Transcript of Sept. 28, 1993 meeting of U.S. Interagency Coordinating Committee for CFS. Transcript provided by HHS staff, scanned by Barry and Marcella Feinsod and stored at the CFS/ME/FMS BBS of Long Island tel. 1-516-736-6810. ======================================================================= CENTERS FOR DISEASE CONTROL PUBLIC MEETING OF THE CHRONIC FATIGUE SYNDROME INTERAGENCY COORDINATING COMMITTEE Atlanta, Georgia September 28, 1993 Transcribed by Barbara Hilger, RPR DR. ESBER: Let me just say good morning to everyone. My name is Elaine Esber. I'm a pediatrician with a specialty in pediatrics hematology oncology. I am with the FDA. I am the current chairman of the Interagency Coordinating Committee for Chronic Fatigue Syndrome of the Department of Health and Human Services. And, as that, I have the privilege of opening and chairing the meeting today. We appreciate your coming and we appreciate your keen interest and the fact that there are so many of you that wish to speak. I'm sure that you are all aware that Dr. Lee is unable to attend the meeting today. And so in that regard I will be sharing some of his thoughts with you in a moment as I cover some of the goals of this meeting. But first I'd like to provide some details or housekeeping items. First let me just say thank you to CDC for having made these arrangements. As most of you know, most of the committee is from the Washington area, and we opted to hold the meeting here in Atlanta in order to make it easier for those who wanted to attend the Case Definition Meeting sponsored by CDC yesterday and to just stay over for this meeting today. CDC has not only made these arrangements for us hut also has reserved some resting areas for those of you who may need to take advantage of it. As I understand -- Bill, help me -- they are right behind this wall on the back. And if you need some help in directions, please just ask anyone here. You should have all received by this time now two pages of what we call an agenda. The first page has the times and names of those from the agencies and the times for lunch breaks and for allotment of sessions. The second page is a listing of all of the public representatives who have requested to speak. The order in which the public is listed is arbitrary, just based on how the names were handed to us, Nancy Carpenter and myself, in terms of putting them in the list. You can see from the page that it's incomplete, and you can also see that the order, as I mentioned, is arbitrary. If you'd like to change it at all, please see me at lunch time and I'd be delighted to rearrange it to make it more orderly. There are 19 public members who have asked to speak and one has provided written comments. If everyone keeps to their schedule during the afternoon session, we'll certainly have time for everyone to speak, and then I'll be prepared to read the written comments from the twentieth person. Although there has been some criticism of my role as chair of the Coordinating Committee and chairman of this meeting, we are all needing to go forward. And I apologize in advance to any of you who feel wronged, but I intend to do my best. Part of doing my best will also be an attempt to keep on schedule, because everyone has a right to be heard and everyone that is here from the agencies want to hear what you have to say, because we firmly believe that it's only through this kind of interaction that we can be aware and make progress. We've worked very hard to arrange this meeting in order to communicate, and this is one in a series of steps for Is. And although the pathway and format is a bit different than what we are used to, we've had to learn as we have progressed, and this meeting in fact is recurring, which is a sign of progression. Unfortunately, as I mentioned, Dr. Lee, the Assistant Secretary for Health, was unable to join us as he had planned. Dr. Lee intended to chair the meeting of the Interagency Coordinating Committee on chronic Fatigue Syndrome today. However, last week Vice President Gore asked Dr. Lee to go with him to California to discuss the President's health security plan. And Dr. Lee was unable to say no to the Vice President. Let me just say on behalf of Dr. Lee that he is very committed to the work of this committee, and he said to tell you that he intends to chair a meeting of that committee as soon as possible. He asks that we use this meeting today to describe our accomplishments that have been made thus far, to discuss the challenges that remain before us, and to define future opportunities. These discussions that we will have today should provide the basis for the meeting of the committee that Dr. Lee will chair. Dr. Lee recognized that this meeting today is part of an ongoing process to bring us closer to the day when etiology of this complex syndrome is understood and effective tools for treatment and prevention are at hand. This meeting provides an opportunity for the agencies of the Department of Health and Human Services, including both the agencies of the Public Health Service and the Social Security Administration, to present reports that describe programs and activities that are currently underway or already completed. Of equal importance, this open meeting provides an opportunity for all interested members of the public, including those affected by Chronic Fatigue Syndrome, to present their views and to submit questions to representatives of the department, and we will be happy and prepared to try to respond to your questions as we can. At that, let me suggest that we would appreciate if your questions are written , and Nancy Carpenter and others will be happy to provide paper for your questions to be submitted to us. As you can tell, the proceedings of this meeting are being recorded and will be available to interested members of the public. In order to facilitate the transcribing service, please, if you get to a microphone to ask a question or so, please identify yourself in order to make the transcribing service more useful. Following the Interagency Committee today there will be one held in the near future, as I mentioned, that Dr. Lee himself will chair. And following that, then we'll plan to submit an annual report to Congress. That is sort of the order of events. I'd like to spend a few moments if I could just providing some history of our Coordinating Committee, because it became clear that its not clear to everyone how we got started and why. We started because there was a request from the Assistant Secretary of Health at that time to CDC to organize a planning committee. This planning committee resulted in the establishment of the Interagency Committee or the Interagency Coordinating Committee, and it was first established on November 14th of 1990, almost three years ago now. During this planning committee there were several structural and procedural functions that were established by the planning committee. First, it was decided that it would consist of the Public Health Service Agencies who would seek opinions from others as needed, and four agencies were asked to participate: the FDA, the CDC, the NIH, and at that time the NIMH. NIMH is now part of NIH, and so they are not recognized as a separate agency at this time. Second, it was determined that we would meet either in person or by phone about three to four times a year. And, in fact, it's been four or more times a year that we've had opportunities to communicate with each other. Third, it was decided that the chair would be selected from the membership and would rotate at yearly intervals. The first chair was the NIH, and Dr. Ann Schluederberg served in this role in fact for two years. And I've been serving since November of 1992, as was outlined in the original. The planning committee provided this outline and framework for us. It is also acknowledged that the primary function of the committee was in fact to promote communication of the government agencies regarding CFS research and other related issues. This was felt necessary in order to facilitate the departments' and the agencies' awareness of CFS research and educational needs. Prior to that time there was very little communication except for spontaneous between the agencies. It was wanted to facilitate the development of complementary research programs in order to minimize overlap, as well as recognition of opportunities for collaboration and/or coordinated reports in research and education. And, finally, it was intended to facilitate the development of informed responses to constituency groups regarding our efforts and our progress. We believe that our Coordinating Committee has been highly successful in increasing our interagency communication and the coordination of our CFS research activities. This success is in fact exemplified by the intent to make our committee functional beyond the coordination function, in other words, to turn it into a directing and a planning committee. This is all well and good, and we should move forward, and we should make progress, and we will, but we should not lose sight of the value that the Coordinating Committee has served us all to date. We have outlined a number of major PHS priorities in December of 1992. These covered in broad amounts the area of research priorities and strategies as well as the dissemination of information. You will hear much more about these priorities in the presentations of the individual agencies today. In closing, let me just once again repeat the statement of Dr. Lee. This meeting should not be used today to describe our accomplishments made thus far, to discuss the challenges that remain before us, and to define future opportunities. It is not to be a decisional meeting. It is that these discussions will provide the basis of the meeting of the committee that will be chaired by Dr. Lee in the near future. And I hope these comments can help to get us started. At this point, I'd like to start the agency presentations, and we'll start with Dr. Bill Reeves who will present on behalf of the CDC. And I'll ask each of the agency representatives to introduce themselves and give some history of what their role and responsibility is in Chronic Fatigue Syndrome. DR. REEVES: What I'm going to do is summarize the CDC Chronic Fatigue Syndrome research Program. You heard a fair amount about it yesterday from Dr. Fukuda in our area of case definition. I won't spend a lot of time on the case definition. The first thing I want to deal with is the organization of Chronic Fatigue Syndrome research within the CDC. At CDC the Chronic Fatigue research program is the responsibility of the National Center for Infectious Diseases, and this is highlighting our aim right now to look at infectious and measurable laboratory etiologies for this. There are several other centers within the Centers for Disease Control which have other interests, but our major focus is in laboratory areas and in infectious areas. Within the National Center for Infectious Diseases, the program operates out of the Division of Viral and Rickettsial Diseases, and Dr. Brian Mahy is the director of that division. And within that division, the primary research effort operates out of my branch, the Viral Exanthems and Herpesvirus Branch--it's easier for most people to call it VEHB--with a substantial amount of input from the biometrics activity within the division. The Viral Exanthems and Herpesvirus Branch involves, obviously, herpes group viruses and involves many of those viruses which cause chronic or latent infections with delayed sequelae because of those infections. And within our branch we have a rather wide-ranging activity. And, again, you saw many of those people yesterday. We have a large epidemiology group headed by Dr. Dobbins. Within that group is Dr. Fukuda, who is heading up the majority of the studies, Ms. Reyes and Ms. Steele. We have an immunology section within the branch, again engaged in immunologic research. I'll discuss some of that. Dr. Schmid is the chief of that section, and Dr. Alison Mawle is directly responsible within that section for immunolgical studies. And we have a clinical virology section headed by John Stewart, a well-known infectious disease physician and expert in clinical virology. So what we are trying to do within the branch and within the division is bring together a multifaceted program with people with multiple talents, those talents involving both epidemiology and the epidemiology of acute and chronic infectious diseases. The objectives of the CDC progress fit within the overall Public Health Service objectives. It's my opinion that the Interagency Coordinating Committee has actually been quite successful in assuring that the different agencies' objectives fit well with the overall Public Health Service objectives. The general objectives of our program are to determine the prevalence and incidence of Chronic Fatigue Syndrome, to define the clinical course, to identify risk factors. And the bottom line of all of this and the reason that we need to do this is that we need to develop intervention strategies. That's the entire approach to this sort of disease. Intervention strategies involve both treatment, which is obviously not optimal, as well as prevention. And that requires, obviously , knowledge in all of these areas. Now, how are we getting at them objectives? Our program involves the following areas, and I'll go through these areas. It involves surveillance, population surveys, case control studies, cluster investigation, informational services. And I will not go into these. We spent yesterday on the case definition. It's obviously a very important part of any program. And interaction and coordination through the PHS Interagency Coordinating Committee. What I am going to do, I'm going to work through these different areas and describe to you what the objectives if the area are and what we've accomplished. The surveillance program, I think as most of you are aware, is a program in four sentinel cities: Atlanta, Reno, Wichita and Grand Rapids. We'll go into some detail on that. It's an ongoing program. We've gotten some very interesting and exciting data from that. We are just beginning what I think would be some extremely interesting population surveys. We've not really started them yet. Ms. Grambs briefly discussed yesterday, which I think is one of the more interesting ones, the collaboration with the San Francisco CFIDS group to do some cross-sectional studies. This involves both the group in San Francisco, the San Francisco Health Department, and the Centers for Disease Control. And this is a unique kind of collaboration involving patient groups and public health sector both at the state and at our level. And there is various talents that come in there. We are planning a study in Wichita to get a different look at the surveillance study. I won't go into these in detail because they are just starting. We've done a variety of case control studies -- I'll discuss them in detail -- mainly looking at retroviruses; however, we do have a collaborative case control study also with Dr. Natelson, an NIH CFS Center investigator, and we've completed two cluster investigations. What I'd like to do now is go through these one by one. CFS surveillance again is in Atlanta, Grand Rapids, Reno, and Wichita. These were selected for a variety of reasons: Atlanta because it's where we are and we can do a study in a relatively large metropolitan area, but we have direct access to materials for laboratory studies from the patients we might identify here--it gives us a very powerful handle on laboratory studies; Reno because it was the center of the most recent, well-documented cluster of Chronic Fatigue Syndrome; Grand Rapids and Wichita because they are relatively representative of the U.S. population and they have relatively well-defined patient and stable physician populations. The studies began in 1989. They involve sentinel physicians. These are physicians that are identified as most likely to see Chronic Fatigue patients. This is both a strength and weakness of this study design. We have about 50 percent participation of the physicians we invited to participate. And this is essentially what we call a passive surveillance system. Patients are referred to us. Patients receive a standard evaluation and review by a physicians research group, and they are classified into subcategories according to how they meet the case definition. We have enrolled and completely worked up 491 patients between 1989 and 1992. This is a very intense effort now to analyze this data. Group I or Classic Chronic Fatigue Syndrome, which meets the rigid, published case definition and has no other possible underlying cause, accounted for 22 percent of the patients. Group II, which we could not identify a possible preexisting psychiatric or medical cause but was not quite severe enough to meet the case definition of completely, contributed 17 percent of the patients. Nineteen percent were what we call Group III, which had an underlying medical diagnosis not appropriately treated which could account for the symptoms. And Group IV patients had preexisting psychologic or psychiatric disorders which could account for the symptoms by did not necessarily account for the symptoms. We've kept every patient identified in surveillance, and these groups are being looked at separately as well as together. I will focus on Group I because that is the group that is the least ambiguous. And, again, we realize there may be problems with this. This is very much like other people's data that we saw yesterday. The patients that we pick up in surveillance have been ill a little over four and a half years. Most of them are women. Most of them are white. The mean age at onset is relatively young. And this is a very productive group. The median income, 50 percent earned at least $50,000. What I'm going to do is just give you now, without delving really deeply into the epidemiology, our current prevalence estimates . Prevalence estimates are the risk of a patient in the population sample being detected with disease. These are prevalence rates per hundred thousand population 18 years and older. These are different than rates that we have discussed before and that you've seen before, and I will stress that this sort of thing is not concrete. It is very complicated trying to work these out, and they may change again. The overall average age- and race- and sex-adjusted prevalence in the four sites was 5.2. It ranged from 3.5 in Atlanta to 6.1 in Reno. Most of this was in women, and so I'll go through some female prevalences. The female prevalence is 9.1 per hundred thousand, again ranging from 5.8 in Atlanta to 11.5 in Reno. The significance of these different prevalences remains to be looked into in more detail. I wouldn't put a lot in just these types of crude numbers right now. This affects white women predominately, so my last prevalence slide we'll look at this in white women. Again, what we are trying to do is reflect the risk in various population groups, and this is what's important. This is why it's very hard to go just from a crude prevalence to something else that is meaningful. The average age-adjusted white prevalence in the four sites is 11.4. It ranged from 7.8 in Atlanta to 15.3 in Reno. We are continuing to look at this data. There is a wealth of material that needs to be gleaned from this, and these are our analyses to date. This is one of our more active projects now, going through this and looking at it. I want to move now to etiologic studies or case control studies. The first study which we accomplished was a study of retroviral involvement which followed soon after Dr. Defreita's preliminary reports of possible retroviral involvement. We became very interested in this, as did other people. We did a study in 1991 using patients identified in the Atlanta surveillance system. We were unable to find any markers of retroviral involvement in those patients or matched controls in that study. We presented that information at the CIBA Symposium last year. It's been published in the proceedings of that symposium. We have presented that material at the Albany meeting, and we've published that in the " Annals of Internal Medicine". We are very interested in getting scientific material out as quickly as possible. We feel very strongly that it should come out in the peer-reviewed literature and come out in the peer-reviewed literature as rapidly as possible, so that physicians can read this and interpret it and use it within a common forum. MR. RONK; Excuse me. DR REEVES: I don't want to take questions in the middle of the talk, so I'll go through the talk and we will have time for questions I think at the end of it. MR. RONK; I was in that study. I tested negative for Epstein-Barr in '91 and '92, but now I test positive for it. I was in that. DR. REEVES; Epstein-Barr virus is not a retrovirus. And there are some technical questions we might wish to deal with in viruses. And there are always problems with any kind of case control study in which one is monitoring one's infectious status at the time. All of these studies have limitations. We have recently begun analysis of a study we conducted between June and November of 1992. It used the same group of Atlanta patients; used somewhat more rigorously selected and matched controls. And this attempted to obtain information by questionnaire. This involved immunology, infectious and other possible associated factors. We did an extensive interview, an extensive battery of immunologic studies, attempts at virus isolation, seroepidemiologic studies and several others. The questionnaire attempted to get at exposures that had been hypothesized as risk factors for this disease, exposures to solvents, insecticides and heavy metals. We asked a large number of questions on contact or possible contact with a variety of animals and insects. This gets at both allergies to theses vectors as well as agents that they may carry. And we asked a variety of what I call miscellaneous questions dealing with diet, travel, job and health history. The immunologic component again was very, very extensive. Part of the problem or the cumbersomeness with this study was that we attempted to look at patients and their age-matched and race-matched, sex- matched controls at the same time, the same day in the laboratory. So a patient and the two controls came in at the exact same time and every specimen was worked up that day in the laboratory. These are the immunologic markers that we've looked at. I think they are the majority of markers that are of current interest . We have made extensive efforts to isolate the known retroviruses, both human and animal, using every marker that we know of, HHV 6/A, 6/B and 7, and a variety of enteroviruses, using both culture methods and polymerase chain-reaction methods. Seroepidemiology, we are looking serologically at essentially every virus that the Center for Disease Control is able to look at, which is a lot. We are looking at Lyme Disease -- we have a rather large and very good Lyme disease program--and assorted other infectious agents, Chlamydia, Mycoplasma, et cetera. The other, as far as laboratory markers, we are looking at red blood cell magnesium, lead, mercury and arsenic levels. So this is a very wide net. We are right now in the process of working up this data. We are just beginning to break the code. Almost all the results are in, and, as you I think can appreciate, it's going to take a large amount of work just to make sense out of this to put it together. We are also collaborating with Dr. Natelson in New Jersey--he is one of the NIH collaborating centers for CFS--collaborating with him in analysis of a case control study he conducted, 20 cases, 20 controls matched for age, race and gender. This involved a questionnaire with physical behavior and psychological variables. And this analysis is essentially complete and we are working with him to prepare a manuscript for publication. We are also conducting active cluster investigations. We have completed two cluster investigations, one in Pigeon, Michigan, one in Sacramento, California. Again, these are very, very current. We are just in it to the analysis again. The study