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© 2009 American Public Health Association
DOI: 10.2105/AJPH.2008.143081
FRAMING HEALTH MATTERS |
Marie R. Griffin is with the Departments of Preventive Medicine and Medicine, School of Medicine, Vanderbilt University and the Mid-South Geriatric Research Education and Clinical Center and Clinical Research Center of Excellence, VA Tennessee Valley Health Care System, Nashville. At the time this article was written, M. Miles Braun was with the Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD. Kenneth J. Bart was with the National Vaccine Program Office, Office of Public Health and Science, Office of the Secretary of Health and Human Services, Washington, DC.
Correspondence: Correspondence should be sent to Kenneth J. Bart, MD, MPH, 9917 Conestoga Way, Potomac, MD 20854 (e-mail: kennethbart{at}yahoo.com). Reprints can be ordered at http://www.ajph.org by clicking on the "Reprints/Eprints" link.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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In 2007 the National Vaccine Program, along with the Centers for Disease Control and Prevention, the Food and Drug Administration, the National Institutes of Health, and the Health Resources and Services Administration, sponsored a public conference titled "Vaccine Safety Evaluation: Post Marketing Surveillance." The objective was to discuss enhanced approaches to postlicensure evaluation of vaccine safety, including active and passive surveillance systems and special studies. The conference participants reviewed the evolution of the assessment of vaccine safety, detailed current national approaches to postmarketing safety, and offered new approaches to evaluating vaccine safety. A number of the participants recommended that information systems be expanded to include reliable information on vaccination and health outcomes in large populations. We summarize the major meeting presentations and discussions.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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Preventing infectious diseases through immunization programs is critically dependent on ensuring the safety of vaccines and effectively communicating their benefits and risks. Vaccine-preventable diseases are rare when vaccines are effective and high coverage levels are sustained. Ironically, the decline in disease resulting from the success of vaccines often contributes to a concurrent increase in the visibility of and public concerns about vaccine-associated adverse events.
Prelicensure clinical trials can demonstrate that most adverse events associated with licensed vaccines are minor and that serious adverse events are not common. However, rare, serious events are much less likely to be detected before licensure, even in relatively large clinical trials. It is important to be able to determine whether vaccines cause such events after licensure. If a serious adverse event is causally related to a vaccine, the balance between vaccine benefits and risks could shift, possibly leading to changes in recommendations for vaccination or stimulating efforts to improve vaccine safety. Robust safety studies that convincingly demonstrate that a causal relationship is unlikely should help maintain confidence in vaccine programs.
In 2007, the National Vaccine Program, in conjunction with the Centers for Disease Control and Prevention, the Food and Drug Administration, the National Institutes of Health, and the Health Resources and Services Administration sponsored a public conference titled "Vaccine Safety Evaluation: Post Marketing Surveillance." The objective of the conference was to discuss enhanced approaches to postlicensure evaluation of vaccine safety, including active and passive surveillance systems and special studies. The participants reviewed the evolution of vaccine safety assessments, detailed current national approaches to postmarketing safety, and offered new approaches to evaluating vaccine safety. Transcripts and slides from the conference are available at http://www.hhs.gov/nvpo.
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BACKGROUND |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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In 1901, Jim, a former milk wagon horse whose serum was used to produce diphtheria antitoxin, developed tetanus. Although Jim was euthanized, the deaths of 13 children in St. Louis, Missouri, were linked to their having received Jim's contaminated serum through a series of avoidable errors. This incident and a similar one involving contaminated smallpox vaccine that resulted in the deaths of 9 children in Camden, New Jersey, led to the passage of the Biologics Control Act of 1902 (32 Stat 328); responsibility for the development and enforcement of regulations and their organizational placement was assigned to the Hygienic Laboratory of the Public Health and Marine Hospital Service, the predecessor of the Center for Biologics Evaluation and Research of the Food and Drug Administration (FDA). The act also included the first governmental controls over production of a biological product.
