Summary
of Fourth Meeting
April 21-22, 2005
Washington,
DC
The
Secretary’s Advisory Committee on
Heritable Disorders and Genetic Diseases
in Newborns and Children was convened
for its fourth meeting at 9:00 a.m. on
Thursday, April 21, 2005, in the Rotunda
Ballroom at the Ronald Reagan Building
and International Trade Center in Washington,
D.C. The meeting was adjourned at 2:30
p.m. on Friday, April 22, 2005. In accordance
with the provisions of Public Law 92-463,
the meeting was open for public comments
from 1 p.m. to 2:00 p.m. on Thursday,
April 21, 2005, and Friday, April 22,
2005.
Committee
Members Present:
R.
Rodney Howell, M.D.
Committee Chairperson
Professor
Department of Pediatrics
The University of Miami School of Medicine
Duane
Alexander, M.D.*
National Institutes of Health
William
J. Becker, D.O., M.P.H.
Medical Director
Bureau of Public Health Laboratories
Ohio Department of Public Health
Coleen
Boyle, Ph.D., M.S.*
Centers for Disease Control and Prevention
Amy
Brower, Ph.D.
Executive Director
Medical Informatics and Genetics
Third Wave Molecular Diagnostics
Peter
B. Coggins, Ph.D.
Senior Vice President
PerkinElmer
President
Denise
Dougherty, Ph.D.*
Agency for Healthcare Research and
Quality
E.
Stephen Edwards, M.D., FAAP
American Academy of Pediatrics
Past President
Gregory
A. Hawkins, Ph.D.
Assistant Professor
Center for Human Genomics
Wake Forest University School of Medicine
Jennifer
L. Howse, Ph.D.
President
March of Dimes Birth Defects Foundation
Piero
Rinaldo, M.D., Ph.D.
Professor of Laboratory Medicine
Mayo Clinic College of Medicine
Department of Laboratory Medicine and
Pathology
Mayo Clinic Rochester
Derek
Robertson, J.D., M.B.A.
Attorney-at-Law
Powers, Pyles, Sutter & Verville,
PC
Joseph
Telfair, Dr.P.H., M.S.W., M.P.H.**
Secretary's Advisory Committee on
Genetics, Health, and Society
Department of Maternal and Child Health
School of Public Health
Peter
C. van Dyck, M.D., M.P.H., M.S.*
Health Resources and Services Administration
Associate Administrator
Executive Secretary
Michele
A. Lloyd-Puryear, M.D., Ph.D.
Health Resources and Services Administration
Committee Executive Secretary
CONTENTS
1.
WELCOME, OPENING REMARKS
2.
ACMG REPORT ON NEWBORN SCREENING
Update
on the American College of Medical Genetics
(ACMG) Report on Newborn Screening
Committee Discussion of the ACMG Newborn
Screening Report
3.
PUBLIC COMMENT SESSION, April 21
4.
SUBCOMMITTEE MEETINGS
5.
EDUCATING PARENTS ABOUT NEWBORN SCREENING
NNSGRC
Survey of States for Policies and Procedures
for Public and Professional Education
Related to Newborn Screening
Parental Education Project—Informing
Parents About Newborn Screening: Sickle
Cell Disease Newborn Screening Education
Project
6.
COMMITTEE BUSINESS—APPROVAL OF MINUTES
7.
NEWBORN SCREENING FOLLOW-UP AND QUALITY
ASSURANCE
Introduction
Proposed Clinical Laboratory Standards
Institute (CLSI) Guideline on Newborn
Screening Followup
The Newborn Screening Program Evaluation
and Assessment System (PEAS)
8.
COMMITTEE BUSINESS—SUBCOMMITTEE
REPORTS
Education
& Training Subcommittee
Treatment & Follow-up Subcommittee
Laboratory Standards & Procedures
Subcommittee
9.
PUBLIC COMMENT SESSION, April 22
10.
COMMITTEE BUSINESS—SETTING COMMITTEE
PRIORITIES
WELCOME,
OPENING REMARKS
Rodney
Howell, M.D.
Chair, Secretary’s Advisory Committee
on Heritable Disorders and Genetic Diseases
in Newborns and Children
Dr.
Howell opened the meeting by noting that
the Committee would welcome suggestions
for a new name and thanking Committee
members and Dr. van Dyck and Dr. Lloyd-Puryear
and the staff of the Health Resources
and Services Administration (HRSA) for
their hard work. He added that voting
to approve the minutes for the third meeting
of the Advisory Committee on Heritable
Disorders and Genetic Diseases in Newborns
and Children held January 13-14, 2005,
would be delayed to allow time for the
Committee members to review the corrected
minutes, which were not in their briefing
books.
Next,
Dr. Howell drew attention to the new Charter
for the Committee, signed by the Secretary
of Health and Human Services (HHS) on
February 8, 2005. The new Charter is
very similar to the previous Charter but
makes Dr. Howse and Dr. Edwards voting
members and includes a few other organizational
changes. Dr. Howell also reported that
Secretary Michael Leavitt had been confirmed
as the new HHS Secretary.
