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An Introduction to Clinical Trials
An Introduction to Clinical Trials
Choosing to participate in a
clinical trial is an important personal decision. The following frequently asked questions provide introductory information about clinical trials. In addition, it is often helpful to talk to a physician, family members, or friends about deciding to join a trial. After identifying some trial options, the next step is to contact the study research staff and ask questions about specific trials.
Participation in Clinical Trials
For those considering participation in a clinical trial, the
following frequently asked questions are important in understanding the role of
the participant and the unique process of clinical trials.
Glossary
The following glossary was prepared to help the consumer become
familiar with the most common terms used in clinical trials.
What is a clinical trial?
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.
Why participate in a clinical trial?
Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research
Where do the ideas for trials come from?
Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and in animal studies, the treatments with the most promising laboratory results are moved into clinical trials. During a trial, more and more information is gained about a new treatment, its risks and how well it may or may not work.
Who sponsors clinical trials?
Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians, medical institutions, foundations, voluntary groups, and pharmaceutical companies, in addition to federal agencies such as the National Institutes of Health (NIH), the Department of Defense (DOD), and the Department of Veteran's Affairs (VA). Trials can take place in a variety of locations, such as hospitals, universities, doctors' offices, or community clinics.
What is a protocol?
A protocol is 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.
What is a 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. In some studies, the participants in the control group will receive a placebo instead of an active
drug or treatment.
What is a control or control group?
A control is 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.
What are the different types of clinical trials?
Treatment trials test new treatments, new combinations of drugs, or new approaches to surgery or
radiation therapy.
Prevention trials look for 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.
Screening trials test the best way to detect certain diseases or health conditions.
Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.
What are the phases of clinical trials?
Clinical trials are conducted in phases. The trials at each phase have a different
purpose and help scientists answer different questions:
In Phase I trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase II trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase III trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase IV trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
Participation in Clinical Trials
For those considering participation in a clinical trial, the following frequently asked questions are important in understanding the role of
the participant and the unique process of clinical trials.
Who can participate in a clinical trial?
All clinical trials have guidelines about who can participate. Using inclusion/exclusion criteria is an important
principle of medical research that helps to produce reliable results. The
factors that allow someone to participate in a clinical trial are called "inclusion
criteria" and those that disallow someone from participating are called "exclusion
criteria". These criteria are based
on such factors as age, gender, the type and stage of a disease, previous
treatment history, and other medical conditions. Before joining a clinical
trial, a participant must qualify for the study. Some research studies seek participants with illnesses or
conditions to be studied in the clinical trial, while others need healthy participants.
It is important to note that inclusion and exclusion criteria are not used to
reject people personally. Instead, the criteria are used to identify
appropriate participants and keep them safe. The criteria help ensure that
researchers will be able to answer the questions they plan to study.
What happens during a clinical
trial?
The clinical trial process depends on the kind of trial
being conducted (See What are the different types of
clinical trials?) The clinical trial team includes doctors and nurses as
well as social workers and other health care professionals. They check the
health of the participant at the beginning of the trial, give specific
instructions for participating in the trial, monitor the participant carefully
during the trial, and stay in touch after the trial is completed.
Some clinical trials involve more tests and doctor visits
than the participant would normally have for an illness or condition. For all types of trials, the participant
works with a research team. Clinical trial participation is most successful when
the protocol is carefully followed and there is frequent contact with the
research staff.
What is informed consent?
Informed consent is 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. If the participant's native language is
not English, translation assistance can be provided. Then the research team provides an informed
consent document that 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.
What kind of preparation should a potential participant
make for the meeting with the research coordinator or doctor?
- Plan ahead and write down possible questions to ask.
- Ask a friend or relative to come along for support and to hear the responses to the questions.
- Bring a tape recorder to record the discussion to replay later.
What should people consider before participating in a trial?
People should know as much as possible about the clinical trial and feel comfortable
asking the members of the health care team questions about it, the care expected
while in a trial, and the cost of the trial. The following questions might be helpful for the participant to discuss
with the health care team. Some of the answers to these questions are found in
the informed consent document.
