1. A Real World Application of the Scientific Method
Clinical Trials
Information from this presentation comes from:
A Real World Application of the
Scientific Method
Copyright PEER.tamu.edu

2. How do you know if the medicines you take are safe?
Did you know that all medical drugs, treatments, preventions and even medical devices have to go through a thorough process before they are available to you?
This process is call a Clinical Trial.
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3. What are Clinical Trials?
Clinical Trials are medical or health-related research studies done in human beings (or in animals if the study is a veterinary study).
Point out the symbols for Human Medicine and Veterinary Medicine.

4. Why are Clinical Trials Important?
In Clinical Trials, researchers take the results from basic scientific research and translate them into ways to prevent, treat, or diagnose disease.
Without them, we would could not ensure safe, effective treatments for diseases.

5. The Scientific Method
Clinical Trials are “real world” applications of the Scientific Method.
Each time a drug, medical device or procedure, is tested, a question is asked, a hypothesis is made, an experiment is conducted, results are analyzed, and a conclusion is reached.

6. Think Break: What are Clinical Trials?
Why are Clinical Trials important?
How are Clinical Trials like the Scientific Method?

7. Types of Clinical Trials: (as defined by the National Institutes of Health)
Treatment Trials - test new treatments, new combination of drugs or new approaches to surgery or radiation.
Prevention Trials - look for better ways to prevent diseases.

8. Types of Clinical Trials:
Diagnostic Trials - determine better tests or procedures for diagnosing a particular disease or condition.
Screening Trials - test the best way to detect or treat diseases.
Quality of Life Trials - explore and measure ways to improve the comfort and quality of life of people with a chronic illness.

9. Sponsors Clinical trials are usually sponsored or funded by
companies that make pharmaceuticals or medical devices.
Trials can occur at sites as varied as hospitals, universities, doctors’ offices, community clinics, or in the offices of clinical-trial contractors.
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10. Clinical Trials are Done in Phases:
First, a Pre-Clinical Trial must be done before the Clinical Trial starts.
Preclinical trial – research on a new drug or a new medical device or procedure, usually done on animals, to learn about mechanisms of action, determine how well the treatment works, and see if it is safe to test on humans.
See Powerpoint in this module on Pre-Clinical Trials for more information.

11. Think about it: Who sponsors Clinical Trials?
Why is it important to test drugs, treatments and devices on animal cells or subjects before testing them on humans?

12. Clinical Trials are Done in Phases:
Phase I
Researchers test an experimental drug or treatment in a small group of people (approximately 20-80) for the first time. The purpose is to evaluate its safety and identify side effects. If this is a veterinary study, it is conducted in animals.

13. Where do the people come from?
Clinical Trials require people to volunteer to be tested! They are often paid.
Would you volunteer to be a subject in a Clinical Trial?
What if it meant you received a treatment for a disease that wasn’t available to anyone else?
The biggest barrier to completing studies is the shortage of people who take part. All drug and many device trials target a subset of the population, meaning not everyone can participate. Some drug trials require patients to have unusual combinations of disease characteristics. It is a challenge to find the appropriate patients and obtain their consent, especially when they may receive no direct benefit (i.e. they are not paid, the study drug is not yet proven to work, or the patient may receive a placebo). In the case of cancer patients, fewer than 5% of adults with cancer will participate in drug trials. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), about 400 cancer medicines were being tested in clinical trials in Not all of these will prove to be useful, but those that are may be delayed in getting approved because the number of participants is so low.

14. Phases of Clinical Trials:
Phase II
The experimental drug or treatment is administered to a larger group of people/animals (approximately ) to determine its effectiveness and to further evaluate its safety.

15. Phases of Clinical Trials:
Phase III
The experimental drug or treatment is administered to a large group of people/animals (300-3,000 or more) to confirm its effectiveness, monitor side effects, and compare it with standard or equivalent treatments.

16. Research Concepts
In many studies, the new drug is compared to a placebo. A placebo is a product that looks like the new drug, but it does not have the active ingredient in it. People do not know that they are getting the placebo.
Sometimes the test compares the new treatment against an existing treatment to see if better results can be obtained.

17. Research Concepts Blind and Double Blind Trials are frequently done.
A Blind Trial is a trial in which the patients do not know if they are receiving the treatment or a placebo.
A Double Blind Trial is a trial in which the patients and the researchers do not know who is receiving the treatment.
Why would the above be good ideas?
Having a blind or double blind trial helps prevent any bias the patients and researchers might have. For example, patients think they feel better just because they are getting a medicine! Physicians might want the drug to work, so they might be biased when it comes to looking at results.

18. Research Concepts
Randomization is the process by which patients are assigned a group for the Clinical Trial.
Groups are assigned randomly, not purposefully.
Some people will receive the new treatment, some may receive an already approved treatment, and some may receive a placebo.
If one treatment is found superior, the trial is stopped so that the fewest patients possible receive the less beneficial treatment.
True randomness is not always a good idea. For example, you might want each treatment group to have an equal number of people with certain characteristics, such as half male, half female in each group, or equal numbers in each category of physical characteristics. With proper statistical significance, the results could show that the new treatment works only on certain people (age group, sex, etc.)

19. Approval must be gained:
Once a drug has proven satisfactory after Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life.
This collection of information makes up the "regulatory submission" that is provided for review to the appropriate regulatory authorities like the U.S. Food And Drug Administration (FDA) so they can then grant the sponsor approval to market the drug, device or treatment.
An example on how the whole process works is available at
This details how a treatment for osteoporosis was taken from an idea to a new approved drug.

20. The Results!
For approximately every 5,000 to 10,000 compounds that enter preclinical testing, only one is approved for marketing.
Cost of the failures has to be borne by the price of the one success.
From article in the Journal of the American Board of Family Practitioners vol. 14 no. 5 that can be found at:

21. Phases of Clinical Trials:
Phase IV
After a drug is licensed (approved by the FDA) or treatment is launched, researchers track its safety, seeking more information about a drug or treatment’s risks, benefits, and optimal use. These long-term studies involve large groups of participants and are designed to reveal if any unexpected side effects occur in a small percentage of individuals.
2010
2011

22. Timeline Estimate
Below are some estimates on the amount of time it takes for this process in cancer treatment research.
Pre-clinical Trials years
Phases I-III years
FDA Approval years
Phase IV - Ongoing for the duration of the use of the drug
How long is this whole process?
Answer: years
And this is just an estimate- many trials take longer than this!

23. Costs
On average, pharmaceutical companies are spending anywhere between $100 and $800 million per each drug tested!
Spending on clinical trials in the U.S. is forecasted to rise to $32 billion by 2011.
Why would anyone spend that much money on drug development?
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Answers will vary:
The drug will cure people and save lives.
The drug companies can make more money from selling the drug than they did in developing the drug.

24. Think about it: Why does it cost so much to conduct a clinical trial?
Why does it take so much time to conduct a clinical trial?
Clinical Trials cost so much because of the numbers of people that are being tested, the numbers of physicians and veterinarians that must monitor the patients, the cost of all of the supplies needed in the trials, and the cost of the clinics or other facilities in which the trials are conducted.
Research takes time. In cancer trials, it may be years before the researchers know whether the treatment was effective. Physical processes take time. Data collection and analysis also take time.