eClinical Forum and Risk-based Monitoring


This week, Dean Gittleman, Sr. Director of Operations at Target Health will be attending and chairing a panel on risk-based monitoring at the North American Autumn Workshop/Meeting of the eClinical Forum which is being hosted by Oracle at their offices in Reston, VA. For information on becoming a member, please contact Suzanne Bishop.


The following are the discussion topics for this meeting:


1. Operationalizing Risk-based Monitoring

2. Meeting Regulatory Challenges for EDC

3. Site eSource-Readiness

4. Trial Supply Management and Randomization


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.

Managing Change While Dealing in the Complex World of Risk-based Monitoring


We met Dr. Merom Klein and Dr. Louise Yochee Klein on a trip to Israel last year and we were impressed. We asked these innovation and change-management experts on how to thrive with all of the uncertainty and the new pressures we face as Clinical Research professionals as we deal with “risk-based monitoring.” Their answer was: “Courage.” The following is an abstract of some of their thinking directed at the concerns of senior management at Target Health.


“Anyone can see how much more uncertainty and complexity we face getting new therapies approved and on the market. You wouldn’t be the first leader to listen to the latest imperatives in a project team or portfolio review meeting and say, “Yikes! You can’t be serious! How can anyone be expected to perform that much faster, better and capital-efficiently?!? Don’t you know how things are done?” Courage. That’s what it takes to break out of our indignation and to look beyond established best-practices. Courage. That is what is needed in order to learn and adapt, as regulatory, clinical, quality, pharmacovigilance, finance and other professionals may challenge our plans to introduce new technologies and up the ante. Courage. That’s what it takes to turn off the news about the latest corporate downsizing or merger and stay focused on what you can do to make a difference and built strong partnerships. Research from Israel’s Weizman Institute shows that we all have a “courage centre“ in the subgenual anterior cingulate cortex (agACC) region of our brains – which lights up when we grapple and engage with scary forces that we’d rather avoid. When we are threatened, research on the sgACC shows that we’re as hard-wired for adaptive creative innovative problem-solving as we are to fight or take flight. All we have to do is flip the switch. Our research with thousands of R&D and commercial teams shows how leaders activate the “courage centres” of smart capable teams – and enable them to face adversity, risk, uncertainty and seemingly unreasonable standards with the courage to adapt, innovate, accelerate, orchestrate and thrive. If you’d like to know more about the 5 Courage Activators that leaders switch on – and how you and the leaders in your enterprise measure up – take a look at the FREE courage assessment.”


Heart’s Own Stem Cells Offer Hope for New Treatment of Heart Failure




Stem cells under a microscope. (Credit: Image courtesy of King’s College London)



Researchers at King’s College London have for the first time highlighted the natural regenerative capacity of a group of stem cells that reside in the heart. This new study shows that these cells are responsible for repairing and regenerating muscle tissue damaged by a heart attack which leads to heart 1) ___. The study, published August 15, 2013 in the journal Cell, shows that if the stem cells are eliminated, the heart is unable to repair after damage. If the cardiac 2) ___ cells are replaced the heart repairs itself, leading to complete cellular, anatomical and functional heart recovery, with the heart returning to normal and pumping at a regular rate. Also, if the cardiac stem cells are removed and re-injected, they naturally ‘home-in’ and repair the damaged heart, a discovery that could lead to less-invasive treatments and even early prevention of 3) ___ failure in the future.


The study, funded by the European Commission Seventh Framework Programme (FP7), set out to establish the role of cardiac stem cells (eCSCs) by first removing the cells from the hearts of rodents with heart failure. This stopped regeneration and recovery of the heart, demonstrating the intrinsic regenerative capacity of these cells for repairing the heart in response to heart failure.


Heart failure — when the heart is unable to pump 4) ___ around the body adequately — affects more than 750,000 people in the UK, causing breathlessness and impeding daily activities. Current treatments are aimed at treating the underlying causes, such as coronary heart disease, heart attack and blood pressure through lifestyle changes, medicines and in severe cases, surgery. These treatments are sometimes successful in preventing or delaying heart failure. However, once heart failure develops the only curative treatment is heart transplantation.


