Clinical trials help determine whether a drug is safe and effective for MS. Here is a glossary of terms commonly used in clinical trials descriptions and forms.
Also called Adverse Event. An unwanted effect caused by the administration of drugs. Onset could be sudden or develop over time. (See also Side Effects)
In the United States, the Food and Drug Administration (FDA) must approve a substance as a drug before it can be marketed and administered. The approval process involves several steps including pre-clinical laboratory and animal studies, clinical trials for safety and efficacy, filing of a New Drug Application by the manufacturer of the drug, FDA review of the application, and FDA approval or rejection of the application. (See also Food and Drug Administration)
Any of the treatment groups in a randomized trial. Most randomized trials have two "arms," but some have three "arms," or even more. (See also Randomized Trial)
The initial time point in a clinical trial, just before a participant starts to receive the experimental treatment being tested. Safety and efficacy of a drug often are determined by monitoring changes from the baseline values.
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. (See also Blind and Randomization)
A randomized trial is "Blind" if the participant is not told which arm of the trial they are on. A clinical trial is "Blind" if participants are unaware whether they are in the experimental or control arm of the study. Also called “masked.” (See also Single Blind Study and Double Blind Study)
Pertaining to or founded on observation and treatment of participants, as distinguished from theoretical or basic science.
A clinical trial is a research study to answer specific questions about vaccines, 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 (See also Phase I, II, III, and IV Trials):
- 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.
- Phase IV takes place after the drug or treatment has been licensed and marketed.
A group of individuals with some characteristics in common.
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.
COMPLEMENTARY AND ALTERNATIVE THERAPY
Broad range of healing philosophies, approaches, and therapies that Western (conventional) medicine does not commonly use to promote wellbeing or treat health conditions. Examples include acupuncture and herbs.
The study has concluded normally. Participants are no longer being examined or treated, i.e., last patient's last visit has occurred. (See also Recruitment Status)
A specific circumstance when the use of certain treatments could be harmful.
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. (See also Placebo and Standard Treatment)
Control is a standard against which experimental observations might be evaluated. In clinical trials, 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.
CHRONIC-PROGRESSIVE (CP) MS
Former "catch-all" term for progressive forms of MS, now categorized as two separate forms of disease. (See also Secondary-Progressive MS and Primary-Progressive MS)
A study design that has each patient in two or more treatments in a specified order.
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 could recommend that a trial be stopped due to safety concerns or if the trial objectives have been achieved.
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.
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, because the expectations of the doctor and the participant about the experimental drug do not affect the outcome. Also called double-masked study. (See also Blinded Study, Single-Blind Study, and Placebo)
A modification of the effect of a drug when administered with another drug. The effect could be an increase or a decrease in the action of either substance, or it could be an adverse effect that is not normally associated with either drug.
Of a drug or treatment. 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. (See also Food and Drug Administration (FDA), Phase II and III Trials)
Summary criteria for participant selection. Includes Inclusion and Exclusion criteria. (See also Inclusion/Exclusion Criteria)
Based on experimental data, not on a theory.
Overall outcomes that the protocol is designed to evaluate. Common endpoints are time to first relapse, toxicity, or disease progression. (See also Outcome Measure)
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.
The branch of medical science that deals with the study of incidence, distribution, and control of a disease in a population.
A drug that is not FDA licensed for use in humans or as a treatment for a particular condition. (See also Off-Label Use)
The U.S. Department of Health and Human Services agency responsible for ensuring the safety and effectiveness of all drugs, biologics, vaccines, and medical devices.
A supposition or assumption advanced as a basis for reasoning or argument, or as a guide to experimental investigation.
The medical or social standards determining whether a person might or might not be allowed to enter a clinical trial. Those criteria are based on factors such as age, gender, 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 and keep them safe.
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.
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 also are explained in the informed consent document. Based on the informed consent document, the individual decides whether or not to sign the form and participate in the study. Informed consent is not a contract, and the participant may withdraw from the trial at any time.
INSTITUTIONAL REVIEW BOARD (IRB)
A committee of physicians, statisticians, researchers, community advocates, and others who ensure that a clinical trial is ethical and that the rights of study participants are protected. All clinical trials in the United States must be approved by an IRB before they begin. 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 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 (See also Randomization) even if they never received the treatment.
Primary interventions being studied. Types of interventions are Drug, Gene Transfer, Vaccine, Behavior, Device, or Procedure.
Introduced into the skin.
Injected into the muscle.
Injected into the vein.
INVESTIGATIONAL NEW DRUG
A new drug, antibiotic drug, or biological drug that is used in a clinical investigation. It also includes a biological product used in vitro for diagnostic purposes.
Magnetic resonance imaging. A non-invasive process of producing an image, especially of internal soft tissues of the body, from electromagnetic energy. MRI is used in MS to reveal lesions in the brain and spinal cord. It is used to confirm a diagnosis of MS and to track disease progression during clinical trials.
A clinical trial involving patients at more than one site open-label study—a study in which all patients receive the experimental treatment.
MULTIPLE SCLEROSIS, MAJOR FORMS
Although potential exists for the course of multiple sclerosis to progress from one pattern to a more severe one, the clinical course of MS usually falls within one of the following categories: relapsing-remitting, primary-progressive, progressive-relapsing, secondary-progressive.
