[Senate Hearing 114-606]
[From the U.S. Government Publishing Office]

                                                        S. Hrg. 114-606

                         MEDICINE FOR PATIENTS



                                 OF THE

                          LABOR, AND PENSIONS

                          UNITED STATES SENATE


                             FIRST SESSION




                              MAY 5, 2015


 Printed for the use of the Committee on Health, Education, Labor, and 


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                  LAMAR ALEXANDER, Tennessee, Chairman

MICHAEL B. ENZI, Wyoming             PATTY MURRAY, Washington
RICHARD BURR, North Carolina         BARBARA A. MIKULSKI, Maryland
JOHNNY ISAKSON, Georgia              BERNARD SANDERS (I), Vermont
RAND PAUL, Kentucky                  ROBERT P. CASEY, JR., Pennsylvania
SUSAN COLLINS, Maine                 AL FRANKEN, Minnesota
LISA MURKOWSKI, Alaska               MICHAEL F. BENNET, Colorado
MARK KIRK, Illinois                  SHELDON WHITEHOUSE, Rhode Island
TIM SCOTT, South Carolina            TAMMY BALDWIN, Wisconsin
ORRIN G. HATCH, Utah                 CHRISTOPHER S. MURPHY, Connecticut
PAT ROBERTS, Kansas                  ELIZABETH WARREN, Massachusetts
BILL CASSIDY, M.D., Louisiana

               David P. Cleary, Republican Staff Director
                  Evan Schatz, Minority Staff Director
              John Righter, Minority Deputy Staff Director

                            C O N T E N T S



                          TUESDAY, MAY 5, 2015


                           Committee Members

Alexander, Hon. Lamar, Chairman, Committee on Health, Education, 
  Labor, and Pensions, opening statement.........................     1
Murray, Hon. Patty, a U.S. Senator from the State of Washington..     3
Hatch, Hon. Orrin G., a U.S. Senator from the State of Utah......    22
Franken, Hon. Al, a U.S. Senator from the State of Minnesota.....    23
Cassidy, Hon. Bill, a U.S. Senator from the State of Louisiana...    25
Bennet, Hon. Michael F., a U.S. Senator from the State of 
  Colorado.......................................................    27
Collins, Hon. Susan M., a U.S. Senator from the State of Maine...    29
Warren, Hon. Elizabeth, a U.S. Senator from the State of 
  Massachusetts..................................................    30
Whitehouse, Hon. Sheldon, a U.S. Senator from the State of Rhode 
  Island.........................................................    32
Baldwin, Hon. Tammy, a U.S. Senator from the State of Wisconsin..    34


Collins, Francis S., M.D., Ph.D., Director, National Institutes 
  of Health, Bethesda, MD........................................     6
    Prepared statement...........................................     8
DeSalvo, Karen B., M.D., MPH, MSc, National Coordinator for 
  Health Information Technology, Washington, DC..................    10
    Prepared statement...........................................    12
Shuren, Jeffrey, M.D., J.D., Director, Center for Devices and 
  Radiological Health, Food and Drug Administration, Silver 
  Spring, MD.....................................................    13
    Prepared statement...........................................    15

                          ADDITIONAL MATERIAL

Statements, articles, publications, letters, etc.:
    Senator Klobuchar............................................    40



                         MEDICINE FOR PATIENTS


                          TUESDAY, MAY 5, 2015

                                       U.S. Senate,
       Committee on Health, Education, Labor, and Pensions,
                                                    Washington, DC.
    The committee met, pursuant to notice, at 2:41 p.m., in 
room SD-430, Dirksen Senate Office Building, Hon. Lamar 
Alexander, chairman of the committee, presiding.
    Present: Senators Alexander, Collins, Hatch, Cassidy, 
Murray, Casey, Franken, Bennet, Whitehouse, Baldwin, Murphy, 
and Warren.

                 Opening Statement of Senator Alexander

    The Chairman. The Senate Committee on Health, Education, 
Labor, and Pensions will please come to order.
    This morning, we're holding a hearing on Continuing 
America's Leadership: Realizing the Promise of Precision 
Medicine for Patients. Senator Murray and I will each have an 
opening statement. Then we'll introduce our panel of witnesses, 
who are getting to be very familiar to us.
    We're very grateful to you for coming.
    After that, we'll have time to ask 5-minute rounds of 
questions or two, depending on how many Senators are here.
    We're here today to discuss an exciting new direction in 
our healthcare called precision medicine. What does that mean?
    Well, if those of us in this room were a good 
representation of the U.S. population, the Centers for Disease 
Control and Prevention estimates that nearly 1 in 10 of us 
would have diabetes. If doctors could use precision medicine--
that is, if they could look at our individual DNA and the 
genetic and molecular makeup of our disease--perhaps they could 
then potentially tailor treatments to each individual, rather 
than to the more general category of diabetes.
    I was visited this morning by the head of Philadelphia 
Children's Hospital, who talked about their work in identifying 
a genetic defect that causes blindness and how they have 
developed a therapy that restores the sight in a child because 
the therapy is directed for that specific genetic defect.
    This is happening with cancer treatment. Doctors can look 
at the mutations of the cancer cell and assess how to treat it. 
Newsweek reports that genetic sequencing of tumors is already 
starting to become the norm. In the big cancer hospitals like 
Sloan-Kettering, Dana-Farber, and MD Anderson, all incoming 
patients automatically have their tumors sequenced.
    This is all possible because of the extraordinary 
achievement by a great many individuals of sequencing the human 
genome, none more important than Dr. Collins, who is here with 
us today, and we are grateful for that.
    Today, we want to discuss what the National Institutes of 
Health and private industry are doing in precision medicine, 
how the Food and Drug Administration will regulate these 
innovations, how electronic health records can affect our 
ability to innovate, and what this means for the American 
patient and for our health care system. This is one of the most 
exciting new frontiers in medicine.
    Senator Murray and I are working on an initiative to ensure 
that our Federal agencies are equipped to review the medical 
products and processes produced by this kind of cutting edge 
medicine, so that American patients aren't waiting on the 
sidelines because regulatory science can't keep up. Our 
innovation initiative is not just about precision medicine, but 
precision medicine is an important part of our initiative.
    President Obama announced a Precision Medicine Initiative 
in the State of the Union this year. He detailed his plans in 
an event at the White House. I attended that to demonstrate my 
support for it.
    The President has proposed, as part of his plan, mapping 
the genomes of 1 million individuals and making that 
information available to medical researchers across the 
country. I look forward to hearing more about that from our 
    I also know there are similar private efforts underway and 
I am interested in hearing about that competition and about 
possible collaboration. For example, the Children's Hospital of 
Philadelphia that I mentioned also has genome sequences of 
children at their hospital, and I wonder how useful that would 
be to the 1 million that Dr. Collins is putting together and 
how these scientific entrepreneurs, Dr. Venter in California, 
the doctors at CHOP in Philadelphia, and other places--how that 
relates to the President's proposal for 1 million individuals.
    I look forward to hearing more about the potential cost of 
precision medicine. We know that costs to sequence the human 
genome have been reduced significantly in the last two decades. 
Dr. Collins testified--I believe that he said 15 years ago, it 
cost us about $400 million to sequence the first human genome, 
whereas today it's about $1,000.
    Very often in health care, innovation initially increases 
our costs. That doesn't mean we shouldn't innovate. Innovative 
new products can increase costs, but in the long term actually 
decrease health care costs.
    Take Alzheimer's, which, according to the Alzheimer's 
Association, will cost us $226 billion this year along with 
other dementias. If we could use precision medicine to delay 
onset or cure that disease, we could save precious dollars in 
our healthcare system and alleviate some of the grief and pain 
associated with it.
    The committee has also spent some time and will spend more 
on improving electronic health records. The Federal Government 
has spent $28 billion to drive the adoption of these records 
systems, and the result is that doctors don't like the systems. 
Many say they disrupt workflow, they interrupt the doctor-
patient relationship, and that haven't been worth the effort.
    Senator Murray and I have begun a working group 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.
    Dr. DeSalvo, we look forward to working with you on that 
and with Secretary Burwell and being able to report maybe early 
next year some results, either that you take administratively 
or that we do legislatively or some of both. We have to get to 
a place where the systems can talk to one another--
interoperability--and where doctors, particularly the smaller 
physicians' offices, want to adopt these systems, can afford 
the cost, and can be confident that their investment will be of 
    Dr. Collins has told us--and I've heard from many others--
that a properly functioning electronic medical records system 
is tremendously important to the President's Precision Medicine 
Initiative. No. 1, it can help to assemble the genomes of the 1 
million individuals; and, second, if we want to make genetic 
information useful it's going to take computers that operate 
easily and with the click of a mouse to help make it possible 
for doctors to actually prescribe prescriptions for individual 
    I also would like to hear if we know, Dr. DeSalvo, at some 
point, how the $11 billion effort by the Defense Department on 
electronic medical records would relate to the $28 billion 
we've already spent and whether those will be compatible and 
whether you'll be working with them.
    There's a lot to talk about today. This is a tremendously 
interesting and important effort, and I look forward to the 
witnesses' comments.
    Senator Murray.

                      Statement of Senator Murray

    Senator Murray. Well, thank you very much, Mr. Chairman.
    Thank you to all of our witnesses for being here today. 
Each of your agencies plays a critical role in the topic we're 
going to be talking about, and I'm grateful to have you all 
here to share your expertise.
    I've approached our bipartisan effort to advance medical 
innovation focused on one question in particular, and that is: 
What can Congress do to help all patients and families get the 
safest, most effective treatments and cures more quickly? Our 
conversation today is about the promise of precision medicine, 
and it is a crucial and truly exciting piece of the puzzle.
    There's no question we are at a critical moment in the 
medical field. Researchers and medical experts are increasingly 
finding ways to treat patients not just as the average patient 
but, instead, based on their own unique characteristics and 
    This is like the difference between getting eyeglasses 
based on the average prescription and getting eyeglasses based 
on your own prescription. It's huge, especially for patients 
and families across the country who are waiting and hoping for 
better treatments and cures.
    I'm proud that my home State of Washington is home to 
several institutions that have been pioneers in this area. 
These include the Fred Hutchinson Cancer Research Center and 
the University of Washington, which are using precision 
medicine technology to tackle breast cancer, eye disease, and 
Alzheimer's disease, among others.
    I'm glad we have the opportunity today to discuss the ways 
in which precision medicine is changing and improving lives and 
how Congress can help advance this new frontier in biomedical 
innovation for patients and families.
    The President has proposed making significant investments 
in precision medicine. His fiscal year 2016 budget supports a 
bold new initiative to exploit the recent advances in genomics, 
molecular biology, and data management to support the shift 
away from this one-size-fits-all medicine and toward treatment 
tailored to specific individuals. This proposal could do an 
enormous amount to accelerate the advancement of precision 
medicine. But as I discussed with Dr. Collins in our 
appropriations hearing last week, I am deeply troubled by the 
steady erosion of NIH's purchasing power over the last decade.
    Last Congress, Democrats and Republicans were able to come 
together to replace harmful sequestration cuts to investments 
in NIH, FDA, and other critical priorities, like education, 
infrastructure, and defense. I am really hopeful that this 
year, despite the budget proposals put forward by my Republican 
colleagues, we will be able to work across the aisle and find a 
way to prevent these shortsighted cuts from kicking in again.
    This is absolutely critical to the kinds of investments we 
need to make to help families and grow our economy, including 
precision medicine. One of my top priorities on this committee 
is looking for ways to continue improving the quality of care 
patients receive, and supporting precision medicine is 
essential to this goal.
    By offering patients and providers more and much better 
health information, patients, in consultation with their 
doctors, will be empowered to make informed decisions about 
their care. Our health care system will be better equipped to 
put their needs first.
    I do want to note that protecting privacy will be an 
important challenge throughout this process. Just in the last 
few months we have seen serious security breaches impacting 
families' personal health information, and that is 
    As researchers, providers, and patients gather and use more 
health information, we need to be aware that data is being 
created that cyber criminals will want to exploit, and that 
means we will need to develop strategies to protect privacy 
that meet today's challenges. Chairman Alexander and I are 
investigating the current state of cyber security in the health 
sector, and it is clear that this needs to be an all-hands-on-
deck effort with providers, insurers, and government working 
    Again, thank you to all our witnesses for being here today. 
I want to thank Chairman Alexander for holding this hearing on 
a topic of such importance for patients and families in 
Washington State and across the country.
    I look forward to working together, Mr. Chairman, with you 
and other members of the committee to support this important 
    The Chairman. Thank you, Senator Murray.
    To underscore what Senator Murray said, this specific topic 
is an initiative of the President in which the committee, in a 
bipartisan way, is very interested. We expect to get a result, 
and we welcome the expert advice.
    We have three witnesses, and I'll ask Senator Cassidy if 
he'd like to introduce the first one.
    Senator Cassidy. Yes, Dr. Karen DeSalvo. Dr. DeSalvo and I 
know each other from way back when I was full-time with LSU and 
she with Tulane, and I told her that just in her honor, we made 
the spread Tulane green today.
    Dr. DeSalvo is the National Coordinator for Health 
Information Technology at the Office of the National 
Coordinator of Health Information Technology, or ONC. ONC is 
the lead agency charged with formulating the Federal 
Government's health IT strategy and coordinating Federal health 
IT policy, standards, programs, and investment.
    I've been impressed. Dr. DeSalvo has come to me personally. 
There's a friend back home who is having a lot of problems with 
her electronic medical record and adapting to it. She called 
her, and they spoke at length. She clearly recognizes 
interoperability as key. She is working with and listening to 
physicians and developers of these products.
    Before joining HHS, Dr. DeSalvo was the Health Commissioner 
for the city of New Orleans, including and after Hurricane 
    The Chairman. Thank you, Senator Cassidy.
    Dr. DeSalvo, we look forward to your testimony. We expect 
to get to know you pretty well here, because all of us are 
interested in fixing the electronic medical record system, and 
you're on point for that, according to Secretary Burwell. We 
look forward to that.
    Our other two witnesses are here about every other day, it 
seems, and we're grateful for that. Dr. Collins, the Director 
of the National Institutes of Health, who oversees the work of 
the largest supporter of biomedical research in the world, has 
been the Director since 2009. Of course, he is known, among 
other things, for his leadership of the International Human 
Genome Project, completely sequencing the human genome in 2003.
    Dr. Jeff Shuren was here just last week. He has been the 
Director of the Center for Devices and Radiological Health at 
the Food and Drug Administration for more than 5 years. They're 
responsible for assuring the safety, effectiveness, and quality 
of medical devices; assuring the safety of radiation-emitting 
products; and fostering device innovation.
    He's had a lot of experience, and 1 year of that experience 
was being detailed to this committee as a part of Senator 
Kennedy's staff. So we welcome him back.
    If the witnesses would summarize their remarks in about 5 
minutes, we would appreciate it. We have Senators here who want 
to have a conversation with you. Let's start with Dr. Collins.


