- What are clinical trials?
- Where do the ideas for trials come from?
- Who sponsors clinical trials?
- What is randomization?
- What is standard of care?
- Are clinical trials safe?
- Why should patients participate in a clinical trial?
- How will patients know if they are eligible for a clinical trial?
- How do patients pay for clinical trials?
- What kind of preparation should a potential participant make for the meeting with the research coordinator or doctor?
- What should people consider before participating in a clinical trial?
- Does a participant continue to work with a primary health care provider while in a clinical trial?
- What are the different types of clinical trials?
- What is a phase in a clinical trial?
- What are Phase I trials?
- What are Phase II trials?
- What are Phase III trials?
- What are Phase IV trials?
- How do drugs and procedures qualify for clinical trials?
- What happens during a clinical trial?
- What are side effects and adverse reactions?
- What are the benefits and risks of participating in a clinical trial?
- How is the safety of the participant protected?
- Can a participant leave a clinical trial after it has begun?
- After the clinical trial ends, what happens to the information and results?
- What is a protocol?
- What is informed consent?
- What is the Institutional Review Board (IRB)?
- What is a Clinical Investigator?
- What is the Food and Drug Administration (FDA)?
- What is a placebo?
- What is a control or control group?
Clinical trials or research studies are organized tests of medicines and new treatment options. These studies rely on patient volunteers who try the new or changed treatment. Patients may enter a trial with their own doctor or with another local doctor who is running a trial they are interested in. If patients go to a doctor other than their own, they are always free to go back to their own doctor for routine medical care. Questions relevant to the trial should always be addressed to the trial doctor for the duration of trial participation. Any clinical trial participation is always voluntary.
Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and in animal studies, the experimental treatments with the most promising laboratory results are moved into clinical trials. During a trial, more and more information is gained about an experimental treatment, its risks, and how well it may work.
Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians, medical institutions, foundations, voluntary groups, and pharmaceutical companies, in addition to federal agencies such as the National Institutes of Health (NIH), the Department of Defense (DOD), and the Department of Veteran's Affairs (VA). Trials can take place in a variety of locations, such as hospitals, universities, doctors' offices, or community clinics.
Randomization is a process used in some clinical trials to prevent bias. Bias occurs when a trial's results are affected by human choices or other factors not related to the treatments being tested. Randomization helps ensure that unknown factors do not affect trial results. If patients participate in such a trial, they will be assigned by chance to either an investigational group or a control group. This assignment will be determined with a computer program or table of random numbers.
- Patients assigned to the control group will get the most widely accepted treatment (standard treatment) for their cancer.
- Patients assigned to the investigational group will get the new treatment being tested or a combination of standard treatment plus the new treatment being tested.
Comparing these groups to each other often clearly shows which treatment is more effective or has fewer side effects. If patients are thinking about joining a randomized clinical trial, they need to understand that they have an equal chance to be assigned to either one of the groups. The doctor does not choose the group for patients.
A standard of care is a medical or psychological treatment guideline, and can be general or specific. It specifies appropriate treatment based on scientific evidence and collaboration between medical and/or psychological professionals involved in the treatment of a given condition.
Clinical trials are conducted in a healthcare setting (a hospital or clinic) and are monitored by a trained healthcare professional. An Institutional Review Board (IRB) approves all clinical trials. This is a committee made up of doctors, ethicists, administrators, and members of the general public. This group is held responsible for agreeing that a trial does not represent an unreasonable risk to patients who are participating. Trials are also reviewed by the Food and Drug Administration. Doctors are responsible for their patient’s well being and are the best person to decide whether their patient is eligible to participate in a trial. Whenever patients agree to enter a trial they are given the names and telephone numbers of a contact in their local physician's office and a member of the IRB who will answer questions or address concerns.
There are many reasons people take part in research studies. Often it gives them a chance to access a medicine that is not available on the market for prescription. If this is the case patients should remember that the study is being performed to find out if the drug works and if it is safe. This means that there is some information that is unknown about the drug and it is considered experimental. Often the process of collecting information in the study will allow doctors to find out more about a patient’s disease and the effects it has on them. This may help patients benefit from better treatment after they’ve completed a trial. A trial may not benefit a patient directly, but the information gathered may be of help to other patients with the same condition. Many patients derive satisfaction from knowing that they are part of the effort to potentially reduce the suffering of other people.
