Why Not Get Rid of the Paper and Save Millions?

 

Large pharma companies are telling us that they are managing 5,000 to 8,000 clinical research sites per year. So let’s say we take the top 10 pharma companies from the Transcelerate list of companies, and if we assume that:

 

1. They average 6,000 sites/year each (or use your numbers)

2. There are currently 7 monitoring visits/site/year (or use your numbers)

3. The all-in cost of a single monitoring visit is $3,000 (or use your numbers)

 

Then: The total annual cost for just these 10 companies = $1,260,000,000 (yes, BILLION)

60,000 (sites) x 7 (monitoring visits/site) x $3,000 (all-in cost/visit)

 

Therefore, would like to propose to the industry that we can drop onsite monitoring costs by around 50% and save these 10 companies an aggregate of about $600,000,000 (or $60,000,000 each), by using our eSource solution, which can be integrated with any modern EDC system.

 

This business model is not theoretical as we have been doing this for three years now. There are also savings not directly associated with the monitoring visit itself such as:

 


1.  Less screen failures as reasons for screen failures early in the study can be visualized and evaluated in real time and site behavior can be changed (e.g. stop screening subjects with known exclusion criteria and do a pre-screen of known medical histories before asking subjects to sign informed consent)

 

2.  Fewer protocol violations since data are entered in real time, the EDC system can pick up violators as opposed to finding out about violators when transcribing from the paper

 

3.  Expediting the initiation of protocol amendments before there is too much damage

 

4.  Increase clinical site satisfaction as they can now see more study subjects during the day as they are done when the subject leaves the office and there are fewer burdensome monitoring visits

 

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.

Biophysicists Grow Bacteria In Petri Dishes To Find Antibiotics

 

20131014-4

Biophysicists are growing Petri dishes of different species of bacteria in order to develop new antibiotics. The 1) ___ are subjected to different temperatures and have limited food sources inside the dish. Despite these conditions, most colonies tend to communicate and reproduce. Their growth results in unique patterns of varying colors–a sort of “bacteria painting.” Researchers are hoping to learn more about the strategies the bacteria use to thrive, in order to find weaknesses that new 2) ___ could exploit.

 

There was a time when doctors thought 3) ___ could cure all. It’s a different story today as drug-resistant bacteria emerge in places like hospitals and schools. To keep up with changes in bacterial behavior, scientists are fighting bacteria using an artistic approach.

 

Biophysicist Herbert Levine’s Petri 4) ___ look like an exhibit at a modern art museum. His beautiful images are actually made from bacteria similar to the ones that cause deadly diseases. Dr. Levine uses bacteria in Petri dishes in his quest to discover the next super drug. He’s fighting a new generation of bacterial 5) ___ that includes MRSA, a flesh-eating disease resistant to antibiotics. “We thought we had a whole arsenal of antibiotics and these would always work but the bacteria are smarter than we used to give them credit for being,” said Dr. Levine, who works at the Bioengineering Department of Rice University in Houston, Texas. Dr. Levine and his team have gone back to the basics of 6) ___. They have created bacteria patterns by changing the temperature and limiting the food sources inside Petri dishes. Despite harsh conditions, the colonies find ways to communicate and reproduce. “If we can understand what strategies they’re using, we can devise methods to defeat those strategies,” Dr. Levine said.

 

Through Dr. Levine’s work, scientists have learned bacteria are very resourceful. They enclose themselves in areas antibiotics can’t find. They also soak up antibiotics to keep the rest of their colony safe and transform themselves into new 7) ___ that are less sensitive to the drugs. “If that basic understanding of nature leads to better life for humanity, then, of course, that makes us even more excited,” Dr. Levine said.

 

Along the way, scientists turned the study of bacteria into an art form.

 

Dr. Levine and his colleagues, use the patterns to create computer models. One day those models could be the basis for new medicines that fight all types of bacteria. MRSA is a common cause of skin infections; it can also cause pneumonia, ear infections and sinusitis. MRSA bacteria are sometimes dubbed 8) ___ because they are highly resistant to common antibiotics like penicillin, making infections difficult to treat effectively.

 

Bacteria are highly adaptive, and over time they naturally develop resistance, protecting them from incoming germs (and antibiotics) and making them harder to 9) ___. If MRSA enters the body through the skin, it can cause irritating skin infections, but if it enters the lungs or bloodstream, it can cause serious blood infections, pneumonia, even death. MRSA infection rates in the US have been increasing since 1970, largely because surveillance programs to monitor its spread are not effective. Other countries, such as the Netherlands, Sweden and Denmark have all but eliminated MRSA from their hospitals through such surveillance programs, which focus on screening patients for MRSA at admission and isolating any carriers.