    Dr. Collins. Well, good afternoon, Chairman Alexander, 
Ranking Member Murray, and distinguished committee members. 
It's an honor to appear before you today to discuss how we can 
advance America's health by accelerating progress toward a new 
era of precision medicine.
    Earlier this year, the administration unveiled the 
Precision Medicine Initiative, a bold new research effort to 
revolutionize how we diagnose and treat disease. We believe the 
time is right for this ambitious initiative, and the NIH and 
our partners, the FDA and ONC, will work hard to achieve this 
    Historically, physicians have had to make most 
recommendations about disease prevention and treatment based on 
the expected response of the average patient. This one-size-
fits-all approach works for some patients and some conditions 
but not others.
    Precision medicine is an innovative approach that takes 
into account individual differences in patients' genes, 
environments, and lifestyles. The concept is not entirely new. 
Blood typing, for example, has been used to guide blood 
transfusions for almost a century.
    The identification of the BRCA1 and BRCA2 genes has made it 
possible to provide options for women at high risk of breast or 
ovarian cancer. The gene implicated in cystic fibrosis, 
discovered in my own laboratory 25 years ago, has led to 
widespread availability of carrier screening and targeted 
    The prospect of applying this concept broadly has been 
dramatically improved by the development of powerful and 
affordable methods for characterizing personal biological 
information. That includes genomics, the widespread adoption of 
electronic health records, the recent revolution in mobile 
health technologies, and the emergence of computational tools 
for analyzing large biomedical datasets. Furthermore, patients 
are increasingly interested in taking part in research.
    All of these developments will help make possible the dream 
of personalizing a wide range of health applications. With this 
in mind, we are thrilled to take a lead role in the multiagency 
Precision Medicine Initiative.
    In the near term, this initiative will focus on cancer, 
accelerating efforts to develop precision medicine strategies 
for a wide range of adult and pediatric cancers. This component 
will include the molecular analysis of large numbers of 
individual tumors to see what gene mutations are actually 
driving the malignancy, and then matching that information with 
available targeted therapeutics provided by pharmaceutical 
industry partners to optimize responses for the individual.
    Simple blood tests will be developed that can detect early 
response or resistance to drug therapy. Combinations of 
targeted drugs will be tested to see how best to achieve not 
just a remission, but a cure.
    To put a human face on this, I'd like to paint you a 
forward-looking picture of what the Precision Medicine 
Initiative could deliver for cancer in a few years. Consider 
the hypothetical case of Lily, a 52-year-old woman of Asian 
descent. In 2018--this is a hypothetical case--after battling 
bronchitis and a persistent cough for several months, Lily goes 
to her doctor, who orders a lung CT scan, along with a new 
blood test developed through research supported by the 
Precision Medicine Initiative, to look for DNA and other 
biomarkers circulating in her blood.
    The CT scan, as you can see from the arrow there, detects a 
tiny spot that could be either inflammation from bronchitis or 
cancer--not clear. The biomarker test clinches the diagnosis, 
revealing a genetic mutation that occurs only in patients with 
    In 2015, today, her prognosis from this cancer would likely 
be pretty grim. In 2018, that could all change. Lily is treated 
with surgery to remove the tumor, and the tumor DNA then 
undergoes additional molecular analysis.
    Based on those results, Lily is treated with a targeted 
drug that was originally developed for skin cancer but has just 
the right properties for her tumor. She also receives a course 
of immunotherapy specifically designed to kill any tumor cells 
that may still be lurking in her body. With this treatment, a 
decade later, Lily remains cancer free. That is a hypothetical 
but quite realistic example of what the cancer component of 
this initiative could achieve.
    As a longer term goal of this initiative, NIH will launch a 
National Research Cohort of 1 million or more volunteers who 
will play an active role in how their medical, genetic, and 
environmental information is used to prevent and manage a broad 
array of diseases. Participants, some recruited from existing 
NIH-supported cohorts and some new volunteers, will be 
centrally involved in the design and implementation of this 
process. They will be true partners.
    With appropriate privacy protections, they will be able to 
share genomic data, lifestyle information, and biological 
samples, all linked to their electronic health records. 
Participants will be able to have access to their own health-
related information.
    New approaches for detecting and analyzing a wide array of 
biomedical variables will be initially tested in small pilot 
studies focused both on prevention and management of disease. 
Ultimately, the most promising approaches will be utilized in 
greater numbers of people over longer periods of time to 
collect valuable data that will be of great benefit to both 
researchers and patient partners.
    Let me quickly give you an example of how this could 
benefit a specific participant in the Precision Medicine 
Initiative but could also provide evidence for a new strategy 
for health maintenance that could be extended across the 
    Consider the case of 38-year-old Precision Medicine 
Initiative participant Carla. It's 2020. Carla feels perfectly 
healthy. She welcomes the chance to try out a wearable sensor 
that continuously monitors her pulse, blood pressure, physical 
activity, and sleep patterns, but discovers that her blood 
pressure usually runs about 150 over 100, too high, increasing 
her risk of stroke, heart attack, kidney failure, and other 
life-threatening conditions.
    Carla is not alone, by the way. Nationwide, about 78 
million Americans, one out of three adults, have high blood 
pressure. Many, like Carla, don't even know it. What's worse, 
nearly 50 percent of those diagnosed with hypertension do not 
have it under control.
    Carla consults with her doctor who confirms the need for 
treatment and suggests she take an inexpensive diuretic drug. 
Carla obtains a smart bottle that sends a message to her smart 
phone if a dose is missed, so she takes her pills on schedule, 
returning her blood pressure to the normal range, avoiding 
future medical crises.
    The Precision Medicine Initiative will also bring many 
other types of healthcare monitoring into this new century. 
Current evidence suggests that the venerated annual physical 
exam and associated screening lab tests may not be as useful as 
one would hope.
    New opportunities to incorporate much more sensitive and 
specific indicators of individual health are emerging. This 
National Research Cohort will provide a powerful opportunity to 
assess such strategies rigorously to see if they really provide 
clinically valid information and, most importantly, to better 
health outcomes for the American people.
    In closing, let me emphasize that the impact of the 
Precision Medicine Initiative will extend far beyond the 
individuals who volunteered to participate. It will push the 
frontiers of discovery across the entire spectrum of biomedical 
research, from basic science aimed at finding new therapeutic 
targets to translational science intent on moving research 
discoveries into practice for maximum public health benefit.
    Given the size of the project and its real-world nature, 
evidence of improved health outcomes derived from this 
initiative will be attractive for immediate application across 
U.S. medical care. With sufficient resources and a strong, 
sustained commitment of time, energy, and ingenuity from the 
scientific, medical, and participant communities, the future of 
precision medicine appears very bright. We really look forward 
to working together to make stories like those of Lily and 
Carla a reality.
    That concludes my testimony. I look forward to answering 
your questions.
    [The prepared statement of Dr. Collins follows:]
         Prepared Statement of Francis S. Collins, M.D., Ph.D.
    Good afternoon, Chairman Alexander, Ranking Member Murray, and 
distinguished members of the committee. I am Francis S. Collins, M.D., 
Ph.D., and I am the Director of the National Institutes of Health 
    It is an honor to appear before you today, alongside my dedicated 
colleagues, to discuss how we, as a Nation, can advance the health of 
the American public by accelerating progress toward a new era of 
precision medicine.
    As the Nation's premier biomedical research agency, NIH's mission 
is to seek fundamental knowledge about the nature and behavior of 
living systems, and to apply that knowledge to enhance human health, 
lengthen life, and reduce illness and disability. I can report to you 
today that NIH leadership, employees, and grantees continue to believe 
passionately in that mission.
    In January of this year, the President announced a new Precision 
Medicine Initiative--a bold, new research effort to revolutionize how 
we diagnose and treat disease, including a $215 million investment in 
the President's fiscal year (FY) 2016 Budget. We believe that the time 
is right for this ambitious initiative, and the NIH and our partners, 
the U.S. Food and Drug Administration (FDA) and the Office of the 
National Coordinator for Health Information Technology (ONC), will work 
hard to achieve this vision.
    Historically, physicians have had to make most recommendations 
about disease prevention and treatment based on the expected response 
of the average patient. This one-size-fits-all approach works for some 
patients and some conditions, but not others. Precision medicine is an 
innovative approach that takes into account individual differences in 
patients' genes, environments, and lifestyles. This concept is not new; 
blood typing, for example, has been used to guide blood transfusions 
for more than a century. Prescription eyeglasses are tailored 
specifically to the patient's individual needs. Moreover, the 
identification of the BRCA1 and BRCA2 genes has made it possible to 
provide options for women at high risk for breast and ovarian cancers. 
The gene implicated in cystic fibrosis has led to widespread 
availability of screening and targeted therapeutics.
    The prospect of applying this concept broadly has been dramatically 
improved by the development of powerful and affordable methods for 
characterizing personal biological attributes (such as genomics and 
metabolomics), the widespread adoption of electronic health records, 
the recent revolution in mobile health technologies, and the emergence 
of computational tools for analyzing large biomedical data sets. These 
advances will help make possible the dream of personalizing a wide 
range of health applications.
    With this in mind, we are excited to take a lead in the two key 
components of the President's Precision Medicine Initiative that will 
be managed by NIH: a near-term goal that will focus on cancer and a 
longer term aim to generate knowledge applicable to the whole range of 
health and disease. Both components are within reach, due in large part 
to scientific breakthroughs in basic research. Furthermore, the 
initiative will tap into converging trends in connectivity, through 
social media and mobile devices, and Americans' growing desire to be 
active partners in medical research in a way that protects their 
    Oncology is the clear choice for enhancing the near-term impact of 
precision medicine. Cancers are common diseases and are among the 
leading causes of death nationally and worldwide, and their prevalence 
is increasing as the population ages. They are especially feared 
because of their lethality, their symptoms, and the often toxic 
therapies used to treat them. Cancer research has been leading the way 
in precision medicine for many years. Thanks to advances in DNA 
sequencing and efforts such as The Cancer Genome Atlas project, we now 
have a better understanding of the molecular changes that drive many 
cancers and we can define the driver mutations in individual tumors and 
use this information to design the ideal therapy for each patient. 
Genomic information has already helped shape the development of some 
cancer treatments. For example, the drug, imatinib (Gleevec), was 
designed to inhibit an altered enzyme produced by a fused version of 
two genes found in chronic myelogenous leukemia.
    While we've made significant strides in recent years to learn the 
molecular signatures of many cancers, much more remains to be done. The 
National Cancer Institute will accelerate the design and testing of 
effective, tailored treatments for cancer by expanding genetically 
based clinical cancer trials, exploring fundamental aspects of cancer 
biology, and establishing a national ``cancer knowledge network'' that 
will generate and share new knowledge to fuel scientific discovery and 
guide treatment decisions. Furthermore, we aim to understand the 
development of resistance to targeted therapy, apply non-invasive 
methods to track patients' responses to treatment such as liquid 
biopsies, and explore the efficacy of new drug combinations targeted to 
specific tumor mutations.
    As a longer term goal of this initiative, NIH will launch a 
national research cohort of one million or more volunteers who will 
play an active role in how their genetic, environmental, and medical 
information is used for the prevention of illness and management of a 
wide array of chronic diseases. This component will pioneer a new model 
for doing research; one in which people who participate are true 
partners. Not subjects, not patients--partners. The goal will be to 
expand the benefits of precision medicine into myriad aspects of health 
and health care. Participants will voluntarily share clinical data from 
electronic health records, results of imaging and laboratory tests, 
lifestyle data and environmental exposure recordings tracked through 
real-time mobile health devices, and genomic information--all with 
appropriate privacy protections.
    Participants will be at the center of the project design, and they 
will have access to their own health data, as well as research using 
their data, to help inform their own health decisions. As volunteers, 
each individual will participate because they choose to be a partner in 
this bold research effort. Through this dynamic community, researchers 
will be able to advance the information derived from this cohort into 
new knowledge, approaches, and treatments. Researchers from many 
organizations will, with proper protection of patient information, have 
access to the cohort's data so that the world's brightest, scientific 
and clinical minds can contribute insights.
    In order to help inform the vision for building the national 
research cohort of one million or more volunteers, a Precision Medicine 
Initiative Working Group was recently created. This group of experts in 
precision medicine and large clinical research studies is seeking 
public input from the diverse stakeholder community interested in the 
development of this initiative, including the patient community, and 
will articulate the vision for advancing participant engagement. They 
will help define what can be learned from a study of this scale and 
scope, what issues will need to be addressed as part of the study 
design, and what success would look like in the near and longer term. 
With the guidance from this team of experts, we will move ever closer 
to realizing the goals of this ambitious research program.
    A project of this magnitude will lay the foundation for a myriad of 
new prevention strategies and novel therapeutics. Although the 
initiative will likely yield its greatest benefits years down the road, 
there will be successes in the relatively near future as well, 
especially in the areas of cancer and pharmacogenomics--how to provide 
the right drug at the right dose to the right person at the right time. 
Moving forward, this pioneering research initiative will require the 
involvement of many different sectors of science and society, including 
biologists, physicians, technology developers, data scientists, and 
especially the American people. Given related efforts in a few other 
countries, we will aim to forge collaborations on a global scale.
    With sufficient resources and a strong, sustained commitment of 
time, energy, and ingenuity from the scientific, medical, and 
participant communities, precision medicine's full potential can be 
realized to give everyone the best chance at good health. There's no 
better time than now to embark on this ambitious new enterprise to 
revolutionize medicine and generate the scientific evidence necessary 
to move this individualized approach into everyday clinical practice.
    With your support, the future of medicine can be very bright. This 
concludes my testimony, and I look forward to answering your questions.

