Madam Speaker, as chair of the congressional Lyme Disease Caucus and a person who has been closely involved in Lyme disease issues for over twenty years, I want to bring to your attention extremely troubling issues regarding Lyme disease.…
Madam Speaker, as chair of the congressional Lyme Disease Caucus and a person who has been closely involved in Lyme disease issues for over twenty years, I want to bring to your attention extremely troubling issues regarding Lyme disease.
Lyme disease is the most common of all vector-borne infections in the U.S., with approximately 290,000 new cases in 2008. With the increase in Lyme cases, problems due to poor diagnostics and ineffective treatments for Lyme disease have become almost overwhelming--affecting larger numbers of people over longer periods of time.
Many patients are angry because progress in addressing Lyme disease has been impeded by entrenched bias and a lack of accountability in the science of tick borne diseases. It is critical that we identify biases and impediments that are constraining the science on Lyme and to open up the dialogue to honest and transparent debate. The scientists who have long been marginalized, the treating physicians who have felt intimidated and threatened, and most importantly the sick patients and their families need our help.
My main purpose here today is to introduce for inclusion in the Congressional Record the following statement ``The Patient Perspectives on the Research Gaps in Tick Borne Diseases,'' written by three of the Nation's largest Lyme disease advocacy organizations, who represent tens of thousands of patients. I believe that this statement provides important perspectives that need to be heard and taken to heart.
Patient Perspectives on the Research Gaps in Tick Borne Diseases
(Submitted by Time for Lyme, the national Lyme Disease Association, and
the California Lyme Disease Association on behalf of our patients
across the United States)
In December 2009, Labor HHS 2010 appropriations language,
signed into law by President Obama, encouraged the National
Institutes of Health (NIH) to ``sponsor a scientific
conference on Lyme and tick-borne diseases . . . the
conference should represent the broad spectrum of scientific
views . . . and should provide a forum for public
participation and input from individuals with Lyme disease.''
The language also requires NIH to identify research gaps to
understand the ``mechanisms of persistent infection.'' The
passage of this language represents a significant opportunity
to summarize and solidify the issues that prevent scientific
progress for a disease recognized here for 35 years, if, and
only if, this process occurs without bias. Progress can be
accomplished if the stewards commit to the elimination of
predisposition by key decision makers.
It is not clear why the NIH elected to subcontract this
issue to the Institute of Medicine (IOM), given that the
existing NIH conference structure contains the best process
to address the appropriations language requirements.
According to the NIH Consensus Development Program, which
explains the two relevant types of conferences offered by
NIH, ``when the available evidence is weak or contradictory,
or when a common practice is not supported by high-quality
evidence, the State-of-the-Science label is chosen.'' This
conference format would appropriately address the research
gaps that exist for Lyme and tick-borne diseases as it
provides a ``snapshot in time'' of the state of knowledge on
the conference rather than a policy statement of the NIH or
the Federal Government.
In Lyme disease, there are two distinct disease paradigms,
each providing science to support its claims. One paradigm
views the disease as ``hard to catch and easy to cure'' and
denies the existence of chronic Lyme disease--persistent
infection with Borrelia burgdorferi, the spirochete that
causes the disease. Under this paradigm, the state of the
science for patients with chronic Lyme disease is closed. Any
treatment is considered too risky because practitioners are
unable to determine the cause or extent of patient symptoms,
or they view the symptoms
as insignificant and write off the patients' complaints as
psychiatric in nature. This leaves seriously ill patients
without any viable therapeutic avenues. It also shuts the
door on future research necessary to get patients to a state
of wellness.
The alternative paradigm says that the science is too
unsettled to be definitive and there can be one or more
causes of persistent symptoms after initial treatment in an
individual who has been infected with the agent of Lyme
disease. These causes include the possibility of persistent
infection, or a post-infectious process, or a combination of
both, with the Lyme bacterium itself driving the autoimmune
process. This paradigm allows doctors the ability to exercise
their clinical judgment and provide therapies that are
helping their patients.
Patients with Lyme disease need a research agenda that
reflects outcomes that matter to patients, namely effective
diagnostic tools and effective treatments that restore them
to health. The reason there are two disease paradigms in Lyme
disease is because central pieces of the puzzle are missing
or are inadequate. The first area of concern involves
testing.
