For more information, visit http://www.nhlbi.nih.gov/health/health-topics/topics/clinicaltrials/

What Are Clinical Trials?

Clinical trials are research studies that explore whether a medical strategy, treatment, or device is safe and effective for humans. These studies also may show which medical approaches work best for certain illnesses or groups of people. Clinical trials produce the best data available for health care decisionmaking.

The purpose of clinical trials is research, so the studies follow strict scientific standards. These standards protect patients and help produce reliable study results.

Clinical trials are one of the final stages of a long and careful research process. The process often begins in a laboratory (lab), where scientists first develop and test new ideas.

If an approach seems promising, the next step may involve animal testing. This shows how the approach affects a living body and whether it's harmful. However, an approach that works well in the lab or animals doesn't always work well in people. Thus, research in humans is needed.

For safety purposes, clinical trials start with small groups of patients to find out whether a new approach causes any harm. In later phases of clinical trials, researchers learn more about the new approach's risks and benefits.

A clinical trial may find that a new strategy, treatment, or device:

Improves patient outcomes
Offers no benefit
Causes unexpected harm

All of these results are important because they advance medical knowledge and help improve patient care.

Who Sponsors Clinical Trials?

The National Heart, Lung, and Blood Institute (NHLBI) and other National Institutes of Health (NIH) Institutes and Centers sponsor clinical trials.

Many other groups, companies, and organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations.

NIH Institutes and Centers (including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study explored whether the benefits of lowering high blood pressure in the elderly outweighed the risks.

Other examples of clinical trials that test principles or strategies include studies that:

Explore whether surgery or other medical treatments produce better results for certain illnesses or groups of people
Look at the best age and frequency for doing screening tests, such as mammography
Compare two or more screening tests to see which test produces the best results

Some companies and groups sponsor clinical trials that test the safety of products, such as medicines, and how well they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. The NIH may partner with these companies or groups to help sponsor some trials.

All types of clinical trials contribute to medical knowledge and practice.

Why Are Clinical Trials Important?

Clinical trials are a key research tool for advancing medical knowledge and patient care. Clinical research is done only if doctors don't know:

Whether a new approach works well in people and is safe
Which treatments or strategies work best for certain illnesses or groups of people

Some clinical trials show a positive result. For example, the National Heart, Lung, and Blood Institute (NHLBI) sponsored a trial of two different combinations of asthma treatments. The trial found that one of the combinations worked much better than the other for moderate persistent asthma. The results provided important treatment information for doctors and patients.

The results from other clinical trials show what doesn't work or may cause harm. For example, the NHLBI Women's Health Initiative tested whether hormone therapy (HT) reduced the risk of heart disease in postmenopausal women. (When the trial began, HT was already in common use for the treatment of menopausal symptoms. It also was increasingly being used for prevention of heart disease.)

The study found that HT increased the risk of heart disease in the first few years, and it also increased the risk of stroke and blood clots. In women who took a combination of estrogen and progestin, the risk of breast cancer also increased.

As a result, the U.S. Food and Drug Administration now recommends never using HT to prevent heart disease. When HT is used for menopausal symptoms, it should be taken only at the smallest dose and for the shortest time possible.

Clinical trials, like the two described above, help improve and advance medical care. They also can help health care decisionmakers direct resources to the strategies and treatments that work best.

How Do Clinical Trials Work?

If you take part in a clinical trial, you may get tests or treatments in a hospital, clinic, or doctor's office.

In some ways, taking part in a clinical trial is different from having regular care from your own doctor. For example, you may have more tests and medical exams than you would otherwise.

The purpose of clinical trials is research, so the studies follow strict scientific standards. These standards protect patients and help produce reliable study results.

Clinical Trial Protocol

Each clinical trial has a master plan called a protocol (PRO-to-kol). This plan explains how the trial will work. The trial is led by a principal investigator (PI), who often is a doctor. The PI prepares the protocol for the clinical trial.

The protocol outlines what will be done during the clinical trial and why. Each medical center that does the study uses the same protocol.

Key information in a protocol includes:

How many patients will take part in the clinical trial
Who is eligible to take part in the clinical trial
What tests patients will get and how often they will get them
What type of data will be collected during the clinical trial
Detailed information about the treatment plan

Eligibility Criteria

A clinical trial's protocol describes what types of patients are able to take part in the research—that is, who is eligible. Each trial must include only people who fit the patient traits for that study (the eligibility criteria).

Eligibility criteria differ from trial to trial. They include factors such as a patient's age and gender, the type and stage of disease, and whether the patient has had certain treatments or has other health problems.

Eligibility criteria ensure that new approaches are tested on similar groups of people. This makes it clear to whom a clinical trial's results apply. These criteria also are a safety measure. They ensure a trial excludes any people for whom the protocol has known risks that outweigh any possible benefits.

