[House Hearing, 111 Congress]
[From the U.S. Government Publishing Office]


 
                          HOW CAN NIST BETTER 
                           SERVE THE NEEDS OF 
                        THE BIOMEDICAL RESEARCH 
                     COMMUNITY IN THE 21ST CENTURY? 

=======================================================================

                                HEARING

                               BEFORE THE

               SUBCOMMITTEE ON TECHNOLOGY AND INNOVATION

                  COMMITTEE ON SCIENCE AND TECHNOLOGY
                        HOUSE OF REPRESENTATIVES

                     ONE HUNDRED ELEVENTH CONGRESS

                             SECOND SESSION

                               __________

                           FEBRUARY 24, 2010

                               __________

                           Serial No. 111-79

                               __________

     Printed for the use of the Committee on Science and Technology


     Available via the World Wide Web: http://www.science.house.gov

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                  COMMITTEE ON SCIENCE AND TECHNOLOGY

                   HON. BART GORDON, Tennessee, Chair
JERRY F. COSTELLO, Illinois          RALPH M. HALL, Texas
EDDIE BERNICE JOHNSON, Texas         F. JAMES SENSENBRENNER JR., 
LYNN C. WOOLSEY, California              Wisconsin
DAVID WU, Oregon                     LAMAR S. SMITH, Texas
BRIAN BAIRD, Washington              DANA ROHRABACHER, California
BRAD MILLER, North Carolina          ROSCOE G. BARTLETT, Maryland
DANIEL LIPINSKI, Illinois            VERNON J. EHLERS, Michigan
GABRIELLE GIFFORDS, Arizona          FRANK D. LUCAS, Oklahoma
DONNA F. EDWARDS, Maryland           JUDY BIGGERT, Illinois
MARCIA L. FUDGE, Ohio                W. TODD AKIN, Missouri
BEN R. LUJAN, New Mexico             RANDY NEUGEBAUER, Texas
PAUL D. TONKO, New York              BOB INGLIS, South Carolina
STEVEN R. ROTHMAN, New Jersey        MICHAEL T. MCCAUL, Texas
JIM MATHESON, Utah                   MARIO DIAZ-BALART, Florida
LINCOLN DAVIS, Tennessee             BRIAN P. BILBRAY, California
BEN CHANDLER, Kentucky               ADRIAN SMITH, Nebraska
RUSS CARNAHAN, Missouri              PAUL C. BROUN, Georgia
BARON P. HILL, Indiana               PETE OLSON, Texas
HARRY E. MITCHELL, Arizona
CHARLES A. WILSON, Ohio
KATHLEEN DAHLKEMPER, Pennsylvania
ALAN GRAYSON, Florida
SUZANNE M. KOSMAS, Florida
GARY C. PETERS, Michigan
JOHN GARAMENDI, California
VACANCY
                                 ------                                

               Subcommittee on Technology and Innovation

                      HON. DAVID WU, Oregon, Chair
DONNA F. EDWARDS, Maryland           ADRIAN SMITH, Nebraska
BEN R. LUJAN, New Mexico             JUDY BIGGERT, Illinois
PAUL D. TONKO, New York              W. TODD AKIN, Missouri
DANIEL LIPINSKI, Illinois            PAUL C. BROUN, Georgia
HARRY E. MITCHELL, Arizona               
GARY C. PETERS, Michigan                 
BART GORDON, Tennessee               RALPH M. HALL, Texas
                 MIKE QUEAR Subcommittee Staff Director
         MEGHAN HOUSEWRIGHT Democratic Professional Staff Member
            TRAVIS HITE Democratic Professional Staff Member
            HOLLY LOGUE Democratic Professional Staff Member
             DAN BYERS Republican Professional Staff Member
                  VICTORIA JOHNSTON Research Assistant



















                            C O N T E N T S

                           February 24, 2010

                                                                   Page
Hearing Charter..................................................     2

                           Opening Statements

Statement by Representative David Wu, Chairman, Subcommittee on 
  Technology and Innovation, Committee on Science and Technology, 
  U.S. House of Representatives..................................     5
    Written Statement............................................     5

Statement by Representative Adrian Smith, Ranking Minority 
  Member, Subcommittee on Technology and Innovation, Committee on 
  Science and Technology, U.S. House of Representatives..........     6
    Written Statement............................................     7

                               Witnesses:

Dr. Thomas M. Baer, Executive Director, Stanford Photonics 
  Research Center, Ginzton Lab
    Oral Statement...............................................     8
    Written Statement............................................    10
    Biography....................................................    13

Ms. Sharon F. Terry, MA, President and CEO, Genetic Alliance
    Oral Statement...............................................    14
    Written Statement............................................    16
    Biography....................................................    19

Dr. Daniel Sullivan, Professor and Vice Chair, Research in 
  Radiology, Duke University Medical Center and Science Advisor, 
  Radiologic Society of North America
    Oral Statement...............................................    20
    Written Statement............................................    21
    Biography....................................................    29

Discussion.......................................................    30

              Appendix: Additional Material for the Record

Testimony of Dr. Karen Mann, PhD, President of the Association 
  for Molecular Pathology........................................    37


    HOW CAN NIST BETTER SERVE THE NEEDS OF THE BIOMEDICAL RESEARCH 
                     COMMUNITY IN THE 21ST CENTURY?

                              ----------                              


                      WEDNESDAY, FEBRUARY 24, 2010

                  House of Representatives,
          Subcommittee on Technology and Innovation
                        Committee on Science and Technology
                                                    Washington, DC.

    The Subcommittee met, pursuant to call, at 2:10 p.m., in 
Room 2318 of the Rayburn House Office Building, Hon. David Wu 
[Chairman of the Subcommittee] presiding.
                            hearing charter

                     U.S. HOUSE OF REPRESENTATIVES

                  COMMITTEE ON SCIENCE AND TECHNOLOGY

               SUBCOMMITTEE ON TECHNOLOGY AND INNOVATION

                     How Can NIST Better Serve the

                    Needs of the Biomedical Research

                     Community in the 21st Century?

                      wednesday, february 24, 2010
                             2:00-4:00 p.m.
                   2318 rayburn house office building

1. Purpose

    On February 24, 2010, the Subcommittee on Technology and Innovation 
will hold a hearing to examine ways in which NIST could better serve 
the needs of the biomedical community. This hearing is a follow-up 
hearing to the hearing held on September 24, 2009, entitled: The Need 
for Measurement Standards To Facilitate Research and Development of 
Biologic Drugs.

2. Witnesses

Dr. Thomas M. Baer is the Executive Director of Stanford Photonics 
Research Center at Ginzton Lab.

Sharon F. Terry, MA is the President and CEO of Genetic Alliance.

Dr. Daniel Sullivan is a Professor and Vice Chair for Research in 
Radiology at Duke University Medical Center and Science Advisor to the 
Radiologic Society of North America.

3. Background

    On September 24, 2009, the Science and Technology Committee for the 
House of Representatives, Subcommittee on Technology and Innovation, 
held a hearing to examine the need to develop measurements, reference 
materials, reference standards, standard processes, and validation 
procedures to improve the research, development and regulatory approval 
of biologics.\1\ In the September 24th hearing, industry and the FDA 
expressed that there is a need for NIST to perform basic measurement 
science research to support the growth of the biologics industry.
---------------------------------------------------------------------------
    \1\ Hearing available at: http://science.house.gov/publications/
hearings-markups-details.
aspx?News1D=2597.
---------------------------------------------------------------------------
    Additional initiatives in the biomedical field have been proposed 
by NIST, including performing metrology research to support better 
diagnostic testing and the development of personalized medicine. 
Developing reference standards and materials in each of these areas 
could potentially lead to a substantial savings in the cost of 
healthcare, supporting innovation in the biomedical field, leading to 
job creation. For example, in the area of personalized medicine, the 
development of basic measurement science, particularly in the area of 
proteomics and biomarker discovery, could enable small biotech 
companies to utilize their more limited resources to develop therapies 
targeted to specific populations of patients. This, in turn, could lead 
to the growth of the biotech industry which has traditionally fostered 
innovation through small and start-up biotechnology companies.
    As another example, interpreting the results of diagnostic tests 
can be inconsistent and inaccurate, leading to the need for multiple 
testing of the same patient and/or the use of less effective treatment 
options. In the area of imaging tools, such as x-rays, magnetic 
resonance imaging (MRI) and positron emission tomography (PET), 
interpretation of the results is a subjective task; however the 
treatment of disease is an increasingly objective process given the 
multiple options available to patients. In addition, medical imaging 
devices vary from hospital to hospital, thus increasing the likelihood 
that results obtained from different machines using different standards 
and methods will not be comparable. Hence, better reference standards 
are needed to assist doctors in interpreting diagnostic medical imaging 
results objectively and consistently to improve patient treatment 
options.
    In a third example, as recently as 1980, the measurement 
uncertainty for cholesterol tests was more than 10 percent. This wide 
margin of uncertainty meant that large numbers of people were 
misdiagnosed as needing treatment when they did not, or not needing 
treatment when they did. After an investigation by the Subcommittee, 
NIST, in collaboration with the Centers for Disease Control and 
Prevention, developed a Standard Reference Material, which reduced the 
uncertainty level of these tests to 5 percent saving millions of 
dollars per year in unneeded treatment costs and improving the quality 
of health care for patients.\2\
---------------------------------------------------------------------------
    \2\ See http://www.nist.gov/public-affairs/techbeat/
tb9709.htm.
---------------------------------------------------------------------------
    All of the initiatives proposed by NIST in the biomedical field 
will require a substantial investment of resources and funding. As 
suggested in the September 24th hearing, in addition to providing 
increased funding to NIST for these programs, structural and managerial 
improvements would also be desirable to help NIST accomplish its goals 
in the biomedical area.\3\ The National Research Council, while 
approving of the efforts of NIST in the biomedical area, has indicated 
that improvements may also be made to NIST, and particularly to the 
Chemical Science and Technology Laboratory (CSTL), in order to maximize 
the impact of these efforts on the advancement of biomedical 
science.\4\
---------------------------------------------------------------------------
    \3\ The Potential Need for Measurement Standards to Facilitate the 
Research and Development of Biologic Drugs, Hearing before the 
Subcommittee on Technology and Innovation, Committee on Science and 
Technology, House of Representatives, 111th Congress, 1st Session 
(September 24, 2009), Ser. No. 111-53 at p. 86.
    \4\ The National Research Council, for example, suggested that:

       GThe Biochemical Science Division should identify what it 
      considers to be success in the context of NIST. There may 
      be too many small efforts to make a major impact. An 
      overarching strategy should be articulated and priorities 
      set, based on identifying what kinds of activities can best 
      be done in the NIST environment. Many of the groups have 
      done this, but a top-down alignment of research with the 
      division mission is missing. Once this is achieved, the 
      management team will have less difficulty in sifting 
      through the projects to determine which are the most 
---------------------------------------------------------------------------
      important to pursue going forward.

  An Assessment of the National Institute of Standards and Technology 
Chemical Science and Technology Laboratory, Fiscal Year 2009, Panel on 
Chemical Science and Technology Laboratory Assessments Board, Division 
on Engineering and Physical Sciences, National Research Council of the 
National Academies (p. 17).
    The Subcommittee will examine ways in which the NIST Director could 
improve biomedical research at NIST to accurately and effectively 
reflect the needs of the biomedical community. In particular, 
biomedical research at NIST should be structured to achieve the 
following: (1) increase NIST's technical expertise through 
collaborations with academic institutions, private industry and 
nonprofits; (2) increase and improve NIST's outreach efforts to 
industry, academia and nonprofits; and (3) develop mechanisms that 
allow for NIST to obtain effective and targeted input and feedback from 
industry, academia and nonprofits.
    As examples, the Subcommittee, with input and comments from experts 
in the biomedical field, will examine whether the following proposals 
may improve the ability of NIST to serve the needs of the biomedical 
community:

        1.  Development of an advisory board or panel of experts, 
        largely from industry, in the biomedical field to provide 
        guidance on focal areas and to discuss CSTL's official 
        activities.

        2.  Proving for the establishment of joint NIST university 
        centers for biomedical research at universities with strong 
        reputations for their biotechnology programs.

        3.  The establishment of a user facility at NIST that could be 
        used by industry and academia, similar to the NIST Center for 
        Neutron Research.

    Further, the Subcommittee has asked witnesses to provide comments 
on any additional changes that the NIST Director may implement that 
would improve NIST's ability to achieve the goal of providing the most 
effective service to the biomedical community, patients and doctors.

4. Witness Questions

    The following questions were asked of each witness:

          If NIST expands its involvement in performing 
        measurement science to develop measurements, reference 
        materials, reference standards, standard processes, and 
        validation procedures in the biomedical area, what future and 
        nascent areas of biomedicine will be most affected and how?

          Would the following elements assist NIST in 
        ascertaining current and future metrology needs for the 
        biomedical community? If so, how?

                  an advisory board for CSTL.

                  a NIST university center for biomedical research.

                  a user facility at NIST that could be used by 
                industry and academia.

          What other recommendations would you make regarding 
        the implementation of these or other elements?
    Chairman Wu. This hearing will come to order. Good 
afternoon. I would like to welcome everyone to today's hearing 
on improving the biomedical program at NIST [National Institute 
of Standards and Technology].
    This is the second hearing of this Subcommittee to examine 
how NIST can better serve the needs of the biomedical 
community. Our first hearing focused on what NIST could do to 
meet the metrology needs of the biologics industry.
    Today, the Subcommittee will hear testimony on how NIST can 
better respond to the metrology needs of the broader biomedical 
community, including performing research support, not just 
biologic drug development, but also personalized medicine and 
diagnostic testing.
    We all know that people across the country have recently 
been engaged in an ongoing debate over healthcare reform. We 
will not be debating that issue today, but that debate has 
focused, in part, on who should bear the costs for providing 
healthcare. This Subcommittee will take the discussion further 
and examine how we can use science to potentially reduce our 
healthcare costs, while improving care for patients.
    The growth of the biomedical sciences is essential to 
providing better care for patients, and better treatment 
options for doctors. Earlier, more accurate diagnoses of 
chronic diseases, such as heart disease and cancer, would save 
billions of dollars each year in medical costs. Moreover, 
better diagnostic tools, and the use of personalized medicine 
can lead to more effective treatments that are tailored to a 
patient's needs.
    In short, advancing the biomedical sciences promotes 
patient health and will lead to job creation in biotechnology 
and healthcare industries. We have heard from the biomedical 
community that metrology research is necessary to take 
biomedical science to the next level, and that NIST needs to be 
more connected to industry and academia to innovatively respond 
to the demands of this rapidly changing industry.
    That is the focus of today's hearing: innovation. Today, we 
will hear about new, innovative biomedical treatments, and how 
NIST may develop new, innovative processes to better provide 
service and support to this growing industry.
    I want to thank our witnesses for being here, for making a 
long trip on the part of many, and we plan to act on their 
guidance in the process of reauthorizing the America COMPETES 
legislation.
    And now, I would like to recognize the ranking member, Mr. 
Smith, for his opening statement.
    [The prepared statement of Chairman Wu follows:]
                Prepared Statement of Chairman David Wu
    Good afternoon. I'd like to welcome everyone to today's hearing on 
improving the biomedical program at NIST.
    This is the second hearing the Subcommittee has held to examine how 
NIST can better serve the needs of the biomedical community. Our first 
hearing focused on what NIST could do to meet the metrology_or 
measurement_needs of the biologics drug industry. Today the 
Subcommittee will hear testimony on how NIST can better respond to the 
metrology needs of the broader biomedical community, including 
performing research to support not just biologic drug development, but 
also personalized medicine and diagnostic testing.
    We all know that people across the country have recently been 
engaged in an ongoing debate over health care reform. That debate has 
focused in part on who should bear the costs for providing health care. 
This Subcommittee will take the discussion further and examine how we 
can use science to reduce our health care costs while improving care 
for patients.
    The growth of the biomedical sciences is essential to providing 
better care for patients and better treatment options for doctors. 
Earlier and more accurate diagnoses of chronic diseases, such as heart 
disease and cancer, would save billions of dollars each year in medical 
costs. Moreover, better diagnostic tools and the use of personalized 
medicine can lead to more effective treatments that are tailored to a 
patient's needs.
    In short, advancing the biomedical sciences promotes patient 
health, saves medical costs, and will lead to job creation in the 
biotechnology and health care industries.
    We have heard from the biomedical community that metrology research 
is necessary to take biomedical science to the next level and that NIST 
needs to be more connected to industry and academia to innovatively 
respond to the demands of this rapidly changing industry.
    That is the focus of today's hearing_innovation. Today we will hear 
about new, innovative biomedical treatments and how NIST may develop 
new, innovative processes to provide better service and support to this 
burgeoning industry.
    I want to thank our witnesses for being here. We plan to act on 
their guidance in the process of reauthorizing the America COMPETES 
Act.

