Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Each clinical trial is designed to find new or better ways to treat cancer patients. In oncology, clinical trials are especially important because, in the absence of high cure rates, nearly all therapeutic approaches are developmental in nature. All new cancer drugs that are currently available in the United States were once only available in clinical trials. Patients should decide whether or not participation in a clinical trial is an appropriate treatment option as early in their evaluation as possible because, once treatment of their cancer has been initiated, patients may become ineligible to participate in some clinical trials.
- What are Clinical Trials?
- Phases of Clinical Trials
- How are Clinical Trials Conducted?
- Clinical Trial Safeguards
- Why Participate in Clinical Trials?
- What are the Costs of Participating in Clinical Trials?
- How Can I Find Specific Clinical Trials?
What are Clinical Trials?
A clinical trial is a research study designed to evaluate potential new treatment options. These studies are the result of a long and deliberate cancer research process that often takes years. Clinical trials test the safety and effectiveness of new or modified cancer drugs, new drug doses, unique approaches to surgery or radiation therapy, and varied combinations of treatments. Clinical trials are an integral component for improving the treatment of medical conditions because they lead to higher standards of care. In the United States all new cancer treatment products must proceed through an orderly clinical trials evaluation process to ensure that they have an acceptable level of safety and demonstrate benefit to helping patients with a specific cancer before they become commercially available to other patients.
Clinical trials essentially fall into two general categories.
1. The first general category of clinical trials are designed to evaluate new drugs, compounds, or biologic agents that have not yet been approved by the Food and Drug Administration (FDA) for administration to patients. All substances must go through several phases of clinical trials to document their safety and effectiveness before the FDA approves them for routine use to treat cancer patients. Prior to FDA approval, these substances are only available through clinical trials; however, after FDA approval, they are commercially available.
2. Clinical trials may also evaluate drugs, compounds, or biologic agents already approved by the FDA for the treatment of one type of cancer. These substances have already been determined to be safe by the FDA and they are now being evaluated in different doses, schedules, and combinations to determine how to optimally use them for the treatment of a variety of cancers.
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Phases of Clinical Trials
Development of new anticancer agents and treatment strategies occurs in four phases. Each phase is designed to determine specific information about the potential new treatment such as its risks, safety and effectiveness compared to standard therapy. The hope is that the new therapy will be an improvement over the previous standard therapy.
Phase I Trials:
This phase is probably the most important step in the development of a new drug or therapy. These trials usually involve a small number of patients for whom other standard therapies have failed or no known alternative therapy is available. Phase I therapy may produce anti-cancer effects and a small number of patients may benefit. However, the primary goals of this phase are to determine anticancer activity in humans, the maximum tolerated dose of the treatment, the manner in which the drug works in the body, the toxic side effects related to different doses and whether toxic side effects are reversible. Upon completion of phase I trials, the information that has been gathered is used to begin phase II trials.
Phase II Trials:
Once the information is gathered and analyzed from phase I trials, phase II trials are designed to determine the effectiveness of the treatment in a specific patient population at the dose and schedules determined in phase I. These trials usually require a slightly higher number of patients than phase I trials. This number may increase depending on the number of responses as the phase II trial progresses. Drugs or therapies that are shown to be active in phase II trials may become standard treatment or be further evaluated for effectiveness in phase III trials.
Phase III Trials:
Phase III trials compare a new drug or therapy with a standard therapy in a randomized and controlled manner in order to determine proof of effectiveness. Phase III trials require a large number of patients to measure the statistical validity of the results because patient age, sex, race, and other unknown factors could affect the results. To obtain an adequate number of patients, several physicians (investigators) from different institutions typically participate in phase III clinical trials.
Phase IV Trials:
Once the drug or treatment becomes part of standard therapy, the manufacturer of the drug may elect to initiate phase IV trials. This phase includes continued evaluation of the treatment effectiveness and monitoring of side effects as well as implementing studies to evaluate usefulness in different types of cancers.
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How are Clinical Trials Conducted?