By revealing this robust homing mechanism, which causes cardiac stem cells to home-in and repair the heart’s damaged muscle, the findings could lead to less invasive treatments or even preventative measures aimed at maintaining or increasing the activity of the heart’s own cardiac stem 5) ___.


Dr Georgina Ellison, the first author of the paper and Professor Bernardo Nadal-Ginard, the study’s corresponding author, both from the Center of Human & Aerospace Physiological Sciences and the Center for Stem Cells and Regenerative Medicine at King’s, said: “In a healthy heart the quantity of cardiac stem cells is sufficient to repair muscle 6) ___ in the heart. However, in damaged hearts many of these cells cannot multiply or produce new muscle tissue. In these cases it could be possible to replace the damaged cardiac stem cells or add new ones by growing them in the laboratory and administering them intravenously.”


Dr Ellison added: “Understanding the role and potential of cardiac stems cells could pave the way for a variety of new ways to prevent and treat heart failure. These new approaches involve maintaining or increasing the activity of cardiac stem cells so that muscle tissue in the heart can be renewed with new heart cells, replacing old cells or those 7) ___ by wear and tear. The cardiac stem cells naturally home-in to the heart because the heart is their home — they know to go there. Current practices involve major operations such as injection through the heart’s muscle wall (intramyocardial) or coronary vessels (intracoronary). The homing mechanism shown by our research could lead to a less invasive treatment whereby cardiac stem cells are injected through a 8) ___ in the skin (intravenously).”


Professor Nadal-Ginard added: “Although an early study, our findings are very promising. Next steps include clinical trials, due to start early 2014, aimed at assessing the effectiveness of cardiac stem cells for preventing and treating heart failure in humans.”


New Way to Treat Chronic Kidney Disease and Heart Failure


Researchers at St. Michael’s Hospital in Toronto are using adult bone marrow stem cells as they investigate a completely new way of treating chronic kidney disease and heart failure in rats.


Dr. Darren Yuen and Dr. Richard Gilbert were the first to show, in 2010, that enriched stem cells improved heart and 9) ___ function in rats with both diseases. But they and other scientists wondered about the potential side effects of returning those cells to the body, such as forming tumors.


In a paper published online October 16, 2013, in the journal Stem Cells, Drs. Yuen and Gilbert said they have since found that enriched 10) ___ marrow stem cells secrete hormones in the petri dish that, if injected into rats, has the same positive impact as the stem cells. “We’ve shown that we can use these hormones, collected in the dish, to replicate the beneficial effects of the stem cells in treating animals with chronic kidney 11) ___ and heart failure,” said Dr. Yuen, a nephrologist. “In our view, this is a significant advance for stem cell therapies because it gets around having to inject stem cells.”


Dr. Yuen said they do not yet know what kind of hormone the cells are secreting. Identifying the hormone would be the first step toward the goal of developing a synthetic drug.


Chronic kidney disease is much more prevalent than was once believed, with recent estimates suggesting that up to 5% of the Canadian population may be affected. The number of people with CKD and end-stage renal failure is expected to rise as the population ages and more people develop Type 2 12) ___. People with kidney disease often develop heart disease, and many of them die from heart failure rather than kidney failure.


ANSWERS: 1) failure; 2) stem; 3) heart; 4) blood; 5) cells; 6) tissue; 7) damaged; 8) vein; 9) kidney; 10) bone; 11) disease; 12) diabetes


Source:, Wikipedia,

Dick Cheney (1941 to present) Survival Due to Medical Innovation



Dick Cheney and Condoleezza Rice, the national security adviser, in an underground center at the White House on Sept. 11, 2001. On that day, Mr. Cheney’s doctors had just received a blood test that indicated he was in serious risk of another heart attack.



Born in Lincoln, Nebraska, Richard (Dick) Cheney was primarily raised in Sumner, Nebraska, and Casper, Wyoming. In 1964, he married Lynne Vincent, his high school sweetheart, whom he had met at age 14. When Cheney became eligible for the draft, during the Vietnam War, he applied for and received five draft deferments.


