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Eczema Update-September
Clinical Trials: Basic Facts and Answers
People with serious and/or chronic diseases
have usually heard about clinical trials and wonder if this is a treatment
option they should consider. Clinical trials
are investigational studies
of new therapies, new uses of current therapies, new ways to detect
disease, and new approaches to making patients comfortable.
What are clinical trials?
Clinical trials are medical investigative
studies in which human beings are the test subjects. The word "clinical" tells you
that humans are the subject of an investigative study.
"Clinical" pertains to the observation and treatment of human
patients, as distinguished from theoretical, laboratory or animal studies.
Clinical trials are a building-block of
science-based medicine.
A clinical study provides information when
the study is completed, but that isn’t the end of its usefulness. The
paper or papers that report results of the study are usually referenced in
a data bank such as MedLine, the data retrieval system of the National
Library of Medicine. At any future time for decades, the papers are
available for retrieval by physicians, non-physician scientists and any
interested person. If a study was well-designed and its results
scientifically and statistically valid, it may be referenced in
future studies and future studies may seek to build upon or critically
examine its results. Thus, it becomes a building block in a constantly
evolving information base.
There are several types of clinical
studies, which may be described in an increasing order of complexity.
Case reports
are studies of isolated or carefully selected individual patients. A case
is usually reported because of some unusually interesting aspect—for
example, eczema in an unusual presentation. Investigators select the cases
to report. You cannot volunteer for a case report.
Retrospective studies
use case records from hospitals and medical centers to identify trends or
patterns over a period of years. For example, a retrospective study might
examine patterns of atopic dermatitis treatment over a 30-year period in
several hundred patients. The study investigators might conclude that one
technique was shown to be associated with a lower rate of recurrence. The
patients whose records are reviewed for retrospective studies are
participants only in the sense that data from their cases was reviewed.
Patient identities are never disclosed.
Controlled observational studies
of new therapies typically use a group of patients who are the study
group, and a control (comparison) group of people who do not receive the
treatment under study. The control group may be healthy volunteers, or may
be people who have the same disease as the patients but do not receive the
treatment under study. The control group may receive a placebo—a
nonactive substance with no medicinal effects--or a standard therapy
rather than the investigational therapy. The investigator may decide who
does or does not receive treatment, or a person other than the
investigator may make that decision. The patients and members of the
control group are usually "blinded"—that is, they do not know
which treatment they are receiving. The principal investigator may also be
"blinded" as to which subjects are receiving treatment.
Prospective experimental studies
are exemplified by the randomized, double-blind controlled trial (RCT)—the
"gold standard" for unbiased study results. In this type of
study, patients are randomly assigned to study groups or control groups,
and neither investigators nor patients and controls know who is receiving
investigational treatment and who is receiving placebo or standard
treatment—thus, "double blind." RCTs are the most persuasive
study design for proving the effect of a therapy or exposure of a
treatment outcome. These studies are expensive and time-consuming, tending
to require more study subjects and long periods of follow-up in order to
achieve the statistical power necessary to prove or disprove the study
hypothesis.
In RCT studies of new drugs and new
treatments, volunteers are usually patients who have the disease for which
the treatment is being developed. In RCT studies of treatments for a
disease such as atopic dermatitis, volunteers may be randomized to receive
the investigational therapy, or a standard therapy which is the best
treatment currently available.
Pharmaceutical firms often sponsor RCTs to
gather the data necessary to win Food and Drug Administration (FDA)
approval for a new drug or new uses of an existing drug. The studies are
conducted by investigators in hospitals and medical centers, or by
physicians in private offices, independent of any involvement by the
sponsoring company.
RCTs are also conducted by large medical
centers and by government-supported institutions such as the National
Institutes of Health and Veterans Administration. The hypotheses tested in
these trials may involve new therapies, comparison of existing therapies,
new applications of existing therapies, new screening methods for earlier
detection of disease, or new methods of prevention.
Clinical trials are required by the FDA for
approval of a new drug or new uses for an existing drug
After basic science, laboratory and animal
studies have indicated that a drug may be safe and effective for treatment
of a specific disease, human clinical trials may be planned as the next
step toward FDA approval. Animal studies are important, but the major
limitation of animal studies is that animal models are not the same as
humans due to differences in animal and human biology and other factors.
Clinical studies of a new drug or treatment
are usually conducted in three phases.
Phase 1
is the initial study of the drug in humans. The study subjects are usually
not more than 20 to 80 volunteers. The purpose of Phase 1 study is to
determine the metabolic and pharmacologic actions of the drug in humans,
side effects associated with increasing doses, and indications of
effectiveness. If Phase 1 studies are completed satisfactorily, Phase 2
trials may be conducted.
Phase 2
are uncontrolled clinical studies, (a study that does not include a
"control" or "comparison" group), designed to obtain
data regarding the effectiveness of the drug for specifically-designated
uses (indications), in patients with the disease the drug is designed to
treat. Several hundred volunteers may be enrolled in a number of Phase 2
studies, which may be observational studies, a study that looks at an
intervention. Volunteers are selected by criteria outlined by the
investigators in the study protocol (study plan). If Phase 2 trials are
satisfactorily completed, Phase 3 studies are conducted.
