`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`209089Orig1s000
` 209090Orig1s000
`
`
`
`
`
`STATISTICAL REVIEW(S)
`
`
`

`

`S T A T I S T I C A L R E V I E W A N D E V A L U A T I O N
`
`NDA/BLA #:
`
`Drug Name:
`
`Indication(s):
`
`Applicant:
`
`Date(s):
`
`Review Priority:
`
`Biometrics Division:
`
`Statistical Reviewer:
`
`Tertiary Reviewer:
`
`Medical Division:
`
`Clinical Team:
`
`U.S. Department of Health and Human Services
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Translational Sciences
`Office of Biostatistics
`CONSUMER BEHAVIOR STUDIES
`NDA 209089 (tablets) and NDA 209090 (oral solution)
`Levocetirizine dihydrochloride (Xyzal® Allergy 24 HR)
`For the treatment of seasonal allergic rhinitis and perennial
`allergic rhinitis
`(Rx to OTC Switch, Partial)
`UCB Inc.
`Submission Date: March 31, 2016
`PDUFA Goal Date: January 31, 2017
`Standard
`DBVII
`Rongmei Zhang, PhD
`Concurring Reviewer: Rima Izem, PhD, Team Leader
`Mark Levenson, PhD, Division Director
`Division of Nonprescription Drug Products (DNDP)
`Brenda Gierhart, MD, Medical Officer, DNDP
`Steven Osborne, MD, Team Leader, DNDP
`Amanda Pike-McCrudden, MAA, Social Science Analyst, DNDP
`Sherry Stewart, PharmD, DNDP
`label comprehension study
`
`Project Manager:
`
`Keywords:
`
`Reference ID: 4031759
`
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`

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`3
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`Table of Contents
`1
`LIST OF TABLES ..............................................................................................................................................................3
`1
`EXECUTIVE SUMMARY.................................................................................................................................................4
`2
`INTRODUCTION...............................................................................................................................................................5
`2.1
`OVERVIEW....................................................................................................................................................................5
`2.2
`DATA SOURCES ............................................................................................................................................................6
`STATISTICAL EVALUATION FOR CONSUMER BEHAVIOR ...............................................................................6
`3.1
`DATA AND ANALYSIS QUALITY ...................................................................................................................................6
`3.2
`THE PIVOTAL LABEL COMPREHENSION STUDY (SESAME - #15060) .........................................................................6
`3.2.1
`Study Design............................................................................................................................................................6
`3.2.2
`Study Population .....................................................................................................................................................7
`3.2.3
`Endpoints.................................................................................................................................................................8
`3.2.4
`Statistical Methodologies ......................................................................................................................................10
`3.2.4.1
`Primary analysis (Analysis for primary objectives).............................................................................................................10
`3.2.4.2
`Secondary analysis (Analysis for secondary objective) .......................................................................................................10
`3.2.4.3 Analysis for other questions.................................................................................................................................................10
`3.2.5
`Patient Disposition and Demographic Characteristics ........................................................................................11
`3.2.5.1
`Patient Disposition ...............................................................................................................................................................11
`3.2.5.2 Demographic characteristics ................................................................................................................................................11
`3.2.6
`Analysis Findings ..................................................................................................................................................13
`3.2.6.1
`Findings in Primary Analysis/Objectives.............................................................................................................................13
`3.2.6.2
`Findings in Secondary Analysis/Secondary Objectives.......................................................................................................15
`3.2.6.3
`Findings for additional questions .........................................................................................................................................16
`3.2.7
`Findings in Subgroup populations ........................................................................................................................17
`3.2.7.1
`Low vs. Normal Literacy......................................................................................................................................................17
`3.2.7.2
`Teen vs. Adult ......................................................................................................................................................................17
`3.2.7.3 Male vs. Female ...................................................................................................................................................................18