Cheney’s political career began in 1969, as an intern for Congressman William A. Steiger during the Richard Nixon Administration. He then joined the staff of Donald Rumsfeld, who was then Director of the Office of Economic Opportunity from 1969-70.  Cheney and Rumsfeld would become close political colleagues and life-long friends.  When Rumsfeld was named Secretary of Defense, Cheney became White House Chief of Staff, succeeding Rumsfeld. He later was campaign manager for Ford’s1976 presidential campaign. In 1989, The Washington Post writer George C. Wilson interviewed Cheney as the next Secretary of Defense; when asked about his deferments, Cheney reportedly said, “I had other priorities in the ’60s than military service”.

President George H. W. Bush nominated Cheney for the office of Secretary of Defense immediately after the U.S. Senate failed to confirm John Tower for that position and Cheney served in that office from March 1989 to January 1993. Cheney recalls watching the elder George Bush deliver his “read my lips” convention speech in 1988 from a hospital bed as a male nurse shaved off his body hair for bypass surgery. Regarding war in the Middle East, Cheney regarded the Gulf War as an example of the kind of regional problem the United States was likely to continue to face in the future.


In early 2000, while serving as the CEO of Halliburton, Cheney headed then-Governor of Texas George W. Bush’s vice-presidential search committee. On July 25, after reviewing Cheney’s findings, Bush surprised some pundits by asking Cheney himself to join the Republican ticket. Halliburton reportedly reached agreement on July 20 to allow Cheney to retire, with a package estimated at $20 million. Other sources estimate his present net worth at $90 million.


No matter which political party you favor, no one can say that Dick Cheney’s life, from a medical perspective, is not extremely interesting. The story of his struggle with heart disease over many years, acknowledges the high level of American medicine and medical research.


In 2010, former Vice President Dick Cheney was so close to death, that he said farewell to his family members and instructed them to have his body cremated and the ashes returned to Wyoming. Mr. Cheney ultimately survived the emergency surgery that night and went on to have a heart transplant at age 71 that has left him re-energized five years after leaving office.


A new book, just published last week, which Mr. Cheney wrote with his cardiologist, Dr. Jonathan Reiner, represents a glimpse into the personal side of the former vice president. Among other things, the book discloses that on Sept. 11, 2001, as Mr. Cheney, in President George W. Bush’s absence, was effectively managing the response to the terrorist attacks on New York and Washington from the White House bunker, his doctors had just received indications that he was in serious risk of a heart attack. A blood test that morning showed Mr. Cheney with a “potentially lethal” level of potassium that suggested hyperkalemia, which could trigger cardiac arrest that even the defibrillator in his chest would not stop. As Mr. Cheney left the White House by helicopter that night for an undisclosed location, later revealed to be Camp David, a doctor handed him a note asking to take more blood to confirm the result. Mr. Cheney put him off until the morning, when the new test came back with a healthier potassium reading.


He suffered his fourth heart attack in November 2000 as he and George W. Bush awaited the Florida recount; he was checked into the hospital under the pseudonym Red Adair. By the time he left office, Mr. Cheney was having trouble breathing and walking up stairs. In December 2009, he lost consciousness while backing up his car at his Wyoming home. Soon he was experiencing nosebleeds so serious that one required emergency surgery. Then came his 5th heart attack. By summer 2010, he was entering end-stage heart failure. His appetite was gone, and he could not even walk out to pick up the newspaper. Doctors decided to implant a left ventricular assist device, but when he checked into the hospital two days before the operation, his condition was so dire they rushed him into surgery. “Cheney was dying,” Dr. Reiner writes. He spent 35 days in the hospital, much of it unconscious.


Cheney’s long histories of cardiovascular disease and periodic need for urgent health care raised questions of whether he was medically fit to serve in public office. Having smoked approximately 3 packs of cigarettes per day for nearly 20 years, Cheney sustained the first of five heart attacks in 1978, at age 37. Subsequent attacks in 1984, 1988, 2000, and 2010 have resulted in moderate contractile dysfunction of his left ventricle. He underwent four-vessel coronary artery bypass grafting in 1988, coronary artery stenting in November 2000, urgent coronary balloon angioplasty in March 2001, and the implantation of an implantable cardioverter-defibrillator in June, 2001.