 

DRUG RESISTANCE: Bacteria are highly adaptive, and over time they naturally develop 10) ___, protecting them from incoming germs (and antibiotics), which makes them more difficult to kill. If someone has strep throat, for example, repeated exposure to penicillin and amoxicillin can result in a throat full of bacteria that can shield strep germs from the older drugs. The surviving bacteria then reproduce more and become more dominant. Sometimes parents discontinue antibiotic medication prematurely when they or their children begin to feel better, so the strep germ isn’t entirely killed off, leading to much more severe infections requiring the use of even stronger drugs later on. This can also happen with many other infections inside the body and on the skin.

 

The American Physical Society contributed to the information contained in the TV portion of this report. This report has also been produced thanks to a generous grant from the Camille and Henry Dreyfus Foundation, Inc.

 

For more information, click on the following link for a fascinating video:

 

ANSWERS: 1) bacteria; 2) drugs; 3) antibiotics; 4) dishes; 5) infections; 6) biology; 7) strains; 8) ‘superbugs’; 9) kill; 10) resistance

Herbert Levine, PhD, Theoretical and Biological Physics

 

20131014-3

In the Quiz this week, we reported the exciting work of Dr. Herbert Levine. We thought it would be of interest to our readers to learn more about him, so we are sharing some of his biography and thoughts.

 

Dr. Herbert Levine is the Hasselmann Professor of Bioengineering and Director, of the Center for Theoretical Biological Physics (CTBP) at Rice University in Houston, Texas. This center studies: Theoretical Biological Physics (CTBP), Physics of Cancer, Physics of Living Systems

 

Dr. Levine’s has a MA and Ph.D. in Physics from Princeton University and a B.S., in Physics from the Massachusetts Institute of Technology (MIT).

 

“I am interested in the physics of nonequilibrium systems, especially in how these systems create nontrivial spatial patterns. Nonequilibrium dynamics usually involves the time evolution of a spatially extended set of degrees of freedom which evolve nonlinearly while interacting with each other via transport processes. Falling within this framework are problems that arise in physics and material science, chemical reaction kinetics and biological morphogenesis. Most recently, my work has emphasized structures formed in micro-organism aggregation (both bacteria colonies and cellular slime mold), rotating waves that appear in a variety of nonlinear chemical systems (CO catalysis on a metal surface, e.g.), and the use of field theoretic approaches for the study of disordered and fractal patterns in crystallization.”

 

In terms of his research, Dr. Levine spends his time examining the dynamics of non-equilibrium systems, both deterministic and stochastic, to explain and quantify the intricate processes that govern biological systems. He is a pioneer in using theory to expand experimental findings and in the development of well-parameterized computational models that can be used to garner new insights into biomedical systems. A main research project in his group combines theoretical approaches with advanced laboratory experiments to understand directed cell motion in eukaryotic cells and to elucidate both signal transduction and cellular mechanics aspects of this critical process. Additional areas of research include calcium-based cell signaling (most recently at the neuronal synapse), the statistical mechanics of Darwinian evolution, and pattern formation in microorganism colonies.

 

Dr. Levine is one of the originators of the “microscopic solvability” approach to diffusively unstable systems. The theory has revolutionized the understanding of several phenomena, including the structures that bacteria create when they colonize surfaces and form antibiotic resistant biofilms. This work demonstrated how microscopic degrees of freedom, (which for biological cases, ultimately relates to genetic expression dynamics), interacts with macroscopic transport physics to determine structure.

 

Specific areas of current focus include:

 

1. Eukaryotic chemotaxis, using Dictyostelium as a model system

2. Mechanics of cell motility, being studied both at the single cell and multicellular levels

3 Spatial organization of bacterial colonies, including coupling to genetic decision-making circuits

4. A new effort on the Physics of Cancer

 

Working with collaborators at Rice’s BioScience Research Collaborative, the Texas Medical Center, and the Center for Theoretical Biological Physics (CTBP) – a Physics Frontiers Center funded by the National Science Foundation, Levine is expanding his focus to address complex issues in cancer progression and treatment. Through additional funding from a grant from the Cancer Prevention and Research Institute of Texas (CPRIT), new approaches are being devised that will help form an integrated picture of the many changes that occur in cells, tissues and organs due to cancer.

 

Levine is an elected member of the American Academy of Arts and Sciences, an elected member of the National Academy of Science, a fellow of the American Physical Society, past chair of the American Physical Society’s Division of Biological Physics. He is the author of more than 225 peer-reviewed publications, has served as member of the editorial board for the journals Chaos and Physical Biology, and was associate editor for the Biophysical Journal for six years. His research has been featured in the New York Times, Scientific American, the Today Show and many other popular science forums. Levine is a co-director of CTBP and consultant for JASON, which is an independent group of scientists that advises the U.S. government on matters of science and technology.