Similarly, the 1955 "Cutter incident," during which insufficiently inactivated polio vaccine was associated with 260 cases of symptomatic poliomyelitis,1 led to new mandates about oversight of vaccine production. More recently, the recommendation that infants be immunized with RotaShield (Wyeth Laboratories, Marietta, PA), the first licensed rotavirus vaccine, was withdrawn within a year of the vaccine's 1998 licensure as a result of the association of the vaccine with an increased risk of intussusception, even though the absolute risk for vaccinees was small.2 This rapid response can be viewed as evidence of a well-functioning vaccine safety system. However, addressing issues surrounding the safety of RotaShield required investing significant resources to assemble a large amount of data because no comprehensive database including sufficient numbers of vaccinees was available to provide the needed answers in a timely way.
The ongoing evaluations of the meningococcal conjugate vaccine, Menactra (Sanofi Pasteur, Swiftwater, PA), and its possible causal association with Guillain-Barré syndrome (GBS) show that it is possible to respond rapidly to safety questions, including evaluations of risks and benefits and use of the best available data to clearly communicate these results to the public.3 More definitive answers will depend on the results of a large, ongoing epidemiological study; however, if data were easily available, we would have those answers already.
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VACCINE AND DRUG SAFETY |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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Although many aspects of vaccine safety are similar to those recently outlined for drugs,4 there are notable differences. Given that most vaccines are administered for purposes of prevention rather than treatment, that vaccines are often given to healthy individuals (including newborns, infants, children, and adults), and that states frequently mandate them for school entry, safety requirements are high to ensure that expected benefits outweigh risks. In certain instances, such as rotavirus gastroenteritis, mumps, and hepatitis A in US children, selected vaccine-preventable diseases rarely cause death or permanent disability. Therefore, the benefits of these vaccines are largely limited to preventing short-term morbidity. In such situations, rare adverse events that can cause permanent disability or death will strongly influence the benefit-to-risk relationship.
In regions where certain diseases have become uncommon or have been eradicated (e.g., measles, poliomyelitis, Haemophilus influenzae, type b meningitis), unvaccinated individuals are at very low risk of acquiring disease but are vaccinated so that they are protected from reintroduced disease and its spread in their communities. Thus, vaccination serves to protect not only vaccinated individuals but also society at large.
When vaccines are given to healthy individuals, adverse events that closely follow vaccine administration create compelling anecdotes. Many people may assume a causal relationship between the vaccine and the adverse event. When almost everyone is vaccinated, addressing such causal hypotheses through epidemiological investigations is challenging because of the difficulty in identifying a comparable control group of unvaccinated people. Although a causal relationship is most likely to be suspected with events that are unusual and that closely follow vaccination, concerns have been raised about more common outcomes as well as those that may occur long after vaccination. These latter situations present substantial methodological challenges with respect to conducting causality assessments in postlicensure settings.
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THE VACCINE SAFETY SYSTEM |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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Vaccine safety activities are undertaken by various federal agencies acting in concert with each other, the states, providers, and industry. Agencies of the US Department of Health and Human Services that participate in immunization safety and safety-related activities include the FDA, the Centers for Disease Control and Prevention (CDC), the National Institutes of Health, the Health Resources and Services Administration, the National Vaccine Program, and the Office of Disease Prevention and Health Promotion. In addition, the Department of Defense, the US Agency for International Development, the Agency for Healthcare Research and Quality, the Veterans Administration, and the Centers for Medicare & Medicaid Services collaborate on specific high-priority efforts or participate in policy discussions.
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LIFE-CYCLE APPROACH TO SAFETY |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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Nearly 2 million children were enrolled in the polio vaccine trials that were completed in 1955, which remain the largest randomized vaccine trials to date. However, until recently, the final step before licensure of a vaccine typically involved clinical trials including several thousand individuals, and these trials constituted the bulk of the clinical experience available for making decisions about both licensure and immunization recommendations for children.