On September 24, 2005, Cheney underwent a six-hour endo-vascular procedure to repair popliteal artery aneurysms bilaterally, a catheter treatment technique used in the artery behind each knee. The condition was discovered at a regular physical in July, and was not life-threatening. Cheney was hospitalized for tests after experiencing shortness of breath five months later. In late April 2006, an ultrasound revealed that the clot was smaller. On March 5, 2007, Cheney was treated for deep-vein thrombosis in his left leg at George Washington University Hospital after experiencing pain in his left calf. Doctors prescribed blood-thinning medication and allowed him to return to work. CBS News reported that during the morning of November 26, 2007, Cheney was diagnosed with atrial fibrillation and underwent treatment that afternoon.


On July 12, 2008, Cheney underwent a cardiological exam; doctors reported that his heartbeat was normal for a 67-year-old man with a history of heart problems. As part of his annual checkup, he was administered an electrocardiogram and radiological imaging of the stents placed in the arteries behind his knees in 2005. Doctors said that Cheney had not experienced any recurrence of atrial fibrillation and that his special pacemaker had neither detected nor treated any arrhythmia. On October 15, 2008, Cheney returned to the hospital briefly to treat a minor irregularity.


On January 19, 2009, Cheney strained his back “while moving boxes into his new house”. As a consequence, he was in a wheelchair for two days, including his attendance at the 2009 United States presidential inauguration. On February 22, 2010, Cheney was admitted to George Washington University Hospital after experiencing chest pains. A spokesperson later said Cheney had experienced a mild heart attack after doctors had run tests. On June 25, 2010, Cheney was admitted to George Washington University Hospital after reporting discomfort. In early July 2010, Cheney was outfitted with a left-ventricular assist device (LVAD) at Inova Fairfax Heart and Vascular Institute to compensate for worsening congestive heart failure. The device pumped blood continuously through his body. He was released from Inova on August 9, 2010, and had to decide whether to seek a full heart transplant. This pump was centrifugal and as a result he remained alive without a pulse for nearly fifteen months.


On March 24, 2012, Cheney underwent a seven-hour heart transplant procedure at Inova Fairfax Hospital in Falls Church, Virginia, at the age of 71. He had been on a waiting list for more than 20 months before receiving the heart from an anonymous donor. Cheney’s principal cardiologist, Dr. Jonathan Reiner, advised his patient that “it would not be unreasonable for an otherwise healthy 71-year-old man to expect to live another 10 years” with a transplant, saying in a family-authorized interview that he considered Cheney to be otherwise healthy. Mr. Cheney says his survival was possible only because of medical innovation: “The health care system that produced such rapid development and has driven the dramatic reduction in the incidence of death from heart disease over the past 40 years is a national treasure and deserves to be preserved and protected.”


 Sources: Peter Baker and Julie Bosman for The New York Times;  Conor Friedersdorf for The Atlantic;  Wikipedia

Fungal Infections Associated with Contaminated Methylprednisolone Injections


This article demonstrates the need for FDA oversight of all medications and how our response to a potential public health crisis can be rapidly and effectively mobilized for the common good.


Fungal infections are rare complications of injections for treatment of chronic pain. In September 2012, an investigation was initiated into fungal infections associated with injections of preservative-free methylprednisolone acetate that was purchased from a single compounding pharmacy. The following, published in the New England Journal of Medicine (2013;369:1598-1609), summarizes the findings.


As part of the investigation, three lots of methylprednisolone acetate were recalled by the pharmacy and fungus was observed as part the examination of unopened vials. Following this observation, notification of all persons potentially exposed to this formulation of methylprednisolone acetate was conducted by federal, state, and local public health officials and by staff at clinical facilities that administered the drug. The authors collected clinical data on standardized case-report forms, and tested for the presence of fungi in isolates and specimens by examining cultures and performing polymerase-chain-reaction assays and histopathological and immunohistochemical testing.


Results showed that by October 19, 2012, more than 99% of 13,534 potentially exposed persons had been contacted. As of July 1, 2013, there were 749 reported cases of infection in 20 states, with 61 deaths (8%). Other morbidities included 40 patients (5%) with stroke Laboratory evidence of Exserohilum rostratum was present in specimens from 153 case patients (20%). Additional data were available for 728 case patients (97%); 229 of these patients (31%) had meningitis with no other documented infection. Case patients had received a median of 1 injection (range, 1 to 6) of implicated methylprednisolone acetate. The median age of the patients was 64 years (range, 15 to 97), and the median incubation period (the number of days from the last injection to the date of the first diagnosis) was 47 days (range, 0 to 249).


