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should go forth with any vaccines in an efficacy trial at this particular time, in this country or worldwide. The overwhelming recommendation of the group was to establish efficacy after a challenge in an animal model and before we went ahead and conducted a large scale efficacy trial on humans, and that is in fact what we are doing.
Certainly the MicroGeneSys product is one that is well on its way. It is proven to be safe, and it is proven to be immunogenic in that it induces both humoral and cellular immunity. That certainly would be one of the candidates that we would look very favorably upon when we get to the stage of looking at an efficacy trial in humans.
Senator HARKIN. My follow-up question on that was you are going to test this in animals first.
Dr. Fauci. Before we go, in this country, into an efficacy trial
Senator HARKIN. But I understand, if I'm not mistaken, that the AIDS vaccine has already been proven safe for humans. Is that right?
Dr. Fauci. It has been proven safe, yes, sir.
Senator HARKIN. Then why would you not go ahead and test this on humans rather than going—
Dr. Fauci. The reason for that is that it was the overwhelming recommendation of our committee that, given the limited target populations that you have in this country that you could use for a vaccine trial, it was important to determine efficacy in animals first. Although we know it is safe, there is no indication, given the complexity of the immune response to HIV, that it would be effective in humans.
The animal studies are not for safety. They are for giving the animal a vaccine and then challenging the animal with a live virus to prove that the particular candidate is effective. It has more to do with efficacy than it does with safety.
Senator HARKIN. I just have a hard time understanding. If it's safe, why not try the efficacy on humans? You are talking about people that have AIDS.
Dr. Fauci. Right.
Senator HARKIN. I went through this a year or two ago with a friend of mine who was dying of AIDS who is since deceased. He was willing to try anything. He didn't care. He knew he was dying. So, why not go ahead and try
Dr. Fauci. It is a different story when you are talking about prevention versus treatment. If you have someone who is already ill and is deteriorating, then the philosophical approach of trying something that might necessarily be a high risk is a different situation than consuming a population for immunization that you would want to save for something that has been shown experimentally to be effective. The overwhelming recommendation by our advisors is that you should not utilize populations in this country that could be candidates for a vaccine until you have an indication that the vaccine would be effective.
Now, the situation would likely be different because I know that MicroGeneSys is now negotiating with doing an efficacy trial in foreign countries in which the rate of new infection is extraordinary because those individuals would have such a high rate of infection,
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they could tell right away and very quickly whether it would be effective or not.
Senator HARKIN. Well, I don't know that I understand that completely.
I am told—and again, this is not of my own knowledge that almost all of the vaccines currently in use were not developed using animal models and that some vaccines which looked extremely promising in animals did not achieve significant results in humans.
Now you are saying that the animal tests should come before human efficacy tests even when the vaccine is proved to be safe. . Dr. Fauci. Mr. Chairman, there have been no vaccines to date that have been tested for efficacy. The information you are getting are situations in which a product was tested in an animal and shown to be safe and then gone on and done a phase I trial in humans to show if it is safe in humans. The recommendation of the groups that I am talking about has less to do with safety than it has to do with proving that it can work. There have been no
Senator HARKIN. I guess I just don't understand, if it is safe and you can get a control group who volunteer for efficacy tests, to see that it works, why you couldn't go ahead and do that rather than going through animals first. I can understand that in some cases, but in the AIDS situation, I have a hard time understanding.
Dr. Fauci. In order to prove efficacy in a population, you would have to have a population that has a reasonably high risk of getting infected because you will have to test the vaccine on individuals who are not yet infected. There should be no imminent danger to them of dying because they are not infected yet.
However, there are some populations in which there is a high rate of infection, and the recommendation is that you should use a vaccine in those populations only after you have shown that that vaccine can be effective in preventing an infection in an animal that has been challenged because otherwise you might vaccinate a high-risk population, and then you look around and you do not have any more populations to vaccinate because you have used up the high-risk populations in this country.
Senator HARKIN. I may have to get some more information on this.
Dr. Fauci. I would be happy to discuss that with you in more detail.
Senator HARKIN. I think I understand it. It's just my limited scientific knowledge is what is preventing me from fully comprehending it.
I recognize Senator Reid for any questions you may have.
Dr. Fauci, what type of research is being done to pursue the chronic fatigue syndrome?
Dr. Fauci. The research associated with the chronic fatigue syndrome is several-fold. One is looking at the epidemiology and natural history. As you are probably aware, this has been a very elusive disease in trying to determine what the criteria for diagnosis is. As we are learning more and more about that, there is research now into looking at the pathogenesis and at what are in fact the defects in individuals who have chronic fatigue syndrome. And that is moving along right now. In fact, we have issued a request for applica
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tions for cooperative groups to study chronic fatigue syndrome. It is really a question of getting the natural history down and then looking at the pathogenesis. And we have actually done some more surveillancing in association with the CDC and epidemiological studies.
Senator REID. Is the National Institute of Allergy and Infectious Diseases cooperating with CDC in this endeavor?
Dr. Fauci. Yes, sir, we are.
Senator REID. How many staff members at NIH, full or parttime, are working on this chronic fatigue syndrome?
Dr. Fauci. Well, we do not have individuals who specifically are involved in chronic fatigue syndrome. We have a Division of Microbiology and Infectious Disease with a large number of individuals. One of the areas that we are concerned with is chronic fatigue syndrome. We do not specifically assign an individual to chronic fatigue syndrome. We do in our intramural research program have one of the leading scientists in the world in chronic fatigue syndrome, Dr. Steven Strauss, who has been responsible for a number of very important studies over the last several years.
