CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`207202Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`HUMAN FACTORS RESULTS LABELS AND LABELING REVIEW
`Division of Medication Error Prevention and Analysis (DMEPA)
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`Office of Surveillance and Epidemiology (OSE)
`Center for Drug Evaluation and Research (CDER)
`
`*** This document contains proprietary information that cannot be released to the public***
`
`Date of This Review:
`October 20, 2017
`Requesting Office or Division:
`Division of Psychiatry Products
`Application Type and Number: NDA 207202
`Product Name and Strength:
`Abilify MyCite (aripiprazole + ingestible event marker) tablets
`2 mg, 5 mg, 10 mg, 15 mg, 20 mg and 30 mg
`Combination Product
`Rx
`Otsuka Pharmaceutical Company, Ltd.
`April 21, 2017
`2017-969
`Loretta Holmes, BSN, PharmD
`Lolita White, PharmD
`QuynhNhu Nguyen, MS
`
`Product Type:
`Rx or OTC:
`Applicant/Sponsor Name:
`Submission Date:
`OSE RCM #:
`DMEPA Safety Evaluator:
`DMEPA Team Leader:
`DMEPA Associate Director for
`Human Factors:
`DMEPA Deputy Director
`(Acting):
`
`Danielle Harris, PharmD, BCPS
`
`Reference ID: 4170268
`
`1
`
`

`

`REASON FOR REVIEW
`1
`The Division of Psychiatry Products (DPP) consulted the Division of Medication Error Prevention
`and Analysis (DMEPA) to evaluate the human factors (HF) patient interface validation study
`results (document #DC-001830 ver. 3.0), labels, labeling and packaging submitted for NDA
`207202 to determine if they are acceptable from a medication error perspective.
`1.1
`PRODUCT INFORMATION
`The proposed Prescribing Information (PI) states that Abilify MyCite is a drug-device
`combination product comprised of Abilify tablets (an atypical antipsychotic) embedded with an
`Ingestible Event Marker (IEM) sensor that communicates with a Patch (wearable sensor) and a
`medical software application. MyCite is a system that tracks the ingestion of aripiprazole tablets
`embedded with an IEM, and is indicated for the treatment of schizophrenia, acute treatment of
`manic and mixed episodes associated with bipolar I disorder, and adjunctive treatment of major
`depressive disorder. The system consists of the following:
` Abilify MyCite (aripiprazole + IEM) tablets
` Mycite Patch (a wearable sensor)
` Mycite App (a compatible mobile patient application)
` Web-based portal for healthcare professionals (HCP)a
` Web-based portal for caregiver (CG)a
`REGULATORY HISTORY
`2
`NDA 207202 was originally submitted on June 26, 2015. DMEPA reviewed the human factors
`patient interface validation study results that were submitted at that time and found the study
`results unacceptable.b A Complete Response Letter was issued on April 26, 2016. The NDA was
`resubmitted (Class II resubmission) on April 21, 2017. As part of the resubmission, Otsuka
`submitted the results from a new human factors patient interface validation study which is the
`subject of this review.
`3 MATERIALS REVIEWED
`We considered the materials listed in Table 1 for this review. The Appendices provide the
`methods and results for each material reviewed.
`
`a Based on the information submitted by Otsuka in the original NDA submission, we determined that the caregiver
`and healthcare provider portals do not provide clinical decision support features that are intended to alter
`physician or caregiver behavior. Based on Otsuka’s description of the portals, they function as tools which allow for
`monitoring only. No additional functionality is proposed to the portals in the current submission. Therefore, this
`review focuses on the human factors patient interface validation study, which includes the aripiprazole with IEM
`tablets, wearable patch, the App, and associated drug and patch labeling, packaging and electronic instructions for
`use (IFU).
`b Holmes L. Human Factors Results Labels and Labeling Review for Abilify MyCite NDA 207202. Silver Spring (MD):
`FDA, CDER, OSE, DMEPA (US); 2016 Mar 09. RCM No.: 2015-1602.
`
`2
`
`Reference ID: 4170268
`
`

`

`
`
`Table 1. Materials Considered for this Label and Labeling Review
`Appendix Section
`Material Reviewed
`(for Methods and Results)
`A
`B
`C
` D (N/A)
` E (N/A)
`F
`G
`
`Product Information/Prescribing Information
`Previous DMEPA Reviews
`Human Factors Study
`ISMP Newsletters
`FDA Adverse Event Reporting System (FAERS)*
`Other (Supporting Documents)
`Labels and Labeling
`N/A=not applicable for this review
`*We do not typically search FAERS for our label and labeling reviews unless we are aware of
`medication errors through our routine postmarket safety surveillance
`
`4 OVERALL ASSESSMENT OF THE MATERIALS REVIEWED
`The Applicant conducted a HF validation study to evaluate the changes to the patient user
`interface of the Abilify MyCite system (also referred to as MIND1 Systemc in this review).
`Study Design
`A total of 35 representative participants participated in this simulated use HF validation study.
`There were three distinct user groups based on diagnosis [schizophrenia (12), bipolar 1 disorder
`(12), and major depressive disorder (11)]. The participants were randomly assigned to an
`assisted onboardingd or unassisted onboarding group. Each participant completed two sessions
`separated by a period of approximately 24 hours. Onboarding tasks were conducted on Day 1
`and the remaining tasks conducted on Day 2. The user groups and use scenarios (assisted and
`unassisted) are representative of real world use. As such, we agree with the user groups and
`methodology used in the study (see Appendix C for a more detailed description of the study).
`
`c MIND1 System: The MIND1 App, Patch, packaging, aripiprazole + IEM, and labeling. Note that the Abilify MyCite
`proprietary name was blinded in the study. Instead, the names “MIND1 or “Mindxx” were used.
`d Onboarding: First-time use of MIND1, including all parts of system setup. The assisted group was introduced to
`the system by an in-serviced health care provider (HCP) and was assisted, as necessary, in completing the
`registration and expected first-use with the integrated kit and a study phone. The unassisted group was provided
`the kit and set up the system for use on their own without assistance.
`
`3
`
`Reference ID: 4170268
`
`

`

`Critical Tasks Failures and Close Calls
`There were 4 failures and 1 close call that occurred with the following critical taskse:
`1. Acts on Daily Tile Summary Tile (n=3)
`2. Pill registered (n=1)
`3. Pill doesn’t seem to be registering (n=1)
`
`1. Acts on Daily Summary Tile (Task 25b), n=3
`In the assisted group, two participants failed and indicated that they would take another
`pill, which is not the intended action that should be taken by the user when viewing the
`daily summary tile. In addition, there was one participant who experienced a close call
`with the task:
`
`In response to seeing the Daily Summary Tile (DST) for the previous day, one
`participant stated she would take another pill. The participant did not recognize that
`the DST contained historical information. The sponsor’s root cause analysis
`indicated that since all the tiles on the Home screen are on the same scroll, it led her
`to believe that the DST was also referring to that day’s information. The participant
`also demonstrated confusion with the task simulation.
`
` 
`
`
`
`The other participant acknowledged and demonstrated understanding that the DST
`displayed yesterday’s information but indicated that she would take another pill
`“just to get back on track”. When probed further, the participant clarified that if she
`would not take another pill if she had already taken her pill on the present day. The
`sponsor’s root cause analysis indicated that the participant forgot the test scenario
`regarding having already taken a pill that day and indicated that she might react to
`taking another pill based on the DST information.
`
` One participant had a close call with the task. Upon reviewing the DST, the
`participant expressed that the pill was not registered and that the pill had not been
`taken. The participant acknowledged and demonstrated understanding that the DST
`displayed yesterday’s. She stated that she would want to take two pills the next day
`but then added that she would not do it. The sponsor’s root cause analysis indicated
`that she did not have adequate information about the medication and dosing
`schedule and her initial assumption that she would want to, if appropriate,
`compensate for a missed dose.
`
`Our independent review of the App and the sequencing of tiles as the user scrolls to the
`DST found that when the DST tile is displayed, the banner above the DST tile reads
`“Yesterday” and yesterday’s date, whereas, the banner at the very top of the screen
`
`e Critical Task: User task which, if performed incorrectly or not performed at all, would or could cause serious
`harm to the patient or user, where harm is defined to include compromised medical care.
`
`4
`
`Reference ID: 4170268
`
`