 

Research Statement

Biological systems operate in nonequilibrium states, using free energy derived from metabolism to run all the various processes needed for survival. Understanding the chemical and physical mechanisms that govern these processes is an essential component for advancing our quantitative understanding biological systems. Ultimately, this new level of understanding should prove crucial for tackling currently intractable diseases such as metastatic cancer.

 

Also, Dr. Levine is the coordinator of an international network of graduate students conducting research into the Physics of Living Systems (see http://pols.rice.edu)

 

Professor Herbert Levine elected to membership in the National Academy of Sciences, one of the highest honors bestowed on U.S. scientists and engineers.

Possible Treatment for Batten Disease

 

According to an article published online in Nature Neuroscience (7 October 2013), researchers at the National Institutes of Health have identified a potential new drug that could help in the treatment of a form of Batten disease, a fatal childhood disorder. The term Batten disease refers to a group of disorders resulting in deterioration of the nervous system. These disorders occur in 1 of every 12,500 births, according to the study authors. The investigational drug is derived from hydroxylamine, a molecule chemically similar to ammonia. Hyroxylamine is toxic, but a slight change in the molecule’s chemical structure results in a non-toxic molecule, called NtBuHA, short for N-(tert-Butyl-Hydroxylamine). The drug was tested in mice with the disease and it was found that it slowed the loss of coordination seen in the disorder, and extended the animals’ life span.

 

The authors hope that NtBuHA will be useful for treating a particular subtype of the disease, infantile Batten disease. With infantile Batten disease, children appear normal at birth, but experience a gradual, but steady, loss of brain tissue. By 11 to 18 months, they experience difficulty with physical coordination and begin to lose their vision. By age 4, they go blind and have no apparent brain activity. They may live in a vegetative state for several more years before dying.

 

Children with infantile Batten disease have a genetic deficiency of an enzyme, PPT1 (palmitoyl-protein thioesterase-1). Ordinarily PPT1 breaks down ceroid, a waxy substance. Without PPT1, ceroid builds up in brain cells, and results in infantile Batten disease. The researchers knew that the compound hydroxylaminemimics the function of the PPT1 enzyme. However, the compound is also toxic. After testing a panel of chemically modified hydroxylamines, they found that NtBuHA could mimic PPT1 in cultured cells from infantile Batten patients, preventing the waxy buildup, but without hyroxylamine’s toxic effects.

 

Next, the authors tested NtBuHA on a strain of mice genetically modified to lack the PPT1 enzyme. They added NtBuHA to the animals’drinking water and found that it reached the animals’ brains, where it broke down and depleted the waxy deposits. Although NtBuHA did not prevent all of the damage that typically occurs in the mouse form of the disease, the waxy buildup was greatly reduced in the treated mice as compared to the untreated mice. The authors found that NtBuHA protected the neurons in the animals’ brains, slowed the deterioration in motor coordination and extended the animals’ life span.

Long-Term Cognitive Impairment after Critical Illness

 

Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. As a result, a study published the New England Journal of Medicine (2013;369:1306-1316) was performed to further evaluate this observation.

 

The study enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean +[SD] score, 100+15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, gender-, and education-adjusted mean score, 50+10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders.

 

Results showed that of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer’s disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer’s disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months.

 

According to the others, patients in medical and surgical ICUs are at high risk for long-term cognitive impairment and that a longer duration of delirium in the hospital is associated with worse global cognition and executive function scores at 3 and 12 months.

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

 

Medical Product Activities During the Federal Government Shutdown

 

The following summarizes the anticipated scope of FDA’s activities during the Federal Government Shutdown beginning on October 1, 2013, and continuing until the date of enactment of an FY 2014 appropriation or Continuing Resolution for FDA (the “lapse period”). Please note that FDA’s anticipated activities are subject to resource constraints on the Agency due to the lapse in appropriations and may change in the event of a protracted lapse period.

 

OVERVIEW

  1. During the lapse period, FDA activities related to medical products generally will be limited to the following:
    1. Excepted work involving the safety of human life or the protection of property, including Criminal law enforcement work; and
    2. Activities funded by carryover user fee balances, including user fee balances under the Prescription Drug User Fee Act (PDUFA), Generic Drug User Fee Amendments (GDUFA), and the Medical Device User Fee Amendments (MDUFA).
  2. Carryover user fee balances will be spent on activities for which the fees are authorized under PDUFA, GDUFA, or MDUFA, as applicable.
  3. FDA will not have legal authority to accept user fees assessed for FY 2014 until an FY 2014 appropriation or Continuing Resolution for FDA is enacted. This means that FDA will not be able to accept any regulatory submissions for FY 2014 that require a fee payment and that are submitted during the lapse period.
  4. We do not anticipate that the lapse in appropriations will affect our routine product review process for submissions within the scope of the PDUFA or GDUFA programs, provided that applicable fees were paid before October 1, 2013. We cannot predict whether we will experience delays in these programs in the event of a protracted lapse in appropriations.
  5. Due to resource constraints, certain review activities for products within the scope of the MDUFA program may be suspended during the lapse period.
  6. Generally, scheduled advisory committee meetings regarding the approval of, or post-marketing safety issues regarding, products within the scope of the PDUFA, GDUFA, or MDUFA programs may go forward during the lapse period, subject to constraints on resources and travel. Other advisory committee meetings that can be conducted with carryover user fee balances will be handled on a case-by-case basis.

