Geoffrey Evans

Risky Business: Challenges in Vaccine Risk Communication

* Abbreviations: AAP = : American Academy of Pediatrics • ACIP = : Advisory Committee on Immunization Practices • IPV = : inactivated polio vaccine • FDA = : Food and Drug Administration • DTwP = : diphtheria and tetanus toxoids and whole-cell pertussis vaccine • DTaP = : diphtheria and tetanus toxoids and acellular pertussis vaccine • DTP = : diphtheria, tetanus, and pertussis vaccine • CDC = : Centers for Disease Control and Prevention • NCVIA = : National Childhood Vaccine Injury Act • VICP = : Vaccine Injury Compensation Program • IOM = : Institute of Medicine • OPV = : oral polio vaccine • VIS = : Vaccine Information Statements Concern over vaccine safety has been a major determinant of immunization policy—from passage of the Biologics Control Act in 1902 to the recent American Academy of Pediatrics (AAP) and Advisory Committee on Immunization Practices (ACIP) recommendations for expanded use of inactivated polio (IPV) and acellular pertussis vaccines.1-4 With the availability of new vaccines and vaccination options comes the challenge of how best to communicate these options to patients and their parents. Lessons from the field of risk communication on predictors of risk acceptability and vaccination decision heuristics provide insight into why some parents resist vaccination. This article provides a historical perspective on vaccine adverse events and applies lessons from risk communication research to help physicians improve their ability to discuss vaccine risks. Immunizations have been described as the single most effective health intervention after clean water and sewage disposal,5 and have an extraordinary safety record. However, public policy has long reflected concern for the safety of vaccines and related biologics. In 1902, Congress passed the Biologics Control Act in response to the death of 13 children who had received injections of diphtheria antitoxin contaminated with tetanus toxin.6 This act required biologics to be manufactured in a manner that assured their safety, purity, and potency. Responsibility for these regulations was assigned originally to the Hygienic Laboratory of the Public Health Service, which evolved into the National Institutes of Health. The regulation of biologics including vaccines was transferred to the Food and Drug Administration (FDA) in 1972. The first published accounts of serious adverse events after whole cell pertussis vaccine occurred in 1933 with Madsens7 report of two deaths within 48 hours of immunization, and in 1948 with the report in Pediatrics by Byers and Moll8 of encephalopathy after diphtheria and tetanus toxoids combined with whole-cell pertussis …

Acute Encephalopathy Followed by Permanent Brain Injury or Death Associated With Further Attenuated Measles Vaccines: A Review of Claims Submitted to the National Vaccine Injury Compensation Program

Objective. To determine if there is evidence for a causal relationship between acute encephalopathy followed by permanent brain injury or death associated with the administration of further attenuated measles vaccines (Attenuvax or Lirugen, Hoechst Marion Roussel, Kansas City, MO), mumps vaccine (Mumpsvax, Merck and Co, Inc, West Point, PA), or rubella vaccines (Meruvax or Meruvax II, Merck and Co, Inc, West Point, PA), combined measles and rubella vaccine (M-R-Vax or M-R-Vax II, Merck and Co, Inc, West Point, PA), or combined measles, mumps, and rubella vaccine (M-M-R or M-M-R II, Merck and Co, Inc, West Point, PA), the lead author reviewed claims submitted to the National Vaccine Injury Compensation Program. Methods. The medical records of children who met the inclusion criteria of receiving the first dose of these vaccines between 1970 and 1993 and who developed such an encephalopathy with no determined cause within 15 days were identified and analyzed. Results. A total of 48 children, ages 10 to 49 months, met the inclusion criteria after receiving measles vaccine, alone or in combination. Eight children died, and the remainder had mental regression and retardation, chronic seizures, motor and sensory deficits, and movement disorders. The onset of neurologic signs or symptoms occurred with a nonrandom, statistically significant distribution of cases on days 8 and 9. No cases were identified after the administration of monovalent mumps or rubella vaccine. Conclusions. This clustering suggests that a causal relationship between measles vaccine and encephalopathy may exist as a rare complication of measles immunization.

