Rotavirus vaccine withdrawal in the United States:

26 Jan

By the beginning of October 1999, 101 confirmed and pre­sumed cases of intussusception had been reported to VAERS. The rate of reporting increased greatly after the July 1999 an­nouncement of the temporary postponement of rotavirus vac­cination. Fifty-two patients required surgery, nine required bowel resection and one patient died. Fifty-seven of these chil­dren developed intussusception within seven days of vaccine dose, and 70% developed their intussusception after the first dose. There was a clear clustering of cases from day 3 to day 8 after the dose of vaccine. In case-control studies, risk ratios of developing postvaccine intussusception varied from seven to 30, depending on the study and type of analysis. It was esti­mated that these data would have translated into around 1200 potential additional cases of intussusception annually in the United States if rotavirus vaccine policy had been fully implemented. Based on these data, the ACIP concluded that in­tussusception frequency was significantly increased in the first one to two weeks after vaccination, particularly after the first dose, and decided to withdraw its rotavirus vaccine rec­ommendations. The American Academy of Pediatrics also withdrew its recommendations. On October 15, 1999, Wyeth- Lederle Vaccines announced that it was withdrawing the Rotashield vaccine from the market and requested the imme­diate return of all distributed doses.

These events demonstrate very clearly that postmarketing surveillance is an essential component of vaccine program im­plementation. Data obtained before licensure did not reveal an excess risk of intussusception following vaccination with rota- virus vaccine. However, postlicensure surveillance showed quite convincingly that rotavirus vaccine administration was associated with an increased risk of intussusception, particu­larly in the week following administration of the first dose. These events also demonstrate the power of active surveil­lance systems: Preliminary data from active systems in Minne­sota and the Northern California Kaiser Permanente Health Maintenance Organization suggested an increased risk of in­tussusception following RRV-TV. Further accumulation and analysis of the data both from the VAERS and from the various postmarketing surveillance systems led the expert committees to withdraw their recommendations concerning the use of this vaccine.

In Canada, the vaccine had not yet been approved for use by the Therapeutic Products Program when data suggesting that the vaccine might be associated with an increased risk of in­tussusception became known. This vaccine is not expected to be approved in Canada, at least in the foreseeable future. How­ever, other vaccines have recently been approved for use, for example, varicella, and others should soon be approved for use (conjugate pneumococcal and meningococcal). The events surrounding the introduction of the rotavirus vaccine show clearly that Canada needs to have a strong postmarketing sur­veillance system in place, particularly for newly introduced vaccines.

What systems exist in Canada? The Immunization Moni­toring Program ACTive (IMPACT), an active surveillance sys­tem for severe side effects following immunization, is a cen­tral component of the postmarketing surveillance system in Canada. This program is operated under contract by the Canadian Paediatric Society, with funds provided by Health Canada, for the primary purpose of postmarketing surveil­lance of vaccine safety. The surveillance system is based upon 11 pediatric referral centres (soon to be 12) extending from St John’s, Newfoundland to Vancouver, British Columbia. These centres comprise over 2000 paediatric beds and admit over 90,000 children annually, encompassing about 80% of paediatric admissions to Canadian academic centres. The in­vestigators are infectious diseases specialists who act as vol­unteers. Each centre employs a nurse monitor who carries out the routine active surveillance activities in each centre. In ad­dition to IMPACT, Health Canada operates a passive surveil­lance system similar to VAERS in the United States, which col­lects data on adverse reactions following immunizations reported by physicians and public health units. Finally, Health Canada has set up the Advisory Committee on Causal­ity Assessment, whose task is to evaluate the role of immuni­zation as the cause of reactions reported either by IMPACT or through other sources. These systems are complimentary to one another and form a network of surveillance activities that ensure adequate safety monitoring of licensed vaccines in Canada. The recent rotavirus vaccine story illustrates the use­fulness of these activities, and should convince Health Canada that continued funding of IMPACT and of the other compo­nents of the vaccine safety monitoring program is of great im­portance to the health of Canadians.
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