 

PDUFA

  1. During the lapse period, FDA will not accept PDUFA applications or supplements that require payment of a fee (e.g., New Drug Applications (NDAs) or certain Biologics License Applications (BLAs)), unless the FY 2014 fee was paid prior to October 1, 2013. FDA expects to continue to review PDUFA applications and supplements for which all applicable user fees were received prior to October 1.
    1. For example, for an application or supplement that requires a fee, if the FY 2014 fee was received on September 30, 2013, FDA expects to review the application, even if the application or supplement itself is submitted during the lapse period.
    2. However, if an application or supplement was received on September 30, 2013 and the fee was received on October 1, then FDA will not review the submission, because it cannot accept the fee.
  2. During the lapse period, FDA will accept new regulatory submissions for which no fee is required, if the product is within the scope of the PDUFA program. These types of submissions include, for example:
    1. Investigational new drugs applications (INDs)
    2. Annual reports
    3. Supplements to NDAs and BLAs for which clinical data with respect to safety or effectiveness are not required for approval (this includes most manufacturing and labeling supplements)
    4. NDAs or BLAs that only have orphan designated indications, or a supplement for an orphan designated indication
    5. Submissions that fall within the exemption for previously filed applications or supplements
    6. Applications for which FDA has waived the application fee (e.g., small business waiver)
    7. General correspondence
  3. Sponsors who have not yet paid PDUFA product or establishment fees for FY 2014 should not remit payment during the lapse period, because FDA cannot accept the fees. Sponsors will not be in arrears for FY 2014 product or establishment fees during the lapse period. The due date for these fees will be the first business day after enactment of an appropriation for FY 2014 or a Continuing Resolution for FDA.

 

Cauliflower Roasted with Cumin Seed, Topped with Feta, Yogurt, Mint and Pomegranate

20131014-1

What is it about cauliflower, that invites a variety of interesting herbs and spices? It never loses its mild distinctive flavor, which, in this recipe, becomes enhanced by the cumin, mint, feta and pomegranate. This recipe is, indeed, comforting and easy to make and truly delicious.

 

Ingredients

2 Tablespoons olive oil, divided

1 large head cauliflower

1 teaspoon whole cumin seeds

1/2 teaspoon kosher salt (optional)

1/2 teaspoon freshly ground black pepper (or grind to your taste)

1 pint plain whole yogurt, Greek style

6 ounces crumbled feta

2/3 cup chopped fresh mint leaves, save a few for garnish

1/4 – 1/2 cup pomegranate arils, for garnish

 

Directions

1. Preheat oven to 4250F. Brush a large baking sheet or roasting pan with 1 tablespoon of the olive oil.  Or take the broiler pan and line it with foil and brush that with olive oil.

2. Break, don’t cut, the cauliflower into bite-size florets.  Toss florets with the remaining olive oil, cumin seeds, salt and pepper. Be sure to coat each floret with this mixture.

3. Now, spread the cauliflower, out on prepared, oiled pan. Roast for 20 to 30 minutes, until cauliflower is tender and its edges are toasty. The florets can turn brown but not burnt.

4. While the cauliflower is in the oven, do the quick and easy sauce. Into a food processor, add the yogurt, salt (optional), pepper (grind to your taste), feta, and most of the mint leaves.

5. When you take the cauliflower out of the oven, put it in a serving bowl and pour the sauce over the florets. Sprinkle, over the sauce, the remaining (chopped) fresh mint leaves and the pomegranate arils (you can buy them in seed form, which saves a lot of time).

 

Be sure to serve this right after you take it out of the oven, so it remains warm and delicious.

 

Last night, after rushing back from a 2 hour meeting, in San Diego, my husband needed lots of TLC, something warm and yummy. We had crudités, red wine, kale patties and this cauliflower dish. He loved it! (blueberries for dessert).

 

I must say, when I think how easy and quick it was to make, it’s amazing how delicious this was. BTW, you might have noticed that there was mint-garnish missing from the photo. That’s because when I made the sauce, I put all the fresh mint into the food processor and had nothing left for garnish, except the pomegranate. Of course, it didn’t change the flavor, at all. The first time I made this dish, it looked beautiful with the fresh green mint and red pomegranate scattered over the cauliflower sauce, I should have taken a photo then, but, oh well. Hope you make this soon. You’re gonna really enjoy it.

 

20131014-2

Bon appétit!