Scott Mellis, MD, PhD on Safari

 

Our very good friend and colleague, Dr. Scott Mellis, Vice President, Early Clinical Development and Experimental Sciences, Rare Diseases at Regeneron Pharmaceuticals, took an adventurous trip to Africa and came back with some extraordinary photos.

Cheetahs enjoying a family meal in the Serengeti. ©Scott Mellis, M.D., Ph.D.

 

Lion outside safari vehicle.  Ngoro Ngoro crater © Scott Mellis, M.D., Ph.D.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. 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

 

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Serotonin – Mens Sana in Corpore Sano

Source: http://worldhappiness.report/ed/2017/

 

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract (GI tract), blood platelets, and the central nervous system (CNS) of animals, including humans. It is popularly thought to be a contributor to feelings of well-being and 1) ___Approximately 90% of the human body’s total serotonin is located in the enterochromaffin cells in the GI tract, where it is used to regulate intestinal movements. The serotonin is secreted luminally and basolaterally which leads to increased serotonin uptake by circulating platelets and activation after stimulation, which gives increased stimulation of myenteric neurons and gastrointestinal motility. The remainder is synthesized in serotonergic 2) ___of the CNS, where it has various functions. These include the regulation of mood, appetite, and sleep. Serotonin also has some cognitive functions, including memory and learning. Modulation of serotonin at synapses is thought to be a major action of several classes of pharmacological antidepressants. Serotonin secreted from the enterochromaffin cells eventually finds its way out of tissues into the blood. There, it is actively taken up by blood platelets, which store it. When the platelets bind to a clot, they release serotonin, where it serves as a vasoconstrictor and helps to regulate hemostasis and blood 3) ___. Serotonin is also a growth factor for some types of cells, which may give it a role in wound healing. There are various serotonin receptors.

 

Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver. Metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. This is followed by oxidation by aldehyde dehydrogenase to 5-HIAA, the indole acetic acid derivative. The latter is then excreted by the 4) ___. In addition to animals, serotonin is found in fungi and 5) ___. Serotonin’s presence in insect venoms and plant spines serves to cause pain, which is a side-effect of serotonin injection. Serotonin is produced by pathogenic amoebae, and its effect on the gut, causes diarrhea. Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds.

 

Serotonin syndrome (SS) is a group of symptoms that may occur following use of certain serotonergic medications or 6) ___. The degree of symptoms can range from mild to severe. Symptoms include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. Body temperature can increase to greater than 41.1 oC (106.0 oF). Complications may include seizures and extensive muscle breakdown. Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, St. John’s wort, triptans, ecstasy, metoclopramide, ondansetron, or cocaine. It occurs in about 15% of SSRI overdoses. It is a predictable consequence of excess serotonin on the CNS or 7) ___ ___ ___. Onset of symptoms is typically within a day of the extra serotonin. Diagnosis is based on a person’s symptoms and history of medication use. Other conditions that can produce similar symptoms such as neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic toxicity, heat stroke, and meningitis should be ruled out. No laboratory tests can confirm the diagnosis. Initial treatment consists of discontinuing medications which may be contributing. In those who are agitated benzodiazepines may be used. If this is not sufficient, a serotonin antagonist such as cyproheptadine may be used. In those with a high body temperatures active cooling measures may be needed. The number of cases of serotonin syndrome that occur each year is unclear. With appropriate treatment the risk of 8) ___ is less than one percent. The high-profile case of Libby Zion, who is thought to have died from serotonin syndrome, resulted in changes to graduate medical education in New York State and hospital procedures. The symptoms of serotonin syndrome are often described as a clinical triad of abnormalities.

 

Non-pharmacologic ways to raise serotonin levels in humans are: light therapy, meditation, psychotherapy, exercise and diet. Another important factor that could play a role in raising 9) ___ levels, is diet. According to some evidence, tryptophan, which increases brain serotonin in humans is an effective antidepressant in mild-to-moderate depression. Further, in healthy people with high trait irritability, it increases agreeableness, decreases quarrelsomeness and improves mood. Although purified tryptophan increases brain serotonin, foods containing tryptophan do not. This is because tryptophan is transported into the brain by a transport system that is active toward all the large neutral amino acids, and tryptophan is the least abundant amino acid in protein. After the ingestion of a meal containing protein, the rise in the plasma level of the other large neutral amino acids will prevent the rise in plasma tryptophan from increasing brain tryptophan. The idea, common in popular culture, that a high-protein food such as turkey will raise brain tryptophan and serotonin is, unfortunately, false. Another popular myth that is widespread on the Internet is that bananas improve mood because of their serotonin content. Although it is true that bananas contain serotonin, it does not cross the blood-brain barrier. Researchers have studied the tryptophan content of both wild chickpeas and the domesticated chickpeas that were bred from them in the Near East in Neolithic times. In the cultivated group, the tryptophan content was almost twice that of the wild seeds. Interestingly, the greater part of the increase was due to an increase in the free tryptophan content (i.e., not part of the protein). In cultivated 10) ___, almost two-thirds of the tryptophan was in the free form. Editor’s note: In our reading for this article so far, domesticated chickpeas appear to be the best dietary source contributing to healthy human serotonin levels. There may be other foods, but we have not come across them yet.

 

In an article in Nature Biotechnology, Morris and Sands argue that plant breeders should be focusing more on nutrition than on yield. They ask, “Could consumption of tryptophan-rich foods play a role in reducing the prevalence of depression and aggression in society?“ The constitution of the WHO states “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.“ This may sound like simple common sense, but it’s worth stating that positive mood within the normal range is an important predictor of health and longevity. Research confirms what might be intuitively expected, that positive emotions and agreeableness foster congenial relationships with others. This in turn will create the conditions for an increase in social support. Several studies found an association between measures related to serotonin and mood in the normal range. Lower platelet serotonin receptor function was associated with lower mood in one study, whereas better mood was associated with higher blood serotonin levels in another. Low serotonin may predispose healthy individuals to suboptimal physical as well as mental functioning. There is a strong possibility that the interaction between serotonin synthesis and mood may be 2-way, with serotonin influencing mood and mood influencing serotonin.

 

The first World Happiness Report was published in April 2012, in support of the UN High Level Meeting on happiness and well-being. Since then the world has come a long way. Increasingly, happiness is the proper measure of social progress and the goal of public policy. In June 2016 the OECD committed itself “to redefine the growth narrative to put people’s well-being at the center of governments’ efforts.“ In February 2017, the United Arab Emirates held a full-day World Happiness meeting, as part of the World Government Summit. Clearly, health, happiness and non-pharmacologic serotonin levels, are closely related. Sources: www.ncbi.nlm.nih.gov; WebMD.com; Wikipedia

 

World Happiness Report video

 

ANSWERS: 1) happiness; 2) neurons; 3) clotting; 4) kidneys; 5) plants; 6) drugs; 7) Central Nervous System; 8) death; 9) serotonin; 10) chickpeas

 

Serotonin Research & Three Great Scientists’ Contributions

Vittorio Erspamer MD, Photo credit: Unknown; Public Domain, Wikipedia Commons

 

Dr. Vittorio Erspamer (1909-1999), the well-known discoverer of serotonin and octopamine, was an Italian pharmacologist and chemist, known for the identification, synthesis and pharmacological studies of more than sixty new chemical compounds, most notably serotonin and octopamine.

 

Erspamer was born in 1909 in the small village of Val di Non in Malosco, a municipality of Trentino in northern Italy. He attended school in the Roman Catholic Archdiocese of Trento and then moved to Pavia, where he studied at Ghislieri College, graduating in medicine and surgery in 1935. He then took the post of assistant professor in anatomy and physiology at the University of Pavia – one of the oldest universities in Europe, founded in 1361. In 1936, he obtained a scholarship to study at the Institute of Pharmacology at the University of Berlin. After returning to Italy in 1939, he moved to Rome where he took up the position of professor in pharmacology. In Rome, the focus of his research shifted to drugs and he used his past biological experience to focus on compounds isolated from animal tissues. In 1947 he became professor of pharmacology at the Faculty of Medicine at the University of Bari. In 1955, he moved from Bari to Parma, to assume an equivalent position of professor of pharmacology at the Faculty of Medicine, University of Parma. Erspamer was one of the first Italian pharmacologists to realize that fruitful scientific research benefits from building a relationship with the chemical and pharmaceutical industries. In the late 1950s, he established a collaboration with chemists at the Farmitalia company. The collaboration was useful, not only for the analysis of the structure of new molecules which he isolated and characterized pharmacologically, but also for the subsequent industrial synthesis of these chemicals and their synthetic analogs.

