Note: Intermittent technical difficulties with the recording equipment at this meeting resulted in the loss of brief portions of the audio, which are indicated in this transcript by "(Inaudible)" or by underscores.

http://www.hhs.gov/nvpo/nvac/transcript_apr08.html

DR. CORNELIA DEKKER: - professor of pediatrics and infectious diseases at Stanford. I'm a ____ member. I'm a PI for our ____ site at Stanford. My research in vaccine clinical trials is funded by NIH and through CDC I have to ___ funding for the vaccine safety - immunization safety assessment centers. Thank you.

DR. CARMEN COLLAZO-CUSTODIO: Good morning, my name is Carmen Collazo. I am at the Food and Drug Administration Office of Vaccine.

DR. FLORENCE HOUN: Florence Houn, Food and Drug Administration Office of Vaccine.

DR. ROBERT BALL: Food and Drug Administration Office of Biostatistics and Epidemiology.

DR. BENJAMIN SCHWARTZ: I'm Ben Schwartz. I'm in the National Vaccine Program Office as the Senior Science Advisor.

(INAUDIBLE)

MS. TAWNY BUCK: Good morning, I'm Tawny L. Buck and I am the one with the very short bio in the program. By profession, I'm a high schoolteacher, but I believe I'm here because I am the parent of a vaccine-injured child. I have three children and my oldest daughter was injured by Pertussis vaccine in 1995. I am also the Vice-Chair of the Advisory Commission on Childhood Vaccines.

DR. STEVEN GOODMAN: Hi, I'm Steven Goodman, I'm the acting director of the Division of Biostatics in the Johns Hopkins Oncology Center. I was trained as a pediatrician but then become an epidemiologist and biostatistician. I have joint appointments in the Department of Pediatrics, Epidemiology, and Biostatics and I was also a member of the IOM Immunization Safety Review Committee that Dr. McCormick so ably chaired.

DR. DANIEL SALMON: Good morning, I'm Dan Salmon, I'm a vaccine safety specialist with the National Vaccine Program Office.

DR. ANDREW PAVIA: And we have additional members who aren't able to join us in person who should be on the phone and if you are able to, I would like you to go ahead and introduce yourself; otherwise, I'll mention who is on the phone link.

DR. ELIZABETH MILLER: (INAUDIBLE)

DR. PAVIA: We can hear you very well, thanks.

DR. MILLER: Okay, I'm part of the Immunization Department of the Health Protection Agency in London. Our responsibility is monitoring the National Vaccination Program, looking at the efficacy of vaccine. ______ for monitoring safety, but my department does ____ where there is a problem identified ____ or other methods. And we are funded via the government and ___ sponsorship. And previously, I had been a member of the London ____ Advisory Committee on Vaccine Safety.

DR. PAVIA: Thanks.

MS. TRISH PARNELL: (INAUDIBLE) of infectious diseases and ____

DR. PAVIA: Thank you Trish.

UNKNOWN MALE VOICE: (INAUDIBLE) ____ I'm chairman of the _____ for Vaccine Safety.

DR. PAVIA: Thank you very much.

DR. RENATA ENGLER: (INAUDIBLE)

UNKNOWN MALE VOICE: Thanks. And you've got a lot of static on your line so if you could mute when you're not speaking, that would be helpful.

DR. ENGLER: Okay.

DR. PAVIA: Is there is anyone else who needs to introduce themselves who's on the phone bridge? Well good. Again, thank you very much everyone for participating, for your interest, and for the work you're going to do. I think as you can see, we're all getting to know each other. This is the beginning of a process. We are going to be working out exactly how we are going to proceed with writing our report after today's session. In today's session, we are going to hear from the CDC about their five year safety agenda from the Office of Immunization Safety and we are going to hear about more of that in detail. I think, ____, can people hear me? It's probably a good time to mention that this meeting is going to be transcribed so that it is available for everyone to review the records of what happened in the future. There are a number of other mechanisms for taking public input so if there are moments when the sound system fails us, you can go back and find out what was said, but hopefully we'll work smoothly from here. What I think you're seeing is that in putting together the working group so far, we have assembled members of ____ and by charter that includes representative - of industry representatives of the public and a variety of academic interest, but we've also brought in expertise in areas that are quite broad including but not limited to genetics, drug safety, immunology, statistics, ethics and law. Dr. Gosta is not on the phone with us and we've also included very purposely experts from systems outside of the U.S. so we can get an independent perspective on how to do things best and we're very grateful to Drs. Miller and Lambert for joining us in this effort. As I have said, the process today for this working group is predominantly to hear about the long term five year strategy that has been put together by CDC's Office of Immunization Safety. It will become very clear as we talk about things that that is one piece of the puzzle and the machinery that's involved in determining vaccine safety. And we're very cognizant about it, so we are charging this working group with two tasks.

The first, and there is - I'll read it just so that we're a little more clear cut. The first is to undertake and coordinate a scientific review of the ISO's five year agenda and there are specific questions that we are going to try and address and we will offer up additional questions as well. But these include, are the topics on the agenda appropriate, are there other topics that should be answered - that should be included, and we've been asked to try and come up with a sense of priority, that is which of these questions are most important and should be the ones that receive the greatest amount of resources. I think it's very incumbent on us to also think about where extra resources may be needed in the future. We're going to look at possible scientific barriers to ___ research agenda and to the degree that we can come up with suggestions to CDC for how to implement these. Karen is going to explain the process at CDC but they will take our advice as well as input from a broad range of public participants and use that to refine their scientific agenda as they go forward.

But what I wanted to mention briefly is the second task that we are asking the working group to undertake which I think is a larger one but perhaps even more important and that is to review the current status of the vaccine safety research efforts and to work on creating a what I've called the white paper for lack of a better term, but a report on the system and where it should be moving in the 21^st century to get the best possible science and that will be an effort to identify gaps and opportunities and the kinds of resources and the kinds of partners that need to be brought in going forward.

I want to talk a little bit about our expected outcomes. We are not going to leave here with a report on the safety agenda. We are really going to be here to hear about it and to listen to vast questions. The committee will then - the working group will then go forward and do its work and perhaps a report. Now, advice to the government has to come through the NVAC, so the working group's report will go back to the NVAC that will vote on it and then it gets presented to the government from there. But the second piece of what we're doing today is to try and begin what I hope is a long and much better process of improving transparency, improving communication, and public trust. There's been a lot of anger and a lot of distrust over issues of vaccine safety and what's needed in my opinion and I think we'll hear a great deal more is a very comprehensive and thoughtful way for different voices to be engaged and to do that we have asked a panel of people representing different voices and different expertise at 2 o' clock to speak to that specific issue. What are some of the mechanisms that can be used and that will work to make sure there is real public dialogue ___ engagement that people's voices are heard? We then have about an hour for public comments. That's quite limited, I know. We have asked people to register in advance and to limit the comments to five minutes but there are going to be many other opportunities for comment here. I want to make that clear from the front. One is since we are in the modern era, one is electronically. Written comments that come to NVPO working group will be posted on the NVPO website so that we will all have a chance to review them but they will be there for the public to see. So, if you have material to submit please be aware that it is going to be in the public domain but we would appreciate that. This meeting is being transcribed and I hope that what comes out of the session this afternoon are some novel ideas for how to move forward and from that a commitment I think for ways in which this working group can hear from the public, but probably much more importantly since we are independent outside people that the government scientist and physicians who are responsible for vaccines and vaccine safety, have much better ways to interact with the public and have meaningful dialogues.

I think with that, I am just going to ask members of the working group if they have questions or comments they want to make at this point - one thing that I do want to throw out to the working group for us to think about as we go forward is have we done an adequate job of constituting this working group? Do we have all the experts around the table? Do we have all the voices represented? Are we going to want to bring additional people into the working group? Are there questions or comments about the process or anything we have talked about so far?

DR. GUTHRIE BIRKHEAD: Could you just say a little bit about the anticipated timeframe of this process?

DR. PAVIA: Yeah. Thanks Gus. Clearly, we need time to put together a report that's going to take a series of conference calls and some drafting. We need time to digest and hear the public comments that are both made today and that are going to be posted and to put that together. I'm anticipating, based on past experience and Dr. McCormick has far more experience at this than I do, but we're looking at three to four months to draft a report and submit it to NVAC so it would probably - I think we might commit to having it ready for consideration at the fall meeting.

UNKNOWN FEMALE VOICE: Just one question. I was reading through this. There were two things that struck me in terms of variants where there are some important questions and I am not sure if we have the expertise on this subcommittee to just flag these. And one is the area of hereditary immunodeficiency syndromes and the other is the area of hereditary metabolic syndromes and ___ mitochondrial defects and I think that it might be good in the future. I know that today we're not even really poised to dig down that deeply but in the future it might be good to have one or two experts in this specific ___ areas as a member of this working group.

UNKNOWN MALE VOICE: Thanks.

DR. PAVIA: That reflects thought that I've had as well. Any comments along those lines? (INAUDIBLE)

UNKNOWN MALE VOICE: My suggestion - we've put (INAUDIBLE) who we'd have in the working group and we find to be fairly complete. My suggestion would be that we have some discussion among the working group regarding what additional areas might be useful. We give consideration to comments we have already received among - from the public and then as the ____ you know, we go from there.

MS. BUCK: I would like to just make a quick comment. I am basically the consumer voice on the panel and I would encourage perhaps additional consumer representation. I represent an injury from quite a time back and I believe that there is a lot of expertise out there for working on and identifying that public - improving public trust in this process is important. I believe one way to do that is to include more than one consumer voice on this. So I would like you to consider that.

DR. CHRISTOPHER CARLSON: Thanks and I think that's pretty much what we want to do in this discussion this afternoon - how to do that. I was going to ____ given that I don't think anybody here knew I had a child with Asperger's. I wasn't selected as to represent that community and given the current public - public debate/discussion, it would be helpful to have a _______.

DR. PAVIA: Part of what we wanted to do was to have the group itself refine its composition. We didn't know - I didn't quite how to lead consumer groups in a fair and balanced way and I felt we needed to work on that together and then as far as scientific expertise we though that would evolve as we spoke. You'll notice that we also put up ____. There are many ways we're sort of capturing the ideas here, but it would be helpful as key issues come up if we write them down and it's clear that - there will also be questions about - I anticipate that are not CDC ISO issues but that we want to keep very much in our mind for our later deliberations about the white paper and so that this may help us just take issues that we cannot really address today put in what facilitators like to call parking lot and then have them so we can come back to them. Are there comments from the ___ about composition or about the process? We're actually running just a little bit of ahead of time so _______ turn it over to you and your colleagues to introduce the main topic.

DR. JOHN ISKANDER: Thanks very much. The purpose of these introductory remarks is to provide a brief scientific and historical context to NVAC's review of the Immunization Safety Office or ISO scientific agenda.

UNKNOWN MALE VOICE: John, would you pull your microphone down just a bit, please?

DR. ISKANDER: First, I would like to thank the Deputy Secretary, Troy, for his attendance and support. I would like to express CDC's sincere appreciation to NVPO for organizing this meeting and thank the NVAC reviewers for agreeing to undertake this important review. I also want to thank the members of the public in attendance today for their interest and last but not least I want to acknowledge the contributions of the large number of scientists who have contributed to the development of the draft ISO agenda. The ISO mission is focused on assessing the risk of vaccines and we are strongly committed to fulfilling that mission. We recognize that no medical product is completely without risk but risks must ultimately be weighed against benefits and that vaccine safety research is a broad field that encompasses numerous areas other than risk assessment. Our office is engaged in broader science and policy initiatives related to vaccine safety, for example the revision of the national vaccine plan as well as activities at CDC and FDA around patient safety and medical product safety.

In 1986, Congress asked the Institute of Medicine to assess the causal relationship between vaccines and specific safety concerns referred to as adverse events. 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 Institute of Medicine attributed a poor understanding of adverse events to limitations in knowledge and research capacity. Deficiencies identified included insufficient or inconsistent information from case reports. In 1990, CDC and FDA created the Vaccine Adverse Event Reporting System or VAERS in response to the National Childhood Vaccine Injury Act. 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 follow up of many population-based epidemiologic studies and limited ability to provide persuasive evidence for or against vaccine causation. The Vaccine Safety Datalink or VSD, a collaboration between CDC and eight managed care organizations, was established in 1990. VSD investigators have published more than 80 peer reviewed studies and have established themselves as leaders in both scientific methods and infrastructure development for medical product safety. The IOM also noted inadequate understanding of biologic mechanisms underlying adverse events. The Clinical Immunization Safety Assessment Network or CISA serves as ISO's clinical research platform for addressing such questions.

It is reasonable to ask why gaps still persist in vaccine safety knowledge. Reasons include the rarity of serious adverse events, the difficulty of high quality scientific study, the newness of vaccine safety science relative to the field of vaccinology, and the broad scope of the field which encompasses all licensed vaccines and numerous known or suspected adverse events. There is, therefore, a need to collect, organize, and prioritize vaccine safety studies using tools such as the development of this scientific agenda so that we can continue to address the most important safety issues of concern and the remaining gaps in our knowledge of vaccine safety. We are looking forward to working with NVAC and NVPO in this endeavor. This slide provides an overview of presentations you will hear from ISO this morning and this afternoon. Dr. Karen Broder will be our presenter for the background information and draft recommendation sections. Dr. Dixie Snider will present considerations for prioritization as part of this afternoon's session. I will turn it over to Dr. Karen Broder.

DR. KAREN BRODER: Thank you. Good morning and I appreciate the opportunity to present some background information about CDC's Immunization Safety Office Scientific Agenda Development for the NVAC Vaccine Safety Working Group on behalf of the Immunization Safety Office of CDC. More information is also provided in this first talk in a background document that the working group received in their passage. This document is also posted on the CDC website. Resources are provided at the end of this first talk.

As we heard earlier, Centers for Disease Control and Prevention is one of several programs and agencies involved in vaccine safety in the federal government. At CDC, the Immunization Safety Office or ISO leads most of the agency's vaccine safety research and surveillance activities for vaccines used in the civilian population. Since 2005, ISO has been a part of CDC's Office of the Chief Science Officer, Office of the Director, and its mission as well as its supervisory and funding chains are distinct from other immunization programs at CDC. As Dr. Iskander describes, the mission of the Immunization Safety Office is to assess the safety of vaccines administered to children, adolescents, and adults. And we seek to accomplish our mission by working closely with partners to support and develop high quality research and surveillance, to communicate this work in a clear and transparent manner, and to develop scientific methodology and standarized case definitions in the field of vaccine safety science.

Our office has four principal research and surveillance components that conduct vaccine safety activities. These are reviewed in detail in the materials that the working group received. Briefly, the Vaccine Adverse Event Reporting System or VAERS is a passive surveillance system that is jointly operated by CDC and the Food and Drug Administration. VAERS identifies vaccine safety areas of potential concern and generate hypotheses. The Vaccine Safety Datalink Project is a collaboration between CDC and eight managed care organizations. VSD provides comprehensive medical and immunization histories for more than 5.5 million people annually and VSD tests hypotheses suggested by signals from VAERS or other sources. In addition, VSD conducts vaccine safety surveillance in near realtime. The Clinical Immunization Safety Assessment Network or CISA is a collaboration between CDC and six epidemic centers with vaccine subject matter experts. CISA studies the pathophysiology and adverse events following immunization. In addition, CISA studies risk factors including genetic associations for the development of adverse events following immunization. Finally, the Brighton Collaboration is a global collaboration that develops standardized case definitions related to vaccine safety by improvising a common vocabulary for vaccine safety research and surveillance that is used throughout our office and in other venues as well. The fourth component is interrelated and the slide shows how we work very closely together in our office. In addition, the Immunization Safety Office collaborates with many immunization and other partners not shown here including other CDC programs and FDA on a daily basis.

In the rest of this presentation, we will focus on development of the first office ISO scientific agenda which is referred to throughout these talks as the agenda. As Dr. Gellin mentioned earlier, one of the driving forces behind this agenda was a recommendation out of the IOM report in 2005 titled Vaccine Safety Research Data Access and Public Trust. And I'll just note that this report was different from the reports that came out of the Immunization Safety Review Committee earlier. In this 2005 report, IOM recommend that a subcommittee of NVAC that includes representatives of a wide variety of stakeholders review and provide advice on the Vaccine Safety Datalink research plan. They went on to state that the group should meet publicly and allow interested persons to observe the process and provide input through established mechanisms. In addition to being responsive to this 2005 IOM recommendation we just discussed, carrying out effective vaccine safety science activities requires integration across the Immunization Safety Office research and surveillance activities. So focusing on the entire office agenda rather than just VSD makes sense. Also, an agenda will promote scientific excellence and public trust through transparency and it will contribute to vaccine safety science and other patient safety initiatives. The objective is to develop a comprehensive five year Immunization Safety Office scientific agenda with extensive expert input. The scope covers vaccine safety research, selective surveillance, and selective clinical guidance activities that are part of ISO's mission, are in ISO's realm to lead, and could be implemented during the next five years with infrastructure generally accessible to CDC. The ISO's scientific agenda focuses on scientific activities. It does not cover other very important activities of vaccine safety such as communication activities.

During 2006 through 2007, CDC, the National Vaccine Program Office or NVPO, and the NVAC Subcommittee on Vaccine Safety established and implemented a process for developing the scientific agenda. First, ISO and CDC developed a draft agenda which the working group has received and this is what we will discuss today. In developing this draft agenda, we solicited external and internal input from scientists with diverse expertise. ISO staff synthesized input to establish the draft recommendations which we will review this morning. Starting today, the NVAC through its working group will facilitate a scientific review of the draft ISO scientific agenda and after the NVAC scientific review is complete, ISO and CDC will respond to the feedback from the NVAC review process and finalize the scientific agenda. ISO and CDC will carefully consider the feedback from the NVAC review process, but it is important to notes that it is the responsibility of ISO and CDC to make final decisions about the content and priority on the ISO scientific agenda.

We recognize that obtaining external input before this and the scientific review would enhance the quality of the agenda and help inform the review which we are beginning today. During May 2007 through November 2007, CDC and NVPO convened three scientific meetings to obtain input on the agenda from the following groups and many of these people are represented in the room today. External expert scientists, vaccine safety representatives, federal government, HHF agencies in the Department of Defense, and U.S. vaccine manufacturer representatives. Reports from these meetings were included in the working group briefing package and these will be posted for everybody on the CDC website in the near future.

In addition to the planned meetings, ISO obtained input from its day to day partners including ISO Research and Surveillance Team and ISO Writing and Reviewing Group which was formed in January 2008 and CDC immunization experts and other stakeholders including persons involved with the advisory committee on immunization practices. We also obtained unsolicited input by reviewing selected ___ key statements, IOM reports, and the literature as well as other sources. Public input is important and approaches for obtaining public input for the scientific agenda as you heard earlier will be discussed during the meeting today.

This is just a reminder of the charge that Dr. Pavia discussed earlier. CDC has asked that the NVAC Vaccine Safety Working Group undertake and coordinate a scientific review of the draft agenda and specifically we are asking the working group to advise on the content of the agenda which we will review shortly, to help us learn about prioritization for the topics, and to identify and suggest ways to address possible scientific barriers for the agenda. Today, we will begin discussions about the agenda's content and priorities. We appreciate the working group's efforts and look forward to collaborating today and during the coming months. And the next recommendations could be about the draft recommendations.

In closing, on behalf of the office I would like to thank the more than a hundred people represented by the groups listed on this side who during the past year have contributed to the development of this draft agenda including Dr. Pavia, Dr. Gellin, and Dr. Salmon. And we also really want to thank Dr. Skillen from the Immunization Safety Office for her assistance in preparing the documents for this meeting. Resources are provided on this slide. Thank you.

DR. PAVIA: Thank you Dr. Broder. I think perhaps what would be most efficient is if we go on to the next section you talked - then we have some time to talk about the process that you want ___ develop these recommendations, as well as this first portion. Then I think rather than do the specific content areas in question and then break, we will take our break before that, have you present the content variants, then we can discuss those because that will, I think, take a good deal of our time.

DR. BRODER: Thank you. In this next very brief presentation, we'll provide an overview at the draft ISO scientific agenda recommendations. This is the document that we will be following. The working group should have this document titled Centers for Disease Control and Prevention Immunization Safety Office Scientific Agenda Draft Recommendations April 4. In addition, we provided one additional handout as a late breaker for this discussion. What we will be talking about now are the three recommendations which are sections one to three of the document.

The agenda makes three broad recommendations. The first is to respond to emerging issues and conduct core required scientific activities. These are all for the Immunization Safety Office at CDC. The second is to enhance vaccine safety, public health, and clinical guidance capacity in seven areas. And the third it to address five year research needs. To respond to emerging issues and conduct core required scientific activities, ISO ___ to do the following. We need to monitor the safety of all newly licensed and ___ recommended vaccines and previously licensed vaccines with new recommendations. The office needs to respond to new vaccine safety concerns and hypotheses which continuously emerge and are generally not predictable. We provide technical consultation to CDC, immunization experts, and multiple other stakeholders on a daily basis for collaborative and multidisciplinary scientific activities including activities that are not directly a part of our mission but involve subject matter expertise investing safety. And lastly, we need to be prepared to monitor vaccine safety in the event of a mass vaccination campaign or other vaccine safety emergency for example as part of pandemic influenza preparedness.

The second broad area of the recommendation section 2 is two enhance vaccine safety public health and clinical guidance capacity in seven areas - an infrastructure for vaccine safety surveillance in our Vaccine Adverse Event Reporting System which again is jointly operated with CDC and FDA, an infrastructure for Vaccine Safety Surveillance and Research using our Vaccine Safety Datalink Project. We need to enhance capacity in epidemiologic and statistical methods for vaccine safety science and laboratory methods for vaccine safety science in the newly emerging field of genomics and vaccine safety, for case definitions, data collection, and data presentation for adverse events following immunization. And in addition, we strive to enhance capacity in vaccine safety clinical practice guidance.

