This example is provided to illustrate some of the many considerations and studies that go into recommending any vaccine.  Similar studies have been done on all of the vaccines currently recommended. 

Rotavirus example:

     Rotavirus is a virus that causes vomiting and diarrhea.  Almost all children are exposed to rotavirus by the time they are 5 years old.  In most children, it causes gastroenteritis characterized by fever, diarrhea and vomiting, which can sometimes lead to dehydration and electrolyte imbalances.  This resulted in an estimated 400,000 physician visits, 250,000 emergency department visits, 60,000 hospitalizations, and 20-60 deaths per year. Although children of any age can get rotavirus, the age group 3 months – 5 years are th ones most likely to require hospitalization.  After a natural infection with rotavirus, 40% of people develop immunity to all further rotavirus and 88% are protected from severe disease.  Subsequent infections with rotavirus are more likely to result in further immunity, especially against severe disease.  Vaccinations have been developed against rotavirus.  The expectation is that, while the vaccine may not protect entirely against rotavirus infection, if given early in life it may take the place of a “first” infection.  Thus, subsequent infections with rotavirus would be less likely to result in the more serious effects requiring hospitalization.

            In 1988, a rotavirus vaccine RRV-TV (Rotashield^®) was recommended for routine vacations in the US.  Through monitoring via routes such as the VAERS,  a number of cases of intussusception were noted.  Upon review, it was found that there was an increased rate of intussusception within 3-14 days after the first dose of the vaccine.  Although the rate of intussusception was 20 times higher than the background rate, the overall incidence was still only 1 case per 10,000 vaccine recipients.  Because of the rarity of this complication, it was not noticed in smaller trials. Because of this adverse effect linked to the vaccine, the product was removed from the market after less than one year. 

            In 2006, another vaccine to rotavirus, RotaTeq^®  was licensed.  Because of safety concerns from the previous vaccine, RotaTeq^® had to prove itself even more vigorously.  The phase three (safety) trial enrolled approximately 70,000 children.  The study had to be done on this order of magnitude in order to detect changes in the relatively rare occurrence of intussusception.  In this trial, 5 cases of intussusception occurred in the placebo group, while 6 cases occurred in the vaccine group.  Thus, there did not appear to be an increased risk in those getting the vaccine.  Post-marketing research continues to monitor rates of intussusception and other adverse events. 

            Because of previous concerns of possible age-related risks, it is recommended that RotaTeq^® only be administered within strict age guidelines.  The first dose is recommended to be given between ages 6-12 weeks.  Subsequent doses are given at 4-10 week intervals and all three doses need to be finished by 32 weeks of age.  It is recommended that the vaccine not be started in infants over 13 weeks old and should not be given to infants over 32 weeks of age because of insufficient safety data. 

            The efficacy of  RotaTeq^®  was also studied.  As a sign of immunoginicity, rotavirus specific IgA levels were monitored in the control group and in the group given three doses of the vaccine.  Seroconversion rates were 93-100% in the vaccinated group and 12-20% in the non-vaccinated group.  Those in the non-vaccinated group who seroconverted were likely exposed naturally to rotavirus during the study. 

            More important than laboratory seroconversion, however, is the clinical outcomes of patients given the vaccine.  In trials, after getting three doses of RotaTeq^®  74% of patients did not get any clinical rotavirus disease.  Only 2% of those vaccinated still got severe disease.  In addition, the incidence of visits for rotavirus during the first year after vaccination was reduced 86% for doctor’s offices, 94% for ED visits, and 96% for hospitalization.  Based on their studies, a nationwide vaccination program could prevent 44,000 fewer hospitalizations and 13 fewer deaths per year. 

            A cost analysis was also performed to determine if the cost of providing vaccinations to children nationwide would be offset by a decreased cost of office visits and hospitalization.  When considering only health care costs directly (not loss time form work for parents and other such factors), they determined that the vaccine would be cost effective if it cost less than $66 per child.  If estimated societal costs are also included in the calculations, the vaccine remains cost effective up at $156 per child. 

Link to source article:

Prevention of Rotavirus Gastroenteritis Among Infants and Children: Recommendations of the Advisory Committee on Immunization Practices