Lyme Disease – One Of The Most Controversial
Illnesses In The History Of Medicine.
Attorney General forces Infectious Diseases Society of America
to redo Lyme guidelines due to flawed development process
L Johnson,1 R B Stricker2 1 California Lyme Disease Association,
Ukiah, California, USA;
2 International Lyme and Associated Diseases Society, Bethesda, Maryland, USA Correspondence to:
Dr R B Stricker, 450 Sutter Street,
Suite 1504, San Francisco,
California 94108, USA;
Received 30 June 2008 Accepted 25 February 2009
Lyme disease is one of the most controversial illnesses in the history of medicine.
In 2006 the Connecticut Attorney General launched an antitrust investigation into the Lyme guidelines development process of the Infectious Diseases Society of America (IDSA). In a recent settlement with IDSA, the Attorney General noted important commercial conflicts of interest and suppression of scientific evidence that had tainted the guidelines process. This paper explores two broad ethical themes that influenced the IDSA investigation. The first is the growing problem of conflicts of interest among guidelines developers, and the second is the increasing centralisation of medical decisions by insurance companies, which use treatment guidelines as a means of controlling the practices of individual doctors and denying treatment for patients. The implications of the first-ever antitrust investigation of medical guidelines and the proposed model to remediate the tainted IDSA guidelines process are also discussed. The diagnosis and treatment of Lyme disease is highly controversial, and most patients are aware that obtaining a diagnosis and treatment for this tick-borne illness can be difficult. One group of doctors, the Infectious Diseases Society of America (IDSA), issued Lyme treatment guidelines in 2000 that promoted a narrow definition of the disease.1 These guidelines excluded most Lyme patients and denied them treatment for their illness. The IDSA viewpoint has been adopted without question by government agencies, insurers, medical boards and hospitals. As a result, the diagnosis and treatment of Lyme disease has been suppressed, with profound healthcare implications for patients, their families and their communities. The level of disability of patients with Lyme disease is equal to that of patients with congestive heart failure and there are at least 21 studies documenting death in patients with this potentially devastating tickborne illness.1 AN INVESTIGATION AGAINST THE IDSA When the IDSA sought to revise its Lyme treatment guidelines in 2006, patients and their treating doctors tried to obtain a voice in the guidelines process. The IDSA denied their requests for participation and limited the guidelines panel to researchers known to have a bias against the diagnosis and treatment of Lyme disease. The IDSA panel then selectively ignored evidence of persistent infection or clinical improvement with antibiotic treatment in patients with persistent symptoms of the disease. From the perspective of antitrust law, the behaviour of IDSA drew attention to its monopoly power, the fact that its guidelines were treated as mandatory and that members of the guidelines panel had commercial conflicts of interest and intentionally excluded divergent viewpoints and evidence. These facts dovetailed with IDSA’s power to control the playing field and enforce its guidelines by providing insurers with second opinions while instigating and testifying at unprofessional conduct actions against doctors who did not comply with the IDSA guidelines. In addition, the IDSA’s ability to further suppress the debate through its role as the gatekeepers (on editorial boards and as peer reviewers) for medical journals, medical conferences and grand rounds supported the antitrust argument when patients started complaining that they were being denied care for their disease. The California Lyme Disease Association (CALDA), the national Lyme Disease Association, Connecticut-based Time for Lyme and other groups affected by the guidelines approached the Connecticut Attorney General, Richard Blumenthal, and expressed their concerns about patients being denied care. In late 2006, the Attorney General launched an antitrust investigation into IDSA and its Lyme guidelines panel for misuse of monopoly power and exclusionary conduct in the development of the guidelines. The antitrust theory is that when a medical society has monopoly power such that its guidelines can take on the force of law, as the IDSA guidelines do, it has an obligation to ensure that the development process is fair, does not exclude competing points of view, and that its panel is not driven by commercial conflicts of interest. To our knowledge, this is the first-ever antitrust investigation into the development process for medical guidelines. In May 2008, after an extensive investigation, the Attorney General announced a settlement of the antitrust investigation into the IDSA guidelines development process. The settlement stipulates that the IDSA must put together a new panel free from conflicts of interest, permit the introduction of evidence opposing its viewpoints, and hold a public hearing (aired live on the Internet) on controversial recommendations of the guidelines panel. While this is an important victory for the Lyme community, the settlement has broader implications for medical guidelines generally because it represents the first time that conflicts of interest in the guidelines development process have been addressed using antitrust theories. Clinical ethics J Med Ethics 2009;35:283–288. doi:10.1136/jme.2008.026526 283 There are two broad themes that set the stage for the investigation by the Attorney General. The first is the growing problem of conflicts of interest among guidelines developers, and the second is the increasing centralisation of medical decisions by insurance companies, who use treatment guidelines as a means of controlling the practices of individual doctors.