Finally,
Dr. Howell reviewed the agenda for the
2-day meeting:
- The
American College of Medical Genetics
(ACMG) report on newborn screening.
Following an update by Dr van Dyck
on the status of the ACMG report Newborn
Screening: Toward a Uniform Screening
Panel and System, Committee members
would have an opportunity to ask both
Dr. van Dyck and ACMG’s Executive
Director Dr. Michael Watson questions
and to make comments about the report.
- Two
public comment sessions. Members
of the public would be given two opportunities
to make statements to the Committee,
one on Thursday and one on Friday.
- Meetings
of the three subcommittees of the Committee.
The three subcommittees established
at the January 2005 meeting of the Committee—the
Education & Training Subcommittee
chaired by Dr. Howse, the Treatment
& Follow-up Subcommittee chaired
by Dr. Boyle, and Laboratory Standards
& Procedures Subcommittee chaired
by Dr. Brower—would hold concurrent
meetings open to the public.
- Educating
parents about newborn screening. Committee
members would hear three presentations
related to parental education.
- Guidelines
for newborn screening follow-up. On
Friday, Committee members would
hear additional presentations related
to guidelines for newborn screening
follow-up and quality assurance.
- Committee
business—subcommittee reports.
Also on Friday, the three newly established
subcommittees would report on their
plans and activities to date.
ACMG
REPORT ON NEWBORN SCREENING
Update
on the American College of Medical Genetics
(ACMG) Report on Newborn Screening
Peter
van Dyck, M.D., M.P.H.
Associate Administrator
Health Resources and Services Administration
(HRSA)
Dr.
van Dyck reminded everyone that the ACMG
report Newborn Screening: Toward a
Uniform Screening Panel and System was
prepared under contract to HRSA, which
asked ACMG to analyze the scientific literature
and gather expert opinion to develop recommendations
in five areas: (1) a uniform condition
panel, including implementation methodology;
(2) model policies and procedures for
state newborn screening programs, with
consideration of a national model; (3)
model minimum standards for state newborn
screening programs, with consideration
of national oversight; (4) a model decision
matrix for consideration in state newborn
screening expansion; and (5) the value
of a national process for quality assurance
and oversight. The report is available
online at http://mchb/hrsa/gov/screening and can
be downloaded for review.
After
the January 2005 Advisory Committee meeting,
HRSA received permission from the Secretary
of HHS’s office to release the ACMG
report. The report was placed in the
public domain for a 60-day comment period
on March 8, 2005. Public comments may
be sent via a special fax line (301) 443-8604;
by e-mail to screening@hrsa.hhs.gov; or by mail to
HRSA’s Maternal and Child Health
Bureau, 5600 Fishers Lane, Parklawn Bldg.,
Room 18A-19, Rockville, MD 20857. They
must be received by HRSA’s Maternal
and Child Health Bureau by May 8, 2005.
HHS is encouraging public comment. It's
very important to us to receive a wide
range of comments and to hear from everybody.
HHS will take the public comments and
inputs from the Committee and other sources
and prepare a report and recommendations
from HHS.
Committee
Discussion of the ACMG Newborn Screening
Report
Rodney
Howell, M.D.
Chair, Secretary’s Advisory Committee
on Heritable Disorders and Genetic Diseases
in Newborns and Children
Professor of Pediatrics
University of Miami School of Medicine
Committee
members discussed the ACMG newborn screening
report at length, focusing on (1) the
process for dealing with the ACMG newborn
screening report; (2) the methodology
used in the report; and (3) the process
and criteria for evaluating the recommended
newborn screening panel recommended in
the ACMG report.
Process
for Dealing with the ACMG Report.
The first topic was what happens to the
ACMG newborn screening report once the
public comment period ends on May 8, 2005.
Committee members asked the following
questions, and Dr. van Dyck responded
to them:
When
and how will HRSA make available public
comments on the ACMG report to the Committee?
Dr. van Dyck and Dr. Lloyd-Puryear said
that HRSA has received dozens of public
comments on the ACMG report. After May
8, 2005, HRSA will assemble the comments
and send them to the Committee in the
form of a compilation. There was some
discussion about whether the public comments
should be dealt with by the Committee’s
subcommittees first or should be considered
by the Committee as a whole. Several
Committee members indicated that they
would like to be able to read all of the
comments. The final decision by Dr. Howell
was to let all Committee members see all
the public comments; then have a conference
call to allow Committee members to comment
on the public comments; and if needed,
to ask the subcommittee members during
the conference call to think about responses
to specific issues.
- What
process will HRSA use to review the
public comments? Dr. van Dyck said
that HHS would begin an internal department
process of reviewing the public comments
and making recommendations to the HHS
Secretary. Federal agencies, which
have already had an opportunity to make
comments during the 60-day public comment
period, would have an additional opportunity
to weigh in on the report and public
comments during this internal process.
The timetable for completion of the
internal process is not known.
- What
are the next steps with respect to communicating
the Committee’s comments regarding
the ACMG report to the HHS Secretary.
Dr. van Dyck said the Committee’s
purpose at this meeting was to comment
on the ACMG report during the public
comment period, which ends on May 8th;
then at its July meeting, the Committee
could make additional comments related
to the public comments.