    Mr. Smith. Thank you, Mr. Chairman, Chairman Wu, for 
calling today's hearing to examine ways in which the National 
Institutes of Standards and Technology can better serve the 
needs of biomedical researchers.
    At our first hearing on this topic last September, we had 
the opportunity to hear from NIST and the Food and Drug 
Administration [FDA] regarding what they believe to be their 
appropriate roles in supporting biomedical research, and about 
new initiatives NIST would like to implement to support this 
rapidly advancing field of research.
    It is clear from past experience there is a constructive 
role for NIST to play as a standard-setting body in biomedical 
research. Past advances by NIST have improved the accuracy and 
comparability of medical research and testing in numerous 
fields, and as diagnoses and treatments become more and more 
individualized, the need for such criteria will certainly only 
increase.
    As we work to ensure NIST's authorization meets the 
evolving needs of the biomedical research community, we must 
also remain mindful of our responsibility to ensure NIST's 
standardization efforts enhance and ease ongoing research, but 
actually do not replace it. Although this has not often been an 
issue, we would be remiss to not continue monitoring this 
concern.
    We must also address how expanded activities at NIST will 
be funded. One idea discussed at our last hearing was whether 
benefiting agencies such as FDA and NIH [National Institutes of 
Health] should fund NIST's work in these areas from their 
budgets. Although shifting funding from these agencies to NIST 
may appear less than ideal, if NIST's work catalyzes these 
agencies' efforts, it may be an option worthy of pursuit, as 
such arrangements are not without precedent.
    Thank you again, Mr. Chairman. I am looking forward to a 
constructive session with today's witnesses, and I yield back 
the balance of my time.
    [The prepared statement of Mr. Smith follows:]
           Prepared Statement of Representative Adrian Smith
    Thank you, Chairman Wu, for calling today's hearing to examine ways 
in which the National Institute of Standards and Technology can better 
serve the needs of biomedical researchers.
    At our first hearing on this topic, last September, we had the 
opportunity to hear from NIST and the Food and Drug Administration 
regarding what they believed to be their appropriate roles in 
supporting biomedical research and about new initiatives NIST would 
like to implement to support this rapidly advancing field of research.
    It is clear from past experience there is a constructive role for 
NIST to play as a standards-setting body in biomedical research. Past 
advances by NIST have improved the accuracy and comparability of 
medical research and testing in numerous fields, and as diagnoses and 
treatments become more and more individualized, the need for such 
criteria will only increase.
    As we work to ensure NIST's authorization meets the evolving needs 
of the biomedical research community, we must also remain mindful of 
our responsibility to ensure NIST's standardization efforts enhance and 
ease ongoing research, but do not replace it. Although this has not 
often been an issue, we would be remiss to not continue monitoring this 
concern.
    We must also address how expanded activities at NIST will be 
funded. One idea discussed at our last hearing was whether benefiting 
agencies such as FDA and NIH should fund NIST's work in these areas 
from their budgets. Although shifting funding from these agencies to 
NIST may appear less than ideal, if NIST's work catalyzes these 
agencies efforts, it may be an option worthy of pursuit, as such 
arrangements are not without precedent.
    Thank you again, Mr. Chairman. I am looking forward to a 
constructive session with today's witnesses and I yield back the 
balance of my time.

    Chairman Wu. Thank you very much, Mr. Smith. Other Members 
who wish to submit additional opening statements, your 
statements will be added to the record at this point.
    Now, it is my pleasure to introduce our witnesses. First, 
Dr. Thomas Baer is the Executive Director of the Stanford 
Photonics Research Center at the Ginzton Lab, and is a 
consulting professor in the Applied Physics Department at 
Stanford University.
    Now, I would like to recognize the gentlelady from 
Illinois, Ms. Biggert, to introduce our next witness.
    Ms. Biggert. Thank you, Mr. Chairman, and I am honored to 
introduce Sharon Terry, who is the President and CEO of the 
Genetic Alliance, a network that is transforming health by 
promoting an environment of openness, centered on the health of 
individuals, families, and communities.
    I have had the opportunity to work with her for quite a few 
years, on what we consider as a very important bill. It is 
called GINA, that is the Genetic Information Nondiscrimination 
Act, which passed two years, and I think the regs have just 
come out. But it was something that Louise Slaughter of New 
York and Ted Kennedy and Olympia Snowe and I worked on, and it 
took over ten years. And it passed out of the House with about 
420 to 2 votes. You wonder why it took that long, but there was 
a lot of work that it went into it, and it really is going, I 
think, to change healthcare, and I am very proud of that.
    And Sharon put it all together, with her enthusiasm, and 
her way of bringing together advocates and, diverse advocates, 
and get them all to work together.
    I welcome her here.
    Chairman Wu. Thank you very much, Ms. Biggert.
    And our final witness is Dr. Daniel Sullivan, who is 
Professor and Vice Chair for Research in Radiology at Duke 
University Medical Center, and Science Advisor to the 
Radiological Society of North America [RSNA].
    You will each have five minutes for your spoken testimony. 
Your written testimony will be included in the record in its 
entirety, and when you complete your testimony, we will begin 
with questions, and each Member of the panel will have five 
minutes to question the panel.
    Dr. Baer, please proceed.

 STATEMENT OF DR. THOMAS M. BAER, EXECUTIVE DIRECTOR, STANFORD 
             PHOTONICS RESEARCH CENTER, GINZTON LAB

    Dr. Baer. Thank you, Chairman Wu. And I would like to thank 
you and the rest of the Committee for the opportunity to 
testify about how NIST can better serve the needs of the 
biomedical research community in the 21st Century.
    I am a physicist, but I have worked in the biomedical area, 
primarily in the private sector, for the last twenty years, 
developed instrumentation and technology for HIV and AIDS 
diagnosis, as well as bone marrow transplant quality control, 
and breast cancer diagnostics, and know very well the 
importance of accurate measurement for precise diagnosis.
    I also have a background with NIST. I served for six years 
on the NRC [National Research Council] panel for both the 
Physics Lab and Chemistry Science and Technology Lab, as well 
as served for the last four years on the Visiting Committee for 
Advanced Technology [VCAT], and chaired the Biosciences 
Healthcare Subcommittee as a part of my VCAT responsibilities.
    Today, I will be presenting my personal perspective, and 
not speaking for the VCAT Committee, but of course, my opinion 
has been shaped by many discussions with my colleagues on the 
VCAT Committee, and they share many of the opinions that I will 
be presenting today.
    My long history with NIST has instilled in me a great 
respect for what NIST can accomplish when it focuses its effort 
to support U.S. industry through world-leading measurement 
research and standards development.
    I am very pleased to be here with my colleagues, Sharon 
Terry and Dan Sullivan. Sharon is going to present, very 
eloquently, a patient point of view, and Dan, a clinical point 
of view. And I thought I would take my time to present my 
perspective on the industry, the biomedical and bioscience 
industry, and the exciting potential that new technology offers 
there.
    We are here today because of a technological revolution 
that has occurred over the past several decades. In general, 
new products bring benefit to society through creating new 
industries, and these new products are based on innovative 
engineering. And engineering usually has its foundation in the 
quantitative sciences, which have traditionally been 
mathematics, physics, and chemistry.
    However, over the last 30 years, there has been tremendous 
progress in the life sciences, and it has entered into this 
regime of quantitation. Through remarkable advances in 
technology, which allow very precise measurements of DNA, RNA, 
and proteins. Many of these advances were developed here in the 
United States, based on research funded by the U.S. Government, 
the polymerase chain reaction, DNA microarrays, four color 
sequencing, all evolved here in the United States.
    There are many industries that depend on this industry, 
besides the healthcare industry, and they are listed here, but 
the healthcare industry, which we are focusing on today is a 
$2.5 trillion industry. It represents 20 percent of the U.S. 
gross domestic product, and it employs ten million people. And 
it is truly an enormous industry here in the United States.
    It is a rapidly growing industry. It is not only big, it is 
one of the fastest growing. It is one of the largest areas of 
investment in Silicon Valley for venture capital. Dozens of 
companies are formed each year, creating thousands of new jobs.
    The goal of these companies, and of this industry, is to 
improve the quality of healthcare and save lives. It is to 
reduce the cost of healthcare, to create new jobs, and to keep 
the U.S. biomedical healthcare industry competitive worldwide.
    As an example of the types of advances that have occurred, 
here is one illustration. In 1975, if you used a sequencing 
instrument back then, you could generate about a nucleotide 
sequence of about 2,000 base-pairs. And if you printed out this 
data, it would take up one half a page in a book. To sequence 
the human genome using a single instrument from that technology 
would have taken 4,000 years. In 1990, when lasers were 
introduced as a part of the instrumentation in capillary 
electrophoresis, you could generate data on 100,000 base-pairs 
per day, and to sequence the human genome would have taken 
about 80 years. To print out all this data would have taken a 
chapter in a book. Today, a single instrument can generate two 
billion base-pairs of data in a single day, and that data would 
fill ten encyclopedia's worth, to print out all of that data.
    Chairman Wu. Dr. Baer.
    Dr. Baer. Yes.
    Chairman Wu. Let me interrupt you just for a second. Your 
slide says, it takes--it would take one day to sequence a 
single human genome.
    Dr. Baer. Yes.
    Chairman Wu. You mean, like, the entire genome of a human 
being?
    Dr. Baer. Yes. A single human genome has three billion 
base-pairs in it, and one of these instruments now_one of the 
state of the art instruments_can do that process in a single 
day.
    Chairman Wu. You have to understand that, given that I am a 
child of the mid to late '70s doing biochemistry, I was in a 
basement lab at Stanford, at Stanford Medical School. This is 
just jaw-dropping. Sorry to interrupt.
    Dr. Baer. Not a problem. And to put it in perspective, some 
of the testimony from Sharon Terry, her accomplishment, 
searching for the PXE [pseudoxanthoma elasticum] gene, would be 
like looking for one misspelling in a word within that ten 
encyclopedias. It is a phenomenal accomplishment that she and 
her husband worked on. Yes. So, this example is one of the 
challenges facing medical science today, what to do with this 
enormous amount of data.
    As another example, the type of data that is generated by a 
high resolution CT [CAT/computer tomography] scan that Dr. 
Sullivan will be talking about, that CT scan generates a 
comparable amount of data, about two billion data points.
    So, the role of NIST is to make sure that this data is high 
quality, to be able to develop the technology and software to 
extract from this data the critical elements that can be used 
in diagnosing diseases.
    Currently, NIST is primarily organized by discipline. It 
has a number of very high quality laboratories, primarily 
focused around the traditional areas of mathematics, physics, 
and chemistry. It does not have a life science laboratory 
focused on the biomedical and healthcare industry, or the 
technology that has evolved over the last several decades. And 
I think, it is clear to us that NIST needs to expand its 
efforts in the biomedical area, and to do so effectively, and 
optimize its interface to the biomedical industry. It may be 
necessary for NIST to consider forming a separate operating 
unit and laboratory in the bioscience and healthcare area.
    Let me close my remarks by commenting on the strong 
leadership provided by the current director of NIST, Dr. 
Patrick Gallagher. Dr. Gallagher indicated at the last VCAT 
meeting that we had in February that he is working with the 
NIST lab directors and senior managers to develop a new NIST 
structure that will improve NIST's ability to address the 
pressing needs of U.S. industry and fellow government agencies.
    NIST can best be organized to service its many diverse 
stakeholders, I believe, and capitalize on this great 
opportunity to reorganize and expand NIST resources, by 
potentially introducing a new biomedical and healthcare 
laboratory. I look forward to working with Dr. Gallagher to 
bring about these types of changes.
    Thank you very much, Mr. Chairman.
    [The prepared statement of Dr. Baer follows:]
                  Prepared Statement of Thomas M. Baer
Chairman Wu, Congresswoman Edwards and Biggert, and Committee Members:

