Connecticut Attorney General Richard Blumenthal has a problem and it is just not his military record that he is exaggerating about.  He has also exaggerated in promoting his medical/scientific agenda.   Mr. Blumenthal believes that all relationships with industry constitute a conflict of interest.  In doing so he forced a medical society to spend over a half a million dollars and countless hours of staff and voulenteer time defending themselves against trumped up anti-trust charges for issuing clinical guidelines and the state resources on the hopeless investigation.

Over the last four years he has been attacking a renowned group of scientists over Lyme’s Guidelines designed to help patients. 

Recently those attacks have been discredited by an independent review of the guidelines and an excoriation of the scientists involved.  But Blumenthal has remained conspicuously quite on this issue.

The Infectious Diseases Society of America (IDSA)[1] represents physicians, scientists and other health care professionals who specialize in infectious diseases. IDSA’s purpose is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases.

One of the many responsibilities of IDSA is to create disease practice guidelines, which are systematically developed statements to assist practitioners and patients in making decisions about appropriate health care for specific clinical circumstances.[2]  In 2000, and updated in 2006 the IDSA released their guidelines for Lyme disease entitled “The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America.”[3] [4]

Despite a multi-year investigation by Connecticut Attorney General Richard Blumenthal regarding IDSA Lyme disease guidelines, an independently appointed review panel agreed in its 2010 final report that all of the 69 original IDSA recommendations were “medically and scientifically justified.”[5]  The investigation, which was heavily charged by patient advocacy groups and Mr. Blumenthal’s individual advocacy for Lyme disease, revealed that politics and patient beliefs have no place in guideline making committees.  

Lyme Disease

Lyme disease, which was first identified in the Connecticut town of Old Lyme in 1981, is caused by bacteria related to syphilis that enter the body through a tick bite. The typical Lyme infection responds to simple antibiotics, although symptoms like arthritis and fatigue may linger in a subset of patients.  

Researchers at academic medical centers who study the disease say that chronic Lyme, or post-Lyme, is not very common, hard to detect and not treatable with any further doses of antibiotics.

Over 20,000 cases of Lyme disease are reported annually[6], although patient advocates assert that diagnostic testing may fail to identify up to 50% of patients with Lyme disease.[7]

IDSA’s 2006 Guidelines recognized that some patients who have had Lyme disease have persistent symptoms, including musculoskeletal pain, chronic fatigue, and cognitive problems sometimes called “brain fog.”  But panel members agreed that there was no convincing evidence that persistent B. burgdorferi infection causes the symptoms and there is no evidence that it can exist undetected.

As a result, IDSA proposed calling the symptoms “post-Lyme disease syndrome” and suggested a definition. Basically, the IDSA guidelines found “no convincing biologic evidence” for chronic Lyme infection.  The guidelines also recommended against antibiotic therapy beyond short-term treatment of acute infections. 

Treatment for Chronic Lyme Disease

While patient advocate groups believe treating chronic Lyme disease with long-term antibiotics is effective, various studies and experiences show the contrary.  For example, an early study identified 25 patients with gallstones or bile blockage resulting from antibiotic treatment of unsubstantiated chronic Lyme.[8] In another more recent study of infused antibiotics published in the New England Journal of Medicine, the study was cut short after Lyme sufferers with persistent symptoms did not respond to a course of antibiotics any better than they did to a placebo.[9]

One patient getting antibiotics had a pulmonary embolism; another had gastrointestinal bleeding. In addition, a 2007 review article in the NEJM noted that “chronic Lyme disease, which is equated with chronic B. burgdorferi infection, is a misnomer, and the use of prolonged, dangerous, and expensive antibiotic treatments for it is not warranted.”[10]

There was also a paper in the Annals of Internal Medicine called chronic Lyme a “functional somatic syndrome,” similar to other nebulous ailments like Gulf War Syndrome, chronic fatigue and fibromyalgia. Another study in the same journal found that 60% of Lyme disease patients lacked any evidence of previous or active Lyme infections. Some of these patients suffered from depression, arthritis or other diseases.[11]

Then there are the cases of various doctors who have been disciplined for treating patients with Lyme disease, such as Dr. Joseph Jemsek, who received a “suspension with stay” after a patient of his ended up in the intensive care unit after his antibiotic infusion regime to treat her Lyme disease (Lyme, Inc.). Vithaldis Shah, a New Jersey doctor, had his license yanked for five years in 1993 for sickening Lyme patients with long-term antibiotic treatments and receiving a payment from the infusion company. In 1996 a doctor in Michigan was suspended after conspiring with a home infusion company and misdiagnosing Lyme patients.

