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Statement on Risk vs Benefit of Vaccinations by David Satcher, M.D., PH.D.
Assistant Secretary for Health and Surgeon General
U.S. Public Health Service
U.S. Department of Health and Human Services

Good afternoon. I am Dr. David Satcher, Assistant Secretary for Health, Department of Health and Human Services (HHS), and Surgeon General of the United States . I thank you, Mr. Chairman and members of the Committee, for your invitation to testify at this important hearing on vaccines. With me today are technical experts from the HHS agencies involved in vaccine and immunization activities. They are: Mr. David Benor, Office of the General Counsel; Dr. Robert Breiman, National Vaccine Program Office (NVPO); Dr. Walter Orenstein, Centers for Disease Control and Prevention (CDC); Drs. Kathryn Zoon and William Egan, Food and Drug Administration (FDA); Mr. Thomas Balbier, Health Resources and Services Administration (HRSA); and Dr. Regina Rabinovich, National Institutes of Health (NIH).

Protecting our society from debilitating and deadly diseases that can be prevented through the administration of vaccines is a cornerstone for ensuring the health and well-being of our citizens. Vaccines are highly effective in preventing death and disability, and save billions of dollars in health costs annually. We are working diligently to ensure that vaccines licensed in the United States are as safe and effective as they can be. We have a stringent regulatory process for licensing vaccines that serves as a model for all countries.

To achieve optimal prevention of dangerous infectious diseases, we must have confidence in our immunization programs. Thus, the trust of this Committee as well as parents, providers, and the general public is critical. We must be united in recognizing and overcoming our common enemy, the microbes that cause infectious diseases and threaten the health and lives of our citizens, especially the Nation’s children and elderly.

This afternoon, I will briefly discuss issues related to the benefits of vaccines, the process for licensing them, what we are doing to ensure that vaccines are as safe as possible, and what we must do to continue to enhance vaccine safety.

Benefits of Vaccines

Vaccines are among the 20^th century’s most successful and cost-effective public health tools for preventing disease, disability, and death. Not only do they prevent a vaccinated individual from developing a potentially serious disease, vaccines routinely recommended for children also help protect the entire community by reducing the spread of infectious agents.

Childhood immunization has been one of the earliest priorities of this Administration. Under the Childhood Immunization Initiative, a wide range of efforts, such as outreach campaigns, disease monitoring and vaccine research, have been enhanced. Overall, immunization coverage among children in the United States is higher today than ever before. These high immunization coverage levels translate into record, or near record, low levels of vaccine-preventable diseases. For most of the vaccine-preventable diseases, there has been a 95 percent or more reduction in cases. This has occurred because States, Territories, and local governments have instituted effective immunization programs.

Today there are far fewer visible reminders of the suffering, injuries, and premature deaths caused by diseases that can now be prevented with vaccines. So that we do not forget the past, allow me to share some examples:

• Polio vaccine was licensed in the United States in 1955. During 1951 to 1954, an average of 16,316 paralytic polio cases and 1,879 deaths from polio were reported each year. As of 1991, polio caused by wild-type viruses had been eliminated from the Western Hemisphere. We have a goal that by the end of the year 2000, polio, like smallpox, will be a disease of the past.
• A physician entering practice today may never see a case of meningitis due to Haemophilus influenzae type b (Hib). Before the introduction of effective vaccines, in 1988, approximately one in 200 children, under the age of five, developed invasive Hib disease. Hib was the leading cause of bacterial meningitis in children under age five-- accounting for about 60 percent of all cases. From 15 to 30 percent of affected children became hearing impaired and about 420 children died every year despite antibiotic therapy. In addition, Hib vaccine has prevented the leading cause of acquired mental retardation in the U.S. By 1998, vaccination of pre-school children reduced the number of Hib cases by more than 99 percent.
• In the 1960s, many people witnessed first-hand, the terrible effects of rubella, commonly known as German measles. During an epidemic between 1964 and 1965, about 20,000 infants were born with deafness, blindness, heart disease, mental retardation, and other birth defects because the rubella virus infected their pregnant mothers. Today, thanks to nearly universal use of an effective vaccine, the rubella virus poses virtually no threat to the children of expectant mothers.