    Thank you for this opportunity to testify before the Technology and 
Innovation subcommittee on How NIST Can Better Serve the Needs of the 
Biomedical Research Community in the 21st Century.
    My name is Tom Baer, and I am the Executive Director of the 
Stanford Photonics Research Center and a Consulting Professor in the 
Applied Physics Department at Stanford University. Although my early 
training and scientific research was in Physics, I have spent most of 
my career working in the fields of biotechnology and biomedicine, 
primarily in the private sector. I have been a research scientist, 
founder, CEO, and senior manager in several biomedical companies in 
Silicon Valley and have developed technology used in the diagnosis of 
AIDS, quality control of bone marrow transplants, and the molecular 
analysis and diagnosis of breast and lung cancer.
    I have a long association with NIST, having worked with several 
directors and lab managers, serving six years in the 1990s on the NRC 
review panels for both the Physics and Chemical Science and Technology 
Laboratories. I have also served for the past four years on the 
Visiting Committee for Advanced Technology (VCAT). I want to clearly 
state that in my testimony today I am presenting my own perspective on 
the topics being discussed, and I am not speaking on behalf of the VCAT 
committee. However, my perspective has been influenced by many in-depth 
discussions held with my colleagues on the VCAT, and we share similar 
views on many of these issues.
    My long association with NIST has instilled in me a deep respect 
for this government agency, its personnel, and its unique mission. 
NIST's world class measurement science and standards development 
activities can form an important framework for innovation, enhancing 
competitiveness of US industry, and supporting job creation. This is 
particular true in the area we are discussing today of bioscience and 
healthcare.
    As one of the largest sectors of our economy, estimated at $2.5 
trillion, healthcare makes up 20% of the total US gross domestic 
product and employs approximately ten million Americans. These workers 
provide services essential to our quality of life in this dynamic, 
rapidly growing sector. In spite of the recession, US venture capital 
firms clearly foresee tremendous growth potential in biomedicine and 
biotechnology. Venture capital firms in Silicon Valley continue to fund 
life science startups, creating dozens of companies each year, 
employing thousands of workers. Startup companies translating 
scientific advances into important, new therapeutic and diagnostic 
medical procedures have been one of the largest areas of venture 
capital investment in Silicon Valley for the last ten years. This area 
is clearly one of the most important, dynamic sectors of our economy, 
and one in which NIST can and must play a vital role.
    What is causing this tremendous growth? Technology innovation and 
new product engineering historically have been based on a foundation 
provided by the quantitative sciences: physics, chemistry and 
mathematics, strong areas of focus at NIST. However over the past 30 
years tremendous advances in instrumentation and new technologies have 
stimulated extraordinary progress in the life sciences. Innovative 
instrumentation has opened up unprecedented capabilities for precise 
measurement of biological macromolecules such as DNA and proteins. 
Thirty years ago, using an instrument of that era, it would have taken 
several thousand years to sequence a human genome. The newest 
generation of high throughput gene sequencing instruments can sequence 
a human genome in less than one day. Similarly, 3 decades ago measuring 
the expression level of a single gene in a tumor would have taken 
several days or weeks in a biomedical research lab. Today we can 
measure the expression levels of thousands of genes simultaneously in 
under an hour. These measurements provide the possibility for more 
precise classification of cancer tumors and much more effective methods 
for quickly and effectively choosing optimal drug therapy. These 
advances make possible personalized medicine where custom therapies are 
developed and prescribed based on a patient's individual genetic 
makeup. Medicine is being transformed by these developments, moving 
from a primarily observational science to a truly quantitative 
discipline, hopefully soon to fully join the ranks of physics, 
chemistry and mathematics.
    This progress presents tremendous potential for lowering medical 
costs by reducing the number of tests necessary to diagnose disease and 
by helping physicians choose the best therapies and thus helping 
patients avoid unnecessary medical procedures. However, capitalizing on 
these therapeutic and diagnostic opportunities presented by recent 
advances in biotechnology requires the development of standardized 
procedures, new reference materials, instrument calibration protocols, 
and a much better understanding of the science underlying these new 
technologies, areas where NIST can make critical contributions.
    Despite the introduction of many new, effective diagnostic tests 
numerous challenges remain: the lack of standards, cross platform 
inconsistencies, and lab-to-lab variability are significant barriers to 
optimizing their impact. Two examples of current problems are 
illustrated by tests performed millions of times each year in the US: 
measuring levels of prostate specific antigen (PSA) to diagnose 
prostate cancer and thyroid stimulating hormone (TSH) essential to 
diagnose and treat thyroid disease. Results of PSA or TSH tests cannot 
be reliably compared if they are performed at different diagnostic 
laboratories using different measurement methods. A recent laboratory 
report had the following warning in a footnote ``PSA values from 
different methods cannot be used interchangeably.'' Patients are warned 
to be careful about interpreting TSH laboratory results if they have 
moved to a new location or change laboratories. This lack of 
reproducibility in test results confuses patients, causes much concern 
in medical practitioners, makes appropriate therapeutic intervention 
much more difficult, and often increases medical costs by creating a 
demand for multiple, repeated testing. NIST, specializing as it does in 
measurement science and standards development, could help to vastly 
improve test consistent and accuracy, substantially reducing medical 
costs.
    Translating the tremendous advances in quantitative biology 
instrumentation into effective diagnostic tests will require developing 
standard reference materials, reproducible consensus protocols, and 
understanding the basic measurement science underlying these new 
quantitative biomedical instruments. Much of this work has yet to be 
done and lack of this standards framework is impeding the translation 
of these new technologies into medical practice, affecting the lives of 
many critically ill US citizens who could benefit from accelerated 
introduction of these breakthrough technologies. NIST can play a 
pivotal role in accelerating deployment of these remarkable new 
instruments and procedures. Other government agencies, such as the FDA 
and NIH focus, on different aspects of health care, regulatory affairs 
and disease research respectively. Both of these agencies have strongly 
encouraged greater involvement by NIST in supporting the health care 
industry by developing standards and by expanding its ongoing research 
efforts bioscience and healthcare.
    As part of my VCAT responsibilities I chaired the Subcommittee on 
Bioscience and Healthcare. This Subcommittee included fellow VCAT 
members Lou Ann Heimbrook and James Serum, two highly experienced 
senior executives from the pharmaceutical and biotechnology industries. 
We have been working with several of the laboratory directors at NIST 
to help guide formation of a strategic plan to address the wide ranging 
needs of the Biomedical Health Care industry and research communities, 
as well as coordinate this program with the ongoing efforts at NIST to 
develop electronic medical records standards. I have found working with 
NIST senior management to formulate a roadmap for NIST in biomedical 
and healthcare to be a challenging but rewarding task, and it is still 
a work in process. NIST does not have a completely conceptualized and 
articulated a vision for how to best serve US industry needs in this 
area. I do feel strongly, however, that NIST management recognizes that 
there is an urgent need to complete this process and that there is a 
very exciting, critical role for NIST to play in the rapidly expanding 
arenas of healthcare and bioscience. One of the results of this 
planning was a conference designed to initiate a dialogue between NIST 
and stakeholders in the Biomedical Industry. The proceedings of this 
conference have been published in a document summarizing the opinions 
of the participants.
    NIST is at present organized by discipline with very strong 
laboratories in the traditional quantitative sciences. The Physics, 
Chemical Science and Technology, and Information Technology 
laboratories provide essential support to many US industries. 
Unfortunately NIST does not have a laboratory devoted specifically to 
supporting the biomedical and healthcare industry. In my opinion, NIST 
currently needs to add more staff familiar with the challenges facing 
the pharmaceutical, diagnostic and medical device industries. NIST also 
needs additional resources for expanding its facilities and acquiring 
the equipment to develop the research programs necessary to meet the 
needs of these industries. Currently there are several excellent groups 
within NIST making very important contributions, focused on research 
impacting significant, specific biomedical problems. However, the VCAT 
has commented in past annual reports that these groups are often 
isolated from one another in different NIST laboratories, their efforts 
are not well coordinated, and they often lack sufficient resources to 
optimize their impact. I believe that to be truly effective NIST needs 
to be provided with additional resources to expand efforts in this area 
and establish an operating unit or laboratory specifically focused on 
servicing the needs of the US Biomedical/Healthcare industry.
    For over a century NIST has played a very important role in many 
areas of quantitative science and technology providing standards and 
world-leading measurement science for precise reproducible measurement 
of many physical constants, chemical analytes, and important 
information on material properties. The standards and technologies 
developed by NIST have led to many very important and diverse advances 
such as GPS navigation, microelectronics and software standards, and 
critical standards for building materials which are integral parts of 
US fire codes. It is thus very appropriate for NIST to develop the 
expertise and facilities to play a comparable pivotal role in the 21st 
century in this new era of quantitative biomedicine.
    Let me close my remarks by commenting on the strong leadership 
provided by the current director of NIST, Dr. Patrick Gallagher. Dr. 
Gallagher indicated at the last VCAT meeting in February, 2010 that he 
is working with NIST lab directories and senior managers to develop a 
new NIST structure that will improve NIST's ability to address the 
pressing needs of US industry and fellow government agencies. He is 
formulating a significant, exciting new vision for how NIST can best be 
organized to service its many, diverse stake holders. I believe that 
this is a great opportunity to reorganize and expand the NIST resources 
supporting the US biomedical and healthcare industry, and I look 
forward to working with him to bring about these changes.
    In my testimony, Mr. Chairman, you asked me to address several 
specific questions:

    If NIST expands its involvement in performing measurement science 
to develop measurements, reference materials, reference standards, 
standard processes, and validation procedures in the biomedical area, 
what are the current, future and nascent areas of biomedicine that 
could be best served by NIST and how?

    The areas where I see NIST providing the greatest service are:

        1.  Diagnostic medicine

                  In particular developing standards, consistent 
                protocols, and advancing measurement science in 
                applying quantitative molecular analysis technology to 
                diagnostic tests

                  Supporting the application of the newest generation 
                of quantitative imaging instruments (CT, MRI, 
                ultrasound)

        2.  Working with the drug development industry to accelerate 
        the drug development process

                  Improving our understanding of the technology needed 
                to perform the measurements necessary to provide 
                accurate assessment of the safety and efficacy of new 
                drugs.

        3.  Working with universities and private industry to 
        development methods for new classes of therapy enabled by 
        advances in stem cell science. With applications, in diseases 
        such as diabetes and organ replacement

        4.  Providing a sound basis for measurement science in the area 
        of neuroscience and neuromedicine. With applications in 
        Parkinson's disease and Alzheimer's disease.

    Would the following elements assist NIST in ascertaining current 
and future metrology needs for the biomedical community? If so, how?

          An advisory board made up of industry experts.

    I recommend that NIST develop several advisory boards comprised of 
experts from the private sector and other government agencies 
representing different sectors of the biomedical industry. For example, 
separate panels could be formed with experts from molecular 
diagnostics, imaging diagnostics, drug development, medical devices and 
biomedical materials. These advisory panels should meet regularly with 
NIST personnel working in these areas to help identify the critical 
problems that need to be addressed and to establish the most effective 
strategic and tactical focus for biomedical programs at NIST.

          A university center for biomedical research

    University collaborations and joint institutes have played an 
important and very successful role in other NIST programs, and I 
believe this approach would work extremely well in the biomedical 
healthcare area. Specifically a university center focused on research 
into the fundamental measurement science underlying biomedical 
instrumentation and a joint institute studying the measurement science 
challenges inherent in the measurement of complex biological systems.

          A user facility that could be used by industry and 
        academia

    A separate operating unit or laboratory would provide a critical 
central focus for research at NIST in biomedicine. Such a facility 
could support visiting scientists from industry to provide input to 
NIST research activities, as well as physical location for NIST 
researchers, postdocs, and graduate students to associate with 
multidisciplinary teams working in similar or related biomedical areas.

                      Biography for Thomas M. Baer
    Thomas Baer is the executive director of the Stanford Photonics 
Research Center. He has been active in many scientific areas employing 
optics: atomic and molecular spectroscopy, optical metrology, ultrafast 
lasers, pulse compression, solid-state lasers, laser scanning 
fluorometry of blood cells, laser capture microdissection of biopsy 
samples and microgenomics. He has worked in industry and academia, and 
has participated in a number of successful collaborations with academic 
and government research groups, resulting in numerous commercial 
products that incorporate lasers and optics.
    Tom graduated with a BA in physics from Lawrence University and 
received his PhD in 1979 from the University of Chicago, where he 
studied atomic physics with Isaac Abella and Ugo Fano. After that, he 
worked with John Hall at JILA on high resolution spectroscopy and co-
invented new techniques for frequency stabilizing lasers.
    In 1981, he joined Spectra-Physics (SP), where he held positions as 
vice president of research and Spectra-Physics Fellow. His research 
there focused on ultra-fast lasers, pulse compression, diodepumped 
solid-state lasers and non-linear optics. His group developed and 
patented the first commercial optical pulse compressor, high power, 
fiber-coupled diode-pumped solid-state lasers, and mode-locked Ti-
Sapphire lasers. His commercial products received several industry 
awards for design innovation.
    After leaving SP, he joined Biometric Imaging (BMI) and changed his 
research focus to biophotonics. At BMI, he led an interdisciplinary 
group that developed the scanning laser instruments used in diagnostic 
tests for bone marrow transplant therapy and immune system monitoring 
in AIDS patients.
    Following his departure from BMI, Tom founded Arcturus Bioscience 
and served as CEO and chairman until 2005. Arcturus Bioscience 
pioneered the area of microgenomics_the precise molecular analysis of 
microscopic tissue samples. Arcturus technology is widely used in life 
science research laboratories and in molecular diagnostic tests for 
cancer. He left the company in 2005 and joined Stanford University, 
where he is the executive director of the Stanford Photonics Research 
Center and a member of the Applied Physics department. Tom has co-
authored scientific publications in the fields of atomic physics, 
quantum electronics, laser applications and biotechnology.
    He is an inventor on over 60 US patents and a co-author on many 
scientific papers. He was named Entrepreneur of the Year for emerging 
companies in Silicon Valley in 2000 by the Silicon Valley Business 
Journal. He is an alumnus of Harvard Business School, and has received 
the Distinguished Alumni Award from Lawrence University. Tom also 
serves on visiting committees and advisory groups with NIST, NIH and 
the Physical Sciences Division of the University of Chicago. He is a 
Fellow of The Optical Society and the American Association for the 
Advancement of Science. He served as President of the Optical Society 
of America in 2009 and is currently serving as Past President.

    Chairman Wu. Thank you very much. Thank you very much, Dr. 
Baer.
    I think that many of us are very excited about Dr. 
Gallagher's installation at NIST, and look forward to a long 
and stable administration there.
    And thank you very much for this perspective on the 
progress of gene sequencing. I don't know if I am more 
gratified about the progress made, or more concerned about how 
long it has been since I was a college student.
    Ms. Terry, please proceed.