`SUMMARY AND CONCLUSIONS................................................................................................................................19
`4.1
`STATISTICAL ISSUES...................................................................................................................................................19
`CONCLUSIONS AND RECOMMENDATIONS...................................................................................................................20
`4.2
`APPENDICES ...................................................................................................................................................................21
`5.1
`APPENDIX A: THE PROPOSED PACKAGE INSERT USED IN LABEL COMPREHENSION STUDY ......................................21
`
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`Reference ID: 4031759
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`1 LIST OF TABLES
`Table 1 Study procedures..............................................................................................................................................................7
`Table 2 Primary Communication Objectives with Corresponding Scenarios and Follow-up Questions in the LCS...................8
`Table 3 Additional Questions included but unrelated to the objectives in the LCS .....................................................................9
`Table 4 Coding algorithms used for responses to Questions 1 to 4 in the LCS............................................................................9
`Table 5 Coding algorithms used for response to Question5 in the LCS .....................................................................................10
`Table 6 Demographic characteristics: overall and by literacy. ...................................................................................................12
`Table 7 Overall correct responses for primary objectives (Study Population N=417) ...............................................................14
`Table 8 Net Code response for Question 2 (Study Population N=417)......................................................................................14
`Table 9 Net Code response for Question 4 (Study Population N=417)......................................................................................14
`Table 10 Net Code response for Question 5 (Study Population N=417)....................................................................................15
`Table 11 Sub-net codes and net-code for 94 mitigated answers for Question 2.........................................................................16
`Table 12 Overall correct responses for Questions 1 and 3 (Study Population N=417) ..............................................................16
`Table 13 Primary Communication Objectives for Normal vs. Low Literacy.............................................................................17
`Table 14 Primary Communication Objectives for Teen vs. Adult..............................................................................................18
`Table 15 Primary Communication Objectives for Male vs. Female...........................................................................................19
`
`Reference ID: 4031759
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`1 EXECUTIVE SUMMARY
`This statistical review evaluates the consumer behavior study in NDA 209089 and NDA 209090. UCB Inc. (the
`applicant) submitted an application (NDA 209089) for levocetirizine dihydrochloride (Xyzal® Allergy 24 HR)
`tablets to partially switch from prescription to over-the-counter (OTC) status. The applicant submitted a related
`application (NDA 209090) for levocetirizine dihydrochloride (Xyzal® Allergy 24 HR) oral solution to partially
`switch from prescription to OTC status.
`
`The applicant conducted one pivotal Label Comprehension Study (LCS) for tablets. The results are shared for the
`NDA’s submissions of tablets and oral solution. The purpose of the LCS was to evaluate subjects’ comprehension
`of specific warnings and directions on the proposed Drug Facts Label (DFL) related to kidney disease and urinary
`retention.
`
`This was a multi-site, single-visit, LCS in consumers aged 16 years and older. A total of 417 unique subjects
`completed interviews and included in the final dataset. Among the 417 subjects, 116 (27.8%) of them were low
`literacy, 176 (42.2%) of them were male, and 20 (4.8%) of them were under 18 years old.
`
`The study included three primary communication objectives and each objective was tested by an initial question
`and a follow-up question in the questionnaire. All questions were open-ended. The answers were coded as
`correct or incorrect using pre-specified coding algorithms. For those objectives which failed to meet the
`comprehension threshold, the applicant further evaluated the incorrect answers by mitigation. For the objective
`“Do not use if you have kidney disease”, the comprehension rate was 92.1% (n=384) with 95% two-sided exact
`confidence interval (CI) (89.1%, 94.5%). For the objective “Stop use and ask a doctor if you have trouble
`urinating or emptying your bladder”, the comprehension rate was 97.4% (n=406) with 95% two-sided exact CI
`(95.3%, 98.7%). The lower bound of the 95% CIs for these two objectives exceeded 85%, the pre-specified
`threshold. The objective “Ask a doctor before use if you have ever had trouble urinating or emptying your
`bladder” had a low comprehension rate. In pre-mitigation analysis, the comprehension rate was 66.2% (n=276)
`with two-sided exact 95% CI (61.4%, 70.7%). After mitigating 94 responses, the comprehension rate for this
`communication objective increased to 88.7% (n=370), with two-sided exact 95% CI (85.3%, 91.6%). Therefore,
`the lower bound of the 95% CI exceeded the threshold 85% after mitigation.
