comscoreClinical Trials

Clinical Trials

Clinical trials are carefully designed research studies that depend on human volunteers to improve medical care over time.

Clinical trials are carefully designed research studies that depend on human volunteers to improve medical care over time.

In cancer research, pre-clinical studies first test new treatments that show promise in the lab or in animals. These treatments may ultimately be tested in clinical trials involving people.

Clinical trials are conducted to:

  • ensure a new cancer treatment is safe to use in people, and to see if it works better than the best therapy that is currently available (known as the standard of care)

  • study new ways of diagnosing cancer

  • reduce the risk of cancer developing or returning

  • manage treatment side effects

  • help people feel better during or after cancer treatment

Virtually every treatment we have today for cancer (and other diseases) was first tested in clinical trials — which is why it's so important for people to participate.

 

Who can consider a clinical trial?

You might think that clinical trials are only an option for people with cancer that does not respond to standard treatments. But that’s not the case. You can consider a clinical trial at any point in your experience with breast cancer, including if:

  • you’ve been told you’re at higher-than-average risk for developing breast cancer

  • you’ve just been diagnosed with breast cancer

  • you’re in the middle of treatment

  • you’ve finished treatment, whether recently or long ago

  • you’re facing a recurrence of breast cancer

  • you have metastatic breast cancer that requires ongoing treatment

Although trial participation is a personal decision, some people with breast cancer choose to take part because they want access to the newest treatments being studied by researchers that may not be available outside of a trial. Many people like knowing that they will be followed closely by a research team, and that they may be contributing to future advances in breast cancer treatment.

Even in early-stage breast cancer, researchers are looking for better ways to prevent future recurrences and improve short- and long-term treatment side effects. Right now, only about 5 percent of adults with cancer take part in clinical trials, so there is always a need for more candidates.

 

Types of clinical trials

Depending on your individual situation, there are different types of clinical trials to consider.

Therapeutic clinical trials

In therapeutic clinical trials, people agree to try new therapies under careful supervision to help doctors identify the best treatments with the fewest side effects. These studies help improve the standard of care for breast cancer and other diseases. Before a new treatment can be approved by the U.S. Food and Drug Administration (FDA) and similar government agencies in other countries, it must be tested in clinical trials.

A therapeutic clinical trial may study a new medication that has shown promise in lab research, animal studies, or previous clinical trials. It also might test new combinations of existing medicines, new types of surgery or radiation therapy, or new ways of giving treatments, such as the dosage, timing, or delivery method (by mouth vs. through an IV, for example). Therapeutic trials can study first-line treatments, which are given after an initial cancer diagnosis, or treatments for cancer recurrence or metastatic disease.

Therapeutic trials are just one type of research that's done before a new treatment becomes widely available to people. New medicines must first be discovered, purified, produced, and then tested in pre-clinical studies that are done on cells in petri dishes or on animals. Clinical trials in people are started only after several years of pre-clinical trials suggest that a new treatment will be safe and beneficial for people.

Therapeutic trials are designed to answer two major questions:

  1. Is the new treatment safe for people? All breast cancer treatments have side effects. In clinical trials, researchers try to find out if the benefits of a new treatment or procedure outweigh potential side effects.

  2. Does the new treatment work in people, and if so, how effective is it? Once a new treatment is proven to be safe, more clinical trials are needed to answer additional questions: Is the new treatment better than standard treatments? Does it cause more or fewer side effects? Does it work in a group of people who don't benefit from standard treatments?

Researchers don't know what the results of a therapeutic clinical trial will be. Sometimes participants have no benefit from the study treatment. And study treatments may have unknown side effects, especially if they are completely new. In rare cases, clinical trial volunteers have been hurt by the treatment or procedure being tested.

On the other hand, many people receive effective treatments through clinical trials. And hundreds of thousands of others are helped because those volunteers chose to participate in a trial that resulted in a new, more effective treatment. Virtually every standard treatment
for breast cancer available today was first studied in clinical trials.

Basket and umbrella trials

Basket and umbrella trials are newer types of therapeutic trials designed to study new treatments in people with cancers that share specific gene mutations or biomarkers. A mutation is a change in a gene related to the cancer’s development. A biomarker is a substance found in the blood or tissue that can be a signal or “marker” of cancer development.