   STATEMENT OF MS. SHARON F. TERRY, MA, PRESIDENT AND CEO, 
                        GENETIC ALLIANCE

    Ms. Terry. Thanks very much, Chairman Wu, and thank you 
very much, Congresswoman Biggert, for your introduction. 
Congresswoman Edwards, and to the Committee.
    Today, you are hearing from accomplished researchers and 
leaders in the fields of their study, from Stanford and Duke. 
These individuals are scientists, entrepreneurs, biotechnology 
innovators, and certainly great leaders.
    I come here primarily as a mom. I am here today to address 
the critical link between my experience as a mother, striving 
for treatments for my kids and millions of others, and the 
question before this Committee, how could NIST be more 
effective in influencing innovation in the life sciences?
    I begin with a plain statement about NIST and its 
activities. It can appear to be boring, non-interesting, and 
terribly esoteric. NIST suffers from being hidden, embedded in 
the foundational infrastructure of the scientific and early 
commercial enterprise of innovation, as well as having the 
thankless task of creating measurement standards for a whole 
array of scientific disciplines. However, it is precisely 
because of these elements that this Committee needs to champion 
a more active role for NIST in the life sciences.
    Some have quite convincingly argued that the next century 
of scientific and technological innovations will be the most 
profound in the life sciences. NIST is critical to a robust 
medical, biomedical enterprise, and must contribute high 
quality materials, methods, and expertise for the field to 
advance on a platform of certainty and high quality 
measurements.
    My two children were diagnosed with a genetic disease, 
pseudoxanthoma elasticum, 15 years ago. As a result, I chose to 
leave my career as a college chaplain, and become involved with 
the life sciences and biotechnology in search for a solution 
for their disease. I started a foundation called PXE 
International, organized patient populations around the world, 
created a bio-bank, isolated the disease gene, developed a 
commercial diagnostic, created animal models, and have 
supported clinical interventions for adults living with the 
disease.
    We still do not have a treatment intervention for my 
children or any of the individuals with this disease, and we 
are still hard at work. This is typical of most diseases. We 
have been stymied by a number of measurement and experimental 
roadblocks in advancing clear understanding of the disease, and 
the function of the altered protein that causes pseudoxanthoma 
elasticum. We have run smack into the wall of both scientific 
and technological limitations.
    My foundation's research work has been written about in 
prestigious journals as a model of innovation, and an example 
of the power of patient-driven translational research. Some 
have said our work will change the field. But I am telling you 
that we are limping toward the finish line of our objective, 
because of the current limitations in measurement science. This 
science has real world impact on patients, families, and 
communities.
    At this time, each provider of biomedical tests and 
therapies is creating their own system, leading to widespread 
inconsistencies between these practices. Americans believe they 
are receiving healthcare that is high quality, accurate, valid, 
and consistent. They do not realize that a PSA [prostate-
specific antigen] test from one lab cannot be compared to 
another lab. They have no idea that the four million newborns 
who are screened every year are subjected to different 
screening cutoffs in every state program, for the somewhere 
between 29 to 54 tests. The states count the number of screens 
they conduct differently from one another, because there are no 
standards. The 2,700 genetic tests that are now protected by 
GINA, thanks to Congresswoman Biggert and others, listed in 
gene tests, are purported to be actually hundreds of thousands 
of tests, because of the variability across labs performing 
these tests. No one knows how many tests there are, and there 
are only standards for 35 of the analytes used in all these 
tests.
    Every technology manufacturer applies relevant measurement 
technology with their own standard references and controls. For 
example, housekeeping genes and control agents. The FDA, as a 
regulatory agency, is challenged with ascertaining the accuracy 
and precision of these technologies based on the manufacturer-
supplied standards. Ultimately, they must trust the 
manufacturers.
    Just this morning, I was at NIH, where Secretary Sebelius 
announced a collaboration between NIH and FDA, and Drs. Collins 
and Hamburg announced that they will be doing regulatory 
science and the study of that science. Very seriously, there is 
not any way they can do it without the standards that NIST 
needs to produce, and a collaboration in that regard is 
necessary.
    NIST must take a leadership role in creating the standards 
necessary to integrate new technologies into medicine. These 
technologies, in genetics, genomics, laboratory science and 
imaging, are migrating into healthcare, sometimes to the point 
of care. It is critical that patients know that these 
healthcare services are based on the certitude that only 
standards can bring.
    With Congress' increased support, I believe NIST should 
create a life sciences infrastructure catalog and distribution 
system for reference materials and standards for quality 
assurance for all clinical diagnostic tests, integrate 
measurement standards and technologies into the FDA regulatory 
regime, partner with the National Institutes of Health on 
resolving the measurement challenges at the intersection of 
patient care, and conduct a comprehensive analysis of the life 
sciences to determine the highest needs for measurement 
science.
    In this age of emerging personalized medicine, delivered 
through new technologies to patients today, we cannot wait any 
longer, having far outstripped the standards available to 
biomedical enterprises. Leading Genetic Alliance and feeling 
the urgency of the hundreds of millions of people who need 
answers today, I know we need excellent leadership in an 
exceptional age.
    Let us take this charge seriously. Every one of us has a 
role to play, and NIST is poised to do great things.
    Thank you for the opportunity to contribute to the 
important work of your Committee.
    [The prepared statement of Ms. Terry follows:]
                 Prepared Statement of Sharon F. Terry

Introductory remarks

    My name is Sharon Terry, I am the mother of two children with a 
genetic disease, pseudoxanthoma elasticum (PXE). If it takes its 
course, they will loose their vision at about age 40. They both already 
experience moderate to severe wrinkling of the skin, another 
manifestation of the disease. I was catapulted into the world of 
genetics and biomedical research when they were diagnosed 15 years ago. 
I now run not only a genetic disease foundation for PXE, but also 
Genetic Alliance. Relevant to this testimony, I also serve on the 
Health and Human Services Office of the National Coordinator's 
Standards Committee for Health Information Technology.
    Genetic Alliance is the world's leading nonprofit advocacy 
organization committed to transforming health through genetics. We 
bring together diverse stakeholders to create novel partnerships in 
advocacy; we integrate individual, family, and community perspectives 
to improve health systems; we revolutionize access to information to 
enable translation of research into services and individualized 
decision-making. Genetic Alliance's network includes more than 10,000 
organizations, including disease-specific advocacy organizations as 
well as universities, private companies, government agencies, and 
public policy organizations. The network is a dynamic and growing open 
space for shared resources, creative tools, and innovative programs. 
Over the past 24 years, Genetic Alliance has been the voice of advocacy 
in health and genetics.
    Advocacy in the 21st century, however, requires new definitions and 
new focus. We dissolve boundaries to foster dialogue that includes the 
perspectives of all stakeholders: from industry professionals, 
researchers, healthcare providers, and public policy leaders to 
individuals, families, and communities. In a rapidly changing world, 
Genetic Alliance understands that nothing short of the transformation 
will suffice to transform health.
    My world revolves around the hundreds of millions of men, women and 
children in the US and throughout the world that wait, and sometimes 
die, for tests and therapies. It is my passion to accelerate 
translation of the phenomenal explosion of information surging through 
the biomedical research pipeline today. I grow more certain each day 
that the outcomes we seek, better health for all, are dependent on a 
solid foundation. That foundation is standards that allow high quality 
diagnostics and therapeutic development.
    I have witnessed enormous waste and disparities in test and drug 
development. I will give some examples and recommendations that 
illustrate the enormous payoff we would have as a nation with increased 
participation of NIST in the biomedical enterprise.
    The National Institute of Standards and Technology is the premier 
standards agency in the world. The success of the biomedical research 
enterprise, and America as a leader in innovation depends on NIST 
providing standards upon which to build personalized medicine.
    At this time, each provider of biomedical tests and therapies is 
creating their own system, leading to widespread inconsistencies 
between these practices. American's believe that they are receiving 
healthcare that is high quality, accurate, valid, useful and 
consistent. They do not realize that a PSA test from one lab, cannot be 
compared to another lab. They have no idea that the 4 million newborns 
who received screening at birth this year, are subjected to different 
screening cutoffs in each of the 51 programs in the states and 
territories. Most measurements are relative, internal to one lab, or 
one state, or one company. Every manufacturer applies relevant 
measurement technology with their own standard references and controls, 
for example in housekeeping genes and general control reagents. The 
Food and Drug Administration, as a regulatory agency, is challenged 
with ascertaining the accuracy and precision of these technologies 
based on the manufacturers supply control and references. Ultimately 
they must trust the manufacturers' standards.
    These technologies, in genetics, genomics, laboratory science and 
imaging, are migrating into clouds of care. At this point, the 
iterative cycle is over because a static product is being introduced 
into healthcare. We absolutely need new standards. They can be called 
clinical standards, but this should be a regulatable gray clinical 
standard in which all technology is measured if it's going to be used 
to treat patients. NIST needs to take a leadership role in creating the 
standards necessary to integrate new technologies into medicine.
    Metrology can be considered less than exciting science, because it 
is thankless and invisible in the medical system. The valiant work of 
NISTs scientists produce incredible standards of temporal and spatial 
value with little recognition.
    I have witnessed public health laboratories and companies develop 
precise measurements, and have them eschewed by their peers. However, 
the community won't use them because they are not independently judged 
or assessed, and because they would create the opportunity for 
comparisons that might be good for public health, but are generally not 
welcome by industry or laboratories. The community will use the least 
expensive alternative. If NIST standards, underpinned FDA requirements, 
the industry would be incentivized to improve life science measurement. 
Then companies and academic labs would not be differentiating 
themselves against the least expensive alternative. They'd be 
differentiating themselves against a performance standard, which is a 
completely different exercise.
    The highest standard for laboratory performance is Clinical 
Laboratory Improvement Amendment (CLIA). CLIA is structured in such a 
way that it avoids standards because it doesn't have them to use. Labs 
just need internal standards for the laboratory, the machines, the 
operators, and the protocol. At the present time, every single standard 
for every single test is unique to the test provider. This has created 
an untenable morass. The 2700 genetic tests currently listed in 
GeneTests (http://www.ncbi.nlm.nih.gov/sites/GeneTests/?db=GeneTests) 
are actually somewhere in the hundred thousands tests because of the 
variability across the labs performing these tests in the US and 
beyond.
    Current, future and nascent areas of biomedicine that could be best 
served by NIST if it expands its involvement in performing measurement 
science to develop measurements, reference materials, reference 
standards, standard processes, and validation procedures in the 
biomedical area.
    In the future, schizophrenia, rheumatoid arthritis, asthma, 
attention deficit disorder, autism and other spectrum disorders may be 
treatable if there were control standards to measure various attributes 
of phenotype. At present, these all rely on subjective patient 
reporting.
    Linearity studies can be conducted that show standards are accepted 
and work well for the technologies. This is the challenge for substrate 
microarrays for DNA measurement. There is a need an artificial control, 
a ladder control. It would create a benchmark for accuracy in 
measurement that would bring biomedical research and technologies a 
level of evidence it sorely needs to move to personalized medicine.
    In all cases, handling, storage, preparation all have influence on 
the accuracy of a laboratory measurement. It is difficult to control 
for all these variables in a measurement science. NIST at times appears 
paralyzed because of the large number of variables, wondering where to 
start, and seeming to be overwhelmed. If the biomedical universe is too 
big for one to tackle everything, then NIST should begin by producing 
methods standards.
    We need measurement standards of controls for pseudoxanthoma 
elasticum (PXE). The gene, ABCC6 has a 99% homology fossil gene that 
can produce erroneous test results for patients. In addition, at least 
17 other genes that have similar profiles and there are no controls. 
How many of these scenarios exist in the humane genome? Many, perhaps, 
but the genome is a fixed repository. It's a recipe and a cookbook for 
biological processes that has 23,000 functioning genes and probably 
100,000 alternate transcripts that could be mapped today and easily 
catalogued. These could have standards created for them. NIST could 
collaborate in a much more effective way with the FDA in the 
submissions they receive and integrate standards more frequently into 
the regulatory regime. Certainly at first we would be demanding more of 
a perfection standard from new technologies than what was cleared in 
the predicate standard, but one hopes science improves medicine. A good 
point for the intervention of high standards can be the point where 
something migrates into a regulatory schema for clinical use.
    Genetic Alliance submitted a citizen's petition for the creation of 
a genetic subspecialty under the Clinical Laboratory Improvement Act 
(CLIA). CLIA's response indicated that there were few standards for the 
2700 hundred tests that are being offered to patients. They indicated 
that they would be able to create a specialty when there were 
standards. This was in 2002, and there has been no progress since.

Assisting NIST in ascertaining current and future metrology needs for 
                    the biomedical community:

          Advisory board of industry experts

    I believe advisory boards can be very effective, provided they are 
given authority to make recommendations and the leadership of the 
agency is receptive. I am serving at this time on the HIT Standards 
Advisory committee and am impressed with the level of commitment of the 
members from industry and academia alike. We feel urgency and we feel 
like we are having an impact. A body with these attributes would be 
very good for NIST.

          University center for biomedical research

    The creation of multiple standards in many disciplines may be too 
broad a waterfront for NIST to tackle alone. A granting mechanism would 
be very effective. For example, academic groups could reply to RFPs 
that asks for referencing control standard for the biology of the 
highest priority cancers for NIH, including the encyclopedic genome of 
these cancers; for standards for all of the conditions in the current 
recommended panels for newborn screening, and/or the 2700 or so 
Mendelian disorders. Another RFP could ask for standards that would 
allow comparison of the fidelity of one machine to the next for 
mutation detection.

Other recommendations for implementing these elements (advisory board, 
                    university center and/or user facility) or others?

    It may be beneficial to set up a laboratory network dedicated in 
part to standards. The Collaboration Education and Test Translation 
program of the Office of Rare Disease Research at the National 
Institutes of Health has such a network associated with it. 
Laboratories share reference standards and controls for rare diseases. 
These could be codified in a standards based system at NIST. The model 
of this network might be deployed to other problems.

Concluding remarks:

    NIST must take a leadership role in creating the standards 
necessary to integrate new technologies into medicine. These 
technologies, in genetics, genomics, laboratory science and imaging, 
are migrating into health care, sometimes to point-of-care. It is 
critical that patients know that these healthcare services are based on 
the certitude that only standards can bring.
    With Congress's increased support, NIST should:

        1.  Create a life sciences infrastructure, catalog, and 
        distribution system for reference materials and standards for 
        quality assurance for all clinical diagnostic tests

        2.  Integrate measurement standards and technologies into the 
        FDA regulatory regime

        3.  Partner with the National Institutes of Health on resolving 
        the measurement challenges at the intersection of patient care

        4.  Conduct a comprehensive analysis of the life sciences to 
        determine the highest needs for measurement science

    In this age of emerging personalized medicine, delivered through 
new technologies to patients today, we cannot wait any longer, having 
far outstripped the standards available to biomedical enterprises. 
Leading Genetic Alliance, and feeling the urgency of the hundreds of 
millions of people who need answers today, I know we need excellent 
leadership in an exceptional age. Let us take this charge seriously. 
Every one of us has a role to play, and NIST is poised to do great 
things. Thank you for the opportunity to contribute to the important 
work of this committee.

                     Biography for Sharon F. Terry
    Sharon F. Terry is President and CEO of the Genetic Alliance, a 
network transforming health by promoting an environment of openness 
centered on the health of individuals, families and communities. She is 
the founding Executive Director of PXE International, a research 
advocacy organization for the genetic condition pseudoxanthoma 
elasticum (PXE). Following the diagnosis of their two children with 
pseudoxanthoma elasticum (PXE) in 1994, Sharon, a former college 
chaplain, and her husband, Patrick, founded and built a dynamic 
organization that enables ethical research and policies and provides 
support and information to members and the public.
    She is at the forefront of consumer participation in genetics 
research, services and policy and serves as a member of many of the 
major governmental advisory committees on medical research, including 
the HIT Standards Committee for the Office of the National Coordinator 
for Health Information Technology, liaison to the Secretary's Advisory 
Committee on Heritable Disorders and Genetic Diseases in Newborns and 
Children and the National Advisory Council for Human Genome Research, 
NHGRI, NIH. She serves on the boards of GRAND Therapeutics Foundation, 
the Center for Information & Study on Clinical Research Participation, 
The Biotechnology Institute, National Coalition of Health Professional 
Education in Genetics, and the Coalition for 21st Century Medicine. She 
is on the steering committees of Genetic Association Information 
Network of NHGRI, the CETT program, the EGAPP Stakeholders Group, and 
the editorial boards of Genetic Testing and Biomarkers, and 
Biopreservation and Biobanking, and the Google Health and Rosalind 
Franklin Society Advisory Boards. She is the chair of the Coalition for 
Genetic Fairness that was instrumental in the passage of the Genetic 
Information Nondiscrimination Act. She is a member of the IOM 
Roundtable on Translating Genomic-Based Research for Health. In 2005, 
she received an honorary doctorate from Iona College for her work in 
community engagement and haplotype mapping; in 2007 received the first 
Patient Service Award from the UNC Institute for Pharmacogenomics and 
Individualized Therapy; and in 2009 received the Research!America 
Distinguished Organization Advocacy Award. She has recently been named 
an Ashoka Fellow.
    Ms. Terry is a co-founder of the Genetic Alliance Biobank. It is a 
centralized biological and data [consent/clinical/environmental] 
repository catalyzing translational genomic research on rare genetic 
diseases. The BioBank works in partnership with academic and industrial 
collaborators to develop novel diagnostics and therapeutics to better 
understand and treat these diseases. Along with the other co-inventors 
of the gene associated with PXE (ABCC6), she holds the patent for the 
invention. She co-directs a 33-lab research consortium and manages 52 
offices worldwide for PXE International.
    Terry is committed to bringing together diverse stakeholders that 
create novel partnerships in advocacy; integrating individual, family, 
and community perspectives to improve health systems; and 
revolutionizing access to information to enable translation of research 
into services and individualized decision making. She lives with her 
husband Patrick and their two children in Maryland.

