Exploring the Use of Placebo in Cancer Clinical Trials

July 27, 2018
Melissa Mills, BSN, RN, CCM, MHA

Oncology Nursing News, August 2018, Volume 12, Issue 6

Why are more oncology trials incorporating placebos today?

Melissa Mills, BSN, RN, CCM, MHA

Although placebo use in cancer clinical trials has been rare, it is becoming more common in today’s advanced pharmaceutical environment.1 Some trials have started to incorporate randomization and placebo.2 Placebo-controlled trials are justifiable when they are supported by sound methodologic consideration and when their use does not expose research participants to excessive risk of harm.3 What do you need to know regarding placebo in cancer clinical trials? Below is a look at the use of placebos in oncology practice.


The use of placebos dates back to at least the end of the 18th century.3 After World War II, randomized controlled trials gained in popularity, making the inclusion of placebos more common. A placebo is a pharmaceutically inert substance, often a sugar pill.1 Investigators use placebos to prove a new treatment is effective above and beyond the simple belief in the ability of the drug to cure.3

During a trial, one group will be given a placebo, and the other group will receive the new active drug therapy being studied. The results of the outcome of the drug use are then compared between the 2 groups. The placebo-controlled trial is considered the gold standard for testing the efficacy of new treatments in most clinical research areas other than oncology.3


During a recent interview with Cancer.Net, Richard L. Schilsky, MD, senior vice president and chief medical officer of the American Society of Clinical Oncology, discussed recent changes in the structure of clinical trials for cancer treatments. In past years, he said, it was not necessary or even possible to use placebos in cancer clinical trials.1

A randomized double-blind, placebo-controlled study is considered the benchmark of epidemiologic research.3 Randomly assigning treatment reduces complicating variables.2 In double-blind studies, the participants, the investigators, and the staff do not know which patient is receiving which treatment.

One of the reasons placebos were not used in cancer research is that investigators could easily identify patients randomized to the placebo group based on the change in tumor size.1 Another was related to adverse events (AEs). Many past chemotherapeutic agents caused severe and easily identifiable effects, potentially unmasking randomization of patients to placebo or active treatment groups.2

In the interview, Schilsky went on to report that today, many of the newer, targeted drugs slow tumor growth rather than shrinking the tumor, thus allowing placebo use in cancer trials.2 Because visible changes are now more difficult to see, a control group in these trials is beneficial to show whether the stabilization of tumor growth is from the treatment or the natural behavior of the tumor.1

The other change Schilsky discussed is related to the pharmacokinetics of the newer cancer treatments. Many of the latest cancer drugs are given by mouth and have fewer AEs, such as fatigue, for which the cause—the cancer itself or the drug—is difficult to determine.2 So, this study design, once not used in cancer clinical trials, is on the rise.1

Schilsky offered this support for the necessity of the advancement of cancer research: “The fastest way to improve access to new cancer treatments for all patients is the timely completion of well-designed, definitive clinical trials that provide evidence of the safety and effectiveness of a new drug and lead to marketing approval.”1 To achieve this goal, the inclusion of placebo control may be necessary in some circumstances.


Ethical concerns about placebos have existed for as long as they have been in use. It is important that the use of placebos be disclosed to all study participants upon entry into a clinical trial.1 Because clinical trials use human subjects, there must be a balance of science, ethics, and human protection.4 When there is no standard treatment, the use of a placebo is typically accepted. However, in placebo-controlled trials, ethical concerns arise when an effective treatment exists.2 If a placebo increases the risk of the control group’s having an adverse outcome, such as death, irreversible illness, disability, or other injuries, it should not be used.1 If a highly effective or potentially curative treatment is available, the use of placebo is considered unethical.1

“The bottom line is that there are no ‘ethical considerations’ when placebos are used appropriately in cancer clinical trials,” said Lisa Schulmeister, MN, RN, FAAN, in an interview with Oncology Nursing News®. “The important thing is that a placebo is not being compared to known effective cancer treatment. They are being used alone in symptom management trials. They’re being used alone when there is no known effective treatment. They’re being used in conjunction with known effective treatment.”


The increased use of placebos in oncology makes it important for nurses to familiarize themselves with how they are used. Patients may have misconceptions about placebos in clinical trials, and it is a nurse’s role to provide education about them. Schulmeister also says that nurses need to reinforce the importance of noting and reporting side effects during a trial. If patients have questions or concerns regarding the use of placebo in a clinical study, nurses should contact the research coordinator or primary investigator for more information and support. They can also refer patients to their informed consent document, which should clearly explain the purpose of the study and any placebo use.

Melissa Mills, BSN, RN, CCM, MHA, is a freelance healthcare writer and owner of the website makingspace.company. She has been a registered nurse for 20 years and is passionate about case management, nursing leadership, and finding the right care for patients in every setting.


  • Milestones in cancer research and discovery. National Cancer Institute website. cancer.gov/research/progress/250-years-milestones. Published January 21, 2015. Accessed June 14, 2018.
  • Placebos in cancer clinical trials. Cancer.Net website. cancer.net/research-and-advocacy/clinical-trials/placebos-cancer-clinical-trials. Published April 2018. Accessed June 8, 2018.
  • Misra S. Randomized double blind placebo control studies, the “gold standard” in intervention based studies. Indian J Sex Transm Dis. 2012;33(2):131-134. doi: 10.4103%2F0253-7184.102130.
  • Gupta U, Verma M. Placebo in clinical trials. Perspect Clin Res. 2013;4(1):49-52. doi: 10.4103/2229-3485.106383.
  • Millum J, Grady C. The ethics of placebo-controlled trials: methodological justifications. Contemp Clin Trials. 2013;36(2):510-514. doi: 10.1016/j.cct.2013.09.003.