Making Surgeries Safer

Recently Dr. Stuart Mitchell gave a talk at www.bio2devicegroup.org zoom meeting on “Making Electrically Stimulated Surgical Devices Safer”.  Electrically stimulated surgical devices are now ubiquitous, said Dr. Mitchell. Some of the large players in the electrically stimulated surgical device space are Ethicon holding the largest market share, followed by Medronic, Olympus, Hologic, and Conmed. There are many such devices in use but two of the most dominant types are RF devices and Harmonic devices. Radio Frequency or High Frequency devices are the most common type of surgical units on the market. They transform mains current into HF current. One such device Bovie is used to incise tissue, destroy tissue through desiccation, and to control bleeding by causing the coagulation of blood. The harmonic device is used to simultaneously cut and cauterize tissue by using ultrasonic vibration to generate mechanical friction at the active blade site. 

Sharing the history of electrically stimulated surgical devices, Dr. Mitchell began with the fact that despite many hazards in the usage, surgical devices though not perfect, often make surgeries easier, faster and lead to lesser post surgical complications. It is an accepted truism in surgery that the time a patient spends under anesthesia, the better the outcome and electrically stimulated devices vastly lessen the time spent in the OR. 

However, 33% of surgeries result in complications. In the USA alone 16M patients experience surgical complications and 49% or nearly half of those are avoidable complications of which 77% were due to technical errors. Nearly 1 out of every 200 uses of RF devices result in severe burns or fires and that number is as high as 80,000 patients per year. And sometimes this impact goes beyond the patients and affects medical personnel as well. 

Of great concern, among the complications caused with these devices, are fires, burns, and smoke. 

One out of 200 uses of RF devices result in severe burns or fires. That affects 80K patients per year. Sometimes the fires affect medical personnel. Sometimes smoke causes the images to get blurred and impairs the ability of the surgeons to see clearly. Smoke can also create other health hazards post surgery, including toxic gas buildup, viruses, bacteria etc. There are now smoke evacuators available. However, that becomes one more equipment to be used in OR and the compliance can be low.

Some surgeons simply refuse to use electric surgical devices for certain procedures, due to these complications. 

Dr. Mitchell then shared about their company, Novuson’s range of surgical devices. Novuson’s Direct Therapeutic Ultrasound technology potentially can vastly improve surgical outcomes. DTU offers a range of next gen advanced emergency electrosurgical devices. These are electrically neutral, and they are effective in blood or liquid, cause no burning or charring, do not create smoke, and lead to considerably less thermal damage. Dr. Mitchell played a couple of videos showing how the device works. These devices can be used for all surgical procedures including for open, robotic, minimally invasive surgeries and lead to smaller scars, improve precision, speed and control and are far safer. 

This exciting talk was followed by Q&A around the regulatory pathway ahead for various Novuson devices.

Speedy identification of pathogens: Reduces sepsis, saves lives, cost & lowers antibiotic resistance problem

At a recent Bio2DeviceGroup (www.bio2devicegroup.org) event, Kevin Hacker, CEO of BioAffinity Sciences talked about their new technology that when fully developed will identify pathogens more than 100 times faster than the traditional blood culture and related technologies currently in use.

Sepsis Problem

Every year, in the US, 500 thousand people die due to sepsis related complications. Sepsis is a final common pathway for many infections, particularly when an individual’s immunity is low. Body normally releases chemicals into the bloodstream to fight an infection. When the body’s response to these chemicals is out of balance, it results in Sepsis. That is when body’s immune system launches a massive counter attack that harms body’s own tissues and organs. The triggering changes begin to damage body’s vital organ systems that results in dramatic drop in the blood pressure, ultimately leading to death.

Sepsis and septic shock are more common if the individual is very young or very old, have a compromised immune system, have diabetes or cirrhosis, is already sick and frequently in a hospital intensive care unit, have wounds or injuries or severe burns, have invasive devices inserted into the body, and have previously received antibiotics or corticosteroids. Often people can recover from mild sepsis. However, if the body goes into septic shock, the average mortality rate for septic shock is about 40%. Additionally, an episode of severe sepsis may place a person at higher risk of future infections.

Given that widespread infections can progress to Sepsis and Sepsis shock in a matter of few hours, it is imperative that such infections be treated immediately with antibiotics. When given the right antibiotics, there is often a dramatic improvement and speed of cure.

Problem with speedy identification of pathogens

Given that early treatment of sepsis is associated with vastly improved outcomes, rapid diagnosis is essential. However blood culture work is slow and often takes 1-3 days. The diagnosis of sepsis in critically ill patients, housed in hospitals is also challenging because it can be complicated by the presence of inflammation resulting from other underlying diseases and from prior use of antibiotics, making cultures negative. Most testing is done through mass spectrometry that gives mass to charge ratio of ions. Since culture-dependent diagnosis of infection is slow, sometimes patients are given antibiotics, before the results of the culture are available. Patients are given broad spectrum antibiotics and 40% are not effective. In such instances, antibiotics are withdrawn after one cycle of treatment, when the cause of the illness is found to be something else and this can lead to antibiotic resistance.