    Chairman Wu. Thank you very much, Ms. Terry. Thank you for 
your work as an advocate. I think that many children would 
benefit from your work.
    Your testimony has already opened eyes on this panel, in 
that I don't think any of the Members knew that no two PSA 
tests are comparable. That is really quite stunning.
    Dr. Sullivan, please proceed.

  STATEMENT OF DR. DANIEL SULLIVAN, PROFESSOR AND VICE CHAIR, 
   RESEARCH IN RADIOLOGY, DUKE UNIVERSITY MEDICAL CENTER AND 
      SCIENCE ADVISOR, RADIOLOGIC SOCIETY OF NORTH AMERICA

    Dr. Sullivan. Thank you, Chairman Wu and Members of the 
Committee. Thank you for this opportunity to offer brief 
testimony on how NIST could help better serve the needs of the 
biomedical research community in the 21st century.
    It is increasingly clear that the value of medical scans 
would be significantly greater if we could extract more 
objective, quantitative information from scans, rather than 
relying on radiologists' subjective, qualitative 
interpretations.
    This is an important priority for the RSNA, and we have 
several related activities, including the Quantitative Imaging 
Biomarkers Alliance, which brings together representatives from 
the medical scanner manufacturers, the pharmaceutical industry, 
and academicians, to work with manufacturers, to have them 
engineer medical scanners to be accurate measuring devices and 
not simply imaging devices. And also, the Imaging Biomarkers 
Roundtable, which facilitates communication among many 
organizations.
    In my brief testimony today, I would like to show you three 
examples of common diseases, using three different scanning 
methods, to illustrate why standards for extracting 
quantitative information are critically needed. First, the CT 
scan of a patient with chronic obstructive pulmonary disease, 
or emphysema. All digital images are made up of numbers. Here 
are some of the numbers behind the pixels in this scan. These 
numbers carry tissue information, but to be useful in medical 
care, these numbers have to be standardized, so that we know, 
for example, what tissue quality each number signifies on a 
given scanner, and what it means when that number changes. 
Right now, such standardization does not exist.
    For example, here, the red areas are areas of destroyed 
lung tissue, identified by a computer analyzing these numbers. 
A percentage number is what the treating physicians want to 
know, so that they could determine from future scans whether 
the patient is responding to therapy or not. If the patient is 
not improving, or getting worse, physicians have other 
treatment options they could use.
    However, right now, we radiologists cannot provide this 
kind of objective information about the actual percentage of 
lung destroyed, or other measurements, because the numbers are 
not standardized.
    The second example is cancer. These are PET [positron 
emission tomography] scans of a patient with lymphoma. PET 
scans show a radioactively tagged glucose that is being used in 
the body. In these scans, yellow is the highest level of 
glucose uptake. Because tumor cells are growing so rapidly, 
they take up much more glucose than normal cells, and the 
yellow areas represent tumor. If this glucose activity 
decreases after a couple of weeks of therapy, as shown here, it 
is a good sign the therapy is working. Oncologists need to know 
this early, because if the therapy is not working for a 
particular patient, there are usually alternatives that can be 
given.
    However, there are insufficient standards for PET scanners 
to ensure that you would get the same number for the amount of 
glucose measured in a tumor on one scanner as on another 
scanner, or even on the same scanner after an interval of a few 
weeks.
    My third example is Alzheimer's disease. We desperately 
need objective measures to determine whether lapses of memory 
are due to the ordinary stresses of everyday life or early 
dementia. Without objective markers for diagnosis, or to 
determine whether the disease is responding to new drugs or 
not, it will be impossible to develop effective therapies.
    One objective measure that could be used is the volume of 
the hippocampus on MRI [Magnetic Resonance Imaging] scans, as 
shown here. However, subtle volume differences in this small 
brain structure cannot be discerned by radiologists 
subjectively reading MRI scans. The scans have to be done on 
scanners that are calibrated with appropriate reference objects 
so that computer algorithms would calculate the same accurate 
and reproducible hippocampal volume no matter which scanner was 
used.
    These are just a few examples where clinicians clearly need 
more objective diagnostic tests. NIST can be a critical 
participant to help manufacturers meet this need. We need NIST 
to develop reference materials, standards, and validation 
procedures in the biomedical imaging area, especially for CT, 
PET, MRI, and medical optical imaging.
    To determine the metrology needs for the biomedical imaging 
community, NIST should appoint an advisory board made up of 
both industry experts and representatives of the imaging device 
users, such as patient advocates and professionals.
    Prior collaborations between scientists at NIST and 
university centers have been very productive. Such 
collaborations should be fostered by establishing one or more 
NIST academic centers for biomedical research. The private 
sector will continue to be a source of innovative reference 
objects, algorithms, and other devices for quantitative 
imaging. A NIST managed user facility that could be used by 
industry and academic developers to test their devices under 
standardized, controlled conditions would be an important 
asset.
    Finally, and very importantly, there is a critical need for 
a neutral broker, trusted by the public, to develop an 
accreditation and performance levels program, with associated 
policies and procedures. NIST is ideally suited to perform this 
role.
    Thank you again, Mr. Chairman and Members of the Committee, 
and I appreciate this opportunity to express the imaging 
community's view on this important topic.
    [The prepared statement of Dr. Sullivan follows:]
                 Prepared Statement of Daniel Sullivan
    Chairman Wu and Members of the Subcommittee_Thank you for this 
opportunity to offer brief testimony on How NIST Can Better Serve the 
Needs of the Biomedical Research Community in the 21st Century.
    I am Daniel Sullivan, Professor and Vice Chair for Research in 
Radiology at Duke University Medical Center, and Science Advisor to the 
Radiological Society of North America (RSNA). RSNA is an international 
organization with more than 40,000 members (http://www.rsna.org/). Its 
mission is to improve patient care through education and research. RSNA 
hosts one of the world's largest annual medical meetings, publishes two 
highly respected peer-reviewed journals, offers opportunities to earn 
CME, and provides research and education grants to young investigators. 
It is not a lobbying organization and has no government relations 
office or staff. My area of expertise is in diagnostic radiology and my 
remarks will therefore focus on that topic.

Statement of the Problem:

    The quality and cost of health care are major issues facing all 
Americans. In the past decade, discoveries about the basic biology of 
disease and technological advances in computers, imaging devices and 
laboratory methods have made it possible to imagine treatment plans 
that are individualized and optimized for each patient's unique pattern 
of disease. The term ``Personalized Medicine'' is used frequently these 
days. Of course, physicians have always, probably from the time of 
Hippocrates, tried to personalize their approach to treating patients 
based on the information available. What's different now is that we can 
get basic molecular information from each patient about the genetic and 
biochemical basis of their disease. Using each patient's unique 
biochemical signature of disease to individualize treatment is what the 
modern use of the term ``personalized medicine'' refers to.
    However, there are some major roadblocks on the path toward that 
vision. One is that diagnostic medical tests suffer from a lack of 
standards_in far too many cases we do not know whether test results are 
either accurate or comparable over space and time. Even though 
approximately 70 percent of health care decisions are based upon 
results from a test performed in a clinical laboratory, standards exist 
for only about 10 percent of the 700 most commonly ordered clinical 
tests. In the area of medical imaging, where it is estimated that U.S. 
healthcare consumers spent a combined $50 billion on medical imaging 
tests (MRI, CT scans, etc.) in 2008, the software and standards needed 
to enable physicians to extract and compare relevant data and to make 
definite determinations as to whether or not a tumor actually shrank or 
grew do not exist. These measurements and standards shortcomings result 
in repeat testing, misdiagnosis, and ineffective treatment decisions--
all of which contribute to a second major roadblock on the path toward 
personalized healthcare, the dramatic rise in health care spending. 
These dramatic cost increases are being driven by multiple 
inefficiencies throughout the health care system. One area in which 
significant improvements could be made, which would both decrease costs 
of and improve the overall quality of healthcare, is in developing and 
implementing better validated standards for laboratory medicine and 
medical imaging. Although modern clinical imaging methods are widely 
used, it is increasingly clear that the value of clinical imaging would 
be significantly enhanced if we moved toward extracting more objective, 
quantitative information from scans rather than relying on 
radiologists' variable, subjective, qualitative interpretations, which 
is the norm now. My comments today are focused on the need to develop 
measurements and standards infrastructure for medical imaging.

Background Activities:

    In addition to its high standing in the professional communities, 
RSNA enjoys a reputation as trusted, neutral party for industry. My 
role with the RSNA is to develop and coordinate programs to move 
radiology from subjective interpretations to objective, quantitative 
interpretations (i.e., ``imaging biomarkers''). In November 2006 the 
RSNA convened a group of stakeholders to advise the organization on 
what role it could most constructively play with regard to imaging 
biomarkers. The RSNA subsequently launched, and continues to sponsor, 
multiple initiatives to promote the quantitative, objective extraction 
of information from clinical images, focusing on imaging in clinical 
trials as an appropriate approach to establishing the necessary 
groundwork to support the use of imaging as biomarker.
    Among our various activities I would like to highlight just two: 
the Quantitative Imaging Biomarkers Alliance (QIBA) explicitly brings 
together representatives from the medical device imaging companies, 
representatives from the pharmaceutical industry and academicians to 
improve the accuracy and reproducibility of numbers extracted from 
medical scans (http://www.rsna.org/Research/giba-intro.cfm). 
Current scanners can be thought of as elaborate cameras, designed to 
produce exquisite pictures. They are not engineered to make precise 
measurements. A ``sound bite'' version of QIBA's mission is to 
encourage the vendors to produce measuring devices rather than just 
imaging devices.
    The second activity to mention today is the Imaging Biomarkers 
Roundtable, which brings together representatives from any and all 
organizations with an interest in or activities related to improving 
quantitative imaging biomarkers (http://www.rsna.org/Research/
roundtable.cfm). These activities were in fact started by a joint 
meeting including various government agencies, with a particularly 
important workshop in 2005 hosted by the NIST. Although I am not 
speaking on behalf of all these organizations today, my remarks are 
informed by the opinions of a diverse array of stakeholders. The 
Imaging Biomarker Roundtable and the technical committees formed under 
QIBA together comprise a collaborative enterprise addressing the need 
for quantitative imaging methods. Over the last two years, it has 
convened regular working groups for specific actions needed for 
specific imaging biomarkers, and proposed an organizational context 
that has potential to be self-sustaining to move the industry forward.

Clinical Examples:

    In my brief time for testimony today I would like to show you three 
examples of common diseases, using 3 different scanning methods, where 
standards for extracting quantitative information are critically 
needed. NIST's participation in this endeavor is essential.
    First, some technical background. All digital images, whether on 
your digital cameras, your computer screens, or a medical scanner, are 
made up of numbers. Every pixel or voxel has a number associated with 
it. Figure 1 shows a chest CT scan with some of the underlying numbers 
superimposed on the scan. Those numbers carry information, but to be 
useful in medical care those numbers have to be standardized so that we 
know, for example, what tissue quality each number signifies, and what 
it means when that number changes over time. Right now, such 
standardization does not exist.

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]


    Figure 1. Pixel numbers superimposed on a chest CT scan.

    The first clinical example is chronic obstructive pulmonary 
disease, COPD, often called emphysema. Figure 2 shows a patient who has 
COPD, and all the black areas are areas of destroyed lung tissue. The 
radiologist's interpretation would include a general statement about 
the degree of COPD present, but no objective information about, for 
example, the actual percentage of lung destroyed, or the thickness of 
the walls of the airways. Those objective measures are what the 
treating physician wants to know, so that he or she can determine on 
the next scan whether the patient is responding to therapy or not. If 
the patient is not improving or getting worse, the physician has other 
treatment options that he or she could use. The treating physician 
needs to have such objective measures of response prior to the time 
that the anatomic changes are so obvious that a radiologist can see it 
on the film. Right now we radiologists cannot provide that information 
because the numbers are not standardized.

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]


    Figure 2. Chest CT scan of a patient with COPD.

    The second clinical example is cancer. PET scans, or positron 
emission tomography scans, are now widely available at hospitals in the 
US and reimbursed by third-party payers for cancer. These scans show 
where glucose is being used in the body. Tumor cells take up much more 
glucose than normal cells because they are so rapidly growing. For PET 
scanning, patients receive an intravenous dose of glucose that has a 
radioactive label. The amount of radioactivity is very small, but the 
amount of uptake activity in the tumor tells us how actively the tumor 
is growing. If this activity has decreased after therapy has been given 
for a couple of weeks, it is a very good sign that the therapy is 
working. Oncologists need to know this with accuracy because, if the 
therapy is not working for a particular patient, there are often 
alternatives that can be given. However there are insufficient 
standards for PET scanners to ensure that you would get the same number 
for the amount of glucose measured in a tumor on one scanner as on 
another scanner, or even on the same scanner after an interval of a few 
weeks or more. NIST has already been extremely helpful in this area by 
developing a reference object with a source of germanium-68 
radioactivity that is traceable back to a source at NIST. This paves 
the way for groups such as QIBA to promulgate recommendations for 
calibrating scanners that will improve the comparability of 
measurements from one scanner to another. However, there is much that 
remains to be done, and continued participation by NIST experts is 
essential. Figure 3 is a combined PET/CT scan of a patient with 
lymphoma, showing a decrease in glucose uptake (yellow) after therapy 
has been given.

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]


    Figure 3. Combined PET/CT scans of lymphoma before and after 
therapy.

    The third clinical example is Alzheimer's disease. Many of us 
experience lapses of memory such as forgetting where we left our keys 
or what we came into the kitchen for, and sorting out whether such 
symptoms are due to early dementia or simply the stress of everyday 
life is extraordinary difficult. We desperately need objective measures 
for Alzheimer's and other dementias. This is true not only for routine 
clinical diagnosis in individual patients but also for drug trials to 
develop therapies for Alzheimer's. Without objective markers of whether 
the disease is responding to a drug or not, it will be impossible to 
develop effective therapies. A reliable diagnosis of Alzheimer's will 
probably require a combination of objective tests, as is increasingly 
true for many diseases, and there are several imaging candidates for 
such a multi-factorial approach for Alzheimer's disease. One such 
imaging test, for which there is considerable supporting evidence, is 
the volume of the hippocampus on MRI scans (Figure 4). However, the 
subtle volume differences between normal and abnormal in this small 
brain structure, or small changes over the course of several months, 
cannot be discerned by radiologists subjectively reading MRI scans. The 
scans need to be done on scanners that are calibrated with appropriate 
reference objects, and the images need to be acquired with standardized 
image acquisition methods, so that computer algorithms would calculate 
the same accurate and reproducible hippocampal volume no matter which 
scanner was used.