When cancers in different people share the same gene mutations or biomarkers, it suggests there may be similar processes that cause the cancer to grow and affect how the cancer cells behave. Therefore, these groups of people may respond to similar types of treatment.

Basket and umbrella trials are designed to test and potentially approve new treatments more quickly than traditional clinical trials.

Basket trials — also called bucket trials — enroll people with different types of cancers that have the same gene mutation or biomarker. Participants receive a treatment that targets the specific molecular process that is believed to play a role in the development of these cancers.

For example, there could be a basket trial with multiple groups that include people with breast, lung, colorectal, or other types of cancer that are activated by the same molecular trait. This is a different approach from more traditional therapeutic trials, which usually enroll patients with the same type of cancer, based on where the cancer is found in the body.

Umbrella trials enroll people with the same type of cancer — such as breast cancer — but with different gene mutations or biomarkers that may play a role in the cancer’s development. This type of trial is designed to look at how new therapies work in people with different molecular subtypes of the same cancer. Participants are grouped by the specific mutation or biomarker found in their cancer. The study treatments may change during an umbrella trial as researchers learn more about the different subtypes of cancer and how people respond to therapies.

Non-therapeutic clinical trials

Not all clinical trials test treatments for cancer or other diseases. Non-therapeutic clinical trials study ways to improve the detection or diagnosis of cancer, prevent it from developing or returning, reduce side effects, or improve quality of life for people affected by cancer.

Prevention trials investigate new ways of reducing the risk of breast cancer or its recurrence. Examples could include medicines or lifestyle changes like diet or exercise. For people with a higher risk of breast cancer, prevention trials may study cancer risk reduction with strategies like medications or surgery.

Screening and diagnosis trials look for new and better ways to detect breast cancer, such as imaging techniques and tissue sampling (biopsy) approaches.

Supportive care and symptom management trials — also called quality-of-life trials — study ways to reduce treatment side effects and improve peoples’ overall functioning during and after cancer treatment. These strategies may include medications or lifestyle changes such as exercise or diet.

 

How clinical trials are conducted

Each clinical trial is led by a head researcher (called a principal investigator or PI), who works with a team of other scientists and healthcare professionals. The way the research team designs and conducts a clinical trial can vary based on the study's goals and other factors.

Learn more at How Clinical Trials Are Conducted.

 

How clinical trial participants’ safety is protected

Any research team conducting a trial of a new medication must first submit an investigational new drug (IND) application with the FDA. The FDA reviews the IND application and decides whether there is enough evidence to support moving ahead with the clinical trial. This helps protect participants because the FDA looks at previous study results, the study plan (or protocol), and the qualifications of the research team that will conduct the trial.

In the United States, most clinical trial protocols — whether for therapeutic or non-therapeutic trials — have to be reviewed by an Institutional Review Board, or IRB. An IRB is a committee that reviews research to make sure people’s rights and safety are protected, both before the study starts and as it proceeds. IRB members may include physicians, PhD-level scientists, nurses, statisticians, or pharmacists who are not involved in the study. There also has to be a “non-scientist” member of the IRB, such as a lawyer, clergy member, patient advocate, or ethicist. In Europe, Ethics Committees play a similar role to IRBs.

The IRB considers several questions when making its decision about whether or not to approve the trial:

  • Is it ethical to ask people to volunteer for this investigational treatment, intervention, or other approach?

  • Has the study been designed to make sure the people involved will be safe?

  • In a therapeutic trial, will the participants receive a treatment that is at least as good as or better than what they'd get if they weren't in the study?

If the clinical trial is approved, the IRB monitors the trial and formally reviews it each year.

Some trials also may be reviewed by a data monitoring committee, also called a data and safety monitoring board, which is an independent group of experts who conduct ongoing reviews of data from the trial to make sure it is valid and that participants are protected. Federal organizations such as the FDA and the Office of Human Subjects Research Protection also play a role in making sure that trial sponsors have protections in place for participants.

