Research

Patient guide to clinical trials

Seattle Cancer Care Alliance (SCCA) has one of the most active clinical trial programs in the world — providing new hope for our patients every day.

Through clinical trials, our patients gain access to promising new treatments. Every advance in cancer treatment has resulted from clinical trials. For example, bone marrow transplantation, which is considered the most important advance in cancer treatment of the last quarter century started right here.

Today’s clinical trials turn cancer research into real-world treatments and cures.

Dr. Renato Martins talks clinical trials on New Day Northwest. SCCA has more than 300 open clinical trials for patients. Dr. Martins answers frequently asked questions about trials.
How does SCCA research benefit me?

It’s always up to you whether to take part in a clinical trial. One potential benefit is that you may be among the first to get access to a promising new treatment. Even if you decide not to participate, the fact that SCCA provides treatment for patients in trials is a good reason to come here for your care.

Because of SCCA’s commitment to developing advances in treatment and our reputation as a hub for research, we attract the best and most experienced doctors, who can offer you access to the latest treatment options. SCCA also attracts patients who are more likely to be savvy health care consumers: patients who are interested in treatment options beyond those offered in the community setting and who expect — and receive — a high standard of care.

SCCA, Fred Hutch and UW Medicine form the only National Cancer Institute-designated Comprehensive Cancer Center in Washington state.

Why do clinical trials matter?

Clinical trials are essential to disease research and are a key component of SCCA’s mission to translate scientific discoveries into prevention, diagnosis, treatment, and cure for cancer and all the conditions we treat. Without clinical trials, new interventions could not be approved.

Every advance in cancer treatment in recent years has come out of clinical trials.Take just one important example: Bone marrow transplantation, among the most significant medical advances of the 20th century, was developed by researchers at Fred Hutch. Now used to treat many kinds of cancers and noncancerous blood disorders, this life-saving treatment would not exist without patients who were willing to participate in clinical trials.

Who are clinical trials for?

The goal of clinical studies is to increase our knowledge about diseases and to develop safer, more effective treatments in the fight against them. Cancer is complex, and there are clinical trials that look at many aspects and stages of the disease — trials are not just for patients in the final stages of their illness. There are trials:

  • To examine ways to prevent cancer in healthy people
  • To better detect and diagnose cancer
  • For patients starting initial treatment and for patients who relapse
  • To assess the quality of life of cancer patients and survivors
What do clinical trials test?

Many clinical trials test new interventions or new combinations of interventions in people, sometimes referred to as human subjects or study participants. New interventions include:

  • Medical products, such as drugs and devices
  • Procedures, such as surgery and radiation therapy techniques
  • Behavior changes, such as diet and exercise

Some clinical trials focus on the long-term effects of treatments already in use.

Before reaching clinical trials, a new intervention typically will have been studied in the laboratory (nonclinical studies) and in animals (pre-clinical studies). Clinical trials are carefully designed to answer questions about the safety and effectiveness of the intervention in people. Clinical trial participants are closely monitored throughout the study.

Clinical trial types

There are several types of clinical studies (also called clinical trials), including treatment studies, quality-of-life studies, detection and diagnostic studies, prevention studies, and correlative studies.

Treatment

A large number of clinical studies offered at Seattle Cancer Care Alliance (SCCA) are treatment studies. These studies attempt to find better ways to treat people with cancer or other diseases, and they are available for all stages of disease, from early to advanced.

The studies test new treatments or new ways of using current treatments, including drugs (such as chemotherapy agents, vaccines, blood products, or gene therapies), medical devices (such as infusion pumps), techniques for surgery or radiation therapy, or a combination of treatments, as well as no treatment or delayed treatment.

Quality-of-life

These studies typically explore and measure ways to use supportive care to improve the comfort and quality of life of patients and survivors. This may include ways to manage disease symptoms or ways to manage or decrease side effects associated with treatment. These studies may be:

  • Agent studies, in which the participant takes something—for example, a drug to improve mouth sores or lessen nausea
  • Action studies, in which the participant does something—such as begins an exercise regimen or makes dietary changes

Some studies are even designed to help families and caregivers cope with their needs. For example, a study might test whether spouses of women with breast cancer have less depression and anxiety and better communication with their spouse if they participate in an educational counseling program.

