March of Dimes Foundation
January 5, 2016
Jerry Menikoff, MD, JD
Office for Human Research Protections
Department of Health and Human Services
1101 Wootton Parkway
Suite 200
Rockville, MD 20852
Office of Government Affairs
1401 K Street, NW Suite 900A
Washington, DC 20005
Telephone (202) 659-1800
Fax (202) 296-2964
marchofdimes.org
nacersano.org
Dear Dr. Menikoff,
The March of Dimes, a unique collaboration of scientists, clinicians, parents, members of the
business community, and other volunteers affiliated with chapters representing every state, the
District of Columbia and Puerto Rico, appreciate this opportunity to comment on proposed
changes to the Federal Policy for the Protection of Human Subjects (the Common Rule), as
contained in the Notice of Proposed Rulemaking (NPRM) published in the Federal Register on
September 8, 2015.
The March of Dimes concurs wholeheartedly with the NPRM’s assessment that the Common
Rule is in need of modernization. In recent decades, a striking array of new research techniques
and approaches have been developed, including advances in genetics and genomics,
environmental health, large-scale data analysis, wearable technology, and precision medicine.
In addition, social norms and expectations have changed regarding individuals’ participation in
research. The Common Rule must be updated and recalibrated to accommodate new research
methods and participant wishes while continuing to promote autonomy, privacy, justice and
beneficence. We appreciate the thoughtful, deliberate approach taken to the changes proposed
in the NPRM and the effort to engage stakeholders in a constructive dialogue about them.
The March of Dimes brings multiple perspectives to this review of the Common Rule. Having
been founded in 1938 to lead and fund efforts to develop a polio vaccine, the March of Dimes
has over 75 years of history in funding groundbreaking scientific research. At present, our
research portfolio averages over $20 million per year in biomedical research studies funded
directly by the March of Dimes through a competitive grant process. In addition, the March of
Dimes conducts or supports a wide range of other activities that may fall under the Common
Rule, such as by:
 Utilizing government-generated data on maternal and child health on our online
perinatal data clearinghouse, Peristats (www.marchofdimes.org/peristats);
 Conducting focus groups and surveys on health education messages for consumers;
 Performing evaluations of provider-based quality improvement projects, such as our
Healthy Babies are Worth the Wait program to reduce non-medically indicated
deliveries before 39 weeks of gestation;
 Undertaking assessment of maternal and child health promotion programs we support
directly through community-based grants; and
 Assessing the performance of various programs or initiatives we carry out through
grants received from governmental entities or foundations.
Finally, the March of Dimes also views the Common Rule through the lens of public health and
public policy, examining its impact on maternal and child health in these arenas. We are
pleased to bring these multiple viewpoints to our comments on the changes proposed in the
NPRM.
Expanding the Definition of Human Subject to Cover Research with Non-identified
Biospecimens
In general, the March of Dimes supports the concept of obtaining prior informed consent for the
secondary research use of biospecimens. The entire research community must maintain a high
degree of respect for both the autonomy of individuals in deciding whether to participate in
studies, and for the privacy of those generous enough to do so.
A key question around the use of biospecimens will be the length of time for which
biospecimens in existence prior to the effective date of the final rule may continue to be used
for secondary research. These biospecimens, which were obtained under the laws and
guidelines in existence when they were collected, may represent many decades of information.
It is reasonable to expect that it may require decades into the future to accumulate a
comparable database of samples obtained under the new consent rules, especially for less
common conditions and diverse populations. The March of Dimes urges that the final rule allow
researchers a high degree of flexibility in using grandfathered biospecimens for studies,
recognizing that locating and obtaining consented samples may present a considerable
challenge for many years.
Finally, the expanded definition of human subject has significant implications for the secondary
research use of residual dried blood spots collected as part of universal state newborn screening
(NBS) programs. The March of Dimes has joined with numerous other organizations in
submitted detailed comments about these issues. We would emphasize, however, that the
NPRM must strike an appropriate balance between autonomy and beneficence in the secondary
research use of residual bloodspots. The March of Dimes is unaware of any case in which an
individual has suffered harm due to the secondary research use of their de-identified bloodspots
in the over fifty years of the existence of NBS programs. In contrast, we can point to major
research advances that came from studies utilizing bloodspots, including the development of
new NBS tests that have saved thousands of lives. We remain concerned that requiring prior
informed consent for the secondary research use of these biospecimens will impose undue
burdens on health care providers and the public health system.
Exclusion and Exemptions of Activities from the Common Rule
The March of Dimes greatly appreciates the NPRM’s efforts to clarify and expand both
exclusions and exemptions in an effort to reduce the burden surrounding minimal-risk research.
