[Federal Register Volume 85, Number 130 (Tuesday, July 7, 2020)]
[Notices]
[Pages 40663-40666]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-14516]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-N-5973]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Health Care 
Providers' Understanding of Opioid Analgesic Abuse Deterrent 
Formulations

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 (PRA).

DATES: Fax written comments on the collection of information by August 
6, 2020.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. 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 ``Health Care Providers' Understanding of 
Opioid Analgesic Abuse Deterrent Formulations.'' Also include the FDA 
docket number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Ila S. Mizrachi, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-7726, 
PRAStaff@fda.hhs.gov.

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.

Health Care Providers' Understanding of Opioid Analgesic Abuse 
Deterrent Formulations

OMB Control Number 0910-NEW

I. Background
    Section 1701(a)(4) of the Public Health Service Act (42 U.S.C. 
300u(a)(4)) authorizes 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.
    Prescription opioids play a significant role in the opioid misuse 
and abuse epidemic in the United States. Opioid analgesics with 
properties designed to deter abuse, commonly known as abuse deterrent 
formulations (ADFs), may play a role in helping to curb this epidemic. 
Currently available ADFs have been demonstrated to deter some forms of 
abuse (injection, snorting, or, in some cases, chewing and swallowing). 
FDA's own research and other evidence suggests considerable variability 
in health care providers' (HCPs) knowledge of and attitudes toward 
prescription opioid products and practices (Ref. 1), including 
understanding of ADFs. ADF prescription practices may present 
opportunities for HCPs to reduce opioid abuse. Conducting a 
comprehensive evaluation of opioid prescribers' knowledge, attitudes, 
perceptions, experiences, and behaviors related to ADFs will help to 
inform FDA's approaches to ADFs.
    Given the significance and far-reaching nature of the opioid 
crisis, along with FDA concerns about potential misunderstanding among 
HCPs about ADF terminology and capabilities, FDA determined that 
systematic research was necessary to provide the detailed and 
comprehensive evidence on which to base the Agency's ADF-related 
policy, regulatory, and communication decisions, including potential 
alternative language that may be necessary to describe and explain 
these products. This work aligns with Priority 1 of the FDA's Strategic 
Policy Roadmap (https://www.fda.gov/about-fda/reports/healthy-innovation-safer-families-fdas-2018-strategic-policy-roadmap), and the 
Department of Health and Human Services (HHS) and the Administration 
have similarly placed high priorities on addressing the epidemic of 
misuse and abuse of opioid drugs harming U.S. families.
    The study's purpose is to explore and assess the ADF-related 
knowledge, attitudes, and behaviors among opioid prescribers 
(physicians, nurse practitioners and physician assistants) and 
dispensers/pharmacists, including the related terms addiction and abuse 
deterrence, and to explore possible alternative language for describing 
these products. Phase 1 consisted of focus groups (OMB approval under 
control number 0910-0695). The research described in this notice 
represents Phases 2 and 3 of the overall project.
    Phase 2 will consist of a survey based on the Phase 1 focus group 
findings related to: (1) Health care provider understanding of 
addiction, abuse, and abuse deterrent formulations; (2) attitudes 
toward, perceptions about, and experiences with abuse-deterrent opioid 
analgesics and abuse deterrence, including prescribing decisions and 
practices, potential barriers to using ADFs, the quality and 
understandability of the ADF nomenclature, and the underlying reasons 
for these perceptions; and (3) HCPs' ideas for minimizing confusion 
about ADFs, the kinds of ADF training needed, and suggested language/
terms they believe would best convey the concept of abuse deterrence to 
HCPs. The objective of the survey will be to determine the prevalence 
of HCP knowledge, attitudes, behaviors, and perceptions identified 
through the qualitative discussion occurring in the Phase 1 focus 
groups and to uncover any subgroup differences among opioid prescribers 
and dispensers. We will conduct one pretest, averaging not longer than 
20 minutes, to pilot the main survey