in Pigeon, Michigan, we have completed a phase one cross-sectional survey. The possible cluster area was Pigeon, closely bordered by Caseville. Two control communities were Elkton and Umbly. We did this by mail and telephone. We mailed out 3100 forms. We have a not terribly good response rate, 58 percent. The very preliminary data--we want to go at this from a fatigue point of view, and Dr. Fukuda discussed some of this yesterday, look at the overall prevalence of fatigue and then subsets of fatigue, trying to get very specifically at Chronic Fatigue and Chronic Fatigue Syndrome. Eighteen percent of the population surveyed had fatigue lasting one month or greater. Sixty-one percent have been women. And this analysis again is very actively in process. We have completed a phase one cross-sectional survey in Sacramento, California in an office building. We did the sentinel office building and two control office buildings. We distributed 5,000 forms within those buildings. We had an extremely good response rate, 85 percent. Again, this is just coming in right now. Nineteen percent of this population had fatigue for one month or longer at the time of this study. Sixty-nine percent of them have been women. And, again, we are very actively involved in the analysis of this data. The last slide that I will cover is on our efforts in informational services. Again, as I want to stress, we want to get information out as rapidly as possible in the peer-reviewed literature so it can be interpreted very objectively. We publish I think increasingly well in peer-reviewed journals. I mentioned some of those with the retroviruses. We are presenting the information as rapidly as possible in any of the scientific meetings to which it is applicable. We recently published an article in the MMWR with Drs. Gunn and the group looking at retroviral involvement. It was presented at the Albany meeting, in order to get this out quickly and get a wide distribution I think of their very important findings, which is the largest study so far done in multiple centers. We have a liaison representative in the American Association for Chronic Fatigue Syndrome, so that CDC is represented in that body. We maintain a telephone voice information system, which many people don't feel is perfect, and it probably isn't but we'll try to make it better. We have regular contact with patient groups, speak regularly with patient groups at their meetings, and have a variety of other sources that we try to get information out in. I think that would be my summary of the CDC program, the objectives and the various components of that program. DR. ESBER; Thank you very much, Bill. If I could just right now, let me also introduce Dr. Brian Mahy of the CDC. Dr. Mahy is the Director of the Division of Viral and Rickettsial Diseases, of the National Center for Infectious Diseases, and I'm sure you all are quite familiar with him from yesterday. As we go through the table, not everyone at the table will be speaking. Nancy, could you just stand up for a moment? Nancy Carpenter is the person that was also mentioned in the Federal Register who works for FDA and has been volunteered to help us. Nancy would you provide and pass out some papers on which people could write questions? It's clear as we are going along that you may have questions come up as you are thinking, and if you could start writing those down now, we'll be happy to discuss those at the question and answer session, and we intend to have one at the end of this particular session. Also, I mentioned earlier that there is a page for this afternoon's session that lists a number of people in an arbitrary order. For those of you who walked in later, I've asked that, if you don't like the order for some odd reason -- again, it was just arbitrary based on when names were provided to me -- please let me know at lunch and we'll try to do some rearrangement of that listing in order to make it more logical and informative. And also, if I could, just one more comment for those who would like copies of the transcription when it's available. If you'll make sure you give to Nancy your name and address so that we can have that listing, then we'll be happy to try to provide copies to you. Let me now go to the next person in our agenda, Dr. Ann Schluederberg form NIH. DR. SCHLUEDERBERG: My title is Chief of the Virology Branch within the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases. That's a long name. The reason I'm here is because I have responsibility for the CFS extramural program in NIAID. Before telling you what CFS research NIH is supporting, I want to tell you a little bit about NIH. Like CFS, it is a little bit complex in the way decisions are made and the way awards are made. It's not always clear. I want to tell you where the CFS research is being done and how research funding decisions are made. We seem to be gaining institutes very rapidly. There are now 18, including the National Library of Medicine. We also have six centers and divisions that are very important in our structure. Ostensibly, only five institutes and one center, which I'll enumerate later, currently support CFS research. But I would venture to say that research that will help unravel the mystery of CFS is being conducted in almost every institute of the NIH. I'll list a few of the related research programs that I think are important in a little while. Because NIH's CFS research effort began in the National Institute of Allergy and Infectious Diseases and NIAID, as we call it for short, continues to be the prime funder of CFS research at the NIH., it is the designated lead institute, with primary responsibility for reporting CFS activities to the director of the NIH. That is another reason why I am here talking to you today. NIAID's office if Communications is also on the front line for NIH in handling inquiries, preparation of information booklets--I'll call your attention to a booklet that is outside -- and press releases about CFS. Laurie Doepel is here with today, and you may want to meet her. This slide shows how a typical institute is organized. There are laboratories and clinics in campus in Bethesda where intramural research is conducted, and laboratories all over the country where extramural research is conducted. There are two advisory boards made up of nongovernment experts who meet with institute directors at least three times a year to review the research programs and provide advice concerning research funding priorities. The intramural programs operate much like universities, with tenured and nontenured faculty who pursue research programs within the mission of the institute according to their own scientific interests and expertise. The Board of Scientific Councilors reviews the research performance of each NIH intramural laboratory and faculty member at least every three years, about as often as research grant awards get in- depth peer review. The extramural program, divided into areas of programmatic interest, administers the grants and contracts. Research programs in the extramural part of the NIH are reviewed by National Advisory Councils. Most of the intramural research is centered in Bethesda in the Laboratory of Clinical Investigation in NIAID's Division of Intramural Research under the direction of Stephen Straus. That laboratory is in the Clinical Center at NIH. Intramural investigators in the National Institute of Neurologic Diseases and Stroke, the National Institute of Child Health and Human Development, and the National Institute of Mental Health are collaborating with Dr. Straus and also conducting independent CFS studies. The National Cancer Institute also has a substantial independent intramural CFS research effort. All in all, NIH's intramural support totaled $1.4 million in FY '93. The extramural program at NIH are organized into divisions, branches and programs according to areas of scientific emphasis. Extramural program staff administer the grants awarded following review of proposals submitted to NIH by scientists from all over the world. Workshops are organized and research initiatives are developed within these limits to advance programmatic needs. These initiatives are reviewed and prioritized by senior staff and the institute director before selection for advertising to the outside community as institute program announcements, RFAs and RFPs. All the extramural CFS grant activity at NIH up until now has been in the Virology Branch of NIAID's Division of Microbiology. The National Cancer for Research Resources also has played an important role earlier by providing some support for pilot studies through their former Biomedical Research Support Program and more recently and currently through their General Medical Research Centers Program. CFS research is going on now in two of these GMRCs. Extramural support for CFS research totaled $3.3 million in FY'93. Extramural awards make up to 83 percent of the total NIH budget and represent 88 percent of the research effort. Thousands of investigators submit proposals which are reviewed each year, mostly through the Division of Research Grants, who organizes the initial review of these unsolicited research proposals for all of the institutes. Proposals solicited by RFAs and RFPs are handled by institute review staff. The amount of money available for solicited research I would be quick to add is very limited and tightly controlled. Initial review groups are made up of outside experts from the scientific community who review each proposal for scientific and technical merit and assign a priority score. Each proposal receives a percentile rank that is dependent upon its priority score in comparison with the scores of other applications received over the previous year. NIH does not receive a lot of CFS grant applications, only an average of seven per round last year. In the past, due to the small numbers of applications, the broad scope of the research and the need for experts from many diverse fields, CFS applications were sent to many different study sections, some of which had little knowledge of CFS. Because applications were scattered, there was also little continuity. To address this problem, last year the Division of Research Grants set up a special emphasis panel just for CFS applications. We view this as a major step forward in assuring that CFS applications will be reviewed by persons knowledgeable about the illness and about the work going on in the field. After the initial review, summaries of the proceedings are sent forward to the institute program staff for consideration at advisory council meetings where recommendations for funding are made. That is the second level of the NIH two-tier, peer-review system. What determines what awards are made? Scientific merit is the most important factor in choosing proposals for funding. The vast majority of NIH awards go to proposals that are in the top percentiles. The second most important consideration is programmatic need. For example, if there is only one measles research grant in the virology program and 30 polio grants, a measles proposals might take precedence over a polio proposal that has a better percentile rank. In the last analysis, availability of funds is the ultimate governor. Currently NIAID's pay line for non- AIDS research for FY '94 is the 10th percentile, the worst situation in the history of the institute. Not shown in this slide is yet another factor, Congressional interest. With your help, support for CFS research has grown steadily since it began in the early 1980's. Over the time period shown, it has increased at NIAID, which does represent the largest continuous interest with recorded data on the subject, from $425,000 to $3,800,000 in 1993. To stimulate CFS research, NIH has organized four workshops during this period and issued two program announcements and one RFA. This represents equal spacing across this time period and goes up through November 1993. Three kinds of grant awards have been made: cooperative agreements where NIAID has some role in facilitating research and encouraging and supporting exchange of information; research project grants, the RO-1; and a First Award, which we call an R-29. There are ten projects within the research centers program under the cooperative agreement mechanism. That mechanism also embraces in this case a provision for funding of pilot projects, and ten pilot projects have been funded through the developmental funding provision of that program. But this is only a part of the picture of what NIH is doing to support research that can advance our understanding of CFS. The next two slides list just some of the relevant research areas that are being encouraged. Neuroimmunology and neurovirology I think we would all agree are very important parts of this, and recently there have been initiatives in those areas put out by NIMH and NINDS. NIDDK has a committed interest to determining the effects of stress on immunity. NIAMS, Arthritis, Musculoskeletal Institute, has a program in fibromyalgia. The National Institute on Nursing Research has a longstanding interest in patient care and management of fatigue. The NIMH is interested in mechanisms of psychosocial intervention. In our own institute, we have an interest not only in viruses, which I have of course a bias towards listing, but other infectious agents and the impact on immunity and immunity to them. Persisting viruses, again we have a program of persisting viruses within our branch, and Dr. Susan Spring directs that program. It includes all of the herpesviruses and other viruses that perhaps have received a little less attention in this meeting. An area that I think is very important and is being looked at under several different names is the effect of gender and immunity. Obviously, our Office of Research on Women's Health listed at the bottom has an interest in that. We think this is an underserved area of emphasis, and it's coming to the attention, possibly through this renewed interest and stimulation of women's health, at NIH. But why do we find CFS more often in women than in men? I don't think we can attribute it to nonbiological factors to any great extent, but all aspects of course, have to be considered. The psychological factors and how they interdigitate with physical factors in physical health is a very important emphasis within the National Institute of Mental Health. How are all these research efforts being coordinated at NIH? Dr. John La Montagne, Director of NIAID's Division of Microbiology and Infectious Diseases, is the NIH coordinator. He truly was disappointed not being able to be here. There was a scheduling mixup when this original date was established. And he had planned to be here and then realized that he did have a prior and irreversible commitment to the National Academy of Science meeting that's going on now on emerging disease. But he expects me to fully represent him at this meeting and report to him. We have the CFS Research Working Group, which is the most comparable to the research working group that Dr. Reeves described at CDC. Those are the investigators from the different institutes I mentioned that are working hands-on with patients and in the laboratory to study CFS. They meet every two weeks to discuss their particular research progress, problems and so forth. We have the NIH CFS Coordinating Committee, and it's largely made up of representatives who have responsibility for extramural programs. Members of that are appointed by institute directors. There is one person appointed as the official representative, to be sure that we are preparing our reports in an accurate fashion with regard to budget and all other aspects, but those meetings are open to other members of the NIH community that have an interest in that. Finally, as mentioned, we are represented on the DHHS Interagency CFS Coordinating Committee, the NIH CFS coordinator. There are several key questions concerning CFS: What is it? Who gets it? What causes it? How can it be treated? Can it be prevented? To answer these questions, researchers supported by NIH are using several approaches. The first is the classical clinical tool: observation. Begun at NIAID with a long-term study of CFS patients and continuing in our fairly newly established field CFS cooperative research centers, clinical and laboratory parameters are being entered into a large data base that is being used to look for diagnostic and prognostic markers that will help us to know what CFS is. Patient demographics and physiologic characteristics collected in both epidemiologic and clinical studies will help to answer who gets it. Epidemiologic and clinical studies we hope also will reveal what causes it. Experimental intervention and challenges we hope will give us treatment clues and increase the chances that we can identify characteristics that are specific for CFS and will help us in the diagnosis. The study of model systems, like persisting Lyme disease in humans, and development of small animal models, may lead to a better understanding of it pathogenesis and help in the search for preventions and treatments. Specifically what's going on? Within the intramural research, current efforts are concentrated on expanding and extending to broader control groups the immunologic profile which was recently reported. The neuroendocrine deficits, which were identified in reports a couple of years ago, are being followed up by an intervention approach and a multicenter effort including collaborations with CDC. To pinpoint the site of cognitive impairment is another emphasis. Patient care, interactions with rehabilitation medicine at NIH and other approaches are being explored. Reproductive endocrinology, again harking back to the query of why is it occurring more often in women, that's being carried on with most emphasis at the National Institute of Child Health and Human Development. The National Cancer Institute is continuing to do their workup of clusters and to look for viral associations that might obtain within those clusters. And virology at the laboratory and at the epilevel is an interest of NCI, particularly the HHV 6 viruses and how they might not only relate to CFS but how they might relate, looking at mechanisms, the interactions of these viruses with cells of the immune system. Extramural research supported by NIAID is focused on epidemiologic studies related to prevalence, case definition issues, risk factors, prognostic factors, diagnosis, definition of clinically useful patient subsets. A second major effort lies in the search for biologic markers. Currently studies are underway to identify immunologic, neuroendocrine, viral and other infectious agents, neuropsychologic, physiologic and brain imaging markers. These efforts in general are directed at two basic etiologic hypotheses. These are certainly not exclusive and just intended to show you there is some method. Is there an infectious or environmental cause or is CFS the consequence of abnormal host response to infectious agents and/or stress? As you are aware, we face many obstacles to research goals. Case definition is problematic, as evidenced by all the discussion yesterday and ongoing. We have no biologic marker. Suitable control data are very difficult to obtain. Is it fair to make comparisons between highly debilitated CFS patients and healthy controls? How far will that take us? We are finding we have to refine more and more our choice of controls by looking for deconditioned controls and other patient subgroups that might give us more insights. Medication usage confounds many tests, and yet it's difficult to ask patients to limit their very few avenues they have for symptomatic relief in order to participate in these studies. There are cyclical effects like time of day, time of year, and time in the menstrual cycle that can affect test results. We've done very little to standardize these effects. There are problems in distinguishing between cause and effect. Does viral reactivation contribute to CFS or do viruses reactivate because of CFS, or are these epiphenomenon? Outbreaks are unpredictable, heterogeneous and relatively infrequent. We can be poised, as CDC well knows, to go investigate, but there may not be an appropriate setting to get meaningful information. NIH researchers are working hard to overcome these obstacles, and we have formally sought input, with some encouragement to do so I will add, from the National Chronic Fatigue Syndrome Association, from the American Association for CFS, the CFIDS Association of American, Inc. and we have informally sought input from others. We look forward to expanding this dialogue in the future. I'd like to share with you the input that has been given to us so you can see how it fits in with what we are doing and what we've proposed to do. The National Chronic Fatigue Syndrome Association pointed out that they would like to see us continue to search for a virus as etiologic agent. They'd like to see sleep abnormalities defined; to find a mechanism of fatigue and determine what metabolic studies are needed; develop an animal model for CFS; continue studies on CFS and how attributes of this illness compare to attributes of depression, to aid in some of the differential diagnostic problems; continue research to confirm or refute that this is basically an immune system disorder; studies to define the impact that CFS may have in regard to pregnancy; studies to define the impact of the illness. Is a person more prone to cancer, to autoimmune disorders ? Research to define why CFS is more common in women than in men; research to define if CFS is caused by many of the other things that cause severe fatigue; studies to improve quality of life for CFS patients; longitudinal studies to define the course of the illness. They want to see more widespread epidemiologic studies and work towards objective criteria for the diagnosis of CFS. The CFIDS Association of America had most of their emphasis on process, the process of decision making and finding ways of access of patient representatives to this process. With regard to the kind of research, they did encourage us to develop a clinical care model. Marya Grambs at the CFIDS Foundation of San Francisco wants to encourage us to continue to establish the credibility of CFS among the scientific community and to provide evidence for the physical aspects of the illness. Judy Basso of the CFS Association of Minnesota urged us to look at more of the familial aspects. The American Association for CFS encouraged us to identify the physiologic markers, etiology, refinement of case definition, provide a minimal set of diagnostic tests, and to evaluate the promising treatments, and continued studies to derive and define prevalence and incidence. Finally, in our just completed annual report to the director of NIH, we recommended that besides continuation of ongoing research programs, which I think address at least to some degree many of these recommendations that we have received, that we give particular attention to the following research areas: That we derive the biologic and epidemiologic explanations for the observed increases in frequency of CFS associated with gender and with age and with race, socioeconomic class. These are the clues. That's what epidemiology is all about. We do it to get clues of risk factors and then we proceed to test hypotheses dependent upon those factors. To investigate familial risk factors including the genetic, the behavioral and environmental factors that may contribute to the expression of this illness; to develop methods to evaluate the clinical impact of viral reactivation, including measurement of viral burden; to expand research on gender, gender-specific interactions between the immune system and the hypothalamus-pituitary-adrenal network; and to develop normative data and objective methods for interpretation of brain scans. I apologize for running over my time. I took a liberty, and I hope it will cover and anticipate some of the things you may want to query about. Thank you. DR. ESBER: Thank you, Ann. While Dr. Murphy is walking to the microphone, let me just mention something about FDA. We are a regulatory agency, not a research agency, fundamentally, although we