Year 2: BIRD Foundation Grant to Integrate EDC with the EMR
Target Health and Life-On-Key are pleased to announce that Year 2 of a 2 year project, sponsored by a grant from the BIRD Foundation, has begun. The goal of the project is to integrate any electronic medical record (EMR) with any electronic data capture (EDC) system used in clinical trials. To date we have been able to send clinical trial data from Target e*CRF to the Life-On-Key EMR. The next phase will include extracting data from the EMR, combining the EMR data with other clinical trial data entered at the time of the clinic visit, creating the eCRF and then creating Target e*CTR®, the eClinical Trial Record, a 21CFR Part 11 compliant source record.
This grant compliments Target Health’s mission to transform the pharmaceutical industry from paper-based clinical trials to technology-based clinical trials with increased productivity and quality, and decreased time to database lock time and decision-making.
Springtime in NYC – Park Avenue Armory at 67th and Park ©Target Health
ON TARGET is the newsletter of Target Health Inc., a NYC-based 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. Mitchelor 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 Chief Editor of On Target
Jules Mitchel, Editor
Space and telemedicine – Cardiothoracic surgeon launches research into space
When an unmanned supply mission launched into space on April 18, bound for the International Space 1) ___, it meant something extraordinary to Dr. Peter Lee, a cardiothoracic surgeon at The Ohio State University Wexner Medical Center. That’s because his research experiment is on board. Lee has been fascinated by space exploration since he was a child. Now, that fascination has evolved into a passion for space medicine and learning about the effects of space travel on the heart. It’s more than the joy ride of traveling in space. I don’t have to do that. What excites me is being a part of the science, the learning and the research, Lee said.
In a small box, on board the private rocket, Lee sent approximately 200 fruit flies into space, to be exposed to the effects of microgravity and space radiation for 30 days while docked with the International Space Station. It is one of only eight research studies on this mission sponsored by Space Florida, an aerospace economic development agency that supports space exploration. When the flies return, Lee and his collaborators will examine their hearts, looking for cardiovascular changes and changes in gene expression. About three-fourths of known human disease genes can be matched in the genome of 2) ___ flies, Lee said. I hope the analysis will help us learn what happens to the hearts of astronauts and how to prevent cardiovascular problems in the future. Eventually, our findings could someday help astronauts explore or even live in deep space.
Lee’s research into space medicine has spanned decades and he has been involved in other missions. One of Lee’s experiments flew with John Glenn when he made his return to space in 1998 at the age of 77. While working at Brown, Harvard, and Stanford Universities, Lee led several student groups that researched ways to perform CPR in 3) ___ gravity, practiced airway intubations, and tested various medical techniques and equipment to see if they can be used for space travel. Lee says he’s looking forward to leading similar student groups at Ohio State.
NASA medical monitoring
Microgravity accelerates biological aging
As nations strive to put humans farther into space for longer periods of time, the real loser in this new space race could be the 4) ___ themselves. That’s because experiments conducted on the International Space Station involving cells that line the inner surfaces of blood vessels (endothelial cells) show that microgravity accelerates cardiovascular disease and the biological aging of these cells. These findings are presented in a research report published in the The FASEB Journal. Understanding the cellular and molecular events of senescence might help in finding preventive measures that are useful to improve the quality of life of millions of people, said Silvia Bradamante, a researcher involved in the work from the CNR-ISTM, Institute of Molecular Science and Technologies in Milan, Italy. Our study further supports the role of oxidative 5) ___ in accelerating aging and disease.
In this report, Bradamante and colleagues examined endothelial cells in real microgravity aboard the International Space Station and conducted deep gene expression and protein analysis on the cells. They compared space-flown endothelial cells to endothelial cells cultured under normal gravity, looking for differences in gene expression and/or in the profile of secreted proteins. Space-flown cells differentially expressed more than 1,000 genes and secreted high amounts of pro-inflammatory cytokines. Ultimately, this induced significant oxidative stress, causing 6) ___ among endothelial cells, which in turn, led to atherosclerosis and cell senescence (biological aging). As we plan to send people deeper into space than ever before, and for longer flights, we’ve got to make sure that they remain in best health possible, said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. We’ve evolved to rely on gravity to regulate our biology, and without it, our tissues become confused. Worst of all: they age faster!