The third recommendation area is to address five year research needs. These needs are classified into specific vaccine safety questions and three scientific thematic areas. The thematic areas are vaccines and vaccination practices. We will discuss these more after the break. There are eight items. There were seven vaccine specific questions. In the thematic area of special population, there are seven items. And in the thematic area of clinical outcomes, there are eight items. This concludes the overview presentation and the last content presentation is a more detailed look at the five year research needs.

DR. PAVIA: Thanks. So Karen if you would not mind putting slide 22 back up. There is a lot of information on that slide and I think that was a very large portion of this first group of recommendations and what I would like to do now is to throw it open to questions and comments about the presentation so far and particularly about the areas that we have shown up here, the area of capacity improvement. I'm going to move over so that I'm in the front, not speaking from the side.

DR. GOODMAN: I just have a question. It was mentioned that the issues of communication are not part of the ring yet. Who handles that and how is that coordinated?

DR. ISKANDER: Vaccine safety communication which might include risk communication activities might include communication activities related to scientific publications. Our office does have a communication staff and we also would coordinate that with other relevant communication staff in relevant CDC centers including the National Center for Immunization and Respiratory Diseases, the Office of Director's Communication staff, as well as communication staff from other federal agencies. So communication is actually a very significant portion of the day to day work that we do and again we do have some staff dedicated to that, but there is also - one of the themes I think that is sort of emerging is there is a very heavy piece of ___ that is coordinating with partners with other parts of CDC and other federal agencies.

DR. GOODMAN: Is that an area that is thought to be an area where research can be done or is it just an issue of communicating conclusions?

DR. ISKANDER: To answer that question, let me provide a brief historical context to that. At one time, there was a group within our office that focused on vaccine risk communication research. Their expertise were in areas such as behavioral science and survey research. As part of a review of our office which was undertaken about four years ago, at that time it was determined that those activities while important were not consistent with a focus on risk assessment and so those activities were moved to another part of CDC. It is important to note that that group did produce I think some very important research and my understanding is there are now some sort of targeted communication materials that they helped develop that are being pilot tested. So while we recognize that as in fact a very important area of research, right now it is neither part of our office as a mission nor do we have the capacity in terms of specific subject matter expertise to be able to undertake or lead that type of research.

DR. PAVIA: ___ part of our second charge, if we find areas like this that don't fit into ISO that we think need to be addressed, that's for us to keep in mind and to work on.

DR. DIXIE SNIDER: This is Dixie Snider. I just wanted to elaborate a bit - reemphasize what John said that this is really a very important activity. One of the problems, and I'm speaking because as a science officer I was involved in making this decision, is that as people do work on communication, some aspect of that work is clearly or can be perceived as work to allay people's concerns or to help promote vaccines and one of the reasons that the Immunization Safety Office was moved out of the National Immunization Program and into what was my office at that time, now Dr. Boboik's office was to address issues that had come up that some of the people in the room are very familiar about the vaccine safety people being focused on vaccine safety and not being perceived as being part of a vaccine promotion enterprise.

DR. MARIE McCORMICK: In thinking about your office, who do you see as your primary audience? Who are you talking to and to whose concerns are you listening?

DR. BRODER: For the agenda recommendations?

DR. McCormick: Yes.

DR. BRODER: Our primary users of the agenda will actually be the scientists in the office that will be carrying out the agenda. The agenda also will help define scientific areas that will guide other vaccine initiatives, other patient safety initiative. We are writing our agenda to try to define the best science in a transparent manner and to try to involve and obtain input from a wide variety of stakeholders.

UNKNOWN MALE VOICE: Be specific Marie.

DR. McCORMICK: (Crosstalk) If you are designing the research, you better design the research for somebody and so my question is who are - and even if you're talking about the agenda, the agenda is to set a research priority for an office that is responding to someone and so my question is who do you see is your primary audience?

DR. SNIDER: John may have some additional comments, but I do want to point out that users of the information from the studies that have come out of the Immunization Safety Office include the Advisory Committee on immunization practices as they develop their recommendations, they include the Food and Drug Administration which uses this information to make regulatory decisions and obviously the public is of a particularly important target audience for the risk assessment information comes. There are others as well but I think those policy making groups are particularly important and on our minds as we complete these studies and communicate the findings. John?

DR. ISKANDER: Just to reinforce that, we do see an important part of our mission is to make sure that while we are not the policy making body for vaccines that we work very closely with the advisory committee and immunization practices and we want to make to sure that we have the very best vaccine safety data and information available, again recognizing - coming back to one of my initial points that ultimately while we do not- we have been separated from the policy making body, that those decisions of weighing known risks and known benefits must ultimately be made to have well informed vaccine decisions and we see are pieces of the puzzle as providing that best available safety data to inform those recommendations.

DR. LARRY PICKERING: Marie, one thing from - Larry Pickering, ACIP. At each ACIP meeting, there is a vaccine safety slot on the agenda during which safety issues for all new vaccines are discussed. So those discussions may resolve in changes, enhancements, alterations, or whatever to the recommendations of the ACIP has made and that is done at each meeting. In addition to that, the work groups, there are 14 ACIP workgroups and on each appropriate workgroup where immunizations recommendations may be considered, there is a member of the Immunization Safety Office and so vaccine safety issues are considered through the whole course of development of recommendations.

DR. PAVIA: I am going to try to keep track of the order in which people have their hands up and I think - Mark were you next? And then Dr. Goldman and then -

DR. MARK FEINBERG: These are not specifically scientific questions but I think they do relate to our ability to assess the agenda and the first one is - yeah with any activity it has to be right sized and funded appropriately and it's a little difficult to know how to define what the appropriate scope of the research agenda is for ISO without having a sense about what the funding available for that research is and how decisions are made of about funding. The second issue that I would like to raise for the chair or maybe Bruce's input is there is this associated process that this group will be responsible for working is looking at the federal government's response to the very important area of vaccine safety overall and I am wondering how assessment of the ISO as an appropriate piece of that pie as done in the context of what the broader federal response is and what is the appropriate part of federal government to address each specific vaccine safety component.

DR. PAVIA: Thanks. I think that's something that we ought to again keep on our board as something that's very much in our thought process.

DR. ISKANDER: And to provide just some at least minimal degree of specificity to answer Mark's question. You know, our office's budget is a matter of public record and so let me just give some broad outlines in that area. So our appropriation is approximately $21.6 million, approximately $12 million of that goes to the VSD, approximately $4.2 million of that goes to the CISA Network, approximately I believe $2.8 million goes to the VAERS system, and the rest is made up by the remaining activities. As far as the budget process, our appropriation goes to the same you know congressional appropriation process as all other federal appropriations. We have in the past year received some supplemental funding, approximately $1.85 million related to pandemic influenza preparedness. Karen gave some general outlines of the needs in the area, the need to be able to prepare for mass vaccination campaigns and monitoring their safety. So again, just so that in the interest of again full disclosure and so people know in a sense that if you will the general size of the pie that we're talking about you.

DR. LYNN GOLDMAN: ___ continuation of Mark's comments but it struck me when I heard the list of the people who are kind of on the receiving end of the office's work that I did not clearly hear NIH and whether there is any interest in an AID and of course NICHT and some of the areas that are identified by the office as being important in terms of research because some of that could be carried out in those contexts as well.

DR. PAVIA: Anyone - perhaps just leave that up on the board unless somebody wants to comment on that. I think that is a very important question.

DR. GOODMAN: Yeah, just briefly, and I may just be a little confused about all the boxes and circles and charts of the committee, but where - I understand better why issues of risk communication aren't specifically in the ISO Office, but do we - is it appropriate to have that expertise on this panel or is it already on the larger NVAC panel? Where is that input in this process?

DR. PAVIA: That's a very good question that I think I would dodge a little bit by saying we should chew that over as a group. I can see a couple of answers to that. One is we have some risk communication expertise on the NVAC itself. Trish Parnell who is a member of the public and on the phone with us and Sharon Humiston led a group for about two years that dealt with risk communication and public participation, but I think there's probably a lot more that could be done there. The other thing - I'm just - just to reflect back, I think I have heard a lot of times that risk communication is an area that has been separated out from the Immunization Safety Office but we are not sure where it resides and maybe that is something we want to explore in more detail, in particular research in terms of how people think about risk, but I turn that over to the group and their thoughts about it. Sharon, you -

DR. SHARON HUMISTON: I think that is an important point. I don't know that it fits in a logistic section, but I do think that it needs - the science behind risk communication around that seems - needs to be strengthened. We've seen that in the proposals we get for the NVPO grant raise.

DR. PAVIA: Just to reiterate. What we thought would happen is that as we have this discussion with ISO, that many things are going to come up that don't fall into their charge or ability and are going to loom very large and that is why we emphasize that we would be reminisce if we didn't have a second piece where we look for what else needed to be done and who else needed to be charged. And already risk communication has come up, development, and basic science has come up and I'm sure we're just beginning.

DR. CARLSON: So Karen - Dr. Broder had brought up unexpected avenues for research and a five year agenda versus unexpected avenues is always a little bit of a tension. And I am simply curious about within - this budget is going to be a little bit small if there is a lot of investigator initiated research coming from the outside of the office. Is there another avenue for investigator initiated research or is this the official avenue through which investigator initiated research would happen?

DR. ISKANDER: At this time, this is basically be the avenue within such research would happen. There is certainly great interest not only within our office, but I think broadly withIn CDC many of you may be aware of CDC's express desire to have more and broader opportunities for extramural research. There is a small extramural research activity which, although if you kind of trace the budget line item, it is linked to our office but we are actually not involved in the scientific conduct or oversight of that work but it is very small. So - Is that a sufficient answer?

DR. SNIDER: Yeah, if I could just elaborate John? I want to make it clear Julie Gerberding, the Director of CDC, and I have discussed this a number of times. We at CDC would very much be pleased if all those who are involved in the federal budgeting process were to see fit to make additional resources available and use not only to us but to NIH and other places, perhaps, you know, FDA to support the extramural research program would be very open to that.

DR. PAVIA: I ask the question myself because it follows on to the previous line of research. You identified one of capacity building areas as genomics in vaccine safety and I wonder if you could just give us a little bit of your thoughts about where that research might occur within ISO, what portion of it would go outside, what portion might be appropriate for investigator initiated research.

DR. ISKANDER: Okay, I may ask Karen or others to add some follow on thoughts. So NBPO did sponsor a workshop which our office led along with the CDC Office of Public Health Genomics. This occurred in late January of this past year and the objectives of that meeting were to, if you will, provide some introductions among the researchers with relevant expertise and to help set some reasonable research objectives. So to the extent that there is in fact some expertise within the CISA network in this area and in fact it is very congruent with CISA's mission of looking at individual level variation as a potential risk factor for adverse events. We see CISA as the primary platform, again using those criteria that can Karen outlined as sort of things reasonably accessible to us. We also understand that again one of the purposes of the meeting was to make introductions and create potential collaborations that these research platforms, you know, raise and other, you know, whole genome association studies and are more resource intensive and in fact some of the existing studies that are going on right now are collaborations with NIH or have been read by FDA and so we recognize that there is the need for collaboration in that area to undertake, you know, a research program.

DR. BRODER: If I could just add, there are - although it's a new area and certainly there is a need for collaboration and a need to almost define a subagenda in that area, in that session, we have described some activities that are going on in that area, for example a study evaluating genetic risk factors for Guillain-Barr� syndrome after vaccination is going on. There is a study looking at development of rheumatoid arthritis in persons receiving hepatitis B vaccine, a study looking at wheezing, genetic influences on wheezing after live attenuated influenza vaccine, and in addition the CISA network has established a biological depository. So there are some beginnings of that platform in place and I certainly welcome Dr. Dekker or anybody else with more expertise in this area that could elaborate.

DR. SNIDER: So the bottom line is that we are doing what we have the capacity to do. I don't think that we want to present to you any notion that this is completely adequate response to the questions around genomics and vaccines and it's clearly an area where we would really appreciate recommendations not only for us but as you do a broader agenda how the nation especially - I hope Bruce it's not interrupting your authority, but how the whole department can move forward better in this whole area of genomics and vaccines.

DR. PAVIA: Thanks Dixie. I think if I'm, you know, just sort of putting words in your mouth you can stop me, but we have heard over the last couple of questions is a lot of interest in areas that in part CDC can work on through CISA projects but that also requires significant extramural funding programs which are not really in CDC's portfolio and work with a lot of other scientist both within government and outside. Is that fair to say?

DR. SNIDER: Correct.

UNKNOWN MALE VOICE: ___ In the past year, how much NIH funded vaccine safety research has there been? However you want to define that.

DR. PAVIA: Now, I am not sure we have anyone in the room who can answer that, but can - what I think I am going to suggest we do is that we - to some degree we are not an IOM Committee but we can act a little bit like the IOM and ask, if thinks come up like we can request from the department to get back to us and provide us these kinds of information for deliberation. So as we go forward maybe as a group, we out to think that way, the way we would if we were an IOM, when there are questions we want answered that are being asked if can get those through the staff. So one would I think ___ government portfolio on this.

UNKNOWN MALE VOICE: I mean, we have some parts, I mean how many institutes are there in NIH, 30, 23? So we have some representatives. I think part of the what the deputy secretary acknowledges is that there is a lot of this throughout the department and across NIH as well. So I can think that obviously you're welcome to speak here but I think your questions are important ones to see how this strand crosses the federal government particularly within the HHS family.

DR. MCCORMICK: Could you check - this is Marie McCormick. Could you tell me or describe a little bit more detail the organizational locus of the ISO and in particular, was I misunderstanding that this is part of a larger patient safety agenda or did mishear that completely?

DR. SNIDER: No, the Immunization Safety Office as John explained at one time was part of the National Immunization Program and with input from a panel which Dr. Lee Cooper who is here chaired and a large number of public comments subsequently the director, the executive leadership board of CDC decided to put it in the office of the Chief Science Officer. The Chief Science Officer reports directly to the Director of CDC. And so the number of options were laid out and it was decided to put it in the office of the Chief Science Officer at least for a while. And the point Karen sort of subtly made was that what we were responding to were perceptions of that vaccine safety group as being part of a larger immunization program whose interests are perceived as being promotion of vaccines would perhaps not have an unbiased approach to vaccine safety. And so they were moved to the office of the Chief Science Officer so that their supervisor would change and decisions about their funding and so forth would be made in a completely different part of CDC than decisions about immunization ____

UNKNOWN FEMALE VOICE: ____ now that you've had experience for a little while, is this optimal? Is your thinking about your pursuing scientific agenda would this be the place you'd like to stay or is there - are there other places or other organizational loci that might be useful?

DR. SNIDER: The Immunization Safety Office currently, being in the office of the Director, I think to be perfectly honest, I would have to say that anytime you put program activities in an office that deals lot with policy issues presents a challenge. I won't admit to doing a bad job of trying to separate the two and trying to support the ISO and I believe Dr. Popoik has done that. Our patient safety worker that I mentioned is a group that is recently formed while working on a number of things including working with Dr. Woodcock at FDA on the sentinel network which you may have heard about and so part of our charge is to look at where the various components of vaccine - of patient safety including medical product safety, how they might be best organized at CDC and we have not completed our work yet so I don't know the answer of what we think the optimal is.

DR. ISKANDER: Can I just make a brief follow on comment? I think that despite the separation if fact, our work, in my eight years of working with this office we have really never had a more - more collaborations with the immunization center and more issues that we have had to work very closely with ACIP on and you know that has continued and in many ways strengthened despite the organizational separation. The other observation I would make is that if you look at other models internationally. This sort of separation of risk assessment from risk management does really seem to be the model that is, you know, that does seem to be the way that things are going. And so it may suggest that there is for public policy and for transparency reasons that that may be an important consideration.

DR. PAVIA: I was reminded that we should all identify ourselves before we speak so the transcriptionist can recognize our voice and before Sean Hennessy speaks, I just wanted to remind the members on the phone that we are anxious to hear from them if they have questions.

DR. SEAN HENNESSY: Thank you, this is Sean Hennessy. When deciding on a research agenda, it may be helpful to know a little bit more about the infrastructure and the research trajectory that's going on so far and I do not know very much about the Vaccine Safety Data Link or the Clinical Immunization Safety Assessment at work. And I couldn't tell from today's agenda whether we are going to hear more about the details of that or not.

DR. BRODER: If I could just respond. In the - in the interest of time, we've kept goals, took the talk to a very brief overview. In the binder that you received, there is a section both for CISA and for VSDL as well as for VAERS and the Brighton Collaboration where we've describe some more background. We have included project lists and there is also some information about ____ and some web links and so we are certainly happy if - to address any specific questions later if there are specific questions that are not address. I just wanted to bring that to your attention.

UNKNOWN MALE VOICE: Excellent.

DR. GOLDMAN: I have a question, kind of a follow up question about the budget. And what I was curious about is how much do we have in the budget in terms of - I guess Congress has appropriated it, in terms of being able to shift resources between different activities or reserve a certain amount of lock-in in terms of the way you receive the money.

DR. ISKANDER: Well, I will give a, sort of a relatively high level answer, and Dixie we may wish to follow on. Because of congressional concerns dating back 15 years or perhaps even longer than that, there is - when Congress, you know, appropriates certain amounts of funds for certain activity, there is the expectation that those funds will be expended on those activities so not only just across CDC, you know, my understanding is that there is limited ability to undertake that.

DR. GOLDMAN: I guess I was specifically wondering in terms of the appropriation for the ISO. Within that, do you have flexibility or how much flexibility do you have within that?

DR. ISKANDER: My answer would really be the same.

DR. PAVIA: Any questions from members? Members on the phone? Ms. Parnell, Dr. Miller and Dr. Lambert, do you have questions on the first portion. Thank you. I have one last - one question ____. We started to talk about patient safety and we were specifically in constructing this panel wanted to get people involved in the drug safety side of things because the parallels are enormous and in the IOM review recently of the drug safety apparatus, a number of suggestions were made. To what degree are you looking for synergies in developing methods in developing capacities in using resources that can deal with patient safety issues in both drug and vaccine?

DR. ISKANDER: I'll respond briefly but I will ask Dixie also to respond. So many of the methods, you know, scientific methodologies as well as the kind of infrastructure establishment that the Vaccine Safety Data Link has led, you know, we had our annual VSD meeting last year and the constant theme I heard was �it's not just the data� meaning that what they have established is a network of expertise. They are constantly developing and refining new methods and so the extent that those methods may be applicable to broader fields, that is certainly one potential connection that, for example let me give you a specific example, the so called distributed data model - the idea that there is not a single VSD database but rather there are eight sites that maintain strict confidentiality and privacy of their data but that allow again through a distributed network allow studies to be conducted with pre-specified IRB approved protocols. That is a model that is really being look to in many not only FDA read but other product safety read initiatives. So that is my answer kind of from my prospective, but again Dixie may have more policy level issues to add.

UNKNOWN MALE VOICE: Well, let me first go back to Lynn's question because I don't think Lynn - I think there's miscommunication across the table. So let me try to back up. The Immunization Safety Office receives $22 million or $21.6. The way this system works, I think you know this from your prior experience, is that, as John said, you know, Congress has certain expectations that if the appropriate money for X they expect it to be worked - that work is done on X. Agency directors can ask to reprogram money. I was the recipient of that I was Director of the TB Division when we had the problems with multidrug resistant tuberculosis and we reprograms from HIV money to support TB efforts until Congress could convene and provide us more resources. So in terms of possibilities, the CDC Director could request through the department that additional resources be put in vaccine safety through those channels and you know, either Congress would approve or not disapprove and that could be done. So that's - all I can do at this point is just speak for complete openness that that could be done.

With regard to the $21.6 million, it is a determination then of the supervisory team at CDC how to allocate the $21.6 million to VSD versus CISA, versus VAERS, etc. At the same time, I am sure you can appreciate with 30,000 various reports coming in and being joint venture with FDA, that flexibility is sometimes more theoretical than it is realistic and that our contractor is under tremendous pressure already with reports - processing the reports they are trying to get right now. So try to take money out of there right now would have severe implications.

So I hope that that gives you a better kind of idea and then you know with regard to the VSD and CISA, money could be transferred at the same time ____ have been made to certain institutions and individuals and at least for a certain period of time. I'm not saying CDC could make a decision to allocate funds differently and would be interested in your, you know, advice and counsel about, again not specific funding, but where we should put focus on along some of these activities. That's one of the things I am going to ask at the end of the day about some of the relative priorities and how you would allocate resources across some of these activities. But adjustment could theoretically be made but putting them in to the practice on the other hand, you know, presents its challenges.

DR. ISKANDER: Just another brief - I alluded earlier to a small amount of supplemental funding we have received for pandemic influenza activities and undergo circumstances. We do have some ability to develop a �spend plan� for that money as long as it again meets the objectives of pandemic influenza preparedness.

DR. PAVIA: Thanks John. I think what we are going to do now unless there are any questions on this specific section that people would like ask is going ahead and take our break and when come back, we are going to hear about the specific topic areas that have been developed as part of the agenda and have a chance to take down our notes and then we'll again have a chance to come back after lunch and talk about those in addition. I have 10:15, we're going to start again promptly at 10:30.

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UNKNOWN FEMALE VOICE: _______ an MRB human papilloma virus vaccine ____ the licensed product. Two products for tetanus ___ pertussis vaccine for adolescents and adults as well as influenza vaccine. I just wanted to bring that to your attention.

UNKNOWN MALE VOICE: So my sense is that a large percentage of the VSD, particularly rapid cycle analysis studies are done without the need for additional funding, is that right?

UNKNOWN MALE VOICE: Yes, that's correct.

UNKNOWN MALE VOICE: Thank you.

MS. BUCK: This is Tawny Buck and I have a question, forgive me if it's not a real educated one, but I'm every interested in knowing about prevention of adverse events to begin with. Can you tell me how that's being addressed?

