AHRQ Research Helps Biopharmaceutical Company Evaluate Rotavirus Vaccine Marketing

November 2006

BIOVIRx, a biopharmaceutical company with exclusive worldwide license for the RotaShield rotavirus vaccine, used AHRQ-funded research to inform its efforts in attempting to return RotaShield to the domestic and international marketplace.

RotaShield is a live, rhesus-human reassortment rotavirus tetravalent vaccine developed by the National Institutes of Health (NIH). and Wyeth-Lederle Vaccines and Pediatrics. Rotavirus is a leading cause of childhood diarrhea that results in 20 deaths, 50,000 hospitalizations, and 500,000 physician office visits in the U.S. each year.

In 1998, the U.S. Advisory Committee on Immunization Practices (ACIP) recommended the RotaShield vaccine for routine use in healthy infants via a three-dose sequence administered orally at two, four, and six months. However, nine months later, after up to 1 million U.S. infants received the vaccine, the ACIP suspended approval for RotaShield due to 15 cases of intussusception thought to be related to this vaccine were reported to the Centers for Disease Control and Prevention (CDC)-Food and Drug Administration (FDA) Vaccine Adverse Events Reporting System. Intussusception is a rare cause of bowel obstruction in young children. Subsequent CDC case-control, case series, and cohort studies projected 1,200 to 1,600 cases of intussusception related to the vaccine, and RotaShield was voluntarily withdrawn from the U.S. market.

After the vaccine was withdrawn, a research group at NIH and AHRQ carried out a study identifying cases of intussusception prior to routine vaccination with RotaShield and during the interval of RotaShield vaccination using AHRQ's Healthcare Cost and Utilization Project (HCUP) data. The data not only raised the question of the direct correlation between intussusception and RotaShield use, but also demonstrated a significantly lower risk than the projected risk estimates in the initial CDC studies.

Leonard P. Ruiz, PhD, President and CEO of BIOVIRx, states, "Without the research by NIH and AHRQ, we really would not have been able to move forward with this project. The research has been critical to demonstrate the safety of the RotaShield vaccine with a modified dosing sequence. RotaShield is an affordable vaccine that can be made available in areas of the world that need it most."

In 20 high-use states, more than 10 percent-about 250,000 infants in the study-had been vaccinated. Overall, the study found a three-percent decrease in hospitalizations for intussusception during the time RotaShield was used. Infants aged 45-210 days were analyzed separately, and a five-percent increase in hospitalizations for intussusception was observed in high-use states. Importantly, there was an even greater increase (over 14 percent) in hospitalizations in low-use states.

In 2005, a second study conducted by NIH and AHRQ, also based on HCUP data, demonstrated the relationship between intussusception and age of the infant at time of vaccination with RotaShield in a cohort of more than 433,000 infants. No cases of intussusception were reported in infants receiving the vaccine prior to 60 days of age, suggesting a change to a two-dose sequence before 60 days of age and elimination of "catch-up" dosing where infants receive vaccines later than routinely suggested.

BIOVIRx is a privately held biopharmaceutical company based in Minneapolis, Minnesota, formed in 2004 to market and distribute pharmaceutical and health products in the domestic and international markets. BIOVIRx acquired the RotaShield vaccine in 2004 and has partnered with Impfstoffwerk Dessau-Tornau GmbH (IDT), based in Tornau, Germany, to manufacture and distribute the vaccine.

Impact Case Study Identifier: 
AHRQ Product(s): Healthcare Cost and Utilization Project (HCUP)
Topics(s): Pediatrics
Geographic Location: National
Implementer: BIOVIRx
Date: 11/01/2006


Simonsen L, Morens D, Elixhauser A, Gerber M, Van Raden M, Blackwelder W. Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception. Lancet 2001; 358:1224-9.
Simonsen L, Viboud C, Elixhauser A, Taylor RJ, Kapikian AZ. More on RotaShield and intussusception: the role of age at the time of vaccination. Journal of Infectious Diseases 2005; 192(Suppl 1):S36-S43.


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