There was also a 2000 study that described the death of an anonymous woman from complications arising from treating unsubstantiated Lyme with antibiotics (Lyme, Inc.).  Even in Connecticut, Dr. Charles Jones, a pediatrician, is under investigation by the state medical board for prescribing, over the phone, antibiotics for chronic Lyme to two children in Nevada, a desert state with few ticks.[12]

Advocates however point to “studies of chronic Lyme disease that show a failure rate of 26% to 50%, using the short-term antibiotic approaches currently advocated by IDSA.”[13] One group, the International Lyme and Associated Diseases Society (ILADS), a physician’s group established in 1999 and closely allied with patient advocates, even published its own Lyme treatment guidelines recognizing chronic Lyme and endorsing long-term treatment with antibiotics in 2004.[14] 

Connecticut Investigation

Soon after the guidelines were published, patient advocacy groups reignited a 20-year-old war over whether persistent infection with the Lyme pathogen, Borrelia burgdorferi, is responsible for long-term symptoms resembling fibromyalgia. The physicians and patients who insist that the symptoms are a chronic form of Lyme infection, treatable with long-term or repeated courses of antibiotics, were outraged with the 2006 guidelines. To address this controversy, the New Jersey-based Lyme Disease Association, Connecticut-based Time for Lyme and the California Lyme Disease Association took their concerns to Connecticut Attorney General Richard Blumenthal, who has long supported efforts by chronic-Lyme enthusiasts. 

In 1999, he held a hearing on whether health insurance companies were improperly denying coverage for Lyme treatment. He helped draft a state law assuring patients access to prolonged antibiotic therapy, and has been active in patient groups, including a term on the advisory board of Time for Lyme, according to the organization’s co-president, Diane Blanchard. He has also criticized the state’s health department for underreporting Lyme infections.

After meeting with chronic-Lyme activists, Blumenthal initiated an antitrust investigation in November 2006 to determine whether IDSA’s guidelines were an illegal attempt to monopolize medical treatment of patients with potentially Lyme-related symptoms.[15]  In response, IDSA maintained that it had developed the 2006 Lyme disease guidelines based on a proper review of the medical/scientific studies and evidence by a panel of experts in the prevention, diagnosis, and treatment of Lyme disease. 

On May 1, 2008, Blumenthal and the IDSA reached an agreement to end the investigation, in part because the Federal Trade Commission and Department of Justice had previously stated a policy that medical-society guidelines do not inhibit competition.[16] Under the Agreement and its attached Action Plan, the 2006 Lyme Guidelines remained in effect, and the Society agreed to convene a Review Panel to determine whether the 2006 Lyme Guidelines were based on sound medical/scientific evidence and whether these guidelines required change or revision.[17] The Review Panel was not charged with updating or rewriting the 2006 Lyme Guidelines and any recommendation for update or revision would be conducted by a separate IDSA group.

IDSA was responsible for paying the costs in conducting the re-evaluation, but it did not pay any fines or penalties, and the agreement is not an admission of wrongdoing. The costs for numerous meetings, conference calls and legal fees, cost the association close to $1 million.  In his press release about the agreement Blumenthal stated that the society’s 2006 guidelines “process lacked important procedural safeguards requiring complete reevaluation — in effect a comprehensive reassessment through a new panel.” Blumenthal’s findings include the following:

• The IDSA failed to conduct a conflicts of interest review for any of the panelists prior to their appointment to the 2006 Lyme disease guideline panel;

 

• Subsequent disclosures demonstrate that several of the 2006 Lyme disease panelists had conflicts of interest;
• The IDSA failed to follow its own procedures for appointing the 2006 panel chairman and members, enabling the chairman, who held a bias regarding the existence of chronic Lyme, to handpick a likeminded panel without scrutiny by or formal approval of the IDSA’s oversight committee;
• The IDSA’s 2000 and 2006 Lyme disease panels refused to accept or meaningfully consider information regarding the existence of chronic Lyme disease, once removing a panelist from the 2000 panel who dissented from the group’s position on chronic Lyme disease to achieve “consensus”;
• The IDSA blocked appointment of scientists and physicians with divergent views on chronic Lyme who sought to serve on the 2006 guidelines panel by informing them that the panel was fully staffed, even though it was later expanded;
• The IDSA portrayed another medical association’s Lyme disease guidelines as corroborating its own when it knew that the two panels shared several authors, including the chairmen of both groups, and were working on guidelines at the same time. In allowing its panelists to serve on both groups at the same time, IDSA violated its own conflicts of interest policy.