Bioaffinity Sciences solution will be able to identify pathogens within 10 minutes, 430 fold faster than blood culture. This is cell affinity based, low cost technology. Pathogens are run through microchannels comprising of a surface- grafted scaffold of reactive polymer onto which affinity molecules (sugars, aptamers, vancomycin, and methicillin) have been bio-conjugated. High capacity of the channels allows low numbers of microbes to be quickly identified. The unknown pathogen’s pattern of binding to the channels is recorded, and this pattern is compared to a library of known pathogens. When a match is made, the identity of the pathogen is reported. In addition to speed, this is also more sensitive in terms of the number of different pathogens detected than blood culture.

Disease burden to the healthcare system in the US due to Sepsis

Sepsis management is a major challenge and results in disproportionately high burden in terms of hospital utilization. The average length of stay for sepsis patients in the US is approximately 75% greater than for other conditions. The cost of sepsis management ranks highest among hospital admissions for all disease states. The cost is estimated to be between $25 billion and $27 billion, and represents 13% of total US hospital costs.

Considering that poor sepsis outcomes are directly tied to the delay in diagnosis and treatment, such a dramatic improvement in speed and accuracy of diagnosis leading to speedy and accurate treatment can not only dramatically improve outcome and quality of patient care but also significantly reduce cost of care for hospitals.

The talk was followed by Q&A.

 

Hope for Devastating Small Bowel Syndrome Disease

Andre Bessette, CEO & Co-founder at Eclipse Regenesis talked about Short Bowel Syndrome at an event by Bio2DeviceGroup (www.bio2devicegroup.org) held at Wilson Sonsini (WSGR) in Palo Alto. Bessette shared information on prevalence of the disease, it’s impact, and the new technology that offers hope for restoration. 

Feel free to skip the short tutorial below and jump to SBS and the technology solutions for treatment of SBS

Movement of the food

Typically digestion begins in the mouth where chewing and saliva begin to break down the food. As it passes through the esophagus, the contractions in the esophagus moves the food forward towards the stomach. In the stomach, the food breaks down further into liquid or paste and is mixed with acids and enzymes. The stomach slowly empties the contents, called chyme, into the small intestine. 

Small Intestine
It is the tube shaped organ and is located between the stomach and large intestine. The small intestine is regarded as the workhorse of the digestive system. It is 20 FEET LONG and includes the duodenum, jejunum, and ileum. 

Duodenum is the first part of the small intestine where typically iron and other minerals are absorbed.
Jejunum is the middle section where cabs, proteins, fat and most vitamins are absorbed.
Ileum is the lower end of the small intestine where bile acids and vitamin B12 are absorbed.

From small intestine the food travels to the large intestine which is about 5 feet long in adults and helps in absorption of water and other remaining nutrients. It then changes waste from liquid to a solid matter called stool. 

Short Bowel Syndrome (SBS)

Short Bowel Syndrome or SBS is a devastating condition where the small intestine is simply too short. The inadequate length of the small intestine leads to a whole host of problems primarily related to malabsorption of nutrients and depending on the degree of shortness, sometimes it drastically shortens lifespan. Typically SBS is diagnosed when people have at least half of their small intestine removed and sometimes all or part of their large intestine removed due to disease or injury and significant damage of the small intestine. Sometimes it is a congenital abnormality, where a baby is born with very short small intestine. Depending on the length, SBS may be mild, moderate or severe. 

Malabsorption

People with SBS cannot absorb enough water, vitamins, minerals, protein, fat, calories and other nutrients from food. Difficulty in absorbing nutrients depends upon the area of small intestine that is removed or non-existent. This inability to absorb nutrients and water causes severe and frequent diarrhea, weight loss and other symptoms related to loss of essential vitamins and minerals. 

Disease prevalence 

There are about 8 thousand new cases of SBS in the US, each year. About 65% of them are due to congenital or acquired defect. Typically pediatric patients die before they reach 3 years of age. Their short life is marked with TPN (Total Parenteral Nutrition) treatment where by nutrients are given directly into the bloodstream bypassing the gastrointestinal tract. Gattex (teduglutide) is a prescription medicine given through intravenous (IV) feeding or subcutaneous injection. Not only is it a costly treatment, averaging around 200-300K annually without much improvement but a baby would need to continuously be wearing or accompanying a backpack. Surgical treatment costs 150K to 400K and transplants cost over a million dollars and require life long care, possibility of rejection and infections and has about 5 year mortality for 50% of patients. NONE OF THE CURRENT TREATMENT OPTIONS RESTORE FULL BOWEL FUNCTION.