Senator REID. So, do you feel that enough attention is being focused on this disease? Within the limits of your budget I assume is what you are going to say.
Dr. Fauci. It is a frustrating situation, Senator, because since there is such a poor handle on just what this disease is. We would like to be able to do more, but before we can do that, we have to have something to grasp onto. And that is the reason why it is important to delineate, as best as possible, what the natural history is, what the criteria for making a diagnosis of this disease is, and then to determine alternative therapies to treat it. So, in a broad sense, I am not satisfied with the amount that we are doing because we have not yet reached that stage in understanding the disease to be able to apply specifically more effort into it.
Senator REID. As you are aware, in Douglas and Lyon Counties in Nevada there are large numbers of these cases that have been identified. And the University of Nevada Medical School has been doing research in this area for a number of years. Has the NIH used the benefit of the University of Nevada at Reno Medical School for the work that has been done?
Dr. Fauci. We recently issued a request for applications to establish chronic fatigue syndrome cooperative groups. Hopefully, the University of Nevada will submit a competitive application. Regarding the broader question of prevalence in Douglas and Lyon Counties, that is one of the areas that is being very closely looked at in the collaborative effort between the Centers for Disease Control and the NIH.
Senator REID. One reason I mention this is that there are hundreds and hundreds of samples of chronic fatigue syndrome patients whose blood has been stored at the University of Nevada at Reno. Are you aware of this?
FAUCI. Yes, sir; in fact, we did a significant large study at the NIH on those individuals looking at every available parameter that we have immunologically and otherwise, and we did not come up with any pattern at all that we could pursue. But that does not mean that we are not continuing to try and find inroads into the
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pathogenesis. If we knew what we were looking for, then getting those samples and going through them to try and identify some of the components of the pathogenesis would be a relatively easy task. The mystery is we do not know what we are looking for, so we just look for the parameters that are available to us right now, and so far they have come up short.
Senator REM. Has funding been a problem to study this disease?
Dr. FAUCI. Well, it has not been a problem. I wish we had more to be able to fund. We have put out a request for applications, and we look forward to the response for that request. If we get good requests, we would be happy to fund as much as the science allows.
Senator REID. Thank you, Mr. Chairman.
I thank this panel. I am going to follow up with you on this thing. I don't understand all that completely, but perhaps I can get into it and understand it a little bit better. Thank you all very much.
We will call our next panel up, if you don't mind, Dr. Raub.
I have to break in about 20 minutes. If we do not finish, we will pick it back up at 1:30.
Senator REID. Mr. Chairman.
Senator RED. I will come back whenever you say. I have some questions of Dr. Gorden on the next panel.
Senator HARKIN. He is on the next panel?
- QUESTIONS SUBMITTED BY THE SUBCOMMITTEE Senator HARKIN. Thank you very much. There will be some addi. tional questions which will be submitted for your response in the record.
[The following questions were not asked at the hearing, but were submitted to the Institute for response subsequent to the hearing:)
QUESTIONS SUBMITTED BY THE SUBCOMMITTEE
Question. The Committee has provided funding and encouragement for the development of a Children's Vaccine. This would be one vaccine which would cover seven or eight of the more common childhood vaccines all in one dose. How optimistic are you that such a vaccine can be developed in the relatively near future?
Answer. The World Health Organization and the United Nations Children's Emergency Fund articulated the goal of a single, oral, temperature-stable vaccine that would be effective against the major child-killing infections in the world and produce life-long immunity. While this type of vaccine remains an idealistic goal and a challenge to all who work in the field of vaccinology, practical and scientific considerations encouraged that the concept of a "Children's Vaccine". be recast into a "Children's Vaccine Initiative" (CVI). This initiative has as its goal the continued targeted improvement of childhood vaccines.
The CVI calls for expanding the front line of existing and emerging vaccine technology within a framework that is both feasible and achievable over the next 10 years. By accelerating the application of vaccine technology, CVI targets vaccines that will require fewer doses, can be given earlier in life, can be combined in novel ways, are more stable, and are effective against a variety of diseases. Each step will continue to facilitate improved immunization of high risk children in all countries.
PEDIATRIC CLINICAL TRIAL UNITS
Question. Last year the Conference Committee directed an increase for Pediatric Clinical Trial Units. I understand that with this additional funding 37 percent of all clinical trial funding will go to Pediatric Clinical Trial Units. This compares to approximately 1.5 percent of all the AIDS cases being children. Doctor, has funding been skewed too heavily towards the Pediatric Clinical Trial Units?
Answer. Basic research on pediatric AIDS continues to be a high priority and we will be placing more emphasis on this critical health problem. Our current research program focuses on efforts to define the means for early diagnosis, timing of transmission of the virus, pathogenic mechanisms involved in pediatric research, and the roles of immune response in protection or delay of clinical progression.
By way of background, the level of funding for pediatric AIDS clinical trials has increased markedly over the last several years in response to the changing demography of the disease. As a result of the increase in pediatric AIDS clinical trials, more treatment protocols are now being sponsored.
Despite this progress, the recent congressional earmark to double the amount of resources committed to pediatric AIDS clinical trials causes us some concern because of the vastly disproportionate level of effort that would exist between pediatric and adult clinical trials. Specifically, pediatric AIDS cases represent approximately 1.7 percent of all reported AIDS cases. Currently, 11.8 percent of