Questions about clinical trials? The MMRF provides answers.
Clinical Trials are part of clinical research and at the heart of all medical advances. Clinical trials look at new ways to prevent, detect or treat disease. Treatments might be new drugs or new combinations of drugs, new surgical procedures or devices, or new ways to use existing treatments. The goal of clinical trials is to determine if a new test or treatment works and is safe. Clinical trials can also look at other aspects of care, such as improving the quality of life for people with diseases, including multiple myeloma.
People participate in clinical trials for a variety of reasons. Healthy volunteers say they participate to help others and to contribute to moving science forward. Participants with an illness or disease also take part to help others, but also to possibly receive the newest treatment and to have the additional care and attention from the clinical trial staff.
Many different types of people participate in clinical trials. Some are healthy, while others may have illnesses.
A healthy volunteer is a person with no known significant health problems who participates in clinical research to test a new drug, device, or intervention. Research procedures with healthy volunteers are designed to develop new knowledge, not to provide direct benefit to study participants. Healthy volunteers have always played an important role in research.
Healthy volunteers are needed for several reasons. When developing a new technique, such as a blood test or imaging device, healthy volunteers (formerly called “normal volunteers”) help define the limits of “normal”. These volunteers serve as controls for patient groups and are often matched to patients on characteristics such as age, gender, or family relationship. They receive the same test, procedure, or drug the patient group receives. Investigators learn about the disease process by comparing the patient group to the healthy volunteers.
Factors like how much of your time is needed, discomfort you may feel, or risk involved depends on the trial. The research procedure may also carry some risk. The consent process for healthy volunteers includes a detailed discussion of the study’s procedures and tests.
A patient volunteer has a known health problem and participates in research to better understand, diagnose, treat, or cure that disease or condition. Research procedures with a patient volunteer help develop new knowledge. These procedures may or may not benefit the study participants.
Patient volunteers may be involved in studies similar to those in which healthy volunteers participate. These studies involve drugs, devices, or interventions designed to prevent, treat, or cure disease. Although these studies may provide direct benefit to patient volunteers, the main aim is to prove, by scientific means, the effects and limitations of the experimental treatment. Consequently, some patients serve as controls by not taking the test drug, or by receiving test doses of the drug large enough only to show that it is present, but not at a level that can treat the condition. A study’s benefits may be indirect for the volunteers but may help others.
All clinical trials have guidelines about who can participate, called Inclusion/Exclusion Criteria. Factors that allow someone to participate in a clinical trial are “inclusion criteria.” Those that exclude or do not allow participation are “exclusion criteria.” These criteria are based on factors such 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 volunteers.
Inclusion and exclusion criteria are not used to reject people personally; rather, the criteria are used to identify appropriate participants and keep them safe, and to help ensure that researchers can find new information they need.
Only through clinical research can we gain insights and answers about the safety and effectiveness of drugs and therapies. Groundbreaking scientific advances are possible only because of participation of volunteers, both healthy and those diagnosed with an illness. As clinical research opens new doors to finding ways to diagnose, prevent, treat, or cure disease and disability, clinical trial participation of volunteers is essential to help us find the answers.
Clinical research is medical research that involves people like you. People volunteer to participate in carefully conducted investigations that ultimately uncover better ways to treat, prevent, diagnose, and understand human disease. Clinical research includes trials that test new treatments and therapies as well as long-term natural history studies, which provide valuable information about how disease and health progress.
The idea for a clinical research study – also known as a clinical trial – often originates in the laboratory. After researchers test new therapies or procedures in the laboratory and in animal studies, the most promising experimental treatments are moved into clinical trials, which are conducted in phases. During a trial, more information is gained about an experimental treatment, its risks, and its effectiveness.
Clinical research is conducted according to a plan known as a protocol. The protocol is carefully designed to safeguard the participants’ health and answer specific research questions. A protocol describes the following:
• Who is eligible to participate in the trial
• Details about tests, procedures, medications, and dosages
• The length of the study and what information will be gathered
A clinical study is led by a principal investigator (PI), who is often a doctor. Members of the research team regularly monitor the participants’ health to determine the study’s safety and effectiveness.
Each clinical trial in the United States must be approved and monitored by an Institutional Review Board (IRB) to ensure that the risks are minimal and are worth any potential benefits. An IRB is an independent committee that consists of physicians, statisticians, and members of the community who ensure that clinical trials are ethical and that the rights of participants are protected. Federal regulation requires all institutions in the United States that conduct or support biomedical research involving people to have an IRB initially approve and periodically review the research.
Clinical trials are sponsored or funded by various organizations or individuals, including physicians, foundations, medical institutions, voluntary groups, and pharmaceutical companies, as well as federal agencies such as the National Institutes of Health and the Department of Veterans Affairs.