`

`reads “Today” and today’s date. Additionally, the “footer” at the bottom of the screen
`shows “Today” which may be confusing (see screen shot below).f
`
`We note that failure to recognize the DST displays information from the previous day
`and acting on the pill information that the DST displays (i.e., “registered” or “not
`registered”) may lead to the user not taking a dose or taking an extra dose. For such an
`error to occur, the user would have to scroll past (and overlook) the present day pill
`status tile which clearly and prominently indicates whether the present day pill has
`registered or not registered. Once the user scrolls past the present day pill status tile to
`the DST on the app display, the user must then overlook the banner that states
`“yesterday”, overlook the tile title that reads “yesterday’s summary”, and overlook all of
`the other historical information on the tile from the previous day (mood, rest, activity).
`The user must then act on the previous pill status in a manner that results in an
`, and
`overdose or dose omission. Additionally, the medication guide,
`instruction videos all provide cautionary statements stating that an extra dose should
`not be taken based on what is shown in the app. Therefore, we find the risk to be
`minimized to as low as reasonably practical given the multiple points of failure that
`must occur to result in a medication error. Additionally, based on our discussions with
`the review team, we understand that infrequent ingestion of an extra dose or dose
`
`f The screen shot shown is only intended to be representative of the information that is displayed on the DST. It is
`not intended to show the specific mood, rest, pill and activity information shown to participants in the study.
`
`5
`
`Reference ID: 4170268
`
`(b) (4)
`
`

`

`2.
`
`omission is unlikely to result in clinically significant harm to the patient. When the task
`failure root causes are considered in totality with the existing mitigations, and clinical
`consequences of such error, we find that the residual risk is mitigated to an acceptable
`level.
`
` (First) Pill Registered (App Messaging Knowledge Assessment (Task 28), n=1
`One participant in the assisted group failed this task. The participant interpreted the
`statement correctly in stating, “It is telling me I took my first pill and that it is registered
`in the system.” However, in response to the comprehension question (“Is there
`anything you would do if you saw this screen”) she stated she would take her first pill in
`response. The sponsor’s root cause analysis indicated the failure was due to participant
`slip. The participant stated she did not intend to take two pills. No mitigation is
`proposed by Otsuka.
`Our assessment indicates that based on the subjective feedback and the root cause of
`this failure, the patient clarified she did not intend to take a second pill. Furthermore,
`the (first) “Pill Registered” screen only appears during onboarding so there is no concern
`for repeated misinterpretation of the message. Therefore, we find that no further
`mitigation is needed.
`3. Pill Doesn’t Seem To Be Registering (App Messaging Knowledge Assessment Task 28),
`n=1
`One participant in the unassisted group failed this task. The participant noted the
`“Patch OK” button in the background and added that the screen was telling him to wait
`but that he did not know how long after taking the pill he needed to wait. The
`participant also stated he would consider taking a second pill because he misunderstood
`the task scenario. The sponsor’s root cause analysis indicates task confusion since the
`participant was not clear on the task to be performed. No mitigation has been
`proposed by Otsuka.
`Our assessment of this failure finds that based on the subjective feedback, the root
`cause of this failure, and the availability of a call center number on the screen, we do
`not believe further mitigation is needed. Additionally, this screen only appears during
`onboarding so there is no concern that repeated misinterpretation of the message
`would occur.
`
`Reference ID: 4170268
`
`6
`
`