- How
does HRSA plan to monitor the impact
of the ACMG report? Dr. van Dyck
indicated it was important to examine
the report and to examine the recommendations
in the report. But HRSA feels a primary
responsibility to monitor how well state
programs are functioning rather than
monitoring the report itself—and
will report to the Committee on how
programs are functioning as a whole.
Dr. Howse, noting that no entity within
the Federal Government has yet adopted
a formal position with respect to disposition
of the recommendations, said she thinks
it is important to figure out how to
advance the recommendations in the ACMG
report. Dr. Howell said that many things
seem to be happening as a result of
the ACMG report, regardless of where
it stands, and he is especially pleased
that the National Library of Medicine
is doing an information sheet on its
genetics home reference page on each
of the ACMG’s core recommendations.
Comments
about the ACMG Report’s Methodology.
Dr. Howell asked ACMG Executive Dr. Michael
Watson to join Committee members at the
table, so that Committee members could
ask him questions and make comments on
the report. Committee members engaged
in a lengthy discussion about the methods
used to arrive at the conclusions of the
report and whether the findings were scientifically
justified.
Dr.
Edwards indicated that the American Academy
of Pediatrics (AAP) would like to be reassured
by the scientists on the Committee that
the information in the report is very
good information—if not the best,
then at least among the best. Committee
members, Dr. Boyle and Dr. Telfair, asked
Dr. Watson to clarify the methodological
approach used in the ACMG report.
Dr.
Boyle commented it is not clear in the
ACMG report how the expert review and
scientific literature were brought together.
The weight of the process seemed to be
expert review, with scientific literature
being brought in at the end of the process.
In a systematic review, one would do just
the opposite—that is, start with
the science and then fill in the remaining
information gaps with expert review.
Dr. Boyle further noted that the scientific
base on using expert review did not seem
to have been brought into the report.
Dr. Rinaldo asked whether Dr. Boyle was
questioning the end product, the process
that led to the end product, or had specific
issues for specific diseases. Dr. Boyle
said that although she could not say that
she had problems with the final product,
as an epidemiologist, she considers understanding
how the conclusions were derived essential
to understanding the final product. Dr.
Boyle said she believes that it is important
for the Committee to arrive at a consensus
about what process should be used in the
future to evaluate conditions for inclusion
in newborn screening programs. She also
thinks that it is part of the Committee’s
responsibility to emphasize the importance
of developing scientific evidence. Dr.
Rinaldo said he thought the concerns that
had been raised by Dr. Boyle were valid
but he wanted to press people to provide
specifics about what was wrong with the
ACMG report or how it was done. Were
we asking the wrong questions? Were we
asking the wrong people? Should the questions
have been different? What are the specifics?
ACMG
Executive Director Dr. Watson indicated
where there were higher levels of evidence
available; either because there were clinical
trials around therapeutics or in more
common conditions like hyperbilirubinemia
and such, there were certainly a large
number of very strong evidence reports,
such as the Cochrane reports and others
in some of the more common conditions.
But if the reference is to rare disorders,
the findings in the literature about many
of the rarer disorders are meager. Therefore
the findings in the ACMG newborn screening
report—especially for the newer
and rarer disorders—were based on
expert opinion. That expert opinion is
not anecdotal but is based also on evidence.
We ultimately did have to rely heavily
upon experts in providing the information
on which we based the evidence, on telling
us whether or not they felt the evidence
was strong or weak. In addition, in its
contract with HRSA, ACMG was required
to give credence to views of the public,
consumers, scientists from state health
laboratories, and a wide range of people.
Thus, ACMG started by soliciting a wide
range of opinion and then folded in the
evidence base. Dr. Watson agreed that
expert opinion is not the highest base
of evidence, but he believes that the
ACMG report presents the best evidence
we have available. When higher levels
of evidence (e.g., clinical trials) were
available, that evidence was used. In
addition, Dr. Watson explained, ACMG took
into account that newborn screening yields
benefits for affected children and their
families even in the absence of effective
treatment—value that is typically
not acknowledged in the approaches taken
in some of the more common evidence-based
approaches that just analyze the literature
and do not include input from the public.
Dr.
Howell, noting that the ACMG report used
experts who had published articles about
the conditions, said he thinks the evidence
in the ACMG report is the best evidence
available to us at this point in time.
Dr. Brower said that as a scientist, she
thought the methodological approach used
in the ACMG report was elegant—and
that starting with a survey, though not
standard, was a great thing to do in addressing
these types of rare disorders. Dr. Watson
stated his belief that the ACMG report
advances the field in a very substantial
way and presents a model that can be improved
upon over time. Dr. Rinaldo observed
that most decisions about newborn screening
states made in the past were very subjective,
but the ACMG report is a sizable step
in the right direction, and we can now
work to improve it. The whole process
is moving to create an evidence base that
currently does not exist. Dr. Alexander
indicated that in a “perfect world,”
we could have gathered this information
ahead of time for these rare disorders,
but there's really been no organized way
to do it. Only with implementation of
screening for these disorders in a broad
way, in a manner that we will be able
to identify larger numbers of patients
even with rare disorders and enter them
with their parents' permission into studies
of the available therapies is it ever
going to be possible to gather the size
of population that we need to get the
evidence that we're all asking for.
