by Dr. C.H. Weaver M.D. & Mia James, updated 4/2022
When you or a loved one are diagnosed with cancer, it is important to know all of the treatment options available in order to make the best decision about your cancer treatment. This may include clinical trials.
Cancer clinical trials are studies that evaluate the effectiveness and safety of new cancer drugs or cancer treatment strategies. The development of more effective cancer treatment 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 cancer treatment approaches are developmental in nature. All new cancer drugs that are currently available in the United States were once only available in clinical trials. In the U.S. 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 patients with a specific cancer before they become commercially available to other patients.
Many medical professionals encourage those diagnosed with cancer to at least consider participating in a clinical trial in addition to other treatment options. Furthermore, many treatment options for cancer patients are only available through clinical trials, making participation in a trial the only way to access certain therapies. So if you are not evaluating potential cancer treatments accessible through the clinical trials process alongside current standard therapies, you’re not considering all your options.
Is Participating in a Clinical Trial Right for You?
While the decision whether or not to enroll in a clinical trial of a novel cancer treatment is ultimately very personal, a clear understanding of the nature of clinical trials can help you make the choice that’s right for you. Once you carefully weigh the pros and cons of clinical trials, you’ll be prepared to make a thoughtful and informed decision that supports your cancer treatment plan.
In the United States, the Food and Drug Administration (FDA) oversees the conduct of clinical trials.
What does the FDA do?
The FDA is a government agency that is responsible for making certain that the food we eat and the drugs we take are safe. The FDA does not make drugs or directly test drugs to determine if they are safe and effective. The FDA’s role is to oversee the research conducted by pharmaceutical companies, university research centers, and physicians to make certain that federal regulations governing research are being followed.
The FDA requires that the drug company’s plan must be reviewed by community research review board (IRB), and that patients participating in the clinical trial are informed about the trial and consent to participate. Once the drug company has completed its clinical trials, the data are tabulated and submitted to the FDA in an application known as a New Drug Application (NDA). The FDA evaluates the outcomes reported in the NDA and determines whether the new drug will be approved and made available to patients in the United States. In order to be approved, the drug must be safe and effective.
Can I get a drug before it is approved by the FDA?
Until a drug receives FDA approval, it cannot be sold and the drug company may only provide it to patients through clinical trials. Furthermore, each clinical trial has specific criteria that patients must meet to be included. Occasionally, a cancer patient who is not eligible for a clinical trial may receive a promising unapproved drug, if the patient’s doctor, the drug company, and FDA each agree. The FDA’s primary interest is helping to ensure that the drug company’s research will not subject cancer patients in the clinical trial to undue risks. The FDA drug review process guarantees that the risks and benefits of a cancer drug have been carefully considered before it is approved and helps to ensure the public that marketed drugs are safe and effective.
How can I learn more about a drug that has been approved?
The FDA requires that all drugs have an information document for healthcare providers and consumers called a “package insert.” This document is a summary of the essential scientific information needed for the safe and effective use of the drug. You can ask your doctor for this information. Also, most package inserts are available on the internet. A package insert typically includes the following information:
- Chemical structure
- Information about how the body absorbs, distributes, metabolizes, and excretes the drug
- Results from some clinical trials
- What specific circumstances the drug is used for
- Dosing and administration schedules
- Side effects
It is important to understand that once it has been determined that a drug is safe and it is approved by the FDA, physicians often use the drug for the treatment of medical conditions other than the specific condition that the FDA has approved it for.
Is a clinical trial right for you?
The Pros of Clinical Trials
- Participating patients are treated with carefully designed cancer treatment regimens that are either the best standard treatments available or approaches that may become standard treatments.
- Participation is an integral part of the research process. Small improvements in cancer treatment can only be detected in Phase III clinical trials, the phase in which the experimental drug or treatment is given to large groups of people to confirm effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will contribute to safe use of the drug or treatment. A greater number of patients allows for a more efficient and thorough process.
- In some cases the best cancer treatment may be available only in a clinical trial.
- Participants receive correct dosages as a result of carefully designed regimens and strict protocol, and correct dosage often contributes to the effectiveness of a cancer treatment regimen.
- Thanks to “stopping rules”, which are included in all cancer research protocols, clinical trials are stopped when one cancer treatment is proven to be superior so that no patient is intentionally given an inferior treatment.
- The medical community gains knowledge about the treatment of cancer that can be used to treat other cancer patients and to develop newer cancer treatments.
The Cons of Clinical Trials
- Clinical trials are not available for all cancers or all patients.
- Patients in Phase III clinical trials are assigned at random to either the experimental or control group—a process that makes some people uncomfortable.
- Participation in a clinical trial may offer no benefit.
Understanding the pros and cons of clinical trials in oncology may help you decide whether or not participation in a clinical trial is an appropriate choice, but it’s important to remember that the decision is entirely your own. In other words, you shouldn’t feel pressure from any outside sources to enroll in a clinical trial. If you do choose to participate or further research clinical trial opportunities, you may wish to discuss with your physician the potential risks and benefits of these studies as well as your other treatment options.
Are all clinical trials the same?
Development of new anticancer drugs 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. 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 safety issues, which include:
- 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.