According to the authors, analysis of data from a large, multistate outbreak of fungal infections showed substantial morbidity and mortality. The infections were associated with injection of a contaminated glucocorticoid medication from a single compounding pharmacy. Rapid public health actions included prompt recall of the implicated product, notification of exposed persons, and early outreach to clinicians.

Association Between Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients


Among nontraditional cardiovascular risk factors, recent influenza-like infection is associated with fatal and nonfatal atherothrombotic events. As a result, a study published in the Journal of the American Medical Association (2013;310:1711-1720) was performed to determine if influenza vaccination is associated with prevention of cardiovascular events.


For the study, a systematic review and meta-analysis was performed studies reported in MEDLINE (1946-August 2013), EMBASE (1947-August 2013), and the Cochrane Library Central Register of Controlled Trials (inception-August 2013). Studies included randomized clinical trials (RCTs) comparing influenza vaccine vs. placebo or control in patients at high risk of cardiovascular disease that also reported cardiovascular outcomes either as efficacy or safety events.


Two investigators extracted data independently on trial design, baseline characteristics, outcomes, and safety events from published manuscripts and unpublished supplemental data. High-quality studies were considered those that described an appropriate method of randomization, allocation concealment, blinding, and completeness of follow-up.


Five published and 1 unpublished randomized clinical trials of 6,735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; P = .003) in published trials. A treatment interaction was detected between patients with and without recent acute coronary syndrome (ACS) (P for interaction = .02).


The authors concluded that based on a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events with the greatest treatment effect seen among the highest-risk patients with more active coronary disease. The authors suggested that a large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area



FDA Issues Proposed Rule to Help Ensure the Safety of Food for Animals


Yes, the FDA is the Food and Drug Administration


The FDA has issued a proposed rule under the FDA Food Safety Modernization Act (FSMA) aimed at improving the safety of food for animals. This proposed regulation would help prevent foodborne illness in both animals and people and is open for public comments for 120 days. The proposal is part of the Food Safety Modernization Act’s larger effort to modernize the food safety system for the 21st century and focus public and private efforts on preventing food safety problems, rather than relying primarily on responding to problems after the fact.


The proposed rule would require makers of animal feed and pet food to be sold in the develop a formal plan and put into place procedures to prevent foodborne illness. The rule would also require them to have plans for correcting any problems that arise. The proposed rule would also require animal food facilities to, for the first time, follow proposed current good manufacturing practices that address areas such as sanitation.


The proposed rule would help ensure the safety of food for animals and prevent the transmission of agents in food for animals that could cause foodborne illness in both animals and people. People can get sick by handling contaminated food, such as pet food.


This proposed rule on animal food complements proposed rules published in January 2013 for produce safety and facilities that manufacture food for humans to set modern, prevention-based standards for food safety.


The FDA will hold three public meetings on the Proposed Rule for Preventive Controls for Animal Food Facilities. The first meeting will be held on November 21, 2013 at the FDA Center for Food Safety and Applied Nutrition in College Park, MD. The second meeting will be on November 25, 2013 at the Ralph H. Metcalfe Federal Building in Chicago. The third meeting will be held on December 6, 2013 at the John E. Moss Federal Building in Sacramento, CA.

Cauliflower Parmesan Cake with Yogurt/Feta Topping


This recipe is smashingly good!




This week, while my husband with his endless energy, was presenting at the CBI conference on Risk-based Monitoring, in Philly, I was enjoying “Norma”** at the Metropolitan Opera and experimenting with getting this recipe right. Don’t get me wrong, I work 10 to 7 five days a week, but love my hobby of trying to keep us from getting too fat and flabby, by putting together healthy fresh ingredients that taste good and usually are fairly low in calories. Then, we share these recipes with readers in the weekly newsletter, ON TARGET.





1 cauliflower
1 large red onion, peeled
7 1/2 Tablespoons olive oil
1/2 teaspoon finely chopped rosemary
10 medium or 8 large eggs
Handful fresh basil, chopped
Scant 1 1/2 cups almond flour
2 1/2 teaspoons baking powder
1 teaspoon ground turmeric
2 cups finely grated parmesan cheese
Salt and black pepper
Olive oil, for greasing pan
2 Tablespoons black sesame seeds



Preheat oven to 350°F degrees. Break, don’t cut, cauliflower into medium florets. Steam florets, until soft. Strain and let dry in a colander for a few minutes so they cool.


