Disruptive Innovations Meeting in Boston – Save the Date
The DPharrm meeting is the meeting for those committed to change and modernization of the clinical trial ecosystem by involving modern technology, the patients’ voice, virtual trials, crowd sourcing, etc. Dr. Mitchel is honored on the esteemed Advisory Boardand Target Health was fortunate this week to host the first planning meeting.
Six years ago, the first DPharm addressed virtual clinical trial models, adaptive design thinking, the role of EMRs in clinical data, open source, telemedicine, and self-reported patient data among many other ideas. By the time the 2nd annual DPharm program took place, the concept of applying disruptive thinking to clinical development had taken root, with many attendees bearing titles with clinical innovation in them. Fast forward to 2015, the 5th annual program addressed a jam packed agenda on the latest in innovative thinking to advance clinical trials.
Not all innovation is disruptive, of course, but as a community, we must continue to drive those changes that enhance the patient experience and ultimately bring more drugs to those who need them most in the most in an efficient and cost-efficient way.
Save The Date! September 20 – 21, 2016 The Fairmont Copley Plaza, Boston, MA
A Foggy Day in the Big Apple
Last week an unusual dense fog hit the city. While foggy days of course happen, the unusual weather patterns all over the world, including tornados in the winter in the US are ominous signs of climate change.
View Form the 24th Floor ©Target Health Inc. 2016
ON TARGET is the newsletter of Target Health Inc., a NYC – based, full – service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212 – 681 – 2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Sanofi’s Dengue Vaccine Made Widely Available for First Time
Source: Mikael Haggstrom (Wikipedia)
The Philippines plans to immunize schoolchildren starting in April 2016, as Sanofi Pasteur, the vaccines division of France’s Sanofi SA, made the Philippines the first country where its 1) ___ for dengue fever will be widely available. Conchita Santos, manager for Sanofi Pasteur in the Philippines, said the company’s facility in France is expected to produce 100 million doses of the vaccine a year when it is fully operational to cover global needs.
Dengue has become the most rapidly expanding 2) ___-borne infectious disease on the planet, surpassing malaria and infecting at least 390 million people per year. The mayor of Hawaii’s Big Island declared a state of emergency to deal with a growing outbreak of dengue fever, spread by infected mosquitoes, with 250 cases confirmed over the past four months, making it the largest outbreak in Hawaii since the 1940s, according to Hawaii health officials, and the largest 3) ___ in the United States.
Dengue fever causes flu-like symptoms and can develop into the deadly dengue hemorrhagic fever. There is no effective treatment for dengue illness other than supportive care, especially for severe cases. Symptoms can be mild or life-threatening as in dengue hemorrhagic fever and dengue shock syndrome. Vector control has been only partially successful in decreasing dengue transmission. The potential use of safe and effective tetravalent dengue vaccines is an attractive addition to prevent disease or minimize the possibility of 4) ___. Currently five candidate vaccines are in human clinical trials. One has completed two Phase III trials, two are in Phase II trials, and three are in Phase I testing.
Dengue virus (DENV) is a mosquito-borne flavivirus that infects at least 390 million people per year. It is estimated that nearly half the world’s population is at risk for dengue infection. A recent report from the Pan American Health Organization points out that reported dengue cases in the Americas rose by a factor of five in the last ten years. The primary mosquito vector for dengue, Aedes aegypti, continues to spread widely and into new habitats due to increased urbanization as well as 5) ___ change. The less efficient vector A. albopictus is also rapidly expanding its habitat, as temperatures climb and flooding continues. Dengue has become the most rapidly expanding mosquito-borne infectious disease on the planet, surpassing 6) ___. Dengue infection and illness are caused by four distinct DENV serotypes that cross-react immunologically. Because of the magnitude of the dengue problem worldwide, more than one of these vaccine candidates will be needed to ensure an adequate vaccine 7) ___ in the long run.
As of this date, only the Sanofi CYD vaccine has made it through phase III trials. This vaccine has been shown to be safe and has different levels of efficacy against the four serotypes, with highest efficacy against serotypes 3 and 4. In addition, it has been shown to have very high efficacy against severe clinical disease and hospitalization due to dengue. This vaccine has also been shown to work better in people with some prior dengue 8) ___, and to be less efficacious in those with no prior dengue immunity. Mathematical modeling has shown that a vaccine with suitable characteristics could be quite effective in reducing overall dengue illness levels in populations that receive such a vaccine over time by routine vaccination of 9) ___ with a single catch-up campaign in older children and possibly adults. Much more work needs to be done to determine how dengue vaccines, once licensed, could be deployed, but it is clear that dengue vaccines will soon join vector control as a means for dengue control.
Johns Hopkins has a contract with 10) ___ to study vaccines, including dengue vaccines that are developed by the NIH. Other pharmaceutical companies in clinical trials with dengue vaccines are Takeda, Merck, GSK with Walter Reed Army Institute of Research.
ANSWERS: 1) vaccine; 2) mosquito; 3) outbreak; 4) epidemics; 5) climate; 6) malaria; 7) supply; 8) immunity; 9) children; 10) NIH
The mosquito Aedes aegypti feeding on a human host
The first record of a case of probable dengue fever is in a Chinese medical encyclopedia from the Jin Dynasty (265-420 CE) which referred to a water poison associated with flying insects.
The primary vector, A. aegypti, spread out of Africa in the 15th to 19th centuries due in part to increased globalization secondary to the slave trade. There have been descriptions of epidemics in the 17th century, but the most plausible early reports of dengue epidemics are from 1779 and 1780, when an epidemic swept across Asia, Africa and North America. From that time until 1940, epidemics were infrequent. In 1906, transmission by the Aedes mosquitoes was confirmed, and in 1907 dengue was the second disease (after yellow fever) that was shown to be caused by a virus. Further investigations by John Burton Cleland and Joseph Franklin Siler completed the basic understanding of dengue transmission. The marked spread of dengue during and after the Second World War has been attributed to ecologic disruption. The same trends also led to the spread of different serotypes of the disease to new areas, and to the emergence of dengue hemorrhagic fever. This severe form of the disease was first reported in the Philippines in 1953; by the 1970s, it had become a major cause of child mortality and had emerged in the Pacific and the Americas. Dengue hemorrhagic fever and dengue shock syndrome were first noted in Central and South America in 1981, as DENV-2 was contracted by people who had previously been infected with DENV-1 several years earlier.
The origins of the Spanish word dengue are not certain, but it is possibly derived from dinga in the Swahili phrase Ka-dinga pepo, which describes the disease as being caused by an evil spirit. Slaves in the West Indies having contracted dengue were said to have the posture and gait of a dandy, and the disease was known as dandy fever. The term break-bone fever was applied by physician and United States Founding Father, Benjamin Rush, in a 1789 report of the 1780 epidemic in Philadelphia. In the report title he uses the more formal term bilious remitting fever. It was called break-bone fever because it sometimes causes severe joint and muscle pain, that feels like bones are breaking. The term dengue fever came into general use only after 1828. Other historical terms include breakheart fever and la dengue. Terms for severe disease include infectious thrombocytopenic purpura and Philippine, Thai, or Singapore hemorrhagic fever.
Figure 1. Average annual number of dengue fever (DF) and dengue hemorrhagic fever (DHF) cases reported to WHO and average annual number of countries reporting dengue (Source: World Health Organization).
Possible factors for dengue fever spread include:
1. Unplanned urban overpopulation of areas leading to inadequate housing and public health systems (water, sewerage and waste management)
2. Poor vector control, e.g., stagnant pools of water for mosquito breeding
3. Climate change and viral evolution (increased virus transmission has been linked to El Nino conditions)
Increased international travel (recreational, business or military) to endemic areas
All of these factors must be addressed to control the spread of dengue. Unplanned urbanization is believed to have had the largest impact on disease amplification in individual countries, whereas travel is believed to have had the largest impact on global spread.
Association of Triple Therapy With Improvement in Cholesterol Profiles
According to an article published online in Arthritis and Rheumatology (24 February 2016), a study was performed to evaluate long-term changes in cholesterol levels in patients with early rheumatoid arthritis (RA) who were randomized to begin treatment with methotrexate (MTX) monotherapy, MTX plus etanercept, or triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial.
For the study, levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed in 416 patients participating in the TEAR trial, during 102 weeks of followup. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated-measures analysis with mixed-effect linear models to model within-subject covariance over time.
Results showed, after models controlling for traditional cardiovascular (CV) risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in the 28-joint Disease Activity Score, the C-reactive protein level, or the erythrocyte sedimentation rate (ESR) were associated with increases in levels of HDL cholesterol, LDL cholesterol, and total cholesterol in all treatment groups (P <0.001-0.035). Triple therapy was strongly associated with higher levels of HDL cholesterol, lower levels of LDL cholesterol, and higher ratios of total cholesterol:HDL cholesterol (P <0.001 for all) compared to MTX monotherapy or MTX plus etanercept therapy over the 2-year follow-up.
The authors concluded that decreases in RA disease activity over long-term follow-up were associated with increases in cholesterol levels in patients with early RA treated with either biologic or nonbiologic therapies, and that the use of triple therapy during 2 years of follow-up was associated with higher HDL cholesterol levels, lower LDL cholesterol levels, and lower total cholesterol:HDL cholesterol ratios compared to those observed in patients who received MTX monotherapy or MTX plus etanercept combination therapy. The authors stated that additional studies are needed to assess the effects of these cholesterol changes on CV events in patients with RA.
