OnTarget (March 5, 2007)
I. WHAT'S NEW?
Why Companies Work With Target Health
II. QUIZ - (Fill In The Blanks)
Memories Are Made of This
III. HISTORY OF MEDICINE
Imhotep - First Physician
IV. EPIDEMIOLOGY
Second
Hand Smoke – Not Good
V. IMMUNOLOGY
Vaccine Against Hepatitis E is Effective
VI. RHEUMATOLOGY
Macrophage Activation Syndrome in Juvenile RA
VII. REGULATORY AFFAIRS
New Drug Safety Guidance
VIII. TARGET HEALTH
I.
WHAT'S NEW
Why
Companies Work With Target Health
- We are an eCRO with hand’s-on expertise
in drug/device development.
- We own our proprietary EDC and Target Document
source code.
- We are not just a technology company.
- We integrate EDC with data management and project management.
- We have 2 NDAs approved and one PMA approved
which used Target e*CRF.
- One PMA submitted in January (we did the entire submission plus eCopy).
- NDA submission planned for Q1, 2007.
- Over 100 EDC studies, including global studies.
- 10 flawless FDA clinical site pre-approval inspections.
- International approvals (
Canada
,
Europe
).
- Stable employee base
- We represent 19 companies at FDA, so regulatory compliance is key.
For more
information, please contact Dr.
Jules T. Mitchel.
Visit our Blog and Website.
II. QUIZ (Fill In The Blanks)
Memories Are Made of
This
The function of
an 1) ___ in the brain, strongly linked to a number of major brain diseases
such as Alzheimer's, schizophrenia and bi-polar disorder, has been identified
for the first time. These findings, published in the March edition of the
journal Neuron, should help in the understanding of how 2) ___ are laid down
and what goes wrong in these disorders. The research shows how controlling the
activity of glycogen synthase kinase-3 (GSK3) might
prevent a memory being 3) ___ by improving the strength of connections between
neurons in the brain, thus allowing better consolidation of new information. While GSK3 has previously been implicated in major 4) ___
disorders, until now its role in normal neuronal function has been largely
unknown. This new understanding will help 5) ___ companies develop drugs
to inhibit it when things go wrong. The activity of GSK3 facilitates a form of
'cross-talk' between the two major forms of synaptic plasticity in the 6) ___.
Synaptic plasticity is the strength of a connection between neurons and forms
the basis of 7) ___ and memory.
ANSWERS: 1) enzyme; 2)
memories; 3) erased; 4) neurological; 5) pharmaceutical; 6) brain; 7)
learning
III. HISTORY OF MEDICINE
Imhotep - First Physician
Imhotep (sometimes spelled Immutef, Im-hotep, or Ii-em-Hotep)
(2667 BCE - 2648 BCE) is the first architect and physician known by name in
written history. As one of the officials of the Pharaoh Djoser,
he designed the Pyramid of Djzoser (Step Pyramid) at Saqqara in
Egypt
around 2630-2611 BCE during
the 3rd Dynasty. He may also have been responsible for the first known use of
columns in architecture. The Egyptians also credited him with the discovery of
many inventions. Imhotep was also a poet and
philosopher. He urged contentment and preached cheerfulness. His proverbs
contained a "philosophy of life." He coined the saying "Eat,
drink and be merry for tomorrow we shall die." His name means "the
one who comes in peace." Imhotep is credited as
being the founder of Egyptian medicine, and as author of the Edwin Smith
papyrus, detailing cures, ailments and anatomical observations. The Papyrus was
probably written around 1700 BCE but may go back to texts written around 1000
years earlier. Imhotep also served as chancellor to
the pharaoh and high priest of the sun god Ra at
Heliopolis
. He was said to be a son of Ptah, his mother being a mortal named Khredu-ankh. Imhotep was the only mortal in all of civilization to
be recognized on the foot-stone of a king's statue. The location of Imhotep's tomb is still unknown. Many Egyptologists have
tried to find it but so far haven't succeeded. The general consensus is that it
is at
Saqqara
.
IV. EPIDEMIOLOGY
Second-Hand Smoke – Not
Good
Exposure to
second-hand smoke has been associated with a disproportionately high risk of
coronary heart disease, thought to be mediated through inflammation, platelet
aggregation, and/or endothelial dysfunction. The epidemiological association
between objectively measured exposure to second-hand smoke and biomarkers of
heart disease risk has not been investigated. As a result, a study published in
Circulation (2007;115:990-995) was performed to investigate the cross-sectional
relation between secondhand smoke exposure, measured objectively as cotinine, and recognized biomarkers of heart disease risk,
namely C-reactive protein, homocysteine, fibrinogen,
and white blood cell count. The study was performed in 7599 never-smoking
adults from the Third National Health and Nutrition Examination Survey. Results
showed that compared with subjects with no detectable cotinine,
those with detectable but low-level cotinine (range,
0.05 to 0.215 ng/mL) had significantly higher levels
of both fibrinogen (adjusted mean difference, 8.9 mg/dL;
P=0.03) and homocysteine (0.8 µmol/L; P<0.001),
but not C-reactive protein or white blood cell count. Effect estimates of
similar magnitude and significance were seen in subjects in the high category
of cotinine exposure (>0.215 ng/mL).
The increased levels of fibrinogen and homocysteine seen in relation to second-hand smoke exposure were equivalent to approximately
30% to 45% of those seen for active smoking. According to the authors, passive
smokers appear to have disproportionately increased levels of 2 biomarkers of
cardiovascular disease risk, fibrinogen and homocysteine,
and that this finding provides further evidence to suggest that low-level
exposure to second-hand smoke has a clinically important effect on
susceptibility to cardiovascular disease.
