On Apr. 30, 2025, the U.S. Department of Health and Human Services (DHHS) announced that all newly developed vaccines will now be required to undergo placebo-controlled clinical trials before being licensed by the U.S. Food and Drug Administration (FDA). This landmark policy shift comes after years of advocacy from consumer organizations critical of vaccine safety science knowledge gaps, such as the National Vaccine Information Center (NVIC).1
Public Comment on Licensure Pathways for Pandemic Influenza Vaccines. FDA Vaccines & Related Biological Products Advisory Committee (VRBPAC) Meeting Feb. 29, 2012.) and mounting public scrutiny over the rushed development and widespread rollout of the experimental COVID-19 shots—for which placebo-controlled trials were unblinded early, sacrificing critical safety signals and long-term risk data.2
“Under Secretary Kennedy’s leadership, all new vaccines will undergo safety testing in placebo-controlled trials prior to licensure—a radical departure from past practices,” the DHHS said in a statement last month. There was no elaboration on how DHHS officials would implement the new policy, nor to which vaccines the new requirement would apply, but the department did suggest that the annual COVID biologics would be included in the new standard. “The COVID vaccines, including new ones by Pfizer and Moderna, are new and must have more gold standard science to ensure safety and efficacy for the public,” a spokesperson for the HHS said in a news interview.2
The Importance of Placebo-Controlled Studies in Medicine
Placebo-controlled testing is the gold standard method used in clinical trials to determine whether a new drug or treatment is truly safe and effective.3 In these studies, one group receives the product being tested, while another group receives a placebo—typically a harmless, inert substance like a sugar pill or saline injection with no biological activity or therapeutic effect that could alter study conclusions. This allows researchers to assess both the effectiveness and potential side effects of the experimental pharmaceutical product, providing critical data before approval and widespread use of the product.
Historically, randomized clinical trials of new vaccines—which are classified as “biological products—4 have included comparison of groups of people who receive the experimental vaccine with groups of people who either receive a “true” inert placebo (like saline).5 6 or a bioactive “placebo,” like another vaccine or component of a vaccine, such as an adjuvant.)7 8
How Failing to Follow Placebo Arm Protocols Clouded mRNA COVID-19 Shot Risk Assessments
As part of the process granting vaccine manufacturers an Emergency Use Authorization (EUA) to fast track mRNA COVID-19 shots to market, manufacturers Pfizer and Moderna initially conducted placebo-controlled trials. Trial participants were randomly assigned to receive either the experimental COVID biologic or a saline placebo, which adhered to the inert placebo “gold standard” of clinical research. However, after the two manufacturers were granted an EUA to distribute mRNA COVID shots in December 2020, the studies were quickly unblinded. In other words, clinical trial participants in the control group were informed they had received a placebo rather than a COVID shot.9
Researchers and public health officials claimed it would be unethical to withhold a now-available vaccine for a “deadly” virus, especially amidst a global pandemic crisis. As a result, many clinical trial participants in the placebo groups were offered and received the COVID biologic shortly after Pfizer and Moderna received an EUA from FDA to distribute the shots.
Without being able to monitor the placebo control groups for all health outcomes, researchers lost the ability to accurately measure long-term safety and efficacy of the experimental biologic, which used mRNA technology never before deployed in a vaccine distributed to millions of Americans. Questions were rasied about whether the unblinding and administration of an experimental product to placebo control groups in clinical trials before all the health outcome data could be collected was truly based on “ethical” concerns or a convenient way for federal officials and drug companies to check a regulatory box and fast-track the new mRNA biological to market.
The decision to unblind and administer the experimental mRNA biological to the placebo groups in clinical trials effectively ended the possibility of collecting meaningful long-term safety and efficacy data. Once both groups received the same intervention, the trial lost its ability to compare health outcomes over time—a core function of placebo-controlled studies. This move undermined the scientific integrity of the trials and left regulators, researchers, and the public without a reliable control group to assess delayed adverse events (which often surface after a drug or vaccine is widely used) or measure short and long term protection. Because the placebo groups in the clinical trials were prematurely dismantled, outstanding remain about long-term safety, rare side effects, and waning immunity of the mRNA COVID biologicals manufactured by Pfizer and Moderna, which captured market share for COVID shots in the U.S.
