Maria Bartiromo, host and managing editor of one of the most watched financial news programs in America, “Wall Street Journal Report with Maria Bartiromo,” moderated a panel of corporate and venture leaders that addressed the difficulties in dealing with Corporate Venture Capital (CVC) that has been changing with the economic downturn of the financial industries since 2007. This was an in depth look into how the business of healthcare innovation is working now. Present for this discussion are industry movers like Mr. Darren Carroll, VP of New ventures Division of Eli Lilly, Mr. Roy Davis, President of Johnson and Johnson Development Corporation, Mr. Ven Manda, VP of Medtronic Ventures and New therapies, Mr. Harry Rein General Partner of Foundation Medical Partners and Mr. Mark Vachon, President and Chief Executive, Office of America, GE healthcare.
Corporate Venture Capital (CVC) is a form of investment by a corporate entity for assisting the start-up of a company with a promising product which has a potential for profit in the long run. I was familiar with the idea of venture capitalism but the logistics and details I learned from this conference were informative but however somewhat daunting, I must say!
The largest player in healthcare related CVC are made by the venture arms of firms who focus on biotechnology and pharmaceutical products. Eli Lilly for example spun out Lilly Ventures with a $200 million investment. They are focusing on human therapeutics in oncology. They are working with investors from Asia and with new partnerships with venture capital, to help small pharmaceutical companies in Shanghai grow. Building funds that have more capital and help making sure that the manufactured products are what are in demand. Actual profit gathering can take 8-10 years, with 3 ½ years just for the return of the investment amount. New innovations and technologies are always in demand, and so are the means for development and production of those new ideas and technologies. Venture capitalism can be a good way to create advancements in technology and foster innovation.
Dr. Joseph Hahn gave us a few thoughts to wrap up this year’s Medical Innovations Summit.
Dr. Hahn expressed a sincere thank you to all the people who made this successful. Dr. Hahn recognized all the effort and work that Chris Coburn, our Executive Director of the Cleveland Clinic Innovations program, for all of his work, enthusiasm, and commitment to our program. He also recognized Dr. Derek Raghavan, our Director of the Taussig Cancer Institute, for all of his contribution and dedication that were critical to the success of this Summit.
He discussed that, during the past few days, several themes came through and he wanted to comment on a few. The first theme that he highlighted was the emphasis placed on gene mapping and personalized genomic care. We all recognize the importance and potential. However, where is this heading? He believes it is still not ready for primetime yet. The overall consensus seems to be that we do not quite know how this is going to be useful and in what setting - whether for screening, treatment, or for prevention.
The second theme is wellness. He discussed a question that also came up throughout our sessions - who’s responsibility is it? Is it the responsibility of the government? Is it necessary to protect ourselves from ourselves? Or is it a personal responsibility? And how do we measure it? How do we reward it? How do we provide incentive for it?
The final theme is technology. There is a lot of interesting technology. There are a lot of things that could make it work. He reiterated Sam Palmisano’s sentiment – “The system isn’t broken. That would imply that we have one.” Using technology, is there a way to bring it all together? Could the electronic medical record be for our industry what the barcode is for retail industry?
Dr. Hahn challenged us to look ahead. He discussed that 45% of illnesses are related to behavior – obesity, drinking, and smoking. Obesity costs in this country exceed all the costs related to cancer therapy combined. Next year’s focus will be on Obesity, Diabetes, and Metabolic Diseases. We look forward to having you join us for the next Medical Innovations Summit in 2010!
David Ewing Duncan, best-selling author and science journalist, interviews Dr. Margaret "Peggy" Hamburg, Commissioner of the US Food and Drug Administration...
How do you grade FDA? The FDA is incredible institution. It is an agency with a long, venerable history. It is the gold standard for consumer safety. It is responsible for the oversight and safety protection of over 2 trillion dollars of goods. Affecting lives of Americans every single day in so many fundamental ways. Overall, I believe it does an excellent job.
You have a public health background, I thought you would go to the CDC. How does having this background bring a different flavor to FDA? I hope to return the FDA to it’s core mission of public health. It is a science-based regulatory institution with a primary focus on public health. I come with a strong background in public health, but initially began my career in medicine as lab researcher and clinical researcher in neuroscience. This also shapes my background and thinking.
What are your priorities for the FDA? It is viewed by many as a beleaguered agency, under-funded, under-resourced, pillaried on the hill, attacked by critics, cirticized by the media. It wasn’t an easy decision to take the job. Setting priorities is essential to setting the tone and goals. We need to restore trust and confidence in FDA as a science-based industry for public health. We need to open ourselves up. Explain how we do things. Provide insight into our standards and decision-making. I plan on being a vocal advocate for our agency. Advocating for the resources we need. It is stunning the under-funding given the importance of what we do and the uniqueness of what we do. We fulfill critical activities for the health of the public. I have to be an advocate to ensure that we have the resources to do this.
How can FDA be supportive and gateway of innovation? By being able to really affect health and well-being of public by leveraging all that it is going on in science. By ensuring that we do our review process in a more regulatory, efficient, and helpful way. It is a new paradigm is that we are all in this together.
We also have to strengthen the field of regulatory science…essential to improve nation’s health and healthcare system and economy. We need to develop and embrace this together.
How to restore trust? We live in a world with risks. There will always be problems. Always will be a crisis for us to respond to. There is a great deal more we can do to prevent these things from happening and how we can respond to things that do occur. Transparency does make a big difference. Have to demonstrate that we want to contribute to regulatory system that is of the highest standards.
How about the power to regulate tobacco? Tobacco has so many negative effects on our health. We have banned flavored cigarettes. Tobacco is now designated as regulated substance. We are planning on regulating marketing. We are examining the composition of cigarettes and tobacco products. Tobacco is the number 1 risk modification that we can target.
This session was moderated by Debra Lappin, the President of the American Council of Innovation. Here are a few highlights...
The speakers included: Edward Buckley (EB) - Director of Economic Policy, Biotechnology Industry Organization David Nexon (DN) - Senior Executive Vice President, AdvaMed Dr. Beth Seidenberg (BS) - Partner, Kleiner Perkins Caufield & Byers Richard Smith (RS) - Senior Vice President, PhRMA
DL - Innovation is not at the forefront of politics right now. Medical innovation is quite popular in Washington, DC. President Obama discusses a war in cancer and that we will find the cure in our time. He says that we will devote 3% of the gross domestic product to research and development and a new innovation economy, and yet, in Washington, DC, we are looking at the largest positive impact on innovation through healthcare reform.
DN – A change is coming. It is just a question of whether a bill is going to pass before Thanksgiving or before Christmas, it is certain to pass. The real issue – is it going to achieve the goal that every American has a fundamental right to healthcare and how will it affect quality/efficiency of care? How will this affect medical innovation?
RS – We will see a passage of a bill. Probably at this stage, we are at the end of the beginning. There is still a great deal that may move around as bills are put around and votes are gathered and financial requirements are met and people react to specifics of receiving proposal. A great deal still may change, but a passage of bill will occur.
TB – It certainly will increase access for today’s patients to today’s innovations. The bigger question is what will it do for future patients. The answer is in a state of flux.
How will healthcare reform affect medical innovation? DN – The key goals of health reform are to improve quality and efficiency. This is an important upside for medical innovation and progress. The goal is to improve quality by better organization, care, management of disease, universal practice, and reward for innovative products. There are potential negative concerns – freezing innovation in place, raising the bar for market approval that stifle products before they get to market. To improve efficiency, we need to reward those who develop new and better ways to treat disease or whether we are going to degenerate.
