Neurology -- Correspondence for Halperin et al., 69 (1) 91-102

Correspondence published:

Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review): Raphael B. Stricker, Lorraine Johnson (1 November 2007)

Reply from the authors: John Halperin, MD, C. T. Bever MD, A. L. Belman MD, L. Dotevall MD, G. Gronseth MD, L. Krupp MD, E. Logigian MD, E. D. Shapiro MD, G. P. Wormser MD (1 November 2007)

Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review) 1 November 2007

Raphael B. Stricker,
ILADS
450 Sutter Street, Suite 1504, San Francisco, CA 94108,
Lorraine Johnson
Send Correspondence to journal:
Re: Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review)

rstricker{at}usmamed.com Raphael B. Stricker, et al.

We wish to point out a serious ethical problem with the recently adopted Lyme disease treatment guidelines of the American Academy of Neurology (AAN). [1] These guidelines have been touted as an “independent corroboration” of the Lyme guidelines published by the Infectious Diseases Society of America (IDSA) in November 2006. [2] Nothing could be further from the truth.
The IDSA and AAN guidelines committees were clearly not independent in terms of personnel or philosophy. The AAN guidelines were put together by a committee of nine members, three of whom also served on the IDSA Lyme guidelines panel, including the chairman of each committee. The overlapping chairs virtually assured that the form and substance of the AAN guidelines would be “like-minded”—essentially a repackaging of the IDSA guidelines—by controlling the panel selection and scope of the process.
AAN published its guidelines after the Attorney General of Connecticut launched an unprecedented investigation into potential anti-trust violations in the IDSA guidelines formulation. The AAN guidelines were, not surprisingly, quickly endorsed by IDSA and presented to the medical community as “independent corroboration” despite the overlapping panels and questions raised by the Connecticut investigation. Thus the timing of the AAN guidelines and the IDSA endorsement compounded the conflict of interest for both organizations.
Two medical societies, IDSA and the International Lyme and Associated Diseases Society (ILADS), have published peer- reviewed, evidence-based guidelines listed by the government-sponsored National Guidelines Clearinghouse and offering divergent treatment approaches for Lyme disease. [2,3] Under the IDSA guidelines recapitulated by AAN, patients who fail to respond to the IDSA protocols are denied longer antibiotic treatment. In contrast, the ILADS guidelines consider these patients to have chronic Lyme disease and provide the only viable treatment option for them. The conflicting guidelines have established two standards of care for Lyme disease. [4]
Responsible medical societies have an obligation to acknowledge scientific uncertainty and lack of consensus when controversy exists regarding the treatment of medical conditions such as tick-borne diseases. [4] It is unacceptable to repackage the beleaguered guidelines of another medical society and allow overlapping panel members with clear conflicts of interest to control the process. To ignore the conflicts of interest in these circumstances represents a serious ethical breach that discredits AAN and misleads the broader medical community, which relies on the ethical accountability of guidelines panels. [5]
References
1. Halperin JJ, Shapiro ED, Logigian E, et al. Practice parameter: Treatment of nervous system Lyme disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2007;69:91-102.
2. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006; 41:1089-1134.
3. Cameron D, Gaito A, Harris N, et al and the ILADS Working Group. Evidence-based guidelines for the management of Lyme disease. Expert Rev Anti-Infect Ther 2004;2(1 Suppl):S1-13.
4. Johnson L, Stricker RB. Treatment of Lyme disease: A medicolegal assessment. Expert Rev Anti-Infect Ther 2004;2:533-557.
5. Steinbrook R. Guidance for guidelines. N Engl J Med 2007;356:331-333.
Disclosure: The authors report no conflicts of interest.

Reply from the authors 1 November 2007

John Halperin, MD ,
C. T. Bever MD, A. L. Belman MD, L. Dotevall MD, G. Gronseth MD, L. Krupp MD, E. Logigian MD, E. D. Shapiro MD, G. P. Wormser MD
Send Correspondence to journal:
Re: Reply from the authors

halperin{at}lineuro.com John Halperin, MD, et al.

