Vaccine Policy Issues
Released: 2005-05-19T00:00:00

Background

What Is A Vaccine?

Vaccines are biologics -- their basic components begin as living material -- that introduce"weakened or killed disease-causing bacteria, viruses, their components" (1) (such as proteins, recombinantproteins, or polysaccharides) or toxoids into a person or animal to stimulate an immune reaction thatthe body will remember if exposed to the same pathogen in the future. Most vaccines are given byinjection.

Although many people use the words vaccination , immunization , and inoculation interchangeably, the terms are not technically synonymous. Vaccination is "the physical act ofadministering any vaccine ..." and immunization is a "more inclusive term denoting the process ofinducing or providing immunity artificially by administering an immunobiologic." (2) Inoculation also involvesintroducing a microorganism but not necessarily intentionally; the term vaccination was coined tomean intentional inoculation with the vaccinia virus that causes cowpox to provoke an immuneresponse to protect against the smallpox virus.

The U.S. Food and Drug Administration (FDA) licenses 46 vaccines, covering 20 diseases,now available for public use in the United States. (3) Dozens more are in active development; research teams worldwideare working to develop vaccines against tuberculosis, malaria, HIV/AIDS, Alzheimer's disease, somecancers, and other diseases of which most Americans have never heard. The National ImmunizationProgram, part of the U.S. Centers for Disease Control and Prevention (CDC) and its AdvisoryCommittee on Immunization Practices (ACIP), issues recommended immunization schedules forchildren, adolescents, and adults in the United States. (4)

Procedures for the Approval and Regulation of Biologics

FDA procedures to approve a biologic for marketing in the United States follow the samebasic format as the procedures for new drug approvals. (5) Animal testing is extensive, including the safety assessment of theviruses grown in animal or human cells. After satisfactory animal safety testing, clinical trials inhumans begin.

Phase I clinical trials, which include a small number of human volunteers, test for safety. The sponsor continues with Phase II and Phase III trials to gather evidence of the biologic'seffectiveness in larger groups of individuals, while continuing to monitor safety data. If the productremains feasible, the sponsor, based on data collected in the clinical trials, submits two licenseapplications to FDA: a product license for the vaccine and an establishment license for themanufacturing plant.

FDA scientists review the clinical data, along with the proposed labeling and manufacturingprotocols; inspect the manufacturing facility to assess whether it can produce a consistent product;and performs test on the vaccine and its components. Advisory committees, made up of expertsfrom outside of FDA, also review the data, are available for consultation, and makerecommendations to FDA regarding approval.

Because contamination is a greater threat with vaccines than with drugs because they aremade from living organizations, FDA maintains an active presence even after a vaccine is approved. It requires extensive testing of vaccines and all ingredients (e.g., diluents, preservatives, oradjuvants) for characteristics including identity, purity, and potency. FDA continues to assess theproduction process, too, including samples of each lot and data regarding purity and potency.

Finally, because even large clinical trials can identify only common potential adverse effects,FDA maintains postmarketing surveillance programs and sometimes works with a manufacturer inPhase IV studies of long term safety and effectiveness.

Stakeholders

Many groups have a stake in vaccine-related issues, including the government entitiesresponsible for research and development, licensing, post-licensing surveillance of adverse reactions,provision of health care, protection of the population, interstate and international trade, intellectualproperty protections, and homeland security.

There is no central authority for vaccine policy within the federal government. In theDepartment of Health and Human Services (HHS), the National Vaccine Program Office (NVPO)coordinates vaccine-related activities and the FDA is responsible for the regulation of humanvaccines and other biologics. (6) The National Institutes of Health (NIH) conducts intramuralvaccine research and development and funds research in universities, for example. CDC, chargedwith protecting the health and safety of the population, houses the National Immunization Program(NIP) and its ACIP, which work to coordinate nationwide activities, including the Vaccines forChildren (VFC) program and the state immunization grants program. (7) CDC also maintains theStrategic National Stockpile (SNS), which includes some vaccines against bioterror agents. TheNational Vaccine Injury Compensation Program (VICP), which is jointly administered by the HealthResources and Services Administration (HRSA), where it is located, and the U.S. Court of FederalClaims and the U.S. Department of Justice, "provides compensation for injuries judged to have beencaused by certain vaccines." (8) Also administered from HRSA is the Smallpox Vaccine InjuryCompensation Program, set up in 2003. (9)