 

Thanks to funding received from Farmitalia, over the years Erspamer collected more than five hundred species of marine organisms from all around the world, including amphibians, shellfish, sea anemones and other species. For this purpose, he spent much time in traveling, and was known among his colleagues for his careful preparation of expeditions and knowledge of geography. Using these world-wide observations he developed a theory of geo-phylogenetic correlations among the different amphibian species of the world, which was based on analysis of the peptides and amines in their skin.

 

The research activities of Erspamer spanned more than 60 years and resulted in the isolation, identification, synthesis and pharmacological study of more than sixty new chemical compounds, especially polypeptides and biogenic amines, but also some alkaloids. Most of these compounds were isolated from animals, predominantly amphibians. In the late fifties his research shifted to peptides. In the laboratories of the Institute of Medical Pharmacology, University of Rome, he isolated from amphibians and mollusks more than fifty new bioactive peptides. These became the subjects of numerous studies in other laboratories in Europe and North America. In 1979, he focused on opioid peptides specific to Phyllomedusa, a genus of tree frog from Central and South America. These were used by the native Indians in initiation rites, to increase their prowess as “hunters” and make them feel “invincible”. They applied secretions from the skin of these frogs that resulted in euphoric and analgesic effects. The peptides studied by Erspamer have become essential to characterize the functional role of opioid receptors.

 

Erspamer retired from administrative positions in 1984 because of the age limits, but continued his research and writing until his death in Rome in 1999. His last, unfinished review was completed by his collaborators and published in 2002. During his lifetime he was twice nominated for the Nobel Prize.

 

Between 1933 and 1934, while still a college student, Erspamer published his first work on the histochemical characteristics of enterochromaffin cells using advanced techniques, not normally used at that time, such as diazo reactions, Wood’s lamp and fluorescence microscopy. In 1935, he showed that an extract prepared from enterochromaffin cells made intestinal tissue contract. Other chemists believed the extract contained adrenaline, but two years later Erspamer demonstrated that it was a previously unknown chemical, an amine, which he named enteramine and which was renamed, later as serotonin. In 1948, Maurice M. Rapport, Arda Green, and Irvine Page of the Cleveland Clinic discovered a vasoconstrictor substance in blood serum, and since it was a serum agent affecting vascular tone, they named it serotonin. In 1952 it was shown that enteramine was the same substance as serotonin. Another important chemical, also an amine, was discovered by Erspamer in 1948, in the salivary glands of the octopus, and therefore named by him octopamine.

 

Maurice Rapport (1919-2011) was a biochemist who is best known for his work with the neurotransmitter serotonin. Rapport, Irvine H. Page, and Arda A. Green worked together to isolate and name the chemical. Alone, Rapport identified its structure and published his findings in 1948. Research since its discovery has implicated serotonin with mood regulation, appetite, reproductive drives, and sleep as well as gastrointestinal roles. After his work with serotonin, Rapport did important research with cancer, cardiovascular disease, connective-tissue disease and demyelinating diseases.

 

Maurice Rapoport was born on September 23, 1919 in Atlantic City, New Jersey. His mother changed the spelling of the family name to Rapport. His father was a furrier from Russia who left the family when Rapport was a small child. Rapport graduated from DeWitt Clinton High School in the Bronx, New York and went on to earn a bachelor’s degree in chemistry from the City College of New York in 1940. He obtained his doctorate in organic chemistry in 1946 from California Institute of Technology. In 1946, Maurice Rapport began working in the Cleveland Clinic Foundation which was directed by Irvine H. Page. Since the 1860s, a substance was known about, in the serum of blood vessels, that promoted clotting. Rapport was assigned the project of isolating this serum. They enlisted the help of Arda A. Green, a physical biochemist. The substance was acquired by leaving a test tube of the reagents in a cold room while Rapport went on vacation. When he returned he isolated the crystals of the desired substance. In a paper published in 1948, they gave it a name: serotonin, derived from “serum“ and “tonic“.

