
[Federal Register Volume 84, Number 47 (Monday, March 11, 2019)]
[Notices]
[Pages 8721-8727]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-04307]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-0215]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Healthcare 
Professional Survey of Professional Prescription Drug Promotion

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: Fax written comments on the collection of information by April 
10, 2019.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
Fax: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All 
comments should be identified with the OMB control number 0910-New and 
title, ``Healthcare Professional Survey of Professional Prescription 
Drug Promotion.'' 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.

Healthcare Professional Survey of Professional Prescription Drug 
Promotion

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

[[Page 8722]]

FDA to conduct research relating to drugs and other FDA regulated 
products in carrying out the provisions of the FD&C Act.
    The FD&C Act prohibits the dissemination of false or misleading 
information about medications in consumer-directed and professional 
prescription drug promotion. As part of its Federal mandate, FDA 
regulates whether advertising of prescription drug products is 
truthful, balanced, and accurately communicated (see 21 U.S.C. 352(n)). 
FDA's regulatory policies are aligned with the principles of free 
speech and due process in the U.S. Constitution. To inform current and 
future policies, and to seek to enhance audience comprehension, the 
Office of Prescription Drug Promotion conducts research focusing on (1) 
advertising features including content and format, (2) target 
populations, and (3) research quality. This proposed research focuses 
on healthcare professionals (HCPs). In 2002 (Ref. 1) and again in 2013 
(Refs. 2 and 3), FDA surveyed HCPs about their attitudes toward direct-
to-consumer (DTC) advertising and its role in their relationships with 
their patients. The 2013 survey included multiple types of HCPs: 
Primary care physicians and specialists, as well as nurse practitioners 
and physician assistants. Whereas the focus of both previous FDA 
surveys was on DTC advertising and promotion, the current study is 
designed to address issues related to professional prescription drug 
promotion. The goal is to query a representative sample of HCPs about 
their opinions of promotional materials and procedures targeted at 
HCPs, clinical trial design and knowledge, and FDA approval status. We 
will also take this opportunity to ask HCPs briefly about their 
knowledge of abuse-deterrent formulations for opioid products.
    To educate themselves about prescription drugs, HCPs sometimes rely 
on professionally directed promotional information (Refs. 4-8). In 
2012, pharmaceutical companies spent more than $24 billion on marketing 
to physicians (Ref. 9). The industry exposes healthcare professionals 
to promotional materials through a variety of mechanisms, including 
communication with pharmaceutical representatives, journal ads, 
prescribing software, presentations at sponsored meetings, and direct 
mail ads (Ref. 10). Several studies indicate that data presented in 
promotional materials may not be fully comprehended and may even 
potentially be misleading due to a variety of causes, such as 
insufficient information, unsupported claims, or a failure to disclose 
limitations of the information presented (Refs. 11-15).
    Although HCPs are learned intermediaries, like most people, they 
may rely on heuristics, or rules of thumb, in making decisions and may 
have cognitive biases in the type of information they attend to at any 
given time. They may be persuaded by strong statements and may not have 
the time to ascertain accuracy of such information (Ref. 16).
    The proposed survey is designed to provide further insights about 
how professionally targeted prescription drug promotion might influence 