Vaccine responsibilities lie outside of HHS as well. The Department of Defense (DOD)maintains research and development programs for vaccines against both naturally occurringinfectious diseases and bioweapons. DOD administers routine and deployment-related vaccines tomilitary personnel and some civilian employees and contractors. As a primary health care provider,DOD also administers vaccines as necessary to its retirees and current personnel and their families. The Department of Veterans Affairs administers vaccines to U.S. veterans who seek care in itsfacilities. The U.S. Agency for International Development (USAID) supports routine immunizationprograms in developing countries and works to reduce the impact of vaccine-preventable diseaseworldwide. State and local governments conduct vaccine activities within their public health role,such as conducting vaccine clinics, maintaining immunization registries, and establishingimmunization requirements for school attendance. Veterinary biologics are regulated by the U.S.Department of Agriculture, Animal and Plant Health Inspection Service, under authority of theVirus, Serum and Toxin Act. These products must meet similar standards of safety, efficacy, purityand potency as do human products.

Interested parties outside government include individuals and private entities, both for-profitand not-for-profit, such as current and potential vaccine recipients and their families, employersoffering health care benefits, insurers, traditional vaccine manufacturers, biotechnology firms, tradeassociations such as the Pharmaceutical Research and Manufacturers of America, academicbiomedical researchers, economists, trial lawyers, health care professionals and institutions, andpatient and disease-specific advocacy groups.

Laws Approved by the 107th Congress

Concerned about bioterrorist attacks in the United States, the 107th Congress approvedseveral bills that included vaccine-related issues:

The USA PATRIOT Act ( P.L. 107-56 ) includes a sense-of-Congress statement expressingthe need to provide funding for bioterrorism preparedness and response (Section 1013); the NationalDefense Authorization Act for Fiscal Year 2002 ( P.L. 107-107 ) directs the Secretary of Defense toaccelerate research, development, and production of items such as vaccines for defense againstbiological agents used as weapons, and includes authorization to build a government-ownedcontractor-operated vaccine production facility (Section 1044). The Public Health Security andBioterrorism Preparedness and Response Act of 2002 ( P.L. 107-188 ) directs the HHS Secretary toundertake specific activities with regard to national stockpiles of drugs and vaccines and theaccelerated approval of high-priority countermeasures (Sections 121-126).

The Homeland Security Act (HSA) of 2002 ( P.L. 107-296 ) protects manufacturers and healthcare workers who administer the smallpox vaccine from tort liability and restricts that liabilityassumed by the United States to negligence of those parties (Section 304). Other sections of theHSA of 2002 that related to vaccines have since been repealed. (10) , (11)

Legislative Activity in the 108th Congress

The 108th Congress passed some vaccine-related legislation. The Smallpox EmergencyPersonnel Protection Act of 2003 ( P.L. 108-20 ) created a mechanism to compensate individuals who,in response to a Secretarial request for smallpox vaccine preparedness, are injured by the vacciniavirus used in smallpox vaccines. Vaccinees and their contacts are eligible for medical care expensereimbursement, lost income benefit, and death benefits, administered through the HHS HealthResources and Services Administration. (12) Other enacted laws that include references to vaccine coverageor funding are the Consolidated Appropriations Resolution, 2003 (108-7); the United StatesLeadership Against HIV/AIDS, Tuberculosis, and Malaria Act of 2003 ( P.L. 108-25 ); the NationalDefense Authorization Act for Fiscal Year 2004 ( P.L. 108-136 ); the Medicare Prescription Drug,Improvement, and Modernization Act ( P.L. 108-173 ); and the Consolidated AppropriationsResolution, 2004 ( P.L. 108-199 ).

Dozens of bills relating to vaccine research, purchase, and coverage were introduced in the108th Congress. The Improved Vaccine Affordability and Availability Act ( S. 754 ),introduced by Senate Majority Leader Frist, received the most attention, but scheduled markups ofthe bill were postponed several times in spring 2003. The bill would "amend the Public HealthService Act to improve immunization rates by increasing the distribution of vaccines and improvingand clarifying the vaccine injury compensation program...." In fall 2004, in response to the suddenshortage of influenza vaccine, additional bills were introduced and several hearings were held. (13)

Continuing Legislative Issues

In its final three sections, this report organizes the range of legislative issues pertaining tovaccines that Members of Congress may consider into three groups:

availability,

safety and effectiveness, and

access.

Cost -- of research, development, production, regulation and oversight, for example -- underlies eachof these concerns.

