FDA Published Draft Guidance on Use of Placebo Control Groups

Recommends their use only in certain clinical trials for therapies to treat hematologic malignancies and cancers.

In clinical trials, it has been common to divide participants into two groups – those receiving the drug and those receiving a placebo – with no one involved in the study knowing who belongs to which group. Ethical questions have been raised about the use of placebos, particularly in studies for therapies designed to treat patients with advanced and serious diseases.

The US Food and Drug Administration (FDA) has tackled this issue in a recent draft guidance document entitled “Hematologic Malignancy and Oncologic Disease: Considerations for Use of Placebos and Blinding in Randomized Controlled Clinical Trials for Drug Product Development.” 

In the draft guidance, the FDA recommends that placebo groups only be used in certain circumstances, including “where surveillance is standard of care,” or with specific trial “design features (e.g. if the trial uses an add-on design, when the endpoint intended to support a labeling claim has a high degree of subjectivity, such as patient reported outcomes).” 

In addition, study sponsors should provide the reasoning behind trial designs that include placebo groups in trials investing treatments for hematologic malignancies and cancers, as well as a detailed description in the protocol and statistical analysis plan of the proposal for blinding and unblinding. 

For trials with placebo groups, to allow for the best patient care, unblinding of patients in the control group should occur when disease recurrence or progression is detected. Maintaining blinding could lead to incorrect or unnecessary treatments for patients in the control group that experience adverse events or progression. Unblinding is also recommended for patients receiving the investigational drug that experience adverse events and require treatment with one or more additional drugs that have substantial toxicity or surgery.

Furthermore, “If a sponsor intends to maintain the treatment blind when disease recurs or progresses or a suspected adverse event occurs, the informed consent document should specify the risks and potential disadvantages of this approach, and the protocol should include justification for the potential added risk.”

The FDA also noted that due to the side effects experienced with many drugs, patients and investigators often know whether they are receiving the drug or are in the placebo control group.


Emilie Branch

Emilie is responsible for strategic content development based on scientific areas of specialty for Nice Insight research articles and for assisting client content development across a range of industry channels. Prior to joining Nice Insight, Emilie worked at a strategy-based consulting firm focused on consumer ethnographic research. She also has experience as a contributing editor, and has worked as a freelance writer for a host of news and trends-related publications