We thank Stricker and colleagues for the opportunity to address the differences between ILADS’ positions and the AAN Lyme disease Treatment Guideline’s evidence-based conclusions. [1,3]. We agree it is essential to consider both Guidelines’ development process and their substance.
The letter asserts that the AAN and IDSA panels were not independent of each other, that the AAN Guideline ‘repackaged’ the IDSA’s, that the authors had conflicts of interest, and that the timing of the AAN Guideline ‘compounded the conflict of interest for both organizations’. The AAN panel was constituted by the AAN from published experts in the field and was approved by its Quality Standards Subcommittee. The process followed by the panel was specified in the AAN’s published manual (at http://www.aan.com/globals/axon/assets/2535.pdf), which explicitly addresses conflict of interest issues. Specified procedures were followed throughout. As part of the standard AAN Guideline development and publication process, AAN staff and a subcommittee member provided independent oversight to assure all aspects were in accord with AAN procedures. The document went through 7 cycles of review over the course of 2 years. Approximately 140 individuals had the opportunity to review the document; their input was incorporated. The timing of publication was determined by this complex process.
The letter states that the conflicts between the ILADS published recommendations and the AAN and IDSA Guidelines ‘have established two standards of care’. However, the ‘Summary & disclaimer’ section of the ILADS document states ‘they were not intended to be a standard of medical care’. [3]
Finally, the letter emphasizes the ‘obligation to acknowledge scientific uncertainty’. We agree completely. The AAN explicitly acknowledges scientific uncertainty in its Classification of Recommendations (Appendix 3), requiring consistent Class I studies for a Level A recommendation, etc. [1] Each recommendation is reached by systematically reviewing all relevant studies, explicitly specifying the Class of evidence of each. Insofar as the ILADS Guidelines are presented as an alternative ‘evidence-based guideline’ it is helpful to assess them by the same standards. The processes of ILADS Guideline development and review are not explicitly stated. The evidence cited consists of 66 references. Almost half are reviews, meeting presentations, opinion pieces, studies in progress or articles from non-Medline journals. One is a self-published web site. Of the remainder, three address treatment response and are not cited in the IDSA or AAN Guidelines. Two of these are anecdotal case series (2 and 4 patients); one involves treatment of erythema migrans (in Europe). No studies were explicitly assessed for quality of evidence. Table 1, summarizing Strength of Evidence, compares ILADS conclusions to the 2000 IDSA Guideline. [6] For five items IDSA reached no conclusion because data were lacking; ILADS rates the data II or III for these items, without identifying additional studies. In five conditions ILADS rates the strength of the evidence ‘A’ but data quality II or III. ‘A’ conclusions require at least two Class I studies (AAN criterion).
We agree with Stricker that Guidelines must be based on an unbiased rigorous assessment of the available data. We believe the AAN Guideline easily meets this standard.
Reference
6. Wormser GP, Nadelman RB, Dattwyler RJ, et al. Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Clin Infect Dis 2000;31 Suppl 1(2):1-14.
Disclosures: Dr. Halperin holds equity in Abbott, Bristol Myers Squibb, Johnson & Johnson, Schering Plough and Vasogen. He has served as an expert witness in medical malpractice actions. Dr. Shapiro has received funds for reviewing disability claims from Metropolitan Life Insurance Company and has served as an expert witness in malpractice actions. He has also received honoraria from Merck, Inc. and Aventis for speaking engagements. Dr. Shapiro receives funding from NIH grants K24RR022477, KL2RR024138, and UL1RR024139. Dr. Logigian has been a consultant to Actelion Pharmaceuticals, Ltd. and served as an expert witness in a Lyme disease case in 2004. Dr. Belman has nothing to disclose. Dr. Dotevall has received monies from Pfizer for lecturing. Dr. Wormser reports having received research grants related to Lyme disease from the Centers for Disease Control and Prevention, the National Institutes of Health, Immunetics, Inc., and BioRad. He was part owner of Diaspex, LLC, a company with no products or services. He has been an expert witness for the United States in a medical malpractice case and has been retained in other medical practice cases involving Lyme disease. Dr. Wormser has overseen educational grants to New York Medical College to support Infectious Diseases grand rounds from Merck and AstraZeneca, and one from Pfizer is expected in 2008. Dr. Krupp has no conflicts of interest to report. Dr. Gronseth holds financial interests in Pfizer and GlaxoSmithKline, has received speaker honoraria from Boeheringer Ingelheim and has received honoraria from Ortho-McNeil for serving on the IDMC Committee. Dr. Bever has received honoraria from Teva Pharmaceuticals, Berlex Laboratories, Serono, Pfizer, Senofi-Aventis and Accorda Therapeutics. Dr. Bever has received research funding from Serono and Accorda Therapeutics