Availability

Thirty-seven American companies made vaccines in 1967; in October 2004, there werenine. (14) Why? Reasonsgiven are mostly economic. The road to a shot in the arm can take decades of research anddevelopment and, according to industry estimates, about $800 million per licensed vaccine, (15) requiring great financialreserves to sustain a company through the research and development and clinical trial process. Oncea vaccine is licensed, its continued production remains complex, as the 2004-2005 flu vaccineshortage in the United States illustrates.

Problems

Production Costs. Because vaccines arebiologics, even routine manufacture involves care, expertise, and expense much beyond that requiredfor pharmaceuticals. To produce a drug, the manufacturer essentially repeats a chemical formula. Vaccines require dedicated production facilities that include physical and chemical barriers to protectworkers from pathogen exposure and finely regulated temperature and ventilation to keep thebiologics viable while stored. Also, because the product is injected, the purity standard has to bemuch higher than for a pill. Although FDA inspects both drug- and vaccine-production facilities,it inspects every lot of vaccine produced and only a sample of drug production lots. (16)

For example, manufacturers ceased production of licensed vaccines against plague becauseof manufacturing difficulties, and against adenovirus infection because of contract cost issues. Torestart production, these or other manufacturers must submit new license applications to FDA,conform to current good manufacturing practice standards, and demonstrate the safety andeffectiveness of the new vaccines -- all before they can make the vaccine available to the public.

Production Failures. In October 2004, when theU.S. manufacturer Chiron announced that the British drug regulatory authorities had shut itsLiverpool plant, the United States was instantly plunged into a flu vaccine shortage. Chiron wasslated to supply approximately half of the vaccine for U.S. use in the 2004-2005 flu season. TheBritish agency -- and then with FDA concurrence -- found some bacterial contamination andmanufacturing practices that could not assure the safety of the rest of the vaccine production. (17)

Liability. Why go to the trouble for a product thatdoes not promise the sales volume common to pharmaceuticals -- particularly when manufacturersmay be liable if vaccines cause injury? The huge claims for compensation that followed the swineflu immunization program in the mid-1970s have made the vaccine industry wary. Manufacturerexecutives recall, for example, discussions of unindemnified liability in their decisions to declineplans to produce anthrax or Lyme disease vaccines.

Market. For some diseases, scientists know howto produce protective vaccines but manufacturers have chosen not to pursue the time-consuming andexpensive steps necessary to obtain FDA approval. For some, there is insufficient market size in theUnited States to warrant the effort. An example is the tick-borne encephalitis vaccine that DODadministered to troops in Bosnia during the 1990s. Although licensed in Europe where thedisease-carrying ticks are more widespread, the vaccine is not FDA-licensed. To get FDA approvalrequires U.S. clinical trials for safety. Neither the interested manufacturer nor DOD has been willingto bear the expense of those trials. (18)

Malaria, tuberculosis, and HIV/AIDS kill 7 million and sicken 400 million worldwide eachyear. (19) Yet, aside fromHIV, manufacturers have little incentive to develop vaccines because U.S. incidence is low,involving mostly travelers or immigrants and their contacts, and preventive and treatmentmedications are readily available. In countries where vaccines could make a big difference, fewresources are available to support development or purchase. Interestingly, private benefactors havebeen stepping in to support public-good-focused research. The Bill and Melinda Gates Foundation,for example, gave $150 million to the Malaria Vaccine Initiative, which announced in October 2004initial findings that a malaria vaccine it is developing with industry was somewhat effective in youngchildren. (20)

Planning. Finally, difficulties with planning canrender even licensed vaccines temporarily unavailable. In 2002, such problems created shortagesof licensed vaccines for eight of the 11 vaccine-preventable childhood diseases. (21) , (22) , (23)

Aside from production set-backs, influenza vaccine poses a perennial challenge involvingchoice of vaccine components and amount to manufacture. Each year, public health authorities andmanufacturers analyze worldwide surveillance information to determine which flu virus strains arelikely to put humans at risk in the coming year. Sometimes, the viral strain that most threatens theU.S. public is not among those chosen for that year's vaccine, the situation in 2003 when vaccinedevelopers could not formulate a Fujian component in time for the season's distribution. (24)