Carlos Fierro, MD, who led one of the placebo-controlled studies for Moderna’s Spikevax COVID shot, said that when participants were called back to ask if they wanted to get the vaccine, he was shocked that some participants wanted to stay the course. He speculated that they must have succumbed to “rumors” about the vaccine. Commenting on the unblinding of the study, he said, “It’s a loss from a scientific standpoint, but given the circumstances, I think it’s the right thing to do.”9
Proof Before Prescription: The Case for True Placebo Controls
Several high-profile drugs were halted before FDA licensure specifically because rigorous placebo-controlled clinical trial testing exposed serious safety issues early on. These drugs include Pfizer’s cholesterol drug Torcetrapib, linked to a 25 percent increase in cardiovascular events compared to the placebo group; Eli Lilly’s Semagacestat, which worsened Alzheimer’s symptoms; and Bristol-Myers Squibb’s Brivanib, which showed unexpected toxicities.10 Had these drugs skipped placebo comparisons or relied on less rigorous safety protocols—like those used for many vaccines currently on the market—they could have been approved and administered to millions, potentially causing widespread harm.
Industry Quietly Expands Definition of “Placebo” to Include Active Treatments, Procedures
The definition of a placebo has traditionally been clear and consistent: According to Oxford, it’s “a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect.” The National Cancer Institute defines it as “an inactive substance or other intervention that looks the same as, and is given the same way as, an active drug or treatment being tested.” However, in 2021, the U.S. National Library of Medicine quietly amended its definition to include “treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol.
Harvard Pilgrim Health Care Study Finds Less Than One Percent of Vaccine Injuries Are Reported
The DHHS statement announcing the placebo testing requirement for new vaccines also acknowledged that a Harvard Pilgrim Health Care study, commissioned by the DHHS and published in 2009, found that fewer than one percent of vaccine adverse events are ever reported. The study noted that “adverse events from drugs and vaccines are common, but underreported,” with less than 0.3 percent of all adverse drug events and only one to 13 percent of serious events reported to the FDA. The report warned that low reporting rates prevent or delay the identification of “problem” drugs and vaccines that may pose public health risks.11
Requiring true placebo-controlled safety trials for all new vaccines reaffirms a core principle of medicine: that every product administered to the public should be held to the highest standard of safety, transparency, and accountability. In addition to the HHS announcement requiring all new vaccines to undergo blind inert placebo safety testing, there are also suggestions that improvements should be made to the vaccine adverse events reporting system to more accurately assess vaccine risks.2
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Click here to view References:1 Fisher BL. Public Comment on Licensure Pathways for Pandemic Influenza Vaccines. FDA Vaccines & Related Biological Products Advisory Committee (VRBPAC) Meeting Feb. 29, 2012.
2 Tirrell M. HHS to require placebo testing of ‘all new vaccines,’ raising questions about approval of updated Covid-19 shots. CNN Apr. 30, 2025.
3 Misra S. Randomized double blind placebo controlled studies, the “Gold Standard” in intervention based studies. Indian J Sex Transm Dis AIDS 2012; 33(2): 131-134.
4 FDA. What Are Biologics Questions & Answers. Feb. 6, 2018.
5 Meldrum M. “A calculated risk:” the Salk polio vaccine field trials of 1954. BMJ 1998; 317(7167): 1233-1236.
6 Reisinger KS, Block SL, Lazcano-Ponce E et al. Safety and persistent immunogenicity of a quadrivalent human papillomarvirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial. Pediatric Infect Dis J 2007; 26(3): 201-209.
7 Darkes MJM, Plosker GL. Pneumococcal Conjugate Vaccine (Prevnar; PNCRM7). Pediatric Drugs 2002; 4: 609-630.
8 National Vaccine Information Center. Merck’s Gardasil Not Proven Safe for Little Girls. June 27, 2006.
9 Harris R. Long-Term Studies Of COVID-19 Vaccines Hurt By Placebo Recipients Getting Immunized. NPR Feb. 19, 2021.
10 U.S. Food and Drug Administration. Drug approval reports: FDA drug approval reports from 2007–2016. May 2017.
11 Lazarus R, Klompas M, Bernstein S. Electronic Support for Public Health–Vaccine Adverse Event Reporting System (ESP:VAERS): Final report. U.S. Department of Health and Human Services, Agency for Healthcare Research and Quality 2011.
