Skip Navigation

United States Department of Health & Human Services

Print Print    Download Reader PDF


The National Vaccine Advisory Committee (NVAC)

Vaccine Safety Working Group
Meeting Summary
Friday, April 11, 2008


Robert Ball, M.D., M.P.H.
Guthrie S. Birkhead, M.D., M.P.H.
Karen R. Broder, M.D.
Tawny L. Buck
Christopher S. Carlson, Ph.D.
Carmen M. Collazo-Custodio, Ph.D.
Cornelia L. Dekker, M.D.
Geoffrey Evans, M.D.
Mark Feinberg, M.D., Ph.D.
Bruce G. Gellin, M.D., M.P.H.
Lynn R. Goldman, M.D., M.P.H.
Steven N. Goodman, M.D., Ph.D.
Sean Hennessy, Pharm.D., Ph.D.
Florence Houn, M.D., M.P.H.
Sharon G. Humiston, M.D., M.P.H.
John Iskander, M.D., M.P.H.
Marie C. McCormick, M.D., Sc.D.
Barbara Mulach, Ph.D.
Andrew T. Pavia, M.D. (Chair)
Larry K. Pickering, M.D.
Daniel Salmon, Ph.D., M.P.H.
Peter C. Scheidt, M.D., M.P.H.
Benjamin Schwartz, M.D.
Dixie E. Snider, Jr., M.D., M.P.H.
Tevi D. Troy, Ph.D.
By Telephone
Renata J.M. Engler, M.D.
Paul-Henri Lambert, M.D.
Gerald Medoff, M.D.
Elizabeth Miller, M.B.B.S.
Trish Parnell

Invited Speakers
Peter Bell, M.B.A.
Barbara Loe Fisher
Catherine A. Morris, M.R.P.
Lisa Randall, J.D.

Public Comment
Louis Z. Cooper, M.D.
Kelli Ann Davis
Vicky Debold, Ph.D., R.N.
Patty Healy, J.D.
Nadia Karimi
David Kirby
Charles A. Mohan, Jr.
James A. Moody, J.D.
Terry Poling, R.N., J.D.
Tracy Stewart
Douglas C. Wallace, Ph.D.

Introductory Remarks—Bruce Gellin, Tevi Troy, Andrew Pavia

Dr. Bruce Gellin, Director of the National Vaccine Program Office, welcomed the assembled scientists and interested members of the public to the first meeting of the NVAC Vaccine Safety Working Group and introduced Dr. Tevi Troy, Deputy Secretary of Health and Human Services (HHS).

Dr. Troy thanked the Working Group members and guests for their participation in this meeting to begin to study the long-term Scientific Agenda of the Centers for Disease Control and Prevention (CDC), Immunization Safety Office (ISO). He pointed out that the meeting and the ISO Scientific Agenda had been long planned and were not a response to recent headlines.

Dr. Troy spoke briefly about diseases that have been virtually eliminated from the United States because of vaccines. He said that he plans to increase cooperation among all HHS agencies to prevent and eradicate diseases.

Dr. Andrew Pavia extended his appreciation for the concern for public health shared by the members of the Working Group. The Working Group, he said, was created to fill a need within NVAC for additional expert advice on vaccine safety.

Dr. Gellin spoke briefly about the vaccine safety system, stressing the need for cooperation among HHS agencies and between HHS and other U.S. government bodies, business, professional, and advocacy groups, and international organizations.

Dr. Pavia asked the Working Group members, some of whom had not met before, to introduce themselves and to state any potential conflicts of interest.

Review of the Working Group Charge and Composition—Andrew Pavia

Dr. Pavia reviewed the NVAC charge to the Working Group. In brief, this is

  • To review the draft ISO Scientific Agenda and to offer advice on such things as its
    • Content
    • Prioritization of research topics
    • Possible barriers to implementation
  • To review the current federal vaccine safety system and develop a white paper describing the infrastructure necessary for this system to
    • Fully assess vaccine safety in a timely manner
    • Reduce adverse events following immunization
    • Improve and maintain public confidence in vaccine safety

Dr. Birkhead asked about the timeframe for review of the ISO Scientific Agenda. Dr. Pavia said that he hopes to have a draft report ready for presentation at the September 2008 NVAC meeting.

Dr. Pavia asked about additional expertise that might be needed by the Working Group. The following suggestions were made:

  • Hereditary immunodeficiency syndromes
  • Hereditary mitochondrial syndromes
  • Additional consumer representation

The ISO Scientific Agenda—John Iskander, Karen Broder, Dixie Snider

Background—John Iskander

Dr. John Iskander opened the presentation of the ISO Scientific Agenda. He noted that ISO’s mission focuses on the assessment of the risks of vaccines. Dr. Iskander said that ISO recognizes that no medical product is completely without risk, that risks must be weighed against benefits, and that vaccine safety research is a broad field that encompasses numerous disciplines.

In 1986, Dr. Iskander said, Congress asked the Institute of Medicine (IOM) to assess the relationship between vaccines and specific safety concerns, referred to as adverse events (AE). Either no or inadequate scientific evidence to accept a causal relationship was found for two thirds of 76 adverse events reviewed by the committee. The IOM attributed our poor understanding of AE to limitations in knowledge and research capacity.

One specific IOM finding was that there was insufficient or inconsistent information from case reports. In 1990, the CDC and the Food and Drug Administration (FDA) created the Vaccine Adverse Events Reporting System (VAERS). VAERS serves as a national vaccine safety surveillance system and last year received more than 30,000 reports.

Another weakness cited was inadequate size and length of followup of population-based epidemiologic studies. The Vaccine Safety Datalink (VSD) was established in 1990 to address this concern. VSD investigators have published more than 80 peer-reviewed studies.

The IOM also noted inadequate understanding of the biological mechanisms underlying adverse events. The Clinical Immunization Safety Assessment (CISA) network serves as ISO’s clinical research platform for assessing adverse events.

