Public Health Implications and Tensions

The public health implications of childhood immunization and vaccine policy are considerable. They reach far beyond individual children and families into society as a whole and contribute to tensions between the public and the private sectors over the research, development, and manufacture of vaccines. These tensions are over and above those surrounding prescription drugs, because of the different role that vaccines play in public health. For example, unlike prescription drugs, vaccines are administered to healthy people, most often infants and children. Also unlike prescription drugs, they are (with some exceptions) compulsory—children cannot enter or attend school or day care in most states without documentation showing receipt of the minimum vaccine dose required by the state.

Despite vaccines’ wide acceptance and use after the initial controversy that surrounded them,⁵ over the last several years there has been evidence of a shift in public attitudes concerning their use in children. This rising concern has been fueled in part by fears about vaccine safety as well as by religious objections and resentment of government-mandated vaccine policy by “parents’ rights” advocates. Nevertheless, most recognize that, as the public health community often notes, dangerous infectious diseases that are largely under control in this country are “only a plane ride away” and that, consequently, immunization is important to everyone.

Immunizing a child not only protects him or her, but also helps to protect the community at large, particularly those with chronic diseases and suppressed immune systems. Immunization can also reduce disease outbreaks. Ironically, many health officials are concerned that the very success of vaccine programs actually may contribute to their downfall. For example, most parents have never seen an active case of measles, whooping cough, polio, or lockjaw (an effect of tetanus infection). Some who do not want their own children exposed to the potential risks associated with vaccines argue that, since the majority of other children have been inoculated, chances of a disease outbreak are slim.

Many health officials are concerned that the very success of vaccine programs actually may contribute to their downfall.

The dangers inherent in relying on community immunity—or “herd immunity,” as it is sometimes called—are numerous. Children run the risk of contracting a communicable disease while traveling outside the country. Even if they do not leave the United States, they may be exposed to an unimmunized person carrying disease: immunization levels among U.S. residents are not 100 percent, and the United States is visited by nearly 1 million people each day whose immunization status is not checked and who may therefore carry vaccine-preventable disease. Experience has shown that, when the childhood immunization rate, or “coverage level,” drops, epidemics ensue, and at that point it may be too late to protect the youngest and most vulnerable children. A recent paper put out by the PATH (Program for Appropriate Technology in Health) Children’s Vaccine Program underscored this point:

Many people in North America and Europe have become complacent about vaccines, assuming that since certain diseases rarely appear, they are no longer a threat. Others fear that the vaccine itself is more dangerous than the disease. These misperceptions have caused underimmunization rates that have led to a resurgence of highly contagious diseases such as measles, diphtheria, and pertussis. A measles outbreak in the United States in 1989 led to 123 deaths—ninety percent of those who died had not been vaccinated.⁶

In the United States, outstanding progress has been made in immunizing children by the time they are two years of age. According to Walter A. Orenstein, M.D., director of the National Immunization Program of the Centers for Disease Control and Prevention:

Coverage for most vaccines is 90 percent or higher.…[E]very day in the U.S., 11,000 babies are born who must be vaccinated. To be protected against 11 vaccine-preventable diseases, they require 16–20 doses or injections by 2 years of age, a challenge for any health care delivery system. Recent small, but significant, decreases in coverage for some vaccines indicate we cannot take for granted that past successes will automatically translate into future successes.⁷

Recent shortages have made it particularly difficult for physicians and other health providers to keep track of who has been vaccinated and who requires follow-up. They have also placed added burdens on parents to ensure that their children are adequately immunized.

The shortages have also exacerbated the tensions that exist between the public and the private sectors over vaccines. While the government plays an early role in vaccine research, through the National Institutes of Health (NIH) and other agencies, most of the research, development, and manufacturing takes place in the private sector. On the one hand, while vaccines represent an individual medical intervention, they are also considered by most to be a social good. Therefore, it has been argued, society has an obligation to make vaccines available at the lowest possible price to ensure widespread access. But the vaccine development system is grounded principally in the private sector, which must earn a profit in order to satisfy Wall Street and shareholders. Vaccine companies share society’s goals but also must balance them with the commercial viability, product liability, and market potential of the products they research, develop, and manufacture.