The costs of caring for a child with congenital rubella syndrome are staggering, which brings me to my next point. Vaccines not only save lives, reduce pain, suffering and disability, they save money. The individual and community protection provided by vaccines help make immunization one of our most cost-effective medical and public health interventions. Most vaccines recommended are cost-saving even if only direct medical costs--and not lost lives and suffering--are considered. Our country, for example, saves $8.50 in direct medical costs for every dollar invested in diphtheria-tetanus-acellular pertussis (DTaP) vaccine. When the savings associated with work loss, death, and disability are factored in, the total savings increase to about $27 per dollar invested in DTaP vaccination. Every dollar our Nation spends on measles-mumps-rubella (MMR) vaccination generates about $13 in total savings—adding up to about $4 billion each year.

The value of vaccines also extends beyond childhood. The greatest vaccine-preventable disease burden for the U.S. population today is among adults. We estimate an average of 23,000 persons, primarily 65 and older, die from complications of influenza illness during epidemics. Over 10,000 more die from pneumococcal infections such as pneumonia annually. Many of these deaths could have been prevented by vaccination. We have safe, effective, but highly under-utilized vaccines that can help us reduce the $10 billion a year in societal costs brought about by vaccine-preventable diseases in adults.

A decision to vaccinate is a decision to help protect not only individuals, but to also protect entire communities from diseases spread by person-to-person transmission. A decision to not vaccinate is to put the individual and community at risk. When immunization programs achieve high levels of "community" immunity—or what scientists sometimes refer to as "herd" immunity (the indirect protection of a community, including unvaccinated individuals), the likelihood that an infected person will transmit the disease to a susceptible individual is greatly reduced. Community immunity provides indirect protection to children who may be too young for certain vaccinations or have other health problems that prevent them from being immunized, yet are still susceptible to the disease. For example, children under one year old are too young to receive the measles vaccine but receive some protection from the vaccination of older individuals. Also protected are children who cannot be vaccinated with some vaccines for medical reasons—such as children with leukemia.

Vaccine Licensure

FDA’s Center for Biologics Evaluation and Research (CBER) is responsible for regulating vaccines in the U.S. Current authority for the regulation of vaccines resides primarily in Section 351 of the Public Health Service Act and specific sections of the Federal Food, Drug and Cosmetic Act.

Vaccine clinical development follows the same general pathway as drugs and other biologics. A sponsor who wishes to begin clinical trials with a vaccine must submit an Investigational New Drug application (IND) to FDA. The IND describes the vaccine, its method of manufacture and quality control tests for release. Also included are information about the vaccine’s safety and ability to elicit a protective immune response (immunogenicity) in animal testing as well as the proposed clinical protocol for studies in humans.

Pre-marketing (pre-licensure) vaccine clinical trials are typically done in three phases, as is the case for any drug or biologic. Initial human studies, referred to as Phase 1, are safety and immunogenicity studies performed in a small number of closely monitored subjects. Phase 2 studies are dose ranging studies and may enroll hundreds of subjects. Finally, Phase 3 trials typically enroll thousands of individuals and provide the critical documentation of effectiveness and important additional safety data required for licensing. At any stage of the clinical or animal studies, if data raise significant concerns about either safety or effectiveness, FDA may request additional information or studies or may halt ongoing studies.

If successful, the completion of all three phases of clinical development can be followed by the submission of a Biologics License Application (BLA). To be considered, the license application must provide the multidisciplinary FDA reviewer team (medical officers, microbiologists, chemists, biostatisticians, etc.) with the efficacy and safety information necessary to make a risk/benefit assessment and recommend or oppose the approval of a vaccine. Also, during this stage, the proposed manufacturing facility undergoes a pre-approval inspection during which production of the vaccine as it is in progress is examined in detail.

Following FDA’s review of a license application for a new indication, the sponsor and the FDA present their findings to FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC). This expert Committee (scientists, physicians, biostatisticians, and a consumer representative) provides advice to the Agency regarding the safety and efficacy of the vaccine for the proposed indication.

Vaccine approval also requires the provision of adequate product labeling to allow health care providers to understand the vaccine’s proper use, including its potential benefits and risks, in order to communicate with patients and parents and to safely deliver the vaccine to the public. Vaccines are also subject to lot release testing and protocol review to further ensure their quality.