TB – How do we value innovation? Do we look at one step or look at societal benefit and how treatment affects caregivers and others? Healthcare reform can be an incredible tool to drive forward scientific knowledge. If undervalued, however, it could be major detriment.
Where does comparative effectiveness fall in healthcare reform? RS – I am optimistic about where this will end up. Strong consensus that we don’t want to end up with a structure that ends up like UK Nice or any analogues in other countries. No proposals currently that would do that. There are other proposals on the table that are different. We need continued access to innovative products for patients, on an individualized basis. There is a proposal in the Senate, the Baucus bill, that does this. There are distinguishing characteristics – public private entity, public private partnership. This proposal is oriented towards clinical effectiveness. The Baucus bill recognizes that research needs to move in a direction with personalized medicine. This is generating a lot of excitement. House proposal would house the enterprise in Government and this doesn’t have the same orientation towards recognizing differences in patient subgroups and patient populations. Baucus bill is hopefully a template for what is enacted.
How do you see incentives that are being discussed aligning with health care reform? DN – We need to look consciously at how this affects innovation. We need to get politically involved and strengthen our voice at the table.
BS – To the Venture Capital community, everything is ambiguous. We have to make decisions with millions of dollars upfront and hope that things will turn out 5-10 years later. Most will probably not bet on innovation. Most will wait until there is clarity. It is very frightening that there is lack of specificity and definition in these bills, so much debate is left open…venture capitalists may stall and innovation may be stalled. We need to increase our voice at the table.
RS – We are sitting here today at an Innovation Summit sponsored by the Cleveland Clinic. As DC politicians talk about what kind of systems they want, they frequently refer to CCF as a model system. As this effort to improve our health care system continues and we focus on bringing the kind of quality of care that patients receive here across the country, it will be impossible to do this without tapping into new medical technologies.
TB – Unfortunately, our society doesn’t realize that great innovation is built on incremental steps. It can take many years for progress to become apparent.
In regards to standardization or electronic medical record? BS – “Standardization is a core pillar of reform - but we are talking about standardization of IT, the system by which you record patient information and use at point of care. This will improve quality, care, However, we do not want to standardize innovation.”
This session was moderated by Dr. Ernest Borden, Director of the Center for Hematology and Oncology Molecular Therapeuties, Taussig Cancer Institute.
Speakers included: Dr. Richard Schilsky (RS) - Immediate Past President of the American Society of Clinical Oncology Dr. Nancy Simonian (NS) - Chief Medical Officer, Millennium: The Takeda Oncology Company Dr. Mark Trusheim (MT) - President, Co-Bio Consulting Dr. John Wiggington (JW) - Director, Discovery Oncology, Bristol Myers Squibb
RS - At this time, the focus of cancer care, as highlightings ASCO’s theme this year, is personalizing cancer care. It is about giving the right care to the right person and now is the right time. Why now? Because we now have a better understanding of tumor biology. Current technology enables assessment of germ-line and somatic variation. We have a new opportunity to match treatment to tumor, select optimal dose, optimize drug development, and reduce the cost of care.
It is important to recognize that each tumor has a unique profile (unique biology and unique disease response). The drug effects can be highly variable - depending on genetics, metabolic processes, drug interaction, and environmental factors. Dr. Schilsky also introduced the term “pharmacoethnicity”, ethnic diversity in pharmacodynamics. Environmental differences, local practice differences, drug interactions, and genetic differences also affect outcomes. This brings importance to the power of personalized care.
Personalized care pays off. Better care is enabled by more effective treatment, lower morbidity, and fewer complications. The reduced used of ineffective therapy and less time in the hospital results in lower cost.
Dr. Schilsky also discussed that more than 800 new drugs are in development for cancer. However, only 5-8% ever move to marketing. Why is there such a high failure rate? There are several reasons. There is inadequate understanding of tumor biology. We have only poorly predictive animal models. Patient populations are heterogeneous and biomarkers are inadequate to enable enrichment (many biomarkers show what will not work and doesn’t predict what WILL work). There is lack of agreement on the definition of what is clinically beneficial.
So how can we do this better? We need to obtain biospecimens from every patient. We need validate biomarker assays. We need a more flexible regulatory system. There must be reimbursement and regulatory incentives for diagnostics. Pharma need to be willing to trade off market shares for treatment decisions.
We need to screen more patients and focus on finding biomarkers that can help select the patients that are likely, or predict if they are unlikely to benefit from treatment. We need larger effects and smaller sample sizes that may lead to more rapids results and greater benefit.
He highlighted that there are many complicated steps that need to be undertaken to open or activate a study. There are barriers to patient accrual including physician time/interest, dedicated research staff, lack of reimbursement for physician management of patients on trials, insurance coverage for clinical trials. There are regulatory challenges as well, including human subject protection, integrity of study conduct and data, drug/device accountability, adverse event reporting, and billing for clinical services. In this era of personalized medicine, we also face the challenges of co-development of drugs and molecular diagnostics, and combination therapy.
There needs to be a policy proposed for “targeted approval”. We need to facilitate the accelerated development and approval for a cancer therapy used in a population defined by a specific diagnostic test. The drug must be indicated for cancer. The diagnostic assay must be analytically valid. The drug must demonstrated clinical benefit. Regulatory processes must be in place that would approve the drug for the intended use of the subpopulation defined.
Are there other things that panel members wish to highlight or emphasize or add? JW – There is terrific interest in targeted therapy and new developments in immunotherapy. There is new success in antibody therapy. Historically, real challenges in the failure of vaccine approaches and immune stimulants but now we are stepping forward. New findings demonstrate levels of clinical benefit that are refocusing enthusiasm in these fields.
NS – Personalized medicine is vitally important to how drug developer thinks about our decisions. Small incremental benefits are not going to have much value. We have to go for a selected patient population that will have the greatest benefit ratio. Combining novel therapies - we need to be more bold in our approach, let go of old standards, and be willing to use 2 new drugs together to see if there is greater benefit. Especially if old standards don’t make much biologic sense.
How about the FDA? It is often criticized and pillaried. RS – Yes. However, you need to understand that the review done by the FDA comes way at the end of the process. To be objective, it is fairly expedient compared to the rest of the drug development.
NS – The science piece and trial conduction takes much, much longer.
MT – Science and the desire for real evidence prior to approval of a drug leads to a lot of human functional genomics happening in phase III. The need to understanding biomarkers early, understanding patient’s disease biology early, are critically important. We need to set phase II and III selection criteria sooner, this will have tremendous market impact as well. Setting inclusion criteria will set up marketability of a drug later on. It will make the process more efficient. Good science always works.
The highlight of our Medical Innovation Summit occurred today with the unveiling of the “Top Ten Medical Innovations of 2010”. Dr. Michael Roizen moderated this session and several prominent physicians at the Cleveland Clinic participated in introducing these exciting new developments.
10. Whole-slide imaging for management of digital data in pathology – Dr. Kandice Kottke-Marchant, our Chair of the Pathology and Laboratory Medicine Institute, introduced this transformative technology. Whole-slide imaging allows for glass slides to be converted into digital slides. These images can then be sent immediately and shared with pathologists anywhere in the world.
9. Devices for occluding left atrial appendage to reduce stroke risk – Dr. Samir Kapadia, a physician in the Department of Cardiovascular Medicine, introduced these new devices which could eventually obviate the need for long-term anticoagulation therapy for atrial fibrillation.
8. Oral thrombopoietin (TPO) receptor agonist that stimulates platelet production – Dr. Alan Lichtin, a prominent physician in our Department of Hematologic Oncology and Blood Disorder, discussed the importance of this advancement. We have growth factor support for white blood cells (i.e. growth-colony stimulating factor) and red blood cells (i.e. erythropoietin), however platelets have been harder to stimulate. This promising new treatment is important for patients with chronic immune thrombocytopenic purpura (ITP) and may also have use in other areas where thrombocytopenia occurs. It may also decrease the need for platelet transfusion support, which is often in short supply.
