Notice2023-09268

Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Perceptions of Prescription Drug Products With Medication Tracking Capabilities

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Published
May 2, 2023

Issuing agencies

Health and Human Services DepartmentFood and Drug Administration

Abstract

The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995.

Full Text

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<title>Federal Register, Volume 88 Issue 84 (Tuesday, May 2, 2023)</title>
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[Federal Register Volume 88, Number 84 (Tuesday, May 2, 2023)]
[Notices]
[Pages 27518-27521]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-09268]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; 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) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Submit written comments (including recommendations) on the 
collection of information by June 1, 2023.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to <a href="https://www.reginfo.gov/public/do/PRAMain">https://www.reginfo.gov/public/do/PRAMain</a>. Find this particular information 
collection by selecting ``Currently under Review--Open for Public 
Comments'' or by using the search function. The title of this 
information collection is ``Perceptions of Prescription Drug Products 
with Medication Tracking Capabilities.'' Also include the FDA docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: 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, 
<a href="/cdn-cgi/l/email-protection#08585a495b7c696e6e486e6c692660607b266f677e"><span class="__cf_email__" data-cfemail="adfdffecfed9cccbcbedcbc9cc83c5c5de83cac2db">[email&#160;protected]</span></a>.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

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

[[Page 27519]]

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 
<a href="https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research">https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-prescription-drug-promotion-opdp-research</a>, 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, 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 <a href="https://www.federalregister.gov/documents/2018/11/20/2018-25206/prescription-drug-use-related-software-establishment-of-a-public-docket-request-for-comments">https://www.federalregister.gov/documents/2018/11/20/2018-25206/prescription-drug-use-related-software-establishment-of-a-public-docket-request-for-comments</a>.
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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). These 
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 and 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:
    <bullet> Whether the fictitious prescription drug product includes 
technology that tracks medication use;
    <bullet> Whether the prescription drug promotional communication 
includes a disclosure describing what is known about the tracking 
technology's effect on medication adherence; and
    <bullet> 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
                                          existence of          Disclosure about
       Experimental condition          medication tracking   technology's effect on     Content of disclosure
                                           technology               adherence
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1. Drug............................  No....................  No....................
2. Drug + medication tracking        Yes...................  No....................
 technology.
3. Drug + medication tracking        Yes...................  Yes...................  No data are available on
 technology + no adherence data                                                       the technology's effect on
 collected.                                                                           adherence.
4. Drug + medication tracking        Yes...................  Yes...................  Data show the technology
 technology + data show no effect                                                     has no effect on
 on adherence.                                                                        adherence.

[[Page 27520]]

 
5. Drug + medication tracking        Yes...................  Yes...................  Data show the technology
 technology + data show a positive                                                    has a positive effect on
 effect on adherence.                                                                 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 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.
    In the Federal Register of September 23, 2022 (87 FR 58103), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received one submission that was not 
PRA-related (<a href="http://regulations.gov">regulations.gov</a> tracking number lar-vv69-9wok).
    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     Total hours
                                  respondents     respondent      respondents     per response
----------------------------------------------------------------------------------------------------------------
Screener Consumers............             680               1             680  .08 (5 minutes).            54.4
Screener Primary Care                      680               1             680  .08 (5 minutes).            54.4
 Physicians.
Pretest Consumers.............              50               1              50  .33 (20 minutes)            16.5
Pretest Primary Care                        50               1              50  .33 (20 minutes)            16.5
 Physicians.
Main Study Consumers..........             350               1             350  .33 (20 minutes)           115.5
Main Study Primary Care                    350               1             350  .33 (20 minutes)           115.5
 Physicians.
                               ---------------------------------------------------------------------------------
    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 
<a href="https://www.regulations.gov">https://www.regulations.gov</a>. References without asterisks are not on 
public display at <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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 <a href="https://apps.who.int/iris/handle/10665/42682">https://apps.who.int/iris/handle/10665/42682</a>, 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 <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-pill-sensor-digitally-tracks-if-patients-have-ingested-their-medication">https://www.fda.gov/news-events/press-announcements/fda-approves-pill-sensor-digitally-tracks-if-patients-have-ingested-their-medication</a>, 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.

[[Page 27521]]

* 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 <a href="https://medcitynews.com/2021/01/smart-pill-startup-etectrx-strikes-partnership-with-pear-therapeutics">https://medcitynews.com/2021/01/smart-pill-startup-etectrx-strikes-partnership-with-pear-therapeutics</a>, accessed May 16, 2022.
12. The Medical Futurist, ``The Present and Future of Digital 
Pills,'' July 21, 2020, available at <a href="https://medicalfuturist.com/the-present-and-future-of-digital-pills">https://medicalfuturist.com/the-present-and-future-of-digital-pills</a>, 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,'' <a href="http://KevinMD.com">KevinMD.com</a>, December 2, 2017, available at <a href="https://www.kevinmd.com/blog/2017/12/psychiatrists-perspective-digital-pill.html">https://www.kevinmd.com/blog/2017/12/psychiatrists-perspective-digital-pill.html</a>, accessed May 16, 2022.

    Dated: April 27, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-09268 Filed 5-1-23; 8:45 am]
BILLING CODE 4164-01-P


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