Dr. Iskander recognized that gaps still exist in vaccine safety knowledge. Reasons include the rarity of serious adverse events, the inherent difficulties of high-quality scientific study, the relative newness of vaccine safety science, and the broad scope of the field, which encompasses all vaccines and numerous known or suspected adverse events. There is, therefore, Dr. Iskander said, a need to collect, organize, and prioritize vaccine safety studies using tools such as the proposed ISO Scientific Agenda to address the remaining gaps in our knowledge of vaccine safety.

Overview—Karen Broder

Dr. Karen Broder addressed the mission of ISO: To assess the safety of vaccines administered to children, adolescents, and adults. ISO seeks to accomplish this mission by working closely with national and international partners to foster high-quality research, transparent communication, sound scientific methodology, and standardized case definitions.

Dr. Broder briefly outlined the roles of the various ISO research and surveillance components involved in vaccine safety and described VAERS, VSD, and CISA in somewhat more detail than had Dr. Iskander in his initial remarks. She discussed the Brighton Collaboration, created to provide the standardized case definitions necessary to ensure a common vocabulary for vaccine safety research and surveillance. Dr. Broder noted the interrelationships among these components of the vaccine safety infrastructure.

In February 2005, Dr. Broder said, the IOM recommended that NVAC review and provide advice on the VSD research plan. However, ISO has put forward an overall scientific agenda for review, which includes VSD but focuses more broadly on the scientific priorities for the entire office. The rationale for the more inclusive plan is that carrying out effective vaccine safety scientific activities requires integration across ISO research and surveillance components.

ISO’s comprehensive draft 5-year scientific agenda includes vaccine safety research and selected surveillance and clinical guidance activities that

  • Are part of ISO’s mission
  • Are such that ISO could lead them
  • Could feasibly be implemented within the next 5 years given the available infrastructure, generally accessible to CDC

To develop the draft Agenda, ISO solicited input from scientists with diverse expertise. Three meetings were held:

  • One with external scientific consultants
  • One with scientists from various HHS agencies and the Department of Defense
  • One with scientists representing vaccine manufacturers

ISO synthesized the input from these meetings to establish the draft recommendations for consideration by the Working Group. ISO and CDC will respond to the feedback from the NVAC review process and then finalize the ISO Scientific Agenda.

The agenda makes the following broad recommendations. ISO should

  • Draft Recommendation 1—Respond to emerging issues and conduct core required scientific activities:
    • Monitor the safety of all newly licensed and Advisory Committee on Immunization Practices (ACIP)-recommended vaccines and previously licensed vaccines with new recommendations
    • Respond to new vaccine safety concerns and hypotheses
    • Provide technical consultation to CDC immunization experts and other stakeholders for collaborative and multidisciplinary scientific activities
    • Prepare to monitor vaccine safety in the event of a mass vaccination campaign or other vaccine emergency
  • Draft Recommendation 2—Enhance vaccine safety public health and clinical guidance capacity in the following areas:
    • Infrastructure for vaccine safety surveillance in VAERS
    • Infrastructure for vaccine safety research in VSD
    • Epidemiologic and statistical methods for vaccine safety
    • Laboratory methods for vaccine safety
    • Genomics and vaccine safety
    • Case definitions, data collection, and data presentation for adverse events following immunization
    • Vaccine safety clinical practice guidance

Dr. Pavia asked that Dr. Broder pause for questions at this point before going on to the third recommendation, addressing the 5-year research needs.


Dr. Steven Goodman asked who was responsible for handling issues of communication. Dr. Iskander replied that communication is a significant part of CDC’s day-to-day work. Vaccine safety communication might include risk communication activities or activities related to scientific publications. ISO has a communications staff that coordinates its efforts with communications staff in other relevant CDC centers, such as the National Center for Immunization and Respiratory Diseases or the Office of the Director, or with other federal agencies.

Dr. Goodman asked whether communication is an area in which more research can be done. Dr. Iskander said that at one time, there was a group within ISO that focused on vaccine risk communication research and included individuals with expertise in such areas as behavioral science and survey research. During a review of ISO 4 years ago, it was determined that those activities, while important, were not consistent with a focus on safety assessment. Dr. Dixie Snider added that another reason the group was moved was so that ISO would not be perceived as being part of the vaccine promotion enterprise.

Dr. Broder was asked who would be the primary audience for ISO’s published research agenda. She responded that the primary audience would be the scientists who will carry out the research. Dr. Snider said that the ACIP and the FDA will use the information generated to make decisions. Dr. Larry Pickering added that ISO representatives serve on ACIP Working Groups.

Dr. Mark Feinberg observed that it would be difficult to decide which actions are appropriate for ISO to take without knowing its funding. Dr. Iskander replied that currently ISO’s appropriation is approximately $21.6 million; approximately $12 million of that goes to VSD, approximately $4 million to the CISA network, and approximately $2.8 million to VAERS. He added that ISO had received some supplemental funding related to pandemic influenza preparedness.

Dr. Christopher Carlson asked about investigator-initiated research. Dr. Iskander said that there is great interest—not only in ISO but throughout CDC—in having more opportunity for extramural research. He said that there are a small number of extramural research programs, but ISO is not involved in the scientific conduct or oversight of this work.

Dr. Pavia noted that genomics is one element of the agenda. He asked what portion of this could be done intramurally and how much extramurally. Dr. Iskander replied that CISA would be the primary platform for that research and that there had been a meeting to set reasonable objectives congruent with CISA’s mission. He observed that genomics studies are particularly resource intensive. There is a need, he said, for collaboration with scientists in other Government agencies. Dr. Broder cited some studies currently underway. Dr. Snider said that CDC is doing, in this regard, what its capacity allows but would be glad to have suggestions.

A question arose as to how much government-funded vaccine safety research there had been within the last year. Dr. Pavia suggested that the Working Group could ask HHS for this information.

