Target Health Software Update

Target Health runs a paperless and transparent company and so can you.

Target Document Version 1.5 will be released mid-March 2010. We are making Target Document® even better. We are integrating Target Document® and Target e*CTMS™ over the next 2 months which will also allow the study sites to maintain their Trial Master File (TMF) within Target Document. Finally, the Sponsor will be able to see the sites’ TMF documents remotely.

Target Health software products for clinical trials include:

  • Target e*CRF® – EDC Made Simple (Part 11 Compliant) – 18 Unique Regulatory Approvals since 1999.
  • Target e*CTR® – Electronic Health Record for Clinical Trials (Part 11 Compliant) – Direct data entry of clinical trial data
  • Target Document® – Document Paperless TMF and eSignatures (Part 11 Compliant)
  • Target Encoder® – Automatically and manually code MedDRA and WHODrug terms (Part 11 Compliant)
  • Target e*CTMS™ – Clinical Trial Management System for All
  • Target e*Pharmacovigilance™ – Creates CIOMS and MedWatch 3500A Forms from EDC (Part 11 Compliant)
  • Target Newsletter™ – Newsletter updates from Target e*CRF®
  • Target eStudio™ – EDC designer coming Q4 2010 (Part 11 Compliant)

 

For more information about Target Health and our software tools for paperless clinical trials, please contact Dr. Jules T. Mitchel (212-681-2100 ext 0) or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health website at www.targethealth.com

Detecting Cancer Early

The earlier a tumor is diagnosed, the better the chances for recovery. A new testing method aims to detect the disease in its initial stages. The technology is based on a microfluidic chip with tiny channels in which a blood sample from the patient circulates. The chip traces marker proteins which are indicative of 1) ___. The measured concentration of the tumor marker in the blood will help to diagnose cancer at an early stage. Similar testing systems already exist, but their measurements are not very precise and they can only detect molecules that are present in the blood in large 2) ___. What’s more, the tests have to be carried out in a laboratory, which is time-consuming and costly. Biofunctionalized nanoparticles developed by research scientists at the Fraunhofer Institute for Silicate Research ISC in W?rzburg, Germany are the key element in the new sensor. Whereas previously a hundred molecules were needed in a certain quantity of 3) ___ to detect tumor markers, now there is only one. This means that diseases can be diagnosed much earlier than with present methods. But how does the biosensor integrated in the chip register the few biomolecules swimming around in the blood that are indicative of a certain 4) ___? Nanoparticles connected to antibodies are luminescent in two spectral ranges. This makes it possible to check the homogeneous occupation of the sensor electrode. Antibody-occupied nanoparticles have been placed on the sensor electrode which fish out the relevant proteins. For this purpose, the blood is repeatedly pumped across the electrode surface. As with a river, the flow is fastest in mid-channel and the water runs more slowly near the bank. The nanoparticles register the antibodies in the middle of the blood flow where most 5) ___ swim by per unit of time. If an antibody catches the matching protein, a tumor marker, the electrical charge distribution shifts and this is picked up by the electrode. The researcher groups are now developing a first demonstrator combining four independent single-molecule-sensitive biosensors. They are also working on the simultaneous detection of several tumor markers, which will increase the clarity of tests. The system will be ready to enter the market in a few years’ time.