Phase 3
are expanded clinical studies. They are controlled, and are often
randomized, double-blind controlled trials. In Phase 3 trials, the overall
benefit-risk value of the investigational treatment is evaluated. Several
hundred to several thousand volunteers are enrolled as patients and
controls. It is usually at the point of Phase 3 trials that large numbers
of patients are sought as volunteers in the trials.
Clinical trials offer patients the
opportunity to;
- Participate in clinical investigations of new
treatments, and
- Contribute to the knowledge base of medicine.
A well-designed, well-conducted clinical
trial provides important data for future investigators and for physicians
currently treating patients with the disease that was studied.
The results from a single study may be
persuasive, but the results will be interpreted in a context of other
evidence that links the treatment to health outcomes in patients of
different ages, genders, and overall health status. This is the body of
evidence a physician will consider when planning treatment for a patient.
Other Questions About Clinical Trials:
Eligibility, Safety, Costs, Finding Trials
Who is eligible to volunteer for clinical
trials?
The question of eligibility is answered in
the protocol (study plan) for each trial. The investigators conducting the
trial will have established selection criteria for volunteers who will
most effectively test the hypothesis of the trial.
Does being in a clinical trial require
being away from home?
The type of trial, the study protocol, and
the severity of a patients’ illness determines where a trial is
conducted. When patients are very ill, or when 24-hour monitoring is
required, the trial may be conducted at one or more large medical centers
and require the volunteers to remain at the centers during the trial.
Other trials may have many dispersed locations and only accept volunteers
who can get from location to location, and who are not required to stay at
the study locations. Most dermatologic illnesses do not require a hospital
stay unless 24-hour monitoring is a condition of the trial.
How long does a clinical trial last?
The duration of a clinical trial can be
many days to many weeks, depending on the time required to test the study
hypothesis adequately. In RCTs, a volunteer may be asked to return for
follow-up testing for several weeks or months after the treatment phase is
over.
How does a volunteer know what will be
required during a clinical trial?
Federal regulations, and the rules of each
institution involved in a clinical trial, require that (1) every trial
must be approved by an Institutional Review Board (IRB) to assure that
volunteer rights and safety are adequately protected, and (2) a volunteer
must give informed consent. The process of informed consent requires the
study investigators to thoroughly inform volunteers about a study
protocol, treatment to be given during the trial, tests that will be
carried out, and follow-up procedures after the trial. If the study is
blinded and placebo-controlled, the volunteer must be told that he or she
may receive placebo or standard treatment rather than the investigational
treatment. The volunteer is urged to discuss informed consent with family
and physicians before deciding to volunteer to enter a trial. Informed
consent means that the volunteer agrees to participate in the trial under
conditions explained by the investigators. However, the volunteer is not
legally bound to remain in the trial, and may leave at any time without
penalty. It is hoped that volunteers will remain in the trial so that
study results are not skewed by "drop-outs."
What are the major risks and benefits of
being in a clinical trial?
Major risks include side effects of the
investigational treatment, and the possibility that the treatment will not
be effective. The volunteer may be randomized to receive placebo or
standard treatment rather than the investigational treatment—a risk to
which the volunteer agrees in informed
consent.
Major benefits include having access to a
new treatment while it is still under study, being under the care of some
of the nation’s top physicians, and contributing to medical knowledge.
Is the volunteer liable for any of the
costs associated with a clinical trial?
Health insurance may not pay for some or
all of the costs of treatment received in a clinical trial. Some insurance
plans regard clinical trials as "investigational" treatment
which they will not cover in cost. Trials underwritten by a pharmaceutical
firm pay some, but not all costs of treatment; the volunteer may be liable
for costs of some tests, etc. Before entering a clinical trial, a
prospective volunteer should gather all information regarding what costs
will be covered by the study sponsor, what costs will be covered by health
insurance, and what costs may have to be covered by the volunteer.
How does one find clinical trials?
The easiest ways you can find clinical
trials conducted by authoritative sponsors are:
- Talk with your physicians about clinical
trials—whether clinical trials are a treatment option you should
consider, and which one(s) would be best for you
- Contact large medical centers and
pharmaceutical firms regarding any trials they may be conducting or
planning, in the area of your interest
- Search the Internet and World Wide Web
for web sites of medical centers, pharmaceutical firms, the Food and
Drug Administration (FDA), and government-sponsored research centers
such as the National Institutes of Health (NIH). Information on clinical
trials sponsored or approved by the NIH and FDA is available at: www.clinicaltrials.gov/
References
Agency for Health Care Policy and Research:
Methodology Perspectives. AHCPR Pub. No. 95-0009.
National Academy of Science. Institute of
Medicine. Guidelines for Clinical Practice. 1992.
Guyatt GH, Sinclair J, Cook D et al. Users’
guide to the medical literature: XVI. How to use to treatment
recommendation. JAMA 1999; 281:1836-1843.
Guyatt GH, Sackett DL, Sinclair J et al.
Users’ guide to the medical literature: IX. A method for grading health
care recommendations. JAMA 1995; 274:1800-1804.
www.FDA.GOV
(Website for the Food and Drug
Administration)
www.NLM.NIH.GOV
(Website for the National
Institutes of Health and National Library of Medicine—MedLine)
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