Detection and diagnostic

Detection and diagnostic studies test new ways of finding and identifying cancer or another disease early or with better accuracy. When cancer is found early, it may be easier to treat, and there may be a better chance for a cure.

  • Detection studies usually involve screening healthy volunteers who do not have any signs or symptoms of the disease being studied. Often these studies enroll participants who have a higher risk of developing the disease; for cancer, this may mean they are at higher risk as a result of their family history (genetics) or exposure to cancer-causing substances (carcinogens).
  • Diagnostic studies usually are trying to improve the accuracy of diagnosing a disease in people who have some signs or symptoms.
Prevention

In cancer research, the goal of a prevention study is to find ways to prevent people from getting cancer in the first place or to prevent a recurrence or new cancer in people who have had the disease. In these studies, volunteers who don’t have cancer may be recruited to participate, often because they are at high risk, due either to genetics or to exposure to carcinogens. Participants may take something, such as a drug, or do something, such as change their diet, to lower their risk.

Most prevention studies compare groups of people while the study is underway, rather than waiting until the end of the study, to see if there is a difference. If there is a distinct benefit or risk to a particular group, the study will be stopped or changed so everyone receives the best option.

Correlative

In addition to testing the safety and effectiveness of new interventions, clinical studies provide the opportunity for researchers to do correlative studies. These studies look for relationships between factors. The idea is that noticing trends and investigating them might improve doctors’ knowledge about how to prevent, detect, and treat a disease.

Correlative studies may use specimens from study participants, including their blood, tumor cells, or other tissue. Researchers must obtain permission from participants before using their specimens—which may have been taken before, during, or after treatment—for research purposes.

An example of a correlative study is one that compares biomarkers in a patient’s feces and blood to their colonoscopy results to see whether the biomarkers may be as accurate as a colonoscopy for detecting colon cancer early.

Clinical trial phases

Clinical studies, which test interventions in people, occur in several steps, known as phases. While each phase is designed to answer different research questions, studies in all phases evaluate the safety of the intervention.

Typically, there are four phases of clinical studies:

  • Phase I: Safety
  • Phase II: Efficacy
  • Phase III: Comparison
  • Phase IV: Post-Marketing

If a new treatment (also called an investigational or experimental treatment) is successful in one phase, it may move on to the next phase. The information gained in each phase helps researchers design subsequent studies. As a treatment progresses through the phases, the number of participants in the studies typically increases. For example, a Phase I study will have a small number of participants, perhaps as few as 10, while a Phase III study may enroll hundreds or even thousands of people.

Sometimes two phases may be combined (as in Phase I/II or Phase II/III studies) to provide a smooth transition between phases and allow the research questions to be answered more quickly or with fewer participants.

Although treatment studies are typically assigned a phase, other types of clinical trials, such as prevention studies, may not be labeled this way.

Phase I: Safety

Phase I is typically the first time the treatment is tested in humans, the first time it is studied for a particular condition, or the first time it is being administered in a particular way (for example, in a new combination with other drugs).

Even though the investigational treatment has been studied in the laboratory (nonclinical studies) and in animals (pre-clinical studies), the risk to participants can be significant. For this reason, Phase I studies often enroll small numbers of participants (about 15 to 30) who typically don’t have any other treatment options—patients who cannot be treated with the standard (most widely accepted) treatment or for whom there is no standard treatment. In cancer research, these tend to be patients with advanced disease.

Phase I studies evaluate the safety of a new treatment, including side effects, dose, and impact on the body. For a new drug, Phase I studies are designed to find the safe dose amount and schedule as well as the best way to give the drug, such as orally or by injection. To determine the highest dose that can be safely given (maximum tolerated dose), researchers may start by giving a low dose to a small group of participants, a slightly larger dose to the next group, and so on, while closely monitoring the participants for side effects.

