Clinical Trials Frequently Asked Questions

Clinical trials are studies conducted to find new ways to prevent, detect and treat cancer. A physician called an investigator carefully designs each clinical trial.

Clinical trials are carried out according to strict scientific and ethical principles:

• Each clinical trial has a protocol (action plan) that explains how the study will be carried out.
• The investigator, or person in charge of the study, prepares the protocol for the study. This protocol explains what will be done, why, how many people will participate, what medical treatments participants will receive and how often, as well as the treatment plan.

Each doctor who takes part in the study uses the same protocol.

Protocols go through a strict approval process for patient safety. This process includes review by the organization sponsoring the study. At Penn, the protocols are reviewed by Penn’s Institutional Review Board (IRB) and the Abramson Cancer Center’s Clinical Trials and Scientific Review and Monitoring Committee.

Enrollment

Each study's protocol describes the characteristics all patients in the study must have. These key characteristics are called eligibility criteria. Eligibility criteria differ from study to study, depending on the research purpose. They may include such factors as age, gender, and the type and stage of cancer.

Today, more and more people are surviving cancer. It is because of clinical trials – many of which are conducted at Penn Medicine – that patients around the world are benefiting from breakthrough therapies and treatments.

A clinical trial is one of the final stages of a long and careful cancer research process. Studies are done with cancer patients to find out whether new approaches to cancer prevention, diagnosis, and treatment are safe and effective.

Clinical trials are important for:

• Providing options for people with cancer, while allowing physicians to improve the way they prevent, diagnose and treat cancer
• Giving patients access to the latest advances available in cancer care
• Benefiting future generations with new and improved treatments

As an academic medical center, Penn Medicine holds research as an important component of its three–partite mission, which is patient care, education and research. Clinical research teaches doctors and nurses how to help patients live longer, healthier lives. All medical advancements are the result of organized, academic investigation.

Choosing to participate in clinical research is a personal decision. Many patients choose to participate, but enrolling in a clinical trial may not be the best decision for every cancer patient. Clinical trials also give patients access to the latest advances available in cancer care. Others participate as a way to prevent or treat cancer that may arise in their family or community at large.

There is no guarantee that you will experience any direct benefit from participating in a study, but there is the potential that you could experience adverse events. The clinical research team discusses the potential problems (and how they can be handled) with you before you agree to be in the study.

You should discuss the risks and benefits of clinical trials with your physician and family since each study is unique.

The Abramson Cancer Center oversees one of the largest clinical trials programs in the country, with more than 200 trials available at any one time.

The National Cancer Institute (NCI) named the Abramson Cancer Center as an "exceptional comprehensive care centers dedicated to creating new models for cancer treatment and prevention with cancer research. This exceptional rating is the highest designation given by the NCI, the U.S. government's principal agency for cancer research. The Abramson Cancer Center receives $10 million annually from the NCI to maintain and obtain resources to support groundbreaking research that gives hope to cancer patients.

Because of its excellence in clinical trials, the Abramson Cancer Center has been selected to participate in important national clinical trials for such recognized groups as:

• Eastern Cooperative Oncology Group
• Gynecologic Oncology Group
• National Surgical Adjuvant Breast Bowel Project
• Radiation Therapy Oncology Group
• Southwest Oncology Group

• Treatment trials test new treatments. New treatments for cancer may include a new cancer drug, new approaches to surgery or radiation therapy, new combinations of treatments, or new treatment methods such as immunotherapy.
• Prevention trials test new approaches to cancer prevention. New approaches may include medicines, vitamins, minerals, or other supplements that doctors believe may lower the risk of a certain type of cancer. These trials look for the best way to prevent cancer in people who have never had cancer, prevent cancer from coming back or prevent a new cancer from occurring in people who have already had cancer.
• Screening trials test the best way to find cancer, especially in its early stages.
• Quality of life trials (also called supportive care trials) explore ways to improve comfort and quality of life for cancer patients.

Most clinical research that involves the testing of a new drug progresses in an orderly series of steps, called phases.

Phases allow researchers to ask and answer questions in a way that results in reliable information about the drug and protects the patients.