Dr. Snider was asked to describe the position of ISO within CDC. He said that ISO was once part of the National Immunization Program but that it is now in the Office of the Chief Science Officer, who reports directly to the head of CDC. This was done in an effort to prevent a perception of bias that might arise if ISO were part of a group whose interests include the promotion of vaccines.

Dr. Snider was asked if he thought the organizational placement of ISO was optimal. He said that anytime program activities are made part of an office that deals extensively with policy issues, there will be challenges, but he did not know what would be optimal. Dr. Iskander reported that ISO’s working relationship with the ACIP has continued to be strong despite the organizational separation. Dr. Iskander also said that internationally there seems to be a move to separate vaccine risk assessment from risk management.

Dr. Lynn Goldman asked how much flexibility ISO had in budgeting. Dr. Iskander replied that when Congress appropriates funds, it expects them to be spent specifically as budgeted. Dr. Snider said that agency directors can, however, ask to reprogram money. He said, too, that while ISO can determine how to allocate its resources, the possibility of such decisions is sometimes more theoretical than realistic; funds moved to one area will create a shortage elsewhere.

Dr. Pavia asked to what degree ISO is looking at patient safety issues that would apply not only to vaccines, but to pharmaceuticals more generally. Dr. Iskander said that the methodologies, infrastructure, and the network of expertise may be applicable to the broader field.

Five-Year Research Needs—Karen Broder

Dr. Broder reported that ISO proposes 30 research needs for the next 5 years for consideration by the NVAC Safety Working Group. (Draft Recommendation 3):

  • Specific vaccine safety questions (7 items)
    • Are vaccines associated with an increased risk of Guillain-Barre syndrome (GBS)?
    • Is live, attenuated influenza vaccine (LAIV) associated with increased risk for asthma or wheezing?
    • Is exposure to thimerosal associated with increased risk for clinically important tics or Tourette syndrome?
    • Are acellular pertussis vaccines associated with increased risk for acute neurological events?
    • Is immunization associated with increased risk for neurological deterioration in children with mitochondrial disorders?
    • Is combination measles, mumps, rubella, and varicella (MMRV) vaccine associated with increased risk for febrile seizure, and if so, are there sequelae?
    • Are varicella vaccines (including MMRV) associated with increased risk for clinically important events related to varicella vaccine virus reactivation?
  • Scientific thematic areas
    • Vaccines and vaccination practices (8 items)
      • Bivalent human papillomavirus vaccine (Cervarix)—not currently licensed, but under FDA review
      • Zoster vaccine (Zostavax)
      • Annual influenza vaccination in children and adolescents
      • Nonantigen components of vaccines (other than thimerosal or ASO4 in bivalent HPV vaccine)
      • Simultaneous vaccination
      • Safety of different products within the same vaccine category
      • Off-label use of vaccines
      • Vaccine-drug interactions
    • Special populations (7 items)
      • Premature and low-birth weight infants
      • Pregnant women
      • Adults aged 65 years and over
      • Persons with primary immunodeficiency
      • Persons with secondary immunodeficiency
      • Persons with autoimmune disorders
      • Children with inborn errors of metabolism
    • Clinical outcomes (8 items)
      • Autoimmune diseases
      • Central nervous system demyelinating disorders
      • Encephalitis/encephalopathy
      • Neurodevelopmental disorders, including autism spectrum disorder
      • Vasculitis syndromes
      • Myopericarditis not associated with smallpox vaccine
      • Clinically important outcomes related to postimmunization fever
      • Postvaccination syncope and sequelae


Dr. Birkhead said that he was struck by the specificity of the research questions and the generality of the items that followed. He asked whether the list represented the full spectrum of ideas from the three meetings or whether some culling had already taken place.

Dr. Broder acknowledged that the list of research questions is the most specific part of the agenda and that the thematic areas are somewhat less so. ISO, she said, distilled the list from multiple sources. It was recognized, during the process of gathering the input, that some of the suggestions fell more into the area of capacity building whereas others fell more into the area of hypothesis testing; this had not been anticipated. There was also a need to refine the list of questions. Each suggested question was looked at to see whether it met inclusion criteria; e.g., ISO could take a lead role, the infrastructure requirements were feasible, the vaccine is—or would be—routinely used in civilian populations. Also, some of the questions involved routine processes and would be answered in the normal course of events; these were not included. ISO then sought additional feedback about the relative importance of the questions. A list of about 60 items went through a series of three reviews by ISO research partners and CDC immunization experts (comprising about 40 scientists, excluding ISO staff). From that process, another document was compiled examining the recommendations from those groups, and the decision was made about how the items should finally be classified.

Dr. Sharon Humiston asked about long-term effects, in the range of 10 to 20 years. Dr. Iskander said that he was aware that there is concern about long-term outcomes, particularly with regard to autoimmune and chronic diseases. He said that the Defense Medical Surveillance System is undertaking such studies and that CDC’s Vaccine Analytic Unit has a number of such studies on their research agenda; in some cases, he said, these may sit under other categories, such as autoimmune diseases. Dr. Broder observed that each thematic area in the list could be broadened to include questions of long-term outcome.

Dr. Goodman asked whether VSD can be used in a rapid-fire way. Dr. Iskander replied that while most people think of VSD as involving planned studies, there is also a rapid cycle analysis that can provide near real-time studies for vaccine safety surveillance. He said that the ways in which VSD can be used have expanded in the last few years. Dr. Snider added that there is no need to reallocate funding when moving from the surveillance component to the investigation component of VSD.

Ms. Tawny Buck asked how the prevention of adverse events is being addressed. Dr. Iskander said that this is an emerging area of vaccine safety science. He said that the last item in the list of research topics—postvaccination syncope—may be preventable; there are existing recommendations for a vaccine waiting period. ISO is interested in collaborating on studies to answer questions such as whether the recommendation for a waiting period is followed and whether it is effective when it is followed. Dr. Iskander observed that issues of patient safety are different from other scientific studies. Another category of preventable adverse events, he said, is vaccine administration errors. ISO collaborated with the FDA on a study of this subject. Dr. Iskander said that as the science of vaccine safety builds incrementally, he expects that more events will be added to that list of what is potentially preventable.

