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We’ve all heard of them, but what exactly are clinical trials?

Put simply, a clinical trial is a scientific study of how a new medicine or treatment works in people. Through clinical studies, doctors find new and better ways to prevent, detect, diagnose, control, and treat illnesses.

People who participate in clinical trials are not guinea pigs. A therapy reaches the point where it can be evaluated in a clinical trial only after it proves successful in animals and the laboratory. The researchers who run the trials are actively trying to offer the participants the best available treatment that will be successful against their disease.

New medicines and treatments that are helpful and safe in test tubes and in animals must also prove safe and effective in humans before doctors can prescribe them. This testing in humans is permitted only if a person volunteers to participate and understands the risks and benefits of taking part in a study. This informed consent to participate must be based on a patient volunteer’s understanding of what is involved in the study, including potential risks and benefits. Volunteers may leave a study at any time.

Types of clinical trials   Top
There are several types of trials, according to the National Institutes of Health:

• Treatment trials test new therapies that may increase the life expectancy or reduce suffering in people who have a serious illness.
• Prevention trials test new approaches, such as medicines, vaccines, vitamins, minerals, or other supplements that doctors believe may lower the risk of a certain disease.
• Screening/early detection trials test the best way to find a disease, especially in its early stages.
• Quality of Life trials (also called Supportive Care trials) explore ways to improve comfort and quality of life for patients with a disease.
• Genetics trials are meant to improve the ability to look for an inherited risk of illness.

Clinical Trial Phases    Top
Testing of a new therapy (i.e., treatment trials) progresses in an orderly series of steps, called phases. This allows researchers to ask and answer questions in a way that results in reliable information about the drug and protects the patients. Clinical trials are usually classified into one of four phases by the U.S. Food and Drug Administration, which oversees the approval process:

• Phase I trials: These first studies in people evaluate how a new drug should be given (by mouth, injected into the blood, or injected into the muscle,) how often, and what dose is safe. In particular, these studies are also looking for the highest dose that can safely be given with the fewest serious side effects (maximum tolerated dose). In addition, a Phase I trial might evaluate a new combination of 2 drugs where one or both of the drugs, alone, might be well known but doctors have never before studied the two together. In these combination studies, doctors are watching closely for potential interactions and new side effects when the two drugs are given together.

  By the time a new treatment reaches the phase I level, it has proved beneficial in several animal models and in the laboratory. A Phase I trial usually enrolls only a small number of patients, sometimes as few as a dozen, and is offered only at major cancer centers. It is important to realize that there is no chance that a patient will receive a placebo in a Phase I clinical trial. Patients enrolling in Phase I trials are the first to help doctors identify promising new drugs and the scientific knowledge that will ultimately help future patients.

  Phase I trials usually enroll patients with advanced disease for whom no standard therapies are available. Patients considering Phase I trials should have a reasonable expectation that the new drugs (or drug combinations) might shrink their tumors or reduce their tumor burden. However the risks associated with being one of the first people to try a new drug-or a new drug combination-should be weighed very carefully since the side effects of the new drug/combination will not be well understood at the beginning of a Phase I study.

• Phase II trials: A phase II trial continues to test the safety of the drug, and begins to evaluate how well the new drug works. Phase II studies usually focus on a particular aspect of a disease. Like phase I trials, these trials do not test the difference between two therapies, so the participants will almost always get the experimental treatment. There is still no chance that a participant in the trial will receive a placebo.

• Phase III trials: These studies test a new drug, a new combination of drugs, or a new surgical procedure in comparison to the current standard for treatment. A participant will usually be assigned to the standard treatment group or the new treatment group at random (called randomization). Phase III trials often enroll large numbers of people and may be conducted at many doctors’ offices, clinics, and disease centers nationwide.

  In phase III trials, patients rarely receive a placebo – in fact, only when there is no standard therapy for the disease. Otherwise, people who participate in phase III clinical trials will either receive the best available standard therapy or the experimental therapy, with an equal chance of receiving either treatment.

• Phase IV trials: These are often required when a drug manufacturer wishes to test an already approved therapy for a different medical condition or in a different formulation than it was originally approved for. The manufacturer is not allowed to make new claims about their product until it is properly tested. It is possible (though unlikely) that a placebo may be used in the control group in a phase IV trial.

Inclusion/exclusion criteria    Top
When designing a clinical research study, an investigator must first decide who should be in the study and who should be excluded. Unless the researchers are very firm and diligent about sticking to those inclusion/exclusion criteria, the entire study can be weakened. The researchers must therefore try and find a balance between identifying those people who are most appropriate to test a new therapy and casting a wide enough net to ensure that they will have enough participants to make the results statistically significant.

Inclusion/exclusion criteria might be such factors as the age of the participants – many studies will only include people over 18 years old, for example – the date of diagnosis of the illness, other therapies, and other illnesses that the participant might have. Other inclusion/exclusion criteria might be the stage of the illness – many studies try and exclude patients who have very advanced illnesses – how active the participants are in their day-to-day routines, and the ability to take oral medications.

Inclusion/exclusion criteria should be explained to each potential participant in a clinical research trial before they are enrolled in the study.

The initial screening visit    Top
After a person has decided to participate in a clinical study, they will be scheduled by the study coordinator for a preliminary screening visit. During that visit, the inclusion/exclusion criteria will be detailed for the participant. The study coordinator will also explain the study, the procedures that need to be followed and answer any questions that may arise. This process is called informed consent and is essential before any volunteer is enrolled in any clinical trial. More on the concept of informed consent can be found below

The initial screening visit is also an opportunity for the study coordinator to obtain a full medical history from the participant. He or she will also usually perform a physical exam and schedule any laboratory tests that may be necessary before participation in the study can begin.

Informed consent    Top
The United States government is very strict about the guidelines of medical research performed on people. An Institutional Review Board (IRB) approves and monitors every clinical trial performed in the US to minimize the risks to the study participants and to make sure that the potential benefits of the new therapy outweigh those risks. An IRB is usually made up of physicians, experts in biomedical ethics, statisticians, and members of the community and its sole charge is to make certain that clinical research adheres to the strictest ethical guidelines.

Every participant in a clinical trial in the United States has the right to informed consent. In fact, nobody should even consider joining a trial without access to key information that must be provided by the investigators in easy-to-understand language.

This information (adapted from the NIH) includes:

• why the research is being done
• what the researchers are hoping to accomplish
• what the different therapies being tested are and how they are thought to work
• any risks associated with the therapies
• the potential benefits for the participant
• other available treatments (with a discussion of their efficacy and side effects)
• the fact that participants may leave the study at any time

Getting paid to participate in clinical trials    Top
Some clinical trials will pay people for participating in the research but they are rare, primarily because the National Institutes of Health wish to discourage patients from participating in clinical trials solely for financial purposes.

Most clinical trial sponsors, however, will reimburse participants for reasonable travel and food expenses accumulated while they are in the trial. The article below describes specific legislation meant to ensure that people who participate in clinical research are not harmed financially by their involvement.

Where to go for more information    Top
The National Institutes of Health have a very comprehensive website that deals exclusively with clinical trials and the issues described above. It can be found at www.clinicaltrials.gov.