[House Hearing, 114 Congress]
[From the U.S. Government Publishing Office]
EXAMINING THE REGULATION OF DIAGNOSTIC TESTS AND LABORATORY OPERATIONS
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED FOURTEENTH CONGRESS
FIRST SESSION
__________
NOVEMBER 17, 2015
__________
Serial No. 114-100
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
___________
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99-657 PDF WASHINGTON : 2016
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COMMITTEE ON ENERGY AND COMMERCE
FRED UPTON, Michigan
Chairman
JOE BARTON, Texas FRANK PALLONE, Jr., New Jersey
Chairman Emeritus Ranking Member
ED WHITFIELD, Kentucky BOBBY L. RUSH, Illinois
JOHN SHIMKUS, Illinois ANNA G. ESHOO, California
JOSEPH R. PITTS, Pennsylvania ELIOT L. ENGEL, New York
GREG WALDEN, Oregon GENE GREEN, Texas
TIM MURPHY, Pennsylvania DIANA DeGETTE, Colorado
MICHAEL C. BURGESS, Texas LOIS CAPPS, California
MARSHA BLACKBURN, Tennessee MICHAEL F. DOYLE, Pennsylvania
Vice Chairman JANICE D. SCHAKOWSKY, Illinois
STEVE SCALISE, Louisiana G.K. BUTTERFIELD, North Carolina
ROBERT E. LATTA, Ohio DORIS O. MATSUI, California
CATHY McMORRIS RODGERS, Washington KATHY CASTOR, Florida
GREGG HARPER, Mississippi JOHN P. SARBANES, Maryland
LEONARD LANCE, New Jersey JERRY McNERNEY, California
BRETT GUTHRIE, Kentucky PETER WELCH, Vermont
PETE OLSON, Texas BEN RAY LUJAN, New Mexico
DAVID B. McKINLEY, West Virginia PAUL TONKO, New York
MIKE POMPEO, Kansas JOHN A. YARMUTH, Kentucky
ADAM KINZINGER, Illinois YVETTE D. CLARKE, New York
H. MORGAN GRIFFITH, Virginia DAVID LOEBSACK, Iowa
GUS M. BILIRAKIS, Florida KURT SCHRADER, Oregon
BILL JOHNSON, Ohio JOSEPH P. KENNEDY, III,
BILLY LONG, Missouri Massachusetts
RENEE L. ELLMERS, North Carolina TONY CARDENAS, California7
LARRY BUCSHON, Indiana
BILL FLORES, Texas
SUSAN W. BROOKS, Indiana
MARKWAYNE MULLIN, Oklahoma
RICHARD HUDSON, North Carolina
CHRIS COLLINS, New York
KEVIN CRAMER, North Dakota
Subcommittee on Health
JOSEPH R. PITTS, Pennsylvania
Chairman
BRETT GUTHRIE, Kentucky GENE GREEN, Texas
Vice Chairman Ranking Member
ED WHITFIELD, Kentucky ELIOT L. ENGEL, New York
JOHN SHIMKUS, Illinois LOIS CAPPS, California
TIM MURPHY, Pennsylvania JANICE D. SCHAKOWSKY, Illinois
MICHAEL C. BURGESS, Texas G.K. BUTTERFIELD, North Carolina
MARSHA BLACKBURN, Tennessee KATHY CASTOR, Florida
CATHY McMORRIS RODGERS, Washington JOHN P. SARBANES, Maryland
LEONARD LANCE, New Jersey DORIS O. MATSUI, California
H. MORGAN GRIFFITH, Virginia BEN RAY LUJAN, New Mexico
GUS M. BILIRAKIS, Florida KURT SCHRADER, Oregon
BILLY LONG, Missouri JOSEPH P. KENNEDY, III,
RENEE L. ELLMERS, North Carolina Massachusetts
LARRY BUCSHON, Indiana TONY CARDENAS, California
SUSAN W. BROOKS, Indiana FRANK PALLONE, Jr., New Jersey (ex
CHRIS COLLINS, New York officio)
JOE BARTON, Texas
FRED UPTON, Michigan (ex officio)
(ii)
C O N T E N T S
----------
Page
Hon. Joseph R. Pitts, a Representative in Congress from the
Commonwealth of Pennsylvania, opening statement................ 1
Prepared statement........................................... 3
Hon. Gene Green, a Representative in Congress from the State of
Texas, opening statement....................................... 4
Prepared statement........................................... 5
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 6
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 8
Prepared statement........................................... 9
Hon. Fred Upton, a Representative in Congress from the State of
Michigan, prepared statement................................... 65
Hon. Renee L. Ellmers, a Representative in Congress from the
State of North Carolina, prepared statement.................... 66
Witnesses
Jeffrey Shuren, M.D., Director, Center for Devices and
Radiological Health, Food and Drug Administration, Department
of Health and Human Services................................... 10
Prepared statement........................................... 12
Answers to submitted questions \1\........................... 84
Patrick Conway, M.D., Acting Principal Deputy Administrator,
Deputy Administrator for Innovation and Quality, and Chief
Medical Officer, Centers for Medicare and Medicaid Services,
Department of Health and Human Services........................ 24
Prepared statement........................................... 26
Answers to submitted questions............................... 85
Submitted Material
Discussion Draft, H.R. ___, submitted by Mr. Pitts\2\
Letter of November 16, 2015, from American Clinical Laboratory
Association, et al., to the Honorable Lamar Alexandar, et al.,
submitted by Mr. Pitts......................................... 67
Letter of November 11, 2015, from Action to Cure Kidney Cancer,
et al., to Mr. Upton, et al., submitted by Mr. Pitts........... 70
Letter of November 16, 2015, from Dick Woodruff, Vice President,
Federal Relations, American Cancer Society Cancer Action
Network, to Mr. Upton and Mr. Pallone, submitted by Mr. Green.. 72
Statement of the Association for Molecular Pathology, November
17, 2015, submitted by Mr. Burgess............................. 74
Letter of November 16, 2015, from Jan A. Nowak, Clinical Chief of
Molecular Pathology, Roswell Park Cancer Institute, to Mr.
Collins, submitted by Mr. Collins.............................. 77
----------
\1\ Dr. Shuren did not answer submitted questions for the record by the
time of printing.
\2\ The discussion draft has been retained in committee files and also
is available at http://docs.house.gov/meetings/IF/IF14/20151117/
104127/BILLS-114pih-HR--------.pdf.
Report by the Office of Public Health Strategy and Analysis,
Office of the Commissioner, Food and Drug Administration, ``The
Public Health Evidence for FDA Oversight of Laboratory
Developed Tests: 20 Case Studies,'' November 16, 2015,
submitted by Mr. Green \3\
Letter of November 17, 2015, from David D. Koch, President,
American Association of Clinical Chemistry, to Mr. Upton, et
al., submitted by Mr. Burgess.................................. 79
----------
\3\ The report has been retained in committee files and also is
available at http://docs.house.gov/meetings/IF/IF14/20151117/104127/
HMTG-114-IF14-20151117-SD009.pdf.
EXAMINING THE REGULATION OF DIAGNOSTIC TESTS AND LABORATORY OPERATIONS
----------
TUESDAY, NOVEMBER 17, 2015
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 10:03 a.m., in
room 2322, Rayburn House Office Building, Hon. Joseph R. Pitts
(chairman of the subcommittee) presiding.
Members present: Representatives Pitts, Guthrie, Barton,
Shimkus, Murphy, Burgess, Blackburn, Lance, Griffith,
Bilirakis, Long, Ellmers, Bucshon, Brooks, Collins, Green,
Capps, Butterfield, Castor, Schrader, Kennedy, Cardenas, and
Pallone (ex officio).
Staff present: Rebecca Card, Assistant Press Secretary;
Carly McWilliams, Professional Staff Member, Health; Graham
Pittman, Legislative Clerk; Heidi Stirrup, Health Policy
Coordinator; John Stone, Counsel, Health; Christine Brennan,
Democratic Press Secretary; Jeff Carroll, Democratic Staff
Director; Tiffany Guarascio, Democratic Deputy Staff Director
and Chief Health Advisor; Samantha Satchell, Democratic Policy
Analyst; and Kimberlee Trzeciak, Democratic Health Policy
Advisor.
Mr. Pitts. The subcommittee will come to order. The Chair
will recognize himself for an opening statement.
OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
Throughout the 21st Century Cures initiative, biomarkers,
precision medicine, and targeted therapies were a few of the
most consistently uttered terms and concepts. In order to
advance each of them, we must establish a regulatory
environment that fosters the development of, and access to,
innovative, accurate, and reliable diagnostic testing. Such
tests are increasingly important not only in diagnosing the
onset of a specific disease or condition, but in determining
the right course of treatment or procedure.
It goes without saying that tests providing information to
a doctor or consumer are fundamentally different products than
traditional medical devices, which actually deliver therapy to,
or are implanted in, a patient. Nonetheless, while FDA has used
its medical device authorities to review and oversee tests
developed by outside entities that are then sold to
laboratories, the agency has not actively regulated laboratory-
developed tests, or LDTs.
Last year, a week after we held a roundtable downstairs
that highlighted the importance of this very topic, FDA
announced that it would no longer exercise such enforcement
discretion and detailed how the agency proposes to apply its
medical device authorities to LDTs.
Today, I am far less interested in litigating the
boundaries of current FDA or CMS legal authority, but in
hearing from our witnesses how such authority could be
clarified or improved, understanding the unique and evolving
nature of what is being regulated and each agency's area of
expertise.
In response to a white paper the committee circulated at
the end of last year asking these very questions, we heard from
a number of labs and pathologists that FDA should only have a
limited role, if any, in regulating a select set of tests as
medical devices. The rest, in their opinion, should be overseen
by CMS through an updated Clinical Laboratory Improvement
Amendments program. This is despite the fact that CMS has
stated that they do not have the resources, the expertise, or
the willingness to take on what is being asked of them. I am
eager to hear what Dr. Conway has to say on this matter.
We also received comments from a number of manufacturers,
as well as over 40 patient groups, that FDA, not CMS, needs to
be in the driver's seat, and that tests that have the same
impact on a patient should be held to the same standards,
regardless of who does the development. This is despite the
fact that laboratories are uniquely nimble environments where
pathologists continually modify and improve tests in ways that
manufacturers cannot.
I am well aware that this has been at times a heated debate
with passionate advocates on both sides. With such a backdrop,
I want to particularly commend the manufacturers, the
laboratories, and other healthcare institutions that have been
willing to roll up their sleeves and find as much common ground
as possible through constructive dialogue, a willingness to
compromise, and a pragmatic understanding of what a viable,
modern framework entails.
I do not believe that imposing a new regulatory reality on
an increasingly important component of our healthcare system
via guidance is the best way to address these issues. These
products warrant a regulatory system designed with them in
mind. They should not be shoehorned into a system that was
drafted in the 1970s.
This committee has clearly shown that we are willing and
able to move complicated, comprehensive, bipartisan
legislation. The discussion draft the committee circulated,
along with the hearing notice, is of course not perfect, but it
is a serious document based on significant consensus, and I
would ask that all of the stakeholders out there, including our
two distinguished witnesses, help us improve it as the process
continues.
With that, I would like to thank Dr. Shuren, a frequent,
always welcome visitor, as well as Dr. Conway, for their
willingness to testify today, and I look forward to working
with them on these issues going forward.
[The discussion draft is available at http://
docs.house.gov/meetings/IF/IF14/20151117/104127/BILLS-114pih-
HR--------.pdf.]
[The prepared statement of Mr. Pitts follows:]
Prepared statement of Hon. Joseph R. Pitts
Throughout the 21st Century Cures initiative,
``biomarkers,'' ``precision medicine,'' and ``targeted
therapies'' were a few of the most consistently uttered terms
and concepts. In order to advance each of them, we must
establish a regulatory environment that fosters the development
of and access to innovative, accurate and reliable diagnostic
testing.
Such tests are increasingly important, not only diagnosing
the onset of a specific disease or condition, but in
determining the right course of treatment or procedure. It goes
without saying that tests providing information to a doctor or
consumer are fundamentally different products than traditional
medical devices which actually deliver therapy to or are
implanted in a patient. Nonetheless, while FDA has used its
medical device authorities to review and oversee tests
developed by outside entities that are then sold to
laboratories, the agency has not actively regulated laboratory
developed tests, or LDTs.
Last year, a week after we held a roundtable downstairs
that highlighted the importance of this very topic, FDA
announced that it would no longer exercise such enforcement
discretion and detailed how the agency proposes to apply its
medical device authorities to LDTs.
Today, I am far less interested in litigating the
boundaries of current FDA or CMS legal authority than in
hearing from our witnesses about how such authority could be
clarified or improved, understanding the unique and evolving
nature of what it is being regulated and each agency's areas of
expertise.
In response to a white paper the committee circulated at
the end of last year asking these very questions, we heard from
a number of labs and pathologists that FDA should only have a
limited role, if any, in regulating a select set of tests as
medical devices. The rest, in their opinion, should be overseen
by CMS, through an updated Clinical Laboratory Improvement
Amendments program. This is despite the fact that CMS has
stated that they do not have the resources, the expertise or
the willingness to take on what is being asked of them. I am
eager to hear what Dr. Conway has to say on the matter.
We also received comments from a number of manufacturers,
as well as over forty patient groups, that FDA-not CMS-needs to
be in the driver's seat and that tests that have the same
impact on a patient should be held to the same standards,
regardless of who does the development. This is despite the
fact that laboratories are uniquely nimble environments where
pathologists continually modify and improve tests in ways that
manufacturers cannot.
I am well aware that this has been, at times, a heated
debate with passionate advocates on both sides. With such a
backdrop, I want to particularly commend the manufacturers,
laboratories, and other healthcare institutions that have been
willing to roll up their sleeves and find as much common ground
as possible through constructive dialogue, a willingness to
compromise, and a pragmatic understanding of what a viable,
modern framework entails.
I do not believe imposing a new regulatory reality on an
increasingly important component of our healthcare system via
guidance is the best way to address these issues. These
products warrant a regulatory system designed with them in
mind. They should not be shoehorned into a system that was
drafted in the 1970s.
This committee has clearly shown that we are willing and
able to move complicated, comprehensive, bipartisan
legislation. The discussion draft the committee circulated
along with the hearing notice is of course not perfect, but it
is a serious document based on significant consensus. I would
ask that all of the stakeholders out there, including our two
distinguished witnesses, help us improve it as this process
continues.
With that I would like to thank Dr. Shuren-a frequent and
always welcome visitor-as well as Dr. Conway, for their
willingness to testify today. I look forward to working with
them on these issues going forward.
Mr. Pitts. And I now recognize the ranking member, Mr.
Green, 5 minutes for his opening statement.
OPENING STATEMENT OF HON. GENE GREEN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TEXAS
Mr. Green. Thank you, Mr. Chairman, and thank you for
calling this hearing today, and I want to welcome our witnesses
from the FDA and the CMS.
The role of diagnostic tests in our healthcare system has
changed dramatically since Congress passed the medical device
amendments in 1976 and added in vitro diagnostics to the device
definition. It has been almost 4 decades, and the evolution of
modern medicine and the advancement of science has surpassed
what everyone could imagine at the time. The enthusiasm around
precision medicine is high, and the potential of diagnostics to
further transform the treatment of disease is limitless.