All clinical trials have guidelines about who can participate. Using inclusion/exclusion criteria is an important principle of medical research that helps produce reliable results. The factors that allow someone to participate in a clinical trial are called "inclusion criteria" and those that disallow someone from participating are called "exclusion criteria." These criteria are based on such factors 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 participants. It is important to note that inclusion and exclusion criteria are not used to reject people personally. Instead, the criteria are used to identify appropriate participants and keep them safe. The criteria help ensure that researchers will be able to answer the questions they plan to study.
The clinical trial sponsor (whether it is the government or a company) may pay for the experimental treatment, special testing, extra doctor visits, travel time, and travel expenses. Some health insurance companies will also cover routine costs in clinical trials. Some health insurance companies will cover the costs of procedures that the patients would have even if they were not in a clinical trial (routine costs). For Medicare patients, routine costs are covered in all Medicare-qualified clinical trials. Patients will be responsible for any costs not covered by the clinical trial sponsor or their health insurance company. Therefore, patients should be sure to ask questions before deciding to participate, especially to confirm what costs their health insurance company will cover.
- Plan ahead
- Ask a friend or relative to come along for support and to hear the responses to the questions
- Write down possible questions to ask
People should know as much as possible about the clinical trial and feel comfortable asking the members of the health care team questions about it, the care expected while in a trial, and the cost of the trial. The following questions might be helpful for the participant to discuss with the health-care team. Some of the answers to these questions are found in the informed consent document.
- What is the purpose of the study?
- Who is going to be in the study?
- Why do researchers believe the experimental treatment being tested may be effective? Has it been tested before?
- What kinds of tests and experimental treatments are involved?
- How do the possible risks, side effects, and benefits in the study compare with my current treatment?
- How might this trial affect my daily life?
- How long will the trial last?
- Will hospitalization be required?
- Who will pay for the experimental treatment?
- Will I be reimbursed for other expenses?
- What type of long-term follow up care is part of this study?
- How will I know that the experimental treatment is working? Will results of the trials be provided to me?
- Who will be in charge of my care?
Yes. Most clinical trials provide short-term treatments related to a designated illness or condition, but do not provide extended or complete primary health care. In addition, by having the health-care provider work with the research team, the participant can ensure that other medications or treatments will not conflict with the protocol.
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 are 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.
Most clinical trials are carried out in steps called phases. Each phase is designed to find different information. Patients may be eligible for studies in different phases depending on their general condition, the type and stage of their condition, and what therapy, if any, they have already had. Patients are seen regularly to determine the effect of the treatment, and treatment is always stopped if side effects become too severe. (Please continue for a description of each of the four phases involved in a clinical trial.)
Phase I clinical trials are first-time tests of drugs or treatments on human patients. Though the drug or treatment has not yet been tested on people, researchers have reason to believe it will be beneficial. At this stage, researchers do not know the drug’s effectiveness, the best dose to administer, or what side effects may occur. A suggested starting dose for humans is found through laboratory experiments. All patients involved in Phase I clinical trials receive a form of treatment for their cancer; none areadministered placebos (medically inactive agents sometimes used in medical research for comparison purposes).
Phase II clinical trials begin once an appropriate dosage of the drug is defined through Phase I trials. In this stage of testing, researchers will determine the drug's effectiveness in treating a specific kind and stage of cancer. As in Phase I clinical trials, all patients involved in Phase II clinical trials receive active treatment; none are administered placebos.
Phase III clinical trials test therapies that have proven to be effective in the first two stages of testing. Phase III clinical trials put the new (investigational) therapy in perspective. For example, a phase III trial may compare the current standard therapy against the new investigational therapy. Or, it may compare patients given the investigational therapy and standard therapy with those who are administered only the standard therapy. Patients participating in Phase III trials are randomly assigned to one of the treatments in the study. This means a patient is selected by chance to be in one treatment group or another. This randomization is essential to allow investigators to determine which therapy is truly more effective. While Phase I and Phase II trials may involve a few dozen patients, Phase III trials can include hundreds of patients.
