2. Purpose of Clinical Trials Assess safety and efficacy of Experimental treatments New combinations of drugs New approaches to surgery or radiation therapies Better disease prevention approaches Better diagnostic approaches

3. Clinical Trial Phases Phase I trials Phase II trials Phase III trials Phase IV trials

4. Phase I Trial Test small group of people (fewer than 100 people) Evaluate safety of drug Determine safe dosage range Identify side effects

5. Phase II Trial Test larger group of people (up to 200 participants) Learn more about safety and side effects Sharpen estimates of proper dosage Determine effectiveness

6. Phase III Trial Test large groups of people (1,000-3,000 participants) Determine effectiveness Determine side effects

7. Phase IV Trial Collect additional information after the drug enters the market, such as: Drug’s risks Drug’s benefits Optimal use

8. Types of Clinical Trials Randomized, double-blind trials Open trials Factorial trials Crossover trials Orphan drug trials

9. Controlled, Randomized, Double-Blind Trials Controlled: One group receives the treatment and another group does not. Randomized: control group and treatment group are chosen at random. Double-blind: Neither subjects nor scientists know who is assigned to which group until after the data are collected.

10. Treatment Group vs. Control Group Treatment Group: Given experimental drug Control Group: Given standard treatment or a placebo Placebo: an inactive pill, liquid, or powder that has no treatment value

11. Why Double-Blind? Prevents subjects in different groups from behaving in different ways Prevents scientists from introducing any unconscious bias into the data collection process

12. Single-Blind Subjects do not know which group they are assigned to. Researchers know who is assigned to which group. Prone to researcher bias.

13. Open Trials Set-up where researchers and subjects know what treatment is being given Often used to test surgical procedures and medical devices, that by nature, cannot be done without subject or researcher knowing who is receiving the treatment More prone to error and bias than double-blind studies

14. Factorial Trials Used to test medicines in combination Set-up in the following manner: First group tests therapy A Second group tests therapy B Third group tests therapy A and therapy B combined Fourth group, the control group, tests neither therapy A nor therapy B Difficult to interpret results

15. Crossover Trials Used to test two treatments Set-up where each participant gets both treatments being tested Some participants are assigned at random to receive drug A and when done, receive drug B Other participants receive drug B and when done, receive drug A

16. Orphan Drug Trials Used to test drugs designed to treat rare diseases (affecting fewer than 200,000 Americans) Tested on small number of participants who are very sick If drug works, improved health is usually readily apparent

17. Safety and Ethical Regulations Clinical trials are designed to safeguard the health of the participants. Clinical trials done in the United States must be approved and monitored by an Institutional Review Board (abbreviated IRB)

18. Institutional Review Boards IRBs are independent committees comprised of physicians, statisticians, community advocates, and others. The role of the IRB is to do the following: Ascertain that clinical trials are scientifically worthy and that ethical guidelines are met Potential benefits for participants should outweigh risks Participants must be informed of all potential risks and agree to willingly participate and can drop-out at any time (called informed consent) Monitor the trial during its run and may even halt the trial if serious problems are reported

19. Examples of Unethical Clinical Trials: Prisoners in Nazi concentration camps during WWII were experimented on. conducted high-altitude experiments, using a low-pressure chamber, to determine the maximum altitude from which crews of damaged aircraft could parachute to safety freezing experiments using prisoners to find an effective treatment for hypothermia scientists tested immunization compounds and sera for the prevention and treatment of contagious diseases, including malaria, typhus, tuberculosis, typhoid fever, yellow fever, and infectious hepatitis. sterilization experiments determine how different "races" withstood various contagious diseases.

20. Examples in the U.S. Tuskegee airmen – 400 African-American men left untreated from syphillis despite cure available so that scientists could study the “natural course of the disease” http://oreilly.com/medical/trials/news/ethics_of.html

21. What Happens After Clinical Trial When the trial ends, the drug company submits all data to the Food and Drug Administration (FDA) for approval to market the drug. If FDA agrees that the drug is safe and effective, it grants approval and the drug is moved into everyday medical practice. Once on the market, the FDA continues to survey the side effects experienced by patients within the general population.