Researcher to grow human cells in space to test treatment for stroke
Abba Zubair, M.D., Ph.D, believes that cells grown in the International Space Station (ISS) could help patients recover from a stroke, and that it may even be possible to generate human tissues and organs in space. The Center for the Advancement of Science in Space (CASIS), a nonprofit organization that promotes research aboard the ISS, has awarded Dr. Zubair a $300,000 grant to send human stem cells into space to see if they grow more rapidly than stem cells grown on 7) ___. Dr. Zubair, medical and scientific director of the Cell Therapy Laboratory at Mayo Clinic in Florida, says the experiment will be the first one Mayo Clinic has conducted in space and the first to use these human stem cells, which are found in bone 8) ___. On Earth, we face many challenges in trying to grow enough stem cells to treat patients, he says. It now takes a month to generate enough cells for a few patients. A clinical-grade laboratory in space could provide the answer we all have been seeking for regenerative medicine. He specifically wants to expand the population of stem cells that will induce regeneration of neurons and blood vessels in patients who have suffered a hemorrhagic stroke, the kind of stroke which is caused by blood 9) ___. Dr. Zubair already grows such cells in his Mayo Clinic laboratory using a large tissue culture and several incubators — but only at a snail’s pace.
Experiments on Earth using microgravity have shown that stem cells — the master cells that produce all organ and tissue cell types — will grow faster, compared to conventionally grown cells. If you have a ready supply of these cells, you can treat almost any condition, and can theoretically regenerate entire organs using a scaffold, Dr. Zubair says. Additionally, they don’t need to come from individual patients — anyone can use them without rejection. Dr. Zubair is working with engineers at the University of Colorado who are building the specialized cell bioreactor that will be taken to the ISS within a year for the experiment. I don’t really think growing cells in space for clinical use on Earth is science fiction, he says. Commercial flights to the ISS will start soon, and the cost of traveling there is coming down. We just need to show what can be achieved in space, and this award from CASIS helps us do that.
Space research may lead to new cancer treatments
Exposure to microgravity has been shown to weaken astronauts’ immune systems and increase the activity of harmful microorganisms. The news from space medicine is not all bad, however. New research suggests that thyroid cancer cells enter a less aggressive state under the influence of 10) ___. By understanding the genetic and cellular changes that occur in space, scientists may be able to develop new cancer treatments for use on Earth. Daniela Gabriele Grimm, MD, from the Department of Biomedicine at Aarhus University in Denmark, said, Research in space or under simulated microgravity using ground-based facilities helps us in many ways to understand the complex processes of life and this study is the first step toward the understanding of the mechanisms of cancer growth inhibition in microgravity. Ultimately, we hope to find new cellular targets, leading to the development of new anti-cancer 11) ___ which might help to treat those tumors that prove to be non-responsive to the currently employed agents. Grimm and colleagues from Denmark and Germany used the Science in Microgravity Box facility aboard the Chinese Shenzhou-8, which was launched on October 31, 2011. Cell feeding was performed automatically on day 5 of the mission and automated cell fixation was conducted on day 10. An onboard centrifuge was used for inflight control cultures. On the ground, additional cells were tested using a random-positioning machine, which aims to simulate microgravity by rotating a sample around two axes. Cells were studied for gene expression and secretion profiles, using modern molecular biological techniques such as whole genome microarrays and multi-analyte profiling. Results suggest that the expression of genes that indicate high malignancy were down-regulated in microgravity.
We are just at the beginning of a new field of medicine that studies the effects of microgravity on 12) ___ and molecular pathology, said Gerald Weissmann, MD, editor-in-chief of The FASEB Journal. Space flight affects our bodies, both for good and bad. We’ve known that microgravity can cause some microorganisms to become more virulent and that prolonged microgravity has negative effects on the human body. Now, we learn that it’s not all bad news. What we learn from cells in space should help us understand and treat malignant tumors on the ground.
1) Ohio State University Wexner Medical Center; Cardiothoracic surgeon launches research into space;
2) Federation of American Societies for Experimental Biology; S. Versari, G. Longinotti, L. Barenghi, J. A. M. Maier, S. Bradamante. The challenging environment on board the International Space Station affects endothelial cell function by triggering oxidative stress through thioredoxin interacting protein overexpression: the ESA-SPHINX experiment. The FASEB Journal, 2013; 27 (11): 4466 DOI: 10.1096/fj.13-229195;
3) Mayo Clinic. Researcher to grow human cells in space to test treatment for stroke;
4) Differential Gene Expression Profile and Altered Cytokine Secretion of Thyroid Cancer Cells in Space was published in the February issue of The Journal of the Federation of American Societies for Experimental Biology;
ANSWERS: 1) Station; 2) fruit; 3) zero; 4) astronauts; 5) stress; 6) inflammation; 7) Earth; 8) marrow; 9) clot; 10) microgravity; 11) drugs; 12) cell
Space, the New Medical Frontier – Part 1
A NASA illustration of a medical emergency at a lunar colony
Space nursing is the nursing specialty that studies how space travel impacts human response patterns. Similar to space medicine, the specialty also contributes to knowledge about nursing care of earthbound patients. Since the beginning of commercial aviation in the 1920s, nurses have been part of aviation and flight. In 1958, President Eisenhower signed the National Aeronautics and Space Act to form NASA. Part of this act was to recruit nurses to work closely with medical teams to determine the fitness of astronauts for space exploration. Nurses helped observe the effects of spaceflight on astronauts upon their return from missions.