do have research laboratories in many of our centers, and therefore we do not have a line-item budget for Chronic Fatigue Syndrome as you've heard in two other agencies today. We also have a number of centers that are divided by product category, and my specific role is in the Center of Biologics. My center deals with biological products. Dr. Murphy represents the Center for Drugs, and we'll ask her to introduce herself beyond that. DR. MURPHY: Good morning. Glad to be here. Like everyone else, I do want to spend a few minutes talking about the FDA's function. I think it's particularly important, or we feel it's particularly important. Since our division has assumed responsibilities for Chronic Fatigue therapies, it's become clear to us in talking to the patients who have this entity that they don't understand what we do, and we certainly are learning about Chronic Fatigue. so I will spend a minute going over what we can do and what we can't do, talk a bit about what we have been doing in this arena since the responsibilities for Chronic Fatigue were transferred to the Center for Drugs, and finish with comment about where we see our future activities in this arena. First of all, the FDA's function is to assess and assure the safety and effectiveness of a therapy. Things that we do not do: We do not research chemicals; we do not produce drugs; we do not provide therapies. What we can do, and Dr. Esber commented on this, we do have some limited research. Mostly this research is related to regulatory issues. We think of it a little bit as those issues that we think are important in helping define how a therapy is used optimally but may not be of significant interest to a sponsor or company to pursue that. So we do have some research in that area. In addition, we do have some limited funds for research which are distributed to look at particularly pharmacokinetics in certain therapies and also in developing animal models. The major thrust of our work is to provide guidance on both the design and evaluation of preclinical and clinical trials. The one thing that we frown upon is false hope. We consider false hope a study that is not properly powered or properly designed to answer the questions that it seeks to address. We wish to come to help the companies, to help the investigators develop the data base that they need to prove that their therapy is safe and efficacious. We do evaluate the submitted data that is provided to us to prove the safety and the efficacy of the therapy, and I'm sure you've heard of the truckloads of data that come into us. It is a rather extensive feat. We look at all the animal models, all the laboratory information, in addition to the chemistry, the manufacturing of how the product gets to the consumer, and in addition to how the trials are designed. Are they going to answer what they purported to answer? And have they done so in a manner that we feel we can say to the public this drug is safe and it does what it's purported to do? And finally, we do also facilitate communication between the sponsor of an experimental therapy and a physician whose patient may have a serious or life-threatening disease in which there is no alternative therapy. Because a drug is not yet marketed, it will still be experimental, and there are times in which we will facilitate those types of connections in providing the patient or a physician information as to whom they should contact if they wish to be provided some access to a therapy. I do have a few slides which I would like to review that summarize the activities that the Division of Antiviral Drug Products has been participating in since April of 1992. The responsibilities, as I mentioned, for Chronic Fatigue therapies for Chronic Fatigue Syndrome were transferred from the Center of Biologics to the Center for Drug Evaluation and Research in April of 1992. And some of the irony is reflective of the problems that have plagued Chronic Fatigue. There were a number of meetings and decisions that had to be made as to where one puts--where the home will be for a syndrome for which we do not have an etiologic agent. I think in the final analysis it's the resources that may be available, the experience of the people. It was decided that Chronic Fatigue's home would be in the Division of Antiviral Drug Products. In the summer of 1992 we had a number of discussions with patients, activists, hearing their concerns. We had meetings in which we learned about what had been done in the way of therapeutics involving Chronic Fatigue, and we met with the sponsors or industry that were developing therapies for Chronic Fatigue, reviewed the data that had been already submitted. Just to give you a little background about the types of people who are involved looking at these therapies, every drug is assigned a team. That team consists of a chemist, pharmacologist, a medical officer; and eventually, when the drug is farther along in its development, it will also be assigned somebody from our statistical and biofarm area. So there is a team of people who are responsible for reviewing the data that's being developed and for helping to design or helping the sponsor and investigator in designing the trials that are supposed to prove whether a therapy works or does not work. In September of 1992 we presented to our advisory committee the information that Chronic Fatigue was now under our purview and one of our responsibilities, and at least familiarized them with some of the broad-stroke issues that many of you are vary familiar with, such as a lack of an etiologic agent and some of the design issues that had to do with end- point definition. This committee is composed of experts in the field of that are -- there is a sitting panel, and then there are always individuals who are invited as expert consultants for a specific disease or drug when that drug comes before this committee. What usually happens is, after the division or the FDA has reviewed the information submitted to support an application, a drug or therapy as being safe and efficacious, we will frequently take this information to our advisory committee for their expert opinion also. So we wanted the committee to become familiar. It's like anything else. We wanted them to know this is now on your plate, pay attention to it, be thinking about it, be reading about it, and we will provide ongoing updates to you. It also became apparent to us that we needed to have an organized approach at talking to people, and communicating to people, and so we have done that within the FDA involving both the Office of Consumer Affairs and the Executive Secretary's Office, in addition to our division. I want to spend just a few minutes talking about the advisory committee meeting in February 1993, because I think it was an important meeting, in that we brought to the committee in an open public forum what we saw as the issues that need to be addressed in designing trials to decide whether a therapy works or doesn't work. And, again, many of them you are familiar with. At this meeting, as I said, we wanted to familiarize them with some of the trial design issues involving Chronic Fatigue Syndrome. We wanted to seek their comments and expert advice. We did ask as additional guests some expert individuals, who are here and participated in the other part of this meeting, to attend this session. It was open to the public, and there were eight speakers who either had Chronic Fatigue or had a family member with Chronic Fatigue who came and spoke very eloquently and I think were very persuasive in their comments to the committee. In addition, Dr. Fukuda was a guest speaker, Dr. Reeves was invited audience, Dr. Ann Schluederberg was invited audience, and Dr. Komaroff was a guest speaker. I mention that because I want to emphasize that we are all trying to keep each other informed as to what each agency is doing on an ongoing basis, as has been emphasized today. Hemp Pharmaceuticals was put up there, not that we were bringing that particular product to the committee, but because it was an example, a product that was trying to conduct trials and having to address some of these issues. And so we asked the sponsor to present some of their problems that they had had in trying to develop trials for Chronic Fatigue Syndrome. Since that February meeting we have participated in a number of other meetings, which I have listed here, and will continue to be very actively interested, obviously, in maintaining the type of communication not only among the agencies but also with the patients who are involved. Our division began to participate with this Coordinating Committee in June of 1993. That's all I have to say as far as our activities that have occurred since April of 1992. Where do we see the FDA's role in future activities? I would summarize it by saying that we will continue to promote development of studies or research on validating or the validation of end points relevant to Chronic Fatigue. This should include physical activity or endurance measurements, quality-of-life instruments, and other potential metrics measuring fatigue. Some of the things that are occurring is that we will continue to work with the present sponsor to complete a pilot study, encourage them to complete their pilot study on looking at appropriate use of physical activity monitors. We will pursue a broad-based conference to establish the field of available end points to make recommendations as to priorities and approaches as far as clinical trial design is concerned and evaluating effectiveness of the therapy. We'll continue to participate in the Interagency Coordinating Committee's activities and provide our advisory panel progress reports in this field, so tat, if and when a therapeutic agent that dies appear to have an impact on the health of patients who are suffering Chronic Fatigue is submitted, our committee will be prepared and able to move expeditiously in this area. One last comment. Again, Dr. Esker did allude to this. I would like to say I think that the commitment of the FDA to this area is sort of demonstrated by the fact the agency does not receive any funding for Chronic Fatigue activities. Any activities that are not directly related to product review, such as the manpower to attend meetings, transportation and support functions, have been the result of commitment of the FDA to continue to work in this filed and to be ready to bring any therapeutic intervention that is proven to be both safe and efficacious for this disease entity to the marketing arena. Thank you. Dr. Esber: Our last speaker from this morning is the Social Security Administration, Barry Eigen. I hope you are writing your questions. And Nancy will be happy to pick them up as soon as this particular speech is done. Dr. Eigen: Good morning. My name is Barry Eigen, and, as you can see from your programs, I am what you call the Deputy Director of Social Security's Division of Medical and Vocational Policy in our Office of Disability. We are the people who write all of the disability issuances for Social Security, beginning with regulations which interpret the laws that Congress gives us and ranging through to the various manuals and other instructions that we give to the people out in the field who actually decide disability cases. With me today sitting at the table is Dr. Karen Ezrine, who is a physician in our Office of Medical Evaluation and is the person who has the expertise and responsibility from the medical side for Chronic Fatigue Syndrome. When we get to the questions, I hope that she'll be an excellent resource. unlike the previous speakers who have a direct involvement with examining the causes and treatments for CFS, we have a different role. We merely pay benefits to people who claim to be disabled because of Chronic Fatigue Syndrome, whatever that syndrome may be. We don't enter into the kinds of discussions that you all heard yesterday about what the definition of CFS is and those kinds of things. For this reason, I thought it would be most fruitful to talk to you about what disability means and how we decide disability, with particular attention to Chronic Fatigue Syndrome and some of the problems which no doubt many of you have already encountered, and what we are doing about it. I don't have slides, but I have overheads which I am afraid might be a little more difficult to see. I apologize for that. Social Security pays two basic kinds of disability benefits. The first kind is paid under the regular kind of Social Security that most people know about, the plan that pays retirement benefits. It's the SSDI program, which is sometimes called Disability Insurance Benefits or Title II, which is a reference to the various chapters in the Social Security Act. They are called titles. It pays disability benefits to workers who have worked under the Social Security plan, paid Social Security taxes for a given number of quarters, and become disabled , become unable to work. It also pays disability benefits to some of their relatives. There is a disability benefit for disabled widows and widowers under certain circumstances -- you have to be a particular age--and also for disabled children of workers as well. Under Title XXVI we administer another plan called Supplemental Security Income, SSI, which is not actually a Social Security benefit that comes from Social Security taxes. It's a benefit that comes from regular income taxes. And it's a benefit for needy people, for the aged, blind and disabled, and so, as is appropriate to this discussion, for the blind and disabled. As you can see from the overhead, both of these benefit programs also carry with them medical benefits as well as cash benefits. In the case of Title II, the regular Social Security SSDI Program, Medicare benefits come after a person has been disabled and receiving benefits for two years. This is written into the law. Under SSI, Medicaid, which is a benefit that's paid both combined by the federal government and the state in which the person resides, comes immediately, as soon as the person is found to be disabled. Now, it turns out that the statutory definition, the definition in the law that Congress gave us for disability, is the same under both Title II and Title XXVI. As an aside, I need to tell you that there is a separate definition of disability for children who are disabled under the SSI program, but because of the limits in time today, I won't be able to go into that. But suffice it to say, the rules for children are in most respects comparable to what I'm about to discuss, and this will give you the basic principles whether it be for adults or children. There are three things to notice about this definition, beginning with that it is very strict. It requires that a person be unable to do any substantial gainful activity, which is a carefully defined term that uses a money amount -- it turns out to be currently $500 per month -- and also considers what the person does, the kinds of activities the persons does and how many hours they do it. But essentially it's an inability to work because of, by reason of, any medically-determinable physical or mental impairment. So that's the second part. The primary reason a person is disabled must be their medically-determinable impairment. And the third part of the definition is a duration requirement. Not only must the person have a medically-determinable impairment that makes them be unable to work, but they must be unable to work for a continuous period of a year or have an impairment that we expect to result in death. Now, the language of the continuous period of a year needs to be explained, because as you can see, it provides in the statute that a person may already have been disabled for 12 months but also that we may predict that the person may have an impairment of recent onset in which we find that it's expected to last for 12 months. Now, there is more to the definition of disability. The very next statement in the statute underscores the severity of impairment needed to be found disabled. It explains that the person's impairment must be so severe that it not only prevents the person from doing work he or she did in the past, but also any other kind of work that exists in the national economy. However, the law is softened some by the remainder of this definition, which says that we are supposed to consider what we in Social Security call vocational factors, that is, the person's age, education and work experience. The effect of that last clause is that it is possible for a 60 year old person and a 20- year old person to make an application, have the same impairments with the same limitations, but that under our rules we would find the 60-year old person disabled but the 20-year old person not disabled. Still the important point here is that the law underscores that it must be the impairment that is the primary cause of disability even if we do consider age, education and work experience. As it says, the person's impairment or combinations of impairments must be so severe that it is the thing that results in inability to work. Now, there are many ways to look at the definition of disability. But for purposes of this discussion, you can break the definition up into two parts. The first part, which is a threshold question, is: Does the person have a medically-determinable impairment? The second question is: When a person is found to have a medically-determinable impairment, is that impairment in fact disabling? We'll take them in order. Congress tells us what a medically-determinable impairment is. Those three words, which are a term, are defined in the statute. And they require and the law requires that a medically-determinable impairment must be shown by anatomical, physiological or psychological abnormalities that are demonstrable by medically-acceptable clinical and laboratory diagnostic techniques, in other words, objective clinical and laboratory findings and not symptoms. One thing you can notice from this language is that it's ambiguous. It does not say a diagnosis. It only say s a medically-determinable impairment. We have always interpreted this to mean that a person need not demonstrate to us exactly what he or she has, only that he or she has something medically demonstrably wrong with him or her. This obviously is an important point in Chronic Fatigue Syndrome and with regard to the CDC's definition. In effect, the CDC's working definition of Chronic Fatigue Syndrome is immaterial to our consideration to this point. We need only have some clinical or laboratory finding showing that there is something medically wrong with a person in order to cross this very low initial threshold. We need not know what the diagnosis is exactly. Still, we have some interest in knowing how the research comes out, because as you all well know, it's often difficult for individuals with Chronic Fatigue Syndrome to demonstrate objective findings, or at least it's sometimes difficult. And therefore, as more information comes out, it will make our jobs easier as we find more and more objective markers of the disease. So we are very interested in following the research for that reason. The other important point about this is, as I have already pointed out, that Congress explicitly excluded symptoms from the definition of a medically-determinable impairment. In fact, in our regulations, which are rules that we write to implement the law that I've just been showing you, we do include symptoms. Even though it's not necessary for us to show exactly what's wrong with a person, it's sometimes desirable to try to determine what the diagnosis is, for instance, when we are trying to determine whether an impairment is expected to last for 12 months, that duration requirement I told you about before. Nevertheless, since the law does not include symptoms in the definition of a medically-determinable impairment, we also provide in our regulations that we can never find that a person has a medically-determinable impairment based on symptoms alone. Very important point to you guys. Now, as I said, this is a low threshold. Many people can show that they have something medically wrong and we can decide now whether the medically- determinable impairment is in fact disabling. And the way we do that is using this system that we call the sequential evaluation process, which is what you call an algorithm. It's a system of steps, in our case five steps, which you take in order. And at each step it's possible to either make a decision or to decide that you can't make a decision and move on to the next step. For instance, the definition of disability begins "inability to engage in substantial gainful activity." That's what SGA means up there. If a person is actually engaging in substantial gainful activity, not matter how severely impaired he or she is, that person would be not disabled because they could never meet the definition of disability, and we would stop. Most people of course who come to us are not working, and so we usually proceed to the next steps. Most of the remaining steps consider symptoms heavily. In fact, symptoms are not only required to be considered at every step but they can be decisive at each step. For instance, step two asks whether the person's medically-determinable impairment could possibly be the primary basis of disability. In other words, is it severe enough that we might find the person disabled and need to proceed, or is it so minor that there is no point in proceeding in the sequence because we will not find the person disabled because of his or her impairment. As I explained, the only proscription against considering symptoms in the statute is when we determine whether a person has a medically-determinable impairment. Therefore, we provide in our regulations that symptoms may be used to decide whether a person has what we call a severe impairment, which means an impairment that has more than a minimal impact on the person's ability to do basic work activities, like sitting, standing, walking, remembering instructions, and getting along with people. A person's dizziness or pain or fatigue, however you define that term, can in fact be the factor that makes us decide that the person's impairment is severe. The flip side of the second step is our third step, which is our listing step. In our regulations we have a list of typical impairments, over a hundred examples of commonly occurring impairments, which we say are so severe that we will automatically find that a person is disabled without considering how old they are or what they've done in the past or how much education they've had. The way we do this is by listing diagnoses with particular medical signs associated with them, signs, symptoms and laboratory findings, for instance, diabetes with a certain number of diabetic crises and some other findings, such that if a person happens to have those particular findings, that disease and those particular findings, we'll find the person disabled. Furthermore, since no list could ever be complete, we have a concept called "equivalence" to the listings -- sometimes we say "equals" the listings -- whereby a person who has an impairment that happens not to be in our listings or that is in our listings but doesn't have the specific exact symptoms, signs and laboratory findings we listed by t whose impairment is just as bad as one of the impairments in our listings, can be found disabled automatically. If a person has a severe impairment that doesn't meet or equal one of our listings, that is not the end of our inquiry. We never deny a person because his or her impairment does not meet or equal a listing. The third step of our sequence is only and allowance step. When a person has the impairment I just described, it does not meet or equal the listings, we proceed and we do a very individualistic assessment of the particular effects of that person's impairments on the ability to work. And the way we do that is, first of all, you see by the dotted lines up there, we do a residual functional capacity assessment--that's what RFC stands for--which is an evaluation of what the individual is still able to do despite any limitations they have from their impairment. This consideration relies heavily