ANSWERS: 1) cancer; 2) quantities; 3) blood; 4) disease; 5) proteins

Variolation at the Time of Washington

Variolation, also called, inoculation, was a primitive and risky form of live-virus vaccination that involved intentionally giving individuals a mild case of smallpox to prevent them from acquiring a more deadly form “the natural way”. Inoculees gained immunity but also became temporarily infectious and could easily spark outbreaks unless quarantined for the duration of their induced illness. Complicating the process was that variolation could be fatal. About 2 people died for every 100 variolated. Prior to Jenner’s cowpox vaccine, many New England settlers were variolated by means of making small incisions in the arms of the healthy patient, scraping a pustule from a smallpox victim, and spreading the pus in the arm incisions. The variolated, or inoculated patients were often sick for weeks but generally recovered. The procedure reached the New World in 1721 where it was used to stop an epidemic in Boston. From then on, variolation quickly spread throughout the colonies. In Europe and England, smallpox was endemic. People usually caught smallpox during their youths, when they were most likely to survive the infection. Those infected between ages five and 14 had the lowest mortality rate. During the American Revolutionary war, with the bulk of its army thus rendered naturally immune, the British did not need to worry about either seizing smallpox-infested towns or inoculating the small percentage of its forces not infected as children. When the War of Independence broke out in 1775, the Continental Army at first dug in its heels and forbade inoculation for fear of spreading the disease and incapacitating the fighting forces. According to General Benedict Arnold’s February 1776 orders “The Surgeons of the Army are forbid, under the severest penalty, to inoculate any person.” Officers found submitting to inoculation would be “immediately cashiered” and privates “punished at the discretion of a Court-Martial.” Yet troops were so desperate to avoid the scourge that they’d inoculate themselves in secret with pinpricks under their nails. Abigail Adams, wife of President John Quncy Adams wrote to her husband (then in Congress in Philadelphia) that she was taking their children to Boston to be inoculated after a severe outbreak near their rural home had killed entire neighboring families. In 1776, the colonial soldiers under George Washington failed to take Quebec from England because a smallpox epidemic had cut their size in half. The Americans soon learned they could scarcely battle two enemies at once – smallpox and the British. The disastrous experience of the siege of Quebec in 1775, when smallpox ravaged up to one-third of the assembled Americans, began to change the Americans’ minds about inoculation. Captain Lemuel Roberts concisely captured the problem during the retreat from Quebec by boat: “My pock had become so sore and troublesome that my clothes stuck fast to my body, especially my feet; and it became a severe trial of my fortitude, to bear my disorder and assist in managing the boat.”  Wave after wave of smallpox decimated the soldiers during the first two years of the war. New recruits would come down with the disease immediately upon enlistment, and thousands of potential fighters stayed away for fear of infection. By the winter of 1777 (the winter of Valley Forge), Gen. George Washington made a momentous decision to inoculate all new recruits and finally halt the pestilence’s progress. The inoculation campaign had to be conducted with great secrecy. Though it would protect soldiers in the long run and decrease fear of enlistment, it would also incapacitate large numbers for weeks at a time, rendering the Continentals vulnerable to assault. Ultimately, however, it became clear that the spread of smallpox through the ranks presented a graver threat to the army – and would kill more individuals – than the Redcoats. Recruits were quarantined in camps and inoculated before being sent out to fight. Washington’s unheralded and little-recognized resolution to inoculate the Continental forces must surely rank with the most important decisions of the war. The general had outflanked his enemy. After the inoculations were complete, the Continentals were able to fight at full strength without fear of the epidemic. This was critically important in the Southern campaign in the final years of the war. Irregular militias refused to march on Charleston, South Carolina, to retake the town because smallpox was loose there. But an inoculated army of soldiers paid to fight was able to engage in battles that had scared off the militias, and to withstand the British attempts at biological warfare that preceded the surrender at Yorktown.