There are no reliable biomarkers of the disease.\1\ Current
diagnostic tests commonly used do not detect the spirochete
that causes Lyme disease, rather, they detect only whether
the patient has developed antibodies to the pathogen.
Antibody production, if it registers on the tests at all,
takes weeks to appear, thus rendering the current tests
ineffective in the earlier and more easily addressed stage.
Additionally, the Lyme antibody has been shown to form a
``complex'' with the bacterium itself--and tests cannot
detect ``complex'' antibodies. Once triggered, antibody
reactions may remain long after an infection has been
treated, also clouding the diagnostic and treatment picture.
The two-tier testing system endorsed by the Centers for
Disease Control and Prevention (CDC) is very specific for
Lyme disease (99%), so it gives few false positives. But the
tests have a uniformly low sensitivity (56%)--missing 88 of
every 200 patients with Lyme disease. By comparison, AIDS
tests have a sensitivity of 99.5%--missing only one of every
200 infected patients.\2\ Sensitive AIDS tests were developed
less than 10 years into the disease, while archaic Lyme tests
remain unreliable 35 years later. There is a critical need
for research exploring newer technologies such as polymerase
chain reaction (PCR), which is used with many other diseases,
and cutting-edge proteomics. Strain variations and co-
infections with other organisms, often transmitted by the
same tick bite, obscure the diagnostic picture further.
A vast number of strains of Borrelia burgdorferi have been
identified. Variation in strain may cause differing symptoms
or severity of symptoms as well as determine the appropriate
antibiotics and duration of treatment needed to clear the
infection.\3\ Different strains may also express different
proteins. Preliminary research shows that proteins need to be
examined to find the ones most often expressed, then using
microarray technology, doctors may be able to diagnose
patients using a chip which contains the proteins.
Research is needed concerning the role of mutation on
persistence. Some research indicates that bacteria can
exchange genetic material, probably contributing to its
ability to invade different systems in the body--some may
have a proclivity for the heart muscle, others for the brain,
and some for muscles and joints. By exchanging genetic
material, bacteria may be able to form a symbiotic
relationship to avoid detection by the immune response or to
further invade the body.
To date, every NIH-funded treatment research study has been
designed using the inaccurate diagnostic test results as part
of the entry criteria. The entry criterion in these studies
excluded the vast majority of Lyme patients and created
sample sizes too small (less than 220 patients to date) to
detect clinically important treatment effects or generalize
to the clinical population. Moreover, Lyme has not attracted
industry funding for treatment approaches, which places the
disease at a considerable research disadvantage. To detect
clinically relevant treatment effects requires much larger
treatment trials with sample populations that reflect those
seen in clinical practice.\4\
One thing that past research has demonstrated is that
patients with Lyme are a heterogeneous population. Hence, the
course of illness and responsiveness to treatment may vary
depending on the duration of onset of the disease to its
diagnosis and treatment, the presence of co-infections,
comorbid factors, other genetic characteristics of the
patients, and the virulence of the strain(s) with which
the patient is infected. Research sample populations must
reflect those seen in clinical practice to yield
clinically relevant results.
As advised by the Appropriations language, research on the
pathophysiology of Lyme disease is necessary. Research
projects need to be designed which determine the course of
the disease from inception, and which utilize treatments that
effectively interfere with the mechanisms that allow the
infection to persist. Little to no government sponsored
science has been dedicated to the effects on persistence of
the different forms of the Lyme bacterium (cyst vs.
flagellar), the role, if any, of biofilms, sequestration of
the organism from the immune system, the exchange and
mutation of genetic material of the spirochete, and the role
that components of the bacterial genome may play in
protecting it from eradication by the immune system or
antibiotics. Understanding the pathology of the organism can
greatly enhance targeted diagnostics and treatment
modalities.
Patients also need studies that explore a range of
treatment options. The ideal antibiotics, route of
administration, and duration of treatment for any stage of
Lyme disease are not established. No single antibiotic or
combination of antibiotics appears to be capable of
completely eradicating the infection in all patients, and
treatment failures or relapses are reported with all current
regimens, although they are less common with early aggressive
treatment.\5\ Treatment failure rates suggest the need to re-
examine the effectiveness of the currently recommended
monotherapy as a treatment approach. Studies need to explore
combination treatments and longer term treatment regimens,
which have been critical to the successful treatment of AIDS
and tuberculosis.