When the FDA first began regulating medical devices,
applicable regulatory requirements for lab-developed tests, or
LDTs, were not enforced because they were relatively simple
tests, generally combined the local labs, and frequently used
for rare conditions.
Today, LDTs have increased in complexity and availability.
They are often used to diagnose serious medical conditions, and
many have major impact on patient care. Not only have LDTs
become sophisticated, the role that these tests play in
delivery of health care has expanded.
The Centers for Disease Control and Prevention estimated
that approximately 6.8 billion laboratory tests are
administered each year. An analysis found that results from the
clinical laboratory tests influence about 70 percent of
healthcare decisions.
The clinical laboratory amendments of 1988 created minimum
standards of quality for all clinical labs in the country. The
Centers for Medicare and Medicaid Services, CMS, has
jurisdiction over the program, and CLIA has successfully
improved the quality of the clinical labs in accuracy of
testing for nearly 25 years.
However, under CLIA CMS does not confirm the clinical
validation of LDTs, meaning that they do not look as to whether
it is a particular test accurately that identifies, measures,
or predicts the absence or the presence of a clinical
condition. These known gaps in oversight have been a source of
concern to this committee and to the healthcare community at
large.
Yesterday, the Food and Drug Administration released a
report that included 20 case studies of problematic tests from
labs that were following the minimum requirements of CLIA but
proposed real risk to patients. In an area of so much promise
and significance to patient care, the accuracy, reliability,
and clinical meaningfulness of all diagnostic tests, regardless
of where they are created, must be a top priority for
healthcare providers, test developers, regulators, and
lawmakers.
Last year, the FDA issued a draft regulatory framework to
phase in enforcement regulatory requirements, including
premarket review, adverse event reporting for LDTs that pose
greater risk to patients if their results are not accurate and
reliable. And I appreciate FDA's efforts to ensure that tests
are supported by rigorous evidence and that patients and
healthcare providers can have confidence in their results.
That said, I share the opinion of my colleagues that
legislation is both appropriate and necessary to modernize
clinical laboratory diagnostic oversight. The legislative
solution is surely the surest way to establish a framework that
will be embraced by stakeholders, avoid litigation, extended
uncertainty, and foster innovation of new clinical diagnostic
tests.
The FDA's approach to this draft guidance let to a number
of important questions, but the guidance documents also spurred
a larger conversation about the overarching need to modernize
oversight of these unique and increasingly important tests.
During the 21st Century Cures initiative, as part of the
broad effort to close the gap between science of cures and how
we regulate medical products, the committee hosted a roundtable
on precision medicine and advances in diagnostic testing. The
committee also released a white paper on diagnostic test
regulation and received outpouring of feedback from
stakeholders.
While all parties did not agree on all the principles, much
less specifics, it was abundantly clear that any regulatory
framework for diagnostic tests must prioritize patient benefit
and allow for continued innovation and investment through
regulatory certainty and appropriate regulatory controls.
There is urgent need to establish clear and logical lines
separating the practice of medicine and the actual conduct of
the diagnostic tests and the development and manufacturing of
diagnostic tests so that the promise of 21st century medicine
can be fully realized.
Today, we will hear from FDA and CMS about each agency's
respective role in the oversight and regulation of clinical
laboratory tests. Members of the committee will have questions
about the appropriate role of each agency and any updated
framework, and how Congress can best promote robust investment
and innovation while protecting patient safety.
Mr. Chairman, I look forward to hearing from our witnesses,
and I yield back.
[The prepared statement of Mr. Green follows:]
Prepared statement of Hon. Gene Green
Good morning, and thank you all for being here today.
The role of diagnostic tests in our healthcare system has
changed dramatically since Congress passed the Medical Device
Amendments in 1976 and added in-vitro diagnostics to the device
definition.
It has been almost four decades, and the evolution of
modern medicine and advancement of science has surpassed what
anyone could have imagined at that time.
The enthusiasm around precision medicine is high, and the
potential of diagnostics to further transform the treatment of
disease is limitless.
When FDA first began regulating medical devices, applicable
regulatory requirements for lab-developed tests or ``LDTs''
were not enforced because they were relatively simple tests,
generally confined to local labs, and frequently used for rare
conditions.
Today, LDTs have increased in complexity and availability.
They are often used to diagnose serious medical conditions, and
many have a major impact on patient care.
Not only have LDTs become more sophisticated, the role
these tests play in the delivery of health care has expanded.
The Centers for Disease Control and Prevention estimated
that approximately 6.8 billion laboratory tests are
administered each year.
Another analysis found that results from clinical
laboratory tests influence around 70 percent of healthcare
decisions.
The Clinical Laboratory Amendments of 1988 created minimum
standards of quality for all clinical labs in the country.
The Centers for Medicare and Medicaid Services (CMS) has
jurisdiction over the program, and CLIA has successfully
improved the quality of clinical labs and accuracy of testing
for nearly 25 years.
However, under CLIA, CMS does not confirm the clinical
validity of LDTs, meaning they do not look at whether a
particular test accurately identifies, measures, or predicts
the absence or presence of a clinical condition.
These known gaps in oversight have been a source of concern
to this committee, and to the healthcare community at large.
Yesterday, the Food and Drug Administration (FDA) released
a report that included 20 case studies of problematic tests
from labs that were following the minimum requirements of CLIA,
but posed real risk to patients.
In an of area so such promise and significance to patient
care, the accuracy, reliability and clinical meaningfulness of
all diagnostic tests--regardless of where they are created--
must be a top priority of healthcare providers, test
developers, regulators, and lawmakers.
Last year, the FDA issued a draft regulatory framework to
phase in enforcement of regulatory requirements, including
premarket review and adverse event reporting, for LDTs that
pose greater risk to patients if their results are not accurate
and reliable.
I appreciate the FDA's efforts to ensure that tests are
supported by rigorous evidence, and that patients and
healthcare providers can have confidence in their results.
That said, I share the opinion of my colleagues that
legislation is both appropriate and necessary to modernize
clinical laboratory diagnostics oversight.
A legislative solution is the surest way to establish a
framework that will be embraced by stakeholders, avoid
litigation and extended uncertainty, and foster innovation of
new clinical diagnostic tests.
The FDA's approach in its draft guidance led to a number of
important questions, but the guidance documents also spurred a
larger conversation about the overarching need to modernize
oversight of these unique and increasingly important tests.
During the 21st Century Cures Initiative, as part of the
broad effort to close the gap between the science of cures and
how we regulate medical products, the committee hosted a
roundtable on precision medicine and advances in diagnostic
testing.
The committee also released a white paper on diagnostic
test regulation, and received an outpouring of feedback from
stakeholders.
While all parties did not agree on all principles, much
less specifics, it was abundantly clear that any regulatory
framework for diagnostic tests must prioritize patient benefit,
and allow for continued innovation and investment through
regulatory certainty and appropriate regulatory controls.
There is an urgent need to establish clear and logical
lines separating the practice of medicine, the actual
conducting of a diagnostic test and the development and
manufacturing of such tests, so that the promise of 21st
century medicine can be fully realized.
Today, we will hear from FDA and CMS about each agency's
respective role in the oversight and regulation of clinical
laboratory testing.
Members of the committee will have questions about the
appropriate role of each agency in any updated framework, and
how Congress can best promote robust investment and innovation,
while protecting patient safety.
I look forward to hearing from our witnesses and I yield
back the balance of my time.
Mr. Pitts. The Chair thanks the gentleman, now recognizes
Dr. Burgess in lieu of Chairman Upton, 5 minutes.
OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF TEXAS
Mr. Burgess. Thank you, Mr. Chairman.
I appreciate the opportunity that we have before us with
this hearing, but I do want to say at the outset, with
everything else that is going on, this may be one of the most
important and at the same time the most frightening concepts
that is before the Congress right now. We are talking about a
proposal that may not just stifle but eliminate medical
innovation, something which this country has excelled for
decades, and we are also opening the door for the first Federal
regulation of the practice of medicine, not the needles and IV
solutions, the actual diagnostic thought processes that go in
to practicing medicine.
Let me just say at the outset I do strongly believe in the
potential of genomic medicine. I understand how important it is
to really understand illness at a molecular level, quickly
diagnose it, and get the treatment that is appropriate for the
patient with a minimal amount of side effects.
A year and a half ago, when the President talked about
precision medicine during his State of the Union Address, I
thought that was a very positive development. There are not
many places where the White House and I agree on anything, but
here was some common ground, and I took it to heart.
Laboratory testing produces the informational building
blocks that are at the heart of precision medicine. As former
Administrator Mark McClellan at CMS said, we have got to get
the right treatment at the right time to the right patient.
We are not talking about test kits that are put in a box
and shipped across State lines but medical procedures that are
carried out by highly trained and qualified health
professionals engaged in the practice of medicine.
As we discuss the oversight of laboratory-developed tests,
it is crucial that we do not slow innovation or create
unnecessary regulatory hurdles. We have got to ask ourselves
first, what is the problem that we are trying to solve, and is
our response appropriate, and are there unintended consequences
that could result?
Requiring premarket review by the FDA will impose new and
arguably unnecessary requirements and costs on clinical
laboratories, hospitals, and doctors. Although an additional
review of certain tests may be warranted, I actually have a
greater confidence in a CLIA-centric approach, but there are
others--and certainly people on this committee--who suggested a
different track. But it remains unclear to me how we can
separate the practice of medicine from these laboratory
processes, and if we cannot, are we effectively opening the
door to the Federal regulation of the practice of medicine? I
reject that notion and believe by segmenting this process out
has to be the fundamental first step of any proposal.
Let me just reiterate I do want to be involved in this
discussion. There is no question in my mind that CLIA can be
improved. I was not a fan when CLIA came to my medical practice
in 1988. I was not a fan of having to become a CLIA-certified
location. I was not a fan of having to apply for a CLIA waiver.
But since that time, I think arguably you can make the case
that CLIA has been a useful enterprise.
Look, we want doctors and patients to benefit from
clinically valid tests, and the current FDA proposal, as such,
creates regulatory uncertainty that will not be a catalyst for
innovation.
We talk a lot about the Administrative Procedures Act, we
talk a lot about notice of proposed rulemaking. This is not
coming through the normal regulatory process. It is coming as a
guidance. My understanding is to be issued at the end of this
year, and like it or not, there you have it.
But, you know, it is hard. On this committee I still retain
that romantic notion that our Government exists with the
consent of the governed. In my mind that would not include
issuing guidances, fiats that are expected to be followed, but
rather, you go through the normal administrative procedures,
hear people out, and make the best decision based on the
information.
Thank you, Mr. Chairman. I yield back the balance of my
time.
Mr. Pitts. The Chair thanks the gentleman.
I now recognize the ranking member of the full committee,
Mr. Pallone, 5 minutes for an opening statement.
OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Mr. Chairman. I want to also thank
Dr. Shuren and Dr. Conway for being here today to discuss the
regulation of lab-developed tests.
There has been a lot of discussion over how to
appropriately oversee lab-developed tests, and it is important
that, as the committee considers this issue, we have a better
understanding of the strengths and limitations of both FDA and
CMS's authority in this area.
Congress gave FDA authority over lab-developed tests under
the Medical Device Amendments in 1976, and at that time, most
LDTs were relatively simple tests used more often for rare
conditions. Since then, advances in technology and medicine
have resulted in LDTs that are increasingly more complex, more
readily available to physicians and patients, and used to
diagnose and treat a wider range of diseases, including breast
cancer and heart disease. LDTs are also increasingly used to
provide personalized treatment such as through genetic tests
that help physicians to detect the risk of certain diseases
earlier or to choose more targeted therapies.
Unfortunately, many of these tests have not been reviewed
or cleared by FDA prior to coming to the market to confirm that
these tests are accurate, reliable, or provide clinically
accurate results. This can result in patients going undiagnosed
with certain medical conditions or undergoing treatment that is
not medically necessary.
For example, tests have been developed to identify certain
gene sequences that can help determine appropriate treatment
for ovarian cancer. I am sure many Members here are familiar
with the example of OvaSure, which claimed to detect early-
stage ovarian cancer in high-risk women. This test, though, was
not properly validated and was found to provide high numbers of
false positive and false negative results, and this means many
women who received a false positive result may have undergone
unnecessary surgery to remove healthy ovaries, or some women
may have gone undiagnosed after receiving a false-negative
result.
Patients deserve to know that the test results they are
relying on to diagnose or treat a condition is accurate, a
comfort that they do not always have today. And as we have
heard from many organizations, patients and their physicians
should be able to trust the results of their tests, regardless
of how or where a test is developed or performed. It does not
make sense to regulate tests differently based on who develops
them.
I also believe that we can provide patients and providers
with this certainty without endangering or inhibiting the
medical innovation that is occurring today. Scientific progress
has been made to help facilitate the development and use of
personalized medicine, which you all agree is the future of
medicine, but this development can only be successful if we
know that these complex, sophisticated tests are clinically
valid.
So I am glad that today we will have the opportunity to
better understand FDA and CMS's authority in this area and hear
their perspective on what regulatory changes, if any, are
needed to address the future development of lab-developed
tests. And I hope moving forward that both agencies will work
with the committee on the discussion draft circulated today to
ensure that any legislation that moves forward will ensure that
LDTs are accurate, reliable, and safe for patients.
I yield back.
[The prepared statement of Mr. Pallone follows:]
Prepared statement of Hon. Frank Pallone, Jr.
Mr. Chairman, thank you for holding today's hearing. I also
want to thank both Dr. Shuren and Dr. Conway for being here
today to discuss the regulation of lab developed tests.
There has been much discussion over how to appropriately
oversee lab developed tests and it is important that as the
Committee considers this issue, we have a better understanding
of the strengths and limitations of both FDA and CMS's
authority in this area.
Congress gave FDA authority over lab-developed tests under
the Medical Device Amendments in 1976. At that time, most LDTs
were relatively simple tests used most often for rare
conditions. Since then advances in technology and medicine have
resulted in LDTs that are increasingly more complex, more
readily available to physicians and patients, and used to
diagnose and treat a wider range of diseases, including breast
cancer and heart disease. LDTs are also increasingly used to
provide personalized treatments, such as through genetic tests
that help physicians to detect the risk of certain diseases
earlier or to choose more targeted therapies.
Unfortunately, many of these tests have not been reviewed
or cleared by FDA prior to coming to the market to confirm that
these tests are accurate, reliable, or provide clinically
accurate results. This can result in patients going undiagnosed
with certain medical conditions, or undergoing treatment that
is not medically necessary.
For example, tests have been developed to identify certain
gene sequences that can help determine appropriate treatment
for ovarian cancer. I am sure many Members here are familiar
with the example of OvaSure, which claimed to detect early
stage ovarian cancer in high-risk women. This test though was
not properly validated and was found to provide high numbers of
false-positive and false-negative results. This means many
women who received a false positive result may have undergone
unnecessary surgery to remove healthy ovaries, or some women
may have gone undiagnosed after receiving a false negative
result.