Most clinical trials are classified into one of three phases:

Cancer clinical trials are carried out in three different phases. Each phase answers different questions about the new treatment.

• Phase I trials are the first step in testing a new treatment. In these studies, researchers look for the best way to give a new treatment, and dosage for that treatment. They also monitor for treatment side effects. Because less is known about the possible risks and benefits, these studies usually include only a small number of patients who would not be helped by other known treatments.
• Phase II trials focus on learning whether the new treatment has an anticancer effect. It answers questions such as: Does the treatment shrink tumors or improve blood test results? Because less is known about the possible risks and benefits, these studies usually include only a small number of patients.
• Phase III trials compare the results of people receiving the new treatment with results of people receiving standard treatment. In most cases, studies move into phase III testing only after a treatment shows promise in phases I and II. Phase III trials may include hundreds of people around the country.

Yes. Cancer clinical trials differ according to their primary purpose. They include the following types:

• Treatment. These trials test the effectiveness of new treatments or new ways of using current treatments in people who have cancer. The treatments tested may include new drugs or new combinations of currently used drugs, new surgery or radiation therapy techniques, and vaccines or other treatments that stimulate a person's immune system to fight cancer. Combinations of different treatment types may also be tested in these trials.
• Prevention. These trials test new interventions that may lower the risk of developing certain types of cancer. Most cancer prevention trials involve healthy people who have not had cancer; however, they often only include people who have a higher than average risk of developing a specific type of cancer. Some cancer prevention trials involve people who have had cancer in the past. These trials test interventions that may help prevent the return (recurrence) of the original cancer or reduce the chance of developing a new type of cancer.
• Screening. These trials test new ways of finding cancer early. When cancer is found early, it may be easier to treat and there may be a better chance of long-term survival. Cancer screening trials usually involve people who do not have any signs or symptoms of cancer. However, participation in these trials is often limited to people who have a higher than average risk of developing a certain type of cancer because they have a family history of that type of cancer or they have a history of exposure to cancer-causing substances (e.g. cigarette smoke).
• Diagnostic. These trials study new tests or procedures that may help identify, or diagnose, cancer more accurately. Diagnostic trials usually involve people who have some signs or symptoms of cancer.
• Quality of life or supportive care. These trials focus on the comfort and quality of life of cancer patients and cancer survivors. New ways to decrease the number or severity of side effects of cancer or its treatment are often studied in these trials. How a specific type of cancer or its treatment affects a person's everyday life may also be studied.

Every clinical trial is managed by a research team that includes doctors, nurses, research assistants, data analysts and other specialists. The research team works closely with other health professionals, including other doctors and nurses, laboratory technicians, pharmacists, dietitians, and social workers, to provide medical and supportive care to people who take part in a clinical trial.

The research team closely monitors the health of people taking part in the clinical trial and gives them specific instructions when necessary. To ensure the reliability of the trial's results, it is important for the participants to follow the research team's instructions. The instructions may include keeping logs or answering questionnaires. The research team may also seek to contact the participants regularly after the trial ends to get updates on their health.

Every clinical trial has a protocol, or action plan that describes what will be done in the trial, how the trial will be conducted, and why each part of the trial is necessary. The protocol also includes guidelines for who can and cannot participate in the trial. These guidelines, called eligibility criteria, describe the characteristics that all interested people must have before they can take part in the trial.

Eligibility criteria can include age, sex, medical history and current health status. Eligibility criteria for cancer treatment trials often include the type and stage of cancer, as well as the type(s) of cancer treatment already received.

Enrolling people who have similar characteristics helps ensure that the outcome of a trial is due to the intervention being tested and not to other factors. In this way, eligibility criteria help researchers obtain the most accurate and meaningful results possible.

Quick Facts About Trial Eligibility, Costs and Payment

Every clinical trial has a protocol, or action plan that describes what will be done in the trial, how the trial will be conducted, and why each part of the trial is necessary. This protocol also includes guidelines for patient eligibility. These guidelines, called eligibility criteria, describe the characteristics and requirements all interested people must have before they can take part in the trial.