Generally, the study is only intended to determine the safety of the new treatment, not to show whether it is effective; however, results may provide an indication of whether it is effective.

Learn about the Seattle Cancer Care Alliance Phase I program.

Phase II: Efficacy

Phase II studies are done to determine if a treatment is effective for a certain condition. In the case of cancer, researchers look at the response to the treatment in participants who have the same cancer or similar types of cancer. In Phase II studies, participants are usually given the treatment in whatever way (dose, schedule, method of administration, and so on) researchers determined was best during Phase I studies; sometimes Phase II studies test variations in dose or schedule.

Phase II studies often include more participants than Phase I studies but are usually limited to fewer than 100 people.

Phase III: Comparison

Phase III studies compare the effectiveness and side effects of treatments, typically a new treatment and the standard treatment, in patients with a particular type of cancer. The goal is to determine whether the investigational treatment is more effective than the standard.

To make this comparison, patients may be randomized—that is, randomly assigned to one of the two (or sometimes more) arms of the study. Neither you nor your doctor can choose or influence the arm (or group) you will be in.

  • If you are assigned to the investigational group, you will get the new treatment being tested.
  • If you are assigned to the control group, you will get the standard treatment for your cancer.

Randomization, used in some Phase II and nearly all Phase III studies, is important to the scientific validity of the research. It eliminates bias in selecting which patients get which treatment. This helps ensure that differences between the groups’ results are due to the different treatments they received and not other factors. Often, randomized studies are single blind, meaning you don’t know which treatment you are getting, or double blind, meaning neither you nor your doctor knows.

Phase III studies enroll a large number of participants—typically between 100 and several thousand—and often take place at a number of cancer centers throughout the country (which is why they may be called multicenter studies).

In the United States, after successful Phase III clinical studies, the developer of the treatment (such as a pharmaceutical company in the case of a drug) may apply for U.S. Food and Drug Administration (FDA) approval of the treatment. If the FDA approves the treatment, it may become a standard therapy.

Phase IV: Post-Marketing

Some treatments that are approved by the FDA are tested in Phase IV clinical studies. In these studies, also known as post-marketing studies, researchers may monitor the effectiveness and safety of the treatment over a long period of time and in a larger, more diverse, or different population than in previous studies.

How are placebos used in clinical trials?

In cancer research, placebos, which are inactive treatments, may be given to the control group in randomized studies to test interventions that might prevent cancer in people who do not have the disease. Placebos are almost never used in cancer treatment studies. They might be used in these situations:

  • If no standard treatment exists for the study participants, researchers might compare the effects of a new treatment with the effects of a placebo. This helps them distinguish between the actual benefits of the investigational treatment and the benefits of believing you’re getting effective treatment.
  • More often a placebo is given along with a standard treatment so researchers can compare this with an investigational treatment plus the same standard treatment.

You will be told in advance if the study you’re considering uses a placebo and you could be assigned to the placebo group.

Safety of clinical trial participants

Patient safety is extremely important to us at Seattle Cancer Care Alliance (SCCA). We do everything we can to protect you against unnecessary risks during your treatment, whether you are in a clinical study or not. At the same time, we recognize that no clinical study is without some degree of risk, and we have a number of safety procedures and practices in place.

State, national, and international regulations and policies protect the rights, safety, and well-being of people who are enrolled in clinical studies, also called clinical trials, and ensure the studies are conducted according to strict scientific and ethical principles. In the United States, the Office of Human Research Protections oversees clinical studies and protects study participants. The U.S. Food and Drug Administration (FDA) has authority over clinical studies of drugs, biologics, and medical devices.

Your rights and safety are protected through the clinical study protocol, which undergoes scientific and human subjects–protection reviews and approval, as well as through ongoing monitoring of safety throughout the study.

What is a clinical trial protocol?