Patients deserve to know that the test results they are
relying on to diagnose or treat a condition is accurate, a
comfort that they do not always have today. As we have heard
from many organizations, patients and their physicians should
be able to trust the results of their tests regardless of how
or where a test is developed or performed. It does not make
sense to regulate tests differently based on who develops them.
I also believe that we can provide patients and providers
with this certainty without endangering or inhibiting the
medical innovation that is occurring today. Scientific progress
has been made to help facilitate the development and use of
personalized medicine, which we all agree is the future of
medicine. But this development can only be successful if we
know that these complex, sophisticated tests are clinically
valid.
I am glad that today we will have the opportunity to better
understand FDA and CMS's authority in this area and hear their
perspective on what regulatory changes, if any, are needed to
address the future development of lab-developed tests. I hope
moving forward that both agencies will work with the Committee
on the discussion draft circulated today to ensure that any
legislation that moves forward will ensure that LDTs are
accurate, reliable, and safe for patient use.
I yield back.
Mr. Pitts. The Chair thanks the gentleman.
As usual, all the written opening statements of the Members
will be made part of the record.
That concludes the opening statements.
I would like to submit under U.C. request the following
documents for the record: a November 16 letter from a number of
organizations and laboratory directors, and a November 11
letter from organizations representing patients, advocates,
caregivers, and healthcare professionals.
Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Pitts. On our panel today we have two witnesses, and I
welcome them, thank them for coming. First, Dr. Jeffrey Shuren,
Director, Centers for Devices and Radiological Health, Food and
Drug Administration, Department of Health and Human Services;
and Dr. Patrick Conway, Deputy Administrator for Innovation and
Quality, and Chief Medical Officer, Office of the
Administrator, Centers for Medicare and Medicaid Services,
Department of Health and Human Services.
Thank you for coming. Your written testimony will be made
part of the record. You will each be given 5 minutes to
summarize.
Dr. Shuren, you are recognized for 5 minutes for a summary.
STATEMENTS OF JEFFREY SHUREN, M.D., DIRECTOR, CENTER FOR
DEVICES AND RADIOLOGICAL HEALTH, FOOD AND DRUG ADMINISTRATION,
DEPARTMENT OF HEALTH AND HUMAN SERVICES, AND PATRICK CONWAY,
M.D, ACTING PRINCIPAL DEPUTY ADMINISTRATOR, DEPUTY
ADMINISTRATOR FOR INNOVATION AND QUALITY, AND CHIEF MEDICAL
OFFICER, CENTERS FOR MEDICARE AND MEDICAID SERVICES, DEPARTMENT
OF HEALTH AND HUMAN SERVICES
STATEMENT OF JEFFREY SHUREN
Dr. Shuren. Well, thank you, Chairman Pitts, Ranking Member
Green, members of the subcommittee. Thank you for the
opportunity to testify today.
We are excited about scientific developments in genomics
and molecular biology that are leading to advances in health
care, particularly in precision medicine. Getting the right
treatment to the right patient at the right time, though,
depends upon having accurate, reliable, and clinically valid
tests. If not, we give the wrong treatment or we give no
treatment, and patients get hurt.
FDA has been regulating in vitro diagnostics for almost 4
decades, and when such a test is made by a laboratory, we call
it a laboratory-developed test, or LDT. And the law doesn't
distinguish on who makes it. We regulate the test regardless of
who makes that test. And we ensure that those tests are
analytically and clinically valid.
Now, when we first started regulating IVDs, as a matter of
policy, we decided not to actively enforce existing
requirements on LDTs because at the time they were generally
simple, low-risk tests used on uncommon conditions in often a
local setting, typically in a hospital for patients in that
hospital. But over time they have come increasingly more
complex, higher risk, they are used on common conditions like
heart disease, and they may be offered on a national basis. In
addition, we have been coming across increasing examples of
problematic LDTs. We put out examples of 20 of them just
yesterday, and there are others.
As a result of this, the problems we have seen and the
increasing complexity, there have been calls on the FDA to
actively enforce existing requirements that started in the
1990s, NIH and the Department of Energy. In the 2000s two
advisory committees to the Secretary of Health and Human
Services called on us to regulate. The Institute of Medicine
has asked us to regulate.
So in 2007 we put out draft policy to begin to actively
regulate a subset of LDTs, and what the lab community said is
don't pick off tests one by one. Please put in place an
overarching framework. So in 2010 we had a public meeting to
get input, and we were told put in place a risk-based phased-in
approach.
And then in response in October of last year we did just
that. We put out draft policy to now put in place that
framework. And what we heard from the lab community then, oh,
no, there are no problems with LDTs. We don't need FDA
oversight of anything, maybe a little beefing up on CLIA, but
that is it.
And now, just a few months ago, we started to see several
proposals come out from the lab community that now, for the
first time, acknowledge that LDTs must demonstrate that they
are analytically valid and clinically valid, that they should
be subject to premarket review, at least moderate- and high-
risk tests, the some modifications need to be subject to
premarket review, that certain problems need to be reported to
the Government, and they need to be under a risk-based approach
with a three-tier risk classification system. None of those are
currently enforced on them today. They all exist under an FDA
framework.
But what most of these proposals except one would do is it
would create a duplicative program under CMS and a bifurcated
system, leading to more inefficiencies, higher costs, and still
putting patients unnecessarily at risk. For example, you can
have a conventional manufacturer who makes an IVD we regulated.
Now, a laboratory makes a big enough change to it, which
laboratories do, and it is regulated by CLIA. Then the original
manufacturer makes a change to that test and it bounces back to
the FDA. So we will be stuck in a game of regulatory ping-pong,
and the real loser here is patients.
Doctors and patients don't care about who makes a test.
They do care that their tests are accurate, reliable, and
clinically valid.
Now, some labs have already been working with us, and we
congratulate them for crossing that picket line. But our
message in our invitation to the rest of the lab community is
to put down the swords, that for the sake of our patients it is
time to end the saber-rattling and instead partner with us
moving forward.
Thank you.
[The prepared statement of Dr. Shuren follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. The Chair thanks the gentleman, now recognizes
Dr. Conway, 5 minutes for his summary.
STATEMENT OF PATRICK CONWAY
Dr. Conway. Thank you, Chairman Pitts, Ranking Member
Green, and members of the committee. Thank you for the
opportunity to talk about our work at the Centers for Medicare
and Medicaid Services related to ensuring accurate and reliable
laboratory testing.
The Clinical Laboratory Improvement Amendments of 1988,
commonly referred to as CLIA, of which CMS has primary
jurisdiction, created minimum standards of quality for all
clinical laboratories in the United States. CLIA successfully
worked for approximately 25 years and has contributed to major
improvements in the quality of clinical laboratories, promoted
accurate testing, and improved patient safety.
As of July of 2015 there were roughly 250,000 laboratories
that have registered with CMS and held CLIA certificates. CLIA
responsibilities are divided between three agencies: CMS; the
Centers for Disease Control, or CDC; and the Food and Drug
Administration. CMS conducts laboratory inspections to make
sure that laboratories have appropriate controls, expertise,
training, and procedures to ensure that tests are accurate and
reliable. CMS also approves accreditation organizations and
manages the laboratory certification process. CDC conducts
laboratory quality improvement studies that guide policy
determination and development of laboratory practice
guidelines.
FDA's primary responsibility under CLIA is to classify
clinical tests into one of three categories--waived, moderate
complexity, and high complexity--based on their level of
complexity and risk to patients. FDA also has a critical role
in determining clinical validity of tests and premarket
evaluation. Standards that laboratories must meet under CLIA
are based on the complexity of the tests they perform.
Laboratories that perform more complex must meet higher
standards.
Laboratories that perform moderate- and high-complexity
tests must meet requirements on quality assessment, quality
control, personnel qualifications and education, general
laboratory systems, and proficiency testing, among others.
Laboratories that only perform waived tests, simpler tests that
pose a low risk to patients, are exempt from most CLIA
requirements. In addition, laboratories performing the same
tests must meet the same standards, whether located in a
hospital, doctor's office, or other site.
This framework is designed to reduce the risk of potential
harm and ensure patients receive the same high-quality clinical
laboratory testing no matter where the test is performed.
CLIA's provisions apply to all laboratories in the U.S.,
not just those that receive Medicare payment in order to ensure
uniform quality across all laboratories.
CMS enforces CLIA standards by requiring laboratories to
obtain certificates in order to operate. CMS conducts onsite
surveys prior to issuing a certificate to a lab that performs
high- or moderately complex tests. Labs are resurveyed every 2
years, and the surveys also assist laboratories in improving
patient care through education.
Laboratories may also receive CLIA certification by
obtaining accreditation from one of the seven private nonprofit
accreditation organizations approved by CMS. To receive CMS
approval, the accreditation organization requirements must meet
or exceed CLIA's requirements.
Moving forward, we believe CLIA and our implementing
regulations create the necessary framework to effectively
oversee laboratories day-to-day operations and into the future,
including those operations that pertain to the use of
laboratory-developed tests and other high-complexity tests. We
have several principles that have helped guide our work in
CLIA, which may also be useful when informing future efforts of
this committee.
First, we aim to prevent duplicative oversight efforts
across agencies. CLIA requires coordination across CMS, FDA,
and CDC. We have worked to ensure our oversight efforts are
consistent and complementary and not duplicative. In doing so,
we have ensured that we take advantage of the unique expertise
of each agency and its staff.
Second, we focus on our agency's oversight strengths. When
CLIA was implemented in the early 1990s, the responsibility to
conduct certifications of laboratories was a natural fit for
CMS because of our survey and certification experience. On the
other hand, CMS does not have scientific staff capable of
reviewing complex medical and scientific literature in
determining clinical validity. This expertise resides within
the FDA, which assesses clinical validity in the context of
premarket reviews and other activities aligned with their
regulatory efforts under the Food, Drug, and Cosmetic Act.
Third, we value our relationship with our private
accreditor organizations and State-based partners. These
organizations play an important role in evaluating and
certifying laboratories.
Fourth, we take targeted, risk-based approaches to
oversight to improve patient safety without creating burdensome
administrative requirements. We believe the current approach in
which laboratories must meet higher standards if they are to
perform more complex tests has paid dividends in improving the
quality of the testing process.
Finally, as a practicing physician who works clinically on
weekends, I know the importance of tests being assessed for
clinical validity, as well as the need for assessment for
laboratory standards. FDA and CMS can work together utilizing
their respective authorities and strengths to assess premarket
clinical validity and laboratory standards respectively.
Thank you again for the opportunity to discuss CMS's work
related to ensuring accurate and reliable laboratory testing. I
look forward to your questions. Thank you.
[The prepared statement of Dr. Conway follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. The Chair thanks the gentleman, both witnesses
for your opening statements. I will begin the questioning. I
will recognize myself 5 minutes for that purpose.
The discussion draft, which the committee circulated before
the hearing, divides FDA and CMS responsibilities based upon
the type of activity being conducted by the regulated entity.
FDA would regulate test development activities in a risk-based
manner, and CMS would regulate lab operations.
Unlike the discussion draft, some alternative proposals
being floated would divide regulatory oversight between CMS and
FDA depending on the type of test.
I would like each of you to respond. Dr. Shuren, would you
comment on the implications of an approach that would divide
oversight between CMS and FDA based on the type of test, as
opposed to the type of activity?
Dr. Shuren. So such a system is going to lead to
inefficiencies. It is going to lead to inconsistent standards,
treating the same kind of test differently depending upon who
makes the test. And as a result, you can go to one institution,
get a test, and it is regulated by FDA. You can get the same
kind of test across the street and it is regulated by CMS. And
the people who are put at risk, it is patients.
If we are going to assure that tests work, we need one
unified system that we are applying consistent standards and we
are assuring that those tests are accurate, reliable, and
clinically valid.
Mr. Pitts. Dr. Conway, would you comment on that, the
implications of an approach that divides oversight between CMS
and FDA based on the type of test, as opposed to the type of
activity?
Dr. Conway. Yes, I agree with Dr. Shuren. The concern here
is we want to reduce and avoid duplication and ensure
coordination across agencies. You know, from a CLIA construct
we really are focused on post-market review, laboratory by
laboratory, and we are really focused on the things such as the
protocols in place in the laboratory, the equipment and
equipment maintenance, the training of staff and personnel. So
CLIA's focus really is on that laboratory-by-laboratory
assessment of quality standards.
Mr. Pitts. And expand a little bit more on whether such an
approach would create administrative duplication or any
inconsistencies, Dr. Shuren?
Dr. Shuren. That is correct. It will create inefficiencies
and higher costs because essentially we have duplicative
systems in FDA and CMS, and the real distinction is just simply
who makes the test, which doesn't make sense. And we will have
inconsistent standards. We can try to coordinate between
ourselves, but quite frankly, that becomes much more
challenging as tests also begin to bounce between FDA oversight
and CMS oversight.
Mr. Pitts. OK. Dr. Conway, you stated in your testimony
that ``CMS does not have a scientific staff capable of
determining whether a test is difficult to successfully carry
out or likely to prove detrimental to a patient if carried out
improperly. This expertise resides within the FDA.'' From your
perspective at CMS, what would be the impact on patients if FDA
were precluded from reviewing the clinical validity of most
LDTs?
Dr. Conway. Yes. So as Dr. Shuren mentioned, I think the
challenge is if FDA is not reviewing the test in a premarket
manner for clinical validity, then our surveyors in CLIA are
not assessing clinical validity. They are assessing laboratory
practices and the protocols and standards in those
laboratories. So as a practicing physician, it is critical, as
Dr. Shuren said, that we know that a test is clinically valid,
meaning it is truly detecting the presence or absence of
disease. Therefore, the premarket review by FDA is important.
Mr. Pitts. Now, some stakeholders have said that CMS should
be tasked with reviewing tests for clinical validity. What are
your thoughts on that approach?
Dr. Conway. So our survey staff are not trained to assess
clinical validity, and then let me build on that. Our survey
staff are trained in laboratory protocols, equipment, standards
around those protocols, whereas--and Dr. Shuren can certainly
speak directly to FDA's staff--is, you know, physicians,
Ph.D.'s, biostatisticians who are trained in assessing the
scientific literature in its entirety and assessing clinical
validity.
Mr. Pitts. Now, some stakeholders have suggested that CMS
should regulate tests developed by labs. FDA should regulate
tests developed by manufacturers. Some have proposed carving
out a role for FDA only when a test developer chooses not to
publicize their methodologies. Shouldn't the test's impact on
the patient, regardless of who developed it, be the primary
factor in developing a regulatory framework? Dr. Shuren and
then Dr. Conway.
Dr. Shuren. Well, we agree that this should be a risk-based
framework. We also think that you should have one agency that
is reviewing those tests to assure that they are accurate,
reliable, and clinically valid. That assures consistency.
But also, one of the things we have found is when someone
makes a test, another lab or another entity makes a similar
test, we learn from that, and we sometimes identify problems or
common problems and we are able to feed that back to test
developers. If you split it between two agencies, we are going
to lose all that learning that ultimately benefits innovation
and benefits patients.
Mr. Pitts. Dr. Conway, do you want to comment?
Dr. Conway. So I agree with Dr. Shuren. I believe one
agency doing the premarket review, as Dr. Shuren said, and that
agency being FDA, makes sense given the training and expertise.