Although extensive studies are required for licensure, post-marketing research and surveillance are necessary to identify safety issues which may only arise or be detected following vaccination of a much larger population. Rare events may not come to light before licensure, or, if noted, the evidence may not be adequate to prove that such events were due to a vaccine. The Vaccine Adverse Event Reporting System (VAERS) is a valuable post-marketing tool for just such safety surveillance. I will describe VAERS later in the testimony. In addition, post-marketing studies of a specific vaccine are required by FDA in order to obtain additional safety or other data. Also, after licensure, monitoring of the product and of production activities, including periodic facility inspections, must continue as long as the manufacturer holds a license for the product.

No system is perfect and no medicine or vaccine can ever be guaranteed to be 100 percent free of possible side effects or adverse events, particularly when administered to millions of people. For these reasons, the Department, its constituent agencies (FDA, CDC, NIH, HRSA), the scientific community, and industry strive for continuous improvements in vaccine safety. Speaking for the Department and its agencies, we welcome all constructive input and criticism in this regard. While we will always seek regulatory and scientific improvements in areas where safety and effectiveness are critical to protecting the public’s health, we are gratified that the extensive prelicensing and post-marketing efforts have resulted in the United States setting the standards worldwide for development and use of safe and effective vaccines.

Vaccine Recommendations

Vaccine recommendations are derived through a careful, deliberative process involving advice and guidance from the CDC’s Advisory Committee on Immunization Practices (ACIP). The ACIP is a Federally chartered, scientific advisory Committee of outside experts with the goals of providing to CDC’s Director and the Secretary of HHS, advice on decreasing disease through the use of vaccines and other biological products, and on improving the safety of their use.

The ACIP makes recommendations on vaccine use to CDC. If the CDC accepts the ACIP’s advice, the recommendations are published in the Morbidity and Mortality Weekly Report (MMWR) as ACIP recommendations. As new data become available on the effectiveness of disease prevention or on adverse events, these also may be discussed and may lead to published updates or revisions of previous recommendations.

Immunization Requirements for School Entry:

State laws requiring immunization date from the early 1800s, when Massachusetts enacted a smallpox vaccination requirement for its residents. The modern era for school and licensed day care immunization laws began with efforts to eliminate measles in the U.S. in the 1960's and 1970's.

All school and licensed day care immunization laws are State-based. There are no Federal laws mandating immunizations for school entry and day care attendance in this country. The U.S. Supreme Court, however, has affirmed the right of States to pass and enforce compulsory immunization statutes, and has upheld the constitutionality of State vaccination laws. Currently all 50 States have school immunization laws in effect although the specific vaccines, number of doses, and vaccine schedules vary by State. All States allow exemptions to immunization for medical reasons. In addition, 48 States allow religious exemptions and 15 States allow philosophical exemptions.

State-based, school-entry immunization laws establish a safety net to ensure a high level of protection from deadly diseases. Implementation and enforcement of school immunization laws have played a key role in reducing vaccine-preventable diseases in the U.S. For example, during the first 31 weeks of 1978, six States that enforced school laws reduced measles incidence by more than 90%, compared to the rest of the country.

Vaccine Safety

The public has a right to and should expect safe vaccines. While vaccines are among the safest pharmacologic interventions available, no drug or vaccine is 100 percent without risk. Even with a risk level as exceedingly low as it is for vaccines, we are working to find ways to reduce the risk even further. We are committed to vaccine safety through enhanced surveillance systems, vaccine safety research, adopting safe vaccine administration policies, and educating and providing information to parents, health care providers, and the general public.

Two recent examples reflect the emphasis we place on providing the safest vaccines possible. Beginning in 1996, to prevent pertussis in infants, we began use of a safer, newly-licensed vaccine. In recent years, we have switched our polio immunization strategy from primary reliance on oral polio vaccine, which very rarely causes polio (1 in 2.4 million doses), to inactivated polio vaccine which never causes polio. The additional cost of full implementation of these two changes to improve the safety of our immunization schedule will be approximately $110 million, which comprises 10 percent of CDC’s immunization budget.