In November 2000, several federal agencies sponsored a vaccine safety workshop in which there was substantial support for setting minimum sample sizes for prelicensure trials of vaccines likely to be recommended for universal use; however, there was no consensus on a "floor" value or criteria for determining the numbers required.5–9 Because of the pragmatic limits of the sample sizes of preliminary studies, there are inherent limitations in the extent to which such studies can detect very rare adverse events related to vaccination.
However, even when very large prelicensure clinical trials are conducted, safety and effectiveness questions that must be evaluated after licensure will remain or emerge. The FDA's guidelines for industry on pharmacovigilance planning,10 developed through the International Conference on Harmonization, recognized the need for an effective immunization safety system from prelicensure through ongoing postlicensure monitoring. In addition, these guidelines, along with the conference participants, noted the need for a systematic approach to safety that takes into account the current knowledge base and includes a comprehensive international assessment. Specific safety concerns and limitations of extant research should be outlined prior to licensure, with a plan for addressing these important questions and gaps via well-designed postmarketing studies.
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POSTLICENSURE SURVEILLANCE TOOLBOX |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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There was broad consensus among the conference participants on the need for postlicensure surveillance capabilities that are timely, efficient, sufficiently large, and in place for the life of the vaccine. Routine pharmacovigilance plans are needed for all vaccines. Specific vaccines require additional specialized studies depending on the limitations of prelicensing studies or concerns that emerge from those investigations. Postmarketing activities can be broadly classified into passive surveillance, active surveillance, and special studies.
Passive Surveillance
Monitoring of a vaccine continues as long as the manufacturer holds a license for the product. Postmarketing regulations require the manufacturer to collect, review, and report to the FDA all suspected adverse events associated with the vaccine. Passive surveillance, which involves voluntary reporting of vaccine-associated adverse events and the circumstances surrounding vaccine administration, has been the most frequent type of postlicensure surveillance conducted in regard to adverse events. The main goal of passive surveillance systems is to detect previously unreported reactions or any changes in the reporting of known reactions.
Because of their national scope, passive reporting systems are frequently the only means available to monitor extremely rare events. However, these systems are limited by underreporting, reporting of temporal associations and unconfirmed diagnoses, reporting bias (more severe adverse events are more likely to be reported than less severe events), and the difficulty in calculating incidence rates in the absence of population-based active surveillance in a well-defined population.
The National Childhood Vaccine Injury Act of 1986 (Pub L No. 99-660, 100 Stat 3756) mandated reporting of certain adverse events and led to the establishment of the Vaccine Adverse Events Reporting System, a unified national system jointly operated by the CDC and FDA since 1990. The main role of this system is to detect early warning signals about adverse events that follow vaccine administration. As mentioned earlier, the system was shown to function effectively when, in the year after the first rotavirus vaccine was licensed, 15 reports of intussusception among exposed infants led to further investigation, suspension of vaccination, and ultimately vaccine withdrawal. These cases were detected early in part because prelicensure safety testing data led to a specific search for such reports.
This reporting system is a necessary and important tool, but it is limited by the voluntary and selective nature of reported events. The system might be more useful if the reporting forms provided more comprehensive information and were standardized across countries, allowing similar data to be collected and assessed according to prespecified definitions. A similar Canadian system is testing new reporting forms that incorporate standard adverse event definitions from the Brighton Collaboration to ensure comparability of vaccine safety data.11
Active Surveillance
Active surveillance denotes a proactive search for adverse events. Large, active postmarketing surveillance systems are usually necessary to rigorously evaluate the possibility of rare vaccine-associated adverse events. Active surveillance can detect rare, serious events not detected in the limited prelicensure clinical trials conducted, and it can validate signals of potential adverse events detected through passive reporting. Active surveillance programs can, in theory, determine whether an adverse event is causally linked to vaccination and, if there is in fact a link, the approximate rate of the event. Active surveillance is carried out through a variety of activities, including postlicensure studies targeted toward specific safety issues and surveillance of and responses to adverse events reported after vaccination. Active systems involve more rigorous scientific designs than passive systems and, thus, allow more precise conclusions to be drawn from the data.
