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 9^th Annual Personalized Medicine Conference on November 6^th 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 21^st 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.

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Harvard Medical School, Harvard Business School and the Partners HealthCare System in Boston will convene the 9^th Annual Personalized Medicine Conference on the campus of Harvard Medical School this November 6 and 7. As has been the practice since the Conference’s inception, this year’s meeting is in association with the Personalized Medicine Coalition (PMC). For the first time, we also welcome the participation of the American Association for Cancer Research (AACR), a member driven organization that has been dedicated for more than a hundred years to promoting cancer research and cancer care, as a co-convener.

For more information and to register for the 9^th Annual Personalized Medicine Conference, please visit www.personalizedmedicineconference.org.

Levin, O’Kelly Provide Perspective on Decades of Personalized Medicine Progress, Urge Action and Support

On Tuesday, May 8, 2012, the Personalized Medicine Coalition (PMC) welcomed our chairman, Stafford O’Kelly, President of Abbott Molecular and keynote speaker, Mark Levin, Partner and Co-Founder of Third Rock Ventures to its Eighth Annual State of Personalized Medicine Luncheon. The event brought together PMC’s members, partners and other stakeholders involved in realizing the future of personalized medicine for researchers, industry leaders, patients, caregivers, advocates and policymakers.

Stafford O’Kelly reminded us, in his introductory remarks, of the progress and success we’ve made toward achieving personalized medicine in practice within the past year alone. Just last week we saw that Xalkori is showing progress in fighting certain childhood cancers. O’Kelly pointed out the assurances by the FDA that co-approval of drugs and diagnostics will occur more frequently. He also challenged attendees to think about what they can do “to accelerate the shift toward personalized medicine in a way that will improve treatment outcomes for the patient while, at the same time, lower overall costs for our health care system.”

Mr. Levin sought to use his significant experience and background in venture capital, product development and marketing to answer O’Kelly’s provoking question during his keynote address. He urged attendees to support personalized medicine. He explained that “personalized medicine is one of the most important things in medicine today” and lauded its potential to reduce safety challenges, increase efficacy, and improve productivity in the pharmaceutical industry.

I agree that we are at a point where the scientific and clinical progress made in personalized medicine is undeniable. But to echo Stafford O’Kelly’s call to action:  “We need to get the right stakeholders involved to help develop pathways for accelerating growth in the field….We need commitment from payers, providers and patients.”  In order to continue to make progress against disease and improve outcomes for patients, it is necessary as O’Kelly and Levin said, for the entire ecosystem of players to focus efforts in the direction that scientific discovery points us – toward targeted, patient-centric approaches to research and care.

We hope to continue the discussion around these themes and the future of innovation, specifically in cancer research and care at “Turning the Tide Against Cancer Through Medical Innovation,” a national conference that the Personalized Medicine Coalition, American Association for Cancer Research and Feinstein Kean Healthcare are co-hosting on June 12, 2012.  I encourage you to join us in Washington, D.C. as we look to identify and build support for an environment that sustains innovation and drives our evolution toward personalized cancer care.

PCORI Research Priorities, Will They Support Personalized Medicine?

The Board of Directors of the Patient-Centered Outcomes Research Institute (PCORI) met last week, outlined research priorities, and asked for public feedback. What I found most interesting, and a little disheartening, is that the priorities are drafted in vague language, making it difficult to determine how they may (or may not) support personalized medicine.

I hope that as PCORI moves forward, it will give assurance to the Personalized Medicine Coalition (PMC) and other stakeholders that its research supports personalized medicine, as was the intent of Congress at the time of the Institute’s formation.

Specifically, research conducted in the category, “Comparative Assessment of Options for Prevention, Diagnosis, and Treatment,” will compare treatments, but at what level?  Researchers now know more about individual response to some drugs based on biomarker information. For example, when comparing a red pill to a blue pill, it is imperative that biomarker information be included in those examinations, especially when biomarker information is in the label for the drug. A list of drugs with biomarker information in the label can be found on pages 20-25 of The Case for Personalized Medicine, 3^rd edition. But, without clearly defining the details of PCORI’s research, we really can’t know whether or how the Institute will consider biomarker information in its priorities and research agenda.

