All drugs and procedures accepted today by doctors had to once be proven as safe and effective in the clinic. The research in the clinic may take a decade to finish and cost hundreds of millions of dollars. The studies are so complicated that they often are done in 3 separate phases.

1. Phase I: Screening for Safety

   This first stage of a clinical study, looks at whether a drug is safe to give to humans. These studies are done with about 10 to 100 volunteers. The drug would have already been tested in animals and been found to be generally safe. However, humans respond to drugs differently than animals (even monkeys) and no animal can tell you if they are feeling dizzy, anxious or sick to their stomach. If the drug or procedure is expected to be nearly harmless, healthy people would be asked to volunteer. The first dose would be very low. The research team would then watch the volunteers very closely to spot problems early. They would watch their behavior, ask questions and measure physical signs like blood pressure and temperature. If all seems fine, the doctors would raise the amount of drug given to the levels they would like to use eventually to treat a condition. Again, the research team will monitor for any danger signs. If the volunteers are bothered by anything, they will be taken off the study. Phase I studies will also collect the volunteers' blood and urine. This is collected so that researchers can follow where the drug is in your body, where and how quickly it builds up, and how it is cleared. The final question a Phase I study tries to answer is, "What is a safe dose of this new drug to give people?"

   Cancer is a serious disease and the medications used to treat it are also quite serious. All chemotherapy involves strong drugs that have side effects too severe for healthy volunteers to take on as a risk. For chemotherapy research, Phase I studies are done in people with cancer. For those whose lives are threatened with cancer, the potential benefit outweighs the potential risks. However the same careful dosing and monitoring will be done to make sure that these people are not harmed more than they are helped.

2. Phase II: Establishing a Protocol

   A phase I study gives researchers an idea of how much of a new drug people can take before it does more harm than potential good. A phase II study builds on this information to ask how can an experiment be done to prove the drug is effective in preventing or treating cancer. Phase II studies are done with 50 to 500 volunteers who have cancer.

   Before you start any experiment you must first understand the question and how to ask it. The obvious question is "Will this drug cure cancer?" but to answer that you need to work out all of the little details that the study will need to define exactly what you mean. It would be a waste of everyone's time if a large study was done but no one could understand or use the results. These definitions can be enormously complicated. Below is an example of two definitions taken from a research study.

   Question	Rough Idea	Precise Idea
   Who will be cured?	People with cancer.	Patients with advanced or metastatic NSCLC who have failed prior ABC chemotherapy and express at least one member of the XYZ family of receptors.
   How will you know the drug worked?	The cancer got better.	The endpoints shall be 1 year survival rate, overall response and disease control rates, duration of response progression free survival and changes in patient reported outcomes.

   Treatments are compared by organizing the patients into groups with each group receiving a different treatment. Besides precision, definitions will be used to keep the groups of people as similar as possible. That way, the difference you see between the groups is due to the treatments and not due to something else. One way to do this is to sort people into the treatment groups by chance. Which group you go in will be figured out randomly like flipping a coin.

   A common way to look at a new treatment is to compare it with the treatment normally given. The usual treatment is sometimes called a "control" because it is the standard which all new treatments must exceed in order to be judged as better. Cancer patients will always be offered either the usual treatment now accepted by doctors or the new experimental treatment. If a treatment proved ineffective or too toxic, a cancer patient would not be forced to continue. All patients will be carefully watched for any changes.

   When a Phase II study is done, you will have discovered all of the definitions and directions you will need to do the final study to find out if your drug or procedure is useful in the clinic. These set of rules are called a "protocol". The protocol will define and control who can or can't join the trial, how the treatments and exams will be scheduled, how long to wait for results and how to collect and interpret the information. Since all the researchers have the same directions to follow, the results from each hospital can be put together.

3. Phase III: The Final Test

   In this final stage of a clinical study, researchers hope to learn whether the treatment is effective and what the important side-effects are. A Phase III study is done with 300 to 30,000 or more patients with cancer. A Phase III study will duplicate the clinical conditions that the drug or procedure will be used in every day as part of routine care. If, after careful analysis, the new treatment proves to be better than the control treatment, the researchers would send their report to the U.S. Food and Drug Administration. The FDA may accept the results and approve the treatment or remain unconvinced and reject the new treatment. They may also delay their approval until more testing is done.