1. Clinical Trials Mrs. Stewart Medical Interventions Central Magnet School

2. Essential Question:
How are clinical trials set up to ensure all data collected is valid and that all human subjects are treated ethically?

3. THINK – PAIR – SHARE What is a clinical trial?
Clinical Trials 101: How do we develop and test a new vaccine

4. 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

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

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

7. 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

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

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

10. Direct to Consumer Drug Advertisements
The United States and New Zealand are the only two countries where direct-to-consumer (DTC) advertising of prescription drugs is legal.  
Every $1.00 spent advertising prescription drugs is estimated to increase their retail sales by $4.20. 
Example: Lyrica
Example: Cymbalta
Reference: American Medical Association, "AMA History Timeline,” (accessed Mar. 21, 2014)

11. 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.

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

13. 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.

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

15. 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

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

17. 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

18. 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

19. 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

20. 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

21. 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)

22. Institutional Review Boards
Established by gov’t May 30, 1974
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

23. Grey’s Anatomy Study: New alzheimers drug – phase I Adele
Friend of the doctor’s conducting the study
Wife of the chief of surgery
Has alzheimers
Alzheimer’s Drug Clinical Trial - Adele’s results
Alzheimer’s Drug Clinical Trial – Meredith

24. You Are the IRB: Was this trial ethical?
conducting high-altitude experiments on prisoners, 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.
determine how different "races" withstood various contagious diseases by infecting them against their will.
(Prisoners in Nazi concentration camps during WWII were experimented on.)

25. Examples of unethical experiments in the U.S.
1932
400 African-American men from the Tuskegee Institute left untreated from syphillis despite cure available so that scientists could study the “natural course of the disease”
( ml)

26. How does the US IRB prevent future experiments from violating ethics?
THINK – PAIR – SHARE
How does the US IRB prevent future experiments from violating ethics?

27. Essential Question: Exit Ticket
How are clinical trials set up to ensure all data collected is valid and that all human subjects are treated ethically?

28. Assignment: lab groups
Develop a new drug
Determine what disease/disorder this drug will treat
Describe how it will work specifically
Design the clinical trial to test it for safety and efficacy
(must be approved by an IRB (Mrs. Stewart)
Due Monday at end of class