[Federal Register Volume 89, Number 82 (Friday, April 26, 2024)]
[Notices]
[Pages 32447-32450]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-09028]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-N-1057]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Pregnancy Exposure Registry Enrollment Project: A 
Survey of Healthcare Providers To Advance Pregnancy Safety Data 
Collection and Improve Health Communications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
an opportunity for public comment on the proposed collection of certain 
information by the Agency. Under the Paperwork Reduction Act of 1995 
(PRA), Federal Agencies are required to publish notice in the Federal 
Register concerning each proposed collection of information and to 
allow 60 days for public comment in response to the notice. This notice 
solicits comments on a proposed study entitled ``Pregnancy Exposure 
Registry Enrollment Project: A Survey of Healthcare Providers To 
Advance Pregnancy Safety Data Collection and Improve Health 
Communications.''

DATES: Either electronic or written comments on the collection of 
information must be submitted by June 25, 2024.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of June 25, 2024. Comments received 
by mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are received on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2024-N-1057 for ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; Pregnancy Exposure Registry 
Enrollment Project: A Survey of Healthcare Providers To Advance 
Pregnancy Safety Data Collection and Improve Health Communications.'' 
Received comments, those filed in a timely manner (see ADDRESSES), will 
be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the

[[Page 32448]]

Dockets Management Staff between 9 a.m. and 4 p.m., Monday through 
Friday, 240-402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.

FOR FURTHER INFORMATION CONTACT: Rachel Showalter, Office of 
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 240-994-7399, 
[email protected].

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3521), Federal 
Agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes Agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal Agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information before 
submitting the collection to OMB for approval. To comply with this 
requirement, FDA is publishing notice of the proposed collection of 
information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

Pregnancy Exposure Registry Enrollment Project: A Survey of Healthcare 
Providers To Advance Pregnancy Safety Data Collection and Improve 
Health Communications

(OMB Control Number 0910--NEW)

I. Background

    FDA has a need for data on pregnancy exposure registries 
(registries). The goal of the proposed Pregnancy Exposure Registry 
Enrollment Project survey is to determine healthcare providers' (HCPs) 
perceived barriers to sufficient patient enrollment in pregnancy 
exposure registries. FDA's authority to conduct research related to 
drugs and other FDA-regulated products is set forth in the Federal 
Food, Drug, and Cosmetic Act (FD&C Act), (21 U.S.C. 393(d)(2)(C) and 
(D)).
    To ensure that pregnancy information in product labeling is 
accurately communicated to HCPs so that they can make informed 
decisions about treatment options for their patients, human pregnancy 
safety data are collected postapproval. Registries are an important 
tool for pregnancy safety data collection in the postmarketing setting. 
Their prospective design and ability to collect detailed patient 
information are critical to obtain human data to inform pregnancy 
labeling in a timely manner.
    The pharmaceutical industry typically sponsors registries often as 
a result of a postmarketing requirement (PMR) or commitment (PMC) FDA 
issues at the time of drug approval under section 505(o)(3) of the FD&C 
Act (21 U.S.C. 355(o)(3)). Under a PMR or PMC, pharmaceutical industry 
sponsors often work with private companies, nonprofits, and/or academic 
health centers to operate registries. Other times, private companies, 
nonprofits, Federal agencies other than FDA, or academic health centers 
may develop registries without FDA involvement to facilitate pregnancy-
related research with other scientific goals. When developing registry 
protocols, sponsors and those who operate registries must comply with 
45 CFR part 46 and meet the Criteria for IRB approval of research under 
45 CFR 46.111, which provides protection of human research subjects, 
subjects' privacy, and the confidentiality of subjects' data.
    Although registries are crucial to understanding the safety and 
potential toxicity of prescription products in the perinatal 
population, many registries fail to adequately enroll pregnant 
individuals. HCPs are a trusted source of information about health, and 
they serve as gatekeepers for recruiting pregnant individuals to enroll 
in clinical studies such as registries. Thus, HCPs are integral to the 
registry enrollment process. Publications suggest that low enrollment 
in registries may be related to HCPs' lack of awareness, time, 
incentives, and comfort with discussing clinical research with 
patients. Despite this speculation about the barriers that HCPs face, 
however, researchers have not surveyed HCPs to understand their 
challenges. FDA reviewed existing literature and engaged with other 
Offices and Centers within FDA and external experts and determined that 
this data collection is not duplicative.
    During this voluntary, FDA-funded, qualitative survey, we will 
recruit through an existing panel of HCPs currently licensed to 
practice in clinical settings in the United States who routinely care 
for or counsel pregnant patients. We will engage three groups of HCPs: 
(1) primary HCPs (obstetrician/gynecologists, family practice 
physicians, certified nurse-midwives, physician assistants); (2) 
consulting HCPs (neurologists, infectious disease specialists, 
psychiatrists, rheumatologists, cardiologists, pulmonologists, 
dermatologists), and (3) pharmacists. To be eligible for the study, 
primary HCPs must routinely care for or counsel five or more pregnant 
patients per month, and consulting HCPs and pharmacists must routinely 
care for or counsel three or more pregnant patients per month. All 
eligible HCPs must have either a degree