Dr. Snider offered examples of ISO monitoring of adverse events that had resulted in the removal from the market of the vaccines associated with those events. He added that genomics offers a possibility, which may not be realized for years, of anticipating vaccine adverse events. He said that the literature suggests that it may be possible, once the tools are in hand, to identify children at risk for encephalopathy following vaccination.

Dr. Carlson said that there are already many association studies but that he saw little in the agenda relating to prediction of outcome. He observed that genomics would be too expensive, given ISO’s budget, and suggested that there were less expensive ways, such as preadministration screening, to identify persons at risk for adverse events.

Dr. Broder said that one place in the agenda that this is recognized is under clinical guidance, where procedures could be outlined to identify persons at risk of adverse events. A number of the research questions deal with whether there is an increased risk. A natural followup to a finding of increased risk would be to the nature of that increased risk; questions would arise such as what pathological mechanisms are involved and whether there are sequelae. The agenda is not concerned only with epidemiological questions but there is also a need to determine whether an association exists before further action can be taken.

Addressing another point made by Dr. Carlson, Dr. Snider asked the Working Group not to limit itself to ISO’s current budget. He said that if more funding is needed, they can try to find it.

A Working Group member mentioned population-based studies, remarking that there has been much research on the hygiene hypothesis—that childhood immunization has changed the rates of asthma and allergy. It was suggested that though perhaps somewhat out of scope, such studies, funded elsewhere, might provide an opportunity to look at vaccine safety issues from another perspective.

Dr. Peter Scheidt said that the National Children’s Study could address a number of the questions raised in that there would be enough children enrolled in the study who have not received particular vaccines that comparisons could be made between exposed and nonexposed groups. The hygiene hypothesis, he said, is one of the specific hypotheses of the National Children’s Study. Although the study’s other hypotheses do not specifically address vaccines, vaccination data (by maternal report) will be collected. While there is no current plan to collect some vaccine data, such as manufacturers or lot numbers, that could be done if there is interest and funding. The study will collect toxicological and environmental data, and there is potential for generational followup.

Dr. Marie McCormick asked about the life cycle of such studies; specifically, the timeframe and barriers to release of information on vaccine adverse events. Dr. Iskander said that a planned protocol-approved epidemiological study to determine whether a vaccine is associated with a particular outcome will be on the order of 2 to 6 years. Rapid cycle analysis is faster. Signal detection may happen within weeks to months after the start of the protocol. At that point, the study would shift to an epidemiologic study model. The ability to look at a very specific, very well targeted public health question—such as the utilization of recalled lots of vaccine—can be done within 1 to 2 weeks.

Dr. McCormick asked about the timeframe for reassurance of the public about matters of concern. Dr. Iskander said that if there were information that would be important to the ACIP, ISO would arrange advance scientific presentations to the ACIP Working Groups. Some time will be needed, in rapid cycle analysis, to make certain that the signal detected is not spurious. Information affecting policy will be communicated in a timely manner in advance of any publication. Dr. Broder added that ISO communicates with other agencies, such as the FDA, on a regular basis.

Dr. Carlson asked how often the specific questions may need to be adapted. Dr. Iskander replied that new questions emerge in vaccine safety all the time—from VAERS, for instance, or from the media. The list of specific questions in the agenda is an attempt to strike a balance among emerging issues. The questions on that list have been judged by the scientists that were consulted to warrant specific attention. Some concerns have been around for a long time—those about GBS, for instance, for 100 years. Dr. Broder added that three or four of the specific questions could have been placed on the list last year; the others have emerged more recently. Most of the thematic areas, she said, could have been recommended 2 or 3 years ago.

Dr. Carlson noted that the childhood vaccination schedule had changed considerably in recent times and said that public concern should affect the list as well as scientific concerns. He asked whether alternative schedules might be feasible, in the absence of specific data, so that parents would have more choice.

Dr. Iskander said that this is an issue that has arisen in leadership discussions. He said that the ISO has recently acquired some new expertise related to the vaccination schedule and that they would be willing to examine the issue.

Dr. Snider said that determination of the safety of an alternative schedule would fall to ACIP. If there is a study investigating the issue, he said, ISO could get involved, but it is not within its province to initiate policy recommendations.

Dr. Pickering said that there are two relevant constraints under which the ACIP operates: (1) Vaccines given before exposure to disease have optimal effectiveness. (2) Vaccines are studied under certain conditions with particular age groups, and since all recommendations are evidence based, the ACIP generally stays within the FDA licensures for the various vaccines. However, there are ranges for almost all the vaccines, so more flexibility may be possible. Dr. Pickering said that this is something that the ACIP would consider.

Dr. Goldman noted that licensure studies are conducted one at a time; in practice, vaccines are often given together. She raised a concern that this is communicated as a rigid schedule and that school systems may insist on too literal an adherence to that schedule so that some vaccines may be given too close together.

Dr. Birkhead noted that ISO has not yet formulated specific research questions for certain parts of the Agenda. Dr. Snider replied that in the meetings ISO held to gather input from scientists, hypotheses were not often articulated. Each thematic area in the list, as currently formulated, will require much consultation with experts to tease out specific hypotheses. Perhaps more than a year will be required. All the same, he said, they would like to have the Vaccine Safety Working Group’s general view as to which thematic areas would be most worth pursuing. He said that he would rather ISO make its judgments informed by the Working Group and by public input.

Ms. Buck asked whether the public had been involved in the process so far or whether public involvement is beginning now. Dr. Broder said that the initial meetings had not been open to the public but that some public perspective had been sought by the inclusion of Dr. Geoffrey Evans of the Vaccine Injury Compensation Program and a member of the Advisory Commission on Childhood Vaccines (ACCV). Dr. Snider said that there was no intent to exclude the public; the purpose of those meetings had been to find out what scientists thought was most important. He said that, from pediatricians, ISO had heard indirectly from parents. He added that the area of soliciting public input is one in which ISO has limited expertise. He said that he hoped the Working Group could provide direction on that point.