We also, as you have heard, have a principle of coordination
and using each agency's expertise. CMS's focus and expertise is
in the area of laboratory assessment, laboratory by laboratory,
on protocols, equipment, et cetera.
Mr. Pitts. My time is expired. The Chair recognizes the
ranking member, Mr. Green, 5 minutes for questions.
Mr. Green. Thank you, Mr. Chairman.
I would like to ask unanimous consent to submit a letter
from the American Cancer Society Cancer Action Network for the
record.
Mr. Pitts. Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Green. Dr. Shuren, with other medical devices, FDA has
proposed regulating lab-developed tests based on the risk of
the test to the patient and the public. Under proposed FDA
would classify LDTs into three risk classes: low, moderate, and
high. Can you explain how FDA proposes to finding the low,
moderate, and high risk in the agency's framework describing
how premarket or post-market requirements would vary among
these risk classes?
Dr. Shuren. So we look at risk based upon what the risk is
to patients if that test provides a false result, an incorrect
result. And we estimate that for low-risk tests we do not
conduct premarket review because they are so low risk. We think
about 50 percent of the tests out there--that has been our
experience--are low risk. And then we conduct premarket review
for high-risk and moderate-risk tests. High-risk tests are only
about 1 to 2 percent of the tests out there, moderate risk
about 48 percent.
And the data needed to demonstrate analytical and clinical
validity differs depending upon the risk of the disease. There
is less burden involved when it is a less-riskier test rather
that we are reviewing, and that is the risk-based approach that
we apply.
Mr. Green. FDA's approval standard for drugs and medical
devices safe and effective, can you just please discuss the
approval standard FDA has proposed using for the regulation of
lab-developed tests?
Dr. Shuren. So we would apply the same standard we would
apply to in vitro diagnostic tests that are not made by a lab,
that they are analytically valid, they are clinically valid,
and they are safe to use under their conditions to use. That
means they are accurate on what they measure, they are
reliable, and they will identify they in fact do identify a
disease.
Mr. Green. Companion diagnostics is an area of great
interest and enthusiasm. Can you talk about how the FDA views
this category of tests, in particular the level of risk posed
to patients and how they would be treated under the proposed
guidance?
Dr. Shuren. So companion diagnostics are increasingly
playing a bigger role in health care. Essentially, companion
diagnostic is a test where the safety and effectiveness of the
therapeutic depends upon the diagnostic because the diagnostic
informs whether or not that patient should receive a particular
treatment. And that is why it is critically important that
those tests truly work, because if not, then patients are not
getting the right treatment or they may be getting no treatment
at all.
For example, we had a test for providing treatment for
women with breast cancer and found that LDTs in the past were
producing as much as 20 percent of them incorrect or inaccurate
results. That means that women who should have gotten treated
with the right treatment were not. And that is preventable.
Mr. Green. OK. Thank you. Dr. Conway, I want to thank you
also for participating. As you are aware, following the release
of the FDA's guidance on enforcing requirements for lab-
developed tests, a number of stakeholders called for
enhancement of CLIA as a more appropriate way to regulate the
tests. And I appreciate your testimony on outlining the
difference between FDA and CMS authority over the tests.
One of the key differences is the fact that under CLIA CMS
does not review a test for the clinical validity, that is,
accuracy on which the test identifies measures or predicts the
presence and absence of a clinical condition or predisposition
to a patient. Rather, CMS reviews look at analytical validity.
You noted that the experience and expertise in assessed
clinical validity resides instead with the FDA.
Despite CMS stating on more than one occasion that the
agency does not have the experience or the scientific expertise
to assess clinical validity in premarket review, many
stakeholders continue to advocate for additional authority in
that area for CMS. Can you please discuss further CMS
capabilities in implementing regulations for overseeing LDTs,
and can you also please comment on whether CMS would have the
capability of conducting any type of premarket review or
regulatory review of LDTs?
Dr. Conway. Yes. So our framework that we believe is
working well now is CLIA is focused on assessment of the
protocols, the standards, the equipment, the training, and the
personnel. Even in analytic validity, we are simply looking at,
you know, does the lab test detect the analyte described? That
is very different than clinical validity, which is assessing
whether, you know, the test reliably and accurately detects the
presence or absence of disease, as Dr. Shuren said.
You know, the majority of our staff are--you know, we have
got approximately 25 people in the central office running CLIA,
a little over 100 surveyors across the States, all of the
States. They are generally medical technologists, former
laboratory personnel trained to assess laboratory by
laboratory. They are not trained to assess premarket scientific
literature and determine clinical validity.
Mr. Green. OK. Thank you, Mr. Chairman.
Mr. Pitts. The Chair thanks the gentleman and now
recognizes the vice chair of the full committee, Mrs.
Blackburn, 5 minutes for an opening statement.
Mrs. Blackburn. Thank you, Mr. Chairman.
Dr. Shuren, looking at the LDT guidance, do you plan to
finalize that guidance that you issued last year? Do you plan
to finalize that this year?
Dr. Shuren. Yes, we do plan to finalize that.
Mrs. Blackburn. OK. When?
Dr. Shuren. In 2016.
Mrs. Blackburn. OK. So basically you are going to put it
off another year?
Dr. Shuren. I don't get to determine when, but the plan is
to put it out in 2016.
Mrs. Blackburn. In 2016. Early or late?
Dr. Shuren. Hopefully earlier than later.
Mrs. Blackburn. OK.
Dr. Shuren. I wish I could give you an answer. Again, it is
so far above my pay grade. I don't even know the people who
make the decisions.
Mrs. Blackburn. Well, my goodness, we need to have a meet-
and-greet over at the FDA and see if we can't get some wheels
turning over there. We should help with that.
Let me ask you this. As you finalize that guidance, do you
intend to use what I think is the outdated 1970s definition of
a medical device in order to regulate the LDTs?
Dr. Shuren. Well, so that definition also includes a
distinct definition for in vitro diagnostics, which then
incorporates laboratory-developed tests. It does not
distinguish who makes the tests.
Mrs. Blackburn. OK. Let me ask you this. Each improvement
in an LDT technology or an upgrade or an update, will that need
to go back through the medical device approval process?
Dr. Shuren. No. Most modifications to tests are not
reviewed by FDA. We only focus on those that have the really
big impact, yes.
Mrs. Blackburn. OK. Do you intend to add to the rapid
growth of healthcare costs by taxing LDTs as medical devices in
addition to charging the innovators the user fee?
Dr. Shuren. So we are not responsible for administrating
the device tax. That is IRS. We have nothing to do with it.
That said, one of the reasons we put in place that
laboratories could notify us about their tests as opposed to
registering and listing was that it would not trigger the
device tax.
Mrs. Blackburn. I think your guidance informs the IRS,
though, is that not correct?
Dr. Shuren. No, the IRS would look separately to if that
device has listed.
Mrs. Blackburn. OK. I want to thank you for the report that
you sent to the Congress last night. It was an interesting
read. And what I found most interesting about it was what was
left out and that you didn't discuss the FDA front-end process,
which deserves some attention and some discussion, specifically
the PREDICT program. Twenty-eleven this was put in place. It is
a compliance program. It is an artificial intelligence program
that is supposed to identify high-risk shipments at our ports
of entry. And the problem with PREDICT is that it is
significantly delaying the shipment of needed medicine and
medical supplies. Medical shipments are often sent by express
service to get them to patients in time for critical usage. And
once a shipment is held up by PREDICT, almost all of them are
subsequently released without any physical inspection.
So when you look at it from the outside, Dr. Shuren, what
it appears to be and the impression is that the bureaucracy of
the FDA is keeping medicines and medical supplies from patients
because of concerns that there may have been contamination in
some cilantro that was in the very same shipment. And I would
really like to see the FDA spend the effort to fix this before
they try to regulate another area of commerce.
I noticed in that report also that it is based on 20 case
studies. And how often does the FDA use case studies as
sufficient evidence to approve or deny a medical therapy?
Dr. Shuren. So in terms of approval, we don't tend to rely
on an example. We have used a series of case studies as part of
support for valid scientific evidence as we have approved
certain tests or other products.
I will note one thing about the cases, too, we put out
yesterday. One of the challenges is that we don't have post-
market surveillance in place for laboratory-developed tests as
we do for tests made by other manufacturers. And as a result,
it is very hard to identify when problems arise. And yet we
know on the IVD side, when made by conventional manufacturers,
we do detect problems, the manufacturers detect problems, and
they fix them because that is in place.
One of the other features in the FDA system is the post-
market surveillance to identify problems and to fix problems,
and that is just as important as premarket review to prevent
faulty tests from getting on the market in the first place.
Mrs. Blackburn. Well, as I yield back my time, I hope that
you will fix PREDICT. I yield back.
Mr. Pitts. The Chair thanks the gentlelady and now
recognizes the gentlelady from California, Mrs. Capps, 5
minutes for questions.
Mrs. Capps. Thank you both, each of you, for your
testimony, and thank you, Mr. Chairman, for putting together
this hearing. I appreciate the opportunity to further discuss
the strengths and challenges, have a real conversation about
laboratory-developed tests as they guide medical decision-
making by patients and providers. There are a lot of question
marks and a lot of concern about where do we go from here, how
do we dovetail these two agencies and giving the best outcome
the patients.
I recognize there are many perspectives in this space. I
appreciate this conversation to try to illuminate some of the
issues. Over the years, it goes without saying these tests have
come more tailored and more elaborate, and this conversation is
important to ensure that these tests do produce meaningful and
reliable results for those who trust them.
Dr. Conway, I will turn to you first. In your testimony you
note that there are six key performance specification
assessments for lab-developed tests: accuracy, precision,
reference range, reportable range, analytic sensitivity,
analytic specificity. This committee has heard a lot about how
different research institutions are driving the future of
medicine toward more personalized medicine. This has been
particularly true in the field of cancer where the development
of multi-gene panels is being used to identify important
molecular characteristics of a tumor.
And my question to you is whether the current CLIA
regulations ensure these gene panels developed by different
institutions or manufacturers will produce the same results?
For example, if I am a patient and I am tested with hospital
A's gene panel, how do I know I would get the same result if I
am tested with hospital B's gene panel? Would each hospital
reach the same treatment decision, and where does this lead us?
Dr. Conway. Yes, you have highlighted--thank you for the
question, and you have highlighted one of the challenges. And
Dr. Shuren could certainly speak more.
You know, our assessment of analytic validity is laboratory
by laboratory where we are looking at the areas you described
and the laboratory director's documentation, that they are
following a protocol to detect the appropriate analyte.
And you highlighted a great example, genetic testing. It is
not assessing whether different genetic testing kits or
combination of tests are detecting the disease with the same
clinical validity and rigor. So you could in fact in the
current framework, without premarket assessment of clinical
validity, have different tests giving different answers to
clinicians that could drive treatment that is inappropriate,
which is why we think the assessment of premarket clinical
validity in this area is critical and important.
Mrs. Capps. So that leads me to focus now with you, Dr.
Shuren. Many have argued that there is no need for greater FDA
oversight of lab-developed tests, as we have not had the same
types of problems with LDTs as we have had with drugs such as
the outbreak of adverse events associated with use of
contaminated heparin, for example, or adverse events associated
with contaminated compounded drugs. They assert that if there
are greater health risks associated with LDTs, we would have
heard about them.
I am not sure you agree, but it is clear to me from the
report that FDA released yesterday that lab-developed tests do
present real risks to patients. Can you please explain whether
or not you agree with this criticism that came out? Would
healthcare providers and patients necessarily know if tests
were not giving good advice for clinical decisions?
Dr. Shuren. I don't agree with that criticism. And doctors
and patients would not know who made the device and whether it
is one that was approved by FDA or it was one that was not
approved by FDA. Quite frankly, the reason you don't see as
many problems, you don't have the systems in place to identify
them. So, for example, for IVDs we regulate, in 2014 we had
over 300 recalls. It is not unusual.
Things change, problems arise, but you need the systems to
identify the problems and to fix them. And we have some labs
who have submitted their tests to us, and we have approved or
cleared some LDTs. And when they put the systems in place,
these started to identify problems. One of them has already had
eight recalls, but they only found the problems because they
put in the systems that they should have in place.
Mrs. Capps. Well, now, how can patients--I am just about
out of time, but how can patients, providers, and payers be
assured that the tests they are paying for are providing real
value and enhancing the care of patients?
Dr. Shuren. Well, that is why we would like to have a
uniform, consistent approach to diagnostic tests, regardless of
who makes them. That information will be made available to the
public so they know what tests have been approved. There is
information about what those tests are for. The makers have to
put out information that explains its performance
characteristics, its intended use, how to use it properly, and
all that will provide necessary information to doctors and
patients so they can use those tests appropriately.
Mrs. Capps. Thank you.
Dr. Shuren. Right now, they can't.
Mrs. Capps. OK. It sounds like we need a follow-up. I yield
back.
Mr. Pitts. The Chair thanks the gentlelady and now
recognizes the chair emeritus of the full committee, Mr.
Barton, 5 minutes for questions.
Mr. Barton. Thank you, Mr. Chairman. I want to thank both
our witnesses for attending today. I appreciate the
subcommittee chairman, the full committee chairman issuing the
proposal as a discussion draft, which to me means that their
minds are still open and that we can make some changes and
things of this sort.
I am one of those skeptics that Mrs. Capps just talked
about. I am not sure that we need to get more Federal
regulation. I don't necessarily think more Federal regulation
is going to give us a safer, more efficacious result.
So I guess my first question to either of you gentlemen
would be what is the real problem? I mean why in the world
would a laboratory develop a test that wasn't safe and
accurate? My office is not being overrun with phone calls or
emails from doctors, patients, hospitals, advocacy groups that
there is some terrible laboratory diagnostic test out in the
marketplace.
Dr. Shuren. But those tests are out on the marketplace. So,
for example, a test was developed for something called KIV 6.
It was supposed to predict the risk of heart disease and
response to statin treatment. And the lab came out with it,
promoted it, said they had studies, but then subsequently good
studies were performed and in fact found that there was no
association between KIV 6 and those conditions. And by the time
it came out, though, over 150,000 people had the tests
performed. We estimated the cost to our healthcare system was
over $2 billion. That is not money we can afford to waste on
bad testing.
Mr. Barton. And what happened----
Dr. Shuren. So what happened----
Mr. Barton. I assume that test was taken off the market and
without FDA having to do anything.
Dr. Shuren. It remained on the market and there was
continued use for a while and then use started to dip down. But
is that really the system we want, that we have bad tests,
people can get hurt by it, and then afterwards if you find the
problem and you get on top of it, then something happens to the
test? The whole point of premarket review is and why we do that
for the other tests----
Mr. Barton. You are going to guarantee if we would let your
agency review all these diagnostic tests, the laboratory tests,
that something like that will never happen again, that you all
are perfect and all-knowing and you are going to do it in a
cost-effective way and it will be peace and light from now
until Judgment Day?
Dr. Shuren. I will not promise you perfection, and I will
leave it to God to decide if there will be peace on Earth,
but----
Mr. Barton. Well, I am glad to hear somebody use----
Dr. Shuren. But that said, we have----
Mr. Barton [continuing]. The Divinity's name in a positive
way. That is----
Dr. Shuren. Yes, well, they can fire me.