Dr.
Telfair suggested that the Committee think
about how states and municipalities might
use the information in the ACMG report
to inform the way they make decisions.
He would like the Committee to consider
this as a next step, in addition to seeking
clarification of what was done in the
ACMG report. In addition, Dr. Telfair
recommended that the Committee think about
how to put the ACMG report’s recommendations
into some structure that is useful for
people in decision-making positions that
influence what happens at the national,
state, local, and community level.
Dr.
Howell asked Committee members to comment
on the overarching principles of the ACMG
report, which he thinks will be the basis
on which the report will be used in the
future. One of the principles calls for
broadening the definition of potential
benefit from newborn screening, with the
idea that there are broader benefits from
newborn screening than have historically
been recognized and that benefits accrue
to families even if there is not a curative
treatment at the current time; for instance,
knowing about a condition early and the
possibility of other treatments such as
early childhood intervention or something
of that nature. Dr. Becker said that
just as the ACMG report represents a bit
of a paradigm shift in that it is not
the traditional, well-controlled evidence-based
study that we might like to see, it also
represents a paradigm shift in terms of
overarching principles, in that traditional
public health screening programs do not
just collect information without a specific
benefit or intervention that has been
shown to either be effective at the personal
level or effective at the financial level
to society as a whole. There may be a
slight change in the perspective that
communities or society as a whole are
going to have to get used to thinking
about.
Dr.
Hawkins commented that parents and people
such as those in the audience are interested
in getting beyond methodology questions.
They are interested in what we are going
to do about the problems we have with
not having a uniform panel of diseases
to test for. Dr. Howell noted that there
was tremendous effort to get input from
parents with children who have the conditions,
because their input is extremely important.
One of the things that the ACMG report
quantifies is the burden of disease, which
is the greatest for affected families.
Mr. Robertson concurred with Dr. Hawkins
and Dr. Howell, saying it was important
not to forget the babies and parents behind
the listed conditions. As a parent, he
said that one of the best things about
the ACMG report was its emphasis on follow-up
and training and on getting parents and
providers to understand the diseases.
There will never be a perfect list of
diseases, because something is always
going to be left off, no matter what the
criteria. The important thing is to get
to a point that it doesn’t matter
where your child is born that will determine
whether the child will live or die.
Dr.
Alexander urged the Committee in commenting
on the ACMG report and in its future deliberations
to take into account the fact that newborn
screening yields benefits for affected
children and their families even in the
absence of effective treatment:
-
Newborn screening can help families
of affected children avoid a long and
traumatic search for a diagnosis, which
is valuable whether treatment is available
or not.
-
An early diagnosis can be useful to
the families of affected children for
family planning reasons (e.g., so parents
can at least know about it before they
make a decision about having another
child or can consider options such as
prenatal diagnosis, adoption, etc.,
to avoid another child affected).
-
Affected children and their families
can benefit from interventions other
than treatment to foster healthy development,
motor skills, or other functions even
if the disorder cannot be directly treated.
-
Newborn screening can yield a population
for doing studies of interventions that
will enable us to move from the realm
of expert opinion to the realm of evidence-based
practice based on clinical trials. Newborn
screening can yield a population for
doing studies of interventions that
will enable us to move from the realm
of expert opinion to the realm of evidence-based
practice based on clinical trials.
In the United States, 85 percent of
children with cancer are entered into
research protocols via the children’s
oncology groups that have been operating
for the last 30 years or so, and these
are responsible for marked improvements
and cures for children. We have an opportunity
to do something similar with newborn
screening.
Following
up Dr. Alexander’s comments, Mr.
Robertson said that if the intention is
to try to enroll children into studies,
an emphasis must be placed on educating
the parents about enrolling kids in studies.
In cancer, sometimes the alternative to
not enrolling children in studies is extremely
grave, but for other diseases, there may
be other options. Probably the best way
to get parents of affected newborns to
enroll their children in studies is to
get other parents who have enrolled their
kids to encourage other parents to do
it.
Dr.
Howse thanked Dr. Edwards for putting
the question on the table of the weight
of the report and whether the scientific
evidence in the report was justified.
She said that what she had heard from
the Committee’s discussion reflects
the opinion of the March of Dimes: (1)
that the ACMG newborn screening report
represents the best available information,
the weight of expert opinion, and a rigorous
and lengthy review involving families
and consumers, experts, practitioners,
clinicians, lab directors, etc.; and (2)
that the uniform panel represents conditions
for which there is a test, for which early
detection is essential, and for which
there is efficacious treatment. In Dr.
Howse’s view, this is a sufficient
and appropriate basis for the Committee
to support the report, especially with
its recommendations for tracking and reporting
back, follow-up, etc
Dr.
Watson concluded by urging the Committee
to recognize that its charge extends beyond
newborn screening to include all heritable
diseases and genetic disorders of newborns
and children. For that reason, the Committee
should think broadly about how it is going
to collect information in the long term
not just on the 50 or so newborn screening
conditions but on 800 or 900 other genetic
conditions, including lysosomal storage
diseases, which include adult-onset as
well as the infantile-onset form.
