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How to Understand Clinical Trials

I have often referred to the need for clinical trials to substantiate claims made by makers of various “would be” treatment modalities. With the surge of new proposed treatments available for lymphedema, it becomes even more important for us to insist on the process of clinical trials. This is also one of the foundations of what is known as evidence based medicine.

But, what exactly is a clinical trial, what does it do and what is its value?

If you are in the process of learning about clinical trials or are considering participating in one, you may be interested in looking at Partners in Research (pdf) (Requires Adobe's free Acrobat Reader), which describes the role of a patient in clinical research. In addition, we encourage anyone with questions to call the Patient Recruitment Office at 1-800-411-1222. You may also want to try the “Topics A-Z” tool, an alphabetical index to all visitor- and patient-related subject areas.

What are clinical studies?

Clinical studies are research studies in which real people participate as volunteers. Clinical research studies (sometimes called trials or protocols) are a means of developing new treatments and medications for diseases and conditions. There are strict rules for clinical trials, which are monitored by the National Institutes of Health and the U.S. Food and Drug Administration. Some of the research studies at the Clinical Center involve promising new treatments that may directly benefit patients.

Why should I participate?

The health of millions has been improved because of advances in science and technology, and the willingness of thousands of individuals like you to take part in clinical research. The role of volunteer subjects as partners in clinical research is crucial in the quest for knowledge that will improve the health of future generations. Without your help, the research studies at the Clinical Center cannot be accomplished.

What is a "healthy volunteer"?

A volunteer subject with no known significant health problems who participates in research to test a new drug, device, or intervention is known as a “healthy volunteer” or “Clinical Research Volunteer.” The clinical research volunteer may be a member of the community, an NIH investigator or other employee, or family members of a patient volunteer. Research procedures with these volunteers are designed to develop new knowledge, not to provide direct benefit to study participants. Clinical research volunteers have always played a vital role in medical research. We need to study healthy volunteers for several reasons: When developing a new technique such as a blood test or imaging device, we need clinical research volunteers to help us define the limits of “normal.” These volunteers are recruited to serve as controls for patient groups. They are often matched to patients on such characteristics as age, gender, or family relationship. They are then given the same test, procedure, or drug the patient group receives. Investigators learn about the disease process by comparing the patient group to the clinical research volunteers.

What are Phase I, Phase II and Phase III studies?

The phase 1 study is used to learn the “maximum tolerated dose” of a drug that does not produce unacceptable side effects. Patient volunteers are followed primarily for side effects, and not for how the drug affects their disease. The first few volunteer subjects receive low doses of the trial drug to see how the drug is tolerated and to learn how it acts in the body. The next group of volunteer subjects receives larger amounts. Phase 1 studies typically offer little or no benefit to the volunteer subjects.

The phase 2 study involves a drug whose dose and side effects are well known. Many more volunteer subjects are tested, to define side effects, learn how it is used in the body, and learn how it helps the condition under study. Some volunteer subjects may benefit from a phase 2 study.

The phase 3 study compares the new drug against a commonly used drug. Some volunteer subjects will be given the new drug and some the commonly used drug. The trial is designed to find where the new drug fits in managing a particular condition. Determining the true benefit of a drug in a clinical trial is difficult. Determining the true benefit of a drug in a clinical trial is difficult.

What is a placebo?

Placebos are harmless, inactive substances made to look like the real medicine used in the clinical trial. Placebos allow the investigators to learn whether the medicine being given works better or no better than ordinary treatment. In many studies, there are successive time periods, with either the placebo or the real medicine. In order not to introduce bias, the patient, and sometimes the staff, are not told when or what the changes are. If a placebo is part of a study, you will always be informed in the consent form given to you before you agree to take part in the study. When you read the consent form, be sure that you understand what research approach is being used in the study you are entering.

What is the placebo effect?

Medical research is dogged by the placebo effect - the real or apparent improvement in a patient's condition due to wishful thinking by the investigator or the patient. Medical techniques use three ways to rid clinical trials of this problem. These methods have helped discredit some previously accepted treatments and validate new ones. Methods used are the following: randomization, single-blind or double-blind studies, and the use of a placebo.

What is randomization?

Randomization is when two or more alternative treatments are selected by chance, not by choice. The treatment chosen is given with the highest level of professional care and expertise, and the results of each treatment are compared. Analyses are done at intervals during a trial, which may last years. As soon as one treatment is found to be definitely superior, the trial is stopped. In this way, the fewest number of patients receive the less beneficial treatment.

