Clinical Research Studies Frequently Asked Questions
This material has been excerpted with permission from a comprehensive guide, "Should I Enter a Clinical Trial? A Patient Reference Guide for Adults with a Serious or Life-Threatening Illness" published by ECRI, a nonprofit health services research agency and collaborating center of the World Health Organization, 5200 Butler Pike, Plymouth Meeting, PA, 19462.
What is a clinical trial? The purpose of trials is to gain knowledge about new treatments that might benefit future patients. But in the trial, the new treatment is still under investigation to see how well it works. Although "new" often implies "better" in our culture, the fact is that until clinical research on a new treatment is complete, we do not know if it is better, the same as, or worse than standard treatments. The only way to find out is through well-designed and well-conducted clinical trials.
Is participating in a trial different from receiving treatment outside of a clinical trial? Yes. From a patient perspective, it is important to understand that the main purpose of treatment in a clinical trial is different from the purpose of treatment outside a clinical trial. Treatment in a clinical trial is intended to benefit society and future patients by advancing medical knowledge. It is important to understand that individual patients may or may not benefit from the experimental treatment in a trial; this is why the trial is being conducted - to find out how well it works. However, patients may experience other types of immediate benefits, such as the comfort and support that can come from being part of a group of patients with the same condition being treated and closely monitored by a team of experts.
For patients in trials, there are risks associated with participating because researchers cannot guarantee that a treatment being tested will provide a benefit. In a trial, there is only the hope that it will. The very reason for doing the trial is to find out if the treatment works. Weighing the risks and benefits to make an informed decision about whether to participate can be complicated. In making an informed decision, it is necessary to understand something about the different types of trials, the right questions to ask, and patients' rights as trial participants.
What are the different types of clinical trials, and what do I need to know about them? There are four general phases of trials in humans (phases one through four). Human trials cannot begin until laboratory and/or animal tests on the new treatment under investigation have been completed in "preclinical studies." The results of each phase must show that there are no serious safety problems and that the experimental treatment holds some promise before it can be tested in the next phase.
The risks involved and impact of one trial on quality of life could be very different." The different phases of the trials are as follows:
* Note: NMMC engages in Phase two, three and four trials
- Phase one trials--assess safety and toxicity of the treatment in a small group of healthy volunteers or patients with the disease of interest. Phase I trials are not designed or intended to be therapeutic. These trials cannot promise individual patients any therapeutic benefit because very little is known at this point about the treatment's activity in humans. Phase I trials lay the groundwork for the next phases of trials that begin to test efficacy (how well the treatment works).
- Phase two trials--further test safety and begin to test efficacy, typically in 50 to 300 patients with the condition or disease for which the treatment is intended. Phase II trials may take up to two years.
- Phase three trials--study safety and efficacy in a larger group, perhaps thousands of patients, and look for uncommon adverse reactions. This phase may last several years. Phase III trials typically compare the new treatment to standard treatment(s) and perhaps a placebo, if it is ethical to use one (trials for life-threatening diseases rarely use placebos). Trials that compare treatments are controlled trials and may involve random assignment of patients to different treatment groups.
- Phase four trials--are sometimes done after a new drug or device has received U.S. Food and Drug Administration (FDA) approval and is being used by the general public. Phase IV trials determine longer-term effectiveness and identifies rarer side effects. FDA does not require this phase of trial for all newly approved drugs or devices - it depends on whether FDA believes some questions still need to be answered.
Patient safety, the protection of patients' rights in clinical trials, and the impact of trial participation on a patient's quality of life are the main reasons it is worth taking the time to understand something about the different kinds of clinical trials. Different kinds of trials offer different potential benefits and risks; they also require different levels of participation by patients. For example, a trial that is done on an outpatient basis may have a very different impact on a patient's lifestyle than a trial that requires hospitalization. Some trials may require follow-up tests that are time-consuming and/or invasive, such as a biopsy, and others may just require an office visit and quick exam. Some trials may last less than a year; others may last five years or longer. Factors like these may affect a person's desire and ability to participate.