Recommending
a Process for Modifying the ACMG-Recommended
Uniform Newborn Screening Panel. Several
Committee members recommended that the
Committee provide guidance on the process
for modifying—either adding to or
removing from—the ACMG-report’s
recommended uniform screening panel in
the future and on an ongoing basis. Among
the ideas explored by the Committee were
(1) getting a paper or presentation to
the Committee on evidence-based decision-making
in the context of newborn screening; (2)
having the Committee review and perhaps
make changes to the ACMG-recommended process
for adding or subtracting conditions in
newborn screening programs; (3) doing
a trial run of the Committee’s recommended
process for adding conditions to the ACMG-recommended
panel; and (4) recommending a body to
advise HHS on changes to the uniform newborn
screening panel.
Dr.
Dougherty recommended that the Committee
step back and consider whether the current
fact sheets and approach used in the ACMG
report represent the best mechanism for
modifying the newborn screening panel.
She suggested the possibility of commissioning
a paper by an expert in evidence-based
decision-making to help the Committee
sort through these issues. Such a paper
would lay out the current thinking about
doing an evidence base for newborn screening,
diagnosis, etc., and identify the other
factors to consider in a systematic look
at whether a procedure should be endorsed
and paid for. Although the ACMG report
tried to mix a lot of those kinds of things
into one judgment, she noted, there are
systematic ways of arriving at a systematic
expert consensus and of doing a systematic
evidence review and of bringing these
things together to make a decision.
Dr.
Becker agreed with Dr. Dougherty’s
suggestion, noting that the Committee
is going to have to use the evidence base/expert
opinion commentary as sort of a central
tenet to whatever the Committee decides
to do. Dr. Watson also agreed with Dr.
Dougherty’s suggestion but recommended
asking someone to look very hard at the
nature of genetic diseases and the difficulties
that one has with an evidence base in
genetic diseases such as cystic fibrosis
for which outcomes may depend on genetic
mutations that affect individual families.
Dr.
van Dyck suggested that perhaps someone
could be asked to give a presentation
to the Committee at its July meeting rather
than writing a paper. Agreeing that this
approach would be more expeditious, Dr.
Howell asked Dr. Dougherty and other Committee
members to consult and get back to him
or HRSA in a couple of weeks with recommendations
for experts to make a presentation at
the Committee’s July meeting on
evidence-based decision-making in the
context of the Committee’s work.
Dr. Brower, following up on Dr. Watson’s
previous comment, recommended that the
presentation in July or a second presentation
include a discussion of genetic diseases,
as well as the methodology for modifying
the uniform newborn screening panel.
Dr. Howell added that he also would like
to have someone at the July meeting to
give a presentation on designing a newborn
screening long-term follow-up program.
Dr.
Rinaldo suggested that the Committee institute
a process that would allow proponents
(e.g., parent support groups, experts)
of adding a condition to the uniform panel
of 29 conditions recommended in the ACMG
report to come before the Committee and
make the argument for inclusion of the
condition to the Committee, using the
ACMG report as a starting point. At every
Committee meeting, one session could be
devoted to a presentation by proponents
of adding a condition. Dr. Alexander
said that the Committee might consider
going through the process of evaluating
a few conditions as a trial run to gain
first-hand experience in making such decisions,
but he does not think the Committee should
take on the task of modifying the uniform
panel as part of its formal responsibilities.
Dr.
Brower said she thinks the best thing
the Committee can do is to communicate
to the public and experts about what level
of evidence they need to meet before the
Committee will consider that a disorder
or a test has been validated. She believes
it is part of the charge of the Laboratory
Standards & Procedures Subcommittee
that she chairs to come up with a first
step to define what the process for adding
or subtracting conditions in the uniform
panel ought to be and then present it
to the entire Committee for comments.
Dr.
van Dyck agreed that the Committee should
not take on the task of modifying the
uniform panel itself. He added that the
process for modifying the uniform panel
recommended in the ACMG report is a consideration
that could be in the final output of whatever
HHS recommends the best way to suggest
to states to add new conditions. He said
he thought that the HHS Secretary would
be interested in the Committee’s
recommendations about the best way to
suggest that states add conditions to
their newborn screening programs. Dr.
Rinaldo underscored his belief that HRSA
and the Committee have a moral responsibility
to make sure that that there is a process
for modifying the panel so that the children
affected with whatever diseases where
there is a test and early intervention
can be beneficially served. The newborn
screening panel recommended in the ACMG
report is now a HRSA product, he said,
so it seems that HRSA should be the one
to decide how to modify the panel.
Dr.
Alexander suggested that the Committee
might want to make recommendations about
what type of organization might be best
suited for the task of modifying the uniform
panel. He said he thinks that an organization
along the lines of the Advisory Committee
on Immunization Practices might be best
suited to make such decisions, adding
that perhaps the Committee should have
some sort of presentation on the Advisory
Committee on Immunization Practices model.