 

In 1948, Rapport left the Cleveland Clinic for a position at Columbia University and continued searching for serotonin’s structure. In May 1949, the structure of serotonin was discovered to be 5-hydroxytryptamine (5-HT). Serotonin was found to be the same substance that Dr. Vittorio Erspamer had been studying since the 1930s called “enteramine“. Enteramine had a substantial place in scientific literature due to Erspamer’s research into its role in smooth muscle constriction and intestinal tracts. Erspamer’s research contributed to Rapport’s discovery of serotonin’s structure and allowed other researchers to synthesize the substance and further study its role in the body.

 

The structure of serotonin was given to Upjohn Drug Company where researchers focused on the role of serotonin in the bodily processes such as blood vessel constriction. In 1954, Betty Twarog discovered the distribution of serotonin in the brain. Further research illustrated how serotonin plays a major role in the central nervous system and digestive tract. The understanding of serotonin has led to a progression in our view of mental illness and allowed the development of antidepressants and other drugs for hypertension and migraines. After his work with serotonin, Rapport worked at the Sloan-Kettering Institute for Cancer Research. His contributions involved the activity and structures of lipids in relation to immunological activity. Specifically, he isolated cytolipin H from human cancer tissue in 1958. This led to a better understanding of our immune system. He also was a professor at the Albert Einstein College of Medicine. There he isolated two glysosphingolipids and studied antibodies to gangliosides. These findings were useful to further pharmacological studies relating these substances to demyelinating diseases such as Amyotrophic Lateral Sclerosis (ALS).

In 1968, Rapport returned to Columbia University as chief of pharmacology and professor of biochemistry. The next year, he became the chief of the new neuroscience division which combined the chemistry, pharmacology, and bacteriology divisions. He retired in 1986 and remained in the neurology department of the Albert Einstein College of Medicine as a visiting professor.

 

Betty Mack Twarog (1927 – 2013) was an American biochemist who was the first to find serotonin in the mammalian brain.. She attended Swarthmore College from 1944 to 1948, focusing on mathematics. While studying for an M.Sc. at Tufts College she heard a lecture on mollusc muscle neurology and in 1949 enrolled under John Welsh in the PhD program at Harvard to study this area. By 1952 she had submitted a paper showing that serotonin had a role as a neurotransmitter in mussels. In Autumn 1952 Twarog moved for family reasons to the Kent State University area , and chose the Cleveland Clinic as a place to continue her study of her hypothesis that invertebrate neurotransmitters would also be found in mammals. Although her supporter there, Irvine Page did not believe serotonin would be found in the brain, he nevertheless gave Twarog a laboratory and technician. By June 1953 a paper was submitted announcing the isolation of serotonin in mammalian brain. Twarog left the Cleveland Clinic in 1954 and continued to work on invertebrate smooth muscle at Tufts, Harvard and SUNY at Stony Brook. In later years, at the Bigelow Laboratory for Ocean Sciences in Boothbay Harbor, Maine she worked on how shellfish evade phytoplankton poisons. Twarog died on February 6, 2013, at the age of 85 in Damariscotta, Maine.

 

Twarog’s isolation of serotonin in brain established its potential as a neurotransmitter and thus a modulator of brain action. Her discovery was an essential precursor to the creation in 1978 of the antidepressant SSRI medicines such as fluoxetine and sertraline.

 

Repurposed Experimental Cancer Therapy Treats Muscular Dystrophy

 

Duchenne muscular dystrophy (DMD) is a degenerative muscle disease that usually begins in childhood and has no known cure. It is caused by a faulty gene that leads to progressive muscle weakness, with death often occurring around age 25. Those with DMD lack dystrophin, a protein akin to a molecular shock-absorber that helps keep muscle cells intact. Without dystrophin, muscles are fragile and easily injured. Individuals lose muscle strength and the ability to repair damaged muscle tissue. Most die from heart or respiratory problems.

