As investigators and sponsors plan large-scale clinical trials to test the safety and efficacy of these new vaccines, important ethical issues can arise in trial design, particularly around the use of a placebo control arm when an efficacious vaccine already exists.

While placebo-controlled trials are often considered the gold standard for evaluating medical interventions, the use of inert placebos (e.g., the injection of saline solution) is not always required for vaccine trials and in fact is sometimes unethical.

January 18, 2025 - A systematic review of 24 clinical study reports reveals how and why modern vaccine trials use comparator vaccines instead of saline placebos.

August 12, 2024 - Vaccines are sometimes tested against other vaccines or adjuvants instead of saline placebos to protect participants’ health when an effective vaccine is already available.

May 12, 2025 - Many childhood vaccines were tested originally in randomized clinical trials that included placebo or comparison groups. If the vaccine is for a disease that currently has no vaccine, the placebo may be saline or another substance known to be safe.

July 6, 2020 - Against what does a vaccine need to be tested in the context of a clinical trial? The answer that pops immediately to mind is “a placebo.” In the medical sciences, things get compared to placebos to see if they have inherent potency or if it’s all about the theatre and natural circumstances surrounding them.

July 1, 2023 - ICAN’s lawyer argued that the only true placebos were water or saltwater, which isn’t true. Indeed, a wide range of placebos have been used in vaccine trials. These placebos might contain buffers, stabilizing agents, emulsifying agents, ...

May 6, 2025 - These often were tested in clinical trials in which people were randomly assigned to either receive the new vaccine or an older version, an example of what’s called an active control group.

January 17, 2025 - A systematic review of 24 clinical study reports reveals how and why modern vaccine trials use comparator vaccines instead of saline placebos.

While vaccine supplies are limited, available vaccines are still investigational, or public health recommendations to use those vaccines have not been made, we believe it is ethically appropriate to continue blinded follow-up of placebo recipients in existing trials and to randomly assign new participants to vaccine or placebo. Moreover, under these conditions, we believe that trial sponsors are not ethically obligated to unblind treatment assignments for participants who desire to obtain a different investigational vaccine. People who enroll in clinical trials for altruistic reasons would probably understand the value of gathering data that will further elucidate the safety and efficacy of these vaccines and their appropriate use.

March 14, 2025 - Instead of saline, many vaccine trials use adjuvants like aluminum or even other vaccines as the placebo. Here are some examples of clinical trials and the "placebos" that were used:

May 16, 2025 - Health Secretary Robert F. Kennedy ... evaluating vaccines, the plan did not seem so radical. New vaccines are often tested against a placebo in clinical trials....

May 2, 2025 - Sometimes, during vaccine trials, participants in a comparison group are not given a placebo but another type of vaccine so that they can still receive some benefit from the study, Moss said.

July 23, 2025 - “Those new vaccines are always tested against a placebo control,” says Ellenberg, who monitored the safety of COVID-19 vaccines developed through Operation Warp Speed, a program started under the first Trump administration.

May 22, 2025 - For years, regulators have evaluated new vaccines case by case — sometimes using placebos, sometimes comparing them with existing vaccines — based on what’s ethical and appropriate.

1 month ago - Further, the fact that vaccines cause such serious side effects that the only possible way to keep a trial blinded is to use other vaccines in placebo arms is hardly a general argument for vaccine safety.

June 18, 2025 - There have also been trials that have compared the vaccine to saline placebo. But saline is not the only placebo. There are other kinds of inert salts and stuff, like calcium carbonate, etc.

May 1, 2025 - In fact, all new immunizations already go through the trials - a type of random testing where one test group receives the immunization, and the other gets a placebo, like a saline shot.

The highest health official in the USA, Secretary of Health and Human Services (HHS) Robert F. Kennedy Jr., recently said, “[t]he only vaccine that was ever safety tested in a clinical trial against a placebo was the COVID vaccine.

June 21, 2014 - When the efficacy and safety of a novel vaccine is being assessed for the first time, societies, ethics committees, and parents accept this course of action on the grounds that although the vaccinated infant cannot derive any benefit from participating in the trial, other infants might do so in the future. However, the situation becomes more complex when investigators wish to test a new vaccine against a placebo when a safe and effective vaccine already exists.