Dr. Pavia noted that ISO’s ability to look at some of the groups listed under Special Populations might be limited. Dr. Iskander said that the groups listed fall into two categories. The first three (premature and low-birth weight infants, pregnant women, and adults 65 and over) will be easier to obtain data on. For the other groups, there may be a problem arising from their relative rarity. Dr. Broder said that a strength of CISA is that many of the academic centers have specialty clinics. Dr. Snider added that collaboration with other agencies could afford opportunities to study people in some of those groups.

Dr. Gerald Medoff asked who decides what is an acceptable level of toxicity from a vaccine. He said that such decisions must be made following studies demonstrating a link between a vaccine and an adverse event and that it would enhance public confidence if that process were specified in ISO’s Scientific Agenda. Dr. Iskander answered that this was not within the scope of activities that ISO could lead. Dr. Pickering said that the ACIP gets regular updates on vaccine safety and that changes in its recommendations will be based on the relationship of risks to benefits. He said that a serious consequence would be discussed at a public meeting. Dr. Pavia observed that this seemed to be an issue of communication; though there is a process, it may not be obvious.

Dr. Iskander was asked whether cross-national comparisons were planned. He said that the global vaccine safety science community is not large. Most researchers know one another and are aware of one another’s work. He said that there are proposals to develop international vaccine safety networks.

Dr. Elizabeth Miller, of the British Health Protection Agency (HPA), offered her compliments on “an extremely thorough document.” She said that she had been struck by the fact that some of the research proposals in the ISO Scientific Agenda mirror those that have also been identified in the United Kingdom. She spoke of the possibility of collaboration but also noted that the value of independent research is in the comparison of data derived from separate studies. Dr. Pavia noted that this raises the question of whether there are similar long-term agendas in other countries. Dr. Miller said that the HPA does not have the resources to do long-term planning. There is the possibility of collaboration, though, in the area of methodological development; in that area, she said, it is possible for the HPA to be more proactive than reactive. Dr. Pavia noted for Dr. Miller’s benefit (as she was participating by telephone) that at the suggestion of joint methodological exploration, there had been very vigorous head nodding.

Dr. Scheidt said that the National Children’s Study, jointly with the National Cancer Institute, has forged a consortium of large cohort studies around the world to address outcomes that are less frequent than the National Children’s Study alone could do. It would lend itself, he said, to the study of infrequent outcomes, such as encephalopathy, related to vaccine administration.

Dr. Goldman spoke of the need for long-term planning as well as for the ability to react to immediate concerns and said that ISO’s effort to plan for the next 5 years was commendable. She said that the Working Group’s job is made easier by the fact that ISO, in concert with the scientists it consulted, has already done much work on the agenda.

Dr. Broder said that work has already begun in some of the areas listed in the agenda though the amount of work done varies among the topics. A participant noted that consideration needs to be given to how much ISO should continue to invest in the work underway and how much to allot for new projects. Another question is how much capacity needs to be left over to deal with questions that arise later.

On the issue of public engagement, Dr. Goodman referred the Working Group and ISO representatives to the National Breast Cancer Coalition’s Project LEAD. This project includes seminars where scientists interact with advocates; it contains workshops and didactic components. This kind of public involvement, he said, requires much time but can be constructive. Dr. Goodman acknowledged that this may not be the sort of thing ISO can do, but he pointed out that the scientific/public interface in vaccine safety is currently very formal and that a program of mutual education could be beneficial.

Considerations for Prioritization—Dixie Snider

Dr. Snider presented ISO’s draft prioritization criteria for its draft recommendations.

Draft Recommendation 1, “Respond to emerging issues and conduct core, required scientific activities”—ISO did not suggest prioritization criteria for these activities but does request that the Working Group make an assessment of their relative importance, indicated by the proportion of time that should be devoted to each.

Draft Recommendation 2, “Enhance vaccine safety public health and clinical guidance capacity in seven areas.” The draft prioritization criteria are

  • The importance of strengthening this area for meeting CDC’s mandatory/required vaccine safety activities
  • The importance of building capacity in this area to address the important hypotheses and thematic areas in the agenda
  • The importance of this area to advancing knowledge in vaccine safety science generally
  • The importance of CDC taking the lead in moving this area forward
  • The importance of strengthening this area to CDC’s stakeholders and the public
  • The feasibility of strengthening this area, given current resources

Draft Recommendation 3, “Address 5-year research needs”—ISO suggests the following prioritization criteria:

  • For the specific vaccine safety questions
    • Clinical severity of the vaccine adverse event
    • Biological plausibility
    • Population exposure to the vaccine (considering not only the number of people exposed but the number of doses they may have received)
    • Level of public concern
    • Feasibility of designing and implementing a study
    • Sufficiency of previous or ongoing scientific activities
    • Potential to influence clinical practice or vaccination policy
  • For the thematic areas
    • Severity of outcome
    • Population exposure to the vaccine
    • Biological plausibility
    • Public and scientific concern
    • Projected impact of the work


There was some discussion of whether the age group affected should be a criterion of prioritization; there was also some discussion of the relative importance of the prioritization criteria themselves and whether the relative importance of a vaccine is more a matter for public policy consideration than for scientific evaluation.

In response to a question about how to organize the feedback, Dr. Snider suggested that the Working Group proceed section by section, prioritizing each item, and then, looking at the agenda as a whole, offer an opinion as to how much effort should be expended on each area.

In response to a question, Dr. Daniel Salmon said that the Working Group will make its recommendations to NVAC. NVAC will consider these and make recommendations to the Assistant Secretary for Health, who will refer them to CDC.