The agreement to reevaluate the 2006 IDSA guidelines by a new society committee raised questions about conflicts of interest involving members of the expert panel IDSA had appointed to develop the 2006 guidelines. Specifically, five of the 14 committee members had disclosed outside financial relationships with drug and diagnostics companies as well as having served as expert witnesses in malpractice cases involving Lyme disease, and one member was paid to review disability claims for Metropolitan Life Insurance. No other panelists indicated relationships with insurance firms. IDSA denied that any of these relationships were relevant to the guidelines.[18]

In fact, Gary Wormser, M.D., of New York Medical College in Valhalla, N.Y., who chaired the 2006 IDSA guidelines panel, refuted Blumenthal’s claims.  He asserted that “panel members had no financial interests that would have affected, or been affected by, recommendations in the guidelines.” Specifically, he noted how the guidelines recommended generic drugs and generic diagnostic tests, evidence that “panel members do not stand to profit from any recommendation in the guidelines.” Essentially, panel members “denied themselves and their colleagues an opportunity to generate a significant amount of revenue when they recommended against expensive, repeated, long-term antibiotic therapy.”[19]

Blumenthal also criticized what he called “improper links” between IDSA’s panel and one convened by the American Academy of Neurology (AAN), which also publishes guidelines on Lyme disease treatment because the infection can penetrate the central nervous system and cause neurological symptoms.  AAN’s guidelines, which were published online in May 2007, recommended against prolonged courses of antibiotics for “post-Lyme syndrome,” because “most available data argue against persistent B. burgdorferi infection in patients who have received what are normally curative courses of antimicrobial therapy.”[20]

Although three members served on both panels (John Halperin of New York University School of Medicine and Atlantic Health System in Summit, NJ; Yale’s Eugene Shapiro, M.D., and Dr. Wormser), AAN did not re-evaluate its Lyme guidelines, and rejected Blumenthal’s allegation of “improper links.” The organization asserted that the similarity between the two sets of guidelines is a good thing, because it “avoided conflicting and potentially confusing professional guidance.” AAN General Counsel Murray Sagsveen added that “Blumenthal failed to consider that evidence-based collaboration should actually lead to similar diagnosis and treatment of a disease among specialties.”[21]

2008 Review Panel

To determine the new committee, IDSA and Blumenthal jointly selected Howard Brody, M.D., Ph.D., of the Institute for the Medical Humanities at the University of Texas Medical Branch in Galveston and author of the anti industry book and blog Hooked on Ethics, Medicine and Pharma, to fill the post of “ombudsman” to oversee the conflict-of-interest review.  Dr. Brody primarily helped draft a thorough four-page disclosure form and other procedures for evaluating conflicts of interest and screened all applicants based on their personal practice patterns and practice incomes.  He wanted to ensure that the Review Panel[22] Chairperson was without any beneficial or financial interest related to Lyme disease, any financial relationship with an entity that has an interest in Lyme disease, and any conflict of interest. 

The goal was to create a panel that represented “a balanced variety of perspectives” and included at least one physician who treats Lyme disease patients. If an applicant had combined financial or beneficial interests that exceeded $10,000, in the products or concepts addressed in the guidelines, IDSA considered those to bias a participant’s judgment.  The Chairman chosen was also required to be trained in infectious diseases, but may not have published a viewpoint on Lyme disease diagnosis or treatment.  A committee member who served on earlier Lyme guideline panels was prohibited from selection. 

Eventually, Carol J. Baker, MD, of Baylor College of Medicine in Houston, Texas, was chosen as the Review Panel Chair, along with eight other review panel members (one panel member retired due to family illness, leaving a total of eight).[23]

After the panel members were announced, patient groups released a joint statement calling the new panel “unbalanced and biased,” and they specifically took issue with the Brody recommendation and exclusion of physicians who made more than $10,000 treating Lyme disease. 

Pat Smith, president of the Lyme Disease Association, noted how 18 physicians who treated persistent Lyme applied to the panel and were all excluded (Annals of Neurology). 

IDSA noted that anybody making substantial amounts of money treating people with long-term antibiotics has a clear conflict of interest in the outcome of this board’s deliberation,” and as a result did not meet the criteria.  

After approximately two years, the Review Panel published the Final Report of the Lyme Disease Review Panel of IDSA) on April 22, 2010. In conducting their review, the Panel held a public input period of more than 80 days to allow the public to submit information and to ensure that all points of view were taken into consideration. The Panel received submissions from approximately 150 individuals or organizations, including various sources of information (e.g. medical records, DVDs, etc).

