[Federal Register Volume 87, Number 184 (Friday, September 23, 2022)]
[Notices]
[Pages 58103-58106]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-20636]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-N-1874]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Perceptions of Prescription Drug Products With 
Medication Tracking Capabilities

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 ``Perceptions of 
Prescription Drug Products With Medication Tracking Capabilities.''

DATES: Either electronic or written comments on the collection of 
information must be submitted by November 22, 2022.

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 November 22, 2022. 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

[[Page 58104]]

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-2022-N-1874 for ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; Perceptions of Prescription Drug 
Products With Medication Tracking Capabilities.'' 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 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: 
    Regarding the collection of information: JonnaLynn Capezzuto, 
Office of Operations, Food and Drug Administration, Three White Flint 
North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-
3794, [email protected].
    For copies of the questionnaire: Amie O'Donoghue, Office of 
Prescription Drug Promotion (OPDP) Research Team, 301-796-0754, 
[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.

Perceptions of Prescription Drug Products With Medication Tracking 
Capabilities

OMB Control Number 0910--NEW

    Section 1701(a)(4) of the Public Health Service Act (42 U.S.C. 
300u(a)(4)) authorizes the FDA to conduct research relating to health 
information. Section 1003(d)(2)(C) of the Federal Food, Drug, and 
Cosmetic Act (FD&C Act) (21 U.S.C. 393(d)(2)(C)) authorizes FDA to 
conduct research relating to drugs and other FDA-regulated products in 
carrying out the provisions of the FD&C Act.
    The mission of the Office of Prescription Drug Promotion (OPDP) is 
to protect the public health by helping to ensure that prescription 
drug promotional material is truthful, balanced, and accurately 
communicated so that patients and health care providers can make 
informed decisions about treatment options. OPDP's research program 
provides scientific evidence to help ensure that our policies related 
to prescription drug promotion will have the greatest benefit to public 
health. Toward that end, we have consistently conducted research to 
evaluate the aspects of prescription drug promotion that are most 
central to our mission, focusing in particular on three main topic 
areas: advertising features, including content and format; target 
populations; and research quality. Through the evaluation of 
advertising features, we assess how elements such as graphics, format, 
and the characteristics of the disease and product impact the 
communication and understanding of prescription drug risks and 
benefits. Focusing on target populations allows us to evaluate how 
understanding of prescription drug risks and benefits may vary as a 
function of audience. Our focus on research quality aims at maximizing 
the quality of research data through analytical methodology development 
and investigation of sampling and response issues. This study will 
inform the first topic area, advertising features.
    Because we recognize that the strength of data and the confidence 
in the robust nature of the findings are improved through the results 
of multiple converging studies, we continue to develop evidence to 
inform our thinking. We evaluate the results from our studies within 
the broader context of research and findings from other sources, and 
this larger body of knowledge collectively informs our policies as well 
as our research program. Our research is documented on our home page at 
https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research, which includes links 
to the latest Federal Register notices and peer-reviewed publications 
produced by our office.
    Patient non-adherence to medication regimens is a well-known 
challenge in health care. The World Health Organization defines 
adherence as the extent to which a person's behavior--taking 
medication, following a diet,

[[Page 58105]]

