Archives for August 27, 2013

Precision vs. Personalized Medicine: What’s The Difference?

The age of Personalized Medicine arrived in 2001, following the completion of the Human Genome Project and the publication of the human genome in the journal Science. But a highly anticipated report released in March by the American College of Medical Genetics and Genomics is bound to stir polarizing views about Personalized Medicine in the coming weeks. It certainly raises questions about whether we truly are in an era of Personalized Medicine. Or are we, as I believe, moving toward a future in which Precision Medicine will prevail?

The Back Story on Personalized Medicine

Personalized medicine has grabbed a lot of attention in recent years. It’s the ability to individually profile how genes are put together in sequence. Personalized medicine defines how the expression of these genes will enable physicians to more accurately diagnose and classify diseases and personalize treatment of patients based on this information.

In theory, Personalized Medicine creates a cultural shift within medicine. It would allow physicians to go beyond the “one size fits all” treatment model that’s proven ineffective and that can also lead to undesirable side effects without any benefit from the treatment.

Genetic profiles can help physicians better discern subgroups of patients with various forms of cancer, in addition to other complex diseases. The profiles help guide doctors with more accurate forms of predictive and preventative medicine.

That’s the theory behind Personalized Medicine. However, in practice, few of us are carrying around our genetic profiles when visiting a doctor or when we need urgent care. Though the costs of obtaining genetic profiles have dropped significantly, it’s still too expensive for most people.

Also, the understanding of the biological complexity of our genetic makeup is incomplete. We still don’t which gene or combination of genes are involved in the majority of common, serious diseases, such as diabetes. The role environment factors play is still unknown as well.

The Ethical Discussion About Personalized Medicine

A recent twist to the whole genome-wide sequencing that underlies Personalized Medicine is the concept of incidental findings. The name implies something (usually a mutation) within your genetic sequence that wasn’t anticipated and that predisposes you to a disease other than the one you were being originally screened for.

The topic of incidental findings was explored in the American College of Medical Genetics and Genomics report delivered at its annual conference in March. The report recommends telling patients of incidental findings, even if those findings wouldn’t affect the patient for years—and even if the patient states up front they don’t want to know about any incidental findings.

Incidental findings and their disclosure create a completely separate ethical discussion associated with Personalized Medicine, which is already being discussed in the media. (See the blog by Geneticist Ricki Lewis in Scientific American for a distillation of some of the major points of the AMCG Report). While our scientific and technological advances are making personalized medicine more “real”, however, like with many significant advances there still is a need for physicians and society to catch up. Therefore, while Personalized Medicine sounds exciting and may one day be the standard of care, that day is not today.

Precision Medicine: A Re-Branding of Personalized Medicine?

Precision Medicine is a modified Personalized Medicine. It focuses on patient groups or populations, one step up from the individual focus of Personalized Medicine. Some have called Precision Medicine a re-branding of Personalized Medicine. I don’t believe that’s the case, however.

The concept of Precision Medicine has been around for many years, though it only recently became a more commonly used term among physicians and scientists following the 2011 National Academy of Sciences report, Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. The NAS report defines Precision Medicine as “the use of genomic, epigenomic, exposure, and other data to define individual patterns of disease, potentially leading to better individual treatment.”

The report envisions disease diagnosis as patient-centered and multifaceted, rendered by physicians with access to the latest scientific and technological advances, which in turn will lead to dramatic improvements in patient health. In other words, Precision Medicine is good for patients, doctors and the healthcare system. But as the report points out, these advances haven’t yet made it into clinical medicine in the form of better diagnostics or treatments for patients.

In clinical research, however, biotech and pharma companies are driving clinical development programs forward primarily in oncology. The programs combine targeted therapies with companion diagnostics designed to identify patients with the genetic mutation being targeted. That should make it easier to detect an effect—which is the very nature of Precision Medicine.

Plans to implement the 2011 report’s recommendations are underway. In May, the University of California-San Francisco (UCSF) will host a two-day OME Precision Medicine Summit. (UCSF’s Chancellor Sue Desmond-Hellman, MD, MPH, is co-chair of the NAS committee that generated the 2011 Precision Medicine report and is my former boss at Genentech.) The summit will bring together more than 150 thinkers, creators and innovators from the fields of bioinformatics, biotech, economics, and genomics. The summit’s goals are:

Solidifying a network of people across multiple sectors and organizations who are committed to the cause;

Designing actionable experiments and initiatives that will be implemented after the event; and

Launching an entity to guide, support and help integrate ongoing efforts.

Clearly, the academics are moving forward with Precision Medicine initiatives. Will the industry follow? Pharmaceutical R&D productivity has declined over the last two decades despite increasing investments. Many pharma and biotech companies have realized that after years of clinical trial failures costing millions of dollars, there must be a better way!

Why the Delay in Moving To Precision Medicine?

As its name implies, Precision Medicine requires the development of precise diagnostic tools and criteria (such as genetic testing), identification of relevant drug targets within the diseases, and selection of the right patients to include in clinical trials. The application of these three items should lead to a much higher success rate for drugs and a greater return on investment for each research dollar the industry spends. Companies such as Pfizer are committing significant resources into Precision Medicine and have several success stories already to show for it (Dolsten and Sogaard, 2012). Genentech is considered the original success story in support of Precision Medicine, with the development and approval of Herceptin in patients with HER-2+ breast cancer.

So, why the delay in moving toward Precision Medicine?

First of all, it takes time and resources to acquire the necessary Precision Medicine infrastructure and capabilities within an organization. Second, this approach requires a paradigm shift in the industry, as patient enrichment strategies limit the population eligible for inclusion in clinical trials. Ultimately, you’re effectively reducing your market size once a drug is approved. That means the possibility of having a billion+ dollar-a-year drug, which is the goal of many companies, will become less likely.

However, balance this against the extremely high failure rates associated with big market drugs. Add in the potential cost and time savings gained by having smaller, focused clinical trials that complete more rapidly, with a higher probability of success. When you do that, it becomes abundantly clear that the time for Precision Medicine is now.