Panel Discussion: How To Effectively Engage the Public—Benjamin Schwartz, Barbara Loe Fisher, Peter Bell, Lisa Randall, Catherine Morris

Dr. Pavia acknowledged, in introducing the panel discussion, that it was something of an experiment but that it was necessary to explore models for public involvement in order to lessen mistrust and so that no voices are left clamoring to be heard.

Benjamin Schwartz—National Vaccine Program Office

Dr. Benjamin Schwartz said that over the last several years, CDC has had increasing need for public input. As an illustration, he focused on the Public Engagement Project on Pandemic Immunization (PEPPI).

As there may not be enough vaccine for everyone at the start of a pandemic, a prioritization plan was necessary. Scientific considerations focused on who would be most likely to get sick and die, who would spread the disease in the community, and who would be most likely to be protected by vaccination. At the same time, the question of who would get a potentially lifesaving vaccine was also a question of public values.

In 2005, CDC held a series of public engagement meetings with the general population and with interest groups. The surprising result was that the public held the functioning of society to be a more important goal of pandemic vaccination than the protection of those at highest risk of severe illness or death.

Further public engagement and stakeholder meetings were held to develop guidance on the prioritization of pandemic vaccination. It was found that despite demographics, there was overall agreement when the focus was on values.

PEPPI received many compliments from the Web community for the transparency of its process.

Dr. Schwartz proposed the following principles for public engagement:

  • Commitment. Input from the public is important. Members of the public must know that their voices have been heard.
  • Inclusiveness. Confidence in the outcome is fostered by the inclusion of knowledgeable parties and of critical, but dispassionate, citizens.
  • Fairness. Let there be neutral facilitation by persons with no stake in the outcome.
  • Dialogue before deliberation. Focus on values first to discover common ground.
  • Acknowledge complexity. For the ISO Scientific Agenda, this would include recognizing the complex interplay of genetics and environment and the complexity and limitations of scientific investigations.
  • Focus. Stay focused on the issue at hand—in the present case, the ISO Scientific Agenda and the research infrastructure.
  • Accountability. The Government is obligated to provide feedback to the public and describe how the results of engagement contributed to the final outcome.

Barbara Loe Fisher—National Vaccine Information Center (NVIC)

Ms. Barbara Fisher said that in the past three decades, during which she has served on committees for the FDA and IOM and forums of CDC, her greatest challenge has been to convince government and public health officials to take seriously the concerns of parents about the quantity and quality of information available to them.

With vaccination rates with multiple vaccines at an all-time high in America, Ms. Fisher said, 1 vaccinated child in 6 is learning disabled, 1 in 9 has asthma, 1 in 150 has autism, and 1 in 450 has diabetes.

Ms. Fisher said that the scientific, economic, political, and moral necessity of addressing the new epidemic of chronic disease and disability that has developed in the last quarter century—and that is compromising more children than were ever harmed by any infectious disease epidemic, including polio—makes the vaccine safety research agenda the most important federally funded research priority of the day. It requires independent appropriations by Congress to support a national research program, created in collaboration with those most concerned about vaccine safety, to generate evidence-based information that people will trust.

Ms. Fisher said that the first step in securing public trust is to add at least two more well-informed consumer representatives critical of vaccine safety to this Working Group and to NVAC.

Ms. Fisher said that individuals at high risk should be identified. Parents today, she said, are using mass communication and new technology to educate themselves about vaccines. When they attempt to evaluate the components of vaccines, they find no credible scientific studies of their safety. When they question their pediatricians about the safety of giving their children multiple simultaneous vaccines, they are denied medical care instead of being given proof of safety. When they tell their doctor of a child who has regressed into autism following vaccination, they are told that it is a coincidence, and so no report is made to VAERS. When their children have vaccine reactions and are revaccinated, they lose faith in a mass vaccination system that dismisses individual health as unimportant compared to public health when implementing a one-size-fits-all, no-exceptions policy.

Ms. Fisher called for a study comparing the health, after a number of years, of vaccinated and unvaccinated children.

Ms. Fisher said that in considering the issue of public engagement, she was reminded of a group of young dissidents a century and a half ago who founded a participatory democracy movement in America, a concept that she learned about first hand in her work on the Vaccine Policy Analysis Collaborative, a participatory democracy experiment initiated by CDC that ran from 2002 to 2005. In calling for government institutions to be more inclusive, those dissidents referred to the great chasm that had developed in America between those who govern and those who are governed and described the powerlessness felt by ordinary people. It is the duty of government, Ms. Fisher said, to listen to people and to act when they are suffering.

Ms. Fisher said that young parents today, who trust doctors to give them good advice, do not understand why their children are not well when they have received twice as many vaccines as children in previous generations. They want a full-scale, transparent scientific investigation of all potential environmental causes of autism and other disorders, conducted by extramural researchers who are not connected to vaccine manufacturers or policy makers. They want a greater separation of vaccine risk assessment and safety oversight responsibilities from vaccine policy making and promotion activities.

Peter Bell—Autism Speaks

Mr. Peter Bell spoke of his son Tyler, who was diagnosed with regressive autism in his third year. Tyler received 26 vaccines in his first 2 years, with a total of 187.5 mg of thimerosal. Because of intestinal problems, he was examined and found to have measles virus in his gut.

Mr. Bell does not maintain that vaccines triggered his son’s autism but said that like other parents in similar situations, he wants to know why this has happened. He said that, overall, he is supportive of vaccines.

The goals of Autism Speaks include giving parents the feeling that there is hope for their children; facilitating the understanding, prevention, and reversal of autism; helping to make the lives of autistic children and their parents as good as possible; and fostering understanding of autism as a major public health problem. The organization’s science mission is to increase understanding of autism’s etiology, risk factors, and biology and to improve diagnosis and therapy (both behavioral and medical). The group sponsors an autism tissue program and a clinical trials network.

The group’s belief is that autism is caused by complex gene-environment interactions. It is currently sponsoring an investigation of the prevalence of mitochondrial disease in autism spectrum disorders.