What are single-blind and double-blind studies?

In single- or double-blind studies, the participants don't know which medicine is being used, and they can describe what happens without bias. Blind studies are designed to prevent anyone (doctors, nurses, or patients) from influencing the results. This allows scientifically accurate conclusions. In single-blind (“single-masked”) studies, only the patient is not told what is being given. In a double-blind study, only the pharmacist knows; the doctors, nurses, patients, and other health care staff are not informed. If medically necessary, however, it is always possible to find out what the patient is taking.

Are there risks involved in participating in clinical research?

Risks are involved in clinical research, as in routine medical care and activities of daily living. In thinking about the risks of research, it is helpful to focus on two things: the degree of harm that could result from taking part in the study, and the chance of any harm occurring. Most clinical studies pose risks of minor discomfort, lasting only a short time. Some volunteer subjects, however, experience complications that require medical attention. The specific risks associated with any research protocol are described in detail in the consent document, which you are asked to sign before taking part in research. In addition, the major risks of participating in a study will be explained to you by a member of the research team, who will answer your questions about the study. Before deciding to participate, you should carefully weigh these risks. Although you may not receive any direct benefit as a result of participating in research, the knowledge developed may help others.

What safeguards are there to protect participants in clinical research?

The following section describes safeguards that protect the safety and rights of volunteer subjects. These safeguards include:

  • The Protocol Review Process
  • Informed Consent Procedures
  • The Patient Representative
  • The Patient Bill of Rights

Protocol review

As in any medical research facility, all new protocols produced at NIH must be approved by an institutional review board (IRB) before they can begin. The IRB, which consists of medical specialists, statisticians, nurses, social workers, and medical ethicists, is the advocate of the volunteer subject. The IRB will only approve protocols that address medically important questions in a scientific and responsible manner.

Your participation in any Clinical Center research protocol is voluntary. For every study in which you intend to participate, you will receive a document called “Consent to Participate in a Clinical Research Study” that explains the study in straightforward language. A member of the research team will discuss the protocol with you, explain its details, and answer your questions. Reading and understanding the protocol is your responsibility. You may discuss the protocol with family and friends. You will not be hurried into making a decision, and you will be asked to sign the document only after you understand the nature of the protocol and agree to the commitment. At any time after signing the protocol, you are free to change your mind and decide not to participate further. This means that you are free to withdraw from the study completely, or to refuse particular treatments or tests. Sometimes, however, this will make you ineligible to continue the study. If you are no longer eligible or no longer wish to continue the study, you will return to the care of the doctor who referred you to NIH.

Patient representative

The Patient Representative acts as a link between the patient and the hospital. The Patient Representative makes every effort to assure that patients are informed of their rights and responsibilities, and that they understand what the Clinical Center is, what it can offer, and how it operates. We realize that this setting is unique and may generate questions about the patient's role in the research process. As in any large and complex system, communication can be a problem and misunderstandings can occur. If any patient has an unanswered question or feels there is a problem they would like to discuss, they can call the Patient Representative.

Bill of Rights

Finally, whether you are a clinical research or a patient volunteer subject, you are protected by the Clinical Center Patients' Bill of Rights. This document is adapted from the one made by the American Hospital Association for use in all hospitals in the country. The bill of rights concerns the care you receive, privacy, confidentiality, and access to medical records.

If you are thinking about participating in a Clinical Study at NIH, the information on this page may provide a starting point for discussion—both with your doctor and with the trained staff at the Clinical Center's Patient Recruitment Office. Other documents that may be of interest are Partners in Research (pdf) (Requires Adobe's free Acrobat Reader), the Patient Bill of Rights, and Patient Responsibilities. We encourage you and your doctor to call and find out more, at 1-800-411-1222. You may also want to try the “Topics A-Z” tool, an alphabetical index to all visitor- and patient-related subject areas—and don't forget you can always Contact Us. (1)

Are Clinical Studies For You?

National Institutes of Health

  • What Are Clinical Studies?
  • What Are the Costs?
  • Why Participate?
  • Risks and Benefits
  • Dealing with Fears
  • About Informed Consent
  • Who Participates?
  • Information for Healthy Volunteers
  • What Are the Main Types of Studies?
  • Making the Decision

What Are Clinical Studies?