and/or executing lifestyle changes--corresponds with agreed 
recommendations from a health care provider (Ref. 1). It is estimated 
that only half of all patients with chronic health conditions take 
their medications as prescribed (Ref. 2), leading to as many as 100,000 
preventable deaths and $100 billion in additional medical costs every 
year (Ref. 3). Numerous solutions have been tried to improve adherence, 
including resource-intensive approaches such as directly observed 
therapy, which entails a trained observer watching as the patient takes 
their medications (Ref. 4), and technology-supported tools for patients 
(e.g., smartphone apps) (Ref. 5). As attention to the public health 
issue of medication adherence has grown, OPDP has noted a corresponding 
increase in the number of claims and presentations in prescription drug 
promotion that focus, either directly or through implication, on a 
product's potential to improve adherence to treatment regimens. Many of 
these presentations include information about options and capabilities 
available to help patients track their medication usage.
    One avenue that prescription drug sponsors have begun exploring to 
track medication use includes the development of software that is 
disseminated by or on behalf of the drug sponsor and accompanies one or 
more of the sponsor's prescription drugs. This software is called 
prescription drug use-related software.\1\ Studies exploring drug 
products with prescription drug use-related software have been 
conducted with medications to treat an array of chronic disorders, 
including psychiatric disorders (Ref. 6), uncontrolled type 2 diabetes 
(Ref. 7), end-stage renal disease requiring transplants (Ref. 8), and 
opioid use among patients with acute fractures (Ref. 9).
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    \1\ In 2018, FDA established a public docket to solicit public 
comment on a proposed framework for regulating software applications 
disseminated by or on behalf of drug sponsors for use with one or 
more of their prescription drug products. See https://www.federalregister.gov/documents/2018/11/20/2018-25206/prescription-drug-use-related-software-establishment-of-a-public-docket-request-for-comments.
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    In recent years, new technologies that capture data on medication-
taking behavior and drug administration have been employed. The 
SureClick 2.0 autoinjector for the prescription medication ENBREL, for 
example, has Bluetooth built into the white cap that covers the needle. 
The autoinjector records initial removal of the cap and can send this 
data via Bluetooth to a paired smartphone using a mobile app (Ref. 10). 
Technology can also now support the use of ingestible sensors embedded 
in pills that will emit a weak signal to a receiver (patch or lanyard) 
worn by the patient after the pill has been swallowed (Ref. 11). This 
data can then be transmitted to a paired mobile device and viewed by 
the patient through a smartphone app (Ref. 12). Whether these new 
technologies will have an impact on adherence is currently unknown.
    Very little is known about patient and health care provider 
perceptions of products that track medication use or that work in 
tandem with software to track medication use, with most commentaries 
having been largely theoretical (Refs. 13, 14). The focus of the 
present study is to explore patient and health care provider 
perceptions of a fictitious prescription drug product that is 
accompanied by software that is intended to track medication use.
    We have the following specific questions:
    Research questions:
    1. When prescription drug promotional communications include claims 
about a product's ability to track medication use, do these claims 
influence perceptions about the product's risks and/or benefits 
(including its effect on medication adherence)?
    2. If the promotional claims about the product's ability to track 
medication use are accompanied by a disclosure that describes what is 
known about the effect of medication tracking on medication adherence, 
does this have an influence on perceptions of the product's risks and/
or benefits (including its effect on medication adherence)?
    To complete this research, we propose the design in table 1, which 
varies based on:
     Whether the fictitious prescription drug product includes 
technology that tracks medication use;
     Whether the prescription drug promotional communication 
includes a disclosure describing what is known about the tracking 
technology's effect on medication adherence; and
     What the disclosure communicates about the tracking 
technology's effect on medication adherence (positive effect shown, no 
effect shown, or unknown effect).

                              Table 1--Proposed One-Way, Five-Level Design (1 x 5)
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                                                 Claims about     Disclosure
                                                 existence of        about
            Experimental condition                medication     technology's         Content of disclosure
                                                   tracking        effect on
                                                  technology       adherence
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1. Drug.......................................              No             No.  ................................
2. Drug + medication tracking technology......             Yes             No.  ................................
3. Drug + medication tracking technology + no              Yes             Yes  No data is available on the
 adherence data collected.                                                       technology's effect on
                                                                                 adherence.
4. Drug + medication tracking technology +                 Yes             Yes  Data show the technology has no
 data show no effect on adherence.                                               effect on adherence.
5. Drug + medication tracking technology +                 Yes             Yes  Data show the technology has a
 data show a positive effect on adherence.                                       positive effect on adherence.
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Note: Condition 5 is the only condition in which an adherence benefit has been demonstrated for the fictitious
  product. The evidence required to support a medication adherence claim is not the focus of this study, and the
  evidence will not be described in the disclosure.
Condition 2 is a control because the drug product does include medication tracking technology, but the
  promotional communication does not include a disclosure about the technology's effect on medication adherence.
  Condition 1 is a true control because the drug product does not include medication tracking technology.
  Comparisons between conditions 1 and 2 will show us the baseline of this issue, i.e., will indicate whether
  the fact that the drug product contains a tracking technology will alter perceptions of risks and benefits
  (including adherence).

    We will conduct pretests with 50 consumers who self-identify as 
having been diagnosed with diabetes and 50 primary care physicians who 
treat diabetes (both obtained from a web-based research vendor) to 
ensure that

[[Page 58106]]

the questionnaire programming works as expected. For the main study, we 
will then recruit 350 consumers who self-identify as having been 
diagnosed with diabetes and 350 primary care physicians who treat 
diabetes. Each participant will see one of five versions of a consumer 
web page for a fictitious prescription diabetes treatment, as reflected 
in table 1. They will answer a questionnaire designed to take no more 
than 20 minutes regarding their perception of the product's benefits, 
risks, and effect on adherence.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 2--Estimated Annual Reporting Burden 1 2
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                                                                   Number of
                   Activity                        Number of     responses per   Total annual          Average burden per response          Total hours
                                                  respondents     respondent      respondents
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Screener Consumers............................             680               1             680  .08 (5 minutes).........................            54.4
Screener Primary Care Physicians..............             680               1             680  .08 (5 minutes).........................            54.4
Pretest Consumers.............................              50               1              50  .33 (20 minutes)........................            16.5
Pretest Primary Care Physicians...............              50               1              50  .33 (20 minutes)........................            16.5
Main Study Consumers..........................             350               1             350  .33 (20 minutes)........................           115.5
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Main Study Primary Care Physicians............             350               1             350  .33 (20 minutes)........................           115.5
    Total.....................................  ..............  ..............  ..............  ........................................           372.8
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in decimal format.

