Target e*Studio – Supports the Paperless Clinical Trial
What differentiates Target Health from others in the CRO industry is our commitment and proven ability to allow for the paperless clinical trial. We have been using Target e*CRF® as our EDC tool since 1999 with 25 approvals from Gaucher disease to Head Lice to Companion Diagnostics. Approvals include drugs, biologics and devices.
In July, we will release Version 2 of Target e*Studio®, the most cost-effective EDC software in the Industry. We also “put our money where our mouth is“ in that we use Target e*Studio to build Target e*CRF applications for the clinical trials we run for our clients.
Target e*Studio allows users such as clinical data managers to build EDC applications, usually in more than a week. The following features are fully integrated with all EDC applications:
1. Graphic User Interface (GUI) to build forms and configure online and batch edit checks
2. Monitoring reports
3. Central and site randomization (no need for a separate IVRS system)
4. Drug and device supply management
5. Coding using MedDRA and WHODRUG
6. Risk based and central management reports to replace most features CTMS systems
7. Target e*CTR® (eClinical Trial Record), the most robust and cost effective eSource solution
8. Conversion of the online eCRF to an Adobe .pdf file (fully bookmarked)
9. Create a blank and annotated CRF at will
10. Download SAS datasets at will
11. Self-documentation of edit check specification
12. Compliant with 21CFR Part 11
Our CRO partners using Target e*Studio include LSK in Korea and Technostat in Israel. We will partner with any CRO and welcome any EDC solution to incorporate Target e*CTR so they can offer the best eSource solution in the industry.
Springtime in Central Park – ©Target Health Inc.
ON TARGET is the newsletter of Target Health Inc., a NYC-based, full service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services, including the paperless clinical trial, to the pharmaceutical and device industries.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Two Spine Surgeons Are Three Times Safer Than One
Credit: Image courtesy of Group Health Research Institute
“We can shorten the operation when we have two surgeons in the operating 1) ___ as equal partners: a neurosurgeon and an orthopedic surgeon with specialized spine training,“ said lead author Rajiv K. Sethi, MD.
A new team approach has improved patient 2) ___ by reducing rates of major complications by two thirds for complex spinal reconstructive surgery for spinal deformity. The study was performed in adult Group Health patients at Virginia Mason Hospital & Seattle Medical Center. An article in the March issue of Spine Deformity gives a detailed description of the standardized protocol before, during, and after the surgery, stressing the new approach’s three main features:
1. Two spine surgeons in the operating room
2. A live preoperative screening conference
3. Monitoring bleeding during the operation
The research team reviewed 164 consecutive patients: 40 before and 124 after the new three-pronged approach was implemented. After implementation, patients were three times less likely to develop major complications. Improvements included significant reductions in rates of wound infection, deep vein 3) ___, pulmonary embolism, and urinary tract infections. Patients were also significantly less likely to have to return to the operating room within 90 days after the surgery.
“We can shorten the operation when we have two surgeons in the operating room as equal partners: a neurosurgeon and an orthopedic 4) ___ with specialized spine training,“ said lead author Rajiv K. Sethi, MD. He is an orthopedic spinal surgeon in the neurosurgery department at Group Health Physicians, the director of spinal deformity and complex reconstruction at Virginia Mason, and a clinical assistant professor of health services at the University of Washington (UW) School of Public Health.
“Reconstructive surgery for adults with spine deformities like scoliosis and kyphosis is being done increasingly often,“ Dr. Sethi said. “But this kind of surgery tends to be long and difficult, and it is among the most dangerous and complication-ridden of all operations. And often the outcomes and complications are unacceptable, including some patients losing more blood than they started with.“ That’s why the new approach uses a standardized protocol to monitor and manage any bleeding during the 5) ___.
The new approach also involves a feature that has never been described before: a live conference with clinicians from various disciplines. They are the operative surgeons, an internist, a physical medicine and rehabilitation physician, the nurses who coordinate a class for complex spine patients, and at least two members of the anesthesiology team dedicated to complex spine surgery. Together, they identify and treat health and medication issues that, undetected, might otherwise have derailed an operation at the last minute. Planning well in advance, they discuss — and decide — whether proposed 6) ___ is appropriate for each patient.
