Immunizations

• Vaccines, like other pharmaceutical and medical device products, undergo rigorous testing to ensure they are safe and effective. Brand new vaccines are compared to placebos, and vaccines that are modifications of a previous vaccine are compared to the previous vaccine to ensure it is an improvement over what is currently used. After the initial clinical trials are done, even more long-term surveillance is done to pick up side effects or issues that could arise after the study period. This balances making new pharmaceuticals, medical devices, and vaccines available in a reasonable amount of time to help the people that need them, while still ensuring it has been tested for safety and efficacy. Vaccines generally take 10-15 years of laboratory research to develop. The phases of clinical trials are:
  • Phase I trials: Researchers test a drug or treatment in a small group of people (20–80) for the first time. The purpose is to study the drug or treatment to learn about safety and identify side effects.
  • Phase II trials: The new drug or treatment is given to a larger group of people (100–300) to determine its effectiveness and to further study its safety.
  • Phase III trials: The new drug or treatment is given to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or similar treatments, and collect information that will allow the new drug or treatment to be used safely.
  • Phase IV trials: After a drug is approved by the FDA and made available to the public, researchers track its safety in the general population, seeking more information about a drug or treatment’s benefits, and optimal use.

(Source: National Institutes of Health. https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics)

(Source: Centers for Disease Control. https://www.cdc.gov/vaccines/basics/how-developed-approved.html)

• When vaccines are compared against active placebos, you compare the adverse effects of the vaccine against the active placebo, so you know exactly what adverse effects were caused by the antigen in the vaccine itself. If you want to identify the adverse effects that are due to constituents of the vaccine other than the antigen (the active placebo) you can look at background rates of those symptoms in the same population or other trials where the active placebo is specifically tested.
• Recombivax HB underwent the same safety and efficacy trials that all vaccines undergo. It was approved in 1986 and, while there were some studies that had an active 5 day observation period, surveillance for long-term side effects, such as neurodevelopmental and autoimmune effects, continues even today. In the United States, we use two large scale monitoring approaches for vaccine side effects:
  • Vaccine Safety Datalink (VSD): Uses data pulled directly from electronic health records to identify trends that could be associated with vaccine administration
  • Vaccine Adverse Event Reporting System (VAERS): Physicians and healthcare facilities are required by law to report any adverse effects via the VAERS system, however ANY individual can report an effect, even if it is not actually correlated to the receipt of the vaccine. (For example, in theory, you could report that you had a cold tongue after receiving a vaccine, even if it was actually due to the ice cream you ate that day).
• Recombivax, just like other vaccines, is monitored via the VSD and VAERS since it was approved in 1986. Therefore, it has actually been monitored for over 35 years, which is a lot more than five days!

As above, long-term surveillance studies are being constantly done in the background, both via active reporting and via direct data pulls from electronic health records. Since VSD pulls from medical records, it includes all the vaccines that were given at once in its evaluation.

• The most common adverse events secondary to vaccines include redness, swelling, and fever at the injection site. Since these are all benign, expected side effects, individuals do not usually 1) notify their doctors or 2) submit a report to the VAERS system. Therefore, it makes sense that 99% of adverse events, which are relatively benign, are not captured in the database. The significant adverse effects (<1%) are required by law to be reported by physicians and healthcare facilities, but can also be reported by ANY individual to ensure the most complete capture of data. 
• The CDC, as well as other researchers, are not as concerned about missing the 99% of side effects that are redness, fever, and swelling at the injection site, so instead most efforts are targeted at capturing the <1% of side effects that are potentially more concerning. This is done by multiple avenues including:
  • Vaccine Safety Datalink (VSD): Uses data pulled directly from electronic health records to identify trends that could be associated with vaccine administration
  • Clinician researchers making observations about side effects noted after receipt of vaccines
  • Regular comprehensive literature reviews of published studies looking at vaccine side effects
  • Ensuring that vaccine information sheets (VIS) for each vaccine are handed out to patients at their appointment, which has the information for VAERS provided to encourage patients to notify their providers and the reporting system if they have adverse events

• Yes! Actually, aluminum salts were first used in human vaccines in 1932 and were the only adjuvant used for almost 70 years. They have been monitored for a long time for adverse safety events and long-term outcomes, since we have been using them in vaccines for such a long time!

• If you look at the American Academy of Pediatrics recommended vaccine schedule roundtable in 1948, you can see that an aluminum adjuvanted Pertussis vaccine was recommended as early as 1 month of age. The Diphtheria and Tetanus vaccines at that time each contained 0.45 mg of aluminum each (0.9 mg total), which is actually less than the Diphtheria, Tetanus, and Pertussis combination vaccine that is currently recommended (which contains < 0.625 mg/dose total with all three vaccines). While it may seem like children are getting more aluminum these days than children in the 1930s and 1940s because they receive more vaccines, it’s important to consider that aluminum was used in vaccines previously.