Caesarean Delivery and Risk of Childhood Leukemia
Results from case-control studies have shown an increased risk of acute lymphoblastic leukemia (ALL) in young children born by caesarean delivery, and prelabor caesarean delivery in particular. However, an association of method of delivery with childhood leukemia subtypes has yet to be established. Therefore, a study, published online in Lancet Haematology (26 February 2016), performed a pooled analysis of data to investigate the association between childhood leukemia and caesarean delivery.
For the study, data were pooled from 13 case-control studies from the Childhood Leukemia International Consortium (CLIC) done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births between 1970-2013. The authors analyzed caesarean delivery overall and by indications that probably resulted in prelabor caesarean delivery or emergency caesarean delivery. Multivariable logistic regression models, adjusted for child’s birthweight, gender, age, ethnic origin, parental education, maternal age, and study, were used to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukemia (AML) in children aged 0-14 years at diagnosis.
Overall, the studies provided data for 8,780 ALL cases, 1,332 AML cases, and 23,459 controls, of which the birth delivery method was known for 8,655 (99%) ALL cases, 1,292 (97%) AML cases, and 23,351 (>99%) controls. Indications for caesarean delivery were available in four studies (1,061 ALL, 138 AML, and 1,401 controls). Results showed that the OR for all indications of caesarean delivery and ALL was 1.06, and was significant for prelabor caesarean delivery and ALL (1.23; p=0.018). Emergency caesarean delivery was not associated with ALL (OR 1.02). AML was also not associated with caesarean delivery, prelabour caesarean delivery and emergency caesarean delivery.
According to the authors, the results suggest an increased risk of childhood ALL after prelabor caesarean delivery. The authors then added that if this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism.
FDA Issues Recommendations to Reduce the Risk for Zika Virus Blood Transmission
While there have been no reports to date of Zika virus entering the U.S. blood supply, the risk of blood transmission is considered likely based on the most current scientific evidence of how Zika virus and similar viruses (flaviviruses) are spread and recent reports of transfusion-associated infection outside of the U.S. Furthermore, about 4 out of 5 of those infected with Zika virus do not become symptomatic.
As a safety measure against the emerging Zika virus outbreak, the FDA has issued a new guidance recommending the deferral of individuals from donating blood if they have been to areas with active Zika virus transmission, potentially have been exposed to the virus, or have had a confirmed Zika virus infection.
In areas without active Zika virus transmission, the FDA recommends that donors at risk for Zika virus infection be deferred for four weeks. Individuals considered to be at risk include: those who have had symptoms suggestive of Zika virus infection during the past four weeks, those who have had intimate contact with a person who has traveled to, or resided in, an area with active Zika virus transmission during the prior three months, and those who have traveled to areas with active transmission of Zika virus during the past four weeks.
In areas with active Zika virus transmission, the FDA recommends that Whole Blood and blood components for transfusion be obtained from areas of the U.S. without active transmission. Blood establishments may continue collecting and preparing platelets and plasma if an FDA-approved, pathogen-reduction device is used. The guidance also recommends blood establishments update donor education materials with information about Zika virus signs and symptoms and ask potentially affected donors to refrain from giving blood.
Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research stated that based on the best available evidence, it is believed the new recommendations will help reduce the risk of collecting blood and blood components from donors who may be infected with the Zika virus.
Following the issuance of these recommendations, the FDA also intends to issue a guidance that will address appropriate donor deferral measures for human cells, tissues, and cellular and tissue-based products (HCT/Ps), given recent reports of sexual transmission of the virus. In addition to protecting the nation’s blood supply, the FDA is also prioritizing the development of blood screening and diagnostic tests that may be useful for identifying the presence of the virus, preparing to evaluate the safety and efficacy of investigational vaccines and therapeutics that might be developed, and reviewing technology that may help suppress populations of the mosquitoes that can spread the virus.
Salmon Pies with Dill, Dijon, Capers & Shallots and Easy Yogurt/Mayo/Pickle Topping
I’ve experimented for a long time to get a delicious salmon pie. Finally, this recipe should tell it all. The proof is in this pie. To go with the salmon pies is a very simple, easy, tasty sauce. ©Joyce Hays, Target Health Inc.
Served with the world’s best Caesar Salad. ©Joyce Hays, Target Health Inc.
1 1/2 pounds skinless, salmon fillet (tell fish monger to skin the salmon and cut into large chunks, while you watch him do it)
2 teaspoons Dijon mustard
2 shallots, peeled and cut into chunks
1 heaping tablespoon fresh dill, well chopped
3 garlic cloves, squeezed
1/2 cup large size Panko
1 Tablespoon capers, drained
1 Pinch each, salt and black pepper
2 Pinches chili flakes
1 Tablespoon butter
1 Tablespoon extra virgin olive oil
Serve with lemon wedges and topping.
Beautiful fresh ingredients. The fresh dill smells wonderful! ©Joyce Hays, Target Health Inc.
