Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Healthcare Provider Perception of Boxed Warning Information Survey
| Published date | 06 July 2020 |
| Citation | 85 FR 40292 |
| Record Number | 2020-14377 |
| Section | Notices |
| Court | Food And Drug Administration |
Federal Register, Volume 85 Issue 129 (Monday, July 6, 2020)
[Federal Register Volume 85, Number 129 (Monday, July 6, 2020)]
[Notices]
[Pages 40292-40296]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-14377]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2019-N-3018]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Healthcare Provider
Perception of Boxed Warning Information Survey
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or we) 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 August 5, 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
Comment'' or by using the search function. The title of this
information collection is ``Healthcare Provider Perception of Boxed
Warning Information Survey.'' 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,
[email protected].
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 Provider Perception of Boxed Warning Information Survey
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.
The proposed collection of information will investigate healthcare
providers' (HCPs') awareness, perceptions, and beliefs about the
benefits and risks of an FDA-approved product that carries a boxed
warning. The prescribing information for an FDA-approved drug or
biologic (sometimes
[[Page 40293]]
referred to as the ``PI'', ``package insert'', or ``prescription drug
labeling'') provides a summary of the essential information needed for
the safe and effective use of that medication, described in FDA
guidance entitled ``Warnings and Precautions, Contraindications, and
Boxed Warning Sections of Labeling for Human Prescription Drug and
Biologic Products--Content and Format,'' published in October 2011
(https://www.fda.gov/media/71866/download). In certain situations, a
drug's prescribing information may include a boxed warning in addition
to other sections of the labeling to highlight important safety
information about specific serious risks of that drug. Boxed warning
information may be included as part of prescribing information at the
time of FDA approval. Boxed warning information may also be added or
modified to the prescribing information of drugs already on the market
on the basis of new safety information.
Boxed warnings are an important and frequently used communication
tool. A review of literature has suggested that the addition or
modification of boxed warning information in the postmarket setting
(after a drug has been approved) has had varying effects on HCPs'
practices regarding prescribing, dosing, and patient monitoring (Ref.
1). However, this review and others have identified several gaps in the
existing literature, including the limited number of drugs or drug
classes studied (Ref. 2). Further, little research has focused on
understanding how HCPs receive, process, and use boxed warning
information to support their treatment decisions and patient
counseling.
To address this research gap, we propose conducting a web-based
survey of HCPs. The proposed collection of information will strengthen
FDA's understanding of how HCPs may receive, process, and use boxed
warning and other safety labeling information. This survey will be
conducted as part of a mixed methods research approach to explore HCPs'
beliefs (or ``mental models'') about the benefits and risks of a drug
that carries a boxed warning and how the drug's boxed warning
information may influence their communication with patients, their
treatment decisions and related decisions such as prescreening for risk
factors or monitoring for adverse events (Ref. 3). This survey research
will build upon preliminary qualitative research FDA has conducted,
under OMB control number 0910-0695, with HCPs in this target
population, through indepth individual interviews.
The general research questions in this data collection are as
follows:
1. What awareness, knowledge, and beliefs do HCPs have regarding boxed
warning information for a prescription drug or class of drugs?
2. When making prescribing decisions, how do HCPs consider boxed
warning information about a potential treatment? How does boxed warning
information factor into their assessments of a drug's potential
benefits and risks to their patients?
3. How do HCPs communicate with their patients about boxed warning
information?
4. What factors (e.g., experience treating a condition) are associated
with HCPs' awareness, knowledge, and beliefs about boxed warning
information?
In order to explore a range of potential perceptions and uses of
boxed warning information that may exist under different contexts, this
survey research will evaluate two medical product scenarios involving
an FDA-approved medication or class of medications that include boxed
warning information. The scenarios will include pertinent prescribing
information from the FDA-approved labeling for these medications. We
plan to conduct one pretest survey with 50 voluntary participants and
one main survey with 1,156 voluntary participants. The survey will be
conducted online. Survey response is estimated to take no longer than
20 minutes.
Participants in the pretest survey and main survey will be
recruited online through a web-based HCP survey research panel.