CONFLICTS OF INTEREST MEAN THAT THE QUALITY OF PATIENT CARE MAY TAKE A BACK SEAT TO OTHER COMMERCIAL INTERESTS HELD BY GUIDELINE PANEL MEMBERS
A survey of medical experts who write guidelines for treating conditions such as heart disease, depression and diabetes has found that nearly nine out of 10 have financial ties to the pharmaceutical industry, and the ties are almost never disclosed.2 Drug companies foster relationships with key opinion leaders among academic researchers who can help develop, obtain Food and Drug Administration (FDA) approval and create a market for drugs, diagnostic tests or vaccines. Panel members may also have consulting relationships with insurers. Before this case, there had been no effective remedy for guidelines developed by panels with conflicts of interest. While researchers argue that ‘‘all is well’’ provided conflicts are disclosed, other commentators have pointed out that disclosure is not a sufficient remedy when commercial interests drive the process (including selection and interpretation of evidence) and conclusions of a guidelines panel. Merrill Goozner, director of the Integrity in Science Project at the Center for Science in the Public Interest, testified before the Institute of Medicine3 : ‘‘The system for reviewing the body of evidence in a field; deriving best practices through systematic reviews; writing clinical practice guidelines; conducting and evaluating comparative research; and, vitally important, evaluating evidence for regulatory purposes should be entirely free from conflicts of interest.’’ Goozner emphasises the need to maintain strong boundaries between those who determine how medicine is practised and researchers who conduct industry-funded research. The most influential members of the IDSA guidelines panel had commercial interests related to Lyme vaccines, diagnostic tests, and insurance consulting (table 1 and appendix A). Some of the panellists had been involved in the development of the first Lyme vaccine and had run clinical trials for the vaccine, which was withdrawn from the market after patients reported serious arthritic and neurological side effects.4 Several panellists had been sued as part of a class action lawsuit or served as expert witnesses for the vaccine manufacturer, and some are working on the second generation of Lyme vaccines, which are still under development. Some panellists acknowledged that they owned or had interests in Lyme diagnostic tests or consulted for insurers. The panel was composed of researchers who supported each other’s work and who controlled enormous amounts of government funding for research. These conflicts are disclosed by key panel members themselves in their own publications or statements to the press (table 1 and appendix 1). Commercial conflicts of interest on guidelines panels is a growing problem in healthcare because panellists may no longer hold the interests of the patient paramount, and the guidelines may determine the medical standard of care for patient treatment. When commercial interests drive the train, patient concerns take a backseat. The New York Times reported on a guidelines panel for blood pressure that reduced the threshold level at which patients should receive medication.11 It turned out that many of the panellists on the hypertension panel had links to the drug companies that produced antihypertensive medications. These manufacturers stood to gain from disease definitions that expanded the size of their commercial market and increased sales. Many doctors believe that they can rise above commercial conflicts of interest, but common sense tells us otherwise. Put a little bit of money in the game and the nature of the debate simply