[Federal Register Volume 80, Number 93 (Thursday, May 14, 2015)]
[Notices]
[Pages 27691-27694]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-11623]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-N-1491]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Survey of Pharmacists 
and Patients; Variations in the Physical Characteristics of Generic 
Drug Pills and Patients' Perceptions

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 June 
15, 2015.

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 [email protected]. All 
comments should be identified with the OMB control number 0910-New and 
title ``Survey of Pharmacists and Patients; Variations in the Physical 
Characteristics of Generic Drug Pills and Patients' Perceptions.'' Also 
include the FDA docket number found in brackets in the heading of this 
document.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver 
Spring, MD 20993-0002, [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.

Survey of Pharmacists and Patients; Variations in the Physical 
Characteristics of Generic Drug Pills and Patients' Perceptions (OMB 
Control No. 0910--NEW)

    Generic drugs make up approximately 85 percent of all human 
prescription drugs prescribed in the United States. While generic drugs 
are required to be pharmaceutically equivalent and bioequivalent to 
their brand-name counterparts, generics made by different manufacturers 
may differ substantially from their brand-name therapeutic equivalents 
and from each other in their physical appearance (e.g., color, shape, 
or size of pills). When pharmacists switch generic drug suppliers, 
patients refilling their generic prescriptions may therefore experience 
changes in their drugs' appearances. These changes may result in 
patient confusion and concerns about the safety and effectiveness of 
the generic drug products. Studies indicate that patients are more 
likely to stop taking their generic medications when they experience a 
change in their drugs' physical appearances, leading to harmful 
clinical and public health consequences as well as increased health 
care costs from avoidable morbidity and mortality.
    To provide additional information that may help guide regulatory 
policy or pharmacy business practices, we intend to conduct surveys of 
pharmacists and patients about their perceptions about and experiences 
with generic drug product pill appearance change. These surveys are 
intended to further our understanding of the relationship between 
changes in pill appearance and non-adherence to prescribed therapeutic 
regimens. The surveys may enable us to investigate factors that may 
explain the association between changes in pill

[[Page 27692]]