`

`Necessary Taskg Failures and Use Difficulties
`There were 3 failures and 3 use difficulties that occurred during the performance of paring a
`replacement patch, which was considered a necessary task.
`1. Pairs Replacement Patch (Task 21b), n=6: One participant in the assisted group and two
`participants in the unassisted group failed this task. One participant in the assisted
`group and two participants in the unassisted group had difficulty with this task.
`Two participants failed to press the button long enough to activate the patch. One
`participant stated she did not realize how long she had to keep her finger on the button
`and added that she read the instructions but she read them “too fast or too
`quickly...and missed that part.” She stated that if “Hold” were bold lettering, that would
`have helped her notice it. The other participant stated she did not realize “I had to keep
`my finger on it as long as I should have.” Both participants indicated they would call the
`1-800 number for assistance with pairing the patch. The sponsor’s root cause analysis
`for both failures indicated there was negative transfer from previous patch experience
`(the light on the old patch came on instantly when the button was pressed) and
`insufficiently prominent guidance on the user interface (the instructions did not
`communicate how long to hold down the button). The third participant that failed to
`perform this task had a visual impairment. The sponsor’s root cause analysis indicated
`there was insufficiently prominent guidance on the user interface exacerbated by vision
`impairment.
`Three participants were reported to have difficulty with this task but completed the
`task.
` One participant skipped through, did not pay attention to the screens in the App,
`and received a pairing error. This participant ultimately removed a new patch and
`paired it successfully. The sponsor’s root cause analysis indicated the use difficulty
`was due to participant inattentiveness.
`
` One participant was unable to locate the button on the patch initially but was able
`to locate the button and to turn the green light on to initiate the pairing process.
`The sponsor’s root cause analysis indicated the button on the patch was not
`prominent enough to attract the participant’s immediate visual/tactile attention.
`
` Another participant expected the light to stay on for a longer period of time to
`indicate successful pairing but the patch had already paired successfully. The
`sponsor’s root cause analysis indicated that the use difficulty was due in part to the
`participant’s initial confusion that the green light would stay on longer to indicate
`successful pairing.
`
`g Necessary Task: User task that is necessary for use, but would not cause serious harm to the user in other ways if
`performed incorrectly. Could otherwise be referred to as an “essential” task.
`
`7
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`Reference ID: 4170268
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`

`

`We note that failure to pair the patch successfully will result in lack of system
`functionality but does not result in patient harm. Otsuka did not provide any mitigation
`for this use error, however, in the “Pairing Your Patch” instructions, the patch button
`location is enlarged in a separate illustration and is encircled in an orange dotted line to
`highlight. Our review of the participants’ subjective feedback indicates that using bold
`lettering for the word “Hold” may help users follow the instructions and successfully
`pair the replacement patch and is a mitigation strategy that can be implemented. We
`provide recommendations in Section 5.2 of this review.
`There were other use errors involving necessary tasks. However, we find the risks associated
`with these use errors have been mitigated to an acceptable level and we have no additional
`recommendations. These use errors are described in Appendix E.
`Container Labels, Carton Labeling, Packaging, Instructional Videos,
`
`In addition to the recommendations described above, we identified the following areas of
`concern that should be addressed to promote safe use of the proposed product:
`
`1. There is a discrepancy regarding the number of patches contained in the kit. The paragraph
`in Section 16.1 How Supplied in the Prescribing Information (PI) and the kit carton labeling
`indicate 7 patches are supplied in the kit whereas Table 17 in Section 16.1 of the PI indicates
`patches are supplied in the kit. Thus, the information is inconsistent and may cause
`confusion.
`
`2. The dosage form “tablets” is product identifying information and should follow the
`established name on the container labels and carton labeling. However, the dosage form is
`not present in this location and should be added.
`
`3. The Medication Guide (MG) statement on the container labels and carton labeling does not
`comply with 21 CFR 208.24(d).
`
`4. The statement of strength (i.e., X mg or XX mg) lacks sufficient prominence on the container
`labels and carton labeling. Increasing its prominence may help minimize product strength
`selection errors.
`We provide recommendations to address these concerns in Section 5.2.
`Comparability Protocol
`In our review of the Abilify Mycite Comparability Protocol, we identified concerns
`
`
`
`
`we recommended that Otsuka
`:
`
`address the following
`
`8
`
`Reference ID: 4170268
`
`(b) (4)
`
`(b)
`(4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`The applicant submitted a revised protocol on October 18, 2017, and we find the revisions
`acceptable from a human factors and medication error perspective.
`5
`CONCLUSION & RECOMMENDATIONS
`The patient interface HF validation study results showed there were tasks failures where
`participants indicated they would take or would consider taking an additional pill. Our review of
`the user interface, HF study results, the sponsor’s root cause analysis, and the existing
`mitigation strategies determined that the risks of extra dose and dose omission have been
`minimized to as low as reasonably practical. Additionally, based on our discussions with the
`review team, we understand that infrequent ingestion of an extra dose or dose omission is
`unlikely to result in clinically significant harm to the patient. Thus, we find that the residual risk
`is mitigated to an acceptable level.
`We also note there is a call center telephone number provided throughout the labeling [e.g., in
`the
` inside top panel of the carton labeling] and in the App and is
`available to users who need assistance or experience a loss of system functionality.h
`We identified areas in the PI, carton labeling and container label where information is unclear,
`missing or lacks sufficient prominence. We provide recommendations to address these
`concerns in Section 5.1 and 5.2.
`5.1 RECOMMENDATIONS FOR THE DIVISION
`A. Labeling
`
`1. There is a discrepancy regarding the number of patches contained in the kit.
`Specifically, the paragraph in Section 16.1 How Supplied in the Prescribing
`Information (PI) and the kit carton labeling indicate 7 patches are supplied in the
`kit whereas Table 17 in Section 16.1 of the PI indicates patches are supplied in
`the kit. This discrepancy needs to be reconciled for consistency across all
`labeling.
`
`h The effectiveness of the call center was not assessed in this simulated use validation study.
`
`9
`
`Reference ID: 4170268
`
`(b) (4)
`
`(b)
`(4)
`
`(b) (4)
`
`