    The Chairman. Thank you, Dr. Collins.
    Dr. DeSalvo, welcome.


    Dr. DeSalvo. Thank you, Senator Alexander and Ranking 
Member Murray and to the other distinguished Senators. Thank 
you for the opportunity to be here today with my colleagues, 
Dr. Collins and Dr. Shuren.
    I'm Karen DeSalvo. I'm the National Coordinator for Health 
Information Technology at the Department of Health and Human 
    When I was a medical student at Tulane, I could have never 
imagined that in my career, I would see medicine on the 
frontier of such a significant transformation. As a still 
practicing doctor, it is thrilling for me to know that we are 
on the cusp of being able to customize treatment for the 
patient in front of me based on their genetics, preferences, 
and other key information instead of having to treat them as 
the average patient.
    What is even more exciting is that precision medicine is 
not just a theory. It's already changing practice and saving 
lives in the United States. We wouldn't be on this cusp but for 
health information technology, which is foundational to the 
President's Precision Medicine Initiative.
    The Office of the National Coordinator is the Federal lead 
for health information technology, and ONC's responsibility is 
to advance the health IT infrastructure for what is a sixth of 
the U.S. economy--healthcare. We do this work through a mixture 
of programs, convenings, and technical assistance aimed at 
catalyzing the marketplace. We seek to spur and support 
innovation to help address important advancements like 
precision medicine.
    At the same time, we want to provide clear and steady 
direction. ONC also has responsibility to ensure that all 
consumers are engaged and their interests are protected.
    Congress created significant momentum in health IT when it 
passed the HITECH Act in 2009. The act provided funding to 
support the adoption of electronic health records and technical 
supports for doctors and hospitals on the front lines as they 
made the transition to use them.
    As a result of the HITECH program and the hard work of 
providers, we are bringing healthcare into the digital age, and 
we have reached a tipping point. The strong foundation of 
health information technology makes it possible to bring to the 
bedside personalized treatment through precision medicine.
    The data in electronic health records, married with 
advanced analytics, information from mobile health devices, and 
other sources of data, including patient preferences, will 
provide the fulsome picture of a person's health and needs. 
This comprehensive data picture is necessary to identify the 
right prevention and treatment that is not only the most 
effective, but also most desired by the patient.
    This is not just a vision about what might come but a 
reality already. In places like Tennessee and Maryland, 
Nebraska, Florida--I could go on--thanks to the tools built 
into the electronic health record, doctors are able to tailor 
treatment today.
    I spoke to folks at the University of Florida Health, where 
a patient's cardiologist can order a test to see if they carry 
a particular variant of a gene. This test will help the 
cardiologist know if they are using the best medicine to 
prevent a future clot in the patient's heart. At a critical 
time in someone's life, a doctor is choosing the right 
lifesaving blood thinner, tailored and specific for them.
    Though this kind of treatment is exciting, it is, indeed, 
only the beginning. We have much work to do ahead to see that 
this is available to everyone in this country as part of 
routine care, and ONC stands ready to undertake this work.
    To get there, we will need to stay the course in adoption 
to see that every American has an electronic health record. We 
also need to go beyond the pockets of data exchange and achieve 
true interoperability as described in our nationwide roadmap.
    We will need to establish standards for the most 
fundamental clinical information that are shared by all. We 
will also need to establish standards for new data necessary 
for precision medicine, including genomics, but also 
environmental exposures and patient-generated information.
    We will build a trust framework that respects individual 
privacy and establishes strong security protections. We will 
work with the private sector to establish openly available 
APIs, which are doorways to unlock data.
    In all of this work, we will remember what I hear 
consistently from consumers who are our principal customer. 
They want to be able to access and share their health 
information, including with scientists if they wish, without 
blocking or delay.
    The President's Precision Medicine Initiative is one of the 
most exciting ways that we can bring the right care, the right 
prevention to the right patient, only imagined a few years ago. 
It's because of advances like this and the underlying 
technology that we have to support it that we are on the cusp 
of realizing better care and health for everyone. ONC stands 
ready to help further precision with our colleagues at HHS and 
with Congress.
    Thank you, and we look forward to your questions.
    [The prepared statement of Dr. DeSalvo follows:]
         Prepared Statement of Karen B. DeSalvo, M.D., MPH, MSc
    Chairman Alexander, Ranking Member Murray, and distinguished 
committee members, thank you for the opportunity to appear today. My 
name is Dr. Karen DeSalvo and I am the National Coordinator for Health 
Information Technology. I appreciate the invitation to be here to 
discuss how health information technology plays a necessary role in our 
Nation's precision medicine efforts.
    For far too many diseases, there is no proven means of prevention 
or effective treatment. We must gain better insights into the biology 
of these diseases to make a difference for the millions of Americans 
who suffer from them. Precision medicine is an emerging approach for 
disease treatment and prevention that takes into account variability in 
genes, environment, and lifestyle for each person instead of a ``one-
size-fits-all-approach.'' While significant advances in precision 
medicine have been made for select cancers, the practice is not 
currently in use for most diseases. Many efforts are underway to help 
make precision medicine the norm rather than the exception. To 
accelerate the pace, President Obama has unveiled the Precision 
Medicine Initiative--a bold new enterprise to pioneer a new model of 
patient-powered research that promises to accelerate biomedical 
discoveries and provide clinicians with new tools, knowledge, and 
therapies to select the treatments that will work best for individual 
patients. Working with our colleagues at the NIH and FDA, our mission 
is to improve the lives of all Americans by empowering patients, 
research participants, scientists, and providers to work together and 
turn new knowledge into individualized treatment and prevention 
strategies for a new era of precision care.
    To turn the promise of precision medicine into the reality of 
better health, we require robust and useful information tools, systems 
and practices for participants, providers, and more. As President Obama 
stated when he unveiled this initiative,

          ``This helps us find new cures but also helps us create a 
        genuine health care system as opposed to a disease care system. 
        We want each of us to have sufficient information about our 
        individual differences so that we can make better life 

    This goal cannot be realized without unlocking the data stored in 
various health information technology tools to ensure consumers have 
access to their own health data--and to the applications and services 
that can safely and accurately analyze it--so that in addition to 
treating disease, we can empower individuals and families to invest in 
and manage their health in partnership with their clinicians.
    Health information technology is the foundation required to bring 
precision medicine to operational life. Genomics helps to define us as 
individuals, and is one kind of important data for precision medicine. 
Other data of emerging importance to our health include microbiomes or 
bacteria and other microbes that share our bodies, environmental 
exposures or ``exposome,'' social determinants of health, and personal 
lifestyle choices--all of which provide us with more detailed knowledge 
about ourselves.
    We at the Department of Health and Human Services have recognized 
the importance of this data to advance better health and a healthier 
Nation, and have been working over the years to further refine our 
information infrastructure through health information technology 
adoption, policy development, and innovation by both the public and 
private sector. The Office of the National Coordinator for Health 
Information Technology (ONC) was established by Executive order in 
2004, charged with the mission of giving every American access to their 
electronic health information when and where they need it most. In 
2009, ONC was statutorily established in the Health Information 
Technology for Economic and Clinical Health Act (HITECH), enacted as 
part of the American Reinvestment and Recovery Act of 2009 (ARRA). 
HITECH also provided the resources and infrastructure needed to 
stimulate the rapid, nationwide adoption and use of health IT, 
especially electronic health records (EHRs). In the 6 years since the 
HITECH Act was enacted, we have seen dramatic advancement in the use 
and adoption of health information technology. The combined efforts of 
initiatives like the Regional Extension Centers, the ONC Health IT 
Certification Program, use of standard terminologies, and the CMS 
Medicare and Medicaid EHR Incentives Programs have brought us past a 
tipping point in the use of health information technology. Today, we 
are irreversibly on the path to a digital health care system.
    Since I became the National Coordinator in January of last year, 
HHS has been working intensely to harness both the health care 
industry's energy and consumer demands for interoperability to drive 
improvement in health--we feel the strong sense of urgency and have 
acted on it quickly. The Nation asked for a clear strategy to get to 
interoperability and a learning health system, and we delivered that 
plan in Connecting Health and Care for the Nation: A Shared nationwide 
Interoperability Roadmap Draft Version 1.0. We received broad feedback 
and have heard agreement from critical stakeholders like developers, 
consumers, providers, technologists, and others that this plan is the 
right path forward, and that they would like to work with us to advance 
interoperability. The roadmap explains that to get to interoperability 
as quickly and safely as possible we need to buildupon the current 
infrastructure and we need to pursue three immediate goals.
    First, we need to focus on ensuring that applicable standards are 
consistently used, including standards for application programming 
interfaces, health care terminology, implementation, and security. 
Second, we need to foster an environment of trust where individuals can 
access their data, and where that data is kept private and secure. 
Third, we need to incent, through consumer demand and delivery system 
reform, interoperable movement and use of electronic health information 
that endures and is self-sustaining. These three goals will ultimately 
advance health care and health.
    Our work in interoperability matters because it is what the Nation 
expects, but also because, in order for physicians, scientists, 
researchers, individuals and other partners to provide care tailored to 
the specific needs and characteristics of individuals, they will need 
to be able to access individual level information to learn more about 
how to treat patients, and ultimately improve the diagnosis, treatment, 
and prevention of diseases. This information cannot flow in the form of 
mail or fax to partners across the country--it must be quickly, 
efficiently and appropriately available electronically, and with 
patient consent when required by law, we must be able to apply the 
incredible speed and computing power available in the 21st century to 
help us analyze the data.
    To advance this work in precision medicine, ONC will build on our 
strong foundation through our standards advancement authorities, our 
regulatory authorities, our policy expertise and our deep connection 
with the private sector and consumers, in close coordination with our 
Federal partners. As proposed in the President's fiscal year 2016 
budget, ONC would fund standards--coordination and development--to 
advance the basis on which precision-based medicine can be practiced. 
ONC's $5.0 million funding proposal will lay the groundwork to achieve 
many of the milestones included in the Interoperability Roadmap's 
milestones for how health IT can support a learning health system. ONC 
will engage industry stakeholders to identify the standards, 
technology, and policy necessary to support big data analyses and 
precision medicine with appropriate privacy protections. Working 
closely with our many partners, ONC will aggressively pursue a 
portfolio of standards and technology initiatives that support 
precision medicine and protect user privacy, such as the 
standardization and use with consent of patient-generated health data 
from non-clinical settings; the incorporation of genomic data into 
health IT with appropriate protections; patient identity management and 
matching with consent to permit linked analyses; a patient's ability to 
access their data and contribute it to research projects, and new 
platforms for clinical trial recruitment through the use of health IT.
    Health information technology and information sharing plays a 
fundamental role in the President's Precision Medicine Initiative to 
improve care and speed the development of new treatments. We look 
forward to building on our current foundation and reaching for the 
future of better health for all Americans. Thank you again for inviting 
me today.

    The Chairman. Thank you, Dr. DeSalvo.
    Dr. Shuren.

                       SILVER SPRING, MD

    Dr. Shuren. Chairman Alexander, Ranking Member Murray, and 
distinguished members of this committee, thank you for the 
opportunity to testify regarding FDA's role in the 
administration's Precision Medicine Initiative.
    The success of precision medicine depends upon having 
accurate, reliable, and clinical meaningful tests, because it's 
the results of the tests that determine which patients get 
which drugs or treatment and whether or not they get them. 
Imprecise medicine results from bad tests. You have 
misdiagnosis, you get the wrong treatment, or you get no 
treatment at all when you should, and as a result, patients get 
harmed and healthcare costs go up.
    FDA's role in the Precision Medicine Initiative is 
primarily focused on advancing an emerging technology called 
next-generation sequencing or NGS. NGS tests can sequence long 
segments of a patient's DNA or even the entire genome. As a 
result, we're moving away from the model of one test, one 
disease, but a test that can identify one of many different 
diseases or even the risk of developing that disease.
    Today, there are significant barriers in place for 
advancing that technology. It affects our research, it affects 
development, and it affects our ability to use this optimally 
in healthcare. Let me tell you what some of those barriers are 
and what we're doing about it.
    If you're making a test, and you want to know if it's 
accurate, reliable, and clinically meaningful, two of the 
things you need to know are the following. One, does it 
accurately measure what you're trying to measure, in this case, 
genetic variants, to identify the right variants? We call that 
analytical validity.
    Second, you want to know: If there is a good relationship 
between what you measure and the particular disease? To test 
for breast cancer, is that variant, in fact, associated with 
breast cancer? We call that clinical validity.
    Today, that's difficult to do for next-generation 
sequencing, and here's why. Think about the human genome. You 
have about 3 million variants, and your genes are made up of 
components called base pairs. There are 3 billion of them. You 
want to know: How accurate is next-generation sequencing tests 
to measure all of that?
    Normally, you would look at each of the variants. You can't 
assess the accuracy of 3 million variants. It would take 
forever. There aren't good standards out there to assess it, so 
people are struggling to make sure their tests are accurate.
    Then you want to know: Is it clinically meaningful? Well, 
you need data for that. The problem is many of these variants 
are uncommon, so it's hard to get a lot of clinical data. It's 
difficult to do clinical studies, and that data tends to be 
siloed in the institutions that are doing the testing.
    In December, we proposed an entirely different framework 
for the oversight of next-generation sequencing tests, tests 
we've regulated for a long time, but we and the developers had 
struggled on what to do with it. So for analytical validity, we 
need to have reference standards, essentially subsets of 
genetic variants that if you can show accuracy in measuring 
those, it is reasonable to infer you're good at measuring the 
other variants.
    In fact, we gave $2 million to the National Institute for 
Standards and Technology, NIST, to work with the scientific 
community to come up with the very first reference standard for 
the genome, and they just released that last week. Under this 
initiative and with additional funding support, we will 
continue to work with NIST and the scientific community on 
developing additional reference standards, and as a result, 
developers wouldn't have to come to the FDA to show they're 
analytically valid. They would just meet that standard.
    For clinical validity, we need to leverage databases, 
curated databases, where we get all of that siloed genetic 
information, and then make sure it's standardized and it's of 
sufficient quality that we can make decisions on it. We're 
partnering with Francis and his team to take advantage of a 
database they have called ClinVar and the curation activity 
behind it called ClinGen, and then working with them and the 
scientific community to develop standards and best practices 
for having these databases, for doing the curation, and then 
having consistent clinical interpretation.
    Because you know what happens today? You can send your 
blood to different genetic testing labs, and you can get 
different results. That's what happens. It may be because you 
missed the particular genetic variant, or you interpret it 
differently. With those standards in place, we can now have 
consistent accuracy in testing and consistent clinical 
interpretation and reduce the time and cost to spur research, 
to advance technology development, and ultimately to achieve 
better health outcomes.
    Thank you.
    [The prepared statement of Dr. Shuren follows:]
            Prepared Statement of Jeffrey Shuren, M.D., J.D.
    Chairman Alexander, Ranking Member Murray, and members of the 
committee, I am Dr. Jeffrey Shuren, Director, Center for Devices and 
Radiological Health (CDRH) at the Food and Drug Administration (FDA or 
the Agency). Thank you for the opportunity to be here today to discuss 
the important role FDA is playing in the Administration's Precision 
Medicine Initiative as part of our mission to protect and promote the 
public health by ensuring the safety, efficacy, and quality of medical 
    The President's Precision Medicine Initiative, launched in January 
2015, is a new effort to revolutionize how we improve health and treat 
disease in the United States. The initiative will pioneer a new model 
of patient-powered research that promises to accelerate biomedical 
discoveries and equip clinicians with new tools, knowledge, and 
therapies to select which treatments will work best for which patients. 
Additionally, through collaborative public and private efforts, the 
initiative will leverage advances in genomics, emerging methods for 
managing and analyzing large data sets, and health information 
technology to accelerate biomedical discoveries, all while protecting 
patient privacy.
    A key technology that will advance the Precision Medicine 
Initiative is Next-Generation Sequencing (NGS) technology.\1\ NGS tests 
can rapidly sequence large segments of an individual's DNA and even an 
individual's entire genome. In fact, an NGS test is capable of 
detecting the billions of bases in the human genome, and in doing so 
identify the approximately 3 million genetic variants an individual may 
have. A single use of an NGS test could enable the diagnosis of any 
one, or more, diseases or conditions a patient presents with or help to 
predict a patient's risk for numerous conditions.
    \1\ Next-Generation Sequencing, also referred to as ``massively 
parallel sequencing'' or ``high-throughput sequencing,'' refers to 
technologies that perform DNA sequencing in parallel, allowing for the 
production of thousands or millions of sequences concurrently.
    The use of NGS tests also is accelerating the pace of scientific 
discovery, as the compilation of large amounts of genetic information 
in scientific databases and electronic health records enables 
scientists to perform observational studies and computer modeling to 
better understand whether and how certain genetic variants, including 
very rare variants, are linked to certain conditions and diseases. As 
the Initiative moves forward, we expect NGS technologies to play a 
central role in both research and clinical practice.
    For precision medicine to succeed, NGS tests must be accurate, 
reliable, and clinically meaningful. As with other diagnostic tests, an 
inaccurate NGS test can lead to patients receiving the wrong 
diagnosis,\2\ the wrong treatment, or no treatment at all, even when 
effective therapy is available. Inaccurate NGS tests can impose 
unnecessary costs on the health care system. Inaccurate tests could 
cause healthy individuals to seek further testing and treatment to 
address an erroneous belief that they have, or could develop, a certain 
condition or disease. As an example, if a patient was informed that she 
had a dominant mutation that confers increased risk for breast and 
ovarian cancer, that patient might choose to have complete mastectomy 
and hysterectomy, in order to prevent future cancer. In addition, the 
patient's family would be alerted to their own genetic risk. If the 
test results were inaccurate, the prophylactic surgery and all the 
family followup may not have been necessary. As treatment for cancer 
becomes more influenced by genetic testing of the tumor, and treatment 
based on type of mutation, it is increasingly important to ensure 
accurate and reliable tests. Thus, FDA oversight is critical to protect 
the public health and to maximize the benefits of precision medicine.
    \2\ Here, ``diagnosis'' refers to the ``diagnosis of disease and 
other conditions, including a determination of the state of health, in 
order to cure, mitigate, treat, or prevent disease'' (21 Code of 
Federal Regulations 809.3(a)), and includes but is not limited to 
diagnosis, aid in diagnosis, prognosis, therapy selection/dosing, 
monitoring, and risk prediction.
    The capabilities of NGS tests and their rapid evolution, however, 
pose unique challenges to applying FDA's traditional regulatory 
approach for determining whether a diagnostic test is accurate and 
reliable (analytical performance) and if the results from the test 
correctly identify the relevant disease or condition (clinical 
performance) on a test-by-test basis. Specific challenges related to 
NGS tests include:

     The need to evaluate the ability of the test to produce 
accurate and reliable results. Because NGS can identify an essentially 
unlimited number of variants, it would be difficult, if not impossible, 
to demonstrate performance on every possible detectable variant, as it 
would for other tests. Instead, FDA has accepted novel strategies to 
demonstrate the analytical performance of NGS tests while maintaining 
appropriate oversight to protect patients.
     Because NGS tests can routinely identify variants that are 
shared by only a few individuals, traditional clinical studies 
establishing the link of such variants to disease are not feasible. 
Instead, the clinical performance of NGS tests will rest in many cases 
on the ability to aggregate evidence from many diverse sources.

    Although the unique features of NGS tests create regulatory 
challenges, these same features also provide opportunities for novel 
solutions to regulatory oversight:

     The accumulation of data from NGS testing is enabling 
scientists, clinical labs, and regulators to better understand NGS 
outputs and error modes. NGS used in research and in diagnostic testing 
is generating a large amount of data that can be leveraged in further 
research, clinical trials, databases, and learning health systems to 
further evaluate the analytical and clinical performance of NGS tests.
     The large amount of cross-genome data generated by NGS 
tests could allow unique approaches, such as novel metrics and 
computational approaches, for assessing test performance.
     More generally, the cumulative generation of data through 
the increased use of NGS testing could help spur additional research in 
genomics and precision medicine.

    The challenges and opportunities described above are now presenting 
themselves as realities because of the critical mass of genomic data 
that has been accumulated by researchers and clinicians. Thus, it is 
clear that new regulatory approaches will be needed to enable the 
Agency to provide appropriate oversight, in a way that is more suitable 
to the complexity and data-richness of this new technology, and to 
ensure that NGS tests have adequate analytical and clinical 
    Recognizing the importance of NGS tests under the President's 
Precision Medicine Initiative, FDA is committed to developing a new 
approach for evaluating NGS tests. The work under the President's 
Precision Medicine Initiative builds off of efforts FDA has taken in 
the last several years to understand NGS technologies and to identify a 
regulatory framework that ensures safety and effectiveness while 
enabling innovation in the field.
    Since 2011, FDA has hosted several public workshops examining 
various aspects of NGS, and has interacted extensively with scientists 
and other subject matter experts at conferences and in other 
professional venues. In addition, FDA personnel have also participated 
in developing standards and tools for the scientific community, such as 
the Next-Generation Sequencing: Standardization of Clinical Testing 
(Nex-StoCT) Workgroup and the Genome in a Bottle Consortium. These 
efforts helped to inform the essential elements of a new regulatory 
approach to NGS technologies.
    In 2013, FDA cleared the first NGS instrument as well as two NGS 
tests for cystic fibrosis. In doing so, the Agency adapted its 
traditional regulatory approach to diagnostics. For instance, FDA was 
able to rely on a well-curated, shared database in assessing the 
validity of the 139 genetic variants involved in the assay, rather than 
requiring the test's manufacturer to independently generate data to 
support each variant's association with the disease. This not only 
reduced the burden for the manufacturer, it significantly improved the 
timeliness with which the product was able to be made available to 
clinicians and the public.
    FDA now seeks to build on its successful past approaches to create 
an efficient and dynamic system for providing regulatory oversight of 
NGS tests. In December 2014, the Agency issued a discussion paper, 
Optimizing FDA's regulatory oversight of next generation sequencing 
diagnostic tests--preliminary discussion paper,\3\ to gain public 
feedback. The paper outlines new regulatory approaches under 
consideration for both analytical and clinical performance of NGS 
    \3\ Food and Drug Administration. Optimizing FDA's regulatory 
oversight of next generation sequencing diagnostic tests--preliminary 
discussion paper. http://www.fda.gov/downloads/MedicalDevices/
    For analytical performance, the paper discusses an approach based 
on the development of quality-based standards\4\ for NGS test 
performance. These standards would be created in collaboration with the 
leading experts from the field of genomics. Conformance to such a 
standard could potentially provide assurance that an NGS test meets an 
acceptable level of performance, and that the results generated are 
reliable and accurate.
    \4\ Here, the term ``standards'' encompasses: metrics and tools 
that can assess the metrics, best practices, and more specific 
technical or other standards that would be developed by a recognized 
    For clinical performance, the paper discusses the use of high-
quality curated genetic databases that provide information on genetic 
variants and their association with disease to better establish the 
clinical performance of NGS tests by providing evidence about such 
associations and the strength of that evidence. As an example, NIH has 
created the ClinVar database, which houses information about genetic 
variants and their association with disease that has been shared by 
clinical laboratories, researchers, and other sources. Recently, NIH 
has funded external geneticists to curate entries in the ClinVar 
databases, under a program called ClinGen. FDA is now collaborating 
with NIH to understand how to use the curated data in ClinVar to 
support regulatory review of NGS tests. Use of curated databases, such 
as ClinVar, can provide a dynamic system for test developers to capture 
and update the clinical meaning of their tests, based on the latest 
    Both of these components--a standards-based approach to test 
performance and the use of community-generated evidence--could provide 
a dynamic and efficient regulatory system that could enable developers 
and users to seamlessly alter and improve their NGS tests as needed to 
advance the practice of precision medicine to benefit patients.
    A key component of FDA's work under the President's Precision 
Medicine Initiative is to engage with stakeholders to inform any new 
regulatory approach adopted for NGS tests. Moreover, FDA is committed 
to drawing on the knowledge of the scientific community to help inform 
the Agency's approach to NGS oversight. Thus, the first action taken by 
FDA, after the launch of the Precision Medicine Initiative, was holding 
a public meeting in February 2015, with a broad range of stakeholders 
to discuss the regulatory approaches outlined in FDA's NGS discussion 
paper, and to hear experiences and ideas on NGS from the clinical and 
research communities. Nearly 1,000 individuals attended the meeting, 
and there was general consensus that an innovative regulatory approach 
was needed in order to balance NGS innovation and appropriate 
oversight. FDA is now reviewing feedback from the stakeholders to 
inform the development of more specific regulatory proposals that will 
be released for public comment.
    As a first step to creating these proposals, FDA is meeting with 
the scientific community and other stakeholders to develop the 
standards, technical solutions, and best practices necessary to create 
a comprehensive proposal. In fiscal year 2015 and fiscal year 2016, FDA 
plans to issue additional white papers, and, if necessary, guidance, 
and convene further public workshops to work out the specifics.
    To support this essential work, the President's fiscal year 2016 
budget includes $10 million to FDA to acquire additional expertise and 
advance the development of the regulatory structure needed to advance 
innovation in precision medicine and protect public health.
    We now are entering a time of rapid scientific advancement with an 
eye toward precision medicine occurring in everyday clinical practice. 
For precision medicine to fully succeed, our regulatory approach must 
be crafted in a manner that facilitates innovation, is sufficiently 
nimble to new scientific and technological advances, allows the public 
to have timely access to newly developed tests, and ensures that those 
tests are accurate, reliable, and clinically relevant.
    Thank you for your continued interest in this important topic and 
for the opportunity to testify regarding FDA's contributions to 
progress on this issue. I am happy to answer any questions you may 