How will I learn about the risks and benefits of participating in a trial? An eligible patient cannot enroll in a trial until the known benefits, risks, purpose, and plan for the trial have been thoroughly explained and all the patient's questions have been answered. This is called the consent process. It is also often called informed consent. It is very important to take the time to read and consider all the information provided and to ask questions. That often means taking the consent form home to read it again and discussing it with close family, friends, and advisors. Also, taking a trusted family member or friend along to the consent interview may be helpful so someone else hears the same information and you can discuss it later. If a patient decides to enroll in a trial after the interview, he or she signs a consent form and keeps a copy for future reference. This document contains everything that was explained orally, including the contact information for someone on the research team who can answer questions and respond to emergencies.
Even after a patient enrolls in a trial, he or she can withdraw at any time for any reason. Should you choose to withdraw, it is very important to let the researchers know why you are withdrawing so they can collect important data that may affect the way they are conducting the trial. Patient consent is an ongoing process throughout the trial. If important new information is gained about the experimental treatment during the trial, researchers are required to share it with patients and reconfirm their consent to participate.
The following information may help you determine whether you have received all the information you need for your decision making before signing a consent form:
- Explanation that the trial involves research
- Summary of results from previous trials that led to this trial
- Purpose of the new research and what it is trying to achieve
- Duration of the trial for the patient if he or she remains in it until the end
- Detailed description of each test and treatment that will be given according to the trial protocol
- Timing and location of those tests and treatments and how they are scheduled for the patient
- Identification of any procedures that are experimental
- Description of any foreseeable risks or discomforts from any test or treatment given
- Description of any possible benefits to participants or others
- Description of treatment alternatives that might help participants
- Statement about the extent to which confidentiality of participants' records will be maintained
- Explanation of whether any compensation and/or medical treatments are available if injury occurs from treatment in the trial. If so, what are they and who will provide them?
- Whom to contact with questions about the trial and the participant's rights
- Whom to contact in the event of a research-related injury
- Statement that participation is voluntary and that participants may refuse or discontinue participation at any time without penalty
- Itemization of direct costs to the patient as a result of participation
How can I learn about trials I might be eligible for? The North Mississippi Health Services Institutional Review Board (IRB) currently oversees more than 60 biomedical and behavioral studies.
Will I be eligible for the trial I want to enroll in? When you find out about a trial that you might be interested in, you will need to contact the researchers to find out if you are eligible. Every trial has eligibility criteria (also called inclusion and exclusion criteria). These criteria state what patient characteristics make the patient eligible or ineligible for the trial, such as age, health, disease stage, previous treatment, and other coexisting health conditions. Even when people have the same disease, there can be important differences among patients. For example, patients may be in different stages of the disease, which might mean that they should get different treatment. Or, patients may have other health conditions that exclude them from the trial. So, there are several reasons for eligibility criteria. First, patient safety is a major concern. Second, the researchers have an objective. They are trying to gather data in the trial to answer some very specific questions. They need to be able to account for factors that can affect patient treatment and outcome. Some patient characteristics can get in the way of being able to tell if the treatment works or not; those characteristics may be excluded so that researchers will be able to answer the questions they set out to answer.
Who ensures patient safety and the qualifications of the researchers and research organization involved in the trial? Several federal agencies have different roles for protecting patient safety and rights in clinical trials. Food and Drug Administration (FDA) has oversight of trials that are testing new drugs and medical devices before they are brought to market. National Institutes of Health (NIH) oversees trials that it funds at institutions throughout the country. Office for Human Research Protections (OHRP) works with FDA, NIH, and other federal agencies to provide training to researchers and to help ensure patient protections according to federal regulations. The local Institutional Review Board (IRB) reviews the trial protocol for every trial conducted in its institution and/or affiliated facilities.