Report of a US Public Health Service Workshop on Hypotonic-Hyporesponsive Episode (HHE) After Pertussis Immunization

Hypotonic–hyporesponsive episode (HHE) is a term used to describe a somewhat heterogenous group of clinical disorders that have been reported primarily in association with whole-cell pertussis vaccination. A 1991 review by the Institute of Medicine determined that the evidence available was indeed consistent with a causal relation between whole-cell pertussis-diphtheria-tetanus immunization and HHE, but that the evidence was insufficient to indicate a causal relationship between HHE and the subsequent development of permanent neurologic damage. More recent data from clinical trials conducted in Europe suggest that HHE also occurs after vaccination with acellular pertussis vaccines. The US Food and Drug Administration, in collaboration with the US Public Health Service, sponsored a workshop on HHE in Rockville, Maryland, on June 19, 1997. The primary goals of the workshop were to develop a case definition of HHE and to evaluate the general design and feasibility of possible studies of HHE using the federal Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system. The goals of such studies would be to understand better the acute HHE event and to evaluate the possibility of long-term sequelae. Case Definition. There has been no generally accepted definition of HHE, and a standard definition would be useful for vaccine safety work and would potentially facilitate interstudy comparisons of the growing number of licensed vaccines containing acellular pertussis components. The workshop defined HHE as an event of sudden onset occurring within 48 hours of immunization, with duration of the episode ranging from 1 minute to 48 hours, in children younger than 10 years of age. All of the following must be present: 1) limpness or hypotonia, 2) reduced responsiveness or hyporesponsiveness, and 3) pallor or cyanosis or failure to observe or to recall skin coloration. HHE is not considered to have occurred if there is a known cause for these signs (eg, postictal), if urticaria is present during the event, if normal skin coloration is observed throughout the episode, or if the child is simply sleeping. This inclusive (sensitive) case definition will allow investigators, through the technique of stratification according to certain characteristics (eg, time from vaccination to onset of HHE), to attempt to hone the definition and make it more specific. Refinement of the definition of HHE has been hindered by the lack of information on its pathophysiology and by the lack of pathognomonic signs, symptoms, and diagnostic tests. Another hindrance is that by the time the child presents for medical evaluation, the signs of HHE often have normalized. Moreover, different mechanisms may be involved in different individuals whose events meet this workshops HHE definition. Further Study of HHE. Probably the most important question about HHE is whether it has any permanent sequelae. The workshop assessed the possible contribution VAERS-based studies could make to answering this question and found substantial methodologic problems; however, ongoing studies in Sweden and The Netherlands have the potential to provide useful information on this question. The most useful contribution of VAERS data would be in a descriptive study of HHE, with a possible case–control study of factors that may affect the risk of HHE after vaccination, rather than a study of possible permanent sequelae. The workshop participants felt that a detailed descriptive study of ∼100 HHE events reported during a 1- to 2-year period could provide a more in-depth description of HHE cases in greater numbers than has been published previously, but the study would not address the issue of long-term sequelae of HHE. Better descriptive data may lead to new hypotheses concerning risk factors, etiology, and pathophysiology of HHE that might be evaluated further by studying subsequent cases and controls from VAERS or from other sources, depending on the hypotheses being tested. Workshop participants agreed that the question of possible long-term sequelae of HHE may currently be best answered in studies being conducted outside of the United States. A cohort of 82 892 infants was enrolled in the Stockholm II randomized, double-blind, controlled trial of one whole-cell and three acellular pertussis vaccines in Sweden in 1993–1994. In this trial, 101 infants developed HHE after vaccination. Of these children, 100 (1 had left Sweden) were evaluated subsequently at 18 months of age, using routine screening tests of motor and cognitive development intended to detect moderate to serious developmental problems. All 100 were found to be developing normally. At older ages, when more subtle developmental problems are detectable, comparison of the physical development and neurodevelopment of these children with a sample of trial participants without a history of HHE should be feasible. A protocol for a study to make such a comparison at ages 5½ and 8½ years is being prepared. In The Netherlands, a case–control study of infants who had HHE reported in 1995 is ongoing. The HHE events were detected through national surveillance linked to the health care delivery system. Growth, health, and neurodevelopment are being assessed. Data presented at the workshop concerning children with HHE reported in 1994 indicate that all 101 children followed during the second year of life (mean age, 1.5 years) were in good health and developing normally. An interesting finding of this follow-up study was the low rate of recurrent collapse (subsequent HHE occurrences) after repeat doses of pertussis vaccine. Summary. Despite increasingly widespread use of acellular pertussis vaccine in infants, HHE will continue to occur. The HHE definition proposed by this workshop should facilitate interstudy comparisons of HHE incidence among in the growing number of vaccines containing acellular pertussis components and perhaps of other vaccines as well. This definition also may aid study in VAERS and elsewhere of the etiology, pathophysiology, and descriptive epidemiology of HHE. Ongoing investigations in Sweden and The Netherlands have the potential to expand substantially knowledge of the possibility of long-term sequelae of HHE.