healthcare professionals' decision-making processes and practices and 
how information may be communicated more accurately. It is important to 
note that FDA does not regulate the practice of medicine. However, as 
previously mentioned, FDA does regulate prescription drug promotion. 
This survey is designed to inform FDA of various responses to and 
impacts of prescription drug promotion.
    The general research questions in the survey are as follows:
    1. What methods and/or channels are used to disseminate 
prescription drug promotional information to healthcare professionals/
prescribers?
    2. How knowledgeable and interested are HCPs in clinical trial data 
and design and its presence in prescription drug promotion?
    3. How familiar are HCPs with the FDA approval of prescription 
drugs and how does this affect prescribing behavior?
    In addition, given the critical problem with opioid abuse and 
addiction in the United States at this time, we plan to ask several 
questions about prescription drug promotion of opioid products.
    HCPs who fall into one of four categories will be recruited online 
through WebMD's Medscape subscriber network. We propose to complete 700 
primary care physician, 600 specialist, 350 nurse practitioner, and 350 
physician assistant surveys. HCPs will be included if they see patients 
at least 50 percent of the time. Both Doctors of Medicine and Doctors 
of Osteopathy will be included. Primary care physicians will include 
those who indicate they work in general, family, or internal medicine. 
Specialties were chosen based on prevalence in the United States and 
prescription drug promotional activity. Specialists will include 
cardiologists, dermatologists, endocrinologists, neurologists, 
obstetrician/gynecologists, oncologists, ophthalmologists, 
psychiatrists, rheumatologists, and urologists. The data will be 
weighted to adjust for differential coverage of select characteristics 
such as region and respondent age and gender. Pretesting with 25 
respondents will take place before the main study to evaluate the 
procedures and measures used in the main study.
    In the Federal Register of March 15, 2018 (83 FR 11539), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. Four comments were received. One comment was 
outside the scope of the research and is not addressed further. The 
remaining three comments are addressed below. For brevity, some public 
comments are paraphrased and therefore may not reflect the exact 
language used by the commenter. We assure commenters that the entirety 
of their comments was considered even if not fully captured by our 
paraphrasing in this document. The following acronyms are used here: 
DTC = direct-to-consumer; HCP = healthcare professional; FDA and ``The 
Agency'' = Food and Drug Administration; OPDP = FDA's Office of 
Prescription Drug Promotion.
    The first public comment had 19 individual comments, to which we 
have responded.
    (Comment 1a) The exact reach of the WebMD Medscape subscriber 
network among medical professionals is unclear. With this in mind, the 
study design could introduce bias by self-selecting physicians who do 
not accurately reflect the broader physician population. For example, 
they may be more reliant on internet-based information, have seen more 
web-based pharmaceutical advertisements, and be demographically 
different than physicians outside the Medscape network.
    (Response 1a) It is true that Medscape is not an exhaustive listing 
of the entire universe of HCPs, but the evidence suggests that coverage 
is high. Table 1 below documents the number of providers subscribed to 
WebMD for the four major strata of HCPs included in the study and the 
estimated population totals. The coverage is particularly good for 
primary care physicians (over 80 percent), is reasonable for 
specialists and physicians assistants (between 60 and 70 percent), and 
not as good for nurse practitioners (about 45 percent).