The CDC supports the Vaccine Safety Datalink (VSD),12,13 a consortium of managed care organizations that compiles comprehensive medical information and immunization records on more than 5.5 million people annually. These types of data are needed to conduct routine safety surveillance as well as investigate more pressing vaccine safety questions in a timely way. The functionality and success of the VSD are exemplified by its use in demonstrating the association of RotaShield with intussusceptions and the absence of such an association with Rotarix (GlaxoSmithKline, Morrisville, NC). Although VSD data cover a large number of people, the population is too small to allow testing of hypothesized associations between vaccines and adverse events in the case of certain rare but serious events (e.g., GBS), and the VSD includes only a small portion of the vaccinated population in the United States. Inclusion of a large portion of the vaccinated population would enhance the VSD's ability to monitor vaccine safety and, possibly, effectiveness.
Many countries have devoted resources to the development and maintenance of large linked databases. In Denmark, population-based data registries can be linked through a unique identifier for each citizen, allowing assembly of comprehensive health information on virtually the entire population for research on questions of public health importance.14–16 In Great Britain, efforts are under way to create an expanded, enhanced system similar to the General Practice Research Database17–19 that would include the majority of the population and could be used for both vaccine and drug safety studies.
Although establishing uniform data systems throughout a country or region may be desirable, it would be impossible for many countries in the short term. Fortunately, advances in computing and information technology make it possible to compile common elements from computerized population data with very different structures and create standardized analysis files with personal information removed. Linking information from multiple sources, such as birth and death certificates and disease and immunization registries, as well as electronically accessing medical record information, enhances the usefulness of these types of resources. Such data can aid in surveillance and be used in special studies focusing on drugs, devices, and vaccines, increasing their value. In the United States, calls have emerged for a large linked database in which at least 100 million individuals will participate in drug and device monitoring.20,21
However, accurate and complete vaccination information is not available in many electronic databases. Vaccine registries are one way to collect this information in a standardized manner. In the United States, there are many independent statewide registries, but most are neither comprehensive nor linked to postvaccination events. Registries that can capture accurate and complete immunization information will be crucial to vaccine safety systems. Immunization registries have the potential to strengthen these systems and raise and maintain immunization levels.
Not all states or all counties in all states have registries. Large portions of the private sector do not have registries or are not connected to registries where they do exist. The cost of a nationwide network of population-based immunization registries could be offset by the decreased expenses incurred by health care and school systems in, for example, retrieving records, assessing adequacy of information, and transcribing information to provide records for school entry or change of provider. No permanent mechanism has been identified to support registries nationwide. Federal immunization grants, Medicaid, state funds, managed care organizations, and private foundations have all contributed. Participants at CDC policy discussions have suggested that Vaccines for Children Program funds be used to provide support for registries.
Special Studies
Monitoring needs for new vaccines differ by product; for example, surveillance plans for a new combination vaccine that contains previously licensed products will be very different from plans for a new live attenuated virus vaccine. Nonetheless, in many cases studies will be more efficient if they include the use of a large linked database (as described earlier), if available, because of the need for access to defined populations with accurate exposure information and the need to capture outcomes and assess important covariates (possible confounders). An ideal system would also allow measurements of effectiveness. In addition to large observational studies designed to capture rare adverse events, other types of studies are needed to achieve the goals of maximizing vaccine effectiveness and minimizing adverse events.
Small clinical studies may help delineate predictors of both adverse events and effective immune responses, enhancing safety as well as efficacy and moving toward the goal of "personalized medicine," which would allow tailoring of vaccines to the characteristics of particular populations or individuals. The strides made in the study of the human genome, pharmacogenomics, and immunology may now make it possible to understand an adverse reaction.
