A
Glossary of Terms Used
In Clinical Research
You may hear the following terms connected with clinical research. We hope this glossary is useful. For a current listing of
Meriter's clinical research, visit our main clinical research
page.
Benefit
Something that promotes or protects the well being of the subject; an
advantage.
CFR (Code of Federal Regulations)
A set of rules issued by Federal agencies on
a number of topics. See Ethical Codes and Statement of Ethical Principles.
Class I, II, III Device
Classification by the Food and Drug Administration of
medical devices according to potential risks or hazards. Class I devices pose
the least potential risk such as crutches, band aids, etc. A Class II device
would include a halter heart monitor. Class III devices pose the greatest
potential risk and might include an experimental heart valve.
Clinical Trials Phase 1-4
A clinical trial is an organized, systematic exposure
of subjects to some kind of intervention (drug, surgical procedure, medical
device, etc.). Researchers hope to answer some question about the effectiveness
of the intervention. An intervention progresses from Phase I to Phase III if
results are favorable at each phase. With the successful completion of Phase
III, the FDA may approve a drug or device for commercial marketing to the
public.
A Phase 1 clinical drug trial is the first test of
a drug in a human population. Phase 1 trials are designed to determine toxicity
(level at which a drug becomes poisonous), absorption, metabolism and safe
dosage range and are limited to relatively few subjects (20-80). Although
healthy volunteers are sometimes used, for obvious ethical reasons, Phase l
testing is more properly done in patients. For example, cancer chemotherapy
subjects in a Phase l trial have exhausted all alternative treatments and enroll
in the study hoping for therapeutic benefit. The study often involves increasing
amounts of the drug dose until the maximum tolerated dose is established. This
means the dose is increased until toxicity occurs. The objective of a Phase l
study, is to determine how much of a drug makes subjects toxic and to see
whether the subjects' disease reacts to the drug.
Phase 2 Clinical Drug Trial
A Phase 2 clinical drug trial involves a limited
number of subjects (200-300). It is designed to test how well the drug works and
obtain additional data on the safety of the drug.
Phase 3 Clinical Drug Trial
A Phase 3 clinical drug trial is an expanded trial
(several thousand subjects) which is designed to gain additional evidence of how
well the drug works.
Phase 4 Clinical Drug Trial
A Phase 4 clinical drug trial occurs after a drug
is approved by the FDA and is being used by the public. The objective of a Phase
4 Trial is to gain more information on the drug such as the incidence of a
specific adverse reaction or to determine the long-term effects of the drug on
prolonging a subject's life.
Other Types of Clinical Research
Randomized clinical trial (RCT)A randomized clinical trial (RCT) is a clinical
trial where subjects are randomly assigned (by chance) to different treatments
or interventions, such as "Drug A" versus "Drug B."
Single Masked DesignIn a single masked design, the subject does not know the
treatment assignment but the investigator does.
Double Blind DesignA double blind design is a study comparing two or more
treatments where neither the investigator nor the subject knows who has received
which treatment. This minimizes potential bias, such as in the assignment of a
particular subject to one of the treatments. It also minimizes the researcher's
bias in interpreting the data.
Double Blind RandomizedA double blind randomized design is a study comparing
two or more treatments where the subjects are randomly assigned (by chance) to
different treatments or interventions such as "Drug A" versus "Drug B" and
neither the investigator nor the subject know which treatment was received.
Cross-over DesignA study in which subjects are randomly assigned to different
treatments and then switched at the halfway point in the treatment.
Placebo ControlA placebo controlled study is a study where
subjects are randomly assigned to a placebo group. The placebo group does not
receive the experimental treatment. This allows the researcher to compare the
treatment effects of the experimental treatment to the group receiving no
treatment (the placebo). The researcher can determine if the outcomes are due to
the experimental research or just chance. The placebo control group plays an
important role in determining whether a new treatment is effective. A placebo
control is used when there is no established (standard) treatment for a disease.
However, if a treatment exists that has been shown to be effective, it is
unethical to use a placebo, particularly if the illness is life-threatening.
Retrospective StudyA retrospective study is a study involving data that have
already been collected, such as a review of medical records from the past for a
specific medical treatment.
Compensation
Payment or medical care provided to subjects injured in research;
it does not refer to payment for participation in research.
Confidentiality
Pertains to the treatment of information that an individual has
disclosed in a relationship of trust and with the expectation that it will not
be divulged to others without permission.
