Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease, New England Journal of Medicine, 2001. 345(2):85-92.
Klempner, M. S., Hu, L. T., Evans, J., Schmid, C. H., Johnson, G. M., Trevino, R. P., Norton, D., Levy, L., Wall, D., McCall, J., Kosinski, M., Weinstein, A.
The NIH-funded Klempner study is often cited as important to our understanding of treatment for Lyme disease. At The Serano Group, we find the study interesting mostly because it shows how easy it is to conduct propaganda science and shows how readily scientists, journalists, and the public accept this uncritically.
While the study has been discussed often since its 2001 publication, its primary failure as a piece of research is rarely mentioned: the study measured hardly anything post-treatment. The Klempner study tested a single treatment for patients with persisting Lyme disease and was unable to discern anything. The only question that remains is how hard did they try?
Typically, research not demonstrating anything is hard to get published. But due to social and financial pressures to promote a distorted view of Lyme borreliosis, this study was rushed to press and continues to be cited as important evidence that persisting borreliosis does not exist and should not be treated. Of course, this violates a basic tenet of research. Science just does not work this way. You can do an experiment that indicates something exists because the thing studied seemed to cause an effect. But, you can’t claim something does not exist because you did an experiment and did not demonstrate anything. To have evidence something does not exist requires many experiments trying every possibility of showing the thing exists, making the most sensitive abailable measurements.
There are two possibilities for the Klempner study outcome: either the treatment tested does not do anything or Klempner did not have methodology sufficient to measure the difference. A third possibility is that he did measure differences and failed to disclose them.
We often use the Klempner study as a litmus test. Any individual or organization promoting it or citing it as evidence is suspect for bias. The study shows so little and tries so hard to see nothing that only extremists, academic sycophants, and the uninformed would find it meaningful.
To summarize: 64 subjects with symptoms indicating persisting Lyme disease were treated with two grams intravenous antibiotic ceftriaxone (Rocephin) daily for 30 days, followed by 200 mg daily oral doxycycline for 60 days. Another 65 subjects received a non-drug treatment looking like the real antibiotics, a placebo. Three months after treatment, subjects completed a check-the-box self-assessment of their general health, the standard SF-36 questionnaire. The SF-36 generates eight scores, 0-100, which Klempner does not report or analyze. Instead, he reduces the eight scores to two summary scores of physical and mental status. These scores were not reported either, but simply rated “Improved”, “Worse”, or “Unchanged”. Once each subject was reduced to this single rating for mental and physical health, statistical analysis was performed and the analysis found the treated group did not appear significantly different than the placebo group. (The study also stated subjects filled out a Fibromyalgia Impact Questionnaire, but did not present results.)
That, despite all the fine print, is all the Klempner study shows for evidence.
There were many other places where the cards were stacked. The study selected subjects who had already failed treatment similar to the one being tested. The treatment was light considering how sick the subjects were and then only 75% compliance was required. A negative change in mental score trumped a positive physical score change and vice versa. The limited number of 64 treated subjects was highly likely to miss anything less than a dramatic treatment effect. Many medical studies have thousands, if not tens of thousands subjects.
The study did present detailed data about objective measurements done before treatment, but if similar post-treatment measurements were made, they were not disclosed. If the subjects were evaluated by a nurse or doctor, this was not mentioned. If they were asked if their joints still hurt, if they still had headaches, or whether they could sleep at night, this was not disclosed. Instead, subjects filled out the general health questionnaire which specifically is NOT to be used to assess a medical condition. The SF-36 designers state never to use summary scores without disclosing the eight 0-100 scores. Even the summary scores were not analyzed--the subjects were scored the equivalent of a 1, 2, or 3. This is the sum total of post-treatment data Klempner disclosed.
Repeatedly, Lyme disease ideologues say the study showed that just as many symptoms improve on placebo as on treatment, yet no symptoms were measured nor were subjects even asked about them, except in a very general way. (You can look at the SF-36 here.)
This should give us all great pause. To state the obvious: it does not appear Klempner really wanted to see a difference between the treated and untreated. The paper looks like science, but there really is very little there. Why would the IDSA, AMA, NIH, and CDC use this study as a primary indication to not treat patients with persisting borreliosis?
The Infectious Disease Society of America lets a small number of radicals, including Mark S. Klempner, write its Lyme disease guidelines and then uncritically rubber stamps them, citing their 8000 members who are in support. Philip J. Baker, an extremist for the commercial view of Lyme disease, was Lyme disease program officer at the NIH during the Klempner study. Insurance companies regularly cite the Klempner study to justify not paying for treatment for Lyme disease.
In September 2002, Klempner was named an Associate Editor of The New England Journal of Medicine. Now, not only can he perform bad research but be allowed to censor good research.
In October 2003, the National Institutes of Health awarded Boston University Medical Center, where Mark S. Klempner was assistant provost for research, $128-million to build Biosafety Level 4 laboratories for the study of dangerous microbes. Klempner was the principal investigator receiving the grant.
This is not the way our government should do business. And, none of this has anything to do with providing rational health care for anyone.
(Full disclosure: one of the volunteers for The Serano Group, Inc. analyzed the Klempner study in their private consulting business. You can read that analysis here.)
