Clinical Trial Innovation – eSource Solution Fully Integrated with EDC

 

Target Health is the champion of the paperless clinical trial. A device development project that used direct data entry at the time of the patient visit and risk-based monitoring (RBM) is currently under FDA review. In addition, an NDA submission is expected this year with multiple studies also using direct data entry and RBM.

 

Current and past programs include Phase 1, 2 and 3 clinical trials in: diabetes, oncology, urology, rheumatology, neurology (including migraine, ADHD, Autism). Beyond major cost savings estimated to be around $15,000/site/year, benefits include:

 

1. Efficient central and risk-based monitoring

2. Improved site/sponsor relationships

3. Value of making faster, mid-course corrections

4. Improved quality of data (w/associated cost savings to sites and sponsors)

5. Focus on things that matter and more effective allocation of resources

 

With one login at the same website using any Browser:

 

1. Sites can do real-time data entry fully integrated with Target e*CTR® (eClinical Trial Record)

2. Sites can modify data with audit trails in Target e*CRF® Target e*CTR®

3. Sites and sponsors can manage queries

4. Sites and sponsors can report and manage SAEs

5. Sites and sponsors can manage drug and device supply

6. Study subjects can be allocated to treatment

7. Monitors and project managers can review reports

8. In-house monitors and managers can review risk-based monitoring reports

9. Patients can enter Patient Reported Outcomes

10. Target e*Informed Consent (coming this year)

11: Integration of the EHR and the EDC database (coming this year)

 

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 to the pharmaceutical and device industries, including the paperless clinical trial.

 

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.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

QUIZ

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DNA

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A molecule called deoxyribonucleic acid (DNA), contains the biological instructions that make each species unique. DNA, along with the instructions it contains, is passed from adult organisms to their offspring during 1) ___. In organisms called eukaryotes, DNA is found inside a special area of the cell called the nucleus. Because the cell is very small, and because organisms have many DNA molecules per cell, each DNA molecule must be tightly packaged. This packaged form of the DNA is called a 2) ___. During DNA replication, DNA unwinds so it can be copied. At other times in the cell cycle, DNA also unwinds so that its instructions can be used to make proteins and for other biological processes. But during cell division, DNA is in its compact chromosome form to enable transfer to new 3) ___. Researchers refer to DNA found in the cell’s nucleus as nuclear DNA. An organism’s complete set of nuclear DNA is called its genome.

 

Besides the DNA located in the nucleus, humans and other complex organisms also have a small amount of DNA in cell structures known as mitochondria. 4) ___ generate the energy the cell needs to function properly. During reproduction, organisms inherit half of their nuclear DNA from the male parent and half from the female parent. However, organisms inherit all of their mitochondrial DNA from the 5) ___ parent. This occurs because only egg cells, and not sperm cells, keep their mitochondria during fertilization.

 

DNA is made of chemical building blocks called nucleotides. These building blocks are made of three parts: a phosphate group, a sugar group and one of four types of nitrogen bases. To form a strand of DNA, nucleotides are linked into chains, with the phosphate and sugar groups alternating. The four types of nitrogen bases found in nucleotides are: adenine (A), thymine (T), guanine (G) and cytosine (C). The order, or sequence, of these bases determines what biological instructions are contained in a strand of DNA. For example, the sequence ATCGTT might instruct for blue eyes, while ATCGCT might instruct for brown. The complete DNA instruction book, or 6) ___, for a human contains about 3 billion bases and about 20,000 genes on 23 pairs of chromosomes. DNA contains the instructions needed for an organism to develop, survive and reproduce. To carry out these functions, DNA sequences must be converted into messages that can be used to produce proteins, which are the complex molecules that do most of the work in our bodies. Each DNA sequence that contains instructions to make a protein is known as a 7) ___. The size of a gene may vary greatly, ranging from about 1,000 bases to 1 million bases in humans. Genes only make up about 1% of the DNA sequence. DNA sequences outside this 1% are involved in regulating when, how and how much of a protein is made. DNA’s instructions are used to make proteins in a two-step process. First, enzymes read the information in a DNA molecule and transcribe it into an intermediary molecule called messenger ribonucleic acid, or mRNA. Next, the information contained in the mRNA molecule is translated into the “language“ of amino acids, which are the building blocks of 8) ___. This language tells the cell’s protein-making machinery the precise order in which to link the amino acids to produce a specific protein. This is a major task because there are 20 types of amino acids, which can be placed in many different orders to form a wide variety of proteins.