    The Chairman. Thank you, Dr. Shuren.
    We'll now have a round of 5-minute questioning.
    Dr. DeSalvo, in 1980, when I was Governor of Tennessee, I 
had the big idea that all eighth graders would become computer 
literate. I flew to San Francisco, met with Steve Jobs, and 
bought enough Mac computers--they were big tall things then--to 
put in all the middle schools. It was a great idea. It sounded 
    I forgot something. I forgot teacher training. Nobody 
really knew how to do it. I didn't think it all the way through 
the end. We have something of the same problem with our 
electronic healthcare record system. We spent $28 billion. It's 
a great idea. It holds great promise. It's not working the way 
it's supposed to.
    The current standards for meaningful use aren't clear. 
Upgrades are expensive. The systems don't work well enough to 
share the data. We hear it's expensive to share the data 
because of the relationships between vendors and doctors. Some 
of the doctors call this data blocking. You just released a 
report on data blocking describing these concerns.
    Senator Murray and I have set up a working group to work on 
this because of the large amount of interest in our committee 
on the subject. My question is: Will you work with us, this 
committee, to identify the five or six steps we could take to 
get our electronic medical records system functioning well 
enough so that it supports not just the precision medicine 
effort that we have, but so that it functions and it's 
something that physicians and providers can look forward to 
using instead of enduring?
    Dr. DeSalvo. Yes, Senator. I very much look forward to 
working with you all on identifying ways that we can make this 
work for doctors and others on the ground, on the front lines, 
because that's where it really matters, where the workflows are 
sometimes not the way they ought to be. They can be clunky. We 
look forward to that, and you can count on our participation 
very actively.
    We have some efforts underway. As the Senator is likely 
aware, we've been working through our rules for meaningful use, 
for certification, the blocking reported and other strategies. 
We know there's more work to be done, and we look forward to 
    The Chairman. Well, good. What I'm talking about here is 
actually beginning to get some results. I mean, identifying the 
five or six steps we should take--you should know them better 
than we, really, although Dr. Cassidy has some personal 
experience in this he will give us, I'm sure--and then going 
step by step to get them done. If you can do them by 
administrative order, terrific. If we need to do something, 
we'll include them as part of our innovation initiative and 
begin to do what we ought to do.
    Dr. Collins, 1 million genomes--I mentioned I was visited 
by the head of Philadelphia's Children's Hospital. They have 
250,000 sequenced genomes. I have two questions. Well, one 
question. How many of these are already out there? I mean, you 
want to assemble a million. They've got 250,000 in 
Philadelphia. Dr. Venter wants to assemble a million.
    Can you get your 1 million genomes simply by going to 
places like the Philadelphia Children's Hospital and using some 
of theirs?
    Dr. Collins. That's a great question, Senator. We are, in 
fact, trying to come up with every possible way to assemble 
this million-strong cohort by taking advantage of things that 
have already been done instead of having to start from scratch. 
We will, in fact, have a major meeting in your State on May 27 
and 28 with a number of those who have been managing these 
large-scale cohorts, gathering together to see if there is a 
way to put them together in a way that would prevent us from--
    The Chairman. Can you estimate the number of genomes that 
have been sequenced?
    Dr. Collins. I should be clear. When you say genome 
sequencing, some people are referring to a sampling of some of 
the base pairs in the genome, a genotype. A snip chip is the 
term that's often used. Some are talking about sequencing just 
the parts of the genome that code for protein, and we call that 
the exome, e-x-o-m-e.
    To do a whole genome sequence is substantially more 
expensive but is becoming now quite affordable. Most of the 
cohorts that are out there have not yet done whole genome 
sequencing. The group in Philadelphia is doing that with some 
of their patients, but not with many of them. Dr. Venter 
certainly has the intention in his Human Longevity Institute of 
doing a lot of whole genome sequencing. We believe that to get 
the maximum information, you want that.
    The Chairman. Let me ask you quickly--Senator Murray has 
emphasized the importance of making sure everyone or a 
representative group of everyone is included in this. What 
about children? I mean, the suggestion was made this morning 
that sequencing the genome of a child for a genetic defect 
leading to a particular disease can be less complicated than 
for an older person who may have a more complex disease. Will 
you include children and the single gene therapy treatment as 
part of what you do?
    Dr. Collins. That is an active area of investigation by our 
working group. Let me explain that. We assembled a group of 
both public and private experts on this whole question of this 
million-strong cohort. They have met once, last week. They will 
be meeting again, specifically, to talk about what should be 
the constitution of this cohort. Should children be included? 
What should we do about individuals that may not otherwise be 
asked to participate?
    We want to be sure this covers diversity of our population 
as well. Some of the cohorts that are already out there may not 
be as diverse as what we need. We will figure this out. There 
is a desire, however, Senator, to have this be something that 
represents the broad swath of our country. There will be a 
strong motivation for many people to include children.
    The Chairman. Thank you.
    Senator Murray.
    Senator Murray. Well, thank you again to all of you for 
being with us.
    Dr. Collins, we've heard a lot about how precision medicine 
is revolutionizing the practice of medicine, allowing for 
development of targeted cures for individuals. I'm also 
interested in the economic impact of this work.
    We know that precision medicine is not only about treatment 
but about prevention, and we have a lot to learn about how 
factors like environment and nutrition impact individual health 
outcomes. How might these discoveries impact healthcare costs?
    Dr. Collins. Well, I do appreciate that question, because 
we all agree that healthcare costs need to be brought under 
control, and a lot of the concern about our current system is 
that it is more a sick care system than it is a healthcare 
system. If we had the opportunity to focus more on prevention 
instead of waiting for illness to strike, we would both improve 
the health of the Nation and save money.
    The Precision Medicine Initiative aims with this million-
strong cohort to focus very intensively on prevention and to 
find out what actually works. I mentioned in my opening 
statement something about the fact that our annual physicals, 
which many of us sign up for, probably don't collect the kind 
of data that ultimately you'd like to have that might be a tip-
off to something that needs attention.
    The opportunity to begin to use many of these new tools, as 
well as these wearable sensors that are reporting on the 
environmental exposures and the body's performance under 
various situations, should put us in a much better situation to 
monitor individual health before an illness strikes. I don't 
want to over-promise the value that this will result in as far 
as cutting healthcare costs and bending that curve that we all 
want to see start downward again, because I think it's a longer 
term initiative. I would think over the course of time, this is 
one of the best opportunities we will have to cut our 
healthcare costs.
    Senator Murray. You know, one of the exciting things about 
precision medicine is that it's empowering patients and people 
to participate and be full partners in discovery of new 
treatments. You mentioned the new mobile and wearable health 
technologies that are out there that allow researchers to 
collect data on how participants' behaviors impact their health 
    I know that all of your agencies are working hard to find 
new ways to engage patients in their own health and sustain 
participation among people that are involved in research 
studies. What are the best practices in patient engagement to 
ensure sustained participation throughout these precision 
medicine studies?
    Dr. Collins. Another great question. Certainly, there are a 
number of cohorts that have already engaged a lot of patients 
that we are going to be consulting with about what their 
experience has been. Kaiser Permanente has a large cohort. The 
Mayo Clinic, Marshfield, has one, and Geisinger in 
Pennsylvania. All of these have done a lot of work to figure 
out what it is that people are looking for if they're going to 
    An important part of what we're trying with this initiative 
is not to think of the individuals who take part as patients. 
They're really partners. They're participants. We want to have 
them at the table. We will have a workshop July 1st and 2d 
which is focused specifically on trying to get input from 
individuals about what they're looking for.
    What we could already say is that people expect, if they're 
going to be part of this, that their information is going to 
help people. There's a lot of altruism involved in taking part.
    They also would like to get information back about 
themselves, in terms of what's been learned about their own 
state of health and what has this study led to in terms of 
broader discoveries that might not have happened otherwise. 
They want to be included. They want to be informed. They want 
to be at the table. We promise that is the attitude we will 
bring to this.
    Senator Murray. Very good.
    Let me ask you, Dr. DeSalvo--we've seen several high-
profile sophisticated attacks on healthcare organizations in 
the last few months. Americans expect that healthcare providers 
and researchers are taking the necessary precautions to protect 
their data. That's why I mentioned working with Senator 
Alexander on the current State of cyber security in the 
healthcare industry.
    Can you tell us what steps ONC is taking to help 
researchers keep the large amount of genetic and other health 
information that they are collecting secure?
    Dr. DeSalvo. Thank you for the question, Senator. We agree 
with you. It's a major issue. It's something that's on top of 
our mind every day. The steps we have taken most recently, for 
example, are to require in the electronic health records that 
data is encrypted at rest and in motion so as you move to 
interoperability and data is moving across systems it also 
needs to be secure and encrypted.
    We are working with, for example, the Department of 
Homeland Security, with the National Security Council and 
others to ramp up the additional security expectations, 
because, again, as data begins to move and be more liquid, 
there's more opportunity for there to be security issues. It's 
a top priority. We have taken some actions, and we have some 
additional ones that are underway.
    Senator Murray. Dr. Collins, what is NIH doing to protect 
patient privacy?
    Dr. Collins. We've already initiated a genome data sharing 
policy which has been in place for several years, because we 
have been conducting studies, as you might know, to try to 
understand genetic contributions to diseases like Alzheimer's 
or schizophrenia or heart disease. The conditions under which 
then that data can be shared is rather carefully overseen.
    Qualified researchers can apply to see that data, because 
we think much is gained by having it accessible. It has to be 
overseen in a way to make sure that the individuals who are 
looking at the data are appropriately signing on to various 
restrictions, such as not sharing it with third parties and 
acknowledging where it came from. That has been very successful 
over several years. I think we have a pretty good framework 
    We do think there are some things that are needed in order 
to protect genetic privacy and make sure that it is not 
acquired by individuals who do not have the right to do so, 
that there ought to be something to avoid surreptitious genetic 
testing of individuals without their consent.
    Senator Murray. Thank you very much.
    Thank you, Mr. Chairman.
    The Chairman. Thank you, Senator Murray.
    Senator Cassidy has deferred to Senator Hatch, and then 
Senator Franken.

                       Statement of Senator Hatch

    Senator Hatch. Well, thank you, Mr. Chairman.
    Thanks to all of you. We appreciate the work that you're 
doing. We've been following it for many years and really 
appreciate it. In Utah, we have a large database, too, and I 
wonder if that could be part of the million-person cohort, 
because the Utah population database is the world's largest 
repository of computerized family histories, and it's linked 
with more than 22 million public health and clinical records.
    Scientists at the University of Utah have been able to use 
this non-commercial resource to identify dozens of genes 
responsible for diseases. The Utah Genome Project is harnessing 
the power of Utah's large families to discover new disease-
causing genes that underlie conditions such as diabetes, heart 
disease, obesity, and cancer.
    These large families accelerate the pace of genetic 
discovery by magnifying our ability to identify disease-causing 
genes. By harnessing the advantages gained through using these 
large families and large cohorts, our folks in Utah can make 
significant contributions to what you're trying to do here. I 
would just like to know if you think they would be useful, and 
if I can play a role in getting the University of Utah and you 
to work together.
    Dr. Collins. We are, indeed, and, Senator, thank you for 
the question. Utah has been in a wonderful place as far as the 
ability to do remarkable research in human genetics over many 
decades, research that I've personally benefited from 
collaborating with over decades of my own research career. 
You're right. You have an unprecedented level of depth in terms 
of family collections.
    One of the things that we are going to be wrestling with a 
bit in terms of this cohort is exactly what ought to be the 
involvement of multigenerational pedigrees. It does bring 
considerable strength to the effort, and that will be a topic 
of discussion also at this workshop later this month in 
    I would say that the Intermountain Healthcare system, which 
obviously involves lots of folks in Utah--I should have 
mentioned it on my list a minute ago of those that have already 
generated cohorts. They have a very strong presence in this as 
well. I'm quite sure when the dust all settles, this Precision 
Medicine Initiative will have a Utah connection.
    I saw that wonderful piece this morning in the Deseret News 
talking about some of this, and I think there's a lot of 
excitement across the scientific community and across the 
country about what this might lead to. I appreciate you 
volunteering to help us.
    Senator Hatch. Well, thank you so much, and we do want to 
help you. The University of Utah has a genetics department 
about as good as anybody can have. In fact, we've irritated 
Harvard to death by enticing a number of very top researchers 
to Utah. They like the mountains and the skiing as much as 
anything, but they wouldn't leave once they get there. We'd 
love to be of great assistance to you.
    I, personally, appreciate all three of you. I know a little 
bit about what each of you do, and I've taken a great interest 
in what you do over these many years. As I've been chairman of 
the Finance Committee, I haven't had as much time to spend in 
this committee, which I used to chair.
    I just want to compliment the distinguished chairman and 
Ranking Member here for the good work that they're doing. 
They're terrific leaders in the U.S. Senate, and I just want to 
personally express that.
    Thank you. I appreciate all three of you being here, and I 
appreciate the work you're doing.
    Dr. Collins. Thank you, Senator.
    Senator Hatch. Thank you.
    The Chairman. Thank you, Senator Hatch.
    I almost had to give Senator Warren equal time there, but 
she'll have--just so you'll know, the order I'm calling on 
Senators is based on who was here at the time the gavel went 
down. Based on that, on the Republican side, Cassidy and 
Collins are next, and on the Democratic side, it's Franken, 
Bennet, Warren, and Murphy.
    Senator Franken.