Mix together 1/2 cup yogurt & 1/2 cup Mayo & 1 Tablespoon chopped pickles & a tiny bit of tabasco sauce (3 or 4 squirts)
Making the topping: the pickles add a nice briny depth; the four orange dots are the squirts of tabasco sauce. ©Joyce Hays, Target Health Inc.
Here, fresh dill and capers, are being chopped, same time, saves time. ©Joyce Hays, Target Health Inc.
Cut the salmon into large chunks, and put only about a quarter of it into the container of a food processor, along with the mustard and the slices of garlic. Turn the machine on, and let it run — stopping to scrape down the sides, with a spatula – until the mixture becomes pureed and pasty.
Chopping and dividing the fresh salmon; plus chopping the fresh shallots at the same time. ©Joyce Hays, Target Health Inc.
Multi-tasking is good in the kitchen; it saves time. Chop two things on the same board at the same time. Look at these soft beautiful colors together. ©Joyce Hays, Target Health Inc.
1/4 of the salmon goes into the food processor, to make a quick paste. The rest of the salmon stays chopped, as you see it, on the cutting board. ©Joyce Hays, Target Health Inc.
Now, to the food processor, add the shallots and the remaining salmon. With the remaining ? of the salmon, you are going toCHOP IT now, and NOT PUREE it, the way the first amount of salmon was done. Pulse the food processor, on and off until the fish is chopped but NOT PUREED, and well combined with the puree. No piece should be larger than a quarter inch. BUT BE CAREFUL NOT TO MAKE THE FISH MIXTURE TOO FINE. YOU WANT LITTLE CHUNKS MIXED WITH THE PUREE, FOR A NICE TEXTURE. You can always, chop the ? salmon yourself and not do it in the food processor. In your mixing bowl, everything gets mixed together anyway.
Using a spatula to get every last bit of the fish, scrape the salmon mixture into a bowl. By hand, stir in the Panko, chopped dill, capers and salt, pepper and chili flakes. Shape into four or five little individual pies. Cover and refrigerate the pies for 2 or 3 hours, before cooking.
Here, we’re starting to add ingredients to the large bowl (salmon paste, dill, capers). ©Joyce Hays, Target Health Inc.
Adding the larger pieces of chopped salmon, and chopped shallots. ©Joyce Hays, Target Health Inc.
Adding Panko and the rest of the seasoning. ©Joyce Hays, Target Health Inc.
With your hands scoop a fistful of the salmon mixture and form a ball, then flatten slightly into a little pie. ©Joyce Hays, Target Health Inc.
Place the butter and extra virgin olive oil in a 12-inch nonstick skillet, and turn the heat to medium-high. When the butter foam subsides and the oil is hot, cook the salmon pies for no more than 1 to 2 minutes on each side, turning only once.
Cooking the salmon pies. ©Joyce Hays, Target Health Inc.
Salmon pies are flipped over. ©Joyce Hays, Target Health Inc.
Be careful not to overcook. There’s nothing worse than overcooked salmon. Serve with rice, pasta or baked potato and a green crunchy salad. On the table, put lemon wedges, Tabasco, the Topping recipe given, or any dressing you like.
Moist and delicious for brunch, lunch, snack and dinner. Try a brunch of salmon pies and eggs with bagels and a schmear of Tofutti. Don’t forget your favorite hot coffee with grind it yourself coffee beans. ©Joyce Hays, Target Health Inc.
Some delicious wines come from Australia and New Zealand. Above is one of our favorite Sauvignon Blancs, Cloudy Bay from the Marlborough Area of New Zealand. ©Joyce Hays, Target Health Inc.
This was a simple luscious meal starting with the chilled white wine that you see above, and nibbling on a variety of olives and nuts. The main course was the warm salmon pies with topping, accompanied by the world’s best Caesar salad (my own recipe after months of trial and error) and the jello cake with cool whip, right now our favorite dessert.
Beautiful Marlborough Wine district of New Zealand; internationally recognized for their Sauvignon Blanc.
Marlborough District (Wikipedia)
Marlborough District (Wikipedia)
We had a wonderful relaxing weekend. Went to the theater and saw, She Loves Me, a show that opened many years ago, but is now revived, superbly, by the RoundAbout Theater at their beautifully renovated, Studio 54 Theater. This is a light pouf of a musical comedy, with gorgeous sets and lighting, wonderful music, excellent voices. The live orchestra even has a harp. We enjoyed ourselves. We had dinner at Sardi’s which we go to several times each year. Sardi’s is fun for born/bred New Yorkers, as well as for tourists. We never get tired of Sardi’s. You might not know, but Sardi’s has the very best hamburgers in all of Manhattan, so we always bring some home to enjoy the next day. (we don’t eat hamburgers at Sardi’s).
From Our Table to Yours !