 

The term “double helix“ is used to describe DNA’s winding, two-stranded chemical structure. This shape – which looks much like a twisted ladder – gives DNA the power to pass along biological instructions with great precision. To understand DNA’s double helix from a chemical standpoint, picture the sides of the ladder as strands of alternating sugar and phosphate groups – strands that run in opposite directions. Each “rung“ of the ladder is made up of two nitrogen bases, paired together by hydrogen bonds. Because of the highly specific nature of this type of chemical pairing, base A always pairs with base T, and likewise C with G. So, if you know the sequence of the bases on one strand of a DNA double helix, it is a simple matter to figure out the sequence of bases on the other strand.

 

DNA’s unique structure enables the molecule to 9) ___ itself during cell division. When a cell prepares to divide, the DNA helix splits down the middle and becomes two single strands. These single strands serve as templates for building two new, double-stranded DNA molecules – each a replica of the original DNA molecule. In this process, an A base is added wherever there is a T, a C where there is a G, and so on until all of the bases once again have partners. In addition, when proteins are being made, the double helix unwinds to allow a single strand of DNA to serve as a template. This template strand is then transcribed into mRNA, which is a molecule that conveys vital 10) ___ to the cell’s protein-making machinery.

 

ANSWERS: 1) reproduction; 2) chromosome; 3) cells; 4) Mitochondria; 5) female; 6) genome; 7) gene; 8) proteins; 9) copy; 10) instructions

 

Rosalind Elsie Franklin PhD (1920-1958) – Part One

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Photograph 51

Franklin’s contribution to the decoding of DNA was central. Photograph 51, refers to a “eureka“ image she recorded that made it possible to identify the double helix. Yet she has never been given the credit accorded to her rivals and colleagues, James Watson, Francis Crick and Maurice Wilkins, who received the Nobel Prize in 1962 for their work in the same field.

 

There is probably no other woman scientist with as much controversy surrounding her life and work as Rosalind Franklin. Franklin was responsible for much of the research and discovery work that led to the understanding of the structure of deoxyribonucleic acid, DNA. The story of DNA is a tale of competition and intrigue, told one way in James Watson’s book The Double Helix, and quite another in Anne Sayre’s study, Rosalind Franklin and DNA. James Watson, Francis Crick, and Maurice Wilkins received a Nobel Prize for the double-helix model of DNA in 1962, four years after Franklin’s death at age 37 from ovarian cancer.

 

Franklin excelled at science and attended one of the few girls’ schools in London that taught physics and chemistry. When she was 15, she decided to become a scientist. Her father was decidedly against higher education for women and wanted Rosalind to be a social worker. Ultimately he relented, and in 1938 she enrolled at Newnham College, Cambridge, graduating in 1941. She held a graduate fellowship for a year, but quit in 1942 to work at the British Coal Utilization Research Association, where she made fundamental studies of carbon and graphite microstructures. This work was the basis of her doctorate in physical chemistry, which she earned from Cambridge University in 1945.

 

After Cambridge, she spent three productive years (1947-1950) in Paris at the Laboratoire Central des Services Chimiques de L’Etat, where she learned X-ray diffraction techniques. In 1951, she returned to England as a research associate in John Randall’s laboratory at King’s College, London. It was in Randall’s lab that she crossed paths with Maurice Wilkins. She and Wilkins led separate research groups and had separate projects, although both were concerned with DNA. When Randall gave Franklin responsibility for her DNA project, no one had worked on it for months. Wilkins was away at the time, and when he returned he misunderstood her role, behaving as though she were a technical assistant. Both scientists were actually peers. His mistake, acknowledged but never overcome, was not surprising given the climate for women at the university then. Only males were allowed in the university dining rooms, and after hours Franklin’s colleagues went to men-only pubs.

 

But Franklin persisted on the DNA project. J. D. Bernal called her X-ray photographs of DNA, “the most beautiful X-ray photographs of any substance ever taken.“ Between 1951 and 1953 Rosalind Franklin came very close to solving the DNA structure. She was beaten to publication by Crick and Watson in part because of the friction between Wilkins and herself. At one point, Wilkins showed Watson one of Franklin’s crystallographic portraits of DNA. When he saw the picture, the solution became apparent to him, and the results went into an article in Nature almost immediately. Franklin’s work did appear as a supporting article in the same issue of the journal. At that time, life for a Jewish woman, in a closed world of Anglo-Saxon male scholars, could not have been easy.