Phase IV trials are conducted to further evaluate the long-term safety and effectiveness of a treatment. They usually take place after the treatment has been approved for standard use. Several hundred to several thousand people may take part in a phase IV study. These studies are less common than phase I, II, or III trials.
Patients who participate in a clinical trial receive drugs or procedures that already have been researched in successful laboratory and/or animal studies. Most clinical trials study new drugs or procedures, but some study drugs or procedures that have already received approval by the U.S. Food and Drug Administration.
The clinical trial process depends on the type of trial being conducted (See What are the different types of clinical trials?) The clinical trial team includes doctors and nurses as well as social workers and other health-care professionals. They check the health of the participant at the beginning of the trial, give specific instructions for participating in the trial, monitor the participant carefully during the trial, and stay in touch after the trial is completed.
Some clinical trials involve more tests and doctor visits than the participant would normally have for an illness or condition. For all types of trials, the participant works with a research team. Clinical trial participation is most successful when the protocol is carefully followed and there is frequent contact with the research staff.
Side effects are any undesired actions or effects of drugs or treatments. Experimental treatments must be evaluated for both immediate and long-term side effects.
Benefits may include the following:
- Playing a more active role in one’s own health care
- Gaining access to new research treatments before they are widely available
- Obtaining expert medical care at leading health care facilities during the trial
- Helping others by contributing to medical research
- Helping scientists find new and better cancer treatments
Risks may include the following:
- Unpleasant side effects
- Serious side effects
- Unknown health risks
The ethical and legal codes that govern medical practice also apply to clinical trials. In addition, most clinical research is federally regulated with built-in safeguards to protect participants. The trial follows a carefully controlled protocol, a study plan which details what researchers will do in the study. As a clinical trial progresses, researchers report the results of the trial at scientific meetings, to medical journals, and to various government agencies. Individual participants' names will remain secret and will not be mentioned in these reports.
Every clinical trial in the U.S. must be approved and monitored by an Institutional Review Board (IRB) to evaluate risk and benefits. An IRB is an independent committee of physicians, statisticians, community advocates, and others that ensures that a clinical trial is ethical and the rights of study participants are protected. All institutions that conduct or support biomedical research involving people must, by federal regulation, have an IRB that initially approves and periodically reviews the research.
Yes. A participant can leave a clinical trial, at any time. When withdrawing from the trial, the participant should let the research team know about it, and the reasons for leaving the study.
As a clinical trial progresses, researchers report the results of the trial at scientific meetings, to medical journals, and to various government agencies. Researchers give patients a number or code to protect their identities. When the clinical trial results are published, patients’ names are not used. Medical professionals around the world use information from these presentations and publications to refine their approach to treating clinical problems. In addition, results from clinical trials are used by regulatory agencies (in the USA, the Food and Drug Administration) to evaluate whether to grant regulatory approval to a new drug or medical device.
A protocol is a study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment.
Informed consent is the process of learning the key facts about a clinical trial before deciding whether or not to participate. It is also a continuing process throughout the study to provide information for participants. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study. If the participant's native language is not English, translation assistance can be provided. Then the research team provides an informed consent document that includes details about the study, such as its purpose, duration, required procedures, and key contacts. Risks and potential benefits are explained in the informed consent document. The participant then decides whether or not to sign the document. Informed consent is not a contract, and the participant may withdraw from the trial at any time.
The IRB is a board consisting of health care professionals from the institution where the clinical trial takes place, as well as members of the local community. The board scrutinizes all trial activities including recruitment, advertising, and potential risks. The IRB also makes sure that FDA regulations are being followed in a particular trial.
A clinical investigator is a medical researcher in charge of carrying out a clinical trial's protocol. Researchers are usually doctors, nurses, pharmacists, or other health care professionals.
The FDA is a government agency that enforces laws on the manufacture, testing, and use of drugs and medical devices. All drugs and medical devices must be approved by the FDA before they can be used by the general public.
A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the experimental treatment's effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or experimental treatment.
A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo.