2014: The Year of the Patient

As we reach the end of another year, we once again look back at recent advancements and milestones in the field of personalized medicine. As we celebrated 10 years of progress, we also looked toward the future, identifying changes needed to ensure another decade of discovery. Reflecting upon the highlights of 2014, it is clear that this truly was the year of the patient. A renewed sense of urgency to shift towards a more patient-centered approach to care has been created across the healthcare system.

The following captures highlights from The Age of Personalized Medicine Blog for 2014.

Michael Kolodziej, M.D., National Medical Director for Oncology, Office of the Chief Medical Officer, Aetna, kicked off the year with reflections on the challenges facing the adoption of personalized medicine.

So what are the practical challenges? There are many. And many share the underlying theme that the old paradigms do not work so well. … Perhaps the biggest challenges lie in the area of clinical utility, which impacts providers, payers and regulatory agencies. Patients are impacted in a huge way. Most people have an idea of where we need to go, but we have a shortage of ideas about how to get there. Finally, all of this occurs in the setting of unsustainable growth in health care spending, and the near uniform agreement that we need to spend our money in a more intelligent, impactful way. … We have a lot of work to do together.

In March, we were honored to share the personal and candid story of Stephanie Dunn Haney, a lung cancer survivor, and her experience with molecular testing and targeted therapies. Stephanie’s story continues to remind us of the hope personalized medicine offers to so many.

Molecular testing and personalized medicine gave me my life back, and my sense of a future back. While I’m realistic enough to know that my daughters are fairly certain to lose their mother before they are grown, I also know I have tools to fight with, and a responsibility to share my story.

As we talk about the need to keep the patient at the center of all that we do, we at the Personalized Medicine Coalition (PMC) saw a need to establish a baseline of consumer awareness, knowledge and attitudes about personalized medicine. In July, PMC released a national survey, U.S. Public Opinion About Personalized Medicine, with key findings that will guide future outreach and education efforts.

We’re at the beginning of the golden age of personalized medicine. Armed now with a clear picture of the public’s opinion, we have an opportunity to raise awareness and increase understanding of what personalized medicine is, and how it can transform approaches to healthcare delivery.

Of course, in order to bring molecular tests and targeted therapies to patients, key regulatory and reimbursement areas must be addressed. PMC also published The Future of Coverage and Payment for Personalized Medicine Diagnostics in July, which took a critical look at CMS policies, highlighting specific challenges to the further implementation of personalized medicine diagnostics.  Later that month, the U.S. Food and Drug Administration’s (FDA) released its long-awaited final guidance on the regulation of companion diagnostic devices, as well as proposed framework for regulating laboratory developed tests (LDTs).

Investors have long argued that clarity is necessary in both regulation and reimbursement for continued advancement of personalized medicine. We now have clarity on FDA’s current thinking although many issues remain unresolved. The community has time to consider this framework and may soon have a chance to provide public comments. And finally, the pharmaceutical industry has the FDA’s assurance that targeted treatments will not be held up by co-development challenges.

In October 2014, the PMC, the American Association for Cancer Research (AACR), and Feinstein Kean Healthcare (FKH) convened the second national Turning the Tide Against Cancer national conference, which brought together leaders throughout the healthcare and policy communities for a passionate and engaging discussion on the importance of moving towards a more high-value, patient-centric system of cancer care.

Keynote speaker, cancer survivor, and The New York Times Emmy® Award winning columnist of “Life, Interrupted,” Suleika Jaouad, shared insights into communication challenges patients face during a Q&A session. Suleika’s words serve as a reminder that if we are to increase adoption of personalized healthcare, we must ensure patients are given the tools and education needed to properly understand their treatment options.

Communication is the golden ticket. We live in the WebMD age where patients often consult Google before they consult a doctor. This can be dangerous and can lead to misinformation and misunderstandings. Creating an environment where the patient feels comfortable asking questions and talking to their medical team is crucial.

Following the conference, FKH Chairman, Marcia A. Kean, M.B.A., proposed next steps:

I propose that every individual touched by cancer, and every organization concerned about the nation’s cancer burden, take responsibility for three actions.

1. Review the Issue Brief, and share your thoughts/ideas about the policy options and/or propose other options
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2. Involve your organization in the Turning the Tide Against Cancer Through Sustained Medical Innovation initiative, by participating in our activities and events.