Clinical studies are medical research studies in which people participate as volunteers. Clinical research studies (sometimes called trials or protocols) are a means of developing new treatments and medications for diseases and conditions. There are strict rules for clinical trials, which are monitored by the National Institutes of Health and the U.S. Food and Drug Administration. Some of the research studies at the Clinical Center involve promising new treatments that may directly benefit patients.

Our database of clinical studies being conducted by the National Institutes of Health at the Clinical Center in Bethesda, Maryland is accessible at Search the Studies. If you have any questions about participating in a clinical study here, please contact the Patient Recruitment and Public Liaison Office at: 1-800-411-1222, TTY 1-866-411-1010.

What Are the Costs?

The Clinical Center does not charge patients for participation and treatment in clinical studies at NIH. In addition, incertain emergency circumstances, you may qualify for help with travel and other expenses.

Why Participate?

Patients taking part in NIH Clinical Center studies are seen by a team of expert doctors, dentists, nurses, technicians, and support staff.

Clinical Center patients often are first to receive promising new treatments before they become available in the community.

Patients are helping others with the same disease, both today and in the future.

Risks and Benefits

It is important to understand that some risks are involved in clinical research, just as in routine medical care and activities of daily living. In thinking about the risks of research, it is helpful to focus on two things: the degree of harm that could result from taking part in the study, and the chance of any harm occurring. Most clinical studies pose risks of minor discomfort, lasting only a short time. Some volunteer subjects, however, experience complications that require medical attention. The specific risks associated with any research protocol are described in detail in the consent document, which you are asked to sign before taking part in research. In addition, the major risks of participating in a study will be explained to you by a member of the research team, who will answer your questions about the study. Before deciding to participate, you should carefully weigh these risks against possible benefits. You may or may not receive direct benefit foryourself and your condition as a result of participating in research, but in either case, you will know that the knowledge developed may help others.

Dealing with Fears

Many protections and safeguards for volunteer patients are built into the Clinical Research process. It may help alleviate some of your fears about participating in a clinical study to know what some of these are:

The Patient Bill of Rights.

All patients who take part in studies at the Clinical Center are protected by the Patient Bill of Rights, developed by the American Hospital Association for use in hospitals across the country. The Patients' Bill of Rights contains guidelines to ensure privacy and confidentiality of patients and their medical records.

Hospital Accreditation.

As in any medical research facility, an institutional review board (IRB) must review and approve every new study at NIH before the study can begin. The IRB is made up of medical specialists, statisticians,nurses, social workers, medical ethicists, and members of the community. The IRB reviews protocols to ensure patient safety. In addition, The Joint Commission on Accreditation of Healthcare Organizations (JCAHO), periodically reviews the Clinical Center hospital to see if stringent standards, leading to JCAHO accreditation, have been met.

Informed Consent.

Before entering a Clinical Center study, it is important that you as the patient fully understand the study and what your involvement would mean. Clinical Center staff members will help by providing you with an informed consent statement, which has detailed information about the study, including the length of the study, the number of visits required, and medical procedures and medications included. It also provides expected outcomes, potential benefits, and possible risks.

Clinical Center staff will review the informed consent statement with you and answer your questions. If you decide to participate after reviewing the statement and talking with staff and family members, you will need to sign the informed consent statement. Your signature indicates that you understand the study and agree to participate voluntarily.

Who Participates?

People who take part in Clinical Center studies include:

Children and adults wishing to improve their own health. They may be patients with newly diagnosed medical problems. They may have had the problems over a period of time, or they may have a family history of a certain disease.

Healthy volunteers who seek to advance knowledge about causes, progress, and treatment of disease also can participate in clinical research. They provide important medical information to researchers by helping them compare how healthy people differ medically from those who have a specific disease.

To participate, patients and healthy volunteers must meet certain requirements, which are different for each study.

Information for Healthy Volunteers

There are about 300 studies available to healthy volunteers. You can find information on these studies at Search the Studies. (To search for studies accepting healthy volunteers, type in the keywords: 'healthy' and 'normal'.)

Will I be compensated as a healthy volunteer? Yes. NIH compensates volunteers for their time and, in some instances, for the inconvenience of a procedure. There are standard compensation rates for the volunteer's time; the study's principal investigator determines inconvenience rates.

How can I volunteer?

If you are considering volunteering, please call 301-496-4763 or 1-800-892-3276 to talk to a staff member. You will need to come to the CRVP office to register for participation in a study. More information about the Clinical Research Volunteer Program is available at Program for Healthy Volunteers.