It is unlikely that these tensions can ever be completely resolved, but vaccine shortages undermine the nation’s ability to protect the health of its citizens in the face of threats such as bioterrorism, and both the public and the private sectors have critical roles to play in ensuring that vaccines are available when needed. In an Institute of Medicine (IOM) report entitled Setting the Course: A Strategic Vision for Immunization—Part 2, Bernard Guyer, M.D., highlighted the connection between childhood vaccine shortages and public health in times of crisis:

The quality of the immunization system can be seen as an indicator of the strength of the public health infrastructure. If the nation cannot ensure that the 11,000 children born each day receive the routine immunizations that they need, it may not be able to adequately protect the health of all 280 million Americans in times of crisis. Although crisis can stimulate action, sustained efforts are necessary to maintain the public health infrastructure and achieve immunization goals.⁸

Vaccine shortages undermine the nation’s ability to protect the health of its citizens in the face of threats such as bioterrorism.

Vaccines: What they are and How they Work

The last century has witnessed the spectacular reduction of horrific diseases. Many can remember (or recall seeing pictures of) children in iron lungs, the result of succumbing to paralytic polio. With the launch of the universal Salk vaccination effort in April 1955, millions of people were spared. While, only 50 years ago, polio was the leading cause of paralysis in the world, the polio vaccine has raised the expectation that the world will soon be free from the disease.⁹ Similarly, naturally occurring smallpox was eradicated in 1980 through global vaccination. Other success stories abound.¹⁰

Vaccines are administered via injection, oral administration, or through inhalation by aerosol and powder and can be either a “live” weakened (attenuated) or dead (inactivated) disease germ. Vaccines create immunity—protection against a disease. The primary purpose of the immune system is to identify foreign substances often referred to as antigens. In response to a vaccine, the body produces antibodies (protein molecules) or immune system cells (producing what is known as cell-mediated immunity). These responses assist with the elimination of the antigens and remain in the body, safeguarding the vaccinated person from future disease germs.

Getting Safe Vaccines to Children: Some Federal Roles

The federal government has an expansive commitment to vaccines. More than 20 different agencies have a role in vaccine research.¹¹ A number of agencies and programs within the Department of Health and Human Services (DHHS) play a role in national, state and local immunization efforts. The National Vaccine Program Office within the Office of the Assistant Secretary for Health, for example, has the responsibility to coordinate all federal, state, provider, industry, and other stakeholder efforts around vaccines. In addition to its involvement in research and coordination, the federal government plays an integral role in (a) licensing and regulating vaccines to ensure that they are safe and (b) financing and purchasing childhood vaccines. This section focuses on these last two areas of federal involvement.

Regulation and Licensure of Vaccine Products

Vaccines are biologic agents, that is, complex products derived from living sources. Unlike the structure of most drugs, which are chemically synthesized, that of biologics is not well characterized. Biologic products such as vaccines are subject to licensure (approval for marketing) under provisions of the Public Health Service Act. The Food and Drug Administration (FDA) has the responsibility to regulate vaccines in the United States.

Vaccine clinical development follows the same general pathway as that for drugs. Vaccine licensure is a lengthy process that may take ten years or more. Before a vaccine is licensed by the FDA, it is extensively tested in the laboratory, in animals, and in human beings to ensure its safety. Prelicensure clinical trials are done in three phases: Phase 1 (safety and immunogenicity studies), Phase 2 (dose-ranging studies), and Phase 3 (effectiveness and additional large-scale safety studies). If successful, the completion of all three phases of clinical development can be followed by the submission of a biologics license application, or BLA. During this stage the manufacturing facility undergoes a pre-approval inspection during which vaccine production is examined in detail. Vaccine licensing also requires the provision and FDA approval of adequate labeling information.

Once a vaccine is approved and licensed, the FDA continues to oversee its production to ensure continuing safety. This oversight involves periodic facility inspections. In addition, as part of the manufacturing process, both the manufacturer and the FDA are required to perform certain tests twice on each lot of the product before it is released for distribution.¹²

As part of the post-licensure monitoring, the federal government’s passive surveillance system, VAERS (the Vaccine Adverse Event Reporting System), is designed to capture information on rare side-effects and delayed reactions that may not be evident until the vaccine is administered to millions of people.¹³ Another post-marketing surveillance system established by the federal government is the Vaccine Safety Datalink Project (VSD), a collaborative project involving the Centers for Disease Control and Prevention (CDC) and several large managed-care organizations. A “large-linked” database, the VSD contains medical and immunization information on more than 7 million people. In addition to these systems, individual vaccine companies invest significant resources in developing their own surveillance systems. Merck, for example, has used its own funding to set up quality-control reporting systems, in addition to the government systems already in place. Other vaccine manufacturers have implemented similar programs.

