You may have heard that clinical trials merely treat people like human guinea pigs, random numbers, or just a disease. This is absolutely false! Clinical trials are research studies in which people volunteer to participate in testing new drugs, devices, interventions, screening methods, or diagnostic tests to prevent, diagnose, treat, or manage disease. Each study has a specific goal, such as determining whether a new drug or treatment works.
All clinical trials follow a scientific process to take research from the initial computer, molecular, or animal model to the stage in which it is used by patients (researchers call this going from the bench to the bedside). As with other therapies, the research process for oncology drugs and treatments is conducted in 4 different phases.
This phase addresses the safety of a new drug. Researchers are looking for the most effective dose people can take without any harmful side effects and for the best way to administer the drug, such as orally, intravenously, or topically (through the skin). Phase 1 trials are usually offered at major cancer centers and include a small number of people. They may be healthy volunteers, or people with advanced disease or a condition that has not been helped by other treatments.
Using the dosage and method found to be the safest and most effective in phase 1 studies, phase 2 addresses how safe the drug is and how well it works for a specific cancer. Volunteers will often get the same dose, but in some trials they may be randomly assigned to treatment groups with different dosages or different ways of administering the drug. By randomizing, or by using a computer to place participants in groups, investigators keep bias out of the results. For example, if a researcher believed a volunteer would benefit from a certain treatment and placed the volunteer in that specific study group, the results of the study could be biased. Randomization helps to avoid possibly changing the clinical trial results. The main goals are to address efficacy and to find the safest and most effective way to administer the medication.
In phase 3, the treatment that worked well for volunteers in phase 2 will be compared with the standard-of-care treatment (the current treatment prescribed by most doctors). Phase 3 trials are conducted with hundreds to thousands of people and may take several years. Randomization is a part of the process. In a double-blind study, neither the patient nor the doctor knows what drug the patient is taking. The main goal is to understand how the treatment works in different people. The study looks at the patients’ response to the treatment, changes/ improvements in survival, any harmful side effects, and the impact on daily life. If the drug is shown to be at least as effective and safe as currently available drugs, the new drug will likely be approved by the Food and Drug Administration (FDA).
At this phase, the medication has been FDA approved and additional questions are being explored, such as whether it can be used for a different cancer type, if it can be used in combination with other drugs or treatments, or how well the treatment works over an extended period. Phase 4 trials have a valuable role in checking to make sure that unexpected side effects do not develop over time as the drug is being used by patients in the real-world setting rather than in a controlled clinical trial environment.
There are many types of clinical trials that study aspects of cancer and test drugs and other treatments across the cancer care continuum. Prevention studies may look at people who are at high risk for a particular cancer type and at methods to avert cancer. These may involve genetic studies. Other studies target prevention of recurrence for patients whose cancer is in remission. Screening looks at ways to detect and diagnose cancer. Treatment trials test drugs and drug combinations or medical approaches like surgery or radiation to avoid cancer progression. Quality-of-life studies often explore ways to improve comfort and daily life for patients.
There are many measures to protect the safety of volunteers. Institutional review boards evaluate the research to assure the protection of the rights and welfare of the volunteers. Federal regulations require that the board be made up of at least one expert who can analyze the scientific aspects of the proposed trial, at least one lay member from a nonscientific field, and an independent member not associated with the institution or the trial site.
Every clinical trial has a protocol to help ensure that researchers will be able to answer the research questions about the investigational drug or device in the study. This is a detailed plan that describes what will be done during the trial and how it will be conducted. A critical part of the plan is the eligibility criteria, which state who can and cannot take part in the trial. Criteria may include age-group, gender, type or stage of cancer, past or present medications, medical history, and current health.
Every clinical trial also has an informed consent process to help participants understand their rights, including the option to leave the trial at any time. The participants are constantly observed for safety concerns as they receive regular and careful medical attention. During the clinical trial, if any new benefits or side effects are noticed, the study participants are informed. For example, if one treatment proved to be more effective during the trial, all participants may be moved to that part of the study.
A key safety point is that the participant should let the research team know if the decision to leave the trial is being considered, because it is not safe to stop some medications abruptly. The help of a healthcare team member may be necessary to create a withdrawal plan. Also, if a volunteer withdraws from a trial, the research team will ask to continue monitoring the participant to assess any long-term effects of the treatment.