It is our expectation that much of our program-related research activities will qualify for
exclusions or exemptions, including program improvement activities, quality assurance and
quality improvement activities, surveys, secondary data analysis, and activities that may fall
under the protections provided by HIPAA and HITECH.
We would like to express our concern, however, around the proposal to permit investigators to
self-certify their own work for exemptions. In our judgement, self-certification with no further
oversight should not be permitted, due to the potential for manipulation of an online exemption
tool. The March of Dimes will not permit our own investigators to move forward with any
exempt or excluded activity without some type of internal operational oversight. The March of
Dimes therefore urges you not to permit self-certification
of exemptions for any type of research involving any population unless an additional degree of
internal or external review is in place.
Finally, the March of Dimes strongly supports the development of updated decision charts
and/or an online decision tool that would reflect the new exclusion and exemption criteria to
assist investigators with a more accurate determination of whether their activity is covered or
outside the scope of the Common Rule.
Protecting Information and Biospecimens
The March of Dimes believes strong standards should be in place at all times to protect the
privacy of individuals’ information and biospecimens. We support the NPRM’s proposal that an
additional burden does not have to be placed on the IRB for the review of privacy and security
safeguards if activities meet the minimum privacy and security protections covered under HIPAA
which is further strengthened by HITECH. We look forward to reviewing the proposed lists of
safeguards that will be developed to guide investigators to ensure that these safeguards meet
high standards.
Cooperative Research and Single IRB
The March of Dimes is accustomed to working with numerous IRBs across the nation in the
context of both our biomedical and program research. Whenever possible, the March of Dimes
encourages our grantees to use a single IRB to reduce administrative burdens on all parties. We
support the proposal not to require a single IRB for study sites outside the U.S., since such sites
may have significant differences that require consideration.
Effectiveness and Efficiency in IRB Operations
The March of Dimes is pleased that the NPRM requires the Secretary of Health and Human
Services (HHS) to maintain guidance that includes a list of activities considered to involve no
more than minimal risk, which will in turn reduce any obscurity with the interpretation of the
regulations. In addition, the modified process for continuing review for minimal risk studies will
greatly reduce burden and costs for both IRBs and investigators.
IRB Operational Requirements
The NPRM requests comment as to whether pregnant women and those with physical
disabilities should be included in the category of subpopulations that may be vulnerable to
coercion or undue influence. In the case of pregnant women, the March of Dimes shares the
position of other experts, including the American College of Obstetricians and Gynecologists,
that it would be more appropriate to designate pregnant women as “scientifically complex”
rather than “vulnerable.” The study of pregnant women presents both physiologic and ethical
complexity; however, pregnant women do not suffer from an impaired ability to engage in
autonomous decisionmaking, as compared to their nonpregnant counterparts. Studies involving
more than minimal risk to mother, fetus or both must be weighed carefully both in terms of the
risks of participation and non-participation.
The historic bias toward automatically excluding pregnant women from most research studies
has left us in a position today where our understanding of pregnancy, human development, and
the perinatal impact of drugs, devices and environmental influences is woefully incomplete.
While the March of Dimes strongly supports appropriate protections for pregnant women
participating in research, we would caution against the imposition of superfluous barriers to
their inclusion in studies.
Other Proposed Changes
The NPRM proposes automatically “checking the box” to extend the Common Rule to cover any
study, regardless of funding source, conducted at a U.S. institution that receives federal support
for non-exempt and non-excluded human subjects research. The March of Dimes has no
objection to this requirement and is fully prepared to comply with it. We would note, however,
that very large or complex organizations and institutions may have chosen not to “check the
box” in the past in order to avoid covering small, minimal risk studies whose initiators did not
realize they were covered by the Common Rule.
Please note that the March of Dimes has a range of concerns with implications of the proposed
changes for other programs and populations, which we have expressed in separate comment
letters. Our concerns regarding the ramifications of the NPRM for newborn screening programs
are set out in comments cosigned by a dozen organizations, while our concerns on issues related
to pregnant women, women of childbearing age, and children are explained in a second letter
submitted with several other major maternal and child health advocacy organizations.
In conclusion, the March of Dimes sincerely appreciates this opportunity to comment on the
landmark changes to the Common Rule proposed in the Notice of Proposed Rulemaking. We
stand ready to provide to HHS any additional expertise or information that would be of
assistance in this considerable undertaking. If we may be of further assistance, please contact
Senior Vice President for Public Policy and Government Affairs Cynthia Pellegrini at 202/6591800.
Sincerely,
Dr. Jennifer L. Howse
President
Dr. Edward R.B. McCabe
Chief Medical Officer