[[Page 8723]]



                     Table 1--Estimated Counts and Coverage by Healthcare Professional Group
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                                                                                     Estimated
                  Healthcare professional group                      WebMD \1\      population       Estimated
                                                                                       total        coverage %
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Primary care physicians (PCPs)..................................         197,980     \2\ 242,800            81.5
Specialists (SPs)...............................................         465,020     \2\ 724,249            64.2
Physicians assistants...........................................          62,874      \3\ 92,000            68.3
Nurse practitioners.............................................         102,552     \4\ 220,000            46.6
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\1\ WebMD estimated counts of Medscape subscribers by HCP group as of July 2017.
\2\ American Medical Association (https://www.mmslists.com/data/countspdf/AMA-SpecialtyByTOPS.pdf).
\3\ Kaiser Family Foundation (https://www.kff.org/other/state-indicator/total-physician-assistants/?currentTimeframe=0&sortModel=%7B%22colId%22:%22Location%22,%22sort%22:%22asc%22%7D).
\4\ American Association of Nurse Practitioners (https://www.aanp.org/all-about-nps/np-fact-sheet).

    The Medscape frame has a smaller frequency of out-of-scope records 
(retirees, for example, who have not been dropped from the list), and 
much better contact information (including email addresses), compared 
to other possible frames. Potential frame competitors, such as the 
American Medical Association list of providers, have higher coverage of 
PCPs and SPs, but also many out-of-scope records. Sampling these 
records would lead to ineligibles in data collection. Considering both 
coverage and ineligibility rates, Medscape is of better quality than 
the alternatives. We are planning to calibrate the weights for the 
sample providers who answer the questionnaire, using the National 
Ambulatory Medical Care Survey (NAMCS) estimates as benchmarks, based 
on gender, age, year of graduation, and practice size. Use of these 
calibrated weights will guarantee that the percentages across provider 
type, gender, age, year of graduation, and practice size match the 
NAMCS percentages, which are our best unbiased estimates of the true 
population percentages. Thus, the under-coverage from the use of the 
Medscape frame will not lead to significant imbalances in the 
distribution of these characteristics which could lead to bias. 
Calibration eliminates bias-producing imbalances for cells defined by 
the calibration characteristics, but does not eliminate imbalances 
within these cells. It may be the case that within the provider type-
gender-age-graduation year-practice size cells, the Medscape population 
differs from the universe because of their self-selection into 
Medscape. This will generate coverage biases of unknown magnitude, but 
we anticipate that the size of these biases will be small as a 
component of overall mean-squared-error in this study and will not 
materially affect the analyses.
    (Comment 1b) If specialties are planned to be analyzed 
individually, the sample size should be at least 50 respondents from 
each specialty.
    (Response 1b) Our analysis plan does not include a separate full-
scale analysis for each specialty, though specialty will be included in 
the analyses as a covariate along with other provider characteristics. 
Thus, the 50-respondent minimum per specialty is not necessary given 
the goals of this study.
    (Comment 1c) We did not have access to the full screening criteria 
and have several suggestions for the criteria: a mix of age, practice 
experience, practice setting, number of patients seen each month, and 
gender.
    (Response 1c) Our screening instrument captures the suggested 
items, including age, gender, race/ethnicity, practice setting, percent 
of time seeing patients, and clinical specialty. The survey instrument 
collects information on the number of patients seen weekly and number 
of years in practice.
    (Comment 1d) Q[uestion]2 currently asks how often physicians visit 
commercial prescription drug websites. This is a broad question, and we 
suggest adding followup questions to understand why the physician went 
to the website (i.e., interested in getting specific product 
information, patient assistance program information, etc.), what 
specific information was sought (i.e., promotional information, 
educational resources, patient support services, prescribing 
information) and how helpful was the information.
    (Response 1d) Prescription drug websites are one of several 
information sources that are asked about in the survey. The primary 
goal of our questions about sources of information is to capture the 
amount of exposure or use of various information sources by HCPs. This 
may be a good avenue for further research.
    (Comment 1e) Responses to Q3 could skew towards more frequent use 
than the average prescriber since the sample is being recruited from a 
network of physicians subscribing to a reference website (WebMD 
Medscape).
    (Response 1e) We acknowledge there may be a coverage bias from the 
use of the WebMD Medscape as a frame, but do not know exactly the 
magnitudes of bias for particular items. We will document the nature of 
our frame and the potential implications of that. See response to 
comment 1a for more details on WebMD sample.
    (Comment 1f) Q7a asks respondents to gauge the influence of various 
information sources on their colleagues' prescribing decisions. Q7b 
asks about the influence of various information sources on the 
respondent's prescribing decisions. Influence is subjective and 
respondent answers to these questions are inherently unreliable. We 
suggest asking about behavior to help understand influence. If these 
questions are retained, we suggest reordering the questions.
    (Response 1f) We are interested in HCPs' perceptions of relative 
influence of different information sources. An assessment of the actual 
influence of these sources through prescribing data is beyond the scope 
of this project. This is a valuable avenue for future research. 
Moreover, this question is designed to build on research literature 
which suggests that HCPs typically rate promotional materials as being 
more influential on colleagues than on themselves (Refs. 17 and 18). 
Thus, we ask about the influence of promotional information for both 
colleagues and the respondent. We will randomize the presentation order 
of these two questions in the survey.
    (Comment 1g) For Q9-Q10, questions and answer choices are overly 
broad to provide actionable insight. For example, respondents might 
define ``information about clinical trial designs or clinical trial 
outcomes'' differently, along with what ``Some'' versus ``Lots'' of 
information represent. We suggest revising Q9 to ``Do you need more 
clinical trial design information in order to understand or interpret 
the clinical