Dr. Howse agreed that a connection to
the Public Health Service as an ongoing
mechanism to advise states in a formal
and timely way as to the recommended newborn
screening tests to be done might be a
good idea. Dr. Howell summarized his
understanding the Committee’s discussion,
saying that the Committee should have
an opportunity to look at and comment
about any changes in the recommended newborn
screening panel, but there would be some
other type of structure—whether
a subcommittee or parallel committee or
some other structure—that would
review things and make recommendations
that would come to the Committee, and
then go to the HHS Secretary.
Dr.
Alexander then returned to the idea of
doing a trial run of a process to evaluate
the process for deciding whether conditions
should be added to the uniform panel to
gain first-hand experience that would
inform the Committee’s recommendations
as to how such a process might be carried
out. Dr. Howell said he thought that
was an excellent suggestion and that maybe
the Committee could get some expert proponents
of a condition that is moving toward prime
time to come and make the presentation.
Dr. Rinaldo suggested that they develop
a short list of about 10 conditions rather
than leave it to outside proponents, then
the Committee could choose which ones
it wanted to use for a trial run. Dr.
Watson recommended that the Committee
do a trial run of two conditions—one
rare condition (e.g., any lysosomal storage
disease) and one relatively common condition
(e.g., use of pulse oximetry for congenital
heart disease, hyperbilirubinemia, asthma).
Dr. Howell suggested perhaps the Committee
should -do a trial run of one condition
with effective treatment and one where
knowledge of early benefits is more predominant.
Mr.
Robertson asked for clarification: Are
you saying we would first look at developing
a process and then pick two diseases?
Dr. Alexander responded by suggesting
that the Laboratory Standards & Procedures
Subcommittee chaired by Dr. Brower take
the lead in reviewing and suggesting modifications
to the criteria that are currently in
the ACMG report for making decisions and
then put together a list of five to seven
conditions that might be added to the
panel. Then the Committee could review
and possibly modify the criteria that
the Laboratory Standards & Procedures
Subcommittee suggests and go from there
in terms of setting up a presentation
by a proponent of adding a condition to
the uniform panel as a trial run of the
modified process for adding a condition.
Dr. Dougherty agreed that the Committee
might want to settle on a process for
adding disorders before asking proponents
for adding disorders to give presentations
to the Committee as a trial run.
Dr.
Rinaldo said he was thinking of something
simpler than what Dr. Alexander proposed—asking
someone with clear knowledge of a condition
to look at conditions that did not make
the cut for the ACMG-recommended uniform
panel, review what happened in the ACMG
survey process, and then come before the
Committee to make the argument that the
reason the condition did not make the
cut for the ACMG-recommended uniform panel
was that incorrect information was used.
Then the Committee could agree or disagree.
Dr.
van Dyck suggested that one way to approach
things might be this. First, the Committee
could hear from a couple of people who
were involved in developing the ACMG report
go through either a condition included
in the uniform panel or one on the second
panel to get a feeling for the process.
Then, the Committee could hear from an
outside speaker or speakers on a process
that they would recommend. That way the
Committee could absorb the differences
if any between what was done in the ACMG
report and what is recommended.
Dr.
Alexander said that he was going to suggest
something very similar to what Dr. van
Dyck just suggested. He emphasized that
the Committee does not want to get into
revisiting the ACMG report and making
the judgments made in the report; it is
just trying to gain some first-hand experience
to guide its recommendations for adding
new conditions to an existing list. In
terms of process, Dr. Alexander suggested
the following:
-
At the Committee’s July meeting,
one item on the agenda would be a presentation
by an expert in evidence-based decision-making
on a process for modifying the uniform
panel, as suggested by Dr. Dougherty.
At the Committee’s July meeting, one
item on the agenda would be a presentation
by an expert in evidence-based decision-making
on a process for modifying the uniform
panel, as suggested by Dr. Dougherty.
Another agenda item would be a report
from the Laboratory Standards &
Procedures Subcommittee on what information
the Committee might ask a proponent
of adding a new condition to provide
that is relevant to the criteria that
were used for the ACMG report and whatever
modifications to those criteria the
subcommittee recommends. Then Committee
members would deliberate on what they
liked from both pieces and come up with
some final guidance for a process for
modifying the uniform panel.
-
At the Committee’s October meeting,
one item on the agenda would be a presentation
from a proponent of adding a new condition
to the ACMG-recommended uniform panel
based on the guidance that the Committee
gives in light of its discussions at
the July meeting. At the Committee’s
October meeting, one item on the agenda
would be a presentation from a proponent
of adding a new condition to the ACMG-recommended
uniform panel based on the guidance
that the Committee gives in light of
its discussions at the July meeting.
Dr.
Howell got a sense from Dr. Robertson
and other Committee members that they
were comfortable with the process outlined
by Dr. Alexander, and he asked Dr. Lloyd-Puryear
to work on the agenda items for the next
meeting. Dr. van Dyck summarized his
understanding of what would happen next
as follows: At the July 2005 meeting,
the Committee would hear a presentation
from the Laboratory Standards and Procedures
Subcommittee chaired by Dr. Brower on
the recommendations in the ACMG report,
modified by whatever the subcommittee
suggests, as well as a peer presentation
by an outside expert on a process for
modifying the ACMG-recommended uniform
panel; then Committee members will deliberate
on what they like from both pieces and
come up with some final process for modifying
a panel. Then at the Committee’s
October 2005 meeting, the Committee would
have a proponent of adding a condition
to the panel come before the Committee
to give the newly recommended process
a trial run. Dr. Howell said he believed
that was what he heard, adding that the
Laboratory Standards and Procedures Subcommittee
would also come up with some suggestions
about what conditions might be appropriate
for the October meeting.