Vaccine Safety Issues and Responses — Among the goals of the federal government in the regulation of vaccines, ensuring that they are safe is paramount. It is expected that the safety of a product administered to healthy children and adults will be continuously scrutinized and questioned. Both Congress and the FDA have responded vigorously to concerns about vaccine safety to maintain public confidence and thereby ensure the health of the public.

Both Congress and the FDA have responded vigorously to concerns about vaccine safety.

Although vaccines are among the safest of all medical interventions, in the mid-1980s, the number of lawsuits related to potential vaccine injuries began to rise. As litigation costs soared, prices escalated and several vaccine manufacturers halted production. The number of vaccine manufacturers plummeted and shortages occurred. Public health officials were concerned about the potential return of disease epidemics. In response to the situation, Congress passed the National Childhood Vaccine Injury Act (NCVIA) of 1986. Key among the many provisions of the NCVIA were the establishment within DHHS of the National Vaccine Program Office, the creation of the National Vaccine Injury Compensation Program within the Health Resources and Services Administration (to compensate those injured by vaccines on a “no fault” basis), and the requirement that all health care providers report certain adverse events following inoculation to the secretary of health and human services.

Since the mid-1990s, accusations about the safety of vaccines have proliferated in some circles, largely through the use of the Internet. Increased attention to vaccine safety issues, coupled with the widespread use of childhood vaccines, resulted in a request by the CDC and the NIH to have the Institute of Medicine “convene an independent committee that could provide timely and objective assistance to the Department of Health and Human Services in reviewing emerging immunization-safety hypotheses.”¹⁴ The first report specifically reviewed the alleged relationship between the measles, mumps, rubella vaccine and autistic spectrum disorders (ASDs). At the end of their analyses, the IOM committee members concluded:

although…the evidence favors rejection of the causal relationship at the population level between MMR vaccine and autistic spectrum disorders, the committee nevertheless recommends that this issue receive continued attention. It does so in the recognition that its conclusion does not exclude the possibility that MMR vaccine could contribute to ASD in a small number of children, as well as the following factors: the identified limitations of the evidence, the burden of ASD, the burden of the diseases prevented by the vaccine, the immense concern of parents, and the prominence of the issue in public debate.¹⁵

Another prominent issue regarding vaccine safety in recent years has been the use of preservatives, particularly thimerosal, a mercury-containing organic compound (an organomercurial). Since the 1930s, thimerosal has been used as a preservative in many biological and drug products, including vaccines, to prevent potentially life-threatening contamination from microbes such as staphylococci. Because of the “theoretical potential for neurotoxicity of even low levels of organomercurials and because of the increased number of thimerosal containing vaccines that have been added to the infant immunization schedule,”¹⁶ concerns about its use have been brought center stage. As a result, the FDA has worked with vaccine manufacturers to reduce or eliminate thimerosal from most vaccines.¹⁷

The FDA has worked with vaccine manufacturers to reduce or eliminate thimerosal from most vaccines.

In addition to regulating the manufacture of vaccines, the U.S. government has a strong interest in efforts being made by other governments and by vaccine companies to improve the safety of vaccine delivery systems. Among the technologies that hold the promise of increasing vaccine safety, both in developing countries and in the United States, are auto-disposable syringes and safety boxes, monodose prefilled injection devices, needle-free injections, and thermostable vaccines that eliminate the need for refrigerated equipment and its associated maintenance.¹⁸ Table 1 highlights the impact of such technology change on immunization services.

Table 1

Impact of Technology Change on Immunization Services.

