Re: Controlled trial ABX persistant lyme

From: A_Weisman (a_weisman_at_yahoo.com)
Date: 07/08/04 

Date: 7 Jul 2004 22:16:19 -0700

derdrittemann2003@yahoo.com (derdrittemann) wrote in message derdrittemann2003@yahoo.com (derdrittemann) wrote in message news:<f2af2263.0407070622.5531f228@posting.google.com>...
 
> I have not seen the study since its original publication...but it was
> my recollection that the largest single group at the time the study
> was prematurely terminated was the group that was taking
> antibiotics...and reported that they were doing better. (Although the
> numerical differences were slight...the study was ceased on the basis
> that the percentage difference could not approach statistical
> signifigance...which is somewhat misleading in and of itself...given
> the very samll numbers).

I don't understand WHY the DSMB halted the study. It makes no sense to
me. The only reason is that people didn't seem to be doing better on
abx than placebo. But isn't that the point of the study? DIdn't people
know going in that this could be the result? And didn't they consent
to this experiment on those terms?

It isn't as if everyone on abx was getting better and it would be
cruel to withhold a treatment of obvious efficacy.

It isn't as if there were serious unanticipated adverse events.

So why stop this study before conclusion?

This is NOT what the DSMB usually does.

I really don't get it.

But also I'm going to post full text. The truth was that an equal
number were improving or having no change in both studies (37/29 in
one and 40/26 in the other and the number worsening was identical). So
the truth is that an equal amount were worsening with or without the
antibiotics so how did that put people at risk? and total number (56%)
were having either a benign or positive result. So why halt the study?
No one was being hurt and certainly the study was not producing
anything unanticipated or severe in terms of adverse reactions. So
what was the harm? Anything happening was expected and thus by
definition within acceptable limits. Nothing cruel. No violation of
Nuremberg principles or medical or scientific ethics.

So what gives?

Relevant excerpt of article/summary in professional journal:

==============================================================================
An interim data analysis planned into the design of the trials was
carried out last November by a Data and Safety Monitoring Board
(DSMB), an independent group of doctors and researchers. The DSMB
unanimously recommended that NIAID stop the treatment arm of both
trials because the data showed no significant difference in the
percentage of patients who received either antibiotic treatment or
placebo who felt their symptoms had improved, worsened, or stayed the
same -- a little more than one-third felt better, about one-third felt
worse, and slightly less than one-third felt the same. The DSMB's
review suggested that even with continued accrual of another 131
patients, the number needed to reach full enrollment, there was only a
slight chance difference between the antibiotic treatment and placebo
groups would e found. NIAID agreed with the DSMB's recommendation, as
well as heir recommendation that the investigators continue to follow
the patients to monitor them for safety and to learn more about
possible causes of chronic Lyme disease.

Medical Laboratory Observer: Chronic Lyme disease symptoms not helped
by intensive antibiotic treatment - Brief Article
http://www.findarticles.com/p/articles/mi_m3230/is_8_33/ai_78057528

Chronic Lyme disease symptoms not helped by intensive antibiotic
treatment - Brief ArticleSymptoms of patients with a stubborn form of
Lyme disease are not relieved by an intensive course of antibiotics,
recent studies have shown.

According to the National Institutes of Health, results of the first
randomized, placebo-controlled, double-blind trials testing
antibiotics in patients with a stubborn form of Lyme disease -- those
whose symptoms persist after standard courses of antibiotics --
validate that these patients suffer significant pain and other
disabling symptoms. The two trials found, however, that a 90-day
course of intravenous and oral antibiotics was no better than placebo
at improving these chronic symptoms.

Because of their potential importance to Lyme disease treatment, the
New England Journal of Medicine has published these findings online at
http://www.nejm.org, and the report appeared in the July 12 print
edition of the journal. The studies were funded by a National
Institute of Allergy and Infectious Diseases (NIAID) contract to Mark
S. Klempner, MD, of Boston University School of Medicine.

"Our results suggest that we need to define the cause or causes of the
debilitating, persisting symptoms experienced by some patients with
Lyme disease. Understanding the origin of these symptoms should lead
to more effective therapeutic approaches to ameliorate these symptoms,
said Klempner. "Based on experience with other chronic infectious
diseases caused by persisting bacteria -- syphilis, tuberculosis, and
ulcers, for example -- we think it is unlikely that a longer course of
treatment or different antibiotic combination would result in greater
improvement than what we found in these studies."

