Vaccines have significantly contributed to worldwide reductions in morbidity and mortality by reducing the incidence of serious infectious diseases (IOM, 2012). Today, people all over the world experience the benefits of immunizations, beginning in infancy. Most adults in the United States have not witnessed firsthand the devastating illnesses against which vaccines offer protection, for example, polio, diphtheria, and Haemophilus influenzae meningitis. However, as the incidence of vaccine-preventable disease has declined, many do not appreciate the potential of these diseases to reemerge, and the potential adverse effects of the vaccines themselves take on greater saliency among certain stakeholders. Indeed, vaccine safety concerns exist among a diverse range of individuals, institutions, and formal and informal networks worldwide.
Healthy individuals are immunized with immunogenic materials that induce immunity to serious pathogens. A “schedule” is a tool that is used to ensure that the recommended immunizations are provided to shield both children and adults from disease when they are the most vulnerable. In the United States, schedules recommended by the U.S. Advisory Committee on Immunization Practices (ACIP) (schedules for children from birth to age 6 years, children and adolescents ages 7 through 18 years, and adults) are based on the immunogenicity of vaccines and the burden and timing of disease (CDC, 2011a). Each schedule is designed and updated yearly on the basis of new evidence (see Appendix A). This report focuses on the vaccines that protect young children under age 6 years against 14 different pathogens because that time period is when multiple inoculations are given (see Appendix A).
Children may receive as many as 24 injections by 2 years of age and up to 5 injections in a single visit (see Appendix A). Immunization schedules vary around the world, however, with the variability being due in part to the different patterns of disease that exist globally (Lopalco et al., 2009; WHO, 2012). Additionally, levels of antigens and immunization timing and number differ. Some countries also have differing approaches to postmarketing surveillance systems, as will be described in Chapter 3.
Although the number of vaccinations recommended is greater than ever before, the vaccines used in the current immunization schedule actually have fewer antigens (inactivated or dead viruses and bacteria, altered bacterial toxins, or altered bacterial toxins that cause disease and infection) because of developments in vaccine technology (Offit et al., 2002). For example, the vaccines to prevent whooping cough used before 1991 contained 3,000 different potentially antigenic proteins (IOM, 2002). From 1980 to 2000, the immunization schedule’s total number of antigens decreased by approximately 96 percent (from 3,041 to 123-126) (Offit et al., 2002).
Ever since vaccines were introduced in the 18th century, questions and concerns about their safety have been voiced. However, the protection against feared, deadly diseases that vaccines offer encourages the majority of health care professionals and laypeople to support immunization (Stern and Markel, 2005). Although research on the adverse effects of individual vaccines is robust and a required part of the approval process by ACIP, questions about the safety of the entire recommended immunization schedule for children persist. Moreover, how safety is interpreted varies according to the severity of an adverse event and the benefit of the vaccine. For example, some might believe that one serious adverse event that occurs once in 1 million doses is “safe enough” compared with the benefit of prevention of serious disease, whereas others may consider that risk unacceptably high.
As the number of recommended vaccines has increased in recent years, some parents and advocacy groups have expressed the concern that the immunization schedule is too crowded and complex because of the increasing number of vaccines administered during the first 2 years of a child’s life (Offit et al., 2002). In addition to the complexity of vaccine delivery, some people have raised questions about the potential for adverse health outcomes as a consequence of the simultaneous or sequential administration of childhood vaccines (Gregson and Edelman, 2003). Even though the current childhood immunization schedule offers flexibility for administration of recommended vaccines (see Appendix A), some parents elect not to follow the recommended schedule (Dempsey et al., 2011).