Public- and Private-Sector Cooperation: Providers, Registries, and Education

Providers in both the public and private sectors are the key to a successful vaccine program. Until recently, immunization providers in the United States had not been well defined. A February 2002 article published in the American Journal of Public Health attempted to provide such a characterization, specifically seeking answers to the following questions: How many practices and clinics provide vaccinations to children? How many children are served in the public and the private sectors? What is the overall capacity of the system to deliver vaccinations to the birth cohort? How evenly is this capacity distributed? Relying upon 1997 data from the National Immunization Survey²³ and the VFC programs, the researchers concluded that “U.S. childhood vaccination provider capacity is adequate. Efforts to raise coverage rates should focus on increasing preventive care use among children, improving the vaccination performance of providers, and ensuring continuity of care.”²⁴

Traditionally, individual health care providers have been required to report vaccine-related adverse events as well as disease outbreaks. Some argue, however, that there is room for improvement and are calling for greater private-sector assistance in monitoring patterns of vaccine coverage and disease outbreaks within a community. Bruce Gellin, M.D., executive director of the National Network for Immunization Information, for example, has underscored the need for systematic tracking of vaccine delivery. “There is a practical issue here. If the vaccine is not available when you need it, someone needs to keep track and reschedule doctor visits. The confusion and chaos is substantial.”²⁵

Increasingly, states are relying upon registries to keep track of immunizations—identifying areas of need and monitoring adverse effects.²⁶ For a registry to be successful, however, it must have the support of parents and the providers administering the vaccines. These systems must be compatible with the operations of the private physician office and have the backing of health professionals. Similarly, health officials stress that parents need to recognize the value of having access to immunization registries and have confidence that their child’s privacy will be protected.

Increasingly, states are relying upon registries to keep track of immunizations.

Aware of the difficulties in reaching all children, some officials are calling for the creation of a national educational campaign, designed to explain the merits of childhood vaccine policy. Such a campaign, they stress, will need to address the broad constellation of concerns raised by parents and others. The direct support and involvement of the private sector are critical to its success.

Highlighting the success of one state’s efforts to improve immunization rates, via registries and education campaigns, the National Conference of State Legislature’s Kristine Goodwin gave the following example:

In Utah, which has one of the highest birth rates in the nation and a history of ranking at the bottom of states in immunization levels, officials have had impressive success in boosting vaccination rates, doubling the percentage of immunized two-year olds, from 37 percent in 1991 to 82 percent in 1999. Linda Abel, immunization program manager in the Department of Health, said the state turned a corner in 1994, when First Lady Jacalyn Leavitt championed an aggressive “Immunize by Two: It’s Up To You” campaign. Since then, she said, there’s been a “consistent message” and tenacity and coordination on the part of public- and private-sector partners, including the state’s largest HMO, the Utah PTA and corporations like McDonald’s, Wal-Mart and Krogers. Accomplishments include: a statewide registry, a media promotion, a home visiting program and a high profile “Care-A-Van” that brings the campaign to local stores and schools. While the van dispenses vaccines, Abel said its more important contribution is “getting the message out” about the value of immunizations.²⁷

Vaccine Manufacturer Concerns and Challenges

Beginning in the 1980s, with the rise in childhood vaccine safety lawsuits, a number of companies dropped out of the vaccine market. The passage of the NCVIA and the no-fault compensation it provided under the National Vaccine Injury Compensation Program created what many believed was a win-win situation for patients and companies, although parents and providers remain concerned about the cumbersome process and low payouts. Recently, a proliferation of class-action suits, the great majority of which are related to thimerosal, has companies concerned.

Beginning in the 1980s, a number of companies dropped out of the vaccine market.

Childhood Vaccine Shortages: Proposed Solutions and Policy Changes

In the short term, recent vaccine shortages have caused the federal government temporarily to scale back recommendations regarding the timing of immunizations and to advise directing the available supply of vaccines to those children at higher risk of contracting vaccine-preventable diseases. They have also led many states to suspend some immunization requirements related to day care and school attendance and ration the amount of vaccines distributed to providers.³⁰

For the long term, a number of possible solutions have been suggested as health officials, manufacturers, and the government have sought to resolve the complex issues that have contributed to the shortages and to prevent their recurrence. Experts readily acknowledge that these solutions have implications for the country’s emergency preparedness capabilities.

In addition to their day-to-day vaccine-related responsibilities, several federal committees and agencies function to address vaccine shortages, as summarized in Table 2.

Table 2

Federal Agency and Committee Functions Related to Averting or Mitigating Vaccine Shortages.

