During a National Institutes of Health Precision Medicine workshop held in Nashville at the end of May, NIH Director Francis Collins, MD, PhD, and Sen. Lamar Alexander (R-Tenn.) discussed the steps necessary to roll out a national effort to deliver highly personalized care.
The Precision Medicine Initiative (PMI) has near-term goals focused on diagnosing and treating cancer and longer-term goals that look to expand the scope to the full continuum of health and disease. In announcing the initiative earlier this year, President Barack Obama highlighted the impact of ivacaftor – a new class of drug to target the underlying cause of cystic fibrosis that is now approved for patients with 10 different mutations to the CF transmembrane conductance regulator (CFTR) gene. For those with one or more of the mutations, ivacaftor has demonstrated improvement of CFTR function and has significantly extended quality and quantity of life.
Collins, a physician-geneticist who is known for his landmark discoveries in disease genes and his leadership in mapping the human genome, said the plan is to launch a million-person (or more) PMI research cohort in the next few months.
“We do expect by the fall to begin the process of implementing what we are designing right now,” Collins said. He spoke from Vanderbilt University where he was onsite for a two-day PMI workshop focused on digital health data and research cohort design.
In order to deliver individually tailored approaches to prevention and risk assessment, health maintenance, diagnosis and treatment, Collins said it was critical to build a large evidence base encompassing gender, race, ethnic, age and geographic variances. By sharing genomic information from participants, along with important clinical data from electronic health records and lifestyle and environmental information from mobile health devices and applications, researchers hope to better understand how genomic variations, in concert with other factors, impact the development and progression of disease.
Some participants will have their entire genome mapped, which has become much more cost effective over the past decade. Collins, who was director of the National Human Genome Research Institute when human DNA sequencing was completed in April 2003, noted that first map cost about $400 million. Today, the price is about $2,000.
Collins said the hope is that individuals already enrolled in several large research cohorts like those with Kaiser Permanente, Mayo Clinic, Geisinger and the Veterans Administration might give permission to roll their data into this national effort. In addition to ‘stitching together’ some of the existing cohorts, Collins noted, “We will also have to find ways to fill gaps and invite highly motivated people who want to take part to come join.”
The goal is for patients at a family practitioner’s office in a small town to be able to participate as easily as those at major academic centers or large health systems. However, Collins stressed, having an electronic health record would be crucial to participation. Even with EHRs, Collins admitted interoperability and data sharing could be an issue.
Alexander, who has been a vocal critic of the current EHR program, said problems ranging from excessive documentation to disrupted workflow to interoperability issues have electronic health records “in a ditch, nationally.”
Alexander, who is the Senate health committee chair, and Patty Murray (D-Wash.) recently announced a bipartisan work group to pinpoint ways to improve EHRs. "The goal of this working group is to identify the five or six things we can do to help make the failed promise of electronic health records something that physicians and providers look forward to instead of something they endure,” Alexander said in announcing the new committee at the end of April.
That work, he noted in Nashville, would be critical to the success of personalized medicine. While there is a long road from the $215 million included in the president’s proposed fiscal 2016 budget for PMI and congressional approval, Alexander did say this was an area where bipartisan support exists. ”Precision medicine – tailoring treatments and cures to individuals – has the potential to affect and improve the life of every American,” he said.
Another concern addressed by Alexander and Collins was the impact … in terms of time and cost … of creating new therapies tailored to smaller numbers of people.
“I’m working with Sen. Patty Murray, the committee’s top Democrat, to examine how we can get safe, cutting-edge drugs, medical devices, and treatments from the discovery process through the regulatory process into medicine cabinets and into doctors’ offices more quickly,” Alexander said. He added work groups currently are looking at ways to lower costs and shorten timeframes while maintaining safety. “We hope to have that legislation ready by the first of next year,” Alexander said.
Collins noted precision medicine might actually help get more drugs on the market. “The era of blockbusters may no longer be one that is going to apply as we understand more and more differences between people,” he said.
“But look at it the other way,” he continued, “The failure rate in developing a new therapeutic is about 99 percent.” Collins noted after spending an average of 14 years from idea through human trials, most therapeutics don’t wind up approved. “That’s why the cost of the whole pharmaceutical industry is so high … because you have to pay for all those failures,” Collins said. “What precision medicine gives you is an opportunity, first of all, to pick the right target because we really understand at a much more detailed level what is happening with diabetes or cancer or heart disease.”
He added researchers not only start with more evidence before embarking on developing new therapeutic agents, but they also have the ability to pick groups that fit the target profile. A drug crafted to impact a specific mutated gene would not be tested in patients without that genomic profile. “”That means you can run a clinical trial that is much smaller, and therefore much cheaper … and you also will have a much higher likelihood of success.”
Collins pointed out such a drug used in a broad trial, as is often the case now, might look like a massive failure because it only worked 10 percent of the time. However, he added, if only tested in the 10 percent of patients that fit the target profile, that ‘failure’ suddenly becomes a roaring success.
For more information on Precision Medicine Initiative and upcoming workshops, go online to nih.gov/precisionmedicine.
RELATED LINKS:
White House PMI Page:
Dr. Collin’s Perspective Article in the New England Journal of Medicine (Feb. 26, 2015):
http://www.nejm.org/doi/full/10.1056/NEJMp1500523?query=featured_home