In 1962. NASA announced the Space Nursing Program which required applicants to have a previous bachelor’s degree in nursing. In 1991, the Space Nursing Society was founded by Linda Plush with the help of Dr. Martha Rogers. It is based on Rogers’ Theory, the Science of unitary human beings. The Space Nursing Society is an international space advocacy organization devoted to space nursing and space exploration by registered nurses. The society is an affiliated, non-profit special interest group associated with the National Space Society. The society was founded in 1991 and has members from around the world including Australia, Canada, Czech Republic, England, Germany, Greece, Scotland and the United States. The society serves as a forum for the discussion and study of issues related to nursing in space and the impact of these studies on nursing on Earth.
Astronaut John H. Glenn Jr., pilot of the Mercury-Atlas 6 earth-orbital space mission, confers with Astronaut Nurse Dolores B. O’Hara, R.N., during MA-6 prelaunch preparations.
The International Space Station 2014
One of the space laboratories
Space medicine is the practice of medicine on astronauts in outer space whereas astronautical hygiene is the application of science and technology to the prevention or control of exposure to the hazards that may cause astronaut ill health. Both these sciences work together to ensure that astronauts work in a safe environment. The main objective is to discover how well and for how long people can survive the extreme conditions in space, and how fast they can adapt to the Earth’s environment after returning from their voyage. Medical consequences such as possible blindness and bone loss have been associated with human spaceflight.
After World War 2, the US encouraged German physicians to join with American docs to form the School of Aviation Medicine (SAM) at Randolph Air Force Base, Texas, which is now called the US Air Force School of Aerospace Medicine, at Brooks Air Force Base, Texas. The pressure suit worn by early American astronauts, was developed at this time in the late 1940s.
Astronauts are not the only ones who benefit from space medicine research. Several medical products have been developed that are space spinoffs, that is practical applications for the field of medicine arising out of the space program. Because of joint research efforts between NASA, the National Institutes on Aging (a part of the National Institutes of Health), and other aging-related organizations, space exploration has benefited a particular segment of society, seniors. Evidence of aging related medical research conducted in space was most publicly noticeable during STS-95
Medical space spinoffs: pre-Mercury (1957-65), Gemini (1965-66) through Apollo (1968-72)
1. Radiation therapy for the treatment of cancer: In conjunction with the Cleveland Clinic, the cyclotron at Glenn Research Center in Cleveland, Ohio was used in the first clinical trials for the treatment and evaluation of neutron therapy for cancer patients.
2. Foldable walkers: Made from a lightweight metal material developed by NASA for aircraft and spacecraft, foldable walkers are portable and easy to manage.
3. Personal alert systems: These are emergency alert devices that can be worn by individuals who may require emergency medical or safety assistance. When a button is pushed, the device sends a signal to a remote location for help. To send the signal, the device relies on telemetry technology developed at NASA.
4. CAT and MRI scans: These devices are used by hospitals to see inside the human body. Their development would not have been possible without the technology provided by NASA after it found a way to take better pictures of the Earth’s moon.
5. Muscle stimulator device: This device is used for 1/2 hour per day to prevent muscle atrophy in paralyzed individuals. It provides electrical stimulation to muscles which is equal to jogging three miles per week. Christopher Reeve used these in his therapy.
6. Orthopedic evaluation tools: Equipment to evaluate posture, gait and balance disturbances was developed at NASA, along with a radiation-free way to measure bone flexibility using vibration.
7. Diabetic foot mapping: This technique was developed at NASA’s center in Cleveland, Ohio to help monitor the effects of diabetes in feet.
8. Foam cushioning: Special foam used for cushioning astronauts during liftoff is used in pillows and mattresses at many nursing homes and hospitals to help prevent ulcers, relieve pressure, and provide a better night’s sleep.
9. Kidney dialysis machines: These machines rely on technology developed by NASA in order to process and remove toxic waste from used dialysis fluid.
10. Talking wheelchairs: Paralyzed individuals who have difficulty speaking may use a talking feature on their wheelchairs which was developed by NASA to create synthesized speech for aircraft.
11. Collapsible, lightweight wheelchairs: These wheelchairs are designed for portability and can be folded and put into trunks of cars. They rely on synthetic materials that NASA developed for its air and space craft
12. Surgically implantable heart pacemaker: These devices depend on technologies developed by NASA for use with satellites. They communicate information about the activity of the pacemaker, such as how much time remains before the batteries need to be replaced.
13. Implantable heart defibrillator: This tool continuously monitors heart activity and can deliver an electric shock to restore heartbeat regularity.