Eclipse Regenesis Solution

The Eclipse XL1 therapy is a restorative solution designed to grow a longer, healthy intestine rapidly in the course of 2-3 weeks. The solution is entirely mechanical and repeatable, without any harmful or toxic effects. Eclipse has devised a nitinol coil that is introduced into the small intestine via a stoma. Plication sutures are then applied outside the intestine to hold it in place. During the course of the therapy of 2-3 weeks, while the device is in place, nutrients continue to flow through the intestine. Over 2-3 weeks period, the coil gradually expands. As it expands, it gently pulls the small intestine, stimulating new tissue growth and lengthening the treated region 2 to 3 times. The solution is striking in its simplicity and beautiful uncomplicated. After expansion, the sutures dissolve, allowing the coil to move forward and finally get passed out naturally.

Besssette shared information on the team of co-founders with impressive credentials and answered various questions from the audience. Yes, the contractile function continues in the newly lengthened intestine, no the length sustains and does not snap back and the process is repeatable to produce clinical significant length of the intestine and all of these is indicated by the animal trials. 

Small Bowel Syndrome is an orphan disease and as such the Eclipse XL1 has received a HUD designation (which requires incidence rate of less than 8000 new cases a year, in the US). Eclipse is anticipating using the HDE regulatory pathway which requires safety and probable benefit data. Eclipse plans to commercialize in pediatric market, in the near future.  

 

Medical Device Innovation & Pressure Ulcer Monitoring Technology

Dr. Barrett Larson, physician at Stanford University School of Medicine, Co-founder of Leaf Healthcare, and director of the Stanford Anesthesia Innovation Lab (SAIL), talked about the medical device innovation process and shared stories about his experience developing new medical technology at http://www.bio2devicegroup.org event.

A recipient of numerous medical technology and innovation awards, Dr. Larson emphasized that the innovation process begins with clinical observations and problem identification.  The next step is to define the clinical need, which should initially be defined in broad terms in order to maximize the number of potential solutions that can be conceived.

His company, Leaf Healthcare, is expanding the applications for wireless patient monitoring by introducing inexpensive, disposable, and easy to use wireless sensors.  One of the first application areas for the technology has been to address hospital-acquired pressure ulcers (HAPUs). Pressure ulcers, commonly referred to as bedsores, are injuries to the skin that result from prolonged surface pressure. Pressure ulcers put an enormous strain on the healthcare system and upwards of $9B is spent annually treating pressure ulcers in the US.   Since pressure ulcers are considered “never events”, they are not reimbursable and are a source of fines, penalties, and litigation exposure. The Leaf system has been shown to dramatically improve compliance with patient turning schedules, improve nursing efficiency, and reduce the incidence of pressure ulcers.

Dr. Larson also talked about a new device he developed that enables non-optical, magnetically-guided endotracheal intubation. The technology has won first place at the regional level (Western Anesthesia Residents’ Conference) and the national level (Society for Technology in Anesthesia). Dr. Larson also talked about other award-winning projects that he is working on in the context of the Stanford Anesthesia Innovation Lab (SAIL).

The talk was followed by Q&A.

High Performance Computing Solution to Overcome Current Limitations in Mass Spectrometry

Jeff Peterson, Chairman at Veritomyx and CEO of parent company, Target Discovery, talked about how Veritomyx is focusing on convergence of high performance computing and state-of-the-art signal processing algorithms, to deal with the challenges encountered in identifying protein/isoform and metabolite biomarkers, due to limitations in mass spectrometry and supporting software.  The talk was in Sunnyvale, at event hosted by www.bio2devicegroup.org .

Modifications of proteins are responsible for exerting about 90% of the control of biochemical pathway changes. Accurate detection and validation of these changes offers hope for much stronger diagnostic insights into disease status and valuable treatment guidance decisions, enabling new effectiveness to advance the field of personalized medicine.  In turn, this is expected to help determine specific potential responses of therapeutic compounds in individual patients, allowing for more customized and successful treatment regimens.  Selection of properly validated therapies would save huge amounts of resources, money, and most importantly improve patient outcomes.

In the US, healthcare expenditure currently averages around $3T per year, said Peterson.  About 85% of that is spent on doctors, hospitals, ER, and end of life management.  Drugs make up only 12-15% of the total expenditure and diagnostics represent 2-3%.  The dawn of personalized medicine diagnostics now allows the right diagnostic to better select for the right therapeutic, and to minimize the patient’s descent into the chasm of other healthcare expenditures.  This paradigm shift is upending the value proposition in favor of newly recognized value in personalized medicine diagnostics leveraging overall healthcare expenditure decreases with improved outcomes.