Because influenza changes slightly each year, healthy adults have partial immunity to newstrains; each year, the virus typically makes healthy people sick, but not too sick. Several times acentury, however, the virus changes enough that there is no partial immunity. This situation can leadto rapid worldwide spread of the virus, called an influenza pandemic, with severe illness and death,even in healthy people, and possible serious disruptions in services and social order. Some haveexpressed concern that the problems evident in the national response to the 2004-2005 flu vaccineshortage serve as a relevant drill -- and warning -- for pandemic preparedness. (25)

Also a topic of international surveillance and planning is avian influenza ("bird flu") -- aninfluenza strain affecting poultry in Asia -- in anticipation of its possible joining with a viral strainthat infects humans. Rather than a unique circumstance, this international investigation is part ofthe intensive, ongoing process of animal and human (clinical and laboratory) surveillance, testing,and action that is public health practice. For example, CDC laboratories collaborate with the WorldHealth Organization in testing and describing avian viruses to help in developing a potentialvaccine. (26)

Possible Legislative Solutions

Congress may consider at least four kinds of measures to enhance vaccine availability: financial incentives, public-private partnerships, improved coordination, and alternatives to safetyand effectiveness documentation.

Financial Incentives. Most people in the UnitedStates now view protections against bioterrorism or biowarfare agents, such as vaccines, as in thepublic interest. Many also so categorize all vaccines, whether intended against naturally occurringor bioterror-related infectious diseases. The bottom line in persuading companies to producevaccines is largely one of opportunity cost: whether they can afford to put aside other potentiallylucrative projects to do so.

Over the years, Members of Congress have proposed changes to the Internal Revenue Codeinvolving tax credits for certain vaccine research and distribution activities to effectively lower thecost to manufacturers. Another way to provide a financial incentive is to assure that a primarypurchaser is available to generate demand for the vaccine. When the government is the primarypurchaser, such as for anthrax or smallpox vaccines, it can develop contracts with manufacturers thataddress volume, liability protection, and long-term plans, for example, that make productionpractical.

In his 2003 State of the Union speech, President George W. Bush proposed a federalinitiative, Project BioShield, to encourage private industry to develop medical countermeasures tobioterrorism threats. The Project BioShield Act of 2004 was signed into law in July 2004 ( P.L.108-276 ). (27)

Liability. Because some manufacturers havenamed liability concerns among reasons to forgo vaccine production, legislative proposals haveaddressed indemnification, liability insurance, and injury compensation plans. Protection ofpotential manufacturers, seen as a necessary incentive to participation, was included in the HomelandSecurity Act of 2002 and the Smallpox Emergency Personnel Protection Act of 2003. The AmericanJobs Creation Act of 2004 (28) added the influenza vaccine to those that the National VaccineInjury Compensation Program covers.

Partnerships. Some Members of Congress haveexpressed interest in industry consortia or public-private partnerships to accelerate vaccine researchand development and manufacture. This may involve considering issues of intellectual propertyprotection among collaborators and anti-trust law accommodations to allow private manufacturersto make joint decisions. Such partnerships have been recommended as ways to spread financial risk,thus making vaccines available for diseases that are prevalent among small or impoverished groups.

Improved Coordination. Better coordinationamong federal regulators, private manufacturers, government scientists, and purchasers could avoidmany supply shortages, such as occurred with childhood vaccines in 2002. Coordination could alsoshorten the time between initial research and product licensure. Policy analysts look for mechanismsto streamline FDA administrative -- but not human safety and effectiveness assurance -- procedures. Some, including the Institute of Medicine (IOM), have suggested establishing a National VaccineAuthority. (29) Two otherIOM committees, in DOD-sponsored reports addressing naturally occurring infectious diseases (30) and biowarfareagents, (31) recommendedbetter coordination within the DOD vaccine acquisition programs and between DOD and otherentities, particularly HHS. These groups anticipate that a coordinated decision and budget authoritycould present a coherent front to private manufacturers and within government. After the 2002reports, DOD assigned vaccine acquisition responsibilities to a higher administrative level (32) and interagency agreementsand working groups have been formed. Cutting down on frustrations arising from getting differentanswers or timetables from different offices could make vaccine work more appealing to those inresearch and development and manufacture.

While almost any change in research and development, production, monitoring, and saleswould involve FDA, some questions focus on FDA itself. These include the extent to which itsbudget limits the scope and timeliness of its activities. Some analysts suggest that FDA standardsare too high to be reasonably feasible.