The Clinical Immunization Safety Assessment (CISA) Network, a collaborative effort between the CDC and 7 clinical centers in the United States that are designing studies to help elucidate genetic and host factors associated with adverse vaccine reactions, brings together infectious disease epidemiologists, immunologists, dermatologists, and other subspecialists. CISA centers have undertaken assessments of hypotonic–hyporesponsive episodes,22 extensive limb swelling after diphtheria–tetanus–pertussis vaccinations, and GBS after conjugate meningococcal vaccinations. Genomic studies are in process, but their results have not been published as of yet.
Registries of individuals inadvertently exposed to vaccines can contribute to the knowledge base regarding prognosis in these populations, and registries of those with rare adverse events allow exploration of genetic or other predictors of such effects. Examples of potential candidates for registries include pregnant women given live viral vaccines and individuals who have developed myocarditis after smallpox vaccinations.
In some situations, vaccines may be "rolled out"—or introduced in phases—so that safety and effectiveness can be intensively monitored at the same time vaccination is gradually implemented in the target population. This was done in New Zealand with a newly licensed meningococcal vaccine developed specifically to address a sustained epidemic of group B meningococcal disease.23,24 The government of New Zealand used observational methods during the introduction of the experimental vaccine to evaluate its safety and effectiveness. The need to respond rapidly to the epidemic stimulated an innovative response in terms of not only the development of an epidemic-specific vaccine but also a safety and immunogenicity trial designed to gradually increase the population vaccinated and the geographic area covered.
During the vaccination campaign, a comprehensive safety monitoring program was established. The presence of a computerized national immunization registry enabled monitoring of disease incidence and adverse events. Experience was gained as the trial proceeded; for example, because of the rapid decline in serum antibodies, a fourth dose of vaccine (to be administered 4 months after the third dose at 10 months) was recommended for infants who received their first dose before 6 months of age. The iterative nature of the evaluation and the size of the population receiving the vaccine (1.5 million vaccinees) were important constraints.
Phased roll outs of influenza vaccines against anticipated pandemic strains are being proposed in some countries. In these situations, background rates (i.e., rates of occurrence of an event of interest in the absence of vaccination) of specific adverse events can be determined, and stopping points can be established if postvaccination rates of these events exceed prespecified thresholds. Independent safety monitoring committees can boost confidence in vaccines introduced and monitored in this manner. Large postlicensure clinical trials can also address remaining safety or effectiveness issues as a condition of licensure (e.g., the trials that the pharmaceutical company Merck agreed to undertake for its shingles vaccine).
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APPROACHES TO VACCINE SAFETY |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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Vaccines are generally very safe, and serious adverse events attributable to currently licensed vaccines are rare. However, there are limitations in our ability to rapidly detect rare events and monitor health care data and then to determine whether adverse events are actually caused by or are unrelated to vaccines. More than 130 studies have been or are being conducted in association with the VSD, including disease- or syndrome-specific investigations (e.g., autism, multiple sclerosis, thyroid disease, ataxia, alopecia, rheumatoid arthritis, asthma, diabetes, and immune thrombocytopenia purpura following vaccination). In addition, rapid cycle (i.e., near real time) and case series (i.e., relative risk measurements involving case patients but not controls) analyses are among the newer methods being applied to large linked data sets to address vaccine safety issues in a timely and rigorous way.
The VSD project is not large enough to examine the risk of extremely rare events such as GBS after each influenza season. Nor are the Health Maintenance Organization (HMO) populations currently involved in the project wholly representative of the United States in terms of geography or socioeconomic status. More problematic, because of the high coverage rates attained in these HMOs for most vaccines, is that few nonvaccinated controls are available. The VSD project must therefore rely primarily on risk-interval analyses (e.g., assessing whether outcome x is more common in time period y following vaccination in comparison with other time periods). This approach is limited with respect to the ability to assess associations between vaccination and adverse events in which onset is delayed or insidious (e.g., autism).