changes. The IDSA has said that it was not exclusionary in its panel selection and that it listened to competing points of view. This is not true. The association rejected out of hand requests for a seat at the table by patient groups, doctors’ organisations and individual treating doctors—even those who were IDSA members. In its previous guidelines panel, IDSA summarily tossed off the panel one researcher who disagreed with the panel chair on the best approach for treatment of chronic Lyme disease. Dr Gary Wormser, who chaired the Lyme guidelines panel, scoffs at the notion that commercial interests could have played a role in the development process12: Table 1 Summary of disclosed conflicts of interest by five key guideline panel members Author Conflict Source G Wormser Lyme diagnostic tests (Immunetics, Bio-Rad, Biopeptides, Diaspex, Abbott Laboratories) Self-disclosure, IDSA Guidelines 20065 Self-disclosure, New England Journal of Medicine 20076 Lyme vaccines (Baxter, AstraZeneca, Biopeptides) Expert witness for medical malpractice involving Lyme disease R Dattwyler Lyme diagnostic tests (Biopeptides and Baxter) Self-disclosure, IDSA Guidelines 2006 Lyme vaccines (Baxter, Biopeptides) Self-disclosure, BMJ Lyme Wars 20077 US patent 7008625 Recombinant Constructs of Bb Self-disclosure, see individual patents listed in conflict column Provisional patent 60/812,595 on a live ‘‘bacterial vaccine’’, PCT/US2005/023106 ‘‘oral vaccine for Borrelia’’, a wildlife vaccine Brook Technologies Release8 Provisional patent 60/799,016, ‘‘Peptide Diagnostic Agent for Lyme’’ Expert witness for medical malpractice involving Lyme disease E Shapiro Vaccines: Sanofi-Aventis, NIH Grants K24RR022477, KL2RR024138, and UL1RR024139. Self-disclosure, IDSA Guidelines 2006 Self-disclosure, New England Journal of Medicine 2007 Expert testimony: medical malpractice and unprofessional conduct actions Self-disclosure, American Academy of Neurology 20079 Insurance: reviews Lyme disease disability claims for Metropolitan Life Insurance A Steere Lyme vaccines (Baxter, GlaxoSmithKline) Self-disclosure, IDSA Guidelines 2006 Lyme diagnostic tests (Viramed) Self-disclosure, Nature 200610 J Halperin Vaccines: serves as an expert witness on behalf of Lymerix (GlaxoSmithKline) in litigation regarding adverse effects from first generation vaccines (ongoing) Self-disclosure, IDSA Guidelines 2006 Clinical ethics 284 J Med Ethics 2009;35:283–288. doi:10.1136/jme.2008.026526 ‘‘There’s no potential financial gain for generic drugs that are recommended for short courses. It’s inconceivable that anyone would think so. To me it seems disingenuous to make these allegations when they are so absurd.’’ In Wormser’s view, because the panel members were not promoting drugs for treatment there could be no conflict of interest. People are used to thinking about conflicts of interest in terms of drugs used for treatment, but the arena is much broader than that. There is tremendous financial gain in Lyme disease through vaccines, diagnostic tests and consulting with insurance companies. The IDSA guidelines restrict the definition of the disease and mandate laboratory testing. Guidelines that restrict the disease definition are favourable to vaccine manufacturers because they increase the effective rate for the vaccines so that fewer people taking the vaccine ‘‘get’’ the disease. Guidelines that mandate testing for disease diagnosis promote the interests of those who develop and manufacture diagnostic tests. Guidelines that deny treatment to patients are favourable to insurance companies and those who are paid to consult with them. The IDSA Lyme guidelines panel members had commercial interests in each of these areas.