Eligibility criteria can include:

• Age
• Sex
• Medical history
• Current health status

Eligibility criteria for cancer treatment trials often include the type, stage of cancer, and genetic make-up of the cancer.

Financial Requirements

Financial requirements to participate in a clinical trial vary depending on the type of trial. The costs of care for people participating in a clinical trial fall into two general categories:

• Routine care costs
• Research costs

Routine care costs are costs associated with treating a person's cancer whether or not they are in a trial. These costs are usually covered by health insurance, but requirements vary by state and type of health plan.

Research costs are costs associated with conducting a clinical trial; these costs may include the costs of extra doctor visits, extra tests, and procedures that are required for the trial but would not be part of routine care.

Research costs are usually covered by the organization that sponsors the trial. For example, if the US government or a pharmaceutical company is sponsoring the trial, the costs will be covered by that organization.

Role of Private Insurance in Clinical Trial Costs

The total costs of participating in clinical trials are rarely covered for US residents by public or private insurance programs due the experimental nature of the treatments being tested. Coverage by foreign government programs for non-U.S. residents is even less likely.

In order to participate in a clinical trial at Penn Medicine, you will need to be able to pay for needed services not provided as part of the clinical trial directly or through your insurance company/health plan, if coverage can be secured. You will also need to be able to secure living arrangements, and pay for living expenses throughout the course of the trial if you do not live within the Philadelphia region.

Learn Your Financial Options

Penn Medicine has financial counselors to help with this process and review financial responsibilities with you. To speak with a financial counselor, and learn your options, please contact 800-789-7366 (PENN).

National and international regulations and policies have been developed to help ensure research involving people is conducted according to strict scientific and ethical principles. In these regulations and policies, people who participate in research are usually referred to as "human subjects."

Clinical trials that are conducted or supported by agencies of the U.S. federal government or that evaluate new drugs or medical devices that are subject to regulation by the U.S. Food and Drug Administration (FDA) must be reviewed and approved by an Institutional Review Board (IRB). The IRB reviews all aspects of a clinical trial to make sure that the rights, safety, and well-being of trial participants will be protected. The IRB must also review ongoing trials at least yearly and, based on those reviews, can decide whether the trial should continue as initially planned or if changes should be made to improve participant protection. An IRB can stop a clinical trial if the researchers are not following the protocol or if the trial appears to be causing unexpected harm to the study participants.

An IRB must have at least five members, including one scientist, one person who is not a scientist, and one person who is not affiliated with the institution where the trial is taking place and who is not an immediate family member of someone who is affiliated with that institution. The non-scientist and the non-affiliated member can be the same person. IRBs can also include doctors, nurses, social workers, chaplains, patient advocates, and other health care or community professionals. All members of an IRB are required to be educated about the IRB's purpose, functions, and responsibilities, as outlined in federal regulations. Trials taking place at multiple locations can involve multiple IRBs.

In addition, some clinical trials, especially phase III clinical trials, use a Data and Safety Monitoring Board (DSMB) to monitor the safety and progress of the trials. In contrast with IRBs, each trial has only one DSMB.

A DSMB is a committee of doctors, statisticians, and others who are independent of the people, organizations, and institutions that are sponsoring, organizing, and conducting the clinical trial. Similar to IRBs, DSMBs review the progress of a clinical trial and participant safety, but they also review data on the effectiveness of the trial interventions. DSMB members are experts in clinical research and clinical trials. They ensure that trial data are complete, and they can stop a trial early if safety concerns arise or if an answer to the main research question is obtained earlier than expected. Stopping a trial early because the main research question has been answered may make it possible for people who are not in the trial to get access to an effective intervention sooner. DSMBs have scheduled meetings to review clinical data, and their meeting minutes or recommendations are forwarded to the IRBs.

Informed consent is a process through which people:

• Learn the important facts about a clinical trial to help them decide whether or not to take part in it, and
• Continue to learn new information about the trial that helps them decide whether or not to continue participating in it.