All clinical studies follow a plan (protocol) that includes:

  • The reason for doing the study
  • Rules about who can join the study (eligibility, or inclusion and exclusion, criteria)
  • The number of people needed for the study
  • Details of the treatment and safety information
  • Schedule and details of tests and evaluations that will be done
  • Details about information that will be collected from study participants

Eligibility criteria may include many factors, such as a certain type and stage of cancer, previous treatment history, age, gender, medical history, and current health status. Eligibility criteria help protect people from getting treatment that may harm them; these criteria also reduce differences among study participants, which helps ensure that study results are due to the intervention provided rather than other factors.

Who reviews and approves a new trial?

At SCCA, study protocols go through internal scientific review, safety review, and clinical review prior to being submitted for review by an institutional review board (IRB), a human subjects–protection entity. IRB review is a federal requirement of all clinical studies: No participants may be enrolled in a clinical study until the protocol has been approved by an IRB.

The IRB is made up of researchers (doctors, nurses, and scientists) and laypeople and is responsible for making sure the rights and welfare of human subjects are protected in studies. The IRB also evaluates proposed studies for ethical research practices, proper attention to safety of participants, and respect for participants’ rights.

What is informed consent?

It is up to you whether to participate in a clinical study. The informed consent process—giving people enough information about the purpose, plan, treatment, tests, procedures, duration, risks, benefits, and alternatives of a study to allow them to make an informed decision—is important to participant safety. Your doctor or nurse should explain the study to you in detail in terms you can understand and answer any questions you may have about the study.

There are special procedures in place to provide informed consent for non-English speaking participants so they too can consider taking part in clinical studies. Learn more about interpreter services and other resources for international patients.

Feel free to ask questions and discuss the study with family and friends so you can make a decision you are comfortable with. If you decide to participate in the study, you will be asked to sign an informed consent form. You must sign the form to enroll in the study before you undergo any procedures that are part of the study.

During the study, researchers must inform you of any new risks, benefits, or side effects they discover.

You can decide to stop participating in the study after signing the informed consent form or at any time during the study. Also, your treatment team may decide before or during the study that it’s not in your best interest to begin or continue in the study—for example, if there’s an unexpected change in your health.

Discuss your decision about participating in or withdrawing from a clinical study with your treatment team. They can tell you how your decision may affect your health and discuss other treatment options with you. Your relationship with your SCCA treatment team and the quality of care provided will not change based on whether you join or stay in a clinical study.

How are studies monitored?

The IRB that approved the study continues to monitor the study while it is in process. This includes conducting reviews of the study at least once a year, reviewing any changes to the study protocol or the informed consent form during the study, and reviewing any new information about the study.

In addition, for some clinical studies—usually Phase III studies—a data and safety monitoring board (DSMB) monitors and reviews the study data periodically to ensure the safety of study participants. The DSMB is an independent committee made up of statisticians and doctors who are experts in clinical research. A study may be stopped early if safety concerns arise or if the answer to the main research question has been answered by the study.

The FDA also may inspect study records and sites to make sure participants are protected and studies are being done correctly.

Special Populations

Some populations, such as children, prisoners, and other groups that may be vulnerable to influence, have additional safeguards to protect them. For example, since children often cannot understand study details, they cannot give true informed consent. Instead, their parents or guardians must give permission for them to participate. 

Older patients and clinical trials

If you are an older patient, you may think clinical studies, also called clinical trials, are not for you simply because of your age. But this is not necessarily the case. Older people have different levels of health and independence and different expectations of treatment. In many cases a person’s age need not be a major factor in determining their treatment options for cancer or another serious disease.

Historically, older patients have been underrepresented in clinical studies. But the trend is improving.

“Attitudes toward enrolling older patients in clinical studies are changing for the better,” said F. Marc Stewart, MD, medical director at Seattle Cancer Care Alliance (SCCA). “Many of our studies use approaches that previously might have been limited to younger patients but that now, due to research advances, are very appropriate for older people.”

Decisions about treatment are personal. No matter what your age, if you have cancer or another serious disease, you should consider all available treatment options, including clinical studies. Ask your SCCA treatment team about the risks, benefits, and goals of each treatment option to decide which is best for you. 

