There are three stages in clinical trials. Stage one is a basic trial to see if a particular drug or other form of therapy works. For example, if interleukin has been successful with some diseases and forms of cancer, and lab results indicates positive results, a clinical trial would be used to see if it works by reducing the size of tumors, improving survival, or displaying other helpful results. Thus individuals entering the study would be prescribed interleukin, measurements would be made, and the study authors would attempt to ascertain whether the drug positively impacted patients. The stages are progressive, stage one, being a basic test to see if a drug has some effect, if it does appear to work, stage two is designed to refine the dose and assess side-effects, and finally, stage three, measuring the drug against conventional treatments being used. Once a drug shows positive results in stage 3 it is generally ready to be marketed.

10.21 Stage One

Here is how the American Cancer Society describes stage one:

"During a phase I trial-the initial investigation of a treatment’s safety and effectiveness in humans- a promising new therapy is tested to learn if it is worthy of further investigation. In the case of a new drug, this is when researchers learn about its effects by gradually increasing the dosage in a step-wise fashion and carefully analyzing the response among the participants.

These are preliminary trials in which the researchers learn, for example, how well the drug is absorbed by the body, how much of it reaches the blood stream, and how it is metabolized and eliminated from the body." American Cancer Society, Informed Decisions 230 (1997)

As a basic test, results in stage 1 are not given tremendous credence since so much more needs to be done. The average cancer patient should question why it would be in his or her interest to enter a stage 1 clinical trial. The treatment might not turn out to be useful. The patient must recognize that the researcher and patient can have varying interests. The patient’s goal is to get well, the researcher’s task is to assess the validity of a particular treatment. Sometimes these are the same, and sometimes not. For example, given the tremendous risks associated with a new drug or form of treatment, perhaps only seriously ill patients would want to participant in a stage 1 trial. However, the researcher will not want people extremely ill since that may play a role in generating poor results, and many clinical trials restrict who can participate and exclude patients with certain health problems.

10.22 Stage Two

Stage two clinical trials refine treatments shown to have some promise in stage 1. The American Cancer Society describes stage two trials this way, " Once researchers confirm the possible value of a drug (or other treatment) and determine the safe dosage and other specifics of administering it, they focus on how effective it is one people with (a particular form of) cancer.... to gather information about how well people are responding, researchers may measure the size of tumors for shrinkage.... The study may also involve monitoring the patient’s blood for substances called tumor markers that often indicate whether their cancers are growing or shrinking." American Cancer Society, Informed Decisions 230 (1997)

In our interleukin example, if the treatment had initial positive results, the researchers might vary the doses to see which amount was more effective, but did not cause harmful side effects. Thus, a stage 2 trial could compare twice a day interleukin with once a day interleukin. Note that there are risks for both sets of patients. If the interleukin turned out to create harmful side effects, the group receiving twice a day treatments might become more ill. Alternatively, the group receiving less might not get the benefit of the drug. Note that a participant in a clinical trial does not select his group, and that is done by the research protocol, frequently on a random basis. Where there is effective available conventional treatment, it makes sense for the patient to get it, rather than be randomly assigned a form of treatment which may or not be effective. That is why participants in clinical trials are generally limited to those for whom conventional treatment has not been proven effective. Thus, stage 3B and stage 4 lung cancer patients are eligible for clinical trials, because conventional treatment is not usually curative.

10.23 Stage Three

Assume that the interleukin proved effective in stage 1, was modified for dose and side effects in stage 2, and is now ready for stage 3 comparison testing. The interleukin will be compared with conventional methods of treatment. If the interleukin is to be used with chemotherapy, then our stage 3 trial will compare interleukin with chemotherapy in stage 3b patients, versus chemotherapy alone.

To accurately assess a form of treatment, the participants must be restricted to those with a particular form of disease at a particular stage. Thus non-small cell and small cell trials would almost always be done separately, and usually trials would be restricted to stage. Thus our hypothetical trial could be called, Assessment of the Effect of Interleukin with Chemotherapy versus Chemotherapy Alone in Stage 3 B non-small cell lung cancer patients. Since the study authors, (sometimes with a pharmaceutical company’s assistance) are interested in demonstrating a positive result, they will frequently restrict participation to those in otherwise good health. Thus, a clinical protocol, the summary of how and what will be done, may restrict the trial, and prohibit those with other health problems from participating.

If the stage 3 trial shows a positive result, then other trials might be conducted to further refine the dose and assess side effects. Sometimes clinical trials will display inconsistent or contradictory results, which is why a series of trial is more reliable than one. For example, a dramatic average increase in survival in a 20 person clinical trial might be due to one patient doing very well for reasons which could be unrelated to the particular drug tested. A meta-analysis is combining the results of many tests to reach particular conclusions.

American Cancer Society, Informed Decisions 230 (1997).

Control group refers to the people in a clinical trial receiving the standard treatment, and not the experimental treatment. Randomization means the participants are randomly assigned to either an experimental or a control group. In a double-blind study, neither the physicians nor the participant’s know which treatments are administered to whom until the study is completed. This is done to prevent some types of conscious or unconscious bias.

Here are some of the advantages and disadvantages of clinical trials:

ADVANTAGES

Treatment can sometimes occur in a distant medical center, rather than a local hospital,

For advanced stage patients, clinical trials are clearly an option, but must be discussed with the treating oncologist.