Prepare the batter. Cut red onion in half and cut a few thin rings off the end of one side; set them aside. Coarsely chop the remainder of onion. Heat all olive oil in a saucepan, and sauté the chopped red onion and rosemary together until soft, about 8 minutes. Remove from heat and allow to cool.


Whisk eggs and olive oil and onion mixture together. Stir in basil. Whisk almond flour, baking powder, turmeric, cheese, 1 teaspoon salt and pinch black pepper together in a separate bowl and add to egg mixture, whisking to remove lumps. Stir in cauliflower gently, so most pieces remain intact.


Line the bottom of a 9-inch round springform pan with parchment paper, or just oil the sides. Put the sesame seeds in the pan and toss them around so that they stick to the sides. Pour in the cauliflower batter, arrange the reserved onion rings on top and bake cake in the center of the oven for 45 minutes, until golden brown and set. Shake it to be sure it’s not wiggly. If it wiggles, bake a little longer, but keep your eye on it, so it doesn’t burn.


Serve warm or at room temperature. Before you serve the cake, be sure to run a knife around the pan, to loosen it, before removing the springform band.



1 pint plain Greek yogurt

6 ounces Feta cheese, crumbled

1/2 cup, fresh mint leaves, chopped

1/2 cup pomegranate seeds, called arils, for garnish

Pinch salt (optional)

Pinch black pepper (or grind to your taste)


Directions For Topping


Into a food processer, (or whisk it by hand) add the Greek yogurt, (scrape it all out), the Feta, salt (optional), black pepper. Leaving some of the chopped mint leaves out, for garnish, add the rest to the food processer. Now, blend everything until the sauce is smooth. As you cut and serve the cake, add a dollop of the topping, then sprinkle with mint leaves and pomegranate arils.



A slice without the Yogurt/Feta topping, but more delicious with it.



I’m really pleased; this recipe turned out this well! In fact, it’s so-o good, that I’m going to recommend that you have it on a chilly evening, in front of a fireplace (if you have one) or some cozy place in your home, with this warm (just out of the oven) cauliflower parmesan cake, with topping, as the main feature of your meal. Serve it with chilled white sauvignon blanc or your favorite red wine. And plan to have more than one piece. If this seems too bare bones, then make a simple tossed salad. Add a fresh fruit plate, along with some dates and figs, and you will be happy and satisfied.


Naturally, this scrumptious cake would be good as a superb appetizer, a wonderful lunch and at a brunch buffet, it would be the star attraction. Speaking of star attractions, as I mentioned above, I saw “Norma” at the MetOpera and want to share my favorite aria from it, “Casta Diva,” sung by the great American soprano, Renée Fleming, in a matchless performance (I have heard countless versions by others). The new young soprano in town, Angela Mead, is singing this week and next; and received many ovations for her beautiful singing, but I still say that Renée Fleming’s version is the most gorgeous and memorable. Listen to the delicate perfect trills, at the end. Most cannot get that exquisite sound.


Enjoy everything!



Bellini, Norma, Casta Diva by Renée Fleming 


Just out of the oven



Bon Appetit wherever you are!

Target Health Presenting on Risk-Based Monitoring


This week, in Philadelphia, Dr. Jules Mitchel will be presenting a talk at a CBI conference on Risk-based Monitoring. The topic will be on How to Leverage Risk-Based Monitoring and Direct Data Entry to Assess Quality Metrics in Real-Time. The presentation will address how a combination of risk-based monitoring and direct data entry (DDE) results in significant increases in the efficiency of clinical trial operations, and at the same time, reduces overall monitoring costs and expedites the delivery of safe and effective drugs to the market. The case study to be presented, shares the considerations and processes employed by Target Health during their implementation of a risk-based approach.


If you will be there, you will see:

1. Lessons learned from studies and items to consider

2. Results of studies that have and have not executed this risk-based monitoring with eSource methodology

How to save time and money while complying with regulations


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.

Could the Timing of When You Eat, Be Just as Important as What You Eat?