- What is the purpose of the study?
- Who is going to be in the study?
- Why do researchers believe the new treatment being tested may be effective? Has it been tested before?
- What kinds of tests and treatments are involved?
- How do the possible risks, side effects, and benefits in the study compare with my current treatment?
- How might this trial affect my daily life?
- How long will the trial last?
- Will hospitalization be required?
- Who will pay for the treatment?
- Will I be reimbursed for other expenses?
- What type of long-term follow up care is part of this study?
- How will I know that the treatment is working? Will results of the trials be provided to me?
- Who will be in charge of my care?
Does a participant continue to work with a primary
health care provider while in a trial?
Yes. Most clinical trials provide short-term treatments
related to a designated illness or condition, but do not provide extended or
complete primary health care. In addition, by having the health care provider
work with the research team, the participant can ensure that other medications
or treatments will not conflict with the protocol.
What are side effects and adverse reactions?
Side effects are any undesired actions or effects of drug or
treatment. Negative or adverse effects may include headache, nausea, hair loss,
skin irritation, or other physical problems. Experimental treatments must be
evaluated for both immediate and long-term side effects.
What are the benefits and risks of participating in a
clinical trial?
Benefits
Clinical trials that are well-designed and well-executed are the best treatment approach
for eligible participants to:
- Play an active role in their own health care.
- Gain access to new research treatments before they are widely available.
- Obtain expert medical care at leading health care facilities during the trial.
- Help others by contributing to medical research.
Risks
There are risks to clinical trials.
- There may be unpleasant, serious or even life-threatening side effects to treatment.
- The treatment may not be effective for the participant.
- The protocol may require more of their time and attention than would a non-protocol treatment, including
trips to the study site, more treatments, hospital stays or complex dosage
requirements.
How is the safety of the participant protected?
The ethical and legal codes that govern medical practice also apply to clinical trials. In addition, most
clinical research is federally regulated with built in safeguards to protect
the participants. The trial follows a carefully controlled protocol, a study plan which details what researchers will do
in the study. As a clinical trial progresses, researchers report the results of
the trial at scientific meetings, to medical journals, and to various
government agencies. Individual participants' names will remain secret and will
not be mentioned in these reports (See Confidentiality
Regarding Trial Participants).
Every clinical trial in the U.S. must be approved and monitored by an Institutional
Review Board (IRB) to make sure the risks are as low as possible and are
worth any potential benefits. An IRB is an independent committee of physicians,
statisticians, community advocates, and others that ensures that a clinical
trial is ethical and the rights of study participants are protected. All
institutions that conduct or support biomedical research involving people must,
by federal regulation, have an IRB that initially approves and periodically
reviews the research.
Can a participant leave a clinical trial after it
has begun?
Yes. A participant can leave a clinical trial, at any time.
When withdrawing from the trial, the participant should let the research team know about it, and the reasons for leaving the study.
Glossary of Clinical Trials Terms
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 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/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 which is being tested.
At this reference point, measurable values such as CD4 count are recorded.
Safety and efficacy of a drug are often determined by monitoring changes from
the baseline values.
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.
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, including those used in the diagnosis, treatment, and prevention of
HIV infection, AIDS, and AIDS-related opportunistic infections. 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 ( See Randomization) 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 are 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 pharmacologic actions of drugs in humans, the side effects associated with increasing doses, and to gain early evidence of effectiveness; may include healthy participants and/or patients.
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, and are intended to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide and adequate basis for physician labeling.
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. In some studies, the participants in the control group will
receive a placebo instead of an active drug or treatment. No sick participant
receives a placebo if there is a known beneficial treatment. (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 (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 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 which 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 which 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 marketing a new 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 which test new treatments, new combinations of drugs, or new approaches
to surgery or radiation therapy.
General Information on Clinical Trials
The following U.S. government web sites guide consumers to answers to questions and provide contacts to clinical trials, and to information on drugs and important health care issues. The clinical trials discussed in these sites are all available in ClinicalTrials.gov
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