DR. ISKANDER: Yes, I can. Thank you for that question Tawny. In fact, this is an emerging area of vaccine safety science. It's actually - one of the categories on this slid, post-vaccination syncope or fainting. We think it may be preventable. There are existing recommendations for a post-vaccine waiting and so we are interested in pursuing and collaborating with studies to answer question like is the waiting period followed? Is the waiting period effective when it is followed? This is where - in fact, we have to recognize that this is now - we're talking about now patient safety issues that have a different scientific focus. We are very interested in this because, as you say, we want to be able to prevent things we can prevent. Another category is that vaccine administration errors which the reporting of those appears to have increased over the last several years, not surprisingly with many new vaccines, products with potentially similar names, and so we have collaborated with one paper on FDA that they actually led where we looked in both drug and vaccine safety databases. One of Dr. Ball's medical offices led that study which is going to be published soon.

So recognizing that these - that that science of analyzing systems is a little different from what we traditionally do. We are still you know very interested in preventable adverse effects and we would anticipate that as the science of vaccine safety builds incrementally, we would hope to add more events to that list of what is potentially preventable.

DR. SNIDER: And I am sure you are very aware of this, but you know examples in the past where we have taken action to prevent adverse events were what the first Rotavirus introduced and when we started getting signals through VAERS and subsequently began to do epidemiologic studies. Even the ____ studies were a complete - we consulted with the CDC Director and with the CIP and withdrew our recommendation and FDA and the manufacturer subsequently made decisions that led to withdrawal of that product from the market. Similarly, you know, despite the lower cost of oral polio vaccine and its value for global polio eradication, we were seeing, I believe the number was seven or eight vaccine associated polio cases in the United States and so the advisory committee on immunization practices recognized the efforts of people like John Salomone and _______. We made a decision to move to inactivated polio vaccine so that we would have _______ vaccines associated polio cases. So sometimes, you know, we can take action and sort of on a grand scale if you will to prevent these things from occurring. I think the other thing I wanted to point out is that we were talking about genomics earlier and this offers a potential opportunity to the future that may not be realized for a number of years. But I think there's enough literature to suggest that certain outcomes such as encephalopathy for example might be, once we have the tools in hand, we might be able to identify children at risk of post-vaccination encephalopathy, the so called post-vaccination encephalopathy by identifying genetic markers for that kind of health outcome.

DR. PAVIA: Thanks, Dixie. Let's - can we move on to a few other questions because _____ do you want to?

UNKNOWN FEMALE VOICE: No thank you.

UNKNOWN MALE VOICE: Okay, good.

DR CARLSON: Chris Carlson. Conveniently, I actually had a follow up on that one. I'm sorry. In the context of what I see here, the prediction of outcome is something that I think is very important and very interesting and I don't see a lot on the agenda. There's a tremendous _____ associated, but we know about things that are associated and I really want to see more research done on predicting those people and genomics, excuse me, I'm sorry, genomics is too expensive for your budget. We - there are some cheaper technologies we might be able to use. I don't see a lot here done about looking at ____ distribution in the population of response to vaccines because we might be able to do pre-administration screening to see who is at risk of an adverse event. I know it's perhaps a ____. I don't mean to put this out to there, but there may people who don't need a particular vaccine because they are at too a high risk of a particular adverse event if we can predict that.

DR. BRODER: If I could just comment on that. A couple of places where we've tried to articulate that. One of them is clinical guidance section where we do recognize the value of putting forward clinical guidance based - based on the evidence for trying to prevent these vaccine adverse events and managing them. Within the research needs topics, I think it may need to be stated, but I think a follow up question in addition to is there increased risk would be, if there is increased risk then we need to understand a little more about the nature of this increased risk and that was what we talked before in the general principle is that if there is an increased risk we're not just asking epidemiologic questions, then we want to know are there particular host factors involved? What is the pathophysiology? Are there sequelae? And in the ____ areas, obviously those kinds of discussions could happen. Certainly open to suggestions on how to improve the wording on the questions to articulate that point. Obviously, if there is no risk on an epidemiologic study then one might need to go back and ask do we need to keep looking at special subpopulations or can we just stop and so I think those are two different issues whether you have a risk and need to move forward ______.

DR. SNIDER: You know today, I mean, in this process what we're trying to - we've learned from you folks is what we should be doing, you know, to try help move this forward, recognizing that there are - there is the need for other players and other people to come in and help complete the portfolio if you will. So we want to do what is in your view and ultimately in our view as well seems to be the right way to help move areas forward even if we can't do the whole thing, but we realize we can't do it all so now - and we're not saying also that just tell us things we can do within the constraints of our budget. I mean, if you tell us what we need to do then, you know, we will do the best we can by allocating resources or obtain resources to do it, but we we're not really ____ have a budget, you know, discussion or a discussion about what other agencies should be - should be doing. We hope you will take that up later on. I feel that you probably will and make it part of your larger ____.

DR. PAVIA: We appreciate that. It sounds like you really want to see what needs to be done and then you and we will go out and figure out where that money is going to come from.

UNKNOWN FEMALE VOICE: I'm looking over the list. I'm hard pressed to think of other issues in terms of individual matters, ____, and some of the literature that I'm aware of when the hypothesis ____ as well. I think _______ which is the area of population base effects and there has been a lot of research for example on a ____ hypothesis, children being immunized has changed the rates _____ I think that may be slightly out of the scope of the safety office but I do think it's important and one reason I'm raising it is that I do think that that kind of research is being funded elsewhere and might provide an opportunity to look at some other issues.

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UNKNOWN FEMALE VOICE: We're still on the drawing board, and I've had an opportunity and the NIAD has an awful lot going, on and some of the areas that kind of connect with this ______(INAUDIBLE) what's going on in relation to this.

BARBARA MULACH: This is Barbara Mulach. So I haven't had a chance really to go through the exact specific medicines that you questioned and talked about, specifically what we're doing, but I will say in particular some of the things we're doing that's flu vaccine research. I'm sure there are areas of collaboration, and we were close to the CDC on specific issues. Some of the things that are listed here are post-licensure activities that are less of a focus of what NIAD is doing unless there's a specific hypothesis that we're trying to address, so some of those things generally do fall into the CEC category, but we are more than glad to work with them, you know, where there's good connections.

DR. PETER SCHEIDT: I should just declare a something of a conflict in interest in that University ______(INAUDIBLE) on the National Children's Study, so I have a - and my boss is a principal investigator. ______(INAUDIBLE) the National Children's Study could address a number of the questions that came up here to the extent that children enrolled in the study � there are enough children in the study that do not receive any particular vaccines, and we're going to have an opportunity to compare exposure and non-exposure outcomes, outcomes _____(INAUDIBLE) non-exposures. The ______(INAUDIBLE) hypothesis is one of the specific hypotheses of the National Children's Study as well. The hypotheses of the National Children's Study, other than the hygiene hypotheses, are not specifically targeted in vaccines. We do attempt to collect vaccine data by report from the caretaker or parent and there's ongoing, you know, personal health records being maintained and fed into a database. We do not currently plan to collect specific vaccine data, lot numbers, manufacturers, and that level of data without extra effort. We were asked to look at what would be involved in collecting those kinds of data, which would allow a much more fine-grain, in-depth detailed kinds of study, and we had those, the information ________(INAUDIBLE) several years ago and asked us to think through what it would take to get those kinds of data, and so we're prepared to entertain that if the interest in funds, you know, are available to do it, and to the extent that that electronic _______(INAUDIBLE) information becomes available over the next decade or decades, you know, we would welcome that opportunity to collect those data electronically.

That gives you a sense of where their position is.

UNKNOWN MALE VOICE: And to those who, not to spend too much time on the National Children's Study, but it intends to collect a great deal of toxicologic and environmental exposure data, genetic data and to have many, many years, perhaps generational follow-up.

UNKNOWN MALE VOICE: That's great, so that's a tremendous opportunity for looking at subgroups at risk's interactions with either genetic factors or other environmental exposures that might place it generally at risk when exposed to a vaccine.

UNKNOWN FEMALE VOICE: I can add something in regard -- specifically regarding autism research and ICHD is one of the members of inter-agency autism coordinating committee, and we are in the processing of setting research priorities and in a broader scope, not necessarily vaccination but gene, environmental interactions in, you know, effecting at a prevalence of the phenotypes of autism is definitely within the scope of strategic planning. So that's in the drawing board, and the committee is working on it.

UNKNOWN MALE VOICE: Just to remind everyone that's speaking now, say your name into the microphone for the purpose of the transcripts.

MARIE McCORMICK: Getting back to the VSD, this is Marie McCormick, what's sort of the life cycle of one of these studies, sort of from start to publication because the main part of this is actually getting communication of your results out, so what kind of timeframe and, I guess, more importantly, for some of the recommendation that we might make, what do you see as potential barriers that would -- might impede or slow down the release of important information on vaccine adverse events?

DR. ISKANDER: Okay, so let me again follow that sort of three type, three-tier model that I outlined earlier, so the planned protocol approved epidemiologic study is on the order of years from start to, if you define finish as publication; however, that's on the order of two years to greater than that if it's a particularly, you know, complex or challenging study. The Bill Thompson study on neurodevelopment and exposure to thimerasol took something more like six years to complete. That's really an outlier in that it was a very, you know, extraordinarily, you know, rigorous study with individual level standardized assessment, so the sort of standard, typically hypothesis testing is vaccine X associated with outcome Y on the order of, again, years.

Rapid cycle analysis can go from, you know, the start of the protocol to signal to detection to, you know, the follow-up planned studies within a shorter timeframe than that. The signal detection, of course, can happen within weeks to months after the start of the protocol. At that point, you shift more into an epidemiologic study model where you have to adjust for confounders, and so again it's, you know, more rapid than a planned study. The ability to look at, you know, a very specific, very targeted urgent public health question again, such as, you know, utilization of loss of recalled vaccine, we can do that within realistically one to two weeks. So, if you want to think of it as sort of, you know, weeks versus months versus years in a very over, you know, kind of deliberately oversimplified manner, that's probably a reasonable timeframe.

DR. McCORMICK: But I just, to follow up on that question, you say, you can look at it one to two weeks, but I am thinking about reassurance of the larger community for professional and public how that gets communicated in terms of, you know, what is your timeframe there?

DR. ISKANDER: Well obviously, you know, for planned studies, I mean, those typically the results of those planned studies are communicated at the time of publication. Certainly if it is information that is going to be important to the advisory committee on immunization practices or to safe vaccine recommendations, we will of course arrange advanced scientific presentations of that typically to the ACRP working groups at ACIP public meetings, and basically the standard for the rapid cycle, obviously there is a balance there between wanting to make sure that the signal is not related to, you know, just data issues, and but again wanting to make sure that findings such as the MMRV vaccine findings that in fact may lead to a policy change are communicated in a timely manner and in advance of any, you know, formal scientific publication, and that was done for Proquad, and again you know, if the urgent looks require urgent communication then we do that.

DR. BRODER: Just to follow up on the - and I'll defer to Dr. Pickering, as was mentioned earlier, we do serve on a number of ACIP working groups and we do make routine updates to the ACIP, and those presentations are public. Our slides are posted. In addition, we commonly with the communications efforts around - often around those ACIP presentations and so forth. The most recent ACIP presentation of the MMRV data not only from the immunization safety office, but also interim data from the company, both data were presented to the ACIP and then a communication -- several communication materials were prepared including an MMWR article, which came out about two weeks of the ACIP meeting.

Another example over the summer, there were some reports there to Kawasaki syndrome following RotaTeq vaccine, and that information led to a small change in the product label, and that we -- the Food and Drug Administration and CDC work together to coordinate communication material, so publication is certainly one important form of communicating work, but on a routine basis, we communicate findings and coordinate closely with other groups, particularly the FDA through web postings and through other venues.

DR. CARLSON: Chris Carlson. I have a specific question that may be a symptom of the larger question, and so we'll start at the large _______(INAUDIBLE). On the life scale, the specific accident safety questions in ________ (INAUDIBLE), how many of these would we have had last year? If we're developing a five-year program, how fast do we need to adapt the specific questions to specific questions that have come up, and you can answer that, and I'll get into the specific question.

DR. ISKANDER: I think what we've tried to do is balance, you know, new and emerging questions. New questions do emerge in vaccine safety all the time. They emerge from our reviews of the VAERS system, they emerge from our review sometimes of pre-licensure data. They do often emerge from media or from other reports that make us aware of concerns that we then feel that we need to pursue. So, I think the specific question list is an attempt to balance emerging issues. If something is on that specific emerging, it's been judged by our scientists we've been talking with to be important, to warrant specific attention. Again, many of the concerns about vaccines and Guillain-Barr� syndrome date back literally more than 100 years, so that's sort of one far end of the spectrum. Clearly, you know, some of the other issues, particularly about, you know, aspects of neurological deterioration clearly are more contemporary and yet they, you know, we felt they warranted some focused scientific attention.

DR. BRODER: Just to try to put some numbers around your question, I think if you look at the seven specific questions, in looking at them and just marching through them, it looks like three or four we would have had enough information to have put on last year and about three or four would have either not been on there last year, for example, the MMRV febrile seizure issue because we didn't see it as a special need because the concerns hadn't yet emerged to the level where we needed a focused investigation or it would have fallen into a thematic area, however, with the thematic areas when we look at those, there are few exceptions that are related to new vaccines coming up that are in biologic license application phase or where there's been a new ACIP recommendation that stimulated adding the area, for example, annual influenza vaccine that is on as a thematic area mainly because now we have repeat vaccination in that population, but I think most of these I you look through the list, most of these thematic areas would have been reasonable to put on the list two or three years ago.

DR. CARLSON: I absolutely agree. I mean B through D, I can see most of those being longstanding issues. So now sort of going down to the specific question, we've got simultaneous vaccination in vaccine and vaccine practices, we've got vaccine-drug interactions, but I don't see anything on here about the schedule, and the schedule has change a lot for the pediatric vaccination schedule in the last couple of decades. My three kids have seen a lot of pincushions, and this is something where for public reassurance, I -- scientifically the evidence may be not be as strong, but if there is a very serious public concern with this and I am curious about why it's not.

DR. BRODER: If I could just clarify, I think, a couple of other --when you say the schedule, I think what you're meaning is the - let me make sure that the recommended multiple immunizations --

DR. CARLSON: The recommended series across the person's --

DR. BRODER: And there's a separate one for children, adolescents, and adults. We have a couple of other questions that are related, one is off-label use, or a couple other areas, one is off-label use of vaccines and other is interchangeable use of vaccines in different product categories, as well as the one you mentioned, as well as within each of the other themes, one could think about for example, the schedule as it relates to one of the special population. I guess what I might ask you is what -- beyond what is articulated in the list, is there a -- can you bring a little more clarity to the schedule?

DR. CARLSON: In more specific terms, it's my understanding through reading to the ACIP recommendations is that there's basically a series where across the first couple of years of life at day zero one gets Hep B and day 31 gets this series. A lot of concerns that have been raised in the community were really addressing this once one size fits all. Is there an alternate schedule, is an alternate schedule feasible, just so that people have the opportunity to opt for an alternate? We all have to have our kids vaccinated by the time they go into daycare or kindergarten, sure, but we don't have to have them in the first two years if our kids aren't going to daycare and should parents have some choices? This is a scientific/public perception question. I mean I'm not saying that it's - there's proof one way or the other, but the lack of options is a concern I think we should think about.

DR. PAVIA: Just to clarify. It sounds like you're making two points. One is what's the safety of the schedule as it now exists or the safety of alternative schedules, and the other is policy question of in the absence of data should alternate schedules be evaluated for efficacy and feasibility.

DR. ISKANDER: I think, you know, again, part of it, as Karen pointed out, is this was an area where we in a sense split the issue, but I think we're happy to, you know, consider other ways of looking at that question. We certainly are partly -- we will be involved in some of these broader looks at, you know, this is an issue that has arisen within immunization leadership discussions, and we certainly have been invited to be part of those, you know, discussions/scientific investigations and we will certainly pursue that. You know, we also do have in fact some newly added expertise in our office related to, you know, the creation of the vaccine schedule and so I think again we would definitely consider what you are proposing as I think very well within the spirit, if not the exact letter of what we are proposing.

DR. SNIDER: But I do think, you know, I do need to point out as Andy broke it out, what we are asking today is hopefully pretty clear to you by now, and the parts of that that would fall to ISO would be asking those safety questions that Andy articulated. So we could take out the piece that - where you're raising questions about the safety of the crunch schedule, and if people were using or there was, you know, some kind of pilot going where alternate schedules were being used and we could get involved, and we being ISO, could get involved to evaluate safety, but ISO cannot be the, you know, is not, the part of CDC. We work through the advisory committee on immunization practices on what the policies are. So the policy piece would have to be handled by another part of the organization and not ISO.

UNKNOWN MALE VOICE: Okay, thank you.

DR. LARRY PICKERING: Couple of things from the ACIP point of view, there are couple of constraints that ACIP works under. Number one is vaccines are given before exposure to disease, which optimizes their protection. So that's one major consideration, and secondly is that vaccines are studied under certain conditions; age groups and so on, and that's the - they're the data that are presented to the ACIP, and since all the recommendations are evidence based, generally we stick within those FDA licensures for various vaccines, but thirdly, there are ranges for almost all of the vaccines. There are ranges that they can be given in. They don't have to be all be given in one visit. They can be ranged out, and that's something that in under active discussion. I will take this back to ACIP, which is another major group that needs to consider it because there are several members that are -- seem interested in this also. So I think it's something that does need to be looked at.

DR. PAVIA: And I think just to add, there's obviously a large FDA component to these questions about whether or not you can go beyond the data that was presented at the time of licensure and off-label use, and perhaps some of the data that you're receiving the FDA would be helpful for answering these questions as well.

DR. GOLDMAN: Just to add to this that the kinds of questions that I hear have to do with if there are multiple immunizations, separate immunizations given at same visit at certain time points, are there possible safety impacts that would not have been predicted from the trials, which tend to look at the immunizations one at a time. That's just the question that I hear and, you know, some people have asked me, �Well, should I ask, you know, my doctor to use an alternative schedule?� There is a range around it.

The other thing that I think, and this gets more into a communications issue, I think that one of the issues is that the way that the schedule gets communicated is that it's often used very rigidly by school systems and so forth and so then I've also gotten calls about things such as, you know, the child gets the immunization one day short of birthday, and then the physician consultant for the school insists that the immunization must be given again because they've taken that very literally. It's one, and this is a true story, one day short, that it's not a good take and I think that's been, you know, just more created friction I think about the whole issue.

DR. PAVIA: Karen did point out very clearly I think in the background documents that licensure studies are usually done without multiple simultaneous immunizations and then in practice we are giving them in a very large set of combinations. It sounds like what you've raised in own agenda and what we're saying here is that that's something that that requires some thought about how to get around those difficulties in the future.

UNKNOWN FEMALE VOICE: I've heard perhaps one additional question about alternate schedule that might not fit. Most of what I heard I think if I am understanding correctly -

UNKNOWN FEMALE VOICE: _______(INAUDIBLE).

UNKNOWN MALE VOICE: And the light are right behind you, so I apologize.

DR. FLORENCE HOUN: Just that the Food and Drug Administration encourages for licensure that manufactures conduct of portion of their safety and efficacy data in the United States to try to address the issue of concomitant use according to our immunization schedule, which is different from Europe and Asia and the type of vaccines licensed. So you'll even see in this recent Rotarix approval that a component of the study was done in the US with concomitant administration under our schedule, our ages, so that we can get that kind of data.

DR. PAVIA: I should remind everyone to identify themselves again. Sorry.

DR. HOUN: Florence Houn, Food and Drug Administration.

DR. BIRKHEAD: Gus Birkhead. Just in reading through the information, and particularly the background to each of the questions, I note that you haven't at this point formulated specific research questions or scientific questions in each of these areas. You've sort of summarized what's going on right now. Is the plan for this particular document to have more fleshed out the specific types of questions or -- and I think that would have implications for the methodology then and the feasibility and the cost. That all seems to me to be part of the equation at some point. I just wonder when.

DR. SNIDER: Yeah. Through the process that Karen described, we were able to extract some specific hypotheses, but a lot of the discussion in retrospect and going back through, people gave us general thematic areas that they apparently had some concern about, but didn't really articulate, you know, a hypothesis associated with it, and that - so that fell into our purview to try to decide if that thematic area, you know, might be under ISO's capacity to lead d take responsibilities for.

The thematic areas, as Karen has said earlier, are areas that were flagged by this process that's been previously described as areas that needed to be put before NVAC, but each one of them will require some element of significant consultation with a variety of experts, and so it was impossible prior to this meeting and it would be impossible even over probably a course of a year to explore every one of these thematic areas and tease out what the specific hypothesis would be, and so I guess the reason to bring it to you in this forum is to try to get a sense in a narrative way or in a numerical priority way, we can discuss that later, which ones will be thematic areas should we really be concentrating on.

You've heard about the resources that we have, you've heard about the ongoing required activities, so you know, rather than just saying, you know, we should pursue all of these areas and start trying to simultaneously doing it would be impossible. So, what we're asking you to tell us, you know, is among these thematic areas which ones stand out to you, and we're open in terms of how you do that. Which ones of these thematic areas you think are really, really terribly important to pursue and whether you want to do, you know, as your top ten or in a narrative form or how ever you want to convey that information, we can talk about later. What we really need, we need some sense, otherwise we'll just have to - we have to make our own judgments, and we'd rather make it informed by this group and public input, and to even know that we should start those engagements with neurologists and neuro-developmental people around one set of questions or another group of people around another set of questions, adjuvants, for example, immunologists and so forth to understand how these new ______(INAUDIBLE) agonist adjuvants modulate the immune system. Those are all different conversations, and they are going to take a lot of time.