7. Outpatient diagnosis of sleep-related breathing disorders – Dr. Charles Bae, from the Sleep Disorders Center, emphasized the importance of this innovation. Obstructive sleep apnea is a disorder that is highly under-diagnosed and highly under-treated. It can have significant long-standing effects and increases the risk of heart attack, stroke, and other disorders. Outpatient diagnosis could lead to better diagnosis and early treatment.
6. Forced exercise to improve motor function in patients with Parkinson’s Disease – Dr. Michael Modic, our Chief Emerging Business Officer introduced this innovation. Dr. Modic quoted Jean-Martin Charcot. “Disease is very old, nothing about it has changed, it is we who change as we learn to recognize what was once imperceptible. Dr. Modic described this as a classic discovery leading to innovation. Patients with Parkinson’s Disease who received “forced exercise” had 35% improvement in motor function.
5. Fertility preservation through oocyte cryopreservation – Dr. Nina Desai, a staff physician from our OB/GYN and Women’s Health Institute introduced this exciting innovation. Although sperm banking has been available for some time, oocyte preservation has been much more complicated. This has improved with a technique called vitrification, in which the cells are frozen at an extremely rapid rate. This allows for maintenance of the integrity of the oocyte. This is extremely exciting, allowing for women to be able to choose to have children at a later age and also allowing for those who have to undergo therapies (such as certain chemotherapy agents) that may cause infertility to be able to have children. This year, the Cleveland Clinic celebrated their first 2 births from cryopreserved oocytes.
4. Non-Vitamin K antagonists as oral anticoagulants – Dr. Roy Silverstein, our Chair of the Department of Cell Biology introduced this innovation. Anticoagulants are widely used, both for short-term purposes (peri-operative prophylaxis of venous thromboemoblism) and long-term use (i.e., treatment of venous thromboembolism). Warfarin has been used in this setting, however this medication can be difficult to monitor, difficult to dose, and can be unpredictable. These new oral anticoagulants are promising alternatives.
3. Continuous-flow ventricular assist devices - Dr. James Young, Chair of the Endocrinology and Metabolism Institute, discussed these impressive devices. “For patients whose hearts are unable to effectively pump blood due to severe heart problems, this remarkable device can help them improve their heart function as they await a heart transplant.” He believes that this is going to be the wave of the future in treating hearts that have been irreversibly damaged.
2. Low volume, low-pressure tracheal tube cuff to reduce ventilatory-associated pneumonia - Dr. Edward Noguera, a staff physician in the Department of General Anesthesiology presented our next innovation. These devices dramatically reduce the risk of VAP by providing continuous effective airway seals at low pressures. These devices can be left in place for up to 30 days.
1. Bone conduction of sound for single-sided deafness - Dr. Craig Newman, Section Head of our Department of Audiology, presented our #1 innovation of the year. Single-sided deafness affects 9 million people in the US. This device is non-surgical, removable hearing device that is designed to transmit sound via the teeth, through bones, to both cochleae.
Dr. Ernest Borden, Director of the Center for Hematology and Oncology Molecular Therapies, moderates this informative session.
Dr. James Doroshow, Director of the Division of Cancter Treatment and Diagnosis, National Cancer Institute, opens our session today. Dr. Doroshow discusses that the past 5 years have noted several exciting innovations. There have been proof-of-concept advancements in anti-angiogenesis, epigenetic therapy, the role of developmental biology. There have emerged proof-of-mechanism advancements in pharmacodynamics, gene expression-based therapeutic signatures. There have been advancements in combination targeted therapy and epigenetic therapy.
In the next 5 years, he anticipates advancements in non-invasive biomarkers of therapeutic effects, convergence of receptor- and metabolically-mediated growth signally. There will be discoveries into metabolic genomics, pathway and stem cell therapeutics, expansion of academic drug and biomarker discovery with new hard targets and new clinical trial design paradigms. Pre-clinical imaging technologies for drug development will be developed. New initiatives will be undertaken to decrease the timeline to personalize medicine in cancer treatment.
This led into a very interesting panel discussion.
Richard Gaynor, Vice President, Cancer Research and Global Oncology for Lilly… There is a move from not only developing new biomarkers, but also being able to develop standardization (such as transcript profiling, immunohistochemistry studies, search for genetic mutations). We need standardization to compare data. We need new trial designs with new trial endpoints (i.e., MRI, PET, circulating tumor cells). The next important areas will include targeted therapy, directed at tyrosine kinase inhibitors, mutated kinases, and metebolic targets will be important. We need to find new target classes.
Richard Scheller, Executive Vice President, Genentech Research and Early Development… An important thing to emphasize is what an exciting time this is in human biology. This century will go down as the century of human biology. It is now possible to really take a comprehensive approach to attacking cancer (through anti-angiogenesis, cell cycle targets, tyrosine kinase inhibitors, metabolic targets, cancer stem cells, etc). All of this is breaking way to an unbelievably exciting future. Trying to understand which therapy best and which combination best for each patient. Changing cancer to chronic disease and hopefully to cure. He is most excited about additional anti-angiogenic approaches. If we can understand the developmental biology around blood vessels, then new targets will be found. We can make good drugs to great drugs. Armed antibodies will becoming increasingly important. These proverbial magic bullets have been around for a long time, but this technology is really coming into it’s own now.
David Epstein, President and Chief Executive Officer of Novartis Oncology… We need to move further down drug development paradigm. We need to move away from era of small incremental improvement towards patient population selection to find big improvements. Understanding molecular basis of disease and crosstalk of pathway and hitting multiple targets in a selected patient population is what it is all about. We need to build molecular diagnostics capabilities. Focus on developing biomarkers as we are developing drugs. We need to identify the correct patient.
Dr. Borden asked Mr. Epstein – In this era of focused targeted molecular treatments, how does the executive board deal with and manage pushing forward a niche-related drug? Is the executive board willing to wait for proof-of-concept studies? Mr. Epstein described Gleevec as a classic example of success in this area. He said that if the drug works, the economics will work themselves out. Also, the executive board does not micromanage. They recognize that every drug is not going to pan out.
Dr. Borden asked Dr. Doroshow – What about quality control of targeted tests? Are initiatives underway in FDA or NCI? Dr. Doroshow responded that they are continually trying to establish central facilities and work with major medical centers to a level that would satisfy the FDA. To the highest level and the highest standard.
How can we deal with the problem of resistance? Dr. Scheller – We need better genetic mouse models, in order to cycle therapy and generate resistance and analyze molecularly and see that it’s the same that can occur in humans. Dr. Gaynor – We also need to see how to study resistance and predict for it before getting therapies out into the clinic. Mr. Epstein - We need to improve our ability to predict resistance and there is an increasing interest of finding ways to kill stem cells.
Closing remarks and moving forward in next 5 years… Dr. Doroshow emphasized the importance of obtaining specimens from patients for research.
Mr. Epstein highlighted the need for increasing dialogue between pharma and to continue to pursue combination therapy regimens. Dr. Scheller also emphasized the need for obtaining specimens as it is critically important to understand how tissue is responding to therapy.
Dr. Gaynor emphasized the need for more clinical data with combination targeted treatments. More clinical data, observations, and lots of serendipity!
This is certainly an exciting time in clinical trials and translational research!
