expensive study would not be statistically powerful enough to detect the relatively rare neurologic events of interest. Data from the pilot study (Gale et al., 1990) were reviewed by the Committee to Study the Adverse Consequences of Pertussis and Rubella Vaccines; the same data have recently been published in final form (Gale et al., 1994).
Vaccine Safety Committee
After completion of the IOM report Adverse Effects of Pertussis and Rubella Vaccines (IOM, 1991) IOM convened the Vaccine Safety Committee under the mandate of the National Childhood Vaccine Injury Act. The Vaccine Safety Committee reviewed evidence about possible adverse events caused by vaccines against diphtheria, tetanus, measles, mumps, polio, hepatitis B, and Haemophilus influenzae type b. The committee's report was released in 1993 (IOM, 1994). With regard to diphtheria and tetanus toxoids and encephalopathy, the Vaccine Safety Committee concluded that the evidence favors rejection of a causal relation between encephalopathy (acute or chronic) and (a) diphtheria and tetanus toxoids for pediatric use (DT), (b) tetanus and diphtheria toxoids for adult use (Td), and (c) tetanus toxoid. The committee was not charged with reexamining the adverse effects of DPT.
THE CHARGE TO THE 1993 COMMITTEE TO STUDY NEW RESEARCH ON VACCINES
The U.S. Public Health Service, recognizing the possible significance of the newly published data from the NCES, enlisted IOM in a new assessment of the relation between DPT and permanent neurologic damage. The IOM convened the Committee to Study New Research on Vaccines in December 1993. The charge to the committee was to evaluate the contribution of the new data from the NCES to answering the question of whether DPT is causally related to permanent neurologic damage. The committee's conclusion could be phrased in terms of the impact that it might have on the conclusion of the 1991 IOM report Adverse Effects of Pertussis and Rubella Vaccines regarding the causal relation between DPT and permanent neurologic damage.
The six members of the Committee to Study New Research on Vaccines had expertise in pediatrics, neurology, and epidemiology. Each committee
Miller et al., 1993). This report reconsiders the causal relation between DPT and permanent neurologic damage in light of the new data from the NCES.
HISTORY AND BACKGROUND
In the past several years, the IOM has undertaken two other reviews that bear on the issues addressed by the Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines. Brief descriptions of the two reviews follow.
Review of an Epidemiologic Study of Neurologic Illness and Vaccination in Children
In 1987, the Centers for Disease Control (CDC) contracted with IOM to review and critique a pilot epidemiologic study of vaccine-associated acute neurologic illness being performed at the University of Washington under a CDC contract and designated the Study of Neurologic Illness in Children (SONIC). IOM appointed a committee to (a) review the SONIC protocol and make suggestions for changes, and (b) review the final report of the SONIC investigators and make recommendations about the advisability of conducting a more definitive study of neurologic illness and vaccination. At a meeting in 1987, the IOM committee reviewed the protocol for the pilot study and recommended relatively minor changes in what it considered as a well-designed study without major methodologic flaws.
Midway through the pilot study, CDC requested that IOM sponsor a workshop on the NCES, a study that was conducted in the United Kingdom in the late 1970s and the results of which were published in 1981 (Alderslade et al., 1981; Miller et al., 1981). At a workshop that the committee held in 1989, epidemiologists reviewed the NCES report and the criticisms that had arisen since publication of the study 's results. The purpose of the workshop was to encourage scientific discussion about the NCES and to inform the committee's deliberations relative to the SONIC study. No conclusions or other official IOM report resulted from the workshop; however, a summary of the discussion was published by two of the participants (Marcuse and Wentz, 1990).
The SONIC project ended in 1990, with a finding that pilot study data did not show a statistically significant increased risk of serious acute neurologic illness following vaccination against pertussis; the investigators noted that the study “had limited power to detect significant elevations of risk for individual conditions.” The IOM committee reviewed the results of the pilot project and recommended that the CDC not attempt a more definitive study, primarily for reasons of epidemiologic feasibility and the likelihood that even a large,