Sometimes all the necessary pieces of potential solutions exist, but without an organizingforce. For years, various representatives of HHS, DOD, and private manufacturers had met overcontracts to develop and produce vaccines to protect, for example, against smallpox and anthrax. The September and October 2001 attacks on the U.S. population quickly dissolved the stickingpoints. Political will -- and its ability to get all the right people and their checkbooks in the roomat the same time -- fueled action to acquire smallpox vaccine, both doses of previously made andlicensed product and contracts to develop new products. In the years since then, HHS has announcedcontracts to develop new vaccines against smallpox, plague, and tularemia; (33) and, with Project BioShieldfunding, a second-generation anthrax vaccine will be stored in the Strategic National Stockpile. (34)

Ensuring Safety and Effectiveness May DelayAvailability. It takes a long time from the start of clinical trials to FDAlicensure. (35) Manyobservers consider much of that time as necessary to ensure that vaccines produced and sold are safeand effective. FDA has formal mechanisms to expedite the review process: fast-track drugdevelopment, priority review, and accelerated approval. Its "Animal Rule" and provisions under theProject BioShield Act of 2004 also support shorter time from idea to approved public use. (36) The Congress could assessthe extent to which the laws that direct HHS and DOD to facilitate or accelerate research anddevelopment and approval of bioterrorism countermeasures as well as needed vaccines for seriousconditions (37) aresucceeding and consider legislative ways to help those processes along.

Fast-Track Mechanism. The Food and Drug Administration ModernizationAct of 1997 (FDAMA, P.L. 105-115 ) described a "Fast Track" mechanism whereby themanufacturer and FDA discuss development plans and strategies before the formal submission ofa Biologics License Application (BLA, for a vaccine application, for example) or a New DrugApplication (NDA, for a drug). The early interaction can help clarify goals and work throughobstacles that would delay approval decisions if they became evident only at BLA submission. (38)

Accelerated Approval. For the treatment of a serious or life-threateningillness, FDA regulations allow "accelerated approval" of a biologic product that provides a"meaningful therapeutic benefit ... over existing treatments." The approval is based on clinical trialsthat, rather than using standard outcome measures such as survival or illness, use "a surrogateendpoint that is reasonably likely ... to predict clinical benefit." FDA usually requires postmarketingstudies of biologics approved this way. (39)

Animal Rule. Scientists use clinical trials and field trials to test a vaccine'seffectiveness. Clinical trials designed to test vaccines for most infectious diseases usually involverandom assignment of individuals to groups -- members of one group are given the new vaccine andmembers of the other (the control group) are given a placebo or an existing licensed vaccine -- toassess whether the investigational vaccine would effectively prevent disease. When the diseaseunder study has no known treatment and has severe outcomes (including death), it is unethical tochallenge human research subjects, because if the vaccine is not effective, the subjects are irreparablyharmed. Field trials, in which scientists observe naturally occurring disease among vaccinated andunvaccinated groups, are not feasible for diseases that occur sporadically or would occur only in thecontext of bioterror or biowarfare action. For these reasons, researchers and regulators maysometimes need alternative models for demonstrating vaccine effectiveness.

In 2002, FDA published its long-debated final Animal Efficacy Rule. The regulations applyonly "when adequate and well-controlled clinical studies in humans cannot be ethically conductedand field efficacy studies are not feasible." They allow submission of data from animal studies ofeffectiveness as evidence to support licensure applications of new drug and biological products thattarget "serious or life-threatening conditions" in humans. (40) It could apply, for example, to inhalational anthrax, for whichthere is no surrogate of immunity and no natural endemic disease. Although no vaccine has yet beenapproved under this rule, FDA used the rule for the first time in February 2003 to approve adrug. (41) Congress mayfollow the implementation of this rule and discuss alternative actions in its oversight of safety,effectiveness, and availability goals.

Priority Review. Unlike Fast Track, Accelerated Approval, or Animal Ruleactivities, the Priority Review process begins only when a manufacturer officially submits a BLA(or an NDA). Priority Review, therefore, does not alter the steps taken in a drug's development ortesting for safety and effectiveness. It does, however, for products believed to address unmet needs,shorten the anticipated amount of time until approval decision from 10 months to 6 months. (42)

Medical Countermeasures to Bioterrorism Attack. Although FDA, NIH,and DOD had been working on vaccines against potential bioterrorism or biowarfare agents, theevents of September and October 2001 infused the efforts with resources and political capital. Product development was supported with increased interaction among and within governmentagencies and with manufacturers, and consideration of fast track, accelerated approval, and animalefficacy mechanisms to bring products to review. The Project BioShield Act of 2004 allows theHHS Secretary (with directions regarding potential risk and benefit and required recordkeeping) toauthorize the emergency-use of products that do not have FDA approval in the event of potentialserious or life-threatening effects of a biological agent for which there is no approved product. Otherprovisions of the act address spending authority for medical countermeasure (such as vaccines)development and purchase.