DR. BRODER: If I could just add if in the __________ (BLANK)

MS. BUCK: This is Tawny Buck. I'm curious to know was the public involved in the process of developing this document that I'm looking at right now or is the public input coming now?

DR. BRODER: The ________(BLANK) a starting place for us to have a good high-quality discussion that involves the public as well as scientific partners. In developing this, we did indirectly, although the meetings were not open to the general public, we did I think indirectly trying to obtain input from public perspective by, for example, inviting Geoff Evans from the ACCV and a member from ACCV to participate in our consultancy meeting, by having a broad range of federal experts provide input from their experience, and by reviewing a variety of sources that in the development of those sources might have captured some public input, but we did not in the first phase have a formal process for involving the public.

DR. SNIDER: The point was not to exclude the public, but to try to figure out from scientists what are the questions or indications we were just discussing, what are the thematic areas from in their view we ought to be thinking about. I must say that many of the pediatricians that we involved conveyed the concerns of parents and, you know, pediatricians were out there on the front lines, so I think we indirectly heard from the public around some of these things and that's why some of the things appear on the agenda, but so general idea was we'll hear what the scientists have to say about these areas, what can they come up with in terms of specific hypotheses questions or thematic areas, and the whole issue of the public input is a complicated issue of which we, and I don't really have expertise, and in fact we have limited expertise within CDC and so part of today's discussion is devoted to how we might move forward to get public input, you know, into this, and so we always had the intention of doing that, but the question has always been how, and we still haven't answered that question and we're hoping that you can help us answer that question.

UNKNOWN FEMALE VOICE: Okay.

UNKNOWN MALE VOICE: The short answer was I guess that it's coming.

MS. BUCK: It's just that clearly there's a lot of work done to this point, and I feel a little bit bad in some ways of having to, you know, revisit a lot of these topics because there is concern from the public that perhaps a lot of work has been done without their input, and so I appreciate being here and being given the opportunity to sit here and I just needed to clarify in my head at what point the expectation is for the public to be involved, and I appreciate that.

DR. PAVIA: Let me go ahead and ask a question if I could, or it's only partially a question. As I look at the agenda, the items under C, the special populations ring as very important for the specific populations, and as we talk about moving towards understanding individual risk more than the whole population, but a look through some of the special populations, I think your ability to look at them varies a great deal with the tools that you've told us about. We talk about our children what inborn errors of metabolism, for instance, and thank you for using that term instead of focusing on just one small category of inborn errors like mitochondrial disorders, but your current systems as I understand it with 5.5 million people of all ages under surveillance may be very limited in their ability to ask specific questions there, and I guess to make this more of a form of a question, have you thought through, or is that a process yet to come, how to expand the ability to look at that population? The same applies for people with primary immunodeficiency because I think secondary immunodeficiency you captured within 5.5 million to probably be able to answer those questions.

DR. ISKANDER: Okay. I think we'll sort of divide our answer into two parts. I will ask Karen and others to fill in. It somewhat falls into two categories, so C1 through C3, premature and low birth weight infants, pregnant women, adults age greater than 65 years, we either - you know, we've already produced some vaccine safety research in this area. I don't want to overstate the amount or the size of that research, but, you know, VAERS and VFD have produced some studies in those areas. I think and I believe something like 13% of the birth cohort needs some minimal criteria for prematurity. So, I think in fact looking at specific outcomes in those categories, I think our infrastructure is able to look at the certain -- its piece of the puzzle. I think we're able to do studies in those areas, and you know, we're also involved in some of these, again broader activities about, you know, interest in looking in other systems that might be able to study, for example, birth outcomes in pregnant women and it may be, as one of our potential collaborators said in a meeting last week, that CDC can support this with a little S. In other words, not monetarily support, but be, you know, engaged in the work and be, you know, be coordinating in a sense our studies with theirs.

C4 through C7, then you clearly do run into issues there of how common or rather how rare are these conditions, and I think our CISA network they are, again, meant to focus on the individual rather than at the population, and I would potentially ask either Karen or Corey or others to amplify.

DR. BRODER: Well, I think that that's exactly right. They do fall into two kinds of categories, those that could be assessed with a population-based system like Vaccine Safety Data Link and those where CISA would be more well suited to studying at, and so the CISA and Dr. Dekker is welcome to add, but CISA has six sites, and one of the strengths of CISA is these academic centers that have access to specialty clinics that, you know, people from around the state or country will come to these clinics, and so in the area, for example, of inborn errors of metabolism, one of the CISA sites already has determined that there are what looks like at least 150 children in a center that might be accessible, for example, in some further follow-up. So, I think that would be the part of the discussions in the thematic areas would be looking towards CISA and their six sites in the specialty centers for access to some of these specific populations.

UNKNOWN FEMALE VOICE: Just to add to that, I think the list of -- and by the way, for people who haven't found this yet, table 3 that starts on page 28 of the draft, that really does flesh out the list. It gives much more background information about what we know and what is currently ongoing, but in the area of primary immunodeficiency, we're doing study in children with DiGeorge syndrome and determining whether they have received live virus vaccinations, gathering that information, gathering information about the disease, and we'll be pulling all that together to hopefully be able to make a recommendation of that.

We've got probably 200 patients that we can access at Stanford for that. We've gotten consent from 46 parents, and we're continuing to work on that particular study. Similarly, we are doing studies with rotavirus transmission where there's a household with immunocompromised patients. We are about to put forward a concept sheet for the study of rotavirus starting in premature infants who are leaving the NICU and have that approved through our NICU investigators. So there are smaller studies that are better tailored for the CISA abilities, and we of course partner with our VSD colleagues on some of the larger medical information-based studies, but we actually I think can do a little bit better job in gathering data information, having to consent patient, and also samples.

DR. SNIDER: Andy, this is Dixie Snider. I'd like to just add that in my roll as a co-chair CDC patient safety work group, which by the way we now have a joint FDA-CDC patient safety work group formed, and part of the activities that are going on particularly around the single network that FDA has been charged to build, has resulted in right now all the different entities inside government and out submitting to FDA the systems they might have that could be looked at medical product safety, and I think this offers an opportunity, as John was talking about collaborations, it offers an opportunity to look through those list of systems that are in place and approach those who are running those systems to see if it would be possible to put a vaccine safety question into one of those systems, and so, you know, I don't want to be looking through this, you know, through rose-colored glasses, but nevertheless seeing all the things that are going on and the openness that many of the managed care organizations and many of the operating physicians have to having their systems used for other purposes, I think it presents ISO a unique opportunity to build new collaborations, and finally I just wanted to say to Tawny, since I have to take responsibility for the sequence in which we did this, ______ (INAUDIBLE) we started outside CDC. __________(INAUDIBLE) insists that we start outside CDC and get ideas from outside CDC, but it's always a problem inside an organization and outside an organization when you start trying to engage people about, you know, an agenda or a piece of work, and you know, some people respond by saying, �Yes I'd like to be part of the initial process and offer some of my ideas,� but a lot of people say, �Well, I'm really very busy and I don't have a lot of time. I'd really like to see a draft of what you come up with and comment on that,� and so there is always that, you know, that tension there and so, as I said, there's always been --our intention has always been to somehow get public input, but since we couldn't quite figure out what was the best format to use to get, you know, truly representative public views on this and get that in place, we've talked about it endlessly, but we're hoping NVAC can help us or point us in a direction that we should go. We'll do our best, and so that really is the only point I wanted to make about that.

DR. PAVIA: I think we got - let's see, I've got three more people; Sean, Steve, and Lynn. Anybody else, so I can keep my list intact and not miss anyone?

DR. GERALD MEDOFF: Can I ask a question by telephone?

DR. PAVIA: Okay. I'm going to let you jump in just because of the telephone, and then we'll go to Sean. Go ahead.

DR. MEDOFF: This is Gerald Medoff. I'm sorry I'm not at the meeting. My trip was delayed by American Airlines.

(Laughing)

DR. PAVIA: Go ahead.

DR. MEDOFF: I wanted to commend all the people involved in this work. It certainly involved an enormous amount of work. My question is pertains to the _______(INAUDIBLE) of this process. __________(INAUDIBLE), for example, who decides what is an acceptable level of toxicity from the vaccine? I know the FDA has a project for that, but shouldn't that be outlined in this __________ (INAUDIBLE)? In other words, I think one of the charges _______(INAUDIBLE) adverse events _________(INAUDIBLE), and I think that over ________(INAUDIBLE). So shouldn't the effective process of what happened _________(INAUDIBLE) reactions to vaccines, the level of toxicity, and then the decision making in terms of whether or not special populations are excluded or vaccine is removed from the market, or the toxicity is acceptable in terms of the value of the _________(BLANK).

DR. PICKERING: One of the things - Larry Pickering, sorry. One of the things that the ACIP does when it approves of that or when it gives recommendations for vaccine after license by the FDA, as I said, is that we have regular updates on vaccine safety. These updates sometimes change regarding changes in recommendations to -- from what were originally made. Those changes will be based on risk versus benefit. In other words, if there's a side effect or an adverse event that's very minor like local pain, that would not be considered as important as if it were Guillain-Barr� or some other major adverse event, and when you look at the major adverse events if an adverse event occurs that one in a million and the disease itself is a hundred times that and it's a significant disease resulting in death or significant morbidity, those are all taken into account and discussed in a public forum at the ACIP meetings with regard to making changes in recommendations that have been established.

DR. MEDOFF: I understand all of that, but shouldn't that process be outlined in a book like this?

DR. ISKANDER: I can comment briefly. In fact, you know, many of our consultants did in fact make this point. We --

DR. ISKANDER: - and ISO still practice regularly and so we're very well aware of the very important need to balance, you know, risk and benefit. The basic judgment we made was that it was, you know, out of scope activities for us to lead. I think it is certainly, and I certainly included in my introductory remarks of the need to recognize this. So again I think there are probably other ways that that very important concept and process that you describe can be incorporated. We just again did not feel it was in our purview to be able to really lead such scientific activities.

DR. PAVIA: I think the fact that it was raised at all suggests that maybe there is an issue of risk communication here and that, although there is a very clear process, it isn't obvious necessarily how some of these things are weighed and maybe that's something we can take away from this. We've got two more questions before we break so if we can move along, then we can all go to lunch.

DR. HENNESSY: Sean Hennessy. I suspect that there is more variability in heterogeneity internationally in what vaccines children get than within the United States and I'm wondering if there is opportunity or infrastructure to use cross-national comparisons to look at some of these questions.

DR. ISKANDER: I think that's an excellent suggestion. We certainly, although we do not have necessarily formal scientific collaborations that cross borders, we certainly - the global vaccine safety science community is really not that large and so, you know, NVPO actually sponsored a post-licensure vaccine safety surveillance meeting last year where you had probably 80% of the world's top vaccine safety researchers all gathered, did not quite fill up a medium-sized NIH auditorium, so I think there is a lot of ability for certainly, you know, dialogue, understanding what studies are being undertaken in other countries that might be, you know, relevant or that we might want to have some perhaps informal input into. There are also some proposals to develop international vaccine safety networks that would essentially use the existing research capacity of the GPRD in the UK, that's their general practice research database which is a large link database which they use primarily for drug safety, but they do vaccine safety studies as well. Other important models such as Denmark, so I think there has been recognition that there is a lot of that the global community can learn from each other's studies and from more or less formal collaborations in that area and I think that's something that we can incorporate.

UNKNOWN MALE VOICE: Thanks ____.

DR. ELIZABETH MILLER: (INAUDIBLE) _______ at this point.

DR. PAVIA: Yeah, go ahead please.

DR. MILLER: (INAUDIBLE)

DR. PAVIA: Not only does it ____, but it raises the issue of whether or not there is a similar long term agenda from European investigators that could be looked at in your process going forward with the final agenda to see where - what synergies could be discovered.

UNKNOWN MALE VOICE: So that we can get our last -

DR. MILLER: (INAUDIBLE)

DR. PAVIA: There is very vigorous head nodding rather than giving you a formal answer towards the idea of developing methodology and that was I think in the document is given quite a bit of priority.

UNKNOWN MALE VOICE: (INAUDIBLE)

DR. SCHEIDT: Let me just very briefly add to Sean's answer - Sean's question. The National Children's Study jointly with the National Cancer Institute have forged a consortium of large cohorts around the world to attempt to be able to address outcomes that are less frequent than the National Children's Study alone could do. This consortium includes the National Children's Study as it comes along, the Danish cohort study, the Norwegians, the Chinese, the _____ study in England, and ____ cohort in Australia, and other emerging ones. Concept hypotheses are already underway and proposals to test, for instance, folic acid levels in relation to childhood cancer, you know, translocations in relation to childhood leukemia and so on, but it would lend itself for the very infrequent outcomes of encephalopathies in relation to ____ differences in vaccine practices to answer those kinds of questions.

DR. PAVIA: What captured that, I think, when we talk in six months to a year about new ways to go forward, new concepts for research, that's a terrific one. Lynn you've been waiting patiently and then Steve and then we'll have to break for lunch.

DR. GOLDMAN: Yeah, I just had a comment about the overall process, just you know, and in response to a couple of the earlier comments and one is that I think it's very positive as I am hearing this that this office is starting to craft a five year or longer term agenda because I am seeing that there is a tremendous need obviously for the office to be able to respond when there are immediate concerns and if there are changes in the schedule or new vaccines, but that there is a longer term agenda and I am starting to sense that that has not really taken shape yet because of kind of the course of things, you know, the immediate need is always to address immediate problems and I think it's very commendable that the office is coming forward with an effort to develop a five year agenda. I just wanted to say that because I don't think that any of us has yet. And the other thing that it seems to me is that I'm taking this as a list of ideas, as possible avenues to explore. I mean, I'm looking at this, none of these cakes have been baked yet, you know, this is kind of like a menu of things that could be done and so I'm thinking that this is a very excellent time for us to be reviewing this as well as the public because in the sense what you've done and it's a marvelous favor to us all you've created almost like as strong end. This is the list of the things that you're thinking on the basis of, you know, expert consultations that you've undertaken, the people you've worked with, your knowledge, your thinking these are directions that can be taken, and so it gives us enough to be able to grab hold off to be able to say "yes, we like that" or "no, we don't like that," rather than if you had come to us a year ago with, you know, an empty table and said �fill this in�, I think that would have been a lot more effort, it would have been a lot more difficult, and so I kind of think this is a good way to approach this with this and I think for the public as well. I just wanted people in the public who are here also to feel the same way. I mean, I really see this as a list of things that are up for, that you know, can either be accepted or rejected. None of this has gone so far that, you know, we can say this is set in stone. So I appreciate that.

(INAUDIBLE)

DR. BRODER: Karen Broder. I do want to highlight, I think it's obvious for people who are reading the background, that in some of these areas we actually have done a fair bit of work. We have studies underway. I just want to make the point that the level of work that has been done in these areas varies across the topics. In some topics, we have done very little work because they are new topics or new ideas. In other areas, for example in the Guillain-Barr� syndrome area, there are a number of activities underway in our office, in other settings as well. And that will - those issues will come up, I think, later when prioritization is discussed and we left them on the list because there may be more work that needs to be done in a variety of areas, but I did want to make that point that there are various activities underway already in some of these areas. Thanks.

(INAUDIBLE)

UNKNOWN MALE VOICE: Sure.

UNKNOWN FEMALE VOICE: It seems to me, you know, managing a very large research program, although some of us might think it should be larger, but as we heard from the UK, this is, relatively speaking, pretty large and so you are going to have choices, I think, about three things and that is the things that you are working on, how far do you take those, how much do you continue to invest in these areas, what are new things that you're going to take on? And then I think the third thing is, and I don't know quite how to put this, but how much search capacity do you need to have? How much capacity do you need to have left over for dealing with contingencies? The questions that will come up next year that we don't know about this year. And so, you know, and that's a difficult management, you know, but -

DR. PAVIA: Yeah, I'm not sure if we can - we could talk about whether we can help with that in terms of talking about how much should be held in reserve as capacity or we may have to leave it up to them to salvage difficult issues. Last question.

DR. GOODMAN: You mentioned the difficulty of figuring out exactly how to engage the public. I just wanted to mention a model from the cancer world which I think - and I don't live in the vaccine safety world so if this has been done before or maybe Sharon's work has covered some of this, I apologize. But one example in the breast cancer world is as something called Project LEAD. LEAD stands for leadership, for education, advocacy, something, I'm not sure exactly. Anyway, the important thing is that it's hosted now by the National Breast Cancer Coalition and what it sponsors really year round are two to four to five day courses where interested, usually breast cancer survivors, but also other women and persons interested in breast cancer advocacy come together with scientists to learn the science, to learn also the politics, they come together with advocates, and all dimensions of the issues, but they spend a lot of time on the science. And this has a tremendous number of benefits.

First of all, a lot of mistrust, misunderstanding between the two, between the advocates and the scientists, and others gets diffused. They become full scientific partners in the discussions where they're being trained for and they're being trained to serve on IRB's, to serve on data monitoring committees, to serve on protocol review panels, and they serve in all of these capacities. And just two years ago, there was the 10^th anniversary of this which was a big celebratory dinner that was attended by leading scientists from the NCI, other breast cancer scientists, and hundreds of advocates, hard to image that occurring in the vaccine field these days, and it was directly a result of the time, not only that the attendees spent, but that the scientific community devoted to teaching them and partnering with them. And it wasn't just a one way interaction, all of these courses and the reason that they take so long is because they involve a lot of both workshop components as well as sort of didactic components, and both sides have to commit to a fair amount of time together. So it shows both goodwill, but also sharing of both concerns and information that the two sides find extraordinarily useful and ends up in much more constructive engagement in meetings like this. I think one of the problems is for public representatives like Tony or anybody is that the points of contact occur, you know, in very abbreviated formal settings like this and it doesn't make for the kind of exchanges that are really needed. So this is not something your office can do, but you could participate in these if the others took it upon themselves and it may be the advocacy committee itself to sponsor these kinds of forms which really focus on education. Of course, in the vaccine field it may be a little bit more difficult because the people who might come to these workshops themselves may not be "representative" of the community whatever that means. I think that's a very, very complicated topic and I won't go there, but to have these forms available and other domains where the "public" and the scientific community can interact in both formal and informal ways for mutual education, I really want to stress that, could have tremendous pay off for forums like this and many, many others where the two interact.

DR. PAVIA: I think you've said that beautifully for the effort we want to make between two and four where we want to think about better ways to do this. I think the breast cancer community and the HIV world where I've lived for many years have done a much better job than we have in vaccines and the whole idea of what we are doing this afternoon is to brainstorm about ideas that will work better. With that, I am going to call a break for lunch. We've run just a couple of minutes over so I'm going to have us still try and get back together by about 1:05 back in this room. And the members of the working group, we have a room set aside. We're just going to talk about conference calls and schedules, and the like so -

DR. PAVIA: There are a number of people on the committee and ex-officio's who have very tight flight connections and in light of it problems with American Airlines and lack of alternative flights. I think you'll understand if people have to leave on time to make their flights so they don't spent an extra night here. So they will read the transcript, they will be available, and I am one of those people who has to be out at exactly 4:30. So we are going to be very - unfortunately, be forced to be fairly rigid on closing the meeting, but I assure it's the beginning and not the end of that process. The next piece, and we're going to foreshorten this a bit so that we don't take any time out of the discussion of the role of the public here, but the next piece is going to be by Dixie Snider. Dixie is going to talk a little bit about ways in which we might think through the process of prioritization and ways in which it might be most useful to them at CDC. So Dixie-

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DR. BENJAMIN SCHWARTZ: This is scientific agenda. I wouldn't propose a specific approach to public engagement. If there is something that needs to be discussed further with stakeholders and experts, however what I would like to do is I would like to define what I consider the important principle that should underlie this process and the first principle is that of commitment. That is commitment that input from the public is important and that the continued success of our vaccination program depends on good decisions on where research if needed to address importance vaccine safety questions, to address public concerns, and to assure the public that their voice is being heard.

The second principle is that of inclusiveness and what this means if including and learning from those who are already knowledgeable and have a particular point of view on vaccine safety as well as from the general population. In our pandemic vaccine prioritization experience, we found that a group of dispassionate citizens were able to effectively contribute their values as well as their specific suggestions giving us the knowledge that the plan we developed reflected the views of population broadly.

A third principle is that of fairness to be achieved through mutual facilitation in planning and carrying out the meetings given that some mistrust exists between various groups and the government, and I don't think I am overstating that. We recognize the value of having the process planned and coordinated by those with expertise in public engagement but no stake in a specific outcome, and related to this is a fourth principle. That is dialogue before deliberation. Through a dialogue process one can create the conditions where common ground can be discovered. In this process, I suggest it might be useful to focus on our values before discussing specific research needs, as our experience suggests that these values are going to be broadly shared and will help bring people together.

A fifth principle is to acknowledge complexity and this has several components. It includes recognizing the complexity of people's genetic backgrounds and environmental conditions and illnesses, which might affect them, as well as the complexity and limitations of scientific investigations that might be done to explore vaccine safety hypotheses.

Sixth, I would emphasize the importance of focus; that is staying focused on the question at hand, and while there are many issues in the area of vaccine safety where community engagement may be a value, the process to be undertaken here would lead to engage specifically on the immunization safety offices, scientific agenda, and success in doing this may lead to further opportunities to address these other vaccine safety questions, and finally I would suggest a principle of accountability, and that is that the government has an obligation to provide feedback to the public on their input and how it contributed to the final outcome. The national vaccine program was established in 1986 by congressional legislation, and this legislation identified twin goals of improving disease prevention by vaccination and improving vaccine safety. These goals and the link between prevention and safety remain as important today as they did then. Public engagement on this research, scientific research agenda will help CDC, NVPO, and HHF address this congressional charge. Moreover, by building on successful public engagement activities that already have been undertaken, it will strengthen the commitment that our department has to a process which can best assure that public health addresses public means.