on the person's symptomatology and all the other evidence in the record, including things his or her doctor might tell us about how they think the person can function, as well as objective medical findings. With that assessment, we then run out the rest of the sequence by deciding whether the person is able to still do work they've done in the past; or if they can't or have never had any work in the past, which happens under SSI, whether they are able to do other work considering how old they are and their age, education and work experience. To summarize and add a little additional information about symptoms, we have regulations that derive from law that has since expired, but we have reason to believe that it's still Congressional intent, which say that in order for us to consider a person's symptoms, they must, (a), have a medically-determinable impairment -- we've been through that -- but, (b), there must be some relationship between the medically- determinable impairment and the symptoms the person is experiencing. In actual practice, we say that there is a loose nexus between the reasonable expectations of production, which means only that we recognize that different people feel their symptoms different from everybody else. What is extremely painful to one person may be only minor pain to another person. And so in effect, if there is any connection between the person's impairments and what they are feeling, we will consider their symptoms when we decide whether they are disabled. That's what it says down here too. We have a caveat to that which says all we are telling you is that we will consider the symptom. That still does not tell us whether you are actually disabled, whether the person is disabled, only that we are allowed to now go ahead and consider the symptom and its severity and how it impacts on the person. Whether it's disabling will depend on the totality of the evidence, because in the final analysis our decisions are legal-type decisions which rely on evidence provided from medical sources and nonmedical sources. With regard to our activities in Chronic Fatigue Syndrome, I think it's fairly clear how the law and regulations apply to the impairment. Congress has since 1988 almost annually asked Social Security to follow the research of the people who consider what CFS is and how to treat it, and also to do whatever inquiries we could possibly do to make sure that we are evaluating cases appropriately. To that end we have done some small studies which confirm, as you might expect, that there is really no correlation between the CDC's working definition and who we find disabled. However, they've also shown us some other information which we have used hopefully to improve our adjudications. In March of this year we issued an instruction, what we call a Disability Digest, which had several purposes, but chief among them was to remind all of our adjudicators that people with CFS often have subtle but objective medical findings, and to look for them diligently, even if that means going out and purchasing evidence of physical or mental impairments by which we can establish that a person does have a medically-determinable impairment. We've also been to visit a clinic and have other studies planned and other case reviews. And that's it. I'm finished. Thank you. DR. ESBER: I'd like to ask everyone to hand their questions towards Nancy now so we can get started on trying to be responsive. And if anyone feels better walking to the microphone, that's fine as well. MS. KENNEY: We have a number of questions we'd like to address from the floor. First of all. I'd just like to start out by -- DR. ESBER: Excuse me. Would you identify yourself. And also, just in order that we do have time for everyone's questions, if you could take one at a time, and we'll just try to take questions in sequence. MS. KENNEY: Kim Kenney, CFIDS Association of America, Executive Director. We are pleased with this meeting but we are disappointed that Dr. Lee could not be here, and we are anxiously awaiting the next meeting of the Interagency Coordinating Committee which we hereby request take place within the next 30 days. First, I'd like to address CDC. The draft document that is circulating, "Facts About DFS," Dr. Reeves, can you tell me what the document is for and how soon you expect that to go out in final form? DR. REEVES: The draft document, "Facts About CFS," is an update of our informational brochure which is intended for patients and physicians. It's currently going through the clearance process. We wanted to have a draft of that available for this meeting for people to look at, offer any comments that they might want to offer. But that is an update of the old one that we had, trying to get at the more current issues, and it is currently going through CDC and PHS clearance. MS. KENNEY: We have some severe objections to some materials that are in that pamphlet and we'll be submitting those in writing. Should that be addressed to you. DR. REEVES: Yes. MS. GRAMBS: My name is Marya Grambs. I'm with the CFIDS Foundation in San Francisco. This is to the Social Security Administration. Can you tell us how many people in this country are currently receiving Social Security benefits for Chronic Fatigue Syndrome? MR. EIGEN: Unfortunately not. However, I'm glad you reminded me. There is something else we did just in August. We don't have a listing for Chronic Fatigue Syndrome, and so, because of the way our computer system is set up, we can't track the cases. However, in August we created a special computer code just for people with Chronic Fatigue Syndrome, and we are hoping that in the next few months we'll be able to at least tell you about the new cases both that we allowed and denied. MS. GRAMBS: We would very much be interested in receiving that information. DR. ESBER: Let me just take some of the written questions. These are two that deal with Ampligen, if I could address these to Dr. Murphy. The first question is from Donna Sundberg: "What is the status of Ampligen?" The second question is from Barbara Humphreys: "We need to know about the long-time effects felt by the former Ampligen patients." DR. MURPHY: I can only state what is publicly known. I can tell you that Hemp Pharmaceuticals has announced that they will be beginning a second randomized control trial of Ampligen. I can't give you any times or dates but that should be occurring in the near future. And the second question was? DR. ESBER: "We need to know about the long-term effects felt by the former Ampligen patients." DR. MURPHY: We couldn't agree more, and actually we have just recently asked Hemp Pharmaceuticals to provide us follow-up data on patients who have been continued on therapy and for outcomes on any of those who have been off. We do agree that you need to follow patients after they come off a therapy. Obviously you have to balance reasonableness as to how long you can follow them. And we have put into place some of these mechanisms to collect data on patients after they completed a therapy. DR. ESBER: Would you like to ask your question. MS. SHANNON: Meghan Shannon from San Diego Support Group, North County. I have several questions -- one at a time, I know. DR. ESBER: Thank you. MS. SHANNON: When receiving Social Security, when you finally get it -- which I did on CFS the end of March, but I got it ten years after the onset, and I went through a whole Worker's Comp. thing. My question is when I went back to work and didn't make it and got sick again, when do you get paid and how much? I was making $25,000 a year in 1980. I'm not getting the comparable kind of disability that I should be getting for the kind of work I was doing 11 years ago. Is there a way that you can track back to that, the original? I'm very well documented. People are like that. This is a disease that's been denied. MR. EIGEN: Unfortunately, and this has been decided by the Supreme Court actually more than once, there is an absolute requirement that you file an application. If you didn't file an application at the time, there is no way to go back. There is some retroactivity from an application, however. You are able to apply for the Title II benefits, the ones that you would be entitled to because you worked, I assume. You can receive benefits for up to a year before you actually file an application. Plus, there is a waiting period. There is a lot of details I didn't go into. The other thing, though, is -- this is small consolation, but the work you did would have increased the benefit amount you got because you were paying Social Security taxes. So you got something from it. But otherwise no. You absolutely must file an application. MS. SHANNON: Is there any way to change that? DR. EIGEN: Congress. That's the law. MR. RONK: Don't feel bad. I got it 23 years ago, and I don't get diddlysquat because I haven't been able to work. I don't get nothing. DR. ESBER: Let us go on to the next question. Would you identify yourself again, please? MS. KENNEY: Kim Kenney, CFIDS Association of America. Dr. Reeves, the case control data you said had not been analyzed yet, as far as the immunologic markers, the case control data that you've done from the Atlanta group? Is that right? DR. REEVES: We are in the process of analyzing that data now. MS. KENNEY: You've got a statement in the "Facts About CFS" that says: " In other words, if a CFS patient and a healthy friend went to the same physician and received any of these immunologic tests, the healthy friend could have a more pronounced defect than the patient." And since that case control data hasn't been analyzed, how can a statement like that be made? DR. REEVES: You are going to have to repeat the statement. I'm sorry. Tell me which page it is so I can just look at it here. MS. KENNEY: Page 6, the second question on page 6. DR. REEVES: What's the problem with the statement? MS. KENNEY: If the case control data hasn't been analyzed yet, how can you make the statement that there is no immunologic defect or that it might be the same in a healthy friend if you don't know that? DR. REEVES: There is no way to answer the question that you just posed. In point of fact, what we are talking about is that a patient or anybody and a healthy friend can have any immunologic test at any point in time and, because of the nature of these tests, a, quote, defect or abnormality may appear by chance alone in either one of those patients. It really has nothing to do with the case control study. The problem is and what we are trying to get at in this is -- and we may want to discuss this in more detail, the nature of immunology and immunologic testing. What we are trying to get at is that we are all very interested in immunologic abnormalities and the possibilities of those. What we are also very interested in as a public health agency is using that sort of testing on a population basis to attempt to distinguish between people who have Chronic Fatigue Syndrome and those who do not. That's why we are going the case control study. Again, we are dealing in a population basis and not on an individual basis. Things on an individual basis can go one way or the other. But I have no problem whatsoever with that particular statement in the book, although we won't resolve it here. MS. KENNEY: I'll just state our objection is based on published research from private and public sector scientists. DR. ESBER: I'd like to now, if you would bear with me, try to deal with some of these written questions before we run out of time, and then we'll come back to microphone questions. It is already after 12:00 when we were to stop for lunch. MS. GRAMBS: Could I just ask one question and then go to those? DR. ESBER: All right. MS. GRAMBS: My name is Marya Grambs with the CFIDS Foundation in San Francisco. As you gathered yesterday, the patient advocacy movement is very interested in being a partner in all the government's work on CFIDS. And to that end we have two points to make. One is we understand that the Congressional language that mandated this Interagency Task Force requires consumer participation, so we are very eager to understand when that consumer participation will be finalized, and we consider that very important. The second point is yesterday's panel that will be deciding the case definition, again, while we are not requesting at this time that patients be included on that panel, we are very concerned at the lack of wide clinical expertise in diagnosing and treating CFIDS on that pane.. Therefore, we are going to be submitting a list of nine clinicians who we know to have long-term and in-depth clinical experience in diagnosing and treating CFIDS, and we'll be requesting that you select three clinicians to be added to that panel. Thank you. DR. ESBER: Again, if you'll bear with me, I'd like to go through a number of these. There are several questions that seem to deal with clinical diagnosis. Let me just read one, and I'm not sure who from the panel would like to address it. "How and when will CFS be given a clinical diagnosis? The medical diagnosis books I've seen do not include CFS." Does anyone want to or feel prepared to address questions like that? DR. REEVES: It's a difficult question to address, and I'll give a partial cop-out answer. The CDC, the National Institutes of Health, the Food and Drug Administration are charged with public health, with public health research. We are not charged with determining standards of care and standards of essentially clinical diagnosis. We are trying to come up in this particular case with a research case definition which for all practical purposes will probably be used in a clinical setting. There is also - - I think the question pertains to this -- the International Classification of Diseases which codifies names, et cetera, of diseases. That is not determined by people on this panes or by these agencies. This is an internationally codified and unified type system. So there are some things we just cannot deal with. We are interested in them for the same reasons, but they are really beyond our scope and beyond what we should be doing. Dr. Esber: There are again about four questions or five that seem to focus around education of physicians, whether it's education in terms of diagnosis, education in terms of therapy, inquiry to physicians about help in their own understanding of the disease in patients, education of physicians in terms of where to direct patients to get more information. What are we doing about educating the healthcare providers? Do multiple agencies want to address that? Ann, do you want to start? Dr. Schluederberg: Yes. When did we first publish the -- I'm asking Laurie Doepel. We have a physician's pamphlet that 40,000 copies were distributed in the first printing. I don't know how many in the last. It's currently being considered for update with input from CDC. And that's been our primary effort. Mr. Ronk: The problem is physicians do not consider this pamphlet or your agency a credible source of information. If you try to hand it to them, they pull back their hands. Dr. Schluederberg: There is another thing that's a formal happening, but I do know that there is to be a chapter on CFS included in a major internal medicine textbook. I can't give you details on that. But this will be a learning process that will happen through the medical community themselves. They want to know more about it and are convening meetings at their nationally convened meetings to address this topic. The Infectious Diseases Society of America has had several reports on this at their meetings, and this year is no exception. There is going to be a discussion of the controversial issues that are involved in medical treatment of the illness. Dr. Esber: I would like to ask the audience to bring up the question of education once again this afternoon as part of your comments. I think it's a very important subject and maybe one that new initiatives or new efforts can be focused on, and it would be useful to hear your proposals of how we might do this, if we are not doing it well enough. One of the questions, for example -- and I'd like to ask Dr. Mahy and Dr. Reeves to address this -- said that when they were asking CDC for direction, they were given an 800 number in Charlotte. And the question was why wasn't the CDC itself answering these questions. And I don't know if there is some sort of network or understanding so that questions can be addressed. How are you doing this? Dr. Reeves: I can't answer that specific question. We get a variety of requests for information. We have a telephone voice information system. We do mailings. We are quite frequently asked by patients for the names of physicians in an area they live in. We are quite frequently asked by patients for the names of support groups. We routinely -- we have a directory that is as up-to-date as we can have it -- provide the numbers, addresses, et cetera, of the various support groups in an area someone might be living in. So I can't answer that specific question. If someone is living close to a support group that we know of, we will give them the address of the support group that's either closest to them or a variety of support groups. We attempt to answer the questions in the most specific fashion possible. I can't deal with the question. I don't know, but I suspect that's what happened there. DR. ESBER: I have four more questions. I'm going to pose one to each agency and then we'll go back to the microphones. For NIH: "Why is CFS falling under allergy and infectious diseases when it's supposedly not an infectious disease?' DR. SCHLUEDERBERG: Things come into our program in a variety of ways which I tried to outline a bit to you. As you know, in the '80's, early '80's, when this was a focus, beginning focus at NIH, it was thought that the syndrome might be comparable or the result of infectious mononucleosis, a continuing persisting infection that expressed itself in this way. And our institute is responsible for the infectious disease aspects of Epstein-Barr virus. That's where it began. That's where the interest expanded. And we've taken the ball. DR. ESBER: And as you pointed out, multiple institutes are involved at this point. It's just a coordination. To CDC: "What can we say is the actual or estimated prevalence of CFS in the U.S. population?" DR. REEVES: I think our estimate of the prevalence or the range that we can get at is the information I presented in the slide from the four city areas that we are doing. We are, again as I pointed out in the talk, trying to do some cross-sectional studies to see how good that surveillance system is. It's undoubtedly an underestimate. How much of an underestimate we don't know. I suspect those figures are close to the ballpark figures. One of the reasons I gave the data in the fashion I did is that it's not a simple answer. And we are again trying very much to get away from just counting up the number of people who may have this. I don't think personally that is the major impact. I think the major impact is why people get it, and what it does to them, what the clinical course is. And I think personally that's more important than trying to spend a large amount of effort counting up the number of people that have it, which is going to be imprecise no matter how we do it. It's important information but it's information that leads to risk factors and occurrence in populations. But I can't give you a number. DR. ESBER: One question for FDA. And Dianne, I'm not sure whether you or I are the better one to answer this one. The question is: "Are there any known hazards to taking flu vaccines for CFS patients? Are there any side effects experienced long-term by average patients to the vaccines?" I guess we'd both say vaccines is my field, not yours, but I'm not aware of any data in this area. I'm just wondering if you are. Otherwise, we'll have to find it. DR. MURPHY : I do receive the adverse event reports, and they are supposed to be sent in annually, no matter what happens to a patient, in other words, whether they think it's caused by their having received the drug or not. I realize you are saying for those -- DR. ESBER: For vaccines, flu vaccines. DR. MURPHY: I know. What I was getting to is that, if someone had a reaction, they would have had to have been in the study -- it doesn't mean they would have had to have been in therapy. They would have had to have been in the study for me to get this report. So that it doesn't cover obviously all those patients who have never been or aren't in the study. But if somebody in a study or had been in a study had an adverse event to a vaccine, we should get it in their annual report that event. If it were life-threatening or serious, we would get out before that. And so from the limited numbers of data that we do have, and I just got the annual report recently, I can tell you that I haven't seen any reactions to vaccines in that very small population that we would be receiving reports on. DR. ESBER: In the area of general use of flu vaccines in immunocompromised people, there's generally not thought to be any side effects, but I honestly don't know the data on CFS. And I'm prepared to follow up on it if whoever wrote the question will give me your name and phone number and address. It's not listed. Would you like to identify yourself and go with the next question. We'll go for about three more minutes, and then we probably need to break. MR. LANDAU: My name is Robert Landau from the New Jersey CFS Association and the United CFS Federation. My question is addressed to the representatives from the Social Security Administration. I know at one point there was a listing in the manual for Chronic Epstein-Barr Virus. I was just curious whether that had been excised or never put into effect. And my other question is: For those of us who are receiving Social Security Disability or SSI due to Chronic Fatigue Syndrome, most of us are subject to periodic reevaluations to be clear that we are continuing to be disabled. How, when we are reevaluated, will we then be put in the new classification that you instituted in August? In other words, will we add to the numbers that you are going to be keeping? MR. EZRINE: In response to your first issue, we never really had Chronic Epstein-Barr virus in our listings. We have an instruction manual for our adjudicators called the POMS, Programs Operation Management Systems, and we do have information in there about previously Chronic Epstein-Barr. It's been changed to Chronic Fatigue Syndrome in an updated version. So there is still information that is published and given to our adjudicators so that they are aware of this entity but it's not in the medical listings. So, yes, it's still there but it's in a newer form. And also the Disability Digest has also updated some instructions. As far as the coding is concerned, I would assume -- MR. EIGEN: That's a decision that gets made by a bureaucrat somewhere, but I would assume that they would keep it. I can't imagine that they wouldn't also use the code for that as well. The whole point is to keep track of people who have Chronic Fatigue Syndrome. MR. LANDAU: Right. Because my determination was some years ago before that name even came into general use. In other words, when I am reevaluated, should I make a specific request that they make a notation of my number? MS. EZRINE: That's a bureaucratic decision. Usually there is a new form generated that the agency uses for entering into the computer system, and that has a diagnosis code and that sort of thing on that form. We can only assume that that would be entered in at the time the redetermination was made, but we are not clear on that right now. MR. EIGEN: The current instruction says they are supposed to use the code when the person claims to be disabled because of CFS. So I assume that would also apply if the person says that he continued to be disabled because of CFS as well. I just can't promise, because we don't get to make those decisions. DR. ESBER: One last question. We can talk in a moment about what we'll do about the rest of the questions. Go ahead please. MR. HENNESSEY: My name is Tom Hennessey. I'm President of an international group called RESCIND, which means Repeal