Why it’s important for older adults to join clinical studies

Worldwide, the population of older adults is increasing. Since the greatest risk factor for cancer is age, it is no surprise that the majority of new cancer cases and cancer-related deaths are in people over age 65. This is also why experts predict the number of older cancer patients and survivors seeking treatment will increase exponentially in the future.

Studies of many different cancers have demonstrated that age may be a factor in the tendency for cancer to spread, and older patients may need to take different dosages of medications and may experience different side effects than younger patients. Since the course of cancer and the effects of treatment may be different in older people, studies that involve older people with cancer are needed to find the best interventions for this growing population.

Participation by older adults now

Despite this need, few older people participate in clinical studies. As recently as the mid-1990s, less than one in four clinical study participants was 65 years old or older; yet this same age group made up almost two-thirds of new cancer diagnoses and nearly three-quarters of cancer-related deaths.

There are many reasons why more older adults don’t participate in clinical studies, including:

  • The standard treatment, not a clinical study, may be the best option for them.
  • Older patients are less likely to be offered a clinical study.
  • Medical histories and conditions common in older patients—such as diabetes, high blood pressure, heart disease, lung disease, kidney disease, arthritis, or dementia—can affect compliance and survival, and make analysis of study results more difficult.
  • Older patients and their doctors may be concerned about the potential side effects of an investigational intervention.
  • Exclusion criteria for studies—such as advanced age, reduced life expectancy, physical disabilities, illnesses, and functional limitations—disproportionately affect older patients.

Other factors that tend to decrease the number of older patients in studies include preference for treatment from their community doctor (who is less likely to offer studies), difficulty getting to health care centers where studies take place, additional time required for enrollment and follow-up, and costs of care.

Certainly studies in older populations are complicated by these factors, but with modifications more clinical studies could be appropriate for older adults. For example, studies could evaluate outcomes that are more relevant to older adults, such as how their quality of life is affected (like how long they go without symptoms or how toxic the treatment is for them), instead of how long it takes for their disease to progress.

Even though older patients have been underrepresented in clinical studies in the past, this is starting to change. In the United States, the increase may be due to expanding Medicare coverage for studies. In addition, as reported by the American Society of Clinical Oncology in 2013, three-fourths of patients over 70 said they would be willing to take part in a study, so perhaps more patients and their doctors are considering studies as an option.

Learn more

Whatever your age, consider clinical studies. Ask your doctor whether you qualify for any studies and whether any of them might be a good option for you. For more information, be sure to read the rest of this patient guide to clinical studies. Also, there are several other websites where you can learn more, including websites specific to older adults.

Older patients and clinical trials

If you are an older patient, you may think clinical studies, also called clinical trials, are not for you simply because of your age. But this is not necessarily the case. Older people have different levels of health and independence and different expectations of treatment. In many cases a person’s age need not be a major factor in determining their treatment options for cancer or another serious disease.

Children and clinical trials

Luckily, cancer in children is rare — less than 1 percent of cancers diagnosed in the United States are in children. Of course, that is probably little consolation if you are a parent or family member of a youngster with this disease.

The relatively low rate of pediatric cancer makes it especially important for doctors and scientists nationwide to work together on research studies that gather data from different treatment centers so they can learn more, more quickly, about how to get the best results for patients. Nearly all children diagnosed with cancer in this country are cared for at one of more than 200 institutions that make up Children’s Oncology Group (COG). Seattle Children’s, an SCCA founding organization, is one of them.

Through cooperative efforts such as COG, doctors continue to make significant progress in treatment. Clinical studies, also called clinical trials, are the backbone of this success. In fact, more than half of all American children with cancer receive their therapy as part of a clinical study.

“We believe passionately in clinical trials, because they work,” said Jeffrey Russell Geyer, MD, a pediatric oncologist with Seattle Children’s and SCCA. As a result of the progress made through research, the outlook for most children with cancer is promising—about 80 percent of children diagnosed today survive. This is a significant improvement compared to the 10 to 20 percent survival rate seen 50 years ago.

