What Is a Clinical Trial?

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Valerie DeBenedette, Senior Medical Editor

Valerie DeBenedette is a science writer who specializes in keeping people informed about medicine and their health. She has more than 20 years of experience writing for newspapers, magazines, and websites and has written about most areas of medicine. For many years, she was a contributing writer to Cosmetic Dermatology and to Drug Topics, the leading pharmacy trade magazine. She also was a contributing editor to The Physician and Sportsmedicine for many years. She has written about most fields of medicine, including dermatology, sportsmedicine, ophthalmology, general surgery, orthopedics, and women's health; as well as public health policy and the pharmaceutical industry. In addition, she is the author of Caffeine, a book for young people. She is a member of the National Association of Science Writers.


December 17 2008

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On a TV show, a doctor tries something on a very sick patient, it works, and the doctor immediately knows the same treatment will work on every patient with that problem. Problem solved; cue the closing credits. In real life, medical research is always a long, slow process.

In real life, medical research takes years, must follow very specific rules, and often goes down blind alleys that lead nowhere. A drug looks promising in animals and then looks like it works in small tests in people, but it's subsequently found not to work in larger trials. Or maybe it is found to have such severe side effects that it is unusable.

So how is most medical research conducted? The main tool in medical research is the clinical trial. A clinical trial is a structured method of conducting medical research. It is the way that medical researchers find out if a treatment, drug, or medical device works safely and effectively on a given disease or condition. The treatment being tested may be a breakthrough against a disease that previously had no cure or treatment, or something that is more effective against a problem than what is in current use. In many cases, the treatment may be safer, or may have some other benefit, such as a lower cost, or greater ease of use.

Some clinical trials are prevention trials, where researchers examine ways to prevent a disease through vaccines or lifestyle changes. Some trials look at surgical treatments, such as a new technique for a cosmetic surgery, for example, a face lift. Clinical trials can also examine medical devices and several plastic surgery clinical trials are underway that are evaluating different types of breast implants.

In most clinical trials, the treatment being tested (which may be a drug, a medical device, or a type of surgery) is compared to either a placebo, which is an un-medicated pill or treatment, or a treatment that has already been shown to work against the condition. The patients who get the placebo or standard treatment are called the control group. Generally, the new treatment is tested against a placebo when there is no other treatment or when withholding that treatment for the duration of the clinical trial will not cause harm or would be unethical.

Clinical trials are started after a treatment has been shown to be promising in animal studies. If a treatment shows promise, researchers create what is called a clinical trial protocol, which outlines the design of the study and its purpose. Trials are divided into four phases. In Phase I, a small number of human volunteers — 20 to 80 — are given the treatment to check its safety, to find out what the right dosage range is if the treatment is a drug, and to identify side effects or adverse reactions. Usually, the subjects in a Phase I study are healthy, but sometimes people with the targeted disease are enrolled.

If all goes well and the new treatment still shows promise, a Phase II study is started. Here, the treatment is used on a larger group of volunteers who have the condition to be treated. In most studies, these volunteers will be divided into two groups: one to get the treatment and one to get a placebo or whatever the standard of care is for the condition. Up to 300 subjects may be enrolled in Phase II and they are carefully chosen to eliminate other factors such as other diseases, age discrepancies, or lifestyle habits like smoking that can disguise side effects or disadvantages of the treatment. This phase may last a couple of years, depending on how long it takes to enroll subjects, apply the treatment, and conduct the follow-up. Safety is still a concern and the researchers watch out for adverse reaction and side effects.

If the treatment is still showing promise, it moves along to a Phase III study. Much larger groups of patients are enrolled in the study, up to many thousands, but usually in the range of 1000 to 3000. Several medical centers or research sites may be involved, each enrolling a few hundred patients. In a Phase III study, the treatment being studied is more likely to be compared to whatever is commonly used for the condition. Because many more patients are being enrolled, it is more likely that adverse reactions may show up.

Relatively few drugs that get past animal testing make it to Phase III testing. Still, the larger numbers of patients in a Phase III trial may show that a treatment that still looked promising in Phase II was a statistical fluke. The new treatment may be shown to be no more useful than the placebo or standard treatment. Or it may be found to have serious side effects or adverse reactions. Phase III trials usually take many years, since it takes time to enroll patients and run the study.

The majority of Phase III studies are conducted in ways to prevent any bias for or against the new treatment (or the placebo) from affecting the data. Patients are usually randomly assigned into groups that get the treatment and those that act as the controls — known as a randomized trial—and the protocol may require that the placebo pills or treatment resemble the active pills or treatment as much as possible. Patients don't know whether they are getting active treatment or a placebo (a blind study), or both the patients and the researchers may be kept from knowing (a double-blind study).

Side effects and adverse reactions can happen with any treatment. Safety is relative, since even as common a drug as aspirin causes side effects in many people and deadly allergic reactions in some. What is acceptable in a drug may depend on the severity of the disease or condition being treated. A drug to treat a potentially fatal condition such as cancer may have side effects that would be unacceptable in a drug to treat a less serious condition. Effectiveness may also be relative as well, since a new treatment may be no more effective than what is in use, but may have fewer side effects or be easier to use or less expensive.

In the United States, after all the data from Phase III trials are collected and studied, the sponsor of the clinical trial—often a pharmaceutical company or the maker of a medical device—will apply to the U.S. Food and Drug Administration for approval to market the treatment. If the FDA approves the drug or device, it may require the company to conduct what are called Phase IV studies. These are post-marketing studies that look for any side effects or adverse reactions (or unexpected patterns in their incidence) after the drug or device is put into wide use.

Clinical trials are extremely important and are vital for continued progress in the field of medicine. A patient may be asked to join a clinical trial, but patients are not supposed to be enrolled in them against their will or without their knowledge. Before you enroll in a clinical trial you must read and sign a very extensive document called an informed consent form that will detail the purpose of the study and the entire protocol. You will be told about any side effects or adverse reactions that are known and told that some others may occur. You will also be told what role you will have to take, such as showing up for doctor appointments on a regular basis for several years. Two advantages of taking part in a clinical trial are that some of your care may be free or at a reduced cost and you will be followed by experts in the disease or condition you have.

To learn more about clinical trials, check out www.clinicaltrials.gov, which is a website run by the U.S. National Institutes of Health. You can search for clinical trials for a given condition.

In the next part of NewImage.com's series on clinical trials, we will be discussing the role of clinical trials in plastic and cosmetic surgery, and will include information on what trials are currently underway.