Existing Stereotypes about Chronic Immunological and Neurological Diseases. First I'd like to congratulate Dr. Ann Schluederberg on her presentation this morning. You mentioned, I believe, that epidemiology is clues, a search for something. We have tens of thousands of hours of man- and woman-collected data on this illness, but it's kind of like Apple computer and IBM computer. They both do great things but they are not compatible. Can you provide us with a successful outline so how we can put the information we have collected into a paradigm that you will accept for review so we can get some research money for the people who are in the trenches? That's question number one. Question number two is: If it is not an infectious agent involved, why does the FDA tell us not to donate blood? Thank you. DR. SCHLUEDERBERG: On the first question, we would be happy to send you a grant application packet which describes the general procedures and tell you how applications are reviewed. I personally would be glad to discuss with you and put you in touch with good epidemiologists that would provide specific guidance to you in your efforts to organize your information. MR. HENNESSEY: I'd appreciate it myself, but I'm in bed 22 hours a day 363 days a year. I'm talking about like the 221 doctors who attended the Albany Conference. I can get you a mailing list. If they could be sent some kind of flyer -- I would be willing to chip in a couple of hundred dollars toward the mailing cost -- they could fill out or look at and then they could get this information. Because those are people who gave up their own time and money to come and speak, and there were over 220 of them and there were 750 people in the audience. DR. SCHLUEDERBERG: The consolidation of data from the many people that were in attendance at that meeting will truly have to be worked with those individuals. I'd be glad to talk with them and whoever represented that group. I have been in talk with one person that did make a presentation that was epidemiologic in nature, and working with that group on their specific application. But the kind of thing that you are talking about, this is the first I've heard of the intent or the problem of putting that together. MR. HENNESSEY: We would appreciate that consideration, because we have a lot of information and we would like to put it in a form that is acceptable to you for searching for further clues for this painful illness. Thank you. DR. ESBER: I'll try to respond to your statement about blood, if I could. Blood is collected from normal healthy donors, not limited to just transmission transfusion diseases. I think we must stop now. I do want us to reconvene promptly at 1:00 so we can be aware of all the comments that people want to make. I will remind you once again, as I've said twice before, if you'd like to rearrange the order on that sheet that I've passed out, please let me know in the next few moments. And the remainder of the questions, we'll try to see if we can deal with them this afternoon, if there is time. MS. KENNEY: Will there be a specific question-and-answer session at the end of the day? DR. ESBER: That's what I'm saying, if there is time. We've had 20 requests to present, and that should take about an hour and a half. And if that's the case, we should have about a half an hour for questions. (Lunch Recess) DR. ESBER: There are some changes that have been requested, as I had promised, that we would entertain on the public presentations. And if you'll bear with me, I'll just take them and we'll deal with it. We've had a request to try to have ten minutes of questions before we start, and that was if we started at 1:00. Unfortunately, it is already 1:18, and I think at this point we'll just go with five minutes of questions, and then we'll go through the planned presentations. To the extent that we have time at the end, we will reopen the floor to questions. I am going to have to be somewhat rigid about the five-minute time frame. I apologize, but that's just the nature of the beast right now so we can have time for you to ask questions again. So, as I understand it, there were questions. We'll take as many as we can in the next five minutes. MS. KENNEY: Kim Kenney, CFIDS Association of America. First of all, I'd just like to state for the record, Dr. Schluederberg, there is a correction to the presentation that I presented May 20th to the NIH CFS Coordinating Committee. When we stated our research priorities, our first priority was not for you to develop a patient care model. While we feel that's important, we have four other priorities we feel are more important at this time. The first one is to give high priority to funding science that identifies a marker or the etiologic agent for this disease; to attract a greater number of scientists to the study of CFIDS through the Small Grants Program, which, by the way, has been passed by the Senate Appropriations Committee and will be law in a few days. Number three is to consider existing qualified multidisciplinary centers for cooperative research center funding, expanding the existing centers that we already have to include a fourth or fifth possibly; and to invite private sector CFIDS clinicians who raise interest as credible patient advocates to serve on relevant advisory committees throughout the institute. That is one of the provisions of the NIH Revitalization Act that was signed by President Clinton on June 10th. Dr. Schluederberg, can you tell us, of the provisions that are in the NIH Revitalization Act that are specific to CFIDS, what are the progress steps on those action items and what are the programs that are in place to make sure that that law is carried out? DR. SCHLUEDERBERG: One of the things that was in there was the establishment of a study section, and I mentioned the establishment of the special emphasis panel for that purpose. Would you prompt me on some of the other actual provisions in the law? ` MS. KENNEY: Inclusion of private sector researchers and patient advocates on relevant advisory committees throughout the NIH. DR. SCHUEDERBERG: Well, people have been nominated for inclusion on those committees. MS. KENNEY: Who would that be from the patients? DR. SCHLUEDERBERG: We aren't in a position to make that public until a selection is made. It puts everybody in a bad position. Those things are approved at the level of the Assistant Secretary and so forth. So it's not appropriate to say we've nominated so-and-so and so-and-so has been turned down. That's why we can't tell who has submitted a grant application. MS. KENNEY: Can you tell us what advisory committees you are looking to place people on so that there is representation? DR> SCHLUEDERBERG: Our own advisory committee, that is , the NIAID's as lead institute. That's one of the key things. Our review panels are advisory committees. And a great deal has been done on that over the last two years, I would say, in providing information how to place a name on the NIH consultant file and to get people on the NIH reviewers reserve. At that time, if you have an ad hoc member that had knowledge of CFS and was brought into a study section that was designated for another purpose, they would not be able to vote. They could provide their advise, but only people from the reviewers reserve, by law, were able to enter a vote. So we have, I think, about 20 people with knowledge of CFS that have been appointed to -- not appointed, but have been put through the system to be on the reviewers reserve. MS> KENNEY: Will there be any action steps taken to include patient advocates or private sector researchers on the NIH CFS Coordinating Committee, since it operates most closely with CFS- related research? DR. SCHLUEDERBERG: We certainly have opened the meetings to that participation, and so I would say that, even as presently constituted, patient representatives would have as much say as anyone else that is not a member officially appointed by a director with interest and responsibility for reporting and institute responsibility. so that I don't see a need for another more formal one, but that's my opinion. It hasn't really been discussed any further. DR. ESBER: We are going to need to go on. Again, I'm sorry. We just must go for the planned presentations. The first one will be Mr. Thomas Hennessey. And since he and his colleagues have agreed to consolidate, he'll be speaking slightly longer that five minutes. MR. HENNESSEY: Dr. Esber, distinguished guests, ladies and gentlemen, I'm going to be speaking a little bit for Dr. William Crook and a little bit for Jane Perlmutter of CAN, so there's three support groups, 15 minutes, and I'll try to consolidate it to eight. Thank you again for convening this all-important meeting. This gathering is much long overdue, but finally some of the major players in this disease are in this room. My name is Tom Hennessey. I am the founder and President of RESCIND, Incorporated, a nonprofit advocacy group. Webster's Dictionary says that rescind means to repeal, roll back or abolish. RESCIND is and acronym for Repealing Existing Stereotypes about Chronic Immunological and Neurological Diseases. Our members are concerned with the mistaken public and private opinion regarding the severity of Chronic Fatigue Syndrome, Immune Dysfunction Syndrome, multiple chemical sensitivities and Fibromyalgia Syndrome. And, as usual, I get the duty of saying things that most of you do not want to hear. Far from being chronic somatizers, hypochondriacs or valitudinarians, the great majority of us were hardworking, ethical, compassionate taxpayers before being suddenly struck down in the prime of our lives with this vicious disease. And with all due respect -- I say Dr. Reeves because this was for yesterday -- even the makeup of yesterday's speakers panel, which I believe includes several members of the Flat Earth Society, shows that you still do not fully understand how to even look for answers to this tragic illness. Please remember that multiple sclerosis was called hysterical paralysis for more that 150 years. In the 1920s diabetes was thought to be caused by weak character. In the 1940s asthma was considered a psychological illness. Even Dr. Stephen Straus cites a textbook written in the 1750s that describes an illness very much like CFIDS/ME that was called little fevers and the vapors. And I believe Dr. Schluederberg said this morning that over 40,000 copies of that brochure were sent to physicians in the first printing. There have been additional printings since then. I thought long and hard about what to say today. I've lost more that 20 friends to this extremely painful and debilitating illness. Thousands more have been sentenced to a lifetime of unspeakable pain. I personally feel like I've been the recipient of a Rodney King style beating every day for the last six years of my life. There is nothing that you can take away from me that this terrible illness has not already stolen. So I've decided to say the things that many of us feel but most are afraid to say. There was an Oscar-nominated movie last year called "A Few Good Men." In the climatic courtroom scene the hotshot young attorney, Tom Cruise, turned to the grizzled bas commander, Jack Nicholson, and demanded, "We want the truth!" And Nicholson shot back across the stunned courtroom, "You can't handle the truth!" Well, ladies and gentlemen, up until this meeting of yesterday and today, a better script could not have been written to describe the abysmal response of the United States government and the U.S. medical community to this vicious epidemic. I personally believe that this illness combines stress, which is a very misunderstood and disagreed-about position, but in the preliminary studies by the CDC and their epidemiologists, stress is a major factor that they've found that is reproducible everywhere. Not fatigue, by stress. I believe genetic predisposition. Dr. Renner mentioned yesterday family history. I believe that is critical. Especially with President Clinton's new plan of an affordable healthcare system, we need accurate histories with clear, concise, cogent information that can be passed along. Psychological predisposition. We are the exact antithesis, the antipod, diametrically opposed to being called hypochondriacs. We were very hard-working, ethical, compassionate people. There is a reactivation of viruses. I don't believe personally there is one retrovirus, adenovirus, lentivurs, fungivirus. Many viruses could be involved in this. Diet. You can get an MD degree in the United States without taking one course in nutrition. With an $820 billion medical cost last year, over 20 percent was directly related to heart disease. There was only one brief presentation for five minutes yesterday about heart problems. We have very significant, measurable heart problems with this illness. Exercise. Dr. Tony Komaroff mentioned that those of us who do not have premorbid exercise habits often have less chance of recovery. Pollution. Back in 1988 when I first gave this talk, CNN had said that there are more than 19.8 billion, with a B, pounds of toxins dropped into our air, water, streams and grounds throughout the history of just the last from 1985 to 1988. Overgrowth of yeast. Dr. William Crook talked about that yesterday. There are many pamphlets outside. In the interest of time I will not go into them. Overuse of antibiotics. Most of us have a mean age of 37.1. So that means we are at the tail end of the baby boomers when a lot of our mothers were taking antibiotics. You can add to that birth control pills or other precipitating events. The last one I left open, because it could be a blunt trauma, blow to the head, a virus, infection, whatever. The other thing I want to say is last night I attended a cocktail party with some of the panel, and often you can learn more after the meetings than during the meetings. And I was told that a name change is not in the cards. All I can say is calling this terrible illness Chronic Fatigue Syndrome is akin to calling General Sherman's march to Atlanta the story of a boy with a match. For somebody who is not from Atlanta, it's akin to calling Hurricane Andrew, which did $30 billion worth of damage, a tropical breeze. You have to change the name. As I mentioned yesterday when Dr. Renner asked me, I went in 1989, asked for ten years of medical data on the computers at NIH. They said there are 17,000 entries of Chronic Fatigue. It is too incorrect a label and too generic a label to be given this disease. I believe what Dr. Hyde said is very good, Gilliam's Disease. How about Charles Darwin, Origin of the Species? He was kept in his room for 40 years. Florence Nightingale, a founder of the first ever school of nursing. She was bedridden for 40 years. Name it after a person, and then we can decide the definition later. The next thing is about money. Power is money. We live in a capitalistic society. If you researchers want more money, you can't keep calling it fatigue. We've had NBC, CNN, CBS, MacNeil-Lehrer News Hour. The first question from Larry King: "Tom, are you tired?" No, I am not tired. I feel like I've been hit by a steam roller. The next is listen to your patients. Thank you very much for the presentations so far today, especially Dr. Schluederberg saying that epidemiology is a search for clues. As I mentioned this morning, we want to help you. We want to be equal partners for this search. Number seven, combine high-tech with low-tech. Build a 250-question questionnaire. Have 20 questions from every single expert here about family history, all the things I mentioned on there, that can show that CFIDS/ME, fibromyalgia and multiple chemical sensitivities overlap about 70 percent of the time. We want to find the differences. Number six, please, I beg of you, find something, anything that you can all agree on that is reproducible and quantifiable that can be used as a diagnostic tool for clinicians. Everyone says research division, clinical division. We have to make that distinction. We have some of the best minds in the world studying this illness right here in this room. Stop working against each other. Start working with each other. Millions of lives are at stake and billions of dollars. I brought with me an example of an MMPI Minnesota Multiphasic Inventory, by Sheila Bastion and Linder Miller Eiger, 451 questions that show a distinct profile of people with CFIDS that is different from brain injury, different from major depression. Number five, get rid of all exclusivity clauses in this definition. This illness is some kind of autoimmune response to something, be it a chemical toxin, a virus, whatever. We have to realize that you can have this and any other illness. If a woman has ovarian cancer and then she gets depression, no one says, "Oh, now you've got depression. You can't have ovarian cancer, That is negated. " That is ridiculous. The six month rule, very hard to please. In today's modern capitalistic society, if you miss more than two months work, you are out of a job, which is going to add to your stress and lead to that train wreck that I described up there. I would recommend naming it Ramsey's Disease after Dr. Melvin Ramsey who studied this illness for 35 years. He said, quote: "The degree of debility varies greatly but the people who are the sickest are the ones who persist in working the longest before collapsing." Put it another way, those who get early detection and enforced bed rest have the best chance of recovery. That is why it's critical that you intervene early. That is why so many of us got called the Yuppie flu. That's all over the media. And I'll punch you out if you guys put just only the Yuppie flu on tonight's evening news. Number two, you got to stop nickel-and-diming this problem. Two, three, five million dollars a year is never going to cut it. Throwing five million dollars a year at this epidemic is like cutting the toenails of a terminal cancer patient. We are losing tens of billions of dollars every year. And number one and final, two nights ago I couldn't sleep because I was nervous about friends dying, and I turned on the TV and I saw a movie on HBO called "And The Band Played On." Please, I beg of you, change the name and do not replicate that movie so that ten years from now the story of CFIDS will be "And The Band Played On Number Two." Thank you. DR. ESBER: Thank you very much, and thank you for keeping the time. To the extent you do have prepared written remarks and you can leave them or we can copy them -- and this is for all the presenters - - we are interested in these prepared presentations. They will guide us for the future. We don't want to lose it. Is there a Jane Perlmutter? MR. HENNESSEY: No. I spoke for her. DR. ESBER: Fine. Then the next person will be Wihelmina Jenkins. Is she here? MS. HUMPHREYS: I'll speak for her. I'm Barbara Humphreys from the Northeast Atlanta CFIDS Support Group, and I'm speaking for Wilhelmina Jenkins and Bill Rucker, both of whom are too sick to come here. I want to thank everybody from the CDC. I want to thank all the CFIDS Support groups, everybody present, the clinicians in particular, Dr. Hyde, Dr. Crook, the people that have dealt with us. I want to tell you that we would be here in force but these are the only people who can come. Everybody else is sick. It's hard to recognize that. We look well. We are barely here, but all of the people that we have in our groups -- and that's many, many, many people -- cannot come because they are too sick with this illness. I'm married to a doctor. I've been married to him for 36 years. I've had this for 14. We are not hysterical people. Talk to him about it, if you want to talk to doctors. Thank you very much for trying to take us seriously. This is very difficult to go through, and we appreciate whatever you all are doing. DR. ESBER: Thank you very much. Again, if you could write your name and provide it to the recorder so we do have it. As we will be convening Dr. Lee's meeting that I mentioned earlier, we will need to know how to get to people. And so if you could leave your name and address at the desk, then it would be easier for us to send a mailing list. Dr. Byron Hyde, who is currently listed as number 17, has asked, since he has a plane to catch, to go next. DR. HYDE: Dr. Esber, Dr. Reeves, who I believe is still here, and Dr. Schluederberg, I'd like to apologize for the intensity of my remarks yesterday, and if you could give those apologies to the panel. But I cannot apologize for the contents of what I said. I find it abhorrent that you have a person on your committee who publicly on several occasions to large numbers of people has ridiculed people with Chronic Fatigue Syndrome. I think it's counterproductive. Yesterday every patient group, every group that had anything to say about this disease, begged you to change the name. The term "fatigue" and "chronic fatigue" never existed in this disease entity until it was put in in 1988. And I'd like to tell you a little story. I was at the original meeting here at the Centers for Disease Control. It was an hour-long meeting, as you know, a very interesting meeting in chronic viral infections chaired by Carlos Lopez. And at that meeting there was a Dr. Alexis Shelkov who is the dean of knowledge in this disease and has written many wonderful and dedicated papers, scientific papers, and has served the community of the United States well. Questions were asked in that committee, and would anybody like to add anything to this, and Dr. Shelkov started to talk. The committee chairperson who didn't know Dr. Shelkov apparently, said, "Look, we don't have time." And Dr. Shelkov, who spent a lot of time on epidemiological studies in this nation on this disease, turned to me and said, "If they don't want to hear what I've got to say, then I'm leaving." And he got up and left. And I think that this committee suffers from this problem. We know now that you are not going to listen to the name change, even though the term "fatigue" and the whole concept of fatigue in this disease has warped our understanding of this illness. It is great that you have decided to take out physical findings that never occurred with this disease after five years of us bugging you to take them out. But had your committee had clinicians who understood the disease and listened to Alexis Shelkov in the first place, they would have never put those symptoms in. And yet there are many physical findings in this disease. Excuse me. Not symptoms, but physical findings. There are many physical findings in this disease, and I think you are going to gloss over those. And you know what that is going to do to these patients. What it is going to do to those patients is insurance companies across Canada and the United States are going to say there's no physical findings, there's no diseases. And I wonder if you are aware of this and the enormous effect. What should you be doing is doing what I suggested yesterday. Stick a thermometer in somebody's mouth. And I don't mean that just in terms of a thermometer. I pointed out yesterday and in the document that I gave you, and there are others, definite physical findings in this disease. You don't have to take my word for it. It is very easy for you to ask a hundred patients in any one clinical practice to be tested for these findings and find that they are there. But your committee does not have enough hands-on clinicians to understand what is going on in this disease, and this disease is not about fatigue. It is, as I pointed out yesterday, two very important areas. One final thing I would like to sum up, and that is we've just completed an epidemiological study of 1,826 cases. The majority of those individuals we passed through our clinic, and we excluded all of those individuals who we believed do not have Chronic Fatigue Syndrome. And when we graphed them, what we found is the following, and I'll end up with this. Patients felt ill during all 12 months, but the single biggest increase in numbers of patients developing morbidity was between July and August, suggesting the greatest initial activity of the disease at the same period as that of paralytic poliomyelitis. The peak was in October, with a rapid falling off