(Complimentary Newsletter from Target Health Inc.)
(Complimentary Newsletter from Target Health Inc.)
9 November 2003
I. WHAT'S NEW?
Combination
Products
II. HISTORY OF MEDICINE
A Gladiator's Blood as a Cure For Epilepsy
III. CARDIOLOGY
Recombinant ApoA-I
Milano/Phospholipid Complexes on Atheroma Burden in Acute Coronary Syndromes
(ACS)
IV. IMMUNOLOGY
Development of
Autoantibodies Before the Clinical Onset of Systemic Lupus
Erythematosus
V. NEUROLOGY
Exercise Plus Behavioral Management in Patients With
Alzheimer Disease
VI. INFECTIOUS DISEASES
Transfusion Malaria
VII. FDA
Pharmacogenomics - A New FDA
Guidance
DIA Annual Meeting
Target Health will again be attending the annual meeting of the DIA this coming June. At the meeting, we will be exhibiting our expertise in drug and device development, our second generation Internet-based clinical trial system, Target II, and our clinical trial document system. Let us know if you will be attending as we will be arranging personalized demonstrations for senior management and key decision makers. For more information, please contact Dr. Jules T. Mitchel (julesmitchel@targethealth.com).
A Gladiator's Blood as a Cure For Epilepsy
Between the first and the sixth century a single theologian and several medical
authors reported that the consumption of a gladiator's blood or liver could
cure epilepsy. The origins of the sacred or apoplectic properties of blood of
a slain gladiator, likely lie in Etruscan funeral rites. Although the influence
of this religious background faded during the Roman Republic, the magical use
of gladiators' blood continued for centuries. After the prohibition of gladiatorial
combat in about 400 AD, an executed individual (particularly had he been beheaded)
and his blood, became the "legitimate" successor to that of the gladiator. Occasional
indications in early modern textbooks on medicine as well as reports in the
popular literature of the 19th and early 20th century document the existence
of this ancient magical practice, even into modern times. Spontaneous recovery
of some forms of epilepsy may be responsible for the illusion of therapeutic
effectiveness and for the confirming statements by physicians who have commented
on this cure.
III. CARDIOLOGY
Recombinant ApoA-I Milano/Phospholipid Complexes on Atheroma Burden in Acute Coronary Syndromes (ACS)
ApoA-I Milano is a variant of apolipoprotein A-I identified in individuals in rural Italy who exhibit very low levels of HDL. Infusion of recombinant ApoA-I Milano-phospholipid complexes produces rapid regression of atherosclerosis in animal models. Although low levels of high-density lipoprotein cholesterol (HDL-C) increase risk for coronary disease, no data exist regarding potential benefits of administration of HDL-C or an HDL mimetic. As a result, a study published in the Journal of the American Medical Association (2003;290:2292-2300), was performed to assess the effect of intravenous recombinant ApoA-I Milano/phospholipid complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes (ACS). The study was a double-blind, randomized, placebo-controlled multicenter pilot trial comparing the effect of ETC-216 or placebo on coronary atheroma burden measured by intravascular ultrasound (IVUS). Between November 2001 and March 2003, 123 patients aged 38 to 82 years consented, 57 were randomly assigned, and 47 completed the protocol. In a ratio of 1:2:2, patients received 5 weekly infusions of placebo or ETC-216 at 15 mg/kg or 45 mg/kg. Intravascular ultrasound was performed within 2 weeks following ACS and repeated after 5 weekly treatments. The main outcome measure was the change in percent atheroma volume (follow-up minus baseline) in the combined ETC-216 cohort. Prespecified secondary efficacy measures included the change in total atheroma volume and average maximal atheroma thickness. Results showed that the mean (SD) percent atheroma volume decreased by -1.06% (3.17%) in the combined ETC-216 group (P = .02 compared with baseline). In the placebo group, mean (SD) percent atheroma volume increased by 0.14% (P = .97 compared with baseline). The absolute reduction in atheroma volume in the combined treatment groups was -14.1 mm3 or a 4.2% decrease from baseline (P<.001). The authors concluded that recombinant ApoA-I Milano/phospholipid complex (ETC-216) administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS. While the results are promising, they will require confirmation in larger clinical trials with morbidity and mortality end points.