The Review Panel held an all-day open public hearing on July 30, 2009, in Washington, DC, to offer a forum for the presentation of relevant information on the diagnosis and treatment of Lyme disease. An open application process was held to identify hearing presenters. Thirty-five applications were received and were reviewed and approved by the AG’s Office to determine the final list of presenters for the July hearing. Two patients and 16 physicians or researchers were chosen to present. The hearing was broadcast live via webcast, on the IDSA website and transcripts, slides, and testimony were posted.

In addition, Panel members and staff used PubMed and the Cochrane Collaboration Library for research to look for various terms associated with Lyme disease, and reviewed full-text articles.  All together, the panel reviewed over 1,000 sources of information.

Each Review Panel member was then assigned a section of the 2006 Lyme Guidelines and was tasked with the careful review of the evidence and other information submitted and/or presented relevant to that section. All Review Panel members were required to comprehensively review the section on Post-Lyme Syndromes. The Panel met several times in person and via conference call, to present the findings of their research on their assigned sections. An open discussion among Panel members took place, and each member made an individual determination as to whether each recommendation in the 2006 Lyme Guidelines was medically/scientifically justified in light of the evidence and information collected and provided, and whether or not a change or revision was needed. Each member’s vote was recorded.[24]

Accordingly, after a review of the 2006 guidelines, the panel agreed that all of the 69 original recommendations were “medically and scientifically justified” in the light of the evidence.[25] The agreement had stipulated that any committee recommendation would require a 75% “supermajority” vote. The vote was unanimous (8-0) for 68 out 69 of the recommendations.  The recommendation approved by a 7-to-1 margin specifically regarded the issue of chronic Lyme disease.

For that particular issue, the panel recommended that when the 2006 Lyme Guidelines are next updated, to change the phrase “no convincing biologic evidence” to something more specific, such as “reports purporting to show the persistence of viable B. burgdorferi organisms after treatment with recommended regimens for Lyme disease have not been conclusive or corroborated by controlled studies.” The panel also stated that to date, drug-tolerant reservoirs of B. burgdorferi, including intracellular cystic forms, has not been shown to correlate with symptom persistence, nor has eradication of these forms been shown to correlate with symptom improvement.

According to Dr. Baker, the panel’s Chair, the review panel came down on the side of patient safety because “what they found after a thorough review of all the evidence is that there was significant risk for patients treated beyond about four weeks, and certainly for patients treated for years with intravenous therapy.”[26] This view is shared by the CDC[27] and NIH.[28] She further added that not only is the treatment costly and unlikely to have a benefit, but the catheter increases the risk of bloodstream infections that can require intensive care and may even cause death.

Specifically, the report tells physicians that the symptoms often blamed on chronic Lyme disease — arthralgias, fatigue, and cognitive dysfunction — are seen in many conditions, so that it is “clinically imprudent to make the diagnosis of Lyme disease using these nonspecific findings alone.”

On the other hand, the panel added, some classic complications of Lyme disease — aseptic meningitis, AV nodal block, inflammatory arthritis, and cranial or peripheral neuropathies – that can be “sufficiently convincing as to constitute an.”  The panel said that exception should be used only when other diagnoses for a patient have been excluded or are unlikely.

Panel member Paul Lantos, MD, of Duke University Medical Center, said it’s important for physicians faced with a putative case of chronic Lyme disease to keep an open mind and not rely in previous diagnoses.  He noted that he has treated several patients who thought they had chronic Lyme disease and turned out to have other serious conditions, such as endocarditis and multiple sclerosis.

Discussion

There is no doubt that Lyme disease is real, and affects the lives of thousands of people and their families. But this case exemplifies the politicization of health policy, with elected officials advocating for health policies against the weight of scientific evidence.  In fact, as an article in the Journal of the American Medical Association (JAMA) entitled “Science, Politics, and Values: The Politicization of Professional Practice Guidelines,” explained, advocacy groups and Blumenthal “should have sought other answers” when high quality research repeatedly was inconsistent with the group’s hypotheses.[29]

While it is understandable that in times of pain and suffering people will look for answers, insisting on a link between the symptoms and chronic infection as evidence to call for long-term antibiotic treatments is contrary to scientific evidence. As Kraemer and Gostin point out, “the scientific process is not democratic, and no amount of desire for different results can establish them.” Instead, as David Volkman, an emeritus professor at the State University of New York at Stony Brook pointed out, what is needed are better diagnostic tools and objective science.[30]