Vaccine Adverse Event Reporting System:

The National Childhood Vaccine Injury Act of 1986 led to the creation of a unified national system to collect, manage, and evaluate the reports of possible adverse events. This system, initiated in 1990 and jointly managed by CDC and FDA is the Vaccine Adverse Event Reporting System mentioned earlier in my testimony. It is the only surveillance system that covers the entire U.S. population.

VAERS is a passive surveillance system that relies on physicians, health care providers, parents, and vaccine manufacturers to submit reports of adverse reactions that occur during a period following vaccination. To encourage reporting of any possible vaccine-induced adverse event, the criteria for reporting VAERS are non-restrictive. The system accepts and includes any report submitted, no matter how unlikely the possible connection with vaccination. For this reason, extreme care must be used in interpreting claims based on VAERS data. VAERS reports are helpful for suggesting adverse events—they do not however, allow us to say anything about whether a vaccine causes or caused the reported event.

VAERS receives 11,000 to 12,000 individual reports per year from vaccine manufacturers, private practitioners, State and local public health clinics, parents, and individuals who receive vaccines. Vaccine manufacturers and providers are required to report every potential adverse event of which they learn, regardless of the type of event. Approximately 15 percent of the reports describe events considered serious, defined as an event that is fatal, life-threatening, requires or prolongs hospitalization, results in permanent disability, or in the judgment of the physician could lead to such an outcome in the absence of medical intervention. Most of the remaining reports describe self-limited, transient events such as injection site reactions, irritability, prolonged crying, and fever. The serious events, unfortunately, are much more difficult to evaluate with regard to their causal association with vaccines. Most tend to be of a type known to occur in the absence of vaccines, so in an individual case it is almost never possible to definitively assess the role of the vaccine.

Case reports of serious adverse events obtained through VAERS may not always represent direct consequences of vaccination. The timing, for instance, between a vaccination and a reported adverse event may simply be coincidental. In other words, there is a time-based, or temporal association, but not a causal association. By chance alone, since children receive several vaccinations in their first year of life, some children who develop symptoms of illness will do so within several days of receiving a vaccine. Reports to VAERS can provide valuable information regarding serious adverse events that may be associated with a vaccine and are useful for generating warning signals. It takes other types of studies to determine whether or not they are indeed due to vaccines.

Spontaneous report-based surveillance programs, such as VAERS, perform a critical function by generating signals of potential problems that may warrant further, more detailed investigation. It is especially valuable in assessing the safety of newly marketed vaccines. Careful review of reports during the initial months following licensure can provide additional assurance about the safety of a new vaccine, and uncover previously unexpected events that occur when a vaccine is used more widely than was possible during clinical trials. FDA may take information obtained from VAERS to its advisory Committee (VRBPAC) for making recommendations on vaccine labeling and use.

A good example of how the vaccine safety monitoring system works is in alerting us to and helping address the recent concern about rotavirus vaccine and a type of bowel obstruction called intussusception.

Between September 1998 and June 1999, 15 cases of intussusception following rotavirus vaccine were reported to VAERS. The cases tended to be younger than most cases of intussusception normally occurring in the absence of vaccination. This signal led to special studies to evaluate whether there is a truly causal role of rotavirus vaccine in intussusception. Additional information has been collected on the cases reported to VAERS and a multi-state study has been initiated to evaluate whether or not rotavirus vaccine is associated with intussusception. On July 16, based on preliminary suggestive but not definitive data, CDC recommended that vaccination of children scheduled to receive the rotavirus vaccine before November 1999 be postponed until the studies are completed and the findings available.

Vaccine Safety Datalink:

Because of the limitations of VAERS, another system has been developed to evaluate whether vaccines are the cause of an adverse event. Determining the association between vaccination and a potential adverse event often requires documentation that the event is more likely to occur in someone who recently has received the vaccine than in someone who has not. Because serious potential adverse events are usually rare, documenting an association between an adverse event and vaccination requires a large population of vaccinated and unvaccinated persons. In 1990, CDC established the Vaccine Safety Datalink (VSD) that links computerized vaccination, hospitalization, and medical records for members of four large managed care organizations serving about 2 percent of the U.S. population. Vaccine Safety Datalink evaluations include identifying the health outcome of interest (i.e., the potential adverse event), linking these data with vaccination records, and comparing the frequency of the health event in persons who recently were vaccinated with those who are unvaccinated or had been vaccinated at a different time. All analyses must carefully be controlled for other factors that may be associated with disease occurrence or with the likelihood of being vaccinated.