in that month in number if new cases of morbidity. Again, the same period as paralytic poliomyelitis. I need not remind those who are present of the numerous cases reported of epidemics in the literature, and the period of incubation of this disease has been frequently stated at four to five days. Again, we are looking at the same incubation period of poliomyelitis. I'm not saying this disease is poliomyelitis, but I think a large number of the people who are falling ill with Chronic Fatigue Syndrome are indistinguishable from what we used to call posterior polio. Thank you very much. DR. ESBER: Thank you very much. Back to the top of the list, Bill Rucker. Is Bill Rucker here? MR. HENNESEY: I spoke for him. DR. ESBER: You spoke for bill. Okay. The next is Ms. Kim Kenney. MS. KENNEY: Good afternoon. Again, I'm Kim Kenney, Executive Director of the CFIDS Association of America, the world's largest and most active nonprofit organization dedicated to conquering CFIDS. Since 1987 our organization has grown to represent more than 23,000 members, and we've funded over a million and a half dollars of private research grants, responded to 200,000 inquiries about the disease. And I should note that there were as many as 15,000 in a single day. And we've published and distributed hundreds of thousands of copies of our journal, "The CFIDS Chronicle." Our primary purposes and goals are to fund private research, validate and disseminate current information, and influence government to aggressively pursue all aspects of a comprehensive public health response to this disease, including research, prevention, care and education. And we work to accomplish these goals by collaborating with more than 400 state and local support groups nationwide. Because the association was founded by a group of patients working with thousands of other patients and a handful of clinicians exploring CFIDS, from the beginning we've known that CFIDS, was not just chronic fatigue, that it's not chronic depression. It is a distinct clinical entity, a real disease, a serious disease, and that it is spreading. As an organization, we focused our research efforts on finding the cause or causes of and markers for CFIDS, establishing the basic epidemiologoy of this disease, and identifying effective treatments for it. Because finding the cure of the disease is our ultimate goal, we feel these three avenues are the most rewarding. In addition to our research initiatives, through our public policy advisory committee and our professional Washington, D.C. representative, Tom Sheridan, our association leads the national grassroots advocacy effort. Our modest accomplishment in terms of dollars of promising research funded provide an important and critical foundation for furthering the understanding of this disease. But in order to conquer CFIDFS, we know that the government must take the lead and provide a vigorous investigation of this disease. We are committed to making that happen. Through our legislative initiatives, we have enrolled the considerable assistance of the Congress to help us secure adequate funding, to make sure that federal agencies are responsive to the needs of and demands of PWCs, persons with CFIDS. The very existence of and funding for this committee in its recent days and time has been legislated by Congress through our efforts. And as a direct result of our efforts, Dr. Phillip Lee will now chair the meetings from the next meeting forward. And at the next meeting we look forward to CFIDS-specific presentations that describe program priorities, seek appropriate budget levels and provide oversight accountability for CFIDS research. I'd like to take this opportunity to review with members of this committee our public policy initiatives for each of the federal agencies represented here today. We've outlined our initiatives in a letter that was delivered to then President-Elect Clinton's transition team on December 9th of last year, and a copy of the memo was provided in a packet which you either have or will have shortly. I'll follow the order of this morning's presentations. Center for Disease Control. We feel yesterday's meeting addressed one of our top priorities for action at CDC. And, as I stated yesterday, we feel the current case definition has become outdated over the last five years and is in need of revision. In the interest of time, I won't reiterate the ten recommendations we made to the panel but summarize by saying that the case definition should be amended to more accurately describe the sign-symptom complex as one of a multiple systemic disorder of the entire body, not just Chronic Fatigue. We are very troubled by the presentations that were made to drop all the symptom complex and would echo Dr. Hyde's feelings that without better representation by clinicians on that panel, it's going to be difficult for people who are more engaged in science and academia to distinguish what characteristics of this syndrome might be helpful in discerning patients from controls, whether they be healthy or ill with other diseases. The surveillance study that Dr. Reeves reported on has been underway since 1989 and has served its original purpose as a prototype study. The study must be replaced with a community-based study to more accurately determine the nationwide prevalence of CFIDS under the revised case definition. The U.S. Senate Appropriations Committee has recently passed legislation that will mandate this. We feel strongly that the current surveillance study underrepresents the prevalence of this disease, not Chronic Fatigue, in people with color and lower socioeconomic groups, and I think that was clear when the median income of the people who have been identified in the study was $50,000 a year. Further, we request a full debriefing of current investigations into the two cluster outbreaks in Sacramento and Pigeon, Michigan. And we also need to know these outbreaks can be reported to CDC so that outbreaks we might hear of from patients of physicians can be reported to CDC for follow-up. It's imperative that this information be disseminated to state and local public health agencies so that the people might be able to inform CDC officials as well. As part of the big responsibility to document the basic epidemiology of CFIDS, CDC must work diligently to understand how this disease is transmitted and must prepare to provide appropriate educational programs for the medical community and the public at large about CFIDS and any health risks associated with it. It is absolutely imperative that we stop the continued spread of this disease. National Institutes of Health. NIH should be the lead agency for the critical biomedical investigations into the causal agents for the disease, but through collaborative efforts of the many NIH institutions and extramural researchers, we feel there is an excellent chance that definitive markers and also a causal agent will be identified. We are encouraged by Dr. Straus's publication earlier this year and feel that continued focus of investigations into virology, immunology, rheumatology and autoimmune and infectious disease specialties will prove to be enlightening. We look forward to working with Dr. Schluederberg and others to accomplish the intentions of our President and the Congress in the NIH Revitalization Act to accomplish the provisions specific to CFIDS in that Act. And we understand that present funding levels at NIH remain far below those needed to pursue comprehensive investigations and are committed to working with Congress to increase the resources, provided our partnership remains strong and our participation in the activities at NIH is welcomed and appreciated. Just briefly on Food and Drug Administration. We understand that only one application for a drug to be used to treat persons with CFIDS has been pushed through FDA, and that drug, of course, would be Ampligen. We have serious concerns for the people who have been on Ampligen and were recently taken off. And for the sake of those people, we ask FDA to develop a full policy for the compassionate care of patients who need to remain on, return to, or be placed on Ampligen. We are encouraged by the activities through the advisory committee at the antiviral drugs division and ask that patient advocates be formally invited to and participate in each of those meetings. Social Security Administration. Our greatest concern there is that the Social Security Administration officials continue to be updated with respect to new science that occurs that might change the way disability claims are handled and that they play an active role in this committee and that they continue to be trained so that the adjudicators and the claims people who are doing it on the lowest level can get claims pushed through much more quickly. It seems to be spotty. In areas where there are local support groups that are willing to train Social Security people within their area, the claims go through much more quickly and they don't have to go up to the ALJ level. The message I'd like to leave with this committee and this audience as it prepares for its first meeting with Dr. Lee is that the CFIDS Association of America is committed to achieving a unified and dedicated response to CFIDS from all federal public health agencies. We wish to make use of our political resources to expand the resources each of you has so that we can work together to beat CFIDS. We look forward to forming and maintaining a productive partnership characterized by mutual respect and reciprocity. Thank you. DR. ESBER: Thank you very much. Those of you who are clock-watching, as I am, you'll recognize that she went quite a bit over. The reason I've been patient, or whatever the word, nonrigid, is because four talks have been condensed into two. Claudia Wendlandp. MS. WENDLANDP: I'm Claudia Wendlandp and I'm with the Atlanta CFS Association. I'd like to thank the panel here for having us these past two days, for listening to us. I'd like to echo what Barbara Humphreys had said. The people you see here with Chronic Fatigue are the ones that are well enough to be here. You will not see us for the next few days when many of us will have a hard time getting out of bed. It will be difficult. With the Atlanta CFS Association, I handle the hot line. I hear from mothers or women whose husbands have left them and their husbands are filing for divorce and their children are in danger of being taken away. I know these are all things that you have all heard before. I hear from people who are fighting for Social Security and have no money and don't know where their next mortgage payment or rent check is coming from. It's an extremely sad situation. I hope that our being here has meant something and that you've invited us to truly listen to our concerns. Thank you very much for the opportunity to be here and speak with you. DR. ESBER: The next on my list would be Robert Landau. MR. LANDAU: Thank you very much. Again, I appreciate the opportunity to address the panel and the audience today. My name is Robert Landau. I'm the state coordinator for the New Jersey CFS Association. I'm here to represent 700 members. I'm also representing the United CFS Federation, which is an umbrella organization whose member groups cover more than a dozen states and have thousands of members. I'm here on their behalf to present some ideas for your consideration. Yesterday's meeting regarding an update of the CFS working case definition was most enlightening. As members of lay organizations, the most important item on my agenda to present to you today is visibility, your visibility. Time and again we hear from our members: "What is the government doing? Why aren't they doing any research? Nothing is happening. Don't they care about us? Why aren't our tax dollars at work?" This, of course, is an age-old hue and cry, but age-old problems are age-old because they have no easy solutions, and we recognize that. It's very clear from recent medical conferences and yesterday's presentations that the government is doing a great deal of research, and our tax dollars through you are hard at work. Naturally, we want more funding, we want more research, but we must acknowledge the strides that have been made, and we thank you for that. Today I ask you to increase your visibility. Our patients and the public at large need to know your progress and your accomplishments. When I address support group meetings and seminars, as I shall when I return to New Jersey, I often spend a significant amount of time on the subject of progress, progress in the medical understanding of this illness. The audiences are often astonished by the amount of the research, the diversity of that research, and the caring nature of you who are engaged in that research. They say, "We didn't know. No one told us what was going on." This of course indicates that we who work in the support networks need to redouble our efforts at education so that they are aware of the progress that has been made. Now, we are not asking you to take over our jobs educating the public, acting as advocates on behalf of patients. What we are asking is that you better inform the public of the progress that you are making. I would like to commend Laurie Doepel and the NIAID Office of Communications for the fine work and assistance that they have done. The "Pamphlet for Physicians" from NIAID is a excellent example, one that we hope will continue to be updated as appropriate. Another example is the CFS booklet from the "Medicine for the Public" series, also published by the NIH. We've been gratified to see that the "Medicine for the Public" booklet has been repeatedly listed in the "Consumer Information Catalog" which is produced by the General Services Administration. This catalog, which is advertised both on TV and in the print media, reaches millions of people. Unfortunately, the general public more often sees only sensationalistic articles in the press and on TV, and the public comes to erroneous conclusions as a result. The situation is sometimes worsened by a few researchers who seem to prefer getting interviews and holding press conferences over the proper forum for their work: publication in peer-reviewed journals. This situation is regrettable since retractions are never made if scientific papers were never published. I, for one, am tired of mopping up after the latest public relations disaster, whatever its source. One example of improvement in this area would have been wider distribution and publicity of the periodic reports issued by ABT Associates on the CDC's surveillance study. Now, some patient newsletters have reprinted this information, but even more of them seem unaware of the very existence of the reports. I don't believe the newspapers or television have given the reports from ABT any significant amount coverage. Please make our jobs easier. Continue to inform the public of the progress you make. While you are, of course, prohibited from lobbying for more research funds, most of us are not. We can lobby much more effectively for increasing your funding when we can show the progress already made and when the proper impression is in the public minds that productive research has been performed and more needs doing. Your increased visibility will also be of great comfort to our patients, our members. When they can see the work being done, the lines of research that are being pursued, the progress being made all too slowly but just as surely, they gain hope. And hope in lieu of a cure is the greatest comfort known to humankind. Thank you again for your time and attention. DR. ESBER: Next is Ruth Robin. MS. ROBIN: My name is Ruth Robin, and I'm President of Chronic Fatigue Syndrome Society of Illinois. The establishment of the Interagency Coordinating Committee on Chronic Fatigue Syndrome appears to be a good-faith endeavor to coordinate the activities of several government agencies. We appreciate and welcome the opportunity to participate in this committee meeting. We hope the concerns we express today will facilitate the implementation and direction of CFS-related activities. A key concern of our organization is the manner in which Social Security disability claims are being handled. While we understand the necessity to make sure that only legitimate disability claims are honored, we are troubled by the length of time it often takes for CFS patients to have their claims approved. Too frequently expert opinions seem to be sought from medical and vocational consultants who do not understand CFS. Relying on these, quote, expert opinions, claims are denied in error, benefits are delayed, and CFS patients endure more hardships than should be necessary. The highly negative impact CFS has on the afflicted individual's ability to work should be conveyed clearly and regularly to all SSA personnel who make decisions pertaining to whether claimants are awarded disability benefits. When their benefits are finally awarded, CFS patients who might have faced financial ruin during the lengthy process must continue to struggle until their Medicare benefits become effective 29 months after the onset of their disability. This constitutes an excessive waiting period. Additionally, under Medicare, medications are not covered. If there is a private insurance available for a CFS patient, there are no medications covered specifically for CFS. Healthcare claims for pharmaceuticals often must be submitted for diagnosis other than CFS if coverage is to be triggered. We would like to see a cooperative effort between FDA and pharmaceutical companies directed towards the approval of drugs specifically for CFS. While we do understand that approval of such drugs would be make in response to applications from pharmaceutical companies, such applications should be encouraged by the FDA and acted upon expeditiously. If there is any evidence suggesting a drug is effective for CFS, efforts should be made to expedite the approval process without compromising safety. It is unlikely that any single drug will be universally effective for CFS. However, even if a drug appears to help only a small number of CFS patients, this drug should be given priority in the approval process. Empirical research is needed to develop a better understanding of which type of drugs might be effective for treating CFS. However, such research is apparently being thwarted by another type of research directed at establishing that CFS is solely a psychiatric disorder. One instrument that has been frequently used in measuring the psychiatric status is the Diagnostic Interview Schedule. Unfortunately, this test has inherent bias, in that, if a symptom cannot be explained or measured, then it is, quote, probably psychological. The inappropriate use of this instrument has added credibility to the opinion that CFS is a psychiatric condition. We hope any committee that approves CFS-related research will consider the confounding impact of the use of the DIS and favor studies more focused on the biomedical aspect. Having observed previously well patients, colleagues or family members become stricken is probably the most persuasive argument to a clinician that CFS is a real organic illness. Preliminary epidemiological research by the CDC has utilized the DIS, and an early estimate of the prevalence of CFS has been exceedingly low as the DIS unduly diagnoses psychiatric morbidity in this population of patients and psychiatric conditions have precluded a diagnosis of CFS. At the same time, epidemiology researchers in Chicago have been unable to get funding from the NIH for a study assessing a more accurate prevalence rate of this disease. The design of the Chicago study would not preclude a diagnosis of CFS because of psychiatric morbidity. We sincerely hope today's meeting will lead to a better understanding between all parties involved with CFS-related matters and thereby bring about more progress towards finding medical, social and economic solutions for those whose lives have been touched by CFS. Thank you for your time and attention. DR. ESBER: Next is Orvalene Prewitt. MS. PREWITT: Again, I'm Orvalene Prewitt, President of the National Chronic Fatigue Syndrome Association in Kansas City, Missouri. Our organization is a nonprofit, all-volunteer organization. We formed to educate and inform the public on the nature and the impact of Chronic Fatigue Syndrome. In our beginning, we sought conscious and competent help from the scientific and clinical communities. The primary focus of our organization is to offer accurate information on Chronic Fatigue Syndrome. Such efforts are accomplished by relying on various peer-reviewed, scientifically accurate medical publications, medical advisors, and information published by the agencies represented on this panel today. It is through meetings of this nature we can achieve our goal. Thank you for asking us to participate. We try not to provide false hope as an organization. We realize education is the key to understanding. Thus, we have a hot line. We've created eleven different brochures. We publish a quarterly newsletter, provide an educational videotape, hold monthly support group meetings and seminars, et cetera. To accomplish the creation of those educational tools, we rely on many publications, some of which are from the Centers of Disease Control, such as the information on the surveillance network. We have received many updates from ABT Associates and have published that in our newsletter. The information pamphlet that CDC has put out has been very beneficial for patients. From the FDA, when the Ampligen hit the press as a potential treatment for Chronic Fatigue Syndrome, immediately we contacted the FDA, got their written information about the treatment IND status of that, and reprinted that for the patients. Additionally, we were just recently provided a new drug development booklet that I saw on the table here today. We are reprinting that in our newsletter with permission, to give understanding to patients about how the drug process works. There's been publications from the Social Security Administration that we've given back to our people for those who might be needing Social Security Benefits. Quite helpful in helping them to understand the process and know what they might need to document the course of their illness and document the availability of funding for that. From the National Institutes of Health, we've had many publications from them, being the physician's pamphlet, the "Medicine for the Public" booklet, as well as various other things that have been printed as far as minutes of meetings and updates. Such information can provide hope and understanding for persons whose lives have been so devastated by this illness. Based upon the input that we receive from calls, correspondence and surveys, such tools have given credibility to this illness. Any efforts that can be made to facilitate such education will help organizations such as ours build a bridge of understanding between the patients and the agencies represented here today. We look forward to future publications from your agencies. Thank you. DR. ESBER: Nancy Klimas, Dr. Klimas. DR. KLIMAS: I'm Nancy Klimas from the University of Miami. And I am speaking to voice the opinion of one clinician investigator and speaking to issues pertaining both to patient care as well as research. One of the concerns in talking to this interagency committee would be to bring up the concerns of investigators such as myself that are in academic or private practice settings doing research in the area of Chronic Fatigue Syndrome. And I would have to bring up a dilemma that we see every single day. Our interests to do good science, good research, often conflict with our interests in providing good clinical care or access to clinical care for this patient population. And as many of these patient groups have talked today and in past years about problems finding well-informed physicians that are caring and have the time to spend with each patient that has Chronic Fatigue Syndrome, I would speak from the point of view of one of those clinicians who has found my practice overwhelming and found my research time dwindling because of clinical demands by my private practice and having