During the first part of the informed consent process, people are given detailed information about a trial, including information about the purpose of the trial, tests and other procedures that will be required, and the possible benefits and harms of taking part in the trial. Besides talking with a doctor or nurse, potential trial participants are given a form, called an informed consent form that provides information about the trial in writing.

People who agree to take part in the trial are asked to sign the form. However, signing this form does not mean that a person must remain in the trial. Anyone can choose to leave a trial at any time—either before it starts or at any time during the trial or during the follow-up period.

It is important for people who decide to leave a trial to get information from the research team about how to leave the trial safely.

The informed consent process continues throughout a trial. If new benefits, risks, or side effects are discovered during the course of a trial, the researchers must inform the participants so they can decide whether or not they want to continue to take part in the trial. In some cases, participants who want to continue to take part in a trial may be asked to sign a new informed consent form.

New interventions are often studied in a stepwise fashion, with each step representing a different "phase" in the clinical research process. The following phases are used for cancer treatment trials.

Phase 0

Phase 0 trials represent the earliest step in testing new treatments in humans. In a phase 0 trial, a very small dose of a chemical or biologic agent is given to a small number of people (approximately 10-15) to gather preliminary information about how the agent is processed by the body (pharmacokinetics) and how the agent affects the body (pharmacodynamics). Because the agents are given in such small amounts, no information is obtained about their safety or effectiveness in treating cancer. Phase 0 trials are also called micro-dosing studies, exploratory Investigational New Drug (IND) trials, or early phase I trials. The people who take part in these trials usually have advanced disease, and no known, effective treatment options are available to them.

Phase I (also called phase 1)

Phase I trials are conducted mainly to evaluate the safety of chemical or biologic agents or other types of interventions (e.g., a new radiation therapy technique). They help determine the maximum dose that can be given safely (also known as the maximum tolerated dose) and whether an intervention causes harmful side effects. Phase I trials enroll small numbers of people (20 or more) who have advanced cancer that cannot be treated effectively with standard (usual) treatments or for which no standard treatment exists. Although evaluating the effectiveness of interventions is not a primary goal of these trials, doctors do look for evidence that the interventions might be useful as treatments.

Phase II (also called phase 2)

Phase II trials test the effectiveness of interventions in people who have a specific type of cancer or related cancers. They also continue to look at the safety of interventions. Phase II trials usually enroll fewer than 100 people but may include as many as 300. The people who participate in phase II trials may or may not have been treated previously with standard therapy for their type of cancer. If a person has been treated previously, their eligibility to participate in a specific trial may depend on the type and amount of prior treatment they received. Although phase II trials can give some indication of whether or not an intervention works, they are almost never designed to show whether an intervention is better than standard therapy.

Phase III (also called phase 3)

Phase III trials compare the effectiveness of a new intervention, or new use of an existing intervention, with the current standard of care (usual treatment) for a particular type of cancer. Phase III trials also examine how the side effects of the new intervention compare with those of the usual treatment. If the new intervention is more effective than the usual treatment and/or is easier to tolerate, it may become the new standard of care.

Phase III trials usually involve large groups of people (100 to several thousand), who are randomly assigned to one of two treatment groups, or "trial arms":

• A control group, in which everyone in the group receives usual treatment for their type of cancer, or
• An investigational or experimental group, in which everyone in the group receives the new intervention or new use of an existing intervention.

The trial participants are assigned to their individual groups by random assignment, or randomization. Randomization helps ensure that the groups have similar characteristics. This balance is necessary so the researchers can have confidence that any differences they observe in how the two groups respond to the treatments they receive are due to the treatments and not to other differences between the groups.

Randomization is usually done by a computer program to ensure that human choices do not influence the assignment to groups. The trial participants cannot request to be in a particular group, and the researchers cannot influence how people are assigned to the groups. Usually, neither the participants nor their doctors know what treatment the participants are receiving.

People who participate in phase III trials may or may not have been treated previously. If they have been treated previously, their eligibility to participate in a specific trial may depend on the type and the amount of prior treatment they received.

In most cases, an intervention will move into phase III testing only after it has shown promise in phase I and phase II trials.