“Our findings could help medical teams at Group Health and around the country reduce complications — and likely cut costs too — while improving performance and 7) ___ outcomes,“ Dr. Sethi said. “But all clinicians at Group Health and Virginia Mason are paid on salary. By contrast, at medical centers where doctors are paid on a fee-for-service basis, with more pay for doing more procedures, it might be harder to institute this kind of systems approach, because it entails up-front costs and commitment from leadership.“
Sources: Group Health Research Institute; ScienceDaily.com; Wikipedia;
Rajiv K. Sethi et al. The Seattle Spine Team Approach to Adult Deformity Surgery: A Systems-Based Approach to Perioperative Care and Subsequent Reduction in Perioperative Complication Rates. Spine Deformity, March 2014 DOI: 10.1016/j.jspd.2013.12.002
1) room; 2) safety; 3) thrombosis; 4) surgeon; 5) operation; 6) surgery; 7) patient
Hugh Owen Thomas, MD (1834-1891)
Hugh Owen Thomas
Hugh Owen Thomas (23 August 1834-1891) was a Welsh surgeon. He is considered the father of orthopedic surgery in Britain.
Hugh Owen Thomas descended from a young boy who had been shipwrecked in Anglesey in 1745. This boy was given the name Evan Thomas by the family that adopted and raised him. This survivor, the first Evan Thomas, established a family tradition of bone-setting. The second, Evan Thomas, the grandson of the original survivor, and Hugh’s father, moved to Liverpool at the age of 19, where he set up a successful practice as bone-setter. Evan, however, was not a trained physician, and three times was taken to court to defend his practice. Although he was never convicted, the constant jealousy and antagonism of the medical community took a great toll on him. At one point his cottage was burnt down. As a result, he decided to send all five of his sons, to train and qualify as doctors.
Hugh Owen Thomas, one of those sons, trained first with his uncle, Dr. Owen Roberts at St. Asaph in North Wales for four years. He then studied medicine at Edinburgh and University College, London where he qualified as MRCS in 1857. Returning to Liverpool, he first worked with his father, but incompatible temperaments did not allow this for long. In 1859 he set up his own practice in the poorer part of town.
Hugh Owen Thomas, by Hermann Fleury (National Portrait Gallery)
Hugh was known as an eccentric and rather temperamental man. Rumor had it, that he would attack victims himself, and break their bones, in order to have patients on which to practice. He was short, just over five feet tall, always wore a black coat buttoned all the way up, a patch over one eye, and constantly had a cigarette in his mouth. However, among the poor people ofLiverpool, he stood in great esteem. He practiced from his home at 11, Nelson Street, where he worked all day from five or six in the morning, to dusk. Every Sunday he would treat patients without compensation.
Thomas’ contribution to British orthopedics was manifold. In the treatment of fractures and tuberculosis he advocated rest, which should be ?enforced, uninterrupted and prolonged’. In order to achieve this he created the ?Thomas Splint’, a traction splint, which would stabilize a fractured femur and prevent infection. Prior to the introduction of the Thomas splint, mortality from femur fractures ran as high as 80%. He is also responsible for numerous other medical innovations that all carry his name: ?Thomas’s collar’ to treat tuberculosis of the cervical spine, ?Thomas’s maneuver’, an orthopedic investigation for fracture of the hip joint, Thomas test, a method of detecting hip deformity by having the patient lie flat in bed, ?Thomas’s wrench’ for reducing fractures, as well as an osteoclast to break and reset bones. His work was never fully appreciated in his own lifetime, but when his nephew, Sir Robert Jones, applied his splint during the First World War, this reduced mortality of compound fractures of the femur from 87% to less than 8% in the period from 1916 to 1918. Some of Thomas’ Works:
1. Diseases of the hip, knee and ankle joints (1876)
2. A review of the past and present treatment of disease in the hip, knee, and ankle joints: With their deformities (1878)
3. The past and present treatment of intestinal obstructions (1879)
4. The treatment of fractures of the lower jaw (1881)
5. Intestinal disease and obstruction (1883)
6. Nerve inhibition and its relation to the practice of medicine (1883)
7. Principles of the treatment of diseased joints (1883)
8. The collegian of 1666 and the collegians of 1885: Or, what is recognized treatment? (1885)
9. The principles of the treatment of fractures and dislocations (1886)
10. Fractures, dislocations, diseases and deformities of the bones of the trunk and upper extremities (1887)
11. A new lithotomy operation (1888)
12. An argument with the censor at St. Luke’s Hospital, New York (1889)
13. Fractures, dislocations, deformities and diseases of the lower extremities (1890)
14. Lithotomy (1890)
Drug Combination May Be Highly Effective in Recurrent Ovarian Cancer
According to a study reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago, a significant improvement was observed with the use of a combination drug therapy for recurrent ovarian cancer. This is the first ovarian cancer study to use a combination of drugs that could be taken orally. The trial compared the activity of a combination of the drug olaparib (which blocks DNA repair) and the blood vessel inhibitor drug cediranib, vs. olaparib alone.