Development of Autoantibodies Before the Clinical Onset
of Systemic Lupus Erythematosus
Lupus erythematosus (lupus), is an autoimmune disease in which the body attacks
its own tissues. Patients with lupus, have autoantibodies (proteins that attach
to the body's healthy tissues by mistake) in their blood years before the symptoms
of lupus appear. The early detection of autoantibodies may help in recognizing
those who will develop the disease and allow physicians to monitor them before
they might otherwise be noticed. Lupus can affect many parts of the body, including
the joints, skin, kidneys, heart, lungs, blood vessels and brain. People who
have lupus may have many different symptoms, but some of the most common ones
include extreme fatigue, painful or swollen joints (arthritis), unexplained
fever, skin rashes and kidney problems. Many more women than men have lupus.
It is three times more common in African American women than in Caucasian women
and is also more common in women of Hispanic, Asian and Native American descent.
A new study published in the new England Journal of Medicine (2003; 349:1526-33)
has shown that people diagnosed with systemic lupus have long-standing antibodies.
For the study, blood was tested from 130 U.S. armed forces servicemen and women,
without knowing their identities, who were once healthy but later developed
lupus. Using many years of previously collected samples from the Department
of Defense Serum Repository, the authors compared samples from the lupus patients
to samples from those who never developed lupus. When testing early samples
from both groups, they found that those with lupus had the autoantibodies in
their blood for months to years before symptoms appeared. Some of the autoantibodies,
such as antinuclear antibody, had been present longer than others. The lupus
autoantibodies, tended to accumulate in the blood in a predictable pattern up
until diagnosis, when the rate of new autoantibodies slowed down. According
to the authors, it is not known whether the virtual halt in the accumulation
of new autoantibodies was a result of therapy now typically used or whether
the relative stability in the autoantibodies found after diagnosis is a feature
of the natural history of lupus.
V. NEUROLOGY
Exercise Plus Behavioral Management in Patients With
Alzheimer Disease
Results from a
study published in the Journal of the American Medical Association
(2003;290:2015-2022), suggest that exercise training for patients with Alzheimer
disease (AD), combined with teaching caregivers how to manage behavioral
problems, may help decrease the frailty and behavioral impairments that are
often prevalent in patients with AD. The objective of the study was to determine
whether a home-based exercise program combined with caregiver training in
behavioral management techniques would reduce functional dependence and delay
institutionalization among patients with AD. The study was a randomized
controlled trial of 153 community-dwelling patients meeting National Institute
of Neurological and Communicative Diseases and Stroke/Alzheimer Disease and
Related Disorders Association criteria for AD. Patient-caregiver dyads were
randomly assigned to the combined exercise and caregiver training program,
Reducing Disability in Alzheimer Disease (RDAD), or to routine medical care
(RMC). The RDAD program was conducted in the patients' home over 3 months. The
main outcome measures were 1) physical health and function (36-item Short-Form
Health Survey's, physical functioning and physical role functioning subscales
and Sickness Impact Profile's Mobility subscale), and 2) affective status
(Hamilton Depression Rating Scale and Cornell Depression Scale for Depression in
Dementia). Results showed that at 3 months post intervention, in comparison with
the routine care patients, more patients in the RDAD group exercised at least 60
min/wk (P = .01) and had fewer days of restricted activity (P<.001). Patients
in the RDAD group also had improved scores for physical role functioning
compared with worse scores for patients in the RMC group (mean difference,
19.29; P<.001). Patients in the RDAD group had improved Cornell Depression
Scale for Depression in Dementia scores while the patients in the RMC group had
worse scores (mean difference, -1.03, P = .02). At 2 years, the RDAD patients
continued to have better physical role functioning scores than the RMC patients
(mean difference, P = .003) and showed a trend (19% vs 50%) for less
institutionalization due to behavioral disturbance. For patients with higher
depression scores at baseline, those in the RDAD group improved significantly
more at 3 months on the Hamilton Depression Rating Scale (mean difference, 2.21,
P = .04) and maintained that improvement at 24 months (mean difference, 2.14, P
= .04). According to the authors, exercise training combined with teaching
caregivers behavioral management techniques improved physical health and
depression in patients with AD.