Informed consent is the process of providing potential participants with the key facts about a clinical trial before they decide whether to participate. The process of informed consent (providing additional information), continues throughout the study. To help someone decide whether or not to participate, members of the research team explain the details of the study. Translation or interpretive assistance can be provided for participants with limited English proficiency. The research team provides an informed consent document that includes details about the study, such as its purpose, duration, required procedures, and who to contact for further information. The informed consent document also explains risks and potential benefits. The participant then decides whether to sign the document. Informed consent is not a contract. Volunteers are free to withdraw from the study completely or to refuse particular treatments or tests at any time. Sometimes, however, this will make them ineligible to continue the study.
Types of clinical trials
• Natural history studies provide valuable information about how disease and health progress.
• Prevention trials look for better ways to prevent a disease in people who have never had the disease or to prevent the disease from returning. Better approaches may include medicines, vaccines, or lifestyle changes, among other things.
• Screening trials test the best way to detect certain diseases or health conditions.
• Diagnostic trials determine better tests or procedures for diagnosing a particular disease or condition.
• Treatment trials test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
• Quality of life trials (or supportive care trials) explore and measure ways to improve the comfort and quality of life of people with a chronic illness.
Phases of clinical trials
Clinical trials are conducted in “phases”. Each phase has a different purpose and helps researchers answer different questions.
• Phase I trials: Researchers test an experimental drug or treatment in a small group of people (20-80) for the first time. The purpose is to evaluate its safety and identify side effects.
• Phase II trials: The experimental drug or treatment is administered to a larger group of people (100-300) to determine its effectiveness and to further evaluate its safety.
• Phase III trials: The experimental drug or treatment is administered to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the experimental drug or treatment to be used safely.
• Phase IV trials: After a drug is approved by the FDA and made available to the public, researchers track its safety, seeking more information about a drug or treatment’s risks, benefits, and optimal use.
Some concepts to understand
Typically, clinical trials compare a new product or therapy with another that already exists to determine if the new one is as successful as, or better than, the existing one. In some studies, participants may be assigned to receive a placebo (an inactive product that resembles the test product, but without its treatment value).
Comparing a new product with a placebo can be the fastest and most reliable way to demonstrate the new product’s therapeutic effectiveness. However, placebos are not used if a patient would be put at risk – particularly in the study of treatments for serious illnesses – by not having effective therapy. Most of these studies compare new products with an approved therapy. Potential participants are told if placebos will be used in the study before they enter a trial.
Randomization is the process by which two or more alternative treatments are assigned to volunteers by chance rather than by choice. This is done to avoid any bias with investigators assigning volunteers to one group or another. The results of each treatment are compared at specific points during a trial, which may last for years. When one treatment is found superior, the trial is stopped so that the fewest volunteers receive the less beneficial treatment.
In single- or double-blind studies, also called single- or double-masked studies, the participants do not know which medicine is being used, so they can describe what happens without bias. “Blind” (or “masked”) studies are designed to prevent members of the research team or study participants from influencing the results. This allows scientifically accurate conclusions. In single-blind (“single-masked”) studies, only the patient is not told what is being administered. In a double-blind study, only the pharmacist knows; members of the research team are not told which patients are getting which medication, so that their observations will not be biased. If medically necessary, however, it is always possible to find out what the patient is taking.
Risks and benefits
Clinical trials involve risks, just as routine medical care and the activities of daily living do. When weighing the risks of research, you can consider two important factors:
• The degree of harm that could result from participating in the study
• The chance of any harm occurring
Most clinical studies pose the risk of minor discomfort, which lasts only a short time. However, some study participants experience complications that require medical attention. In rare cases, participants have been seriously injured or have died of complications resulting from their participation in trials of experimental therapies. The specific risks associated with a research protocol are described in detail in the informed consent document, which participants are asked to sign before participating. Also, a member of the research team explains the major risks of participating in a study and will answer any questions you have about the study. Before deciding to participate, carefully consider possible risks and benefits.
Well-designed and well-executed clinical trials provide the best approach for participants to:
• Play an active role in their health care
• Gain access to new research treatments before they are widely available
• Receive regular and careful medical attention from a research team that includes doctors and other health professionals
• Help others by contributing to medical research
• There may be unpleasant, serious, or even life-threatening side effects to experimental treatment.
• The study may require more time and attention than standard treatment would, including visits to the study site, more blood tests, more treatments, hospital stays, or complex dosage requirements.
If you are offered a clinical trial, feel free to ask any questions or bring up any issues concerning the trial at any time. The following suggestions may give you some ideas as you think about your own questions.
• What is the purpose of the study?
• Why do researchers think the approach may be effective?
• Who will fund the study?
• Who has reviewed and approved the study?
• How are study results and safety of participants being checked?
• How long will the study last?
• What will my responsibilities be if I participate?
Possible risks and benefits
• What are my possible short-term benefits?
• What are my possible long-term benefits?
• What are my short-term risks, such as side effects?
• What are my possible long-term risks?
• What other options do people with my disease have?
• How do the possible risks and benefits of this trial compare with those options?