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]


    Figure 4. MRI scan of Alzheimer's Disease.

Discussion:

    It has been well-established in many industries and in scientific 
research that reference standards play a critical role for all 
stakeholders. Reference standards provide a transparent and widely 
available toolkit that enables regulators, manufacturers, researchers, 
and others to know whether a product is what it purports to be. 
Comparable processes do not exist today for many biomedical products 
and activities. NIST could apply its in-house expertise to enhance 
existing and develop new analytical tools for the biomedical sector, 
characterizing relevant reference standards and providing a repository 
for such reference standard materials. These improvements are necessary 
not only to improve routine clinical care, but also to reduce the size 
and time of clinical trials. The ``statistical noise'' due to the 
current variability in diagnostic methods forces investigators to 
accrue large numbers of subjects to clinical trials to achieve 
statistical validity. In addition, the adoption of standardized 
analytical methods and consistent reference standards would greatly 
enhance the interactions of companies with the FDA. Such improvements 
would establish a consistent approach to comparability assessments and 
create a level playing field for all companies.
    NIST has the potential to develop the measurement tools to support 
improved accuracy and reproducibility of current clinical diagnostics, 
enable quantitative and comparable medical imaging on current and 
future imaging platforms, and develop the methods necessary to enable 
and validate the next generation of medical measurement tools. 
Improvements to the accuracy and precision of clinical and diagnostic 
measurements will have significant short- and long-term economic 
impacts in the areas of drug/therapeutic development, and most 
importantly, the quality of patient care.
    It is clear that the development of standard methods, validation 
procedures, and reference materials for a variety of imaging methods 
will be of direct benefit to patients as well as to the biotechnology 
industry. If researchers working in Federal agencies such as NIST, 
government regulators, industry and academic scientists work together 
in this effort, it is much more likely that the outcomes will be 
successful_for government, for industry, and ultimately for the benefit 
of patients. NIST has begun to work with industry, academia, and other 
government agencies to identify the measurement tools and standards 
required to improve the quality of current biomedical measurements. 
NIST has made notable contributions already in the area of reference 
standards for x-ray, CT, PET and MRI (http://www.nist.gov/
public-affairs/releases/mri.html) (http://
collaborate.nist.gov/twiki-div818/bin/view/Div818/BioMagneticlmaging). 
A list of representative publications is included in the Appendix to 
this written testimony. This preliminary work has set the stage (and 
raised community expectations) to establish a coordinated program aimed 
at providing national standards for all the major imaging diagnostic 
methods being used clinically, and supporting industrial and medical 
researchers in developing new and better medical imaging instruments 
and methods.
    An expanded NIST program in quantitative medical imaging should be 
focused on:

          Developing quality assurance processes for CT, PET, 
        MRI, and Medical Optical clinical imaging.

          Identifying, evaluating, and minimizing or 
        eliminating sources of variability and error in imaging 
        modalities.

          Developing well-characterized phantoms (reference 
        objects) to reliably and accurately calibrate a variety of 
        instruments and systems.

          Developing measurement methods traceable to NIST-
        maintained standards.

          Developing standardized image databases for comparing 
        internal dose models for radiation-based imaging modalities, 
        and also for evaluating image processing algorithms.

          Conducting and evaluating round-robin inter-
        comparisons of devices and software.

          Working with industry and agencies to optimize image 
        processing and reconstruction software, and to develop 
        automated (or semi-automated) image analysis.

          Implementing a proficiency testing process to ensure 
        the inter-comparability of imaging data across different 
        clinical sites and across different modalities.

          Developing standards and methods for inter-
        comparability of clinical imaging data to support improved 
        analysis of change to determine drug efficacy.

    This work will improve healthcare quality and lower costs through:
    Improved reliability of medical imaging, resulting in:

          Increased accuracy of medical imaging

          Greater comparability over time and space

          Fewer misdiagnoses and unnecessary repeated tests.

          More accurate monitoring of disease progression and 
        therapeutic response

          Earlier detection of disease facilitating more 
        effective treatment decisions

          Improved reliability and accuracy of clinical trial 
        data.

    Increased quality of the information that goes into electronic 
health records, resulting in:

          Fewer medical errors

          Increased efficiency in healthcare delivery to mobile 
        patients

          Greater confidence for patients and healthcare 
        providers in the information used to make medical decisions.

    NIST scientists have had productive interactions with academic 
scientists in the imaging community, and the expanded program described 
above would be enhanced by NIST-Academic Centers of Excellence for 
Biomedical Research. Industry could contribute to NIST-academic centers 
in terms of problem specification.
    Another important collaborator would be the American Association of 
Physicists in Medicine (AAPM). Currently, the AAPM produces many 
detailed scientific, educational and practical reports for technology 
and procedures in medical imaging and radiation therapy. These reports 
include specific processes for radiation dose measurement and 
calibration, quality assurance and peer review. These are presented in 
educational forums at national and regional meetings and are also 
publicly available. AAPM has recently called attention to the need for 
a technology assessment institute to provide industry with independent 
pre-market or post-market evaluations. AAPM could provide key 
complementary expertise to the scientists at NIST. For example, when 
well-defined physical or engineering differences exist between 
products, unrelated to different anatomic or physiological phenomenon, 
comparative effectiveness can be determined by assessing technology 
using quantitative metrics. This would be particularly useful and cost-
effective in situations where simple modifications of an existing 
medical technology are introduced or a new technology is available that 
is changing rapidly in its potential for proving efficacy. An example 
includes the optimization of radiation dose in CT. Image quality can be 
assessed quantitatively on different CT scanners at the same radiation 
dose levels, providing an objective measure of comparative 
effectiveness that may not require a clinical trial. These comparisons 
could also include the analysis of safety mechanisms to avoid 
accidental over doses as well as a review of quality control 
procedures. Another example is the comparative evaluation of 
mammography, breast CT, and breast tomosynthesis in detecting and 
assessing the extent of breast cancer using various metrics of physical 
and psychophysical image quality (e.g., spatial resolution, noise, or 
conspicuity) and balancing the results in terms of cost and radiation 
dose level. In those cases and at those times, relatively inexpensive 
physical measurements or observer-based diagnostic accuracy studies may 
be very appropriate. A biomedical research group or institute focusing 
on the science behind those topics would be valuable.
    In addition to scientists at NIST and at academic centers, the 
private sector will continue to develop reference objects, software and 
other products that can contribute to the goal of more accurate and 
reproducible quantitative measurements in imaging. A valuable activity 
for NIST would be to create a user facility where industry and academic 
scientists can test, demonstrate and calibrate their products for 
optimal use in this arena. For example, different imaging modalities 
currently have either none or too many phantoms that are not 
standardized, evaluated etc. There are many proprietary solutions that 
are difficult to compare and to integrate. The imaging industry would 
benefit from a standard for equipment development and sales. The 
pharmaceutical industry needs it for clinical testing and having a 
comparable quality information source (comparable to clinical lab data 
with its existing quality standards).
    Very importantly, there is a critical need for a neutral broker, 
trusted by the public, to develop an Accreditation of Performance Level 
program, with accompanying policies and procedures. NIST is ideally 
suited to perform this role. An example of one function of such an 
accreditation program would be for NIST to be the secure holder of 
image databases. For the independent test of a new algorithm, NIST 
could have the system run on randomly selected scans from its database 
based on the type of population requested. NIST would give the 
sensitivity and specificity of the system, without informing the 
company about the specific cases. For each testing event a different 
distribution of cases would be selected for the examination. This would 
preserve the integrity of the testing cases and also allow testing 
across applicable populations.

Conclusion:

    Clinicians clearly need more objective diagnostic tests, and the 
imaging device manufacturers want to provide their customers with such 
tools. NIST can be a critical participant in this endeavor because of 
its Mission, because of its experience in working with industry on 
metrology issues, and because of its expert staff. Though it is 
possible for the private sector to pursue many of these ideas without 
NIST help, it is easy to believe that they would be strengthened were 
NIST to be involved on one or more of these ways. Since the 
foundational meeting in 2005, we have made great progress in the 
private sector and continue to do so. Now is a very auspicious time to 
loop back and again consider the most appropriate role that NIST can 
play in what is arguably an inevitable development in the radiology 
community for the public good.

          Speaking on behalf of the imaging community in 
        general, we need NIST to expand its involvement in performing 
        measurement science to develop reference materials, reference 
        standards, standard processes, and validation procedures in the 
        biomedical imaging area, especially for CT, PET, MRI, and 
        medical optical clinical imaging.

          To determine current and future metrology needs for 
        the biomedical imaging community, NIST would be well served by 
        an advisory board made up of both industry experts and 
        representatives of imaging device users (patient advocates and 
        professionals).

          There is precedent for excellent progress being made 
        from collaborations between scientists at NIST and university 
        centers. Such collaborations would be enhanced in the future by 
        establishing one or more NIST-Academic Centers for Biomedical 
        Research. An example of such a Center would be one to determine 
        the sources of variability in numbers derived from CT, MRI, PET 
        and optical scanners, and developing mitigation strategies for 
        the sources of variance. This is an activity that no single 
        manufacturer can do alone, and is an activity that academic 
        physicists or engineers are not funded to do.

          The private sector will continue to be a source of 
        innovative reference objects, algorithms, and other devices to 
        improve accuracy and reproducibility of imaging devices. A 
        NIST-managed user facility that could be used by industry and 
        academic developers to test their devices under standardized, 
        controlled conditions would be an important asset for this 
        work.

          Finally and very importantly, there is a critical 
        need for a neutral broker, trusted by the public, to develop an 
        Accreditation of Performance Level program, with accompanying 
        policies and procedures. NIST is ideally suited to perform this 
        role.

    Thank you again Mr. Chairman and Members of the Committee. I 
appreciate this opportunity to express the imaging community's views on 
this important legislation. I welcome your questions.

Appendix

    Representative Medical Imaging Publications from NIST:

1. Coletti JG, Pearson DW, DeWerd LA, O'Brien CM, Lamperti PJ. 
        Comparison of exposure standards in the mammography x-ray 
        region. Med Phys 1997;24:1263-7.

2. DeWerd LA, Micka JA, Laird RW, Pearson DW, O'Brien M, Lamperti P. 
        The effect of spectra on calibration and measurement with 
        mammographic ionization chambers. Med Phys 2002;29:2649-54.

3. Clarke LP, Sriram RD, Schilling LB. Imaging as a Biomarker: 
        Standards for Change Measurements in Therapy Workshop Summary 
        (2006). Acad Radiol 2008;15:501-30

4. Baer TM, Clark CW, Karam L. ``Programs Supporting Quantitative 
        Imaging in Biomedicine at the National Institute of Standards 
        and Technology,'' In: Mulshine JL, Baer TM, editors. 
        Quantitative Imaging Tools for Lung Cancer Drug Assessment. New 
        York: Wiley; 2008. p. 111-22.

5. Zimmerman BE, Cessna JT, Fitzgerald R. Standardization of 68 
        Ge/ 68 Ga Using Three Liquid Scintillation Counting 
        Based Methods. J Res Natl Inst Stand Technol 2008;113:265-80.

6. Levine ZH, Grantham S, Sawyer DS IV, Reeves AP, Yankelevitz DF. A 
        Low-Cost Fiducial Reference Phantom for Computed Tomography. J 
        Res Natl Inst Stand Technol 2008;113:335-40.

7. Karam LR, Radiation-based quantitative bioimaging at the National 
        Institute of Standards and Technology. J Med Phys 
        2009;34(3):117-21.

8. Zimmerman B, Kinahan P, Galbraith W, Allberg K, Mawlawi O. 
        Multicenter comparison of dose calibrator accuracy for PET 
        imaging using a standardized source. J Nucl Med. 2009;50:123.

9. Levine ZH, Li M, Reeves AP, Yankelevitz DF, Chen JJ, Siegel EL, 
        Peskin A, and Zeiger DN. A Low-Cost Density Reference Phantom 
        for Computed Tomography. Med. Phys. 36:286:288 (2009)

                     Biography for Daniel Sullivan
    Daniel C. Sullivan, M.D. is Professor and Vice Chair for Research, 
Department of Radiology at Duke University Medical Center, coordinator 
of imaging activities for the Duke Comprehensive Cancer Center (DCCC), 
and Director of the Imaging Core of the Duke CTSA program. He is also 
Science Adviser to the Radiological Society of North America (RSNA). He 
completed radiology residency and nuclear medicine fellowship in 1977 
at Yale-New Haven Hospital, and was in academic radiology for 20 years 
before joining the National Cancer Institute at NIH in 1997. From 1977 
to 1997 Dr. Sullivan held faculty appointments at Yale University 
Medical Center, Duke University Medical Center, and University of 
Pennsylvania Medical Center. His areas of clinical and research 
expertise are in nuclear medicine and oncologic imaging. From 1997 to 
2007 Dr. Sullivan was Associate Director in the Division of Cancer 
Treatment and Diagnosis of the National Cancer Institute (NCI), and 
Head of the Cancer Imaging Program (CIP) at NCI. Dr. Sullivan's current 
responsibilities at Duke include heading the Imaging Core of Duke's 
CTSA program, and the Imaging Program in Development for the Duke 
Comprehensive Cancer Center. These activities focus on improving the 
use of imaging as a biomarker in clinical trials and facilitating 
translational research involving new and established imaging methods. 
In his role with the RSNA Dr. Sullivan coordinates integration of a 
wide range of national and international activities related to 
quantitiative imaging, including the evaluation and validation of 
imaging methods as biomarkers in clinical research.