References

    The following references marked with an asterisk (*) are on display 
at the Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852) and 
are available for viewing by interested persons between 9 a.m. and 4 
p.m., Monday through Friday; they also are available electronically at 
https://www.regulations.gov. References without asterisks are not on 
public display at https://www.regulations.gov because they have 
copyright restriction. Some may be available at the website address, if 
listed. References without asterisks are available for viewing only at 
the Dockets Management Staff. FDA has verified the website addresses, 
as of the date this document publishes in the Federal Register, but 
websites are subject to change over time.

*1. World Health Organization, ``Adherence to Long-Term Therapies: 
Evidence for Action,'' p. 3, 2003, available at https://apps.who.int/iris/handle/10665/42682, accessed May 16, 2022.
2. Frias, J., N. Virdi, P. Raja, et al., ``Effectiveness of Digital 
Medicines to Improve Clinical Outcomes in Patients with Uncontrolled 
Hypertension and Type 2 Diabetes: Prospective, Open-Label, Cluster-
Randomized Pilot Clinical Trial,'' Journal of Medical Internet 
Research, vol. 19, Issue 7, Article e246, 2017, doi:10.2196/
jmir.7833.
3. Kleinsinger, F., ``The Unmet Challenge of Medication 
Nonadherence,'' The Permanente Journal, vol. 22, Issue 3, Article 
18-033, 2018, doi:10.7812/TPP/18-033.
4. Karumbi, J. and P. Garner, ``Directly Observed Therapy for 
Treating Tuberculosis,'' Cochrane Database of Systematic Reviews, 
Issue 5, Article CD003343, 2015, doi:10.1002/14651858.CD003343.pub4.
5. Dayer, L., S. Heldenbrand, P.O. Gubbins, et al., ``Smartphone 
Medication Adherence Apps: Potential Benefits to Patients and 
Providers,'' Journal of the American Pharmacy Association (2003), 
vol. 53, Issue 2, pp. 172-181, 2013, doi:10.1331/JAPhA.2013.12202.
*6. FDA, ``FDA Approves Pill with Sensor That Digitally Tracks If 
Patients Have Ingested Their Medication,'' FDA News Release, 
November 13, 2017, available at https://www.fda.gov/news-events/press-announcements/fda-approves-pill-sensor-digitally-tracks-if-patients-have-ingested-their-medication, accessed May 16, 2022.
7. Browne, S.H., Y. Behzadi, and G. Littlewort, ``Let Visuals Tell 
the Story: Medication Adherence in Patients with Type II Diabetes 
Captured by a Novel Ingestion Sensor Platform,'' JMIR mHealth 
uHealth, vol. 3, Issue 4, Article e108, 2015, doi:10.2196/
mhealth.4292.
8. Eisenberger, U., R.P. W[uuml]thrich, A. Bock, et al., 
``Medication Adherence Assessment: High Accuracy of the New 
Ingestible Sensor System in Kidney Transplants,'' Transplantation, 
vol. 96, Issue 3, pp. 245-250, 2013, doi:10.1097/
TP.0b013e31829b7571.
9. Chai, P.R., S. Carreiro, B.J. Innes, et al., ``Oxycodone 
Ingestion Patterns in Acute Fracture Pain with Digital Pills,'' 
Anesthesia and Analgesia, vol. 125, Issue 6, pp. 2105-2112, 2017, 
doi:10.1213/ANE.0000000000002574.
*10. Amgen Inc., ``Enbrel (etanercept): Highlights of Prescribing 
Information,'' revised April 2021, available at https://
www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/enbrel/
enbrel_pi.pdf, accessed May 16, 2022.
*11. Reuter, E., '' `Smart Pill' Startup EtectRx Strikes Partnership 
with Pear Therapeutics,'' Med City News, January 14, 2021, available 
at https://medcitynews.com/2021/01/smart-pill-startup-etectrx-strikes-partnership-with-pear-therapeutics, accessed May 16, 2022.
12. The Medical Futurist, ``The Present and Future of Digital 
Pills,'' July 21, 2020, available at https://medicalfuturist.com/the-present-and-future-of-digital-pills, accessed May 16, 2022.
13. George, C.E., ``Should a Psychiatrist Prescribe a Nanodrug to 
Help Parents Monitor a Teen's Adherence?,'' AMA Journal of Ethics, 
vol. 21, issue 4, article e317-323, 2019, doi:10.1001/
amajethics.2019.317.
*14. Yang, M., ``A Psychiatrist's Perspective on the Digital Pill,'' 
KevinMD.com, December 2, 2017, available at https://www.kevinmd.com/blog/2017/12/psychiatrists-perspective-digital-pill.html, accessed 
May 16, 2022.

    Dated: September 19, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-20636 Filed 9-22-22; 8:45 am]
BILLING CODE 4164-01-P