DR. PAVIA: I think we're going to move to _______(INAUDIBLE). So our next speaker on the agenda is Barbara Loe Fisher and do you have slides or - then I don't have to sit in the back. Thanks. Please welcome.

MS. BARBARA LOE FISHER: The National Vaccine Information Center is a non-profit educational organization founded in 1982 to prevent vaccine injuries and deaths through public education. We represent the vaccine injured as well as families with healthy children and health care professionals united in support of the ethical principle of voluntary, informed consent to vaccination.

I am the mother of three children, including a son who suffered a brain inflammation within hours of his fourth DPT shot and was left with multiple learning disabilities. I worked with parents and Congress on the National Childhood Vaccine Injury Act of 1986, which created the National Vaccine Injury Compensation Program and vaccine safety provisions, including mandatory adverse event reporting and recording, as well as the Institute of Medicine's 1991 and 1994 reviews of the scientific literature for evidence that vaccines can cause injury and death. During the past three decades that I have served on committees at the FDA, Institute of Medicine, and forms of the CDC, including acting as chair of the subcommittee on vaccine adverse events for the National Vaccine Advisory Committee between 1988 and 1991, the greatest challenge has been to convince public health officials and pediatricians to take seriously the concerns of parents that parents have about the quality and quantity of scientific information available to them when making informed vaccination decisions for their children. From the parent's perspective, as Mark Blaxill of Safe Minds, and I pointed out in the white paper we co-authored after the Blue Ribbon Panel on Vaccine Safety in 2004, which is on the table outside, a comprehensive and transparent scientific examination of vaccine risks is long overdue because today the number one question for many parents raising young children is, �Why are so many of our highly vaccinated children so sick?�

Vaccination rates with multiple vaccines in America are at an all-time high and with one in six vaccinated child in America now learning disabled; one in nine suffering with asthma; one in 150 developing autism, and one in 450 becoming diabetic, this is a legitimate question. America spends more than 75 percent of the $2 trillion price tag for health care to treat the chronically ill and disabled, and it is estimated that by 2025, one in two Americans will be chronically ill or disabled. The scientific, economic, political and moral imperative for addressing the new epidemic of chronic disease and disability, which has developed in the last quarter century and is compromising more children than were ever harmed by any infectious disease epidemic, including polio, makes the vaccine safety research agenda you are developing the most important federal health research funding priority today. It is a funding priority that must not take money from the Vaccine Injury Trust Fund created in 1986 to compensate vaccine-injured children, but urgently 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.

With more than 2,000 clinical trials worldwide that will bring dozens of new vaccines to market soon the first step in securing public trust is to add at least two more well-informed consumer representatives critical of vaccine safety to this NVAC Working Group and to the general committee, NVAC. In 1995, the Institute of Medicine convened a Vaccine Safety Forum of stakeholders to examine and publish reports on vaccine safety issues. During that four year public engagement initiative, a time when autism was affecting ONE in 1,000 children, I provided statements on behalf of concerned parents outlining vaccine research priorities and methods for detecting and responding to vaccine adverse event reports, which I will make available to this Committee for your further consideration, and yet again to the IOM Immunization Review Committee, which generated the following statement in their 2002 report on Multiple Immunizations and Immune Dysfunction.. Quote, �The Committee was unable to address the concern that repeated exposure of a susceptible child to multiple immunizations over the developmental period may also produce atypical or non-specific immune or nervous system injury that could lead to severe disability or death, Fisher, 2001. There are no epidemiological studies that address this. Thus, the committee recognizes with some discomfort that this report addresses only part of the overall set of concerns of some of those most wary about the safety of childhood immunizations.� End of quote.

Whether you believe vaccines rarely, if ever, cause injury or death and the government should force everyone to take vaccines without exception, or whether you believe that vaccines are pharmaceutical products that carry risks which are greater for some than others, and that government should allow voluntary informed consent to taking a vaccine risk that is not equal for all, most reasonable people do agree that individuals genetically or otherwise biologically at high risk should be identified so their lives can be spared.

Parents today are using mass communication and new technology to educate themselves about vaccines. When they evaluate the components of vaccines from mercury, aluminum and formaldehyde to animal and human cell substrates that can become contaminated with adventitious agents they are finding no credible scientific studies proving safety. When they question pediatricians about the safety of giving their babies eight vaccines on one day, they are being denied medical care instead of being given proof of safety. When they tell their doctor their child regressed after vaccination into autism, they are often told it is all a coincidence, and so no report is ever made to the Vaccine Adverse Event Reporting System, and when their children suffer vaccine reactions and are re-vaccinated again and again, despite deterioration into chronic poor health, they are losing faith in a mass vaccination system that dismisses individual health as unimportant compared to public health when implementing one-size-fits-all, no exceptions policy.

We have the technology today to investigate and define the pathology involved in vaccine induced brain and immune system dysfunction at the cellular and molecular level. A 20-year study that prospectively enrolls and compares the health outcomes of two groups of children, one group who will be vaccinated with the CDC recommended 48 doses of 14 vaccines by age six and 60 doses of 16 vaccines by age 12 versus another group, who will remain unvaccinated, will give us preliminary answers in six years about measured pathological changes in immune and brain function in both groups, including information about genetic variability and the development of learning disabilities, ADHD, autism, asthma severe allergies, juvenile diabetes, and other chronic disease and disability.

In considering the question posed to this panel �How Do We Effectively Engage the Public,� I am reminded of a statement drafted a half century ago by a young group of dissidents who founded a participatory democracy movement in America, a progressive concept that I learned about first-hand during a participatory democracy experiment initiated by the CDC between 2002 and 2005 called the Vaccine Policy Analysis Collaborative. In calling for a reform of government institutions to be more inclusive and transparent in their operation, the students referred to the great chasm that has developed between those who govern and those who are governed in America. They described the quote, �felt powerlessness of ordinary people, the resignation before the enormity of events, the actual structural separation of people from power, from relevant knowledge, from pinnacles of decision-making, the very isolation of the individual, from power and community and the ability to aspire.� End of quote.

It is the duty of a government of, by, and for the people to listen to the people and act when they are suffering, whether they are in a minority or the majority. Respect for the people and a willingness to share decision-making power with them is an approach that will foster trust in government officials and public policy. Threats and coercion will destroy it. What doctors in positions of power in the Department of Health and Human Services need to know at this critical point in time is this: Young parents today, who trusted doctors to give them good advice about how to keep their children well do not understand why their children are never well when they have been given twice as many vaccines as children in previous generations received. They want a full-scale, transparent scientific investigation into all potential environmental causes of autism and other chronic immune and brain disorders conducted by extramural researchers who are not connected to vaccine makers and policymakers with a bias toward existing policy. They want a greater separation of the vaccine risk assessment and safety oversight responsibilities from the vaccine policymaking and promotion activities more in the model of the National Transportation Safety Board.

Just as we did a quarter century ago, they are asking you to listen to what happened to their children after vaccination and take immediate steps to modify current vaccine policies to demonstrate a respect for preventing vaccine reactions, biodiversity, and the right to informed consent. If we can agree that individual health and life is to be valued and that the most vulnerable among us should be protected, if we can agree that when one of us is sick or suffering, we are all diminished if we do nothing, if we can agree that the individual biological differences among us must be acknowledged when making vaccine policies because biodiversity is what strengthens the human race and distinguishes our humanity, then there is no reason we cannot find answers to outstanding questions about vaccine risks and develop public health policies that truly protect the biological integrity, the health and well being of our individual children, our communities, our nation and the world.

DR. PAVIA: Thank you very much. Thanks. Our next speaker is Peter Ball from Autism Speaks.

MR. PETER BELL: Good afternoon. Actually technically my name is Peter Bell. I think there is a Ball down here, but that's fine. Currently, I am the executive vice president for Autism Speaks and up until a year ago I was the president and CEO of Cure Autism Now, which was another national autism advocacy organization that merged into Autism Speaks just over a year ago. My most important title however, is that of being a father of three wonderful children, the oldest of whom Tyler who is 15, and Tyler has autism. Tyler was diagnosed right after his third birthday at the Children's Hospital of Philadelphia, and he had what was known as, or what is known as a regressive form of autism. We took him to his two-year well check. We expressed some concerns about the amount of language that he had, but otherwise our pediatrician assured us that he was a developmental star and we had nothing to worry about.

Over the course of the next year he deteriorated in front of our eyes. He developed significant GI complications, had persistent diarrhea, 12 stools a day, lots of sores on his rear end and so forth, and we eventually after a lot of pushing and prodding with our pediatrician come to a developmental pediatrician where he received his diagnosis of autism. Tyler was fully vaccinated. He received 26 vaccines during his first two years of life. Like most parents in this community, we went back and we looked at his vaccines records. He received 187.5 mg of thimerosal, actually mercury, and later on we, because of his GI problems we did an endoscopy and he did test positive for having the measles virus in his gut.

I tell you these things not because my wife and I believe that Tyler's autisms were triggered by vaccines, but I think it's representative of what parents in our community go through. We are looking for answers. We want to know what happened to our children, and particularly those of us who have regressive children where everything seems to be going along normally and then all of sudden they get derailed and they go off the tracks, we want to know why that was the case.

Tyler is the oldest of our three children. He has a 13-year-old brother and a 9-year-old sister. We did choose alternative vaccines schedules for them. We are still very much pro-vaccine. We recognize the benefits from a public heath prospective as well as individually with our children of how important vaccines are, and we obviously never want them to develop an infectious disease that we have vaccines to prevent. So again, I just tell you these things in the spirit of full disclosure.

Let me tell you a little bit about Autism Speaks. It's a very relatively young organization. It's barely three years old. Our mission is to ultimately find a cure for autism. In addition to that we want to make sure that world knows about this major epidemic and we also want to empower families to make them feel that there is hope for their children so that we can provide as much as possible and to maximize their lives and not to forget about this generation of kids that have autism. Our programs involve three, actually four areas. First of all, and what received the most attention from our programmatic standpoint, is science. We want to find a cure for autism, we want to find better treatments. We want to find the causes of autism, and we wanted to able to prevent autism.

We also have a family services arm, which is targeted towards improving the quality of life for those that have autism today. Yes, we hope ultimately we can rehabilitate those who have the autism today and so forth, but we also want to make sure that we provide everything possible to make the lives of those who have autism today as best as possible. We also are very involved in advocacy. We want to make sure that federal government understands the need of this community whether be from a research standpoint , a services standpoint, or even just making sure our children are entitled to fair compensation from an insurance perspective. We are very active both here and Washington DC and state capitals all across the country, and the last area of programmatic spending is awareness, and as I said before, we want to make sure that people understand what a major public health crisis autism is today.

All in all, we will spend over $35 million this year doing all of those things. From a science perspective our scope is very broad. We have a research portfolio that includes specific areas to address for really important thing that are part of our science mission. First of all is an area called etiology of risk factors. We want to understand what is behind autism and why it exists, what are the causes of autism. Our second area is biology. We need to understand what autism is at a biological level. Our third area is diagnosis. We want to make sure that we can diagnose autism as early as possible because we know that that is best route to the best outcomes for our children, and lastly the last area is treatment. We want to make sure that we can treat our children both from a behavioral as well as a biomedical standpoint.

It wasn't more than five years ago that most people believed that you could not treat autism or that it could not improve, but we know that is not the case. Children are improving on a daily basis and that's because of the interventions that they are getting, and we want to make sure that we provide standards so that as many kids possible stand the best chance of improving.

In addition to funding grants that cover all four of those areas, we have a variety of research resources and clinical programs. We have a gene bank called the Autism Genetic Resource Exchange, which has been in existence for over 10 years. We have over 1,500 families, multiplex families, families that have more than one child available for study. We have an autism tissue program, which is a collection of postmortem brain so that we can understand the neuropathology of autism. We have an autism treatment network, which is designed to build standards so that we can better address the clinical care and improvement of our children, and we also have the clinical trials network, which is available to test certain medications in a quick fashion so that we know whether or not they are effective in safe to use in our population. It is our belief that autism is caused by a complex gene environment interaction. It's a heterogenous disorder, and as a result we believe that there are multiple etiologies. We have an etiology group, as I mentioned, that in integrates a variety of risk factors from genetics to environmental factors, and we use epidemiology to probe these differences. Because we don't have all the answers, a programmatic commitment is to explore all potential environmental factors. In fact, we just recently issued an RFA for environmental sciences where we have encouraged the research community to submit grant proposals to us that will explore every factor that is available out there. Listed in as part that are vaccines.

One of our priorities is to explore the possible role of vaccine-related trigger for autism in a potential subgroup of individuals who might be medically vulnerable. We are currently planning projects to explore the role of any of vaccines in adverse populations as well as unvaccinated populations, and we are currently exploring projects to ascertain the prevalence of mitochondrial dysfunction and disease and in the autism community. Mitochondrial disorders are not in your concept of autism, and clearly more research is needed to fully understand its purported connection to autism spectrum disorders.

How can the federal government expand community participation and setting priorities in the immunization safety research? First and foremost, we need to acknowledge that there is a gap in our knowledge. We need to acknowledge that we don't have all the answers and that this is not a 100% safe system. We need to enhance vaccine safety research. We heard today that the CDC had a budget last year in fiscal 2007 of $21.6 million. We have been told that of that only $78 million of it was actually for research. The other was to collect the data and add overhead. We need an investment and coordination of basic and clinical research at the CDC, the FDA, and the NIH. All activities must have transparency in consumer involvement. We know the autism community is diverse and has many views. We encourage the committee to include as many of those views as possible.

I would also encourage you to look at a model that the Department of Defense uses in advocating their research program. Autism two years ago was given a specific program within the DOD medical research program. There are at least five members of the consumer committee that are involved in that integrations panel. Several of those people are here today, and it's been a wonderful process, one in which I think both the scientists as well as the consumers feel that this works very well. Policymaking must be based on the best evidence available. If you don't have it, go out and get it. We need to recognize that this is not an autism issue per se, but a basic public health issue. We need to involve more neutral open-minded parties. The autism community is generally not anti-vaccine, contrary to popular belief. We strongly believe in the merits of safe vaccination and children should continue to get vaccinated, but more research is needed to address important unanswered scientific questions including medically susceptible subgroups, the timing of vaccines, the cumulative effects of them, the dosage, multiple vaccines versus single vaccines, as well as the frequency of them, and my last point is very much heartfelt. We cannot demonize parents for asking these questions.

I am standing here before you because -- quite frankly, it is a nerve-wracking experience because I know there are two sides of this and I am kind of standing in the middle. There are those people who say, �You are not going far enough, you are not saying that autism is caused by vaccines,� and so forth, and there is the other side who is saying, �How dare you even question our vaccine program?� At the end of the day I'm a dad and I want to make the best choices for my child, and I don't feel as if as a parent I have those answers, and I'm left in the driver's seat to figure out what's best for my child, and that's very scary experience.

We need you to step up and to really embrace the need for vaccine safety research. We need answers. We need true answers. We want things that are transparent, and we want to make sure that all of you have the best interest not for children in general, for each one of our children because not one of our children is ready to be sacrificed.

So, in summary we all know autism is a very complex developmental brain disorder, has multiple causes and it stems from a complex interaction of genes in the environment. We at Autism Speaks have that diversified portfolio of research, one that�s going to leave no stone unturned. We have an understanding of the role environmental factors play, and pathophysiology of autism is of paramount importance to us, and we will make sure that we get all the answers. This includes understanding the role of vaccines, the ingredients that are used in it, and may play as a contributing factor in the subset of the population. Clearly, more research is needed to enhance the safety of vaccines especially since they play such a critical role in public health, and as you set your priorities for this process please their mind knowledge gaps exists, transparency is key, all decisions must be based on evidence, and think about each and every one of our children because no one life is more important than the other. Thank you.

DR. PAVIA: Thank you very much. I feel worse for getting your name wrong after that, and I'll blame it on lack of reading glasses. Our next speaker is Lisa Randall from Voices for Vaccines.

MS. LISA RANDALL: Am I okay on the microphone? All right.

Thank you for having me here today. My name is Lisa Randall and I am from St. Paul, Minnesota. My husband and I have two children. Two years ago, I started to notice a lot of negative thoughts about vaccines among other parents, and it's difficult because (INAUDIBLE) anything to the rumors. I'm not a scientist. I'm a lawyer by training. (INAUDIBLE) practicing, but when I looked into it, even I could tell that a lot of the information that (INAUDIBLE) was on shaky scientific ground, and this bothered me because it meant that kids were missing out on their childhood vaccines.

I finally started following this issue, and I've gotten to know some other people who are interested in vaccine policy around the country. As part of this I've done some work with the Immunization Action Coalition, but mostly on a volunteer basis, but occasionally as a paid consultant on certain research and writing projects. My concerns for vaccine policy also motivated me to go to public health school. I enrolled in the Johns Hopkins (INAUDIBLE) program, and I'm a year into that now.

Most recently some of the people who are concerned about trust for successful immunization programs have been incubating a new organization called Voices for Vaccines, which is the nonprofit with the aim of minimizing endless disability and death from vaccine preventible diseases. By speaking out with valid information that will help individuals to make their choices about vaccination for themselves and their children and will seek (INAUDIBLE) also in the media and policy-making arenas.

We've already started signing up numbers to join us in this effort, and I set up some information about Voices for Vaccines on the table outside. I sometimes get a puzzled reaction when I mention to people that in my spare time I advocate for vaccines. I think that they _________ (INAUDIBLE) in favor of gravity or the sun rising in the east. We all know the value of vaccines so there's no need to do anything about it. We in this room, of course, have been made very aware of it. Not everyone sees vaccination as an unequivocally good thing, but I would submit that the concerns of the most vocal contingent don't necessarily track, those are the mainstream parents. I think there are ideological distinctions between parents who assume the worst about vaccines and those who have realistic assumptions about the people and practices involved in vaccine research and administration.

So, the first thing I would suggest, and I see that this is already part of the discussion, is active effort to solicit the opinions of parents who haven't made vaccine activism their mission in life. No offense to the National Vaccine Program Office, but it's not going to be enough to announce a meeting and see who shows up. Average parents have T-ball games and field trips and piano lessons with other kids as much as anybody, and we want them to be safe and healthy, but some government meeting on vaccines just isn't going to make onto our calendars most of the time. So the average parent is going to have to do more active outreach. We're developing of questionnaire for moms' groups around the country, maybe _______ (INAUDIBLE) focus groups and _______ (INAUDIBLE) areas. There are lot of ways this could happen, and I'm happy to see that ideas _______ (INAUDIBLE) today.

With respect to the vaccine and autism issue particularly, the _______ (INAUDIBLE) of community has a famous diversity of viewpoints, and in examination of the concerns of this group, which include not only an effort to collect the opinions of non-activists, but also consideration of the thoughts of people who are actually autistic. I would encourage the working group to the extent that it accomplishes public engagement by preparing information on materials to consider going and little heavier on the science than has traditionally been done. What I see for the most part is public health materials written to be acceptable to a broad range of reading abilities, and I perceive that this may create a little bit of suspicion on my people who feel they're comfortable pursuing more technical information. They _______ (INAUDIBLE) being told, �Trust us, we're the government.� Offering more details and reference to primary sources, might go a long way towards dispelling this impression, even someone who doesn't take the time to read the fine print or look up the journal article. It was like feeling a little better knowing that nothing's being _______(INAUDIBLE).

Another suggestion on the top of goods science is that I believe the public is best served by a research agenda that's driven exclusive way by the most current and reliable scientific findings. Not only does this avoid allocating scarce research money toward impossible hypotheses, which the Institute of Medicine warned against back in 2004, but particularly with regard to the autism issue, I think we come to the point when it makes sense to ask whether prolonging the research efforts does more harm and contains ________ (INAUDIBLE) that the evidence is equivocal and good in terms of likelihood, the informative findings.

I �d like to encourage the working group to do what it can to get people to consider the wider ramifications of their decisions about vaccines. We should talk about vaccination as an individual decision or family decision but, that's just not realistic when you consider that when an individual is vaccinated in most cases that act helps protect a whole array of other people _______ (INAUDIBLE).

Thinking on the path I know, I think most of them would understand and agree that if they want their kids to enjoy the benefit of _______ (INAUDIBLE) immunity and their kids don't have contraindications, they need to step up and help provide it. This is relative to vaccine safety engagement because every time we make a decision about a vaccine we compare risks; the risk of an adverse reaction against the risk of disease, and we actually reminded that the disease side of that equation improves the protection they can provide to others, particularly considering that those who can't be vaccinated because they're too young or in fragile health, other ones who must need the protection.

So let me tell you how I really feel about all this. As a mom I think my children have the right to the very best of modern medicine including protection from vaccine preventable diseases. Of course, they're fully vaccinated, but I then myself can give them the benefit _______ (INAUDIBLE) immunity, and I don't know whether they're in the small percentage who didn't become immune after one or more of the vaccines, and that's vulnerable to the hypothetical kid in the desk who went to Switzerland and is now incubating a case measles because his parents weren't sure vaccines were safe.

Right now in America, as you know, there are active cases of measles in Wisconsin, New York, and Arizona, on top of the recent outbreak in California. I'm quite sure I'm not the only one who doesn't want to have to start worrying about a disease that kills about 100 children every year before there was a vaccine, and so as much as I want to encourage the working group's efforts towards identifying people concerns about vaccines, I also want to ask that the motivators of non-vaccination be measured. There should be more study of parents who refuse immunization because of their fears about safety including looking up information sources to rely on and which ______ (INAUDIBLE) because out of all the licensed vaccines, maybe the most dangerous one was the one that doesn't get used. Thanks.

DR. PAVIA: Thank you very much. I think so far we've accomplished the first part of our mission, which is to hear a wide variety of voices, and our next speaker is Catherine Morris from the Keystone Center, who I think is going to help us think a little bit more about how we can get people speaking together and making progress forward.