Participants will be HCPs with prescribing authority who prescribe
medications to treat one of medical conditions in the medical product
scenarios. Participants will include primary care providers (including
internal medicine, family medicine, and general medicine, as well as
nurse practitioners, and physician assistants) and relevant medical
specialists. Participants will be screened for their current amount of
time spent in direct patient care, prescribing volume, and experience
treating the relevant medical condition. Demographic soft quotas will
be used to help ensure that the survey population is generally
reflective of the demographic composition of physicians in the United
States, according to the American Medical Association.
The pretest and main studies will have the same design and will
follow the same procedure. In advance of the pretest survey, we will
conduct cognitive testing of the survey questionnaire to refine the
survey instruments. The main survey will be refined as necessary
following the pretest survey.
In the Federal Register of August 8, 2019 (84 FR 38996), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. FDA received three comments that were PRA
related. Below is a response to each of the commenters' questions. For
brevity, some public comments are paraphrased and therefore may not
reflect the exact language used by the commenter. The entirety of the
public comments was considered even if not fully captured by our
paraphrasing in this document.
(Comment 1) The first public comment ``agrees with the data
collection,'' but finds the intent of the data collection unclear and
expresses concern that ``the data will be collecting in the survey will
be used adversarially [sic] [against providers]''. The commenter
described experiences ``as a healthcare provider, [battling] daily with
both ends of the spectrum,'' including patients who want a ``brand new
drug'' even though it will likely provide little therapeutic benefit,
as well as patients who would benefit from a product but ``adamantly
refuse based on a [boxed warning].'' The commenter further stated that
``As a provider, I can present the information I have at hand, but how
do I combat new information that is identified specifically, a [boxed
warning] post prescribing a new medication?''
(Response 1) FDA appreciates the commenter's experience, which is
relevant to the research question that the proposed data collection is
intended to inform: how HCPs consider boxed warning information when
making treatment decisions and how they communicate boxed warning
information to their patients. As described in Section A.2, the intent
of the data collection to better understand the range of HCPs'
experiences and informational needs regarding boxed warning
information.
(Comment 2) The second public comment expressed concern regarding
how ``[a] voluntary commitment to participating in a professional
assessment survey demonstrates some level engagement and awareness [and
therefore this] survey will assess an already engaged section of
providers, potentially skewing the data.''
(Response 2) In accordance with the requirements set forth by
institutional review boards and OMB, any research must involve
voluntary participation of research participants. FDA acknowledges
there may be a coverage
[[Page 40294]]
bias from the use of an opt-in web panel as a sample frame (i.e., HCPs
who choose to be part of a research panel may differ from HCPs who do
not choose to be part of a research panels). As a basic check, in our
analysis of the study findings, we will compare the demographic
characteristics of the population of survey respondents to the
population of U.S. prescribers within the relevant medical specialties.
We will document the nature and limitations of our sampling frame and
the potential implications of that on the interpretation of the
research findings.
(Comment 3) The third public comment comprised 2 overarching
comments (3a and 3b below) and 13 additional (3c to 3p) comments on
individual items on the questionnaire, to which we have responded
below.
(Comment 3a) We recommend considering two different ``archetypes''
for the medical product scenarios to gain insight on different
situations. Consideration should be given to a drug/class with specific
risk factors identified in a BW [boxed warning], a drug/class launched
with a BW, or drug/class with a BW that was established post approval.
(Response 3a) FDA agrees with the importance of capturing different
archetypes (e.g., characteristics or features) of the medical scenario
and of the boxed warning. The identified scenarios, vaginal inserts to
treat vulvo-vaginal atrophy (VVA) in post-menopausal women and direct-
acting antivirals to treat chronic hepatitis C viral (HCV) infection
were identified because they differ along some important
characteristics. These characteristics include seriousness of
condition, characteristics of the safety concerns, length and nature of
the boxed warning information, and length of time since the boxed
warning was included.
(Comment 3b): We also recommend that FDA consider additional study
designs such as retrospective analysis on prescribing habits. Data
could be collected on prescribing habits of medications before and
after inclusion of a BW in labeling. This study could be used as a
complementary evaluation on the understanding the impact of BW.
(Response 3b): FDA agrees that there is value in complementary
research approaches using the same scenarios and appreciate the
suggestion. We will explore the feasibility of undertaking a related
outcomes-focused study looking at prescribing behaviors in future
studies.