Phase I trials usually involve a small number of patients for whom other standard therapies have failed or no known alternative therapy is available. Upon completion of phase I trials, the information that has been gathered is used to begin phase II trials.
Phase II 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. In general, all of the patients participating in a phase II trial will receive the treatment that is being investigated. 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.
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Phase IV Trials: Once the drug or treatment is approved and 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.
Clinical Trials and Development of Precision Medicines
Historically, clinical trials enrolled patients with a single type of cancer, such as lung cancer. A treatment was administered to that group of patients, and the response to that treatment was measured without ever assessing the genomic makeup of the cancer. In order to evaluate precision medicines clinical trials are being revised because evaluating precision medicines requires measuring the genetic makeup of the cancer before beginning treatment.
To conduct clinical trials of precision medicines, patients must be evaluated and enrolled early so that a sample of the cancer can be genotyped.
One new clinical trial model, a so-called “basket” trial, enrolls patients with similar genetic mutations, rather than simply the same type of cancer.
There is currently no single source of all clinical trials. The following are clinical trial resource is a good place to start.
National Cancer Institute
The NCI provides a listing of government sponsored clinical trials.
CAM clinical trial listing service.
NCI’s CAM clinical trial listing service.
TrialWize is a New York based digital patient recruitment network that connects patients with clinical trials.
Clinical Trials and Insurance: Understanding Your Coverage
Currently, a very small percentage of eligible patients actually participate in clinical trials, research studies required by the U.S. Food and Drug Administration to prove safety and efficacy of new medications. While many concerns may discourage patients from considering clinical trials, the biggest deterrent is often whether insurance will cover the costs associated with participation. If you’re interested in joining in a clinical trial but uncertain whether your insurance will cover it, read on to learn how to determine your plan’s clinical trials coverage and how to appeal a denial.
Some costs of a clinical trial may be covered by the trial’s sponsor, which can be a government agency, a pharmaceutical company, or even the National Cancer Institute (NCI). This information can be found in the informed-consent document that you’ll sign when you are accepted into the clinical trial.
Once you have decided to participate in a clinical trial, you’ll undergo admission testing to make sure that you are indeed eligible. If so, the clinical trial provider can make a formal request to your health insurance company for approval or preauthorization. If you haven’t already done so, this is a good time to read your insurance policy or plan summary to make sure that you understand the specifics of your coverage.
It’s not uncommon for health plans to limit participation in clinical trials or to exclude them altogether. To see if clinical trial preauthorizations are denied, look for terms like investigational or experimental. Plans may also specify the type of trials they will cover. For instance, only NCI studies or trials within Phases III or IV may be covered. Your insurance company will normally notify both you and the requesting institution of its decision regarding your participation.
If your insurance company denies your preauthorization request, you may appeal that decision. You can start the appeal process yourself, or a nurse, study coordinator, patient advocate, or other medical professional can help you with your appeal. It’s important that whoever formally appeals your denial is knowledgeable about the trial as well as your treatment plan and insurance policy. All insurance plans, including Medicare and Medicaid, have an appeal process for denied preauthorization of benefits and claims. They may vary slightly, but the overall principles are consistent.
The Appeal Process
Although the appeal process can often be confusing and arduous for the patient, the necessary steps are usually explained in your policy or plan summary. Be sure to read your policy carefully. If you can’t locate it, request a copy in writing from your employer or insurance agent.
The first step in any appeal process is to get a written copy of the denial of your initial request. This is critical because the appeal must address the specific reason for the denial. For example, if you send an appeal to the insurance company, stating that the trial you are requesting is medically necessary for you, but the reason the insurer initially denied your request was because it was not an NCI-sponsored trial, your appeal would not address the reason for the denial and would likely be ineffective. Unfortunately, such an unsuccessful appeal would delay your ability to start the clinical trial.
Knowing who actually carries your insurance coverage as well as the specific benefits and limitations of your plan is vital during an appeal. For example, you may work for a large employer that has structured your health plan as “self-funded” with a third-party administrator (TPA). The TPA administers the health plan on behalf of the employer. The outward appearance to you as well as to any providers you use is that the TPA is the insurance company, but that’s not really the case in this example. If your company is “self-funded,” you may have additional avenues to pursue in your appeal process.
It is important to note that self-funded plans are not subject to local or state laws and are regulated by federal laws. In such a case, you may live in a state that mandates clinical trail access to its citizens, yet you work for a company that is not obligated to comply with state laws. Many states have enacted laws regarding clinical trial access. You can learn more about your state by contacting your state insurance commissioner’s office. In 2002 Medicare began covering costs related to clinical trial participation, and many state Medicaid programs extended similar coverage.
The Patient Advocate Foundation (PAF) has authored a full-length publication titled Your Guide to the Appeals Process, which is available in English and Spanish. You can download this guide from www.patientadvocate.org or request a copy by calling PAF directly. This easy-to-read guide features sample appeal letters, specific strategies to use when negotiating the internal and external appeals processes, and precise instructions to follow when all appeals have been exhausted and it’s time for the next step. It offers insight into the principles that PAF case managers use to overturn coverage denials. The PAF publications and services are provided at no cost to patients with chronic, life-threatening, or debilitating conditions. If you need assistance with issues related to clinical trial participation or would like a copy of any of the PAF publications, call PAF toll-free at (800) 532-5274.