14. EMS communications: Technology used to communicate telemetry between Earth and space was developed by NASA to monitor the health of astronauts in space from the ground. Ambulances use this same technology to send information – like EKG readings – from patients in transport to hospitals. This allows faster and better treatment.
15. Weightlessness therapy: The weightlessness of space can allow some individuals with limited mobility on Earth – even those normally confined to wheelchairs – the freedom to move about with ease. Physicist Stephen Hawking took advantage of weightlessness in NASA’s Vomit Comet aircraft in 2007. This idea also led to the development of the Anti-Gravity Treadmill from NASA technology.
Medical investigations in space during the Space Shuttle era
John Glenn, the first American astronaut to orbit the Earth, returned with much fanfare to space once again on STS-95 at 77 years of age to confront the physiological challenges preventing long-term space travel for astronauts?loss of bone density, loss of muscle mass, balance disorders, sleep disturbances, cardiovascular changes, and immune system depression?all of which are problems confronting aging people as well as astronauts. Once again Glenn stepped forward to play a historic role in the future of space exploration, but this time he would provide new medical research in the field of gerontology as well.
FAST FORWARD: American scientists now have a national laboratory on the International Space Station (ISS), for health and medical research. Agreements between NIH, NASA and NSBRI (National Space Biomedical Research Institute create unique partnerships between these government agencies and academic and industrial communities. This cooperation is advancing biomedical research with the goal of ensuring a safe and productive long-term human presence in space. By developing new approaches and countermeasures to prevent, minimize and reverse critical risks to health, the Institute plays an essential, enabling role for NASA and bridges the research, technological and clinical expertise of the biomedical community with the scientific, engineering and operational expertise of NASA.
The ISS, which has been taking shape for much of the past decade, is an orbiting laboratory for many kinds of research. This relationship between the nation’s premier medical laboratories and the national space effort is a first, and already there is much excitement about the various advances to come from space-based research. There are many new frontiers and considerable new knowledge that medical researchers can gain from using the space station, says Stephen I. Katz, M.D., Ph.D., director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and NIH’s liaison with NASA. Continuously inhabited by astronauts and scientists since 2000, the ISS is a perfect place to research all manner of scientific, technical, and medical questions. In fact, some medical research can only be performed in orbit. That means aboard the space station, where there is no gravity. The same weightlessness that lets space-suited astronauts move massive objects easily also offers a unique learning opportunity. Zero-gravity’s effects on astronauts’ skeletal systems and loss of bone and muscle mass have long attracted scientific interest, Dr. Katz says. Research on the space station will help generate better understanding of how weightlessness affects the bone, muscle, and inner ear systems.
The more we know about how the various systems of the human body react to weightlessness and the other conditions found only in space, the better able we will be to ensure the health of ISS crew members, as well as those future astronauts and researchers who will journey to the moon (again), Mars, and beyond.
The benefits also will pay off back on earth:
1. Increased understanding of bone-strength and loss of bone-mass may help patients suffering from delicate bones or muscle wasting diseases.
2. Without gravity to help orient them, astronauts experience changes in their sense of balance. Studying this phenomenon may yield insights into dizziness, vertigo, and balance problems and disorders related to the inner ear.
3. Observing the behavior of microbes and other organisms in space can generate insights into the behavior of organisms on earth, and perhaps lead to better understanding of infectious diseases and the immune system’s response to them.
Our health and medical knowledge and capabilities have grown greatly because of space exploration and the equipment and techniques developed for it. Remote health-monitoring sensors and temperature-lowering cool suits are just two examples derived from the lessons learned from orbital space suits. And medical imaging technologies and ultrasound procedures are based, in part, on NASA innovations. Until the advent of the ISS, research missions in space were necessarily brief?usually only a few days or weeks, at best. With long-term human residence in space now made possible by the ISS, it is important that a certain percentage of each ISS crew be dedicated to vital medical research. As with everything connected with space travel, results will take time because of the planning, preparation, and training involved.
An enormous amount of time will be required to develop the questions and experimental models for use on the space station, says Dr. Katz. First, you have to make sure you’re asking important questions. Also, the scientists’ time is valuable, and it’s very expensive to put the experiments together and transport them to the space station. Added to this is additional training the astronauts – many of whom are scientists – must complete to be able to perform the experiments correctly. Thanks to the formal agreement between NIH and NASA, the research will be carefully coordinated into high-priority areas, with promise of practical results. Both NIH and NASA are committed to real cooperation, Dr. Katz says. This cooperation may serve as the foundation for a potential flowering of both space medicine and earth-based health care.000. We are extremely pleased that this collaborative effort is moving forward, adds NIH Director Dr. Elias Zerhouni. The International Space Station provides a unique environment where researchers can explore fundamental questions about human health issues, including how the body heals itself, fights infection, or develops diseases such as cancer or osteoporosis. Sources: NIAMS.gov; NASA.gov NIH.gov; NIAMS.gov; NSBRI.gov; Wikipedia.com
Popular Glaucoma Drug Helps Women with Blinding Disorder Linked to Obesity
According to an article published in the Journal of the American Medical Association (2014;311:1641-1651), an inexpensive glaucoma drug, when added to a weight loss plan, can improve vision for women with a disorder called idiopathic intracranial hypertension (IIH). IIH, also called pseudotumor cerebri, predominantly affects overweight women of reproductive age. An estimated 100,000 Americans have it, and the number is rising with the obesity epidemic. The most common symptoms are headaches and visual problems, including blind spots, poor side vision, double vision and temporary episodes of blindness. About 5-10% of women with IIH experience disabling vision loss.