A Shimadzu Ion Trap-Time of Flight mass spectrometer (center), HPLC-UV (left). (Photo credit: Wikipedia)

The search to find, identify and characterize new biomarkers across life science R&D efforts typically employs mass spectrometry.  In MS, ions from the unknown are accelerated and detected electro-magnetically, and software attempts to assemble puzzles of component ions into information identifying the unknown parent.  The output is typically analyzed in the form of a diagram, with X axis reflecting the masses of the individual ions, and the Y axis showing the  “relative abundance” of the ions detected.

 

However, current limitations in mass spectrometry, signal processing and identification algorithms often limit the availability of useful information.  Frequently, critical information remains hidden among overlapping peaks.  Overlapping peaks cause misdirection in mass and abundance results, delivering lower mass and abundance precision, and making it vastly harder or completely failing to correctly identify biomarker compositions.

English: Isotopic pattern of an peptide. Mass spectrum recorded by Q-TOF mass spectrometer. Polski: Obwiednia izotopowa peptydu zmierzona przy pomocy spektrometru Mas Q-TOF (Photo credit: Wikipedia)

The “PeakInvestigator™” software from Veritomyx, helps enhance the quality of science, saving critical time and R&D resources.  PeakInvestigator typically triples the effective resolution and reveals and precisely deconvolves overlapping peaks that go unnoticed by current mass analyzers and software.

Precision problems in the data not only waste a great deal of time, but they can misdirect attention and decrease the effectiveness of R&D efforts.  Abundance and mass errors produce spurious biomarker candidates and incorrect isotopic ratios for peak identification, said Peterson.  The PeakInvestigator software delivers up to 10X improvements in mass and abundance precision across a wide dynamic range when deconvolving previously hidden overlapping peaks.

The PeakInvestigator is based on statistically robust and reproducible methodologies, said Peterson and it enhances identification of unknown proteins, peptides, and metabolites to improve the ability to correctly detect and validate biomarkers.  Further, it’s advanced signal processing algorithms automatically adjust for differences in instruments and tuning variations.  These algorithms provide adaptive baselining and signal-to-noise thresholding.  This easy to use software solution eliminates the need for manual estimation of centroiding parameters or visual inspection of data before processing.  When summing up the advantages, Peterson also added that PeakInvestigator is being designed to be 21CFR11 and HIPAA compliant.

For companies interested in PeakInvestigator software-as-a-service solution, it can be easily integrated into the existing workflow.  Their simple public application-programming interface (API) inserts directly into company’s existing mass spectrometry workflow.  While already validated workflow remains intact, the PeakInvestigator algorithms can be leveraged on the existing data.  Currently Veritomyx has launched Free Beta Services collaborations for its PeakInvestigator deconvolution and centroiding software.  Free Beta Services will allow collaborators to apply certain PeakInvestigator high performance computing capabilities to their own mass spectral raw datasets at no charge.   Please contact www.veritomyx.com for further information.

 

2014 – Year-end Review ——- Theme: Confront Reality & Get Things Done!

English: Biosafety level 4 hazmat suit: researcher is working with the Ebola virus (Photo credit: Wikipedia)

Year 2014 is coming to a close.  As I see it, it has been a year to confront the reality and get things done.  Affordable Care Act became law in January, increasing the accessibility of healthcare, in the US.  TIME declared Ebola as the defining issue of the 20th century. It was no more in remote regions of Africa but in the capitals and it landed in the USA.  The reality is that we are living in a global world.  

And then President Obama reminded us that even though some of our neighbors entered the border illegally, they have made their home here, are working hard, supporting their families and they should have NOT amnesty, but an opportunity to make it right with the law, and live here temporarily, AND pay their share of the taxes, because people can’t live in the shadows, in a global world of visibility and accountability.   Long overdue immigration reform will enable many people to come out of the shadows and add to the national treasury – a win-win – what’s not to like?

The same applies to our gay neighbors.  They should not have to live in the shadows.  Majority of the states this year, legalized same sex marriages and US supreme court refused to hear appeals from states seeking to keep same sex marriage ban in place.  Many states also legalized marijuana.  But what about our veterans living in the shadows?  Department of Veterans Affairs got more resources (as house passed the bill, at the end of the year, averting shutdown), and it now has to get its act together and make it right with those who defend our freedom and values.

And what about skin color?  We are confronting the reality that more than 50 years after Dr. King laid out his vision for color-fair society, people are still being judged on the basis of the color of their skin and paying with their lives.  This does not just happen when young men turn 22 but prejudice hits in childhood  http://bit.ly/15EInJ4 and it splinters society.  We can heal and move ahead, but scars made by history, and distrust can only heal when there are no new wounds, when there is real dialog, when each side gets to even briefly experience the reality that the other lives with, and have compassion.  We are confronting the reality and lot of dialog is happening.  Much work remains to be done but the issue can’t be ignored any longer.