The VSD project has proven to be a very powerful research tool. It has been used to study potential associations between various vaccines and adverse events reported to VAERS. The results of many of these studies have been published in scientific, peer reviewed publications. One study evaluated the question of persistence of joint complaints following rubella vaccination. The study found no evidence of increased risk of chronic joint problems. A second study looked at the risk of hospitalization because of aseptic meningitis after MMR vaccination in one-to-two year old children. Using data from VSD, the study found no increase in the risk of hospitalization for aseptic meningitis 8 to 14 days after MMR vaccination.

The VSD project is currently being used to examine a range of potential associations between vaccines and numerous alleged but unproven health associations including: 1) hepatitis B vaccination and risk of multiple sclerosis and other neurologic diseases; 2) timing of vaccination and risk of type-1 diabetes; and, 3) risk of seizures following vaccination.

Enhancing Vaccine Safety Efforts:

The Institute of Medicine (IOM) of the National Academy of Sciences has undertaken several broad reviews of vaccine safety. These reviews examined all available data specific to pediatric vaccines and drew independent conclusions on the safety of each vaccine. The IOM reviews also indicated many gaps and limitations in the current knowledge of vaccine safety. At the direction of Congress, the Secretary of HHS established a Task Force on Safer Childhood Vaccines. The Task Force examined vaccine safety issues and made recommendations to ensure development of safer childhood vaccines and improve licensing, manufacturing, processing, testing, labeling, warning, use instructions, distribution, storage, administration, field surveillance, adverse reaction reporting, recall of reactogenic lots or batches, and research on vaccines. A comprehensive report was approved by the Secretary in January 1997.

The Task Force’s recommendations are:

1. Assess and address national concerns about the risks and benefits of vaccines in order to enhance the education of the public, families, and health care professionals;
2. Strengthen the national capability to conduct research and development needed to promote the licensure of safer vaccines; and
3. Strengthen the national capability to conduct surveillance of vaccine-preventable diseases and to evaluate potential adverse events and vaccine efficacy.

The National Vaccine Program Office and its Inter-Agency Group are developing a comprehensive Vaccine Safety Action Plan based on the recommendations of the Task Force.

Progress in vaccine safety can be achieved by building upon what we are currently doing. For instance, improved surveillance and epidemiological capacity will allow improved communication and education and will help focus research and development efforts. Enhanced communication, in turn, will enhance the quality of surveillance by stimulating reporting of potential adverse events.

New research in vaccine development should soon provide us with new tools to prevent additional diseases that threaten our children and our elderly. These tools show great promise for an even healthier America and world by preventing serious diseases once thought not preventable. As the number of vaccines available for our use increases, however, an improved safety assessment program will be critical and effective risk communication will be essential for the Nation’s public health.

Vaccine Injury Compensation Program

Despite all our efforts to make vaccines as safe as possible, a small number of vaccine recipients will experience serious adverse reactions. The National Vaccine Injury Compensation Program (VICP) provides a unique service to families suffering through one of the most difficult experiences imaginable. It is a system through which families can receive financial help for children injured by vaccines in the most efficient and fair manner possible. The VICP, established under the National Childhood Vaccine Injury Act of 1986, minimizes the tension associated with the traditional litigation process for resolving claims arising from injuries thought to be related to childhood immunizations. To date, more than 1,400 families have received the benefit of the Program through awards totaling in excess of $1 billion.

The Department’s Advisory Commission on Childhood Vaccines (ACCV), has worked continuously to make a good program better. The members of the ACCV include parents of children thought to have been injured by vaccines, their attorneys, representatives of vaccine companies, and recognized medical experts in childhood diseases. Together this diverse body has developed and approved a series of recommendations that form the basis for legislation recently proposed by the Secretary. This legislation includes many enhancements aimed at making the VICP even more streamlined and less adversarial for its intended beneficiaries. The proposals would double the statutory time limit for filing a claim, expand compensation to families, and simplify the process for adjudicating claims. A draft bill titled, the "Vaccine Injury Compensation Program Amendments of 1999" was sent to the Congress on June 14, and will hopefully receive expeditious and favorable consideration.

