Diagnostic Procedures—The Importance of Research and Clinical Trials
Have you ever gone to the doctor and had laboratory tests ordered for a routine check-up or perhaps because you were having a medical problem? How did she know those tests might show what was wrong with you? Why did she order those specific tests?
Some diagnostic tests (a test used to identify a disease or condition from its signs and symptoms) that lead to a diagnosis are very straight-forward. If the doctor wants to find out if you broke a bone in your arm, she will order an x-ray. The x-ray will usually show whether or not the bone is broken. If your doctor thinks you have strep throat, she will order that your throat be swabbed and the bacteria grown for identification. Other tests will identify which antibiotic is effective against your type of strep, if you have it.
Other medical conditions are not so easily diagnosed. Think about it for a minute. We know what tests show up as abnormal for certain conditions. For example, we know that an elevated white blood cell count (wbc) can indicate an infection. But, how do we know that? How did we find that out?
Medical researchers perform staggering amounts of studies in order to learn the etiology (the study of the causes and origins of diseases) of a disease or condition. It takes years to study the diseases effectively and many diseases are still not “cured”. After thoroughly studying the disease or condition, how do we know which of the many biological tests will be a good indicator of the disease in most people?
This difficult process involves taking the “pure” research and putting it into a more clinical (or patient-related) environment. It means that the research will be taken out of the theoretical environment and be put into an environment that is more clinical in nature, as scientists attempt to create and study tests which will help them diagnose the condition more efficiently and in less time.
Once a test is created, how do they know it works? How do they know if it is truly effective in diagnosing a disease or condition over time? Once again, this involves studying the tests through clinical trials. Researchers use clinical trials to safely test new procedures, new medicines, or new therapies.
The process of clinical trials begins in the laboratory. Prior to any drug testing in people, extensive testing in laboratories has to occur and the drug, appliance, procedure, or treatment in question has to pass strict qualifications to move on to the next step in testing.
Pre-clinical (before patient) testing usually takes about four years. The entire process is monitored by the Food and Drug Administration (FDA), a consumer protection agency with the U. S. Department of Health and Human Services. If early research and pre-clinical testing yields positive results, “Phase I” testing in clinical trials with people can begin.
Clinical trials are set up in phases. Each phase has a different purpose although it still tests the same medicine or therapy. This is how it works:
Phase I trials—small groups of people (20—80) test an experimental drug or therapy for the first time to find out safety, dosage, and side effect information. Phase I trials could take about two years depending on the nature of the investigation and how fast participants enroll.
Phase I trials involve small numbers of people, but they are still conducted with therapeutic (helping patients) purposes in mind. The participants in these trials are divided into smaller groups of 3 to 6. The dose testing begins with the initial group getting a low, conservative dose of the new drug, the therapy, or new treatment. If no adverse effects are observed in the initial group over a period of time, the second group of participants receives a higher dose. This sequence is repeated, with each group receiving a larger dose until adverse side effects are seen. This dose is called the dose-limiting toxicity level.
Important: All clinical trials have inclusion and exclusion criteria that determine who can be included in the trial and who cannot be included. Exclusion criteria are those characteristics about a participant that will remove him/her from consideration for a clinical trial. Inclusion criteria are those characteristics about a participant, as defined by the clinical trial protocol, that will allow him/her from to participate in a clinical trial. Examples of criteria include age, gender, and previous medical history.
Note: While it may seem strange to run a trial that find a dose limiting toxicity level, these types of trials are primarily run on participants who have a condition that is not responding to standard care. These patients generally are expected to have major organ function and, in the case of some cancers, at least a 1 to two month life expectancy. If the new drug has a positive effect on the cancer, these patients would not have to wait for the drug, but would be the very first people to benefit.
If these tests show positive results, Phase II trials can progress to……
Phase II trials—a larger group of people (100-300) are tested with the drug or therapy to confirm effectiveness, safety, and information about possible side effects. Again, this process could take about two years.
Phase II trials often focus on testing effectiveness and dosage levels for conditions that have not responded to standard care treatment. It is important to remember that all participants in Phase II trials receive the same treatment or drug.
If these tests show positive results, Phase III trials can progress to……
Phase III trials—an even larger group of people (1,000—3,000) are tested to further confirm the data and information obtained in the first two phases. Researchers report trail results in scientific journals and professional meetings to invite more review of their work.
Phase III trials could easily take 3—4 yours to enroll enough participants and additional years to conduct the trial and analyze the results. These trials are conducted at multiple institutions around the country. Participants are randomly assigned to an investigational group (who receives the new drug or treatment) or a control group (who receives standard care (currently accepted treatment). The effectiveness of the experimental drug is compared to effectiveness of standard treatments for the same condition.
Application to the FDA for a new drug license usually occurs after Phase III testing if the new drug or treatment has been shown to be more valuable than standard care.
If these tests show positive results, Phase IV trials can progress to……
Phase IV trials—marketing studies are published outlining the drug’s risks, benefits, and optimal use and data on drug or treatment use continues to be collected.
Note: Testing continues to make sure the drug, treatment or device is “safe”. Realize that “safe” does not mean free of all possible side effects. It means that its benefits outweigh its risks.
Important Points to Consider
• It is important to remember that regardless of what group a participant is in, he or she receives at the minimum the best current standard treatment care.
• If the new drug or treatment turns out to be better than the standard care, the participants are first to benefit from it— long before other patients can receive the treatment.
• There are risks to clinical trial participation. New treatments are not always better than standard care. Even though laboratory results indicate that they should be better, testing with humans is the only way to show if they really are better in humans.
• Even if a new treatment works, it may not help very participant, just as standard care does not help very patient. Still, the only way to find new and better treatments is to test for them.