                      Statement of Senator Franken

    Senator Franken. Thank you, Mr. Chairman, and thank you to 
the Ranking Member for holding this hearing. Precision medicine 
is extremely exciting.
    Those of us in Minnesota thank you, Dr. Collins, because 
Mayo and the University of Minnesota have been doing a genomics 
project funded by you--so very smart on your part.
    This is exciting, because there's really been a paradigm 
shift in the way we think of healthcare in this country. In 
some part, due to the healthcare reform law, healthcare 
providers and insurers are moving more toward person-centered 
care, and I'm talking about coordinated care, medical homes, 
ACOs that provide incentives and information that help doctors 
tailor their practice, their treatments, their therapies to 
meet the needs of individual patients.
    That's, of course, what precision medicine is all about, 
making sure the right patients get the right treatment. The 
right treatment doesn't, as you were saying, Dr. Collins--
doesn't necessarily mean--it isn't treating people when they're 
sick. It's about healthcare, not sick care, and using 
personalized medicine should improve prevention, so that we are 
doing healthcare and not sick care.
    Dr. DeSalvo, I do want to talk to you about what you said, 
which is we're at a tipping point in the adoption of medical 
health records and electronic health records. I just want to 
talk about that, because we had a hearing on that not so long 
ago, and there are some barriers to adoption by certain medical 
providers, some resistance, some because of doctors who feel 
like ``I've got 20 minutes with this patient, and I don't want 
to spend eight of it inputting data.''
    On the other hand, this is where we're going. What are you 
doing to address that, and what are some good models? I've 
heard of things like having a scribe whose job--like a medical 
student who is there with you and who is taking down the 
information. We need to get there. What are we doing to get 
    Dr. DeSalvo. Well, Senator, thank you for raising the voice 
of a lot of doctors in this country. I hear similar things when 
I travel and talk and from my own family members, including my 
husband, that there are--it's been a great advancement. We're 
going forward. Folks want to go there. However, the systems are 
not a part of the workflow in the way that we want or expect in 
clinical practice.
    The opportunities there include giving more time for 
providers to be able to implement the systems on the front 
line. The Senator may be aware that in the last year, we have 
put forward some rules with CMS to provide additional 
flexibility in timing of the adoption of records or upgrading 
to new ones and also to propose in this last set of rules 
giving doctors the option of a more streamlined approach to the 
kinds of ways that they have to report, so reducing the burden 
or the expectation on the amount of clicks that they must do to 
show that they're functionally using the records.
    We are working toward a goal of a shared expectation that 
this is going to be an enabler and really support them, and I'm 
committed to continuing in that path.
    Your point about successes on the ground and tools that 
doctors have used in their office practice and otherwise--is it 
really important we collect those--there are health IT fellows 
program, as an example--and share those. It varies by doc and 
by office what's going to work for them--sometimes using a 
dictation system and then having some assistants to transcribe 
over it. Sometimes it's a scribe.
    Sometimes working with the electronic health record, they 
have had so much time that they've been able to make the 
systems as seamless as possible for them. A State like 
Minnesota is so far advanced in health IT, as I'm sure you're 
aware, and has had many more years in to make sure the systems 
are working. We're not finished with----
    Senator Franken. Thank you. I don't mean to interrupt you.
    Dr. DeSalvo. Yes. I'm sorry.
    Senator Franken. We can talk about this for a long time, 
but I want to get one quick question to Dr. Shuren.
    I have a question about how the tests at FDA--those tests 
that the FDA is going to be assessing. One thing that concerns 
me is that some tests may get quite expensive, and I want to 
make sure that I understand how they and the highly 
personalized care that precision medicine can provide will 
benefit everyone and won't contribute to health disparities in 
our country.
    My questions are: Will these tests be considered diagnostic 
tests or preventative tests? Who is going to be paying for 
    Dr. Shuren. Well, in the case of next-generation 
sequencing, they can be used potentially for both diagnosis and 
for predicting and, therefore, prevention purposes. It all 
depends upon--do you have the data to show that that particular 
test can perform in such a way.
    In terms of reducing cost, there's the opportunity for 
reducing cost for those technologies to be developed, because 
if we have the standards I talked about, and we have those 
databases of information, it will be a lot less expensive to 
have the science. In the past, you do a clinical study to show 
if your test actually predicts or diagnoses that disease. With 
the databases, you might be able to point to that data. 
Essentially, the clinical community is crowd sourcing the 
    We just did that recently with--two years ago with a test 
for cystic fibrosis, where first, we approved that NGS test 
based upon a subset of variants. And, second, they were able to 
use data in a database at Johns Hopkins that was supported by 
the Cystic Fibrosis Foundation and didn't have to do a clinical 
study, dramatically reducing the cost of bringing that test to 
    Who pays for it? Hopefully, the insurers will pay for it at 
the end of the day, because if you have good technology, it's 
of no value to patients if they don't have access to it. If 
they can't afford it, they won't have access.
    Senator Franken. There's no question that precision 
medicine can bring down our costs, and, certainly, as I just 
don't--I worry about a brave new world where certain people 
have access to certain things. I'm out of time. I would just 
ask unanimous consent to submit a statement from Senator 
Klobuchar to the hearing record.
    The Chairman. Of course. It will be done. Thank you, 
Senator Franken.
    [The information referred to may be found in Additional 
    Senator Cassidy.

                      Statement of Senator Cassidy

    Senator Cassidy. Dr. DeSalvo, we've had a GAO report in the 
past that the VA and the DOD needed to do much better to 
coordinate their records. Clearly, electronic medical records 
are critical to precision medicine, both the research thereof 
and the implementation.
    I hear that there's an $11 billion DOD contract going out, 
and I'm not quite sure that it's coordinating with the VA. We 
had testimony recently about how there's a lack of 
interoperability, so one of the systems being considered or two 
of the systems being considered by DOD are those mentioned as 
lacking interoperability.
    I feel like we're in a thicket here, and we can't get out. 
All we know is that we're about to spend $11 billion on 
something that the VA system is not interoperable with. Please 
tell me that I'm absolutely wrong.
    Dr. DeSalvo. Senator, the DOD's acquisition of a new 
electronic health record--you are correct--is one of the most 
important things that's going to happen on the health IT 
landscape, and we are intimately involved in that. The 
Department of Defense, for example, has embedded staff with us 
at ONC to see that we're communicating. The Department of 
Defense has agreed to lead the way in pointing to the 
    The Senator asked me earlier what are the steps we should 
take. If I could, just for a second----
    Senator Cassidy. I only have 3\1/2\ minutes.
    Dr. DeSalvo. One of the most important things is to move 
away from proprietary standards, which is getting in the way of 
the systems being able to----
    Senator Cassidy. There are some open source bidders--Epic 
is one of them. So is Cerner. They are not open source. 
    Dr. DeSalvo. Those vendors will have to agree to use the 
standards that the Department of Defense wants to use, which 
are the ones that ONC has published. We are very pleased that 
we're all moving in a direction to have a core set of standards 
that everyone will agree to so that we don't run into a problem 
where the system is not interoperable.
    Senator Cassidy. So you're telling us that the VA will be 
able to share records or that the local hospital will be able 
to share records with the DOD?
    Dr. DeSalvo. The VA and the DOD is a separate issue, 
because they have a different kind of technology. Yes, sir, the 
goal is that that becomes not only exchange, but 
    Senator Cassidy. Again, I talk to medical students all the 
time, and I don't mean to offend. When you mention the goal, I 
accept that it is a goal, but how likely is it to happen? 
Because it seems like you left some wiggle room, that, indeed, 
the VA has a different system and it may not yet communicate 
with DOD.
    Dr. DeSalvo. What the VA and the DOD have done now is they 
have found a solution to exchange information. If you're at the 
bedside with the patient, you can see the records from the VA 
and DOD. So they've taken that first step.
    The integrating of the data requires having the same core 
data elements, so there's a technology issue, which is 
solvable. There is also a policy and a culture issue, which, 
honestly, is generally the harder one and what we're facing in 
circumstances like information blocking which is one of the 
things getting in the way of interoperability in the broader 
    Senator Cassidy. You spoke of the open source, though. That 
seems kind of, by definition, not to include information 
blocking. Who is blocking the info?
    Dr. DeSalvo. So information blocking can happen sometimes 
from technology, but what we're seeing commonly is that the 
vendor systems will charge----
    Senator Cassidy. I accept that. We've had those hearings 
about how the vendors are blocking. I'm going to take it back 
to where we started. My fear is that the very vendors who are 
blocking data are the ones bidding. Then you mentioned it's 
going to be open source, but you returned to the fact that 
there could be blocking. I guess I'm not clear.
    Will the final $11 billion project be something that I, at 
Our Lady of the Lake in Baton Rouge, can access data? Or will 
there be a problem with vendor blocking?
    Dr. DeSalvo. I would need the DOD to confirm the answer, if 
you would. However, what I would share with you is that since 
we described blocking and since we put out the report, the 
vendors have begun to pull down the fees to make this problem 
start to go away, and we have to keep putting on the pressure. 
I do not think the work is done.
    Senator Cassidy. I apologize, and I'm already over time. If 
I can just ask one--no, I'm almost out of time. Is it part of 
the initial RFP that they cannot block, and that the VA has to 
be able to share, as does the community hospital? Let me ask it 
that way.
    Dr. DeSalvo. That is the intention of the DOD. Yes, that is 
    Senator Cassidy. It is the intention, but is it part of the 
    Dr. DeSalvo. Yes. That's where they're going. That is what 
I understand from our--what we have recommended as ONC to the 
DOD. I would have to defer to the DOD.
    Senator Cassidy. Can you? Because I sometimes find that 
recommendations are not adopted. I find that commonly.
    Dr. DeSalvo. We can certainly get back with you on that.
    Senator Cassidy. Yes. I'm almost out of time. I yield back.
    Dr. DeSalvo. Thank you.
    The Chairman. Thank you, Senator Cassidy.
    Senator Bennet.

                      Statement of Senator Bennet

    Senator Bennet. Thank you, Mr. Chairman.
    I thank the witnesses for your testimony. You're fortunate 
to be on the cutting edge of all this stuff.
    Dr. Shuren, as I know you know, there is a thriving 
movement of innovation in molecular diagnostics underway, 
thanks to the Human Genome Project and investment over the past 
decade. There are a number of Colorado companies like Corgenix 
and SomaLogic and Biodesix, which are developing remarkable new 
advanced diagnostics in areas like Ebola, cardiovascular 
disease, and lung cancer.
    The FDA recently released a draft framework to regulate 
developed tests. As I wrote in a letter to you a couple of 
weeks ago, as always, we need to balance both innovation and 
safety to ensure that we create a fair and workable process. 
There's some concern that the draft framework could require the 
FDA to register and approve thousands of labs or, at a minimum, 
thousands of tests.
    I just wonder if you could speak to this a little bit. 
Given the size and scope of the issue, do you intend to propose 
more formal regulations in this space? Are you open to 
congressional action here? Would that be useful? How do we get 
a handle on this and create predictability for the people that 
are doing this work?
    Dr. Shuren. Well, first, let me say that laboratory-
developed tests play an important role in our healthcare system 
today, and our goal here is not shutting down laboratory-
developed tests, but, in fact, making sure that we are both 
facilitating innovation and that those tests are accurate, 
reliable, and clinically meaningful. Under our proposal, we 
tried to strike that balance.
    I don't know that we'll actually receive thousands of 
tests, because what we've heard from the lab community is that 
a lot of the tests they make are to address unmet needs. One of 
the things we put out in our proposal is to say,

          ``Look, if you're making a true laboratory-developed 
        test, your healthcare facility, healthcare system, is 
        doing this and treating patients, and there isn't a 
        test out there like that that FDA has approved or 
        cleared, you don't come in the door for premarket 
        review. We'll address that unmet need.''

    If, subsequently, someone has that test, and they send us 
the data, and we look at it, and it turns out we know this test 
works, then our expectation is other people who are making that 
test should do the same, because we now have data that that 
test, in fact, is accurate, reliable, and clinically 
meaningful. I don't know that we will actually receive 
    That said, we received a lot of comments on the proposal. 
We're working on it, and we will be making changes before we 
have the final policy.
    Senator Bennet. If there is legislative work that needs to 
be done around this, I hope you'll let the committee know. I'm 
sure that you will.
    I want to turn also to one other topic around innovation. 
Dr. Collins mentioned earlier how important mobile technologies 
have become. Really, in the blink of an eye, this is all 
changing the way doctors practice medicine and patients monitor 
their own well-being.
    As you know, probably, Senator Hatch and I reintroduced the 
Med Tech Act yesterday to ensure that lower-risk medical 
software and mobile apps are not regulated by the FDA. I think 
we share the same goals on this, and I want to thank your team 
for giving us technical advice all the way through.
    Can you talk a little bit about FDA's thinking in this 
    Dr. Shuren. Well, first, let me thank you and Senator Hatch 
and your staffs for the opportunity to work together on the Med 
Tech Act. We agree--as we looked at this space, we were looking 
at functions, device functions, that we had been regulating for 
a long time, and now some of them are being put on mobile 
    What we found as we looked at it is that some of these 
lower risk functions we may better serve by no longer actively 
regulating them and spur a little bit more innovation. They're 
sufficiently low-risk. We don't need to provide that additional 
FDA oversight. Instead, focus on higher-risk medical device 
functions in this space, and that is kind of a nice balance on 
that--facilitate innovation, but still assure good patient 
    Senator Bennet. Thank you.
    I don't know, Dr. Collins, if you have anything you'd want 
to add.
    Dr. Collins. Well, only that your point about mobile health 
technologies is extremely well-taken. The proliferation of 
really exciting opportunities is happening all around us, and 
we certainly see this Precision Medicine Initiative as a great 
opportunity to test those out, because you not only want to 
have an application that's kind of cool and gives you 
interesting information, but you want to know does it actually 
improve health and does it change outcomes.
    If we have a million individuals who are excited about 
participating in research, who are essentially volunteering to 
become users of these kinds of technologies, whether it's the 
next version of a watch that measures all kinds of aspects of 
your body's physiology or something that's detecting in the air 
around you what kind of exposures you're having, this would be 
a great opportunity to find out what works, what actually 
improves healthcare, and then what ought to then be 
extrapolated and utilized across medical care for the whole 
    Senator Bennet. Thank you.
    Thank you, Mr. Chairman.
    The Chairman. Thank you, Senator Bennet.
    Senator Collins.