`
`The results from this LCS showed that the participants generally understood three specific warnings and
`directions related to kidney and urinary retention on the proposed Xyzal OTC label. Specifically, subjects had
`high comprehension rates on what to do if you have kidney disease and what to do if you have trouble urinating
`or emptying your bladder. Subjects had some difficulty in correctly understanding what to do if you have ever
`had trouble urinating or emptying your bladder. However, most of the subjects who had incorrect responses
`chose the more conservative action “Do Not Use” or “Stop Use and Ask a Doctor” than the correct answer “Ask a
`Doctor before Use”.
`
`A few subgroups had difficulty in understanding some particular questions (see Tables 13, 14, and 15). The low
`literacy group did not understand as well as normal literacy group what to do if you have kidney disease. Teens
`did not understand as well as adults, and males do not understand as well as females what to do if you have
`ever had trouble urinating or emptying your bladder. We defer to Social Scientist and Clinical Reviewer whether
`or not these imbalances are concerns in the submissions.
`
`Overall, we do not have any major statistical concern with this pivotal LCS study.
`
`Reference ID: 4031759
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`INTRODUCTION
`2
`2.1 Overview
`Product Description
`Levocetirizine dihydrochloride, an oral histamine H1 receptor antagonist, is the active R-enantiomer of the
`approved racemate, cetirizine. It is solely responsible for the therapeutic antihistaminic activity of cetirizine and
`is without anticholinergic and serotonergic activity.
`
`UBC Inc. submitted NDA 209089 for levocetirizine dihydrochloride (Xyzal® Allergy 24 HR) tablets to partially
`switch from prescription to over-the-counter (OTC) status. The same applicant submitted NDA 209090, a related
`application, for levocetirizine dihydrochloride (Xyzal® Allergy 24 HR) oral solution to partially switch from
`prescription to OTC status.
`
`The proposed nonprescription use of levocetirizine dihydrochloride tablets and oral solution is for the temporary
`relief of symptoms due to hay fever or other respiratory allergies (runny nose, sneezing, itchy, watery eyes and
`itching of the nose or throat).
`
`Regulatory History
`Levocetirizine dihydrochloride tablets were originally approved for prescription use on May 25, 2007 under NDA
`22064 for the relief of symptoms associated with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis
`(PAR) in adults and children 6 years of age or older, and for the treatment of uncomplicated skin manifestations
`of chronic idiopathic urticaria (CIU) in adults and children 6 years of age and older. Levocetirizine
`dihydrochloride oral solution was originally approved for prescription use on January 25, 2008 under NDA 22157
`for the same indication as the tables was approved on May 25, 2007.
`
`Subsequently, the indication for the relief of symptoms associated with SAR was extended to children 2 years of
`age and older and for the relief of PAR and the treatment of CIU for children 6 months of age and older for both
`the tablets and oral solution on August 21, 2009 to address the Pediatric Research Equity Act (PREA)
`requirement.
`
`The CIU indication is not being switched to nonprescription use for both the tablets and oral solution at this
`time, as the result of the Type B meeting between FDA and the applicant on October 1, 20151. No new
`nonclinical pharmacology and toxicology, human pharmacokinetics and bioavailability, clinical pharmacology,
`clinical efficacy or safety studies for the intended use were conducted in support of this switch application.
`
`There was no statistical review on the protocol of the consumer behavior study before the NDA submissions. Dr.
`Higgins in the Division of Biometrics IV reviewed the applicant’s meeting package for the Type B meeting in
`October 20152 without providing statistical comments.
`
`Scope of Review
`This is a statistical review for the consumer behavior in the two NDA submissions. The applicant conducted one
`Label Comprehension Study (LCS) for tablets, which was shared for the submissions of tablets and oral solution.
