What is a clinical trial or clinical study?
Why test experimental/investigational drugs in humans?
What are the benefits of participating in a clinical trial?
What are the risks of participating in a clinical trial?
What is informed consent?
What questions should I ask before agreeing to participate in a study?
How do I know a study is safe?
Will I know what drug I am taking?
Will my privacy be protected?
What is a clinical trial or clinical study?
A clinical trial (also called medical research and research studies) is a research study in human volunteers used to determine whether new drugs or treatments are both safe and effective. Clinical research studies rely on patient volunteers to try new or changed treatments. Sometimes they are new "experimental" or "investigational" medicines that have not been approved by the Food and Drug Administration (FDA) for sale in the United States. New therapies are tested in humans only after laboratory and animal studies show promising results. Sometimes they are drugs that are currently available for sale but are being tested for a new disease or new doses or formulations of the same medicine. Carefully conducted clinical trials are the quickest and safest way to find new treatments that work in people and ways to improve health.
Back to top
Why test experimental/investigational drugs in humans?
Before a medication can be sold over the counter or with a prescription, it must undergo rigorous testing. The process by which new medications are tested so they may ultimately be marketed to treat or cure various diseases or conditions is as follows:
1. Development of a Compound
Chemists in a laboratory develop compounds with a certain chemical structure that the scientists believe may function in humans to alleviate certain symptoms in a disease, or perhaps even cure it.
2. Pre-clinical Testing
To prove that the compound works as is hypothesized and does not produce any negative side effects, it is first thoroughly tested in animals (e.g.., mice, rats, dogs, monkeys). This stage of testing is commonly referred to as the "pre-clinical" stage. The purpose of these animal studies is to prove that the drug is not carcinogenic (cancer causing), mutagenic (causing changes in the genetic material), or teratogenic (causing fetal malformations), and to understand how the drug is absorbed and excreted. Once a pharmaceutical company proves that the compound appears to be safe, and possibly effective in animals, the company will provide this information to the Food and Drug Administration (FDA) requesting approval to begin testing the compound (experimental drug) in humans via an Investigational New Drug (IND) application.
3. Clinical Trials/Studies in Humans
The clinical testing (investigation) of experimental drugs (previously unproven in humans, therefore "experimental") in humans is normally done in three phases (Phase 1, 2 and 3) with more and more people included in each subsequent phase. Although in general the phases are conducted sequentially, they may overlap. The three phases for testing experimental drugs are as follows:
Phase 1 Clinical Studies
Phase 1 studies are primarily concerned with the drug's safety, and are the first time the drug is tested in humans. These studies are typically done in a small number of healthy volunteers (20-100), usually in a hospital setting where the volunteers can be closely watched and treated should there be any side effects. These volunteers are usually paid for their participation and for the most part tend to be men (approximately 30 years of age on average). The purpose of these studies is to determine how the experimental drug works in humans. That is, how is the drug absorbed, metabolized, and excreted. Additionally, they seek to determine what types of side effects occur as the dosage levels (that is, the amount of drug) are increased, as well as to obtain early evidence on drug effectiveness.
Phase 2 Clinical Studies
Once an experimental drug has been proven to be safe and well tolerated in healthy volunteers, it must be tested in the patients that have the disease or condition that the experimental drug is expected to improve/cure. In addition to ensuring that the experimental drug is safe and effective in the patient population of interest, Phase 2 studies are also designed to evaluate the effectiveness of the drug. The second phase of testing may last from several months to a few years and up to several hundred patients. Most Phase 2 studies are well controlled, randomized trials. That is, one group of patients (subjects) will receive the experimental drug, while a second "control" group will receive a standard active treatment or placebo. Placement of the subject into the drug treatment or placebo group is by random chance (as if by the flip of a coin). Often these studies are "double-blinded", that is, neither the patient nor the researchers (investigator, coordinator, etc.) know who is getting the experimental drug. Additionally, Phase 2 studies are often designed to determine the correct dosage, which is the dosage with the least number of side effects that is most effective. These are often referred to as dose-ranging studies. In general, the purpose of Phase 2 studies is to provide the pharmaceutical company and the FDA comparative information about the relative safety of the experimental drug, the proper dosage, and the drug's effectiveness. Only about one-third of experimental drugs successfully complete both Phase 1 and Phase 2 studies.
Premier Research has been heavily involved in the Phase 2 testing of numerous experimental drugs for acute and chronic pain. Many of these experimental drugs moved into Phase 3 testing and were ultimately approved by the FDA for use in acute and chronic pain.
