Philip Baker: My name is Philip Baker and I am the Executive Director of the American Lyme Disease Foundation. Before I accepted that position I served as Program Officer for the National Institute of Allergy and Infectious Diseases, Lyme disease basic research program until my retirement in October 2007. During that time I managed three of the four NIH sponsored clinical trials on the efficacy and safety of extended antibiotics therapy for the treatment of chronic Lyme disease. Because of my experience in that regard, my presentation will focus on the published results of those studies as they relate to the IDSA Guidelines and the treatment of Lyme disease. It should be noted that a fourth NIH support trial was funded by the National Institute of Neurological Diseases and Stroke and since that study was done by another institute, I was not involved in the management of that study. Before I precede any further it’s important to make a distinction between two entities, namely Lyme disease and a condition commonly referred to as "chronic Lyme disease". These terms are often used interchangeably by some who don’t know any better as well as by some people who should know better, and this has generated a great deal of confusion and misleading information.

to implement such therapy. They believe that it is unjustified and harmful. And that is where the controversy stands today.

A major criticism raised by those who oppose the IDSA guidelines is that they fail to provide evidence to support legitimate opposing views, namely, that extended antibiotic therapy is beneficial for the treatment of chronic Lyme disease. That is not an oversight. The simple fact of the matter is that there is no published evidence, derived from a well designed placebo control trial, to show that such therapy is both beneficial and safe. If that were the case, there would be no controversy and we would not be here today discussing this matter. The IDSA guidelines are correct in stating the chronic Lyme disease remains to be defined as a distinct clinical entity so that it can be distinguished from other non infectious conditions such as fibromyalgia and chronic fatigue syndrome. In the absence of a precise definition of chronic Lyme disease, many investigators have used the term "post treatment Lyme disease syndrome" to describe this condition. In so doing, no assumptions are made with respect to the mechanisms or the ideological agent involved. Even when the use of such an unbiased and nonjudgmental term, even the use of such a nonjudgmental term is enough to enrage those who are absolutely convinced that chronic Lyme disease is due to a persistent infection by Borrelia or some other co-infecting pathogen, although, once again, there is no clinical evidence to support such a view. As you can imagine, the lack of a precise definition of chronic Lyme disease was a major challenge in ensuring that appropriate patients were enrolled in the NIH-supported clinical trials. To address this issue, the enrollment criteria stipulated that the medical record of each enrolled patient, must show that at sometime in the past they were correctly diagnosed as having had early acute Lyme disease, given an adequate and standard course antibiotic therapy that resulted in the cure of their initial symptoms, and then returned to their physicians several months or later with symptoms generally described to chronic Lyme disease. Although thousands of patients were screened for enrollment in these trials, only a small percentage --about one to eight percent-- was enrolled. The main reason why so many were excluded was the failure of their medical records to document that they once had an initial episode of correctly diagnosed Lyme disease. This made good sense. How could one have chronic Lyme disease without having a correctly diagnosed episode of Lyme disease in the first place? Admittedly, many patients who might have had "chronic Lyme disease" were not enrolled in the trials. However, those who were

These clinical trials provided additional insights on the nature of this condition. First a placebo affect as high as thirty six percent was noted in the largest study conducted. In another placebo control clinical trial involving patients with mild to moderate arthritis, an improved clinic response after forty eight weeks of treatment with placebo was noted in thirty nine to forty one percent of patients. This means that it is impossible to claim that extended antibiotic therapy is beneficial and safe, without conducting a well designed placebo controlled study using adequate numbers of patients.

Second, the baseline SF-36 values for the largest of these studies showed that some, but not all, of the enrolled patients had significant deficits, with respect to their physical health status. Some experienced a level of pain comparable to that noted for heart failure or osteoarthritis. Although this may not be a general finding, it suggests that other treatment options should be explored to provide relief to such patients. I think this is where we can reach common ground, in this area.

