Different Types of Clinical Research
There are many different kinds and levels of clinical research. As a Research Subject, it is important to understand the type of research study that you are involved in. Some studies are designed by an expert in a particular field to help answer questions about human physiology and disease. The study may include individuals with or without the disease. Some studies are very short, requiring only a single visit to obtain a blood sample or do a procedure. Other studies last for many years and some require frequent visits.
For all studies, it is important to understand that the relationship you now have with your regular doctor is not expected to change because of your decision to participate in a research study.
The development of a new treatment generally progresses through several steps that have become known as phases. There are three major phases (I, II, III) in the development of a new drug or procedure. Volunteer Research Subjects participate in all three of these phases. As an example, we will describe the research testing of a new drug through these phases.
One of the first things we want to know about a new drug is how well humans tolerate it. Phase I trials focus on the safety of a new drug or device. The trial may involve various doses and/or methods of administration to study the symptoms, side effects or laboratory changes that may occur.
Research Subjects should be aware of certain special features about Phase I trials.
- First, in order to increase the safety of these trials, it is required that a new drug has been studied extensively in laboratory animals. Therefore, in the informed consent process with the PI, the Research Subject will have an opportunity to find out the results of those animal experiments.
- Second, the Research Subject must have no expectation of personal benefit because the value of the new drug is unknown at that time.
- Third, the Research Subject must be aware that the risks of unexpected complications will be higher in this phase of research than in the next two phases.
Assuming the Phase I trial of this new drug has shown it to be well tolerated, without serious side effects, the next question to answer is "Does it work?" For example, a sponsor has a new drug it thinks will treat headaches better than available medications. A Phase I trial showed it was well tolerated with few side effects. In the Phase II trial, it will be given to persons with headaches, in various doses, to see if the drug helps relieve headaches. If the persons do experience relief, it may be worth studying further. If they report no relief, it probably isn't worth further study.
Importantly, Phase I and Phase II trials include small groups of Research Subjects. Once a drug or device is determined to have a desirable effect on a specific disease or symptom, a larger study is still necessary to confirm both the safety and effectiveness of the treatment.
Again, assuming that both the Phase I and Phase II trials were successful, we now turn to the questions "How well does this drug work?" and "How good is it when compared with the drugs we already have?" Now the number of Research Subjects must become very large. In order to have enough subjects, these trials often are carried out by many PIs in different institutions throughout the country. The results of the Phase III trial will determine whether or not the new drug or device will get Federal Food and Drug Administration (FDA) approval. FDA approval is required before it can be used in medical practice and sold in pharmacies and/or used in hospitals.
Phase III trials also have special requirements that the Research Subject must understand. These rules include techniques to avoid the effects of bias in the collection of information. The scientific use of the word bias refers to anything that could falsely affect the results of the study. Avoiding bias in a Phase III study obviously is of critical importance. Therefore, it is common that these studies are blinded so that no one, including the PI, knows what drug(s) or treatment(s) any Research Subject is getting.
Another comparison technique that prevents bias is to give some of the Research Subjects as placebo as a control. A placebo is a pill that looks like all the others but has nothing effective in it. It is often referred to as a "sugar pill". Sometimes the control is not a placebo but is the currently accepted treatment for the disease. In contrast to the other Phases, the Research Subjects in Phase III trials will receive information on all the drugs to be used, including the placebo, but will not know which one they are taking!
Phase IV Trials (After Approval and Sale)
Following approval and sale of new drugs on the market, the FDA continues to gather data on these medications. Sometimes complications that did not show up when hundreds of people used a new drug in the clinical trials will appear when thousands of people use them. If serious complications do appear, the FDA or the manufacturer may decide to withdraw the drug from the market, even after all that careful study.