appearance and non-adherence, including which factors could be modified 
to improve the safe and effective use of generic drugs.
    We intend to survey a national cohort of pharmacists about their 
experiences with dispensing generic drug pills that differ in 
appearance from previous refills of the same medication and dosage 
level (e.g., when pharmacies switch generic suppliers). A stratified, 
random sample of U.S.-licensed pharmacists will be obtained based on a 
master list from KM Lists. The target sample includes pharmacists with 
active licenses who practice in traditional community pharmacy settings 
and will be proportionally allocated across the U.S. in relation to the 
number of pharmacists in each state. Based on an 11 percent 
undeliverable rate and a 52 percent response rate, 2,161 questionnaires 
will be mailed to pharmacists to obtain the 1,000 responses required 
for adequate statistical power. The pharmacists' survey will consist of 
a mailed questionnaire rather than a telephone survey or an email 
survey. Prior experience conducting surveys has shown that it is easier 
to guarantee respondent anonymity using an impersonal, mailed 
questionnaire with no individual identifying information. The 
pharmacists will be asked about the frequency with which their pharmacy 
changes suppliers that lead to variations in the appearance of the 
generic drugs that they dispense, as well as strategies they use with 
patients to address the transition to pills that have a different 
appearance (e.g., alert stickers on pill bottles, verbal warnings, and 
other strategies). They will also be asked about patient responses to 
changes in pill appearance, including what types of appearance changes 
seem to affect patients most often (shape/color/size), how often 
patients report confusion about pill appearance, and how often patients 
ultimately refuse to accept the new product. Participation is expected 
to take approximately 20 minutes.
    We also intend to survey two different patient samples using two 
methodologies. The first is a telephone survey of patients who are 50 
years and older and who take one or more generic medications for at 
least one of the following chronic conditions: Epilepsy, diabetes, 
hypertension, hyperlipidemia, depression, and HIV. The telephone survey 
will be generalizable and will consist of well-defined methods to 
minimize sampling bias such as use of random phone numbers for both 
landlines and mobile phones, as well as small-batch sampling to ensure 
a high response rate that meets demographic diversity goals. For the 
second patient survey, patients will be selected from a proprietary 
research database of commercially insured patients containing medical 
and pharmacy claims linked to health insurance enrollment information. 
A nationally representative sample of patients with at least one 
chronic condition and who experienced a change in physical appearance 
of a generic pill will be identified by the research team using medical 
and pharmacy claims data. Both patient surveys will consist of 
questions covering topics similar to those asked in the survey of 
pharmacists and is intended to provide answers to the same topic areas 
from patients' perspectives. As before, topic areas will include 
beliefs about generic drugs, outcomes related to changes in generic 
drug pill appearance, and strategies used by pharmacists or doctors to 
alert patients to the possibility of changes in appearance. 
Participation is expected to take approximately 20 minutes.
    In the Federal Register of October 15, 2014 (79 FR 61872), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. Comments submitted raised several issues 
pertaining to the proposed collection of information. We summarize the 
comments and provide our responses below:
    (Comment 1) Two comments expressed concerns related to trade dress 
protection issues, noting that the requirement that generic products 
differ in appearance from the Reference Listed Drug is well established 
in case law. A pill's physical appearance can qualify as trade dress, 
protected under the Lanham Act (Pub. L. 79-489), which functions to 
distinguish between products from different manufacturers. A drug's 
physical appearance can also be considered a protected form of non-
verbal expression under the First Amendment. If required to change the 
appearance of their medications, the generic industry would face 
additional development costs.
    (Response) The purpose of these surveys is to gather information on 
the awareness of patients and pharmacists about changes in the 
appearance of medications, the frequency with which changes in 
appearance occurs, strategies that pharmacists use to inform patients 
when the appearance of their medications changes, and the outcomes 
associated with these strategies. The results of the surveys will be 
used to inform the development of patient education about differences 
in pill appearance and inform the development of education for 
pharmacists on strategies to counsel patients when the appearance of 
their medications changes. The purpose of these surveys is not to 
reverse existing legal precedents, require the generic drug industry 
change the appearance of their medications, or support the infringement 
of intellectual property, First Amendment, or any other legally 
protected interests.
    (Comment 2) One comment mentioned that the term ``pill'' is used in 
the Federal Register notice to describe oral solid dosage forms such as 
tablets and capsules, but is defined by Merriam-Webster much more 
narrowly to exclude tablets and capsules, which has the potential to 
create confusion.
    (Response) Because the FR notice is seeking opinions from the 
public, we used language accessible to the general public. To avoid 
confusion, the word ``pill'' is defined in the introduction of each 
survey instrument to clarify its meaning, with the statement that the 
word ``pill'' includes both tablet and capsule dosage forms.
    (Comment 3) One comment mentioned that the survey findings may be 
used by FDA to guide pharmacy business practice, which is the 
jurisdiction of the State Boards of Pharmacy.
    (Response) As stated earlier, the purpose of these surveys is to 
gather information on the awareness of patients about changes in the 
appearance of their medications, the frequency with which changes in 
appearance occurs, strategies that pharmacists use to inform patients 
when the appearance of their medications changes, and the outcomes 
associated with these strategies. The results of the surveys will be 
used to inform the development of patient education about differences 
in pill appearance and inform the development of education for 
pharmacists on strategies to counsel patients when the appearance of 
their medications changes. FDA does not intend to, itself, guide 
pharmacy business practices.
    (Comment 4) One comment expressed concern that confidential patient 
information from an insurance database will be identified and shared 
with Federal Government employees, which may violate HIPAA regulations.
    (Response) These surveys received approval from the Institutional 
Review Board (IRB) at the academic medical center where the survey is 
being conducted, which was accepted by FDA's IRB (Research In Human 
Subject Committee). IRB approval ensures compliance with human 
subjects' protection laws, including HIPAA. No FDA personnel will have 
access to any identifiable patient information.

[[Page 27693]]

