BLOGS from 2013
Raju Kucherlapati, Ph.D.
Personalized Medicine Community Gathers in Boston for the Ninth Year to Share Insights and Innovation from the Field
Personalized Medicine was an emerging field of medicine in 2005 when we first held what was to become an annual event, our personalized medicine conference. The importance of personalized medicine was given a boost by the then U.S. Secretary of Health and Human Services, Michael Leavitt, who said in January 2005, “I believe we are moving into a remarkable and powerful new era in medicine and particularly in prescription drugs. I’d refer to it as an era of personalized medicine.” Since then many different names have been given to this approach to medicine. They include “Precision Medicine”, “Genomic Medicine”, “Genetic Medicine”, “Individualized Medicine”, and “P4 Medicine” to name a few.
This year, we gear up for our 9th Annual Personalized Medicine Conference on November 6th and 7th, in Boston, arguments can be made about what name adequately describes the enterprise in which genetic and genomic information informs us about a person’s risk for human disease; about a clear diagnosis on which treatments depend; about prognosis for a disease such as cancer; about genetic variants in an individual patient that may determine that person’s ability to metabolize a particular chemical entity; about genetic and genomic changes that might inform physicians about the appropriate therapeutic approach; and about many other aspects of health and medicine where genetics may play a role. Some people in the scientific community contend that the use of such a diversity of names for the same enterprise is natural and reflects the evolution of the field. What we cannot ignore is the direction that the science is leading us – toward precision diagnosis and treatment of disease at the molecular level.
As I reflect on the past nine years, some aspects of personalized medicine have changed rapidly and others are relatively unchanged. One of the biggest and most exciting changes involves the growing commitment of drug developers to the development of targeted therapies. At the beginning of the 21st century, there were only a few drugs that could be considered “targeted” therapies. Now, in cancer, for example, the development of such targeted therapies is becoming the norm because many of these drugs have few adverse effects and the response rates of patients, whose tumors have the molecular target for the drugs, are very high compared to other non-targeted therapies. We can find similar “personalized” approaches to treatment in the areas of infectious disease, cardiovascular disease and other areas.
Today, much of personalized medicine is fueled by new technologies related to DNA and RNA sequencing. It has been estimated that the cost of sequencing has dropped by a factor of 100 from the beginning of this century. The amount of DNA or RNA required to sequence whole genomes has also been reduced by orders of magnitude and there are now technologies in development that promise to sequence single molecules of DNA in a matter of few hours. As the technologies improve and associated costs decline, the benefits of genome sequencing become more apparent. It is easy to imagine a not-too-distant future when people around the world have their genome sequenced as part of the standard of care. Despite present concerns about the cost to analyze all of these genomic data, I am certain that newer algorithms will enable us to automate much of the analytical and interpretive processes to propel us toward a new level of understanding regarding the prevention and treatment of disease.
As the science evolves and entrepreneurs continue to innovate, we are faced with new challenges.
Open and informed discussions about issues related to personalized medicine are critical for better understanding of the successes, failures and promises of this relatively young medical enterprise. Our Conference in Boston provides one such forum and we hope that you will be able to join us.
The future of medicine is before us.
For more information and to register for the 9th Annual Personalized Medicine Conference, please visit www.personalizedmedicineconference.org.
William Chin, M.D.
TITLE: Advancing Personalized Medicine through Research, Collaboration, and Innovation
The healthcare community is at an important juncture; we must work together to ensure that policies and regulations align to help us meet the unique challenges and full potential of personalized medicine. Science and technology drive what we can achieve, but they also evolve over time. We, too, must evolve and adapt to this rapidly changing environment.
Indeed, as I told participants at the 9th Annual Harvard Personalized Medicine Conference , the continuing development of personalized medicines holds promise to define our age and change everything we do. These treatments will affect how we approach once seemingly intractable medical challenges, how we research and develop new medicines, and how patients interact with physicians and our healthcare delivery system.