`The purpose of the LCS was to evaluate subjects’ comprehension of specific warnings and directions on the
`proposed Drug Facts Label (DFL) related to kidney disease and urinary retention.
`
`There was no self-selection or actual use study in the submissions.
`
`1 Meeting minutes for Type B meeting on October 1, 2015, available in DARRTs under IND 126506 and IND 126507.
`2 Statistical Review and Evaluation by Dr. Karen Higgins on October 9, 2015, available in DARRTs under IND 126506 and
`IND 126507.
`
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`Reference ID: 4031759
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`2.2 Data Sources
`
`The applicant submitted the two NDAs electronically. The submissions included the analysis dataset for the LCS
`(Study SESAME-15060), the SDTM datasets used to create the analysis data, and the LCS report.
`
`The analysis dataset (adir.xpt) for the LCS is available at:
`\\cdsesub1\evsprod\NDA209090\0001\m5\datasets\lcs\analysis\adam\datasets\
`
`The SDTM datasets (dm.xpt, qs.xpt, sc.xpt, ts.xpt, suppdm.xpt, suppqs.xpt) used as the source to create the
`analysis dataset are available at:
`\\cdsesub1\evsprod\NDA209090\0001\m5\datasets\lcs\tabulations\sdtm
`
`The study report for the LCS is available at:
`\\cdsesub1\evsprod\NDA209090\0001\m1\lcs-pirvotal-study-report.pdf
`
`3 STATISTICAL EVALUATION FOR CONSUMER BEHAVIOR
`This statistical review focuses on the consumer behavior for levocetirizine dihydrochloride tablets and oral
`solution. The applicant conducted one LCS for tablets.
`
`Please refer to separate Social Scientist Review by Amanda Pike-McCrudden for overall LCS evaluation.
`
`Please refer to separate Clinical Review by Dr. Brenda S. Gierhart for overall efficacy and safety evaluation.
`
`3.1 Data and Analysis Quality
`The submissions contained the analysis dataset, the SDTM datasets used as the source to create the analysis
`dataset, and the annotated CRF for the LCS study. The submissions also included Analysis Data Reviewer’s Guide
`and Study Data Reviewer’s Guide for the LCS study.
`
`The statistical reviewer was able to reproduce the results in the primary and secondary analyses for the LCS
`study using the submitted data. No major data quality issue was found.
`
`3.2 The Pivotal Label Comprehension Study (SESAME - #15060)
`
`3.2.1 Study Design
`There was a multi-site, single-visit LCS. The purpose of the LCS was to evaluate the consumer’s ability to
`comprehend specific warnings and directions on the proposed DFL related to kidney disease and urinary
`retention.
`
`Table 1 illustrates the study procedures. Upon arrival at the site, qualified subjects read and signed a
`Confidentiality/Disclosure Agreement (CDA) and an Agreement to Participate (ATP) prior to the start of the
`study. To identify participant health literacy levels, subjects aged 18 years and older completed the Rapid
`Estimate of Adult Literacy in Medicine (REALM) test and subjects aged 16-17 years completed the Rapid
`Estimate of Adolescent Literacy in Medicine (REALM-Teen) test.
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`Following the REALM or REALM-Teen test, subjects were then presented with the product carton for the
`proposed Xyzal Allergy 24HR product. They were given the opportunity to independently review the full
`package labeling [mock-up of the product carton that included the Principal Display Panel (PDP) and the DFL] of
`this product at their own pace. Once the subject indicated that he/she had finished reviewing the DFL, the
`pivotal label comprehension interview was conducted. The product labeling was remained in full review of and
`accessible to the subject during the assessment. The label comprehension questions were comprised of
`scenario-based open-ended questions (hypothetical third-party scenarios that required the consumer to make
`decisions about the situation based on the information on the DFL) or direct open-ended questions. All open-
`ended questions were followed by a probe (“Why do you say that?”) in order to obtain the subjects’ rationale
`for their response. These responses were captured verbatim. The subjects were not permitted to change
`answers to any previous questions once they moved to the next questions.