 

According to an article published in Molecular Therapy (June 2017), researchers at the National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS) and the University of Nevada, Reno School of Medicine (UNR Med) have demonstrated that a drug originally targeted unsuccessfully to treat cancer may have new life as a potential treatment for DMD. The candidate drug, SU9516, represents a different kind of approach for treating DMD. Rather than trying to fix or replace the broken gene, SU9516 ramps up the muscle repair process, helping reinforce muscle structure. To accomplish this, the research team screened more than 350,000 compounds to find SU9516, which had been previously developed as a treatment for leukemia. The research demonstrated that this compound improved muscle function in both laboratory and animal DMD models.

 

In earlier research, the senior author of the current study showed that boosting the levels of a cell structural protein, a7beta1 integrin, in affected muscle cells could alleviate DMD symptoms in a mouse model. In addition, increased amounts of the protein slowed the disease’s progress. The screening exercise searched for compounds for molecules that could increase a7beta1 integrin production in mouse muscle cells grown in the laboratory. The screen revealed that SU9516 raised integrin production and promoted the formation of muscle cells and fibers from DMD muscle stem cells, another important indication of its potential as a drug. In a series of pre-clinical experiments, the authors showed that SU9516 increased the production of a7?1 integrin in human and mouse DMD muscle cells. Subsequent tests found SU9516 improved muscle function and slowed indicators of disease progression. The authors suggests that such a drug could be used alone, or in combination, with other therapies yet to be developed, and that there might also be a wide ranging applications to other muscle-damaging conditions, like cachexia, a wasting syndrome characterized by weight loss and muscle atrophy that is often seen in the late stages of cancers, and the effects of aging and injury.

 

Drinking Diet Beverages During Pregnancy Linked to Child Obesity

 

Childhood obesity is known to increase the risk for certain health problems later in life, such as diabetes, heart disease, stroke and some cancers.

 

According to an article published online in the International Journal of Epidemiology (6 June 2017), it was reported that children born to women who had gestational diabetes and drank at least one artificially sweetened beverage per day during pregnancy, were more likely to be overweight or obese at age 7, compared to children born to women who had gestational diabetes and drank water instead. The study showed that as the volume of amniotic fluid increases, pregnant women tend to increase their consumption of fluids. To avoid extra calories, many pregnant women replace sugar-sweetened soft drinks and juices with beverages containing artificial sweeteners. Citing prior research implicating artificially sweetened beverages in weight gain, the study authors sought to determine if diet beverage consumption during pregnancy could influence the weight of children.

 

The study analyzed data collected from 1996 to 2002 by the Danish National Birth Cohort, a long-term study of pregnancies among more than 91,000 women in Denmark. At the 25th week of pregnancy, the women completed a detailed questionnaire on the foods they ate. The study also collected data on the children’s weight at birth and at 7 years old. For the current analysis, the authors limited their analysis to data from more than 900 pregnancies that were complicated by gestational diabetes, a type of diabetes that occurs only during pregnancy. Results showed that approximately 9% of these women reported consuming at least one artificially sweetened beverage each day. Their children were 60% more likely to have a high birth weight, compared to children born to women who never drank sweetened beverages. At age 7, children born to mothers who drank an artificially sweetened beverage daily were nearly twice as likely to be overweight or obese. Consuming a daily artificially sweetened beverage also appeared to offer no advantages over consuming a daily sugar-sweetened beverage. At age 7, children born to both groups were equally likely to be overweight or obese. However, women who substituted water for sweetened beverages reduced their children’s obesity risk at age 7 by 17%.

 

It is not well understood why drinking artificially sweetened beverages compared to drinking water may increase obesity risk. The authors cited an animal study that associated weight gain with changes in the types of bacteria and other microbes in the digestive tract. Another animal study suggested that artificial sweeteners may increase the ability of the intestines to absorb the blood sugar glucose. Other researchers found evidence in rodents that, by stimulating taste receptors, artificial sweeteners desensitized the animals’ digestive tracts, so that they felt less full after they ate and were more likely to overeat. The authors caution that more research is necessary to confirm and expand on their current findings, and that although they could account for many other factors that might influence children’s weight gain, such as breastfeeding, diet and physical activity levels, their study couldn’t definitively prove that maternal artificially sweetened beverage consumption caused the children to gain weight. The authors mention specifically the need for studies that use more contemporary data, given recent upward trends in the consumption of artificially sweetened beverages. They also call for additional investigation on the effects of drinking artificially sweetened beverages among high-risk racial/ethnic groups.