Informed consent

If you find a trial that you’re interested in joining, and for which you appear to be eligible, you would then go through a process called “informed consent.” Members of the research team explain the study in ways you can understand and give you and your family members an opportunity to ask questions. They also will give you an informed consent document that provides information about the study, such as:

  • the purpose

  • who is eligible to take part

  • what is already known about the treatment or intervention being studied

  • any tests or procedures that will be needed, and how often

  • how the study is designed

  • how long it’s expected to last

  • possible risks and benefits

  • alternatives to taking part in the trial

  • the costs of the trial and who is responsible for them

  • a contact person for further information or questions

The document also will state that participating is voluntary and you can leave the trial at any time for any reason. You can take the document home with you to discuss it with family or friends and figure out what additional questions you have. You also can work through the document with your doctor and the trial team to make sure your questions are answered. If you decide to participate, you would then sign the informed consent document.

Giving informed consent does not automatically mean you’ll be accepted into the trial. You may need to have medical tests to make sure you’re eligible to participate.

The informed consent process should continue throughout the trial. If there are changes to the study or the treatments being used, or new information about risks and benefits, you would go through informed consent again and sign a new document. Even if there aren’t any changes in the trial, there should be a process in place for updating your informed consent over time.

 

Common misconceptions about clinical trials

Clinical trials are essential to advancing breast cancer care. Your participation could improve treatments and save lives. But there are a lot of misconceptions about clinical trials. In this animated video, we set the record straight about the top five.

 

How to find out if you’re eligible for a clinical trial

Researchers want to make sure the results of a clinical trial are due to the study treatment and not just chance. So eligible participants are usually limited to a group with very specific characteristics.

These characteristics are known as “inclusion criteria,” and they may include your age, type and stage of the cancer, your treatment history, your current level of daily function, and other factors. A trial might be designed to answer questions about treating patients with a particular stage of breast cancer, or who have not had any treatment yet, or who already received a certain type of chemotherapy.

For example, a study comparing the effectiveness of two types of hormonal therapy — an aromatase inhibitor vs. tamoxifen, for example — might be limited to participants with the following characteristics:

  • post-menopausal women

  • diagnosed with early-stage hormone-receptor-positive breast cancer

  • have had surgery to remove the cancer

  • may or may not have had chemotherapy

  • have not taken tamoxifen or any other hormonal therapy

It’s important for researchers to enroll patients who are alike in certain ways, so that the results are meaningful at the end of the study.

Trials also specify certain “exclusion criteria,” or characteristics that would prevent your participation. These may include past treatments you’ve had or other medical conditions that could make it unsafe for you to participate. For example, a new medicine may be safe only in people with normal kidney or liver function. So people with kidney or liver problems would not be accepted into the study.

If you’re interested in enrolling in a specific clinical trial, you or your doctor can reach out to the principal investigator or research coordinator to find out if you meet the eligibility requirements. You can also read about those requirements by looking up the trial on Clinicaltrials.gov or another listing service. Every trial has different requirements, so if one isn’t a good match, another is likely to be.

If you meet the requirements and give your consent to join, you’ll likely need additional lab and imaging tests to confirm your eligibility and that the trial is safe for you.

If you’re interested in a new treatment that is showing promising results in a phase III trial, but you’re not eligible for the trial, you may still be able to access it through the FDA’s Expanded Access program. Your doctor can help you decide if this makes sense for your situation.

 

Covering the costs of clinical trials

Generally, clinical trials involve three types of costs:

  • The costs of routine care, which is the care that anyone with your type of cancer would normally receive, such as doctors’ visits, lab tests, medications to help with symptoms, and other routine procedures. These should be covered by your health insurance plan. However, if the members of the trial team are outside your plan’s network, your plan may not cover the costs, unless it includes coverage for care from out-of-network providers.

  • Costs associated with the trial itself, such as the new treatment being studied and any tests or procedures needed to follow your progress or collect other data for the study. In most cases, the study sponsor would cover these costs.

  • Costs of participating in the trial, such as transportation, parking, missed time at work, childcare, and possibly lodging if the trial is located far from home. Although a sponsor may cover some of the transportation costs, typically you would need to cover these costs on your own.