3. Join our partners PMC and AACR and advocate for those options that you agree with, integrating them into your own policy platforms and your communications with policymakers in order to drive momentum and catalyze change.

We encourage you to learn more about the Turning the Tide Against Cancer initiative, and the important work we are doing to make a difference for cancer patients.

As an appropriate end to the year, we celebrated the 10th Anniversary Personalized Medicine Conference in November, and conference organizer Raju Kucherlapati, Ph.D., Paul C. Cabot Professor of Genetics, Harvard Medical School, reflected on a decade of developments in personalized medicine.

The past decade has witnessed many exciting new developments in personalized medicine: the significant reduction in the cost of DNA sequencing and related technologies; the use of these technologies for an unprecedented rate of discovery of human disease genes; a near universal acceptance of the importance of genetics and genomics in drug development, especially for cancer; the levels of investment in personalized medicine companies; recognition of the importance of personalized medicine by professional societies; and the deep involvement by the administrative and legislative bodies in the U.S. and throughout the world.

2014 was a milestone year. We look forward to the year ahead, and the continued opportunity to engage with leaders throughout the personalized medicine community, and across the healthcare system, to discuss the future of personalized healthcare and how we can provide the best value to patients.

No Test, No Drug

It is very difficult to select the appropriate therapy for a patient if you don’t know what disease you are treating. For the practicing physician, the patient’s presenting symptoms, history, physical examination, and radiological and biochemical evaluations typically establish the diagnosis by placing the disease in one of many accepted clinical diagnostic categories (phenotypes). The search for more clearly recognizable, homogeneous patient phenotypes has driven much of our early medical progress. Treating congestive heart failure, for example, is much more productive than trying to treat dropsy; a much older and imprecise collection of not-otherwise-specified edematous conditions.

Have we now arrived at the limit of utility of the descriptive phenotypic disease classification? I suggest that genotypic descriptions based on the root cause, or key molecular attribute, of the disease will rapidly replace phenotype-based disease classifications.  This can’t happen fast enough for those in drug discovery where a drug’s mechanism of action (increasingly derived from genetic considerations) must be matched with a recognized clinical indication.

The transition from phenotype-based to genotype-based indications will not be easy. It was not that long ago that we recognized that several distinctly different genetic alterations can lead to the same clinical phenotype. For example, patients with the same clinical presentation of cystic fibrosis are not expected to respond to a therapy such ivacaftor (Kalydeco, Vertex Pharmaceuticals) unless they have the appropriate CFTR mutations among the many CFTR mutations that cause cystic fibrosis.

We have discovered that patients with the same molecular basis of disease may have distinctly different phenotypes. This means that two patients with markedly different clinical presentations may be responsive to the same therapy specifically directed at their shared molecular basis of disease. While this has yet to be reduced to routine practice, recent discoveries are clearly taking us in this direction.

For example, Kevin Strauss and colleagues at the Clinic for Special Children (Human Molecular Genetics, July 2014) have identified a variant of KCNH7 (which encodes a potentially targetable ion channel) that strongly associates with bi-polar spectrum disorder. Especially noteworthy is their observation that patients with the KCNH7 variant do not present as a single psychiatric phenotype but rather with a variety of axis 1 major affective disorders.

But medical progress in this new era depends upon coordinated activity by multiple stakeholders. In this instance, psychiatrists must be comfortable with genetic classifications of disease and be sufficiently knowledgeable to order the correct drug for patients with similar phenotypes but differing genotypes. The drug developer must have established the safety and efficacy of a new drug in patients with the specific genetic alteration and also potentially have established the lack of efficacy in patients with similar phenotypes but lacking the genotype for which the drug was developed. A diagnostic company must have developed and validated a FDA approved genetic test. Finally, there must be a reimbursement scheme that recognizes the contributions of all of the above parties.

For this to become commonplace, the clinical molecular test (at least in a prototype form) will need to exist once one begins to look for the new chemical entity that will become a drug. This will also mean that we need to invest more in genetic epidemiology. The availability of the drug for the target and the test for the target will be essential in early development, especially if there is a plan to enrich for patients with appropriate particular genotype among those with a similar phenotype.