Vaccine Risk Perception Among Reporters of Autism After Vaccination: Vaccine Adverse Event Reporting System 1990–2001

OBJECTIVES We investigated vaccine risk perception among reporters of autism to the Vaccine Adverse Event Reporting System (VAERS). METHODS We conducted structured interviews with 124 parents who reported autism and related disorders to VAERS from 1990 to 2001 and compared results with those of a published survey of parents in the general population. RESULTS Respondents perceived vaccine-preventable diseases as less serious than did other parents. Only 15% of respondents deemed immunization extremely important for childrens health; two thirds had withheld vaccines from their children. CONCLUSIONS Views of parents who believe vaccines injured their children differ significantly from those of the general population regarding the benefits of immunization. Understanding the factors that shape this perspective can improve communication among vaccine providers, policymakers, and parents/patients.

Vaccine injury compensation programs worldwide

Approximately a dozen countries provide some form of compensation for injuries (or deaths) following vaccination. More than anything else, they were instituted in the belief governments have a special responsibility to those injured by properly manufactured and administered vaccines used in public health programs. Administratively, most are managed through the national government, including decisions on eligibility for and amount of compensation. Eligibility may depend on the recipients age, citizenship or residency status, category of vaccine (e.g., recommended, compulsory), the location it is administered (public vs private ambulatory setting), or satisfying certain time frames for filing a claim. Since few vaccine-related injuries have a clinical or laboratory marker, proving actual causation is difficult. Causation decisions are usually based on the balance of probabilities standard of more likely than not. All countries require that the effects be long lasting (e.g., greater than 6 months), and nearly all provide coverage for medical costs, disability pensions, and death benefits, while noneconomic damages (pain and suffering) are included much less frequently. Funding is generally from the national treasury, with some programs receiving support from lower governmental entities or vaccine manufacturers. After nearly 4 decades of operation, vaccine injury compensation program appears to be an increasingly accepted component of immunization programs today. While we have a much better understanding of their statutory purpose, frame work, process and outcome, there is much more to be learned. Future research should focus on vaccine compensation programs and (1) decision-making at the administrative level; (2) the utilization of outcome indicators in order to gauge effectiveness, including immunization acceptance; (3) the knowledge and attitudes of the public and medical community in host countries; and (4) the overall perspective of vaccine manufacturers. Insight into these and other areas will no doubt aid other countries as they consider implementing programs of their own.

Vaccine Risk Communication

Childhood vaccines are among the most effective preventive interventions that exist. In recent years, however, concerns about the risks of vaccination have arisen and, in some cases, have caused parents to consider not having their children immunized. In order to improve the process of communication and decision-making by parents and physicians, the Institute of Medicine’s Vaccine Safety Forum convened a workshop to discuss risk communication. This article summarizes the workshop’s discussions; a more complete report1 is available on the World Wide Web at www2.nas.edu/hpdp/. Health risk communication has traditionally consisted of messages designed to encourage behavior that reduces individual and societal risk (e.g., smoking cessation and seat-belt use).2 Increasingly, risk communication is seen as an interactive process of an exchange of information and opinion among individuals, groups, and institutions.3 To be effective, risk communications must address the experiences, beliefs, values, and attitudes of message recipients as well as providers. Understanding how risks are perceived and the inherent biases of both message providers and recipients is key to good risk communication.4 Although health risk communication has been an active research area for several decades, the science and practice of vaccine risk communication are not yet well developed. Many of the problems with risk communication in general, however, apply to vaccine risks.5 Recent studies illustrate specific factors influencing how vaccine risks and benefits are perceived by and acted on by consumers and vaccine providers. Individuals’ immunization decisions, for instance, are influenced by decisions that others make. People might prefer to do what a majority of others do or may take advantage of the protection afforded by high immunization rates and not be vaccinated; they may also be influenced to vaccinate by the fact that vaccination would protect others. Other factors include perceptions of disease risk and the ability to control those risks, and preferences for the risks of diseases per se over risks of the vaccine against them. In particular, the rarity of vaccinepreventable diseases in the vaccine era makes it more difficult to communicate the risks of these diseases. Information on vaccine benefits and risks is currently limited in availability and scope. Information available to consumers today includes the vaccine information statements (VIS) issued by the Centers for Disease Control and Prevention (CDC), material from other federal agencies such as the Food and Drug Administration (FDA) and National Institutes of Health (NIH), manufacturers’ package inserts that accompany vaccines, oral communications from health care providers, and information provided by a variety of nonprofit and consumer organizations. Three major themes emerged during the workshop. First, risk communication is a dynamic process in which many participate, and these individuals are influenced by a wide range of circumstances, interests, and information needs. Effective risk communication depends on the providers’ and recipients’ understanding more than simply the risks and benefits; background experiences and values also influence the process. Good risk communication recognizes a diversity of form and content needs in the general population. Both the method and content of risk communication should reflect the goals of the communication, which could include advocacy, education, and development of a decision-making partnership (in any combination). To be effective, it was suggested, risk communication about vaccines needs to take into account what people already know or believe about the risks and benefits associated with immunization. Vaccine risk communicators should consider the varied information needs of the audience. Some recipients of risk communication material prefer short, simple messages that explain the risks and benefits of vaccines in nontechnical language; others want as much scientific information as is available. Currently, the primary sources of consumer information on vaccines are criticized either as being too simplistic and incomplete (the VISs, for instance) or having too much technical information for some people to understand and process effectively (for example, From the Institute of Medicine, Washington, DC 20418 Address Correspondence to: Michael A. Stoto, Institute of Medicine, 2101 Constitution Avenue N.W., Washington, DC 20418