`

`5.2 RECOMMENDATIONS FOR OTSUKA PHARMACEUTICAL COMPANY
`We recommend the following be implemented prior to approval of this NDA:
`A.
`Instructional Video
`
`1. When performing Task 21b Pairs Replacement Patch, two study participants failed to
`hold down the patch button long enough for the green light to come on. Failure to
`pair the patch may lead to loss of system functionality. To help mitigate this error
`and facilitate patch pairing, consider revising your instructional video such that the
`words “Press and hold” are in bold font in the “Pairing Your Patch” instructional
`video.
`
`B. Container Labels and Carton Labeling
`
`1. The established name is not followed by the dosage form “tablets”. Add the dosage
`form statement and place it on the same line as the established name or below the
`established name.
`
`2. The Medication Guide (MG) statement does not state how the MG is provided. The
`MG statement should state how the MG is provided. Revise the MG statement to
`one of the following (or use similar verbiage) in accordance with 21 CFR 208.24(d):
`
`a. “Dispense the enclosed Medication Guide to each patient.” or
`b. “Dispense the accompanying Medication Guide to each patient.”
`
`3. The statement of strength lacks sufficient prominence which may pose risk of
`product strength selection errors. Increase the size of the statement of strength on
`all panels.
`
`Reference ID: 4170268
`
`10
`
`

`

`APPENDICES: METHODS & RESULTS FOR EACH MATERIALS REVIEWED
`
`APPENDIX A. PRODUCT INFORMATION/PRESCRIBING INFORMATION
`Table 2 presents relevant product information for Abilify MyCite that Otsuka Pharmaceuticals
`submitted on April 21, 2017.
`
`Route of Administration
`Dosage Form
`Strengths
`Dose and Frequency
`How Supplied
`
`Table 2. Relevant Product Information for Abilify MyCite
`N/A
`Initial Approval Date
`aripiprazole
`Active Ingredient
`Indication
`Treatment of: schizophrenia, acute treatment of manic
`and mixed episodes associated with bipolar I disorder, and
`adjunctive treatment of major depressive disorder
`Oral
`Tablets
`2 mg, 5 mg, 10 mg, 15 mg, 20 mg and 30 mg
`Dosage range: 2 mg to 30 mg once daily
`Kit containing: 30 Abilify MyCite tablets (2 mg, 5 mg, 10
`mg, 15 mg, 20 mg or 30 mg) and seven patches
`Store at 25°C (77°F); excursions permitted between 15°C
`to 30°C (59°F to 86°F)
`Tablets: HDPE bottles with
`
`Storage
`
`Container Closure
`
` closure
`
`Reference ID: 4170268
`
`11
`
`(b) (4)
`
`

`

`APPENDIX B. PREVIOUS DMEPA REVIEWS
`B.1 Methods
`On August 14, 2017, we searched the L:drive and AIMS using the terms, Abilify MyCite and
`aripiprazole + IEM to identify reviews previously performed by DMEPA.
`
`Results
`B.2
`Our search identified two previous reviews that are relevant to this current review, and we
`confirmed that our previous recommendations were implemented or considered.
`
`
`
`
`
`Holmes L. Human Factors Validation Study Protocol Review for Abilify MyCite NDA 207202. Silver Spring
`(MD): FDA, CDER, OSE, DMEPA (US); 2016 Dec 16. RCM No.: 2016-2195.
`Holmes L. Human Factors Results Labels and Labeling Review for Abilify MyCite NDA 207202. Silver Spring
`(MD): FDA, CDER, OSE, DMEPA (US); 2016 Mar 09. RCM No.: 2015-1602.
`
`Reference ID: 4170268
`
`12
`
`