Phase 3 Clinical Studies
In a Phase 3 study, an experimental drug is tested in several hundred to several thousand patients with the disease/condition of interest. Most Phase 3 studies continue to be randomized and blinded. The large-scale testing provides the pharmaceutical company as well as the FDA with a more thorough understanding of the drug's effectiveness, benefits/risks, and range/severity of possible adverse side effects. Phase 3 studies typically last several years. Seventy to 90 percent of drugs that enter Phase 3 studies successfully complete this phase of testing.
4. Marketing of New Drugs
After successful completion of Phase 1–3 testing, a company will submit the results of all of the studies to the FDA to obtain a New Drug Application (NDA). Once the FDA grants a company with a NDA, the company can market the drug (medication) to the public. Additional testing (post-marketing or late Phase 3/Phase 4) to look at the long-term safety continues.
Back to top
What are the benefits of participating in a clinical trial?
Participating in a clinical trial can be a rewarding experience. Consider the following benefits when deciding if you should join a clinical trial:
- You will have access to leading healthcare professionals, cutting-edge new treatments and high standards of care. Subjects can get blood work, ECG monitoring and other rigorous medical care that they might normally not receive.
- Joining a clinical trial can increase your knowledge and understanding of your disease.
- People who take part in clinical trials are contributing to science that may benefit themselves and others. The medications that you take now are available only because people before you have volunteered in clinical trials.
- Although every effort is made to ensure that clinical trials are as safe as possible, clinical trials that test new therapies are experiments and can involve risks.
Back to top
What are the risks of participating in a clinical trial?
Participating in a clinical trial is a personal decision that should be made with the help of family, friends and health care professionals. Since Investigational drugs being tested, typically have been given to a limited number of people, all the risks of an investigational drug may not be known. A health professional will explain the possible risks and side effects during the informed consent process. The informed consent will tell you about known risks associated with the use of the drug and procedures being performed as part of the study, but there is always the potential for unknown, unpleasant or serious side effects. Additionally, the treatment may not be effective for you.
Participating in a clinical trial typically will require more of your time and attention than standard medical care.
Back to top
What is informed consent?
Informed consent is the process of learning the key facts about a clinical trial before deciding whether or not to participate. Before you decide, the doctors and researchers involved in the trial will explain the details of the study. Throughout the trial, they will provide information updates.
You will also receive an informed consent document that explains the potential risks and benefits of the study. The document is not a contract; you can withdraw from the study at any time.
Back to top
What questions should I ask before agreeing to participate in a study?
You should learn as much as possible about any clinical trial you are considering. The first step is to read the informed consent document carefully. If you still have questions, write them down to discuss with the study doctors. It may also be helpful to ask a friend or relative to come along for support and to hear the responses to the questions. The following are sample questions about any study:
- What is the purpose of the study?
- Who is going to be in the study?
- Why do researchers believe the new investigational drugs being tested may be effective? Have they been tested before?
- What kinds of tests are involved?
- How might the test affect my daily life?
- How long with the trial last?
- Will in patient stays/hospitalizations be required? If so, how many and how frequently? How many outpatient clinic visits will I need to make and how long will each visit last?
- What costs, if any, will I be responsible for?
- Will I be reimbursed for other expenses?
- Will I be compensated for my time and effort? If so, how much and when will payments be made?
- What type of long-term follow-up care is part of this study?
- How will I know that the treatment is working?
- Will results of the trial be provided to me? Will I know what treatment I received when the study is over and the results are analyzed?
- Who will be in charge of my care?
Back to top
How do I know a study is safe?
All clinical trials have federally regulated safeguards, mainly via the Food and Drug Administration (FDA) to protect participants. These include:
- An Institutional Review Board (IRB); a board that reviews and approves all protocols and informed consents before enrollment can start; and
- A committee of clinical research experts called a Data and Safety Monitoring Board (DSMB). A DSMB will meet periodically during the conduct of a study to look at the data accumulated to date to determine if there are safety concerns. Such a board may modify or terminate the continuation of a study based on their findings. Not all studies will have a formal DSMB.
Back to top
Will I know what drug I am taking?
Patients should also keep in mind that they may not receive the investigational drug because they may be randomly assigned to the "control" group and receive either, a treatment that is already available that is considered standard therapy for the disease, or a sugar pill (placebo). The control group is used as a basis for comparison. In many studies, the researcher is not aware of who is taking the treatment and who is in the control group. For more information on benefits and risks, see these web sites:
http://clinicaltrials.gov/ct/info/resources
http://centerwatch.com/patient/backgrnd.htm
Back to top
Will my privacy be protected?
Yes! As a study progresses, researchers may report the results of the trial at scientific meetings, in medical journals, and to various government agencies, but individual names will remain secret. Certain professionals involved in the study will require access to your medical records. Their names will be listed in the informed consent document.
Back to top
More Information & Resources
FDA's "Basic Questions and Answers About Clinical Trials"
ClinicalTrials.gov
CenterWatch: Publications for Volunteers and Health Professionals