Our morning started with an exciting introduction to a new neurosurgical therapy for the treatment of brain tumors. This live surgery session was moderated by Dr. Michael Volgebaum, Associate Director of the Brain Tumor and Neuro-Oncology Center and the Director of the Center for Translational Therapeutics. The surgery was performed by Dr. Gene Barnett, Director of the Brain Tumor and Neuro-Oncology Center, Gamma Knife Center, and Vice-Chair of the Department of Neurological Surgery.
Dr. Vogelbaum discussed the majority of primary brain tumors are gliomas and more than half of these are high-grade gliomas. Glioblastome multiforme (GBM)P is the most common type of high-grade glioma. A particular challenge in this disease presents is tumor heterogeneity. Dr Vogelbaum showed several MRI images of brain tumors and noted that they tend to enhance with contrast. However, this is only the tip of the iceberg and tumor cells infiltrate into the brain tissue around the tumor as well. In order to effectively treat this disease, you have to treat all parts of the tumor and surrounding tissue involvement.
There has been progress over the past decades, but the prognosis for GBM remains poor. The median survival is 14 months and the 2-year survival rate is 25%. Several factors are known to influence prognosis, including tumor grade, age, performance status, and the extent of surgical resection. Of these, the only factor that we can have significant improve upon is the extent of surgical resection. We know that complete resection can improve survival advantage.
Factors that limit complete resection include the tumor location in deep, central structures where approach requires transection, infiltration and diffuse spread, involvement of areas that have defined function. For these less accessible tumors, the only non-invasive measure for local treatment previously available was radiosurgery. Radiosurgery requires high-dose radiation stereotactically guided and delivered. There are several limitations to radiosurgery,including that as the volume of tumor increases, the dose of radiation must be decreased (potentially less effective) or a higher toxicity must be accepted. This is not required with laser thermal surgery.
Now, laser interstitial thermal therapy (LITT) may be another option. LITT uses heat to induce apoptosis and cell death. Today, MRI-compatible focused LITT will be demonstrated. Using real-time MR thermometry, we can accurately and quantitatively determine thermal damage and control for this.
Dr. Vogelbaum presented our patient as a young male with recurrent GBM. He had undergone previous attempts at surgical resection and debulking, also received conventional chemoradiation therapy, unfortunately now with relapse.
The screen opens to the operating suite and Dr. Gene Barnett sitting in front of the MRI screens. The MR thermometry sequence is started and the lasing process begins. Initially, the tumor appears green and as the temperature becomes to rise, a central area of red becomes apparent. As the real-time sequencing continues, you can see the site that is being treated and can also monitor the temperature of adjacent sites. The speed develops depending on vasculature of tumor; the whole process can take up to 2 hours or more. The MR thermometry is critically important in monitoring the temperature.
Dr. Vogelbaum explains that the process actually started at 12am. What has occurred up to this point? The patient has undergone preoperative imaging and planning, anesthesia, and the registration process (in which image data is loaded up into a guidance system in OR). The patient has then undergone stereotactic brain biopsy to confirm diagnosis. Following this, the patient was then transported to MRI suite with AutoLITT system. The alignment of the guidance device is confirmed and the LITT probe is placed. The treatment area has been outlined in white and all area within this outline has guaranteed cell death.
What to expect after? Following completion of treatment, the probe and guidance deviced are removed. The patient will undergo a post-treatment CT of his brain. He will remained hospitalized overnight with anticipated discharge the following day.
The key elements of this procedure include the MR compatible stereotactic guidance system which allow for remote, real-time MR-compatible positioning, real-time thermometry and thermal dosimetry (thermal damage threshold). Neurosurgeons have hands-on control (sculpting). There are also several other clinical benefits . This is potentially a single day procedure and hospital stay. There is no limit to how often this treatment can be administered (as it is dependent on heat and not radiation).
Dr. Barnett stated that this serves as an “important surgical tool that provides surgical results for a number of patients that could not undergo surgery.”
Marianne Frantz, from the American Wine School, gave us a personalized wine tasting tour with a twist, emphasizing not only the epicurean delight of a good wine, but also the important health benefits as well. She started the tour with a fairly mild Chardonnay, guiding us through the different paths grapes take to become the different wines we were enjoying, emphasizing the important role of a grape’s skin in influencing not just the flavour but the color of various wines. White wine doesn’t need to be made from a white grape. White wines are made by removing the skins of the grape before pressing, and the skins are where the true health benefits of a wine are found. Of course with all good things moderation is always best, and the same goes for wine. We continued the journey with a very sweet Riesling, pairing nicely with cheeses, artisan breads, and crispy bread sticks to complete the pairings. The selection finished with a merlot to highlight the crispness tannins provide to good red wine. The texture of the foods that paired with the wines was all part of the well planned tour. It made for an enjoyable evening of socializing with colleagues, networking and all the while learning a little bit more how to enjoy a healthy life.
Dr. Michael Roizen, the chief wellness officer of the Cleveland Clinic, discussed the importance of a healthy diet in promoting one’s health and well being. Data was presented on genomic profiling to stress the importance of different dietary lifestyles in relation to one’s health. The goal of the session was to show how people can change to a healthier diet, while still making food that tastes good. The cooking demonstration was conducted by the James Beard award winning executive chef, Eric Zibold, of CityZen, the signature restaurant of the Mandarin Oriental in Washington D.C.. He prepared a lobster gaspacho, a chilled tomato soup. His recipe combined eggplant, barley, walnut, lobster, lemon, and a sachet of parsley, coriander seeds, mustard seeds, peppercorn, thyme, and a bay leaf. Taking extra time to show us how to collect the tomato water, which is the clear juice from a tomato. It is extracted by putting a tomato in a cheese cloth, or more practically a pillowcase, and then allowing the water from the tomatoes to collect over the course of a day. Talk included the importance of balancing different flavour enhancers in cooking, mainly sugar, salt, and acid (i.e. vinegar or lemon.) Salt is import in bringing out water from different foods, and it is balanced out with sugar and acid, but sugar and salt can make an unhealthy dish. William Barum (Senior Director of Hospitality, Cleveland Clinic) and Steve Schimoler (Chef and Partner, Crop Bistro and Bar) culminated the session with a discussion on the strategies currently being used to introduce healthy flavour enhancers. Sugar for example is replaced using the technique of distraction. A peach pie is a lot healthier if it isn’t made with so much sugar. So instead of a filling made from mainly sugar, it is replace with caramelized liquor with a tapioca base, distracting the brain into thinking it is still eating a sugary filling.