MS. CATHERINE MORRIS: Well, after your earlier introduction, I feel like I should show to you my battle scores for credibility, but actually a lot of what Keystone is help groups of people come together; stakeholders, the public for collaborative problem solving and so where there are awards, most of our awards are just verbal, and I wanted to really share with you today some experience not that I bring here from the health and social policy arena because my - most of my 30- year career has been in energy and environmental policies and around those types of conflicts, but I think I believe that a lot of the experience that I have in dealing with - I might need your help here in finding the documents, but in dealing with issues like how much more nuclear power do we need in this country? What are the safety and proliferation risks that we have? Will it help us address climate change? How do we weigh those risks? Those are kinds of questions that I deal with, but I think a lot of the same process and outreach that I'm going to talk you about apply there - apply equally well so what I'm going to do is give you a little bit of walk through the way I would as someone who is trained conflict, mediation, negotiation, and community engagement, how I would assess what type of process you might want to use if you are going to, at many different levels of a public policy decision-making process. So this is not an attempt to make any recommendations. This isn't an attempt to tell you that I have the answers, but just really an attempt to share with you some of my experience about how I would - what questions I would ask and things that you might want to consider as you're trying to figure out how to bring the public into the process of your decision.

I start with this cartoon because I think many of us when we conjure up, you know, an image that goes along with public participation, often think about that room full of the angry public with all the experts at the front of the room and each individual comes up to the microphone to state their objections to the particular policy or the action. They then take their seat, their comments are dispatched into the appendix of the report when the decision comes out much like being dispatched over the cliff, and you know, that's the old style, and one of the messages I want to bring to you is that public engagement has come a long way and there is a lots and lots of different ways to have much more effective dialogue to bring people in and have some mutual learning, and I've heard a lot of the elements of that being discussed today from some of the prior speakers.

I think we both are seeing that being used in some pretty controversial issues. I know many of you are aware of the fact that we used to print a lot of public engagement process to make decisions about the World Trade Center site. They have been over the course of the last two years and ongoing are still bringing in the public in a number of different ways, a number of different processes into the question of what really happened after Hurricaine Katrina, and what we need to do to help recover from it. I think my main message, although there may appear to be some caveats along the way, my main message is that a well-chosen, well-structured public engagement process can really bring the -involve a very broad sector of the public. It can result in mutual learning and it can also help bring new ideas of the problem-solving process.

In the end, the goal is better alignment of public policy decisions we make and our public values. These are -- you know, it's a great goal. It's not entirely easy to accomplish. I can't - don't expect anybody to be able to read this. I did have a handout that was out on the table out there that has this blown up on a full page, and really the point of this is just to give you a sense that there's lots of different levels of public engagement, lots of different objectives, and part of your challenge is trying to match the process with what your objectives are. So you know, for instance, if you want to share information that usually comes very early in the process. You will often have much more of that one-way communication, but that is a legitimate part of process, and it's legitimate for certain circumstances.

If you want to consult with the public that's sort of the beginning of that two-way conversation, and it allows you to start understanding a little bit better what values underlie some of the positions that you hear at the microphone. If you want to, and this is -- debate this turn, but if you want to engage the public then you're starting to talk about a process where you can actually start allowing the public to bring new solutions to the table, solutions that hadn't been thought of by the experts, and then finally I think, you know, at the far end of the spectrum there is the opportunity to actually collaborate in power the public in a way that actually gives them and delegates some of the decision-making authority, and I think again I just want to emphasize that all of these have some legitimate place.

This is just again a way to try to explain how information that's used differently across this continuum. I think it's a very _____(INAUDIBLE) informing again is tends to be the experts who deliver information, and the public who delivers back, but hopefully as you move along the spectrum of collaboration you're actually going to bring into this whole process - you're going to process information together. You're going to decide what information is most useful to solving whatever issue's at hand and you're going to hopefully agree that it's credible together. You'll learn from each other in addition to that, so I think that is - it's that hope of reciprocal learning and some enrichment that this far end of the spectrum offers everybody, and I think that it requires that we give up sometimes as experts, we give up the presumption that the public can't really absorb and learn really technical scientific information. They can't process it in a way that's useful, and it requires experts also I think to be open to the fact that they had something to learn from people who aren't experts, that there may be new - you know, new solutions, new ways of interpreting information that they can learn.

I think again, what I wanted to do was share with you how -- what types of questions you have to ask before you decide what process you want to embark on, and this is little technical but a little, I would say, sort of mediator speak, but you know, it's one of the processes that we go through is in thinking about the different legs of the conflict, the different legs of the process. That includes, you know, what are the facts and the substance and issues here. What are the emotions and the values that are underlying the different positions and then what is the process and the procedure, and here I mean the process and procedure of that will - either led you up to these circumstances as well.

MS. MORRIS: - and then there is another set of questions that I think go one layer below this which is, you know, who do you want to invite into the room? Who needs to be involved? Certainly, you want to have the people who are being affected by the decisions that are being made and you want the people who have some influence over those problems and you want the experts, but you also might want people who I think is - one of the speakers said are not necessarily focused on this issue, the general public. It's not their main concern, it's not a top priority for them but they may, you know, they also may be able to bring something new to the discussion. You need to ask the question, you know, what are the issues that are important to them? And what we need to deal with? What's the level of trust? Does that have to be handled, you know, do we have to build a level of trust before we can get to the question at hand? And again, what information do we have? What information do we need? And how do people in the room interpret that information? Because everybody brings a different interpretation even if you can agree on the facts. You know, this is the beginning of the list. There are many more questions as you get into, I think, the specifics of how you would run the meeting or how you would run the engagement, but I just want to get that started so you have some food for thought.

There's a lot of different models for public engagement, a lot of, you know, some of them have names, some of them don't. Also, this is on the other side of that handout that I put out there so that you could actually read it. I didn't want to specifically go through each of these and explain them to you because I am not sure that is very helpful to you at this point. What I would like to do is just kind of highlight some of the objectives of some of these different processes. Most of them that - I actually hand picked these and you'll see that I hand picked them because they tend to be on the more collaborative end of the spectrum. I think you're probably familiar more with the public hearing format, the surveys, the focus groups. These are, I'm hoping, new ideas to you, and I think ones that you may not have actually participated in before. But some of them - a lot of these on this table, happen to have - their intent is to reach as many people as possible. In some cases, it's to reach people who, you know, that are actually statistically significant representative populations. So, and again the more quantitative you want to translate your results from your public engagement, the more people you have to reach, the more random your selection has to be.

Some of the others here and I would just say that includes, you know, the town hall meeting that the new version of the town hall meeting which is much more of an information sharing which allows you to also get into small group discussions over the course of the day. The consensus conference, deliberative polling, national issues forums, these are all fairly large group processes to try to reach as much of the public in a representative way as possible. There is also, you know, here a couple of examples of smaller group processes that are intended to help you reach consensus on various issues. I think the citizen's jury, the dialogue by design, future search processes, study circles, you really - obviously everybody knows you do not reach consensus with 200 people in the room, but you can hand select specific stakeholders that you think have credibility and represent the interest of a much larger group and work with them to try to achieve consensus on various points.

The last thing I would like to leave you with is just some guiding principles and I think Ben touched on a lot of these. I've heard the term transparency come up on a number of others' comments, but it doesn't hurt to repeat them because I think they are pretty important.

Meet people where they are. And that may mean that they don't trust, that may mean that they don't trust each other, that may mean that they don't have all the information and need more information. But the point is you've got to start where everybody is and rather than, you know, jumping in where you'd like to be because of time constraints and try to actually use that public engagement to decide where you need to go together and then you can design the process around that.

Strive for transparency. We've hear that a couple of times. I think we all know that no process can be completely transparent. It's just difficult to have all the information everybody knows out on the table all the time, but it is pretty important to the credibility of the process.

Encourage a beginner's mind. Beginner's mind, I think that - and I hope I don't offend anybody. There are experts in the room, but you may have heard this saying that, you know, experts have a few ideas but those who aren't experts often have many because they start out without any preconceptions. So the idea is to go into the room with the openness to learn from other people, to be open to new ideas.

Find credible and trusted experts together. I just finished, as I mentioned earlier on, a joint fact finding process. The joint fact finding process is structured so that you can - instead of having your typical dueling experts come in the room and fight it out and then we all take a vote on who we believe and we end up in the same place we started. We should actually try to decide up front who - what experts do we trust? Who are the credible sources of information and work with them from the beginning.

Create a safe environment to explore understanding. And that - that ends up being translated into a couple of key process issues. I mean, sometimes you need a neutral convener if there is a lot of distrust. Sometimes you need - I think all the time you need a good set of ground rules when your are starting your discussions about how you are going to treat each other? How you are going to engage? And then make sure that everybody understands what the path of implementation is. I heard an explanation of, for instance, where some of the recommendations are going to go. Everybody needs to know that. Everybody needs to know who is going to make the decision, what they are going to use - do with the information that you give them from a public engagement, and you know what is the path for implementation. How is it, you know, is the public going to be involved further down the road as you are actually starting to implement this? I think one of the distinctions I didn't make earlier is that as you work collaboratively, it's really a sustained public engagement process. It's not just a one off meeting and it may change over time but it typically involves as many people as you can in the actual implementation.

And then, I guess my final word of advice is don't raise expectations you can't meet. We have all been in situations where, you know, you hear that your input is going to be taken into account, it is going to be addressed in decision making but as I think someone else had mentioned earlier, sometimes that accountability doesn't come back around. You don't really hear how that is going to happen or how your input has been taken into account. And, you know, the other part is, we're all human so sometimes politics can come in and turn upside down the decisions that you've made as a group. That needs to be acknowledged up front too, that's a risk. But I would just like to add on an up note which is that you know I have seen it work. I have seen people walk into a room who don't trust each other, who don't believe each other, who have completely different perceptions of the same issue and over the course, you know, it's not magic -over the course of sometimes a year, two years of being together, of talking together, of learning from each other, at least part of the - there is an understanding of at least part of the issues. And I don't say agreement, I say understanding because that's part of the building of the trust is just getting to the point where you understand why they feel the way they do and so the process has to support that. Thanks.

DR. PAVIA: Thanks. And these were five terrifically useful talks and I thank everyone for that. I would love it if the presenters would be able to come to the microphone if there are questions for them or specific clarifications that people want to hear. I think we heard in spite of the differences, a lot of common themes and I won't spend a lot of time elaborating it but there are a number of things I heard everyone say in one way or another including the need to have these kinds of conversations, to involve a lot of people and it is hard to even find what term to use. When we say the public, we say advocates, we say consumers, but we are really talking about the people who are concerned which is everyone of us citizens and parents. We heard a need to acknowledge that at the beginning of every process that we don't have all the answers. I think that came through loud and clear. And we heard the fact that I think compared to everyone that this needs to be more than a one off process, that this needs to some way in which this dialogue is started and that it continues. So with that, the next question that we can at least chew on for a minutes is having had the beginning of this discussion, how might we do that? I've learned from some of lessons from settings where's it's worked like the breast cancer and HIV world, from some of the mistakes, from some of the experiences, from fields of outside public health.

UNKNOWN MALE VOICE: (INAUDIBLE)

DR. PAVIA: And I can perhaps speak a little more directly instead of being so rabbinical and say two or three speakers from public organizations, you have heard a little bit about different models, you heard some of the models that Ben talked about, and some of the methods and you learn a little bit, just the tip of the iceberg about the complexity of the science of how we might have these kinds of processes. So having heard some of that from the three of you, are there thoughts about types of processes that you heard about that we might want to go forward with? There is a mic right over there if you -

MS. FISHER: Well you know we've been through this before.

UNKNOWN MALE VOICE: Yeah.

MS. FISHER: Yeah. And there had been different forums that we have tried to do this in terms of setting vaccine research priorities and engaging the public. I think one that I would sorry - I feel ____ failed and that was the participatory democracy experiment where there were just a lot of people who had a lot of interest in this issue coming together over a three year period and Keystone was involved in that. And I think - I thought that held great promise because it was not just sitting at meetings where people would come to the microphone and then go home. And it was truly an engaging process where people were talking to each other over a weekend sometimes and getting to know each other and it felt like it was going somewhere and then it collapsed. But I think that, you know, if this is the structure that you are going to use, then at least you have to bring more people and I actually agree the neutral public should be part of this. I was very impressed. I attended one pandemic flu meeting which was in Atlanta which was part of this ___ initiative and I was struck by the fact that the �uninformed public� coming in really was really intelligent about the issue even though they had not been backgrounded about it until they got there. And I think that it has to be a mix of both the interested public, the concerned public, the stakeholders that have already been identified as well as the �mutual or uniformed public.� And I think that when you bring all those people together, it's representative of the U.S., you do get good decisions and I think it was important to see children - children. Why children? Because children are our future. And that - and every parent - they would rather die for their child than live and not have their child live. So I think if we all remember that, then I think we can come to the table and try to put aside some of these prejudices we have about each other and try to truly have a dialogue because after all, you know, if we don't think figure this out we are going to have a tremendous problem to deal with in the future in terms of so many chronically ill and disabled children. I don't what portion of that is due to vaccines, but you know if we are not identifying the high risk groups and we are not doing our best to screen them out, we simply do not know how many children are being injured.

DR. PAVIA: Was there any - let me ask one more question as long as we've got you miked.

MS. FISHER: Yeah.

DR. PAVIA: Is there in a sense reason that the participatory democracy project failed or fell apart do you think?

MS. FISHER: Well, I think that ultimately in the end, those who were in positions of power who did not want the status quo changed, who were threatened by a rapprochement, if you will, between government and the people or the concerned public. Basically, they won and so we did not go forward in the way that it was originally planned. What we were trying to do was create a safe haven for people to come and discuss difficult policy decisions with regard to vaccination and, you know, creating a new model of engagement is very threatening for people who are very comfortable with the old model. And so it became a power struggle and in the end it disintegrated because the people do not have the same kind of power right now. The power lies in the hands of the public health officials, the industry, the pediatricians, everyone who is vested in the mass vaccination system as it is now constructed. So it is very difficult for the people to come forward and be part of the process. And so I really hope this is the beginning of a new way of dealing this very controversial issue.

UNKNOWN MALE VOICE: Yeah. When you and I talked about this, you also brought up another model. That was ILM forum and maybe you could talk -

MS. FISHER: Yes, well that was another one. I thought - I thought ____ this year. That was a four year forum. It was really the first time that the stakeholders had all come together. I actually thought there were some excellent reports that were issued that really have not been paid attention to which is why I wanted to at least submit the statements that I had made in 1995 and 1996 at these forums and there were some, you know, the report that came out of it were truly collaborative. In fact, I co-authored the report on risk communication with, I think, Geoff Evans and Kathleen Sutton, and I mean yes, it can happen but people have to have the will and especially the people in power have to have the will to do it.

DR. PAVIA: Thanks. Did you have the same issues? That would be great.

MS. RANDALL: I don't call myself an expert at all in public engagement. But the only one thought I had is I really liked what Dr. _____ described, that model where it's teaching and learning together, going in multiple directions. The only caution I would have with respect to that is to - before you even try to get to the point of forming consensus or making decisions to really make sure that you are all speaking the same language as far as what is science, what is the use of statistics, what are the relatively different kinds of evidence because I think part of the difficulty is that people have really different ideas about that and then tell you kind of that understanding of it I think it would be hard to make progress.

DR. GOLDMAN: You know, just to comment on some of that and one thing that would be very helpful to all of us to hear from members of the public and that is in terms of the work that we are doing, what's the appropriate kind of involvement of the public and participation? For example, do we - should we have more consumer representatives in this working group or do we need to have scientists added to the group who would be trusted scientists in certain areas? That kind of thing I think would be useful to us very specifically. I guess, and I've participated in a lot of processes in the environmental health side to try to bring people together to develop consensus sometimes. Sometimes just dialogue and I will say that it is a lot easier to do something like the ILM forum where you're bringing people together to engage jointly in an investigation or jointly in a project together and to develop work together versus bringing people together to develop consensus where you are actually asking people to agree can be very different unless the stakes are very high and people are forced into a situation of a consensus where they must make a decision together then they will be motivated to do so, but beyond that people - often these stakeholder groups do fall up apart over people just not being willing to at the end of the day make a compromise if there is no value that they see in it for themselves. And I think that, you know, in addition to the rules that ____ put up there, I think that is another one that I would put up that I think is very important which is in terms of what you are asking people to do. I mean you are asking for - well you can't ask people to come to a consensus unless they've got enough at stake for a consensus to be willing to do that because it always involves some kind of a compromise and that is really hard for people to do. But in terms of this group, I mean we really - we have such a short period of time where we're working and you know what can we do to enhance the involvement of the people in this work and either they can observe what we are doing or participate in it.

DR. SNIDER: Andy can I get up and speak? This time, as a former full time employee of CDC but also as a grandfather and, you know, Barbara and I don't agree on a lot of things, but I just wanted to reinforce what Barbara said about why that broke down and I, you know, it's not useful to name names or anything like that, but the reality is that I have been part of, you know, the federal bureaucracy for now 35 years and there had been attempts in recent years to engage the public around certain issues and some have been successful like the one Ben pointed out recently, but because of some of the people who are no longer here in the department, but who work here, we put forward some ideas for engagement around specific vaccine issues as well as broader issues and there was not support for it and we were not able to execute on it. And I understand some other concerns and frankly, you know, I'm glad ____ here, industry needs to represented as the people who have spoken about the importance of vaccines. I mean, I certainly now wanted my grandchildren to be vaccinated and protected against vaccine preventable diseases and we want viable pharmaceutical industry to provide these vaccines as well as new vaccines but - and we don't, you know, we don't want industry to be threatened by all of this process but at the same time I think that in the larger scheme of things hopefully we really can develop a process where we can have an effective National Immunization Program that will get a large proportion of the population vaccinated, all of those who need to be vaccinated, but at the same time have a process where we can maintain - I mean we can only do that as it was pointed out by Ben, if we have trust. And so I guess I'm just pleading that we, as hard as it is, try to craft away that is non-threatening to those in authority, non-threatening to the industry, to engage the public an honest and open dialogue about these issues so that we can continue to protect our children from vaccine preventable diseases and to the extent we can and against any adverse events caused by vaccines to the extent that we can.

DR. PAVIA: Thank you very much. That was - I am just going to - Bruce, I'm going to put you on the spot. You're the ranking official in the room. I think you have told me that there is a high level of commitment in the department to going forward with these kinds of processes. ____ on the spot, say something about that.

DR. BRUCE GELLIN: That's - we talked about this before and this is a - as Tevi and I said in the beginning, this is a process that led to meeting that started a long time ago. It just happens to be coincident with other events that made headlines, but I think that's the process that's an important one to reinforce, recognizing that a crisis of trust is going to be a crisis of public health before long. So I think that's the - it's with that spirit that there was support throughout this department to have this meeting and in fact to have the kind of discussion we're having now, not only the front end of this about the scientific discussion and looking at the whole system, not just the CDC part, but how best to engage it so that at the end of the day there is trust in the system.

DR. PAVIA: I don't want to eat too much into the time for public comment. All the other speakers engaged - spoke up about what might work for them in terms of public process. Peter do you want to ____ at all? I will give you equal time.

MR. BELL: Pick out - just try to answer Lynn's question and that is, yes I thinks there is an opportunity to expand this group and I think I heard a couple of suggestions both from people within the work group as well as some of the public members. My advice when you do that is do it thoughtfully, pick the right people, and pick people who are willing to be in a constructive dialogue here. I have been very impressed with some of the thoughtful comments I have heard today. So I think you have done a good job today. I think there is an (LAUGHTER) - you've done a wonderful job today, excuse me. But you need to really be conscientious of bringing the right kinds of people who can come to the table, be constructive, who can articulate themselves in a meaningful way, but at the end of the day be respectful of the process. And I had mentioned the DOD process and I think that was one of the key components is that we had people at the table who whether you were a scientist or a parent, there was mutual admiration and we were all able to come together and do what's right for what we all agree on which is our kids and as long as you're willing to check your biases at the door and come to the table and be open-minded, it will prove to be a successful process and I think that that has to be a key ingredient to this group for its success.

DR. PAVIA: Thanks. I just thought I would try and synthesize one thing that is coming out of this. I think - we talked about two things. I want to have this clear. The working group has already started talk about how to round out our membership. We are mindful of the fact that we are already 17, we can't add too many people and still getting any work done, but we have also had a lot of discussion here about an ongoing, thoughtful, broad based public dialogue, presumably one that would not just exist for the purposes of this agenda and this - that crises but one that would not die and would carry forward what the original participatory democracy process might have been trying to achieve. We have promised time for public comment so I think we should probably move ahead with that unless there is anyone else on the working group who wants to make a comment right now.

DR. SCHEIDT: I just wanted to comment that I had an ah-ha moment triggered by Barbara and brought home by Peter that, you know, the National Children's Study has a federal advisory committee and five years ago our advisory committee submitted by some discussion about autism and vaccines, I proposed that - in fact, the National Children's Study might - it be feasible to randomize and embed a clinical trial of delayed immunizations to answer this question to which the advisory committee responded well. The people who feel so passionate about that probably don't accept the evidence today, they probably wouldn't accept that anyway. And the very first serious proposal I have heard for a similar approach was from Barbara today, not from a scientist but from a passionate mother. And it struck me that this trust thing, you know, has to go both ways and it certainly didn't go from the scientific group that we had to the community. And the only other thing I would suggest is that it seems to me we are facing the issues that are embedded in the principles of community based participatory research and the approaches of that community of that discipline that has discovered that if you are going to really engage in community based participatory research, the community needs to be at the table the whole time.