 

Fostering Medical Innovation: A Plan for Digital Health Devices

 

The following was reported by Scott Gottlieb, M.D., FDA Commissioner

 

Dr. Gottlieb indicated that it is incumbent upon FDA to ensure that they have the right policies in place to promote and encourage safe and effective innovation that can benefit consumers, and adopt regulatory approaches to enable the efficient development of these technologies. By taking an efficient, risk-based approach to regulations, FDA can promote health through the creation of more new and beneficial medical technologies. FDA can also help reduce the development costs for these innovations by making sure that our own policies and tools are modern and efficient, giving entrepreneurs more opportunities to develop products that can benefit people’s lives.

 

To this end, FDA will soon be putting forward a broad initiative that is focused on fostering new innovation across our medical product centers. However, today Dr. Gottlieb is focusing on one critical aspect of this innovation initiative: A new Digital Health Innovation Plan that is focused on fostering innovation at the intersection of medicine and digital health technology. This plan will include a novel, post-market approach to how FDA intends to regulate these digital medical devices.

 

According to one estimate, last year there were 165,000 health-related apps available for smartphones. Forecasts predict that such apps would be downloaded 1.7 billion times by 2017. From mobile apps and fitness trackers to clinical decision support software, innovative digital technologies have the power to transform health care in important ways, such as:

 

1. Empowering consumers to make more and better decisions every day about their own health, monitor and manage chronic health conditions, or connect with medical professionals, using consumer-directed apps and other technologies to help people live healthier lifestyles through fitness, nutrition, and wellness monitoring;

2. Enabling better and more efficient clinical practice and decision making through decision support software and technologies to assist in making diagnoses and developing treatment options; managing, storing, and sharing health records; and managing schedules and workflow;

3. Helping to address public health crises, such as the opioid epidemic that is devastating many American communities. In fact, FDA conducted a prize competition to encourage the development of a mobile app to help connect opioid users experiencing an overdose with nearby carriers of the prescription drug naloxone for emergency treatment.

 

For these and other digital technologies to take hold and reach their fullest potential, it is critical that FDA be forward-leaning in making sure that they have implemented the right policies and regulatory tools, and communicated them clearly.In this rapidly changing environment, ambiguity regarding how FDA will approach a new technology can lead innovators to invest their time and resources in other ventures. To encourage innovation, FDA should carry out its mission to protect and promote the public health through policies that are clear enough for developers to apply them on their own. Developers should not have to seek out, on a case-by-case basis, FDA’s position on every individual technological change or iterative software development.

 

Congress has already taken a major step to advance these goals in the 21st Century Cures Act. Expanding upon policies advanced by FDA’s Center for Devices and Radiological Health (CDRH), the Act revised FDA’s governing statute to, among other things, make clear that certain digital health technologies – such as clinical administrative support software and mobile apps that are intended only for maintaining or encouraging a healthy lifestyle – generally fall outside the scope of FDA regulation. Such technologies tend to pose low risk to patients but can provide great value to the health care system. FDA, led by CDRH, is working to implement the digital health provisions of the 21st Century Cures Act and, in the coming months, will be publishing guidance to further clarify what falls outside the scope of FDA regulation and to explain how the new statutory provisions affect pre-existing FDA policies. FDA will provide guidance to clarify their position on products that contain multiple software functions, where some fall outside the scope of FDA regulation, but others do not. In addition, FDA will provide new guidance on other technologies that, although not addressed in the 21st Century Cures Act, present low enough risks that FDA does not intend to subject them to certain pre-market regulatory requirements. Greater certainty regarding what types of digital health technology is subject to regulation and regarding FDA’s compliance policies will not only help foster innovation, but also will help the agency to devote more resources to higher risk priorities.