A well respected group of chief executives were selected to discuss ways of maximizing innovations in pharma. The panel discussion was led by Robert Langreth of Forbes. The opening question was focused on how to decide on whether to take it alone, collaborate or to acquire. Dr. Randy Scott, founder and executive chairman of Genomic Health was the first to respond and stated the importance of diagnostics, the key role played by patients in innovation, and the need for collaboration. Greg Lucier, Chief Executive Officer of life technologies mentioned one of the advantages that collaboration can bring, like bringing in more resources. However, on the flipside, as a company grows there is also the risk of the company becoming more fragmented. Dr. Sol Barer, Chief Executive Officer of Celgene said that to make it work the company depends on the key concept of having innovation being the basic culture of the corporation. Fred Hassan, Chief Executive Officer of Schering-Plough believed that mergers do not stifle innovation instead it is the opposite. One advantage of merging and the resulting bigger sized company is that they are able to deal with shocks of financial loss that can happen with any business. The biggest problem in big companies is the tendency to create silos, both vertical and horizontal. These sentiments were mirrored by the other panelists and there seems to be a general consensus that mergers and collaborations do not seem to slow down innovation especially in this current economic climate. The panelists also recognized the high failure rates that current drugs have experienced and the importance that innovation plays in trying to curb this high failure rates. The moderator briefly touched on special topics including which tool may be the key flagpole in understanding biology? Gene sequencing was mentioned. A follow-up question did ask about the impact of gene sequencing and why it may not have helped yet with the recent innovation. Greg Lucier mentioned that biology is more complex, but the tools are starting to deliver, they are becoming more impactful, it is likely that we will have the quick sequencing technology available to scan the whole human genome in 4 years but we have to bear in mind that the issue is not just being able to do it but the ability to interpret these findings. In as far as clinical interpretation of these complex laboratory date, academic medical centers are currently leading the way. An interesting point was also raised as to whether pharmacogenomics is actually slowing things down. Fred Hassan did say that he agrees that this may slow things down slightly but the key is that success rates will improve, because you are dealing with a more enriched populations. Another important point that was raised by Dr. Sol Barer is that discovering drugs is more than just good science, it is also about inventorship and this is something we always forget -- nothing is perfect. They also emphasized the key role of a good clinician in innovation. In summary, collaboration is key especially in these tough economic times but careful evaluation to prevent fragmentation in the company is clear. It is never bad to have good science but it is not all that matters, inventorship plays a key role in success as well. Scientists and clinicians should work together to try to answer the important medical questions.
Maria Bartiromo, anchor at CNBC, interviews Fred Hassan, CEO at Schering-Plough. She asks the hard questions about health care today; he provides a bird's eye perspective on the issues looming ahead for Americans and their collective health.
A few themes become clear as the session continues. Hassan sees the current health care research agenda as growing from laboratory work, and emphasizes that, instead, clinicians should be initiating research ideas from experiences in the clinic and setting the research agenda to be pursued within the lab. Clinicians are closest, he says, to having the next great idea. Industry should be reaching out to clinicians and forming collaborations to achieve that "eureka" moment in the advancement of science and medicine.
When asked what should be done to improve the NIH, his answer is simple: "a few billion dollars." He is dissatisfied with the current pace of medical advancement in cancer; we are still diagnosing lung and pancreatic cancer too late. Earlier detection and earlier intervention are needed. Financing the NIH could help us unleash information in a systematic manner, so we can finally "crack the code" for cancer, which would ultimately lead the country to reduced health care costs overall.
Health care, Hassan notes, is spending far too much on very sick patients at the end of their disease course and not nearly enough on prevention. He believes a good deal of health outcomes, including in cancer, are influenced by behavioral traits, and could thus be attenuated by behavioral modification. Smoking, diet, and exercise are all contributors to morbidity and mortality, and cause many preventable diseases.
Obesity in America is an issue that is not being properly addressed by our current health care paradigm. The American people need more education as to the myriad negative effects obesity has on the body; knowledge, he believes, is a key component to behavioral change. Hassan mentions that a tax on sugary items, such as cola drinks, is being considered in Washington.
He introduces the concept of personal responsibility in health care. Just as multiple wrecks will increase a person's car insurance rates, bad habits should not be rewarded or ignored in health care. While he strongly supports the notion of personal responsibility in health care, he understands how potentially unpopular the concept may prove to be. When asked if McDonald's should be shunned or taxed, he wryly states "Better educated people than me should make this decision..."
Hassan advocates for a "cocktail" methodology for treatment of disease. Just as we have found in treatment for HIV that response is better with an aggressive three-drug regimen upfront, Hassan posits that a similar response might be seen in cancer as well. With that strategy in mind, he calls for the elucidation of more biochemical pathways in order to open more avenues of targeted therapy. The more therapies we have at our disposal, the more "ingredients" we will have to mix novel "cocktails" of therapy, and the better chance we have at ultimately achieving success in cancer therapy.
John Suh, MD, Chair of Radiation Oncology with the Taussig Cancer Institute of Cleveland Clinic moderates a panel discussion of current issues in radiation therapy.
Panelists: Jean Marc Andral, President Advanced Radio Therapy, IBA (J) Shawn Guse, VP of International Operations, Tomotherapy (S) Tomas Puusepp, CEO, Elekta (T) Eric Lindquist in place of Euan Thomson, PhD, CEO, Accuray (E) Dow Wilson, President, Oncology Systems, Varian (D)
Where is the future of radiation therapy going in terms of the fight against cancer? T: Generally, we are faced with a rapid increase of cancer incidence with more and more chronic disease. New therapies will need to be judged by their true value, that is, the outcome divided by cost of obtaining the outcome. Informatics will figure into this calculation. S: We will be increasing quality and safety. As radiation is invisible, we need to determine, log, and track each voxel and adapt the plan. We will eventually track the dose and location over a patient's lifespan, once we make tools to be able to do those things. E: Radiosurgery has been proven for brain and spine, is emerging for lung and liver, and is in early stages for prostate. The economic challenge is how to deliver benefits en masse, e.g. for liver cancer in china. I think radiotherapy can do that. D: Radiotherapy needs to be versatile, do more at less cost. J: We need to make protons more accessible, to link with investment and throughput. The evolution of RT will be in better understanding of imaging.
What are the biggest challenges to radiation oncology moving forward? T: To make emerging technologies in radiation therapy clinically available and use this wealth of data to improve treatment. S: The capital equipment business. The cost of a machine is substantial, yet hospitals do not want to sacrifice innovation. E: Accessibility is one of the major issues we face. Assuring the patient is informed as to what truly their best options are and then assuring that they have access to that technology. D: I would like to underscore the outcome point. We have become much more outcome oriented, to prove that our technologies are "not just cool tools but measurable in outcome." We are developing a research budget, to innovate tools with clinical and physics partners and fund more outcome research. We have to adjust to the large cancer trial groups, which do not necessarily run the pace of innovation to which we are accustomed. J: Training. We need to teach clinicians how to use the physics. We need to shift to an outcomes focus.
You all have mentioned the problems with coupling an expensive technology with outcome. What in your opinion is the key outcome metric? T: The cost of delivering that outcome. S: The ratio of tumor control to cost quality. E: Survival. With radiotherapy, you can get local control, but ultimately what is the patient’s overall survival? D: Toxicities, e.g. erectile dysfunction in prostate cancer. JM: Tumor control.
Could you elaborate on treatment of lung tumors with your technology? D: Radiotherapy is used mostly in palliative scenarios. Early operable disease has shown promising results with RT. For centrally located lesions, we have good tools; for peripheral tumors that tends to bounce around with breathing, tools need very significant advances in motion management and the ability to radiate a moving target. D: Data is there for hyperfractionated treatment. There is talk about distinguishing the operable from the radiation candidate. If you can truly screen a high-risk lung cancer and determine whether it is cancerous or noncancerous and treat accordingly; that's a compelling benefit.
Does biotargetting fit into the future of RT, perhaps in combination with a modality such as PET? S: It is important to know where to go and how to get there. This involves the imaging modality, delivery, verification, and adaptation. Tools are there and are in development. Notably, the degree of precision does not correlate with expense. Our job is to combine modalities as efficiently as possible 1: Imaging modalities will improve. Biotargetting can be done with radiation sensitizers and protectors; more work is to be done on these compounds. D: Today we use CT and XR in-room. We do not do MR or PET in-room. The GE in me says that is an expensive way to deploy an asset. The best way would be high field imaging with MR and PET, but there is a fair amount of time required to reconstruct these images. While in-room MR and PET may make it to market, the question is whether these would be the most cost effective way to image. S: Proton therapy may be able to use PET for anatomical verification of dose delivery, but certainly cost is an issue.