Mr. Barton. That is a good thing.
Dr. Shuren. But we have almost 40 years of experience of
regulating in vitro diagnostic tests and assuring that those
tests are accurate, reliable, and clinically----
Mr. Barton. I mean, granting your point at least partially,
wouldn't it be better to give FDA or some State regulatory
agency--it doesn't necessarily have to be Federal--some sort of
a penalty assessment that we can immediately put a stop if
there is a bad test? Wouldn't that be a better use of your
agency's resources? So to use your example, if that were to
happen again, boom, we catch it, we stop it, we hit them with a
big penalty and get that test off the market. I am not being a
horse's rear on this, but, you know, if it is not broken, don't
fix it, and it looks to me like we are just looking for ways to
give the CMS and the FDA more authority. And it is obvious that
Chairman Pitts and Chairman Upton and I assume Mr. Pallone and
Mr. Green are concerned, too. But more regulation is not always
the best answer.
I guess my last question would be under the current system
what role if any do the States play in looking at these tests?
Dr. Shuren. So there are States--I can let Dr. Conway talk
about it in terms of States that are involved in accreditation
of laboratories, but they are not involved in premarket review
for those tests with certain exceptions. New York State does do
a review of tests. And quite frankly, under the proposal we
have, we have the opportunity to leverage third parties. If New
York State is meeting appropriate standards, we could leverage
some of the work that they are doing.
But I will tell you the problems are more prevalent than
people want to recognize. You know, one of the medical centers
at the University of Texas was concerned about this----
Mr. Barton. I went to A&M so that doesn't scare me.
Dr. Shuren. No, no, no--well--but I will tell you what they
were finding is----
Mr. Barton. I am going to hear it whether I want to or not.
Dr. Shuren. That is right. Thank you for that. But there
were inconsistencies in what they were seeing reported by labs
for the same kind of tests, so what they did is they took
results from 105 of their cancer patients and they had results
from one laboratory, they sent it to a second laboratory, and
of the 32 gene variants, they found 50 percent disagreement, 50
percent. And so they even concluded that this suggests
physician care would differ based on different interpretations
of different companies. And this is not the only report out
there, other ones reporting 27 percent finding of incorrect or
inaccurate results. This is not uncommon. This goes on.
It is fixable, and it shouldn't be fixed after the fact.
Why should our people get hurt, and only when that happens--and
if we can find it because we don't have the systems to do
that--do we take action. Is that really the kind of health care
we want to provide? Do we want to spend money on unnecessary
care or do we want to spend it on innovation and assuring those
tests work.
Mr. Barton. Well, I am with you on the innovation part.
Mr. Chairman, you know, the other subcommittee's got the
FCC commissioners downstairs, so I am not going to be able to
stay, but I appreciate you holding this hearing and thank you
for the courtesy of the time.
Mr. Pitts. The Chair thanks the gentleman and now
recognizes the ranking member of the full committee, Mr.
Pallone, 5 minutes for questions.
Mr. Pallone. Thank you, Mr. Chairman.
I wanted to ask Dr. Shuren. As you know, various
stakeholders have been circulating legislative proposals
regarding the regulation of lab-developed tests. Among these
various legislative proposals, there seems to be a great deal
of variance around moderate-risk tests. Some proposals have
suggested that no premarket review is necessary for moderate-
risk tests, and one proposal would require premarket review of
moderate-risk tests but would allow such tests to be deemed
approved if FDA did not act in a specified time frame.
So I wanted to ask you a couple questions about this. In
your testimony you noted an example of a test that is moderate
risk would blood glucose strips used by people with diabetes
and tests to help doctors diagnose heart failure. Could you
discuss what FDA considers to be moderate risk and provide some
examples of tests that would be considered moderate risk?
Dr. Shuren. So other moderate-risk tests would be for
diagnosing cystic fibrosis, herpes, heart failure are all
moderate-risk tests----
Mr. Pallone. OK.
Dr. Shuren [continuing]. That we currently regulate.
Mr. Pallone. Does the FDA believe that premarket review of
moderate-risk tests that there should be, and if so, can you
describe when you believe that premarket review of a moderate-
risk test would be necessary?
Dr. Shuren. So we do believe that most moderate-risk tests
would be subject to premarket review. That is what we do now,
but we do find that there are certain circumstances where we
can put other mitigations in place that are good enough and you
don't need premarket review. We just did that a little while
back for next-generation sequencing platforms, when they are
just making tool claims. We just did that for autosomal
recessive carrier screening tests. And that is a natural course
of action. As the science develops, technology evolves, we can
actually change risk classification or what a test will have to
do to come on the market. That is hallmarks of a risk-based
approach.
We are also very concerned about this deemed-approved
approach. It essentially says if we don't make it decision in
time, it is approved. So a test goes on the market that may be
inaccurate simply because we didn't have enough time to finish
up the review or, alternatively, we will not approve it to not
let it go on the market. And yet if we had the time to work
with the lab, we might get a good test on the market. Either
way, bad tests on the market, good tests not going on a market,
the loser is patients.
Mr. Pallone. OK. I think you answered my next question,
which would be, you know, the deemed approval if FDA does not
act. But let me say, can you comment on whether or not--yes, I
think you already talked about the deemed approved. So let me
go to another question, Dr. Shuren.
I understand that once the test is approved or cleared by
FDA and enters the market, laboratories frequently modify the
kits either to expand uses or to make improvements to the way
the test is performed. And some stakeholders in the lab
community have even suggested that manufacturers rely on
laboratories to modify tests in order to expand the uses
because it is too costly or burdensome to have a test approved
for every use. So do you believe that modifications to LDTs
should be subject to premarket requirements, and if so, what
types of modifications would FDA want to look at before they
are put in place?
Dr. Shuren. So we think most changes that are made would
not be subject to FDA review, and that is actually what occurs
now for other IVDs. We would review those changes when there is
a new intended use because it truly is a new test. Even CLIA
have used that as a new test. Or if there is a big enough
change that when a test is approved would determine what its
performance specifications are, if now you make a change and it
goes outside the performance specifications, we would review
that as well.
Mr. Pallone. OK.
Dr. Shuren. But it is those kinds of changes.
Mr. Pallone. Let me go back. There was other thing that I
could have asked you about, these tests are deemed approved if
FDA didn't act in a certain time frame. Can you explain whether
or not you believe patients, physicians, or payers would know
which tests were affirmatively cleared or approved by FDA
versus tests that were deemed to be approved? Is there any way
that they would know that?
Dr. Shuren. No. I mean if the test is approved, the test is
approved.
Mr. Pallone. So that is one of the dangers if you will. In
other words, you said before that you would be concerned that
you might approve something that shouldn't be or not approve
something that could be. But the secondary problem is that the
user is not going to know.
Dr. Shuren. That is exactly right.
Mr. Pallone. All right. Thanks a lot.
Mr. Guthrie [presiding]. Thank you. And the gentleman
yields back. I now recognize myself for 5 minutes for
questions.
Dr. Shuren and Conway, what does premarket review mean in
the context of lab-developed tests, or LDTs? And how important
is it and who should be responsible for such reviews?
Dr. Shuren. So our premarket review is to determine if the
tests are analytically valid, clinically valid, and they are
safe for use under their conditions for use. And it is
important to conduct those reviews for moderate- and high-risk
tests to make sure they work because doctors and patients rely
on those tests to make well-informed healthcare decisions. If
they get inaccurate results, they could make the wrong
decisions and people get hurt as a result.
Mr. Guthrie. Thank you. Dr. Conway?
Dr. Conway. I agree with Dr. Shuren. And from the CLIA/CMS
perspective, you know, we are really focused on laboratory-by-
laboratory post-market review of those laboratory protocols,
equipment, training of personnel, et cetera.
Mr. Guthrie. OK. Thank you. And I have heard that the same
type of diagnostic test that is commonly available as both an
LDT and a manufacturer kit that can be purchased by a lab, and
tests for melanoma are one example. In other words, I could go
to hospital A where they have a lab that developed their own
test or, by chance, I could go to hospital B, whose lab
purchased a test from a manufacturer. Can either of you walk me
through this scenario from a regulatory perspective? In the
case of hospital A, is it true that neither FDA nor CMS will
have reviewed that test for clinical validity?
Dr. Shuren. That is true. The test across the street would
have been reviewed, and therefore, doctors and patients have
the confidence to be able to rely on it, and you don't know in
the case of the other one that has been offered.
Mr. Guthrie. OK. Same----
Dr. Conway. Yes, same. And CMS, once again, would not
review clinical validity as part of the CLIA process.
Mr. Guthrie. OK. Doing the premarket review of these types
of tests, could each of you describe the general education and
professional background and expertise of your reviewers?
Dr. Shuren. So our review, particularly for more complex
tests, tends to be performed by a team of experts. They may
include physicians, Ph.D. scientists, and statisticians that do
a deep dive into the scientific data. We review the science to
see if in fact and not only that test works but what it is
claiming to do matches up with the science.
Mr. Guthrie. Thank you. Dr. Conway?
Dr. Conway. Our CLIA team does not include any medical
officers or other personnel trained in detailed biostatistics
or Ph.D.-level training. Our CLIA team is really focused on, as
I mentioned, laboratory assessment on an accreditation and
quality and survey and certification framework in a post-market
manner laboratory by laboratory.
Mr. Guthrie. Thanks. And, Dr. Shuren, you previously
testified about challenges you face in hiring and retaining
sufficient medical expertise. How would your ability to do so
be impacted if CMS were required to have the same types of
expertise regarding test design and development?
Dr. Shuren. Well, first off, I want to thank the committee
for trying to take actions in 21st Century Cures to help us to
better be able to attract and retain high quality talent. And
that is where the answer lies.
Mr. Guthrie. So the competition if CMS is doing the same
would be----
Dr. Shuren. Well, it makes no sense for competition, so all
we are going to do is create a duplicative system in another
agency. I mean it is interesting that people have raised
concern about do not have duplicative regulatory frameworks in
place, and yet some of the proposals we have seen now to put
this under CLIA would do exactly that. It would create all this
duplication the right now, as you have heard from both of us,
doesn't exist.
Mr. Guthrie. All right. Thank you. And I yield back the
balance of my time.
And I now recognize Ms. Castor from Florida.
Ms. Castor. Thank you, Mr. Chairman. And thank you both for
being here today.
As we continue to develop a greater understanding of the
genetics of individuals who have a wide variety of diseases and
conditions, we are moving away from one-size-fits-all medicine
to more targeted and effective prevention strategies and
treatments and even cures. This is known as personalized
medicine, and I believe it is fundamental to the vision of 21st
Century Cures and holds great promise.
This vision, though, will in large part be dependent upon
accurate genetic tests, so it is imperative that these tests
are scientifically credible. Dr. Shuren, can you provide some
examples of the types of genetic tests that are being developed
to help deliver personalized treatment? And describe in greater
detail the role that these tests play in precision medicine.
Dr. Shuren. So increasingly, we are seeing genetic tests
being developed to help identify what the appropriate treatment
may be for patients who have various conditions, including
cancer. And it is critically important that those tests work,
because if not, people are not getting the right treatment or
they are not getting treatment when in fact they should get
treatment.
I will say that as we approach this, though, Government can
be innovative. Increasingly, we are seeing next-generation
sequencing tests being used, and last December, we put out a
proposal for a new approach on next-generation sequencing that,
rather than your standard model of maybe doing a clinical study
is to leverage data in existing curated databases, which can
allow for the clinical community to crowd-source the evidence,
and as the science ultimately evolves to where it needs to be
to be able to make claims about the use of that test. That way,
the regulatory framework can stay step-in-step with the
evolution of the science.
In fact, we just held a two-day public meeting last week on
this. There is a lot of support for moving forward with this
approach. We have even relied on those curated databases to
approve a test for cystic fibrosis.
So that is where we need to focus our attention, and that
is why we want the lab community at the table with us. Let's
focus on the science. That is what we need to do. We have the
regulatory tools. It is the science we have got to work
together on. And we can do it if people are willing to work
with us.
Ms. Castor. Yes. And during our 21st Century Cures hearings
and briefings, there was a lot of talk about data-sharing. What
is going on--because we can't wait for Congress to act,
frankly. What is going on with FDA and NIH and a lot of those
research institutions across the country in being able to look
at that data, share it, so we can develop the cures and
treatments of the future?
Dr. Shuren. Yes. So NIH has its own database of genetic
variants. They do an assessment. We have other databases out
there. We are now trying to work with these various groups on
what the appropriate standards should be for the quality check
for the curation and what should be the standards for clinical
validity when you are evaluating that science.
Also, we at the FDA have been developing a platform called
precision FDA that would allow these test developers to
essentially either share their genetic data to compare or
providing analytical tools so they can test-drive some of these
next-generation sequencing technologies to see if they are
accurately sequencing the genome. We think this is a great
role, if you will, to provide these common goods to all
developers.
Ms. Castor. Great. I do, too. Thank you. And I yield back
my time.
Mr. Guthrie. Thank you very much. The gentleman from
Illinois, Mr. Shimkus, is recognized for 5 minutes.
Mr. Shimkus. Thank you, Mr. Chairman. And welcome.
Actually, I appreciate the comments from my colleague from
Florida. That is kind of where I was just heading to a little
bit, too, with the personalized medicine and the genetic
testing and really being accurate on that test so then you can,
as we talked about in the other piece of legislation, target
based upon the genetic code or the individual patient. That is
very exciting.
And the other thing I think we have followed through the
hearings and the 21st Century Cures is that then you just don't
go down the route of prescribing remedial health action to
someone without really full information, so the high cost of
health care because you try this, didn't work, try this, didn't
work, now you are trying this, and you can get more specific
information. So it is very exciting times. And I think people
were going around the same issues.
But I wanted to ask this, and it is probably something I
should know if I would have more thoroughly read my briefings,
but when we talk about risk--basic, moderate, or high--so we
are really focusing on moderate and high risk of the tests.
What is the risk component? Is the risk component the risk of
conducting it, the risk of not having accurate information, or
the risk to the patient who hopes to get good information from
a test because of the healthcare environment they presently
find themselves in? So can you both talk on how do we define
risk?
Dr. Shuren. Yes. So the key consideration is the risk to
the patient if they are getting an inaccurate result, they are
getting a wrong result, and that is within the context of what
would otherwise happen to that patient in clinical care. That
is the way we look at it.
Mr. Shimkus. So when you use the example of heart, you put
that in a moderate--when you were giving the examples of--and I
was kind of surprised. I mean, heart disease or heart issues, I
think people would find it pretty risky if you have got heart
disease, a higher risk than just in the moderate category. So
there is some subjectivity to this or----
Dr. Shuren. Well, so when we look at it, you put it within
the clinical context. So in the case of heart failure, when you
are making, you know, a diagnosis, there are other things that
the clinician takes into account in making that determination.
That is a little bit different, though, when I am dealing with
something, let's say, like HIV where not only am I dealing with
a high-risk condition, right, the risk to the patient is huge,
secondly, I don't have another great means of truly determining
is that HIV. And then there is also the risk of if I am wrong
about this and that person goes out and doesn't know they have
HIV, they may engage in activities that they will spread the
disease. So we are really looking at it in the practical
context of what in fact happens to the patient, not just simply
the condition itself.
