Precision Medicine: A Seismic Shift in Treatment Strategy

President Obama’s endorsement of an initiative to promote the study and implementation of precision medicine in his State of the Union address didn’t attract much mainstream media attention, but according to many medical researchers, precision medicine offers tremendous promise for improving the treatment efficacy for a host of diseases — from cancer to autoimmune disorders. And, yet, this is no “war on cancer” or a manned mission to the moon. While President Obama promises a revolution in medical care, he proposes doing it for an extremely modest financial investment.

The president’s proposal is to build on existing medical treatments and technology but apply them in an exponentially more efficient method using the power of modern databases to maximize effectiveness. This approach of adopting a new treatment philosophy built on present and upcoming technologies applied in novel ways is reflected in the funding the White House has proposed for the Precision Medicine Initiative, which includes no money for new primary research into treatments. Indeed, the president’s $215 million pledge toward the Precision Medicine Initiative is less than 1 percent of the National Institutes of Health’s (NIH) annual budget of more than $30 billion.¹

What Is Precision Medicine?

Since it’s a fairly recent concept, the term “precision medicine” remains somewhat fluid and amorphous, with nearly as many different definitions as there are people offering them if the search engines are to be believed. But, as invoked by the president, and as increasingly used by the scientific and medical communities involved in the president’s initiative, precision medicine signifies the use of advanced genetic and biochemical analysis of a specific patient to implement a treatment plan offering the best chance of success. According to a White House fact sheet on the initiative: “Precision medicine gives clinicians tools to better understand the complex mechanisms underlying a patient’s health, disease, or condition, and to better predict which treatments will be most effective.”¹

Writing in the New England Journal of Medicine, Dr. J. Larry Jameson of the Perelman School of Medicine at the University of Pennsylvania and Dr. Dan L. Longo of the Dana-Farber Cancer Institute in Boston gave a more technical description. In their article, they wanted to differentiate precision medicine from the existing concepts of “personalized medicine” and “individualized medicine,” which many physicians have been employing for decades. They defined precision medicine as “treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations.”²

In practice, this means moving away from the historic (and current) one-size-fits-all approach toward treating disease, in which the treatment that has been most successful on the most patients is tried first on all patients, and if it fails, then other treatments or drugs are tried.³ As the president of the Lupus Foundation of America points out, this generalized approach to treating autoimmune diseases (to offer but one example) costs money and, all too often, lives.⁴

Precision medicine offers the promise of being able to tailor-fit a treatment program offering the best odds of success in an individual patient before treatment even begins, minimizing the trial-and-error portion of the treatment process. For this to occur, physicians — both primary care and specialists — will need access to exponentially greater amounts of data, from genetics to pharmacological trial results.

Precision medicine is nothing less than the application of information technology to the field of medicine. After all, if IT models can allow online retailers to predict consumers’ buying habits to the point of having packages ready to ship before they’re ordered, it’s easy to see why proponents of precision medicine are excited about harnessing that kind of data-driven predictive computational power to the medical field.⁵

How Is the Initiative Being Carried Out?

The president’s initiative carved up the $215 million allocation between the NIH, the National Cancer Institute (NCI), the U.S. Food and Drug Administration (FDA) and the Office of the National Coordinator (ONC) for Health Information Technology.

The $130 million NIH component of the initiative will create a one-million-strong volunteer force of study patients, both healthy and ill, as a “biobank” to establish a baseline of data, including genomes and medical histories, and, perhaps, lifestyle, diet and exercise information. Many of these volunteers will be drawn from those already enrolled in existing studies, extending the reach of the program while controlling costs. NCI will receive $70 million to complete the Cancer Genome Atlas, create a shared database and accelerate clinical trials of promising new treatments.⁶ FDA will receive $10 million to create new databases of other genetic mutations that can lead to disease such as those causing cystic fibrosis. And the ONC for Health Information Technology is charged with ensuring that all this new data is treated with respect for privacy.

NIH Director Dr. Francis S. Collins and former NCI Director Dr. Harold Varmus explain in an opinion piece in the New England Journal of Medicine that the primary impetus of the initiative will be on immediate advances in treating cancer, with a parallel goal of achieving increased efficiencies across all disease treatments. Cancer is a particularly promising avenue for applying principles of precision medicine, they wrote, because many of the latest treatments target specific molecules in malignant cells.⁷ Conducting lab work to determine the biomolecular makeup of a tumor to determine treatments is already becoming standard practice in oncology.