Please comment on the recent FDA approval mechanism where a drug has to demonstrate safety and efficacy but devices do not. D: Unlike drug companies, we are not paid by radiation dose. But there's no question the pendulum will swing that way [for us]. We have to work better with academic partners for evidence on efficacy and figure how to handle staggering expense of research. I will note that of 35 million fractions given this year, I can count safety incidences on one hand.
How are you enacting research at your respective companies? T: We have an advisory board and have invested 9-10% of our revenue into R&D, now close to 15%. S: We function bottoms up. Our users tell us what they would like to see, and what they find to be the efficiacious uses of our equipment. Customers dictate where we take the device. E: At Accuray, this is an emerging field. The challenge is that information is faster and esier, but the question remains as to how we funnel the right treatment to the right clinical users to for the right clinical indication. D: Biosynergy started 4-5 years ago to understand what is happening in the genomic realm beside the traditional product planning. J: By collaboration.
It is often asked if RT is better or more cost effective than surgery, e.g. in lung cancer. We have difficulties answering, as so few pts enroll in clinical studies. How do we improve enrollment in clinical trials? T: more expensive to do surgery. informatics. J: You have to consider the total lifetime cost of surgery and of RT. Different patients do not react the same way to treatments. We need to measure effectiveness after the first few fractions and adapt faster to personal variations. This will become an issue of research. R: There are inherent problems with comparing an invasive to a noninvasive technique, e.g. surgery versus cyberknife. When an MD presents the two options, it implies expectation that both treatments are about equal. However, four out of five patients, when randomized to surgery, drop out of the study to avoid the surgery. Studies would have to get big and get worldwide to accrue the numbers needed to power such a study. D: We need to partner with clinical specialists,a nd keep in mind the problem of randomization and the referral pattern of our partners. Some of these things are honestly easier to do outside of the US.
Martin Harris, MD, CIO of the Cleveland Clinic, moderates a much anticipated session with Sam Palmisano, Chairman of the Board and CEO of IBM. With an exemplary record of technological innovation, IBM employs 90,000 employees in 70 countries worldwide. In 8 research labs, IBM sponsors 3200 researchers, some of whom have won Nobel prizes and National Medals of Science.
Mr. Palmisano opines on emerging shifts in business and technology, and how the trends figure in the health care industry. The major pattern of the 21st century is one of disruption, a pattern of events that signal the world’s global integration. The world has become flatter and smaller, simultaneously causing system breakdowns and forcing the world to become smarter.
The world becomes smarter by creating systems and processes that provide integrated services, by being, in essence, connected. In that sense, interfaces matter. For example, we take for granted banking transfers and airline reservations. They just work. They work because there are standards and interfaces that allow information to flow. This is where American health care fails.
A systems approach cannot truly be applied to our current health care in the US. Rather than being a true "system," American health care is a collection of related industries operating in close proximity to each other. At a recent Smarter Cities conference, he heard someone say, "The American health care system isn't broken. That would imply that you have a system to fix.”
Sometimes a seemingly small innovation creates a large system change. Take, for instance, the humble origins of the UPC code. The first UPC code was scanned in Troy, Ohio, on July 26, 1974. Suddenly, checkout at the local store is faster, keeping inventory is faster, returns are simple. The supply chain is streamlined due to an exponential increase in the ease of tracking and transferring information.
Mr. Palmisano wonders if the extensive effect on systems the UPC code brought to stores may be someday replicated by the effect a universal medical record could have on health care. Countless lab tests are repeated due to outside records not being available. Health care dollars are wasted daily in the lack of a system.
Health care woes are not a technology issue. We have the technology; however, we need the system to support it as well as the key regulations to keep the system from abuse. We need leadership, not necessarily from the government. Plenty of revolutionary technologies, like the UPC code and ATM technology, were driven by innovation and return on investment.
To move toward a health care system, Mr. Palmisano suggests four areas of focus. 1. Standards. We must agree on technologic standards for health care content that are open and nonproprietary. 2. Incentives. We need to provide better incentives for patient care. It may be cheaper to pay people to lose weight and not smoke. 3. Collaboration. We should be shoulder to shoulder at the point of care, where the system should be optimized, with more sharing of responsibilities 4. Policy and ethics. As medical professionals, it may be exciting to embrace technology; however we need to keep in mind that not everyone wants to be a human petri dish.
Mr. Palmisano ends his talk with optimism and a charge to action: “The unique moment, where preconditions for change exist, is now. There is a huge acceptance for need of change. When you have this societal mandate for change, it would be crazy to waste it. Take charge of our future and do not wait for it to be mandated upon us.”
Introduction by Charis Eng, MD PhD, Chair and Director of the Genomic Medicine Institute at the Cleveland Clinic
Dr. Eng moderates this lively and challenging session on consumer genotyping and opens with thoughtful comments on the future-is-here-now state of genomic information and clinical practice.
She notes that the goals of medicine in the 21st century are to detect patients at risk and intervene prior to symptom onset.She believes that the way medicine will meet these goals is through discoveries in genetics and genomics.
Genetics and genomics are paving the way to a future of personalized healthcare by way of a phenomenon she coins as “phenomics,” or the meticulous documentation of salient clinical features of genes and genomes.Phenomics allow personalized risk assessment and personalized risk management via information clinicians will, in the future, be able to glean from a person’s individual genetic makeup.
While current direct-to-consumer genomics is "very fashionable" now within the NIH, CDC, and personalized gene coalitions, she observes that, as of yet, there is no clinical validity or utility, that is, no “actionability“ yet. However, she notes this is how all good research and clinical practice begin.
In regards to genomics, we are at an "ugly duckling stage," the necessary immature awkwardness that precedes the development of the ultimate product. In a few short years, she predicts the attainment of “nirvana,” the place when and where all these evolving technologies can be completely integrated with clinical practice.
Comments from Edward McCabe MD PhD, Chairman of Pediatrics at UCLA, American Society of Human Genetics, Pediatric
Dr. McCabe introduces basic concepts of genomics and personalized medicine via genetics. In the past, we defined risk in terms of populations. A person’s risk was assessed based on membership within certain populations, such as gender, ethnicity, or age group. Now medicine is moving toward risk assessment based on a person’s individual genetic code.
In addition, we are discovering the microenvironmental elements outside the genetic code that further influence genetic behavior, known as epigenetics, and cause silencing or activation of genetic sequences.
The technologies that provide genomic information are expanding rapidly.One consumer offering tracks 2 million sites along the genome, with an average of 700 base pairs between these sites.
This technology leads to the problem of too much data.We do not understand the significance of most of the differences we find, often unable to distinguish genetic changes that cause true changes to protein structure from simply benign genetic change.
Our findings in these studies, known as genome-wide association studies (GWAs), are based on guilt by association.To make GWAs useful and relevant, we need very large sample sizes and appropriate inclusion of all ethnic groups.
Comments from Wayne Rosenkrans Jr, PhD, CEO, Personalized Medicine Coalition
Dr. Rosenkrans debates the issue of regulation. Should regulation come from Washington, DC? He notes the FDA has already signaled their interest in this issue. The alternative is self-policing by the industry, which would involve coming up with a standard to measure the scientific validity of genetic testing.
The technology is in such an early phase, he notes, that people are still struggling to define its parameters. Quantifying clinical effectiveness of genetic testing has been elusive. In his own company, a comparative effectiveness study was discussed, and no one on the panel had the faintest idea how to go about such a study.
Another issue revolves around who will pay for this testing. Insurance companies are still learning and figuring out how to provide coverage and reimbursement for such testing.
Perceptions of genetics pose a philosophical conundrum; are we testing "genetics for estate planning" or "genetics for better health?" Inevitably we must ask the deeper question of whether we consider health care to be a social value or market good. To Dr. Rosencrans, health care may well be both.