The trial was funded by NIH’s National Eye Institute, and coordinated by the Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC). The results will also be presented on May 2 during the Clinical Trials plenary session of the American Academy of Neurology meeting in Philadelphia.
Acetazolamide (Diamox) is best known as a glaucoma drug. It has been commonly prescribed for IIH, but without much evidence that it helps. The IIH Treatment Trial tested the benefits of acetazolamide plus a weight loss plan versus the weight loss plan with a placebo pill, over six months. Patients in both treatment groups had improved vision, but those receiving the drug had the greatest improvement. All patients were allowed to take headache medications throughout the trial, and both groups experienced a similar reduction in headache.
IIH is named for one of its key physical findings — an increased pressure within the fluid-filled spaces inside and around the brain. This in turn can cause swelling and damage to the optic nerves that connect the eyes to the brain. A 5-10% weight reduction appears to improve symptoms for many patients, but can be difficult to achieve and maintain. Acetazolamide is known to reduce fluid production in the brain, and is often used as an add-on therapy. In severe cases, surgical procedures may be used to relieve pressure on the optic nerve.
The NIH-funded trial involved 161 women and four men with IIH and mild vision loss, who were enrolled at 38 sites. At enrollment, their average body mass index (BMI) was about 40. A BMI of 30 or greater is considered obese. All participants were put on a weight loss plan to trim salt and about 500 to 1,000 calories from their food intake each day, with the goal to lose 6%of their starting weight. Participants were provided with a weight loss coach and some simple low-cost exercise equipment. This included a step counter and a resistance band, a piece of rubber tubing used for strength training. About half the participants were randomly assigned to receive acetazolamide. The drug was given at 1 gram daily for the first week and increased by a quarter gram each week, to reach the maximally tolerated dosage, or up to 4 grams daily. The other half of participants received a placebo in gradually increasing dosages.
After six months, both groups had improved scores on visual field tests, a measure of side or peripheral vision. However, participants on acetazolamide improved by about twice as much as those on placebo. Compared to weight loss alone, the drug also helped reduce swelling of the optic nerve. The drug-weight loss combination also led to greater improvements in daily function and quality of life compared to weight loss alone, based on the NEI Visual Functioning Questionnaire. In the placebo group, there were six treatment failures — defined as a substantial worsening of vision that required withdrawal from the trial. There was one treatment failure in the acetazolamide group.
Seven people on acetazolamide and one person on placebo stopped taking their assigned study medication because of perceived side effects. Three people on placebo were admitted to the hospital compared to six on the drug, two of whom developed kidney stones. All side effects were reversed by stopping the drug or reducing the dosage.
Another strength of the study was the weight loss program. The New York Obesity Nutrition Research Center designed the program to achieve moderate, sustainable weight control with an emphasis on changing lifestyle, as opposed to just dieting. The trial will follow participants for five years to gauge whether they’re able to maintain a healthy weight and control their symptoms over the long term.
Muscle Weakness in Alcoholism Linked to Mitochondrial Repair
Mitochondria are cellular structures that generate most of the energy needed by cells. Skeletal muscle constantly relies on mitochondria for power. When mitochondria become damaged, they can repair themselves through a process called mitochondrial fusion — joining with other mitochondria and exchanging material such as DNA.
According to a study published online in the Journal of Cell Biology (21 April 2014), muscle weakness from long-term alcoholism may stem from an inability of mitochondria, the powerhouses of cells, to self-repair. In research conducted with rats, scientists found evidence that chronic heavy alcohol use affects a gene involved in mitochondrial repair and muscle regeneration.
According to Dr. George Koob, director of the National Institute on Alcohol Abuse and Alcoholism, the NIH institute that funded the study The finding gives insight into why chronic heavy drinking often saps muscle strength and it could also lead to new targets for medication development.”
Although well known in many other tissues, the current study is the first to show that mitochondria in skeletal muscle are capable of undergoing fusion as a repair mechanism. It had been thought that this type of mitochondrial self-repair was unlikely in the packed fibers of the skeletal muscle cells, as mitochondria have little opportunity to interact in the narrow space between the thread-like structures called myofilaments that make up muscle.