[[Page 8724]]

trial data and outcomes presented in promotional material?'' We suggest 
revising Q10 to ``Do you need more clinical trial outcomes information 
in order to make sound clinical decisions for your patients?''
    (Response 1g) We have made some changes to these questions as a 
result of cognitive testing. For example, we replaced ``clinical trial 
design'' with ``clinical trial methodology'' and included examples of 
what is meant by methodology in parenthesis (e.g., sample, study 
design). We also changed answer choices to make them more distinct. The 
choices are now: All information, a moderate amount, a minimal amount, 
and none.
    (Comment 1h) We suggest revising Q14 into two separate questions. 
One question about the type of training (e.g. formal school, continuing 
medical education, peers) and a separate question on how much training 
in different aspects of clinical trial design the respondent completed.
    (Response 1h) We are using the question about clinical trials 
training as a covariate to other questions in the survey about clinical 
trials. Training may influence the amount of clinical trials 
information HCPs want included in promotions or their level of comfort 
with clinical trials data. We have added the word ``formal'' to the 
question to indicate that we are referring to actual training rather 
than informal discussions with colleagues.
    (Comment 1i) Q18 assumes the physician knows whether the drugs 
prescribed are approved or not approved. We suggest including a 
selection of ``Do not know.''
    (Response 1i) We will add ``Do not know'' as a response option to 
this question.
    (Comment 1j) We have concerns that Q21 fails to define what the 
Agency means by ``promotion.'' As a result, the question as phrased may 
suggest that the Agency has broader authority than delegated by 
Congress or as permitted under the First Amendment to regulate (i.e., 
``allow'') protected manufacturer speech that is truthful and non-
misleading. We suggest revising Q21 to ask respondents if they value 
the ability of pharmaceutical companies to provide truthful and non-
misleading information about their drugs for indications not approved 
by FDA.
    (Response 1j) Q21 has been deleted.
    (Comment 1k) We agree that having an option of ``not sure'' for Q22 
is appropriate since many respondents might not be familiar with this 
approval pathway. However, this could reduce the amount of information 
this question could assess. We suggest modifying the question to 
incorporate the definition of accelerated approval and then ask the 
respondent about his/her comfort level with prescribing. This approach 
would allow the survey to collect responses from the most respondents 
possible. We also suggest adding a question prior to Q22 to ask about 
familiarity or experience with an accelerated approval drug that could 
be used to assess prior behavior as well as understand how experience 
with accelerated approval impacts comfort to use.
    (Response 1k) We have purposefully not included a definition of 
accelerated approval, as we are interested in assessing comfort with 
accelerated approval based on their own understanding of the term. We 
have added an open-ended question prior to Q22 that asks respondents to 
describe what an accelerated approval drug is in their own words.
    (Comment 1l) We recommend modifying the open-ended question (Q23) 
about scientific exchange and offering respondent components for 
consideration (i.e., criteria for who is part of exchange of 
information, description for type of scientific information, 
description of context of scientific information, and the forum or 
setting where exchange of information occurs). We also recommend adding 
question(s) to understand how often respondents engage in settings 
where scientific exchange typically occurs, such as oral presentations/
poster sessions at scientific congresses, review of articles in medical 
journals, data and clinical trial summaries on clinical trial 
registries.
    (Response 1l) The goal of this open-ended question is to assess 
general awareness/understanding of the term ``scientific exchange.'' In 
cognitive testing, we found that several HCPs had never heard this term 
before. Therefore, we need to get a broader sense of general awareness, 
which may be low, before following up with more specific questions. We 
have added the option to check ``do not know'' for this question.
    (Comment 1m) The open-ended question (Q24) seeking a description of 
biosimilars will likely result in an extremely wide range of answers 
with no ability to categorize responses based on the HCP's true 
knowledge of the term. We suggest framing the question along the lines 
of how comfortable the HCP is with prescribing biosimilars, therefore, 
the responses may help correlate knowledge of the term with a greater 
comfort level in prescribing.
    (Response 1m) The goal of this open-ended question is to assess HCP 
general awareness/knowledge of biosimilars. We have added the option to 
check ``do not know'' for this question. We also plan to code open-
ended responses to determine their level of closeness to the 
established definition: a biological product that is highly similar to 
and has no clinically meaningful differences from an existing FDA-
approved reference product (42 U.S.C. 262(i)(2)). We have also added a 
close-ended question prior to Q24 to ask HCPs how comfortable they are 
prescribing biosimilars.
    (Comment 1n) For Q25-26, we recommend including ``don't know'' or 
``it depends'' as answer options for these two questions.
    (Response 1n) While some cognitive effort is required, we believe 
the scenarios included in these questions provide sufficient 
information to allow respondents to make ratings. We also note that 
during cognitive testing, respondents did not have difficulty answering 
these questions.
    (Comment 1o) For Q28, we recommend incorporating a description or 
definition of ``REMS'' materials.
    (Response 1o) We have revised the question to spell out the term, 
Risk Evaluation or Mitigation Strategy (REMS) materials.
    (Comment 1p) For Q28a, we recommend a small modification to the 
question in order to fully capture and connect to the list from the 
previous question. For example, How often do these materials or events 
mention abuse potential?
    (Response 1p) We will revise the question to include ``events.''
    (Comment 1q) We suggest adding a followup question to Q27 and Q28 
to understand the impact of education/information about opioids on 
prescribing behaviors. For example, ``Is the number of patients you 
prescribed opioids for chronic pain in the last 3 months relative to 12 
months ago: (1) the same, (2) less or (3) more?''
    (Response 1q) We have added this question to the survey.
    (Comment 1r) We suggest an additional followup question to Q27 and 
Q28 to capture how the discussion and information on opioids and abuse 
potential has changed over recent years, rather than focusing only on 
the previous 12 months. Asking a retrospective question might capture 
how the type of information physicians receive has changed as the 
critical opioid situation has gained more widespread recognition.
    (Response 1r) The proposed followup question broadens the scope of 
the survey in a way that may prevent us from collecting the most 
relevant data. To capture the element of change in practice over time, 
as suggested, we