Safety and Effectiveness

A pillar of U.S. policy on drugs and vaccines is the protection of the individuals who usethem. Vaccines cannot be marketed within the United States without a license from FDA; and FDAdoes not license a product until it is satisfied that the vaccine is safe and effective and that themanufacturing process can produce it. Congress may be called upon again to discuss issues of bothsafety and effectiveness. This could mean assessing how safe is safe . It will also mean definingeffectiveness: absolute or simply better than nothing or better than the available alternative? It canalso mean assessing effectiveness in terms of value-for-cost.

Safety is assessed by the nature and frequency of adverse reactions attributable to vaccineuse. A vaccine need not be side-effect free for FDA licensure; the licensed smallpox vaccine carriesan estimate, based on data from its routine use 30 years ago, of one or two deaths per millionrecipients. Similarly, effectiveness does not mean that a vaccine must protect permanently orcompletely. Researchers attempt to assess efficacy , generally, with expensive and lengthy clinicaltrials that compare infection or illness rates in two groups, both exposed to the disease-causing agent,but with only one provided with the hypothesized vaccine protection. Effectiveness describes howthe product works in a real-world situation. For drugs, effectiveness is often lower than efficacybecause of interactions with other medications or health conditions of the patient, sufficient dose orduration of use not prescribed by the physician or followed by the patient, or use for a off-labelcondition that had not been tested. Because vaccines are administered by the clinician, some of theseconditions are not relevant. Effectiveness may, however, still be diminished by the health of thevaccinee and whether circumstances permit all shots in a required series to be given according toschedule.

FDA and CDC monitor safety, in part, with their Vaccine Adverse Event Report System(VAERS), which assembles reports from parents, clinicians, and manufacturers of problems that maybe related to vaccination. Another FDA program, MedWatch, informs the public with clinicalinformation about safety issues involving vaccines and other medical products. These so-called passive surveillance systems rely on consumers and physicians to both recognize adverse events aspossibly vaccine-related and to follow through with reporting their concern to FDA. Such reportsare valuable aids to researchers looking for potential risks. The picture painted by the data, however,is incomplete. (43)

Problems

Side-Effects. Some scientists, parents, andconsumer advocates raise concerns that U.S. vaccine policy, with its recommended 20 shots toinfants by age two, (44) endangers the children it aims to protect. They cite hypotheses that the vaccines or preservatives orpackaging might cause autism and other neurodevelopmental disorders. One focus has been onthimerosal, a mercury-containing preservative used in some vaccines. In this case, even though thescience is not definitive, (45) manufacturers have chosen to reformulate many vaccines sothimerosal is not used.

An example of the government's interagency system to protect vaccine recipients involvesthe rotavirus vaccine that the CDC Advisory Committee on Immunization Practices had added tothe list of recommended infant vaccinations in 1998. During the year of mass use, VAERS flaggedreports of bowel obstruction soon after rotavirus vaccination; CDC recommended suspending thosevaccinations until it could study the apparent association. In October 1999, after scientific reviewof the data, the ACIP withdrew its earlier recommendation that the rotavirus vaccine be given toinfants. (46)

Insufficient Knowledge and Inadequate RiskCommunication. Often, decisions of vaccine safety revolve around perceptions ofrisk, methodologic limits of risk assessment, and communication of what is known about risks. Scientists, clinicians, Members of Congress, and public policy analysts continue to face choices onrisk -- hypothetical and real -- that do not offer clear alternatives. These involve uncertainties, bothscientific and political, and, therefore, will reflect personal and communal values. Smallpoxvaccination policy, for example, must weigh risks and benefits whose balance may differ whenconsidered from the perspective of the nation or the perspective of the individual.

Knowledge, therefore, is not an issue only for public policy. Some parents refuse pertussis(whooping cough) and measles vaccines for their children out of concern about vaccine safety. Insome of these cases, and in polio vaccine refusals (reportedly based on misinformation about sideeffects) in developing countries seeking to eliminate disease, (47) avoidable and potentiallyhorrible diseases still occur.