(Comment 3c): In an effort to streamline the questionnaire, [we]
recommend considering the removal of [Question 1] and relying on
Questions 2 to 6 to assess the level of experience.
(Response 3c): FDA appreciates feedback suggesting opportunities to
streamline the questionnaire, and we have considered appropriate ways
to streamline. Q1 elicits a self-assessment of their level of
experience treating the scenario condition, which provides very
important context for understanding HCPs' perceptions. This concept is
distinct from concepts elicited in Q2 to 6. For example, a self-
assessment of experience with a condition may not be associated with
the number of patients the HCP currently sees.
(Comment 3d): [We] recommend consolidating Q5 and Q6 into a single
question. . . [and] including the drug of interest in the list of
options [and] adjusting the [choice] selections so that they become
mutually exclusive. [We] would further recommend screening out
physicians from taking remainder of the survey that do not prescribe
drugs with BW based on their responses to Q4 to 6.
(Response 3d): In the questionnaire draft that the commenter
reviewed, Q5 asks respondents how often they prescribe the scenario
drug and Q6 ask how often they prescribe a number of other types of
products that FDA believes providers may be using to treat the
condition. In the revised questionnaire (now Q4 and Q5), we keep the
two questions as separate, but we have greatly simplified the latter
(now Q5) so that it does not elicit prescribing rates, but rather asks
respondents to indicate which treatments they have used in a typical
month. The elicitation of the frequency (``a few times per month, a few
times a year, etc.'') is important with respect to the scenario drug.
We have modified the response items to be mutually exclusive.
Potential participants are screened based on their experience with
treating each of the medical conditions, but not based on their
prescribing behavior regarding any the particular product. For the
purposes of this research, exclusion due to not prescribing the
specific product with the boxed warning is not appropriate, as long as
the healthcare provide meets the other criteria. If, for example, a
provider chooses categorically not to prescribe a particular product
that has a boxed warning, it could be driven in part by his or her
perception of the boxed warning information. We are still interested in
this prescriber's perception of the benefits and risks of the scenario
product.
(Comment 3e): There may be a need to differentiate HCPs who
initiate vs. those that refill, therefore [we] recommend including a
question to ask what % of prescriptions are initiated vs. refill.
(Response 3e): FDA agrees that there may be a need to differentiate
HCPs who initiate vs. those who only prescribe refills for the scenario
drug. The revised questionnaire (question 4a) now allows
differentiation between HCPs who initiate prescriptions versus HCPs who
have only prescribed a refill for the scenario drug.
(Comment 3f): The description of patient and condition will likely
influence the responses and the physicians' consideration of the BW.
[We] recommend taking into consideration where the patient is in the
treatment journey and where the drug with the BW is in the treatment
algorithm. The instructions also imply that this treatment must only be
prescribed to females. If the treatment is not limited to females [we]
recommend modifying the instructions to be more general neutral.
(Response 3f): Where the patient is in the treatment journey and
where the treatment is within the treatment algorithm are important
concepts. The descriptions of the patient and condition in the revised
questionnaire [preceding Q6] identify where the patient is in the
journey, and the scenarios were constructed such that the scenario drug
with the BW would be considered a commonly considered treatment option
for patients who fit the patient description. One of the scenarios
[estrogens to treat VVA] is only applicable to females. The patient
description in the HCV scenario questionnaire has been modified to be
gender neutral and to apply to patients in general that the responder
sees, not a specific patient.
(Comment 3g): [We] recommend asking an additional question after Q7
and 8 to assess reasoning by respondent. This approach can provide an
initial indicator of unaided awareness and impact of BW for HCPs. For
example, [we] propose: ``what are your safety concerns when considering
[drug] for patients [open end].''
(Response 3g): FDA agrees that eliciting this type of information
from respondents is very important. The questionnaire includes a very
similar open-ended question [Q11 in the revised questionnaire] to
elicit the potential rare but serious side effects that the respondent
discusses with patients. In an attempt to minimize respondent burden,
we therefore did not add the suggested questions because it would be
redundant.
(Comment 3h): A physician's response may be dependent on the
[[Page 40295]]
condition and the contributions of symptoms to the condition. [We]
request rational for inclusion of Q9 to 11 on earlier phase of
condition and Q7 to 8 related to more specific patient and condition
descriptions.