By tagging mitochondria in the skeletal tissue of rats with different colors, the authors were able to observe the process in action and confirm that mitochondrial fusion occurs in muscle cells. They also identified a key protein in the process, mitofusin 1 (Mfn1) fusion proteins, and showed that chronic alcohol use interferes with the process. In rats that were given an alcohol diet, Mfn1 levels decreased as much as 50% while other fusion proteins were unchanged. This decrease in Mfn1 was coupled with a dramatic decrease in mitochondrial fusion. When Mfn1 returned to normal, mitochondrial fusion did as well.
According to the authors, the fact that alcohol can have a specific effect on this one gene involved in mitochondrial fusion suggests that other environmental factors may also alter specifically mitochondrial fusion and repair. For future clinical applications, identifying the proteins involved in mitochondrial fusion may aid in drug development for alcohol-related muscle weakness.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.
FDA Proposes New Expedited Access Program for Medical Devices That Address Unmet Medical Needs
The FDA has proposed a new program to provide earlier access to high-risk medical devices that are intended to treat or diagnose patients with serious conditions whose medical needs are unmet by current technology. The proposed Expedited Access Premarket Approval Application for Unmet Medical Needs for Life Threatening or Irreversibly Debilitating Diseases or Conditions (Expedited Access PMA or EAP) program features earlier and more interactive engagement with FDA staff – including the involvement of senior management and a collaboratively developed plan for collecting the scientific and clinical data to support approval – features that, taken together, should provide these patients with earlier access to safe and effective medical devices.
EAP is not a new pathway to market, but rather a collaborative approach to facilitate product development under the agency’s existing regulatory authorities. While other existing device programs have focused on reducing the time for the premarket review, EAP also seeks to reduce the time associated with product development.
To be eligible for participation in the program, the medical device must be intended to treat or diagnose a life-threatening or irreversibly-debilitating disease or condition where:
1. there is no approved alternative treatment/diagnostic exists, or
2. a breakthrough technology provides a clinically meaningful advantage over existing technology, or
3. the device offers a significant, clinically meaningful advantage over existing approved alternatives, or
4. availability of the new device is in the patient’s best interest
5. there exists an acceptable data development plan that has been approved by the FDA
The EAP builds on the Innovation Pathway pilot, which the FDA launched in 2011, and the FDA’s experience with expedited review programs for pharmaceuticals, including Accelerated Approval and Breakthrough Therapies. When utilizing the EAP program, the FDA will continue to apply the current approval standard of demonstrating a reasonable assurance of safety and efficacy.
In addition to the Expedited Access Program, the FDA published a separate draft guidance that outlines the agency’s current policy on when data can be collected after product approval and what actions are available to the FDA if approval conditions, such as postmarket data collection, are not met. Included in the guidance is advice on the use of surrogate or independent markers to support approval, similar to the data points used for accelerated approval of prescription drugs.
The FDA seeks public comment on both documents.
1. Expedited Access for Premarket Approval Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions – Draft Guidance for Industry and FDA Staff
2. Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval – Draft Guidance for Industry and FDA Staff
©Joyce Hays, Target Health Inc.
1/2 teaspoon Kosher salt (optional)
1 pound ground turkey
1 large egg
2 Tablespoons chopped fresh parsley
2 Tablespoons freshly grated pecorino Romano
1/2 teaspoon ground black pepper
2 Tablespoons Panko
About 2-3 Tablespoons olive oil for cooking
1 garlic clove, juiced
©Joyce Hays, Target Health Inc.
1. In a medium bowl, mix together the meat, 1 egg, garlic, parsley, pecorino, 1/2 teaspoon salt and 1/2 teaspoon pepper.
2. In a small bowl, add 2 Tablespoons water to the bread crumbs. When absorbed, add this to the meatball mixture and combine well. (adding this small step, gives you moist meatballs rather than dry ones)
3. Shape into small (1-inch) meatballs and fry in a skillet with a little oil over medium to medium-high heat until browned all over, about 5 to 7 minutes. Set aside.
4. Make your own marinara sauce and serve with the turkey meatballs plus your favorite pasta.
©Joyce Hays, Target Health Inc.
As you know, we’ve cut way down on our beef consumption and are thriving on all the veggie recipes I dream up, including adapting recipes from other sources. Once in a while we turn back into carnivores. Since we did our semi-fasting for two days this past week, I knew we’d want to sink our teeth into some meat this weekend. I’ve been experimenting with veggie meatballs but so far, have not been successful. The closest I’ve come to anything resembling meatballs, is a combination of chopped cremini mushrooms and cashew nuts pureed, which tasted good, but didn’t hold together well. Don’t worry, I’ll keep trying and will share, when I succeed. In the meantime, here is an easy and quick recipe for turkey meatballs that I’ve experimented with a lot. I think you’ll like this. Serve them with your favorite marinara sauce, pasta and lots of extra freshly grated parmesan. If you plan on making your own marinara, use canned Cento (see below).