`
`There were total five label comprehension questions in the questionnaire. Each label comprehension question
`had two open-ended questions (a) and (b). The comprehension questions were presented in a mixed order and
`not in the order that the communication objectives appear on the label. This was an interview-only study, and
`no drug was administered.
`
`Table 1 Study procedures
`
`Source: Applicant’s Table 8-1 in the LCS report
`
`3.2.2 Study Population
`The following inclusion criteria were applied to all participants:
`
`1. The subject was 16 years of age or older.
`2. The subject was able to speak, read and understand English sufficiently to understand the nature of the
`study procedures.
`3. The subject must have been willing, able and likely to comply with all study procedures.
`4. At the study site, the subject must have read and voluntarily signed the Confidentiality/Disclosure
`Agreement and Agreement to Participate.
`
`The following exclusion criteria were applied to all participants:
`
`1. The subject had ever been trained or employed as a healthcare professional.
`2. The subject or anyone in their household was currently employed by any of the following:
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`a. A marketing or marketing research company
`b. An advertising agency or public relations firm
`c. A pharmacy or pharmaceutical company
`d. A manufacturer of medicines
`e. A managed care or health insurance company as a healthcare professional
`3. The subject had, or could not remember if he/she had, participated in any market research study,
`product label study or clinical trial in the past twelve (12) months.
`4. The subject normally wore corrective lenses, contacts or glasses to read and did not have them with
`him/her.
`5. The subject had any impairment that prevented him/her from being able to read on his/her own.
`
`The overall portion of low literacy subjects included in the overall population was designed to be 25%-30%.
`
`3.2.3 Endpoints
`The study included three primary communication objectives. Table 2 lists each of these primary objectives, along
`with the corresponding hypothetical scenarios and questions.
`
`Table 2 Primary Communication Objectives with Corresponding Scenarios and Follow-up Questions in the LCS
`
`Primary Communication Objective
`Ask a doctor before use if you have
`ever had trouble urinating or
`emptying your bladder
`
`Do not use
`if you have kidney disease
`
`Scenario
`• Last month, Alex was having
`trouble emptying his bladder when
`he went to the bathroom.
`• He also suffers from allergies and
`now he wants to start using this
`product.
`• Sally has kidney disease.
`• She would like to start using this
`product to treat her allergies.
`
`Questions
`Q2a: According to the label, what,
`if anything, should Alex do?
`Q2b: Why do you say that?
`
`Q4a: According to the label, is it
`okay or not okay for Sally to use
`this product?
`Q4b: Why do you say that?
`Q5a: According to the label, what,
`if anything, should Erin do?
`Q5b: Why do you say that?
`
`Stop use and ask a doctor if
`you have trouble urinating or
`emptying your bladder
`
`• Erin has been taking this product
`for several days.
`• She is now having trouble
`urinating and has never had this
`problem before.
`Source: Reviewer’s table (adapted from Applicant Table 10-1 in the LCS report)
`
`The secondary communication objective of this study was to understand the reasons for consumer confusion in
`the primary communication objectives.
`
`Two additional questions unrelated to the objectives were included in the study to help mask the objectives and
`provide a variation of potential responses. Table 3 lists these additional questions.
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`Reference ID: 4031759
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`Table 3 Additional Questions included but unrelated to the objectives in the LCS
`
`Questions
`Q1a: According to the label, what is this product used for?
`Q1b: Why do you say that?
`Q3a: According to the label, is it okay or not okay for Darren to use this
`product?
`Q3b: Why do you say that?
`
`Scenario
`No scenario for this question.
`
`• Darren is 40 years old and has hay
`fever.
`• He would like to use this product
`to treat his itchy nose and throat.
`Source: Reviewer’s table
`
`Coding Algorithm
`
`There were total five label comprehension questions in the LCS. Each question had (a) an initial question and (b)
`a follow up question (“Why do you say that?”) in order to obtain the subjects’ rationale for their response.