A set of codes to guide
medical professionals to treat human research subjects in an ethical way. There
are three major ethical codes that provide general ethical guidelines for the
responsible conduct of research in the United States and which provide the basis
for the Health and Human Services (HHS) and
Food and Drug Administration (FDA)
regulations on the protection of human research subjects. It should be noted
that HHS/FDA regulations are not intended to serve as an ethical code. In fact,
title 45 of the Code of Federal Regulations, part 46.103 requires each
institution's Assurance of Compliance to include a statement of principles for
ethical conduct of research which may be based upon "an appropriate existing
code, declaration or statement of ethical principles." Most institutions use the
Belmont Report, Declaration of Helsinki and the Nuremberg Code.
Nuremberg Code
An international ethical code published in 1947 which
established standards for the conduct of research involving human beings. It
arose out of the Nuremberg War Crimes Trial, where 23 Nazis were charged with
crimes against humanity that involved murderous, pseudo medical experimentation.
Twenty of the individuals charged were physicians.
Declaration of Helsinki
An international ethical code first issued in 1964 by
the 18th World Medical Assembly in Helsinki, Finland. The Declaration contains
12 basic principles which are similar to the Nuremberg Code but represent an
expansion of what constitutes acceptable research and the ethical
responsibilities of investigators. Unlike the Nuremberg Code, the Declaration of
Helsinki addresses the need for peer review (i.e., Institutional Review Board
review). It is interesting to note that the FDA will not accept foreign data
unless the studies in which such data are generated are conducted in compliance
with the Declaration of Helsinki (21 CFR 312.20, 46 Fed Reg 8953, Tuesday,
January 17, 1981).
Belmont Report
A report consisting of ethical principles and guidelines for
protection of human subjects in research. It was issued April 18, 1979, by the
National Commission for the Protection of Human Subjects of Biomedical and
Behavioral Research.
Experimental
Term often used to indicate a therapy (drug, device, procedure,
etc.) that is yet to be scientifically validated with respect to safety and
effectiveness. A procedure may be considered "experimental" without necessarily
being part of a formal study (research) to evaluate its usefulness.
An agency of the federal government,
established by Congress in 1912 and presently part of the Department of Health
and Human Services (HHS). FDA authorizes and regulates use of experimental drugs
and devices used in human research. The FDA also audits Meriter Institutional
Review Board at least once every five years for regulatory compliance. Visit the
FDA Web site for more information.
A department of the federal
government. HHS has regulations that apply to human subject research conducted
at Meriter Hospital and its entities, when that research is sponsored by any
agency of HHS. Visit the HHS Web site for more information.
Human Subject
A living individual about whom an investigator conducting
research obtains: 1) data through intervention or interaction with the
individual, or 2) gathers private information through which you may be
identified. "Intervention" includes both physical procedures by which data are
gathered (for example a blood draw) and manipulation of the subject or the
subject's environment that are performed for research purposes. "Interaction"
includes communication or interpersonal contact between investigator and
subject. "Private information" includes information about behavior that occurs
in a context in which an individual can reasonably expect that no observation or
recording is taking place, and information which has been provided for specific
purposes by an individual and which the individual can reasonably expect will
not be made public (for example, a medical record). NOTE: FDA defines "human
subject" as an individual who is or becomes a participant in research, either as
a recipient of the test article or as a control. A subject may be either a
healthy human or a patient.
Informed Consent
A person's voluntary agreement, based upon adequate knowledge
and understanding of relevant information, to participate in research or to
undergo a diagnostic, therapeutic or experimental preventive procedure.
Investigational Drug
Includes those substances in any of the clinical states of
evaluation which have not been released by the FDA for general use or cleared
for sale to the public. An investigational drug may also be defined by one of
the following:
a. A drug in any of the clinical states of evaluation (Phase I, II, III) which
has not been released by the FDA for general use or cleared for sale in
interstate commerce.
b. Any commercially available drug proposed for a new use.
c. A new dosage form or method of administration of an FDA approved drug.
d. A new combination of two or more commercially available drugs.
Investigational Medical Device
A medical device is defined as any health care
product that does not achieve any of its intended purposes by chemical action or
by being metabolized. For example, an experimental new hip replacement, an
experimental coronary stent, etc. Before 1976, medical devices could be marketed
without a review by the FDA. However, in 1976 the medical device amendments of
1976 to the Federal Food, Drug and Cosmetic Act were passed in order to ensure
that new devices were safe and effective before they were marketed. The FDA
regulations which govern medical devices are Title 21 Code of Federal
Regulations, Parts 812, 814, 860, 861. An investigational medical device is a
device not yet approved for marketing by the FDA.