And then the lowest of the low, terrorists and those plotting terror.  How do we deal with them?  Report on CIA’s use of “enhanced interrogation techniques” in the post-9/11 era reveals that “CIA detainees were tortured”.  When we lose sight of our values, when the boundaries between moral and immoral gets blurry, then we lose, regardless of what we were seeking to gain.  This is a true moment for national soul searching. (the fact some people may be only suspected of being terrorists is whole other story).

Globally, also we are confronting realities.  World’s largest democracy, India, elected controversial Mr. Narendra Modi as Prime Minister.  Mr. Modi has reached out to leaders across the world and declared campaigns to clean up India.  My birthplace has so much to offer to the world and if it cleans up its act, under the helm of Mr. Modi, I couldn’t be happier.  Our neighbors need to clean up their act too, even as they rightfully blame the US for its insatiable appetite for drugs.  Capture of “El Chapo” Guzman in Mexico was a HUGE victory that got overshadowed later by disappearance and ruthless murder of 43 Mexican college students.  “#YaMeCanse12”!  Abduction of 270 high school girls by Boko Haram in Nigeria #BringBackOurGirls and scores of Yazidi women bought, sold, raped, and murdered, underscores the need to define rape during conflict as a war crime and not a woman’s issue.  By some estimates, more than 7 million (50% are children) are displaced by war in Syria (200,000 are killed) and 100,000+ Yazidis are displaced by ISIS.  Let us continue to keep theses issues in the spotlight.

The year is ending on a rather sad note of the children who lost their lives in #PeshawarSchoolAttack in Pakistan.  Here is my short poem in their memory – http://bit.ly/1wfp47D .  It was heart warming to see India support its neighbor in the hour of grief as #IndiawithPakistan was a popular hashtag on twitter. And also deeply heartwarming to see Pakistan echo the sentiments when #PakistanwithIndia and sepecially #PakistanwithIndiaNoToLakhviBail became trendy topics on twitter as overwhelmingly Pakistani people reacted negatively to their government’s decision to give bail to Mumbai terror mastermind Lakhvi.  May the balanced sentiments always prevail over extremism, because the reality is that we live in a global world and terror can’t be nurtured and targeted because sooner or later it would hit home.  Global world also demands secularism.

As a ray of light and hope, Malala Yousafzai, courageous young lady from Pakistan, spearheading girls’ right to education and Kailash Satyarthi from india, a brave and dedicated activist for children’s rights and against child labor, shared the Nobel Prize, sending strong messages that fight to honor children’s rights will continue.

Personal

Hard as it is to confront the reality that one’s parents may not be there forever, I was very happy to spend wonderful time with my mother and my aunty (her sister).  I tried to focus on giving them a break from their routines and enable them to have some fun, some unusual experiences.  Isn’t it amazing that when a mother gives, she gives with her heart and soul, but when she receives from her children, she receives with a feeling of enormous debt and gratitude!  Both my children are focused on their careers; Neil is working with Cisco in IT and Neesha is finishing college this coming year.  Both are my pride and joy :).  It has also been fun hosting my daughter’s friend from UCSD, originally from Palestine, during the holidays, and alternately being “naughty” with the girls, and playing aunty-mom to two daughters :).

This year, I also visited Japan (we were hosted by many amazing friends and you can see all details in my travel blogs), an amazingly polite and most efficient culture, with world’s most interesting toilets http://bit.ly/1sYL5qs.  This year I also started travel blogs and you can see my many blogs at www.darshanavnadkarni.wordpress.com.

And finally, here are links to some of the most amazing things that I blogged about, this year.
Best movie – “Last Days in Vietnam” http://bit.ly/1qFIL28
Best play – “Truce” http://bit.ly/1trGhEG and “Andhera Hone Tak” http://bit.ly/1Aij5Rz
Best book – “The Glass Castle” http://bit.ly/1fchcIo
Best biomedical technologies — so many exciting technologies in early to mid stages of development for — treatment of ALS http://bit.ly/1AP2Yd0, for technology for early detection of cervical cancer http://bit.ly/1jalqEz, technology that aims to deliver drugs via inhalation for AFib, point of care solution to minimize prescription filling errors http://bit.ly/1jdfmgr

Wishing my readers, family & friends, and my clients and colleagues, peace and joy in the year 2015.  Best wishes to my many friends in fantastic groups that I am routinely affiliated with (each of them enhance life for many, personally and/or professionally) http://www.bio2devicegroup.org, http://www.eppicglobal.org, http://www.citylights.org, http://www.thestage.org, http://www.theatreworks.org, http://www.naatak.org, http://www.enacte.org, http://www.iwings.org .