Participation and care
• What kinds of therapies, procedures and /or tests will I have during the trial?
• Will they hurt, and if so, for how long?
• How do the tests in the study compare with those I would have outside of the trial?
• Will I be able to take my regular medications while in the clinical trial?
• Where will I have my medical care?
• Who will be in charge of my care?
• How could being in this study affect my daily life?
• Can I talk to other people in the study?
• Will I have to pay for any part of the trial such as tests or the study drug?
• If so, what will the charges likely be?
• What is my health insurance likely to cover?
• Who can help answer any questions from my insurance company or health plan?
• Will there be any travel or child care costs that I need to consider while I am in the trial?
Tips for asking your doctor about trials
• Consider taking a family member or friend along for support and for help in asking questions or recording answers.
• Plan ahead what to ask – but don’t hesitate to ask any new questions you think of while you’re there.
• Write down your questions in advance, to make sure you remember to ask them all.
• Write down the answers, so that you can review them whenever you want.
• Ask about bringing a tape recorder to make a taped record of what’s said (even if you write down answers).
The goal of clinical research is to develop knowledge that improves human health or increases understanding of human biology. People who participate in clinical research make it possible for this to occur. The path to finding out if a new drug is safe or effective is to test it on patient volunteers. By placing some people at risk of harm for the good of others, clinical research has the potential to exploit patient volunteers. The purpose of ethical guidelines is both to protect patient volunteers and to preserve the integrity of the science. Ethical guidelines in place today were primarily a response to past research abuses.
Informed consent is the process of learning the key facts about a clinical trial before deciding whether to participate. The process of providing information to participants continues throughout the study. To help someone decide whether to participate, members of the research team explain details of the study. The research team provides an informed consent document, which includes details about the study such as its purpose, duration, required procedures, and who to contact for various purposes. The informed consent document also explains risks and potential benefits.
If the participant decides to enroll in the trial, the informed consent document will be signed. Informed consent is not a contract. Volunteers are free to withdraw from the study at any time.
Most, but not all, clinical trials in the United States are approved and monitored by an Institutional Review Board (IRB) in order to ensure that the risks are minimal and are worth any potential benefits. An IRB is an independent committee that consists of physicians, statisticians, and members of the community who ensure that clinical trials are ethical and that the rights of participants are protected. Potential research participants should ask the sponsor or research coordinator whether the research they are considering participating in was reviewed by an IRB.
After a clinical trial is completed, the researchers carefully examine information collected during the study before making decisions about the meaning of the findings and about further testing. After a phase I or II trial, the researchers decide whether to move on to the next phase or to stop testing the agent or intervention because it was unsafe or ineffective. When a phase III trial is completed, the researchers examine the data and decide whether the results have medical importance.
Results from clinical trials are often published in peer-reviewed scientific journals. Peer review is a process by which experts review the report before it is published to ensure that the analysis and conclusions are sound. If the results are particularly important, they may be featured in news media and discussed at scientific meetings and by patient advocacy groups before they are published. Once a new approach has been proven safe and effective in a clinical trial, it may become the standard of medical practice.
Ask the research team members if the study results have been or will be published. Published study results are also available by searching for the study’s official name or Protocol ID number in the National Library of Medicine’s PubMed® database.
Clinical research is medical research that involves people to test new treatments and therapies.
A healthy volunteer is a person with no known significant health problems who participates in clinical research to test a new drug, device, or intervention.
Inclusion/Exclusion Criteria are factors that allow someone to participate in a clinical trial are inclusion criteria. Those that exclude or not allow participation are exclusion criteria.
Informed consent explains risks and potential benefits about a clinical trial before someone decides whether to participate.
A patient volunteer has a known health problem and participates in research to better understand, diagnose, treat, or cure that disease or condition.
Phase I Trials:
An experimental drug or treatment in a small group of people (20-80) for the first time. The purpose is to evaluate its safety and identify side effects.
Phase II Trials:
The experimental drug or treatment is administered to a larger group of people (100-300) to determine its effectiveness and to further evaluate its safety.
Phase II Trials:
The experimental drug or treatment is administered to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects and compare it with standard or equivalent treatments.
Phase IV Trials:
After a drug is licensed and approved by the FDA, researchers track its safety, seeking more information about its risks, benefits, and optimal use.
A placebo is a pill or liquid that looks like the new treatment but does not have any treatment value from active ingredients.
A principal investigator (PI), who is often a doctor, leads the clinical research team and, along with the other members of the research team, regularly monitors study participants’ health to determine the study’s safety and effectiveness.
A protocol is a carefully designed plan to safeguard the participants’ health and answer specific research questions.
Randomization is the process by which two or more alternative treatments are assigned to volunteers by chance rather than by choice.
Single- or Double-Blind Studies:
Single- or double-blind studies (also called single- or double-masked studies) are studies in which the participants do not know which medicine is being used, so they can describe what happens without bias.
This information courtesy of Cancer.gov.