The biopharmaceutical industry is strongly committed to researching and developing personalized medicines. A Tuft’s University survey found that biopharmaceutical companies increased their investment in personalized medicines by 75 percent between 2005 and 2010. In fact, between 12 and 50 percent of all compounds currently being researched are potential personalized medicines, which are targeting a growing range of diseases that may be identifiable through a genetic test or biomarker – from depression to obesity to many forms of cancer. Through these advances, we are shifting from reactive to proactive medicine, possibly enabling us to identify a patient’s risk before symptoms appear, and to transform our approaches to diagnosis and treatment.
But with these hopes, there are hurdles. We all know that we need forward-looking policies that foster innovation and a regulatory system that is in line with advances in science. But we also need strong collaboration among biopharmaceutical companies, academics, patients, hospitals, government labs and others to pave the way for the science and its application.
Achieving the full power and potential of personalized medicine is an urgent priority. But it is an attainable goal only if we work together. On behalf of our patients, I urge everyone in our healthcare community to continue working across sectors and disciplines to advance personalized medicine.
Personalized Healthcare and the Unspoken Benefit
In 1960, toward the end of the American baby boom, healthcare spending in the United States was at 5.2% of GDP. The annual cost of healthcare to every American was $147 or $1140 in 2013 dollars. Today, those numbers stand at almost 18% and over $8,600 respectively . One of the primary reasons is the escalating cost of new medical technologies. The many wonderful life saving diagnostic tests, devices, and drugs introduced in the last half a century and the physician subspecialties required to use them, are a threat to global economies. And while this is well known and documented, it is, in fact, very strange.
In all other industries, without exception, technology has been the primary driver of reducing costs, increasing productivity, delivering higher quality and reliability, and providing greater access. The average family in 1960 in the USA spent 12.3% of their annual income on automobile ownership. This is now 9.4%. Compared to 1960, the cost of flying across the USA has dropped by more than a factor of two (adjusted for inflation) and the cost of making a telephone call dropped by a factor of three. Food production, energy costs, information technology, virtually every sector has technology-induced cost reductions and access increases.
But healthcare seems to be unique. It is the only industry in which technological progress seems to cause, rather than prevent, economic disaster.
As there has been no human endeavor that experienced a large leap forward in productivity and quality without technology, healthcare should be the same. And that, for me, is the unspoken promise of Personalized Healthcare. It is the reversal of centuries of healthcare in which new technologies are broadly applied to all patients who seem to fit a generalized profile. Personalized Healthcare is the triumph of specificity and accuracy over sensitivity and probability. And, as much as we speak of the patient benefits of identifying the “super-responders” to a drug or curing the incurable, it is the avoidance of care to those who will not benefit that may be the largest ultimate benefit. If some estimates of ineffective care are accurate, the financial consequences could be dramatic. If Personalized Healthcare results in an overall cost reduction (and it has the potential), we also avoid rationing and can afford to increase access to care. And that would be a wonderful result indeed.
Stephen Eck, M.D., Ph.D.
Strategies for Accelerating Progress in Personalized Medicine
By Stephen Eck, M.D., Ph.D., Astellas Pharma Global Development
Last year around this time, I wrote a blog aimed toward skeptics of personalized medicine, citing the progress we have made in lung cancer as just one example of how well this approach works for treating diseases. As I have reflected upon the advances we have made in areas like cancer and diabetes and how personalized medicine now seems to be the cornerstone for drug discovery and development for many pharmaceutical companies, it has become clear to me that there are still a number of areas for continued investment and focus.
What can we do to continue to grow the field of personalized medicine, find new and exciting therapies, and maintain the momentum we have seen over the past few years?
I believe that developing a personalized medicine strategy is the answer, but this is far from simple.
It begins by first appreciating that one needs to study the diversity inherent in diseases. When a new medicine is introduced in human clinical trials, for example, it is important to describe and understand the diversity of human responses to the medicine and to determine ways to identify those who will benefit the most from the medicine.
While we would ideally like to have such a clear scientific understanding of a disease that we can predict in advance who the likely benefiting patients are (which can be done in some instances), in most cases the personalization of a medicine comes from the observations made in clinical studies of diverse populations.