Aligning value proposition: From Preclinical to Market for Medical Devices

Tim Pelura, CEO, Surpass Preclinical CRO talked on how medical device companies can align their strategy, from preclinical to market, with a focus on the value proposition, at www.bio2devicegroup.org event.

We are operating under a new reality now where power has shifted to the payers and the providers, said Pelura.  Medical device companies are evaluated based on safety and procedural efficacy as well as cost and value.  Increasingly heightened regulatory scrutiny and tightening FDA regulations have led to increase in audits (which were up 40% in the last year) and warning letters are (which were up 24% over the last 2 years).  Due to regulatory and reimbursement challenges, medical device companies are focusing their R&D efforts on improving already approved devices, rather than developing innovative new products.  Meanwhile startups are finding the landscape challenging due to funding challenges and increasing costs of bringing new products to market.

Healthcare Infostep (Photo credit: Wikipedia)

Inkeeping with the reality of pressures on payers that are transmitted down, new healthcare delivery models are emerging, and therefore, patient pathways are being modified to obtain to obtain better outcomes, with less cost.  Medical device companies will need to work with new business models, that solve significant problems and reduce overall costs.  Companies seeking growth will need to expand their offerings to target underserved populations and lower socioeconomic classes.

In essence, it is about the value proposition offered by the new product or service, “what benefit you provide for who and how you do it uniquely well”, said Pelura.  He advised, these “must-haves” in a business pitch, “describe your target buyer, the problem you are seeking to solve, and why you do it better than the alternative”.

Pelura walked the audience through the process of arriving at the value proposition.  First, companies must define the problem they are seeking to solve and identify correctly the need to solve the problem.  Next, they should try to go after obvious problems, rather than aspirational or “good to solve” problems.  And finally, they should try to address acute or critical problems.

In defining a solution, they should try to generate many ideas and then measure the viability of customer adoption of each idea using gain/pain ratio; what the customer stands to gain versus the cost of adoption of the new solution.  The best solutions are those that offer game-changing benefits, with minimal modifications to the existing process or environments, said Pelura.  Go for “Disruptive Innovations, that are Non-Disruptive to Adopt”, advised Pelura.   Medical device companies must visualize the entire process or patient pathway to ensure that the new solution would cause minimal disruptions, in the whole process.

While new technologies often emerge with a focus on engineering and progress to bench testing and then plan preclinical, and clinical strategies and only then consider navigating regulatory, market, and reimbursement challenges; in actuality, they should invert the process.  They should begin with considering reimbursement challenges, analyze the competitive landscape, study the market opportunity, give thoughtful consideration to the regulatory challenges, then consider clinical and preclinical strategy, before embarking on prototype and bench testing.  Because if the value proposition is wrong then a company can end up with a product that no one wants or needs, resulting in considerable waste of precious innovation dollars and time, said Pelura.

Speaking of Surpass, Pelura shared that preclinical Contract Research Organization, Surpass is doing things differently.  While having deep expertise as a preclinical CRO in helping medical device companies with their preclinical in vivo and human cadaveric studies, Surpass also seeks to impact the system, by probing and assisting their clients with questions that go to the value proposition.  Surpass assists the clients in designing the most translatable preclinical study by understanding issues of clinical end points, product’s desired features and characteristics, all the while keeping in mind who would be operating the device, studies and activities that might need to be completed to demonstrate the products, performance, safety, and efficacy, as well as data that would be required to drive reimbursement and more.  This novel process ensures that any preclinical testing performed is aligned to the new product’s value proposition, hence helping save valuable healthcare innovation dollars.  

The session was followed by Q&A.

 

Lean LaunchPad for Life Science Entrepreneurs

Recently, Karl Handelsman, Founder, Codon Capital, talked about the Lean LaunchPad Entrepreneurship program, at www.bio2devicegroup.org event.  Handelsman, with Allan May (Managing Director at Life Science Angels), are instructors in the Lean LaunchPad for Life Sciences program at UCSF and also will be teaching at NIH, in the future.  Handelsman is the Therapeutics cohort and May is the Medical Device cohort.

It is a mistake to assume that pre-clinical programs are risky and they need to focus on easier low hanging fruit or they must take 10+ years and a billion dollars to create value, said Handelsman.  We have a duty to search for the path to unlock the value of the idea as industrially relevant innovation, and there are examples of biotech startups reaching that point in 18-30 months, said Handelsman.  Lean LaunchPad program teaches scientists and clinicians in startups to do a real world assessment of their idea or technology, before plunking down millions of dollars, in an idea.  Entrepreneurs receive training in determining their product’s market viability, regulatory risk, potential clinical utility, and also likely financing vehicles before making big dollar investments in research, design, and manufacturing.