The research priority “Improving Healthcare System” can support patient-centered care through innovations, but how? PMC suggests that the research be predictive, preventative, personalized and participatory. By emphasizing the “4Ps,” health system evaluation can support personalized medicine. However, without getting more specific about research priorities, we don’t know whether PCORI will include research that addresses these aspects of care delivery.

To support personalized medicine, the “Communication and Dissemination Research” priority should require researchers to answer one question: “Why does this treatment work and for whom?” (or, more frequently, “How likely is this treatment to work for me, and what are the potential trade-offs?”).  It is not enough, in the PMC’s opinion, to say that one therapy works for most people. PMC suggests that the research should explain why a therapy works (or is more likely to work) and for whom. For example, in research comparing red and blue pills, the communication and dissemination of the research results should stress that although the red pill works for most, the blue pill is particularly effective for people with a specific biomarker.

We are at a pivotal stage in the design of an entity that is tasked with assisting patients, clinicians, purchasers and policymakers in making informed, evidenced-based health decisions. PCORI could foster research that answers the important questions about what interventions work, and for whom. Or, PCORI could be another investigator-driven research institute that allows funded researchers to pursue questions of great scientific import, regardless of their practicality. Such a mission would be redundant with many others, most notably the National Institutes of Health, would be less likely to result in a cohesive national research program, and less likely to ensure personalized medicine is appropriately integrated.

It is my hope that PCORI supports the science that will drive personalized medicine forward, and will engage stakeholders in driving personalized medicine forward, by proposing specific research priorities and research questions to get answers to the questions that science, medicine and, ultimately, patients demand.

The Role of Comparative Effectiveness Research in Total Cancer Care™

In my previous entry, I discussed how the launch of the Total Cancer Care™ initiative at Moffitt Cancer Center nearly eight years ago led to the development of one of the largest prospective observational studies in the world.  Through the enrollment of more than 60,000 patients and collection and genetic profiling of tens of thousands of tumors, Total Cancer Care™ collaborators have generated a vast information system to be leveraged as a clinical decision tool, and as a means of quality performance and comparative effectiveness research (CER).

One of the stated aims of Total Cancer Care™ is to raise the standard of care for all patients by integrating new technologies in an evidence-based approach to maximize benefits and reduce costs.  Although we developed this aim over seven years ago, I believe it is completely consistent with the current definition of comparative effectiveness being used by AHRQ and other policymakers. 

As I mentioned in my previous entry, strategic partnerships are an essential component to achieving the goals of Total Cancer Care™, and this is clearly demonstrated in our efforts in CER. Dr. David Fenstermacher and colleagues from Moffitt as well as the Institute of Human and  Machine  Cognition (IHMC), in Pensacola, Fla., are collaborating on a major NIH/NCI grant to enhance the Total Cancer Care™ infrastructure to support CER by expanding data management resources, integrating  automated data extraction methodologies (including natural language processing technology a particular area of expertise for IHMC), and creating user interfaces to data for researchers, clinicians and even patients. 

A major focus of our current efforts in CER is to determine the information and technology gaps in the CER infrastructure for data capture and data sharing.  Ultimately, it will be important to involve the community at large who are enrolling patients in the Total Cancer Care™ Protocol so that they can use the Total Cancer Care™ data warehouse as a decision tool based on evidence generated by the study itself.  The importance of the community network cannot be over emphasized both for populating the Total Cancer Care™ biorepository and database, and the ultimate utilization of the information and evidence generated for delivering the right treatment for the right patient.

To enhance Moffit’ts ability to establish this large research initiative the cancer center formed a wholly owned for-profit company, M2Gen, in 2006.  Merck and Co., Inc., through a Merck affiliate, signed on as our ”Founding Collaborator”. This experience has taught us how to service a global healthcare client and produce measurable scientific insights to accelerate drug candidates through translational medicine advances.

Using Cancer(s) as a Model for Advancing Personalized Medicine

I am pleased to be attending this year’s Personalized Medicine Conference taking place this week and appreciate the opportunity to discuss why I, and many others, believe that cancer, or to be more accurate “cancers”, are an ideal model for the discovery, translation and delivery of personalized medicine.  Sheer numbers alone are reason enough to highlight the need for developing a personalized approach to cancer care: 1 out of 2 men and 1 out of 3 women will develop cancer in their lifetime in the United States.