However, in other cases, symptomatic treatment maybe required to provide relief until the healing process is complete. Recent studies published after the IDSA guidelines were released showed that treatment with Gabapentin, a drug often used to eliminate the neuropathic pain associated with advanced diabetes, alleviated the pain of chronic Lyme disease in nine of ten patients. Although this approach requires more study, the FDA has approved the use of Lyrica which is a drug closely related to Gabapentin for the treatment of fibromyalgia, a condition of unknown causes with symptoms similar to those of chronic Lyme disease.

In closing, I would like to note that the alleged conflict of interest charges that precipitated this review of the IDSA guidelines are reminiscent of similar charges that were made -about nine years ago by various Lyme disease activist groups against the NIH, the FDA, and the CDC. These alleged charges included scientific bias in the interpretation of research data, conflicts of interest with respect to the development and use of diagnostic tests, vaccines and therapeutic regimens, retaliation by employees in the government agencies against others with different points of view, and favoritism in the award of NIH research grants and contracts as well as in the review of scientific publication. After an extensive examination of all of these claims, the General Accounting Office reported that they were false and without foundation. Here we have two similar situations in which the results of government-sponsored and rigorously peer viewed research are being discredited and the integrity of outstanding scientists questioned simply because the results obtained conflict with the unproven views of strident minority.

The controversy associated with chronic Lyme disease is not going to be resolved by debate or prolonged discussion, however eloquent the words and language might be. It is only going to be resolved by doing the hard work needed to obtain evidence required to prove one’s case. To date, the published results of no less than four peer viewed randomized placebo control clinical trials have shown that extended antibiotic therapy is not beneficial for the treatment of chronic Lyme disease. If those who disagree with these findings believe that these studies were flawed and that such treatment is beneficial and safe, it is incumbent upon them to design and conduct a randomized placebo control trial --one that will withstand the rigorous test of peer review-- to demonstrate efficacy and safety. If that can be done I am certain that the results would be accepted by the medical and scientific community and this controversy would come to an end. Until that is done, the current IDSA guidelines for the treatment of Lyme disease, with its more than four hundred peer reviewed reference citations, should be considered the best available and most comprehensive resource on the diagnosis and treatment of Lyme disease extant.

Dr. Carol Baker: Thank you Dr. Baker. Questions for Dr. Baker? Yes, Dr. Moro

Dr. Moro: Dr. Baker thank you for your presentation. I have a couple of questions. Could you clarify the criteria that was used to enroll patients for these clinical trials? I think you mentioned that, they had to have, for example, they had to have diagnosis of Lyme disease.

Philip Baker: It has to be correctly diagnosed.

Dr. Moro: By?

Philip Baker: CDC standards

Dr. Moro: CDC standards, so that means, could you repeat what are the standards?

Philip Baker: Well that would be an erythmia migrans rash of a certain diameter and if that’s not available, ’cause not everybody gets the EM rash then you had to have serological evidence by the two-tiered testing procedure. And that had to be in the medical records. In most cases, there was nothing like this in patients records, so you didn’t know if they every had lyme disease or not and so we were reluctant to enroll them in a study because we wanted to be sure that we had the typical group of patients that were likely to have chronic Lyme disease.

Dr.Moro: One more thing, I think maybe you mentioned that, but I missed it, were those individuals also tested for other co-infections - Babesia or Ehrlichia?

Philip Baker: Yes.

Dr. Duray: Okay thank you.

Philip Baker: We looked for babesia, Powassan virus, I believe, I don’t think we looked for Ehrlichia, but Babesia was one.

Dr. Carol Baker: Other questions? Yes, Dr. Medoff?

Dr. Medoff: I was struck by your statement and it bears repeating that you said that those patients that were not included in the study there may have been some number of them that did have chronic lyme.

Philip Baker: Well you never - because the definition is so – you know we don’t have a precise definition of chronic Lyme disease, so you can never be sure whether you can never be a hundred percent sure whether you were, even the patients you enrolled had Lyme disease, but based on our criteria we felt that gave us a reasonable probability of including the right people.