    Chairman Wu. Thank you very much, Dr. Sullivan.
    At this point, it is appropriate to open for questions. I 
want to let everyone know that votes will be called fairly soon 
on the floor.
    Mr. Smith has informed me that he has some scheduling 
challenges in coming back after the votes, as do I, and unless 
Members object, I will do my level best to get through a first 
round of questions for all Members. And I want to thank the 
witnesses for making the trip here, but we will also get you 
questions in writing through the staff, and look forward to 
your responses to all.
    So, my five minutes. Dr. Baer, you referred to this, and I 
would be interested in hearing from the entire panel about 
this. NIST has had some role in biologics, and yet, it has not 
played a significant role in standards-setting for the 
healthcare industry as a whole.
    What do you see as impediments, what has prevented the 
healthcare industry from using NIST more broadly, and what do 
you think NIST can contribute to some of the current 
challenges. I know that much of the testimony went to that, but 
I would like to give you all another pass at this, because I 
think it is such an important topic.
    Dr. Baer, would you like to go first?
    Dr. Baer. That would be fine, Chairman Wu.
    I think NIST has tremendous capacity to supply the 
perspective on standards development and building consensus 
within the biomedical, bioscience research area. So, there is 
no lack of will or perspective.
    I think that at NIST, they do lack some of the expertise 
and personnel in the drug development area, and they also lack 
the appropriate interfaces to the pharmaceutical and drug 
development industry.
    And I think establishing those interfaces through an 
advisory panel, as has been suggested, is an excellent first 
step. And then, I think we have to do a very serious gap 
analysis, in terms of the personnel and expertise at NIST, to 
see do they have the appropriate personnel there to address 
this rapidly changing industry within the biomedical and 
healthcare sector.
    Ms. Terry. I certainly would agree with that, and I think 
the industry, while not eager for standards in some ways, is 
very eager in other ways. And so, I think in the development of 
diagnostics, of imaging, they are looking for ways to make 
these measures.
    And what I have seen at NIST, also, in my work with them, 
but largely on genetic testing, is excellent individuals who 
really want to do the best job, but don't seem to have the 
overall structural or architectural support they need there, 
and so__
    Chairman Wu. You mean in the organization?
    Ms. Terry. In the organization, and so a division or a 
program of biological or biomedical metrology would seem to 
make the greatest sense to me.
    Dr. Sullivan. I would just add I think it is an 
organizational matter of creating a formal program there, 
because biology is quite complex. Every patient is unique. It 
isn't quite the same as developing other types of devices in 
industry, and I think some of the staff there would benefit 
from an ongoing interaction with what the real clinical 
problems are, and how it relates to the measures.
    Chairman Wu. OK, then let me follow that up, and just go 
right down to how do you see the organizational structure at 
NIST best centered on, say, a joint university/NIST research 
center, biomedical research center, or, and something that 
includes industry, also? Let us just go across the row again.
    Dr. Baer. Well, I think NIST has shown, in many occasions, 
the benefits of working closely with academia, and I think 
joint institutes, joint research centers, have proven to be one 
of the best ways for NIST to advance measurement science.
    So, I think that is an excellent approach. However, I do 
feel that NIST needs at its Gaithersburg or Boulder facility, a 
center of expertise, as Dr. Sullivan was saying, where they can 
guide these interactions, and they also need to have that 
center properly interfaced to industry.
    Chairman Wu. Are they short on personnel, or do they have 
the people, but just not properly organized?
    Dr. Baer. I think there are some distinct gaps. I feel that 
they definitely lack sufficient experts in the drug development 
industry and knowledge of the drug development industry in 
other areas of bioimaging and molecular analysis. So, there is 
definitely a lack of personnel.
    I also think that there is a need for a centralized 
organization. Many of these individuals are located in 
different laboratories. And the VCAT has commented, in several 
reports, that though they do expert work on their own, they are 
not coherent. They are not organized efficiently, because they 
are separated across different locations and different 
facilities.
    So it is both a lack of personnel and a lack of real 
central focus.
    Chairman Wu. Thank you, Dr. Baer. My time is expiring, but 
I want to give Ms. Terry and Dr. Sullivan a cut at this 
question.
    Ms. Terry. So, I will be quick.
    So, I completely agree with that, and in addition, Chairman 
Wu, to your question, I would say that the novel partnership 
between academia, industry, and government, done well, is the 
right thing here. Each of them have very different things to 
bring to the equation, and they really could make the right 
package for biomedical sciences.
    Chairman Wu. Thank you very much. Dr. Sullivan.
    Dr. Sullivan. And I would just add, I think there are two 
separate things here. One is the partnerships, the 
collaborations, that can take place anywhere, sort of 
virtually. Second, I think there does need to be a physical 
user facility, Boulder might be a place, or Gaithersburg, where 
there can be the machines to document compliance with profiles 
and standards.
    Chairman Wu. Would the Neutron Facility be one of the 
important physical assets?
    Dr. Sullivan. Could be. Could be part of that. Yes.
    Chairman Wu. OK. Thank you. Mr. Smith's five minutes.
    Mr. Smith. Thank you, Mr. Chairman, and I will try to be 
quick.
    Dr. Baer, you mentioned in your testimony interaction with 
NIST on development electronic medical standards. Where are we 
in the process?
    Dr. Baer. Well, I think NIST has been tasked to be a key 
player in this whole effort, and the Information Technology 
Lab, under the direction of Cita Furlani, is being very 
effective in leading the discussion of these standards.
    I think this is an enormous challenge, and requires the 
coordination of both the private sector and the government 
sector to accomplish the task. I think they are making great 
progress, and I think it is one of their, if not their highest 
priority, it is one of the major priorities in the ITL 
[Information Technology Laboratory] Lab, and I greatly admire 
the efforts that Cita and her staff have put into this.
    I think they are making tremendous progress.
    Mr. Smith. So, how far off would you say?
    Dr. Baer. I think that is best to ask Cita Furlani. What I 
will tell you is it is an enormous challenge, and they have 
been making good progress. I think that Cita is the best person 
to ask that_answer that question.
    Mr. Smith. OK. All right. Thank you.
    And Dr. Sullivan, in the medical imaging field, what 
percentage of clinics and other organizations use the 
suggestions or standards set out by the Radiological Society of 
North America, RSNA, and what interaction does RSNA have with 
NIST in standards development?
    Dr. Sullivan. The programs that I described on the slide 
are relatively new, only about a year and a half old, and we do 
have representatives from NIST involved in our technical 
committees_been very effective working with the physicists who 
are at academic sites.
    So, the guidelines, we call them profiles from that 
program, because we don't want to call them standards or 
recommendations, but they are relatively immature at this 
point, so we are not yet in a compliance phase, but we do need 
a compliance phase, and that is where NIST could be the key 
player.
    Another organization, the American College of Radiology, 
that I did not mention, which is a large organization, does 
have what is called appropriateness guidelines for clinical 
practice, and virtually all radiologists in all medical centers 
follow those. But they don't get to the kinds of standards we 
are talking about in the scanners.
    Mr. Smith. OK. Anyone else wishing to comment on either of 
those questions? If not, that is fine, but I just__
    Dr. Sullivan. I just want to add, back to your question 
about the electronic health record. I think there are two major 
impediments to that, which are not technical. The technology to 
do this exists, but the impediments_one is a unique patient 
identifier across all of the institutions in the United States, 
and second, is the incentives for the organizations and medical 
centers to do that, from a business/cultural/social 
perspective.
    Mr. Smith. So, when you say unique patient identifier, 
would you elaborate?
    Dr. Sullivan. When patients go to different medical centers 
there, because we don't use Social Security numbers anymore for 
privacy reasons, they get some kind of a new number, their name 
maybe is spelled differently at different places, include the 
middle initial or not, and so, identifying records from one 
place that matches up with the same patient in another place is 
a huge problem. We don't have a standard way to do that across 
the United States.
    Mr. Smith. And what are your recommendations in addressing 
that?
    Dr. Sullivan. I think we need to look at something like the 
bioidentifiers, face recognition, iris scans, something like 
that. OK.
    Mr. Smith. Thank you very much. I yield back.
    Chairman Wu. Thank you very much, Mr. Smith.
    And now, I recognize the gentlelady from Maryland, Ms. 
Edwards. Five minutes.
    Ms. Edwards. Thank you, Mr. Chairman. And thank you to the 
witnesses. I am in the Fourth Congressional District in 
Maryland. It is home to the NIST Gaithersburg facility. I have 
had a chance to visit there, and I think that the folks at NIST 
actually would agree with some of your comments today about the 
need for capacity in some of these areas, and some of the 
organizational challenges that they face, so thanks for 
pointing those out.
    My question actually has to do with this idea of 
establishing an advisory board to address the needs of the 
biomedical community. Because I want to talk for a minute about 
firewalls, and I think we have had other examples, and we don't 
have to name agencies, where we have had these kind of advisory 
boards where you incorporate the private sector, academia, 
government, and you have to deal with issues around conflicts 
of interest, around sort of how you are perceived, whether it 
is perceived or real, in the public, to make sure that there is 
real accountability and transparency in process.
    And so, I wonder if you could give us some suggestions or 
recommendations about how to avoid some of the mistakes that we 
have seen in similarly situated advisory boards, and how that 
could operate differently in the context of the work at NIST.
    Ms. Terry. So, I would like to take a stab at that, 
Congresswoman Edwards.
    So, I think there is the saying that without a conflict, 
there is no interest, and I usually begin things that I speak 
about saying I have the greatest conflict, because I have the 
greatest interest, and children with a disease certainly make 
one, sometimes, crazy.
    I think the way that we avoid this, and in fact, the health 
information standards committee that I am sitting on right now 
is a mixture of the industry, the vendors, the universities, 
and the people who need this information for the electronic 
health record, is by mixing those people together, and by 
having strong leadership for the committee.
    And in many cases, a kind of chairpersonship by industry 
and government, or industry and the nonprofit world, seems to 
be able to balance interests, and also, to lay down the right 
rules. And again, I will use this committee as an example. It 
has been remarkable to see the hard work that everyone is 
doing, the turf battles that happen in public instead of in 
private, and in the resolutions that seem to be able to take 
into consideration those conflicts, because they are named.
    So, I think as long as they are transparent, obvious, 
available to everyone, sunshine on the data, I have seen real 
wonderful advances in groups like these.
    Dr. Baer. I would agree completely with Sharon's comment, 
and stress the importance of having patient advocacy groups, 
which can be somewhat more neutral brokers and watchdogs. I 
think that transparency is the issue, and her statement without 
conflict, there is no interest is absolutely right on.
    The other comment I would make is NIST is used to acting 
like a neutral broker in many, many areas of the industry 
within the United States. So this is not a unique problem, and 
I think NIST has established a tradition of being able to 
function very adequately in this role as a neutral broker.
    Dr. Sullivan. I don't have anything to add. I agree.
    Ms. Edwards. Thank you. Thank you, Mr. Chairman.
    Chairman Wu. Thank you very much, and now, the gentlelady 
from Illinois, Ms. Biggert, five minutes.
    Ms. Biggert. Thank you, Chairman.
    One of the first years that I was here, we had the report 
on the Human Genome Project, which Dr. Francis Collins, of 
course, worked on, so and now, he has moved to chair NIH, which 
I think is fabulous, because he worked so much with us, and did 
so much, obviously, on that project.
    But what is the current interaction between NIH and NIST to 
assist in demand for stricter medical standards? Dr. Sullivan?
    Dr. Sullivan. In the imaging area, I know there have been 
connections between, particularly, the National Cancer 
Institute [NCI] and NIST, going back over about a decade. There 
was a major workshop in 2006, organized by NIST, with 
cooperation from NCI and FDA kind of laying out a path forward 
for some of these issues related to medical scanners.
    And there have been some continued interactions. I 
mentioned that some of the folks involved in that workshop are 
now in the committees we are working with the QIBA 
[Quantitative Imaging Biomarker Alliance] activity, the NCI 
people as well.
    So there some precedent for those kind of interactions. I 
think they could be strengthened by making this more a priority 
from the management perspective within NIST.
    Ms. Biggert. OK, then. And looking at all of your 
backgrounds, and you have all done so much and so many 
different things, but when I look at Sharon Terry, and how she 
got into this because of a family situation, and yet, she has 
got a patent on this genetic disease, finding the gene 
diagnostic and then, the research and having a patent for the 
invention associated with the gene, how do you all get together 
and work on this?
    It seems like you have got the framework with NIST, and you 
have got your offering, but how do you get to this way where 
you are talking about standards, and how the whole group comes 
together?
    Ms. Terry. So, I will take a crack at that.
    I think that is an excellent question, because I think what 
happens is, as I said, you know, in our case, we are sort of 
slammed up against walls. So, essentially, what we do is we 
consult with people like Dr. Sullivan or Dr. Baer and say, ``we 
can't find a way to measure this or measure that, how do we 
make a''_for example, for all of us, a clinical trial is 
important. So, I have colleagues who are trying to do trials 
where imaging is going to be the biomarker, the end mark, 
endpoint, and they can't do the right trial, because they can't 
measure what they need.
    And so, our collaborations, I think, are as good as they 
can be without the standards, but with the standards, I think 
it would be much clearer what is my job, what is their jobs, 
and how we can work with one another toward real endpoints in 
clinical medicine that will produce drugs and therapies and 
treatments that we need.
    Ms. Biggert. Go ahead.
    Dr. Baer. Just to build on Sharon's comment, you know, 
there is a natural tendency within all of these communities to 
want standards. Again, this is not regulation. This is 
consensus building standards, and in the discussions we have 
had at all levels, with NIH, the FDA, and the CDC [Centers for 
Disease Control], they really want NIST's efforts in this area, 
because they do not focus on building these consensus 
standards. It is not their role.
    The same thing is true in the private sector and academic 
research. These standards just accelerate progress, so there is 
a natural tendency for people to want this to happen, and the 
resources provided by the U.S. Government are absolutely 
critical to support these efforts.
    Ms. Biggert. But with the medical costs rising, obviously, 
this is something that we are facing, in the country, and what 
is going on as far as healthcare. And at this rapid pace, is 
there a concern that having NIST decided what methods or 
standards may increase the costs of providing medical care?
    Dr. Baer. I think, again, NIST won't make the decision. 
NIST will lead a discussion which will result in a consensus. 
And quite the contrary. The lead toward personalized medicine, 
and quantitative tests that will enable that, will reduce the 
number of tests that are done. As it was mentioned, tests for 
PSA and TSH, thyroid stimulating hormone, which are done tens 
of millions of times a year, and they are repetitive tests that 
need to be done, because of the lack of reproducibility and 
accuracy.
    Personalized medicine will allow the most effective 
therapies to be prescribed to patients, based on their personal 
molecular diagnosis. I firmly believe that this will 
substantially reduce the cost of medical, and it is a critical 
part of the overall program to do so.
    Ms. Biggert. Well, that is good, because obviously, if we 
eliminate competition or disallow some forms of testing, then 
this would be in the opposite direction. Or, if there is 
picking winners or losers. We have had that in the banking, we 
don't want to get this into the scientific__
    Ms. Terry. I think, in fact, we will have better, cleaner, 
clearer competition in the sense of innovation and competition 
if we have standards. Because innovation will build on 
standards very, very rapidly. We are starting to see that in 
the health information technology field, and I think we would 
see it in other fields as well.
    Dr. Sullivan. Yes, I would endorse that. Two points.
    One is I also agree it would help to reduce duplication in 
the medical imaging area. We don't have good data on this, but 
it is estimated maybe 20 or 25 percent of scans are just 
duplicate scans, because they can't compare them. And they are 
very expensive, so that would be a huge cost.
    In terms of competition, in our work with the medical 
device manufacturers, and these are all of the large companies, 
GE, Phillips, Siemens, Toshiba, they view standards as an 
opportunity for competitiveness. That is, they can work to 
claim that their device is more compliant than their 
competitors with these standards.
    Ms. Biggert. Thank you very much. I yield back.
    Chairman Wu. Thank you very much, Ms. Biggert. Thank you 
all very, very much for this very helpful testimony. We do have 
additional questions, which will be submitted in writing. I 
appreciate the distance that you all have come. I appreciate 
the work that you have done in your respective fields, and look 
forward to hearing more about that work as well.
    Unless there are any other additional questions from the 
panel. Thank you all very, very much for appearing this 
afternoon. The record will remain open for two weeks for 
additional statements from the Members, and for answers to any 
follow-up questions the Committee may ask of the witnesses.
    The witnesses are excused with the panel's great gratitude, 
and the hearing is now adjourned.
    [Whereupon, at 2:45 p.m., the Subcommittee was adjourned.]
                              Appendix 1:

                              ----------                              


                   Additional Material for the Record




  Testimony of Dr. Karen Mann, PhD, President of the Association for 
                          Molecular Pathology
    Chairman Wu and Members of the Subcommittee_thank you for the 
opportunity to provide written testimony on How Can NIST Better Serve 
the Needs of the Biomedical Research Community in the 21st Century.
    My name is Karen Mann and I am the current President of the 
Association for Molecular Pathology (AMP), an international medical and 
professional association representing approximately 1,800 physicians, 
doctoral scientists, and medical technologists who perform laboratory 
testing based on knowledge derived from molecular biology, genetics and 
genomics.
    The modern healthcare system offers great potential for 
personalized and effective medical care. However, the recognition and 
implementation of advances in medical research will be hindered by a 
lack of certified reference materials. Molecular assays provide the 
cutting edge diagnostics for many individualized therapies in oncology, 
transplantation, infectious disease and genetics, but the production of 
certified reference materials has fallen far behind the technical 
capabilities of these assays. Reference materials are important to 
ensure the necessary sensitivity, specificity and level of 
reproducibility of intra- and inter-laboratory test results. The best 
approach to achieve consistent and comparable quantitative data amongst 
laboratories is by the use of internationally established reference 
reagents.\1\
---------------------------------------------------------------------------
    \1\ Robertson JS. ``International standardization of gene 
amplification technology.'' Biologicals 26:111-3, 1998.
---------------------------------------------------------------------------
    To illustrate the challenges of the dearth of reference materials, 
I will provide you with examples from four areas of active innovation 
in molecular diagnostics.

