1. Designing and Managing Drug and Substance Abuse Clinical Trials Chapter 1: What Is a Clinical Trial? (Beta Version)

2. Recognize when research projects are considered clinical trials under US laws and regulations Use appropriate research terminology to describe a clinical trial Learning Objectives

3. 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.Group one - A quart of cider daily 2.Group two – Twenty-five drops of elixir of vitriol (sulfuric acid) 3.Group three - Six spoonfuls of vinegar 4.Group four - Half a pint of seawater 5.Group five - Two oranges and one lemon 6.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

4. The US Government’s Definition of a Clinical Trial

5. US Government’s Definition Clarifies the difference between clinical trials and other types of human research Clinical trials funded or regulated by the US government must meet specific: –Legal requirements –Regulatory requirements

6. Clinical Trial Components Key Components of a Clinical Trial –It is a prospective study –It is in humans –It is designed to answer questions about a biomedical intervention or a behavioral intervention

7. 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

8. 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

9. Important Terms That Describe Clinical Trials

10. Stage (phase) of the study intervention Controls Randomization Blinding Four Major Features of Clinical Trials

11. Key terms to describe the four basic features of a clinical trial FEATURETERMS 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

12. Study Stage: The Four Phases of Clinical Trials

13. 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

14. Controls in Clinical Trials

15. Controls In Clinical Trials An intervention is compared to something else, a “control” Compared to… –What has been done in the past –No treatment –Current treatment (standard treatment) –Similar-looking but ineffective treatment (placebo)

16. Historical Controls All that is necessary when the intervention has a dramatic effect

17. No Treatment Common in evaluating surgical procedures

18. Placebo Duplicate the experience of the intervention without the active component Can provide clear improvement in symptoms (“placebo effect”) Determine the extent to which intervention alone affects treatment

19. Current Treatment Contains an active component Frequently used in Phase III trials –Understand the benefits of a new treatment in a real-world setting

20. Randomization in Clinical Trials

21. What Is Randomization? Assigning of persons to the control group or the intervention group based on chance An essential feature of a good clinical trial Must be unrelated to the variables of interest

22. Why Is Randomization Necessary? Results can differ because of some factor unrelated to the treatment Bias Confounding

23. Common Randomization Schemes Complete randomization Block randomization Urn randomization Stratified randomization Cluster randomization

29. Blinding in Clinical Trials

30. Purpose of Blinding Many clinical trials lack well-defined, objective endpoints Measures are subject to: –Intentional manipulation –Unintentional bias Disguise whether subjects are receiving intervention or the control treatment

31. Types of Blinding Unblinded or Open Label Single blind Double blind Triple blind

32. 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

33. Summary FEATURETERMS 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

34. Credits Content Developer/Author John M. Harris Jr., MD, MBA Medical Directions, Inc. Content Editor/Spanish Translation Jorge G. Ruiz, MD, FACP University of Miami Miller School of Medicine Instructional Designer Rudy W. Picardo Stein Gerontological Institute