CENTRALISED MEDICINE REDUCES CHOICE FOR PATIENTS AND LIMITS THE DOCTOR’S ABILITY TO USE CLINICAL JUDGEMENT
The increased concentration and centralisation of power in medicine was also an important factor leading up to the antitrust investigation. Twenty years ago, individual doctors had more autonomy than they do today in deciding whether to comply with medical guidelines. Medical malpractice and unprofessional conduct actions were always rooted in the standard of care, which was determined by the consensus of practising doctors, but guidelines became a vehicle for driving the standard of care. This transformed a very fluid environment where opinions in medical practice changed as individual doctors’ viewpoints changed based on new information from the latest medical conference or grand rounds, the success or failure in treating patients or the latest study read by the doctors. The opinions of individual panel members on guidelines panels of powerful medical societies became a proxy for the opinions of doctors in the broader community. With ‘‘evidencebased’’ guidelines, someone other than the treating doctors selects, interprets and makes recommendations regarding treatment. The problem arises when the ability of a doctor to select, interpret and exercise clinical judgement is replaced by an obligation to comply with guidelines that do not work or that are not appropriate for the individual patient. Population-based treatment approaches using average results leave individual patients who are not the ‘‘norm’’ out of the equation. This is why it is important to treat the patient rather than the disease, and why displacing the treating doctor’s judgement is risky business. Commercial interests, particularly those of insurers and drug manufacturers, see guidelines as a means of controlling medical costs or furthering vaccines, drugs or diagnostic tests. As a result, guidelines became part of the ‘‘one-stop shopping’’ marketing strategy of pharmaceutical companies and part of the cost-containment strategy of insurers. In addition to the role of commercial interests and conflicts of interest discussed above, an equally important issue is the shift of guidelines from a ‘‘suggestion’’ to a ‘‘mandated standard of care’’ that is intended to displace doctors’ autonomy with centralised medical decisions. Guidelines permit insurers to shift the emphasis from clinical judgement to a centralised, largely administrative function, with an emphasis on actuarially predictable population-based care. Dr David Eddy, senior adviser to Kaiser Permanente, notes that ‘‘if the fight to control health care costs is to be successful, it will have to address [the decisions physicians make about treatments].’’13 Guidelines are the mechanism for doing this. Specialty societies embrace treatment guidelines because these official protocols expand their sphere of influence in an insurance-driven environment. Specialty societies such as the IDSA are extremely insurance-conscious because the livelihood of their members hinges on the acceptability of their guidelines and the role their members play as ambassadors and enforcers of second opinion of those guidelines. According to Eddy, ‘‘[I]t would not be stretching things too far to say that whoever controls practice policies controls medicine.’’14 What this means is that if one can control the development of treatment guidelines and can obtain compliance from doctors, one can effectively control the way doctors practise medicine and also control costs. This is why insurers are driven by guidelines. Insurers control doctors’ practices through economic profiling that compels doctors within the insurer’s network to conform to guidelines or cost parameters on threat of termination from the network. Insurers control out-ofnetwork costs by refusing to reimburse claims for services that do not conform to guidelines. The government is the USA’s largest insurer through Medicare and this fact, plus the drive towards universal healthcare, has placed more emphasis on cost control through guidelines. The health insurance industry relies heavily on third party guidelines (such as the IDSA Lyme guidelines) to provide a shield against potential litigation as well as to control costs. Historically, health insurers have been held accountable for violations of the standard of care (just as doctors can be). However, when powerful third parties develop the guidelines, they can drive the standard of care. When large specialty societies drive the standard of care, no one is accountable for malpractice if these standards are ‘‘wrong’’. The specialty society does not have the individual physician–patient relationship that would create the duty of care necessary for malpractice, and the insurer is shielded because it is relying on an acceptable standard of care. In this case, the IDSA promulgates guidelines that the insurers rely on to justify denials of care, thereby reducing costs. When patients seek out a doctor who does not follow the IDSA guidelines, the insurers require a second opinion from an ‘‘infectious disease’’ expert, thereby creating a highly effective enforcement cycle for insurers using third party guideline developers. Guidelines by specialty societies provide a particularly effective means of controlling general medical practice. The same control issues apply to appeals of insurance denials through the ‘‘independent medical review’’ process sanctioned by most states. This review process assists insurers by having a third party review their claims. Some insurers who are not required by law to use the review process nevertheless elect to use this approach because it is an inexpensive way of disposing of claims as a practical matter without litigation or arbitration. There are only a handful of ‘‘independent review organisations’’ (IROs) used by the states that have adopted independent review processes. These organisations represent insurers as their bread and butter work and perform independent reviews on the side. While the internal processes of IROs are a black box (there is no transparency in their procedures), the general concept is that these organisations also rely on guidelines by third parties, Clinical ethics J Med Ethics 2009;35:283–288. doi:10.1136/jme.2008.026526 285 particularly the guidelines of a specialty society. As a result, specialty society guidelines have a large role in determining the care that may be provided, not only by members of their society but also by family doctors and internists. Insurers can also rely on these guidelines to police doctors within their networks, terminating the contracts of those who are not complying. Hospitals (which can operate like insurance providers these days) can use these guidelines to determine the care provided within the hospital and whether hospital privileges will be extended or revoked for doctors who do not follow the guidelines.
