Download Clinical Trials

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
Clinical Trial Phases
 Phase I trials
 Phase II trials
 Phase III trials
 Phase IV trials
Phase I Trial
 Test small group of people (fewer than 100 people)
 Evaluate safety of drug
 Determine safe dosage range
 Identify side effects
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
Phase III Trial
 Test large groups of people (1,000-3,000 participants)
 Determine effectiveness
 Determine side effects
Phase IV Trial
 Collect additional information after the drug enters
the market, such as:
 Drug’s risks
 Drug’s benefits
 Optimal use
Types of Clinical Trials
 Randomized, double-blind trials
 Open trials
 Factorial trials
 Crossover trials
 Orphan drug trials
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.
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
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
Single-Blind
 Subjects do not know which group they are assigned
to.
 Researchers know who is assigned to which group.
 Prone to researcher bias.
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
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
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
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
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)
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
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.
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
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.