What Are the Main Types of Studies?

There are four types of drug studies:

  • Phase 1 studies test a potential new drug with a small number of volunteers for best dosage and potential side effects.
  • Phase 2 studies test a drug with known dose and side effects with a larger number of volunteers to learn more about side effects, how the body uses the drug, and how the drug helps the condition.
  • Phase 3 and 4 studies compare the new drug with a commonly used drug.

Other research may provide only indirect benefit to the patient by giving researchers information that may be an important first step toward developing a treatment. For example, research may show how a disease progresses or how it affects others systems in the body.

Patients can take part in clinical studies covering a wide range of medical diseases, conditions, and rare disorders affecting both children and adults, including those relating to AIDS, aging, alcohol abuse and alcoholism, allergy, cancer, digestive and kidney problems, diabetes, eye disorders, infectious diseases, genetics, mental health, neurological disorders, stroke, and others. There is an online database of current studies.

Making the Decision

It is important that patients be well informed and feel confident and secure about participating. Before deciding to participate, you should talk with your own doctors, family members, and Clinical Center staff. Be sure you know the answers to the following questions before you make your decision:

  • What is the purpose of the study?
  • What is required of me?
  • What is my role in the study – am I a healthy volunteer or a patient volunteer?
  • Will the study directly benefit me?
  • Will the study benefit others?
  • Are there risks? If so, what are they and what are the chances that they will occur?
  • What discomforts are involved?
  • What is the total time involved?
  • Are there other inconveniences?
  • Have I discussed participation in the study with those who are important to me, such as family and friends?
  • Do I wish to participate in this study?

To take part in studies at the Clinical Center, referral by a medical practitioner is preferable. However, in certain instances, self-referral may be appropriate.

Patients and volunteers become partners in a special relationship with members of the research team who are searching for better ways to understand and treat disease. Their participation is critical for improving health today and in future generations. Please call us at 1-800-411-1222, or e-mail us at prpl@mail.cc.nih.gov with any questions about how you or someone you know might participate.(2)

Types of Clinical Trials

Clinical trials can be divided into observational and interventional studies.

  • Observational studies: individuals are observed and their outcomes are measured by the investigators (e.g., natural experiment). The researchers do not actively manage the experiment; they merely observe the effects of pre-existing factors on the individuals.
  • Interventional studies: the research subjects are given a particular medicine or other intervention, and the researchers measure how their health changes.

The U.S. National Institutes of Health (NIH) organizes trials into five (5) different types:

  • Treatment trials: test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
  • Prevention trials: look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes.
  • Diagnostic trials: conducted to find 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 ways to improve comfort and the quality of life for individuals with a chronic illness.

Responsibilities of the Sponsor

For safety reasons, many clinical trials of drugs are designed to exclude women of childbearing age, pregnant women, and/or women who become pregnant during the study. In some cases the male partners of these women are also excluded or required to take birth control measures.

Throughout the clinical trial, the sponsor is responsible for accurately informing the local site investigators of the true historical safety record of the drug, device or other medical treatments to be tested, and of any potential interactions of the study treatment(s) with already approved medical treatments. This allows the local investigators to make an informed judgment on whether to participate in the study or not.

The sponsor is responsible for monitoring the results of the study as they come in from the various sites, as the trial proceeds. In larger clinical trials, a sponsor will use the services of a Data Monitoring Committee (DMC, known in the U.S. as a Data Safety Monitoring Board). This is an independent group of clinicians and statisticians.

The DMC meets periodically to review the unblinded data that the sponsor has received so far. The DMC has the power to recommend termination of the study based on their review, for example if the study treatment is causing more deaths than the standard treatment, or seems to be causing unexpected and study-related serious adverse events. The sponsor is responsible for collecting adverse event reports from all site investigators in the study, and for informing all the investigators of the sponsor's judgment as to whether these adverse events were related or not related to the study treatment. This is an area where sponsors can slant their judgment to favor the study treatment.

The sponsor and the local site investigators are jointly responsible for writing a site-specific informed consent that accurately informs the potential subjects of the true risks and potential benefits of participating in the study, while at the same time presenting the material in a reasonably short and comprehensible fashion.

Internet Citations

See Also

Lymphedema People Resources

how_to_understand_clinical_trials.txt · Last modified: 2012/10/16 14:40 (external edit)