The IDSA case “sets a precedent for politicians representing the views of aggrieved constituents to challenge the recommendations and guidelines of professional societies.”[31] It raised the possibility that any state attorney general can challenge a clinical practice guideline that is disfavored by the politician’s constituents.  This opens the door for “special-interest organizations to influence clinical practice guidelines to reflect their political objectives rather than accepted, peer-reviewed literature.”  As Robert Buchanan, a medical-antitrust attorney in Boston correctly noted, “medicine must advance by debate, not hampered by lawsuits.”[32]

Upon the announcement of these results, IDSA president Richard Whitley, MD, of the University of Alabama at Birmingham, said he thought Blumenthal had been “misguided by the activists,” and that his “contention against IDSA was neither justified nor warranted.”[33] As a result, the outcome has clearly shown that the guideline making process must be closely protected to “assure that the process and the science are not subverted by advocacy groups or their political representatives.”

In addition, the American Medical Association (AMA) House of Delegates introduced a resolution after the final report to “Support an Independent Clinical Practice Guideline Development Process.”[34]  The resolution recognized how patient groups and policy makers concerns can “improperly influence the clinical practice guideline development process, and also sanction ineffective (and potentially dangerous) medical treatments.”  The AMA also asserted that efforts by policy makers and patient groups “not only hinder the ability of physicians to provide safe and effective medical treatments to their patients but also politicize the clinical practice guideline development process.” 

As a result, the AMA’s resolution supported the authority of medical professional organizations to develop clinical practice guidelines that are based on sound science and medical evidence.  The resolution also opposed all efforts to improperly influence or politicize guidelines, and opposed all efforts to legislate the practice of medicine by mandating coverage of or otherwise sanctioning the provision of medical treatments that are proven to be ineffective and potentially harmful.

After the panel announced its final report, Blumenthal gave a statement saying that his office was “reviewing the IDSA’s reassessment of its 2006 Lyme disease guidelines to determine whether the IDSA fulfilled the requirements of the settlement.”[35]   This is a stark contrast to his 2008 statement “Attorney General’s Investigation Reveals Flawed Lyme Disease Guideline Process, IDSA Agrees To Reassess Guidelines, Install Independent Arbiter  in which he made a presumptive statement that conflicts of interest in the guideline creation process as “flawed”.

The Lyme Disease Association, Inc. (LDA) was disappointed with IDSA’s announcement,[36] especially after significant attention was brought to Lyme disease when a documentary titled “Under Our Skin” was released in 2008.[37]

Conclusion

Although the failure of Mr. Blumenthal’s political investigation brought negative attention towards guideline making committees, the outcome provided irrefutable evidence that the current guidelines process is valid.  This is despite the accusation by anti industry academics, politicians and others that guidelines committees need to eliminate members with relationships with industry.  That by and large because they are committees and not independent judgments, and that these committees are working on reliable peer reviewed evidence to make their recommendations.

Patients depend on their doctors to follow guidelines in their practice to ensure evidence-based treatment. Doctors depend on those guidelines to establish the best plan for their patients based on scientific evidence.  Investigations like Mr. Blumenthal’s with no legal basis show just how much time and money can be wasted reviewing a perfectly legitimate document, when those funds could have been spent on research.

Attempting to control the guideline creation process leaves politicians and others open to accusations of rationing health care, and as the IDSA case demonstrates, politics has no place in determining scientific evidence. Moreover, routing out all perceived “conflicts of interest” is meaningless, and potentially harmful to the guidelines process.  

Guidelines are created by committees of dedicated physicians, and with the Standards for Developing Trustworthy Clinical Practice Guidelines[38] being considered, the Institute of Medicine (IOM) must pay close attention to the IDSA investigation that found no evidence of a conspiracy to shift guidelines.  What IOM should weigh in determining their new standards is how the IDSA case demonstrated that patients and politicians are easily influenced by antidotal evidence.  If politicians continue to investigate proven scientific evidence, “medical and public confidence in guidelines will be irreparably damaged, the guideline development process will be “chilled,” and members will be discouraged from volunteering to author guidelines.” 

 

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Note to Lyme Patients, I have several close friends who have had complications due to the disease, all have recovered but some were quite serious.  I completely understand your concerns and do not hold that guidelines should be used to deny coverage by insurance companies.

This article was written to point out that writers of clinical guidelines by and large are honest people and that this case proves conflict of interest is not an issue in guidelines development.