The sequencing of the human genome has unraveled many mysteries as to how a normal cell can go awry and become cancerous. Further understanding of not only the genetics of cancer, but also the biology and metabolism of cancer, have increased our knowledge of biologic systems that support cancer progression, and this new knowledge has been translated into novel strategies for early detection, prevention and treatment.  And yet, these new discoveries that have heightened expectations of success have, in large part, fallen short in delivering cures anticipated by society.  The reality is that we have learned that cancer is actually an array of many diseases masquerading under the single name of “cancer.”   We need to learn to embrace the complexity of this disease we call cancer and stop the attitude of tunnel vision to cure cancer, and instead focus more on caring for the patient, the individual.  National policy must promote the search for solutions, not just cures.  Ultimately by providing solutions, we will reduce, and in many cases, eliminate death and suffering due to cancer.

In order to accelerate what is a continuum of discovery, translation and delivery of personalized medicine, or in this case personalized cancer care, multiple stakeholders must come together to pursue and deliver this common goal.  These stakeholders include researchers, clinicians, administrators (including policymakers and regulators), and of course, patients themselves.  This week’s gathering of the personalized medicine community in Boston is an example of the value of physically bringing together these stakeholders, and is an important forum for the discussion, exchange of ideas, and aligning of objectives that are crucial to the advancement of personalized medicine.

Total Cancer Care: An Approach to Creating Solutions for the Advancement of Cancer Research and Improved Care

Building on the themes of this year’s event – Personalized Medicine: Impacting Healthcare – I would like to describe to you one approach to personalized cancer care that is having a significant impact on the lives of patients. Nearly eight years ago, the Moffitt Cancer Center in Tampa, Fla., launched the Total Cancer Care™ initiative with the goal of identifying all the needs of a patient and developing a means to meet those needs.  By focusing on solutions to meet individual needs, we believed we could reduce death and suffering due to cancer, and that in order to do so we needed to develop strategic partnerships to perform the five following aims:

1. Create a system to identify the needs of individual patients
2. Identify markers that would predict needs and risks so that interventions could become preemptive
3. Identify molecular signatures for patients who are not likely to respond to standard of care
4. Utilize clinical characteristics and molecular profiling techniques to match the right patient to the right treatment at the right time and the right place
5. Raise the standard of care for all patients by integrating new technologies in an evidenced based approach to maximize benefits and reduce costs

Critical to the pursuit of these solutions was the development of a large regional cancer biorepository in parallel with the development of a relational data warehouse and an information system containing patient’s clinical data and molecular data. 

We soon recognized that although Moffitt had a large patient population to study and engage in this endeavor, to accomplish our goal, we ultimately needed hundreds of thousands (if not millions) of patients to study, and we sought the advice and support of our Florida network of hospitals and physicians.  To our pleasure, there was universal enthusiasm from our statewide colleagues to participate in what became the Total Cancer Care™ Protocol.  Dr. Tim Yeatman at Moffitt was the original Principal Investigator of this IRB- approved protocol which enrolled its first patient in 2006 and basically asked for patients’ consent to do three things:

1. Can we follow you throughout your lifetime by collecting and storing your clinical data and information?
2. May we study any excess tumor or normal tissue using molecular profiling techniques?
3. May we re-contact you?

What began at Moffitt within a year had been extended to eight different communities in Florida.  Within two years, this effort expanded to nine more communities in 10 different states, for a total of 18 participating sites.  Together, the 18 different sites form the Total Cancer Care™ Consortium with the aim of informing and consenting patients to the Total Cancer Care™ Protocol.  As of November 1, 63,754 patients have consented to the Total Cancer Care™ Protocol; 21,331 tumors have been collected and stored in a high technology biorepository located at Moffitt; and 15,093 tumors have been profiled using gene expression profiling technology.  To my knowledge, this effort makes Total Cancer Care™ one of the largest, if not the largest, prospective observational studies with tumor collection in the world. 

Ultimately, our community colleagues are not only contributors to establishing the foundation of personalized cancer care, but also the beneficiaries by being able to use the information system as a clinical decision tool, and as a means of quality performance and comparative effectiveness research.

In coming weeks, I am looking forward to further discussing the role of comparative effectiveness research in Total Cancer Care ™, and how the patient is not only a participant, but also the ultimate beneficiary of everything we do.

