A clinical trial is a research study that targets specific health issues in human volunteers. Performing clinical trials is one of the best methods in the clinical research field for finding new treatments and practices for combating illness.
Participating in clinical trials is a way of becoming actively involved in clinical research relating to one’s own health issues and receiving treatments not otherwise available. Participating in clinical trials may benefit the individual as well as others by increasing understanding of diseases and their treatments.
Every clinical trial has specific criteria for participants in order to maximize the effectiveness of the study and obtain the most reliable results. There are “inclusion criteria” that allow someone to participate in a clinical trial and “exclusion criteria” that exclude someone from participating in a clinical trial. A study may require healthy participants or participants who are affected by the particular disease being targeted in the trial. The stage of illness, previous treatment history, gender, age, and other factors can determine one’s eligibility.
The procedures used for a clinical trial are determined by what type of trial it is. Doctors, nurses, and other health care professionals make up the clinical research team who conduct the trial. They monitor the health of the patient through the entire process of the trial. The trial may or may not include additional doctors’ visits to what one would normally have when treating the condition being studied in the trial.
The participant will be informed of the specific protocol to be followed in the clinical trial, and there will usually be frequent contact between the participant and the clinical research staff.
Before deciding to participate in a clinical trial, a prospective participant should understand the clinical trial process. The purpose of the trial, the duration of the trial, the relevant medical facts of the trial, and the potential risks and benefits involved in the trial and alternative therapies will all be explained to the participant. Agreeing to participate in a clinical trial after coming to an understanding of these details is known as “informed consent”. An informed consent document is provided to the participant detailing these factors and listing pertinent contact information for members of the clinical research team conducting the trial. Before undertaking any of the procedures of the clinical trial, t he participant must sign the informed consent document in order to participate. The process of informed consent continues throughout the clinical trial process as new developments take place. The participant always has the right to discontinue participation in the clinical trial.
Properly conducted clinical trials provide participants an opportunity to:
Clinical trials are federally regulated and include protocols designed to protect the safety of the participants. All legal and ethical standards of medical practice apply to clinical trials. The trial follows strict and detailed guidelines and periodic reports are made to medical journals, medical and scientific conferences, and to government agencies. The anonymity of the participants is maintained in all reports.
Someone considering taking part in a clinical trial should try to learn as much as possible about the clinical trial process, the treatments involved, and the nature of the agreement between the participant and those conducting the trial. One should feel free to ask questions such as:
An Institutional Review Board (IRB) is an independent committee of health care professionals, statisticians, and community advocates. By federal law, all clinical trials must be approved by an IRB. The IRB will review the proposed trial weighing the potential risks and benefits and making sure that the rights and health concerns of trial participants are protected. Once approved, a clinical trial can be conducted and the research will be subject to periodic reviews by the IRB.
Most clinical trials provide experimental treatment directed at a specific health issue and do not provide general primary health care. A participant should continue to receive primary health care from his or her primary health care physician. The primary health care provider should be aware of the clinical trial and work with the clinical research team to ensure that there are no conflicting treatments.
Can participation in a clinical trial be terminated before the trial is finished?
Yes. A participant in a clinical trial is free to discontinue participation at any time.
How do clinical trials originate?
Clinical trials are usually proposed when researchers have identified promising new drug therapies, medical devices or medical procedures. The new ideas usually result from laboratory and animal tests and the clinical trial is the next step in assessing the efficacy of such treatments for humans. The clinical trial will address several aspects of the experimental treatment such as potential risks, methods of administration, dosages etc.
How are clinical trials funded?
There are many different private organizations and individuals as well as government agencies that sponsor clinical trials. These organizations include medical foundations, philanthropic organizations, pharmaceutical companies, the National Institutes of Health (NIH), and the U.S. Department of Defense (DOD). Clinical trials can be conducted in universities, hospitals, doctors’ offices, and clinics.
The following glossary was prepared to help the consumer become familiar with the most common terms used in clinical trials.
Adverse reaction (adverse event): An unwanted effect caused by the administration of drugs. Onset may be sudden or develop over time. (See Side Effects)
Advocacy and support groups: Organizations and groups that actively support participants and their families with valuable resources, including self-empowerment and survival tools.
Approved drugs: In the U.S., the Food and Drug Administration (FDA) must approve a substance as a drug before it can be marketed. The approval process involves several steps including preclinical 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/rejection of application (See Food and Drug Administration).
Arm: Any of the treatment groups in a randomized trial. Most randomized trials have two “arms,” but some have three “arms,” or even more. (See Randomized Trial)
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 that 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.
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. (See Blind and Randomization)
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. (See Single Blind Study and Double Blind Study)
Clinical: Pertaining to or founded on observation and treatment of participants, as distinguished from theoretical or basic science.