Usually, we would have a fresh salad with a meal like this, but this evening we polished off some left-over veggies, like kale patties with avocado sauce. We enjoyed a robust cab, recommended to us by our favorite Italian eatery. Lately, we’ve been endulging in Tesoro from Sonomo Muscardini Vineyards, full bodied and delicious. Someone wondered if we buy beautiful flowers just for a lovely photo with the wine. The answer is that we simply love flowers and have them all over our home all the time.
Hope that all of our friends and colleagues had an excellent weekend, and we raise our glasses this evening to toast a good week to all!
©Joyce Hays, Target Health Inc. Smiling face in the background is my satisfied hub, after a good meal and several glasses of this full flavored cabernet. You can see his glass is nearly empty.
Bon Appetit !
Response to New York City Economic Development Corporation (NYCEDC) Blog That Featured Target Health
Last week the NYCEDC featured Target Health in its Blog. The headline was Made in NYC: Target Health (http://www.nycedc.com/blog-entry/made-nyc-target-health). One highlight in the piece was that Target Health supports the arts in NYC, including the Metropolitan Opera. Here are some of the many responses we had on this.
1. From Europe: Did you go for Werther with Jonas Kaufman at the MET?
2. From Australia: Main reason for writing – was in NYC last week and friends secured a fabulous box at the Met for a brilliant production of Madama Butterfly. Noted in the program that Target Health is a sponsor and just want to thank you guys for supporting a great cause.
Here’s Jonas Kaufman singing “Pourquoi Me Reveiller?” (Why Awaken Me, Oh Breath of Spring) from Werther: https://www.youtube.com/watch?v=3FiWzeBNIWU
Here’s Rene Fleming singing from Madama Butterfly,Un Bel di Vedremo, (One Fine Day):https://www.youtube.com/watch?v=66iKh4KKfME
Springtime in Central Park © Target Health Inc.
ON TARGET is the newsletter of Target Health Inc., a NYC-based 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.
Joyce Hays, Founder and Chief Editor of On Target
Jules Mitchel, Editor
Daylight Saving Impacts Timing of Heart Attacks
Credit: © Les Cunliffe
Still feeling the residual effects of springing ahead for daylight saving time? The hour of sleep lost — or gained — may play a bigger, perhaps more dangerous role in our body’s natural rhythm than we think. It seems moving the 1) ___ forward or backward may alter the timing of when heart attacks occur in the week following these time changes, according to research presented at the American College of Cardiology’s 63rd Annual Scientific Session.
Data from the largest study of its kind in the U.S. reveal a 25% jump in the number of heart attacks occurring the Monday after we spring forward compared to other Mondays during the year — a trend that remained even after accounting for seasonal variations in these events. But the study showed the opposite effect is also true. Researchers found a 21% drop in the number of heart attacks on the Tuesday after returning to standard time in the fall when we gain an 2) ___ back.
What’s interesting is that the total number of heart attacks didn’t change the week after daylight saving time, said Amneet Sandhu, M.D., cardiology fellow, University of Colorado in Denver, and lead investigator of the study. But these events were much more frequent the Monday after the spring time change and then tapered off over the other days of the week. It may mean that people who are already vulnerable to 3) ___ disease may be at greater risk right after sudden time changes.
Heart attacks historically occur most often on Monday mornings. Sandhu explains that in looking at other normal Mondays, there is some variation in events, but it is not significant. However, when he and his team compared admissions from a database of non-federal Michigan hospitals the Monday before the start of daylight saving time and the Monday immediately after for four consecutive years, they found a consistent 34% increase in heart 4) ___ from one week to the next e.g. 93 heart attacks the Monday before compared to 125 the week after the start of daylight saving time for the duration of the study.
Although researchers cannot say what might be driving the shift in heart attack timing after the start of daylight saving time, they have a theory. Perhaps the reason we see more heart attacks on 5) ___ mornings is a combination of factors, including the stress of starting a new work week and inherent changes in our sleep-wake cycle, Sandhu said. With daylight saving time, all of this is compounded by one less hour of sleep. Whatever the reason, he said, the findings may indicate a need to better staff hospitals the Monday after setting our clocks forward.
If we can identify days when there may be surges in heart attacks, we can be ready to better care for our 6) ___, said Sandhu. Gaining an hour in the fall may have the opposite effect, though authors don’t know why there were fewer heart attacks on Tuesday rather than Monday. Researchers used Michigan’s BMC2 database, which collects data from all non-federal hospitals across the state, to identify admissions for heart attacks requiring percutaneous coronary intervention from Jan. 1, 2010 through Sept. 15, 2013. A total of 42,060 hospital admissions occurring over 1,354 days were included in the analysis. Total daily admissions were adjusted for seasonal and weekday variation, as the rate of heart attacks peaks in the winter and is lowest in the 7) ___ and is also greater on Mondays and lower over the weekend.