                      Statement of Senator Collins

    Senator Collins. Thank you very much, Mr. Chairman.
    Dr. Collins, just this morning, I met with some advocates 
from Maine who are pushing for more research into brain cancers 
such as glioblastoma. You mentioned in your written testimony 
that oncology is the clear choice for enhancing the near-term 
impact of precision medicine and that important advances have 
already been made in this area. I very much look forward to 
sharing your testimony with this group of people from Maine who 
are concerned about such devastating brain cancers as 
    I'm wondering if you also see a role for precision medicine 
in neurodegenerative diseases, like Alzheimer's, Parkinson's, 
and ALS. Are investments in these important areas also being 
considered as part of the Precision Medicine Initiative?
    Dr. Collins. Thank you, Senator Collins, for the question. 
Absolutely. We are learning that disorders like Parkinson's and 
Alzheimer's and other neurodegenerative conditions do, in fact, 
have multiple contributions to whether they happen or not to a 
given individual.
    For Alzheimer's disease, we now know of 35 individual 
places in the genome where variations place an individual at 
higher risk. We know about one or two where individual 
variations actually are protective, which is an even more 
potentially actionable finding, because you'd like to 
understand that in order to develop the next generation of 
preventive strategies for people who weren't so lucky as to 
inherit that preventive kind of genetic variation.
    There is, especially for any disease that is common enough 
that you're going to have thousands of individuals in your 1-
million-strong cohort, an opportunity to study those at a scale 
that has not previously been possible and to try to put 
together all of the things we can learn about their genetic 
inheritance using whole genome sequencing.
    Also, their environmental exposures, also everything we can 
learn about their electronic health record experience, also 
using mobile health are the ways that we can come up with 
better detection systems of early trouble in terms of cognitive 
changes. That is very much an intention of this.
    One of the exciting aspects of having this very large 
cohort is that it doesn't have to be just about heart disease 
or just about diabetes or just about Alzheimer's disease. It 
can be about all of those things, because it will have the 
scale to do so.
    We have waited a long time to reach the point where the 
technology would make that possible, and the time is now. We've 
really reached a remarkable inflection point in the potential 
of medical research, and we should not let this moment pass.
    Senator Collins. I could not agree more. Truly, it's so 
    Dr. DeSalvo, despite the Federal support that you mentioned 
in your testimony, I continue to hear from smaller healthcare 
providers about the barriers that they face with electronic 
health record implementation. Just yesterday, I met with a 
physician from Bangor, ME, who shared with me that putting in 
place a comprehensive electronic data collection system for his 
small practice was going to cost in excess of $230,000. This 
was just for the software, not for the hardware. That's no 
small amount, particularly for a smaller, independent practice 
that is not hospital-owned.
    To access information about individuals to improve 
diagnoses, treatment, and prevention of diseases, you discussed 
the important role, the absolutely essential role, of health 
information technology and interoperability, including the 
standards and technology that are going to be needed. As you 
work to build these health IT systems for precision medicine, 
how can we assure that we're not leaving out rural America, 
smaller practices, rural hospitals, health clinics, because of 
the cost?
    Dr. DeSalvo. Senator Collins, thank you for the question 
and for particularly spotlighting one of the challenges of 
small practices and rural. As the Senator may be aware, that 
was a particular focus that we had early on in the HITECH 
funding. That was prior to me joining the Administration, but 
that team really wanted to see that rural America was not left 
behind, and there was great success, actually, in the adoption 
in many of those communities across the country in partnership 
with USDA, as an example.
    They are facing now a challenge of upgrading technology, 
and it is one of the reasons that last year, because of some 
challenges they were having, we put out this flexibility rule 
that gave them some more time to be able to advance. The cost 
that you're describing for that physician sounds fairly 
exorbitant, and I would be very happy to followup with your 
staff and that physician to see if we can understand what is 
happening there, and perhaps the regional extension centers 
that are in your communities could followup.
    You are exactly correct. It's critical that we get this. 
It's critical that nobody is left behind and that we find a way 
to make it successful for everyone.
    Senator Collins. Thank you very much. I'm going to take you 
up on that offer. Thank you.
    Thank you, Mr. Chairman.
    The Chairman. Thank you, Senator Collins.
    Senator Warren.

                      Statement of Senator Warren

    Senator Warren. Thank you, Mr. Chairman. The President's 
Precision Medicine Initiative could be a big step forward for 
more targeted and more effective therapies for any number of 
conditions, and I think it's a great idea. We should have 
started years ago.
    Dr. Collins, you first advocated for a national genetic 
study to examine how people's genes and environments contribute 
to diseases over a decade ago, in 2004. Is that right?
    Dr. Collins. In fact, that is exactly right, and it landed 
with a thud at that point. That's actually the article up there 
on the screen that I published in 2004. In retrospect, this was 
probably a bit ahead of its time because we didn't have the 
technology at the point where this would have been affordable 
or practical. But it is now.
    Senator Warren. I'm glad to hear that it is now, although 
if we had started pushing and funding back then, we can only 
wonder how much further we would be ahead right now. Congress 
didn't make those investments, and, in fact, over the past 
decade, NIH funding hasn't even kept pace with inflation. That 
means we are years behind in doing this work.
    If we are serious about speeding up biomedical innovation, 
about improving health, about reducing long-term costs, we 
start by investing in NIH. The House has a proposal called 21st 
Century Cures that's supposed to accelerate biomedical 
innovation. When it was first released by the Republicans a few 
months ago, it didn't include a single dime of new NIH funding 
for Congress.
    Last week's new bipartisan draft of this bill very much 
seems to be moving in the right direction. It has $2 billion in 
new mandatory funding for the NIH every year for 5 years. I 
applaud the House Republicans for acknowledging what so many of 
us, including Newt Gingrich and the drug industry, have been 
saying for years. NIH funding is critical to accelerating 
    Let's be clear. A few billion dollars in temporary funding 
will not solve a decade of neglect, much less build the future 
that we need.
    Dr. Collins, in the late 1990s, Congress doubled the budget 
of NIH, and then agency funding was left to shrink back down. 
If Congress had never doubled the budget of NIH and had simply 
kept pace with prior investments, where would the NIH budget be 
    Dr. Collins. Well, Senator, I keep a graph in front of me 
all the time about this very question, and I'll just put it up 
on the screen, because this is a documentation of the problems 
that we are now facing. What you're seeing on that screen 
there--the yellow line is basically what NIH has had as far as 
our purchasing power for research, so it's the appropriation, 
but as adjusted by the effects of inflation.
    The dotted green line is the trajectory that NIH was on 
going back to 1970 until 1998 when we had that wonderful 
doubling. Then we've been getting undoubled ever since. If you 
follow the dotted green line, and we had stayed on that 
smoother trajectory, we would be substantially higher, up in 
the neighborhood of a little over $40 billion.
    Senator Warren. Just to get back on track and to reverse 
the damage of the last decade, NIH, if I'm reading this right, 
would need more than $12 billion in just the first year, and 
the House proposal doesn't even put that much in over the space 
of 5 years. Let me just ask, based on what you've got here, in 
your expert judgment, what's the annual rate of increase that 
NIH needs to get back on track on its funding?
    Dr. Collins. Well, first, let me say we were thrilled also 
to see what's in the 21st Century Cures. The $2 billion a year 
of mandatory gave a great jolt of excitement and some relief to 
a community that's been really quite stressed over the past 12 
years as we've been losing ground.
    To get back on a stable trajectory that would result in a 
healthy biomedical research ecosystem which our country has 
depended on with great success over 50 years, I would estimate, 
in my professional judgment, that we need to be in the space of 
inflation plus 4 percent or 5 percent per year. That's pretty 
much--that dotted line was inflation plus 3.7 percent, I guess. 
That was a healthy way to be sure that all the talent and 
capabilities of this country, in terms of biomedical research, 
where we have led the world for decades, could be sustained, 
encouraged, and innovation could go forth in all the ways that 
we want it to.
    Senator Warren. Well, thank you, Dr. Collins. Two billion 
dollars a year for 5 years is certainly better than nothing. 
Let's not pretend that a small, temporary investment that falls 
billions of dollars short of what we're going to need will do 
the job. There is a gaping hole in our NIH budget, and we need 
a serious plan to fix it.
    There are many ways to make that happen. I have a Medical 
Innovation Act, for example, that could add another $6 billion 
a year--wouldn't cost taxpayers a dime. But, whatever we do, 
this committee has to get serious about medical innovation, and 
that means we have to do better than the House proposal on 
    Thank you, Mr. Chairman.
    The Chairman. Thank you, Senator Warren.
    Senator Whitehouse.

                    Statement of Senator Whitehouse

    Senator Whitehouse. Thank you, Mr. Chairman.
    Let me start by echoing the chairman's interest in having a 
review of where we are on health information technology. I read 
with interest the Wall Street Journal piece by, Dr. DeSalvo, 
your predecessor, David Brailer, and it makes a lot of sense 
and provides, I hope, some bipartisan foundation for us to work 
    I think that the meaningful use program has become obsolete 
and needs to be tuned up to meet the new challenges that the 
progress over the last years since it was passed now present to 
us. Thank you for agreeing to work with the chairman and the 
committee on the four or five key goals that we should be 
achieving, and I would urge you to think big in accomplishing 
that. Let's not twiddle around the edges. Let's get this right.
    Dr. Collins, to followup a little bit on what Senator 
Warren was saying, I'm interested in what you've been able to 
document by way of consequences for failures to adequately fund 
our scientific and medical research. It strikes me that you 
could probably tell me that there's a return on investment from 
the research that we do, and if we don't fund the research, we 
lose that return on investment.
    It strikes me also that you probably have examples of human 
benefits from the scientific research which, if foregone, 
become human costs. You probably also pay some attention to the 
country's global competitiveness in this field.
    Could you comment specifically in those three areas on what 
you think is the payback for investment in scientific research, 
or, if you want to put it contrarily, the cost of not funding 
scientific research?
    Dr. Collins. Well, I very much appreciate the opportunity 
to talk about some of those consequences. I'll just put up 
another graph which, in many ways, reveals the difficulties 
that are present in this country, beginning back in 2003. What 
I'm showing you there is the opportunity that an investigator 
who comes to NIH with their best ideas has of actually getting 
    Most biomedical research done in this country in our 
Nation's finest universities and institutes is supported by 
NIH. This is the main place where this work gets done. For most 
of our history, that has been in the space of 25 percent to 35 
percent success rate, about one in three. That's not easy. That 
means two-thirds of the people are sent away. Now it's about 
one in six, and that's very unhealthy.
    We have looked at what happened in the past when we could 
fund up to 30 percent, and there's a lot of great science that 
falls in that space between the 16th percentile and the 30th 
percentile, and we're not funding that now. About half of what 
we should be supporting by historical trends is left on the 
    We don't know what we're missing in that regard. The next 
great idea about cancer may have been one of those things that 
didn't quite make the cut.
    In terms of your question about medical consequences, I'm a 
physician. The reason I love being at NIH and love what we do 
is the hope that this is going to change things for the better 
for people's health. Our track record there is striking in 
terms of what's happened in terms of longevity and prevention 
of disease. It is frustrating that we are going more slowly.
    I promise you that the institute directors and I, when we 
sit around the table and try to figure out what to do in these 
constrained circumstances, we still prioritize, we still try to 
push forward, but we're just going more slowly. We need more 
advances in cancer. We need a universal influenza vaccine. 
We're working on all those things, but we could be going faster 
than we are right now.
    In terms of the financial return on investment, that's been 
documented over and over again. A dollar of NIH grant money 
returns about $2.20 in the first year to the local economy 
because of the goods and services that are generated as a 
result. We support about 400,000 jobs directly across the 
country in all 50 States on the basis of the grants that we 
give out. Those are high-quality jobs.
    You asked about global competitiveness. We were the 
unquestioned leader of the world in biomedical research until 
recently. That is no longer to be taken for granted. When you 
see us losing ground, and we see countries like China and India 
and Singapore and South Korea upping their investment sometimes 
in double digits, we are losing that leadership.
    Senator Whitehouse. A quick question on that. When they are 
making those increases in investments, do they have an eye on 
us as a target----
    Dr. Collins. You bet.
    Senator Whitehouse [continuing]. Or are they just doing 
this in a sort of a general eleemosynary way?
    Dr. Collins. Well, it's a little of both. They basically 
read our playbook from 20 years ago, and they saw what it did 
for America's economy and for the spinning off of small 
businesses that come out of this effort, and they want to do 
what we did. I don't know if you'd say they're gunning for us, 
but they're basically trying to learn from our experience and 
recreate that in their environment.
    One statistic that particularly renders this very serious--
last year, China filed more patents in bioscience than the 
United States did. That was not even a close competition a 
couple of years ago, and they have now jumped ahead of us. 
Those patents result in intellectual property claims that are 
going to ultimately spin off new businesses. We have to take 
that more seriously.
    Senator Whitehouse. Thank you, Chairman.
    The Chairman. Does that mean China will start respecting 
patents more?
    Dr. Collins. I'd better not comment on that.
    Senator Whitehouse. Don't get the man in trouble.
    The Chairman. Thank you, Senator Whitehouse.
    Senator Baldwin.