`
`The coding algorithms included three levels: sub-net codes, net codes, and overall response.
`
`1. The verbatim answers were first sub-net coded into broad category response based on key label
`warnings and direction.
`2. These broad sub-net codes were then linked to the appropriate net codes. Responses to Questions 1 to
`4 were net coded as “correct” or “incorrect”. Responses to Question 5 were net coded as “correct”,
`“acceptable” or “incorrect”.
`3. The overall response for each question depended on the combined initial response and follow-up
`response. Table 4 shows the overall response rule for Questions 1-4, and Table 5 shows the rule for
`Question 5.
`
`The verbatim answers, the sub-net codes, net codes, and overall response for each label comprehension
`questions were all recorded in the submitted analysis dataset.
`
`Table 4 Coding algorithms used for responses to Questions 1 to 4 in the LCS
`
`Overall Response for Q1-Q4
`
`Net Code for Q1-Q4
`(a) Initial question
`(b) Follow-up question
`Correct
`Correct
`Correct
`Incorrect
`Correct
`Incorrect
`Correct
`Incorrect
`Correct
`Incorrect
`Incorrect
`Incorrect
`Source: Reviewer’s table (adapted from Applicant’s table on Page 27 in the LCS report)
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`Reference ID: 4031759
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`Table 5 Coding algorithms used for response to Question5 in the LCS
`
`Overall Response for Q5
`
`Net Code for Q5
`(a) Initial question
`(b) Follow-up question
`Correct
`Correct
`Correct
`Correct
`Correct
`Acceptable
`Incorrect
`Correct
`Incorrect
`Correct
`Acceptable
`Correct
`Correct
`Acceptable
`Acceptable
`Incorrect
`Acceptable
`Incorrect
`Correct
`Incorrect
`Correct
`Correct
`Incorrect
`Acceptable
`Incorrect
`Incorrect
`Incorrect
`Source: Reviewer’s table (adapted from Applicant’s table on Page 28 in the LCS report)
`
`Reviewer’s Comments:
`
`According to the coding algorithms shown in Tables 4 and 5, the overall responses for Questions 1 to 5 were
`solely determined by the follow-up question (“Why do you say that?”). Regardless of the response to the initial
`question, if the follow-up response for Questions 1-4 were “Correct”, the overall responses were “Correct”.
`Regardless of the response to the initial question, if the follow-up response for Question5 were “Correct” or
`“Acceptable”, the overall response was “Correct”.
`
`We defer the validity of the coding algorithms to Social Scientist.
`
`3.2.4 Statistical Methodologies
`
`Primary analysis (Analysis for primary objectives)
`3.2.4.1
`The primary analysis consisted of estimating the comprehension rate for each primary objective (see Section
`3.2.3 Endpoints) in the overall population. Each rate was computed as the number of subjects with a correct
`response divided by the number of subjects in the overall population who answered the question. Two-sided
`95% confidence intervals (CIs) were computed using an exact method (Clopper-Pearson). The success threshold
`for each primary objective was pre-specified as 85%. Therefore, if the lower CI for the comprehension rate was
`equal to or greater than 85%, it was considered that the objective was comprehended.
`
`Secondary analysis (Analysis for secondary objective)
`3.2.4.2
`For the secondary analysis, open-ended comments were reviewed, summarized and analyzed for areas of
`consumer confusion. There was no success threshold pre-specified for the secondary objective.
`
`3.2.4.3 Analysis for other questions
`The comprehension rate for each question was not reported in the LCS, but the data corresponding to the
`questions were submitted in the analysis dataset.
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`Reference ID: 4031759
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`3.2.5 Patient Disposition and Demographic Characteristics
`
`Patient Disposition
`3.2.5.1
`A total of 969 potential subjects were screened at 8 research sites, with 462 subjects qualified and scheduled for
`the study in order to completed interviews. A total of 419 subjects completed in-person interviews, with 417
`subjects included in the final dataset. Two subjects were excluded because of missing or incomplete data.