An application submitted by the manufacturer of a drug to the FDA—after clinical trials have been completed—for a license to market the drug for a specified indication.
The reason for performing a trial in terms of the scientific questions to be answered by the data collected during the trial. The primary objective is the main question to be answered and drives any statistical planning for the trial (e.g., the sample size). Secondary and tertiary objectives are goals of a trial that will provide further information on the use of the treatment.
A drug prescribed for conditions other than those approved by the FDA.
A clinical trial in which doctors and participants know which drug or vaccine is being administered.
Taken by mouth.
An FDA category that refers to medications used to treat diseases and conditions that occur rarely. There is little financial incentive for the pharmaceutical industry to develop medications for these diseases or conditions. Orphan drug status gives a manufacturer specific financial incentives to develop and provide such medications.
Measurement unit used to assess the effectiveness of a program or intervention, such as measures of disease activity, progression, or changes in MRI scans. Read more about Clinical Study Measures used in MS trials.
Review of a clinical trial by experts chosen by the study sponsor. Those experts review the trials for scientific merit, participant safety, and ethical considerations.
The processes (in a living organism) of absorption, distribution, metabolism, and excretion of a drug or vaccine.
PHASE I TRIALS
Initial studies to determine the metabolism and pharmacologic actions of drugs in humans, to observe the side effects associated with increasing doses, and to gain early evidence of effectiveness. Could include healthy participants and/or patients.
PHASE II TRIALS
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.
PHASE III TRIALS
Expanded controlled and uncontrolled trials after preliminary evidence suggesting effectiveness of the drug has been obtained. Phase III trials are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide and adequate basis for physician labeling.
PHASE IV TRIALS
Post-marketing studies to delineate additional information including the drug's risks, benefits, and optimal use.
An early, small-to-moderate sized study, also known as a Phase 2 study. A pilot study follows the Phase 1 study, or "safety study," and is designed to begin determining the effectiveness of the experimental treatment.
A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments often are compared with placebos to assess the treatment's effectiveness. (See also Placebo Controlled Study)
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 whether the investigational treatment is more effective in treating the condition.
A physical or emotional change, occurring after a substance is taken or administered, that is not the result of any special property of the substance. The change could be beneficial, reflecting the expectations of the participant and often the expectations of the person giving the substance.
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.
PRIMARY-PROGRESSIVE (PP) MS
Form of MS characterized by disease progression from onset, with occasional plateaus (leveling of condition) and temporary minor improvements possible.
PROGRESSIVE-RELAPSING (PR) MS
Form of MS characterized by progressive disease from onset, with acute relapses, with or without full recovery. Periods between relapses characterized by continuing progression. Considered to be a rare clinical course.
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 length of the study as well as the schedule of tests, procedures, medications, and dosages. 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. (See also Inclusion/Exclusion Criteria)
Also called Supportive Care trials. Refers to trials that explore ways to improve comfort and quality of life for individuals with a chronic illness.
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. (See also Arm)
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. (See also Arm and Placebo)
Indicates the current stage of a trial, whether it is planned, ongoing, or completed. Possible values include:
- Not yet recruiting—Participants are not yet being recruited or enrolled.
- Recruiting—Participants are currently being recruited and enrolled.
- Enrolling by invitation—Participants are being (or will be) selected from a predetermined population.
- Active, not recruiting—Study is ongoing (i.e., patients are being treated or examined), but enrollment has completed.
- Completed—The study has concluded normally. Participants are no longer being examined or treated (i.e., last patient's last visit has occurred).
- Suspended—Recruiting or enrolling participants has halted prematurely but potentially will resume.
- Terminated—Recruiting or enrolling participants has halted prematurely and will not resume. Participants are no longer being examined or treated.
- Withdrawn—Study halted prematurely, prior to enrollment of first participant.
A sudden worsening of preexisting symptoms, or the development of new neurologic symptoms, which lasts at least 24 hours. Synonymous with "exacerbation" or "acute attack."
Former name for progressive-relapsing MS.
RELAPSING-REMITTING (RR) MS
Form of MS characterized by clearly defined disease relapses (flare-ups) with full recovery or with sequelae (resulting conditions) and residual deficit upon recovery. Periods between disease relapses characterized by a lack of disease progression (gradual worsening).
The risk to individual participants versus the potential benefits. The risk/benefit ratio could differ depending on the condition being treated.
Form of MS characterized by initial RR disease course followed by progression with or without occasional relapses, minor remissions (some recovery), and plateaus (leveling of condition).
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. (See also Blind and Double-Blind Study).
A treatment currently in wide use and approved by the FDA, considered to be effective in the treatment of a specific disease or condition.
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.
Injected under the skin.
Recruiting or enrolling participants has halted prematurely but potentially will resume. (See also Recruitment Status)
Recruiting or enrolling participants has halted prematurely and will not resume. Participants are no longer being examined or treated. (See also Recruitment Status)
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.
IND stands for Investigational New Drug application, which is part of the process to get approval from the FDA for marketing a new prescription drug in the United States. 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 III studies. To be considered for a treatment IND a participant cannot be eligible to be in the definitive clinical trial.
Study halted prematurely, prior to enrollment of first participant. (See also Recruitment Status)
This information is adapted from ClinicalTrials.gov, a service of the National Institutes of Health and developed by the National Library of Medicine.