(Response 3h): In the questionnaire draft that the commenter
reviewed included two descriptions. The first description referenced an
individual patient with specific characteristics of relevance to the
prescribing scenario. With the second description, respondents were
asked to think about a broader patient population. Based on the
commenter's feedback as well as the results of the cognitive
interviewing, we have revised the scenario description to have a single
prototypical description of a population of patients of relevance to
the prescribing scenario. For example, the scenario used for the VVA
questionnaire states: ``For the next few questions, we would like you
to consider your patients who are postmenopausal women complaining of
symptoms such as vaginal itching and discomfort or pain during
intercourse. They have previously tried over-the-counter ointments with
little success.''
(Comment 3i): [Regarding Q12] Because risk/benefit considerations
will likely be a key factor in deciding whether to prescribe the drug,
[we] recommend including risk/benefit as a possible selection. Relevant
for inclusion of the selection ``This patient's preference about mode
of administration'' will be depending on the available treatment
options for condition selected. [We] recommend adding an option in Q12
of ``other (specify)'' instead of including Q12OTH as a separate
question. This approach will enable respondents to rank another option.
(Response 3i): FDA agrees that risk/benefit is a critical
assessment and factor into HCPs' decisions whether to prescribe a drug,
and there are multiple questions in the questionnaire designed to get
at this overarching judgment of the respondent. In the questionnaire
draft that the commenter reviewed, Q12 (Question 11 in the revised
questionnaire) asks respondents to indicate the specific factors that
play the most important role when deciding whether or not to prescribe
the scenario drug. These factors include separate considerations on
both the risks and benefits, such as ``patient's understanding of and
comfort with the risks of this medication'' and medical history as part
of ``patient's medical and health context.'' We did not include a risk/
benefit as an option because that would be redundant. We did, however,
address the commenter's recommendation about Q12OTH (a question to
allow for the respondent to identify other factors). Question 11 in the
revised questionnaire now includes an option: ``other (please
specify)'', rather than asking it as a separate question. Should the
survey respondent feel that we left out risk/benefit assessment as a
separate factor, they may input this in the ``other (specify)'' field.
(Comment 3j): [Regarding Q12l] [We] recommend inclusion of a
description of the specific risks in BW instead of the proposed option
``risks outlined in the boxed warning.''
(Response 3j): FDA believes the commenter meant to reference
Question 15l. In the questionnaire draft that the commenter reviewed,
question 15l asks respondents to indicate specific risks (multiple
choice) they discuss with the patient about the product. In the revised
question, we modified this to an open-ended question, intentionally
designed to elicit spontaneous response about the rare but serious side
effects that they discus. Further on in the survey is a specific recall
question asking respondents to identify the risks (multiple choice)
they recall being discussed in the boxed warning for the specific
product.
(Comment 3k): [We] recommend moving Question 17 and 18 to the end
of the survey, as they seem less important than the following questions
19-22.
(Response 3k): In the questionnaire draft that the commenter
reviewed, Q17 and Q18 ask respondents to indicate where they typically
look for information about the scenario drug or other similar products
(medical journals, search engines, etc.). In the revised draft, we have
simplified Q17 and Q18 into a single question (now Q15). In light of
this comment, we considered other placements for this question. We
believe placement of this question is justified as the last question
respondents' answer regarding their overall perceptions regarding the
scenario drug before they move to focusing their attention on the boxed
warning information specifically. We could not determine a better place
later in the questionnaire to include this question because it would
require the respondent to go back to thinking broadly about information
sources.
(Comment 3l): Consider moving this general perception question 19
about BW earlier in the survey.
(Response 3l): The placement of this question is deliberate. In the
questionnaire draft that the commenter reviewed, Q19 ask respondents
their opinion of the primary role of a boxed warning (e.g., ``to
highlight the most serious potential risks of the product; to disclose
clinical trial and other product safety testing information.''). This
questionnaire has been specifically designed to not prime respondents
to think about boxed warnings at the start of the questionnaire. We do
not disclose that the scenario product carries a boxed warning, nor
does it elicit respondents' perception of boxed warnings until they
have provided their overall perceptions of the safety and benefit-risk
profile of the scenario product. The intent is to generate and see if
concerns about the information relayed in the boxed warning
spontaneously arises. The first mention of boxed warning appears
immediately before Q19 (now Q16 in the revised questionnaire): ``The
next questions refers to the boxed warning information on the product
labeling for [drug].'' Because of this, we have left the question as is
in the revised questionnaire.