[[Page 40664]]

procedures among the target HCP populations. The main survey will also 
average 20 minutes.
    Phase 3 will build on findings from the Phase 1 focus groups and 
Phase 2 survey and will consist of an experimental study examining 
variations in descriptive terminology for abuse deterrent formulation 
products. We will conduct two pretests, each averaging not longer than 
20 minutes, to test the experimental manipulations and pilot the main 
study procedures. The main study procedure will also average 20 minutes 
in length. Participants will be randomly assigned to read a description 
of abuse deterrent formulation opioids that contains one of four terms 
that could be used to refer to these products (ADF will function as the 
control term) and then complete a questionnaire that assesses their 
comprehension and perceptions of the information, including 
terminology, as well as their attitudes, behavioral intentions, and 
experience related to these types of opioid products.
    For all phases of this research, we will recruit adult health care 
professional volunteers 18 years of age or older. We will exclude 
individuals who work for HHS or work in the health care, marketing, or 
pharmaceutical industries. The sample will consist of 10 percent 
pharmacists, at least half of whom dispense ADF opioids. The other 90 
percent will be prescribers who, at the time they are recruited, spend 
at least 50 percent of their time seeing patients and who have 
prescribed opioids to at least five different patients in the last 30 
days, with at least half of the opioids they prescribe being for 
chronic non-cancer pain. The prescriber sample will be segmented to 
include 70 percent primary care providers (i.e., those practicing in 
family practice, or internal or general medicine) and 30 percent a mix 
of specialists practicing in a variety of fields such as rheumatology, 
neurology, anesthesiology, pain management, emergency medicine, 
surgery, orthopedics, and physical medicine and rehabilitation. In each 
of these groups, 60 to 70 percent will consist of physicians, 15 
percent nurse practitioners, and 15 percent physician assistants. A 
minimum of 30 percent must have experience prescribing an ADF opioid.
    We will use soft quotas to ensure that our sample includes a 
diversity of participants, including related to age, race/ethnicity, 
gender, years and location of practice, and opioid prescribing levels. 
We will also exclude pretest participants from the main studies, and 
participants will not be able to participate in more than one phase of 
the project. With the sample sizes described below, we will have 
sufficient power to detect primarily small-sized effects for Phases 2 
and 3.
    In the Federal Register of February 5, 2020 (85 FR 6562), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received three submissions that were 
PRA-related. Within those submissions, FDA received multiple comments, 
which the Agency has addressed below.
    (Comment 1) I believe Phase 2 should include more pharmacists than 
10 percent ratio.
    (Response 1) We have carefully planned the sample for the study to 
ensure sufficient numbers of prescribers, including primary care 
providers and several types of specialists (including neurologists, 
pain management specialists, rheumatologists, neurologists, surgeons, 
orthopedists, physical medicine and rehabilitation specialists), 
physician assistants and nurse practitioners, as well as including a 
group of pharmacists for analysis. Expanding the sample further is 
beyond the scope of what we have planned for the project. Our power 
analysis suggests we will have sufficient power to ensure comparisons 
between groups in the sample. In addition, in the earlier focus group 
phase, pharmacists said they rarely talk with patients about ADFs and 
never talk with health care professionals about them, suggesting the 
feedback we would receive from them would likely be limited.
    (Comment 2) Practitioners chosen should be based on greater 
prescribing habits. Those practitioners who are the larger rate of 
treating chronic non-cancer pain with ADF opioid should be the target 
of information gathering.
    (Response 2) One of our screening criteria is that at least half of 
a provider's prescriptions must be for chronic, non-cancer pain. We 
plan to include approximately equal numbers of low, medium, and high 
prescribers across each prescriber type and field of practice so that 
comparisons can be made between groups. In addition, in the earlier 
focus group phase, current prescribers of ADFs were already aware of 
and had significant knowledge about ADFs, so their feedback likely 
would not provide the kind of insight needed about the misunderstanding 
and confusion we previously observed among other prescribers.
    (Comment 3) We support FDA's decision to conduct a comprehensive 
evaluation of opioid prescribers' knowledge, attitudes, perceptions, 
experiences, and behaviors related to ADFs and agree with the FDA that 
new language is needed to better describe and explain ADFs.
    (Response 3) Thank you for this comment.
    (Comment 4) We strongly encourage testing the impact of terminology 
that more accurately describes the product's abuse-deterrent 
properties. For example, if a pill is formulated to be difficult to 
crush, it should be labeled ``crush-resistant.''
    (Response 4) The survey, in part, will provide HCPs an opportunity 
to propose terms they think best describe these opioids and will test 
both objectively and subjectively numerous alternative terms that were 
commonly cited as appropriate by HCP participants in the earlier focus 
group phase of this study. This includes terms that relate to physical 
manipulation such as ``alteration-resistant opioids'' and ``tamper-
resistant opioids.''
    (Comment 5) We support FDA's efforts to ensure the diversity of the 
sample populations for the three proposed studies. It is important to 
study health care providers with varying opioid prescribing levels, and 
years and locations of practice. We particularly commend the efforts to 
additionally account for diverse ages, ethnicities, and gender of the 
health care providers, as all of these factors can affect knowledge, 
attitudes, and the patients they serve.
    (Response 5) Thank you for this comment.
    (Comment 6) The proposed study plans to include a wide range of 
health care providers, including primary care providers; specialists 
from various fields such as rheumatology, neurology, anesthesiology, 
pain management, emergency medicine, surgery, orthopedics, and physical 
medicine and rehabilitation; nurse practitioners; physician assistants; 
as well as dispensers/pharmacists. However, there is clear evidence 
that dentists, periodontists, and oral surgeons should also be 
included, since research has shown that they often overprescribe 
opioids.
    (Response 6) While the reviewers raises an important consideration, 
the inclusion of dentists and oral surgeons is beyond the scope of the 
current study. Dentists do not typically prescribe for long-term pain 
and are therefore less likely to prescribe an abuse-deterrent 
formulation opioid or ADF, which is the main focus of this study. For a 
similar reason, based on what we heard in the earlier focus group phase 
of this study, we chose to exclude emergency medicine physicians from 
the sample survey populations.
    (Comment 7) The proposed study should explore providers' knowledge 
of