How can anyone decide whether getting immunized is worth the risk? Implementation ofgovernment decisions concerning anthrax vaccination was hindered by concern about similarquestions of uncertainty. Some members of the U.S. armed forces balked at mandatory anthraxvaccination, raising questions of safety. In October 2004, DOD stopped its anthrax vaccinationprogram following a U.S. District Court for the District of Columbia injunction. The Court basedits action on its finding that FDA had not solicited public comment on its finding that the vaccinewas safe and effective for protection against inhalational anthrax. (48)

Assessment of Competing Products. Comparisons of effectiveness among all available products and between a new product and othersalready on the market are possible. One could compare multiple single vaccines with variouscombined (polyvalent) products, or currently licensed smallpox vaccine with both the diluted formbeing tested and products now in the development pipeline. Industry and university researchers haveworked on some analyses of safety, effectiveness, and cost. Is there enough detail and rigor in thesecomparative studies? How can legislators assess the merits of the debate over side effects -- and aproper remedy for injury? Or ensure sound research about competing products? Or that the publicis better informed?

Production of Generic Biologics. Vaccines havenot been prime candidates for generic production in part because of the technologic difficulties inmeasuring whether two products are equivalent. In fact, the Hatch-Waxman Act (The Drug PriceCompetition and Patent Term Restoration Act of 1984, P.L. 98-417 ) amendments to the FFDCA thatdeal with Abbreviated New Drug Applications were not matched with a provision for abbreviatedapplications for biologics licenses under the Public Health Service Act. Now, manufacturers andthe public are looking to newer biotechnology procedures as a possible route to lower medicalcosts. (49)

Possible Legislative Solutions

Improving Post-Licensure Adverse-EventSurveillance. Congressional approval of the National Childhood Vaccine InjuryAct of 1986 ( P.L. 99-660 ) set into motion the VAERS activities in FDA and CDC for monitoringvaccine adverse events. Congress may choose to strengthen surveillance programs such as VAERS,address data coordination, and communicate surveillance analyses in ways that build trust amongconcerned parents and patient advocacy groups.

When it comes to smallpox, Congress has acknowledged the need for the consistentdocumentation of vaccine administration and side effects along with coordination of the manyrelated federal, state, and local activities. (50) As the smallpox immunization program proceeds, Congress maywant to review the completeness of the surveillance program and the usefulness of its output.

Education and Risk Communication. Websitesfor HHS offices, including CDC, the National Immunization Program, the Advisory Committee onImmunization Practices, and the National Vaccine Program Office, and others have hundreds of linksto consumer-oriented health information, addressing reasons to immunize, common misconceptions,safety, and even "evaluating immunization information on the Internet." (51) CDC and state healthdepartments also try to ensure that all health care providers are handing out the federally requestedVaccine Information Statements each time a vaccine is administered. (52)

Despite such Internet efforts and others, government education programs are not reaching allwho should be immunized or who have reservations. Congress might consider additional approachesto public communication of risk and medical choices.

Studies in Pharmacoepidemiology andPharmacoeconomics. Some legislators, in considering cost, would broaden theanalysis to include value-for-cost, arguing that if the government is going to consider paying fordrugs, it may as well pay for the most effective ones. Researchers are adapting the study design andstatistical methods of epidemiology and economics, along with those fields' traditional way offraming research questions, to questions regarding drugs and vaccines.

Because declarations of comparative effectiveness could affect manufacturers' market shareand individuals' access to drugs and vaccines, the success of that activity could depend, in part, onall stakeholders' trusting in the unbiased and expert credentials of the entity analyzing and presentingthe comparisons. Some have suggested that the government, a public-private group, or a"quasi-governmental" institution perform this function. (53) Others may feel such analysis is too fraught with uncertainty forgovernment decisions and is best left to individual physicians.

In its Medicare legislation, the 108th Congress directed the HHS Agency for HealthcareResearch and Quality (AHRQ) to "conduct and support research" dealing with "the outcomes,comparative clinical effectiveness, and appropriateness of health care items and services (includingprescription drugs)...." (54) How to fund these activities -- and to what extent -- remains atopic of debate.