The hospitals included in this study admit an average of 32 patients having a heart attack on any givenMonday. But on the Monday immediately after springing ahead there were on average an additional eight heart attacks. There was no difference in the total weekly number of percutaneous coronary interventions performed for either the fall or spring time changes compared to the weeks before and after the 8) ___change.
This study comes amid ongoing debate about whether daylight saving time is actually needed anymore. Widely implemented during World War I, it was primarily adopted to save 9) ___. But some experts question whether it really saves energy and if it has negative health effects beyond just leaving us feeling groggy and out of sorts. We go through 10) ___ saving time periods twice yearly, Sandhu said. We may want to look more closely at whether the shift in the timing of heart attacks seen after daylight saving time leads to any negative health outcomes.
There are limitations to the study. For example, it was restricted to one state and heart attacks necessitating percutaneous coronary intervention, therefore excluding patients who died prior to hospital admission or intervention. Sandhu said it would be interesting to compare these findings against heart attack trends in Hawaii and 11) ___, which do not have daylight saving time. Future research is also needed to better understand the role of our circadian rhythms on heart health.
We know from previous studies that a lack of sleep can trigger heart attacks, but we don’t have a good understanding of why people are so sensitive to changes in sleep-wake cycles. Our study suggests that sudden, even small changes in 12) ___ could have detrimental effects, he said. This study was simultaneously published online in Open Heart at the time of presentation.
Story: American College of Cardiology. Daylight saving impacts timing of heart attacks. ScienceDaily.com; ScienceDaily.com
ANSWERS: 1)clock; 2) hour; 3) heart; 4) attacks; 5) Monday; 6) patients; 7) summer; 8) time; 9) energy; 10) daylight; 11) Arizona; 12) sleep
Hardened Arteries Found in Ancient Mummies. Did Diet Do It?
Studies of mummies show that the ancients got heart disease too.
There’s a team of cardiologists called The Horus Project who, largely as a hobby, have been taking CAT scans of the hearts of the mummified remains of ancient people, using borrowed machines from hospitals and, in one case, a mobile imaging unit run on gasoline. They started with Egyptian mummies published the first results four years ago. They’ve since expanded their effort to include mummies from other ancient cultures. Unlike the ancient Egyptian mummies, which went through a complicated preservation process to dry out their flesh, most of these corpses were preserved simply by putting them somewhere where moisture was scant.
The team found probable or definite atherosclerosis, the artery disease that leads to heart attacks and strokes, in 47 of 137 (34%) mummies. Of the 47 mummies, 38% were from ancient Egypt, 25% from ancient Peru, and 40% were ancient Puebloans.
Perhaps most important, though were five mummified Unangan hunter-gatherers from the Aleutian Islands in the North Pacific ocean. Sixty percent of them – that’s three mummies – had atherosclerosis. One woman had calcified deposits in her coronary arteries that looked strikingly like someone with serious heart disease showing up in the hospital today. That means data from 4,000 years of preserved corpses shows that serious cardiovascular disease, the leading killer of people in the Western world, has been with us since before we started planting crops.
It tells us that we don’t know as much as we thought we knew, says Samuel Wann, one of the lead investigators and a cardiologist at Columbia St. Mary’s Community Physicians in Milwaukee. We thought we understood the risk factors for heart disease. I’m still surprised that our predecessors 4,000 years ago still had atherosclerosis.
The research was published about a year ago, in The Lancet, a medical journal, and was presented at the annual meeting of the American College of Cardiology last year, in San Francisco.
The Paleolithic diet, the researchers say, was probably better than what we eat today, but it was still not 100% protective. Probably nothing is. We’re not destined to die of heart disease. But we’re all at risk – vegetarians, vegans, hunter-gatherers, says Gregory S. Thomas MD, the lead author of the study. It behooves us to do what’s known to be helpful: exercise, reducing blood pressure. But we’re all at risk. We shouldn’t think we’re protected by any one of these approaches. When someone has a heart attack they’ll often blame themselves. But I can reassure them that it’s a disease that the American Indians had living on the Colorado plains before the invention of the bow and arrow.
There’s only so much that mummies can tell us, and modern hunter gatherers certainly have relatively low rates of heart attack and stroke. But it’s probably a mistake to construct our thinking about how we should eat and exercise through arguments about what people did before the agricultural revolution. Better to use hard data – like the recent study that showed a Mediterranean diet did better at preventing heart disease than what would otherwise be considered a relatively healthy one. And no matter what we eat, having arteries that clog up as we age is part of being human. We just need to slow the process as much as possible.