Transcript What is a Clinical Trial

Designing and Managing
Drug and Substance Abuse
Clinical Trials
Chapter I:
What Is a Clinical Trial?
(version 6)
Learning Objectives
• Recognize when research projects are
considered clinical trials under US laws
and regulations
• Use appropriate research terminology to
describe a clinical trial
The First Recorded Clinical Trial
• In 1747 an English physician, James Lind thought that acidic foods
might cure scurvy. He assigned 12 sailors with scurvy into one of six
groups. All men then received the same daily diet plus:
1.
2.
3.
4.
5.
6.
Group one - A quart of cider daily
Group two – Twenty-five drops of elixir of vitriol (sulfuric acid)
Group three - Six spoonfuls of vinegar
Group four - Half a pint of seawater
Group five - Two oranges and one lemon
Group six - A spicy paste plus a drink of barley water
• At the end of 6 days, one sailor from group five was fit for duty and
the second had almost recovered. Other than these two men, only
the sailors from group one showed some effect of their treatment
The US Government’s
Definition of a Clinical Trial
US Government’s Definition
•
Clarifies the difference between clinical
trials and other types of human research,
such as program evaluations
•
If a research project is funded or
regulated by the US government:
– Legal requirements
– Regulatory requirements
Clinical Trial Components
•
•
•
It is a prospective study
It is in humans
It is designed to answer questions about
a biomedical intervention or a behavioral
intervention
US Government’s Definition of a
Clinical Trial
A clinical trial is a prospective biomedical
or behavioral research study of human
subjects, that is designed to answer
specific questions about biomedical or
behavioral interventions
Drug Abuse Research Projects
That Are NOT Clinical Trials
• Primate testing of a new HIV therapy intended
for humans
• Ethnographic research to understand patterns of
IV drug users
• Program evaluation of a government initiative to
reduce cocaine use by unwed mothers
• An epidemiologic study of drug abuse patterns
among persons receiving naltrexone for alcohol
dependency
Important Terms That
Describe Clinical Trials
Four Major Features of
Clinical Trials
• The stage of the study intervention (study
phase)
• The trial is a controlled study
• The participants are randomized
• The participants are unaware of (or
“blinded” to) treatments and results
Key Terms to Describe the Four
Basic Features of a Clinical Trial
FEATURE
TERMS USED
Study Stage
Phase I
Phase II
Phase III
Phase IV
Controls
Uncontrolled
Placebo
Active Control(s)
Randomization
Non-randomized
Randomized
Blinding
Unblinded
Single-blind
Double-blind
Triple-blind
Study Stage: The Four
Phases of Clinical Trials
The Four Phases of
Clinical Trials
• Phase I – The intervention is new and is being tested in
a small group of people for safety
• Phase II – The intervention looks promising and is being
evaluated in a larger group of people for safety and
efficacy
• Phase III – The intervention appears safe and effective
and is being evaluated in a real-world study
• Phase IV – The intervention is now in use and is being
monitored for safety
Controls in Clinical Trials
Controls In Clinical Trials
• Whenever an intervention is compared to
something else, the alternative is called a
“control”
• Compared to…
– What has been done in the past
– No treatment?
– Current treatment(s) (standard treatment)
– A similar-looking but ineffective treatment
(placebo)?
Placebo Controls
(“Placebo Effect”)
• Why? Recognizes that many health outcomes are
dependent on the patient’s willingness to participate and
the patient’s and physician’s perception of benefit
Placebo controls can
• Duplicate the experience of the intervention without
active component
• Provide clear improvement in symptoms
(“placebo effect”)
• More accurately determine the extent to which the
intervention alone affects treatment
Active Controls
• Contains an active component
• Frequently used in Phase III trials
– Intent is to understand the benefits of a new
treatment in a real-world setting
Randomization in Clinical
Trials
What Is Randomization?
• The assigning of persons to the control
group or the intervention groups based on
chance
• Essential feature of a good clinical trial
• Randomization must be totally unrelated to
the variables of interest
Why Is Randomization Necessary?
• How does the researcher decide who gets which
treatment?
• Possibilities
– every person will get the new treatment (historical
controls?)
– some persons may be willing to accept the new
treatment while others are not
• Good possibility that control and intervention
group are not identical
– results will differ because of some factor totally
unrelated to the treatment
Common Randomization Schemes
• Complete randomization
• Block randomization
• Urn randomization
• Stratified randomization
• Cluster randomization
PROPERTIES
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Blinding in Clinical Trials
What Is Blinding?
• Techniques used to disguise
treatments, and sometimes outcomes
• Types of blinding
–Unblinded or Open Label
–Single blind
–Double blind
–Triple blind
Purpose Of Blinding
• Many clinical trials lack well-defined, objective
endpoints
• Such measures are subject to:
– intentional manipulation
– unintentional bias
• To reduce the possibility of manipulation and
bias, researchers may seek to disguise whether
the subjects are receiving the intervention or the
control treatment
Summary
• A clinical trial is a prospective biomedical or behavioral
research study of human subjects that is designed to
answers specific questions about biomedical or behavioral
interventions.
• There are important features and terms that help describe
clinical trials
• The four phases of clinical trials help define the intent of the
research project than its scientific details
• Controls, randomization, and blinding are tools used in in
clinical trials to reduce data manipulation and bias
Credits
Subject Matter Expert
John M. Harris Jr., MD
President
Medical Directions, Inc.
Tucson, Arizona
E-Learning and Educational
Technology Expert
Jorge G. Ruiz, MD, FACP
Associate Professor of Clinical
Medicine
Director, Geriatric Medicine Fellowship
Program
Division of Gerontology and Geriatric
Medicine
University of Miami Miller School of
Medicine
VAHCS GRECC Associate Director for
Education/Evaluation
Miami, FL
Content Developers
John M. Harris Jr., MD
Jorge G. Ruiz, MD, FACP
Medical Editor/Content Editor
Jorge G. Ruiz, MD, FACP
Reviewers/Consultants
Jorge G. Ruiz, MD, FACP
Bernard A. Roos, MD
Marilyn C. Cheung
Rudy W. Picardo
Technical Development (Stein
Gerontological Institute)
Network Administrator
David Freeman
Credits
Instructional Designer
Rudy W. Picardo
Module Narrator
Rudy W. Picardo
Ownership
GeriU – The Online Geriatrics
University (www.geriu.org)
National Institute on Drug Abuse
Copyright 2008
Date of Release April 2008
Expiration Date April 2010
Contact Information
John M. Harris Jr., MD
Medical Directions, Inc.
6101 E. Grant Road
Tucson, Arizona 85712
E-mail: [email protected]
Jorge G. Ruiz, MD, FACP
VA Medical Center
GRECC (11 GRC)
1201 NW 16th Street
Miami, FL 33125
Telephone: 305-575-7000, ext. 6104
Fax: 305-575-3365
Credits
Estimated Time to Complete This
Activity
1 hour
Key Words: clinical trials
Citation: “Designing and Managing Drug
and Substance Abuse Clinical Trials,
Chapter I: What Is a Clinical Trial?.” ELearning Program. GeriU, the Online
Geriatrics University. Stein
Gerontological Institute, 2008.
Funding Provided by
National Institute on Drug Abuse
Acknowledgments/Special Thanks
Stein Gerontological Institute
5200 NE 2nd Avenue
Miami, FL 33137
GeriU – The Online Geriatrics
University (www.geriu.org)
University of Miami Miller School of
Medicine