UNKNOWN MALE VOICE: That's a great point. The NCS is a community based study but there is nothing more community based in vaccine practice and it's -

DR. PAVIA: I do want to move ahead just so that we don't cut anyone out here. There are 12 people who signed up for response to make public comments. We have offered five minutes each. I realize that can be a short amount of time, but if you could make it even shorter, that would be better. The microphone is over here. I'd appreciate it if you introduce yourself, you say what your affiliation is, as we have done, if there are any significant conflicts or other vaccine related issues you have that relate to your comments, I appreciate you sharing that with us. And the first person who signed up is Kelli Anne Davis. And I'll apologize in advance, the lights are right behind you so some of us will barely be able to see you.

MS. KELLI ANN DAVIS: Should I?

UNKNOWN MALE VOICE: No, that's fine.

MS. DAVIS: I have to put my granny glasses on because I have to read. My name is Kelly. Should I be facing them or you?

UNKNOWN MALE VOICE: Face that side.

MS. DAVIS: Okay. ___ go all the way back, I can see everybody. My name is Kelly Anne Davis and I am a National Autism Advocate and I have a son, Miles 15. That's my most important role, is being mom to him. I just wanted to - I guess as a foundation for what I am going to say, Kelly means bold warrior and anybody who has met me knows that's exactly who I am. I am very passionate, very - just truthful, honesty, that's what I am all about. I have a unique opportunity right now to kind of present kind of the way the autism community is kind of looking at all this. Of course, you all are aware of the recent headlines with the ____ case and, you know, vaccine safety is very, very important. And so I am just going to be completely honest as a mom and an advocate in the community and even though I'm one voice up here, really when I am speaking there are thousands of people who believe the same thing.

There is a lot of mistrust in our community as you all can imagine and I have been in conversations with several people in this room and in the government for several years, and for transparency and I have heard that a lot today and participation is very important in this process. Today, this is just - I'm just being honest and open but an example of that mistrust is already there with a lot of parents in the community. Part of the panel today, for instance, and I have never met Lisa before today, Voices for Vaccines. I was not even aware of this until yesterday and I did a little bit of research. But this issue is not about promotion - vaccine promotion, you know, of course there is the promotion and there is the safety and this is a safety issue. And I believe that my son was injured by his vaccine and there are thousands of parents out there. So that's the role of this group.

So what I would have done if I were setting up this panel a little differently is, you know, of course Lisa being in the audience, she could come up during the public comment time and as a mom express, and I respect you Lisa as a mom, you know, express your views about the promotion of vaccines and that's all and good - that's all fair and good. But on this committee and on this panel, we should have had somebody like Mark Blaxill which I had brought to Bruce and Dr. Robbins and Dan the other day and I'm still going to reiterate that now. I believe that somebody like Mark Blaxill with Safe Minds who works on strategic planning. He happens to be on the IACC strategic planning group, has been doing strategic planning for 25 years, is an advocate, passionate, diplomatic, you know, Dr. Robbins met with him for three years now. I think he would have been a perfect choice to be on this panel and so what happens is the way it was constructed today and you can go out it is already out there on the blogs, is when he have Voices for Vaccines here and the website isn't even up and Lisa is a part-time consultant for the IAC, the Immunization Action Coalition which is funded by five pharmaceutical companies and two branches of the CDC, all that does is perpetuate the mistrust and this is so perfect right after what Peter was saying. It's the - it's that, I mean just do that little bit, make that little difference in the panel would have been that much better. Do you see what I'm saying? So that's - that's kind of the point I am trying to make there. So that was the first point and then the second point of course was -

DR. PAVIA: You're almost out of time.

KELLY ANNE DAVIS: Yeah, I know. I want to see Mark on the committee - on the working group, that would be great. And then John - and I don't know to pronounce that, is that Islander?

DR. ISKANDER: Iskander.

KELLY ANNE DAVIS: Iskander okay. Hi John. You were talking about the - and this is kind of a question to you. You were talking about the ProQuad and then you were talking about the VSD and how the signals and that was what kind of what gave you the signal to pull it off, you know, the market. Now, and I cannot remember, I believe that Dan Oldsted, he did a little bit of investigation into that and it was when his calls - he was doing calls to Merck to find out about some safety testing and it was after he was reporting that, like a week or so after, and I do not have the exact facts down because I can't remember the exact article, but when he started making those inquires, that's when they started pulling the ProQuad. Now that's, you know, again I can send you the information but I believe that's correct so I don't, you know, I guess if you could maybe clarify with the VSD because I, you know, that's kind of my understanding of it. I did read his article several months ago, but I think that was the gist of his article.

(CROSSTALK)

DR. PAVIA: - to discuss that with Kelly afterwards and off-line because I don't want to eat into the time of everyone else.

MS. DAVIS: Right. No, that's what my point - that's all, you know, I'm just being a voice and -

(CROSSTALK)

UNKNOWN MALE VOICE: - get back to you on.

MS. DAVIS: Okay thank you, thank you.

DR. PAVIA: Thank you very much. Our next speaker is David Kirby.

MR. DAVID KIRBY: Thank you very much. My name is David Kirby, I'm a journalist and author. My conflict of interest is I wrote a book about vaccine and autism but I am not trying to sell any copies today. (LAUGHTER) This was a most extraordinary meeting and I am really happy that everybody was keen to have it. I will be reporting about this in various venues and I am not quite sure what my, as we call it, take home message is going to be. I do want to say and at the risk of overstatement, history will judge each and everyone of you. At a year from now, five years from now, ten years from now, people like me will look back on the history of vaccine safety in this country and look at you folks and say what did they do? And I am going to guess from your body language that you know that there is an issue here.

We have a problem with the vaccine schedule. We do not know what it is. Now, you have the power to listen to these community people and make some decisions and maybe make a decision that you are going to look into this and change things. Or you can decide that you are going to protect the status quo. And if you do, you do that with several risks. One risk is there really is a problem perhaps with the vaccine schedule. We know that Hannah Poling was injured by her vaccines, now she has autism. For all we know, some kid right now with mitochondrial dysfunction is getting vaccinated with multiple vaccines, may get seizures, may get fever. We do not know what the ultimate outcome of that child will be. Keep that in mind as you revise the schedule or not. And if you choose to support the status quo and pretend like we don't have a problem here, if you think you have trust problems now, you can imagine how far away you are going to send parents from vaccination.

I am extremely pro-vaccine. I live in Park Slope, Brooklyn. I talk to young parents in my neighborhood all the time. These are not autism parents, these are not vaccine activists. These are frightened young Americans who are looking to you for guidance. And you know what, they don't trust you and I take no pleasure in saying that but you have a real problem on your hand. I am journalist here telling you. Yes, they want to vaccinate their kids. Yes, they want to believe in the medical establishment and the government, but they do not trust you, a good number of them. I know that does not sound nice to hear, but you have to take that in account.

A couple of other comments that were made here today that as a journalist, and I probably will mention these in my reporting, Dr. McCormick said how quickly can we get the information out to the public after these RCA's are done? She wanted to know that so we can reassure the public. Well that data is not always going to be reassuring and I understand the desire to reassure. Everybody wants to reassure. It feels good to reassure people, but when people have genuine concerns about vaccine safety and all they get is reassurances, when their questions are not being addressed directly, that does not built trust, that does not support transparency, that sends parents away from vaccination in very dangerous ____ and nobody in this room wants to see that happen. We all want to protect the children of this country.

I just have a few very quick questions about the vaccine schedule. I have been hearing a lot of talk on the CDC lately about flexibility and my question is if there is flexibility then parents do have the right to talk to their doctor. Hepatitis B vaccine, will that still basically be mandatory at birth or will parents have the right to say �no, I prefer to wait a while?� On that subject, what exactly is the rationale for hepatitis B vaccine at birth? I heard about four or five different rationales from different public health people without knowing the exact reason. It makes it very hard to decide whether it's a good idea or not. I would like to know if MMR titers can be offered to the parents so that after the first round of vaccination, if the child has developed immunity, is it necessary to revaccinate? Would a certificate will be available for that child to prove that they have an immunity and don't need to get revaccinated? On MMR, can we possibly separated out the M, the M, and the R if parents want. Can we encourage industry to produce more monovalent vaccine and can we work with parents who want to go that route again to encourage them to come back and get vaccinated. Nobody wants children to go unprotected, but parents have reasons for asking these questions and if they are not given the proper answers, they may just not vaccinate. Can we get a test on vaccinated versus unvaccinated populations in this country to give us some idea if there are - maybe there are no more adverse reactions in the unvaccinated or vaccinated populations. But if there are, that will at least give us some directions and things to go look at.

Finally, what is being done to identify children with mitochondrial dysfunction before vaccination whether it is a nuclear DNA test, a mitochondrial DNA test, or even just a simple blood test to certain metabolic markers. And if we are able to identify those children, I realize it's very precarious. They should be first in line to get vaccinated because they might be more at risk of regression due to febrile infections. But should recreate a separate schedule for those children? Yes, maybe they should go first, but maybe that one size schedule does not fit all including the children with mitochondria - and finally, my last question. I'm sorry I flipped because I forgot where I was.

When we talk about relative risk, can we also look at lifetime risks particularly with influenza vaccine because most people get that every single year and my understanding is that lifetime risks are actually magnified quite a bit when you talk about yearly vaccination. So those are not just rhetorical questions, I don't expect an answer but I hope it will go into the record.

UNKNOWN MALE VOICE: Thank you very much. I appreciate that. [To panel member] I'm not going to let you answer even if you would like to, but I expect that those questions are on the record and we'll try to deal with them as best - for who have answers. Our next speaker is Clifford Shoemaker. Mr. Shoemaker? Okay, then Jim Moody.

MR. JAMES MOODY: Thank you very much and thank you to committee for making this time available. I'm Director of Safe Minds which is a think tank and funds research. My conflict of interest _____ is we raise money for research that the government is unable to fund so far. I am also a Director of the National Autism Association which is a parent group, actively involved in representing families with autism, providing services, and raising money for research as well.

I just have a - I would like to add to my colleague's ___ just a couple of quick things. The most important - two most important points is there is a public health crisis. CDC issued an autism alarm in 2004, identifying one in six children with autism, asthma, diabetes, juvenile arthritis, and other forms of developmental delays and learning disabilities. Many of the CDC people today talked about using VSD and VAERS to find a signal. That was a scream. One out of six children is profoundly affected and the time series roughly correlates with the dramatic increase in vaccines, use of mercury, use of aluminum, _____ even up until today. That is a scream that calls for urgent action to validate the safety of the vaccine schedule or to find out what is wrong with it and fix it. You have CDC as essentially noticed the signal, but done really nothing about it to address those problems.

As far as I know, the vaccine schedule as a whole has never been subjected to the kind of safety testing that any new drug would be subjected to. And that is, first in animals, then in humans, give the schedule as recommended versus placebo. In this case, that would be without vaccination. There have been a lot of epidemiologic studies or so, lots of clinical trials involving vaccines, but those are generally in fully vaccinated, otherwise fully vaccinated children. We look at acute disorders and acute responses up to 20 to 30 days. As far as I know, in the clinical trials there is generally no look at the chronic outcomes. Vaccines are designed to affect the immune system and that is chronic effect over a lifetime, therefore, adverse events following immunization must also include chronic long term impact. Since the vaccine schedule has never been validated in an experiment and applying a well designed experimental control trial, vaccines themselves must be regarded as a population based experiment on America's children. As such, the ethical guidelines in conventions like the ____ convention and ____ convention apply. And vaccines are presumed to be unsafe as is any drug until they have been validated with solid scientific evidence. Therefore, the government in conducting this war against infectious disease -

(END OF AUDIO)

MR. MOODY: But it's working as a battle against infectious disease because there are unintended casualties and those are entitled to as much respect if not more as the ten percent of vaccine-preventable disease. Let's see - the preventive process, I think CDC to some extent involves sort of a Titanic model. The people on Titanic were certainly involved with participants in the decision making process about maritime safety if I would have to comment on it after the crash, but yet they were involved in the tragedy. Public participation is essentially pointless unless the people who are most vaccine affected sit at the decision-making table. They must be able to make the decisions and have as advisors those who in public health community who favor preventing vaccine injuries aside from preventing vaccine preventable disease and those who are interested in making profits from giving the vaccines, but the people that are making the decisions must be those most directly effected.

DR. PAVIA: Thank you very much.

MR. MOODY: Okay. Thank you.

(Clapping)

DR. PAVIA: The next person's who's going to speak is Tracy Stewart. Could we move the microphone about three feet to the right. That would be nice actually. None of us can see you. Oh that's good.

MS. TRACY STEWART: My name is Tracy Stewart and I am the vice president of the National Autism Research Association of Florida, Florida chapter I have a son with autism. He's nearly five and ______ (INAUDIBLE). He still doesn't speak. I have no conflicts of interest to report. Please let me know if I go over _______(INAUDIBLE).

The information that I am going to discuss is from ________(INAUDIBLE). I have not gotten any of this from anti-vaccine websites. Issues that I would like to ______ (INAUDIBLE) is that clearly there are - there are symptoms of immune y functioning in children and adults with autism. There are also _______(INAUDIBLE) interleukins and _______(INAUDIBLE). In one study they found 50 times in the cerebral spinal fluid _________ (INAUDIBLE) levels compared to serum. This is remarkable. Clearly that doesn't tell us what causes that, but I believe if there's - if we can identify subgroups with problems in - with their immune system and that if there's some lower level of immune dysfunction this was something that we have to identify. I wonder myself if I have high levels of cytokines. These are generally - you can do _______(INAUDIBLE), but not the whole pattern at general labs. I wonder my maternal cytokines could have influenced his brain development. I would implore you to add pregnancy prenatal exposure to vaccine. For instance I think that it's been shown epidemiologically that in humans flu virus, and this is whether it's a vaccine or a natural is elevated -- reached the elevated risk of schizophrenia. I don't think it's the virus itself. I think it's the mother's cytokine expression that does that damage. I say this because in animals they've shown abnormal antisocial behavior whether the actual virus was given to the animals or just the cytokines that the virus would provoke, and so autism has been linked prenatally to exposure to herpes virus, Lyme disease, rubella, measles, mumps, and flu.

I myself last year was diagnosed with Lyme disease, so this is a very compelling question for me and yet overall I think it's -- I personally think it's interesting that we are still recommending for pregnant women to get a flu vaccine in light of this. Just personally too, my son has low carbon dioxide in his serum, high aspartate aminotransferase. He's got high levels of ammonia. He's got levels in the 50s, both times we've tested when _______(INAUDIBLE) thinks is a microgram per liter unit, I apologize if that's wrong, and the reference rate is 11 to 32. This is a subacute hepato-encephalitis.

So anyway to summarize, I do think that there is strong evidence that there is a immune function- immune dysfunction in autism, and so clearly vaccines may be playing a role. This is something that we have to identify. We have to develop these subgroups. I would commit to Lisa and some of the other people that might agree with her that the research is not - and I apologize if this isn't what you meant when you said this, but it sounded like she was saying to me that the research was done and there was no link between autism and vaccine. I don't think it's possible to say that and come to the conclusion, and to have been able to identify the subgroups and do tests, and by the way, we see some big titers on your MMR. It's _________(INAUDIBLE).

I only get angry when I hear people claim that the science is complete and is over and this is redundant. I look at you, and I trust you. I think all of you are trying to do what's right for our children, to helping mothers and brothers and sisters, and excuse me, but I do trust you. I do think that they are trying to do the right thing. We just don't have enough evidence yet and I think we are just coming from kind of different sides because I'm in that less than one percent that has an autistic child, and I did not believe that vaccines caused autism until I started reading on Pubmed. I did not go to anti-vaccine websites. I apologize for being emotional. I trust you. I know that you'll do the right thing. Thank you.

DR. PAVIA: Thank you very much. The next person on the list is Lou Cooper.

DR. LOUIS COOPER: I didn't put myself on the list, but I guess _______(INAUDIBLE) were reading my mind. I know - I suspect I know a majority of people in this room, and the truth is I trust all of you. I trust your integrity. I trust your humanity. You wouldn't be here if you didn't have that extra high level of humanity. What seems pretty clear to me is that what is dividing us and gives us a lot of polarized and conflicting views is the gaps in our knowledge because when we have all the facts it's amazing how we generally tend to think, come to the same conclusion.

What I'm so pleased about is that this function exists, and what I hope all of us can do is continue to give the support for the activity of which this is a part because I think until and unless we have the resources to do the kind of science that we'll all have some trust in we are going to continue to be looking at each other and our unhappiness and our discomfort and our inability to give parents the security that they need ill plague all of us. Those of us who are pediatricians have to look parents in the eye everyday, and for us in some way his vaccination is a routine thing until it's our own child and then you think about it. We want to be able to look our parents in the eye and say yes, we know the benefits of vaccine, yes, we know nothing that we do is zero risk, but we know that our country and our scientists are using all the tools that they should be using to help us clarify what those risks are so we can all make informed choices, and so my comment is I'm so happy to see you all here. I wish you well. I hope all of us can make sure that there aren't any gaps in this process.

I've heard about some gaps in public engagement and so forth, and I don't like those either. I think there is a spirit in the government and amongst us that is not going to let gaps happen and that will allow us to restore the faith of those who've lost it and to maintain deserved trust for all who every day are going to bring their kids to get vaccinated some. So again, thank you. The wisdom of this group is obvious to all of us sitting back here and we look forward to your continuing the work. Don't back off until it's done. Thank you.

DR. PAVIA: Thank you very much. The next is Nadia Karimi.

MS. NADIA KARIMI: Hi my name is Nadia Karimi. I am here on behalf of my 12-year-old brother, Kyle, who has autism, and my mother, who is treasurer of the National Autism Association. My mother was not able to attend today, so I'm giving a statement that she and other members of the National Autism Association have put together for me to read to you today.

In 1986 the National Vaccine Compensation Program was created and took affect for children born after October 1988. Free from potential lawsuits pharmaceutical companies developed numerous vaccines and had access to decision-making bodies such as the ACIP to guarantee these vaccines were given to every child in America. Consequently, the number of vaccines has grown at an alarming rate along with the rates of childhood cancer, juvenile diabetes, asthma, rheumatoid arthritis, ADD, ADHD, bipolar disorder, autism, and others. As a nation we have substituted acute illness with chronic disease and have produce sickest generation of children ever in America.

While the childhood vaccination program grew from 10 vaccines in 1983 to 36 in 2008, the safety of giving multiple vaccines at the same time was never studied. With the exception of a few flawed epidemiological studies conducted to suit parental fears and deflect questions about thimerasol, not one study has been done on the myriad of toxic ingredients found in vaccines. It appears the accelerated scheduled of the 1990's has become the great American immune system experiment with our nation's children used as guinea pigs. A CDC study published in JAMA in September 2007 attempted to reassure parents that thimerasol didn't cause neurological problems. Findings specifically significant relationships in 7 of the 42 listed deficits meant there were no worries about thimerasol. If _______(INAUDIBLE) more than the CDC press releases and study abstracts, they would have found that thimerasol was indeed linked to phonic and motor tics and deficits in attention, behavioral control and verbal IQ, all of which are consistent with autism. In other words, the public is being asked to believe that thimerasol causes the symptoms of autism, but not autism itself.

Today, thousands of parents are convinced that their normally developing children regressed into autism after receiving vaccinations. Unaware of the Vaccine Injury Program until the three-year window had passed, their injured children with left alone with no redress. Born into the world with full expectations for great health, their futures were shattered by illness, yet justice was denied to them. The Vaccine Injury Compensation Law, written to protect the pharmaceutical industry, provided drug companies with unprecedented and complete immunity. These families, often ridiculed by the media, had spent their life savings to trying to treat their children.

In February 2008, HHS conceded that vaccines did cause a normally-developing toddler, Hannah Pauling, to regress into autism. The doctors at Johns Hopkins say she is ______(INAUDIBLE), finding that a large percentage of regressive autism causes follow the exact same medical testing and developmental patterns that as Hannah. In fact, Drs. Kelly, Zimmerman, and Zimmerman have said that the majority of children of the regressive autism phenotype they have tested also have mitochondrial dysfunction, and the defect was found to be in the non-inherited nuclear DNA. With so many red flags appearing this is our wake-up call. As everyone on this committee knows, mitochondrial disorders are caused by stressors such as toxins and viruses. For years parents have told the ACIP, CDC, and FDA that a large number of children regressed after receiving vaccines, but no one listened.

It is now time to investigate our concerns, study our children, and treat their illnesses. The National Autism Association is committed to helping families find out what happen to their children and define successful treatments to restore their children to full health. We believe that thousands of children have suffered needlessly because of the failure of our government to act. We are requesting a comprehensive study of all health outcomes in the vaccinated versus unvaccinated populations and immediate action to change policy if relative risks are discovered. We insist that you conduct all vaccine studies free from conflicts of interest, therefore, investigators should have no ties to the vaccine industry, nor should they are livelihood depend on vaccine promotions.

Vaccine must be tested for safety in terms of multiple vaccines given during one visit and the overall number of vaccines for long-term adverse effects. Phenol formaldehyde, mercury, aluminum, and other vaccine additives should be tested individually and for their combined effects as many of these toxins compete for the same detox pathways in the body. Toxins together in one vaccine and cumulatively over time can have devastating effects to developing neurological and immune systems. We also recommend additional --

DR. PAVIA: I'm sorry. I don't want to be rude, but if you're close to wrap up that would be great, since you're running over.

MS. KARIMI: Yes. We also recommend additional consumer representation within the work group, and that prior to be given to autism and vaccine concerns. Finally, the National Autism Association requests that HHS declare autism an epidemic and treat it with extreme urgency. Thank you.

DR. PAVIA: Thank you very much. The next speaker is Beth Hynes. Beth Hynes. Okay. Halsey and Jody Sullivan have entered material into the record that they want people to be aware of. It's going beyond the website and they can take a look. I am sure others will do so and we saw a look of that. The next speaker is Terry Poling.