The Affordable Care Act requires Medicare and commercial insurers to cover routine care costs for clinical trial participants. A new coverage requirement for Medicaid is expected to be enacted as of January 2022. Generally, the trial has to be:

  • approved or funded by a federal organization, such as the National Cancer Institute (NCI), the Centers for Disease Control and Prevention (CDC), or some other government department, or

  • have an investigational new drug application (IND) approved by the FDA. However, some trials of existing drugs are not required to file an IND.

Insurance plans that existed on or before March 23, 2010, when the Affordable Care Act took effect, are not required to cover routine care costs in clinical trials.

As part of the informed consent process, you and the research team can talk about the costs of participating. Ask about other patients’ experience with getting coverage for routine care costs, and make sure you understand what costs you will be expected to cover. Ask who’s available to help if you encounter any issues with your insurance plan.

 

Benefits and risks of participating in a clinical trial

Each clinical trial has its own benefits and risks, depending on the type of trial and what its goals are. Still, some common risks and benefits are generally associated with clinical trial participation.

Potential benefits
  • Access to a treatment that isn't widely available yet. Through a therapeutic trial, you can gain access to a new therapy that may be better than currently available treatments. Researchers are testing it because they have reason to believe it may be more effective, or have fewer or less serious side effects than standard treatments. Also, if your cancer is no longer responding to standard treatment options, or there are no effective treatments available, a clinical trial can offer a way to access treatment.

  • Regular and careful attention from some of the best cancer doctors. A clinical trial team typically includes top doctors and scientists from around the United States and the world who understand the latest advances in cancer treatment. You’ll likely have more office visits and be watched more closely than you would during standard treatment — and some people find this reassuring. Because of such close monitoring, any side effects you experience are likely to be noticed and dealt with immediately.

  • Treatment that may be free or low cost. The sponsor of the clinical trial will often pay for the non-routine costs of your care related to the study, such as the study treatment, procedures, and tests. You or your health insurance are expected to cover any “routine care,” which means any cancer care you would have received even if you were not on the trial. If you need to travel to participate in a trial, costs such as gas, parking, tolls, taxis, airfare, meals, and overnight lodging may or may not be reimbursed by the trial. Make sure you know exactly what you'll have to pay for before you agree to be part of a clinical trial.

  • Access to an intervention that may improve your quality of life, help reduce your cancer risk, or help to detect cancer earlier. If you participate in a supportive care trial, you may benefit from interventions such as diagnostics, dietary changes, exercise, counseling, or medications aimed at reducing treatment side effects. Prevention and screening trials can give you access to new tests and other strategies that could help reduce your risk of cancer or cancer recurrence, or increase your chances of cancer being detected earlier.

  • Contributing to research that may save or improve lives in the future. The breast cancer treatments we have today are available because large numbers of women chose to participate in clinical trials. Regardless of how much you individually benefit from a trial, you’ll know that you helped researchers gain information about whether or not a new treatment is effective or better than standard treatments.

  • The feeling that you're playing an active role in your care. Deciding to participate in a clinical trial can make some people feel as if they have more control over their situation, which can lead to a more positive outlook and better quality of life.

Potential risks
  • Not being able to choose which treatment you get. In randomized trials, you’re assigned at random (by a computer) to get a specific treatment, and you could receive standard therapy rather than the newer treatment. Some people find this uncertainty quite difficult. Some cancer clinical trials may use a placebo, an inactive treatment that resembles the real treatment. However, if there is an effective standard treatment available for your cancer, you will always receive at least that in addition to the placebo. And before you enroll in a trial, you’ll always be able to find out if it is randomized, blinded, or uses a placebo.

  • The risk of getting a treatment or intervention that doesn’t work for you, even if it benefits other people in the trial. It also may turn out that the new treatment isn't as effective as what's currently available.

  • The risk of more severe side effects than current treatments. Though you will be closely monitored in a clinical trial, there is a chance you could experience serious side effects from an experimental therapy.

  • Possible difficulty with getting your insurance to cover all the costs of routine care during the trial. Although routine care costs should be covered by your health insurance plan, since you'd need this care even if you weren’t in a clinical trial, there may be issues with coverage. Talk to your insurance company and the trial's research coordinator before you agree to participate so you'll understand all of the costs involved and who is responsible for covering them.

