- Overview: Clinical trials are done with human volunteers to add to medical knowledge to try and find new ways to treat, prevent, or detect diseases. They are a way to test if new investigational medications are safe and effective in treating the disease they are intended for. There are two types of clinical trials-interventional and observational.
- Types of studies: Interventional studies are what people typically think of when thinking of research. Individuals are given a certain intervention (medication, surgery, etc.) to see if it is helpful. Observational studies gather important information about diseases and often look at cause and effect relationships. Patients in observational studies are not offered any new treatment options.
- The idea for a clinical trial usually starts in a laboratory. Researchers first test their new product with animals to see if it does what they hope. They look to see if it is safe and helpful. Once this is done, the drug can be tested in humans to see if we get the same results
- Sponsor: Every study is funded by an organization such as a pharmaceutical company, federally funded agencies (such as NIH), or an individual or organization. They are referred to as the sponsor of the study. The sponsor makes a lot of decisions about the study and chooses sites (or locations) that the study will be performed.
- Site: There are many locations that the study can be performed. At each site, there is a principal investigator (PI), who is usually a doctor, and study coordinators that conduct the study. While you are in a study, you will generally see the same study coordinator and provider throughout the study. Most of the study tasks will be done with the study coordinator, and they should be your primary contact throughout the study.
- Protocol: Each study has a written out plan of what everyone conducting the study needs to do; this is called the protocol. The protocol is written to protect the participants’ health and answer a particular research question. The medication and dosages are reviewed in the protocol as well as who is eligible for the study. The protocol also outlines what needs to be done at each visit and what time period they need to be done in.
- IRB review: Studies are reviewed by an independent committee called the Institutional Review Board (IRB). The IRB reviews the protocol and study materials to confirm that, in their eyes, the risk is worth the potential benefit in the study. The primary goal of the IRB is to ensure the rights of the participants are maintained and the study is conducted ethically.
- FDA: The Food and Drug Administration (FDA) also provides oversight to interventional studies to also ensure that volunteers’ rights and welfare are maintained and that the data is accurate. The FDA provides guidance on what should be done during a study. Once a study is completed, the sponsor can submit their data to the FDA to be reviewed. The FDA decides if there is enough evidence that the investigational medication is safe and effective to be approved and prescribed.
- Phase 1: This phase of studies is done with a small number of patients, typically 20-100 people, either healthy volunteers or people with the disease. Phase 1 studies are used to evaluate the safety of the drug, determine a safe dose, and look at side effects. This phase does not look at the effectiveness of the drug at all. The FDA states that approximately 70% of drugs move on from this phase.
- Phase 2: Phase 2 studies are done to determine the effectiveness and further look at the safety of the investigational product. This phase of study is done in up to several hundred patients with the disease. The FDA states that approximately 33% of drugs move to the next phase.
- Phase 3: In phase 3 studies, 300-3000 patients with the disease participate to further look at the safety and efficacy of the investigational product. The FDA states that approximately 25-30% of drugs move to the next phase.
- Phase 4: These studies with several thousands of patients and are done after the drug has been approved by the FDA to provide further long term data including risks, benefits, and optimal use.
Not everyone can, or has the desire, to participate in clinical trials, but finding volunteers is very important. A drug may look promising in animal models, but it needs to be tested in humans to ensure that it is safe and effective. New treatment options cannot be approved without clinical trials. One of the biggest obstacles in getting new medications approved is recruitment. Sponsors consistently have challenges getting enough patients into their studies in the time that they had predicted. This is costly, delays therapy, and can discourage further clinical research.
- Hope: many patients find that working towards new treatment options gives them hope; not only for themselves but also for future generations.
- Medical attention: In clinical research, your safety is our primary concern. Safety is constantly being monitored, and you will be made aware of any concerns that may arise. If, during a trial, we find that we cannot treat you adequately, or your safety is jeopardized, you will be removed from the study. Additionally, you have more frequent visits with doctors who are monitoring your condition while you are participating in the study.
- New options: When you participate in a clinical trial, you have the chance of receiving new, cutting edge therapies that are not currently available. Since this is an investigational product, it cannot be promised to you that this will help your condition. Additionally, in phase 2 and 3 studies some patients do not receive study medication during the study. Some participants receive placebo (a sugar pill) so that they can be compared to the participants receiving the investigational product to see if it does make a difference. Many studies will give patients who complete the study the opportunity to definitely receive the investigation product without a chance of placebo. This is called an open-label.