Dr.
Edwards concluded the discussion by saying
that while new conditions might be added
to the ACMG-recommended uniform newborn
screening panel, it is important to bear
in mind that some conditions that are
currently on the list potentially could
leave the list and move around, move from
a secondary target over to the primary,
depending on developments.
PUBLIC
COMMENT SESSION
The following individuals made public
statements. The written text of their
statements appears in Appendix A.
Bennett
Lavenstein, M.D.
Childhood Neurology Society (CNS)
Dr.
Lavenstein indicated that CNS supports
national minimum standards for newborn
screening for the specified genetic disorders.
He believes that Federal oversight is
necessary for all newborns to have equal
access to identification and interventions
for these disorders and that a combination
of adequate Federal and state funding
should be allocated to initiate and sustain
statewide programs and limit the long-term
effects of these disorders. Mandatory
testing, counseling and follow-up requirements
must be fully supported by designated
Federal funds, since the U.S. health care
system currently either does not support
such services in totality or perhaps does
so somewhat inadequately. Every state
has newborn screening, but there is variability
among states. National minimum uniform
standards would be helpful. Finally,
Dr. Lavenstein commented on the need to
draw upon lessons from clinical experience
and expertise and evidence-based medicine
to make things work.
Jana
Monaco
Parent and Board Member
Organic Academia Association
Ms.
Monaco, the parent of one child with isovaleric
academia who suffered lifelong brain damage
and another child leading a normal life
because of newborn screening, said she
strongly supports the recommendations
for expanded newborn screening in the
ACMG newborn screening report and hopes
the goals of the report are fully achieved.
She reported that Virginia has already
expanded its newborn screening program
in response to the report. She also reported
her observations as one of two parents
serving on the New York-Mid-Atlantic Regional
Genetics and Newborn Screening Collaborative,
which recently had its first meeting.
She noted that the lack of coverage for
metabolic formulas (medical food) leave
families with a big burden and urged the
Committee to address this issue. Finally,
Ms. Monaco underscored the value of parents
in educating, advocating, assisting, and
translating information about newborn
screening. In response to an issue raised
during the Committee’s discussion
in the morning, Ms. Monaco stressed that
parents of affected newborns want to know
what disorder they are dealing with whether
a cure or management exists or not.
Jill
Fisch
Parent & National Director of Education
and Awareness
Save the Babies through Screening Foundation
Ms. Fisch, the parent of two children
affected with Short Chain Acyl-CoA Dehydrogenase
Deficiency (SCADD), said she strongly
supports expanded newborn screening so
that all children in all states are treated
equally and fairly. She also expressed
concerns about legislative maneuverings
in Texas that may prevent the expansion
of newborn screening. Ms. Fisch said
she is looking forward to learning about
the Committee’s approaches to evaluating
new newborn screening tests and technologies.
SCADD is one of the disorders on the secondary
panel in the ACMG report, but there is
still no natural history study for SCADD,
which is necessary for the disorder to
be added to the core panel. How can the
Committee help get these studies implemented?
Ms. Fisch said she is particularly concerned
about the follow-up of children who are
picked up by newborn screening, as well
as children not detected via newborn screening,
to ensure that every child gets what he
or she needs. Ms. Fisch expressed her
concern about several ethicists who have
been speaking out against newborn screening
in the past few months. Finally, Ms.
Fisch stressed the importance and value
of having parents serving on the subcommittees
of the Committee.
Micki
Gartzke
Parent & Director of Education and
Awareness
Hunter's Hope Foundation
Ms.
Gartzke, a parent who lost a child to
Krabbe disease (a lysosomal storage disease)
following a 6-month effort to get a diagnosis,
said she is strongly committed to the
expansion of newborn screening so that
what happened to her family does not happen
to others. She applauded the research
and test development taking place for
many different diseases, including the
lysosomal storage diseases pilot in New
York State, and said that she was particularly
interested in how the Committee will review
new tests and technologies and how the
Committee will recommend and evaluate
translational research. Ms. Gartzke agreed
with a point made earlier in the day -
there are benefits to newborn screening
even if treatment is not availablee.g.,
screening can keep parents of affected
infants from having to go on a long diagnostic
odyssey and can help develop populations
to be studied. Ms. Gartzke stressed the
importance of educating both parents and
professionals about the need for newborn
screening. She also emphasized the importance
of involving parents who have lived through
the lack of early detection and access
to treatment in the deliberations of the
Committee and its subcommittees.
John
Adams
Parent & President/Chief Executive Officer
Elivery Solutions, Inc.
Mr.