Childhood Obesity, Other Cardiovascular Risk Factors, and Premature Death

The effect of childhood risk factors for cardiovascular disease on adult mortality is poorly understood. As a result, a study published in the New England Journal of Medicine (2010; 362:485-493), was performed in a cohort of 4857 American Indian children without diabetes (mean age, 11.3 years; 12,659 examinations) to assess whether body-mass index (BMI), glucose tolerance, and blood pressure and cholesterol levels predicted premature death. Risk factors were standardized according to gender and age. Study subjects were born between 1945 and 1984. Results showed that there were 166 deaths from endogenous causes (3.4% of the cohort) during a median follow-up period of 23.9 years. Rates of death from endogenous causes among children in the highest quartile of BMI were more than double those among children in the lowest BMI quartile (incidence-rate ratio, 2.30). Rates of death from endogenous causes among children in the highest quartile of glucose intolerance were 73% higher than those among children in the lowest quartile (incidence-rate ratio, 1.73). No significant associations were seen between rates of death from endogenous or external causes and childhood cholesterol levels or systolic or diastolic blood-pressure levels on a continuous scale, although childhood hypertension was significantly associated with premature death from endogenous causes (incidence-rate ratio, 1.57). According to the authors, obesity, glucose intolerance, and hypertension in childhood were strongly associated with increased rates of premature death from endogenous causes in this population, while childhood hypercholesterolemia was not a major predictor of premature death.

ONCOLOGY

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Specific Age and Gender Genomic Profiles in Non-Small Cell Lung Cancer

Gene expression profiling may be useful in examining differences underlying age- and sex-specific outcomes in non-small cell lung cancer (NSCLC). As a result, a study published in the Journal of the American Medical Association (2010;303:535-543), was performed to describe clinically relevant differences in the underlying biology of NSCLC based on patient age and gender. The investigation was a retrospective analysis of 787 patients with predominantly early stage NSCLC. Lung tumor samples with corresponding microarray and clinical data were used. All patients were divided into subgroups based on age (<70 vs 70 years old) or gender. Gene expression signatures representing oncogenic pathway activation and tumor biology/microenvironment status were applied to these samples to obtain patterns of activation/deregulation. The main outcome measures were the patterns of oncogenic and molecular signaling pathway activation that were reproducible and correlated with 5-year recurrence-free patient survival. Results identified low- and high-risk patient clusters/cohorts with the longest and shortest 5-year recurrence-free survival, respectively, within the age and gender NSCLC subgroups. These cohorts of NSCLC demonstrate similar patterns of pathway activation. In patients younger than 70 years, high-risk patients, with the shortest recurrence-free survival, demonstrated increased activation of the Src (25% vs 6%; P<.001) and tumor necrosis factor (76% vs 42%; P<.001) pathways compared with low-risk patients. High-risk patients aged 70 years or older demonstrated increased activation of the wound healing (40% vs 24%; P = .02) and invasiveness (64% vs 20%; P<.001) pathways compared with low-risk patients. In women, high-risk patients demonstrated increased activation of the invasiveness (99% vs 2%; P<.001) and STAT3 (72% vs 35%; P<.001) pathways while high-risk men demonstrated increased activation of the STAT3 (87% vs 18%; P<.001), tumor necrosis factor (90% vs 46%; P<.001), EGFR (13% vs 2%; P = .003), and wound healing (50% vs 22%; P<.001) pathways. Multivariate analyses confirmed the independent clinical relevance of the pathway-based subphenotypes in women (hazard ratio [HR], 2.02 P<.001) and patients younger than 70 years (HR, 1.83; P = .003). According to the authors, among a cohort of patients with NSCLC, subgroups defined by oncogenic pathway activation profiles were associated with recurrence-free survival.

Smoking Increases Rheumatoid Arthritis Susceptibility In Individuals Carrying the HLA-DRB1 Shared Epitope, Regardless Of Rheumatoid Factor Or Anti-Cyclic Citrullinated Peptide Antibody Status