Mr. Shimkus. Right. And I think this is a tough area for
conservative Republicans who think Government is too big, costs
too much, but there is obviously a position of we want to make
sure that people are advertising and using tests, that they are
given some stamp of approval, that they meet the requirements
and the desires of what they are.
So, Dr. Conway, real quick, you admit that the volume and
complexity of these tests have kind of grown, I don't know, I
would say exponentially almost. Would you agree with that?
Dr. Conway. Yes. We don't have exact numbers for some of
the reasons described, but it seems exponential.
Mr. Shimkus. But you haven't asked for new authorities
because of this growth, have you?
Dr. Conway. So CMS has not put forward additional requests
for statutory authority. As I mentioned, we think FDA can play
a critical role in the premarket review, and we can play a
critical role laboratory by laboratory, post-market.
Mr. Shimkus. Yes, in your area do you require an individual
review of the area that you have been involved with? Is there
an independent review process of decisions that you are making,
you know, in the CLIA process?
Dr. Conway. Let me try to answer that. So I think we have a
central office that has oversight of State surveyors, and
therefore, oversight of the processes of those State surveyors.
We also oversee accrediting organizations, of which there are
seven. They have to meet or exceed CLIA standards, and we
review that, including if any----
Mr. Shimkus. But you are almost evaluating the
organizations. The organizations aren't evaluating the
independent decisions?
Dr. Conway. We have bidirectional communication both with
the States and their accrediting organizations like in any of
our accrediting organizations, including at times in various
programs accrediting organizations identify regulations or
standards that need updating.
Mr. Shimkus. Great. Thank you very much. I yield back my
time.
Mr. Guthrie. I thank the gentleman. The time is expired.
And I recognize Dr. Schrader from Oregon for 5 minutes for
questions.
Mr. Schrader. Thank you, Mr. Chairman. And I would like to
thank Dr. Shuren and Dr. Conway for being here. Interesting
topic. I would hope that the chair or vice chair and ranking
member would hopefully have us have an opportunity to talk to
the stakeholders, including the physician groups, just to get a
balanced perspective here. This is pretty darn important if we
are going to go down this road, and I think the tender of the
questions so far indicate that.
And I appreciate the fact both of you testified in total
agreement in pretty clear terms about how you guys have two
different jobs in the different agencies. It is tough from a
practitioner's standpoint, being part of the medical community,
to really understand why that has to be. I understand it is
right now, but I am not sure why it has to be. It seems odd to
me that the Center for Medicare Services--medical services
would not have some sort of health regulatory role or clinical
analyzation capability.
And it seems to me both of you are going to have to staff
up, well, particularly FDA if you take on this new role of
premarket approval. There is going to be a huge staffing
increase. Why would that not also be possible for the folks in
CLIA or somewhere in CMS to do the same thing? I ask both of
you that question.
Dr. Shuren. So we already have existing staff who do
exactly these kinds of reviews, and we have years of experience
on it. We have training programs for our people. And in terms
of additional resources, one of the reasons that we put in
place a phased-in approach would be also for tests that are out
there, one, not disrupt the market; two, that we could try to
accommodate what resources we have. But in addition, if we need
additional resources, we have a user-fee program under which we
work with the regulated community about appropriate funding for
services that we then provide back like performance and
premarket review. And that program, as you know, has been in
place for a number of years.
Mr. Schrader. So minimal staffing increase is what you are
suggesting?
Dr. Shuren. It depends on the ultimate framework that goes
into place as to what that workload would look like.
Mr. Schrader. All right. Mr. Conway, if you can.
Dr. Conway. On the CMS side, as I mentioned in the central
office we have approximately 25 people in total overseeing
CLIA. They are trained for their job, which they do well, which
is oversight of laboratories, laboratory by laboratory. There
are no medical officers, there are no Ph.D.'s, biostatisticians
because we do not do premarket review.
Mr. Schrader. I just get concerned still--sorry--because
both your testimonies talk about accuracy, both of you. You
both talk about reliability. And that sounds like overlap to
me. So I am just concerned that we don't go down that road.
Question on peer-review. I mean a lot of treatments and
diagnoses are peer-reviewed in the literature and stuff. Has
that occurred at all with laboratory tests? Is there any
literature reviewing the efficacy of different laboratory
tests?
Dr. Shuren. In our review of tests we do look at published
literature, and in some cases we have relied completely on
published literature for certain tests like hemoglobin A1c for
diabetes.
This issue about accuracy, our look at it, though, for
analytical validity is complementary but it is different. We
truly look at is the test itself and what it measures, is it in
fact accurate? CMS will look at is that test performed properly
to get a result.
Mr. Schrader. That is correct. So I guess my underlying
concern as a medical professional listening to the testimony is
that the consumer, as well as the physician or veterinarian, is
not misled by having premarket review. There is going to be
some certainty that that test is 100 percent appropriate for
them in their situation.
The reason I raised the question about the peer review, I
mean, generally, the test from my standpoint is a secondary
adjunct to helping establish the diagnosis. You got a lot on
clinical sides, you got a lot on knowing your patient, got a
lot to, you know, based on the environment they are living in.
There are false positives all the time in every single test,
false negatives in virtually every single test, whether it is a
genetic test or, you know, a simple blood test for goodness
sakes. I just don't want the consumer to be misled that by
having FDA premarket approval, that that test is going to be
100 percent. I think that is a mistake.
At the end of the day I think it is up to the medical
community, the physician to put that one small piece of the
puzzle into the, you know, whole diagnostic scheme and come up
with whether or not that is actually going to be a valid use of
their patient.
I am just very concerned the tone here is that we are going
to put certainty into the art of medicine when there is not
that much certainty, and the patient will be misled and frankly
lead to greater lawsuits and customers frankly not
understanding what medicine is really all about.
Dr. Shuren. And so the accuracy of that test will also
depend on what the use of the test is for. You know, when you
deal with riskier conditions or where there are some tests you
truly rely on the result of that test. Companion diagnostics,
for example, it is the result of that test that will be telling
you should they get Zelboraf, you know, for melanoma. And in
those cases you want to have a higher accuracy.
You are right, it is not 100 percent, but also what we
assure you is that that information is made available to the
practitioner like you, and you know that when you get that
number for how accurate it is, the result, it is correct. It is
the----
Mr. Schrader. Well, laboratories have different--laboratory
information from one lab to the other is going to be different.
I can send the exact same blood sample in to a different
laboratory. I can send the genetic code in. You testified a
moment ago you are going to get different information back. So
the idea that it is going to be dispositive, I would
respectfully disagree. And I yield my time.
Mr. Guthrie. Thank you. The gentleman's time is expired.
I now recognize Dr. Burgess of Texas for 5 minutes.
Mr. Burgess. Thank you, Mr. Chairman.
Before I start my time, could I asking for a unanimous
consent request?
Mr. Guthrie. The gentleman is recognized.
Mr. Burgess. Ask unanimous consent to enter the statement
of the Association for Molecular Pathology into the record. And
then a further unanimous consent request for a point of
personal privilege, Mr. Chairman.
For the past 7 years I have been joined at these committee
hearings by Mr. Paluskiewicz, whose last name is so difficult
to pronounce we all know him by J.P. And if I ever seem
adequately prepared for these hearings, it is only because I
have had J.P. advising me before we come into the hearing room.
And so it is with great sadness that I announce that J.P. will
be leaving my employment, but he will be joining the committee
staff, so he will be here for all to participate and the
wondrous things that he has to offer to any committee hearing.
Thank you, Mr. Chairman. Now recognize for questions.
Dr. Conway, so if Dr. Shuren puts his guidance out in
January, are you no longer necessary?
Dr. Conway. No, sir, and let me explain why. I think there
will still be a role for CLIA to assess, and this is a
critically important role, that laboratories have the proper
equipment, training, protocols, and quality assurance
procedures in place, and that laboratory-by-laboratory
certification, which a few people have talked about, is a
critical role for CLIA.
Mr. Burgess. But, you know, we have heard several times the
FDA is under-resourced, so why shouldn't the resources that are
going to CMS just simply go to the FDA?
Dr. Conway. So I will speak for CMS. You know, I think in
the CLIA oversight framework we are efficiently using both
central office resources and relying on States, which was a
question earlier, and their State surveyors, obviously a user-
fee funded program based on user fees based on moderate, high
complexity, et cetera, and volume. And then we also importantly
have nonprofit accrediting organizations that are not
Government organizations, that we--seven of them--approve that
they meet or exceed CLIA standards. We are using people outside
of the Federal Government as well to perform these important
functions.
Mr. Burgess. Dr. Shuren, this question has been posed to
you several times in this subcommittee or oversight
subcommittees about what is the problem that we are trying to
solve? And last night at 7:00 p.m. you put out a report that
detailed 20 times where perhaps there were problems with
laboratory-developed tests, is that correct?
Dr. Shuren. Yes.
Mr. Burgess. And I am sure you would make the further
statement that there are more than that, but we have also seen
in testimony that what is the total universe of laboratory-
developed tests? It is in excess of 11,000, is that correct?
Dr. Shuren. It is above 11,000.
Mr. Burgess. So the rate at which you have detected
problems would be, if my math is correct, .18 percent, which
most things in medicine are hardly that reliable. Is that an
unfair statement?
Dr. Shuren. Yes. Reporting systems--first of all, there is
no reporting system on LDTs. You are not monitoring for
problems. And so you can't say what the rate is, quite frankly.
Mr. Burgess. It took you 3 years to provide us with 20.
When I asked you in hearings, when we were doing the FDA
reauthorization, what is the problem we are trying to solve? So
today, now, I have your report, 20 problems that we are trying
to solve, and we have got a universe in excess of 11,000 tests.
So let me just ask you this, since you think the risk is
there from laboratory-developed tests, is there an FDA-approved
kit that has ever had a failure?
Dr. Shuren. Yes. And the point is the reason we can
identify when there are problems and we can deal with it is
because we have the systems in place and the maker of the test
has implemented systems internally to identify those problems.
That is critical. And the work that we are doing doesn't occur
right now in CMS. It is not duplicative, and they don't go
away.
Remember, if you make a test, if you are a conventional
manufacturer, that lab is going to get your test. They still
have to perform that test properly, and that is what CMS is
overseeing, are the laboratory operations conducted properly.
Mr. Burgess. My time is limited. So do you envision any
lack of access to testing because of the changes that you are
proposing in the guidance or the committee is proposing in
their legislation?
Dr. Shuren. So we have tried to--a proposal was put in
place so that we would not disrupt the marketplace. Our goal
here is to try to assure we do have innovation. We think LDTs
are important in health care. There is innovation, but----
Mr. Burgess. I appreciate the recommendation----
Dr. Shuren [continuing]. There is no value to patients if
the tests in fact don't work. And one of the problems is
because we haven't regulated, there has been a disincentive for
innovation by conventional manufacturers. And we have heard
from them, particularly the smaller companies are saying they
are disadvantaged because they make a test and they go through
and they have to demonstrate their test works. And then you can
have a lab make the same kind of test go out the door----
Mr. Burgess. I am going to have to interrupt you because my
time is limited.
Just as far as the labs themselves, who do you expect to be
more greatly impacted, large labs and large hospitals or
smaller rural labs? Is there likely to be a difference in the
impact? It is a yes-or-no question.
Dr. Shuren. The answer is you should regardless be
developing the science that your test is validated, whether we
review it or not.
Mr. Burgess. If you don't know whether the answer is yes or
no, why wouldn't we want to see an economic impact evaluation
such as normally would be required in rulemaking but is not
required in guidance?
Dr. Shuren. Well, just to clarify again, whether we were
overseeing them or not, a lab shouldn't be putting any test on
the market that they haven't gotten the data to validate. What
we are saying is you should have the data and we would look at
it before the test went on the market to make sure that that
test in fact worked.
Mr. Burgess. And to the question----
Dr. Shuren. The tests that wouldn't go on the market are
the ones that in fact don't work.
Mr. Burgess. And to the question of an economic impact
statement, as would be required under normal rulemaking
processes, why shouldn't the committee or the Congress expect
that?
Dr. Shuren. We are not under rulemaking because we are not
imposing new requirements. These requirements already exist
under the law. As a matter of policy, we have not actively
enforced them. And in places where we put an enforcement
discretion policy, we have withdrawn it. We have done that
through guidance. It has been the practice all along.
I would say in terms of economic analysis, too, we now have
seen the lab community has come forward to say LDTs need to
demonstrate analytical and clinical validity. Moderate- and
high-risk LDTs need to be subject to premarket review. So those
pieces, even the lab community has now said, you know what,
that kind of a framework needs to be in place.
Mr. Guthrie. The gentleman's time is expired. Would you
again, Dr. Burgess, make--you had one unanimous consent request
that we did not act on, then you went to a point of personal
privilege. Can you make that once again before we move on?
Mr. Burgess. Yes. It was to add to the record the statement
from the Association of Molecular Pathology for the record.
Mr. Guthrie. Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Guthrie. Thank you.
Mr. Burgess. Thank you.
Mr. Guthrie. The Chair now recognizes Mr. Sarbanes from
Maryland for 5 minutes for questions.
Mr. Sarbanes. Thank you, Mr. Chairman. I thank the two
witnesses for being here.
This is obviously a very important discussion, and I always
try to look at these conversations through the eyes of sort of
my constituents, people out there, and I have got to believe
that if some of them are paying attention to this hearing, they
would be scratching their head, the typical patient out there,
and saying, you mean these kinds of protections and reviews and
guidance and so forth are not already in place?
And I understand that, you know, you start out in a
different time period, and you are now trying to sort of update
the framework that exists to protect patients out there, and I
think the average person would think that this is a very
reasonable undertaking on your part. So there is going to have
to be some heightened degree of oversight and assurance in this
arena.
You have probably touched on all this before I came, but
could you just take maybe two or three or four of the main
categories of kind of constituencies out there and give me a
shorthand on their perspective? What are physicians saying
about this conversation? What are patient advocate groups
saying? I think I can probably guess. You have alluded to the
industry, the lab industry itself, but can you just--and in
particular, I guess the physician perspective on it would be
helpful to me, but if you can kind of shorthand those different
lenses on this discussion.
Dr. Shuren. We have heard mixed perspectives from the
physician community. So oncologists have come out to say, yes,
you need oversight, you need FDA oversight. Pathologists have
felt that, no, we do not. FDA shouldn't be or should have
little role in oversight of LDTs. The patient groups have been
supportive of FDA. The consumer groups, payers have been--the
medical device industry has been, the laboratory community has
been split. Some of the labs have been working and promoting a
proposal with FDA oversight, and the others have been proposing
a system under CLIA.
Mr. Sarbanes. The payers, that is interesting. Can you
expand a little bit on that? Is that because they are seeing a
lot of costs associated with faulty test results in the use of
those?
Dr. Conway. Maybe I will start since I am a large payer. It
is a challenge in the payer aspect, so including in Medicare
and similar and private payers. If the tests haven't gone
through that FDA review, then we have a system of local
contract medical directors in our national office also, you
know, small numbers of people trying to review thousands of
tests that either are identified to us or we identify that we
need to assess reasonable and necessary for coverage. If there
were an FDA review, you could potentially take a whole set of
those that have been through FDA review and have those be
covered and focus on the ones that are leftover. So this is an
issue there.