Public Information and Education

We strongly believe that parents, providers, and the general public should be fully informed about the benefits and risks of vaccination.

Vaccine Information Statements:

In addition to any disclosure that may be required by State laws, all health care providers, public and private, are required to provide parents and patients with vaccine information materials before administering particular vaccines. As required by the National Childhood Vaccine Injury Act, the Secretary is responsible for ensuring the development of vaccine information materials for all vaccines covered by the National Vaccine Injury Compensation Program. Vaccine Information Statements (VIS) are developed by CDC after notice to the public and a 60 day comment period, and in consultation with the Department’s Advisory Commission on Childhood Vaccines, FDA, and health care provider and parent groups. Each VIS includes a concise description of the benefits and risks associated with a vaccine. Information is included on risks that have been scientifically established as published in ACIP statements, the Institute of Medicine report on vaccine adverse events, and expert evaluation of the peer-reviewed medical literature. Alleged adverse events that have not scientifically been associated with a vaccine are not included in the VISs.

Public Information and Education:

CDC also provides additional immunization information to the public. In FY 1998 over 2 million copies of 216 separate documents were distributed to both health professionals and the general public. This distribution included general pamphlets on immunization as well as documents that target certain populations such as senior citizens, adolescents, and persons at high risk of exposure to certain vaccine preventable diseases. CDC also has telephone hotlines in both English and Spanish which provide information on vaccines, the immunization schedule, vaccine-preventable diseases, and contact information on public and private providers by geographic areas. The hotlines receive approximately 9000 calls per month from parents and providers.

In addition, detailed immunization information is available from web sites maintained by CDC, FDA, HRSA, and the NIH. The web sites are updated on a regular basis to assure the provision of the most accurate and current information.

Provider Education:

Professional training and education programs, supplemented with printed information, help keep providers up to date about current policies and recommendations. CDC conducts training on immunization through satellite training courses which are offered to health care providers throughout the United States . The target audience for these courses includes physician Assistants, nurse practitioners, pharmacists, medical and nursing students, epidemiologists, State and local health officials, and others who provide immunizations to and counsel patients. In 1998, CDC trained over 50,000 health professionals through nationally available satellite courses.

What Would Happen If We Stopped or Reduced Vaccination

A study published in the January 1998 issue of Lancet provides empirical evidence of what happens when successful vaccination programs are halted. The research compared countries where immunization with pertussis vaccines was disrupted to countries that maintained high coverage, including the United States . The findings were clear and consistent. Pertussis incidence was 10 to 100 times lower in countries where high vaccination coverage was maintained relative to those countries where unsubstantiated vaccine safety claims temporarily halted use of the vaccines. Australia, Ireland, Japan, the United Kingdom, Italy, the Russian Federation, and the former West Germany Republic all experienced pertussis outbreaks following the suspension of successful pertussis vaccination programs. Each country also found it necessary to reinstate their pertussis immunization recommendations.

We know that vaccines have dramatically reduced the number of people who get infectious diseases. Without vaccines, epidemics of vaccine-preventable diseases would return, resulting in increased and unnecessary illness, disability, and death. History shows that in times of high vaccine coverage and very low incidence of vaccine-preventable diseases, it is common and very easy to shift attention away from the real benefits of vaccines to potential vaccine risks. We should use our past experience with the 1989-1991 measles resurgence which resulted in 55,000 cases of measles and 11,000 hospitalizations—along with experiences in other countries—to remind ourselves of the need to maintain our diligence and perspective when it comes to vaccines.

Conclusion

Vaccination is one of the greatest public health achievements in the United States during the 20^th century. Immunizations have eradicated smallpox; eliminated poliomyelitis in the Americas; and controlled measles, rubella, tetanus, diphtheria, Haemophilus influenzae type b, and other infectious diseases. There are tremendous accomplishments but more remains to be done.

As we enter the 21^st century, promoting optimal health of people through the administration of safe and effective vaccines will continue to be a priority for the Department. Mr. Chairman and Committee members, I assure you, in the interest of protecting and promoting public health, we will continue to make policy decisions and recommendations based on the best scientific evidence.