RESTRICTIVE GUIDELINES ARE VIEWED AS MANDATORY BY THE MEDICAL COMMUNITY
The guidelines published by the IDSA in November of 2006 were extremely restrictive and denied the use of clinical judgement in the diagnosis and treatment of Lyme disease. This is a critical point because when patients fail treatment under the IDSA guidelines (which restrict Lyme treatment to 30 days), they are given no alternative treatment. Doctors are essentially told to sit on their hands and let the patients experience a disability that is equivalent to that of congestive heart failure—with no treatment offered. Doctors are told that they must ignore their clinical experience and ignore the patient’s history, course of treatment and past responsiveness to medication. It is the exclusion of treatment options and denial of the doctor’s right to use clinical judgement that makes the guidelines so restrictive. Add the fact that IDSA is so powerful in the medical community and that its opinions are given the force of law by medical boards and insurers and one has all of the ingredients necessary to deny patients with chronic Lyme disease any treatment whatsoever. The IDSA’s role in instigating and testifying at unprofessional conduct hearings and in supporting insurance denials of care makes compliance with its guidelines mandatory. This enforcement deters doctors who might otherwise treat patients with chronic Lyme disease from doing so.
THE ATTORNEY GENERAL’S INVESTIGATION
Findings of the investigation The Attorney General found that the IDSA Lyme guidelines panel, which was hand-picked by Dr G Wormser, had important conflicts of interest, intentionally blocked the appointment of panel members with divergent viewpoints, and intentionally excluded evidence that was not in conformity with the bias of the panel15: ‘‘The IDSA’s guideline panel improperly ignored or minimized consideration of alternative medical opinion and evidence regarding chronic Lyme disease, potentially raising serious questions about whether the recommendations reflected all relevant science’’. Some of the specific findings were: c Dr Wormser, the panel chair was selected inappropriately, ‘‘held a bias regarding the existence of chronic Lyme’’ and ‘‘handpick[ed] a likeminded panel without scrutiny by or formal approval of the IDSA’s oversight committee’’. c The IDSA panel members had financial interests—‘‘in drug companies, Lyme disease diagnostic tests, patents and consulting arrangements with insurance companies’’ The IDSA failed to conduct a conflicts of interest review for any of the panellists, several of whom had conflicts of interests. c The IDSA’s 2000 and 2006 Lyme disease panels refused to accept or meaningfully consider information regarding the existence of chronic Lyme disease. c The IDSA blocked appointment of scientists and doctors 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. c The IDSA portrayed the American Association of Neurology copycat 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.16 The settlement The settlement is a process—essentially a reassessment of the guidelines by a panel free of conflicts—with safeguards to ensure that evidence and opinions are not suppressed The Attorney General has always been clear that his role is not to make medical judgements or to trump science. Instead, his role is to make sure that the development process is fair, non-exclusionary, and not tainted by conflicts of interest. According to the Attorney General’s findings,15 the IDSA panel members had important conflicts: ‘‘The IDSA’s 2006 Lyme disease guideline panel undercut its credibility by allowing individuals with financial interests—in drug companies, Lyme disease diagnostic tests, patents and consulting arrangements with insurance companies—to exclude divergent medical evidence and opinion.’’ The IDSA settlement establishes a model to redress these conflicts of interest and the consequent suppression of scientific evidence and patient treatment options. The settlement requires the IDSA to reconvene a new Lyme treatment guidelines panel made up of conflict-free panellists under the auspices of an ethicist, to hold a public hearing and to review all recommendations of the guidelines. Panellists from the original guidelines panel are precluded from sitting on this new panel. The Attorney General’s press release concerning the settlement highlights important findings of impropriety on the part of IDSA and forces the organisation to re-examine its guidelines in a public forum (aired live over the Internet) using an open scientific hearing that will consider evidence from a broad spectrum of science. All panelists will be screened for potential conflicts of interest by Dr Howard Brody, a medical ethicist specialising in such conflicts.