Update on Vaccine Liability in the United States: Presentation at the National Vaccine Program Office Workshop on Strengthening the Supply of Routinely Recommended Vaccines in the United States, 12 February 2002

Two decades ago, a liability crisis brought on by concerns about the safety of diphtheria and tetanus toxoids and pertussis vaccine led to supply shortages and calls for rationing of the vaccine. Vaccine prices skyrocketed, and research on new products was threatened. In response, Congress created the National Vaccine Injury Compensation Program, which is tort reform legislation designed to compensate individuals quickly, easily, and generously. Since 1988, the Vaccine Injury Compensation Program has stabilized the marketplace, as evidenced by high immunization rates, stable pricing, and an increasing number of vaccine candidates in development. Although current vaccine shortages do not appear to be related to issues of liability, a new wave of tort litigation alleging that some vaccines cause autism has led to speculation that history could repeat itself.

The National Vaccine Injury Compensation Program

The National Childhood Vaccine Injury Act of 1986 established the National Vaccine Injury Compensation Program to compensate people thought to be injured by certain vaccines. The acts goals are to ensure an adequate supply of vaccines, to stabilize vaccine costs, and to establish and maintain an accessible and efficient setting for providing compensation to people found to have been injured by certain childhood vaccines. In addition, the legislation called for the reporting of adverse events after vaccination, the creation of vaccine-information materials that detail vaccine benefits and risks, and Institute of Medicine studies of possible vaccine-related injuries and encouraged research and development of new and safer vaccines. Over its 22-year history, the National Vaccine Injury Compensation Program has been a key component in stabilizing the US vaccine market through liability protection to both vaccine companies and health care providers and by providing a forum for people, no matter what age, to seek compensation.

Neuropathology of vaccination in infants and children.

AIMS Documentation of clinical-pathological features of 37 infants/children whose parents alleged a relationship between vaccination and death or permanent central nervous system (CNS) damage, and sought compensation through the National Vaccine Injury Compensation Program. SCOPE Of the 5545 claims filed during the 10-year period (1990-1999), CNS tissue was available for evaluation by a pediatric neuropathologist in 37; 33 died and 4 had a biopsy or lobectomy. Most commonly implicated vaccines were DTP/DTaP, followed by MMR and IPV/OPV, but almost all of the vaccines currently given to infants/children were alleged to be responsible for the illness/death. No lesions were found in 5 of 37 (13.5%). The most frequent abnormality consisted of acute anoxic encephalopathy (14 of 37 - 37.8%), consequent to several different causes, such as positional asphyxia, cardio-respiratory arrest during status epilepticus, etc. The remaining children manifested other lesions, including inflammation (5 of 37 - 13.5%), vascular and developmental anomalies (4 each of 37 or 10.6%), cerebral edema and system degeneration (2 each of 37 or 5.4%), and one case of heavy metal exposure in a child living near an abandoned mine (2.2%). CONCLUSIONS There was no obvious relationship between type of vaccine (or vaccines simultaneously administered) to time of onset of symptoms, nature of symptoms or the lesions found.