In Vitro
Literally, "in glass" or "test tube" - used to refer to processes that
are carried out outside the living body, usually in the laboratory, as
distinguished from in vivo (see next term).
In Vivo
In the living body; processes, such as the absorption of a drug by the
human body, carried out in the living body rather than in a laboratory.
Minimal Risk
Minimal risk means "The probability and magnitude of harm or
discomfort anticipated in the research are not greater in and of themselves than
those ordinarily encountered in daily life or during the performance of routine
physical or psychological examinations or tests." Examples of research activities
involving no more than minimal risk include collection of blood samples from
healthy, non-pregnant adults by puncturing a vein with a syringe and withdrawing
an amount not exceeding 450 ml in an eight-week period and no more often than
two times per week; electrocardiography which measures electrical impulses
generated by the heart; electroencephalography which measures electric impulses
generated by the brain; and moderate exercise by healthy subjects.
NCI: National Cancer Institute
Established in 1937 as an institute within the
National Institutes of Health (NIH). NCI leads a national effort to reduce the
burden of cancer related deaths. Its goal is to stimulate and support scientific
discovery and its application to achieve a future when all cancers are uncommon
and easily treated. Through basic and clinical biomedical research and training,
NCI conducts and supports programs to understand the causes of cancer; prevent,
detect, diagnose, treat, and control cancer; and disseminate information to the
practitioner, patient, and public. Visit the
NCI Web site for more
information.
NIH: National Institutes of Health
A federal government agency that falls under
the Department of Health and Human Services. The National Institutes of Health
is the steward of medical and behavioral research for the nation. Its mission is
science in pursuit of fundamental knowledge about the nature and behavior of
living systems and the application of that knowledge to extend healthy life and
reduce the burdens of illness and disability. Visit the
NIH Web site
for more information.
OHRP: Office for Human Research Protection
Responsible for implementing HHS
regulations governing research with human subjects. Visit the
OHRP Web site
for more information.
Placebos are used in studies where one group of subjects receives an
experimental drug and one group does not. The group who does not receive the
experimental drug receives a placebo. A placebo is most often a pill, that is an
inert substance (such as sugar) used in place of the active drug. An active or
impure placebo is one that contains some medicinal ingredients, but these
ingredients have properties unrelated to the patient's condition. The
ingredients are considered harmless but also without benefit to the research
subject. See Placebo Control Group.
Principal Investigator
The scientist or scholar with primary responsibility for
the design and conduct of a research project.
Protocol
The formal design or plan of an experiment or research activity;
specifically, the plan submitted to an Institutional Review Board for review and
approval for research support.
Research
A systematic investigation designed to develop or contribute to
knowledge that will be of interest and benefit to the larger medical community.
The following are a series of relevant terms:
Therapy
Refers to interventions that are applied solely to enhance
the
well-being of an individual patient who is sick. The interventions are
procedures commonly accepted by the medical community and represent the standard
of care.
Therapeutic Research
Refers to interventions that are
designed to determine the effectiveness and safety of a therapeutic or
diagnostic method. The interventions are not applied solely to enhance the
well-being of the individual subject who is sick. Note use of the term "subject"
as opposed to "patient" (see below). Achievement of maximum possible therapeutic
benefit cannot, therefore, be presumed, since the intervention is still being
evaluated. The objective of therapeutic research is to increase the medical
community's knowledge (i.e. test a hypothesis and draw a conclusion), and at the
same time provide the subject with a potential needed health benefit.
Accordingly, the responsibilities of a physician who is also an investigator
must take into consideration the fact that the patient is also a research
subject.
Non-therapeutic Research
Research that has no likelihood or intent of producing
a diagnostic, preventive, or therapeutic benefit to the current subjects,
although it many benefit subjects with a similar condition in the future. For
example, a Phase I Clinical Drug Trial.
Risk
A potential harm that a reasonable person, in what the investigator knows
or should know to be the subject's position, would be likely to consider
significant in deciding whether or not to participate in the research.
A subject is an individual who has agreed to participate
in research. A subject may be a healthy individual or may be suffering from
anything from a very mild medical condition to a life-threatening medical
condition. A patient is someone who has not agreed to participate in research
and is pursuing the standard treatment for their medical condition.
Voluntary
Free of coercion, duress or undue inducement. Used in research
context to refer to a subject's decision to participate (or to continue to
participate) in a research activity.
2/11/2008
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