Do all the patients in a trial receive the same treatment? It depends on the type of trial. For trials that have more than one treatment group, scientific processes may be used to assign patients randomly to treatment groups. The purpose of randomization is to evenly distribute patient characteristics in each group in a trial to ensure valid results. It is also done to prevent researchers from influencing (consciously or unconsciously) to which group patients are assigned. Some patients have said that they do not want to enroll in a trial because they might be randomly assigned to a treatment group. They have expressed feelings that it takes away some control and choice about treatment. They also fear being assigned to the control group, which is the group that receives some other treatment and not the experimental treatment. Some patients believe the experimental treatment is better because it is new. Others fear being assigned to a group that receives placebo (inactive treatment). The following are some key points to keep in mind:
- For patients with a life-threatening disease, the control groups virtually always consist of other treatments that have some proven efficacy. Placebos are very rarely used. Remember, the main point of the trial is to determine how well the experimental treatment works because no one knows yet if it is better than, the same as, or worse than standard treatment. A control group is a group that receives some other treatment of known efficacy in the trial. Results from the experimental treatment group are compared to results from the control group to see how well it works. Placebo is an inactive treatment usually designed to look exactly like the real treatment. It is often thought of as a pill, but can also be an injection, a physical manipulation, a device that is inactive, or any other appropriate procedure that simulates the experimental treatment. There are stringent federal and ethical guidelines about when a placebo can be used. It can only be used when there is no risk of harm to the patient who receives placebo instead of the experimental or standard treatment.
- A treatment that is new and experimental is not necessarily better. The experimental treatment may be the same as, better, or even worse than the standard treatment. Keep in mind that control groups often receive the current gold standard in treatment. The risks may be greater in the experimental treatment group because less is known about the treatment. Also, patients in the control group receive the same close monitoring and evaluation as those in the experimental group. So, no matter which group a patient is in, he or she will receive excellent care for the condition being treated by a team of researchers.
- Several studies have shown that patients participating in trials survive longer than similar patients who were eligible for a trial but chose to receive treatment outside a trial. The reasons for this are not clear, but some believe that this is because, typically, patients in a trial receive closer medical attention and more follow-up visits to monitor their condition than patients who are not in a trial.
Should I be concerned about any conflicts of interest of my personal physician or the research organization? At North Mississippi Health Services, all research doctors are required to sign a conflict of interest form before becoming involved in a research trial.
Will I incur any costs by participating in a clinical trial? There are tangible and intangible costs that patients may want to consider. Tangible direct costs may vary depending on the type of trial you have entered. Decisions about charging trial participants for experimental drugs and devices that are not yet FDA approved are guided by professional ethics, institutional policies, and FDA regulations. In drug trials, there is rarely a cost to the patient for the experimental drug - the sponsor absorbs the cost of this as part of its research and development cost unless FDA has given the company special approval to charge for the drug. For trials that involve a device, there often is a cost for the device. Whatever the direct costs of care, any patient enrolling in a trial must be informed of those costs. Regulations require that the consent form outline all costs for care that will be billed to patients or their insurance companies as a result of participation in the trial. FDA does not prohibit charging participants for treatment or services in a trial. The IRB overseeing the trial has the responsibility to ensure that any such charges are appropriate and fair.
Some costs for clinical trial participation may also be "indirect," but very important to consider. These would include the costs for travel, lodging, and additional lost time from work when participating in a trial. The clinical trial research coordinator or a patient advocate from the trial may be able to help you figure out what those costs would amount to over the full course of the trial. You should also ask who is responsible for paying the costs of treatment for any complications or side effects caused by trial participation, should they occur.
Intangible costs of the trial include separation from loved ones during the trial and other quality-of-life issues affecting a patient's daily life activities. For example, side effects from treatment, even if they are deemed "minor" and "temporary," such as nausea, can significantly affect a patient's activities and feelings. So, it is important to consider the potential impact of the trial on your activities, quality of life, and relationships with loved ones.
Will my health insurance pay? Many health insurers and Medicare now pay for costs of routine care given in the context of a clinical trial. Routine care costs typically include the medical care a patient would need whether or not he or she was in a trial. Examples of a routine cost might be the tests that are needed for diagnosis and staging of the disease or some of the patient checkups needed to monitor disease status. Patients will need to check with their insurers about what costs of trials are covered. Some states have mandated health insurers to cover some of the costs of participation in trials.
Should I be concerned about the privacy of my personal health information when participating in a clinical trial? North Mississippi Health Services is in compliance with HIPAA (Health Insurance Portability and Accountability Act) which ensures the privacy of medical information. The HIPAA regulations also protect personal health information that is used in clinical trials. The NMHS IRB oversees the privacy requirements of all clinical trials and ensures compliance with all state and federal regulations that protect your personal health information.