[[Page 8725]]

have added a question to ask HCPs whether in the last year the content 
of promotional materials for opioid products have contained more or 
less information on abuse potential.
    The second public comment responder had 13 comments, to which we 
have responded.
    (Comment 2a) The public comment responder expressed concern that 
they had difficulty obtaining the proposed survey questionnaire via 
email, but acknowledged that they were able to obtain it promptly once 
they contacted the telephone number provided in the 60-day notice. 
Among other suggestions, the commenter recommended that FDA specify a 
contact that can directly provide the survey in future notices.
    (Response 2a) We appreciate the commenter bringing their experience 
to our attention. While other commenters that requested the survey did 
not report that they experienced difficulty promptly obtaining the 
survey, we take this concern very seriously. Moving forward, in 
addition to the contact information that has been provided, we will 
also include the email address of the research team, 
DTCResearch@fda.hhs.gov, in all notices to facilitate obtaining 
information collection instruments directly from the research team.
    (Comment 2b) The proposed HCP survey is duplicative of other 
information already collected by FDA, such as the previous Healthcare 
Professional Survey of Prescription Drug Promotion (HCP I survey) and a 
project referenced on the OPDP website \1\ entitled, ``Clinical Trial 
Data in Professional Prescription Drug Promotion.''
---------------------------------------------------------------------------