[[Page 32449]]

as a Doctor of Medicine, a Doctor of Osteopathic Medicine, or a Doctor 
of Pharmacy. Although we will recruit with representativeness in mind, 
we will weigh the data to ensure a nationally representative sample of 
HCPs. Generated tables will compare the weighted distributions of the 
variables used for weighting against their corresponding benchmarks.
    A contracted research firm will collect data through internet 
administration. One hundred percent (100%) of participants will self-
administer the internet survey via a computer, which will record 
responses and provide appropriate probes when needed. We will use 
automated technology in data collection, data reduction, and analyses. 
To identify eligible HCPs, we will send a recruitment email that links 
to a prequalifying screener on the internet. The screener will include 
questions about the HCP's specialty, number of years in practice, 
number of pregnant patients counseled per month, and demographics (age, 
race/ethnicity, and gender) and will confirm that the respondent does 
not work for FDA or a pharmaceutical company. We will invite all 
respondents who meet eligibility requirements to participate in the 
survey within 24 hours of completing the screener and obtain informed 
consent from all survey participants. The survey will assess 
experienced HCPs' knowledge of registries, their attitudes toward them, 
the barriers they face to recruiting patients, and their ideas about 
improving registry enrollment. Results from this project will advance 
pregnancy safety data collection from registries and ultimately improve 
health communications through inclusion of human safety data in 
pregnancy labeling. The survey is available on request at 
[email protected].
    We have the following specific research questions:
    1. What proportion of HCPs know about pregnancy exposure 
registries?
    2. What proportion of HCPs have referred patients to pregnancy 
exposure registries?
    3. What proportion of HCPs have provided information from patient 
medical records to pregnancy exposure registries?
    4. What barriers to patient enrollment in pregnancy exposure 
registries are identified by HCPs?
    5. What ideas do HCPs have to improve enrollment in pregnancy 
exposure registries?
    The target sample size for this study is 400 completed surveys. The 
sample will include an equal number of primary HCPs, consulting HCPs, 
and pharmacists. Such a design will help to ensure assessment of not 
only HCPs' perceptions generally, but also potential variations between 
different types of HCPs. HCPs are a difficult group to recruit, so 
several strategies will be put into place to achieve a high response 
rate. These strategies include tailoring contact materials, disclosing 
FDA sponsorship on survey materials, and providing a cash incentive.
    To obtain 400 completed surveys, we estimate that 2,000 experienced 
HCPs will need to be screened. We estimate that participation in the 
study will take 17 minutes.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--estimated annual reporting burden \1\
----------------------------------------------------------------------------------------------------------------
                                                 No. of         Total
           Activity               No. of      responses per     annual        Average burden  per        Total
                                respondents    respondent     responses             response             hours
----------------------------------------------------------------------------------------------------------------
Screener.....................         2,000               1        2,000  0.0333 (2 minutes).........         67
Main Study Survey............           400               1          400  0.25 (15 minutes)..........        100
                              ----------------------------------------------------------------------------------
    Total....................         2,000  ..............  ...........  ...........................        167
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Prior to the main analysis, an outlier analysis will be performed 
for the time spent on any screen visited and total time to complete the 
survey. Extreme survey time will be identified and appropriate 
adjustments will be made prior to the final data analysis. The extent 
of any missing information will also be assessed to determine the data 
quality. Descriptive statistics will afford a look at the frequency of 
responses. Assessment of potential differences between primary HCPs, 
consulting HCPs, and pharmacists can be accomplished with pairwise 
comparisons between groups. We will also produce national-level 
estimates about attitudes toward pregnancy exposure registries and 
other key questions.
    An analysis of item nonresponse will be made in the screener, if 
needed, and in the main survey. Item nonresponse rates will be 
tabulated for the questionnaire items, allowing for skip patterns. An 
analysis will be made of any questionnaire items that register 
unusually high item nonresponse rates. Multivariate item nonresponse 
relationships will be evaluated, including monotonicity patterns such 
as breakoffs (all items dropped after a particular item), and other 
types of ``blocks'' of multivariate item nonresponse. High levels of 
item nonresponse in particular items will have their correlations with 
other questionnaire item results in both the screener and main survey 
analyzed (tabulating how much the item nonresponse is concentrating in 
a particular subgroup of health providers).
    The FDA anticipates disseminating the results of the study after 
final analyses of the data are completed, reviewed, and cleared. The 
information gathered on this topic will be used to inform regulatory 
guidance to sponsors and investigators designing pregnancy exposure 
registry protocols.