English: Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR001081). PDB rendering based on 1a8e. (Photo credit: Wikipedia)

Entrepreneurs need good operational models that build a context of value creation, said Handelsman.  Investors like value, not milestones.  “Investors want to invest money and they want to hear a business case, and operational milestones don’t get you there”,  stressed Handelsman.

Big things often have small beginnings and start with contributions from many small pockets.  Sharing the case of a company that started with collaboration and became the behemoth, Genentech,  Handelsman said, entrepreneurs need to start thinking about collaboration, not competition, and begin to look at models of collaboration that would create true value.  After all, strategic alliances built the Silicon Valley and there are many diverse and creative ways of creating partnerships.  Entrepreneurs need to talk with others and be really good listeners.

Successful entrepreneurs are not thoughtless risk takers, but approach problems in a disciplined way.  Value creation for therapeutics begins with thoughtful consideration of who would benefit from solving a certain problem; patients, payers, insurances companies or any other entity?  Once entrepreneurs can figure that out, they can go to a VC and explain the business case.  Value creation, after all, is not what entrepreneurs think or believe, but an idea or concept that gets external validation from the customer.  “Do not constantly worry about keeping the concept in the stealth mode, and talk to a lot of people”, advised Handelsman.  VCs do not count, they are not potential customers.  In the end, one could have a sexy product, but if it does not solve a pressing problem then it is not creating value.  Real answers to key commercialization questions, in the case of therapeutics, lie outside the lab, and entrepreneurs need to actively engage and talk with customers, partners, regulators and so on to figure out the value of their product.  Lean LaunchPad methodology therefore, helps to validate the product, before commercial strategy is considered, saving time, money, resources and in some cases, helping guide the change in the trajectory, for more meaningful outcome.

 

Diabetes & Cardiovascular Disease Risk Factors among South Asians Compared to other Ethnic Groups

Dr. Alka Kanaya talked about Diabetes and cardiovascular disease risk factors in multi-ethnic groups comparison studies, at a joint event hosted by  www.eppicglobal.org and  www.bio2devicegroup.org .  Dr. Kanaya is Professor of Medicine, Epidemiology, and Biostatistics at UCSF and a principal investigator in Mediators of Atherosclerosis in South Asians Living in America or MASALA study, for short.  Primary objective of the study was to research and understand the high incidence of diabetes and CHD among people of South Asian origin.

Kanaya first shared information on South Asians (will be referred here as SA) and then discussed the study results in the context of multi ethnic comparison.  Currently there are 3.4 M people from South Asia living in the US.  It is the second fastest growing racial/ ethnic minority in the US.  They constitute 20% of all Asians and 75% of them are foreign born.  Although there is little organized medical data on SAs, overall they have relatively lower body weight (BMI), have more central abdominal obesity, and experience higher rates of diabetes and indicate high risk of early heart disease.

MASALA study began in March, 2010 and constitutes a total sample of 906 people, between the ages of 40 and 84.  People with prior history of any cardiovascular disease, those in active cancer treatments, those planning to move out of the area in the next 5 years, and nursing home residents, were excluded.  Data collected included weight, height, waist, seated BP, Ankle-brachial index (ABI predicts the sevearity of PAD, peripheral artery disease), 2 hour OGTT (oral glucose tolerance test), abdominal CT, and several blood tests and extremely detailed questionnaires regarding family history and information about personal habits like alcohol, smoking, sleep, diet and exercise.

Results from MASALA study were compared to results on almost all similar measures with Whites, Latinos, African-Americans and Chinese populations in ongoing MESA study.  See the websites of MESA (www.mesa.nhlbi.org) and MASALA (www.masalastudy.org) studies to see many interesting details on several patterns that emerged.  Kanaya specifically discussed some patterns among South Asians when compared with other ethnic groups.

When adjusted by sex and age, South Asians had significantly high rates of hypertension.  However, there weren’t major or alarming differences in cholesterol.  One of the reasons could be that South Asians were overall more educated, from higher socio-economic background, and were more likely to be using statins and other cholesterol lowering drugs

Most alarming differences were observed in diabetes and pre-diabetes levels.  Almost 30% of men and almost 15% of South Asian women had Diabetes Mellitus, versus 20% or lower among other groups of men, and 13% or lower among other groups of women.  Nearly 37% of SA men and 29% of SA women had IFG (impaired fasting glucose indicative of pre-diabetes), compared to 20% or less for men and 13% or less for women from other groups.  When adjusted for many indicators including age, sex, cholesterol, triglycerides, hypertension etc., South Asians were significantly more likely to have type 2 diabetes.

