Why are clinical trials randomized? Patients and families sometimes ask this question about the Phase 2/3 Toca 5 study. To better understand this challenging and often frustrating topic, I interviewed Asha Das, M.D., vice president of clinical development and medical affairs at Tocagen.
She is also a board-certified neurologist and practiced medicine as a neuro-oncologist. Here is a summary:
What is randomization in a clinical trial?
Dr. Das: Randomization is when a study participant is assigned, by chance, to separate treatment groups in a clinical trial. Physicians, participants and sponsors cannot choose the group. Randomization allows the researchers to assess a new experimental treatment objectively without introducing known or unknown bias, which otherwise may impact the clinical trial outcome and make it harder to interpret the study results. For cancer trials, researchers often compare new experimental therapies to current standard of care therapies by having one group of patients receive experimental therapy and another group receive standard of care therapy.
Why do studies require randomization?
Dr. Das: Agencies that approve new treatments, such as the Food and Drug Administration (FDA), often require randomization data to compare the safety and effectiveness of a new treatment to the standard of care. Alternatively if tumor shrinkage data is available, the FDA may accept this information as support for effectiveness. FDA and investigators share the same goal of finding and advancing effective treatments for patients with cancer, and while sometimes frustrating, randomization is currently part of the clinical trials process, particularly when sufficient tumor shrinkage data is unavailable. When the randomized Toca 5 trial was started Tocagen did not yet have tumor response data, so the trial was designed to randomize patients to either Toca 511 & Toca FC or standard-of-care therapies, namely temozolomide, lomustine or bevacizumab.
Why is randomization so challenging for patients and families?
Dr. Das: When making decisions about clinical trial participation, people with brain tumors and their families want the most effective treatment possible. During the early developmental stages of a new therapy, it is not known whether standard of care treatments or a new experimental therapy is better. From my experience as a practicing neuro-oncologist, I appreciate how difficult it is for patients to decide which trial to participate in and whether to enter a trial without knowing if you will be getting standard care or the experimental treatment. People are very vulnerable when there are such limited options for treatment of their brain tumor. However, many brain tumor patients will decide to participate in a randomized clinical trial, because they are potentially helping themselves or others like them regardless of which group they are assigned to.
Why should a patient stay on the standard-of-care arm of the study?
Dr. Das: The standard-of-care treatment arm is just as important as the experimental arm. The standard of care is known to be effective in treating the disease, and the researcher does not know which is the better treatment. Care is given to ensure the patient will receive an effective therapy in the standard-of-care arm. Follow up is essential in both arms of the study for the doctors to assess differences in drug efficacy, safety and quality of life. Many people find several positive aspects for continuing to be part of a trial regardless of their treatment assignment. They receive expert care and support from research-oriented doctors and nurses at leading brain tumor care facilities.
Anything else we should know?
Dr. Das: To summarize, clinical trials are an essential step in bringing new therapies to patients. An important aspect of late-stage clinical trials in oncology is a control arm where patients may be assigned standard of care as a control for the experimental treatment arm. Standard of care is an effective therapy against which the new, experimental treatment will be evaluated and therefore is a critical component of the study.
Thank you for your interest in this topic. There are many positive factors but also some challenges when evaluating and participating in a randomized trial. It is important that patients take their time to engage with a variety of people including brain tumor healthcare professionals and patient advocates about clinical trials and ultimately choose which clinical trial, if any, is right for him or her. I hope this article provides you with some useful background information about the importance and challenges with randomized clinical trials and I encourage you to learn more about this topic.