Clinical research involves testing an investigational drug or device in humans. Each clinical trial must use a protocol that has been written according to government regulations and that is also approved by the company sponsoring the study. An investigational drug may be:
- a drug that has not been approved for marketing (i.e., a drug that is not allowed to be sold)
- a drug that is currently on the market but that is being studied for a non-approved indication or is being studied in a new route of administration, strength, or formulation;
- a drug that is being sold on the market by one company but that is being considered for in-license or acquisition by another company;
- a drug that contains known and established ingredients but has not been marketed by the company;
- a drug that is currently on the market but is being studied in a population for which the drug has not been approved, such as children or elderly patients.
Before an investigational drug or device can be studied in humans, its safety and effectiveness is carefully studied in the laboratory. However, this early research cannot predict how safe and effective the drug will be in humans. With any new treatment there may be benefits as well as known and unknown risks. Clinical research trials are conducted to determine whether promising new treatments will be safe and effective for patients.
Phase I studies involve testing the investigational drug in a small number of healthy adult volunteers. The sole objective of these studies is safety. These studies are designed to determine how the drug is metabolized by the body and what pharmacologic actions the drug has. One objective of these studies is to determine the best way to administer the drugs (i.e., the preferred route).
Phase II studies help determine how safe and effective a drug is, common short-term side effects of the drug, pharmacokinetic effects of the drug (i.e., the amount of drug that gets into the bloodstream, how quickly it gets there, and how long it stays there) and pharmacodynamic effects of the drug (i.e., the effects of the drug on the body). These studies involve a larger group of patients (e.g., 100 to 200 patients) and are usually conducted in patients who have the medical condition for which the drug is being studied. These studies are used to identify the dose range of the drug that will be tested in subsequent larger studies (i.e., Phase III studies).
Phase III studies provide additional information about safety and efficacy when the drug is used in the way it is intended to be marketed. These studies are initiated only after earlier studies have demonstrated that there is an acceptable risk to benefit profile (i.e., the risk of taking the drug is outweighed by the potential benefit of the drug to the patient). These large studies are usually conducted at many different study centers; up to 10 to 30 study centers and between 500 and 5,000 patients may be included. These studies are used to confirm the indication and best dosage for the drug.
Phase IV studies are conducted after the drug is available for sale (i.e., post-marketing studies) and they evaluate how safe and effective the drug is when exposed to the “real” population. These studies evaluate parameters such as different formulations, dosages, treatment durations, and drug interactions. The Food and Drug Administration (FDA) may require a company to conduct certain Phase IV studies as a provision for product approval. These studies may include new age groups, races and other types of patients. These studies are useful for detecting and defining previously unknown or inadequately quantified adverse events and related risk factors. The size of these studies is broad and can range from 5,000 to 20,000 patients.
Clinical trials are sponsored by government agencies such as the National Institutes of Health (NIH); pharmaceutical companies; individual physicians or investigators; health care institutions such as health maintenance organizations (HMOs); and organizations that develop medical devices or equipment. Clinical trials can take place in a variety of locations, such as hospitals, surgical centers, universities, or doctors’/dentists’ offices.
A Principal Investigator (PI) is a person qualified by education, training, and experience to assume responsibility for the proper conduct of a trial. They are usually, but not always, physicians or oral surgeons. The PI bears ethical responsibility for the study and is the leader of the study team. Final responsibility for the quality control of study procedures and the integrity and scientific merit of study findings rests with the PI.
People choose to take part in clinical trials for many reasons. Usually, they hope for benefits for themselves such as hope for a cure of disease, a longer time to live, an increased quality of life, or a way to decrease or eliminate pain. Some people choose to participate because of the financial compensation they receive. Others may want to contribute to a research effort that may help others.
People who participate in clinical trials are among the first to receive new research treatments before they become widely available. Sometimes these people have the first chance to benefit from a cutting-edge treatment. However, there is no way to know whether an investigational treatment will be effective for a patient. (Even standard treatments, although effective in many patients, do not guarantee benefits for everyone.) Some people in a study may not receive the active treatment and instead will receive a placebo (i.e., a sugar pill). Although all patients in clinical trials are carefully monitored both during and after conclusion of the trial, there are always known and unknown risks associated with new treatments. Patients should decide whether or not to participate in a study only after they understand both the potential risks and benefits.
All clinical trials have criteria that determine who is allowed to participate. You cannot participate in a study if you don’t meet all of the study criteria. These criteria include such factors as age, type of disease, medical history, and current medical condition. Some studies seek volunteers with specific medical conditions and others seek healthy volunteers. It is important to note that these study entry 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 study procedures and process will vary depending on the type of clinical trial you participate in. Before you begin a study, the process and all procedures for that study will be explained to you. Throughout the study, the Study Coordinator and the Principal Investigator will assist you and can answer any questions you have. They will check your health at the beginning of the trial, give you specific instructions for participating in the trial, monitor you carefully during the trial, and stay in touch with you after the study.