 

In addition to these efforts, FDA has announced a new initiative. This fall, as part of a comprehensive approach to the regulation of digital health tools and in collaboration with our customers, FDA will pilot an entirely new approach toward regulating this technology. This will be the cornerstone to a more efficient, risk-based regulatory framework for overseeing these medical technologies. While the pilot program is still being developed, FDA is considering whether and how, under current authorities, they can create a third party certification program. Under this program, lower risk digital health products could be marketed without FDA premarket review and higher risk products could be marketed with a streamlined FDA premarket review. Certification could be used to assess, for example, whether a company consistently and reliably engages in high quality software design and testing (validation) and ongoing maintenance of its software products. Employing a unique pre-certification program for software as a medical device (SaMD) could reduce the time and cost of market entry for digital health technologies.

 

In addition, post-market collection of real-world data might be able to be used to support new and evolving product functions. For example, product developers could leverage real-world data gathered through the National Evaluation System for health Technology (NEST) to expedite market entry and subsequent expansion of indications more efficiently. NEST will be a federated virtual system for evidence generation composed of strategic alliances among data sources including registries, electronic health records, payer claims, and other sources. The Medical Device Innovation Consortium (MDIC), a 501(c)(3) public-private partnership, is serving as an independent coordinating center that operates NEST. In the coming weeks, MDIC will announce the establishment of a Governing Committee for the NEST Coordinating Center comprised of stakeholder representatives of the ecosystem, such as patients, health care professionals, health care organizations, payers, industry, and government. Although FDA does not own or operate NEST, they have been establishing strategic alliances among data sources to accelerate NEST’s launch with the initial version of a fully operational system anticipated by the end of 2019. Applying this firm-based approach, rather than the traditional product-based approach, combined with leveraging real-world evidence, would create market incentives for greater investment in and growth of the digital health technology industry. Such processes could enable developers to deploy new or updated software more rapidly and would help FDA to better focus its resources.

 

Through these and other steps, according to Dr. Gottlieb, FDA will help innovators navigate a new, modern regulatory process so that promising, safe and effective developments in digital health can advance more quickly and responsibly, and Americans can reap the full benefits from these innovations. These efforts are just one part of a much broader initiative that FDA is currently undertaking to advance policies that promote the development of safe and effective medical technologies that can help consumers improve their health. FDA’s goal is to make sure that FDA has the most modern and efficient regulatory approaches when it comes to evaluating new, beneficial technologies. Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

 

Chickpea-Curry-Pistachio Fritters & Garlic Flax Chive Dipping Sauce

Your mouth is gonna love these chickpea fritters! Good with or without the chive sauce. ©Joyce Hays, Target Health Inc.

 

Chive sauce Ingredients

20 garlic cloves, peeled and roasted

Extra-virgin olive oil

1 cup Kraft mayonnaise

Zest of 1 lemon

3 Tablespoons fresh lemon juice

1 teaspoon flax seeds

1 stalk scallion, chopped

Pinch kosher salt

Pinch black pepper

Pinch chili flakes

1/4 cup fresh chives, minced

 

Fritter Ingredients

1 1/4 cups chickpea flour

1 cup shredded white Cheddar

1 teaspoon flax seeds

1 teaspoon turmeric

1 teaspoon ground curry

1/2 cup toasted, then ground pistachio nuts

Pinch kosher salt

Pinch black pepper

Pinch chili flakes

3 garlic cloves, squeezed

2 large eggs

3/4 to 1 cup cold beer

1 cup chickpeas (canned or cook from scratch), drained on paper towels 15 minutes, or longer

1 cup chickpeas (canned or cooked from scratch), drained on paper towels 15 minutes, or longer

1 onion, halved and thinly sliced

1/2 cup coconut oil, or extra virgin olive oil, for frying

 

You can tell just by looking at the ingredients, that this is going to taste good! ©Joyce Hays, Target Health Inc.

 

Directions for Sauce

 

1. Heat oven to 375 degrees, put garlic cloves in a small baking dish and add enough olive oil to cover. Roast until garlic is soft and golden, about 30 minutes. Cool.

Roasted garlic just out of the oven. ©Joyce Hays, Target Health Inc.

