Clinical trial is one of the final stages of a long and careful research process. Studies are done with patients to find out whether promising approaches to disease prevention, diagnosis, and treatment are safe and effective.
A healthy volunteer is a person with no known significant health problems who participates in clinical research to test a new drug, device, or intervention. Research procedures with healthy volunteers are designed to develop new knowledge, not to provide direct benefit to study participants. Healthy volunteers have always played a vital role in medical research.
Healthy volunteers are needed for several reasons. When developing a new technique, such as a blood test or imaging device, healthy volunteers help define the limits of what is considered to be "normal." These volunteers serve as controls for patient groups and are often matched to patients on characteristics such as age, gender, or family relationships. They receive the same test, procedure, or drug the patient group receives. Investigators learn about the disease process by comparing the patient group to the healthy volunteers.
Some studies require a major commitment in time and effort on behalf of the volunteer, and may involve some discomfort. The research procedure may also carry some risk. The consent process for healthy volunteers includes a detailed discussion of the study's procedures and tests.
A patient volunteer has a known health problem and participates in research to better understand, diagnose, treat, or cure that disease or condition. Research procedures with a patient volunteer help develop new knowledge. These procedures may or may not benefit the study participants.
Patient volunteers may be involved in studies similar to those in which healthy volunteers participate. These studies involve drugs, devices, or interventions designed to prevent, treat, or cure disease. Although these studies may provide direct benefits to patient volunteers, the main goal is to prove, by scientific means, the effects and limitations of the experimental treatment. Consequently, some patients serve as controls by not taking the test drug, or by receiving test doses of the drug large enough only to show that it is present, but not at a level that can treat the condition. A study's benefits may be indirect for the volunteers but may help others.
All clinical trials have guidelines as to who can participate. These are specified in the inclusion/exclusion criteria. Factors that allow someone to participate in a clinical trial are known as inclusion criteria. Those that exclude or not allow participation are called exclusion criteria. These criteria are based on factors such as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions. Before joining a clinical trial, a participant must qualify for the study. Some research studies seek participants with illnesses or conditions to be studied in the clinical trial, while others need healthy volunteers.
Some studies need both types. Inclusion and exclusion criteria are not used to reject people personally. The criteria are used to identify appropriate participants and keep them safe and to help ensure that researchers can answer the questions they want answered.
- Treatment trials test new treatments (such as a new drug, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy).
- Prevention trials test new approaches, such as medicines, vitamins, minerals, or other supplements that doctors believe may lower the risk of a certain type of disease.
- Screening trials investigate new methods of diagnosing specific diseases or disorders. These methods of detecting, often called screening tests, can include:
- imaging tests that produce pictures of areas inside the body.
- laboratory tests that check blood, urine, and other body fluids and tissues.
- genetic tests that look for inherited genetic markers linked to some types of disease.
The goal of screening trials is to develop screening tools that will catch a specific disease earlier. For example, for many types of cancer, detecting and treating the disease at an early stage can result in an improved outcome -- a better chance to shrink the cancer, minimize its effects, or cause it to go away completely.
Quality of Life trials explore ways to improve comfort and quality of life for patients. These studies, often called supportive care trials, may study drugs that aim to reduce side effects from chemotherapy and other primary treatments. Other supportive care studies look for beneficial effects of nutrition, group therapy, and other approaches.
Most clinical research that involves the testing of a new drug 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. Most clinical trials are classified into one of three phases:
- 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 tissue), how often, and what dose is safe. A phase I trial usually enrolls only a small number of patients, sometimes as few as a dozen.
- 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. They usually involve several hundred people.
- 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. A participant will usually be assigned to the standard group or the new group at random (called randomization). Phase III trials often enroll large numbers of people and may be conducted at many doctors' offices, clinics, and centers nationwide.
In addition, after a treatment has been approved and is being marketed, the drug's maker may study it further in a phase IV trial. The purpose of phase IV trials is to evaluate the side effects, risks, and benefits of a drug over a longer period of time and in a larger number of people than in phase III clinical trials. Thousands of people are involved in a phase IV trial.
Research participants are randomized in clinical trials so that bias does not weaken the study results. Bias consists of human choices, beliefs or any other factors besides those being studied that can affect a clinical trial's results. If physicians or participants themselves choose the group, assignments might be personally influenced and therefore unevenly slanted toward one side or the other.
For instance, if a study is not randomized, physicians might unconsciously assign participants with a more hopeful prognosis to the experimental group, thus making the new therapy seem more effective than it really is. Conversely, participants with a less hopeful prognosis might pick the experimental treatment, leading it to look less effective than it really is.
Randomization prevents such bias. In a randomized trial, investigators use a computer program or a table of random numbers to assign each study participant to a group.
To further eliminate bias, randomized trials are sometimes "blinded" (also called masked).
- Single-blinded trials are those in which participants do not know which group they are in, and therefore which intervention they are receiving, until the conclusion of the study.
- Double-blinded trials are those in which neither the participant nor the investigators know to which group the participant has been assigned until the conclusion of the study.
Blinded studies are commonly used in cancer prevention clinical trials but are rarely used in trials investigating new treatments.
The website of the National Cancer Institute (http://www.cancer.gov/clinicaltrials)