dose tested against

the illness for which it is prescribed.

ELIGIBILITY CRITERIA:

Summary criteria for participant selection; includes inclusion

and exclusion criteria.

EMPIRICAL:

Based on observation or experience, not experimental data.

ENDPOINT:

Overall outcome that the protocol is designed to evaluate.

EPIDEMIOLOGY:

The branch of medical science that deals with the study of incidence,

distribution and control of a disease in a population.

ETHICS COMMITTEE:

See institutional review board or "IRB" definition below

EUROPEAN MEDICINES AGENCY (EMEA):

The European regulatory agency

responsible for the scientific evaluation of applications for European marketing

authorization for medicinal products (centralized procedure). EMEA’s main mission is to

protect and promote public and animal health, through the evaluation and supervision of

medicines for human and veterinary use.

EXCLUSION/INCLUSION CRITERIA:

The medical or social standards determining

whether a person may or may not be allowed to enter a clinical trial. These criteria are

based on such factors as age, gender, pregnancy status, the type and stage of a

disease, previous treatment history, and other medical conditions. It is important to note

that inclusion and exclusion criteria are not used to reject people personally, but rather to

identify appropriate participants to ensure the integrity of the study and to keep them

safe.

EXPANDED ACCESS:

Refers to any of the regulatory authority procedures, such as

compassionate use, parallel track, and treat

ment Investigational New Drug Application

(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.

EXPERIMENTAL/INVESTIGATIONAL DRUG:

A drug that has been authorized for use

in a clinical trial but has not been granted marketing approval as a treatment for a

particular use.

FIRST-IN-HUMAN/MAN STUDY:

A clinical trial where a medical procedure or medicinal

product, previously developed and assessed through laboratory model or animal testing,

or through mathematical modeling is tested on human subjects for the first time.

FOOD AND DRUG ADMINISTRATION (FDA):

The U.S. Department of Health and

Human Services agency responsible for ens

uring the safety and effectiveness of all

drugs, biologics, vaccines, and medical devices. The FDA also works with the blood

banking industry to safeguard the nation's blood supply.

GENERIC DRUGS:

A medicine with the same active ingredient, but not necessarily the

same inactive ingredients, as a brand-name drug. A generic drug may be marketed only

after the original drug's patent has expired.

HIPAA:

The Health Insurance Portability and Accountability Act of 1996 (HIPAA)

established national standards for electronic health care transactions and national

identifiers for providers, health plans, and em

ployers. It also addresses the security and

privacy of health data. All clinical trial data and activities performed by covered entities

must comply with HIPAA regulations.

HUMAN SUBJECT:

A patient or healthy person participating in a research project.

HYPOTHESIS:

A theory, supposition or assumption advanced as a basis for reasoning

or argument, or as a guide to experimental investigation.

INFORMED CONSENT:

Informed consent is the verification of a person’s willingness to

participate in a research project. Prior to enrollment into a clinical trial, researchers

inform participants about all relevant study

details. Participants are provided an informed

consent document that details all the import

ant study information including its purpose,

duration, risks, potential benefits, required procedures, and key contacts, and they will

be asked to sign this document if they agree to participate in the trial. The informed

consent document is not a contract. Participation in the clinical trial is voluntary and the

participant may withdraw from the trial at any time without penalty or loss of benefits to

which he/she is otherwise entitled. The research team actively maintains informed

consent throughout the trial by providing the participant with any new or developing

information.

INFORMED CONSENT DOCUMENT:

A document that describes the rights of the study

participants, and includes 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. The participant will be asked to sign this document if they agree to

participate in the trial. The informed consent document is not a contract. Participation in

the clinical trial is voluntary and the participant may withdraw from the trial at any time

without penalty or loss of benefits to which he/she is otherwise entitled.

INSTITUTIONAL REVIEW BOARD (IRB):

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. Every institution that conducts or

supports biomedical or behavioral research involving human participants must, by

federal regulation, have an IRB that approves and periodically reviews the research in

order to protect the rights of human participants.

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.

INTERVENTION NAME:

The generic name of the experimental treatment being studied.

INTERVENTIONS:

Primary experimental treatments being studied. Types of treatments may include drug, gene transfer, vaccine, behavior, device, or procedure.

INVESTIGATIONAL NEW DRUG APPLICATION (IND):

The petition through which a drug sponsor requests the FDA to allow human testing of a new drug, antibiotic drug, or biological drug in a clinical investigation.

This includes an application for a biological product used in vitro for diagnostic purposes.