Over 22,000 cases of ovarian cancer are diagnosed annually in the US. Of these, 75% of the cancers are classified as high-grade serous type where the disease is more advanced at diagnosis, and the tumors are more aggressive. Of this high-grade type, about three-quarters of patients respond to initial treatment, but nearly all will recur and need follow-up treatment. That treatment will be based on how the cancers have responded to previous therapies and are broken down into two categories based on patients’ responses to chemotherapy regimens that include platinum:
— Platinum-Sensitive – these are patients most likely to benefit from Poly ADP-Ribose Polymerase (PARP) inhibition. PARP inhibitors, such as olaparib, are targeted drugs that block an enzyme involved in many functions in the cell, including the repair of DNA damage.
— Platinum-Resistant – these are patients whose disease recurred within six months of completion of conventional chemotherapy (using the drugs cisplatin or carboplatin) and are generally less responsive to subsequent treatments and have not responded as well to PARP inhibitors. They are currently treated with non-platinum chemotherapy, single-agents, with or without addition of the blood vessel inhibitor drug called bevacizumab.
Preclinical laboratory studies suggested that the combination of cediranib and olaparib enhance the activity of each other, and an early phase 1 study showed that the combination of cediranib and olaparib was well-tolerated with minimal side effects. For this reason, 90 patients from nine centers were randomly assigned to one of two study arms for a phase II clinical trial: the first taking capsules of olaparib (400 mg twice daily) and the other taking a combination of the two drugs (200 mg olaparib in capsule form twice daily and 30 mg of cediranib by tablets once daily). The study arms were stratified by BRCA gene mutation status and receipt of prior anti-angiogenic therapy. The BRCA gene is one of the most commonly mutated genes in breast cancer.
Patients, whose median age was 58, were enrolled from October 2011 to June 2013. As of March 2014, median progression-free survival was 9.2 months for olaparib and 17.7 months for the combination therapy, which is a significant advantage. The overall rate of toxicity was higher for patients on the combination therapy. Fatigue, diarrhea, and hypertension were the most common toxic effects, all of which were manageable.
Based on these results, two phase 3 trials are being planned for platinum-sensitive and platinum-resistant ovarian cancer patients by one of NCI’s new National Cancer Trial Network Groups, the NRG Oncology Group (formerly 3 cooperative groups: the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG).
This trial was funded by NCI and received supplementary funds from the American Reinvestment and Recovery Act.
Evidence for Camel-to-Human Transmission of MERS Coronavirus
MERS-CoV is a newly identified human coronavirus that has recently emerged in the Middle East region. Current epidemiologic data suggest multiple zoonotic transmissions from an animal reservoir leading to human infection, sometimes with secondary transmission events in humans. According to a report published online in the New England Journal of Medicine (June 4, 2014), a cross infection from a camel was demonstrated based on a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) detection, isolation, and sequencing of MERS-CoV from the camel and from a patient who died of laboratory-confirmed MERS-CoV infection in Jeddah, Saudi Arabia.