    \1\ https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm090276.htm
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    (Response 2b) The HCP I survey was conducted 5 years ago (summer 
2013) and focused mainly on HCPs' attitudes toward DTC advertising and 
its role in their relationship with patients (Refs. 2, 3). The current 
HCP II survey focuses on promotions directed at healthcare 
professionals. The existence of some overlapping questions does not 
constitute in itself a duplicative effort, as there is often a need to 
compare responses at multiple time points for comprehensive analysis of 
the issues at hand. Many federally funded national surveys ask the same 
or similar questions at multiple time points to detect changes and 
identify trends over time.
    We also note the study referenced on the OPDP website is 
qualitative research with a small non-representative sample, so the 
design differs considerably from this proposed study. Having multiple 
studies focusing on differing aspects of a phenomenon, using differing 
designs and modes, is in accordance with OMB standards to avoid 
unnecessary duplication of research efforts.
    (Comment 2c) The commenter recommends that FDA ask questions about 
non-opioid analgesic options, medication-assisted treatment for opioid 
deterrence, and opioid overdose-reversal agents. By asking about this 
broader range of treatments, the survey would be consistent with the 
Administration's emphasis on the whole range of medical advances that 
can help address the opioid crisis.
    (Response 2c) We have added a question to address references to 
these medical advances in prescription drug promotion.
    (Comment 2d) We recommend that FDA amend Q1b to ask how closely 
HCPs read different types of advertisements (e.g., advertisement for 
new products, or for products related to the HCPs practice).
    (Response 2d) We have replaced Q1b with two questions to capture 
how closely HCPs read the suggested types of advertisements. One will 
ask about advertisements for new products and one will ask about 
advertisements for products related to the HCP's practice.
    (Comment 2e) We recommend that FDA reword Q2 to avoid the ambiguous 
term ``commercial.'' Specifically, we recommend FDA revise the question 
to read as follows: ``How often do you visit product-specific or 
manufacturer-sponsored commercial prescription drug product websites, 
such as lipitor.com?''
    (Response 2e) In cognitive testing conducted to develop this 
survey, the word ``commercial'' was easily understood by respondents 
and is needed in this question to differentiate it from ``reference'' 
websites in the subsequent question.
    (Comment 2f) We recommend that FDA include a new question under Q2 
(i.e., 2a) that is similar to 3b (i.e., that asks how closely the HCP 
usually reads the prescription drug websites it visits).
    (Response 2f) We have added this question.
    (Comment 2g) We recommend that FDA clarify whether Q5a applies only 
to in-person visits from pharmaceutical sales representatives.
    (Response 2g) During cognitive interviews, respondents had no 
difficulty understanding that question 5a was asking only about in-
person visits. However, we have revised the question to read, ``How 
often do pharmaceutical representatives bring promotional materials to 
your practice?'' to clarify that the question refers to in-person 
visits.
    (Comment 2h) We recommend that FDA delete responses 2 (``Lunch for 
staff'') and 7 (``Personal use item'') from Q5b. It is not clear how 
these topics relate to FDA's jurisdiction. Other agencies of the 
Department of Health and Human Services, not FDA, regulate such 
practices. In addition, these responses do not seem to fall within the 
stated scope of the survey.
    (Response 2h) We have made a minor change to this question by 
replacing ``lunch for staff'' with ``food and beverages.'' The survey 
includes questions about the various types of prescription drug 
promotions and promotional practices that HCPs might be exposed to. To 
fully understand promotional practices, we also need to know what 
pharmaceutical representatives provide HCPs during an in-person visit.
    (Comment 2i) We recommend that FDA clarify what is meant by the 
term ``conference'' in Q6.
    (Response 2i) We have revised the survey to ask separate questions 
about ``pharmaceutical dinner meetings'' and ``professional 
conferences.'' This distinction should make the meaning of professional 
conference clear.
    (Comment 2j) We recommend deleting Q7, as it asks HCPs to speculate 
about colleagues' perception of promotional materials.
    (Response 2j) This question is designed to build on research 
literature which suggests that HCPs typically rate promotional 
materials as being more influential on colleagues than on themselves 
(Refs. 17, 18). Thus, we ask about the influence of promotional 
information for both colleagues and the respondent. We will randomize 
the presentation order of these two questions in the survey.
    (Comment 2k) We recommend that response 3 for Q8 be amended to 
identify both the number and type of trials: ``Number and type of 
trials conducted.''
    (Response 2k) Including number and type of trials conducted as one 
response option will be confusing for respondents and we believe that 
type of trial is captured by the second response option: ``Study design 
(e.g., blinded or not, cohort study, length of trial, etc.).''
    (Comment 2l) We recommend adding the following language to Q18 to 
ensure consistent use throughout the survey: ``How often do you 
prescribe a drug for conditions for which it is not approved (referred 
to as unapproved use below)?'' We also recommend amending Q20 to use 
the term ``unapproved use'' instead of ``off-label use,'' to correspond 
with