If you don't mind, on the practicing physician point, I am
a practicing physician. I train residents and medical students
on weekends as well. You know, you want an assurance as a
physician that the test is clinically valid and that the report
that says the patient has cancer or genetic disease X is
correct. And the patient wants that assurance as well.
Mr. Sarbanes. Right.
Mr. Guthrie. Thank you. And the gentleman yields back his
time.
Mr. Lance of New Jersey is recognized for 5 minutes for
questions.
Mr. Lance. Thank you very much, Mr. Chairman. Good morning
to you, gentlemen.
Dr. Conway, it is my understanding that it is the Division
of Laboratory Services within the Survey and Certification
Group within the Center for Clinical Standards and Quality at
CMS that has responsibility for administering the program. How
many staff within the division are responsible for inspecting
labs and reviewing the tests they performed?
Dr. Conway. We have approximately 25 central office staff,
and then we have approximately 110 surveyors across the Nation
and all the States, so a small number per State.
Mr. Lance. We have heard that there are tens of thousands
of LDTs out there. Do you believe that the division is capable
of reviewing all of these LDTs in a timely fashion for clinical
validity?
Dr. Conway. No, they are not, either in a timely fashion or
with the current training of the staff that we have.
Mr. Lance. And therefore, do you believe that new
innovation would be effective, I presume, negatively because of
the potential backlog?
Dr. Conway. Yes, I would be very concerned about a
potential backlog and the impact on innovation.
Mr. Lance. Dr. Shuren, how would the FDA handle the
workload and how would these submissions be based in line, on
what priority if this were to be handled by the FDA?
Dr. Shuren. To handle workload, it is one of the reasons we
have put in a phased-in approach over a number of years, and
review would occur--be prioritized based upon risk. What we
proposed is we would start reviewing higher-risk devices before
we would look at--high risk before moving to moderate risk.
Mr. Lance. And to the best of your ability, how long do you
believe it would take to review an LDT, your best estimate,
Doctor?
Dr. Shuren. So for the moderate risk LDTs now, the review
times are--total times are a little over 100 days, thereabouts.
Mr. Lance. Thank you. Thank you, Mr. Chairman. I yield back
the balance of my time.
Mr. Burgess. Would the gentleman yield to me?
Mr. Lance. I yield to Dr. Burgess.
Mr. Burgess. Thank you.
Mr. Guthrie. Dr. Burgess is recognized.
Mr. Burgess. On that point, could you state that figure
again, the moderate-risk LDTs, 100 days? Is that right?
Dr. Shuren. No, a little over 100 days.
Mr. Burgess. So there are 11,000 and some laboratory-
developed tests. You said earlier that 50 percent are low risk,
so presumably, that leaves 50 percent that are in the moderate-
or high-risk category, is that correct?
Dr. Shuren. Yes, that is correct.
Mr. Burgess. So extrapolating out the number of days,
assuming none of them are high risk, they are all low risk, and
that is over 100 days of evaluation at the FDA, I mean that is
a phenomenal amount of work that is ahead of you, is it not?
Dr. Shuren. That is one of the reasons why we have looked
at phased-in approach. We have gotten feedback, too, if we
should consider any changes and take a different approach for
some of the tests that are currently on the market, which we
are doing. And we are also having those discussions about
funding needs as part of user fee discussions, which are going
on right now. They get authorized every 5 years. And that has
been the natural course of business.
We have those discussions with regulated industry--the
laboratory community is that the table--to then talk about if
people want to see a certain performance, what does that look
like. We know in some of the proposals people have said for
moderate-risk tests could that review time be 75 days? We can
have a discussion about what it would take for review in 75
days.
Mr. Burgess. I will say some of the performance metrics
that were introduced after the last FDA reauthorization in
2012, I don't know that we ever got satisfactory answers back
to this subcommittee or the Subcommittee on Oversight as to how
the performance was on that, but there is a general unease that
the FDA is able to perform its function in a timely fashion.
During the time that we were doing the hearings for the FDA
reauthorization, there was hardly a week that went by that
there was not someone in my office with a tale of woe about a
drug or device that just seemed to take forever in development
and that the FDA would sometimes change the rules as that drug
or device went through the development process. What assurance
can we give to the laboratory-developed test community that
they won't encounter similar problems with your agency going
forward?
Dr. Shuren. Well, our review times have been actually
improving under MDUFA III. We are meeting our performance
goals, as we committed to do. So we are seeing things move in
the right direction. And I don't know what is happening to
people coming into your office now. I have heard from other
Members that they don't have the parade of people that were
coming in several years ago.
And you know when I took over the program several years
ago, I was very upfront with this committee and others that
there were challenges in the medical device program. We had
seen roughly a decade of worsening performance, and we
committed to turn that around. We committed to make changes
regardless of what happened with MDUFA, and then MDUFA came
along to give us additional resources. And we have continued to
see improved performance, and we are going to continue to work
on it, as we have been doing all along.
Mr. Guthrie. Thank you.
Mr. Burgess. I don't know that I share your enthusiasm.
Thank you, Mr. Chairman.
Mr. Guthrie. Thank you. The gentleman from New Jersey's
time has expired, and recognizing Mr. Cardenas from California
for 5 minutes for questions.
Mr. Cardenas. Thank you very much, Mr. Chairman.
My first question is to FDA and CMS. Today in your
budgeting, are you being asked to do more with less?
Dr. Shuren. Yes.
Mr. Cardenas. I am not talking about prospectively. I am
talking about in the cycle that you are currently in.
Dr. Shuren. Yes, and that has been even the cycles before
then. We are always asked to do more with less.
Mr. Cardenas. OK.
Dr. Conway. Yes. So it is also true for CMS, long history
of doing more for less. Thank you for the more with less. Thank
you for the question. I mean, I have managed in the delivery
system. I have managed in CMS. I have never managed somewhere
as hard as this. It is ridiculously harder than running a
delivery system. And the reason is the amount of resources for
the job. We are deploying lien and other operational techniques
to increase our efficiency, learning from manufacturing and
health systems, and that is working, but this is a major issue.
Mr. Cardenas. OK. Thank you for clarifying that. I don't
think the public understands how taxing it is for our agencies
to continue to do more and more and more and try to protect the
public and allow the American public to know or feel as though
there are protections and the agencies are trying their best to
look out for making sure that when they are engaged in
something that is a--whether it is FDA-approved or it has gone
through review of CMS, et cetera, that they can feel safe.
So thank you for continuing to wade through the struggle of
doing more with less and doing your best to keep up with that.
I hope that we as the holders of the purse, Congress, will
recognize that and realize that we are impeding on the safety
of our American citizens when we just say no to a reasonable
request of resources and we just say do with what you have and
do a better job and just make it happen, easier said than done.
And thank you for clarifying that in the environment that
you have been and that this is probably the--I interpret that
what you said is this is the most difficult environment for you
to do justice to your efforts than any other environment you
have been in.
Dr. Conway. Yes. And I----
Mr. Cardenas. And understand you are not coming across to
me as complaining.
Dr. Conway. No.
Mr. Cardenas. I think it is important that you just be
honest with us the way you have been. Thank you.
Dr. Conway. Yes. No, do you mind if I----
Mr. Cardenas. No, go ahead, please.
Dr. Conway. This is the best job I have ever had and the
most impactful, which is why I have stayed, but the challenge
of managing in the CMS environment with the resources we have
for the duty we have for the American people is by far the
hardest job I have ever had. And I have led in the private
sector, large groups, large budgets. It is nowhere close. This
is the most challenging job I have ever had in my life.
Mr. Cardenas. And again, I thank you for welcoming the
challenge. It is too bad that we don't lessen that challenge by
giving you the resources for you to be more effective without
worrying about not being effective in your responsibilities.
My family just got the news recently that my wife and I are
going to be grandparents for the first time. And just the other
day, we were invited to my daughter and my son-in-law's house,
and they revealed to us it is going to be a boy. And the reason
why they found is because my daughter underwent a test that
went to a laboratory and the results came back. And one of the
things that they could tell her--it wasn't the purpose of the
test, but one of the things they could tell her is the gender
of the fetus. And so it was a wonderful moment.
However, what if the purpose of that test had been
inadvertent, the results had been inadvertent? I think that is
really what the focus of today is about. It is about safety of
the public. It is about accuracy of what is going on out there.
It is about whether or not they are being effective. And
unfortunately, for those people who want less Government or no
Government, there needs to be oversight from somewhere. I
personally prefer that Government be involved in that oversight
instead of just turning it completely over to private
industries, which happens in some cases.
But my question to you is, going forward, how do we as a
country make sure that between CMS, between FDA, what your role
can be in making sure that these critical tests, these
laboratories are being accurate with the information to the
patient, to the actual end-user?
Dr. Shuren. Well, we have established a task force between
FDA and CMS--NIH and CDC are also participating--to assure that
we are not duplicating efforts. In fact, we have had
conversations with certified laboratories, accrediting lab
organizations under CLIA, two State licensure programs, and
confirmed we are not duplicating efforts, but we do want to
make sure we have good coordination moving forward. And we
provide the education and information out for laboratories as
well as we progress, so that work is happening in the task
force right now.
Dr. Conway. I agree.
Mr. Cardenas. Thank you.
Mr. Guthrie. They gentleman's time expired. And myself, and
I think speaking for the entire subcommittee, we congratulate
you on the good news and to your family, the next generation of
your family, appreciate that very much.
The Chair now recognizes Dr. Bucshon from Indiana for 5
minutes for questions.
Mr. Bucshon. Thank you, Mr. Chairman.
Now, I have heard complaints that the FDA oversight of LDTs
would interfere with the practice of medicine. I am a
physician, cardiovascular surgeon, so I would like you both to
comment as regulators but also as physicians on your view on
that.
Dr. Shuren. So we do not--and as a physician, we do not
regulate the practice of medicine. Congress actually put in a
statutory provision prohibiting us from regulating the practice
of medicine in the medical device program. It is a unique
provision that pertains to us. What we are regulating, talking
about regulating, are the tests, the things that we regulate
already today, reagents, the instruments, the protocol,
instructions are used that go forward with it.
In fact, a group of laboratories who were working with the
device industry, the conventional IVD makers, when they sat
down and went through it, they began to realize, too, you know
what, there are parts here that is just like what happens in
FDA: development, design, validation of tests. Then there are
all these other activities that occur that are lab operations
or the practice of medicine. They are not under our preview and
we have never proposed to ever regulate those.
Dr. Conway. And likewise, CLIA does not regulate the
practice of medicine. It does regulate laboratories in terms of
equipment, personnel, protocols, et cetera, which its focus is
post-market laboratory by laboratory.
Mr. Bucshon. OK. Great. And currently, CMS regulates how
physicians operates a lab, as you described, and performs tests
within it, but I really haven't heard any complaints about
interfering with the practice of medicine myself from people
that I know. Why is it that physicians feel differently maybe
about the FDA oversight of these particular tests, and how can
we address those concerns? Does that make sense?
Dr. Shuren. It does. I think what we are dealing with are
people who haven't dealt with us necessarily beforehand, and so
it is new and they are assuming things that we don't believe to
be the case. I hearken back to Dr. Burgess, who I respect very
much, when he said when CLIA came in the door you were not a
fan, but you began to realize the value of it. I would say the
same thing here. As the lab community works with us--well,
maybe you will allow it.
Well, hopefully, we will see much the same here with the
lab community in working with us. And it is our hope they will
work with us to make sure that when we are doing things, it
also best fits for their operations. Again, we both are
committed and care about that those tests work.
Mr. Bucshon. Yes. I mean I will just make a comment and I
will--I mean, as a physician, obviously I want accuracy and
patient safety to be at the top of the list, right? And again,
I think Mr. Shimkus said I am not one that is generally for
Government regulation, but I think in this area that, you know,
this is a good discussion to be having on behalf of patients,
and that I think the details and how things end up at the end
are what are important. So I commend your hard work on trying
to find the sweet spot as you go about your job.
Thank you. I yield back.
Mr. Burgess [presiding]. The Chair thanks the gentleman.
The gentleman yields back.
The Chair recognizes the gentleman from Florida, Mr.
Bilirakis, 5 minutes for questions, please.
Mr. Bilirakis. Thank you, Mr. Chairman. I appreciate it.
And this question is for the panel.
As we go forward with any new regulation--regulatory
scheme--we need to balance the needs between consistency,
accuracy, and innovation. In disease areas such as cancer,
genetic testing is evolving rapidly, and I am sure you agree
with that. Many major institutions today have developed their
own gene panels that help diagnose or identify potential
treatments for cancer patients.
For example, in Tampa we have the Moffitt Cancer Center,
the only NCI-designated Comprehensive Cancer Center in Florida.
They have developed a TruSight Tumor Gene Set, which is used to
identify lung and colon cancers that will benefit from targeted
therapies. An advantage of the lab-developed tests is the
ability to rapidly innovate current tests rather than the
slower and expensive process of resubmitting to FDA for any
changes. Centers such as Moffitt have the ability to innovate
and rapidly improve their lab tests as fast as science evolves.
Question: How can we resolve issues regarding consistency
and accuracy and not stifle innovation in these labs and
important healthcare institutions?
Dr. Shuren. So one issue for consistency, certainly we
don't--we were recommending not to have two duplicative systems
out there, one under FDA, one under CMS, or we will have
inconsistency. But then we have found that to assure
consistency, we work with the community on trying to develop
standards or in guidance so that, as we learn and the science
evolves, we can have more of a common playing field of what
performance should look like for certain kinds of tests. And
that can help ensure consistency in terms of approach.
Mr. Bilirakis. Thank you. Anyone else?
Dr. Conway. I agree with Dr. Shuren, and I think, you know,
from the CMS perspective, we think our strength is in that
post-market review laboratory by laboratory on the
qualifications, equipment, and personnel.
Mr. Bilirakis. Thank you. Anyone else want to jump in? OK.
Dr. Conway, since both the volume and complexity of lab-
developed tests on the market today have drastically increased
in recent years, why hasn't CMS asked for these new
authorities?
Dr. Conway. So in terms of authorities we think FDA has a
critical role in premarket review of clinical validity. We
think CMS's role through CLIA really is and should be focused
on laboratory-by-laboratory assessment, survey and
certification and oversight of accrediting organizations,
ensuring that the protocols, the equipment, and the standards
are in place in individual laboratories in a post-market
manner.
Mr. Bilirakis. Dr. Conway, does CMS require definitive
review of the clinical claims being made about the tests?
Dr. Conway. And Dr. Shuren can certainly comment for FDA.
On the CMS perspective, we do basic assessment of analytical
validity so the analyte is the actual analyte in the test. We
do not do assessments of clinical validity, meaning the test
actually identifies the condition, the absence or presence of
the condition it is supposed to identify.
In our coverage process, we have occasionally looked at
laboratory development tests for reasonable and necessary
standard. There, we will look at the effect of the test on
patients, but that is a very small number of LDTs we have
looked at through that process.
Mr. Bilirakis. Well, thank you very much, and I yield back,
Mr. Chairman.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
The Chair recognizes the gentleman from New York, Mr.
