Society for Clinical Research Sites
Target Health is pleased that The Society for Clinical Research Sites (SCRS) has highlighted Target Health’s approach to eSource and the paperless clinical trial in their Newsletter, InFocus. As a Site Development Partner, Target Health works closely with key SCRS stakeholders, including its Global Impact Partners and members of the Society’s Leadership Council, to set key initiatives that will elevate site performance and enhance site sustainability.
eSource Conference in Clinical Investigations
Target Health is pleased that Dean Gittleman, Sr. Director of Operations, will be presenting on the topic: Achieve eSource Data Compliance by Eliminating the Need for Paper at the Ensure Regulatory Compliance and Data Integrity Through Effective Electronic Source Data Implementation conference being held in Philadelphia (August 20-21, 2014). This in-depth conference will provide trail-blazing industry case studies and applications of eSource data. Expert will provide their Insights on:
1. Updated FDA guidelines
2. eSource’s impact on risk-based monitoring
3. Data synergy throughout the clinical trial chain
4. Data security and access protocol
5. Onsite management and compliance
View From the Hudson River
World Trade Center in Downtown NYC ©Target Health Inc.
ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Oxidative stress can cause disruptions in normal mechanisms of cellular signaling.
Oxidation is the process of removing electrons from an atom or molecule. The result of this change can be destructive – rusting 1) ___ is a familiar result of oxidation. Here, oxygen is the responsible agent, but other oxidizing agents, such as chlorine, can be as harsh. Although we need oxygen to live, high concentrations of it are actually corrosive and toxic. We obtain energy by burning fuel with oxygen – that is, by combining digested 2) ___ with oxygen from the air we breathe. This is a controlled metabolic process that, unfortunately, also generates dangerous byproducts.
Production of reactive oxygen species (ROS) is a particularly destructive aspect of oxidative stress. Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen. Such species include free radicals and peroxides. Normally, cells defend themselves against ROS damage with enzymes. The most important plasma antioxidant in humans is uric acid.
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides. High blood concentrations of uric acid can lead to gout. The chemical is associated with other medical conditions including diabetes and the formation of ammonium acid urate 3) ___ stones.
Free radicals are electronically unstable atoms or molecules capable of stripping electrons from any other molecules they meet in an effort to achieve stability. In their wake they create even more unstable molecules that then attack their neighbors in domino-like chain reactions. By the time a free radical chain fizzles out, it may have ripped through vital components of cells, causing extensive damage, similar to that caused by ionizing radiation.
Oxidative stress is the total burden placed on organisms by the constant production of free 4) ___ in the normal course of metabolism plus whatever other pressures the environment brings to bear (natural and artificial radiation, toxins in air, food and water; and miscellaneous sources of oxidizing activity, such as tobacco smoke).
Our bodies aren’t helpless in the face of these assaults. We have defenses against oxidative stress in the form of physical barriers to contain free radicals at their sites of production within cells; enzymes that neutralize dangerously reactive forms of oxygen; substances in our diets (such as vitamin C and vitamin E) that can quench free radicals by donating electrons to them and cutting off the chain reactions early in their course; repair mechanisms to take care of oxidative damage to DNA, proteins and membranes; and complex stress responses that include programmed cell suicide if damage is too great.
A good case can be made for the notion that health depends on a balance between 5) ___ stress and antioxidant defenses. Aging and age-related diseases reflect the inability of our antioxidant defenses to cope with oxidative stress over time. The good news is that with strong antioxidant defenses, long life without disease should be possible. Environmental stress is one of the biggest causes of free radicals, which is a process where the body starts producing oxygen much faster. This process is referred to as oxidative stress. Oxidative stress is essentially an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by 6) ___.
There are a number of symptoms which could point towards oxidative stress and if left unchecked could hasten the aging process and also cause a number of neurodegenerative diseases and also a few cardiovascular diseases, as well as cancer. A few such diseases are:
1. Hyperoxia, which is excess oxygen or higher than normal partial pressure of oxygen. It refers to excess oxygen in the lungs or other body tissues, which can be caused by breathing air or oxygen at pressures greater than normal atmospheric pressure. This kind of hyperoxia can lead to oxygen toxicity.
2. Tissue injury
Oxidative stress leads to many pathophysiological conditions in the body. Some of these include neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease, gene mutations and cancers, chronic fatigue syndrome, fragile X syndrome, heart and blood vessel disorders, atherosclerosis, heart failure, heart attack and inflammatory diseases. Oxidative stress is thought to be linked to certain cardiovascular disease, since oxidation of LDL in the vascular endothelium is a precursor to plaque formation. More severe oxidative stress can cause cell death and even moderate oxidation can trigger apoptosis, while more intense stresses may cause necrosis.
Oxygen by-products are relatively unreactive but some of these can undergo metabolism within the biological system to give rise to these highly reactive oxidants. Not all reactive oxygen species are harmful to the 7) ___ body. Some of them are useful in killing invading pathogens or microbes. Free radicals can chemically interact with cell components such as DNA, protein or lipid and steal their electrons in order to become stabilized. This, in turn, destabilizes the cell component molecules which then seek and steal an electron from another molecule, therefore triggering a large chain of free radical reactions.
Every cell that utilizes enzymes and oxygen to perform functions is exposed to oxygen free radical reactions that have the potential to cause serious damage to the cell. Antioxidants are molecules present in cells that prevent these reactions by donating an electron to the free radicals without becoming destabilized themselves. An imbalance between oxidants and antioxidants is the underlying basis of oxidative stress. To counteract oxidative stress, the body produces an armory of antioxidants to defend itself. It’s the job of antioxidants to neutralize or ‘mop up’ free radicals that can harm our 8) ___ cells.
The body’s ability to produce antioxidants (its metabolic process) is controlled by genetic makeup and influenced by exposure to environmental factors, such as diet and smoking, pollution. Changes in lifestyles, which include more environmental pollution and less quality in our diets, expose us to more free radicals than ever before. The body’s internal production of antioxidants can be added to by increasing dietary intake of antioxidant foods.
Tomatoes containing a pigment called 9) ___ lycopene (responsible for the red color) are powerful antioxidants. Tomatoes in all their forms are a major source of lycopene, including tomato products like canned tomatoes, tomato soup, tomato juice and even ketchup. Lycopene is also highly concentrated in watermelon. Oranges, grapefruit, lemons and limes possess many natural substances that appear to be important in disease protection, such as carotenoids, flavonoids, terpenes, limonoids and coumarins. Together these phytochemicals act more powerfully than if they were given separately. It’s better to eat the fruit whole in its natural form, because some of the potency is lost when the juice is extracted.
Black tea, green tea and oolong teas have antioxidant properties. All three varieties come from the plant Camellia sinenis. Common brands of black tea do contain antioxidants, but by far the most potent source is green tea (jasmine tea) which contains the antioxidant catechin. Beta-carotene is an orange pigment that was isolated from carrots 150 years ago. It is found concentrated in deep orange and green vegetables (the green chlorophyll covers up the orange pigment). 10) ___Beta-carotene is an antioxidant that has been much discussed in connection with lung cancer rates.
Studies have shown that people who eat a diet that is rich in fruit and vegetables are less likely to get diseases, such as cancer, heart disease and stroke.
ANSWERS: 1) iron; 2) food; 3) kidney; 4) radicals; 5) oxidative;6) antioxidants; 7) body; 8) cells; 9) lycopene; 10) Beta-carotene
Otto Heinrich Warburg (1883-1970)
Otto Heinrich Warburg (October 8, 1883 – August 1, 1970), son of physicist Emil Warburg, was a German physiologist and medical doctor. Warburg was one of the 20th century’s leading biochemists and was awarded the Nobel Prize in 1931. In total, he was nominated an unprecedented three times for the Nobel Prize for three separate achievements.
Warburg’s father, Emil Warburg, was a member of the illustrious Warburg family of Altona, and had converted to Christianity reportedly after a disagreement with his Conservative Jewish parents. Emil was also president of the Physikalische Reichsanstalt, Wirklicher Geheimer Oberregierungsrat (True Senior Privy Counselor). His mother was the daughter of a Protestant family of bankers and civil servants from Baden. His much older cousin, also named Otto Warburg (1859-1938), was a German botanist, a notable industrial agriculture expert, as well as an active member of the Zionist Organization, for which he served as president from 1911-1921.
Warburg studied chemistry under the great Emil Fischer, and earned his Doctor of Chemistry in Berlin in 1906. He then studied under Ludolf von Krehl, and earned the degree of Doctor of Medicine in Heidelberg in 1911. Between 1908 and 1914, Warburg was affiliated with the Naples Marine Biological Station, in Naples, Italy, where he conducted research.
A lifelong equestrian, he served as an officer in the elite Uhlans (cavalry) on the front during the First World War, where he won the Iron Cross. Warburg later credited this experience with affording him invaluable insights into real life outside the confines of academia. Towards the end of the war, when the outcome was unmistakable, Albert Einstein, who had been a friend of Warburg’s father Emil, wrote Warburg at the behest of friends, asking him to leave the army and return to academia, since it would be a tragedy for the world to lose his talents. Einstein and Warburg later became friends, and Einstein’s work in physics had great influence on Otto’s biochemical research.
Otto Warburg in 1931
While working at the Marine Biological Station, Warburg performed research on oxygen consumption in sea urchin eggs after fertilization, and proved that upon fertilization, the rate of respiration increases by as much as six fold. His experiments also proved iron is essential for the development of the larval stage.
In 1918, Warburg was appointed professor at the Kaiser Wilhelm Institute for Biology in Berlin-Dahlem (part of the Kaiser-Wilhelm-Gesellschaft). By 1931 he was named director of the Kaiser Wilhelm Institute for Cell Physiology, which was founded the previous year by a donation of the Rockefeller Foundation to the Kaiser Wilhelm Gesellschaft (since renamed the Max Planck Society). Warburg investigated the metabolism of tumors and the respiration of cells, particularly cancer cells, and in 1931 was awarded the Nobel Prize in Physiology for his discovery of the nature and mode of action of the respiratory enzyme.
When the Nazis came to power people of Jewish descent were forced from their professional positions. For some reason despite having a Jewish father Warburg was spared. By this time Warburg was studying cancer. While banned from teaching, because he was Jewish, he was allowed to carry on his research. In 1935, Hitler had a polyp removed from his vocal cords. It is believed that afterwards, he feared that could develop cancer, which may have allowed Warburg to survive. In 1941, Warburg lost his post briefly, when he made critical remarks about the regime but a few weeks later a personal order from Hitler’s Chancellery ordered him to resume work on his cancer research. Goring also arranged for him to be classified as one-quarter Jewish. It is believed that Warburg was so totally dedicated to his work that he was prepared not only to stay in Germany but also accept the Nazi treatment of his Jewish colleagues and his Jewish relatives. This was despite his having received an offer from the Rockefeller Foundation to continue to fund his work if he emigrated. In 1943 Warburg relocated his laboratory to the village of Liebenburg on the outskirts of Berlin to avoid ongoing air attacks. After the end of the Second World War he made inquiries about moving to the United States, but was turned down.
In 1944, Warburg was nominated for a second Nobel Prize in Physiology by Albert Szent-Gyorgyi, for his work on nicotinamide, the mechanism and enzymes involved in fermentation, and the discovery of flavin (in yellow enzymes). Some sources reported he was selected to receive the award that year, but was prevented from receiving it by Adolf Hitler’s regime, which had issued a bizarre decree in 1937 that forbade Germans from accepting Nobel Prizes. According to the Nobel Foundation, this rumor is not true; although he was considered a worthwhile candidate, he was not selected for the prize.
Three scientists who worked in Warburg’s lab, including Sir Hans Adolf Krebs, who went on to win the Nobel Prize. Among other discoveries, Krebs is credited with the identification of the citric acid cycle (or Szentgy?rgyi-Krebs cycle).
Warburg’s combined work in plant physiology, cell metabolism and oncology made him an integral figure in the later development of systems biology. He worked with Dean Burk in photosynthesis to discover the I-quantum reaction that splits the CO2, activated by the respiration. In 1924, Warburg hypothesized that cancer, malignant growth, and tumor growth are caused by tumor cells mainly generating energy (as e.g. adenosine triphosphate / ATP) by nonoxidative breakdown of glucose (a process called glycolysis) and the subsequent recycling of the metabolite NADH back to its oxidized form, for reuse in the glycolytic cycle to complete the process (known as fermentation, or anaerobic respiration). This is in contrast to healthy cells, which mainly generate energy from oxidative breakdown of pyruvate. Pyruvate is an end product of glycolysis, and is oxidized within the mitochondria. Hence, and according to Warburg, cancer should be interpreted as a mitochondrial dysfunction. According to Warburg, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar. Warburg continued to develop the hypothesis experimentally, and held several prominent lectures outlining the theory and the data.
The concept that cancer cells switch to fermentation in lieu of aerobic respiration has become widely accepted, even if it is not seen as the cause of cancer. Some suggest the Warburg phenomenon could be used to develop anticancer drugs. Meanwhile, cancer cell glycolysis is the basis of positron emission tomography (18-FDG PET), a medical imaging technology that relies on this phenomenon.
Warburg’s grave in Berlin, Cemetery Dahlem
Warburg edited and had much of his original work published in The Metabolism of Tumours (1931) and wrote New Methods of Cell Physiology(1962). An unabashed anglophile, Otto Warburg was thrilled when Oxford University awarded him an honorary doctorate. He was awarded the Order Pour le Merite in 1952, and was known to tell other universities not to bother with honorary doctorates, and to ask officials to mail him medals he had been awarded so as to avoid a ceremony that would separate him from his beloved laboratory.
Warburg also wrote about oxygen’s relationship to the pH of cancer cells’ internal environments. Since fermentation was a major metabolic pathway of cancer cells, Warburg reported cancer cells maintain a lower pH, as low as 6.0, due to lactic acid production and elevated CO2. He firmly believed there was a direct relationship between pH and oxygen. When frustrated by the lack of acceptance of his ideas, Warburg was known to quote an aphorism he attributed to Max Planck: Science progresses not because scientists change their minds, but rather because scientists attached to erroneous views die, and are replaced. Seemingly utterly convinced of the accuracy of his conclusions, Warburg expressed dismay at the continual discovery of cancer agents and cancer viruses which he expected to hinder necessary preventative measures and thereby become responsible for cancer cases.
In his later years, Warburg, to a large degree, prescient, was convinced that illness resulted from pollution; this caused him to become a bit of a health advocate. He insisted on eating bread made from wheat grown organically on land that belonged to him. When he visited restaurants, he often made arrangements to pay the full price for a cup of tea, but only to be served boiling water, from which he would make tea with a tea bag he had brought with him. He was also known to go to significant lengths to obtain organic butter, the quality of which he trusted.
When Dr. Josef Issels, who became famous for his use of nonmainstream therapies to treat cancer, was arrested and later found guilty of malpractice in what Issels alleged was a highly politicized case, Warburg offered to testify on Issels’ behalf at his appeal to the German Supreme Court. All of Issels’ convictions were overturned.
The Otto Warburg Medal is intended to commemorate Warburg’s outstanding achievements. It has been awarded by the German Society for Biochemistry and Molecular Biology (Gesellschaft fur Biochemie und Molekularbiologie) since 1963. The prize honors and encourages pioneering achievements in fundamental biochemical and molecular biological research. The Otto Warburg Medal is regarded as the highest award for biochemists and molecular biologists in Germany. It has been endowed with prize money, sponsored by the publishing company Elsevier/BBA.
First Drug Candidate From NIH Program Acquired by Biopharmaceutical Company
NIH and US government support are key factors for breakthroughs in science, medicine and health care. Target Health congratulates the NIH for this major milestone.
A drug candidate developed by researchers at the NIH’s National Center for Advancing Translational Sciences (NCATS) and its collaborators has been licensed to Baxter International’s BioScience business. The drug candidate, Aes-103, is the first specifically developed to target the underlying molecular mechanism of sickle cell disease. Baxter now will advance the clinical development activities required for regulatory approval and commercialization. To read more about NCATS and its TRND program, visithttp://www.ncats.nih.gov/trnd.html.
This is the first time a company has acquired a drug candidate developed with NCATS’ Therapeutics for Rare and Neglected Diseases (TRND) program resources. Baxter International recently acquired AesRx, LLC, Newton, Massachusetts — the TRND program collaborator — including Aes-103. TRND and AesRx researchers worked together to develop Aes-103 through a Phase II clinical trial to evaluate safety and effectiveness. The trial data indicated that Aes-103 significantly reduced patients’ pain. Aes-103 works by binding directly to hemoglobin and changing its structure, thereby reducing the sickling of red blood cells. This structural change may lessen sickling-related complications in patients.
This is a wonderful example of why NCATS was created, said NIH Director Francis S. Collins, M.D., Ph.D. The progress made thus far in the development of Aes-103 demonstrates NCATS’ catalytic role in bringing together the necessary players, whether academic, nonprofit or industry, to overcome obstacles to translation and advance badly needed treatments to patients.
Sickle cell disease disproportionately affects African-Americans and is considered both rare and neglected in the United States. African-Americans with sickle cell often face significant health disparities in clinical care. Life expectancy for people with sickle cell disease is only to mid- to late 40s. Sickle cell disease is a genetic blood disorder that affects millions worldwide, including approximately 100,000 people in the United States – among them, 1 in 500 African-Americans. Individuals living with sickle cell disease have defective hemoglobin, the protein in red blood cells that carries oxygen. This defect causes their cells to become rigid and crescent-shaped, blocking small blood vessels and causing inflammation, pain and strokes, and decreased blood flow.
Prior to AesRx’s collaboration with TRND researchers, and despite promising data on Aes-103, the company had difficulty securing private financing because potential investors lacked interest in funding an early-stage project that was considered too risky. AesRx did not have the resources to complete preclinical and early clinical development.
Currently, the only drug approved by the U.S. Food and Drug Administration (FDA) to treat sickle cell disease is hydroxyurea, a drug initially developed to treat cancer. However, the clinical utility of hydroxyurea is limited. Many individuals with sickle cell disease either do not respond to the drug, or they may experience undesirable side effects.
TRND researchers signed a collaborative agreement with AesRx in 2010 and established a project team made up of NCATS and AesRx scientists as well as a leading sickle cell disease clinical researcher at the National Heart, Lung, and Blood Institute (NHLBI). Other key project collaborators received support through NHLBI grants, the NIH Clinical Center and its pharmacy, and NCATS’ Bridging Interventional Development Gaps program. Aes-103 was licensed by AesRx from Virginia Commonwealth University, Richmond, where the compound was discovered.
In less than one year, the team completed the preclinical toxicology, chemistry, manufacturing, controls and regulatory studies necessary to support an investigational new drug (IND) application, which AesRx filed with the FDA. After IND clearance, Aes-103 moved into Phase I clinical trials in healthy volunteers and sickle cell disease patients in 2011 and into a Phase II trial in patients in 2013. The project results also helped AesRx obtain a Massachusetts Life Science Accelerator loan to support development of Aes-103.
Rehabilitation Helps Prevent Depression for those with AMD
Age-related macular degeneration (AMD) is a leading cause of vision loss in the United States. About 2 million Americans age 50 and over have vision loss from AMD, and about 8 million have an earlier stage of the disease, with or without vision loss. AMD causes damage to the macula, a spot near the center of the retina that is needed for sharp, straight-ahead vision. It can affect one eye or both, which is called bilateral AMD. As the disease progresses, it can cause a growing blurred area near the center of vision, and lead to difficulty with everyday activities, including the ability to drive, read, write, watch television, cook, and do housework.
Activities that used to be fun and fulfilling may begin to seem burdensome or even impossible. With loss of the ability to drive and navigate unfamiliar places, it becomes easier to stay at home than to see friends or meet new people. All of this can take a toll on mental health, and past studies have found that as many as one-third of people with bilateral AMD develop clinical depression.
A new study, published online in Ophthalmology( July 2014), shows that a type of rehabilitation therapy can cut this risk in half. The study was funded by the National Eye Institute (NEI), part of the National Institutes of Health. The trial recruited 188 participants with bilateral AMD from an ophthalmology practice affiliated with Wills Eye Hospital in Philadelphia. The participants were 84 years of age on average, 70% were women, and 50% lived alone. All had a best-corrected vision of less than 20/70. (A person with 20/70 vision sees an object from 20 feet away as clearly as a person with normal vision sees it at 70 feet away.) Each participant had mild depressive symptoms and was at risk for developing clinical depression, based on a nine-item depression subtest of the Patient Health Questionnaire, or PHQ-9.
During the trial, the participants had two visits with an optometrist, during which they were prescribed low-vision devices such as handheld magnifiers. After those initial visits, the participants were randomly split into two groups. One group received behavior activation from an occupational therapist specially trained in the approach. The occupational therapist worked with participants to guide them on using the low-vision devices, to make changes around the home (such as using brighter lights and high-contrast tape), to increase their social activities, and to help them set personal goals and break these down into manageable steps. The second group of participants served as a control group. They talked about their difficulties to a therapist, but did not receive behavior activation or low-vision occupational therapy. Both groups had six one-hour therapy sessions in their homes over a two-month period. All participants were allowed to take antidepressants, but less than 10% did so. All received medical management of AMD as prescribed by their primary eye care providers.
By four months, 12 participants in the control group and seven participants in the behavior activation group had withdrawn from the trial or passed away. Of the remaining 169 participants, 18 (23.4%) in the control group and 11 (12.6%) in the behavior activation group developed clinical depression, based on retesting with the PHQ-9. Behavior activation had the most benefit for participants with the worst vision (less than 20/100), reducing the risk of depression by about 60% compared to controls. When the data were adjusted for vision status, physical health and baseline PHQ-9 score, behavior activation reduced the risk of depression by 50% compared to the control treatment.
The authors hope the study will serve as a model for similar approaches to preventing and treating depression in AMD, although stronger links between primary eye care and mental health care workers would be needed to make behavior activation more widely available for AMD patients. Also, specialized instruction would also be needed for occupational therapists, who are not typically trained in behavior activation. The study is continuing to follow participants to see if the benefits of treatment are maintained out to one year.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.
A Blueprint for Helping Children with Rare Diseases
Last week, Target Health obtained orphan drug designation on behalf of 2 clients. The first designation was for a rare GI tumor and the second was for an autoimmune disease that affects blood vessels. This makes a total of 13 orphan drug designation obtained by Target Health, with 2 of the drug products reaching the market. A 3rd product in Cystic Fibrosis was approved in 2012.
The U.S. Congress and the US FDA are committed to bring new therapies to patients with rare diseases, including children. Two years ago this week, Congress made another contribution to this effort by enacting the Food and Drug Administration Safety and Innovation Act (FDASIA). The law directs the FDA to take two actions to further the development of new therapies for children affected by rare diseases:
(1) to hold a meeting with stakeholders and discuss ways to encourage and accelerate the development of new therapies for pediatric rare diseases, and
(2) issue a report that includes a strategic plan for achieving this goal.
There are unique challenges when developing drugs, biological products and medical devices for the pediatric population. Not only is there the potential for children to respond differently to products as they grow but there are also additional ethical concerns for this patient population. But these challenges are further compounded when developing therapies for pediatric rare diseases. For example, rare disease product development, by definition, means there is only a small potential group of patients available to participate in clinical studies that can help determine whether a product is safe and effective.
In a FDASIA meeting in January, a variety of suggestions were provided on clinical trial design and data collection from hundreds of the participating stakeholders from academia; clinical and treating communities; patient and advocacy groups; industry and governmental agencies. These discussions helped inform aStrategic Plan for Accelerating the Development of Therapies for Pediatric Rare Diseases. It outlines how we plan to meet the following four objectives:
Enhance foundational and translational science. Goal is to fill essential information gaps through such measures as fostering the conduct of natural history studies for pediatric rare diseases and by identifying unmet pediatric needs in medical device development. FDA also plans to issue guidance for sponsors on common issues in rare disease drug development and to refine and expand the use of computational modeling for medical devices.
Strengthen communication, collaboration, and partnering. Robust cooperation within FDA, among agencies, governments and private entities is necessary to enable the exchange of information on the issues of developing treatments for pediatric rare diseases. Single entities by themselves usually don’t have sufficient resources or expertise to overcome the product development challenges posed by pediatric rare diseases.
Advance the use of regulatory science to aid clinical trial design and performance. Regulatory science helps develop new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all FDA-regulated products. FDA plans to facilitate better understanding of biomarkers and clinical outcome assessments that are useful for the development of treatments for pediatric rare diseases. FDA also plans to further develop the expedited approval pathway for medical devices intended to treat unmet medical needs; and use FDA’s web-based resources to update and expand awareness of issues involving the development of medical products for pediatric rare diseases.
Enhance FDA’s review process. This strategy includes fostering efforts to learn patients’ and caregivers’ perspectives and incorporating this information into medical product development. FDA plans to further develop and implement a structured approach to benefit-risk assessment in the drug review process and establish a patient engagement panel as part of the medical device advisory committee process.
The report notes the use of expedited programs to speed rare disease medical product development. But it’s important to note that FDA’s regulatory flexibility is reducing the number of approvals under one of these procedures: the accelerated approval program for drugs that treat serious conditions and that fill an unmet medical need based on a surrogate or intermediate endpoint (that is, a measure such as blood test or urine marker that is believed to be indicative of a disease state and treatment effect, but not demonstrative of a direct health gain to the patient). Most of the recent new drug approvals for rare diseases that would otherwise qualify for accelerated approval were given regular or traditional approval instead. As a result, they weren’t required to do confirmatory trials to verify clinical benefit, as required under accelerated approval, because FDA decided that the evidence was already strong enough.
Coleslaw with Buttermilk Dressing
Such beautiful colors; like the Jackson Pollock of salads, and tasty too! ©Joyce Hays, Target Health Inc.
- 4 cups shredded green cabbage ( 1/2 medium head)
- 2 cups shredded red cabbage ( 1/4 medium head)
- 1 medium carrot, peeled and shredded
- 1/2 cup buttermilk
- 3-4 Tablespoons Kraft mayonnaise or low-fat
- 2 Tablespoons low-fat sour cream
- 1 shallot, minced (about 2 Tablespoons)
- 2 Tablespoons minced fresh parsley leaves
- 2 Tablespoons fresh dill, minced
- 2 Tablespoons cider vinegar
- 1/4 teaspoon Dijon mustard
- 1/2 teaspoon Splenda or 1 teaspoon Agave
- Pinch salt or more to taste
- Pinch black pepper
©Joyce Hays, Target Health Inc.
This recipe is easy, quick and delicious. Just what you want on a summer day. Good for lunch, snack and dinner. Low in calories but high in flavor, satisfaction and good health.
1. With a mandolin or shredder, shred the two cabbages and the carrot. The thinner you’re able to do this, the better the taste (my own persona taste)
2. Place the shredded cabbage and carrot in a large bowl.
3. In a small bowl, stir together the buttermilk, mayonnaise, sour cream, shallot, parsley, vinegar, mustard, sugar, salt and pepper.
4. Pour the buttermilk mixture over the cabbage, stir to combine and refrigerate until ready to serve, 1 to 2 hours. Toss well to distribute the dressing before serving.
59 calories; 2 grams protein; 6 grams carbohydrates; 1 gram fiber; 4 grams fat; 1 gram saturated fat; 4 mg. cholesterol; 126 mg. sodium.
I’ve experimented with coleslaw, forever. I’ve tried many different vinegars including red wine, balsamic, cider, champagne and like cider vinegar the best. I had this salad for lunch, and made enough to have it again, with Jules, for dinner. He loved it. Along with the coleslaw we had a seafood dish with scallops and a sauce I’m in the process of creating. (Maybe, ready for next week). I served the seafood over farfalle pasta. He really liked it, but I wasn’t satisfied yet. Orvieto accompanied dinner, which ended with cut up fresh fruit topped with vanilla activa yogurt. We’ve both lost some weight, by eating light, like this meal, and not being tempted by high calorie desserts.
Cooking with Cats (MimiYao in foreground; BillyBob in rear behind flowers; Dodicat not in view) ©Joyce Hays, Target Health Inc.
Wonderful, light, icy Orvieto. ©Joyce Hays, Target Health Inc.
From Our Table to Yours!
Bon Appetit !