Vaccine Safety

Advisory Committee on Causality Assessment (ACCA)

There is little question that vaccines have had a tremendous impact on the incidence of childhood infectious diseases. However, during the years before 1965 when many vaccines were being introduced, the systematic monitoring for adverse events associated with drug products was not being undertaken. It required an international disaster, the discovery of phocomelia (a congenital malformation or birth defect) associated with thalidomide use in pregnancy, to stimulate the creation of formal surveillance programs.⁽¹⁾

Canada is a world leader in the postmarketing surveillance of vaccine products. The Canadian Adverse Events Following Immunization Surveillance System (CAEFISS) (which is distinct from the monitoring program for other drug products) is maintained by the Immunization and Respiratory Infections Division, Public Health Agency of Canada. The Division receives case reports of events suspected to be due to the administration of a vaccine that are submitted voluntarily by health care providers through their provincial public health authorities on an Adverse Event Following Immunization Report Form .⁽²⁾ The program receives about 4,000 reports per year, of which the majority represent minor reactions such as fever or injection site pain and/or swelling.⁽³⁾ Although spontaneous reporting systems are criticized for a number of limitations including under reporting, they remain a key first line activity for detecting problems with vaccines on the market.⁽⁴⁾ Time and again, spontaneous monitoring programs have been the first to detect new signals that have later been confirmed.

Continually improving the capacity of spontaneous reporting systems to detect new and rare events is a challenge, especially in a climate of under reporting. Two activities have been added to supplement the CAEFIS spontaneous reporting system to address the need for more active surveillance and to more fully evaluate and interpret case reports of new or serious adverse events. The first, started in 1990, is an active, pediatric hospital-based surveillance program known as the Immunization Monitoring Program ACTive (IMPACT) which searches admissions for events that may have been due to vaccine administration.⁽⁵⁾ The second initiative, begun in 1994, was the formation of a multidisciplinary expert group, called the Advisory Committee on Causality Assessment (ACCA), to review all case reports meeting criteria for severity or "unexpectedness".

This group is composed of specialists in pediatrics, public health, epidemiology, infectious diseases, immunology, neurology and adverse event surveillance. The committee meets for two days once a year and meets by regular teleconferences 9-10 times a year to review selected cases. Should an emergent concern require intervention, additional ad hoc teleconferences are arranged. Cases that are reviewed are stripped of all identifiers and distributed to each member in advance. Selection criteria for case review include deaths, hospitalization for more than 3 days, life threatening events such as anaphylaxis, and other serious adverse events including meningitis/encephalitis, encephalopathy, and Guilain-Barre Syndrome.

Every year, ACCA reviews approximately 60 to 70 cases submitted to the reporting system as a result of both passive and active surveillance activities. Each case is reviewed using the WHO-UMC (World Health Organization-Uppsala Monitoring Centre) causality assessment criteria of Very Likely, Probable, Possible, Unlikely, Unrelated, or Unclassifiable to determine whether the adverse event was related to the administration of the vaccine(s). Cases that are inadequately documented are followed up with the reporter to obtain more information. Using this method, a number of issues have recently been identified for further detailed research and/or surveillance. If warranted by the results of further work, ACCA can recommend that regulatory action be considered.

In addition, ACCA is in a position to recommend increased education in certain areas such as the recognition and diagnosis, management, and reporting of cases of anaphylaxis. Summary reports of the case evaluations done by ACCA are made available to the Provincial/Territorial Epidemiologists (responsible for immunization programs), to the IMPACT surveillance program and for review by the Canadian Pediatric Society Committee on Immunization and Infectious Diseases.

The functioning of ACCA has attracted attention internationally. Representatives from the U.S. Centers for Disease Control and Prevention (CDC) as well as the U.S. Vaccine Injury Compensation Program attend ACCA meetings.

Together with the participation of practitioners who report suspected adverse events, and the IMPACT surveillance program that maintains active, hospital-based surveillance, the Advisory Committee on Causality Assessment (ACCA) is a key component in the postmarketing surveillance of vaccine products and is contributing to public and health provider confidence in immunization programs.

References

1. Griffin JP, Weber JCP. Voluntary systems of adverse reaction reporting-part II. Adv Drug React Act Poison Rev 1986; 1:23-55.

2. Pless RP, Duclos P. Vaccine-Associated Adverse Events: Surveillance and Reporting. In: Krogh, C (Ed) Compendium of Pharmaceuticals and Specialities 31st Edition. Canadian Pharmaceutical Association, Ottawa, 1996.

3. Division of Immunization. Vaccine-associated adverse events in Canada, 1992 report. Can Commun Dis Rep 1995; 21(13): 117-128.

4. Rossi AC, Bosco L, Faich GA, Tanner LA. The importance of adverse reaction reporting by physicians. JAMA 1988; 259(8):1203-1204.

5. Morris R, Halperin S, Dery P, Mills E, Lebel M, MacDonald N, Gold R, Law B, Jadavji T, Scheifele D, Marchessault V, Duclos P. IMPACT monitoring network: a better mousetrap. Can J Infect Dis 1993; 4: 194-5.