TERRY POLING: Hello everybody. I am Cary Pauling, and I hope that you all know who that is. I'm the mother of Hannah Pauling, and I am so happy to be here, and please forgive me if I go over five minutes, but I have been waiting for years to talk about this and I missed my day in court and I am not complaining, but I really have a couple of things to say and I hope they're helpful. I'm going to tell you little bit about my background. For 13 years I worked as a critical care nurse in both pediatric, neonatal, and adult ICU. I worked in the emergency room. I've seen kids come in with vaccine-induced seizures. I didn't know about VAERS, didn't sing up with VAEARS. I've worked in the post-anesthesia recovery room.

I decided I don't know those. I think Aristotle said that those who do not study rhetoric are victims of it, so I decided to go to law school. So I picked up from California and moved across the country with my 8-year-old son and went to Boston University School of Law. At the same time I was working as a nurse in the ICU and attending School of Public Health. I graduated in 1993, came down to Washington, DC met with my husband or met up with my husband, John Pauling and eventually married. I'm here and I am telling you all of this because I want you to understand the kind of person that I am. I love to read. I love to learn. I love to travel, and I love intense situations and getting things done intense situations.

I had no idea that I was preparing myself to take care of a child with the special needs of a regressive autistic child with mitochondrial dysfunction. I had no idea that I was going to be preparing myself for the type of debate that has occurred between autism and vaccine. I find myself in the middle like a ping-pong net, in the middle of the two conflicting sides. I see both sides. I am here today because HHS agreed that Hannah's receipt nine vaccines in one day triggered her autism. You can now switch semantics, anyway you want but Hannah does have autism and the vaccines triggered it. She also has mitochondrial dysfunction. I am here to talk a few - about three things just to make you aware that I think are important for you as a group, and that is that we know now the autism is not rare, one out of every 150 kids has been diagnosed with autism and although the level of disability very significantly, children like my daughter and, I've have met many, are going to require life-long care.

Mitochondrial autism is not rare, and it can be triggered by vaccines. We know that the mitochondria act like little batteries in our cells to produce energy that is critical for normal function. We also know during the first two years of a child's life their brain development is also critical. They're developing language acquisition, sensory motor skills, and social adaptation. When a child has a mitochondrial dysfunction any trigger that requires a level of energy that the mitochondrial cannot produce, including vaccines, can put them at risk for brain injury and regression. In Hannah's case we know it' was the vaccines. There�s also a problem here, and Hanna's case it not rare.

There is a study out, and most of you know about it, from Portugal that shows that it could be up to 7.2 percent. There's other studies that have not been published yet that could be as high as 20 percent. Currently, autism researchers do not understand whether mitochondrial dysfunction is causative or whether it's just a biological marker, but the important point for you here today is that we now have a biological marker. In the 2004 IOM report they said that they could not prove or there was no connection between vaccines and autism, but they couldn't disprove a connection in an individual because they have no biological markers. We are now telling you, you have your biological marker and it's called mitochondrial dysfunction and you need to research and you need to fund money into mitochondrial dysfunction. Therein lies major promise in trying to figure out what is happening with a lot of these children, and we know it's not necessarily just vaccines, but we still need to find out what that susceptible population is, and in light of this what the IOM can do is if they find out that this - the science determines, once the science checks this mitochondrial susceptibility and determines that number if they find out that the population is relatively uncommon, then every conclusion that you've had so far between vaccines and autism must be discarded and you must do another study with that subpopulation. If that turns out that it is common, you then have to go back and check to see if it was sufficiently powered for the predicted _______(INAUDIBLE).

The body has very promising information. I - I think this is - this is great. We are making strides. We've got something to work with here. In the meantime, I think we've got a problem. I think we need to identify children at risk and we need to learn how to immunize them safely. We need to develop methods and criteria to screen for susceptible children. Maybe we need to wait to vaccinate until critical developmental milestones have been met so that we don't have our parent come in and saying, �Well, they said a few words and then they got the MMR, and they're really just not talking, �because that is the critical time of development. That is when they are starting to talk. Maybe we need to postpone that MMR until they're three. There's a lot of issues there because there childcare and there is daycare, but that's something that people can speak to.

The other thing that I have a major problem with is VAERS. I read your agenda. I'm impressed with the agenda, but one of the problems I have with that is that you rely on VAERS for your safety and accessibility. I am a lawyer and a nurse, and I didn't know about VAERS, and I didn't learn it from anybody here. So that's really not a good assessment tool for determining whether or not the vaccines are safe, and the other problem is I interpret it as the Vaccine Injury Compensation Program. Again, a lawyer and a nurse, I didn't know about it for over year. I did not know that it existed. So you cannot use that as a measure for looking at the safety.

I understand _______(INAUDIBLE). I didn't see anything or discussions that they are actually looking at the individual, but I read from your agenda that in fact they are and I am very, very happy that that is case. I think that's necessary, and at closing I want to say that our public health leaders are facing a new paradigm shift. While it has taken far too long to get here, the point is we are here. Instead of reading the same old stories, we don't know whether there is a real interest in autism. We don't know what causes autism. We have a lead, a very strong lead. We need to look at the mitochondria. We need highly specialized physicians that know how to do this, and we need to fund them and we need to get that research done. Thank you.

(Clapping)

DR. PAVIA: I hope it's all right. I took the chair's prerogative and did give you a couple extra minutes there, so, and we appreciate what you had to say.

The next person is Vicky Debold. Sorry if I'm mispronouncing it.

DR. VICKY DEBOLD: Hi. It's hard for me. I'm here before you with a very heavy heart. I have heard what all these other people have said, and to some extent it's my story, so I am going to try to kind to skip around and try and not bore you with saying the same things that you have heard from other people, but I'm a nurse and I'm a research scientist and I work as the director of Patient Safety at the National Vaccine Information Center. I'm also the research director of Children's Health and Safety Research, and I'm a senior analyst for large statewide patient safety organization. Previously, I was on the faculty of the School of Nursing at the University Of Michigan.

My remarks today deal with patient safety aspects of your work as it relates to both process and contents. Dr. Snider, I was very happy to hear you talking about how patient safety may -- the concepts may be guiding some of your work. Over the past 30 years, I think that by way of background you should know that I have vaccinated hundreds of kids. Like Terry Pauling, I was the critical care nurse. I actually took care of children who died from haemophilus influenza B. I know exactly what that looks like. I know how difficult it is to bring a dead baby to parents who are grieving. I also know what it likes to take care of kids coming in through the emergency room suffering from severe infections from measles, chicken pox, and God forbid, pertussis.

I have a 10-year-old boy and his name is Sam. At his 15-month well-baby he experienced a number of serious adverse reactions after receiving seven vaccines. I don't need to name them. You know every single one of them. He hasn't fully recovered, and it is unlikely that he will. He is pretty much like Peter Bell's son. It took me two years to come to the conclusions, the conclusion that vaccine had anything to do with my son's regression. You would not believe the fights that I got into with people, and it wasn't until that I started actually digging and getting lab results and going back and looking at medical records and looking at videotape evidence that I finally convinced myself that that was indeed what happened to him, and it seems that I kick myself in the butt about was that a kid's -- prior to his 15-month vaccines, he had a mild reaction to a previous set of vaccines and I discounted it, but unfortunately, despite having doctors from both nursing and public health, neither I nor our pediatrician knew that the earlier and milder reactions were warning signs that he was potentially at risk for future and more serious vaccine reactions. This is where I think we have an opportunity to really improve the safety of what we're doing with some of the kids. Although both our pediatrician and I regret what happened, and we've learned from our mistakes. It's way too late for my son. It is not too late for other kids and it's not too late for you to do the right thing. You can do the right thing. I know you can.

I was very happy to see the whole patient safety thing, vaccine safety positioned within patient safety in your documents, and I know you all know that gaps in safety and medical errors are a leading cause of death and disability, and they cost our nation billions of dollars every year. I'm happy to see Kathleen Stratton here. The 1990 book by the Institute of Medicine, �To Err is Human� is a fantastic book. If it is wonderful roadmap, there's a lots of terrific ideas that you can use out of that book to begin to shed some of your thinking. One of the way, and some other things that I think to happening to kids are just clear medical errors. There are things that you can easily have nurses and doctors clean up. It's not necessarily even about making better vaccines. It's about making --having nurses and doctors practice their fields in much better and much safer ways.

One clear area in need of immediate improvement is a medication administration safety. As of August 2007, I took a look in VAERS, and 9.5% of all the VAERS reports that involved Gardasil involved clear medication errors, accidental exposure incorrect dose, incorrect route, incorrect drug, wrong technique, and consistent administration with FDA license and directives, this is just plain bad care, and it happens for lots of reasons, but our nurses and our physicians can clean and tighten this up. An even bigger medication safety administration issue involves co-administration of vaccines. Back to Gardasil, it was only evaluated by the manufacturer when it was given with hepatitis B. Yeah, it's been given with at least two dozen other vaccines, some of which were recommended by CDC. We can look at this. I know we can.

A second area is classified as failure of rescue, and in the case of vaccines it would be pervasive failure on the part of nurses and physicians to recognize the importance of challenge, re-challenge phenomenon and to modify the vaccination schedule accordingly. This is precisely what happened to my son. He had a reaction. He was revaccinated. He should not have been revaccinated. This is a way to minimize risk. Back to Gardasil, Gardasil's manufacturer says that individual who develop symptoms of hypersensitivity should not receive further doses. The CDC's vaccination information statement, however, elevates and restricts the contraindications to the level of life-threatening allergic reaction. CDC's list of contraindication are not specific and they don't adequately warn physicians and consumers about the risk of revaccination after a serious adverse event has already been experienced. The VAERS date, if you take a look at it, contains numerous examples of life-threatening reactions, yet nurses and physicians continue to revaccinate, and the last point I want to make has to do with shared decision making and personalized care. This is very important. This is a big huge piece of improving the safety of our health care system.

At its core the tendency to rigidly stress the need for compliance with a single clinical practice guideline, which in fact that is what the national vaccination schedule is, it's a de facto clinical practice guideline. We need that it's used for all infants. We need to instruct physician that they can meaningfully talk and work with the patients and parents and that the vaccines can be administered in a flexible way so that we can begin to do more towards personalizing vaccination health care in ways that help to reduce unintended harm.

Thank you, I appreciate what you're doing. I am very happy to hear the good work that you are doing today, which is on the right rack Thank you.

(Clapping)

DR. PAVIA: Thank you very much. Our next speaker, and I'm afraid it may be our last, is Douglas Wallace.

DR. DOUGLAS WALLACE: Well, I really want to thank you for the invitation to be here today and to represent the Mitochondrial Medicine Community. My name is Douglas Wallace. I'm both the scientist and a parent. As a scientist I am the ______(INAUDIBLE) professor of Molecular Medicine at University of California, Irvine and I'm also the director of the Center for Molecular and Mitochondrial Medicine in Genetics at that institution. I have been working on mitochondria and role of mitochondria in human health and disease for 39 years. Our laboratory was very important in defining the original genetics in the mitochondria. We showed maternal inheritance to mitochondrial DNA. We were the first to identify mitochondrial DNA disease. So that's my credentials as a scientist. As a parent I have two children, a 39-year old daughter and a 23-year-old son. Our 23-year old son has autism and my very able wife with two Masters degrees has spent her entire life taking care of this child who will never live independently. So we certainly appreciate the complexities of having a disabled child and the lifelong burden that such a challenge will have for a family.

All that said, I am here in part to represent United Mitochondrial Disease Foundation, which is the largest foundation of parents involved in mitochondrial disease throughout the country Chuck Mohan, as CEO, is here with us, and I serve on the Scientific and Medical Advisory Board of that organization. When it became clear that there was a question about vaccines. mitochondria and autism, which was so ably enunciated by Ms. Pauling, the Scientific Medical Advisory Board has had a lot of discussions about what position the UMDF should take on vaccines in relation to people that suffer from known mitochondrial disease. I think, it's fair to say that the Scientific and Medical Advisory Board strongly advocates continued vaccination of children. However, I think it's also fair to say, and this is true for my in practice, that we have always advocated spreading the immunizations out as much as possible because every time you vaccinate you are creating a challenge for the system, and if a child has a impaired system that could in fact trigger further clinical problems.

Unfortunately, we don't have any data to support any of our discussions on this area. We do not know what is safe. We do not know what is not safe. We do not know the actual risk of a person with light mitochondrial disease has and being challenged either by vaccination or by a latent - by a severe infection. We're certainly of the opinion that a severe infection would be far more stress than a vaccination, but in fact we can control the vaccinations. We can't control the infections. So I think we need a much more careful consideration about how to use the vaccinations to the maximum benefit of the patient, even a patient with mitochondrial disease.

Now the question I think then becomes relevant here is, is there a relationship between mitochondrial disease and vaccination and mitochondrial disease and autism. The first question is would a vaccination or infection initiate an incipient mitochondrial disease as has been suggested. Well, we don't of course have any way of proving that, but one thing that is certainly known is that there's a disease called Leigh syndrome, L E I G H. It is called and best known and recognized pediatric disease that's known to be associated with mitochondrial oxidative phosphorylation defects. These children are absolutely normal when they're born. They are fine up to the first several years of life, then invariably they're reported by the parent to have a transient increase in temperature that is B febrile, and then progressively lose intellectual and motor milestones, the vasoganglia dies out, and they die.

So it's clear that mitochondrial disease can be precipitated in some way and it can result in irreversible damage from a person that seemed to be perfectly normal. Moreover, these mitochondrial diseases are not rare in fact mitochondrial disease may in fact be the most common cause of pathophysiology that is known and the question then that you might ask is �Well, why don't we know this?� and the answer is tradition in relation to medicine because medicine traditionally has been organized around anatomy and, therefore, there are specialists in all the different organ systems, and so in fact it is very difficult for an organ specific specialist to understand a systemic disease, but in fact life is related to both structure and energy and energy is systemic even though structure is organ specific. So we've spent most of our care health-care dollars looking about at structure and organ specific symptoms and not thinking about systemic disease, and systemic disease is about energy, and energy is about the mitochondria because mitochondria provides 98% of the energy.

So, the fact is that we really don't have any data that allow you to make these decisions now because that whole area, the energy biology of health and disease is essentially unexplored and the UMDF and the Scientific Advisory Board really has tried to champion redressing this lack of information so that we can provide parents with the right answers and actually formulate the right questions. So I really hope that you will then take the initiative to give us the facts so that we can either make the right decisions or reassure the public, but right now I stand as someone who sees patients regularly and runs a diagnostics lab, and when they asked me about vaccinations have a hard time given them a straightforward answer. Thank you very much.

(Clapping).

DR. PAVIA: We are theoretically out of time Mr. Mohan has asked to speak. What I'd like to do is just if -- I had rather not leave you standing without being able to see, but if I could ask you to keep your comments to about a minute and minute and half that would be terrific.

PATTY HEALY: Actually, I represent a view I don't think has been heard today. So my name is Patty Healy. I am affiliated with the National Vaccine Information Center, and I started as a volunteer and now I am doing some part-time work, answering questions from parents, grandparents, all sorts of people who HAVE questions about vaccinations. I provide them with information. I don't lead them to make a decision any way. believe it's up to that individual. However, I think this issue back in 2000 as a new parent. I have a nephew who has autism. I actually don't know whether that was caused by vaccination at the time. neither does my sister. I came to the issue because there was a lot of talk of it in the air at the time. I had my daughter in 2000. This is during the time that Congressman Burton was holding hearings I believe about the thimerasol issue, which probably many of you attended, and I was really struck by the intelligent, the well-spoken nature of the parents. They sounded like someone that I could relate to. They sounded like me. They look like me and I was really struck by their testimony.

My background is I was a former biomedical researcher and then I went to law school and I became an attorney, a patent litigator representing biotech companies. So when this issue became important to me because I have to make a decision as a parent, and unfortunately these kids don't come with instruction manuals, and I thought how hard could this be raising a child. Passing the Bar exam was hard. How could this be any harder, but it was, and one of the issues what should I do about vaccination, so I went back to what I have always relied on my adult life and that was science because science can provide the answers, and this was a science biomedical issue. So I looked certainly, oh and I would have friends who hadn't vaccinated their children. I would sort of roll my eyes like, �Who actually does that, right? That just seems ridiculous,� but the more I looked into the science the more I found the absence of what I call true real science. What I thought existed would be studies that -

DR. PAVIA: I'm going to give you just 30 more seconds.

MS. HEALY: -- vaccinated versus unvaccinated studies, and those weren't there, or that looked at some of the studies that purported to conclude that there wasn't a link with the MMR didn't look at unvaccinated versus a vaccinated population because I thought well, may be the trigger is there before the actually - from other vaccines, before you have the MMR. Anyway, what I didn't find was science that was conclusionary or, excuse me, that gave me the types of control that I would used to looking at in my science; the proper negative control, the proper positive controls.

So I made the decision that I do not feel entirely comfortable with today and I'm sure that might be a ______(INAUDIBLE) to some people in this room that I haven't vaccinated my child. She is eight years old, healthier than any eight-year old vaccinated child I know. She does not go to the emergency room. The last time she went to the doctor was for a well-child visit. She hasn't had urinary tract infections, ear infections, respiratory diseases none of this. She just tested at a 99^th percentile of IQ for her age group, and what I implore you to do is just, and what I have always looked to and again it's the science, is show me the science. If I am wrong -

DR. PAVIA: Thank you.

MS. HEALY: -- show me the science, and one last thing, okay, I'll be quick. There is an analogy from a TV show I saw once where a trial judge was being brought before the chief judge because he was showing bias to the defense, and when he was questioned by the chief judge he started to show his bias and the chief judge chastised and said, �You know what Arthur? You're the judge. You're not supposed to care who's right,� and I think that's what we need to keep in mind about the science. It is what it is. Show me the science. Let the chips fall where they may. Thank you very much.

(Clapping).

DR. PAVIA: All right. Mr. Mohan, do you want to - if you're still here, do you want to -- I'm sorry we are really running tight, but I really didn't want to cut you out so -

MR. CHARLES MOHAN: I appreciate the opportunity and I just want to thank this committee and the subcommittees for taking this time to get involved in this dialogue. and it's an honor for me to be here and United Mitochondrial Disease Foundation has pledged already over six million dollars on focused mitochondrial dysfunction, and we look forward to participating with our patient base. with any resources that we have available in continuation of this kind of dialogue, and certainly our commitment has been based on the promise that mitochondrial dysfunction is going to unlock the key to many other diseases, not the least of which is autism, but also Alzheimer's, Parkinson's and many childhood cancers as well. Thank you very much.

(Clapping).

DR. PAVIA: Thank you very much. We're coming to the end of what's been, you know, a long, very long contents and I think emotion packed day. It's not been very full of conflict. I think we've actually listened to each other and made a lot of progress. The purpose of course was provided by the CDC and to start that process, and I think they came asking for the best possible advice they could get. This working group is trying to give that. The audience here is contributing to that. Our work is going to go forward. The working group is going to be working very hard. Over a period of time, we will probably try and share some interim results as we start to get a product down for additional comment. We commit to you to listen to the public in whatever public engagement processes are put together as a result of this. I think public will be speaking to CDC and to HHS and we, that is as advisors, as outside scientists would be listening very-very carefully, but you will be speaking with the people who are the decision makers, and I think that's as it should be and then we'll be weighing in our roll as advisors with our own expertise.

Before I wrap up I want thank everyone who is here very, very much for all the time and effort and the work I know you're going to put in. Thank you for caring. I want to give just a last word to Dan Salmon and to put it to, you know, although they worked for the government and we don't always hold that in the highest regard, they and all our colleagues at CDC I think share the same values that we do and are really in this for the same reasons, and I want to thank them for all their hard work, particularly Dan Salmon who made this meeting possible and really pushed the public engagement components of it, and I want to give you guys a chance to have a last word.

DR. DANIEL SALMON: Thank you very much. I'd like to take a minute and thank every one around this table, the ex-officios that found the time to come, in particular the working group members that are very, very busy people and have really shown a strong personal commitment. I'd also like to thank everyone in the audience. I know that everyone in this room and particularly people that don't work in this area professionally have made a big sacrifice to come here and I think that we are starting what is very, very important process and I hope that everyone here and the different groups in the personal experience and the expertise that everyone has can come together so that we can move forward on this important topic, and what we share is a common interest and passion for children and for people, and let's hope we can build on that - on that solid groundwork. Thank you.

DR. PAVIA: I neglected to give the last word to John Iskander on behalf of CCI, so --

DR. ISKANDER: Well first I really would like to thank all of the participants in today's meeting including all of HHS staff here who supported the technical aspects of this meeting. I know it was a great deal of work. I want to take a moment to, you know, I'll start by borrowing a line from my boss, Tanya Popovick. She addresses this meeting, and first thing she said is �I am not a suit.� So I have a story too. That story includes having had people in my family die from vaccine preventable diseases. It includes having a nephew who is a young adult with autism. I am very passionate and my colleagues in ISO are very passionate about the science that we do, and I will make a statement and I do not expect all of you right at this moment to believe it. but I enjoy the work as much when we find a risk and communicate it as when we don't find a risk, and as I said I don't expect you all to believe or trust that statement on its face right now, but is is the honest truth, and I do appreciate all the information that you all have shared, all of the work that you all have done in preparation for this and I look forward to the unfolding process. Thank you.

DR. GELLIN: Thank you. You know, I began this with my slide of this pile of gears and showing what an engine could look like, and essentially that showing what my job is. The National Vaccine Program's offices mandate is to coordinate the vaccine activities across the department and often in concert with other departments, so I often see those gears, and I sometime the engine. sometimes you hear some grinding, but I do want to tell you that as the deputy secretary told you and as the assistant secretary for health _____(INAUDIBLE) a working group, this is a priority of this department beginning with the secretary, and even though you all know that this is an administration that knows when they are finished, this is a process they are choosing to not only initiate, but to accentuate now knowing that this is -

(END OF AUDIO)