Designing and Managing Designing and Managing Drug and Substance Abuse Drug and Substance Abuse

Clinical TrialsClinical Trials

Chapter I: Chapter I:What Is a Clinical Trial?What Is a Clinical Trial?

(version 6)

• Recognize when research projects are considered clinical trials under US laws and regulations

• Use appropriate research terminology to describe a clinical trial

Learning ObjectivesLearning Objectives

The First Recorded Clinical TrialThe 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. Group one - A quart of cider daily2. Group two – Twenty-five drops of elixir of vitriol (sulfuric acid)3. Group three - Six spoonfuls of vinegar4. Group four - Half a pint of seawater5. Group five - Two oranges and one lemon6. 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 The US Government’s Definition of a Clinical TrialDefinition of a Clinical Trial

US Government’s DefinitionUS 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 ComponentsClinical 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 US Government’s Definition of a Clinical TrialClinical 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 Drug Abuse Research Projects That Are NOT Clinical TrialsThat 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 Important Terms That Describe Clinical TrialsDescribe Clinical Trials

Four Major Features ofFour Major Features ofClinical TrialsClinical 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 Key Terms to Describe the Four Basic Features of a Clinical Trial Basic Features of a Clinical Trial

FEATURE TERMS USED

Study Stage

Phase IPhase IIPhase IIIPhase IV

Controls Uncontrolled

PlaceboActive Control(s)

RandomizationNon-randomized

Randomized

Blinding

UnblindedSingle-blindDouble-blindTriple-blind

Study Stage: The Four Study Stage: The Four Phases of Clinical TrialsPhases of Clinical Trials

The Four Phases of The Four Phases of Clinical TrialsClinical 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 TrialsControls in Clinical Trials

Controls In Clinical TrialsControls 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 ControlsPlacebo Controls(“Placebo Effect”)(“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 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 Randomization in Clinical TrialsTrials

What Is Randomization?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?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 SchemesCommon Randomization Schemes

• Complete randomization

• Block randomization

• Urn randomization

• Stratified randomization

• Cluster randomization

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Blinding in Clinical TrialsBlinding in Clinical Trials

What Is Blinding?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 BlindingPurpose 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

SummarySummary• 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

CreditsCreditsSubject Matter Expert

John M. Harris Jr., MDPresidentMedical Directions, Inc. Tucson, Arizona

E-Learning and Educational Technology ExpertJorge G. Ruiz, MD, FACPAssociate Professor of Clinical Medicine Director, Geriatric Medicine Fellowship Program Division of Gerontology and Geriatric Medicine University of Miami Miller School of MedicineVAHCS GRECC Associate Director for Education/EvaluationMiami, FL

Content DevelopersJohn M. Harris Jr., MDJorge G. Ruiz, MD, FACP

Medical Editor/Content EditorJorge G. Ruiz, MD, FACP

Reviewers/ConsultantsJorge G. Ruiz, MD, FACPBernard A. Roos, MDMarilyn C. CheungRudy W. Picardo

Technical Development (Stein Gerontological Institute)

Network AdministratorDavid Freeman

CreditsCreditsInstructional Designer

Rudy W. Picardo

Module NarratorRudy W. Picardo

OwnershipGeriU – The Online Geriatrics University (www.geriu.org)National Institute on Drug Abuse

Copyright 2008

Date of Release April 2008

Expiration Date April 2010

Contact InformationJohn M. Harris Jr., MDMedical Directions, Inc. 6101 E. Grant RoadTucson, Arizona 85712E-mail: sharris@md-inc.com

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

CreditsCreditsEstimated Time to Complete This

Activity1 hour

Key Words: clinical trials

Citation: “Designing and Managing Drug and Substance Abuse Clinical Trials, Chapter I: What Is a Clinical Trial?.” E-Learning Program. GeriU, the Online Geriatrics University. Stein Gerontological Institute, 2008.

Funding Provided byNational Institute on Drug Abuse

Acknowledgments/Special Thanks Stein Gerontological Institute5200 NE 2nd AvenueMiami, FL 33137GeriU – The Online Geriatrics University (www.geriu.org)University of Miami Miller School of Medicine