SETTLEMENT PROCESS PHASES
While no overall timetable is specified, it seems likely that the settlement process will take 6–12 months. The settlement has three phases: c the selection of the chair and the panel; c the internal collection of scientific evidence and call for submissions of scientific evidence from the public; c the public hearing of the evidence, which will be aired live on the Internet. The settlement stipulates that IDSA must set up a panel of 8– 12 members (including the chair) ‘‘who, as a group, reflect a balanced variety of perspectives and experience across a broad range of relevant disciplines, ranging from clinical experience in treating patients with Lyme disease to experience in investigating the best methods to diagnose and treat Lyme disease or other infectious diseases’’ to review the recommendations in its guidelines.15 Clinical ethics 286 J Med Ethics 2009;35:283–288. doi:10.1136/jme.2008.026526 Selection of the chair The chair of the panel is critically important because this person and the IDSA Standards and Practice Guidelines Committee will select the panel members from the pool of applicants. The chair will be selected in an open process—meaning any qualified individual can apply—by the IDSA Standards and Practice Guidelines Committee. The IDSA will post an announcement on its website encouraging qualified doctors or researchers to apply. Those who apply for the chair may also be considered for panel member positions. In addition to the requirements to be on the panel, the chair must: c be trained in infectious disease; c not have published a point of view on Lyme disease; c be knowledgeable on Lyme disease but not necessarily an expert; c have experience in the review and interpretation of the medical scientific literature; c have known abilities to: – complete a task in a timely manner; – consider varying points of view; – bring groups of individuals to consensus. Selection of the panel The panel will be selected by the chair and the Standards and Practice Guidelines Committee. This too will be through an open process with IDSA posting an announcement on its website soliciting applicants. IDSA is required to give ‘‘fair consideration to all reasonable applicants’’. A prospective panel member cannot have previously served on a Lyme guidelines panel, must be free of conflicts of interest, must be a doctor or a researcher, and need not be a member of the IDSA. All panellists will be screened for potential conflicts of interest by Dr Brody, the independent medical ethicist. The panel members selected must as a group15: ‘‘reflect a balanced variety of perspectives and experience across a broad range of relevant disciplines, ranging from clinical experience in treating patients with Lyme disease to experience in investigating the best methods to diagnose and treat Lyme disease or other infectious diseases.’’ Evidence selection The settlement agreement provides for an internal collection of evidence by the IDSA staff and provides a 60-day window for people who are not on the panel to submit scientific studies for review by the panel. The IDSA must post an announcement calling for submissions of evidence by individuals and organisations. The evidence submitted must be distributed to and considered by the guidelines panel. Public presentations and hearing Following the collection and review of scientific evidence, those who want to present evidence to the panel are invited to apply. Any stakeholder may apply to make a presentation, although preference will be given to researchers and doctors. The panel will work with the medical ethicist and the Connecticut Attorney General’s office to finalise the list of presenters and must reserve time for divergent opinions. Presenters must disclose conflicts of interest, but the conflicts will not preclude the presenter from participating. Once the presenters have been selected, there will be a public hearing of the presentations that will be aired live over the Internet. The presenters will identify specific recommendations of the IDSA guidelines that they take issue with and will present the scientific evidence opposing the recommendation. Panel determinations The panel will make a determination whether each recommendation contested ‘‘is medically sound in light of all of the evidence and information provided’’.15 Each determination will require a 75% supermajority vote of the panel members (9/12, if the panel comprises 12 members). So, if the recommendation that a tick bite not be treated is contested, for example, a supermajority of the panel would need to vote in favour of the original recommendation for it to stand. Once each of the contested recommendations has been reviewed, the panel will determine whether the guidelines need to be revised in whole, in part, or not at all. If the guidelines need to be revised, then the new treatment recommendations will also be subject to the 75% voting requirement. The notion here is that a ‘‘consensus’’ of the panel is 75%, and all determinations require a consensus.