Collins, 5 minutes for your questions, please.
Mr. Collins. Thank you, Mr. Chairman.
Before I start my questions, I would ask unanimous consent
to enter into the record a letter from Roswell Park Cancer
Institute.
Mr. Burgess. Without objection.
[The information appears at the conclusion of the hearing.]
Mr. Collins. Thank you very much.
In that letter they do mention the same we have talked
about before, the Association of Molecular Pathology, or AMP,
and their proposal, and I would certainly encourage the FDA, as
we are in the discussion stage, to again take a look at this.
So I guess one thing I am still trying to get clear on, you
know, currently, a commercial test, something sold on the
market which does have to go through FDA approval, premarket
approval, and I assuming that is currently a 510(k)?
Dr. Shuren. For premarket, most of them are 510(k). A very
tiny number are PMA.
Mr. Collins. So as a 510(k) currently, it is a medical
device subject to the medical device tax, correct?
Dr. Shuren. Yes.
Mr. Collins. So if I understand what your guidance is now,
you are going to move on IVDs out of that world, the medical
device world, and have a different classification of class 1,
2, or 3, or low, moderate, whatever. Just a question, does that
mean on the good news side that IVDs will no longer be subject
to the medical device tax since they are not going to be
getting 510(k)s?
Dr. Shuren. So the trigger for the device tax is
registering at the listing with the FDA. What we have proposed
for LDTs is that--and we use that to know what test is being
made, who is making it, and that is a requirement by law. But
we have worked through that instead they can give us a
notification and not list with us, and particularly--and that
is for starters. And for the tests that don't ultimately come
in for premarket review, they also wouldn't end up registering
and listing with us. And that would not trigger the device tax.
Mr. Collins. So current tests would be still covered by the
medical device tax even though there is not a 510(k) because
they would be listed with the FDA?
Dr. Shuren. They are registered and listed with that, and
those are----
Mr. Collins. OK. That clarification is important because I
have heard that kind of going all over the board.
Now, another, you know, concern has been, you know,
accuracy of testing, and I think it is also important to make
clear laboratory-developed tests are not sold to other
facilities. They are used inside a facility such as Roswell
Park, which is looking at very specific treatments for specific
cancers and what we call personalized medicine. They are not
then selling those tests to other folks or making claims, which
is different than a commercialized test, which currently goes
through FDA approvals.
But, you know, Dr. Conway, it is my understanding that over
97 percent of the CLIA laboratory test facilities have
subjected themselves to outside third-party proficiency testing
of their tests. Isn't that correct?
Dr. Conway. So proficiency testing occurs in just 13
specialty areas, occurs approximately three times per year. It
has improved the accuracy over time. It will not assess for
clinical validity of the test, so the premarket clinical
validity, which Dr. Shuren spoke to, the proficiency testing
does not analyze clinical validity.
Mr. Collins. Well, it certainly analyzes whether you are
properly getting--you know, you are identifying the antigen you
are supposed to identify.
Dr. Conway. So it will identify--if that laboratory-
developed test was within those 13 categories, which they are
not all within those 13 areas, but for an LDT that was in one
of those 13 areas--and Dr. Shuren may say more--it will detect
that the analyte is the analyte, but that is not an assessment
of the clinical usefulness or validity of the test.
Dr. Shuren. And it goes to again, if you will, the accuracy
of the performance of the test as opposed to the accuracy of
the test itself, which is a different look, and that is what we
look at for the test.
Mr. Collins. Yes. I guess I would just say it is my belief
anyway that the laboratory-developed tests, certainly in
institutions like Roswell Park, are being done to get better
treatment, quicker treatment to the patients. And a big concern
all of us have, if this goes through, that a test might be used
tomorrow to help a patient with cancer now is delayed 6 months
as it goes through some kind of premarket review at FDA, which
is a life-and-death situation for many of these cancers.
And I think it goes back to--I think I go on to the same
bandwagon as Mr. Barton and Dr. Burgess. This has not been a
problem that I would identify, and putting any type of delay
into this sphere of personalized medicine and treatment
especially in the cancer and oncology world runs the risk
frankly of causing people to die that don't need to die,
treatments that could be given that would be delayed. And in
the cancer world, delay is not a good thing.
So personally, I would throw myself into the category I
believe it is working now. We do have outside proficiency
testing, third-party testing. And we have to remember these are
laboratory-developed tests that are not being sold in the
marketplace to other facilities, which is very different than
what you are doing now.
My time has expired, but if the Chair would like to hear a
response, I would certainly yield a couple seconds.
Mr. Burgess. Sure. He is recognized for a response.
Dr. Shuren. I truly appreciate those comments because we do
not want to stifle innovation in this place. We want to have
patients get timely access to tests. And that is why even under
an FDA mechanism if the test is being reviewed, it is being
developed, it can still be made available to patients on an
investigational basis or for compassionate use. But there at
least you are telling the doctor and you are telling the
patient we haven't validated this test yet. It is
investigational. This may be----
Mr. Collins. You know what, I appreciate that because my
worry was they would develop a test, they couldn't use it until
they had approval, but if on an investigative basis they know
that--they think they have a good test they can use it, then
you have actually helped me in a couple of ways there. Thank
you for that response.
I yield back.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
The Chair recognizes the gentleman from Pennsylvania, Mr.
Murphy, 5 questions for questions, please.
Mr. Murphy. Thank you. Doctor, Doctor, it good to have you
here, appreciate this.
I want to pivot a little bit here to talk about piecing
together post-market and premarket analysis to look at this,
and in particular, a couple of devices used in women's health
care, one is called a morcellator. Are you familiar with the
morcellator, a device that is supposed to shred tumors, et
cetera, but has been associated with complications in women in
terms of actually spreading cancer for them?
Now, it has been on the market for 20-plus years, and the
FDA admitted for the first time it became aware of the safety
issue with power morcellators was after December of 2013,
correspondence from a physician citing the case of a family
member. This is someone who had just recently had another
surgery to remove another recurrence of cancer that was spread
it by the morcellator.
The manufacturer was apparently aware of the dangers of
this device as early as 2006 based upon a report from Dr.
Lamparter, a pathologist from central Pennsylvania, who cited
about 1 out of 300 samples of morcellated tissue from his
hospital had evidence of a hidden cancer, which is morcellated.
So my question is did the FDA have any evidence of these
dangers in 2006 or prior to that? Are you aware of this
problem?
Dr. Shuren. So in the past the thought was what risks of
cancer there may be for a fibroma--for a fibroid actually to
have cancer in there--were significantly less. And one of the
things when we looked into it more recently we came to a
different conclusion, that the likelihood of cancer is higher.
There is still disagreement in the community because, as you
know, the healthcare professional societies disagree. They
think we have overestimated the risk of cancer.
We said we have a different perspective, and that is why we
went out and we put contraindications and warnings on the use
of that device, that it should only be used in a more limited
set or offered as an option in a limited set of women and think
about primarily women who, in the absence of using the device,
would no longer be able to bear children but they want to bear
children. And we felt those cases the risk of the cancer is
very low. They should have the opportunity to weigh in, but we
scaled back dramatically how that should----
Mr. Murphy. So this is a case where the science available,
the premarket analysis has changed, and what is being used in
the data, you have a mechanism to go forward on this and make
some changes. Let me ask another question.
Brigham and Women's Hospital was aware of the dangers in
2012. A patient by the name of Mrs. Erica Katz was seriously
injured in 2012 by the device and then died in 2013 according
to reports. I wondered, do you know if that hospital reported
that to the FDA? Would you know?
Dr. Shuren. I am not aware that----
Mr. Murphy. Is there a mechanism where the hospital is
supposed to report that or the manufacturer is supposed to
report that so you can do the analysis?
Dr. Shuren. So user facilities have certain requirements
for reporting. So do manufacturers if they become aware of
certain events. And what I can tell you is we have been looking
into those concerns that have been raised regarding reporting.
Mr. Murphy. OK. In response to congressional inquiries
about this, the FDA admitted that the 1-out-of-350 risk does
not address other types of malignancies, which you would add to
that risk, you said. They went on to say the FDA also
identified studies showing that morcellated patients had worse
outcomes than patients who had not undergone morcellation.
So this is more than just the issue with just a fibroid or
if it is cancerous. It is also a question of outcomes. Is this
something that the FDA is reviewing also with regard to their
stamp of approval on these things in terms of the outcome
measures?
Dr. Shuren. So in terms of the tests we have looked at, we
think where we have constrained it right now is--for use is
where the benefits outweigh the risks, but we are continuing to
look at new data as it arises, and if so, we will act
accordingly.
Mr. Murphy. Thank you. There is another issue in women's
health that was brought to my attention. It is a product called
Essure. It is a permanent birth control device that went
through FDA's rigorous premarket approval process. Yet despite
getting the agency's approval, it has been linked to at least
four deaths and deaths of five unborn children. Apparently, a
total of 24,000 women have come forward claiming that they have
been harmed by this device. And so the question is how it
remains on the market with a potential for problems. And
because this has the FDA stamp of approval, these women feel at
this point they cannot take their cases forward, and they feel
they don't have any recourse. Is the FDA also reviewing this
issue as well as far as you know?
Dr. Shuren. We are. In fact, we held an advisory committee
meeting a few weeks ago at our behest to give an opportunity to
put what new evidence is on the table to assure that people who
wanted to raise concerns about it had an opportunity to provide
those concerns. And we are now currently reviewing the feedback
we received from the advisory committee, as well as what we
have heard from other people, as well as the state of the
evidence, and we will come out with our conclusions on that to
the public.
Mr. Murphy. Thank you. And as this goes through, since this
hearing has been a lot about premarket analysis, what this
comes down to is I just want to make sure that we are aware of
what mechanism you have, because I understand the science of
1996 is different from the science of 2015 and our knowledge
base, but to have an ongoing mechanism for review and changes,
devices and getting information there and looking at those
things, I mean, I am glad you had some hearings on this, but I
would certainly like to know that that is part of the system.
I am out of time, but I look forward to hearing your
comments on that in the future. Thank you.
Mr. Burgess. The gentleman yields back. The Chair thanks
the gentleman.
The Chair recognizes the gentleman from Texas for a
unanimous consent request.
Mr. Green. Mr. Chairman, I ask unanimous consent to place
in the record ``Public Health Evidence for FDA Oversight of
Laboratory Developed Tests: 20 Case Studies.'' I ask unanimous
consent to place that in the record.
Mr. Burgess. Without objection, so ordered.\1\
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\1\ The information has been retained in committee files and also
is available at http://docs.house.gov/meetings/IF/IF14/20151117/
104127/HMTG-114-IF14-20151117-SD009.
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Mr. Burgess. And I recognize myself for an additional
unanimous consent request to add the statement of the American
Association of Clinical Chemistry to the record. Without
objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Burgess. Seeing no further Members wishing to be
recognized for questions, I do want to remind Members they have
10 business days to submit questions for the record, and I ask
the witnesses to respond to those questions promptly. Members
should submit their questions by the close of business on
December 2.
With that, the subcommittee stands in adjournment.
Dr. Shuren. Thank you.
[Whereupon, at 12:07 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
Prepared statement of Hon. Fred Upton
The 21st Century Cures Act passed this committee 51-0 and
was through the House in July with 344 votes. It was the
product of over a year's worth of ideas Members received at
hearings, roundtables in DC and across the country. Provisions
were proposed and fleshed out with the help of a wide variety
of stakeholders, in and out of Government, of all political
stripes. It goes without saying that for any piece of
comprehensive legislation to garner these vote totals,
compromise is critical and the perfect can't become the enemy
of the good. It also goes without saying that some important
pieces of the puzzle didn't get included because the timing
just wasn't right. Modernizing our regulatory framework for the
review and oversight of diagnostics is one of those pieces.
As I said at our first forum on this topic in July 2014,
these increasingly important and complex tests are providing
researchers and clinicians with valuable tools to match the
right patients with the right treatments. We must ensure that
our laws and regulations keep pace so that innovation in this
space continues and patients benefit from accurate and reliable
tests.
I saw Cures as a unique opportunity to elicit feedback on
what such a framework should look like and what role Congress
could play in developing it. We issued a white paper asking
targeted questions and were overwhelmed with the scope and
thoroughness of the responses we received. We realized early on
that the traditional medical device framework was not ideally
suited for these unique tests, which provide clinicians with
critical information but do not actually provide therapy to a
patient.
It was also apparent that there was quite a difference of
opinion about what the roles and responsibilities of FDA and
CMS should be. Developing legislative language with broad
support on an abbreviated timeframe was not achievable. I told
my staff to table these discussions until we got Cures through
the House but to urge stakeholders to use the time to forge
ahead and find as much common ground as possible.
I was very encouraged to hear that a diverse group of
stakeholders with different points of view came together and,
in the spirit of finding consensus, developed a draft framework
that answered a lot of our questions in a responsible, balanced
manner. Of course there is room for improvement, but folks need
to be realistic in their approach and pragmatic with their
suggestions if the ultimate goal is a bill signed into law any
time soon. We must get this right and we need everyone's help
in order to do so.
Prepared statement of Hon. Renee L. Ellmers
Earlier this year, Democrats and Republicans on the House
Energy and Commerce Committee worked together to develop the
21st Century Cures legislation. I was proud to work with my
colleagues on that landmark initiative in order to reduce
regulation, inspire innovation, improve outcomes for patients
and move our country towards precision medicine. Further, that
legislation helped highlight the increased importance of
diagnostics in modern health care.
Today, diagnostics play a critical role in the rapid
detection and diagnosis of diseases. Diagnostics help identify
targeted, effective and often less invasive treatments-
ultimately leading to reduced costs to both patients and the
Government.
The Committee's current discussion draft legislation
follows the work of 21st Century Cures and focuses on the
future of diagnostics. It would advance innovation, protect
patients, provide a predictable and timely path to market and
avoid duplicative regulation. It does this by tailoring an
appropriate role for the FDA (outside of the medical device
framework) to oversee diagnostic test development activities,
while modernizing CLIA oversight of separate and distinct
laboratory operation activities.
Without this legislation, I am concerned that the FDA would
finalize guidance to regulate laboratory developed tests as
medical devices, which could impact many stakeholders. This
guidance may lead to costly litigation and uncertainty or could
hamper innovation and patient access to critical diagnostic
tests.
Also, I am deeply concerned that this guidance would result
in the medical device tax being imposed on laboratories. Dr.
Shuren confirmed during the hearing in September 2014, that
under the FDA's guidance, labs would ultimately be directly
subject to this medical device tax. Labs already pay the tax
indirectly when they purchase test kits from manufacturers, so
under the guidance they would unfairly pay the same tax twice.
I have many stakeholders in my district, so this discussion
draft legislation represents a good compromise between the
CLIA-centric approach and the medical device framework laid out
in the FDA guidance. In addition, my district is home to many
veterans and military families who rely on TRICARE for their
health care, so ensuring market stability and access to these
crucial tests directly affects my constituents.
I am thankful for stakeholder engagement in finding a
legislative solution that provides a feasible alternative to
FDA's draft guidance. I stand prepared to work with the
chairman and ranking member in order to accomplish this goal.
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