Adams, a parent who has an 18-year-old
son with phenylketonuria (PKU) who is
about to enter the University of Toronto,
said the Canadian government is AWOL on
the question of newborn screening-and
it tears his heart out to know that there
are babies who are dying or being damaged
needlessly. The province of Ontario only
screens for three disorders-PKU, congenital
hyporthyroidism, and hearing loss, and
it is not alone. Mr. Adams said that his
sense of reading the ACMG newborn screening
report was that it was a snapshot of the
state of the art, the best available evidence,
not yet perfected. He also said he is
delighted to be able to participate in
this open forum today, because the Canadian
government is operating behind closed
doors on newborn screening. As a Canadian,
Mr. Adams also said he is grateful for
the American taxpayers' investment in
a number of things, including the National
Newborn Screening and Genetics Resource
Center. He said as the Committee moves
forward, he hopes that it recognizes that
it is performing a service for people
in other countries, not just the United
States. He also suggested that HRSA consider
supporting the development of smart systems
that put the intelligence and best practice
available at the hands of a clinician
when there's a child or an adult who is
in a period of crisis.
Peter
Sybinsky, Ph.D.
Chief Executive Officer
Association of Maternal and Child Health
Programs (AMCHP)
Dr.
Sybinsky explained that AMCHP represents
state public health leaders who direct
programs for mothers and children, many
of which are funded in part by the Maternal
and Child Health Services Block Grant,
Title V of the Social Security Act. Although
state newborn screening programs vary
among the states, most Title V programs
ensure follow-up and access to health
services for children found to be affected.
AMCHP believes the ACMG report on newborn
screening is an exceptional example of
bringing together expert opinion and evidence-based
research to form national recommendations.
Still, state Title V programs have concerns
about issues that the report did not address:
(1) the implications of the recommended
uniform panel on the extensive state responsibility
for providing long-term treatment and
follow-up; (2) the adequacy of funding
to meet the recommendations for implementation
of a uniform panel; and (3) the lack of
a national procedure for adding conditions
to the uniform panel. AMCHP urges the
Committee to address these issues. Finally,
Dr. Sybinsky said, AMCHP would welcome
an opportunity to designate a representative
to the Committee to provide continuing
input.
Scott
Grosse, Ph.D.
Health Economist
National Center of Birth Defects and Developmental
Disabilities
Centers for Disease Control and Prevention
(CDC)
Dr.
Grosse, who works with Dr. Boyle at CDC
on newborn screening issues, responded
to the question that Dr. Rinaldo asked
earlier in the day about specific objections
to the ACMG report. He said that CDC
is concerned that certain statements in
the fact sheets may be inaccurate or misleading.
In particular, CDC believes that the fact
sheets for congenital adrenal hyperplasia
(CAH), cystic fibrosis, hearing loss,
hemoglobin SC disease, and medium chain
co-A dehydrogenase (MCAD) deficiency do
not accurately reflect what is in the
scientific literature.
Jerry
Vockley, M.D., Ph.D.
President
Society for Inborn Metabolic Disorders
(SIMD)
Dr.
Vockley explained that SIMD members are
scientists, physicians, nutritionists,
nurses, and other health professionals
involved in research or the diagnosis
and treatment of individuals with inborn
metabolic diseases. He said that SIMD
unequivocally supports the ACMG report
and urges the Committee to ask the HHS
Secretary to move forward to implement
its recommendations. SIMD looks forward
to the work of the Committee’s three
newly established subcommittees and is
particularly eager to be partner in the
activities of the Treatment and Follow-up
Subcommittee. SIMD urges the Committee
to work to ensure the availability of
adequate resources for long-term follow-up
and treatment.
SUBCOMMITTEE
MEETINGS
Each of the three subcommittees established
at the Committee’s January meeting—Education
& Training Subcommittee chaired by
Dr. Howse, Treatment & Follow-up Subcommittee
chaired by Dr. Boyle, and Laboratory Standards
& Procedures Subcommittee chaired
by Dr. Brower—met for 45 minutes.
The subcommittee meetings were open to
the public.
EDUCATING
PARENTS ABOUT NEWBORN SCREENING
NNSGRC
Survey of States for Policies and Procedures
for Public and Professional Education
Related to Newborn Screening
Donna
Williams, M.S.
Newborn Screening Project Coordinator
National Newborn Screening and Genetic
Resources Center (NNSGRC)
Ms.
Williams reported on the findings from
an NNSGRC survey of state policies and
procedures for public and professional
education in newborn screening. The survey
compared state practices to the set of
recommendations presented in the American
Academy of Pediatrics (AAP) Newborn Screening
Task Force Report published in Pediatrics
in August 2000. That report recommended
that states and state public health agencies
implement public, professional, and parent
education efforts regarding newborn screening.
In
the realm of professional education, the
AAP Newborn Screening Task Force Report
recommended that prenatal health care
professionals, as well as an infant’s
primary care professional, be knowledgeable
about the state’s newborn screening
program through educational efforts coordinated
by the state’s newborn screening
program in conjunction with the newborn
screening advisory board. The NNSGRC
survey found the following with respect
to professional education related to newborn
screening:
-
One of the biggest gaps in professional
education is in the provision of educational
tools and resources to professionals
responsible for pr
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