Analysis of current U.S. data shows that the vaccination rate among children entering kindergarten exceeds 90 percent for most recommended vaccines (CDC, 2012b). However, increases in the prevalence of delay or refusal of recommended vaccines have contributed to the emergence of
vaccine-preventable illnesses across the country. For example, measles and pertussis outbreaks have occurred in recent years in geographic areas with higher concentrations of unimmunized children (Felkin et al., 2000). States with easy procedures for granting exemptions were associated with a 90 percent higher incidence of pertussis in 2004 (Omer et al., 2006). Some vaccine-preventable diseases can be fatal and have caused morbidity and mortality in infants and people with compromised immune systems. The impacts on disease prevention that vaccines have had in the United States are illustrated in Table 1-1.
Vaccinations—like all medical procedures—are neither 100 percent free of risk nor 100 percent effective. Vaccines, in rare cases, can cause illness. Most children who experience an adverse reaction to immunization have a preexisting susceptibility. Some predispositions may be detectable prior to vaccination; others, at least with current technology and practice, are not (IOM, 2012, p. 82). The U.S. Department of Health and Human Services (HHS), through its agencies responsible for vaccine safety, supports such research and surveillance, including studies addressing concerns and fears over the current childhood immunization schedule. The system in the United States designed to ensure vaccine safety is detailed in Chapter 3. While immunization may be one of the greatest achievements in public health, the complex interactions among populations, health care systems,
TABLE 1-1 Comparison of Pre-Vaccine Annual Incidence and Current Morbidity for Vaccine-Preventable Diseases
|Disease||20th Century Annual Morbidity (No. of Cases)a||No. of Cases Reported in 2011b||Percent Decrease|
|Congenital rubella syndrome||152||0||100|
|(<5 years of age)|
a SOURCE: Roush et al., 2007.
b SOURCE: CDC, 2012a.
d Haemophilus influenzae type b among children <5 years of age.
On June 2, 2009, the National Vaccine Advisory Committee (NVAC) reviewed the nation’s vaccine safety system and endorsed the recommendation of the NVAC Safety Working Group for an external expert committee, such as a committee convened by the Institute of Medicine (IOM), “with broad expertise in research methodologies, study design, and the ethical conduct of research to consider the strengths and weaknesses, ethical issues and feasibility including timelines and cost of various study designs to examine outcomes in unvaccinated, vaccine-delayed and vaccinated children and report back to the NVAC” (CDC, 2011b, p. 72).
The recommendation by the NVAC Safety Working Group was based on a series of meetings and discussions on the U.S. childhood immunization schedule in which individuals raised concerns that the schedule could potentially harm children because of immunological or neurodevelopmental adverse effects. Furthermore, in the minds of some parents, concerns about potential harms outweigh the well-documented benefits of immunization for the prevention of morbidity and mortality, with the result being that their children are less than fully immunized (NVAC, 2009).
After years of debate, some people continue to advocate for a study to compare health outcomes among vaccinated and unvaccinated children. The NVAC report stated that “the strongest study design, a randomized clinical trial that includes a study arm receiving no vaccine or vaccine not given in accord with the current recommended schedule, is not ethical, would not pass Institutional Review Board (IRB) review, and cannot be done” (NVAC, 2009, p. 38). (Chapter 6 discusses some of the ethical considerations in detail.) Furthermore, it may be impossible to draw unbiased results from an observational study of this issue because of potential differences in baseline health and social characteristics of populations and subgroups.
The National Vaccine Program Office of HHS asked the IOM to convene a diverse committee of experts in pediatrics, neurology, medical ethics, immunology, statistics, epidemiology, and public health to identify study designs feasible to address questions about the safety of the United States’ childhood immunization schedule. A 14-member committee was selected to
The Institute of Medicine will convene an expert committee to
- Review scientific findings and stakeholder concerns related to the safety of the recommended childhood immunization schedule.
- Identify potential research approaches, methodologies, and study designs that could inform this question, including an assessment of the potential strengths and limitations of each approach, methodology and design, as well as the financial and ethical feasibility of doing them.