Health IT to the Rescue: Managing Data in the Age of Genomics

The 10^th anniversary of the drafted human genome, released by the Human Genome Project in 2000, is a milestone for personalized medicine.  Our mantra – “get the right intervention to the right patient at the right time” – all but mandates the roll-out of genomic information in clinical practice.  As we come closer to the goal of the $1,000 genome, I can now imagine a world in which an individual genomic profile allows us to tailor cancer treatment to a patient’s personal situation. In the next decade, genomics will provide us with the opportunity to refine treatment planning so that we use drugs when they are going to work, spare patients unnecessary side effects, and avoid wasting precious time, emotional resources, or funds on drugs that are unlikely to be effective.  Even intimately personal decisions, such as how to preserve fertility, can be elucidated by and based on genomic data mixed with an understanding of effectiveness and toxic risk.  

Coexisting with excitement at the possibilities of genomically-guided personalized medicine is a pervasive angst.  The profusion of new information can be daunting.  How will I know all of the relevant inputs into decision-making in the era of personalized medicine?  How will I balance multiple important factors for each patient, without a roadmap or algorithm for this new type of clinical decision-making?  In personalized medicine, when treatment choices rely on unique genomic data for each patient, the quantity of potential data points to be factored into any single clinical decision boggle the mind.  How can I intelligently coordinate and consider all of this data?

Recent progress in health information technology (HIT) and in advancing our country’s data infrastructure provide hope that technology may come to the rescue, saving us from a morass of data and helping us make sense of the new plethora of information.  The Human Genome Project yielded vast amounts of data; its completion required development of interoperable data, novel statistical methods, and new HIT systems.  These same tools can also help us use genomic information, as well as rapidly increasing bodies of clinical and research evidence, to inform decision-making.  Genomically-guided biomarkers and predictive tests will help generate personalized information, but tools will be needed to help clinicians understand and use the resulting data, integrated with myriad other personal data types like blood chemistries, clinical exam findings, pre-existing toxic exposures over a life-time, and patient reported concerns. The development of personalized clinical decision support tools and prediction models, tailored and designed for efficient use at the point of care, will assist us in connecting the dots between the promise of The Human Genome Project and the vision of personalized medicine. May this 10^th anniversary energize us to move from theory to action, and to strive for ever more finely individualized care that optimizes outcomes for our patients.

Major Studies Highlight Gains in Personalized Medicine for Lung Cancer and Heart Transplant Patients

Two important studies announced in recent weeks illustrate how continued progress is personalized medicine is leading to better patient care. 

The first study, published in the New England Journal of Medicine, demonstrated that XDx’s AlloMap® gene test is as effective as biopsies in helping doctors identify organ rejection in heart transplant patients, thereby offering patients a non-invasive alternative to painful routine biopsies of heart muscles. Instead, AlloMap, a blood test based upon 11 genes that regulate immune system processes, allows doctors to determine a patient’s overall risk of rejection.

When presenting the results of the study at a meeting of the International Society for Heart & Lung Transplantation, the lead researcher Michael X. Pham of Stanford University Medical Center said, “We found that you’re not going to harm patients by reducing the number of biopsies.” 

The results of a second landmark study were presented at the annual meeting of the American Association for Cancer Research (AACR). In the BATTLE (Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination) study conducted by researchers at the University of Texas M.D. Anderson Cancer Center, tumor biopsies were gathered from 255 patients with advanced lung cancer as they enrolled in the clinical trial. The first 40 percent of patients enrolled in the study were randomly assigned one of four therapies: erlotinib (Tarceva), sorafenib (Nexavar), vandetanib (Zactima) or a combination drug, Targretin (erlotinib with bexarotene). After eight weeks (an accepted indicator for overall survival), the researchers used diagnostic imaging to assess the effectiveness of the assigned treatments. Together with information from the biopsies collected at the beginning of the study, this information on outcomes was then used to assign a particular treatment to new patients enrolling in the clinical trial with similar tumor types – therefore, assigning a drug that had worked effectively for earlier patients with the same tumor biomarkers.

By employing an adaptive clinical trial design, the researchers were able to pave the way forward for a treatment approach to be determined based upon the genetic characteristics of the tumor type, thus circumventing a trial-and-error approach that patients facing a deadly disease cannot afford. In the end, almost half the patients achieved disease control in eight weeks, compared to 30 percent when biomarkers are not a part of treatment decisions.

These studies add to the growing list of recent advances in personalized medicine. More advances are on the horizon that will give physicians and patients new tools to select the right treatment for the right patient at the right time.