Charles Drew University of Medicine And Science - Division of Cancer Research And Training
  
About Clinical Trials


What is a clinical trial?

A clinical trial is a research study that is conducted on human subjects to find new ways to prevent, detect, diagnose, or treat diseases such as cancer. Each study conducted has been designed as per the standards set by FDA and Institutional Review Board (IRB). Every study conducted adheres to the principles of good clinical practices (GCPs), including adequate human subject protection (HSP) by maintaining the rights, integrity, and confidentiality of trial subjects.

New treatments must prove to be safe and effective before they can be made widely available. Carefully conducted clinical trials are the fastest way to find new and better treatments that work in people. Before a treatment is tried in people, it is carefully studied in the laboratory for its efficacy, pharmacological and toxicological profile on laboratory animals. The treatments with the most promising laboratory results are then moved into clinical trials.

Clinical trials can be both interventional and observational types of studies. Interventional studies are those in which the research subjects are assigned by the investigator to a treatment or other intervention, and their outcomes are measured. Observational studies are those in which individuals are observed and their outcomes are measured by the investigators.

 

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, gene therapy and vaccines or other treatments that stimulate a person’s immune system (the body’s defense system) to fight cancer. Combinations of different treatment types may also be tested in these trials.

 

 Prevention: These trials test new interventions (treatments or actions taken to prevent or treat disease, or improve health) 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.

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 trials represent the earliest step in testing new treatments in humans. In a phase 0 trial, a chemical or biologic agent (i.e. a substance made from a living organism or its products) is  exposed to a small number of  patients (perhaps 10 or fewer) for a limited duration of time (i.e. 7 days or less)  to a very small dose (in the range of one 100th of the dose required to yield a pharmacologic effect of the test substance) to gather preliminary information about how the agent is processed by the body (pharmacokinetics (PK)) and how the agent affects the body (pharmacodynamics (PD)). Because these agents are given in such small amounts, no information is obtained about their safety or effectiveness in treating a disease. Phase 0 trials are also called micro-dosing studies, exploratory Investigational New Drug (IND) trials, or early phase I trials. Phase 0 trials in cancer may be designed to determine a statistically significant, treatment-related change from baseline in a PD end point. The people who take part in these trials usually have advanced disease and no known effective treatment options are available to them.

 

 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 are designed to determine the metabolism and pharmacological actions of drug in humans. Phase I is generally carried out to determine side effects associated with increasing doses and early evidence on effectiveness (in humans). The main objective of a phase I trial in oncology is to determine the minimum toxic dose, and the maximum dose (also known as the maximum tolerated dose) that can be given safely administered. Phase 1 trials are short duration trials (2-4 weeks) and are closely monitored. Phase I cancer trials generally 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 I cancer clinical trial is open to patients regardless of the type of cancer. Most people participate in Phase I cancer clinical trial if they either have a rare form of cancer for which there are no Phase II or III trials; or if Phase I trial is designed to test a new combination of drugs rather than a new drug in the hopes that possibly the results of the combination therapy are superior to those with either drug alone.

 

 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.

 

 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”: 1) a control group, in which everyone in the group receives usual treatment for their type of cancer, or 2) 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 (like flipping a coin). 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.

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 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 (Food and Drug Administration) for standard use. Several hundred to several thousand people may take part in a phase IV 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 I/II or phase II/III 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.

 

Protocol

 

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. Studies are carefully designed to safeguard the health of the participants as well as to answer specific research questions.

Some clinical trials test one new treatment in one group of participants. Other trials compare two or more groups. Researchers make sure that participants in different groups are similar in certain ways, such as the nature and stage of their disease.

 

Informed Consent

 

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, the 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, which provides information about the trial in writing. People who agree to take part in the trial are asked to sign the form. Anyone can choose to leave a trial at any time—either before it starts or 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.

 

Research Team

 

Each clinical trial is managed by a research team that can include doctors, nurses, coordinators, 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.

 

Regulations

 

National and international regulations and policies have been developed to help ensure that research involving people is conducted according to strict scientific and ethical principles.

Institutional Review Board (IRB)

All clinical trials must be reviewed and approved by the 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 nonscientist and the nonaffiliated 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.

 

Data Safety Monitoring Board

 

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.

 

Completion of Clinical Trial

 

After a clinical trial is completed, the 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. What to ask when considering participation in a clinical trial.

Learn as much as possible about the trial. Ask the research team questions about the trial. Here are a few:

·         What is the purpose of the study?

·         Who is going to participate in the study?

·         Will the study results be published?

·         Why do researchers think the experimental treatment being tested may be effective? Has it been tested before?

·         What types of tests and experimental treatments are involved?

·         Will the study directly benefit me? Will the study benefit others?

·         How do the possible risks, side effects, and benefits of the study compare with my current treatment?

·         If there are risks, what are the chances they will occur?

·         How might this trial affect my daily life?

·         What will the study require of me?

·         How much of my time will be involved?

·         How long do trials last?

·         Will hospitalization be required? Outpatient visits? How long and how many?

·         Who pays for the experimental treatment?

·         How will I know if the experimental treatment is working? Will I be told about trial results?

·         Who is responsible for my care?

Choosing to participate in a clinical trial is an important personal decision. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They receive regular and careful medical attention from a research team and receive state-of-the-art care from cancer experts.

 

Reference:

 

The Web site of the National Cancer Institute (http://www.cancer.gov)