Significantly, more than 700 different blood and cerebrospinal fluid
samples were collected from the study volunteers. None of the samples
showed evidence of persistent infection with the Lyme agent, Borrelia
burgdorferi. This suggests, Klempner said, that researchers should
investigate autoimmune and other processes to determine whether they
play a role in a least some of the symptoms of chronic Lyme disease.
The trials were carried out by primary investigators and their staffs
at three centers: New England Medical Center in Boston (Klempner's
former affiliation); New York Medical College in Valhalla (Arthur
Weinstein, MD); and Yale-New Haven Hospital in Connecticut (Janine
Evans, MD) Volunteers were recruited through hundreds of screening
clinics set up in schools, hospitals, and town halls located in these
areas where Lyme disease is highly endemic.

A total of 129 volunteers enrolled in the two studies. All
participants had well-documented Lyme disease and had previously
received at least one course of recommended antibiotics. Despite prior
antibiotic treatment, the volunteers currently suffered from
persisting muscle or joint pains and complained of memory and thinking
problems, often associated with fatigue.

Although both trials were identical in design, one trial enrolled 78
chronic Lyme disease patients who tested positive for antibodies to
the Lyme bacterium, while the other trial enrolled 51 people with
chronic symptoms but no evidence of antibodies.

In each study, volunteers were assigned at random to receive either
antibiotic treatment or an inactive placebo. Treatment consisted of
intravenous ceftriaxone, 2 grams daily, for 30 days, followed by oral
doxycycline, 200 milligrams daily, for 60 days. The investigators
evaluated symptom improvement based on the patients' responses to a
health-related quality-of-life questionnaire given 90 days after they
completed the course of antibiotic treatment or placebo.

An interim data analysis planned into the design of the trials was
carried out last November by a Data and Safety Monitoring Board
(DSMB), an independent group of doctors and researchers. The DSMB
unanimously recommended that NIAID stop the treatment arm of both
trials because the data showed no significant difference in the
percentage of patients who received either antibiotic treatment or
placebo who felt their symptoms had improved, worsened, or stayed the
same -- a little more than one-third felt better, about one-third felt
worse, and slightly less than one-third felt the same. The DSMB's
review suggested that even with continued accrual of another 131
patients, the number needed to reach full enrollment, there was only a
slight chance difference between the antibiotic treatment and placebo
groups would e found. NIAID agreed with the DSMB's recommendation, as
well as heir recommendation that the investigators continue to follow
the patients to monitor them for safety and to learn more about
possible cau ses f chronic Lyme disease.

"Although we still have much to learn," said Klempner, "we know much
more about chronic Lyme disease now than we did when these studies
began." Besides the information obtained about the efficacy of
intensive antibiotic treatment, the investigators found that the
impact of Lyme disease on physical health was at least equal to the
disability of patients with congestive heart failure and
osteoarthritis. Some patients were also found to have cognitive
impairment.

"The antibiotic treatment component is only one piece of NIAID's
comprehensive clinical studies on chronic Lyme disease," added Phillip
J. Baker, Ph.D., who oversees NIAID's Lyme disease program. "These
studies have yielded a considerable amount of new information. We
intend to characterize the patients enrolled in the study as
thoroughly as possible to learn more about the mechanisms involved in
chronic Lyme disease," Baker added. "The knowledge obtained from such
studies should be of immense value in developing new, more promising
approaches for treating this disease."

Reference

MS Klempner, et al. Two controlled trials of antibiotic treatment in
patients with persistent symptoms and a history of Lyme disease. New
England Journal of Medicine vol. 345(2), July 12, 2001.

--Source: NIAID, a component of the National Institutes of Health,
U.S. Department of Health and Human Services.

Relevant Pages

  • Re: Controlled trial ABX persistant lyme
    ... patients, the number needed to reach full enrollment, there was only a ... slight chance difference between the antibiotic treatment and placebo ... Chronic Lyme disease symptoms not helped by intensive antibiotic ...
    (sci.med.diseases.lyme)
  • Re: Controlled trial ABX persistant lyme
    ... patients, the number needed to reach full enrollment, there was only a ... slight chance difference between the antibiotic treatment and placebo ... Chronic Lyme disease symptoms not helped by intensive antibiotic ...
    (sci.med.diseases.lyme)
  • Re: Controlled trial ABX persistant lyme
    ... patients, the number needed to reach full enrollment, there was only a ... slight chance difference between the antibiotic treatment and placebo ... Chronic Lyme disease symptoms not helped by intensive antibiotic ...
    (sci.med.diseases.lyme)
  • Re: Controlled trial ABX persistant lyme
    ... patients, the number needed to reach full enrollment, there was only a ... slight chance difference between the antibiotic treatment and placebo ... Chronic Lyme disease symptoms not helped by intensive antibiotic ...
    (sci.med.diseases.lyme)
  • Re: Controlled trial ABX persistant lyme
    ... patients, the number needed to reach full enrollment, there was only a ... slight chance difference between the antibiotic treatment and placebo ... Chronic Lyme disease symptoms not helped by intensive antibiotic ...
    (sci.med.diseases.lyme)
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