Gluttony in a detail from The Seven Deadly Sins and the Four Last Things by Hieronymus Bosch



Americans, today, would be extremely understanding and sympathetic to corpulent President William Howard Taft’s constant search for a diet that resulted in significant weight loss. In fact, compared to some early 21st Century fatties, he would actually be slimmer, by contrast. Taft might well have tried gastric by-pass surgery, or at least the easier lap-band surgery, frequently done with robotic assistance.


Most weight-loss plans center around a balance between 1) ___ intake and energy expenditure. However, new research has shed light on a new factor that is necessary to shed pounds: timing. Researchers from Brigham and Women’s Hospital (BWH), in collaboration with the University of Murcia and Tufts University, have found that it’s not simply what you eat, but also when you eat, that may help with weight-loss regulation.


The study was published on January 29, 2013 in the International Journal of Obesity.


“This is the first large-scale prospective study to demonstrate that the 2) ___ of meals predicts weight-loss effectiveness,” said Frank Scheer, PhD, MSc, director of the Medical Chronobiology Program and associate neuroscientist at BWH, assistant professor of medicine at Harvard Medical School, and senior author on this study. “Our results indicate that late eaters displayed a slower weight-loss rate and lost significantly less weight than early eaters, suggesting that the timing of large meals could be an important factor in a weight loss program.”


To evaluate the role of food timing in weight-loss effectiveness, the researchers studied 420 overweight study participants who followed a 20-week weight-loss treatment program in Spain. The participants were divided into two groups: early-eaters and late-eaters, according to the self-selected timing of the main meal, which in this Mediterranean population was lunch. During this meal, 40% of the total daily calories are consumed. Early-eaters ate lunch any time before 3 p.m. and late-eaters, after 3 p.m. They found that late-eaters lost significantly less weight than early-eaters, and displayed a much slower rate of weight-loss. Late-eaters also had a lower estimated insulin sensitivity, a risk factor for diabetes.


Researchers found that timing of the other (smaller) meals did not play a role in the success of weight loss. However, the late eaters — who lost less weight — also consumed fewer calories during breakfast and were more likely to skip breakfast altogether. These late-eaters also had a lower estimated insulin sensitivity, which is a risk factor for 3) ___. The researchers also examined other traditional factors that play a role in weight loss such as total calorie intake and expenditure, appetite hormones leptin and ghrelin, and sleep duration. Among these factors, researchers found no differences between both groups, suggesting that the timing of the meal was an important and independent factor in weight loss success.


“This study emphasizes that the timing of 4) ___ intake itself may play a significant role in weight regulation” explains Marta Garaulet, PhD, professor of Physiology at the University of Murcia Spain, and lead author of the study. “Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution, as it is classically done, but also the timing of food.”


National Survey Highlights Perceived Importance of Dietary Protein to Prevent Weight Gain



Fat deposits



Atkins Diet, Zone Diet, South Beach Diet, etc., etc., etc. Chances are you have known someone who has tried a high protein diet. In fact, according to the International Food Information Council Foundation, 50% of consumers were interested in including more protein in their diets and 37% believed protein helps with weight loss. In a new study released in the June 2013 issue of the Journal of Nutrition Education and Behavior, researchers found a relatively high proportion of women who reported using the practice of ”eating more 5) ___” to prevent weight gain, which was associated with reported weight loss.


Among a national sample, researchers from the University of Minnesota surveyed 1,824 midlife women (40-60 years old) to (1) describe perceptions about protein sources and requirements, (2) identify the reported frequency of using the ”eating more protein” practice to prevent weight gain, and (3) compare reported protein intake to reported frequency of using the ”eating more protein” practice to prevent weight gain.


Most women correctly identified good protein sources, and the majority could indicate the daily percent of dietary energy recommended from protein. ”Eating more protein” to prevent weight gain was reported by 43% of women (and more than half of obese women) as a practice to prevent weight 6) ___. Reported use of this practice was related to self-reported weight loss over two years. Two factors associated with effective use of this practice included the level of protein intake and self-efficacy toward weight management.