Mr. Bell said that in order to earn public support, all Government research activities must have transparency. Policy making must be based on the best evidence; if a sufficient level of appropriate research does not exist, it must be obtained. More research is needed, he said, on medically susceptible subgroups of the population, the timing of vaccine administration, and the relative safety of multiple versus single vaccines.

Lisa Randall—Voices for Vaccines

Ms. Lisa Randall said that her organization provides solid information to help individuals make appropriate choices about vaccination. She said that the concerns of the most vocal contingent are not those of most mainstream parents and that there are ideological differences between parents who assume the worst about vaccines and parents who have realistic assumptions.

Ms. Randall said that the autism community is notorious for its diversity of viewpoints. She encouraged the presentation of more detailed medical information aimed at the general public, a great many of whom will be capable of understanding more complex information than is usually offered. This would help to dispel the idea, she said, that the public is simply being asked for a blind trust.

Ms. Randall said that it is important to disseminate the idea that one’s own vaccination is necessary to protect the health of others. She said also that a study is needed of the sources relied on by people who refuse vaccines.

Catherine Morris—Keystone Center

Ms. Catherine Morris spoke about public policy decisionmaking processes. A well-structured public engagement process, she said, can result in mutual learning and can bring forward new ideas. The challenge is to match the process to the objectives.

One may seek only to disseminate information. This tends to be experts delivering information to the public. One may consult with the public in a face-to-face or online meeting. One may go further and actually engage the public, allowing for new solutions to emerge, or one may establish a collaborative process in which the public has some decisionmaking authority. Any of these options may be appropriate, depending on the circumstances.

It will be important to understand the emotional climate as well as the facts. Practical questions include how much time and money are available, who needs to be involved, and whether trust needs to be built before the question at issue can be addressed.

Models include the town hall meeting with small group discussions, citizens’ jury, dialogue by design, and the hand-selection of specific stakeholders who have credibility to represent a number of others.

Some guiding principles are the following:

  • Meet people where they are. If trust is lacking, you may be unable to begin directly with the question you want to address.
  • Strive for transparency. This is important for credibility.
  • Encourage a “beginner’s mind”; i.e., be open to new ideas.
  • Find credible and trusted experts. Find out, up front, who are the experts both sides will trust.
  • Create a safe environment.
  • Make sure the pathway for implementation is clear. Who makes the decisions? What will they do? Will the public be involved further?
  • Do not raise expectations you cannot meet.

Andrew Pavia

Dr. Pavia said that he had heard several guiding themes in the five presentations:

  • There is a need for conversations between policymakers and the public.
  • It is necessary for policymakers to admit that they do not have all the answers.
  • The public dialogue should be ongoing.


Ms. Fisher said that such discussions require a mix of stakeholders who come to the table with a background knowledge of the issues and those who come without previous knowledge but without preconceptions as well. Dr. Pavia asked her why she thought the participatory democracy experiment failed. Ms. Fisher said that she believed that those in charge wished to preserve the status quo. She spoke positively of her experience with the IOM Vaccine Safety Forum and said that an open public dialog can succeed but that the people in power have to have the will for it to succeed.

Ms. Randall said that it is important to be sure that all parties are speaking the same language and agree on what constitutes evidence. Until that time, it will be hard to make progress. She said that consensus can be difficult unless the stakes are high. Consensus involves compromise, so the parties involved must perceive a necessity for agreement.

Dr. Snider said that he agreed with Ms. Fisher’s analysis of the fate of the participatory democracy movement. He said that an effective national immunization plan can be achieved only if there is trust and that a process must be crafted that simultaneously is nonthreatening to those in authority and nonthreatening to industry and that truly engages the public. Dr. Gellin said that in this context, a crisis of trust is a crisis in public health.

Mr. Bell said that the Working Group should be expanded thoughtfully, with people who can articulate their positions in a meaningful way but who are able to work constructively with others and who are respectful of the process. Dr. Pavia said that the Working Group is discussing how to round out its numbers meaningfully; if there are too many members, he said, no work will be done.

Dr. Scheidt emphasized that in conducting community-based research, the community needs to be engaged throughout the process.

Public Comment

Ms. Kelli Ann Davis, an autism advocate and founder of CoMeD (Coalition for Mercury-free Drugs), said that there is mistrust in the autism community, so transparency and public participation are very important. She took issue with the inclusion on the panel of Ms. Lisa Randall, who, said Ms. Davis, is a consultant for the Immunization Action Coalition, which, she said, is funded by pharmaceutical companies.

Mr. David Kirby, a journalist and author of “Evidence of Harm: Mercury in Vaccines and the Autism Epidemic,” took issue with Dr. McCormick’s earlier remark about reassuring the public. He said that confidence is not promoted when people have genuine questions and get only reassurance. He spoke about the need to encourage industry to produce more monovalent vaccine, to identify children with mitochondrial disorders before vaccination, to revise the vaccination schedule or to have alternative schedules, and to investigate lifetime risks.

Mr. James Moody is a practicing attorney and executive board member of SafeMinds and the National Autism Association. He said that there is a public health crisis; one in six children is profoundly affected in a pattern that correlates with the increase in vaccine administration. The vaccine schedule as a whole, he said, has not been subjected to the kind of safety testing new products should expect, with animal testing preceding human application. There have been no clinical trials looking at long-term impacts. Mr. Moody said that since the vaccine schedule has not been validated, vaccine administration is a population-based experiment; therefore, in the Government’s war on infectious disease, those promoting vaccine use could be considered war criminals. People, he said, must be able to make their own decisions, not those making the profits.

Ms. Tracy Stewart is Vice President of the Florida chapter of the National Autism Association. She spoke of the need to identify persons who have immune problems before the administration of vaccines. She spoke of concerns regarding prenatal exposure to vaccines in mothers who have high cytokine levels and cited studies retrieved through a PubMed search. Ms. Stewart said that there is strong evidence of immune dysfunction in autism and conjectured that vaccines may exacerbate existing problems. She said that she gets angry when people imply that our scientific understanding of these matters is complete, but she ended by expressing trust in the Working Group members and said she was certain that they would do the right thing.