to constantly weigh the needs of the patients' healthcare versus the needs of the patients' research demands. And it's an issue that I have not found an answer for. I would bring up these concerns to you as a committee that, while your charge is very clear, you want to help people with this illness know more about this illness, help clinicians with this illness understand it and treat it better and so on and so forth, that these very real needs are underscoring every day of these patients' lives and these clinicians' lives that care for these patients. Right now, I know at the University of Miami we are struggling to obtain research funds, as is the struggle of all investigators in any field anywhere in this shrinking pot of research monies in this country. And I know, Ann, that you've worked very hard at trying to answer the questions at the NIH of how to get a fair and decent review for studies from different groups, but I'll show you just one example of how things have been. We have this one proposal, not one of our major areas of study but just shows the dogged persistence of one research group. It's a behavioral medicine approach, a kind of restructuring grant that we first submitted in 1988. It was reviewed. Had a fairly decent review. Made some very appropriate responses and asked us to resubmit. It was resubmitted, having answered those questions. It went to a different committee for re-review. It was re-reviewed and, in fact, the different committee more or less suggested to make it the grant it had been. It went again back a third time, and it was reviewed by a third committee, which more or less suggested it should become the grant it had been on the second time. It wen t back. It was re-reviewed by a fourth committee, which more or less said it should go back in a completely different design with different control groups. It's now back for its fifth round of review, all these scores not being all that bad, enough to encourage you to go back anyway. And it is now going to a new committee, its fifth committee It is not even now being reviewed, has never been reviewed twice by the same pair of eyes. It's been a real dilemma. I understand how these things come to be, and I understand how -- the new committee, hopefully, will come to answer some of these questions. but I'm concerned that that committee be multidisciplinary enough that it have a pool of good minds to pull from and that at least on second reviews in that committee that the pair of eyes might see the grant twice. That is one type of concern that happens within one agency. Another real concern that clinical investigators have is access, patient access to healthcare. We are all hoping that Clinton's new plan will answer this question. I, for one, in an academic, university-based practice have at any given time one- third of my patients uninsured that had been insured, that are in the process of SSI, SSDI, and are no longer covered and in a one- or two- or three-year loop of appeals processes before their insurance comes through to bear. My departmental needs are such that I'm under tremendous pressure to drop those patients from my university private practice and transfer them over to the indigent care clinics of the university. Well, this poses a problem to myself as an investigator, a practical problem. Certainly it's a horrible problem for my patients, the fear of being threatened with the loss of follow-up by my practice. And, in truth, for three years I've been in deficit levels of reimbursement in my clinical population because I've carried so much indigent care in my private practice. I think that's a very real problem, and I'm hearing that concern from patients across the country that perceive various research-type investigators as their physicians, be they consultants or primary care physicians; that they are being worried that they are being squeezed out of practices or not being allowed access to research protocols that are being funded by the NIH because those physicians have backed off from clinical care. It's going to be a bigger and bigger problem. The solution then is going to have to be the education of primary care physicians in every community in the proper care of Chronic Fatigue patients. I mean, that's the obvious solution. And I'm wondering if it could be one of the charges of this interagency committee to take a real point position in educating primary care and consultant care physicians in the care of Chronic Fatigue Syndrome patients. I was concerned in the Social Security Administration's discussions that it didn't seem like you made much progress for we, the people filling out all those forms, in how to properly fill out the forms and hasten our patients' process through the system. It was very educational. I learned a lot about how things came to be, but I don't feel like I know a whole lot more now about helping my patients achieve their disability. Literally, as a clinician, right now I spend six hours a week with attorneys. They are all disability attorneys. I don't need to spend six hours a week with disability attorneys. That's a terrible waste of my time. And I would prefer not to do that. I think that the Social Security Administration could do a lot by helping us work through this process so that the patients win their disability with appropriate documentation on the first round, so it doesn't have to go to appeal, so you don't have to get attorneys, so you don't go through these two-year periods of being without income and without medical insurance. So those are the main points that I would bring up as the most alarming in the practice as I perceive it, for what that's worth. Thank you very much. DR. ESBER: Is Dr. John Renner here? DR. RENNER: I welcome this opportunity to speak with you. I know what a difficult job you have of separating all this information, and I'm probably going to add a new thought or new challenge, because I'm going to talk about something that we haven't heard very much about, and that is the difficulties that patients have in selecting a competent and effective and ethical physician. We have a tragedy across the United States right now, not just for the Chronic Fatigue Syndrome but especially with Chronic Fatigue Syndrome patients in their ability to select a physician who has an interest, a knowledge, and the ethics to take care of Chronic Fatigue Syndrome patients. Patients with Chronic Fatigue Syndrome are especially vulnerable to what appears to be a caring and kind physician by perhaps a physician who is missing deeper knowledge and missing the ethical requirements. I'm not going to list all the physicians that I personally know of that have had their licenses lifted in the last year or so, but several of them have been in several states Chronic-Fatigue- Syndrome-identified experts, both locally and nationally. I think that one of the things that the federal government could do, if it's within your powers, if you are going to give grants to the private sector, that you make sure that you require and have knowledge of a variety of conflicts of interest, of potential outcome, study requirements, that you do not become part of the problem. You inadvertently became part of the problem because a former NIH employee was listed as the credits of one physician who lost his license. It's a minor bit of harm. You are big enough to withstand that blow. But I mention this because I think we do need to have much more information from the private sector about this illness, especially with so many public funds being involved, whether it's Social Security or NIH or CDC or what it is. I believe that if we are truly going to have a partnership with patients and clinicians and researchers and federal and state agencies involved, that accountability is an extremely important activity that we need to think about. We need t put that responsibility on everyone's shoulders, not just those that are represented within the political process. I know that there is a great concern about this within the Clinton administration. Fraud has been identified as one of the things they are concerned about in healthcare reform. And as we go to a potential new healthcare system, with electronic billing being pushed so the paperwork is reduced, as we go to freedom of choice of any physician, and as we emphasize preventive medicine more, we are going to be ripe for problems. Now, for the last eight years I have been studying this, and I can tell you that the misinformation in the Chronic Fatigue Syndrome world is a major problem and, besides finding a marker for the illness, keeping the misinformation to a minimum is part of the responsibility for credibility of the illness, because we still have a large number of physicians out there that are dubious. And the more dubious physicians, the less likely people are to get healthcare close to their own home and are going to have to travel further and further. I am very frustrated when I hear that patients have to go to see five or ten or fifteen physicians that are unable to make a diagnosis with this illness. I've only touched the tip of the iceberg of the information that we have collected. We are trying our best to get a handle on the information that is shared. Separate from the National Chronic Fatigue Syndrome Association, I run a nonprofit operation called Consumer Health Information Research Institute. We run a hot line, and I'm giving you information that comes from that organization. I want to thank you. I hope this will add a little bit to your challenge, which I know is tremendous. Thank you very much. DR. ESBER: Thank you very much. Marya Grambs. MS. GRAMBS: My name is Marya Grambs. I'm Director of the CFIDS Foundation in San Francisco, and originally I was going to talk to you about the San Francisco model. And I was going to tell you about for how many years we have been working very closely with the San Francisco Department of Public Health and the California Department of Health Services; how we've been working with Dr. Phillip Lee, who was the chair of our health commission and the Director of the Institute for Health Policy Studies, and , as a result, together we have developed a grand rounds training on the diagnosis and treatment of Chronic Fatigue Syndrome; we have developed a fatigue algorithm, a lab protocol and a treatment protocol that have been published in the "San Francisco Epidemiological Bulletin" and in the "California Morbidity Report;" and that together we've been doing outreach to clinics serving ethnic minority communities. We are doing an epidemiological study with the Centers for Disease Control, we have worked with the Centers for Disease Control on a cluster outbreak study in Sacramento, and we do physician training. But after yesterday and today, I've become a little discouraged, and I realized I needed to be a little more direct than tell you about what we are doing in San Francisco. And what I want to talk to you about is democracy. I want to talk to you about the democratization of public health. What you are going to hear over and over from people like me and from people I represent is that clinicians and medical researchers must work in collaboration with patients and patient advocates. It's a democracy and we must work as a part of a team. If we are invited to the table at the outset, we will not come with animosity. We will come to collaborate. You know, yesterday people came up to me and they said, "This meeting is a sham. This is just to placate the patients, and then they are going to go off and do behind closed doors what they were going to do anyway." And I said, "Oh, come on." I'm not the paranoid type. I don't go along with that. However, when I saw the composition of the panel and then I saw that indeed they went off behind closed doors, I thought to myself maybe there is some merit to that. I was appalled at the lack of clinical representation on that panel. And no case definition will be valid if it's not based on good, long-term, experienced clinical representation. The Interagency Task Force. You all know that Congress mandated that there be consumer representation. How come there is no consumer representation behind that nice little blue skirt there? The next time you meet there better be consumer representation. We talked yesterday with Dr. Schluederberg. There's an upcoming clinical conference that NIH is putting on. It's going to be two days. And up until now it was going to be two days of clinicians talking about patients. That is not acceptable. Patients must be part of the conference. Doctors must listen to patients as well as talk about them. And Dr. Schluederberg, I'm very glad that some people are being nominated to the NIAID advisory committees, but, again, we want to know who they are. Have they been informed that they've been nominated? Because, if so, I don't know who they are. And we are very interested that the West Coast have some representation. You know, believe it or not, we are the polite ones and we are the reasonable ones. You might not like what we have to say, but there are a lot of less polite and less reasonable ones that could come here and will be here next time if we are not invited at the outset in a collaborative way. Finally, just two comments. In terms of the case definition, I was very disturbed yesterday to see that there was a direction in which some people want to open up the case definition to include anybody with fatigue. And if that happens, it will be a disaster. And the entire patient movement will not support such a case definition. And, finally, Dr. Reeves, I have to say that I think it's irresponsible for you to publish prevalence rates of two to seven per hundred thousand, given the population that you ended up studying of white women earning more than $50,000 a year. I mean, if you took all the patients certified by CDC case definition, all your trials and all the studies, it would be more than 3,000 people starting there. So we really don't want to see those kind of prevalence rates published until better and more comprehensive work is done, unless you add to it some of the other rates that are coming from other countries. Thank you very much. DR. ESBER: Thank you. Laura Hockenbrock FROM THE FLOOR: She is not here. DR. ESBER: Thank you. Dr. Daniel Peterson. FROM THE FLOOR: He's not here. DR. ESBER: Thank you. Meghan Shannon. MS. SHANNON: I am going to read just briefly a little bit of what I had said at NIH at Women of Health June of '91, and then I'm going to read a little bit of what a woman from Indianapolis, an RN who is not practicing right now, has given me permission to read, part of her letter that she wrote me after part of my statement was published in "Cactus." I got many letters from healthcare workers, mostly RNs. I am a former healthcare worker. I was a respiratory therapist, not an RN. I speak for all healthcare workers, paramedics, anybody who is in the hospital, medical transcribers, nurses as well. My experience is exactly what Marya said. I went to NIH for the Women of Health thing, and I really did another red-eye thing. I heard about it like two weeks in advance, got a really good rate to get there. I got there, flew in after traveling all night long. I spoke and then went directly home and collapsed. And I was very disappointed to find out that, indeed, they went back and they didn't give a damn what I said. All they said about RNs and healthcare workers was hepatitis and TB, or maybe they even just said TB. I don't know. so I'm a little leery of it too, Marya. I also would like to say that something that needs to be done -- in Omaha, Nebraska, the university there, they take the blood work of most people in contact in labs and healthcare workers and they freeze it. And then if someone becomes ill, they take their blood then and then they compare. And if they got it on the job -- that makes sense. We need to be doing that. I don't mean we need to be screening for HIV. I really mean we need to be putting this blood away somewhere so that when someone gets ill, then when the RNs come forward, I come forward, I say I got sick working on the job, it can be proven. I can prove it, and I will give you all copies of when the outbreak of the adenovirus from Children's Hospital in San Diego hit in 1980. I did not get sick until 1983, the third outbreak. It came in the fall every time. And I will hand this to you. I will also give you a copy of the statement in the "Clinical Microbiology Newsletter." They only talked about the children that were involved. Four children died in 1980 and 1981. They never talked about the staff. I will also hand you a copy of my statement from NIH, since I didn't have much time to prepare here. But I did want to say briefly this is what I said. There is a growing problem in protecting healthcare workers, especially when it comes to women. This is especially true of women coming complaining about fatigue, aches and pains and depression, and there are no known or revealed tests. Research is desperately needed in women's health. I wrote this for Women and Health. Women are dying, not only physically but emotionally and financially and socially as well. And heart disease is part of it. That needs to be included, very desperately, heart disease. Mitral valve prolapse is very well prevalent in women, and I believe that is partly what is going on with Chronic Fatigue Syndrome. At least, it is with me. Suicide is very high on the list because we are not being heard. That's not been talked about. know it's a very sensitive subject, but I believe it needs to be brought up. I also worked the hot line in San Diego, the one and only paid professional. Six to seven times more women attempt suicide. Men are more successful, but why are we attempting suicide? It's because we are ill. My view is that there is an epidemic going on here. I want to read part of what was responded by Gail Darwin, an RN who lives in Indianapolis now. She was a very successful RN in Long Beach when she became ill. She said: "I worked in Women's Surgery Department at Long Beach Memorial Medial Center. I became ill with a bad case of the flu in June of 1988, which I never recovered. I worked off and on until the end of December until I could push myself no longer. I always had a gut feeling I got this from my employment, especially from a couple of patients I remember who had the six-week flu. These patients were in surgery to determine what was causing their lower abdominal pain. As I found out later, this is a symptom of CFS. "Of course, I was around every conceivable bodily fluid all day, not to mention the now controversial side effects of laser plume smoke generated by laser patients with cancers and herpesviruses still being discovered. We had oncology patients and OB patients who were I.V. drug abusers who were brought straight to the OR for emergency C sections --" she was an OB nurse "-- who were brought straight there and barely their name was on the chart. Of course, it is anyone's guess how many HIV patients we had, since it is rarely known even today. So the possibilities are endless." And then she says: "I am amazed how many medical health professionals have this illness and why it isn't known. Why is it? Is it because most of us are too ill to barely get through the day or because the hospitals are keeping it under wraps or because most of us are female or because of labels this illness has unjustly produced -- the name needs to be changed -- without proof and with the excuse links to mental illness that makes us so embarrassed and guilty because we are indeed very ill? Or is it the noncaring attitude society in general has adopted for its moral fiber? I think it's a combination of them all. I have lost my job, career, my California home, friends, et cetera." Social Security is giving her a hard time. She goes on. I have other letters that I'll submit from several other nurses. I believe that this is a big problem in the healthcare profession. And if the administration, Clinton administration, is looking to change healthcare benefits and stuff, if there are no front-line healthcare workers to take care of you, we have a problem. So I thank you for letting me speak. DR. ESBER: We've had another two request. One is Estelle Ford Williamson. MS. WILLIAMSON: I'm Estelle Ford Williamson. I'm a CFS survivor, patient, whatever you want to call them. I've had the illness for six and a half years. I live here in Atlanta in the small town of Avondale Estates, very close by. I feel very fortunate being able to address this group, the high level of group that it is in terms of your responsibilities and what you are doing in this field, and so I appreciate it very much. "You were so active. You never just everywhere. If I needed anything, you'd get if for me. you were a great personnel director." This interchange occurred over the phone last week when I encountered another person who hadn't heard of my continuing battle with Chronic Fatigue. She had heard about by resigning my position six and a half years ago for medical reasons, but I hadn't surfaced in all those six and a half years so she hadn't had a chance to catch up and find out what a recluse I had been for all that time. She was the branch manager for a bank here in Atlanta. I was the personnel and training director. Previous to that, I trained managers and supervisors in 16 states in communication skills, management training, leadership skills, and I worked with corporations like Coca-Cola, Cox Cable Communications, Denney's Corporation -- I was on their headquarters training staff in California for a short time. So all around, I was a very highly functioning person, as they call it. I had gotten a working scholarship through St. Mary's College at Notre Dame, Indiana. I earned a master's degree in psychology at West Georgia College here in Carrollton. In April 1987 I came down with a flu-like illness that so disabled me I couldn't complete the series of tests my doctor was trying to give me that day. I returned a second day, completed the tests, and a month later, with everything else ruled out, he said that he thought it must be Epstein-Barr virus. He could not decide it was anything else. My IGG levels were elevated. They continued to be elevated for a while and then they went down. At that time, I had a fever. I hadn't had any since, but I still had the debilitating fatigue. Allergic headaches have come and gone. Allergies in general have gotten worse. But what really hasn't changed is that my cognitive functioning has deteriorated so much that I can't even stand at a flip chart and give you a lecture like I used to. I didn't even do lectures. I did more participative training. Sequencing difficulties made me lose my confidence in my ability to reason. Memory loss made my previous occupation impossible because it was hard to lead a class if I couldn't remember what I was going to tell them. Discalculia made it difficult for me to keep my finances straight. And that's essential to anyone in business. Even today it takes me a long time to figure out my checkbook. But the overriding symptom is that fatigue -- debilitating. It was so bad I had to resign that position as personnel and training director and then sleep for two months. That's all I could do. Gradually, with the high-functioning capability that I'd had before, it kept gnawing on me so much that I was able to find a new profession helping advise people on careers. I worked fairly effectively and I got people referred to me because of that previous eight years of experience. So I'm able to see maybe two or three clients a week. And that has kept me going, and I hope I will continue to be able to do that. That is one area where I feel like I've gotten better. I've had less worse symptoms as a result. Why am I here today? My daughter contracted mono about two years ago and has never recovered enough to be fully functioning. She is a 20-year-old student at American University in Washington. She has been unable to take advantage of all the advantages that that school has to offer her. And, believe me, her father is very conscious of this since he pays the heavy tuition every year. Last night she asked me on the phone, "Do people get over this?" Her