First AD

Second AD

Picture the statue of Justice, a blindfolded woman with a scale in her hand presumably weighing the evidence for guilt on one side versus for innocence on the other. The FDA and CDC have a similar task when they consider approving new vaccines, as they weigh the potential population benefit versus side effects and risks. One is willing to put up with more risk and side effects (when a safer drug is not available) when treating a life threatening illness such as a cancer. Vaccines, being given to generally healthy individuals, are held to a higher safety standard and more stringent side effect profile.  

Very effective vaccines, with even a mild-to-moderate safety/adverse effect profile, will often not be approved or be subsequently withdrawn, partly as a result of the desire to maintain public confidence in the vaccination system. 

Here's a short test (1 question) of your memory of controversy that may, or may not, have surrounded some late 20th- and an an early 21st-century vaccine approvals. 

D. None of the above; all were removed from the market for safety reasons. 

Answer: Please read to the end for the correct selection.

 for use in 1998. At that time, rotaviral gastroenteritis put 50,000 children in the hospital every year. Following its approval, a number of reports were sent to the VAERS reporting system of cases of intussusception in the first week after vaccine administration. A number of studies were initiated to determine if use of Rotashield did increase the risk of intussusception beyond the natural background rate.  It was not an expected risk since natural rotaviral disease does not seem to increase the risk for intussusception. Interestingly, in the 27 pre-approval vaccine trials on about 10,000 infants receiving infants receiving Rotashield 5 developed intussusception as compared to one in the placebo group of 4,600. It was not a statistically significant difference, but did result in intussusception being listed as a possible complication in the package insert. The increased risk was eventually felt to be about one extra case of intussusception in every 10,000 children vaccinated. At the same time, the vaccine would have prevented more than 100 hospitalizations for dehydration and even perhaps some deaths in that same 10,000 child cohort. In my opinion, the benefit of this vaccine still outweighed the risk, but the ACIP (the CDC's vaccine committee) disagreed and it was pulled off the market. The current rotavirus vaccines were tested in trials involving over 70,000 children and did not show any association with intussusception. But again, post-marketing studies have found a slight increase in risk of intussusception following vaccination of about 1 in 100,000 children. The FDA and ACIP have decided that this is an acceptable risk for the benefit.

, licensed in 1998 under the name Limerix, was a 3-dose series, and had an efficacy rating of approximately 78%. The side effect profile looked good. The CDC gave it a “permissive” recommendation, meaning it was not recommended for everyone, but should be given to those at increased risk. Anti-Lyme vaccine groups soon organized and reported that the vaccine could cause arthritis. Class action lawsuits were filed. Since the vaccine was not “recommended,” the manufacturer was not protected by the National Vaccine Injury Compensation Program and could be sued directly. Post-marketing studies did not reveal any uptick (pun intended) in arthritis cases. After selling only about 1.5 million doses over 4 years, the manufacturer stopped production in 2002, citing insufficient consumer demand. I suspect the potential future legal costs were a significant factor in their decision as well. Another Lyme vaccine is being tested in phase 1 and phase 2 trials at this time.

 did produce a lot of fever and fussiness in a lot of infants. For a while, it was thought that it might cause brain damage in about 1 in 250,000 children. New research has shown that these individuals had a rare genetic defect that would have led to brain damage eventually even if they had not received the DPT vaccine. As a pediatrician, I was glad to see the new acellular pertussis vaccines. The number of after-hours phone calls from worried parents about their fussy, febrile child following vaccine administration has dropped dramatically.  But, the new acellular pertussis vaccines do not work as well in preventing pertussis as vaccine efficacy wanes within a few years. And so the question of risk versus benefit arises again-I will discuss this further in the next column.

So, what is the best answer to the question?

 Clearly, Rotashield and DPT were removed for safety reasons that were real. The Lyme disease vaccine did not show any significant safety problem and was pulled for economic reasons, albeit some economic reasons related to alleged safety issues. 

A nice look at the Lyme disease vaccine debacle 

http://www.historyofvaccines.org/content/articles/history-lyme-disease-vaccine

http://www.cdc.gov/vaccines/vpd-vac/rotavirus/vac-rotashield-historical.htm

A study that suggests that the lifetime risk of intussusception is not much different

 in recipients of Rotashield, ie, the vaccine caused intussusception to occur earlier in individuals who would have gotten it anyway.


http://jid.oxfordjournals.org/content/192/Supplement_1/S36.full

A good review of the DPT vaccine controversy 

https://iom.nationalacademies.org/~/media/Files/Activity%20Files/Disease/VaccineFinancing/FineBackgroundPaper.pdf

What is the acceptable balance between benefit and risk to prevent a vaccine's being pulled from the market? See what you recall about these 3 cases. 

Weighing Vaccine Risk vs Benefit