In contrast to basic laboratory research, where experimental designs seek to minimize variation, the “noise” in clinical trials can actually provide us with important clues to help form the basis of a personalized medicine. Well-designed studies, therefore, should study both the variation of the response as well as the scientific basis for that variation. When done well this can uncover biologic marker that become diagnostic agents for patient selection.
In addition to designing more clinical trials with these two aspects included, I would propose that those of us working in the field of personalized medicine should continue to support efforts that:
• Fund basic research on the biologic basis of disease. Personalized medicine is based on fundamental scientific discoveries. Without these, there will be no improvement in our understanding of disease.
• Fund research in diagnostic testing. Companion diagnostics can be useful tools to help healthcare providers and their patients make more informed treatment decisions.
• Educate physicians and other healthcare providers about personalized medicine. Patients in specialized populations that may respond to a good therapy for their subgroup need to have access to the appropriate tests. This means making sure that those who can order the tests and use them as a part of standard care are aware that these tests and potential therapies exist. • Reimburse for diagnostic testing. Personalized medicine drugs will not have any benefit if they are not used and a healthcare provider won’t know to use a potentially life-saving drug unless the correct diagnostic tests have been performed.
Together, we can maintain and even accelerate the progress we have already made in delivering the right drug to the right patient at the right dose, every time.
Join Dr. Stephen Eck on November 6, 2013 at the 9th Annual Personalized Medicine Conference hosted by Partners HealthCare Center for Personalized Genetic Medicine, Harvard Medical School, and Harvard Business School.
View Dr. Eck’s video interview “Personalized Medicine: How Progress Happens” online at the Personalized Medicine Coalition.
Blogs from 2012
Raju Kucherlapati, Ph.D.
On November 28th and 29th, Partners HealthCare, Harvard Medical School, and Harvard Business School will host the 8th Annual Personalized Medicine Conference in Boston. As has been customary since the conference began, the meeting is also the venue at which the Personalized Medicine Coalition presents its leadership award. This year, it will go to Randy Scott, Ph.D., a founder and former CEO of Genomic Health, Inc.
During the past seven years, we have seen many changes in personalized medicine. Much of the excitement about personalized medicine continues to be driven by the ever decreasing cost of sequencing DNA and RNA. Whole genome sequencing, estimated to cost a billion dollars or more at the beginning of the century has gone down to a few thousand dollars, and the so called $1,000 genome is not too far behind. All in all, the 20,000 or so genes of the human genome only add up to less than two percent of the genome. If the sequencing cost is directly proportional to the size of DNA that is being sequenced, the cost of sequencing all genes should one day be no more $100. We are not quite there yet, but the rapid decline in costs is fueling the evolution of personalized medicine.
There is also a rapid evolution in our understanding of the genes and genomes of many organisms, including humans. Understanding how a normal gene functions and how changes in it (mutations) alter the cellular function is increasing at a rapid pace. As a result, sequencing whole genomes, whole exomes (all of the coding portions of genes), and subsets of genes for medical purposes is becoming ever more common. The fruits of all of these exciting developments are evident in many specialties of medicine but especially in prenatal testing, diagnosis of newborn and pediatric disorders, and cancer.
This year’s conference will highlight the genomic advances in science and medicine, and how they are being applied to diagnose and treat many disorders. The rapid development of technology also raises many questions about the clinical utility of these advances; about the policy and regulatory issues around what, when, who, and how to regulate; and about how the costs are reimbursed.
Personalized medicine is not just an American issue. Many nations of the world are developing strategies to implement personalized medicine in their own countries, and a number of those efforts will be featured at the conference. Professor Richard Hamermesh of the Harvard Business School and Norman Selby of Perseus LLC developed a business case on companion diagnostics that promises to be thought provoking and, based on previous years’ experience, a highlight of the conference.
Please join us at the end of November and participate in the dialog about how personalized medicine is evolving and what its implications are for your health and that of all peoples of the world.