II. References

    The following references are on display at the Dockets Management 
Staff (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also 
available electronically at https://www.regulations.gov. Although FDA 
verified the website addresses in this document, please note that 
websites are subject to change over time.

1. Gelperin, K., H. Hammad, K. Leishear, et al., ``A Systematic 
Review of Pregnancy Exposure Registries: Examination of Protocol-
Specified Pregnancy Outcomes, Target Sample Size, and Comparator 
Selection,'' Pharmacoepidemiology and Drug Safety, 2017 
Feb;26(2):208-214. doi: 10.1002/pds.4150. Epub 2016 Dec 27. PMID: 
28028914.
2. FDA, ``Postapproval Pregnancy Safety Studies (May 2019).'' 
Available at: https://www.fda.gov/media/124746/download.
3. National Institutes of Health, Task Force on Research Specific to 
Pregnant Women

[[Page 32450]]

and Lactating Women (PRGLAC). Available at: https://www.nichd.nih.gov/about/advisory/PRGLAC.
4. FDA, ``Study Approaches and Methods To Evaluate the Safety of 
Drugs and Biological Products During Pregnancy in the Post-Approval 
Setting,'' May 28-29, 2014. Available at: https://www.fda.gov/Drugs/NewsEvents/ucm386560.htm.
5. Daniels, J.L., D.A. Savitz, C. Bradley, et al., ``Attitudes 
Toward Participation in a Pregnancy and Child Cohort Study,'' 
Paediatric and Perinatal Epidemiology, 2006 May;20(3):260-266. doi: 
10.1111/j.1365-3016.2006.00720.x. PMID: 16629701.
6. Hartman, R.I. and A.B. Kimball, ``Performing Research in 
Pregnancy: Challenges and Perspectives,'' Clinics in Dermatology, 
2016 May-Jun;34(3):410-415. doi: 10.1016/j.clindermatol.2016.02.014. 
Epub 2016 Feb 11. PMID: 27265080.
7. Krueger, W.S., M.S. Anthony, C.W. Saltus, et al., ``Evaluating 
the Safety of Medication Exposures During Pregnancy: A Case Study of 
Study Designs and Data Sources in Multiple Sclerosis,'' Drugs Real 
World Outcomes, 2017 Sep;4(3):139-149. doi: 10.1007/s40801-017-0114-
9. PMID: 28756575; PMCID: PMC5567459.
8. Sarker A., P. Chandrashekar, A. Magge, et al., ``Discovering 
Cohorts of Pregnant Women From Social Media for Safety Surveillance 
and Analysis,'' Journal of Medical internet Research, 2017 Oct 
30;19(10):e361. doi: 10.2196/jmir.8164. PMID: 29084707; PMCID: 
PMC5684515.
9. Sinclair S., M. Cunnington, J. Messenheimer, et al., ``Advantages 
and Problems With Pregnancy Registries: Observations and Surprises 
Throughout the Life of the International Lamotrigine Pregnancy 
Registry,'' Pharmacoepidemiology and Drug Safety, 2014 
Aug;23(8):779-786. doi: 10.1002/pds.3659. Epub 2014 Jun 27. PMID: 
24974947; PMCID: PMC4406353.

    Dated: April 23, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-09028 Filed 4-25-24; 8:45 am]
BILLING CODE 4164-01-P