[[Page 8726]]

question 19 and ensure consistent terminology throughout the survey.
    (Response 2l) We determined through cognitive testing that HCPs are 
familiar with and use the term off-label use. The questions have been 
revised to use ``off-label use'' for all three questions.
    (Comment 2m) We recommend deleting Q21, as HCPs perspectives on 
whether promotion of unapproved uses should be allowed presumes that 
HCPs know the existing regulatory framework. Moreover, the relevancy of 
this question is unclear given the stated research goals.
    (Response 2m) We have deleted this question.
    (Comment 2n) Q31 asks about the respondent's Secondary Specialty. 
However, it is not clear from the survey if and where Primary Specialty 
is recorded; we recommend amending the survey to clearly identify the 
respondent's Primary Specialty.
    (Response 2n) Primary specialty is asked in the screener. We have 
removed the question about ``secondary specialty'' from the survey.
    The third public comment responder had one comment, to which we 
have responded.
    (Comment 3a) We suggest adding questions to the survey about how 
promotional materials and procedures address abuse deterrent 
formulations (ADF) for opioid products. Specifically, we suggest adding 
questions related to the following topic areas to assess HCPs' 
knowledge and understanding of these areas:
     That ADF products have not proven any less addictive than 
standard non-ADF formulations.
     That the potential for patient harm from dose-dependent 
misuse of ADF products (e.g., adverse effects resulting from patients 
taking higher doses of the product than prescribed) or for patients 
that switch to non-prescribed drugs (e.g., heroin) still remains.
     That potential methods for defeating the ``tamper-proof'' 
formulation still exist.
     That there are effective ways to protect against 
accidental ingestion of the drug or theft by others.
    (Response 3a) We address the first bullet in question 28c. Various 
aspects of the remaining bullets are addressed in question 28d. 
Although the specific points mentioned in this comment are important 
public health messages, we think these questions are more appropriate 
for an indepth study of the topic, which is beyond the scope of this 
project. Please also see our responses to Comments 1r and 2c.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 2--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                 Number of
                  Activity                       Number of     responses per   Total annual           Average burden per response           Total hours
                                                respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Pretest Study:
    HCP screener............................              63               1              63  0.08 (5 minutes)..........................               5
    Informed Consent........................              25               1              25  0.08 (5 minutes)..........................               2
    HCP Survey..............................              25               1              25  0.33 (20 minutes).........................               8
Main Study:
    HCP screener............................           5,037               1           5,037  0.08 (5 minutes)..........................             403
    Informed Consent........................           2,000               1           2,000  0.08 (5 minutes)..........................             160
    HCP Survey..............................           2,000               1           2,000  0.33 (20 minutes).........................             660
                                             -----------------------------------------------------------------------------------------------------------
        Total...............................  ..............  ..............  ..............  ..........................................           1,238
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\1\ There are no capital costs and maintenance costs associated with this collection of information.