Register online at www.personalizedmedicineconference.org.
Follow the conversation online at @HarvardPMConf and #PMConf.
Stephen Eck, M.D., Ph.D.
Still Skeptical about Personalized Medicine?
Over century ago Sir William Osler, M.D. stated: “Variability is the law of life and as no two faces are the same, so no two bodies are alike and no two individuals react alike and behave alike under the abnormal conditions which we know as disease.” Despite our deep and longstanding understanding of the heterogeneity of disease and the variations in response to treatment, we are slow to adopt the notion that despite its complexity the heterogeneity of human illness is decipherable. Skepticisms that we can actually deliver on the promise of Personalized Medicine is understandable, since converting such variables as severity of illness, uncertain vulnerability to side effects, co-morbid conditions and our cultural environment, to name a few, to precise algorithms for care seems daunting. So, why has it taken so long for medical science to unravel this heterogeneity and why should we be optimistic that Personalized Medicine will happen? In part, our current views stems from where we have previously focused our attention. “Bergkrankheit “(mountain sickness) was known in the 14th century as an affliction metal ore miners in Europe. By the 20th Century we knew this as lung cancer and attributed it to a variety of environmental exposures. In this century, we have further refined our description of this disease to specific aberrations in molecular pathways, which if not entirely causative, account for much of the disease biology. By contrast, medicinal chemistry as a science started much later than clinical medicine and is now closing the gap between knowing precisely what causes an illness to precisely what to do about it to improve the outcome for individual patients. No doubt we have a long way to go, but the current pace of personalized medicines suggests that it is becoming everyday reality for many lung cancer patients.
Drug Developers Know Personalized Medicine
Anyone who has sought approval of a new drug in many countries across the world understands Personalized Medicine. There are a myriad of varying country-specific rules and requirements. These are not arbitrary bureaucratic obstacles, but rather an attempt by governments to serve their populace by understanding how new medicines meet the specific needs of their country. Personalization of medicine at the country level is good, but personalization at the individual level is better. The observation that Japanese nonsmoking women with adenocarcinomas of the lung were especially responsive to specific receptor tyrosine kinase inhibitors is well known. Why this is so, and how best to manage many types of lung cancer, can now be better addressed with specific molecular diagnostics, rather than the histological and clinical phenotypic descriptors that have been historically used. Similarly, variations in drug metabolism (often the basis of country specific clinical studies) reveal important variations in drug absorption, metabolism and elimination. Much of this heterogeneity can now be ascertained by genetic testing for specific polymorphisms that impact drug metabolism. As this approach and others gain greater acceptance they may soon replace population specific clinical trials. This has important implications for lowering the cost of drug development as well as for selection of the optimal medicine for any one person. The impact of some important genetic variations may go unnoticed if clinical trials were conducted only in one country due to the low prevalence of the variation. In contrast, the role of the same genetic variation may be easily detected in distant geographic regions where these variations have greater prevalence. The latter finding can inform the proper use of a new medicine in all geographies. With the globalization of large-scale phase 3 studies, we have the opportunity to understand the impact of many more genetic variations and how understanding these variations can inform the proper use of new medicines.
Less May Be More
Personalized Medicine has come to be strongly associated with drug-diagnostic combinations (companion diagnostics). While this is a very important aspect of personalized medicine, it is not the goal. The goal of personalized medicine is to find the best possible care for each individual patient so as to maximize the likelihood of the individual achieving his/her personal life goals. While this may seem obvious, this principle has become increasingly harder to identify in every day medical care.
A variety of different motivations has encouraged the healthcare enterprise to view illnesses, or even everyday complaints as the opportunity – if not obligation – to do something for the patient. The better approach is to ask: What is the best thing one can do for a patient, including the possibility of doing nothing?
As we develop better drug-diagnostic combinations, this will become increasingly apparent. Soon we will have the ability (through use of precise molecular diagnostics) to know with reasonable certainty whether there is little or no benefit for a particular individual to pursue a therapy which had historically been the standard of care.