Inclusion/Exclusion: Each study has criteria that the participants must meet called inclusion/exclusion. These include things such as age, gender, disease stage, medical history, and medications that they are currently taking. Inclusion/exclusion criteria are not created to exclude certain patients from research studies. The criteria are created to ensure that participants are safe and that the data is precise.
All clinical research is completely voluntary. Before you decide to participate, it is important that you have been given all the information to make your decisions. It is good to ask questions about the study to decide if it is a good option for you.
- The study
- What is the purpose of the study?
- How does the investigational product work?
- What are the dosages and chance I will be on placebo?
- How long does the study last?
- How many visits are there?
- How long is each visit?
- What is expected of me during the study?
- Does someone have to come with me to the visits?
- Potential risks and benefits
- How many people has this investigational product been studied in before?
- Possible side effects?
- What other options do patients with my disease have?
- Will I be able to continue taking my current medications?
- Who will be in charge of my care?
- Will the doctor be able to change medications if needed during the study?
- Will travel be covered?
- Do I have to pay to be in the study?
- Will I get paid to be in the study?
- Will my insurance be charged?
- Time: Each clinical trial requires your time, but the requirement for each study is different. Before enrolling into a clinical trial, it is important to know how much time you will need to commit to the study.
- You should personally weigh the risks and benefits involved in the study and make sure that you feel comfortable.
- Each study has different risks associated and you should reference the Informed Consent Form for known potential side effects.
- Since these are investigational treatments and medications there may be unknown side effects.
- It is important to consider other treatment options available because while in the trial you maybe limited to other treatment options. However, if another treatment is clearly better at any time during the trial, your doctor will take you out of the trial to provide you with the best possible care.
- Many clinical trials do not help the patients involved.
- Informed consent: The informed consent document is created to ensure that each patient completely understands the study and makes an informed decision about their participation. The consent form contains information about the risks and benefits, the purpose of the study, duration, and procedures.
If you are interested in a study, you will be given a consent form to review. It is encouraged that patients take time to read this document fully and ask any questions that they have during their review. Once a qualified participant reviews the consent and decides that they would like to enroll in a particular clinical trial, they will be brought to the site.
Your first visit will begin by reviewing the informed consent form with the research staff. If you decide to participate, the informed consent document will be signed at this time. If a patient is cognitively unable to sign for themselves, they can verbally agree to the study and their legally authorized representative can sign the consent form on their behalf. The informed consent is not a contract; you are free to withdraw from the study at any time. The informed consent is an ongoing process and the research staff should ensure that you want to continue to participate throughout the study.
- Confidentiality: Confidentiality is important to patients and researchers during clinical trials. When you participate in a clinical trial you are given a random number so that your name is not associated with the data you contribute throughout the study. As with a regular doctor, researchers are required to be HIPAA compliant.
- Drug vs placebo: Most phase 2 and 3 studies are randomized. This means that each patient is randomly assigned to get one of the dosages of the investigational product or placebo. Generally, neither you nor your doctor will know what you were randomized to during the trial. Randomization creates groups that are as alike as possible. This is important in clinical trials because it allows the data from the control group to be compared to the group on the study medication. This comparison provides the best way to prove the effectiveness of a new medication.
- Visits: Each study differs in how many visits there are, the lengths of the visits, and what is done at each visit. During the study, you will be required to come to the research site and perform the procedures outlined in the informed consent document; this generally includes safety measure, like blood draws and vitals, and questionnaires to help determine if the investigational product is working.
- Communication: While you are participating in a clinical trial, it is important that you are open and communicate with your research coordinator. The research coordinator needs to be made aware of any changes to your health; even if you do not think it is related to the study medication. It is also important that you communicate any medication changes that you and your doctors would like to make while you are on investigational product. This is for your safety to ensure that none of your medications interact.
The Common Rule is a federal policy regarding Human Subjects Protection that applies to 17 Federal agencies and offices. The main elements of the Common Rule include: Requirements for assuring compliance by research institutions, requirements for researchers’ obtaining and documenting informed consent, and requirements for Institutional Review Board (IRB) membership, function, operations, review of research, and record keeping. The Common Rule also includes additional protections for certain vulnerable research subjects: Subpart B provides additional protections for pregnant women, in vitro fertilization, and fetuses, Subpart C contains additional protections for prisoners, and Subpart D does the same for children.
The FDA Good Clinical Practice regulations are a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials in a way that provides assurance that the data and reported results are credible and accurate and that the rights, safety, and well-being of trial subjects are protected.