A number of steps have been taken in an effort to understand better the dynamics of childhood vaccine availability and to prevent future shortages. Most recently, Congress requested that the General Accounting Office (GAO) study the matter. The report, Childhood Vaccines: Ensuring an Adequate Supply Poses Continuing Challenges, released in September 2002, made several recommendations to the DHHS secretary to help promote the availability of vaccine products. These included “adding vaccines to the types of products that can be considered under FDA’s authority to expedite the approval of products in development trials and directing CDC to address several operational and strategic issues in expanding childhood vaccine stockpiles.”³¹

In February 2002, the DHHS National Vaccine Advisory Committee convened a group consisting of vaccine companies, physicians, insurers, and federal agency personnel to articulate the problems and develop solutions. Among the group’s recommendations were the following:

• Stabilize the supply by creating additional stockpiles of vaccines that could be used during shortages.
• Increase liability protection for manufacturers and physicians.
• Streamline the regulatory process.
• Require manufacturers to provide adequate notice before they voluntarily stop production.
• Create a national education outreach and advertising campaign on the importance and real value of vaccines.

Sen. Bill Frist (R-Tenn.), along with cosponsors Sens. Kay Bailey Hutchison (R-Tex.), Jim Bunning (R-Ky.), Zell Miller (D-Ga.), Jim Jeffords (I-Vt.) and Gordon Smith (R-Ore.) have introduced legislation, S. 2053, the “Improved Vaccine Affordability and Availability Act,” which would require the federal government to establish and maintain a six-month stockpile of prioritized (childhood and adult) vaccines. In addition, the legislation would expand the funding available for state and local efforts to raise immunization rates among adults and children who are underserved or at a high risk for vaccine-preventable diseases. Lastly, the bill would “restore balance” to the National Vaccine Injury Compensation Program.³² Other provisions of the bill would ensure that claimants, including third parties, file timely claims through the vaccine injury compensation process before suing in court and ensure predictability for manufacturers by clarifying that ingredients in the FDA-approved vaccine may not be considered to be adulterants or contaminants in that vaccine.

In addition to the recommended solutions listed above, other experts have suggested providing additional market incentives, including tax incentives for manufacturers. Pediatricians are calling for increased reimbursement, urging the Centers for Medicare and Medicaid Services to recognize the physician work associated with administering vaccines. “It would be unreasonable to expect that pediatricians can afford to continue to administer vaccines if the costs to the practice are more than the reimbursement.”³³ Increasing FDA funding in the area of vaccine testing research has also been suggested as a necessary step toward strengthening childhood vaccine supplies.

Others, including the Institute of Medicine, have called for a National Vaccine Authority to carry out a number of functions, such as defining the need and assessing the market for vaccines, helping establish and oversee a government-owned factory, spurring private vaccine development by guaranteeing prices for immunizations, financing vaccine research, and assisting companies in the production of pilot vaccine lots. There appears to be little agreement at this point, however, that a new federal entity is the answer. Critics of this approach point out, for example, that any government-owned or operated vaccine facility would experience the same good manufacturing practice challenges and liability challenges that private companies face.

Despite some differences of opinion over some of the recommendations, there is overwhelming agreement that forging stronger public-private partnerships is critical. It is generally recognized and acknowledged that the challenges are too broad for either the private or the public sector to tackle alone. The costs and risks associated with vaccine research, development, and manufacturing are, according to most experts, too high for the private sector to shoulder alone. Similarly, most agree that the patchwork system of federal and state vaccine programs creates confusion and obfuscates the roles and responsibilities of all parties.

The unpredictability of demand and the fluctuations in federal financing urgently point to the need for what the IOM’s Calling the Shots referred to as a “national strategic vision,” one that calls for a strengthening of the federal and state immunization partnership. The IOM identified six fundamental roles for such a system: “to assure the purchase of vaccines, to assure service delivery, to prevent and control infectious disease, to monitor and survey levels of immunization coverage and vaccine safety concern, especially within high-risk settings, to sustain and improve vaccine coverage rates for child and adult populations, and to use primary care and public health resources efficiently in achieving national immunization goals.”

According to the IOM and other experts, long-term vaccine supply and safety issues can be resolved only by a robust public-private partnership and an enhanced public health infrastructure. Ultimately, the answer to the question of what the government’s role in ensuring an adequate childhood vaccine supply should be must be answered in a way that addresses both today’s shortages and tomorrow’s as-yet-unknown shortages and risks.