But, are we truly ready to forgo a potential therapy even if such a decision is based on strong scientific data? Or, will we continue to use a therapy on the off chance it might work? Our desire to do something has to include the possibility that the best treatment might be no therapy, based on the risks to the patient, the likely benefits, and the life goals of the individual. In the end, patients want their healthcare providers to help them make the best choice and personalized medicine can be a strong tool to do that. This will provide the largest benefit for patients as they avoid the risks that come with all therapies when no benefit is realistically to be had.
Personalized Medicine is Waiting on the Shelf
While there's a tendency to paint the future of personalized medicine as sunny, there are a number of issues persistently clouding the horizon. Today, Bob Langreth and I examine one of these concerns in a story you can see here (http://www.bloomberg.com/news/2012-10-24/life-saving-dna-test-overlooked-in-rise-of-colon-cancer.html). Provider education has long stood in the way of patient access to genetic tests for Lynch syndrome, an inherited cause of high cancer risk. While the testing has been available for more than 10 years, enjoys recommendations from clinical and public health groups, and has been shown to save lives in studies, many providers remain unaware of its availability and power. The test costs as little as $300 in families where the mutation has already been identified. People who test positive can take preventive action with frequent monitoring, perhaps having vulnerable tissue removed. Yet in too many cases it remains on the shelf. How are we going to get the benefit of full genomes when simple, straightforward tests like this go unused?
November 6, 2012
From DNA to Diagnosis
One of the persistent arguments against the use of genome sequencing in the general population has been that it will awaken people to mysterious, uncommon conditions for which nothing can be done. When I joined the Personal Genome Project last year, I didn't think I was sick. I considered myself relatively healthy (and still do.) However, a rare mutation in my DNA alerted my doctors that I might have a one of several disorders, called myeloproliferative neoplasms, that are related to overactive bone marrow. Further investigation showed that I did in fact have abnormally high platelet counts, which can lead to dangerous clots. However, this condition, called thrombocytosis, is highly treatable with a daily baby aspirin. Questions about the cost, implementation, accuracy, education and ethics of exploring the DNA of healthy people are significant. Yet the possibility for genome sequencing to alert doctors to unrecognized, treatable disorders in their patients is very real.
Shortening the path to diagnosing babies with baffling disorders
November 12, 2012
Parents of children with rare or never-before-seen disorders can spend years and thousands of dollars searching for answers. Today, the power of next-generation sequencing allows doctors to many of these cases in weeks or even months. http://www.bloomberg.com/news/2012-11-12/new-dna-techniques-end-mystery-of-what-ails-baby-patrick.html The approach is far superior to the one-by-one elimination of known candidate illnesses that doctors have used for years, and in some cases may lead to treatment, as it did for the Beery twins. http://www.bloomberg.com/news/2012-01-30/genome-proving-cure-for-ailing-twins-paves-breakthrough-to-doctor-s-office.html. Some researchers are concerned that using exome or genome sequencing technology in hard-to-diagnose newborns will put the technology on a slippery slope towards use in healthy babies. Scientists are applying for $25 million in grants from the National Institutes of Health to study questions like these related to sequencing infants and newborns.
Sustaining Progress in Personalized Medicine
Last week, I had the opportunity to speak at the Harvard Personalized Medicine Conference in Boston, MA. No other conference on personalized medicine brings together the array of scientists, stakeholders, and experts that this event does. This year the conference drove home to me that the potential to improve patient care via personalized medicine is greater than ever – yet the scientific and clinical challenges remain daunting. It is more important than ever to sustain biomedical innovation, and to ensure that health policy is informed by the enormous opportunity, and complexity, of making continued progress in this field.
The event also underscored that biopharmaceutical research companies are deeply committed to advancing the science of personalized medicine and building it into their research and development strategies. It affirms findings of a report released by the Tufts Center for the Study of Drug Development in 2010 which found that 94% of biopharmaceutical companies surveyed are investing in personalized medicine and 100% are using biomarkers in the discovery stage to learn about compounds. This research has required large up-front investments in new research tools and training. But, as we have seen in the last year-and-a-half with FDA approval of new targeted therapies for lung cancer, melanoma, and cystic fibrosis, it is starting to bear fruit for patients.