We recently reviewed the NIH web pages on Lyme disease. While not as biased as the IDSA treatment guidelines, they still overstate much and spin the interpretation of clinical trials and other research questions.
Past Lyme disease program directors at the NIH have been so extreme in their positions that they have finally gotten the federal government’s equivalent of the boot, meaning you start getting a paycheck for doing nothing. The last holder of the post, Philip J. Baker, recently moved from his government job to executive director of the American Lyme Disease Foundation, a nonprofit dedicated to promoting commercial opinions on Lyme disease. He also just wrote a public relations piece promoting biased and unsubstantiated positions on Lyme disease. So just how were federal funds spent on Lyme research during his tenure?
We wish the new Lyme Borreliosis and Related Diseases Program Director, Joseph J. Breen, great success in increasing our understanding of borreliosis.
Those new to Lyme disease will need to cross a threshold of disbelief. A world where doctors willingly dismiss and mistreat the sick for their own convenience is not a pleasant or comfortable concept. The reality is that patients with a positive Lyme test are routinely denied standard medical care, even for health issues not related to Lyme disease. Doctors’ emotional responses to this disease dominate treatment and diagnosis so greatly that common standards of reason and decency are routinely violated. Patients and their families usually realize this only after one or more patient-doctor encounters that manifest this reality.
Borrelia infections attack the central and peripheral nervous systems and can cause extreme pain, loss of motor function, cognitive decline, and psychological problems—symptoms often associated with another spirochetal disease, syphilis. Endocrine and immune system dysfunction are also common. Blindness, disability, and death can result.
"Lyme disease" is something quite different than a Borrelia infection. It has become a construct of politics and emotions where self-appointed authorities and cooperating institutions try to dictate diagnosis and treatment of Borrelia infections to the medical community. No other disease, particularly among those as common as borreliosis, is treated so much as an ideological issue instead of a medical condition. The Centers for Disease Control collaborate with the Infectious Disease Society of America to violate basic tenets of modern medicine while claiming they adhere to supporting science. Rather than conduct meaningful research and learn from experience, ideologues force fit biological realities into their limited paradigm and reject and censor the preponderance of evidence. Guidelines and theories are manufactured and research manipulated for no purpose but to maintain status quo and commercial interests.
This situation did not develop overnight. When confronted with the reality of increasing prevalence, morbidity, and mortality of Borrelia infections in the 1980s, a small group of researchers, rather than search for effective methods of diagnosis and treatment, instead began a campaign to deny the prevalence and virulence of borreliosis. Their propensity to ignore and misstate basic realities of the infection is extreme. The persistence of these views demonstrates the inability of the scientific community to self-regulate. Particularly harmful is the general acceptance of these reactionary views by the majority of the medical community.
Science has played an embarrassingly small role in Lyme disease except as a tool for larger political and financial forces. Medical journals process Borrelia studies differently than any other research. Papers are published stating most positive Lyme disease test results are false and all negative test results true. DNA evidence, accepted as sufficient to justify capital punishment in the legal system, is regarded insufficient and unreliable for diagnosis of Lyme disease. When patients are given a rote treatment for Lyme disease and remain ill, guidelines state that the infection has been eliminated—because textbooks decree the treatment should always work—therefore, a new unidentifiable disease process has begun. Absurdities compound until new absurdities are not even noticed or debated.
Beyond organizational and institutional involvement, individual responsibility is key to the problems of Lyme disease. Terribly misguided institutions would not exist without willing individual participation.
There is, however, a reality and much can be learned if resources are not squandered on propaganda science. Philanthropist George Soros has said that propaganda does society its greatest disservice by obscuring the truth, thereby preventing advances in knowledge. When truth is obscured, we cannot learn from our mistakes, or successes.
Correcting this abysmal situation requires efforts on two fronts. First, on the global perspective, a new framework for conceptualizing borreliosis is required. Rather than repeat rote theories for the disease—including tick-bite, EM rash, limited geography and inaccurate test definitions for the disease, and single-treatment-cures-all dogma—we need to accurately characterize the scope and boundaries of borreliosis. From an individual’s perspective, which is where all medical treatment should be focused, we must examine detailed realities of the disease and devise the best diagnosis and treatments so we can proceed sensibly. Society cannot allow the irresponsible conclusions institutionalized in the last twenty years to condemn individuals to needless pain, disability, and death.
We are a small organization and conventional wisdom would say we should find some way to work with or influence larger organizations. But, after twenty years of support groups and a few independent researchers attempting reconciliation, it is obvious the CDC, NIH, and the IDSA are unable or unwilling to accept rational approaches to borreliosis. Replacement of the present commercial Lyme disease paradigm is necessary.
None of this is radical or revolutionary. It is a return to basic, sound medical practice where we identify microbial causes of disease, treat with the most effective antimicrobials available until infection is controlled, and provide care necessary to improve individual functioning and overall health. This is conventional, mainstream medicine.
We strive to provide accurate information regarding issues of health and disease and endeavor to expose and publicize medical propaganda killing and crippling our neighbors. Appeals to ignorance where doctors say they cannot act on or consider Lyme disease until there is a definitive clinical trial that tells them what to do is unacceptable. Very little in medicine works this way. We need to look at the realities of our world and then respond to protect our neighbors’ lives and health.