`

`APPENDIX C. PATIENT INTERFACE HUMAN FACTORS VALIDATION STUDY
`[document #DC-001830 ver. 3.0]
`
`Study Report and System Overview
`C.1
`Link to study report: \\cdsesub1\evsprod\nda207202\0030\m5\53-clin-stud-rep\535-rep-
`effic-safety-stud\all\5354-other-stud-rep\hf-patient-interface-validation-report\hf-patient-
`interface-val-report.pdf
`
`System Overview:
`
`Reference ID: 4170268
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`13
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`

`Patient Interface Human Factors Validation Study (Additional Summary of Results)
`C.2
`Necessary Tasksi
`Although the following tasks were not categorized as critical, they are necessary for the safe
`use of the product. Overall, there were 13 failures and 8 difficulties that occurred within this
`group of tasks, below.
`1. Download App (Task 2), n=1
`2. Peels off large tab (Task 5e), n=1
`3. Applies Patch (Task 5b), n=4
`4.
`Ingests First Pill (Task 6c), n=2
`5. Remove Patch (Task 19), n=1
`6. Applies Replacement Patch (Task 24a), n=2
`7. Checks Patch Status (Task 16a), n=1
`8. Checks 0-Day Status (Task 16b), n=1
`9. Only MIND1 Pills Will Work With System (Task 6b), n=1
`10. Do not change your medication unless instructed by your prescribing physician (Task
`CS-21), n=1
`11. Do not take first MIND1 pill until instructed by the App (Task CS-19), n=1
`12. Do not stop or change your medication dosage based on information provided by
`the MIND1 Kit. Consult your healthcare provider. (Task CS-20), n=1
`13. Check the expiration date printed on the Patch packaging (Task CS-01), n=1
`14. Do not place Patch in a location that overlaps the area where the last Patch was.
`(Task CS-12), n=2
`15. Do not wear the same patch for more than one week (Task CS-24), n=1
`The use errors are described in detail below.
`1. Download App (Task 2), n=1
`One participant in the unassisted group failed this task.
`
`The participant failed to download the app. The sponsor’s root cause analysis attributed
`the error to negative transfer and task confusion which led the participant to think that
`he only needed to take a pill during this task as that was the only thing he would
`typically do when taking his medication.
`We find that failure to download the App will result in the inability to use the system as
`intended. No mitigation has been proposed by Otsuka.
`
`
`
`
`
`i Necessary Task: User task that is necessary for use, but would not cause serious harm to the user in other ways if
`performed incorrectly. Could otherwise be referred to as an “essential” task.
`
`14
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`Reference ID: 4170268
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`(b) (4)
`
`

`

` The root causes and participant feedback do not indicate an issue related to the
`product user interface. Therefore, we have no additional recommendations at this time.
`
`2. Peels off large tab (Task 5e), n=1
`One participant in the unassisted group failed this task.
`
`The participant took the patch out of the pouch and applied the patch before watching
`the video that explains how to peel off the patch tabs. He thought he had to peel apart
`the adhesive layer and foam layer rather than removing only the release liner. The
`sponsor’s root cause analysis indicated the failure was due to insufficiently prominent
`guidance on the patch.
`We find that failure to peel off the large paper tab as instructed may result in lack of patch and
`system functionality due to poor skin contact. However, the App will alert the user that there is
`poor skin contact and if not adequately addressed, the App prompts the user to change the
`patch. Furthermore, the App video that describes patch application provides detailed
`instructions for and a demonstration of removing the large and small paper backing from the
`patch. Therefore, we find the risk has been reasonably mitigated and have no additional
`recommendations.
`3. Applies First Patch (Task 5b), n=4
`Two participants in the unassisted group failed this task.
` One participant applied the patch to her right forearm before asking for the App. The
`participant did not appear to be aware that she could move the protective covering to
`another site. The sponsor’s root cause analysis indicated the failure was due to test
`artifact.
`The other participant failed to apply the patch when instructed by the onboardingj
`video. As she was getting ready to apply the patch, the moderator paused the video to
`apply the protective covering which drew the participant’s attention from the last
`several seconds of the video. She was unable to navigate back to the patch applying
`video. The sponsor’s root cause analysis indicated the failure was due to test artifact
`and insufficient guidance on the user interface.
`Two participants in the unassisted group had difficulty with this task.
` One participant initially stated she would apply the patch to the upper right side but
`immediately corrected her response to say “upper left”. The sponsor’s root cause
`analysis indicated the difficulty was due to attention slip (participant stated she was
`“daydreaming”).
`
`
`
`j Onboarding tasks are those tasks associated with first-time use (i.e., account setup, setting up first patch, first pill
`ingestion, viewing the MIND1 overview video and proceeding to the home screen).
`
`15
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`Reference ID: 4170268
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`(b) (4)
`
`