Clinical endpoint: See Endpoint
Clinical investigator: A medical researcher in charge of carrying out a clinical trial’s protocol.
Clinical trial: 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. (See Phase I, II, III, and IV Trials)
Cohort: In epidemiology, a group of individuals with some characteristics in common.
Community-based clinical trial (CBCT): A clinical trial conducted primarily through primary-care physicians rather than academic research facilities.
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.
Complementary and alternative therapy: Broad range of healing philosophies, approaches, and therapies that Western (conventional) medicine does not commonly use to promote well-being or treat health conditions. Examples include acupuncture, herbs, etc. Internet Address: http://www.nccam.nih.gov.
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.
Contraindication: A specific circumstance when the use of certain treatments could be harmful.
Control: A control is the nature of the intervention control.
Control group: 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 Placebo and Standard Treatment)
Controlled trials: Control is a standard against which experimental observations may 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.
Data safety and monitoring board (DSMB): 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.
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 expectations of the doctor and the participant about the experimental drug do not affect the outcome; also called double-masked study. (See Blinded Study, Single-Blind Study, and Placebo)
Double-masked study: See Double-Blind Study
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.
DSMB: See Data Safety and Monitoring Board
Efficacy (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 Food and Drug Administration (FDA), Phase II and III Trials)
Eligibility criteria: Summary criteria for participant selection; includes Inclusion and Exclusion criteria. (See Inclusion/Exclusion Criteria)
Empirical: Based on experimental data, not on a theory.
Endpoint: Overall outcome that the protocol is designed to evaluate. Common endpoints are severe toxicity, disease progression, or death.
Epidemiology: The branch of medical science that deals with the study of incidence and distribution and control of a disease in a population.
Exclusion/inclusion criteria: See Inclusion/Exclusion Criteria
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.
Experimental drug: A drug that is not FDA licensed for use in humans, or as a treatment for a particular condition. (See Off-Label Use)
FDA: See Food and Drug Administration
Food and Drug Administration (FDA): 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. The FDA also works with the blood banking industry to safeguard the nation’s blood supply. Internet address: http://www.fda.gov/.
Hypothesis: A supposition or assumption advanced as a basis for reasoning or argument, or as a guide to experimental investigation.
Inclusion/exclusion 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, 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.
IND: See Investigational New Drug
Informed consent: 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 are explained in the informed consent document. The participant then decides whether or not to sign the document. Informed consent is not a contract, and the participant may withdraw from the trial at any time.
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.
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 precise intervention being studied.
Interventions: Primary interventions being studied, types of interventions: Drug, Gene Transfer, Vaccine, Behavior, Device, or Procedure.
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.
IRB: See Institutional Review Board
Masked: The knowledge of intervention assignment. (See Blind)
Natural history study: Study of the natural development of something (such as an organism or a disease) over a period of time.
New Drug Application (NDA): 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.
Off-label use: A drug prescribed for conditions other than those approved by the FDA.
Open-label trial: A clinical trial in which doctors and participants know which drug or vaccine is being administered.
Orphan drugs: 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, however, gives a manufacturer specific financial incentives to develop and provide such medications.
Peer review: Review of a clinical trial by experts chosen by the study sponsor. These experts review the trials for scientific merit, participant safety, and ethical considerations.
Pharmacokinetics: 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 pharmacological 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.
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; these trials are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide and adequate basis for product labeling.
Phase IV trials: Post-marketing studies to delineate additional information including the drug’s risks, benefits, and optimal use.
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. (See 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 if the investigational treatment is more effective in treating the condition.
Placebo effect: 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 may
be beneficial, reflecting the expectations of the participant and,
often, the expectations of the person giving the substance.
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.
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, vitamins, vaccines, minerals, or lifestyle changes.
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. (See Inclusion/Exclusion Criteria)
Quality of life trials (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 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 Arm)
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. Occasionally placebos are utilized. (See Arm and Placebo)
Risk-benefit ratio: The risk to individual participants versus the potential benefits. The risk/benefit ratio may differ depending on the condition being treated.
Screening trials: Refers to trials that test the best way to detect certain diseases or health conditions.
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. (See Adverse Reaction)
Single-blind study: 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 Blind and Double-Blind Study)
Single-masked study: See Single-Blind Study
Standard treatment: A treatment currently in wide use and approved by the FDA, considered to be effective in the treatment of a specific disease or condition.
Standards of care: Treatment regimen or medical management based on state of the art participant 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.
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.
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 that the drug is used to treat.
Treatment IND: IND stands for Investigational New Drug application, which is part of the process to get approval from the FDA for testing a potential prescription drug in the U.S. 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.
Treatment trials: Refers to trials that test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.