Because vaccines are not delivered in the context of randomized controlled trials, the VSD project may not be able to successfully control for confounding and bias in each analysis, and inferences in regard to causality may be limited. As a result of this limitation, it is very difficult to confirm or reject hypotheses about vaccine safety. Certainty about the small relative and attributable risks identified in epidemiological investigations (e.g., risk of GBS associated with influenza or Menactra vaccine and risk of intussusception associated with RotaTeq [Merck, Whitehorse Station, NJ] vaccine) is limited by the size of the currently available populations for study and the population-based observational cohort methods used in evaluating associations between vaccines and adverse events.
Conference participants recognized that large volumes of data would need to be effectively managed and methods would need to be in place to minimize generation of false safety signals. In addition, there was broad consensus with respect to the need for continual reassessments of the standards applied to vaccine quality and safety, the need for a system capable of providing surveillance of significantly larger portions of the vaccinated population, and the need to undertake additional vaccine safety research to address issues of causation, mechanisms, and genetics. Databases that include a substantial portion of the vaccinated population, with accurate individual-level data such as vaccination and outcome information, would be a highly desirable component of efforts to effectively monitor vaccine safety and effectiveness.
Discussions also addressed conflicts of interest and who should ultimately be responsible for vaccine safety, setting the safety agenda, and managing large safety-related databases. There was no attempt to reach consensus on these difficult issues. In any case, the conference attendees generally acknowledged the need for transparency, a process for weighing the risks and benefits of vaccination in a fair and balanced manner, and the need for effective communication of these issues.
In the past, as immunization programs successfully reduced the incidence of vaccine-preventable diseases, the uncommon and rare adverse events associated with vaccine administration became more visible and became a source of anxiety and uncertainty for vaccinees and the parents of vaccinated children. The success of immunization programs depends on the availability of safe and effective vaccines and accurate risk–benefit communication to the public and providers; it also requires widespread public acceptance of vaccines. Whether an adverse event is causally linked to vaccination or whether there is not shown to be such a link, effective communication of the benefits and risks of vaccination is an integral part of ensuring an informed public.
A safe vaccine is one that is acceptable in the presence of a level of uncertainty. Efforts need to be continually made to ensure that the public has ready access to current information in plain language and appropriate formats and that specific populations are targeted. It has become increasingly important for managers of immunization programs and providers administering vaccines to address vaccine safety concerns through effective risk communication. Although most parents support immunizations for their children, it has been shown that 20% to 25% of parents have misconceptions that could erode their confidence in vaccines.25
Finally, the conference attendees recognized the important role of the National Childhood Vaccine Injury Act in the US vaccine safety system. That is, given that vaccinations do involve some real risks, individuals can be compensated for related adverse events occurring after administration of vaccines routinely recommended for childhood immunization.
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SUMMARY AND CONCLUSIONS |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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Concerns about vaccine safety, along with the increased number of new vaccines being licensed and administered, support accelerated and enhanced efforts to ensure the safety of these products. The vision of an ideal vaccine safety system is one that continuously improves vaccines to maximize both safety and efficacy through systematic surveillance of vaccinated populations.
Both active and passive surveillance are important components of such a system. Effective surveillance will require investment in information resources that capture immunizations and health events in a substantial portion of the vaccinated population in a timely way. Ensuring continued confidence in the country's immunization program depends on effectively communicating accurate information about the risks and benefits of immunizations, demonstrating that efforts are being made to detect and investigate adverse events in a timely way, and investigating the underlying mechanisms of vaccine-associated adverse events to identify at-risk populations, which will aid in the development and production of safer vaccines.
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Human Participant Protection |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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No protocol approval was needed.
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Footnotes |
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Peer Reviewed
M. R. Griffin prepared the initial drafts of the article. M. M. Braun and K. J. Bart participated in the editing process.
Accepted for publication October 18, 2008.
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References |
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TOPABSTRACTINTRODUCTIONBACKGROUNDVACCINE AND DRUG SAFETYTHE VACCINE SAFETY SYSTEMLIFE-CYCLE APPROACH TO SAFETYPOSTLICENSURE SURVEILLANCE...APPROACHES TO VACCINE SAFETYSUMMARY AND CONCLUSIONSHuman Participant ProtectionReferences |
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