`
`Reviewer’s Comments:
`
`We sent an information request to the applicant to ask why the study population reduced from 462 to 419. The
`applicant stated that among the 462 individuals qualified for the study, the 419 subjects were the ones who kept
`their interview. The 43 qualified individuals did not keep their scheduled interview (not arriving at the research
`facilities), and no parts of the interview were conducted. They were never assigned a subject ID. The applicant did
`not collect their information, and no dataset can be provided to FDA for these 43 individuals. Therefore, all the
`datasets submitted for the LCS only included 417 patients.
`
`Ideally, the study population should include everyone regardless he/she had missing data or not and hence the
`two subjects should not be excluded from the analysis because of their missing or incomplete data. However, the
`applicant did not submit the data for these two subjects and this was a decision made in the pre-specified
`protocol. We anticipate that the missing from these two subjects will not make substantial impact on the
`analysis, given the sample size in this LCS.
`
`3.2.5.2 Demographic characteristics
`The distributions of demographic characteristics for overall, normal literacy, and low literacy are shown in Table
`6. In the overall study population (N=417), there were more females (females vs. males were 57.8% vs. 42.2%).
`The majority of the participants were greater than 18 years old (95.2%), Caucasian/white (59.2%), non-Hispanic
`(83.0%), employed full-time or part-time (59.0%), and normal literacy (72.2%).
`
`Among the overall 417 subjects, there were 116 (27.8%) low literacy and 301 (72.2%) normal literacy according
`to the REALM test (for subjects aged 18 and older) and REALM-Teen test (for subjects aged 16-17 years old). As
`shown in Table 6, compared to the normal literacy group, the low literacy group had similar distributions for sex,
`subjects younger than 18 years of age, and ethnicity. However, the low literacy group had more African
`American/black (37.9% vs. 14.0%), and more subjects not completed high school for those who were older than
`18 years old (20.9% vs. 4.2%).
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`Reference ID: 4031759
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`Table 6 Demographic characteristics: overall and by literacy.
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`Reference ID: 4031759
`
`12
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`

`

`(continued)
`
`Source: Applicant’ Table 9-1 in the LCS report.
`
`3.2.6 Analysis Findings
`
`Findings in Primary Analysis/Objectives
`3.2.6.1
`As shown in Table 7, the lower bound of the two-sided exact 95% CI of comprehension rates for two of the three
`primary comprehension objectives exceeded the pre-specified threshold of 85%. For the primary
`comprehension objective “Ask a Doctor before Use if you have ever had trouble urinating or emptying your
`bladder”, the lower bound of the two-sided exact 95% CI of the comprehension rate was 61.4%, lower than the
`pre-specified threshold of 85%.
`
`The Net Code responses for Questions 2, 4, and 5 were shown in Tables 8, 9, and 10, respectively.
`
`Reviewer’s Comments:
`
`Reviewer’s analyses (See Tables 8, 9, and 10) show that the responder rates of subjects who answered both
`initial and follow-up questions as “Correct” for Questions 2, 4 and 5 were 56.8%, 90.2% and 65.2%, respectively.
`Therefore, Question 4 not only had high overall correct response rate, but also had high correct response rate for
`both (a) and (b). For Question 5, the response rate of subjects who answered initial and follow-up questions as
`“Correct” or “Acceptable” was 404/417 or 96.9%. Therefore, Question 5 had high correct/acceptable rate for
`both (a) and (b).
`
`13
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`Reference ID: 4031759
`
`

`

`Table 7 Overall correct responses for primary objectives (Study Population N=417)
`
`Primary Objective
`
`Question
`No.
`Q2
`
`Q4
`
`Q5
`
`Ask a Doctor before Use if You Have
`Ever had trouble urinating or emptying your bladder
`Do Not Use
`If you have kidney disease
`Stop Use and Ask a Doctor if
`You have trouble urinating or emptying your bladder
`Source: Revie