[[Page 40665]]

how ADF opioids are used and abused once they are on the market. 
Opioids considered to be abuse-deterrent are still widely abused 
through the most common oral route.
    (Response 7) Our survey questions will include items about provider 
knowledge of ADFs, including specific questions to test whether they 
are aware that ADFs can still be abused, as well as related to their 
experiences with use, misuse, and abuse of opioids.
    (Comment 8) We applaud the effort to gather information about HCPs' 
understanding of these products. This effort is consistent with the 
Agency's history of extensive and diverse efforts to balance the needs 
of people seeking relief from severe acute and chronic pain and the 
simultaneous need to avoid worsening of the abuse, addiction, and 
diversion of opioid medications in these times of the opioid overdose 
epidemic.
    (Response 8) Thank you for this comment.
    (Comment 9) We believe that the proposed sample design adequately 
accounts for current ADF product prescribers for chronic non-cancer 
pain. It is not clear, however, whether the proposed sample design 
would adequately capture the second relevant population, i.e. 
appropriate potential prescribers of ADF products for chronic non-
cancer pain. Commenter recommends that FDA focus on those HCPs who 
specialize in chronic non-cancer pain management, because these 
relatively few HCPs manage a disproportionate volume of patients with 
chronic non-cancer pain and, therefore, manage a disproportionate 
volume of current and appropriate potential prescriptions of ADF 
products for chronic non-cancer pain.
    Suggestions:
     The proposed threshold of 5 patients treated with opioids 
for chronic non-cancer pain in a typical month is too low. A low 
threshold does not ensure that pain specialists will be included, and 
evidence has shown that the treatment of chronic non-cancer pain with 
opioids has consolidated under such pain specialists in recent years.
     Study should focus on HCPs who specialize in chronic non-
cancer pain management. This small subset of HCPs manage a 
disproportionate volume of patients with chronic non-cancer pain, and 
therefore, they manage a disproportionate volume of current and 
appropriate potential ADF prescriptions.
     Study can capture both intended populations (current and 
``appropriate potential'' prescribers) by recruiting only pain 
specialists and imposing a threshold for experience prescribing ADF 
products.
    (Response 9) Pain management is one of the specialties included on 
our recruitment screener (in addition to rheumatology, neurology, 
anesthesiology, surgery, orthopedics, and physical medicine and 
rehabilitation). Our screening criteria will ensure an approximately 
equal number of low, medium, and high-volume prescribers across each 
provider group. We also have included a requirement that at least 50 
percent of prescriptions must be for chronic, non-cancer pain. A key 
objective of this study is to gain insight into misunderstandings about 
ADF opioids and the terminology and how to best address the confusion 
and misunderstandings that we found in the earlier focus group phase of 
the study as well as in prior research FDA conducted. These data 
indicated pain management specialists already tend to have considerable 
knowledge about and experience with ADFs, suggesting their feedback 
would likely be of limited usefulness with respect to the study's key 
objectives. This is similarly the case for ADF prescribers, which is 
the reason the study populations were purposely inclusive of a broad 
cross-section of opioid prescribers.
    (Comment 10) Include a screening question with a list of ADF 
products to account for respondents' lack of knowledge about which 
products are and are not ADF.
    (Response 10) Thank you for the suggestion. Our recruitment 
screener includes such a question, which asks respondents to identify 
which of 17 different listed opioids they have prescribed, including 
six abuse-deterrent formulations that will not be identified as such. 
The survey questionnaire itself also asks prescribers to specifically 
cite in an open-ended question the ADF opioids they have prescribed, 
which will be used, in part, to asses ADF knowledge.
    (Comment 11) Set quotas to ensure recruitment of representative 
sample sizes for both non-specialists and pain specialists.
    (Response 11) Early in the protocol development we identified the 
need for samples of prescribers working in primary care fields and 
among those in specific specialties, which research has shown generally 
prescribe the most opioids overall, and the sample populations included 
in the study will reflect this necessary diversity.
    (Comment 12) Lower Ns for Phase 2 and 3 to ensure timely 
completion. In the company's experience, a survey of 200 HCPs takes 5 
weeks to complete.
    (Response 12) We identified current sample sizes based on power 
calculations. Any reduction in sample size would reduce our power to 
find effects. We have planned a timeline for the project to complete 
both phases 2 and 3 based experience collecting data using these 
methods but will be adjusting as necessary given the COVID-19 pandemic 
and any other unforeseen factors. This project is an FDA priority, and 
we will prioritize rigorous methodology that ensures representativeness 
and robust data and evidence even if it means taking a little more 
time.
    (Comment 13) Implement appropriate honoraria to ensure feasibility 
and timely results.
    (Response 13) The financial incentive rates were based on going 
rates for incentives in provider panel surveys and on recent research 
on incentives for physician surveys. These will also comport with those 
allowable by OMB. In addition, our experience has shown that the topic 
of this study--opioids and the national crisis--and the fact that the 
research is being undertaken by FDA, the Federal agency responsible for 
regulating these products, are additional incentives for participation.
    FDA estimates the burden of this collection of information as 
follows:

                                                    Table 1--Estimated Annual Reporting Burden 1 2 4
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                                     Number of  respondents   Number of  responses        Total annual       Average burden  per
              Activity                         \3\               per  respondent           responses               response             Total hours
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Phase 2:
    Pretest screener...............  470...................  1.....................  470..................  0.17.................  79.90
                                                                                                            (10 minutes).........

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    Pretest........................  235...................  1.....................  235..................  0.33.................  77.55
                                                                                                            (20 minutes).........
    Survey screener................  2,120.................  1.....................  2,120................  0.17.................  360.40
                                                                                                            (10 minutes).........
    Survey.........................  1,060.................  1.....................  1,060................  0.33.................  349.80
                                                                                                            (20 minutes).........
Phase 3:
    Pretests screener..............  732...................  1.....................  732..................  0.17.................  124.44
                                                                                                            (10 minutes).........
    Pretests.......................  366...................  1.....................  366..................  0.33.................  120.78
                                                                                                            (20 minutes).........
    Main study screener............  2,120.................  1.....................  2,120................  0.17.................  360.40
                                                                                                            (10 minutes).........
    Main study.....................  1,060.................  1.....................  1,060................  0.33.................  349.80
                                                                                                            (20 minutes).........
                                    --------------------------------------------------------------------------------------------------------------------
        Total......................  ......................  ......................  .....................  .....................  1,823.07
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Includes total burden for project phases 2 and 3.
\3\ Includes 10 percent overage.
\4\ With online surveys, several participants may be in the process of completing the survey at the time that the total target sample is reached. Those
  participants will be allowed to complete the survey, which can result in the number of valid completes exceeding the target number. With this in mind,
  we have included an additional 10 percent over our target number of valid completes to account for some overage.

II. Reference
    The following reference is on display with the Dockets Management 
Staff (see ADDRESSES) and is available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; it is not 
available electronically at https://www.regulations.gov as this 
reference is copyright protected.

    1. Hwang, C.S., L.W. Turner, S.P. Kruszewski, et al. ``Primary 
Care Physicians' Knowledge and Attitudes Regarding Prescription 
Opioid Abuse and Diversion.'' The Clinical Journal of Pain, 32(4), 
279-284, 2016.

    Dated: June 30, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-14516 Filed 7-6-20; 8:45 am]
BILLING CODE 4164-01-P


