Question explored with the scientific record
how are vaccines approved
Approval is a paper event. What matters is who ran the trial, what it measured, and who it compared.
The records here show the machinery, not the whole system. A vaccine gets licensed on a randomized trial, usually against placebo, sometimes against another vaccine [1][2][3]. The FDA then weighs benefit against risk in a specific population, as it did for the maternal RSV shot, approving it for 32 to 36 weeks of pregnancy after efficacy against severe infant lung infection was shown, while noting a numerical imbalance in preterm births and pregnancy complications [8].
The design is where the honesty lives. The Moderna mNEXSPIKE license rested on a trial comparing it to Spikevax in already-vaccinated people, not to unvaccinated people, and the pivotal data were a presentation, not a peer-reviewed paper [2]. That is the vaccinated-versus-vaccinated design: it can show a new shot is no worse than the old one, and nothing more. The 9-valent HPV vaccine was licensed partly by "immunobridging," assuming antibody levels predict protection, with clinical endpoints only for the added strains [5].
| Vaccine | Basis for licensure | Comparison group |
|---|---|---|
| mNEXSPIKE | Noninferiority trial, presentation only [2] | Already-vaccinated people [2] |
| 9vHPV | Antibody bridging plus clinical endpoints [5] | Active vaccine, no placebo [5] |
| Abrysvo (maternal) | Phase 3 placebo-controlled [8] | Placebo [8] |
Post-approval safety leans on voluntary reporting, and those systems miss most events by design [6][7]. Rare harms surface late, like the small excess Guillain-Barré signal after RSV vaccines [3][4].
My call: approval tells you a product beat a comparator on chosen endpoints in a selected population. It does not tell you it beats the disease, or that it is safe long-term. Confidence: moderate.
Sources used 8
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PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA)
A large randomized, placebo-controlled trial (CAPiTA) in Dutch adults aged ≥65 showed PCV13 vaccination provides vaccine-type protection against CAP and IPD (notably including serotype 3), with sustained efficacy over ~5 years when considering clinically defined outcomes, inform…
DOI: 10.3390/microorganisms10010127 -
COVID-19 Update: mNEXSPIKE — A New Moderna mRNA Vaccine for COVID-19
A Medical Letter review reports that FDA licensed mNEXSPIKE, a targeted mRNA COVID-19 vaccine, after a randomized noninferiority trial showed similar COVID-19 incidence to Spikevax in previously vaccinated people aged ≥12 years.
DOI: 10.58347/tml.2025.1733h -
Efficacy, effectiveness, and safety of respiratory syncytial virus vaccines in adults: Evidence from clinical trials and real-world effectiveness studies
Current RSV vaccines in adults ≥60 years show clinically meaningful trial efficacy and real-world effectiveness against RSV lower respiratory tract disease and hospitalization, with waning protection and small rare neurologic safety signals.
DOI: 10.12746/swjm.v14i60.1649 -
Prevention of Herpes Zoster: A Focus on the Effectiveness and Safety of Herpes Zoster Vaccines
This narrative review finds real-world vaccine effectiveness of about 46% for live zoster vaccine and about 85% for recombinant zoster vaccine, with mostly local reactions and a small Guillain-Barré syndrome signal to monitor.
DOI: 10.3390/v14122667 -
Design of a large outcome trial for a multivalent human papillomavirus L1 virus-like particle vaccine
A large, randomized, double‑blind Phase II/III trial designed to evaluate the 9‑valent HPV L1 VLP vaccine (9vHPV) against qHPV using immunogenicity bridging for the original types (6/11/16/18) and clinical efficacy endpoints for the additional types (31/33/45/52/58), demonstrati…
DOI: 10.1016/j.cct.2015.02.009 -
Monitoring Vaccine Safety Depends on Reports from Providers
An editorial overview arguing that post-licensure vaccine safety monitoring relies on provider reports to VAERS and MedWatch, highlighting underreporting and the role of FDA/CDC analyses in detecting safety signals and guiding recalls when necessary.
DOI: 10.1016/s1086-5802(15)30390-9 -
Neki čimbenici utjecaja na nedovoljno prijavljivanje sumnji na nuspojave cjepiva
Underreporting of suspected vaccine adverse events in Croatia is shaped by health worker knowledge, attitudes, time constraints, and patient awareness, with nurses playing a pivotal role and calls for enhanced education and communication to improve pharmacovigilance.
DOI: 10.13112/pc.2023.11 -
Regulatory review of benefits and risks of preventing infant RSV disease through maternal immunization
A 2024 FDA perspective describes the regulatory rationale for approving Abrysvo for maternal RSV immunization at 32-36 weeks gestation, balancing efficacy in preventing infant LRTD against potential risks of preterm birth and hypertensive disorders of pregnancy.
DOI: 10.1038/s41541-024-01002-y