According to Noel Aldrich, lead author, those participants’ who had reported weight loss with “eating more protein” had a protein intake that was consistent with the focus on protein suggested by the 2010 Dietary Guidelines Advisory Committee. He said, “Education regarding dietary protein requirements may enhance the use of this practice. Women may need more information regarding protein energy content and effective selection of protein sources to enhance protein intake as a weight management strategy. Given that the majority of Americans are 7) ___, identifying the most effective practices and related factors surrounding successful weight loss and prevention of weight gain are important.”


Epigenetic Biomarkers May Predict If a Specific Diet and Exercise Regimen Will Work



Would you be more likely to try a diet and exercise regimen if you knew in advance if it would actually help you lose weight? Thanks to a new report published in the June 2013 issue of The FASEB Journal, this could become a reality. In the report, scientists identify five epigenetic biomarkers in adolescents that were associated with a better weight loss at the beginning of a weight loss program. Not only could this could ultimately help predict an individual’s response to weight loss intervention, but it may offer therapeutic targets for enhancing a weight loss program’s effects.


“Successful obesity treatment during adolescence could reduce morbidity at later stages of life and lead to a better quality of 8) ___,” said Amelia Martí, Ph.D., Pharm. D., co-author of this study from the Department of Nutrition, Food Science, Physiology and Toxicology at the University of Navarra in Pamplona, Spain. “It is crucial to find new markers for obesity treatment. Here, we describe five putative epigenetic biomarkers that could help to predict the response to a weight loss intervention in obese adolescents.”


To make this discovery, Martí and colleagues first performed a global methylation assay in 24 adolescents who had the best and worst response to the EVASYON weight loss program, and then expanded the sample to include 83 more adolescents. Researchers measured an epigenetic marker, DNA methylation levels, in 9) ___ adolescents from a blood sample at baseline and again at the end of the 10-week program. Participants were then divided into two groups (high and low responders) according to the weight loss achieved. The researchers found that the baseline DNA methylation levels of five epigenetic markers were associated with better weight loss response.


This EVASYON program is a lifestyle and nutritional educational weight loss program that includes a multidisciplinary team of nutritionists, physiotherapists, psychologists and pediatricians. EVASYON was conducted in five Spanish cities: Granada, Madrid, Pamplona, Santander and Zaragoza.


“If you’ve ever wondered why some people seem to do so well on a diet and exercise plan and others fail so miserably, then now we know that the way that genes express themselves (via epigenetics) plays an important role,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “This report moves us a step closer when we will be able to prescribe a weight loss program tailored to more than just the lifestyle and conditioning level of the patient, but also to his or her particular genetic and epigenetic profile.”


Weight Loss Surgery Not Only Shrinks Waists but Also Affects Genes



Venus of Willendorf created 24,000–22,000 BCE



Gastric bypass 10) ___ can drastically reduce the body weight of obese individuals in a short timeframe. For reasons that are not entirely clear, the surgery also leads to early remission of type 2 diabetes in the vast majority of patients. Researchers report online in Cell Reports, published by Cell Press, the discovery of gene-expression alterations in individuals who underwent the surgery compared with obese individuals who did not.


“We provide evidence that in severely obese people, the levels of specific genes that control how fat is burned and stored in the body are changed to reflect poor metabolic health,” says senior author Professor Juleen Zierath, of the Karolinska Institutet, in Stockholm, Sweden. “After surgery, the levels of these genes are restored to a healthy state, which mirrors weight loss and coincides with overall improvement in 11) ___.” When the investigators probed deeper, they found that weight loss after surgery causes changes in DNA modifications that control gene expression in response to the environment. Specifically, changes in methylation, or chemical markings, on two genes that control glucose and fat metabolism (called PGC-1alpha and PDK4) correlate with obesity but are reversed after surgery-induced weight loss. The findings suggest that the environment — in this case food intake or weight loss — can affect gene expression through this mechanism.


“The novelty of our work originates with the finding that DNA methylation is altered by weight loss.” says first author Romain Barrès, of the University of Copenhagen, in Denmark. The findings may be useful for the design of new drugs that mimic this weight-loss-associated control of gene 12) ___.


ANSWERS: 1) caloric; 2) timing; 3) diabetes; 4) food; 5) protein; 6) gain; 7) overweight; 8) life; 9) obese; 10) surgery; 11) metabolism; 12) regulation


Sources:, Wikipedia,,

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