teachers and administrators tell her that people get this and then they get over it. She is experiencing the same cognitive dissonance that occurred when her first symptoms were diagnosed as depression. The only infectious disease specialist that her father's HMO allowed her to see refused to give her any Epstein-Barr titer tests or anything because she had gained weight and his opinion was that Chronic Fatigue patients lose weight. So he refused to give her any test that would help confirm a diagnosis of anything other than his analysis of depression. Finally, I was able to bring her to Atlanta and to get her seen independently, and she did receive an Epstein-Barr test. And nine months after the onset of the mono, they did confirm that her IGG was elevated and she did receive a diagnosis of Chronic Fatigue Syndrome. I have to bring her from Washington to Atlanta to see doctors because I'm so concerned about how to get her treated effectively without her having to spend time traveling around seeing doctors. So Noelle doesn't know how long she'll have this, and I have heard through conversation with NIH a couple years ago that people who are 18 to 35 have a spontaneous remission rate of about an average of every two years. I don't know if that's still true or not, but that was one study that was quoted to me a couple years ago. I shared that information with Noelle, but I don't know what will happen if she doesn't recover by Christmas, which will be the two-year anniversary. Basically i just beg you to keep looking for the physical markers. I've had my insurance company challenge me for six and a half years about this illness. And, finally, out of physical weakness I finally settled with them and I've basically halved my income because I cannot continue to be answering all their questions because there are no physical markers for this disease. So I just ask you to keep working; keep in mind my daughter, as I do; and keep on doing the things that you are doing. But please try to do it more effectively, more efficiently, so people know what you are doing. If NIH is doing all that they are doing, please, where can we read about it regularly and knowledgeably? How can the doctors on the line know that information? So I thank you for your participation and hope that this will inform some of what you do. DR. ESBER: Thank you very much. Wilhelmina Jenkins I understand is back, but, on the other hand, someone spoke for you. MS. JENKINS: I just have a short thing to say. DR. ESBER: Okay, because we did want to try to stay for a few minutes for questions. MS. JENKINS: Before the meeting closes, I just wanted to ask the panel once again to reach out to a larger community in its examination of those who have Chronic Fatigue Syndrome. I hear that once again the 97 percent white number came up today. This is a number that comes out of the study, not a number that comes out of reality. I have been deeply disturbed because in a city like Atlanta where I live, where there are many black professionals in the teaching filed, where we all know Chronic Fatigue Syndrome is rampant, in the healthcare field and in the airline industry, there are a great number of black people in the city of Atlanta suffering from Chronic Fatigue Syndrome who have not been identified. The way to reach this population is by reaching out to their doctors. Every medical person in this room knows there has historically been a great deal of separation between the black medical community and the white medical community. It's historical. It has not been overcome yet. Here in Atlanta, Morehouse Medical School has a great deal of outreach to the community. NIH is near Howard University Medical School in D.C. Both of these populations are overloaded with black people who are suffering from Chronic Fatigue Syndrome. Those of you from the west coast are aware that there must be many Asians and Hispanics who are not being reached by the information concerning Chronic Fatigue Syndrome. With a serious outreach effort, I think the numbers and distribution of the population with CFS will become much clearer, but it does take an effort. I'm sure if you reach out to the medical schools, to the minority medical communities, they will respond. But they must understand this is a serious illness. It's taking away people who are highly trained from minority communities who cannot afford to lose them. Please make the effort and reach out a little bit harder. Thank you. DR. ESBER: Thank you, and thank you also for being brief. We did have one written comment -- I'd like to just summarize it -- from Judy Basso from the Chronic Fatigue Syndrome Association of Minnesota, who is encouraging research in several areas, the first to address and intriguing question based on a small group of patients who recovered significantly after several years of severe illness; the second, to look more closely at the subcategory of patients with well- documented, acute infectious mono as the trigger to the Chronic Fatigue Syndrome; and, lastly, to urge study in the quality-of-life and support services. Copies of these will be provided to each of the committee members. At this point we have about 14 minutes until 3:00 left for questions. I do appreciated that there were a number of people who wanted to ask questions earlier. And each of the committee has agreed to stay to hear your questions. So please go ahead. MS. KENNEY: Kim Kenney, CFIDS Association of America. Dr. Reeves, this year we spent, the association spent considerable time, money and effort getting the Appropriations Committee for the Senate to appropriate $2 million in earmarked funds for the CDC. Can you tell me how that money might be used and what the priorities for research are for that new money that will be coming into your agency? DR. REEVES: We don't have it yet. That would be my answer to that. You saw the program that we are doing. We would continue in the areas we are working on. But what you saw that I presented is how we use any money that we have. Until we actually have money, I really can't deal in that speculation. Presumably we will continue in the areas we are continuing in. We will have the priorities and be able to extend those priorities that we are already working on and make them better. MS. KENNEY: Are there any new program initiatives that you might start when new money is made available? DR. REEVES: Again, I summarized some of those in my talk, for example -- and this wouldn't be new monies -- the program that we are doing with the group in San Francisco. The cross-sectional studies that we want to do in Wichita is an area that we would certainly do given money that we have. If we get money, additional cross-sectional studies, trying to get more, better data on the prevalence is a very high priority of ours, and that will take considerable money to do. MS. KENNEY: Can you tell me what the process is for reporting cluster outbreaks to the CDC? DR. REEVES: We receive reports of cluster outbreaks generally from physicians who find out about this from state health departments, state health officers, organizations such as your own that feel they have an outbreak. We've had several of those from within the Georgia area, for example. Basically someone who feels that they have information on an outbreak need only phone CDC to talk to us about it, and we'll investigate it to the extent that we are able. MR. KENNEY: To whom should those reports be directed? DR. REEVES: They should be directed to me. DR. ESBER: Any other questions? DR. REEVES: Let me just clarify one thing with regard to outbreaks. Again, it is a bureaucratic thing. We are a federal organization. in order to investigate an outbreak, for example, the two that I presented, we must be invited by the state government to do so. And that's the way we investigated the two that we have done. That's as far as investigating outbreaks. We can also collaborate with groups that do that sort of thing to lend our methodology or expertise to their own investigations, and we've done that on occasions also. MS. KENNEY: Dr. Murphy, is there a team at FDA working specifically in Chronic Fatigue Syndrome? You talked in your presentation about teams. DR. MURPHY: I wish we had such manpower. What we have is product related. But to be able to work with a product, we obviously have to become very familiar with the disease or the infection, hypertension if it were an antihypertensive drug, and the literature in the field. so when a product comes in, a team is assigned to that product, so those people I was listing are assigned to that product. We have identified, as I indicated, not only that team but other people within the agency who also have agreed to work with us, because, as is clear, we can't work just with the product and deny that it's associated with a disease. So they are also there to answer questions about Chronic Fatigue Syndrome. It may be, as Dr. Esber was pointing out earlier, it may be if a product came in that was a biologic for the therapy of Chronic Fatigue, it would go to the Center for Biologics. But if it is right now anywhere in the realm of a drug or therapeutic that is not clearly somewhere else, it would come to us. MS. KENNEY: What can you tell us -- and this is probably a complex question but as simply as you can -- what would be done if a manufacturer who has pursued a promising or potentially promising drug for an illness decides not to continue the pursuit of that drug for business-related reasons? Is there some way that FDA of the government can take over that drug if it's dropped by the manufacturer? DR. MURPHY: I'm glad you asked that question, because that's one of the things I was trying to relay, in that our mandate is to assure the safety and efficacy of products. We can connect producers and patients who are afflicted. We cannot provide product. We cannot produce product. And we cannot make people make a product. We can only encourage. This is the division that also handles AIDS and therapies for HIV. I'm also a pediatrician and I'm also a woman, and I know that there are ways that we can encourage companies to look at certain things. And we do work with them in trying to get them to look at children in some situations, analyze data on women, to make sure that we get a study done. But we can't make them do anything as far as producing a product if they don't want to. DR. ESPER: I just might add onto that that there are some incentives that Congress and the government have put forth that would try to accommodate this. One is the Orphan Drug Act of 1986. In that case the agency would try to support by a number of incentives a sponsor who might be willing to take on the orphan product and develop it. But in the absence of that, I would agree with Dr. Murphy. There is very little we really can do in terms of authority. There is a lot we do behind the scenes in working with people and encouraging them. Okay. We probably need to turn to some of the other questions. Why don't we take one more from the floor, and then I have some leftovers from this morning. MR. LANDAU: Robert Landau, New Jersey Chronic Fatigue Syndrome Association. I'd like to direct another question to Mr. Eigen from the Social Security Administration. Has anything actually changed in how SSA is dealing with Chronic Fatigue Syndrome applicants? I should say applicants for disability due to Chronic Fatigue Syndrome. It doesn't sound like there has actually been any change. MR. EIGEN: Well, it's hard to say because of the coding problem I told you about. our informal reviews of cases have shown some improvements. As I told you this morning, one of the things we did notice was that the people who develop the cases, who obtain the evidence to do the cases, could have been doing a better job in some cases. And for that reason, we issued that Disability Digest reminding everybody that they should be more diligent in obtaining evidence. Until we know more about whether there are any patterns, other than that, there isn't much else we would know what to do other that -- I wrote down and I really like the suggestion of putting out public information, especially for the physicians. That's a starred one that I'll definitely bring back to my bosses. That sounds like a really good idea. But I can't tell you for a fact that there has been an improvement, only that we noticed a problem and we tried to fix it. MR. LANDAU: One other thing we've noticed in New Jersey is that there has been a tremendous variation from one center to another. In other words, when people go in to put in their applications to the Social Security Administration, from one jurisdiction to another within New Jersey there has been tremendous variation. It seems very inconsistent and almost haphazard. Some people with what would appear to be milder cases seem to go through the process and are accepted on the first application. Others who seem to have much more profound and severe problems sometimes go on for two or three years. And we haven't really found too much of a rhyme or reason for the inconsistencies. MR. EIGEN: Did you keep track of any of those cases? MR. LANDAU: I have some informal information at home. MR. EIGEN: Could you send it to me? I'll give you my address afterwards. Or give it to me or send it to me. Because that is something we are always interested in. That happens not just in these kinds of case but in all kinds of cases, and we are always interested in those kinds of inconsistencies. MR. LANDAU: Okay. Thank you. I'll do so. DR. ESBER: Maybe I could add a couple of questions to you. One is: "Almost everyone I've talk to or heard about says that they automatically are denied twice. When they pay an ex-Social Security Administration attorney, they get approved. Why?" MR. EIGEN: Before I answer the why question, I don't necessarily agree with the statement, of course. I will say candidly that -- first, let me say this: As a matter of fact, many people with Chronic Fatigue Syndrome are allowed at the first step. For those of you who don't know about the steps, we basically have three steps in our review process. Technically, there are four, but one is a review of the judge's decision. A person applies and gets an initial decision, which if they are dissatisfied with, they can ask for -- and that decision is make by an agency of the state. The state does this for us. We fund the state. When they are denied or otherwise dissatisfied with their decision, they can ask for what's called a reconsideration, which is also done by the state although by different people in the state. That's the step at which we get the most complaints. That's the step at which people tend not to have their decisions changed as much as people would like. But at the first step many people are allowed. In fact, not only for Chronic Fatigue Syndrome by for all impairments, most people who are found disabled are found disabled at the first step. Moreover, and this is also only informal, our informal nonstatistical reviews seem to indicate that -- I mean, nonvalid statistical reviews -- seem to indicate that as a group people with Chronic Fatigue Syndrome have their cases allowed at the reconsideration level at a higher rate than people with other impairments. It's something along the range of 23 or 24 percent of the people at the reconsideration stage win their cases if the have Chronic Fatigue Syndrome; whereas, the average claimant, it's about 17 percent, somewhere in that area. Nevertheless, it is true that many people win their cases at the hearing level, and we don't know why except for -- when I told you earlier that we were going to do more studies, that's one of the things we know we have to look at. We have to see why it is that many people do get allowed at the administrative law judge hearing level rather that earlier on. Because we would always rather have it be earlier on. That's about all I can say, though. DR. SCHLUEDERBERG: I might add that the law journal for the judges did come to us and ask for an article on the topic, which they published in September, I think, of last year. MR. EIGEN: Well, if it's what I think it is, it's the OHA, which stands for Office of Hearings and Appeals. The "Law Reporter" is the journal of the administrative law judges. One last thing I can add to that is it also turns out that as a group, if you count all of the levels of appeal, which is not to justify this, I admit, Chronic Fatigue Syndrome cases are allowed at a higher percentage that the average disability case. If you take them all as an average, it's about five percent higher in allowances. This still doesn't -- I understand the point, but -- DR. ESBER: Just a quick factual question again to you: "What step of the sequential evaluation does the physical examination fall under?" MR. EIGEN: Somebody asked me this at break. DR. ESBER: Well, maybe it's addressed then. MR. EIGEN: It's a good thing to point out. It happens at every step, unless the person is working. There is not a step at which the examination takes place. When we purchase an examination, which was specifically what the question was about, it means that whoever is doing the case, whoever the adjudicator is, believes that we need more evidence. And that could happen at any step, when we are trying to decide whether there are significant functional limitations or if the impairment meets or equals the listings or to do a residual functional capacity assessment. So it could happen at any time. MS. SMITH: Is that more evidence to approve someone or turn someone down? MR. EIGEN: Our rules specify that we should only purchase consultative examinations if we feel we can't make a decision either way. In fact, little by little we'll be writing into the regulations reminding people that if it's possible to allow a case, if there is sufficient evidence to allow a case, there is not need to go out and buy more evidence. DR. ESBER: Okay. One last question and then we need to adjourn. MR. KENNEY: (Inaudible comment.) DR. ESBER: Okay. Two questions and then we will adjourn. Try to make them brief. MS. KENNEY: This is for Mr. Eigen also. Bob Landau says that there are episodic success levels around the country. Is it helpful for support groups to educate the people who process the claims about Chronic Fatigue Syndrome and what things are most disabling about the disease, so that when it comes through, it can go through at the lowest level and save the taxpayers dollars and people get their benefits sooner? MR. EIGEN: Absolutely. I have nothing to add to that. Absolutely, it's helpful. If they are willing to listen to you, absolutely. MS. SHANNON: Actually, I had two very brief. They are not hard. Dr. Reeves, how do we get past the government, like, say, hospitals that are keeping it under wraps, when it is clear that it has been a cluster outbreak? That's what the problem is with the nurses right now, and we can't get to the government to get to you to come out and investigate. DR. REEVES: Fortunately or unfortunately, your federal government cannot just go in and investigate what we may or may not wish to investigate. It's important, if you think or somebody thinks that there is an outbreak, that it be reported. But we cannot just go in essentially on our own or an individual's volition to study that sort of thing. We need to have the information. If the information is reported to us, we will deal with the information the best we can. I think everybody is interested in that sort of thing. I think that I have seen very few instances, in fact, I, myself, have seen none in which an outbreak or problem like that is in fact kept under wraps intentionally. it's quit frequently a level of misunderstanding on one side or another. But if it is reported to us, we will look into that sort of thing to the best extent that we are able. MS. SHANNON: I know in Orange County the medical hospital there had five nurses go out. I know in Long Beach there was an outbreak. Mine was highly publicized in which I'm giving you the stuff, only that was by accident. When it went through the third time, they did not talk about the workers who were ill. They only talked about the children who were ill. SSI, when you get the medical benefits -- and I don't know if you can answer this -- but the medicines that are involved, are you involved in what kind of medicine is -- MR. EIGEN: No, we don't have anything to do with that. Medicaid comes along with SSI, but we don't administer that. MS. SHANNON: Does FDA take care of that? Who takes care of -- DR. MURPHY: Are you taking about an approved therapy? The FDA is in the business of evaluating new therapies. MS. SHANNON: I mean for the insurance people, people on MediCal and SSI. They are very limited medicines and they are the medicines that don't work. DR. MURPHY: The only way FDA gets involved in it is that some companies will not pay for something if there is not an indication on the label. MS. SHANNON: Okay. My last question to NIH, FDA and CDC: What will it take to recognize some of the -- I know this is not going to be easy to hear -- but the vitamins that are highly successful in England and Canada and throughout the world, B-12, B-complex shots? DR. MURPHY: That's easy. A well- controlled randomized study that proves it, studies that prove it. MS. SHANNON: I think they are out there in the world. DR. MURPHY: The data has to be submitted. MS. SHANNON: Okay. Thank you. DR. ESBER: I'm sorry. We really do need to finish. Some of us have airplanes to get. At this point, I'd like to give the committee on opportunity if they'd like to make any final comments. Dr. Schluederberg, and comments? DR. SCHLUEDERBERG: I would just like to say I'm heartened by this effort, which I think has been very effective on both sides, trying to communicate what our problems are and what our needs are and how we can work together. DR. ESBER: Thank you. Mr. Eigen. MR. EIGEN: I learned a great deal these last two days. For what it's worth, I believe you all. I think you have something, and I'm taking that back with me. I think you gave us some really good ideas for interfacing with not only you guys but with the medical community, which I think will make a big difference, or I hope it will make a big difference anyway. But I hope something will come out of this, based on what I've seen. DR.ESBER: Thank you. Dr. Murphy. DR. MURPHY: I just want to repeat what I said earlier, that, obviously, we know we have something real here we are dealing with. And we tolerate zero toleration of false hopes. If somebody tells you they have something that works, as I was discussing at lunch, you either fish or cut bait. You either believe in it enough to pursue it in the proper way, to assess that with randomized controlled studies and let's find out. Don't lead people down a path of what you think works. Prove it. And thank you for being here today. DR. ESBER: Thank you. Dr. Reeves. DR. REEVES: I have no additional comments. DR. ESBER: Dr. Mahy. DR. MAHY: I'd like to thank you on behalf of the CDC for coming here and interacting with us on this very difficult problem that we are all trying to solve. I think the panel which is meeting is going to come up with some useful findings on the case definition, which was the main purpose of yesterday's meeting. And these interactions, opportunities to meet with support groups with the interagency committee, I think will continue on an annual basis in the future. So we look forward to seeing some of you again. Thank you very much. DR. ESBER: Let me also just add in both my role as a representative of FDA as well as speaking on behalf of Dr. Phil Lee that we appreciate very much the time you've taken today, your planning and your presentation, and the fact that you haven't objected to my keeping us on a timetable. Thank you also to the committee and the members who took their time to present and fly here today. With this, we'll adjourn. I would just like to reiterate that Dr. Lee intends to schedule a meeting sometime in the near future. To my knowledge, a date hasn't been set, but I will be in Washington. Again, we'd just like to make sure, if you are interested in attending, that we have your name and address so we somehow don't overlook you. Thank you all very much. 160