Example 1: Targeted therapeutics and tumor markers

    Targeted therapeutics are drugs that directly target genes or 
genetic pathways involved in disease. Molecular testing is used to 
identify patients with these mutations in order to direct therapy to 
the appropriate patients, and, in some cases, to monitor response to 
therapy. Reference materials are necessary to ensure that these tests 
have appropriate sensitivity, specificity, and reproducibility. Chronic 
myeloid leukemia (CML) is a paradigm for molecular diagnosis and 
targeted therapy. Historically, the only definitive treatment was bone 
marrow transplant, a treatment with high morbidity and mortality and 
limited utility. A recently developed novel class of medicines, 
tyrosine kinase inhibitors (TKIs), has revolutionized the treatment of 
CML.
    TKIs specifically target the oncogenic BCR-ABL fusion protein seen 
in CML, resulting in effective control of the tumor cells with 
relatively few side effects. The standard of care for monitoring the 
effectiveness of CML therapy is the quantitative molecular assessment 
of the level of the BCR-ABL fusion transcript in the patient's blood. 
Response to therapy is measured
    by transcript level and rising levels of the fusion transcript 
indicate early relapse, development of resistance mutations, and the 
need to alter therapy. Accurate assessment of the level of BCR-ABL is, 
therefore, essential for both the individual patient and to accurately 
compare results between centers in clinical trials for improvement of 
leukemia therapy.
    These advances have obviated the need for transplant in most CML 
patients, but the lack of standardized reagents has limited the 
reproducibility of these assays within and between laboratories. 
Therefore, if a patient has samples sent to different laboratories, as 
happens if they switch healthcare providers, it is impossible to 
accurately monitor the response to therapy. Therefore, quantitative 
standards for monitoring BCR-ABL are urgently needed. Furthermore, the 
model provided by CML may become the standard for other genes with 
molecularly targetable mutations or mutations suitable for minimal 
residual disease monitoring; e.g. PML-RARA and variants, FLT3, cKIT, 
PDGFRA, PDGFRB, NPM1, ETO-AML1, JAK2, MLL-mutation variants, etc.

Example 2: Companion diagnostic tests

    Molecularly targeted therapies are frequently expensive and 
sometimes have significant side effects. Molecular pharmacogenomic 
assays (also called companion diagnostics) are used to identify 
patients likely or unlikely to benefit from these therapies, providing 
a method for optimizing the cost-effective delivery of healthcare. This 
is exemplified by the recent recognition of the role of KRAS mutations 
in colorectal cancer to identify patients unlikely to benefit from 
monoclonal antibody therapy (Cetuximab/Erbitux) that inhibit the 
epidermal growth factor receptor (EGFR). Mutations in KRAS preclude 
response to this therapy. However, the sensitivity and specificity of 
different molecular assays for identification of KRAS mutations varies 
with technique. Additional activating mutations of KRAS have been 
identified which need further study in order to understand whether they 
also cause resistance to anti-EFGR therapy. Standardized reagents are 
urgently needed to allow comparative analysis between clinical 
protocols. Mutations in the EGFR gene itself also appear to predict 
responsiveness to EGFR small molecule tyrosine kinase inhibitors (TKIs) 
in non-small cell lung cancer (NSCLC). However, EGFR mutations are 
considerably more varied than KRAS mutations, demonstrating the need 
not only for standardized reagents but also for an up-to-date EGFR 
somatic mutation database that can predict TKI response in NSCLC for 
individual mutations.

Example 3: Transplant follow-up care and quantitative standards

    Standardized molecular reagents are also urgently needed in the 
transplant setting. At the end of 2006, over 170,000 people in the U.S. 
were living with a functioning solid organ transplant; 27,578 solid 
organ transplants were performed in 2007.\2\ From its founding in 1986 
through 2004, the National Marrow Donor Program coordinated more than 
20,000 bone marrow and peripheral blood stem cell transplants.\3\ All 
patients who have undergone transplants are given immune-suppressive 
drug therapy and are as a result more susceptible to viral and fungal 
diseases. Viral diseases can result via transmission from the donor 
tissue, exposure to the environment or more typically, reactivation of 
the patient's own latent viruses, held for years within their own body.
---------------------------------------------------------------------------
    \2\ Wolfe RA, et al. ``Trends in organ donation and transplantation 
in the United States, 1998-2007.'' American Journal of Transplantation 
2009;9(Part 2):869-878.
    \3\ U.S. Department of Health & Human Services Health Resources and 
Services Administration (HRSA). 2004 Biennial Report of the National 
Bone Marrow Donor Registry. Available online at http://
wuvwv.marrow.org/ABOUT/Who-We-Are/Publications/
2004-Biennial-Report/PDF/
biennial-report-2004-l.pdf
---------------------------------------------------------------------------
    Several common viruses represent recognized and severe 
complications of organ and bone marrow transplantation, which adds 
excessive costs to US healthcare systems. Quantitative testing for 
viruses (viral load testing, e.g. for CMV, EBV, and BK viruses) is 
considered standard of care for perpetual monitoring of transplant 
patients. Current laboratory tests, however, show marked variability 
among commonly used methods because there are no established 
quantitative virus standards. Because of the variability among 
laboratory tests, repeat testing is often required when a patient 
switches health insurance or travels to a different hospital or city. 
Therefore, quantitative virus standards are urgently needed by the 
clinical laboratory community in order to provide accurate, 
reproducible, and comparable results and to reduce errors and repeat 
testing, all of which add to overall healthcare costs for this already 
costly group of patients.

Example 4: Reference gene sequence database

    Currently, clinical sequencing methods rely either on the use of 
public sequence databases for sequence comparisons or on the use of 
annotated databases owned by commercial companies, which require high 
proprietary fees. Genetic sequence banks such as GenBank are 
unacceptable for use in clinical laboratories because of the open 
platform for those who enter sequences and the limited sequence 
verification for GenBank submission. Clinical laboratories performing 
gene analyses need a ``certified'' reference sequence that is locked 
and annotated.
    Clinical laboratories rely on accurate genotypic bacterial 
identification based on the 16S rRNA gene for many fastidious microbes 
and fungi. The use of the 16S rRNA gene for identification of bacteria 
and fungi provides a faster method to identify slow growing organisms. 
Traditional methods may take up to 3 weeks to identify the microbe and 
delays in adequate treatment can occur, causing mortality and 
increasing hospital costs and in some cases, like tuberculosis, a risk 
to the public health. Two databases services, freely available on the 
Internet, offer an improved scenario, with some level of verification: 
1) The Ribosomal Differentiation of Medical Microorganisms (RIDOM), and 
2) the Ribosomal Database project (RDP) from the University of 
Michigan. These databases offer improvements in secondary-structure 
based alignment that provides better support for short partial 
sequences and improves handling of certain sequencing artifacts. 
However, limitations exist with these databases including, but not 
limited to, limited species representation and research use only 
disclaimers.
    While improved over GenBank, experience in the clinical laboratory 
with analysis of the 16S rRNA gene of patient strains has shown that 
clear-cut results are not the rule as the existing databases are not 
always well annotated and taxonomic changes are not regularly and 
rapidly updated. Commercial databases, such as MicroSeq (Applied 
Biosciences), and databases from reference laboratories such as Mayo 
Clinic and ARUP Laboratories offer better coordination with clinical 
laboratories, yet still rely on the subset of microbes submitted to 
them for identification to populate their databases.
    As many clinical, research, and environmental laboratories 
currently use 16S-based identification of bacteria, including 
mycobacteria, a widely available quality-controlled database that 
interfaces freely and seeks to populate it with medically identified 
microbes from across the globe is long overdue. It is essential to 
accurately identify species or detect true sequence variations leading 
to the discovery of new species, with data validation protocols akin to 
that of 21 CFR Part 11 compliance. Ideally, such a database would 
provide ribosome related data and services to the clinical community, 
including online data analysis and aligned and annotated Bacterial and 
Archaeal small-subunit 16S rRNA sequences, as well as fungal rRNA 
sequences, and genetic sequences related to antimicrobial resistance. 
In terms of ``personalized medicine'' this resource would be valuable 
as sequence analysis of resistance mutations will be integral to 
initiatives such as personalized anti-tuberculosis (TB) therapy so that 
clinical laboratories could quickly identify drug resistant TB (MDR and 
XDR TB), a priority identified by the NIH.
    The need for certified reference sequences extends to human genes, 
for both inherited diseases and acquired disorders (cancers). For 
example, the RET proto-oncogene is associated with Multiple Endocrine 
Neoplasia Type 2 (MEN2). From GenBank, two isoforms are given as well 
as alternative assemblies. One reference sequence lists a known minor 
allele as the wildtype allele. Reference sequences differ as some only 
include the coding region, whereas others include the entire genomic 
sequence. In addition, sequences may include the 5' untranslated region 
or begin with the first base of the transcribed mRNA. All these 
differences can cause confusion between reports from different 
laboratories testing for the same disease, based on which reference 
sequence is used. A clinically certified reference sequence would be 
checked to determine that the most common sequence is listed as the 
reference, and document known benign SNPs. The reference sequence would 
ideally have the chromosome, locus and sequence numbering so that 
results from different laboratories will be consistent. Annotating 
positions of the SNPs could help in designing assays thereby reducing 
the potential of false negative or positive results. A list of known 
benign SNPs can also help in interpretation when these variants are 
detected.

PRIORITIES: STANDARDS ARE URGENTLY NEEDED

    While in the end, we hope to have standardized reference materials 
for all diagnostics targets and certified reference databases for all 
clinically relevant gene sequences, some are more urgently needed than 
others. Specifically,

    1. Immediate

                a.  Cytomegalovirus (CMV), quantitative assay standard, 
                a recognized complication of organ transplantation

                b.  BCR/ABL Adelaide standard; BCR/ABL tests are used 
                to diagnose patients with a specific leukemia and to 
                monitor their response to treatment

                c.  KRAS mutation standards; KRAS mutation analysis 
                testing is used to select patients for a specific 
                chemotherapeutic drug

                d.  EGFR mutation standards; EGFR mutation analysis 
                testing is used to select patients for a specific 
                chemotherapeutic drug

    2. Short term (one year)_all quantitative assay standards.

                a.  BK virus (BKV), a recognized complication of kidney 
                transplantation

                b.  Epstein Barr Virus (EBV), a recognized complication 
                of organ transplantation

    3. Medium term (1-3 years)

    Below is a list of infectious agents, the diagnostic tests for 
which require standardized reference materials as well as note of the 
Certified Gene Sequence Databases (CGSDs). In addition, there is a 
significant need for reference standards for a number of oncology 
tests. AMP recommends that an ongoing program be established at NIST to 
create certified reference standards for molecular diagnostic tests and 
that NIST consult with molecular pathology experts to identify and 
prioritize standardized reference material development.

                a.  Adenovirus, quantitative assay standard; important 
                for directing antiviral treatment in immunosuppressed 
                patients

                b.  Enterovirus, qualitative assay standard

                c.  Hepatitis B virus (important for liver transplants 
                and also in the general population), quantitative assay 
                standard

                d.  Herpes simplex (HSV), types 1 and 2, qualitative 
                assay standard, recognized complications of organ 
                transplantation

                e.  HHV-6, HHV-7, and HHV-8, increasingly common 
                complications of organ transplantation, which may add 
                severity to the more common CMV infections

                f.  HTLV 1 and 2, qualitative assay standard, important 
                for transfusion services

                g.  Human metapneumovirus (HMPV), qualitative assay 
                standard

                h.  Influenza virus, qualitative assay standard

                i.  JC virus, quantitative assay standard, closely 
                related to BKV

                j.  Parainfluenza virus, qualitative assay standard

                k.  Parvovirus B19, quantitative assay standard

                l.  Respiratory syncytial virus (RSV), both qualitative 
                and quantitative assay standards; quantitative assays 
                are used as prognostic markers for patient care

                m.  Varicella zoster virus (VZV), recognized 
                complication of organ transplantation

                n.  Certified Gene Sequence Databases (CGSDs)

                        (1)  Gene mutation sequence database, suitable 
                        for clinical test reference

                        (2)  Infectious agent (bacteria, viruses) 
                        sequence database, suitable for clinical test 
                        reference

                o.  Scientific advisory committee to identify and 
                prioritize areas of needed references materials and to 
                direct resources and the work of the CGSDs

AMP's Ongoing Efforts

    AMP professional committees have collaborated with NIST and the CDC 
previously to identify, characterize and make available reference 
material. For example, characterized cell lines and a NIST standard are 
now available for Fragile X pre-mutation sizing. These can be used for 
test validation, proficiency testing, and controls or calibrators.\4\ 
In addition, AMP provided a detailed list of critical needs gathered 
from the experience of AMP members to NIST in June 2009.
---------------------------------------------------------------------------
    \4\ Amos Wilson J, et al. J Mol Diagn. 2008 Jan;10(1):2-12 
Consensus characterization of 16 FMR1 reference materials: a consortium 
study.
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    A focus of AMP's Clinical Practice Committee is on increasing the 
speed with which the National Institute for Standards and Technology 
(NIST) can prepare quantitative standards, which is critical to the 
national and international laboratory community and their ability to 
deliver accurate test results. The deliverable would be purchasable 
standardized reference materials that would ideally be available for 
inter-laboratory comparison studies and purchase by commercial and 
clinical laboratory communities. AMP estimates that it will cost 
approximately $500,000 to develop each set of reference materials and 
encourages Congress to consider funding this much needed initiative at 
NIST. With some of the costs being offset by the purchasing of 
materials, this is an innovative way for government to not only advance 
biomedical science but generate funds.
    AMP stands ready to collaborate with NIST and work with Congress to 
do its part to hasten the process to achieve available certified 
reference materials for all clinical tests. Thank you very much for 
your attention and continued efforts to advance biomedical research 
through programs at NIST.

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