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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.

 

 

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.
 

 

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...). 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?

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.

 http://www.businessweek.com/news/2012-11-06/my-dna-results-spur-alzheimer-s-anxiety-at-12-000-cost

 

 

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.
 

 

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?