 

A debate about the amount of credit due to Franklin continues. What is clear is that she did have a meaningful role in learning the structure of DNA and that she was a scientist of the first rank. Franklin moved to J. D. Bernal’s lab at Birkbeck College, where she did very fruitful work on the tobacco mosaic virus. She also began work on the polio virus. In the summer of 1956, Rosalind Franklin became ill with cancer. She died less than two years later.

 

A new play, “Photograph 51“ (Nicole Kidman plays Rosalyn Franklin) is now running through November 21st at the Noel Coward Theater in London. Hopefully, it’s coming to Broadway soon.

 

Diet, Exercise, Smoking Habits and Genes Affect Age-Related Macular Degeneration (AMD)

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Age-Related Macular Degeneration (AMD) is a common eye condition and a leading cause of vision loss among people age 50 and older. It causes damage to the macula, a small spot near the center of the retina and the part of the eye needed for sharp, central vision, which lets us see objects that are straight ahead. In some people, AMD advances so slowly that vision loss does not occur for a long time. In others, the disease progresses faster and may lead to a loss of vision in one or both eyes. As AMD progresses, a blurred area near the center of vision is a common symptom. Over time, the blurred area may grow larger or you may develop blank spots in your central vision. Objects also may not appear to be as bright as they used to be. AMD by itself does not lead to complete blindness, with no ability to see. However, the loss of central vision in AMD can interfere with simple everyday activities, such as the ability to see faces, drive, read, write, or do close work, such as cooking or fixing things around the house.

 

Eating a healthy diet and getting exercise have been shown in earlier studies to protect against AMD. Now, according to an observational study of women funded by the National Eye Institute, part of the National Institutes of Health and published online in Ophthalmology (8 Sept 2015), people with a genetic predisposition for AMD significantly increased their odds of developing the blinding eye disorder if they had a history of heavy smoking and consistently did not exercise or eat enough fruits and vegetables.

 

The study evaluated the risk of AMD among women ages 50 to 79 years who had participated in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary investigation of the much larger Women’s Health Initiative, an observational study that has tracked the health-related behaviors and outcomes of more than 160,000 women since 1991. The current study evaluated the diet and exercise patterns of 1663 women and categorized them into lowest-, moderate- and highest-risk groups. The study then evaluated whether the women smoked and, if so, how many years they smoked a pack of cigarettes or more each day. The study also assessed genetic data from the women to determine whether they carried known genetic risk factors for AMD. The authors focused most closely at an allele (version) of the complement factor H (CFH) gene that is known to be associated with greater AMD risk, probing whether the women had zero, one, or two copies of the allele.

 

A total of 337 women in the study developed AMD, of whom 91% had early-stage disease. Results showed that among women with stable diets, those who carried two high-risk genetic alleles, smoked at least seven pack-years, and were in the highest-risk diet and exercise categories were more than four times more likely to have AMD compared to those women who did not have genetic risk factors and who ate a healthy diet and got at least 10 hours/week of light exercise (such as housework or walking at a pace you could sing to) or at least eight hours of moderate activity (such as brisk walking).

 

In addition to lifestyle contributions, vitamin D levels may play a synergistic role with genetic factors, according to the findings of another study involving 913 CAREDS participants. Results from this study showed that blood levels indicating vitamin D deficiency (less than 12 ng/mL of 25 hydroxyvitamin D) were associated with a 1.8-fold increase in the odds of having AMD among women with no risk alleles, but a 6.7-fold increase in the odds of having AMD among women with two risk alleles, compared with women who had no genetic risk alleles and adequate levels of vitamin D. The findings of the vitamin D study were published in JAMA Ophthalmology (27 August 2015).

 

Intensive Blood Pressure Management May Save Lives

 

High blood pressure, or hypertension, is a leading risk factor for heart disease, stroke, kidney failure, and other health problems. An estimated 1 in 3 people in the United States has high blood pressure.