The expectation of the president’s initiative is that this $215 million in federal spending will serve as seed money, spurring much greater spending by the private sector — universities, private researchers, hospitals, pharmaceutical companies and more — to incorporate principles of precision medicine into their ongoing work.¹

The Promise of Precision Medicine

In their analysis of the promise of precision medicine, Drs. Jameson and Longo point out that it is entirely possible — and perhaps likely — that ongoing technological advances in the medical field will have a disruptive impact similar to what digital cameras had on the photography industry a decade ago.² And, a Forbes blog by David Delaney, chief medical officer of German software giant SAP, echoed that argument: “Precision medicine ultimately has the potential to improve both quality and quantity of a patient’s life and also have a ripple effect on the economics of the entire healthcare system. With better, faster treatment and less wasted on ineffective therapies, costs will be better controlled. More effective therapies and better prevention and control of chronic illness will result in fewer and shorter hospital stays and a shift from expensive reactive care to prevention.”⁸

The fact that software companies now have chief medical officers — that SAP is rolling out database management products to cancer research labs and clinicians — may be more powerful testimony about the changing face of medical care than anything published in the medical community. Still, Drs. Jameson and Longo point out that it is the primary care physician and the specialist who will face the most change and challenge in the shift to precision medicine: “They stand on the front lines of the clinical care delivery system with a mandate to prevent disease, identify early signs of disease, and navigate referral paths that now have many more branches as a result of precision medicine. Increasingly, referral pathways will be needed to help connect selected patients to an expert with increased access to the emerging data and clinical guidelines.”⁸

But just as the digital revolution ultimately made photography more affordable and, thus, more popular, precision medicine, they argue, will ultimately provide more effective treatments that increase our quality of life — another point also echoed by Delaney. In fact, Drs. Jameson and Longo are possibly even more effusive in their praise of the promise of precision medicine than are the politicians. From autism to epilepsy, Alzheimer’s disease to cystic fibrosis, ongoing research into the chemical and genetic changes that either cause or indicate these diseases offers hope for cures formerly undreamed of. But those cures, which attack disease at the molecular level, will increasingly be targeted at smaller and smaller groups of patients, requiring physicians to navigate an increasingly complex pool of data in designing effective treatment regimens.

Applying Precision Medicine

A few specific examples of how precision medicine is foreseen by its proponents may provide the clearest illustration of both the promise and the challenges.

The Rutgers Cancer Institute of New Jersey describes one model for delivering precision medicine. In this model, a cancer clinic holds weekly team meetings, bringing together representatives from radiology, surgery, pathology, systems biology and the IT department. At these meetings, any new biomarkers discovered through sequencing would be discussed to see if any member of the team sees new treatment options suggested by these discoveries — whether an already approved therapy, or enrollment in a clinical trial.³

With genome analysis now taking a month or even less, a tumor can be classified down to the molecular level in a timely enough manner to incorporate into a patient’s treatment in real time.³ Again, though, knowing which drugs may interfere with that newly discovered molecule’s normal function requires access to vast amounts of data — all the molecular data for every drug ever submitted to FDA.

This proposed process came to fruition this summer in an unrelated study when researchers discovered that the drug ibrutinib (Imbruvica) is effective against a specific type of diffuse large B-cell lymphoma. The drug locks up an enzyme called Bruton’s tyrosine kinase (BTK) in the cancerous cells, preventing their survival. Testing to determine if a lymphoma patient’s malignant cells have BTK will now allow oncologists to immediately move to treatment with ibrutinib, or cross it off the list and move on to the next possible treatment.⁹

In Great Britain, women diagnosed with breast cancer now routinely have a genetic test performed on the malignancy to see if it contains the HER2 gene. If multiple copies of the gene are discovered, oncologists can immediately begin treatment with trastuzumab (Herclon, Herceptin), which is known to be effective against these tumors. Beyond cancer, precision medicine is now being used to treat other genetically carried diseases as well. Cystic fibrosis patients who carry the so-called “Celtic gene” are now being treated with ivacaftor (Kalydeco).¹⁰

While only about 5 percent of all cystic fibrosis patients have that gene, it is an important illustration of how precision medicine can eliminate the individual trial-and-error process of treating each patient by moving directly from diagnosis to effective treatment.

What’s Next?

As with the analogy to digital photography above, making hard and fast predictions is foolhardy. When NASA developed the first digital camera for use on the Mariner 4 space probe in the early 1960s, few would have thought that 40 years later film cameras would be the domain of hobbyists or that our cell phones would take better photos than a 35mm camera of a generation earlier.

Precision medicine is in its infancy, but when it works, the combination of efficacy and cost-effectiveness makes it difficult to top. The era of the generic “miracle drug” that can cure dangerous diseases in the population at large may not be over, but it does seem highly likely that it is going to at least share the stage (and funding) with narrowly tailored (i.e., precise) drugs that are very effective for a relatively small number of patients.

While precision medicine has already found its early successes — from the HER2 gene in breast cancer to the Celtic gene in cystic fibrosis — millions of other patients await a cure or successful treatment. From lupus to diabetes, epilepsy to rheumatoid arthritis, there are hundreds of diseases with a genetic component that can potentially be cured through the processes of precision medicine described above. Even chronic infectious diseases like HIV or hepatitis that currently have no cure may yet be successfully attacked someday with drugs that operate at the molecular level. But once those treatments are developed, tested and approved, it will then take the infrastructure of precision medicine to get that information out to the physicians on the front lines so that all patients benefit from these advances.