  • More frequent testing and doctor visits, and possibly travel. Because you'll be closely monitored, you may have to undergo testing more often than you would if you weren't in a trial. This could mean more travel and time in the doctor's office or hospital. Also, if you’re in a trial at a medical center that is not located near your home, you may need time off from work or family caregiving responsibilities, and there may be travel-related expenses.

  • The possibility that the trial ends early. A clinical trial may stop earlier than planned if the treatment has unexpected serious adverse events, or if it becomes clear that it is not as safe or effective as standard treatment. This can be difficult emotionally for you and other participants invested in the success of the trial.

 

Questions to ask before enrolling in a clinical trial

Deciding to be part of a clinical trial takes time and is different for everyone. As you're considering options, it can be helpful to ask the research team some questions. Bring along a trusted family member or friend, take notes, and consider asking if you can record any meetings when you discuss the trial.

Questions about the trial itself:
  • Why are you doing this trial?

  • Why do you think this new treatment/intervention will be effective?

  • What phase is this trial?

  • Do I meet the eligibility criteria to enroll in this trial?

  • Has this treatment/intervention been tested before?

  • What were the results of any previous trials?

  • Can I talk to someone who's already in the trial?

  • What are the possible treatments I can get? How often are they given?

  • What side effects am I likely to have and how are they different from side effects with standard treatment?

  • Will I be randomly assigned to a specific treatment or intervention within the trial? Will I know what group I am in, and if not, will I be able to find out after the trial is over? Will the researchers know?

  • Where is the study site and how often do participants have to go there? Can I participate at a site close to home?

  • What are my alternatives if I do not take part in this trial (such as standard treatment, other trials, etc.)?

  • When will the results of this clinical trial be available?

Questions about safety:
  • Who reviewed and approved the trial? Will that review process continue?

  • How is patient safety being monitored? Have there been any unexpected or serious side effects?

  • What are the potential benefits and risks of taking part? How do these compare with standard treatment for my cancer?

  • What if my health gets worse during the clinical trial? Whom should I contact?

Questions about time commitment, costs, and other practical concerns:
  • What types of tests will I need to have and how often will I have to have them? How different are they from the tests I would have outside of a clinical trial?

  • How will being part of this study affect my daily routine?

  • Who is paying for the trial?

  • Will the sponsors of the trial cover the costs of the treatment I receive through the trial? Will my insurance cover any of the costs? What will I have to pay for?

  • Who can help me work with my insurance plan if I face issues with coverage?

  • Will I be reimbursed for any out-of-pocket expenses, such as transportation?

  • How long will the trial last?

  • Will I still be seen by my usual care team? If so, how often?

  • Where will I receive trial-related care?

  • If traveling to access the trial: Can I receive any lab tests or imaging closer to home? Are telemedicine visits an option?

  • Who will oversee my medical care while I am in the trial?

  • Is long-term follow-up care part of the trial? What does it involve?

  • If the treatment or intervention benefits me, can I continue to receive it after the trial is done?

  • How do I get the results of the trial?

  • If I take medications for other medical conditions, can I continue to take them during the trial?

  • If I withdraw from the trial, how will this affect my care?

 

How to find a clinical trial

Talking with your doctor is the best first step to finding a clinical trial that is right for you. But there are also online search tools and helpful organizations that can help you find a clinical trial.

Learn more at How to Find a Clinical Trial.

 

Glossary: Common terms used to talk about clinical trials

As you read about clinical trials, you might see the following terms used:

  • Arm: A term used to describe each group in a clinical trial that is receiving a specific treatment or intervention (or no intervention), according to the trial plan (protocol).

  • Basket trial: Also called a bucket trial, it enrolls patients with different types of cancer that share a key characteristic, such as a genetic mutation or a molecular pathway that is driving the cancer. Participants receive the same treatment, targeted to that particular molecular trait, so that researchers can evaluate its effectiveness.

  • Blinding: A trial design approach to ensure that either the researchers, the participants, or both will not know which treatment or intervention each group is receiving.

  • Control group: The group of people in a treatment trial who are getting therapy that is the current standard of care; a placebo in addition to the standard of care; or, in rare cases, a placebo alone. In non-treatment trials, the control group does not receive the intervention under investigation.