Smoking is associated with rheumatoid arthritis (RA) in individuals with the HLA-DRB1 shared epitope (SE). SE alleles have been shown to be predominantly associated with anti-cyclic citrullinated peptide (anti-CCP)-positive RA. These risk factors have not been identified for anti-CCP-negative RA. As a result, a study published in Arthritis & Rheumatism (2010;62:369-377), was performed to investigate whether SE-containing HLA-DRB1 alleles, smoking, or the combination of these factors contributes to the development of RA, depending on the presence or absence of serologic markers. All of the subjects in the study were Korean; 1,482 with RA and 1,119 controls. Four-digit HLA-DRB1 typing was performed by a conventional polymerase chain reaction-sequence-based typing method. Information about smoking history was obtained through a questionnaire. The patients with RA were tested for anti-CCP antibodies and rheumatoid factor (RF). Results showed that the SE alleles had significant effects on anti-CCP antibody and RF formation. The DRB1*0901 allele was associated with the presence of anti-CCP antibodies (odds ratio [OR] 2.49) and RF (OR 2.09). SE alleles and smoking were associated with both anti-CCP-positive and anti-CCP-negative RA. The combination of smoking and double copies of the SE allele increased the risk of anti-CCP-positive RA 36.11-fold and increased the risk of anti-CCP-negative RA 12.29-fold, compared with the risk among nonsmokers not carrying SE alleles. Interactions between SE alleles and smoking were observed for both anti-CCP-positive and RF-positive RA, although the associations of RF-positive RA could be consequences of the underlying anti-CCP antibody status. According to the authors, the combination of SE alleles and smoking is associated with RA susceptibility regardless of anti-CCP antibody or RF status, but that the combination shows stronger effects in anti-CCP-positive/RF-positive patients with RA than in anti-CCP-negative/RF-negative patients with RA. The SE-smoking interactions were present in anti-CCP-positive and RF-positive RA.

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.

FDA Approves New Indication for Crestor

Crestor (rosuvastatin) is in a class of drugs called statins, which work by stopping an enzyme called HMG-CoA reductase from making cholesterol. High amounts of low-density lipoprotein or LDL cholesterol, the so-called “bad cholesterol,“ is a known risk factor for heart attacks, strokes, and heart disease. Crestor is already approved for use in combination with diet and exercise to lower LDL cholesterol and a related substance known as triglycerides in patients with a high amount of these substances in their blood. The medication is also approved to slow the progression of atherosclerosis – a thickening of the artery wall due to the buildup of cholesterol and other fatty materials. High sensitivity C-reactive protein is a nonspecific indicator of inflammation, which is associated with the buildup of cholesterol and other fatty material in the coronary arteries.

The FDA has approved the cholesterol-lowering medication Crestor for some patients who are at increased risk of heart disease but have not been diagnosed with it. The new indication is for reducing the likelihood of a heart attack or stroke or the need for a procedure to treat blocked or narrowed arteries in patients who have never been told they have heart disease but are nevertheless at increased risk of a cardiac event. Specifically, this includes men 50 years of age and older and women 60 years of age and older who have an elevated amount of a substance known as high sensitivity C-reactive protein in their blood and at least one additional traditional cardiovascular risk factor such as smoking, high blood pressure, a family history of premature heart disease, or low amounts of high-density lipoprotein or HDL cholesterol, the so-called “good cholesterol.“ This new indication does not support the use of Crestor in individuals who have an elevated high sensitivity C-reactive protein but no traditional cardiovascular risk factors. The new indication was based on results from a study called the JUPITER trial, which compared 8,901 patients who received Crestor for two years to the same number of patients who received a placebo. Patients who took Crestor experienced fewer cardiac events, including heart attacks and strokes, and underwent fewer procedures such as coronary angioplasty or coronary artery bypass surgery to treat or revascularize their arteries.

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

Target Health (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 (eCTD), IDE, NDA (eCTD), BLA (eCTD), PMA (eCopy) and 510(k) submissions, Management of Clinical Trials, Biostatistics, Data Management, EDC utilizing Target e*CRF®, Project Management, and Medical Writing.

Target Health has developed a full suite of eClinical Trial software including

1) Target e*CRF® (EDC plus randomization and batch edit checks)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target Newsletter®

6) Target e*CTR™ (electronic medical record for clinical trials).

Target Health ‘s Pharmaceutical Advisory Dream Team assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.

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