                      Statement of Senator Baldwin

    Senator Baldwin. Thank you, Mr. Chairman, and I very much 
appreciate you and the Ranking Member holding this hearing, 
giving us the opportunity to learn more about the 
administration's Precision Medicine Initiative. We're excited 
about it because of its lifesaving potential. We're excited 
about it because of its breakthrough potential.
    I'm excited about it, having the honor of representing a 
State that's been a leader in setting the stage for some of the 
things we're talking about today in precision medicine, from 
the isolation of the first embryonic stem cells to the 
discovery of short tandem repeat polymorphisms at Marshfield 
Clinic, which is a major discovery that has had a big impact on 
the study of human genetics. The clinic has since developed a 
very significant genetic biobank, one of the larger ones with 
information from over 20,000 central Wisconsin residents.
    Dr. Collins, I know you've been asked sort of iterations of 
this question before by my colleagues on the committee. If you 
have more to add, I would like to hear more about how you will 
utilize the existing data, like the data that I just described 
that was collected by the Marshfield Clinic and real-world 
clinical data. How will you use those and share those in new 
ways to create personalized therapies?
    Dr. Collins. That's a great question. Yes, Marshfield is a 
wonderful leader in this enterprise. I visited there myself 
several times, and Dr. Murray Brilliant, who's the person there 
who's overseeing their large cohort, their precision medicine 
effort, is somebody that we are all looking to for his 
experience to share with us. He was at the White House when the 
President announced this on January 30.
    In this workshop we're going to hold at the end of this 
month at Vanderbilt, we will really look hard at the ways in 
which Marsh-
field, Mayo, Intermountain, Kaiser Permanente, Geisinger, and 
perhaps the Million Veterans Project as well, could, in fact, 
be assembled into a synthetic kind of cohort, not having to do 
all of the work from scratch, but making the whole greater than 
the sum of the parts, because this kind of initiative really 
builds power by numbers, and that's one of the reasons we're so 
excited about being able to say that word, million, which would 
not have been in the vocabulary of most people planning these 
things until fairly recently.
    We want to take every kind of opportunity to build on the 
experience that's already been obtained in places like 
Marshfield. One of the things they've done, by the way, is they 
found individuals who, by looking at their DNA sequence, ought 
to be sick, but they're not.
    Senator Baldwin. Right.
    Dr. Collins. They have some kind resilience. Some people 
call them genetic heroes. There's something about them that we 
need to understand, because they have that resistance to 
disease that we perhaps could learn more about and figure out 
how to share with other people by development of new 
therapeutics. That's just one kind of insight that they've got 
a start on, but if you had a million people, you could find a 
lot more.
    Senator Baldwin. I want to followup on a discussion that 
you were just having about the research workforce. You were 
talking about funding and the reducing percentage of research 
grant applications that are actually funded. I'm curious to 
know what impact this initiative may have on the changing 
nature of the research workforce.
    It strikes me that there are doctors who happened on 
discoveries of novel therapies in the course of treating 
patients, but others may not know that their patients' unique 
reaction to a treatment holds the potential for a breakthrough 
in this field. What opportunities for new and nontraditional 
researchers are presented through this initiative?
    Dr. Collins. Oh, Senator, that's another great question, 
and I'm glad you brought it up. This Precision Medicine 
Initiative will not reach its full potential if it doesn't lure 
and recruit all kinds of people from different disciplines to 
get together to work on this. I think of a parallel here with 
the Human Genome Project that I had the privilege of leading, 
where it was such a historic opportunity that people who never 
really thought of themselves as working in that space decided 
to make it their passion.
    The same can happen here. We would want to have 
computational experts, because we have very large datasets. 
This is the world of big data and the best way. We would want 
to have technology developers of all sorts who can figure out 
ways not only to look at your DNA sequence, but what about all 
of those metabolites that are floating around in your system. 
We can begin to look at hundreds of those in a given situation.
    All the technologies we mentioned about mobile health--
there's still lots of opportunities there as well, and 
physicians who can begin to figure out how do you take this 
kind of data and implement that in a real world setting in 
order to improve health outcomes.
    You know, I have to say when I look at the way we practice 
medicine today compared to when I was a resident in medicine in 
1979 or 1980, it's not that different. We have such a long way 
to go here in terms of really incorporating all the new 
technologies that are coming along.
    This is going to be a wonderful laboratory for all kinds of 
people to get involved in and figure out what kind of 
discoveries can be made and what use we can put them to. I hope 
it's going to be filled with that kind of innovative talent.
    Senator Baldwin. I appreciate that.
    Mr. Chairman, with your indulgence, one quick question.
    Dr. Shuren, you can answer this for the record. There's 
incredible potential in what we're talking about. It also 
strikes me that there's incredible potential for fraud, for 
folks, as this develops, offering and selling fraudulent 
interventions that claim to be personalized medicine. I would 
like--and, again, it can be after this hearing--to hear from 
you more about how the FDA will work to prevent fraud and 
ensure patient safety in the age of precision medicine.
    Dr. Shuren. I'll take a quick moment, if it's OK, just to 
    The Chairman. Sure. Senator Murray and I would like to know 
the answer, too.
    Dr. Shuren. All right. Well, thinking even just beyond 
fraud, the whole point of having a test out there that really 
doesn't work and it's being sold--this is one of the impetuses 
in terms of our now deciding to actively regulate that subset 
of in vitro diagnostics laboratory-developed tests, because 
there are some great tests out there, but there are some bad 
tests out there.
    Let me give you an example of one that's in the precision 
medicine space--and there are several--something called KIF6, 
and it's used for predicting people--for people having coronary 
heart disease and their response to statin treatment. This is a 
test where we had seen data on it. We saw the test didn't work. 
Laboratory-developed tests--they're selling it.
    There was a med analysis of 19 clinical studies. The test 
doesn't work. Then they performed a randomized placebo control 
trial on over 18,000 patients. The test doesn't work. When this 
was reported out around 2010, at that point, over 150,000 
people got that test. We estimate the cost to the healthcare 
system may have been upwards of $2.4 billion, and that test is 
still available today.
    That doesn't serve patients well, and it doesn't serve 
precision medicine, because it undermines our efforts to make 
sure that we get accurate and reliable clinically meaningful 
tests out there, and we get the right treatment to the right 
    The Chairman. Thank you, Senator Baldwin.
    Senator Murray, do you have any further remarks?
    Senator Murray. How are consumers supposed to know that?
    Dr. Shuren. Right now, they can't. They don't--because you 
don't have that oversight for some of these tests to know if 
they are, in fact----
    Senator Murray. Does FDA not have oversight for this?
    Dr. Shuren. We do have the authority, and what we proposed 
is it's time for us to exercise it. Years ago, when we set up 
the program, laboratory-developed tests tended to be very 
simple. They were used locally for often rare conditions. In 
setting up the program, we said we would exercise what we call 
enforcement discretion. You are subject to our requirements. 
We're not enforcing them.
    Over time, particularly without our being there, these 
tests have become increasingly more complex. They're being used 
nationally. They've become increasingly more important and 
being relied on for healthcare decisions. As a result of that 
and our seeing some of the bad tests out there is why we moved 
forward to regulate them.
    I've got to tell you, this question has come up since the 
1990s. We had NIH back then and the Department of Energy saying 
the FDA needs to get involved. The Institute of Medicine came 
out in the 2000s to say that--two advisory committees to the 
Secretary of Health and Human Services. We've been trying to 
move forward.
    In 2007, we put out a guidance to say we'll start 
regulating a subset, and what we heard from the lab community 
was, ``Don't pick away, don't chip away at this. Put out an 
overarching framework, make it risk-based, and phase in 
    We held a public meeting in 2010. We got that input, and 
the guidances we put out, the framework we proposed late last 
year, was our attempt to do that, to have a risk-based program, 
to try to balance innovation with patient safety and phase it 
in over a period of time. Right now, we're addressing comments. 
We're still working with the community on what that right 
policy should be, and then come up with a final----
    Senator Murray. So you're engaging providers and patient 
groups as you work through that?
    Dr. Shuren. Yes. We've gotten a lot of feedback on it. An 
example is the American Cancer Society has said they have seen 
tests where they're incorrect. Patients are getting diagnosed 
with cancer when they don't have it, and people who have cancer 
are getting told they don't have cancer. They've said, too, 
that we need better oversight here. We need to make sure we 
have accurate tests and the tests do what they claim to do.
    Senator Murray. Important question. I just have one more 
    Dr. Collins, why is 1 million the right number?
    Dr. Collins. Well, that's a great question. There's nothing 
magic about 1 million except it's a nice round number that we 
could aim for. I actually will admit that I would love it if we 
could go beyond that. As I said a minute ago in the 
conversation with Senator Baldwin, this is all about numbers. 
That's where you get the power of the analysis to find out what 
    A million is very ambitious. It seemed like a goal we could 
set for ourselves to try to achieve. Given the fact that we 
already know there are cohorts out there which collectively 
have enrolled more than a million people, if we can figure out 
how to do this, maybe we'll do better than that.
    Senator Murray. Well, just listening to the committee 
members that you've been talking to over the last few weeks, 
every one of our States apparently has some--we have Fred Hutch 
in my State that is developing a database.
    Dr. Collins. Yes.
    Senator Murray. I don't know how you're going to work 
through all of this to get your cohort. Again, diversity, 
making sure that we represent everybody is really important. 
I'm going to look forward to hearing how you do that.
    Dr. Collins. I totally agree with you on that, because if 
we just tack together the existing cohorts, I don't think we 
would have the kind of representation that we need of the 
    Senator Murray. Thank you.
    Thank you, Mr. Chairman.
    The Chairman. Dr. Shuren, following up Senator Baldwin and 
Senator Murray, this was the high-risk, low-risk difference you 
were talking about in these laboratory tests. You're focusing 
your attention on the higher risk areas. Is that right?
    Dr. Shuren. Well, the high-risk, low-risk we were talking 
about earlier was on mobile technologies. We try to put a focus 
on--when we implement this, try to focus first on the higher 
risk tests as we phase that in.
    The Chairman. Oh, I see, as you phase it in.
    Dr. Shuren. As we phase that in.
    The Chairman. Is any of your enforcement--is it all prior 
approval, or is it where you might be acting on a complaint? In 
other words, to let the marketplace run for a while on the 
lower risk items and police it, in effect.
    Dr. Shuren. For the lower risk tests, we would not enforce 
requirements on them, other than tell us what you are, and if 
there are problems reported--we also wouldn't enforce 
requirements on tests for rare disorders and, again, some of 
these tests for unmet needs as well.
    The Chairman. Well, this has been very useful. As I said to 
Senator Murray, this is kind of like going back to college. 
It's actually very interesting, and we're very privileged to be 
students in a classroom with such distinguished teachers and 
witnesses on a subject that's so important and one that the 
President, the House of Representatives, and this committee all 
are committed to work on.
    It is my hope--and Senator Murray and I will work out 
exactly how we will do this, but it is my hope that we can 
finish our work on our innovation initiative this year and 
report it to the full Senate early next year so it can be acted 
on, or some schedule like that. We've got some other things we 
have to do as well. The precision medicine proposal by the 
President would be incorporated within that, so it'll be a part 
of all of it.
    We didn't talk about privacy today. Who's going to figure 
that out?
    Dr. Collins. A very important question. ONC and NIH and the 
White House OSTP have been engaged in this. We will have a deep 
conversation about this July 1st and 2d with the participants 
at the workshop that's coming forward at that point.
    The Chairman. Well, what we're talking about--if you're 
going to have a million participants or more, and you use all 
their data, you've got to figure out some way to protect that.
    Dr. Collins. To protect that, yes. We are deeply serious 
about doing that in the most high-tech, thoughtful, capable 
way, again, with a fair amount of experience to build on. We 
have to take that with great seriousness.
    The Chairman. Dr. DeSalvo, you heard from a variety of 
Senators in regards to our interest in helping you figure out 
what the steps are to actually improve the electronic medical 
records system, to get to see some real results, coordinate 
properly with whatever the Defense Department is doing. There's 
a lot of work to do there.
    We're not trying to catch anybody here. We're just trying 
to fix a problem, and we'd like to work with you to do that and 
to do it soon, because it affects many, many physicians, many, 
many hospitals, and as we've heard today in a couple of 
important ways, it's absolutely essential to the Precision 
Medicine Initiative.
    If there's no other--I've got a final page I'm supposed to 
read. The hearing record will remain open for 10 days. Members 
may submit additional information for the record within that 
time if they would like.
    I want to thank Senator Murray again for the way she has 
conducted--helped us do this in a bipartisan way. We learn a 
lot more that way.
    The next HELP hearing will be tomorrow on higher education. 
The committee will stand adjourned.
    Additional Material follows.]

                          ADDITIONAL MATERIAL

                Prepared Statement of Senator Klobuchar

    Chairman Alexander and Ranking Member Murray, thank you for 
holding this important hearing today exploring how precision 
medicine can improve care for patients. I would also like to 
thank Dr. Collins, Dr. DeSalvo, and Dr. Shuren for being here 
to offer their views. Your agencies will be at the forefront of 
our Nation's work on precision medicine. I feel confident in 
the future of precision medicine with you three at the helm.
    Without a doubt, doctors have always aimed to treat the 
individual patient, not the disease. Our medical technology 
might finally be catching up with our intentions as medical 
innovation hones in on the level of the individual patient 
through precision medicine.
    In 2003, the National Institutes of Health and their 
international partners completed the mapping of the human 
genome--a scientific achievement equivalent to landing on the 
moon. The Human Genome Project jump-started the field of 
medical genomics and opened up new opportunities to improve how 
we care for patients.
    We have already seen the extraordinary results that 
precision medicine--health care tailored to a person's genes, 
environment and lifestyle--can have, for example, in a 
breakthrough drug to treat cystic fibrosis.
    Great work in the field of precision medicine is already 
being done in research centers around the country, including at 
the Mayo Clinic in Rochester, MN. I had the opportunity to see 
this work first hand when I visited Mayo's Center for 
Individualized Medicine. One great project is Mayo's BEAUTY 
study, which is working to understand why chemotherapy treats 
breast cancer in some women but fails in others. In addition, 
Mayo has a robust biobank with almost 50,000 samples that 
researchers can use to solve the mystery of a host of diseases.
    The United States should remain on the cutting edge of 
health care innovation. Today we have the opportunity to build 
on the success of the Human Genome Project and lead the global 
effort to encourage scientific discovery and clinical 
implementation of precision medicine. To accomplish those 
goals, we need strong leadership from the Administration, 
continued investment in research, and the proper regulatory 
framework to encourage innovation.
    With precision medicine, the health care of our future is 
closer than ever before. It will transform the way doctors 
provide care, making our health care system more efficient by 
providing improved, targeted treatments. Precision medicine is 
just beginning to show its promise, and it offers opportunities 
not just for patients in need of better treatments, but for the 
future of medicine as well. I know the committee and the 
Administration share the goal of supporting precision medicine, 
and that is why you are here today. I look forward to working 
with you toward accomplishing these shared goals.

    [Whereupon, at 4:21 p.m., the hearing was adjourned.]