LYMEPOLICYWONK: Was this important Lyme study hidden for 12 years?

Byldoadmin

A key component of the monkey study recently published by Embers and colleagues was a 90 day treatment trial designed as a companion to the highly-cited Klempner human trial of chronic Lyme disease published in 2001. The treatment regimen in the Klempner companion monkey study was exactly the same as those used for the human study. Unlike the human trials, however, the monkey trials were able to directly demonstrate persistent infection. In fact, the Embers study was proposed by patients on the Klempner advisory committee to act as a fact check on the results of Klempner, with the expectation that the two would be published in tandem.  It is big news for patients that the two trials reached opposite conclusions.

The monkey trials found that the bacteria that cause Lyme disease persist after 90 days in monkeys treated for chronic Lyme disease.  Further, the antibody tests used to diagnose Lyme fail to detect disease in late Lyme at least 50% of the time. Why are these findings important?  Well, the 2006 Infectious Diseases Society of America (IDSA) Lyme guidelines rely heavily on the Klempner study to deny persistent infection and, consequently, antibiotic treatment for patients. After all, why treat an infection that doesn’t exist?  The IDSA guidelines also require that patients have a positive lab test to be diagnosed (and treated) for Lyme disease—lab tests that Embers shows miss 50% of late Lyme disease cases.

But this is all old news, right?  I mean the monkey study was funded in 1998. But, wait—the results of that study weren’t published until 2012. Does that type of a delay in publication matter?  You bet it does.  Here’s why. Science builds upon existing published research.  New research incorporates the work of others into a new hypothesis, refines it, and sometimes transforms it.

Leaders in evidence-based medicine, like Dr. Iain Chalmers, point out that “Peer review cannot take account of what cannot be seen.” Chalmers explains that unreported research stops scientific progress dead in the water and wastes precious resources vital for patient care and research.  Further, it can form the basis for seriously misleading recommendations leading to unnecessary suffering and death. A recent editorial in the British Medical Journal called the crisis of missing trial data a threat to the integrity of evidence-based medicine; they concluded that “[a] current culture of haphazard publication and incomplete data disclosure make the proper analysis of the harms and benefits of common interventions almost impossible for systematic reviewers.”

How does this apply to Lyme disease? Imagine that a scientific result has a bearing on the treatment of a disease. Imagine that the publication of that result would relieve unnecessary human suffering but is delayed for 10 or more years. Imagine then, that these results are not reflected in clinical guidelines, leaving patients inappropriately treated by their doctors for want of knowledge of that scientific result.  And that is what essentially happened here, as the time line below shows:

 

1996-2000: Klempner Study Funded (Grant: AI065308-00096): CLINICAL STUDIES OF CHRONIC LYME DISEASE

1998-1999: Klempner Companion Monkey Study Mario Phillip Funded (NIAID grant R01-AI042352): ANTIBIOTIC [TREATMENT] OF CHRONIC LYME DISEASE IN MONKEYS

2001: Klempner Study Published

2006: IDSA Lyme Guidelines Published

2012: Klempner Companion Monkey Study Published

So the Klempner study and the companion monkey study were funded within two years of each other. But while the results of the Klempner trial on humans were rushed to publication, those of the companion monkey trial languished for another for 11 years. During this period, seriously ill patients were told there was no persistent infection to treat, and physicians who treated patients for persistent infection were brought before medical boards.

I found myself wondering where the NIH – which funded and oversaw the Klempner companion study – had been for the past ten years.  The study was funded and monitored under the watch of Dr. Phil Baker, who has now retired from the NIH and advocates against Lyme patients on behalf of the American Lyme Disease Foundation.

Baker denies allegations that the NIH suppressed publication of the study and claims the decision to delay publication rested entirely with the authors. There are several possible explanations for the delay. It is possible that publication was delayed to ensure the completeness of the study. It is also possible that after the Klempner trial was published and the nature of the Lyme debate became so heated, the political headwinds against publication of contradictory results simply became too challenging.  If so, the publication even at this late date might be regarded as an act of courage on the part of the authors. There can be no doubt, however, that the delay in publication caused patients considerable harm.

This article is part of a series of reviewing the Embers findings for treatment of chronic and early disseminated Lyme disease as well as the effectiveness of the C6 antibody test. You can find these other posts here:

Part 1–New study shows Lyme persists in monkeys

Part 2–Treatment and Persistence

Part 3–IDSA 28-day treatment protocol fails to clear infection

Part 4–Lab tests fail to detect Lyme disease

Part 5–Of mice and men and monkeys

Read the journal article here.

References:

Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, Hodzic E, et al. Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PLoS ONE. 2012;7(1):e29914.