Does this mean that all new drugs in development need a companion diagnostic? Not just yet, though we may be getting there. There is plenty of disease biology for which a drug can be made but for which a test can’t be found, including in the field of immunotherapy. But even here the secrets that regulate immune response will be revealed and genotype testing will be a prerequisite for prescription writing in this field and in almost all indications.

These and other topics will be explored at the Harvard Personalized Medicine Conference in Boston on November 12-13.

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The Personalized Medicine Conference is an annual two-day event co-hosted and presented by Partners HealthCare Personalized Medicine, Harvard Business School, and Harvard Medical School in association with the American Association for Cancer Research and Personalized Medicine Coalition.

For more information and to register for the 10th Annual Personalized Medicine Conference, please visit http://www.personalizedmedicineconference.org.

The History and Future of Personalized Medicine

Many of us in the genetics and genomics community think that this a golden age for our work. During the last thirty years or so, it has become apparent that genetics plays a very important role in virtually all aspects of human health and disease.

The completion of the human genome sequence at the beginning of this century promised that the use of genetic and genomic tools in understanding the basis for disease and in providing novel approaches to care would become available. It was anticipated that genetic and genomic testing would allow accurate diagnosis of disease, determine the prognosis for the patients with disease, and help physicians make the most optimal choices about how to treat their patients.

This promise launched the era of Personalized Medicine. Several academic institutions embraced this concept. In Boston, Harvard Medical School and Partners HealthCare (the parent organization for several major hospitals in Massachusetts including the Brigham and Women’s Hospital and the Massachusetts General Hospital) launched a new center designated the Harvard Partners Center for Genetics and Genomics (HPCGG), and I had the privilege of being its first Scientific Director.

HPCGG wished to promote personalized medicine and decided that one way to accomplish that goal was to provide a forum for review of the advances in personalized medicine, in all of its facets, and to discuss ways in which the field can be advanced and have an impact on patient care. This vision was shared by a few other organizations including Edward Abrahams of the Personalized Medicine Coalition and Marcia Kean of Feinstein Kean Healthcare. Together we launched the annual Personalized Medicine Conference.

We have always felt that to advance personalized medicine, business had to embrace the concept and find value in investing in this enterprise. To promote that goal, we were joined by Regi Herzlinger, Richard Hamermesh and their many colleagues at Harvard Business School.

In 2014, we are celebrating the tenth anniversary of the Conference as well as the anniversary of the birth of the Personalized Medicine Coalition. The past decade has witnessed many exciting new developments in personalized medicine: the significant reduction in the cost of DNA sequencing and related technologies; the use of these technologies for an unprecedented rate of discovery of human disease genes; a near universal acceptance of the importance of genetics and genomics in drug development, especially for cancer; the levels of investment in personalized medicine companies; recognition of the importance of personalized medicine by professional societies; and the deep involvement by the administrative and legislative bodies in the U.S. and throughout the world.

There have been exciting moments such as the passage of the Genetic Information Non-discrimination Act; the successful launch and execution of whole exome and whole genome sequencing to understand diseases such as cancer and several childhood disorders of unknown etiology; and the development of novel drugs and therapies based on the genetic constitution of individuals or tumors. There are frustrations around the lack of certainty about regulation and reimbursement — but such is progress!

The tenth anniversary of the Personalized Medicine Conference, to be held on the campus of Harvard Medical School November 12-13, 2014, will again bring together leaders from many different areas of personalized medicine and promises to provide a lively forum for exchange of ideas. I personally welcome the opportunity to again host this meeting in November and look forward to seeing you and greeting you there.

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The Personalized Medicine Conference is an annual two-day event co-hosted and presented by Partners HealthCare Personalized Medicine, Harvard Business School, and Harvard Medical School in association with the American Association for Cancer Research and Personalized Medicine Coalition. 

For more information and to register for the 10th Annual Personalized Medicine Conference, please visit http://www.personalizedmedicineconference.org.

Strategies for Accelerating Progress in Personalized Medicine

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.

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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.

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.

Still Skeptical about Personalized Medicine?

Over a 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 long-standing 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 seem 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 of 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.

Join Dr. Stephen Eck on November 28, 2012, when he moderates a panel discussion at the 8th Annual Personalized Medicine Conference hosted by Partners HealthCare Center for Personalized Genetic Medicine, Harvard Medical School, and Harvard Business School.