Comments from Dietrich Stephan, PhD, co-founder and chief scientific officer, Navigenics
Dr. Stephan outlines the transition of his company from the research of monogenic and more rare diseases to exploring the underpinnings of complex genetic disorders that we are all going to get. While it is not clear what to do with propensity to get one of these diseases, Dr. Stephen offers a suggestion as to the direction we might take this information
First we need to work on how to communicate genetic information to the physician. Once we articulate the heritable component, medicine needs to work in a focused way for those that are highly loaded. For those individuals, we can start early screening activities, aim to achieve earlier diagnosis, and deliver the right drug at right dose as the patient’s genetic composition dictates.
The purpose of his company is to address these concerns.The overall plan is to sequence an individual’s genetic and epigenetic composition, ascertain copy number variations, and extract heritable risks from that information. He envisions a rank order list of potential disease, a virtual portfolio that a physician can use to extend a lifetime and compress times with morbidity. He hopes this technology can supplant the current newborn screen.
He notes “a strong IT flavor” to this technology; his company uses web service as a model.He also comments on the difficulty of communicating risk models.In a monogenetic system, inheritance is Mendelian, with a “fluff factor” called penetrance. In genomics, the notion of penetrance does not apply; instead, there are gradations of risk that the community at large, lay and clinical alike, must first understand.
Anne Wojcicki, President, 23 and me
If you were diagnosed with colorectal cancer and were started on standard chemotherapy, Ms. Wojcicki asks the audience, would you want access to information suggesting you might be in the 6-8% of people who have a severe reaction to that chemotherapy?
Her company provides access to one’s own genotype with 600,000 data points as well as educational material about what those data points mean.The company emphasizes education about the concepts of genetics, and provides references for each known point of interest along a person’s genome.Because not all literature is of the same quality, each reference is given a grade on a five star scale, providing the educated client a relative weight for the validity of each data point.
Clients of the company are often attracted to information that allows them to trace their lineage.Ms. Wojcicki tells the story of client who thought she was of Northern European descent, but was surprised to find she was a sickle cell carrier and that 5% of her genome was of African origin.
For 23 and me, the goal is to educate clients about the information their genomes can provide to them, with the ultimate goal of having a patient’s genotype in hand a standard of care for all physicians.
Greg Lucier, CEO, Life Technologies
Life Technologies represents a $4 billion company which makes life science tools that sell directly to medical professionals as well as forensics and food testing laboratories. Two billion of the company’s dollars go to research in direct genotype sequencing.
Sequencing as a technology has been incredibly revitalized since 2001, when it cost 3 billion dollars and multiple years to sequence the entire human genome. Today $20,000 and a few weeks can sequence a human genome. In 5 years, Mr. Lucier thinks it is unquestionable the price will come down to $3000, and the time to completion will come down to a couple of days
Life Technologies is interested to use this tool to see if it can change clinical outcomes.In some trials, says Mr. Lucier, outcomes using whole genome sequencing are provoking and may prove important for cancer protocols in the future.
He surmises that diagnostic genomic sequencing can follow one of two paths. Genetic sequencing could become another test in the basement of the hospital; he calls this the “diagnostics view of the world.”Alternatively, genetics may be more lakin in complexity to radiology, taking a whole wing of a hospital with multiple experts to interpret the results and communicate the findings topracticing physicians.
While it is unclear how this all plays out, Mr. Lucier notes "the technology will be there to drive this profound change in medicine in the next couple of years."
This early morning session introduces the audience to technical innovations within the surgical realm. Our moderator, Amr Fergany, MD, of the Glickman Urological and Kidney Institute at the Cleveland Clinic introduces Jihad Kaouk, MD, Director of the Center for Robotic Surgery, also of the Glickman Institute, in the operating room. Dr. Kaouk is preparing to undertake removal of a kidney tumor using robotic assistance within the body cavity, reducing the extent of open wounds and healing time.
Dr. Fergany calls this procedure "the most advanced thing we do for treating kidney tumors" today. This procedure is the product of surgical evolution from larger to smaller, more invasive to less invasive. Once done as an open procedure with a large open incision, the partial nephrectomy has transitioned into minimally invasive surgery, first as a laparascopic procedure and now improved with robotic assistance during surgery via a DaVinci machine, a high definition robot that allows the user greater control of smaller instruments within the patient's body. The robot allows millimeter precision, the goal being to excise all of the malignant tissue yet save as much good kidney as possible.
We open to an overhead view of the operating room. Dr. Kaouk shows us a sleek grey console with a TV screen, two joysticks, and four foot pedals; two pedals control the camera, two control cutting and grasping instruments. The screen displays a real-time image which broadcasts from a tiny camera within the body, as well as intraoperative ultrasound images during key moments. CT images of the patient's abdomen hang on the wall, a blueprint which allows the surgeon, prior to surgery, to visualize the geography and topography of the cutting area and minimize loss of nonmalignant kidney tissue. From the console, a large metal arm arcs over the patient and extends multiple smaller arms which hang immediately over the patient. The machine can use a total of four arms, one for the camera scope and three instruments that can one commands from the console.
Today we are viewing the removal of a 5cm kidney tumor. We enter immediately into a view within the abdominal cavity, with a possible magnification up to 10x. Dr. Kaouk and his assistants move bowel and its adjacent fat to reveal the major vasculature running into the kidney; this vasculature will be clamped at start of surgery to facilitate a relatively bloodless surgery. The next step requires visualization of the tumor mass and dissection of the mass from surrounding organs, being careful not to violate tumor margin and spread disease. Dissection of fat can be quite difficult in some individuals, particularly in smokers, who have more adherent fat due to chronic inflammation. The final layer through which one must cut in order to free the kidney is called Gerota's fascia, an important margin in the staging of kidney cancer.
During the dissection, Doctors Fergany and Kaouk answer questions from the audience. Most are curious about the difference between an open procedure and a robot-assisted laparoscopic procedure. We learn that operating room time is equivalent between the two procedures, but the the real time and money savings lie in the post-operation recovery time, which is much shorter with the laparoscopic procedure. Between robot-assisted and normal laparotomies, the difference is in the tools. Robotic arms have more articulations of movement than instruments used in normal laparoscopic cases; thus robotic arms facilitate access to sharp angles and hidden corners. We also learn that Cleveland Clinic surgeons have collectively logged approximately 1000 of these types of procedures in the last year and have one of the largest experiences of kidney tumor surgery in the country.
Once the tumor is freed from surrounding structures, Dr. Kaouk uses an intra-abdominal ultrasound probe to distinguish the border between normal and malignant kidney tissue. The goal is to cut into normal kidney tissue close to this border, leaving a 2-3mm safety margin around the malignant tissue. He shuts down blood supply to the kidney temporarily by means of specialty surgical clamps called "bulldog clamps" that are designed to be used laparascopically. These clamps cut off renal blood supply without causing harm to the vessels. He has about 30 minutes of what is called "warm ischemia time" to cut off the tumor and sew up the remaining kidney. He runs to 27 minutes, using running stitches to close off the open margin of the kidney and using clips in place of tying knots, thus reducing surgical time. Meticulousness in this part of the surgery is key to reducing hemorrhage from cut kidney tissue. Today he has scant blood loss, only 150cc, less than a quarter of an average sized water bottle.
Operative success has been achieved for this patient today. The surgeons have done their work; the rest will be up to biology, genetics, and perhaps some bit of good luck.
Dr. Derek Raghavan introduced the first speaker Tim Miller, chief executive officer of Siemens workflow solutions. Tim Miller has an impressive record of leadership within Siemens and other multi-national companies. He was asked to speak about the grand challenges in cancer treatment. His presentation focused on the challenges of cancer as related to physics, biology, information, time, and accounting.