Patients need the type of outcomes research advocated by
the IOM to examine how well treatments are working in actual
clinical practice.\6\ While not all patients with chronic
Lyme disease have returned to a state of wellness, many have,
and we need to find out how and why. This information can
then be applied to other patients and used to establish a
research agenda for treatment that has a likelihood of
success, rather than abandoning patients based on limited
treatment trials.
The IOM process does not allow these research ideas to be
heard in an unbiased and transparent fashion with balanced
divergent viewpoints. While the NIH process precludes bias on
the part of panel members, the IOM does not. Four of the six
members of the IOM panel that have been selected belong to
IDSA, a medical society that has a known bias against chronic
Lyme disease diagnosis and treatment. Rather than providing
curative treatments that restore health, the IDSA would
provide costly and long term palliative treatments,
presumably for life. While the NIH requires participation by
major stakeholders (including patients and treating
physicians), the IOM does not.
The summary of the IOM proceedings will reflect this
pervasive lack of objectivity, undermining its integrity and
credibility. Additionally, much IOM deliberation is done
behind closed doors and an anonymous panel will be permitted
to comment on the written record. Because of such flaws in
the IOM proceedings, the three largest patient interest
groups who were offered a brief opportunity to speak (TFL) at
the IOM October 2010 meeting and an opportunity to provide a
commissioned paper--CALDA, the LDA and TFL--pulled out of the
conference in protest.
From a research perspective, strongly held paradigms can
create a closed loop, and experiments may be designed,
implemented and interpreted to support a particular
viewpoint.\7\ The antidote to bias is to balance scientific
perspectives and to ensure that all scientific viewpoints are
being heard and explored. Given the extraordinary stream of
federal funding granted to researchers who support the closed
paradigm which was created and is supported by the Infectious
Diseases Society of America (IDSA) and their vested interest
in maintaining the status quo, it is not reasonable to expect
this group of researchers to serve as neutral arbiters of
scientific debates over competing scientific paradigms. For
example, Lyme related panels dominated by IDSA have time and
time again excluded opposing viewpoints from participating or
controlled the review process to ensure outcomes that
reinforce the IDSA paradigm. If past is prologue, it is
obvious what the future holds for panels dominated by one
group.
Worse, the small treatment trials that have been conducted
have been given an undue amount of weight by IDSA researchers
and in its guidelines and used to apply a degree of certainty
on the science that far exceeds the limitations of the small
sample sizes of the studies. Further, they claim that the
state of the science is sufficient to determine with
certainty that chronic Lyme disease does not exist, is not
treatable with antibiotics, and that no further research on
this topic is needed. Sample size affects the strength of the
conclusions that may be drawn from them: ``Providing
definitive answers in the face of low event rates and small-
to-moderate treatment effects necessitates sample sizes in
the thousands or tens of thousands. . . . Funding for such
mega-trials is very limited, and is often restricted to
industry sources.'' \8\
For that reason, the Connecticut Attorney General antitrust
investigation into the development process of IDSA Lyme
guidelines found exclusionary practices and suppression of
divergent viewpoints on the part of IDSA panels that crafted
IDSA 2000 and the 2006 Lyme disease guidelines. Although IDSA
settled the investigation with the Attorney General by
agreeing to review its guidelines with a panel without
conflicts of interest, the control of the process was in the
hands of IDSA, which again selected a panel consisting almost
exclusively of IDSA members and excluding treating physicians
who held divergent viewpoints.
It was patients who pressed for the language in the
Appropriations bill that called for a review of the state of
the science of Lyme disease. However, patients need that
process to occur in a transparent manner, without bias, and
with the participation of all stakeholders. Albert Einstein
defined insanity as ``doing the same thing over and over
again and expecting different results.''
This process is a perfect example of that insanity.
Patients want research which will restore their health.
Their voice and the voice of the clinicians must be given the
necessary weight to legitimize the research agenda and the
research process. Truth in science can be achieved through
open debate in an independent process free from bias and
conflicts of interest. The scientific process fails when one
side of a debate controls the arena and sets the rules to
ensure that its viewpoint prevails.
Lorraine Johnson, JD, MBA, Chief Executive Officer,
California Lyme Disease Association.
Patricia V. Smith, President, Lyme Disease Association,
Inc.
Diane Blanchard/Deb Siciliano, Co-Presidents, Time for
Lyme, Inc.