Clinical Trial Phases

Clinical trials of new medicines or medical devices are done in phases. These phases have different purposes and help researchers answer different questions.

For example, phase I clinical trials test new treatments in small groups of people for safety and side effects. Phase II clinical trials look at how well treatments work and further review these treatments for safety.

Phase III clinical trials use larger groups of people to confirm how well treatments work, further examine side effects, and compare new treatments with other available treatments.

Steps To Avoid Bias

The researchers doing clinical trials take steps to avoid bias. "Bias" means that human choices or other factors not related to the protocol affect the trial's results.

Comparison Groups

In most clinical trials, researchers use comparison groups. This means that the patients taking part in a trial are assigned to one of two or more similar groups. Each group will receive different medical strategies.

For example, one group may get the current standard treatment for a condition, while another group gets a new treatment. Researchers can then compare the results to see whether one group has better outcomes than the other.

Using comparison groups also ensures that no one in a study is left without treatment for the sake of research.

Sometimes, when no accepted standard treatment exists for a condition, people in one group may receive a placebo (plah-SE-bo). This is an inactive product that looks like the test product. You'll be told if a placebo will be used in a study before you agree to take part.

Randomization

Most clinical trials that have comparison groups use randomization. This involves assigning patients to different comparison groups by chance, rather than choice.

This method helps ensure that any differences observed during a trial are due to the different strategies being used, not to preexisting differences between the patients. Usually, a computer program makes the group assignments.

Masking

The term "masking" refers to not telling the clinical trial participants which treatment they're getting. Masking, or "blinding," helps avoid bias. For this reason, researchers also may not be told which treatments the patients are getting. However, trial records can quickly show this information if safety issues arise.

Who Can Participate in Clinical Trials?

Each clinical trial defines who is eligible to take part in the study. Each trial must include only people who fit the patient traits for that study (the eligibility criteria). For more information about eligibility criteria, go to "How Do Clinical Trials Work?"

Some trials enroll people who have a specific disease or condition. Others enroll healthy people to test new approaches to prevention, diagnosis, or screening.

In the past, clinical trial participants often were White men. Researchers assumed that trial results were valid for other populations as well.

Researchers now realize that women and people in different ethnic groups sometimes respond differently than White men to the same medical approach. As a result, the National Institutes of Health and the National Heart, Lung, and Blood Institute (NHLBI) are committed to sponsoring clinical trials that include women and are ethnically diverse.

Children also need clinical trials that focus on them, as medical treatments and approaches often differ for children. For example, children may need lower doses of certain medicines or smaller medical devices. Their stage of development also can affect how safe a treatment is or how well it works.

Children (aged 18 and younger) get special protection as research subjects. Almost always, parents must give legal consent for their child to take part in a clinical trial.

When researchers think that a trial's potential risks are greater than minimal, both parents must give permission for their child to enroll. Also, children aged 7 and older often must agree (assent) to take part in clinical trials.

Clinical trials for children have the same scientific safeguards as clinical trials for adults. For more information, go to "How Do Clinical Trials Protect Participants?"

For more information about clinical trials for children, go to the NHLBI's Children and Clinical Studies Web page.

What To Expect During a Clinical Trial

During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of your treatment team. They will monitor your health closely. You may have more tests and medical exams than you would if you were not taking part in a clinical trial.

Your treatment team also may ask you to do other tasks. For example, you may have to keep a log about your health or fill out forms about how you feel.

Some people will need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in Bethesda, Maryland, runs clinical trials. Many other clinical trials take place in medical centers and doctors' offices around the country.

What Are the Possible Benefits and Risks of Clinical Trials?

Possible Benefits

Taking part in a clinical trial can have many benefits. For example, you may gain access to new treatments before they're widely available. If a new treatment is proven to work and you're in the group getting it, you might be among the first to benefit.

If you're in a clinical trial and don't get the new strategy being tested, you may receive the current standard care for your condition. This treatment might be as good as, or better than, the new approach. You also will have the support of a team of health care providers, who will likely monitor your health closely.

In late-phase clinical trials, possible benefits or risks of a treatment can be identified earlier than they would be in general medical practice. This is because late-phase trials have large groups of similar patients taking the same treatment the same way. These patients are closely watched by Data and Safety Monitoring Boards.

Even if you don't directly benefit from the results of the clinical trial you take part in, the information gathered can help others and add to scientific knowledge. People who take part in clinical trials are vital to the process of improving medical care. Many people volunteer because they want to help others.

Possible Risks

Clinical trials do have risks and some down sides. For example:

The new strategies and treatments being studied aren't always better than current standard care.
Even if a new approach benefits some participants, it may not work for you.
A new treatment may have side effects or risks that doctors don't know about or expect. This is especially true during phase I and phase II clinical trials. The risk of side effects might be even greater for trials with cutting-edge approaches, such as gene therapy or new biological treatments.
Health insurance and health care providers don't always cover all patient care costs for clinical trials. If you're thinking about taking part in a clinical trial, find out ahead of time about costs and coverage.