Placebos, sometimes called “sugar pills,” are rarely used in a cancer clinical trial but can be part of the protocol. They can come in the form of a medication or a procedure and do not contain any known active element. In other words, it is designed to look like the medicine being tested, but it is not a working treatment. There is a role for them in trials that look at drugs that might prevent cancer, because participants in prevention studies would not have cancer. The placebo group provides an important control with which to compare the treatment group. The protocol and consent form will reveal if a placebo will be used in the course of the clinical trial.
Two general areas of costs connected with a clinical trial are research and patient care. Expenses related to conducting the trial include data collection, management, and analysis; staff and healthcare team members; and tests needed for trial purposes. Research costs may be covered by the institution conducting the trial, a pharmaceutical company, a government agency, or a private foundation, and they are NOT the patient’s responsibility. Patient care costs are ones such as doctor visits, hospital stays, laboratory tests, x-rays, and other activities that would be considered as routine care. Insurance carriers will usually cover routine care. Participants can always ask the clinical trial team member assigned to them about costs, and/ or they can check with their personal insurance carrier about the coverage for clinical trial procedures. It is best if this is completed prior to starting participation in a trial.
The goals of a clinical trial are research based, and there are no guarantees for success. Ideally, clinical trials are beneficial in some way, but they attempt not to be misleading when asking for participants. It is the role of the participant to talk with the medical care staff about the trial protocol and the consequences of participating. The upshot may be an opportunity to receive an investigational drug that is not available to people outside the trial, which can be an overwhelmingly positive experience. The downside can mean additional tests, travel to the study site, and lab work that may not be part of your usual care and may require more time away from work or home life.
It is also the role of the participant to read and understand the informed consent document. The informed consent includes a roadmap of visits and procedures to be done, explanations of potential risks and benefits of participation, as well as the purpose of the trial.
An additional support to any clinical trial participant is patient navigation. Navigators have had an impact on promotion and completion of clinical trials and have influenced survival of patients. They have a trusted role with patients and can make certain patients aware of the clinical trial process, especially patients from minority groups who are eligible, but who are less probable to be approached to enroll. Navigators are invaluable to patients of all races and underrepresented populations as they can remove the fear of the phrase “clinical trial” and help with the jargon and unfamiliar words that are associated with research participation. They have strategies to overcome barriers to clinical trial participation, such as lack of trust with research, financial costs, transportation needs, interference with work/family duties, culturally specific health beliefs, complexity of the clinical trial process (for example, the paperwork involved), and historical factors influencing negative attitudes toward clinical trials. A navigator can increase patient clinical trial access, awareness, and knowledge, as well as appropriately match trials for patients.
Congratulations to current and future clinical trial participants, because they are critical to oncology lifesaving work for today and for future patients. Being a participant provides choices and access to treatments that would otherwise not have been available. The goal is to support healthcare professionals who are studying better ways to prevent, detect, and treat diseases as well as to promote quality of life. Please reach out to a patient navigator in your community or talk with your doctor or a local or national patient advocacy organization if you have an interest in a clinical trial.
The Importance of Diversity in Clinical Trials
Diversity in clinical trials is necessary to ensure our ability to effectively treat all people diagnosed with cancer.
According to the National Cancer Institute, African American women are more likely than white women to die of breast cancer, Hispanic and American Indian/Alaska Native women have higher rates of cervical cancer than women of other racial/ethnic groups, and colorectal cancer incidence is higher in African Americans than in whites.1
Yet, of the 48 drugs approved by the FDA in 2019, African Americans represented 9% of the study participants, Asians 9%, and Hispanics 18%.2
Patients should talk with their doctors about the possibility of participating in a clinical trial. Including people from all races and ethnic groups strengthens study results and will provide better treatment options.
- National Cancer Institute. Cancer Disparities. www.cancer.gov/aboutcancer/understanding/disparities#q1. 2019.
- US Food and Drug Administration. 2019 Drug Trials Snapshots Summary Report. www.fda.gov/media/135337/download. 2019.
American Cancer Society