The subject was a 44-year-old previously healthy Saudi man who had retired from the military, who was admitted to the intensive care unit at King Abdulaziz University Hospital, Jeddah, on November 3, 2013, with severe shortness of breath. Eight days before admission, fever, rhinorrhea, cough, and malaise developed, followed 5 days later by shortness of breath that gradually worsened. The patient owned a herd of nine camels that he kept in a barn about 75 km south of Jeddah. The patient and three of his friends had been visiting the camels daily until 3 days before his admission. The patient’s friends reported that four of the animals had been ill with nasal discharge during the week before the onset of the patient’s illness. As reported by his friends, the patient had applied a topical medicine in the nose of one of the ill camels 7 days before the patient’s onset of illness. None of the patient’s friends had had direct contact with the camels’ secretions or mucous membranes. They all remained well during the 60 days that followed the onset of illness in the patient. Five days after the patient’s hospitalization, symptoms of upper respiratory tract infection developed in his 18-year-old daughter and resolved spontaneously within 3 days without any complications. After admission, the patient’s condition continued to deteriorate, and he died on November 18, 2013.
Five days after the patient was admitted to the hospital, a veterinarian examined the nine camels, a procedure that was repeated for the following 27 days. During these examinations, the camels were found to be completely healthy, with no nasal discharge.
Nasal swabs were obtained from the patient on hospital days 1, 4, 14, and 16. Blood samples were also collected from the patient on days 1 and 14. In addition, a nasal swab was obtained from the patient’s daughter 1 day after the onset of her illness. Six days after the patient’s admission, blood samples were collected from his three friends, who were asymptomatic. Nasal swabs, blood, milk, urine, and rectal swabs were collected from the nine camels 5 days after the patient’s admission. Blood and nasal samples were collected again from the camels 28 days later (i.e., 33 days after the patient’s hospital admission). All nasal swabs, which were immersed in viral transport medium, and other samples were transported in a cold container to the Special Infectious Agents Unit, a biosafety level 3 laboratory at King Fahd Medical Research Center, King Abdulaziz University, Jeddah, for analysis.
For the analysis, Vero cells (ATCC CCL-81) were inoculated with 100 ?l of the nasal swab medium and maintained in complete Dulbecco’s Modified Eagle’s Medium, as described previously.4 The cells were incubated in a humidified atmosphere at 37?C in 5% carbon dioxide and examined daily for a cytopathic effect. Cell-culture supernatants were collected when a cytopathic effect was observed and were analyzed by means of real-time RT-PCR. The MERS-CoV isolate that was generated from the first culture passage was used for whole viral genome sequencing.
Results showed that the nasal swabs that were collected from the patient on hospital days 1, 4, 14, and 16 were all positive for MERS-CoV upE, ORF1a, and ORF1b regions on real-time RT-PCR. The first nasal sample collected from one camel (Camel B) was also positive for the three regions. The second sample collected from this camel 28 days later was negative. Nasal samples that were collected from the other camels on day 1 (seven camels) and on day 28 (eight camels) were negative for MERS-CoV RNA. The milk, urine, and rectal samples collected from all camels were negative for MERS-CoV RNA. The nasal sample collected from the patient’s daughter, who had symptoms of upper respiratory tract infection, was negative for MERS-CoV and H1N1 influenza virus RNA.
Vero cells that had been inoculated with the first samples obtained from the patient and from Camel B showed a cytopathic effect in the form of detachment of cells 3 days after inoculation. Culture supernatants collected 3 days after inoculation with both samples were positive on real-time RT-PCR for the upE, ORF1a, and ORF1b regions. To further confirm these results and to exclude the possibility of cross-contamination between the cultures for the patient and Camel B, RNA samples that had been extracted from the original nasal swabs obtained from the patient and from Camel B were subjected to partial genome sequencing of 242-bp fragments (nucleotides 15049 to 15290) and 312-bp fragments (nucleotides 29549 to 29860) in the RdRp and N regions of the viral genome, respectively. The presence of MERS-CoV-specific sequences in these samples was confirmed. Alignment of these two fragments from the two samples confirmed that they were identical.
