Clinical research is medical research that involves people. Individuals volunteer to participate in carefully conducted investigations that ultimately uncover better ways to treat, prevent, diagnose and understand human disease.

Clinical research includes trials that test new treatments and therapies as well as long–term natural history studies, which provide valuable information about how disease and health progress.

The idea. Ideas for clinical research—also known as clinical trials or clinical studies—often originate in the laboratory or patient-care settings. After researchers test new therapies or procedures in the laboratory and in animal studies, the most promising experimental treatments are moved into clinical trials, which are conducted in phases. During a trial, more information is gained about an experimental treatment, its risks, and its effectiveness.

The protocol. Clinical research is conducted according to a plan known as a protocol. The protocol is carefully designed to safeguard the participants’ health and answer specific research questions. A protocol describes the following:

• Who is eligible to participate in the trial
• Details about tests, procedures, medications, and dosages
• The length of the study and what information will be gathered

A clinical study is led by a principal investigator, who is often a doctor. Members of the research team regularly monitor the participants’ health to determine the study’s safety and effectiveness.

Protocol review. Each clinical trial in the United States must be approved and monitored by an Institutional Review Board (IRB) to ensure that the risks are minimal and are worth any potential benefits. An IRB is an independent committee that consists of physicians, statisticians, and members of the community who ensure that clinical trials are ethical and that the rights of participants are protected. Federal regulation requires all institutions in the United States that conduct or support biomedical research involving people to have an IRB initially approve and periodically review the research.

Sponsors. Clinical trials are sponsored or funded by various organizations or individuals, including physicians, foundations, medical institutions, voluntary groups, and pharmaceutical companies, as well as federal agencies such as the National Institutes of Health, the Department of Defense, and the Department of Veterans Affairs. Trials can occur at sites as varied as hospitals, universities, doctors’ offices, or community clinics.

Informed consent. Informed consent is the process of providing potential participants with the key facts about a clinical trial before they decide whether to participate. The process of informed consent (providing additional information) continues throughout the study. To help someone decide whether or not to participate, members of the research team explain the details of the study. Translation or interpretive assistance can be provided for participants with limited English proficiency. The research team provides an informed consent document that includes details about the study, such as its purpose, duration, required procedures, and who to contact for further information. The informed consent document also explains risks and potential benefits. The participant then decides whether to sign the document. Informed consent is not a contract. Volunteers are free to withdraw from the study completely or to refuse particular treatments or tests at any time. Sometimes, however, this will make them ineligible to continue the study.

Types of clinical trials. The types of clinical trials include the following:

• Treatment trials test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
• Prevention trials look for better ways to prevent a disease in people who have never had the disease or to prevent the disease from returning. Better approaches may include medicines, vaccines, or lifestyle changes, among other things.
• Diagnostic trials determine better tests or procedures for diagnosing a particular disease or condition.
• Screening trials test the best way to detect certain diseases or health conditions.
• Quality of life trials (or supportive care trials) explore and measure ways to improve the comfort and quality of life of people with a chronic illness.

Phases of clinical trials. Clinical trials are conducted in "phases." The trials at each phase have a different purpose and help researchers answer different questions.

1. Phase I trials—Researchers test an experimental drug or treatment in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
2. Phase II trials—The experimental drug or treatment is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
3. Phase III trials—The experimental drug or treatment is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the experimental drug or treatment to be used safely.
4. Phase IV trials—After a drug is licensed (approved by the FDA) or treatment is launched, researchers track its safety, seeking more information about a drug or treatment’s risks, benefits, and optimal use. These long–term studies involving large groups of participants continue to see if any unexpected side effects occur in a small percentage of individuals.

Some concepts to understand. Typically, clinical trials compare a new product or therapy with another that already exists to determine if the new one is as successful as, or better than, the existing one. In some studies, participants may be assigned to receive a placebo (an inactive product that resembles the test product, but without its treatment value).

Comparing a new product with a placebo can be the fastest and most reliable way to demonstrate the new product’s therapeutic effectiveness. However, placebos are not used if a patient would be put at risk—particularly in the study of treatments for serious illnesses—by not having effective therapy. Most of these studies compare new products with an approved therapy. Potential participants are told if placebos will be used in the study before they enter a trial.

Randomization is the process by which two or more alternative treatments are assigned to volunteers by chance rather than by choice. The assigned treatment is administered with the highest level of professional care and expertise. The results of each treatment are compared at specific points during a trial, which may last for years. When one treatment is found superior, the trial is stopped so that the fewest patients possible receive the less beneficial treatment.

In single- or double-blind studies, also called single- or double-masked studies, the participants do not know which medicine is being used, so they can describe what happens without bias. "Blind" (or "masked") studies are designed to prevent members of the research team or study participants from influencing the results. This allows scientifically accurate conclusions. In single-blind ("single-masked") studies, only the patient is not told what is being administered. In a double-blind study, only the pharmacist knows; members of the research team are not told which patients are getting which medication, so that their observations will not be biased. If medically necessary, however, it is always possible to find out what the patient is taking.