II. References

    The following references marked with an asterisk (*) are on display 
at the Dockets Management Staff, OC/Office of Executive Secretariat, 
Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, 
MD 20857 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. References without 
asterisks are not on public display at https://www.regulations.gov 
because they have copyright restrictions. 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. Available at: https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm090276.htm. Last accessed 
February 6, 2019.
2. Betts, K.R., A.C. O'Donoghue, K.J. Aikin, et al. (2016). 
``Healthcare Professional Social Media Membership and Participation: 
Findings From a Nationally Representative Sample,'' Journal of the 
American Association of Nurse Practitioners. Doi: 10.1002/2327-
6924.12383.
3. O'Donoghue, A.C., V. Boudewyns, K.J. Aikin, et al. (2015). 
``Awareness of FDA's Bad Ad Program and Education Regarding 
Pharmaceutical Advertising: A National Survey of Prescribers in 
Ambulatory Care Settings,'' Journal of Health Communication, vol. 
20(11), pp. 1330-1336.
4. Crigger, N.J. (2005). ``Pharmaceutical Promotions and Conflict of 
Interest in Nurse Practitioner's Decision Making: The Undiscovered 
Country,'' Journal of the American Academy of Nurse Practitioners, 
vol. 17(6), pp. 207-212.
5. Fischer, M. ., M.E. Keough, J.L. Baril, et al. (2009). 
``Prescribers and Pharmaceutical Representatives: Why Are We Still 
Meeting?'' Journal of General Internal Medicine, vol. 24(7), pp. 
795-801.
6. C. Robertson, S. Rose, and A.S. Kesselheim (2012). ``Effect of 
Financial Relationships on the Behaviors of Health Care 
Professionals: A Review of the Evidence,'' The Journal of Law, 
Medicine & Ethics, vol. 40(3), pp. 452-466.
7. Srivastava, V., M. Handa, and A. Vohra (2014). ``Promotional 
Tools: Do Physicians Really Bite the Hook?'' Drishtikon: A 
Management Journal, vol. 5(2).
8. Austad, K.E., J. Avorn, J.M. Franklin, et al. (2014). 
``Association of Marketing Interactions With Medical Trainees' 
Knowledge About Evidence-Based Prescribing: Results From a National 
Survey,'' JAMA Internal Medicine, vol. 174(8), pp. 1283-1290.
*9. Cegedim Strategic Data (2013). ``2012 U.S. Pharmaceutical 
Company Promotion Spending.'' Available at: https://www.skainfo.com/health_care_market_reports/2012_promotional_spending.pdf.
10. Spurling, G.K., P.R. Mansfield, B.D. Montgomery, et al. (2010). 
``Information From Pharmaceutical Companies and the Quality, 
Quantity, and Cost of Physicians' Prescribing: A Systematic 
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11. Villanueva, P., S. Peir[oacute], J. Librero, et al. (2003). 
``Accuracy of Pharmaceutical Advertisements in Medical Journals,'' 
Lancet, vol. 361(9351), pp. 27-32.
12. Cooper, R.J. and D.L. Schriger (2005). ``The Availability of 
References and the Sponsorship of Original Research Cited in 
Pharmaceutical Advertisements,'' Canadian Medical Association 
Journal, vol. 172(4), pp. 487-491.
13. Jureidini, J.N., L.B. McHenry, and P.R. Mansfield (2008). 
``Clinical Trials and Drug Promotion: Selective Reporting of Study 
329,'' International Journal of Risk & Safety in Medicine, vol. 
20(1-2), pp. 73-81.
14. Garcia-Retamero, R. and M. Galesic (2010). ``Who Profits From 
Visual Aids: Overcoming Challenges in People's Understanding of 
Risks,'' Social Science & Medicine, vol. 70(7), pp. 1019-1025.
15. Cooper, R.J., D.L. Schriger, R.C. Wallace, et al. (2003). ``The 
Quantity and Quality of Scientific Graphs in Pharmaceutical 
Advertisements,'' Journal of General Internal Medicine, vol. 18(4), 
pp. 294-297.
16. Sah, S. and A. Fugh-Berman (2013). ``Physicians Under the 
Influence: Social Psychology and Industry Marketing Strategies,'' 
The Journal of Law, Medicine & Ethics, vol. 41(3), pp. 665-672. doi: 
10.1111/jlme.12076.
17. Carroll, A.E., R.C. Vreeman, J. Buddenbaum, et al. (2007). ``To 
What Extent Do Educational Interventions Impact Medical Trainees' 
Attitudes and Behaviors Regarding Industry Trainee and Industry-
Physician Relationships?'' Pediatrics, 120, e1528-e1535. 
doi:10.1542/peds.2007-0363.
18. Crigger, N., K. Barnes, A. Junko, et al. (2009). ``Nurse 
Practitioners' Perceptions and Participation in Pharmaceutical 
Marketing,'' Journal of Advanced Nursing, 65, 525-533. doi: 10.1111/
j.1365-2648.2008.04911.x.

    Dated: March 5, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019-04307 Filed 3-8-19; 8:45 am]
 BILLING CODE 4164-01-P