Understanding the options

If your child has been diagnosed with cancer, his or her doctor may talk to you about having your child participate in a clinical study. Participation is completely voluntary. Whether your child participates in a clinical study or not, through Seattle Children’s and SCCA your child will get the same high quality of care.

When considering a clinical study, you will likely want to understand any differences between the standard treatment for your child’s disease and the treatment your child would receive in the study. In a typical randomized clinical study for children with cancer, some children receive the standard treatment, while others receive an investigational treatment. Often this investigational treatment is very similar to the standard; for example, it may be the same drug given at a different dose or given with a different combination of drugs previously shown to be effective. Your child’s treatment team can explain all your child’s treatment options, including standard and investigational treatments.

When talking to parents about clinical studies, Dr. Geyer tries to be “extraordinarily clear” about the possible risks as well as the possible benefits to their child. “We approach most families with the idea that we have an opportunity to cure the child [with a clinical study],” he said. “But it is not a guarantee.”

Ask as many questions of your child’s treatment team as you need to feel comfortable before deciding on a study. Talk with your child’s treatment team about how much time you have to decide on a course of treatment. Depending on your child’s disease, doctors may need to start treatment very quickly, or you may have days or weeks to make a treatment choice.

Doctors understand that you may want a second opinion before deciding, and they will not be offended if you ask about getting one. The ideal way to do this is to discuss it with your child’s primary oncologist to ensure that any consulting doctor has timely access to your child’s full medical information.

Differences between children and adults

Since cancer in children is uncommon, most cancer therapies have not been tested in children. A common approach has been to use data from adult research and adjust for the body weight of the child; however, children aren’t just small adults.

Differences between adults and children in the biology of tumors, metabolism, organ development, and body proportion may cause children to respond differently to treatments. This is one reason why it’s important to conduct studies with children as well as adults. It’s also important that researchers working with children give special consideration to the differences. Even so, it may be comforting to know that in many clinical studies of an intervention not previously used in children, the treatment has already been tested in adults.

Another important difference is that children under the legal age of consent — age 18 — cannot give informed consent, which implies fully understanding the study process, the risks, and other factors. This means you must be involved in the decision and must give permission for your child to enroll in a study.

Depending on your child’s age, he or she may be able to understand at least some aspects of this decision and may have an opinion. According to the National Commission for Protection of Human Subjects of Biomedical and Behavioral Research, children age 7 or older can assent or dissent (agree or not agree) to take part in studies. According to the National Cancer Institute, researchers must obtain a child’s assent unless:

  • The child is not capable of assenting (for instance, the child is an infant).
  • The clinical study offers a therapy thought to be better than those currently available.
  • The clinical study is the only treatment option.

Before your child assents or dissents, the study must be explained to them in terms appropriate to their age. Your child’s treatment team can help with this. Visual aids may help, too.

Children and clinical trials

Luckily, cancer in children is rare — less than 1 percent of cancers diagnosed in the United States are in children. Of course, that is probably little consolation if you are a parent or family member of a youngster with this disease.

Deciding to participate

There are many reasons for participating in a clinical study, also called a clinical trial. Ultimately the decision to take part in research belongs to you, the patient. The decision you make will probably be a result of a combination of diverse reasons—some large, some small, some based on scientific evidence, some based on personal attitudes and feelings about health and disease.

Health insurance and clinical trials

Whether you are thinking about participating in a clinical study or not, health care costs and insurance coverage are major concerns for many patients and their families. An important factor in deciding to join a clinical study may be whether your health insurance will cover the costs.

A common myth is that health insurance won’t cover the cost of treatment provided through a clinical study. Some people might not enroll in a study because of coverage concerns. In fact, the majority of participants in clinical studies do receive at least some reimbursement from their health insurance for routine care, and the study often provides research procedures and the investigational agent for study participants. But health insurance may not pay all the costs.