Phase IV (also called phase 4)

Phase IV trials further evaluate the effectiveness and long-term safety of drugs or other interventions. They usually take place after a drug or intervention has been approved by the FDA for standard use. Several hundred to several thousand people may take part in a phase 4 trial. These trials are also known as post-marketing surveillance trials. They are generally sponsored by drug companies.

Sometimes clinical trial phases may be combined (e.g., phase 1/2 or phase 2/3 trials) to minimize the risks to participants and/or to allow faster development of a new intervention.

Although treatment trials are always assigned a phase, other clinical trials (e.g., screening, prevention, diagnostic, and quality-of-life trials) may not be labeled this way.

The use of placebos as comparison or "control" interventions in cancer treatment trials is rare.

If a placebo is used by itself, it is because no standard treatment exists. In this case, a trial would compare the effects of a new treatment with the effects of a placebo.

More often, however, placebos are given along with a standard treatment. For example, a trial might compare the effects of a standard treatment plus a new treatment with the effects of the same standard treatment plus a placebo.

The benefits of participating in a clinical trial include the following:

• Trial participants have access to promising new interventions that are generally not available outside of a clinical trial.
• The intervention being studied may be more effective than standard therapy. If it is more effective, trial participants may be the first to benefit from it.
• Trial participants receive regular and careful medical attention from a research team that includes doctors, nurses, and other health professionals.
• The results of the trial may help other people who need cancer treatment in the future.
• Trial participants are helping scientists learn more about cancer (e.g., how it grows, how it acts, and what influences its growth and spread).

The potential harms of participating in a clinical trial include the following:

• The new intervention being studied may not be better than standard therapy, or it may have harmful side effects that doctors do not expect or that are worse than those associated with standard therapy.
• Trial participants may be required to make more visits to the doctor than they would if they were not in a clinical trial and/or may need to travel farther for those visits.
• Health insurance may not cover all patient care costs in a trial.

The costs of care for people participating in a clinical trial fall into two general categories: routine care costs and research costs.

Routine care costs are costs associated with treating a person's cancer whether or not they are in a trial. These costs are usually covered by health insurance, but requirements vary by state and type of health plan.

Research costs are costs associated with conducting a clinical trial; these costs may include the costs of extra doctor visits, extra tests, and procedures that are required for the trial but would not be part of routine care. Research costs are usually covered by the organization that sponsors the trial.

It is important to investigate how the costs of care will be covered before participating in a clinical trial.

After a clinical trial is completed, researchers look carefully at the data collected during the trial to understand the meaning of the findings and to plan further research. After a phase I or phase II trial, the researchers decide whether or not to move on to the next phase or stop testing the intervention because it was not safe or effective. When a phase III trial is completed, the researchers analyze the data to determine whether the results have medical importance and, if so, whether the tested intervention could become the new standard of care.

The results of clinical trials are often published in peer-reviewed scientific journals. Peer review is a process by which cancer research experts not associated with a trial review the study report before it is published to make sure that the data are sound, the data analysis was performed correctly, and the conclusions are appropriate. If the results are particularly important, they may be reported by the media and discussed at a scientific meeting and by patient advocacy groups before they are published in a journal. Once a new intervention has proven safe and effective in a clinical trial, it may become a new standard of care.

The FDA Amendments Act of 2007 requires that researchers report the "basic" results of clinical trials that tested FDA-regulated and FDA-approved chemical or biologic agents or medical devices in ClinicalTrials.gov, a publicly accessible database maintained by the U.S. National Library of Medicine (NLM). Basic trial results must be submitted whether or not the results are published in a peer-reviewed scientific journal and include the following items:

• Demographic and baseline information about the participants
• The progress of the participants through each stage of the trial (e.g., the number of participants who left the trial and at which stage)
• Results for the primary and secondary outcomes (also called endpoints) measured in the trial (e.g., tumor response, disease-free survival, overall survival, quality of life, etc.)
• A point of contact for the trial (to obtain additional information about the trial and its results)

More information is available on the About the ClinicalTrials.gov Results Database page. NLM's website also has an FAQ that lists other ways to find clinical trial results.