Lehman R, Loder E. Missing clinical trial data. BMJ. 2012 2012-01-03 00:00:00;344.

The “imagine” exercise is adapted from an article by Valentine Cawley: An Analysis of the Ethics of Peer Review and Other Traditional Academic Publishing Practices. International Journal of Social Science and Humanity, Vol. 1, No. 3, September 2011.

Dickersin K, Chalmers I. Recognizing, investigating and dealing with incomplete and biased reporting of clinical research: from Francis Bacon to the WHO. J R Soc Med. 2011 Dec;104(12):532-8.

Pam Weintraub, Cure Unknown: Inside the Lyme Endemic (Paperback: 2009)

Sir Iain Chalmers, James Lind Initiative (PR 47) written evidence submitted to Parliament, Peer Review. 

The LYME POLICY WONK blog is written by Lorraine Johnson, JD, MBA, who is the Chief Executive Officer of LymeDisease.org, formerly CALDA. Contact her at lbjohnson@lymedisease.org.

 

 

Similar Posts

  • LYMEPOLICYWONK: When is Mandatory, Mandatory? When Medco says so!

    I have gotten a lot of reports from patients that Medco is refusing to dispense antibiotics because of the IDSA guidelines. At $51 Billion, let me repeat that $51 BILLION, dollar in revenue, Medco is the nation’s largest drug dispensing company. And, just for the record, they are over-riding the treatment recommendation of the treating physician and replacing it with, oh yeah, the IDSA “expert opinions” on treatment. This isn’t evidence based medicine, this is “eminence based medicine.” Their mission is to help “clients control the cost and enhance the quality” of prescription benefits. Looks like the IDSA is their friend. Complaints about Medco using these tactics have been becoming more frequent suggesting that this is not an isolated case and may be an across the board policy? If so, its reliance on IDSA guidelines to deny treatment across the board will have a serious adverse impact on patient lives.

  • LYMEPOLICYWONK: ILADS Weighs in on IOM Process

    Today, ILADS sent a letter to the IOM expressing its concerns about the lack of balance in the panel and the speaker list for the Lyme State of the Science conference. Not surprisingly, it was concerned primarily about the exclusion of ILADS physicians from presenting at the conference and with the large roles handed to Dr. Wormer, chair of the IDSA Lyme guidelines panel, and Dr. Aguera-Rosenfeld, who until recently worked at NYMC with him, are both known to have biased views regarding the diagnosis and treatment of Lyme disease. Exclusionary conduct on the part of the IDSA has prevented the type of scientific debate that is essential to understanding where the science in Lyme disease rests. ILADS took issue with the large roles handed to the IDSA in the diagnosis and treatment issues at the conference, stating: “There is a significant disconnect between IDSA and the community of physicians who treat Lyme disease. There is also an urgent need for transparency in recognizing the limitations of the existing Lyme research. The bulk of the research on Lyme treatment has been controlled by IDSA researchers. Their research is based on sample populations that do not reflect those seen in clinical practice.” Lyme treatment research has been plagued by sample sizes that are too small to measure clinically relevant treatment effects and that do not reflect the types of patients seen in clinical practice. The link to the ILADS letter follows the jump. . .

  • JAMA to conflict of interest breaches—silence is golden

    JAMA is having a personality conflict with itself. After publishing 3 very strong articles on the ethics in guidelines development, it has asked those who question ethics violations in JAMA’s publications to keep quiet about them. In JAMA’s view, conflict violation in its journal should be discussed only if and when JAMA decides to discuss them. This sounds like a policy designed to silence whistle blowers at a time when we need more whistles and fewer muzzles. Not surprisingly, the Association of Health Care Journals has come out against JAMA on this one.

  • LYMEPOLICYWONK: Lyme disease abandoned by Pharma

    When I first became involved with Lyme disease, I remember wondering where the pharmaceutical interest was in the disease. Most of your double blind controlled trials are funded by the pharmaceutical industry. This means that if your disease is not on their radar, you’re going to have a long hard slog getting funding for studies on the efficacy of different treatments. Diseases that are on the agenda of big Pharma have a distinct advantage in evidence based medicine because studies, typically large scale studies, have been funded by someone with a dog in the hunt. In other diseases, the dog in the hunt may be overzealous, promoting treatments and selling drugs with little proof of effectively. But when a disease is neglected by big Pharma, the opposite occurs. Research simply isn’t done. And, that becomes a social justice issue when insurers and specialty societies deny patients access to care because research studies haven’t been funded and aren’t likely to be funded. Drugs are expensive to develop and research is expensive to conduct. Recently, GlobalDate releases a report that explains why Lyme disease is neglected and is likely to remain neglected by big Pharma.