Full genome sequencing of culture isolates obtained from the patient and from Camel B showed that the two samples were 100% identical. Phylogenetic analysis of the gene encoding the full spike protein (nucleotides 21450 to 25511) and the whole genome indicated that the MERS-CoV isolates obtained from the patient and from Camel B were closely related to the Riyadh 3/2013 isolate (KF600613.1), the MERS coronavirus isolate (known as the Munich/Abu Dhabi isolate) (KF192507.1), the betacoronavirus England 1 isolate (KC164505.2), and the human betacoronavirus 2c England-Qatar/2012 isolate (KC667074.1), with 99.8% similarity in sequence identity matrix. Similar topology was also observed for other viral genes obtained in this study.
According to the authors, the data suggest that MERS-CoV causes a zoonotic infection that can infect dromedary camels and can be transmitted from them to humans through close contact. They added that data also suggest that the camels were transiently infected, since the virus seemed to be cleared after the acute infection. As a result, camels may act as intermediate hosts that transmit the virus from its reservoir to humans. However, the exact reservoir that maintains the virus in its ecologic niche has yet to be identified.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.
First Antihemophilic Factor, Fc Fusion Protein Approved for Hemophilia A
Hemophilia A is an inherited, sex-linked, blood clotting disorder, which primarily affects males, and is caused by defects in the Factor VIII gene. Hemophilia A affects 1 in every 5,000 males born in the United States. People with Hemophilia A can experience repeated episodes of serious bleeding, mainly into the joints, which can be severely damaged by the bleeding.
The FDA has approved Eloctate, Antihemophilic Factor (Recombinant), Fc fusion protein, for use in adults and children who have Hemophilia A. Eloctate is the first Hemophilia A treatment designed to require less frequent injections when used to prevent or reduce the frequency of bleeding. Eloctate is approved to help control and prevent bleeding episodes, manage bleeding during surgical procedures, and prevent or reduce the frequency of bleeding episodes (prophylaxis). Eloctate consists of the Coagulation Factor VIII molecule (historically known as Antihemophilic Factor) linked to a protein fragment, Fc, which is found in antibodies. This makes the product last longer in the patient’s blood.
The safety and efficacy of Eloctate were evaluated in a clinical trial of 164 patients that compared the prophylactic treatment regimen to on-demand therapy. The trial demonstrated that Eloctate was effective in the treatment of bleeding episodes, in preventing or reducing bleeding and in the control of bleeding during and after surgical procedures. No safety concerns were identified in the trial.
Eloctate received orphan-drug designation for this use by the FDA because it is intended for treatment of a rare disease or condition and is manufactured by Biogen Idec, Inc., Cambridge, Mass.
Rainbow Kale Salad with Mandarins and Sunflower Seeds
1 cup purple kale, chopped
1 cup Tuscan kale, chopped
1/2 cup red cabbage, chopped
1/2 red onion, sliced thinly
1/2 red pepper, sliced thinly
2 large mandarins, peeled and cut into segments
2 Tablespoons sunflower seeds
2 Tablespoons balsamic vinegar
3 Tablespoons freshly squeezed orange juice
1 teaspoon Dijon mustard
Add freshly ground black pepper to taste
1. Combine purple kale, Tuscan kale, red cabbage, red onion, red pepper, mandarins, and sunflower seeds in a salad bowl.
2. In a smaller bowl or measuring cup, mix balsamic vinegar, orange juice, and Dijon mustard. Whisk until combined.
3. Pour the dressing on the salad and toss until the leaves are well coated.
4. Season with freshly ground pepper to taste and serve cold or at room temperature.
We love it that our son is a kale freak! This means that before (or during) he comes to visit, my challenge is to have as many kale recipes tried out, and ready to go, as possible. He’s here and at this point, I have five good kale salad recipes that I think he’ll love. So far, he’s sampled 3 of them with gusto.
The recipe above was the first one offered, which was wolfed down – a great success!
The Orange/Kale salad was followed by a dish that you already know about, the Pineapple Curry Shrimp on a bed of Saffron Jasmine Rice and some Kale Patties made with fresh kale and quinoa.
We’re feeling great this weekend! (hope you didn’t bet on California Chrome, the way I did)
From our kitchen table to yours – hope your weekend was beautiful like the weather here in Manhattan.
Bon Appetit !