IN VIVO:

Testing or action inside an organism, such as a human subject or patient.

IN VITRO:

Testing or action outside an organism (e.g. inside a test tube or culture

dish.)

MARKETING AUTHORIZATION APPLICATION (MAA):

An application submitted by a sponsor to the EMEA for approval to market a new drug (a new, non-biological molecular entity) for human use in Europe.

META-ANALYSIS:

Systematic methods that use statistical techniques for combining results from similar studies to obtain a quantit ative estimate of the overall effect of a particular intervention or variable on a defined outcome. This type of analysis is typically hypothesis generating.

MULTICENTER TRIAL:

Clinical trial conducted according to a single protocol but at

more than one site, and, therefore, carried out by more than one investigator.

MULTIPLE-RISING DOSE STUDY:

see dose ranging study above.

NATIONAL INSTITUTES OF HEALTH (NIH):

Agency within the Department of Health and Human Services that funds research, conducts studies, and funds multicenter national studies.

NEW DRUG APPLICATION (NDA):

An application submitted by a sponsor to the FDA

for approval to market a new drug (a new, non-biological molecular entity) for human use

in interstate commerce in the United States.

OBSERVATIONAL STUDY:

An epidemiologic study that does not involve any

intervention, experimental or otherwise. Such a study may be one in which nature is

allowed to take its course, with changes in one characteristic being studied in relation to

changes in other characteristics. Analytical epidemiologic methods, such as case-control

and cohort study designs, are properly called observational epidemiology because the

investigator is observing without intervention other than to record, classify, count, and

statistically analyze results.

OFF-LABEL USE:

A drug prescribed for conditions other than those approved by a country’s regulatory agency.

OFFICE FOR HUMAN RESEARCH PROTECTIONS (OHRP):

The Office for Human Research Protections (OHRP) supports, strengthens and provides leadership to the nation’s system for protecting volunteers in research that is conducted or supported by the U.S. Department of Health and Human Services (HHS). OHRP provides clarification and guidance to research institutions, develops educational programs and materials, and promotes innovative approaches to enhancing human subject protections.

OPEN-LABEL TRIAL:

A clinical trial in which doctors and participants know which

treatment is being administered.

ORPHAN DRUGS:

A drug category that refers to medications used to treat rare

diseases and conditions. Orphan drug status, provides a manufacturer specific

incentives to develop and bring such treatments to market.

OUTCOMES TRIAL/STUDY:

An outcomes trial evaluates the effect of a treatment on

patients. Treatments may include medications or other therapies and outcomes may

include changes in disease status, morbidity or mortality.

P-VALUE:

A p-value demonstrates the likelihood that sample data do not adequately

represent the population from which they were drawn.

The accepted standard for a statistically significant p-value is <0.05, meaning that the likelihood that the result could occur by random chance is less than 5 in a hundred.

PARALLEL STUDY:

A parallel designed clinical trial compares the results of a

treatment on two separate groups of patients. The sample size calculated for a parallel

design can be used for any study where two groups are being compared.

EER REVIEW:

Review of a clinical trial by independent experts. These experts review

the trials for scientific merit, validity, participant safety, and ethical considerations.

PHARMACOLOGY:

The study of how drugs interact with living organisms to produce a

change in function. Pharmacology deals with how drugs interact within biological

systems to affect function.

PHARMACOKINETICS:

The processes (in a living organism) of absorption, distribution,

metabolism, and excretion of a drug or vaccine.

PHARMACOVIGILANCE:

The science of collecting, monitoring, researching, assessing

and evaluating information from healthcare pr

oviders and patients on the adverse effects

of medications, biological products, herbalism and traditional medicines with a view to

identify new information about hazards associated with medicines and preventing harm

to patients.

PHASE 1 CLINICAL TRIAL:

Sometimes called dosing studies, these trials may test

methods of administering the treatment (e.g. by mouth, injection, etc.) and how often, as

well as the safety of the treatment. These tria

ls usually involve a small number of healthy

participants (20-80).

PHASE 2 CLINICAL TRIAL:

These trials continue to test the safety of the treatment and

evaluate how well the treatment works. Phas

e 2 studies usually evaluate the treatment

in a specific condition. These trials usually involve 100-300 patients.

PHASE 3 CLINICAL TRIAL:

These trials compare the new treatment to the current

standard of treatment for a specific condition, establishing both efficacy and adverse

events. Participants are usually assigned to

either receive the new treatment or the

current standard. Phase 3 trials typically enroll large numbers of patients (1,000-3,000 or

many more) and may be carried out at hospitals and doctors’ offices nationwide.

