Which childhood vaccines were tested with saline-placebo randomized trials and where can the original trial reports be found?

1. Polio: the archetype of a saline-placebo randomized trial

The best‑documented example is the 1954 inactivated polio vaccine field trial led by Jonas Salk, which randomized hundreds of thousands of schoolchildren and gave saline injections to large placebo groups; contemporary accounts and later historical summaries note roughly 200,000+ children in placebo arms and indicate the trial was randomized and placebo‑controlled using saline as an inert comparator ^{[1] [2] [5]}.

2. Rotavirus and other vaccine trials that used inert placebos

Rotavirus vaccines are explicitly cited in authoritative fact‑checks and vaccine reviewers as being licensed following trials that included placebo (inert) control arms, and reviewers note post‑approval surveillance supplements trial evidence for rare events ^{[3] [6]}; Science Feedback and other reviews also list multiple childhood vaccines that have had at least some saline placebo–controlled randomized trials in the published literature (for example measles, polio, influenza, pneumococcus are among those cited) ^[4].

3. HPV (Gardasil‑9) and the nuance of smaller saline placebo subtrials

While many HPV trials used active comparators for ethical reasons, there was a smaller Gardasil‑9 trial in participants who had already received the older Gardasil vaccine that did randomly assign some participants to receive a saline placebo, and this trial is specifically referenced in regulatory and fact‑checking coverage ^{[3] [7]}.

4. Why saline placebos are used sometimes — and why often they are not

Experts and ethicists emphasize that inert saline placebos are legitimate scientific controls when no effective vaccine exists for the target disease, but become unethical once a safe, effective vaccine is available; as a result many modern pediatric vaccine trials use active comparators (older vaccines or adjuvant‑only formulations) instead of saline so participants are not left unprotected—this evolution in trial design explains heterogeneity in control groups across the childhood vaccine portfolio ^{[6] [8] [9]}.

5. Where to find the original trial reports and documented evidence

Primary trial reports and regulatory materials are retrievable in standard medical and historical archives: PubMed and journal archives contain randomized trial publications and historical reports (Science Feedback and the AAP point readers to PubMed searches for saline placebo trials) ^{[4] [10]}; landmark trials like the 1954 Salk field study are detailed in contemporaneous publications and historical reviews (Children’s Hospital of Philadelphia, New York Times coverage, and medical history summaries reference the original field trial) ^{[1] [2] [11]}; consolidated modern inventories and efforts to catalogue vaccine randomized controlled trials—such as the spreadsheet project led by clinicians and reported by CIDRAP—offer references and citation lists that point back to the original trial reports, and regulatory approval packages (FDA/CDC summaries) and systematic reviews typically cite the pivotal trial publications ^{[12] [5]}.

6. Bottom line and reporting caveats

The record shows multiple childhood vaccines were evaluated in saline placebo–controlled randomized trials (polio being the canonical example, and other trials—rotavirus, some influenza/pneumococcus/measles trials and a smaller Gardasil‑9 subtrial—appear in the literature), but modern ethical norms and prior vaccine availability often necessitate active comparators rather than inert saline, so the presence or absence of a saline arm depends on disease context, timing and ethics committees; the sources used here catalog examples and point readers to PubMed, regulatory reviews and curated RCT inventories for the original reports rather than supplying every primary citation in full ^{[1] [3] [4] [12]}.