    (Comment 5) One comment suggested that instead of conducting the 
study, FDA should data mine an internal source of data (product 
complaints received from pharmaceutical companies, healthcare 
providers, and consumers) to gather information on potential confusion 
and medication mistakes.
    (Response) The proposed study focuses on patient and pharmacist 
experiences and outcomes associated with changes in pill appearance, a 
topic of which patient confusion and medication mistakes are only a 
part. Although some medication mistakes and patient confusion data may 
be captured in our internal database (FDA's Adverse Event Reporting 
System), the specific data sought from the proposed study do not exist 
in this database.
    (Comment 6) One comment suggested that if the information on 
potential confusion and medication mistakes cannot be found in current 
databases, FDA should request that pharmacy school students conduct 
this study and publish results in a peer-reviewed journal to assure 
transparency and reduce government spending.
    (Response) High-quality surveys require substantial resources that 
would likely not be available to pharmacy students for class projects. 
These surveys are being conducted by an academic medical institution 
that has expertise in conducting surveys of patients and health care 
providers, which will provide high-quality and valid data and assure 
transparency. The results will be published in a peer-reviewed 
journal(s) and will be made publicly available.
    (Comment 7) One comment mentioned that these surveys will collect 
data on pharmacist and patient perceptions, which may not correlate to 
actual use data and thus may not provide meaningful information on safe 
and effective use of generic drugs or yield substantial evidence to 
support adoption of any regulatory policies. The comment noted that 
further investigations will be needed to understand how pharmacist and 
patient perceptions translate to actual practices and effects, and 
encouraged FDA to consider comments to Docket No. 2013-N-1434 in 
considering what further work will be needed and the level of evidence 
needed to support any regulatory policy changes.
    (Response) These surveys include questions on patient and 
pharmacist perceptions, as well as their actual experiences and 
behaviors as they relate to generic drugs and changes in drug 
appearance. The survey findings will be used to inform the development 
of patient education about differences in pill appearance and inform 
the development of education for pharmacists on strategies to counsel 
patients when the appearance of their medications changes.
    (Comment 8) One comment noted that if this study is conducted, the 
surveys should be carefully crafted to collect useful data using 
validated, well-developed methodology and assumptions. The comment 
requested the opportunity to review the proposed surveys and to submit 
additional survey questions.
    (Response) Well-established survey methods are being used in the 
development and conducting of this survey. The survey questions were 
carefully crafted according to published guidelines for survey question 
development (Refs. 1 & 2) and were further refined by an expert panel 
that included individuals with pharmacy-related professional 
backgrounds and patient representatives. The survey instruments will 
undergo cognitive testing and formal pre-testing to ensure questions 
are clear and answerable, and that study results are valid and useful. 
A copy of the draft surveys have been provided to the commenter.
    (Comment 9) One comment noted that the variations in the physical 
appearance of drug products may help pharmacists and patients avoid 
confusion, facilitate detection of counterfeit drug products, and serve 
pharmacovigilance purposes by providing information about the source of 
a specific product. Variation in pill appearance can also serve to 
notify patients that the source of their medication has changed. FDA 
should acknowledge the ways in which differences in pill appearance are 
beneficial when determining whether and how to conduct the survey.
    (Response) The focus of these surveys is on identifying patient and 
pharmacist concerns and problems related to changes in pill appearance, 
with the goal of informing the development of future patient and 
provider educational interventions and programs to address identified 
problems. However, it is acknowledged that changes in the physical 
appearance of medications could have both negative and beneficial 
effects. Therefore, questions have been added to gauge how changes in 
pill appearance may benefit pharmacists and patients.
    (Comment 10) One comment commended FDA for planning this study. The 
commenter was also pleased that FDA plans to conduct two separate 
patient surveys to ensure that a broad and relevant patient experience 
is reflected in the results.
    (Response) We thank this commenter for the support of our study and 
agree that conducting two separate patient surveys will improve the 
validity and generalizability of the results.
    FDA estimates the burden of this collection of information as 
follows:

                                     Table 1--Estimated Reporting Burden \1\
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   Surveys of pharmacists and
  patients on variations in the                      Number of
   physical characteristics of       Number of     responses per   Total annual   Average burden    Total Hours
generic drug pills and patients'    respondents     respondent       responses     per response
           perceptions
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Pharmacist surveys mailed \2\...           2,161  ..............  ..............  ..............  ..............
Pharmacist pretests.............               9               1               9           0.333               3
                                                                                    (20 minutes)
Pharmacist survey completes.....           1,000               1           1,000             0.3             300
                                                                                    (18 minutes)
Patient #1 survey calls.........           5,000  ..............  ..............  ..............  ..............
Patient #1 surveys screened.....           3,330               1           3,330           0.033             111
                                                                                     (2 minutes)
Patient #1 surveys eligible.....           1,200  ..............  ..............  ..............  ..............
Patient #1 survey pretests......               9               1               9           0.333               3
                                                                                    (20 minutes)
Patient #1 survey completes.....           1,000               1           1,000             0.3             300
                                                                                    (18 minutes)
Patient #2 surveys mailed \2\...           2,000  ..............  ..............  ..............  ..............

[[Page 27694]]

 
Survey of patients #2...........           1,000               1           1,000             0.3             300
                                                                                    (18 minutes)
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    Total.......................  ..............  ..............  ..............  ..............           1,017
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ Eligibility is determined prior to mailing the surveys; screening is not required.

References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday, 
and are available electronically at http://www.regulations.gov.

1. Woodward, C.A., ``Questionnaire Construction and Question Writing 
for Research in Medical Education,'' Medical Education, 22, pp. 345-
363 (1988).
2. Fitzpatrick, R., ``Surveys of Patient Satisfaction: II--Designing 
a Questionnaire and Conducting a Survey,'' British Medical Journal, 
302(6785), pp. 1129-1132 (1991).


    Dated: May 8, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-11623 Filed 5-13-15; 8:45 am]
BILLING CODE 4164-01-P