When adjusted for age, sex, BMI, and waist and excluding those on diabetes meds, this high incidence of Diabetes Mellitus among South Asians seemed to be associated with higher levels of insulin resistance, lower pancreatic B-cell function, and (as confirmed by abdominal CT data) high amount of body fat around abdominal regions and in the liver.

Mercat de la Boqueria, fruits & vegetables (Photo credit: Wikipedia)

Among lifestyle factors, the high rates of DM (Diabetes Mellitus) among SA was attributed to poor diet with less fruits and vegetables and more Western diet (including pizza, pasta etc.), sweets, refined grains, and consumption of high animal based protein in the diet and low levels of exercise.  Considering that even on a relatively leaner body, South Asians carry more fat, the study concluded that guidelines for BMI should be lower for people of South Asian origin.

The study concluded that 75% of South Asians were overweight or obese using the recommended BMI cut-points in Asians.  Compared to other racial/ ethnic groups, South Asians were from higher socio economic status, had low smoking rates, and low to moderate alcohol use.  They also indicated very low physical activity, higher diabetes prevalence (specially among men), second highest prevalence of high blood pressure, and men have more coronary calcium than other groups.

A yoga class. (Photo credit: Wikipedia)

Some of the recommendations for South Asians from the study were, to know the risk factors, work towards ideal BMI goal (less than 23 kg/m2 for SA), remember waist size matters more than BMI, walk at least 30 minutes a day 5 days a week, avoid a diet high in animal protein and refined carbs, and then something interesting – do Yoga!

Kanaya also shared results from her PRYSMS study that assigned subjects with metabolic syndrome into two groups, one practicing Restorative Yoga (included lot of lying down and relaxing poses) and other, Stretching Exercises.  In 6 months, both groups improved their PA and calorie intake.  Favorable changes in the stretching group included, lowered triglycerides and improved mental health.  Restorative yoga group reduced and sustained weight loss and weight girth loss but not visceral fat area.  Finally, only yoga group indicated reduction of fasting glucose and overall favorable metabolic changes in the yoga group included lowering of fasting insulin, glucose, HbA1c and HDL.

One wonders if very determined focus on material wealth goes with more stress.  In any case, it shows once again that stress relief is a key for improved health.  This was a fascinating talk and was followed by Q&A and animated discussion.

Treating ALS – The Story of Neuraltus

Rich Casey, President and CEO of Neuraltus (formerly Chairman and CEO of Scios), talked about treatment option for ALS (Amyotrophic Lateral Sclerosis), also known as Lou Gehrig’s Disease, a fatal neurodegenerative disorder of unknown etiology, at www.bio2devicegroup.org event.

Typically, the age of onset of ALS is anywhere between 40 and 70 years.  Life expectancy after the diagnosis is between 2 and 5 years, although in very rare cases (e.g. in case of Stephen Hawking), it could be an extremely slow progression.  No effective treatments for the disease exist.  Motor neurons degenerate and early symptoms include muscle weakness, specifically involving arms and legs, lack of hand grip, deep tiredness and it progresses to difficulty in swallowing, breathing, and garbled speech.

Macrophage (Photo credit: Wikipedia)

Neuraltus’s lead product,  NP001 is in clinical development, targeted for the treatment of ALS.  While the exact cause of the disease is unknown, there is fair amount of evidence that points to increasing levels of inflammation in the macrophages.  This increased inflammatory activity results in the release of factors in the central nervous system that leads to damage of motor neurons.  Macrophages are cells produced by differentiation of monocytes in the tissues.  Macrophages are highly specialized in removal of dead cells or debris.  Additionally, macrophages also “present” antigen that plays a crucial role in initiating an immune response.  There is an increasing evidence implicating neuroinflammation with the progression of ALS.

English: Amyotrophic lateral sclerosis MRI (axial FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule, consistent with the clinical diagnosis of ALS source:Radiopedia.org (Photo credit: Wikipedia)

Neuraltus’s novel, proprietary drug, NP001 regulates macrophage activation and converts the activated inflammatory macrophages from activated, neurotoxic inflammatory state to a neuroprotective state.  It thus normalizes the critical cellular environment.   Phase I, single dose study indicated that that there are no safety concerns and the drug is well tolerated.  Further, in a Phase II safety, tolerability and preliminary efficacy study, after administration of NP001, there occurred a close dependent reduction of inflammatory macrophages.

The dosing regimen is somewhat cumbersome, said Casey.  First time, the patients come in the hospital and need to stay for 5 days and subsequently for 3 days.  At low dose, phase II study results indicated positive trends in the ability of NP001 to slow the rate of disease progression but did not reach statistical significance.  But at high dose, the drug freezes the disease in a 3rd of the patients.  Additionally, the drug is found to be safe and well tolerated.  This clearly looks like a very exciting potential treatment for a devastating disorder, ALS.  The company is currently looking for funding.  The talk was followed by Q&A.