- Issue a report summarizing their findings.
complete a study addressing the statement of task (see Box 1-1). The committee’s charge was independent of the charges for previous IOM studies of vaccines, and committee members were carefully selected to avoid real or perceived biases or conflicts of interest. Strict criteria for membership prevented any members from having financial ties to vaccine manufacturers or their parent companies, previous service on federal vaccine advisory committees, or delivered expert testimony or written publications on issues of vaccine safety.
To complete its charge, the committee held three information-gathering meetings in two different locations. Before the first meeting and throughout the committee’s deliberations, the committee gathered information on public perspectives and reviewed the scientific literature on the safety of the recommended childhood immunization schedule. At the public forums held in February, March, and May 2012, the committee heard presentations from clinicians, representatives of U.S. federal and state agencies and public health agencies in other countries, vaccine safety researchers, advocacy groups, vaccine manufacturers, and methodological experts. During the public forums, the committee invited comments (both written and oral) from the general public and representatives from numerous organizations with an interest in vaccine safety. Additionally, the committee received and
The committee held 5 deliberative meetings over 6 months between February and August 2012. To fully address its charge, the committee identified a consultant who prepared a commissioned paper on study designs that could be used to assess the safety of the immunization schedule (see Appendix D). The paper, written by Martin Kulldorff, was intended to provide methodological input to the committee, but the paper does not necessarily reflect the committee’s views or deliberations. To solicit stakeholders’ interest and feedback, a draft version of the commissioned paper was posted on the committee’s website on May 14, 2012, and comments on the paper were invited from the public. The comment period extended to May 31, 2012, and approximately 230 individuals provided written feedback. After a review of these comments and committee discussion, the committee requested revisions from the consultant. The commissioned paper was finalized on July 3, 2012, and again posted online for comment. The committee reviewed an additional 700 comments.
Since the late 1970s, the IOM has conducted 60 studies on vaccination (see Appendix G). Each IOM study has relied on scientific evidence as the basis for its findings, conclusions, and recommendations. Committee members reviewed the summaries of 18 IOM studies that focused on vaccine safety. Reexaminations of safety are often prompted by new scientific findings and rising concerns usually in relationship to an individual vaccine and a possible adverse health outcome. However, the study of the present IOM committee is unique in that its focus is on the complete childhood immunization schedule.
This report follows a series of eight reports on vaccine safety that appeared between 2001 and 2004. The eighth report in this series examined the evidence about a possible link between autism and vaccines. That examination of the evidence found no association. A striking element described in each of these IOM reports is society’s sustained interest in vaccines (Fineberg, 2011).
The 2012 IOM committee report Adverse Effects of Vaccines: Evidence and Causality examined 158 pairs of vaccines and putative adverse effects and was the IOM’s most recent study of vaccine safety (IOM, 2012). No evidence to support a link between a vaccine and adverse events was found for the majority of adverse events, but this was often due to the rarity of the adverse event and the lack of evidence in general to support or reject a causal link. However, the committee concluded that very few health problems are caused by or are clearly associated with vaccines.
This report is organized into seven chapters and seven appendixes. Chapter 2 provides background on how vaccines are developed and recommended for U.S. children. Chapter 3 details existing surveillance and data systems for evaluating vaccine safety. Chapter 4 reports on the committee’s review of stakeholder concerns. Chapter 5 describes the methods used to perform and the results of a literature review on the scientific findings of studies of selected health outcomes and the recommended immunization schedule. Chapter 6 presents several methodological approaches for future studies. Chapter 7 summarizes the committee’s findings, conclusions, and recommendations. The appendixes include ACIP’s 2012 recommended immunization schedule for children (Appendix A), a glossary (Appendix B), a list of acronyms used in this report (Appendix C), the commissioned paper by Martin Kulldorff (Appendix D), agendas from public meetings held by the committee (Appendix E), biographical sketches of the committee members (Appendix F), and a chronological list of the IOM’s vaccine publications (Appendix G).
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