  • Data monitoring committee: Also called a data and safety monitoring board, this independent group of experts conducts ongoing reviews of data from the trial to ensure its validity as well as patient safety.

  • Double-blind or Double-blinded: This means that neither the researchers nor the participants in a clinical trial know which treatment any of the participants are getting. Double-blinding keeps the study objective and helps prevent bias.

  • Exclusion criteria: Characteristics that would exclude people from participating in a certain clinical trial, such as medical conditions or test results.

  • Inclusion criteria: Specific characteristics outlined in the trial protocol that make someone eligible to participate, such as age, cancer type, previous treatments, etc.

  • Informed consent: The process through which a person decides whether or not to participate in a clinical trial. Researchers must explain the clinical trial's protocol, share any possible risks and benefits of taking part, describe how participants will be protected, and answer questions.

  • Institutional review board: A committee that is charged with reviewing research to makes sure people’s rights and safety are protected, both before the study starts and as it proceeds.

  • Intervention group (or investigational arm): The group of people in a trial who are getting the new treatment/ intervention that is being studied.

  • Investigational new drug application: An application that researchers submit to the U.S. Food and Drug Administration for review before they can initiate a clinical trial of a new drug.

  • Phase: A term used to describe the different steps in a clinical trial, from phase I through IV. With treatment trials, phase I is the earliest step to test whether a new drug or therapy is safe, while phases II and III evaluate its effectiveness against cancer and whether it is better than current treatments. Phase IV involves ongoing monitoring for effectiveness and side effects after a new treatment is approved.

  • Placebo: A sugar pill or other inactive substance/intervention that looks the same as an active drug or treatment and is given the same way. Placebos are rarely used alone in cancer clinical trials; in most cases, patients in the control group would receive both the current standard of care and a placebo.

  • Principal investigator: The lead researcher on a clinical trial who prepares the protocol, carries out the trial, analyzes the data, and reports any results.

  • Protocol: The plan that describes how the clinical trial will be done; why it’s being done; how many people will participate; who is (or is not) eligible; what treatments or interventions will be given; and any information that will be collected.

  • Randomized or Randomization: The process of assigning clinical trial participants to different treatment or intervention groups by chance, rather than by choice. This helps ensure the reliability of the results.

  • Research coordinator: A research professional who works under the direction of the principal investigator to coordinate and support the day-to-day operations of the clinical trial.

  • Routine care costs: For clinical trial participants, these are the costs of cancer care they would need even if they were not part of a trial. They are typically covered by insurance.

  • Single-blinded: A trial design in which the researchers know which groups are getting which treatment/intervention, but the participants do not.

  • Sponsor: The person, organization, or group that initiates, manages, and/or pays for the clinical trial (or arranges for the trial to be funded).

  • Standard of care: The best current therapy for a given medical condition, based on research to date. Phase III and some phase II clinical trials are often done to compare a new treatment regimen to the standard of care.

  • Umbrella trial: A trial that enrolls patients with the same type of cancer who have different gene mutations or biomarkers associated with the cancer’s development. The trial is designed to look at how a new therapy or therapies work in people with different molecular subtypes of the same cancer.

 

Special Report: Increasing diversity in clinical trials

Disparities in clinical trial participation among Black women could be one of the reasons they have worse breast cancer outcomes than other racial and ethnic groups in the United States.

For this Breastcancer.org Special Report, we spoke with experts and clinical trial participants about why diversity in clinical research matters, and how you can overcome common barriers that may be preventing you from participating in a breast cancer clinical trial. Read the Special Report on Increasing Racial Diversity in Breast Cancer Clinical Trials.

— Last updated on March 8, 2022, 9:19 PM

Reviewed by 4 medical advisers
 
Nadine Barrett, PhD, MS, MA
Duke University School of Medicine, Durham, NC
Jenni Sheng, MD
Johns Hopkins University School of Medicine, Baltimore, MD
Chirag Shah, MD
Cleveland Clinic, Cleveland, OH
Marisa C. Weiss, MD
Lankenau Medical Center, Wynnewood, PA
Learn more about our advisory board
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