PHASE 4 CLINICAL TRIAL:

Post-marketing studies to gain a greater understanding of

the treatment, including its risks, benefits, and optimal use.

PIVOTAL STUDY:

A study, usually Phase 3, which presents the data used by regulatory

agencies to decide whether to approve a drug. A pivotal study will generally be well-

controlled, randomized, and whenever possible, double-blind.

PLACEBO:

A placebo is an inactive pill, liquid or powder that has no treatment value. In

clinical trials, a placebo is administered instead of an active drug or experimental

treatment to assess the experiment

al treatment’s effectiveness.

PLACEBO CONTROLLED STUDY:

A method of drug investigation in which an inactive

substance (a 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 than the placebo in treating the

condition.

PLACEBO EFFECT:

A physical or emotional change, occurring after an inactive

substance is taken or administered, that is not the result of any special property of the

substance. The change may be beneficial, reflecting the expectations of the participant

and, often, the expectations of the person giving the substance.

PRECLINICAL STUDIES:

Experiments performed in the laboratory and in animals to

study a drug before it is tested in humans.

PREVENTION TRIALS:

Conducted 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, vitamins, vaccines, minerals, or lifestyle changes.

PRINCIPAL INVESTIGATOR:

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

who is the responsible leader of the team may be called the principal investigator.

PROSPECTIVE STUDY:

A prospective study identifies subjects, applies a treatment

and follows them over time to measure their progress/outcomes relative to a pre-

determined set of criteria or endpoints.

PROTOCOL:

A protocol is the study plan on which a clinical trial is based. Each trial is

carefully designed to safeguard the health of 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, dosages, and length of 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:

A method based on chance by which study participants are

assigned to different treatment groups. This minimizes the differences among groups by

equally distributing people with particular charac

teristics among all the trial arms, thereby

avoiding “selection bias.” Randomization allows for researchers to comparably test

different treatments in similar groups.

RANDOMIZED TRIAL:

A study in which participants are randomly (i.e., by chance)

assigned to one of two or more treatment arms of a clinical trial.

RESCUE MEDICATION:

A quick-relief or fast-acting medication patients in clinical trials

may be given besides the investigational drug or control that can alleviate symptoms due

to disease or lack of efficacy of the study treatment. It acts quickly to stop symptoms, but

the effects are not long lasting.

RETROSPECTIVE STUDY:

A study in which investigators select groups of patients that

have already been treated and analyze data fr

om the events experienced by these

patients. These studies are subject to bias because investigators can select patient

groups with known outcomes.

RISK-BENEFIT RATIO:

The risk a treatment places on individual participants versus the

potential benefits of the treatment. The risk/benefit ratio may differ depending on the

condition being treated.

SCREENING TRIALS:

Refers to trials which test the best way to detect certain diseases

or health conditions.

SIDE EFFECTS:

Any undesired actions or effects of a drug or treatment. Experimental

drugs must be evaluated for both immediate and long-term side effects.

SINGLE-BLIND STUDY:

A study in which subject or patient is unaware of what

medication they are taking, while the physician does know.

SPONSOR:

A person or an organization that manages and finances a clinical trial.

STANDARD TREATMENT:

A treatment currently in wide use by the medical community

and approved by a country’s regulatory agency considered to be effective in the

treatment of a specific disease or condition.

STANDARDS OF CARE:

Treatment regimen or management based on state of the art

medical care.

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.

STATISTICIAN:

One versed in or engaged in compiling statistics.

STUDY ENDPOINT:

An outcome used to judge the safety or effectiveness of a

treatment.

SURROGATE ENDPOINT:

A biomarker or endpoint that is intended to substitute for a

clinical endpoint. A surrogate endpoint is expected to predict a clinical endpoint or lack

thereof.

TOXICITY:

A treatment-related adverse effect that may be detrimental to the recipient's

health. The level of toxicity associated with a treatment will vary depending on the

attributes of the treatment itself and the condition the drug is being used to treat.

TREATMENT INVESTIGATIONAL NEW DRUG (IND):

It makes promising new drugs

available to desperately ill participants as early in the drug development process as

possible. Treatment INDs are made available to participants before general marketing begins, typically during Phase 3 studies. To be considered for a treatment IND a participant cannot be eligible to

be in the definitive clinical trials.

TREATMENT TRIALS:

Refers to trials which test new treatments, new combinations of

drugs, or new approaches to surgery or radiation therapy.

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