The previous challenges in physics were noted in relation to the field of radiation oncology. CT scanners are now required to for radiation oncology. Originally, Dr. Cormack was criticized for his work on 2D CT scans. Eventually Drs. Hounsfield and Cormack were jointly awarded the Nobel Prize in 1979. Tim Miller then said that, "the real problem is not the physics but it is the prescription."
The second challenge in cancer treatment is the biology. Radiation is not selective and damages both normal cell and tumor cells. If we knew the biochemistry of cancer, it would change everything we do. Although we are making many advancements in the biology of cancer, there is much more we don't understand and many of the advancement take many years. For example, it took 25 years for Judith Fulkman to purify the anti-angiogenesis protein angiostatin from tumor bearing animals.
We know information is important but the main issue is managing all of this data. We have seen this with the genome project. "What do you do when companies are promoting the personal genone and your patient comes to you with their genome on a stick. " Thus the information must be obstracted to offer individualized standard of care.
In regards to time and cost, Tim Miller said, "The real progress will require teams, a network of partnerships, and time." He went on to say, "the biggest problem is that we don't longitutionally calculate costs. We don't know the return on our investiments before we start."
The next speaker, Dr. Sir Bruce Ponder, director of the cancer research UK Cambridge Research Institute, was asked to speak to in regards to personalized medicine in cancer. "You can break this into germline genetic events or somatic genetic variations. Over the past few years, there has been a change of focus from high risk families to a focus on the effects of common genetic variation", said Dr. Ponder. He stated there are differences in susceptibility through normal genetic variation and small increments of individual risk affect the entire population.
He discussed the association studies which have searched for common genetic variants that cause cancer. For a specific DNA sequence, the question is asked what is the frequency of cancer in those that carry the DNA sequence variance. The technology has allowed use to do genome searches to find these disease associations. In the last 3 years, there has been at least 300 genes that predipose to at least 80 diseases and traits. This has caused great promise for new mechanisms for treatment. Some think this is just hype and think it may be a complete waste of money.
The reason that some think this is hype, it that these genes are taking a long time to find and they have small effects. For example, we have only found 25% of genetic variations for breast cancer. When we look at the total risk explained by gene frequency, the total risk is actually small.
The next question is what do we do with this information. How do we target the mechanism of the gene that is consistant with the small benefit to the individual? There are complex decisions that involve risks and benefits. It is really important that we imploy proper education and information so patients can make informed decisions.
Genetics will focus attention on ideas of innovation targeted to individual risk. Major challenges will be proving that any of these tests are beneficial and how to use the information. The is going to be in the background of direct access to consumer testing.
The final presentor was Dr. William Hait, senior vice president and worldwide head of hematology and oncology for Johnson and Johnson. He spoke about the low success rates for oncology drugs entering the clinical setting and our inability to consistantly deliver highly effective drugs to patients.
We start out not knowing where we are going. We then select a target and develop a drug against that target. The better alternative is to use tumor type expertise at the molecular level to design therapies. Thus with the pathways determined, the prototype drug can be developed.
"We now understand that tumors are not just a collection of cells. Malignancy is a combination of tumor cells and the surrounding tissues or microenvironment. Cancer is more than a collection of cells but is an aberrant organ", said Dr Hait. Thus cancer is a disease of tissues that support the growth of tissues.
There are several challenges in cancer treatment.
Challenge number one is understanding the target. Alterations in somatic and/or germline genomes can create different therapeutic targets.
Challenge number two is preclinical models. Mouse models may not represent tumors within humans.
Challenge number three is the regulatory environment. Research and development can take years and massive amounts of money. There can be many delays getting a drug approved through the FDA.
Challenge number four is that its easy to say, but not easy to do. We should be focused on personalized medicine. We are moving away from blockbuster drugs that have a small benefit in a large number of patients and moving toward to the largest benefit in a smaller benefit of patients.
Challenge number five is that we need to develop biomarkers that are used to understand the target of drug development. This has been extremely popular in the oncology literature but few have been found useful. Also looking for circulating tumor cells, "liquid biopsy", will help us move forward in personalized medicine.
Challenge number six is pricing. There is a relatively low activity and benefit compared to drugs in other diseases. The drugs are very expensive to produce, for a small benefit for a small number of patients.
He ended by proposing that academic careers should include the physician scientist, clinical investigator, and clinical physician tracts. He stated that it is impossible to concentrate on bench research, see patients, and develop clinical trials.
Daniel Vasella, chief executive officer of Novartis, has been the CEO since the merger the created the company in 1996. He spoke about the goals of a cancer pharmaceutical company which include reducing mortality, reducing morbidity, and be profitable. Overall, mortality from cancer has decreased and in children the mortality of cancer has been cut in half. Novartis' introduction of Gleevac in 2001 marked the entry of the first tyrosine kinase inhibitor and is now one of the top 10 biologic drugs. With the introduction of Gleevac, which can induce complete remission in over 80% of patients with minimal morbidity and no mortality, the course of CML has been changed. One problem that still remains is that stem cells continue to harbor the mutation. One of Novartis' new innovations is LDE225 which will target the stem cells of CML.
As we have already discussed today, targeted therapy are the drugs of the future. Another targeted therapy, FDA-approved Afinitor is a once-daily oral inhibitor of mTOR (mammalian target of rapamycin) for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. It is also being tested in breast cancer, gastric cancer, and mantle cell carcinoma.
In addition to drugs reducing morbidity and mortality, new drugs must be profitable. Dr. Vasella stated that only 30% of the drugs that are being launched today are profitable and the majority are failures. FDA approvals for new drugs have been flat over the recent years. We all realize that the expense for research and development of these drugs is massive. We must find ways to reduce the expense and quicken the process for drug approval through working closely with FDA, academia, and industry.
Dr. Vasella then spoke about the success of Novaritis as a company includes creating the right environment, sustainable growth and competitiveness, transparency, and health care reform. He stated that the 3 individual keys for success at Novartis include competence, ambition, and integrity.
Health care reform is key to fixing economical issues in our current health care system. Defensive medicine is a source of income and thus vary difficult to break. i.e. The more tests that are ordered, the more money that is made. Dr. Vasella pointed out that the more money spend does not equal better care. Actually clinical studies have shown that clinical outcomes are inversely proportional to the amount spent. Patient do better when less tests are ordered and physicians practice good medicine.
One of the key factors in health care reform is cost reduction and must include prevention. In the UK, there is concentration on diabetes prevention. Patients are given counseling when they develop elevated BMI. When diabetes is diagnosed there is concentration on drug compliance. This translates into a huge amount of health care savings.
In the US, obesity has increased 88% and diabetes 114%. Dr. Vasella asks, "Why do we not better address the problem of obesity. We spend more on the complications of obesity than cancer." We spend trillions on obesity per year and new innovations will decrease costs.
He ended with a quote from Michelangelo, "the greater danger for most of us lies not in setting our aim too high and falling short; but in setting our aim too low, and achieving our mark."
In the question and answer session, Dr. Vasella was asked about TORT reform? What is you proposal? "There should be a cap. Physicians should be encouraged to practice medicine and not order things to cover their backs."
"You said that only 30% of drugs are successful. Is this industry wide?" "Yes, successful is considered a positive value beyond the cost of capital."
"In your presentation you said that we only spend 5 cents per health care dollar on prevention. What would you spend it on?" "I would concentrate on obesity", says Dr. Vasella. "There is a whole change in society that we need to adapt. This would be a cross disciplinary focus."