 

According to the initial results of a landmark clinical trial sponsored by the National Institutes of Health called the Systolic Blood Pressure Intervention Trial (SPRINT), more intensive management of high blood pressure, below a commonly recommended blood pressure target, significantly reduces rates of cardiovascular disease, and lowers risk of death in a group of adults 50 years and older with high blood pressure. The intervention in this trial, which carefully adjusts the amount or type of blood pressure medication to achieve a target systolic pressure of 120 millimeters of mercury (mm Hg), reduced rates of cardiovascular events, such as heart attack and heart failure, as well as stroke, by almost a third and the risk of death by almost a quarter, as compared to the target systolic pressure of 140 mm Hg.

 

The SPRINT study is evaluating the benefits of maintaining a new target for systolic blood pressure, the top number in a blood pressure reading, among a group of patients 50 years and older at increased risk for heart disease or who have kidney disease. A systolic pressure of 120 mm Hg, maintained by this more intensive blood pressure intervention, could ultimately help save lives among adults age 50 and older who have a combination of high blood pressure and at least one additional risk factor for heart disease.

 

The SPRINT study, which began in the fall of 2009, includes more than 9,300 participants age 50 and older, recruited from about 100 medical centers and clinical practices throughout the United States and Puerto Rico. It is the largest study of its kind to date to examine how maintaining systolic blood pressure at a lower than currently recommended level will impact cardiovascular and kidney diseases. NIH stopped the blood pressure intervention earlier than originally planned in order to quickly disseminate the significant preliminary results. The study population was diverse and included women, racial/ethnic minorities, and the elderly. The investigators point out that the SPRINT study did not include patients with diabetes, prior stroke, or polycystic kidney disease, as other research included those populations.

 

When SPRINT was designed, the well-established clinical guidelines recommended a systolic blood pressure of less than 140 mm Hg for healthy adults and 130 mm Hg for adults with kidney disease or diabetes. Investigators designed SPRINT to determine the potential benefits of achieving systolic blood pressure of less than 120 mm Hg for hypertensive adults 50 years and older who are at risk for developing heart disease or kidney disease. Between 2010 and 2013, SPRINT randomly divided the study participants into two groups that differed according to targeted levels of blood pressure control. The standard group received blood pressure medications to achieve a target of less than 140 mm Hg. They received an average of two different blood pressure medications. The intensive treatment group received medications to achieve a target of less than 120 mm Hg and received an average of three medications.

 

The study is also examining kidney disease, cognitive function, and dementia among the patients; however, those results are still under analysis and are not yet available as additional information will be collected over the next year.  The primary results of the trial will be published within the next few months.

 

New Drug Approved to Treat Schizophrenia and Bipolar Disorder

 

Schizophrenia is a chronic, severe and disabling brain disorder affecting about one percent of Americans. Typically, symptoms are first seen in adults younger than 30 years of age and include hearing voices or seeing things that are not there, believing other people are reading their minds or controlling their thoughts, and being suspicious or withdrawn. Bipolar disorder, also known as manic-depressive illness, is another brain disorder that causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. The symptoms of bipolar disorder include alternating periods of depression and high, irritable mood, increased activity and restlessness, racing thoughts, talking fast, impulsive behavior and a decreased need for sleep.

 

The US FDA has approved Vraylar (cariprazine) capsules to treat schizophrenia and bipolar disorder in adults. The efficacy of Vraylar in treating schizophrenia was demonstrated in 1,754 participants in three six-week clinical trials. In each of the trials, Vraylar was shown to reduce the symptoms of schizophrenia compared to placebo. The efficacy of Vraylar in treating bipolar disorder was shown in three, three-week clinical trials of 1,037 participants. Vraylar was shown to reduce symptoms of bipolar disorder in each of the trials.

 

Vraylar and all other FDA-approved drugs used to treat schizophrenia and bipolar disorder have a Boxed Warning alerting health care professionals about an increased risk of death associated with the use of these drugs in older people with dementia-related psychosis. Neither Vraylar nor any other drug in this class is approved to treat such patients.

 

The most common side effects reported by participants receiving Vraylar in the clinical trials for schizophrenia were extrapyramidal symptoms, such as tremor, slurred speech, and involuntary muscle movements. The most common side effects reported by trial participants receiving Vraylar for bipolar disorder were extrapyramidal symptoms, the urge to move (akathisia), indigestion (dyspepsia), vomiting, drowsiness (somnolence) and restlessness.