V. IMMUNOLOGY
Vaccine Against Hepatitis E is Effective
Hepatitis E
virus (HEV) is an important cause of viral hepatitis. As a result, a study
published in the New England Journal of Medicine (2007; 356:895-903), was
performed to evaluate the safety and efficacy of an HEV recombinant protein (rHEV) vaccine in a phase 2, randomized, double-blind,
placebo-controlled trial. The study was performed in
Nepal
, and included 2000 healthy
adults susceptible to HEV infection. Subjects were randomly assigned to receive
three doses of either the rHEV vaccine or placebo at
months 0, 1, and 6. Active (including hospital) surveillance was used to
identify acute hepatitis and adverse events. The primary end point was the
development of hepatitis E after three vaccine doses. The total vaccinated
cohort was followed for a median of 804 days. Results showed that a total of
1794 subjects (898 in the vaccine group and 896 in the placebo group) received
three vaccine doses. After three vaccine doses, hepatitis E developed in 69
subjects, of whom 66 were in the placebo group. The vaccine efficacy was 95.5%.
In an intention-to-treat analysis that included all 87 subjects in whom hepatitis
E developed after the first vaccine dose, only 9 subjects were in the vaccine
group, with a vaccine efficacy of 88.5%. Among subjects in a subgroup randomly
selected for analysis of injection-site findings and general symptoms (reactogenicity subgroup) during the 8-day period after the
administration of any dose, the proportion of subjects with adverse events was
similar in the two study groups, except that injection-site pain was increased
in the vaccine group (P=0.03). According to the authors, in a high-risk
population, the rHEV vaccine was effective in the
prevention of hepatitis E. (ClinicalTrials.gov number, NCT00287469.)
VI. RHEUMATOLOGY
Macrophage Activation
Syndrome in Juvenile RA
Macrophage activation syndrome
is characterized by an overwhelming inflammatory reaction driven by excessive
expansion of T cells and hemophagocytic macrophages.
Levels of soluble interleukin-2 receptor (sIL-2R
alpha) and soluble CD163 (sCD163) may reflect the degree of activation and
expansion of T cells and macrophages, respectively. As a result, a study
published in Arthritis & Rheumatism (2007;56:965-971),
was performed to assess the value of serum sIL-2R alpha and sCD163 in
diagnosing acute macrophage activation syndrome complicating systemic juvenile
idiopathic arthritis (JIA). For the study, enzyme-linked immunosorbent assay was used to assess sIL-2R alpha and sCD163 levels in sera from 7 patients
with acute macrophage activation syndrome complicating systemic JIA and 16
patients with untreated new-onset systemic JIA. The results were correlated
with clinical features of established macrophage activation syndrome, including ferritin levels. Results showed that the median level
of sIL-2R alpha in the patients with macrophage activation syndrome was 19,646
pg/ml (interquartile range [IQR] 18,128), compared
with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P = 0.003).
Similarly, the median level of sCD163 in patients with macrophage activation
syndrome was 23,000 ng/ml (IQR 14,191), compared with
5,480 ng/ml (IQR 2,635) in patients with systemic JIA
(P = 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL-2R
alpha or sCD163 were comparable with those in patients with acute macrophage
activation syndrome. These patients had high inflammatory activity associated
with a trend toward lower hemoglobin levels (P = 0.11), lower platelet counts,
and significantly higher ferritin levels (P = 0.02).
Two of these 5 patients developed overt macrophage activation syndrome several
months later. According to the authors, levels of sIL-2R alpha and sCD163 are
promising diagnostic markers for macrophage activation syndrome. These levels
they may also help identify patients with subclinical macrophage activation syndrome.
VII. REGULATORY AFFAIRS
TARGET HEALTH excels in
Regulatory Affairs and works closely with many of its clients performing 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.
New Drug Safety Guidance
The FDA issued final guidance that
describes FDA’s current approach to communicating drug safety information,
including emerging safety information, to the public. The guidance on "Drug Safety
Information-FDA’s Communication to the Public” also includes the
factors that influence when such information is communicated. The guidance
affirms the agency’s commitment to communicate important drug safety
information in a timely manner, including in some situations, when the agency
is still evaluating whether to take any regulatory action. The information in
the guidance is intended to make emerging information on important drug safety
issues available to the public and will facilitate patient and healthcare
provider access to the most current information concerning the potential risks
and benefits of a marketed drug. The guidance describes the various methods FDA
currently uses to communicate established and emerging drug safety information
to the public. In addition to drug product labeling, FDA’s methods of
communicating important drug safety information includes:
- Public Health Advisories – provide information and advice regarding
an emerging drug safety issue or other important public health information
to the public, including patients and health care professionals.
- Patient Information Sheets – provide concise summaries in plain
language, with the most important information about a particular drug.
- Health care Professional Sheets – provide a summary of important
and often emerging drug safety issues, with information about the
detection of the issue, and points to consider for clinical
decision-making.
- Alerts on Patient Information and Health Professional Sheets –
provide a summary of important, and often emerging, drug safety issues.
Alerts may be placed on public health advisories, or patient and health
care professional sheets. These may include:
- newly observed serious adverse events that may
be associated with a drug;
- information about how such serious adverse
events might be prevented by appropriate patient selection, monitoring of
patients, or use or avoidance of the therapy; and
- information regarding a serious adverse event that FDA
believes may be associated with use of a drug in populations in whom
the drug was not previously studied.
For
more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.
VIII. TARGET HEALTH
TARGET HEALTH INC. (www.targethealth.com) is a
full service eCRO with full-time 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 Clinical Trial 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 your next project.
TARGET HEALTH INC.
261 Madison Avenue
24th Floor
New York
,
NY
10016
Phone: (212) 681-2100; Fax (212) 681-2105
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Dr. Jules T. Mitchel, President
Ms Joyce Hays, CEO