(Comment 3m): Assuming the drug with the BW referenced in the rest
of the survey is the BW explicitly shown at this point in the survey,
[we] recommend not allowing respondents to go back to ``correct''
previous answers.
(Response 3m): FDA agrees with the commenter's suggestion, and we
have set the programming language of the web-based questionnaire to not
allow respondents to go back and change their answers.
(Comment 3n): Please provide rationale for the relevance of asking
Question 28_H.
(Response 3n): In the questionnaire draft that the commenter
reviewed, Q28_H asks respondents to provide their estimate of how many
prescription drugs they think carry a boxed warning. The question has
less relevance compared to other questions in the questionnaire, and it
did not add value in the cognitive interviews. Therefore, to address
this comment, we excluded the question in the revised questionnaire.
(Comment 3o): Assessing ``favorability'' of a BW is an awkward
question. Recommend revising Q29 to an agreement statement. For
example, ``BW provides important information to me.'' If Question 29 is
revised, then recommend removing Q30.
(Response 3o): In the questionnaire draft that the commenter
reviewed, Q29 asks the respondent to rate how favorable their opinion
is of boxed warnings in general. This question is intended to provide
an overall assessment of boxed warnings. The question was not confusing
to participants in the cognitive interviews. In addition, another
question (Q23 in
[[Page 40296]]
the revised questionnaire) asks level-of-agreement questions very
similar to the type of question the commenter proposes (e.g., ``I
counsel my patients differently when prescribing a product with a boxed
warning.''). The revised questionnaire, however, excludes the open-
ended Q30 in the revised questionnaire, in an effort to streamline the
survey and reduce respondent burden.
(Comment 3p): [We] recommend adding an option ``I'm not sure/I
don't know/I'm not familiar'' to Questions 2, 3, 4, 7, 8, 12, 14, 15,
23, 24, 25, 28, 29.
(Response 3p): FDA reviewed the survey and added an Unsure/Don't
know option where we deemed appropriate: Qs 2, 3, 4, 28, 29. Questions
8 and 25 were removed. Q23 has an ``Other (specify)'' option where
participants can elaborate if they are unable to choose an answer. For
certain key questions that elicits respondents' opinions (Qs 7, 12, 14,
15, 24), we did not add Unsure/Don't know in order to encourage them to
thoughtfully pick an answer. However, participants can proceed through
the questions without providing an answer, if they wish.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of
Activity Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
----------------------------------------------------------------------------------------------------------------
Pretest Screener.............. 84 1 84 0.05 (3 minutes) 4
Pretest Informed Consent...... 50 1 50 0.05 (3 minutes) 2
Pretest Survey Completes...... 50 1 50 0.28 (17 14
minutes).
Main Survey Screener.......... 1,927 1 1,927 0.05 (3 minutes) 96
Main Survey Informed Consent.. 1,156 1 1,156 0.05 (3 minutes) 58
Main Survey Completes......... 1,156 1 1,156 0.28 (17 324
minutes).
---------------------------------------------------------------------------------
Total..................... 4,423 .............. .............. ................ 498
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
II. References
The following references are on display with the Dockets Management
(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 are not
available electronically at https://www.regulations.gov as these
references are copyright protected.
1. Dusetzina, S.B., A.S. Higashi, E.R. Dorsey, et al., ``Impact of
FDA Drug Risk Communications on Health Care Utilization and Health
Behaviors: A Systematic Review.'' Medical Care, 50(6):466-478, 2012.
2. Briesacher, B.A., S.B. Soumerai, F. Zhang, et al., ``A Critical
Review of Methods to Evaluate the Impact of FDA Regulatory
Actions.'' Pharmacoepidemiology Drug and Safety, 22(9):986-994,
2013.
3. Morgan, M.G., et al., Risk Communication: A Mental Models
Approach. Cambridge University Press, 2002.
Dated: June 29, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-14377 Filed 7-2-20; 8:45 am]
BILLING CODE 4164-01-P