Clinical trials are designed to test treatments under very specific scientific and ethical guidelines. Clinical trials use written protocols to define the purpose, design and conduct of a specific clinical trial. All of the research centers participating in a particular study use the same research protocol. The protocol is written by the sponsor of the study and explains what the trial will do, how it will be conducted, where it will be conducted, who may participate and how and when the participants will be evaluated. Sponsors of clinical trials include, but are not limited to, the National Cancer Institute, groups or networks of physicians, individuals within a single cancer institution and manufacturers of biopharmaceutical products. In order to protect patients participating in clinical trials, the sponsor reviews the protocol for safety and appropriateness and then the protocol must undergo a second neutral review by an Institutional Review Board (IRB). The Institutional Review Board is responsible for overseeing any clinical trials that are performed in the specific healthcare institution where the clinical trial is offered/conducted. An Institutional Review Board includes physicians, healthcare providers and individuals not involved in healthcare, including the clergy or ordinary citizens/consumers. Institutional Review Board members do not have any personal interest in the results of the trial and, therefore, can ensure that the study is conducted fairly and safely. Committee members serving on Institutional Review Boards address the following questions in reviewing protocols:
- Does this protocol have scientific value?
- Does the protocol have scientific validity?
- Does the study have a valid scientific design and yet pose an inappropriate risk for subjects?
- Are risks to subjects minimized?
- Are risks to subjects minimized?
- Are the risks to subjects reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result?
- Is the selection of subjects equitable?
- Are additional safeguards in place for subjects likely to be vulnerable to coercion or undue influence?
- Will informed consent be obtained from research subjects or their legally authorized representatives?
- Is there adequate provision for monitoring the data collected to ensure the safety of subjects?
- Are there adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data?
The Institutional Review Board also reviews all informed consent documents to make sure that they provide clear and complete information for those evaluating the merits of enrolling in a specific clinical trial.
Clinical trials evaluating cancer treatments or strategies may be offered in large university hospitals, local community hospitals and/or physician practices. The location where a clinical trial is conducted depends on the specific resources required to conduct the trial, the number of patients needed for enrollment in the trial to answer the question and the individual or institution’s interest in performing clinical trials in general.
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Clinical Trials Safeguards
Both standard care and clinical trials have risks, side effects and benefits that vary depending on the individual. However, there are rigorous guidelines in place to protect the well-being and safety of clinical trial participants. The physician and research nurse conducting the study will explain any known or anticipated risks ahead of time. Once a patient’s eligibility for a specific trial is established, the research nurse will explain the informed consent process. Informed consent is one of the patient’s most important rights in the research process, as it outlines the purpose of the study, the exact treatments that will be administered, all possible side effects, and the patient’s right to withdraw from the study at any point. Signing the consent form acknowledges that the trial was explained and is understood. Also, clinical trial participants are constantly monitored to identify any changes in their condition.
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Why Participate in Clinical Trials?
Clinical trials are designed to evaluate the effectiveness of new treatment interventions. The objective of these clinical trials is to test new therapies in patients who have cancer. Patients participate in clinical trials for several reasons, including:
- The potential to benefit from a new drug or treatment procedure
- Improved management of symptoms resulting from treatment from treatment or cancer
- The opportunity to directly contribute to improving the understanding of how to treat a cancer and ultimately, benefit other patients
Patients who participate in clinical trials receive either a promising new treatment or the best available conventional treatment. If a new treatment option is proven to work, patients who are participating in the clinical trial will be among the first to benefit. While there is no guarantee that any treatment will be successful, clinical trials have been proven to offer some of the most effective cancer treatments currently available today.
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What are the Costs of Participating in Clinical Trials?
There are two types of costs associated with a trial:
- Patient care costs; and
- Research costs
Patient care costs: These are costs associated with providing medical goods and services to each patient. Usual care costs include doctor visits, hospital stays, clinical laboratory tests, x-rays, and any other medical costs that occur regardless of whether a patient is participating in a clinical trial or receiving standard treatment. These costs are usually covered by a third-party health plan, such as Medicare or private insurance.
Research costs: Research costs are costs that are associated with clinical trial participation, such as data collection and management, research physician and nurse time, analysis of results, and tests performed purely for research purposes. Such costs are usually covered by the sponsoring organization, such as a pharmaceutical company. The sponsor and the participant’s health plan need to resolve coverage of these costs for particular trials. Be sure to consult with your physician about the financial aspects of any trial you are evaluating.