Dr. Louis Cooper is Professor Emeritus at Columbia University and a past president of the American Academy of Pediatrics. Dr. Cooper said that he was pleased that the Working Group exists and that he trusts the integrity and the humanity of the Working Group members. The source of division, he said, is the gaps in our knowledge; people will give their support when they have evidence they can trust. He added that there are gaps in the existing processes of public engagement as well as in scientific knowledge.

Ms. Nadia Karimi spoke on behalf of her mother, who is the treasurer of the National Autism Association, and her brother Kyle, who has autism. She indicated that the National Vaccine Compensation Program freed vaccine manufacturers from lawsuits and led to the development of many more vaccines. She noted that the increase in the number of vaccines corresponds to an increase in the rates of childhood cancer, diabetes, asthma, rheumatoid arthritis, attention deficit disorder, bipolar disorder, and autism. She said that we have produced the sickest generation ever in America. Ms. Karimi said that with the exception of a few thimerosal studies, there have been no studies of vaccine adjuvants. She claimed that a 2007 CDC-sponsored study that reported no causal relationship between thimerosal and neurological problems did, in fact, show associations between thimerosal and autistic symptoms. She said that thousands of children have suffered needlessly because of the Government’s failure to act. She insisted that investigators should have no ties to the vaccine industry. Vaccine adjuvants should be tested individually and in combination, and she said that the National Autism Association requests that HHS declare autism an epidemic.

Ms. Terry Poling worked as a critical care nurse for 13 years and graduated from Boston University with a degree in law in 1993. Her daughter Hannah developed autism following her receipt of nine vaccines in 1 day in 2000. The Federal Vaccine Court found that the vaccines had aggravated an underlying mitochondrial disorder. Ms. Poling said that she believes the vaccines produced a need for energy that the mitochondria could not produce and that this happened at a critical point in Hannah’s development. She said that mitochondrial dysfunction should be taken as a biological marker for a risk of autism following vaccination and that this should be a focus for research. We need to develop methods and criteria to screen for susceptible children, she said. We need to learn how to immunize them safely; we may need to wait to vaccinate until critical developmental milestones have been met. Ms. Poling said that she was impressed with ISO’s Scientific Agenda but is concerned about a reliance on VAERS, which she feels that few people know about. In closing, she said that public health leaders are facing a paradigm shift; the mitochondria have furnished a very strong lead for future research.

Dr. Vicky Debold is Director of Patient Safety at the NIVC and Research Director of Children’s Health and Safety Research, LLC. Previously, she was on the faculty of the University of Michigan School of Nursing. Dr. Debold said that it took 2 years, following the onset of her son’s long-term health problems, before she was willing to attribute them to the vaccines he received at 15 months of age. She reported that there had been a mild reaction to a previous set of vaccines. Neither she nor her pediatrician had recognized this as a sign that her son was at risk for more serious vaccine reactions. Dr. Debold said that one area in need of immediate improvement is in medication errors such as accidental exposure, incorrect dose, or incorrect route. A larger issue, she said, involves coadministration of vaccines. She also spoke of the failure of medical personnel to recognize the importance of challenge/rechallenge. In closing, Dr. Debold said that we need to instruct physicians that they can meaningfully share decisionmaking with their patients and that vaccines can be administered in a flexible way.

Dr. Douglas Wallace is a professor of pediatrics at the University of California, Irvine, and Director of its Center for Molecular and Mitochondrial Medicine and Genetics. He also serves on the Scientific and Medical Board of the United Mitochondrial Disease Foundation (UMDF). Dr. Wallace offered his credentials as a concerned parent as well as his scientific credentials; his wife, who has two master’s degrees, has spent the last 23 years caring for their autistic son, who will never live independently. The UMDF supports vaccination but has always recommended spacing vaccines as far apart as possible to limit the challenge to the system. He noted that a severe infection would cause more systemic stress than a vaccination but that vaccination is a stressor we can control. Therefore, he said, we need a more careful consideration of how vaccines may be used to maximum benefit. One question to be asked is whether vaccination can initiate an incipient mitochondrial disease. Dr. Wallace said that there are insufficient data to answer that question but cited studies of Leigh syndrome showing that mitochondrial disease can be precipitated. Traditionally, medicine has been organized around anatomy, making systemic questions difficult to grasp. Systemic disease, Dr. Wallace said, is about energy, and energy is about mitochondria.

Ms. Patty Healy, NIVC Director of Counseling, spoke briefly about the lack of studies comparing vaccinated and unvaccinated persons. She said that she has not vaccinated her 8-year-old daughter, who is as healthy, mentally and physically, as any child.

Mr. Charles Mohan, UMDF Executive Director and Chief Executive Officer, said that the UMDF has already pledged over $6 million for research on mitochondrial dysfunction and that he looked forward to being able to contribute the patient base or other resources of the UMDF in continuation of the kind of dialogue being proposed.

Closing Remarks—Andrew Pavia, Daniel Salmon, John Iskander, Bruce Gellin

Dr. Pavia noted that it had been a content- and emotion-packed day but one without conflict. He said he believed that all parties listened to each other. Dr. Pavia committed the Vaccine Safety Working Group to listening to public input through whatever processes are put in place and to sharing information.

Dr. Salmon thanked the Working Group members and the audience for sharing their personal experiences and expertise.

Dr. Iskander was moved to remind some of those offering comments that the people seated at the table were not just “suits”; they, too, have stories. He mentioned that he himself has a nephew with autism as well as family members who have died from vaccine-preventable diseases.

Dr. Gellin said that the National Vaccine Program Office is mandated to coordinate vaccine activities across HHS. He repeated Deputy Secretary Troy’s statement to the effect that this is a priority of the department.


Last revised: July 7, 2008


HHS Home | Questions? | Contact HHS | Accessibility | Privacy Policy | FOIA | Disclaimers

The White House | | Helping America's Youth