`

`
`
`The other participant initially indicated he might apply the patch to his arm but chose
`the correct site. The sponsor’s root cause analysis indicated the difficulty was due to
`mental model (participant speculated about placing the patch on the arm based on his
`exposure to nicotine patch commercials).
`Our assessment of the failures and difficulties with applying the first patch find the risks
`associated with this task have been reduced to an acceptable level.
`
`
`
`
`
`
`
`
`
` We agree with this justification given there are screen
`prompts that will help the user to resolve the patch issue. Moreover, in the event a patch is not
`applied properly, a tile is triggered in the App prompting the user to fix and/or change the
`patch to resolve the issue. We find the App patch application video,
`, and Patch Box Insert
`Card clearly describe and show where the patch should be applied. We find the risk for errors
`with this step have been adequately mitigated to an acceptable level and no further mitigation
`is needed. Therefore, we have no additional recommendations.
`4.
`Ingests First Pill (Task 6c), n=2
`Two participants in the unassisted group failed this task.
` One participant took the first pill before opening the kit and a second pill while
`completing a patch change after she was done with onboarding. She stated her
`“prescription” was to take two pills per day. The report also stated she made up a
`scenario to allow her to take a second pill and that she was unsure what to do during
`the session. The sponsor’s root cause analysis indicated the failure was due to test
`artifact.
`
`
`
`The other participant took a first pill before opening the App and then indicated that he
`had completed the setup and was done with the task. Once the moderator clarified the
`task and asked him to restart, he took a second pill at the instruction of the onboarding
`flow. When asked why he took a second pill, he said, “Because I thought I had to redo
`the setup”. The sponsor’s root cause analysis indicated the failure was due to test
`artifact.
`The reported root cause for these failures is test artifact. We agree with this assessment and
`also considered that the participants took the first pill prior to opening the App. We recognize
`that in “real life” use of the system, the potential exists for taking an extra dose if a user takes
`the first pill, downloads the App later on the same day and follows the set up and instructions
`to take the first pill. We note that the proposed audio portion of the “Taking Your Pill” video
`states, “
`.” This
`message may help to prevent an extra dose from being taken. Additionally, we note this risk
`only exists during the initial onboarding procedure, so there is no concern for a repeated
`
`16
`
`Reference ID: 4170268
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`occurrence of an extra dose being administered. Thus, we find the risk of taking an extra dose
`during this task has been mitigated to a reasonable level and we have no additional
`recommendations at this time.
`5. Remove Patch (Task 19), n=1
`One participant in the assisted group failed this task.
`
`The participant did not fully remove the patch, leaving the adhesive layer on the
`simulated skin. When asked why she did not remove the patch completely, she said,
`“This fake skin is kinda throwing me off base...coz I didn’t want to destroy the skin
`here.” The sponsor’s root cause analysis indicated the failure was due to test artifact.
`Failure to remove the patch may result in skin irritation. Our assessment of this failure finds no
`further mitigation is needed. We agree with the sponsor’s assessment that test artifact
`contributed to the error since the failure was primarily due to the use of fake skin in a
`simulated use environment. Thus, we have no additional recommendations at this time.
`6. Applies Replacement Patch (Task 24a), n=2
`One participant from t