Health insurance companies and managed care companies decide which health care services they will pay for by developing coverage policies regarding the specific services. In general, the most important factor determining whether something is covered is a health plan’s judgment as to whether the service is established or investigational. Health plans usually designate a service as established if there is a certain amount of scientific data to show that it is safe and effective. If the health plan does not think that such data exists in sufficient quantity, the plan may label the service as investigational.
Health care services delivered within the setting of a clinical trial are very often categorized as investigational and are not covered. This is because the health plan thinks that the major reason to perform the clinical trial is that there is not enough data to establish the safety and effectiveness of the service being studied. Thus, for some health plans, any mention of the fact that the patient is involved in a clinical trial results in a denial of payment.
Health plans may define specific criteria that a trial must meet before extending coverage. Some plans, especially smaller ones, will not cover any costs associated with a clinical trial, while other, larger managed care plans have recently announced at least partial coverage of costs associated with clinical research. Policies vary widely, but in most cases the best strategy is to have a doctor initiate discussions with the health plans.
For up-to-date information about Medicare coverage of clinical trials, visit the Web site http://www.cms.hhs.gov/medlearn/refctmed.asp to view the Medicare Clinical Trials Quick Reference Guide. As of January 2001, the following information was accurate:
Medicare Approved Clinical Trials
In general, cancer treatment and diagnosis trials are covered if:
- The trial is funded by the National Cancer Institute (NCI), NCI-Designated Cancer Centers, NCI-Sponsored Clinical Trials Cooperative Groups and all other Federal agencies that fund cancer research. Other trials may be eligible for coverage and doctors can ask Medicare to pay the patients’ costs. Patients should ask their doctor about this before beginning a clinical trial.
- The purpose or subject of the trial is within a Medicare benefit category. For example, clinical trials focused on the diagnosis and treatments of cancer are Medicare benefits, so these trials are covered. Cancer prevention trials are not currently covered.
Medicare patients who wish to participate in a clinical trial that is not described above, or patients who are unsure whether their trial meets all of the requirements should discuss these concerns with their doctor or visit http://www.hcfa.gov/medlearn/refctmed.htm for the Medicare Clinical Trials Quick Reference Guide. Often, there are other available trials that might be covered, so it is important that patients consult with their physician to evaluate their options before beginning a clinical trial that is not covered.
Medicare Covered Costs
- Any medical service normally covered by Medicare (usual care costs) is still covered when it is provided as part of a clinical trial, including tests, procedures, and doctor visits.
- Usual care costs, even if it is a service or item used in the experimental treatment, are covered. For example, Medicare will pay for the intravenous administration of a new chemotherapy drug being tested in a trial, including any therapy to prevent side effects from the new drug. Also, a test or hospitalization that Medicare would ordinarily cover for a cancer patient would still be covered, even though the services required resulted from a side effect from the experimental drug or treatment.
Medicare Non-Covered Costs
- Investigational items or services being tested in a trial (research costs) are typically not covered. Sponsors of clinical trials often provide the new drug free, but patients should be sure to determine whether this is the case before beginning a trial.
- Items or services used solely for the data collection needs of the trial (research costs) are typically not covered. For example, lab tests, x-rays or CT scans that are required more frequently than usual for the purpose of research are not covered.
- Items provided free by the sponsor of the trial, such as drugs or specialized procedures are typically not covered.
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How Can I Find Specific Clinical Trials?
Specific clinical trials that may be of interest to cancer patients are available in many hospitals and clinics throughout the United States. Currently, there are several Internet resources designed to facilitate access and accrual to clinical trials. Unfortunately, no single clinical trials listing service or database contain all the available clinical trials in the United States. Each clinical trials site on the internet provides a slightly different service for cancer patients. The NCI site lists clinical trials that are being performed at federally funded research institutions and those electively submitted by the biopharmaceutical industry and providers of cancer services. The NCI Web site currently has the greatest breadth of clinical trial listings, but is by no means comprehensive in scope.
eCancerTrials.com provides a comprehensive list of oncology clinical trials within the context of several other cancer treatment information resource. Patients and doctors may search for clinical trials on eCancerTrials.com free of charge, or they may retain a clinical trials search specialist to help locate specific trials.