You should learn about the risks and benefits of any clinical trial before you agree to take part in the trial. Talk with your doctor about specific trials you're interested in. For a list of questions to ask your doctor and the research staff, go to "How Do Clinical Trials Protect Participants?"

How Do Clinical Trials Protect Participants?

Protecting the safety of people who take part in clinical trials is a high priority for clinical researchers. Each trial has scientific oversight, and patients also have rights that help protect them.

Scientific Oversight

Institutional Review Board

Institutional review boards (IRBs) help provide scientific oversight for clinical trials. An IRB is an independent committee created by the institution that sponsors a clinical trial. IRB members are doctors, statisticians, and community members.

The IRB's purpose is to ensure that clinical trials are ethical and that the participants' rights are protected. The IRB reviews the trial's protocol before the study begins.

An IRB will only approve research that deals with medically important questions in a scientific and responsible way. The IRB also checks on results during the trial. All U.S. clinical trials are required to have an IRB.

Office for Human Research Protections

The U.S. Department of Health and Human Services’ (HHS’) Office for Human Research Protections (OHRP) oversees all research done or supported by HHS.

The OHRP helps protect the rights, welfare, and well-being of research participants. They provide guidance and oversight to the IRBs, develop educational programs and materials, and offer advice on research-related issues.

Data Safety Monitoring Board

Every National Institutes of Health (NIH) phase III clinical trial is required to have a Data and Safety Monitoring Board (DSMB). This board consists of a group of research and study topic experts.

The NIH also requires DSMBs for large trials comparing alternative strategies for diagnosis or treatment. In addition, the NIH requires DSMBs for some earlier phase trials that involve high-risk procedures (such as gene therapy) or vulnerable patients (such as children).

A DSMB's role is to review data from a clinical trial for safety problems or differences in results among different groups. The DSMB also reviews research results from other relevant studies. These results may reveal unknown patient risks, or they may even answer the NIH study's research question.

Scientific oversight informs decisions about a trial while it's under way. For example, some trials are stopped early if benefits from a strategy or treatment are obvious. That way, wider access to the new strategy can occur sooner.

Sponsors also may stop a trial, or part of a trial, early if the strategy or treatment is having harmful effects.

Food and Drug Administration

In the United States, the Food and Drug Administration (FDA) provides oversight for clinical trials that are testing new medicines or medical devices.

The FDA reviews applications for new medicines and devices before any testing on humans is done. They check to make sure that the proposed studies have proper informed consent (see below) and protection for human subjects.

The FDA also provides oversight and guidance at various stages throughout the studies. For example, before large-scale phase III trials begin, the FDA provides input on how these studies should be done.

Patient Rights

Informed Consent

Informed consent is the process of giving clinical trial participants all of the facts about a trial. This happens before they agree to take part and during the course of the trial. Informed consent includes details about the treatments and tests you may receive and the benefits and risks they may have.

Before you decide whether to enroll in a clinical trial, a doctor or nurse will give you an informed consent form that presents the key facts of the study. If you agree to take part in the trial, you'll be asked to sign the form.

You can and should ask questions about the trial to make sure you understand what's involved. Here are some questions to ask before enrolling in a clinical trial:

What is the purpose of the study?
Who is sponsoring the study, and who has reviewed and approved it?
What kinds of tests, medicines, surgery, or devices are involved? Are any procedures painful?
What are the possible risks, side effects, and benefits of taking part in the study?
How might this trial affect my daily life? Will I have to be in the hospital?
How long will the trial last?
Who will pay for the tests and treatments I receive?
Will I be reimbursed for other expenses (for example, travel and child care)?
Who will be in charge of my care?
What will happen after the trial?

Taking part in a clinical trial is your decision. Talk with your doctor about all of your treatment options. Together, you can make the best choice for you.

Other Rights

The informed consent document is not a contract. You have the right to withdraw from a study at any time, for any reason. Also, during the trial, you have the right to learn about new risks or findings that emerge. If researchers learn that a treatment harms you, you'll be removed from the study.

Rights and Protection for Children

Children (aged 18 and younger) get special protection as research subjects. Almost always, parents must give legal consent for their child to take part in a clinical trial.

Finding Clinical Trials

If you're interested in learning more about, or taking part in, clinical trials, talk with your doctor. He or she may know about studies going on in your area.

You also can visit the following Web sites to learn more about clinical research and to search for clinical trials:

For more information about clinical trials for children, visit the NHLBI's Children and Clinical Studies Web page.

Links to Other Information About Clinical Trials

NHLBI Resources

Non-NHLBI Resources

ClinicalTrials.gov
NIH Clinical Research Trials and You (National Institutes of Health)
ResearchMatch (funded by the National Institutes of Health)