 

2. Drain garlic, reserving oil.

3. Transfer the roasted garlic to food processor, add 1 Tablespoon of the reserved oil, that garlic was roasted in.

4. To the food processor add, mayonnaise, lemon zest, lemon juice, flax seeds, scallion, salt pepper and puree. Transfer to a bowl and stir in chives. Use remaining oil for another purpose.

 

Final step of chive sauce. The fresh chives give the green color to the sauce. ©Joyce Hays, Target Health Inc.

 

Directions for Fritters

1. Toast pistachios with or without oil.

2. Slice the onion

Pistachios add a deep mysterious flavor to this recipe; plus they are the lowest calorie nuts. ©Joyce Hays, Target Health Inc.

 

Slicing the onion. ©Joyce Hays, Target Health Inc.

 

3. In food processor, puree 1 cup of the chickpeas, then scrape into small bowl.

4. In food processor, pulse the second cup of chickpeas, BUT DO NOT PUREE. KEEP LITTLE PIECES OF CHICKPEAS. This will give the fritters a more interesting texture. Scrape this into the bowl with the pureed chickpeas.

 

This second batch of chickpeas is not pureed. Coarsely pulsed, you want small pieces to remain in the batter, to give the fritter more texture. ©Joyce Hays, Target Health Inc.

 

5. In a large mixing bowl, add the flour, Cheddar, flax seeds, salt, pepper, chili flakes, turmeric, ground pistachio nuts and garlic and mix well.

All of step five has been added to this mixing bowl. ©Joyce Hays, Target Health Inc.

 

 6. In a separate small bowl, gently whisk eggs with beer. Pour egg mixture into flour mixture and stir until combined.

Whisking beer with the eggs. ©Joyce Hays, Target Health Inc.

 

 7. Now, stir in all of the chickpea mixture and also add the onion.

All of the fritter ingredients have been added to the (above) mixing bowl. The batter is ready to cook. ©Joyce Hays, Target Health Inc.

  

8. Heat oil (use up any left-over oil from previous cooking) in a large skillet over medium-high flame.

9. Drop about 1 Tablespoon of batter (for each chickpea fritter) into the oil and fry 6 fritters at a time until golden-brown; 2 to 3 minutes a side.

Cooking the fritters, just dropped in pan. ©Joyce Hays, Target Health Inc.

 

 10. When fritters are golden brown and done, remove to paper towels to drain.

Draining fritters on paper towel. ©Joyce Hays, Target Health Inc.

 

11. Serve hot, with the sauce on the side and some fresh lemon & lime segments (optional).

We started the meal with the chickpea fritters (chive sauce) as an appetizer with iced Pouilly-Fuisse; but they were so good, the fritters became my whole meal. Jules gives the fritters a thumbs-up, but also had mushroom deviled eggs, baked string-beans with Panko/parmesan coating, chicken, and fresh cold watermelon for dessert. ©Joyce Hays, Target Health Inc.

 

Fritters and sauce can be as spicy as you wish. Just adjust the seasoning ingredients, to your taste. It’s a wonderful meal when you go from spicy and delicious, to (dessert) cold and sweet. Enjoy! ©Joyce Hays, Target Health Inc.

 

Just spear a piece with your fork and enjoy cool, sweet watermelon for dessert. ©Joyce Hays, Target Health Inc.

 

It was a beautiful late Spring day, here in the Big Apple; so gratifying to end it with this cold Pouilly-Fuisse and all that followed. ©Joyce Hays, Target Health Inc.

 

This weekend we saw, Oslo, awarded a Tony for best play. Oslo also got a Tony for best actor, Michael Aronov. Oslo is a wonderful, thought provoking work, with just the right amount of joking and light-heartedness, interspersed throughout the play. We enjoyed it immensely and recommend that you get tickets if you can. Our only FYI, is that the acoustics at the Vivian Beaumont Theater are not the best.

 

This venue is great for musicals (We saw South Pacific here) but problematic for the spoken word. Nevertheless, we do think you’ll agree it’s time well spent, with lots to discuss afterwards.

 

From Our Table to Yours

Bon Appetit!