I’m hopeful we’ll see more approvals in the months ahead. In the report from Tufts, companies reported that 12-50% of compounds being researched are personalized medicines and over the last five years, they have seen a roughly 75% increase in their investment in personalized medicines. The importance of personalized medicine was illustrated in the reauthorization of the Prescription Drug User Fee Act, which provides FDA with increased resources and staffing to advance the regulatory science in areas such as pharmacogenomics and biomarkers.
This progress, however, doesn’t happen in isolation. The Harvard Conference participants represented, and illustrated, the wide range of organizations and individuals from different sectors that make up the research ecosystem that drives progress in personalized medicine. As the science of personalized medicine advances, research partnerships and collaborations will be more important than ever. To sustain progress in personalized medicine, it is vitally important to ensure that policy and regulation do not erect barriers to these types of partnerships.
Biomedical innovations like personalized medicine will help address major unmet medical needs, and offer a solution to rising healthcare costs. As we face continued pressure to contain healthcare costs, it is crucial to ensure that healthcare policy sustains the innovation ecosystem and incentivizes continued progress in personalized medicine.
Ger Brophy, Ph.D.
Harvard Personalized Medicine Conference Showcases Progress in the Field
Great themes emerged at the Harvard Personalized Medicine Conference last week. This is the third year that I’ve attended and there’s a palpable sense of progress. Examples abound on how precise molecular profiling tools are now being used in clinical practice and the potential going forward is huge.
But this transformation is causing a number of new considerations to come into focus. Working in industry, we have to think about what do these opportunities mean for business? Where can we best add value; what parts of medicine are currently underserved? How can we bring industrial and operational strengths to the emerging new paradigm? And how is the regulatory environment likely to change…for therapies and for diagnostics?
The opportunities and the challenges are breathtaking. Contributors spoke of the opportunity for sequencing data integration into the Electronic Medical Record (EMR) and the subsequent effect on medical decision making. And the emerging Personalized Medicine paradigm should provide opportunity for the sector to make the case of the value of innovation, both clinical and economic. But what will people make of a new generation of EMRs containing contextual individual information across a continuum of patient care…from predisposition, through screening, diagnosis to therapy selection and monitoring.
The audience-sourced data demonstrated how peoples’ acceptance of precision medicine has increased over the years in which the conference has been held. And although oncology still dominates, pharma representatives described case studies in cystic fibrosis and cardiology. Those same pharma contributors acknowledged the absolute necessity for powerful diagnostics to complement the delivery of personalized medicine.
On the first day of the conference, I moderated a session entitled: “Business Models for Genetic Information.” Thought leaders from Siemens, PerkinElmer and Oracle described their companies’ visions for the molecular and digital age.
We had interesting audience feedback. Over 50% of the respondents felt that DNA sequence will become a routine part of an individual’s medical record within the next 10 years. Also interesting was the fact that only about 10% felt that availability of science or technology was the biggest obstacle to the adoption of personalized medicine in the clinic.
We discussed how personalized medicine can become mainstream. This isn’t about enabling personalized medicine for the few, but using technology and scale to deliver to the many. Doing this right not only will benefit patients, but input at the conference from regulators, drug manufacturers, and payors, told us there are a lot of parties interested in the success of this new paradigm.
Making sense of all this data is a real challenge – how to format; how to integrate? Some contributors spoke of a data-driven industry transformation as has happened in other industries – financial services, retail, and communications. The result has been efficiency and transparency and the appearance of new interested parties – such as those capable of integrating workflow and data.
The need for workflow integration will continue to be important as well. There are many players out there making individual contributions – from platforms, to molecular markers, to infrastructure, ordering, fulfillment, billing, and reimbursement. But who should take on the task of integration – which is surely needed if the benefits and efficiencies of personalized medicine are to be realized?
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