 

Vraylar is manufactured by Forest Laboratories LLC of Jersey City, New Jersey and distributed by Actavis Pharma Inc. of Parsippany, New Jersey.

 

Baked Halibut with Caponata Sauce

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Just out of the oven ©Joyce Hays, Target Health Inc.

 

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and on to the plate. ©Joyce Hays, Target Health Inc.

 

Caponata Ingredients

 

Olive oil for frying

1 pound of eggplant, cut into 1“ cubes

1 large onion, chopped

2 celery ribs, thinly sliced

Pinch Kosher salt and black pepper, to taste

Pinch chili flakes

2 Tablespoons tomato paste

1/4 cup water

1 cup Cento crushed canned tomatoes

3 fresh garlic cloves, sliced (not squeezed)

1/2 cup of green olives, pitted, then chopped

1/2 cup white wine vinegar

1/2 cup golden raisins

1/4 cup capers, rinsed, then drained on paper towel

2 Tablespoons agave

1/2 cup finely slivered fresh basil

2 Tablespoons pine nuts, toasted until golden and cooled

 

Halibut Ingredients

1 pound fresh halibut fillet (for 2-4 people)

1 teaspoon olive or canola oil

 

 

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Ingredients are all in one place. ©Joyce Hays, Target Health Inc.

 

Directions

 

Toast the pine nuts and set aside

Slice the basil and set aside (save some for garnish)

 

 

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Toasting the pine nuts ©Joyce Hays, Target Health Inc.

 

In a large skillet (12 inches), heat oil over medium-high heat. Once very hot, working in batches, fry eggplant cubes in one layer at a time, stirring and turning occasionally until deep golden brown, about 3 to 5 minutes. Use a slotted spoon to drain eggplant over skillet, then transfer to paper towel-lined plate and immediately season with a little salt. Repeat with remaining eggplant. Transfer drained and mostly cooled eggplant to a large bowl.

 

 

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Cooking the eggplant cubes ©Joyce Hays, Target Health Inc.

 

Pour off all but 3 Tablespoons olive oil, and reserve the rest. Cook onions and celery with salt and pepper over medium-high heat until beginning to brown, about 10 minutes.

 

Reduce heat to medium, add tomato paste and water and cook, stirring, until caramelized and almost evaporated, 2 minutes.

 

 

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©Joyce Hays, Target Health Inc.

 

Keep heat on medium flame and add crushed tomatoes; cook for 10 minutes.

 

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Draining the capers after rinsing with cold water. Adding the chopped olives to drain. Saves time and space to use the same bowl and toweling for both. ©Joyce Hays, Target Health Inc.

 

Stir in olives, vinegar, raisins, capers, and agave and cook, stirring occasionally, until thickened, about 15 minutes more.

 

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Raisins are ready to add ©Joyce Hays, Target Health Inc.

 

Add basil and pine nuts to the pan, and stir to combine. Season with salt and pepper to taste. Now, it’s ready to pour over the halibut and bake.

You can make the caponata sauce ahead of time and it tastes even better the next day.

 

Bake the halibut

 

Preheat oven to 350 degrees

When you’re ready to bake the halibut, add the 1 teaspoon of oil to a baking dish and brush it around to oil the dish. Add the halibut.

 

 

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Halibut is covered with the caponata sauce and about to go into the oven ©Joyce Hays, Target Health Inc.

 

Now, cover the halibut with the caponata sauce and bake uncovered for 15 to 20 minutes, depending on how thick the fish is.

Finally, remove and serve along with another veggie like broccoli and/or quinoa, rice or pasta and a tasty garden fresh salad.

This fish recipe is quick, delicious and healthy, not to mention colorful.

 

We started our meal with iced Santa Margherita Pinot Grigio and the apple/cauliflower salad shared recently in this newsletter. Then came the halibut with caponata sauce and for dessert a cake made with fresh plums and cool whip. A lovely satisfying repast.

 

We relaxed this weekend. Jules had returned from an important meeting with FDA. We needed to chill together. But I did manage to beat him in Scrabble (again)J Weather is beautiful here in the Big Apple!

 

 

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You can never go wrong with Santa Margherita, Pinot Grigio one of our old white standbys. ©Joyce Hays, Target Health Inc.

 

From Our Table to Yours!

 

Bon Appetit!