Dr. Medoff: So you think the conclusions that you reached from the patients with strict criteria are applicable to those patients who were not serodiagnostic or with their -.

Philip Baker: Well I think under the circumstances we captured the right people to be enrolled in the study. That’s what I mean - the best evidence that we could get being, however, correctly diagnosed as having Lyme disease to begin with, because how can you have a chronic disease if you weren’t diagnosed correctly. Apparently cured by the standard therapy and then they came back with these symptoms. So under the circumstances, that’s the best we could do. There’s no other . . .

Dr. Medoff: I have one more question are you aware of any effort on the part of those people who believe in the existence of chronic Lyme to get NIH support or to apply for support for a clinical study based on what their definitions would be.

Philip Baker: Well, many, a lot of people have applied for, clinical trials, you know, to do clinical trials on Lyme disease and clinical not all of them were successful. Some of them were.

Dr. Medoff: You mean in getting support.

Philip Baker: Getting support, yeah. When I first became Program Officer, some of these studies – the smaller ones - were funded by the grant mechanism, and then they decided that was not an adequate way of doing it because to do the type of monitoring that’s required for an appropriate

clinical study you have to do it on contract. So to do it on contract requires getting additional money from Congress to set aside for that, and that was an impediment for others to come on in and do it. It wasn’t as easy to do before. But we had grant applications for smaller studies that would come in periodically and these were reviewed by the standard peer review process. So there was no, but these were small studies, they had to be because of the limitations on the size of the grant. The study that the Klempner, the Klempner study was funded because we were mandated by Congress to spend X amount of money to do this study. So we had to do it. It was set aside funds.

Dr. Medoff: I just have one more question, what is your background in research.

Philip Baker: I’m a microbiologist by training.

Dr. Medoff: Microbiology.

Dr. Carol Baker: Dr. Charini.

Dr. Charini: Yeah, just one question. One of the criticisms of those four studies with regard to the benefit or lack thereof extended antibiotic therapy is that the studies were underpowered to detect the differences that they were looking for. How do you respond to that criticism?

Philip Baker: I don’t think that was the case, and certainly in the case of the Klempner studies which I was intimately associated with because that was . . .. Early in my career as a Program Officer, I became, I got involved in that study and I can tell you that it was one of the most carefully monitored study that anyone can ever imagine. We had at least four different statistical teams involved in that study from beginning through the study and towards the end and that was an issue that was very carefully evaluated and built into their procedure was an interim analysis at the point when we enrolled a hundred and twenty patients because we knew it was going to be difficult to recruit all of the patients that we wanted to get into these studies. Simply it was a very difficult process to do, as Brian Fallon can probably tell you. And the interim analysis was done by these four teams of biostatisticians, independently and they all arrived at the same conclusion,

that this study had proven its point. The results were not likely to change if we had completed the study to full enrollment and that we should stop recruiting more patients and publish the results. And that is what we did. It wasn’t stopped because it wasn’t working, it was stopped because the interim analysis showed that we got an answer.

Dr. Charini: Thank you.

Philip Baker: Conclusive answer.

Dr. Carol Baker: Dr. Lantos.

Dr. Lantos: It seems that an open question is are there some populations of patients with chronic symptoms who will benefit from prolonged antibiotics as opposed to the broader chronic Lyme disease group that was recruited for the trials. Because of their difficulty in enrolling patients in the 4 prospective trials, how would you change recruitment criteria to identify a small subpopulation that would benefit? Is that even possible do you think?

Philip Baker: I don’t know how that would be possible to do. I really don’t know. Somebody might have an answer but I don’t I think we did the best we could under the circumstances. This is kind of a murky diagnostic situation from the beginning. You know, what is chronic Lyme disease? People in this audience might disagree as to what it is.

Dr. Carol Baker: Thank you very much Dr. Baker.