Transfusion Malaria
According to a report released Thursday by the Centers for Disease Control and Prevention (Morbidity and Mortality Weekly Report, November 7, 2003), an elderly patient in Texas appears to be the first case of transfusion-transmitted malaria in the US since 1998,. The 69-year-old patient was admitted to a Houston-area hospital earlier this year with blood pressure and kidney problems. While hospitalized, the patient was given two units of blood for anemia. Soon after, the patient was sent home. Seventeen days after the transfusion, the patient developed a fever and became confused. Three days later, the patient was admitted to the intensive care unit of a different hospital. Tests revealed the presence of Plasmodium falciparum, the parasite that causes the most severe form of malaria, in the patient's blood. The patient was successfully treated with anti-malaria drugs and sent home three weeks later. With the exception of the recent transfusion, the patient reported receiving no blood in the 12 months before hospitalization. Moreover, the patient reported no travel outside the Houston area since 1995. With the assistance of the Texas Department of Health, the CDC was able to track down the two donors of the transfused blood. One was a middle-aged Texas woman who had never traveled outside the US, and the other was a young man originally from Ghana. Both history and lab test results suggested that the Ghanian donor was the source of malaria. Current CDC guidelines recommend that people from non-malarious areas who travel to a malarious region should not donate blood for at least 1 year after their return, provided that they have no symptoms. For people from malarious areas or those who have been diagnosed with malaria, the recommended waiting period is longer--at least 3 years. According to the CDC, the Ghanian donor did not tell the screener about having malaria during the previous 3 years, and the screener did not defer the donor for immigrating within 3 years from an area with endemic malaria.
TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients and FDA and performs all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.
Pharmacogenomics - A New FDA Guidance
Pharmacogenomics deals with the small genetic differences that help explain
why some people respond positively to a drug, while others don't respond, or may
experience a side effect. Genetic differences also can predict variations in
drug metabolism and how quickly or slowly a drug is eliminated from the body.
The FDA has issued a new document entitled Draft Guidance for Industry:
Pharmacogenomic Data Submissions in which the FDA encourages drug and biologic
companies to conduct pharmacogenomic tests during drug development. The Guidance
also clarifies how FDA will evaluate the resulting data. In the draft guidance,
FDA said that the promise of pharmacogenomics lies in its potential ability to
individualize therapy by predicting which individuals have a greater chance of
benefit or risk; and that pharmacogenomic testing can be smoothly integrated
into drug development processes. This is FDA's first step towards integration of
this new field into the process of demonstrating that new drugs are safe and
effective, and thus the regulatory guidance is intended to facilitate this
integration. This guidance is intended to ensure that evolving regulatory
policies and study designs are 1) based on the best science, 2) provide public
confidence in this new field where scientifically appropriate, 3) facilitate the
use of such tests during drug development, and 4) clarify for industry what
types of pharmacogenomic data to submit to FDA. It is hoped that pharmacogenomic
testing will help identify cancers that have a high probability of responding to
a particular medication or regimen. Pharmacogenomics may also be used to help
track down the cause of certain rare, serious drug side effects. Because there
is a need for scientific exchange, the agency is asking for voluntary
submissions of research information. This data will help FDA gain experience as
the field evolves. In these cases, FDA advises sponsors to clearly label
voluntary submissions; and the agency advises that it will not use information
from voluntary reports for regulatory decisions. If a sponsor subsequently
develops additional data that meet the criteria for submission for regulatory
purposes, the Agency advises sponsors that such data should be submitted as
explained in the guidance. The draft guidance on display today is available on
FDA's website (www.fda.gov/cder/guidance/5900dft.pdf).
VIII. TARGET HEALTH
TARGET HEALTH INC. (www.targethealth.com) is a full service e*CRO with fulltime staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND, IDE, NDA, PMA and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, Web Trials, utilizing Target e*CRF™™, our proprietary Internet-based Remote Data Entry (I-RDE? system, and Medical Writing. TARGET HEALTH's Pharmaceutical Advisory Dream Team (PADT) assists companies in strategic planning from Discovery to Market Launch. Let us help you on our next project.
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