Compensation. For those times when safetyefforts have been unsuccessful, earlier Congresses have addressed compensation. Since its creationby Congress in 1986, the National Vaccine Injury Compensation Program (VICP) (55) has made many awards,primarily to families of children, following injuries deemed to have been associated withACIP-recommended vaccinations. For several years, sentiment has been growing in Congress thatmodifications to the program are needed to make it more fair and efficient. Senator Bill Fristproposed changes to VICP in his Improved Vaccine Affordability and Availability Act( S. 754 , introduced April 1, 2003); committee mark-up of the bill has been postponedindefinitely. (56)

As the nation began to vaccinate certain military personnel and civilian health care workersagainst smallpox, some Members of Congress discussed proposals that would create non-tortmechanisms for smallpox vaccine injury compensation. On April 30, 2003, President Bush signedthe Smallpox Emergency Personnel Protection Act of 2003 ( P.L. 108-20 ), which the House andSenate had adapted from the Administration's proposal. It includes provisions to pay for smallpoxvaccine injury-related medical care, lost employment income under specified circumstances, anddeath benefits. HRSA published the required injury table in August 2003 (57) and the administrativeguidelines for the Smallpox Vaccine Injury Program in December 2003. (58) Because the perceivedurgency for smallpox vaccination diminished coincidentally with the compensation program'spassage, it remains theoretical to what extent the program would have succeeded in recruitingvolunteers.

Access

Successful development and production of a safe and effective vaccine does not ensure thateveryone who needs a vaccine gets it. People have to (1) know about it and believe it will benefitthem; (2) live near a health care provider willing to administer it; and (3) be able to afford the costof vaccination and follow-up care, if necessary.

Problems

Vaccines fare better than prescription drugs in health benefits coverage in the United States. In 2002, 75% of U.S. children between 19 and 35 months old had completed the recommended seriesof vaccinations, not yet reaching the HHS Healthy People 2000 and 2010 objectives of 80%. Recommended adult immunization rates are even farther from HHS goals: 66% ofnon-institutionalized adults at least 65 years of age reported receiving a flu vaccine within the pastyear, far less than the HHS goal of 90% by 2010. (59) Also, there are regional and economic disparities in access toimmunization services. Reasons given for these problems include insufficient coordination ofvarying eligibility rules among private insurers and government vaccine programs; incompletedocumentation of immunizations achieved; and inadequate financing. (60)

As federal and state agencies coordinated options and plans for smallpox vaccination,weaknesses in the U.S. public health infrastructure became apparent. These include the need forimprovements in technology, training, hospital and laboratory capacity, and communication amongparticipants. (61) In manydeveloping countries, inadequate public health infrastructure overshadows any question of access. Congress has gone beyond a domestic focus and showed legislative interest in the lack of access tovaccines in less developed areas around the world.

Possible Legislative Solutions

Congress has the opportunity to touch on access to safe and effective vaccines in itsconsideration of prescription drug benefit bills and broader issues involving global health.

Coordination of Government Financing Programs. Individual states and assorted federal programs work toward increasing childhood immunizationrates. To improve immunization rates among U.S. children as well as the financial efficiency of theefforts, legislative discussions could address difficulties of coordination among the publicly fundedvaccine programs, such as Medicaid, the State Children's Health Insurance Program, and Vaccinesfor Children.

Adult immunization insurance coverage and government financing is less complete. Although Medicare covers the major, recommended vaccines for adults, such as influenza andpneumococcal infections, many younger adults have no coverage for these routinely recommendedvaccines. Congress may consider funding levels and financing strategies for vaccine-related care inthe United States.

Payment for Vaccination and Follow-Up Care. In the context of medical countermeasures to bioterrorism attacks, such as the smallpox vaccine,Congress may consider questions about the payment for the vaccine administration and, then, forfollow-up and treatment, if necessary, of vaccine-related illness. As other vaccine countermeasuresare developed, Congress may need to consider who would have access to that continuum of medicalcare. (62)

Global Health. Concerns about access to vaccinesare not limited to biodefense and domestic use. Many government agencies and private groups worktoward international health objectives, such as eradicating polio. Some Members noted concern forpublic health needs of developing countries worldwide and the need to assist those countries in fightsagainst infectious diseases. Their concern stemmed from both humanitarian impulses and a growingawareness of the links between poor health and economic and political instability. Their workresulted in P.L. 108-25 , the United States Leadership Against HIV/AIDS, Tuberculosis, and MalariaAct of 2003. Legislators may want to increase access to existing vaccines, spur the development ofaffordable new vaccines for which the technology already exists -- an issue of both availability andaccess, and consider increased long-term investment in vaccine development for these diseases.