Some clinical trials involve more tests and doctor visits than you would normally have for your illness or condition. Your participation will be most successful if you carefully follow all instructions you are given and stay in contact with the research staff.
Most all investigative treatments can cause side effects and other health risks. Side effects and health risks vary from patient to patient. The number of side effects, if any, you experience will depend on the type of treatment being studied and your medical condition. Because clinical trials evaluate new medical treatments, the risks of the treatments are not always known ahead of time. However, in every study several safeguards are put in place to protect the safety of the participants. Before you agree to participate in a study, it is important that you know what side effects may occur and, as much as possible, what unknown side effects or risks may occur. This information will be covered thoroughly during the informed consent process before you enroll in the study.
Several safeguards have been put into place that all companies must follow when conducting clinical trials.
The Food and Drug Administration (FDA) is the regulatory agency that oversees all clinical research conducted in the United States. They are responsible for protecting the rights and, to the degree possible, the welfare of subjects participating in clinical trials. They ensure that data collected from clinical trials is of high quality and they are the agency that determines whether a new treatment should be sold in the US. Several organizations and individuals are governed by FDA regulations including clinical investigators, sponsors (i.e., the companies developing the treatments), Contract Research Organizations (i.e., companies that help conduct the studies), and Institutional Review Boards (groups that are responsible for ensuring the safety and welfare of study participants).
Good Clinical Practice (GCP) guidelines are another safeguard implemented to protect the safety of subjects. These guidelines encompass federal regulations and industry-accepted standards that govern clinical trials on humans. These regulations and standards apply to the conduct of the studies, record keeping, informed consent of subjects, collection of scientific data, and submission of information needed for the FDA to determine whether a new treatment should or should not be sold in the US. All companies must follow these guidelines when conducting clinical research.
An Institutional Review Board (IRB) is a committee that is formally tasked by an institution to review, approve, and monitor research involving human subjects. IRBs ensure that the risks to subjects are minimized; that subjects are adequately informed about the trial and the implications it will have on their treatment; that study protocols are modified, when necessary, to ensure safety; that risks are reasonable in relation to the anticipated benefits and the importance of the knowledge to be gained; that subject selection is equitable and that no classes of patients are discriminated against; that informed consent is obtained; that there is a provision for safety monitoring in the research plan; and that here are adequate provisions for the privacy and confidentiality for subjects and the data collected.
A protocol is the set of rules that must be followed during a clinical trial. It describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study. Before a clinical trial can start, the FDA and IRB must review the protocol.
Informed Consent is a freely given agreement on the part of a competent person in full possession of all available, pertinent information to participate as a subject in a clinical research trial. Consent may only be given by the study subject unless the subject is a minor or otherwise incapable of acting on his or her own behalf. In this case, consent may be given by the subject’s parent or legally acceptable representative. Informed consent is documented by means of a written, signed, and dated Informed Consent form. Food and Drug Administration (FDA), International Conference on Harmonization (ICH), Good Clinical Practice (GCP), and Institutional Review Board (IRB) regulations require that Informed Consent be obtained before any subject may participate in a clinical trial.
A placebo is an inactive substance (pill, liquid, or powder) that has no treatment value. It may be referred to as a “blank” or “sugar pill.” In placebo-controlled clinical trials, experimental treatments are compared with placebos to assess the treatment’s effectiveness.
Some participants in these studies may receive placebo rather than active treatment. In pain studies, patients who receive placebo (as well as those who receive active treatment) will always have access to ‘rescue medication’, which is a standard pain medication given for the condition or procedure being studied. As soon as you feel that you need more pain medication, you will be given a rescue dose of the standard pain medication. Asking for rescue pain medication will not in any way have a negative impact on your participation in the study.
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 your health care provider work with the research team, you can ensure that the other medications or treatments you are using will not conflict with the clinical trial protocol.
Yes, you can leave a clinical trial at any time. This is called “withdrawing your consent.” If you plan to stop participating in a study, inform the Study Coordinator or Principal Investigator that you would like to withdraw your consent. You should also inform the Study Coordinator or Principal Investigator of your reason for withdrawing.
You will usually be paid for your time and travel while participating in a clinical study. Surgery, medical exams, and medical procedures may also be performed at no cost to you depending on the type of study. If a study requires you to stay at a research facility for any length of time, you may also receive meals or snacks.