Clinical trial NCT03724981
Conditions: Diabetes Mellitus, Type 2
Sponsor: Eli Lilly and Company
Start date: 2018-10-18; Completion date: 2019-04-12
Enrollment: 312 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
In this study participants will try out two different types of drug injection pens (dulaglutide and semaglutide) on a practice pad and decide which device they prefer. No study drug will be administered.

Detailed description:

Arms: arm 1: Injection of commercial dulaglutide pen on a practice pad. arm 2: Injection of commercial semaglutide pen on a practice pad.
Interventions: intervention 1: Dulaglutide Pen intervention 2: Semaglutide Pen
Intervention descriptions: intervention 1: Injected on a practice pad. intervention 2: Injected on a practice pad.

Protocol documents:
Prot_000.pdf: 
Protocol H9X-MC-B021(b) 
 
Crossover Study Comparing Dulaglutide (Trulicity) Pen and the Semaglutide (Ozempic) Pen 
 
NCT03724981 
 
Approval Date: 30-Nov-2018 


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Approval Date: 30-Nov-2018 GMT
Protocol H9X-MC-B021(b): Crossover Study Comparing the 
Dulaglutide (Trulicity) Pen and the Semaglutide (Ozempic) Pen
Confidential Information
The information contained in this document is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company or its subsidiaries and 
should not be copied by or distributed to persons not involved in the clinical investigation of 
dulaglutide (LY2189265), unless such persons are bound by a confidentiality agreement 
with Eli Lilly and Company or its subsidiaries.
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure. Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release. In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Dulaglutide (LY2189265)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly on
07 Aug 2018
Amendment (a) Electronically Signed and Approved by Lilly on
11 Sep 2018
Amendment (b) Electronically Signed and Approved by Lilly on date below


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Table of Contents
Section
Page
Protocol H9X-MC-B021(b):  Crossover Study Comparing the Dulaglutide 
(Trulicity) Pen and the Semaglutide (Ozempic) Pen ............................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................12
3.
Introduction ......................................................................................................................14
3.1.
Study Rationale............................................................................................................14
3.2.
Background..................................................................................................................15
3.2.1.
Dulaglutide Pen....................................................................................................15
3.2.2.
Semaglutide Pen...................................................................................................16
3.3.
Benefit/Risk Assessment..............................................................................................17
3.4.
Risks and Foreseeable Adverse Events/Device Effects .................................................17
3.5.
Methods to Minimize Risks..........................................................................................17
4.
Objectives and Endpoints..................................................................................................20
5.
Study Design.....................................................................................................................21
5.1.
Overall Design .............................................................................................................21
5.2.
Number of Participants.................................................................................................22
5.3.
End of Study Definition ...............................................................................................22
5.4.
Scientific Rationale for Study Design...........................................................................22
5.5.
Data Collection Process................................................................................................22
5.5.1.
Pilot Phase:  Participant Recruitment and Screening 
Procedures ...........................................................................................................23
5.5.2.
Main Phase:  Participant Recruitment and Screening 
Procedures ...........................................................................................................23
5.5.3.
Overview of Study Visit Procedures for the Pilot Phase .......................................24
5.5.4.
Overview of Study Visit Procedures for the Main Phase.......................................26
5.6.
Justification for Dose ...................................................................................................27
6.
Study Population...............................................................................................................28
6.1.
Inclusion Criteria..........................................................................................................28
6.2.
Exclusion Criteria ........................................................................................................28
6.3.
Screen Failures.............................................................................................................29
7.
Treatments........................................................................................................................30
7.1.
Treatments Administered .............................................................................................30
7.1.1.
Packaging and Labeling .......................................................................................30


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7.1.2.
Medical Devices...................................................................................................30
7.2.
Method of Device Assignment .....................................................................................30
7.2.1.
Selection and Timing of Doses.............................................................................31
7.3.
Blinding .......................................................................................................................31
7.4.
Dosage Modification....................................................................................................31
7.5.
Preparation/Handling/Storage/Accountability...............................................................31
7.6.
Treatment Compliance .................................................................................................31
7.7.
Concomitant Therapy...................................................................................................31
7.8.
Treatment after the End of the Study............................................................................31
7.8.1.
Special Treatment Considerations ........................................................................32
8.
Discontinuation Criteria ....................................................................................................33
8.1.
Discontinuation from Study Treatment.........................................................................33
8.1.1.
Permanent Discontinuation from Study Treatment ...............................................33
8.1.2.
Temporary Discontinuation from Study Treatment...............................................33
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................33
8.2.
Discontinuation from the Study....................................................................................33
8.3.
Lost to Follow-Up........................................................................................................33
9.
Study Assessments and Procedures ...................................................................................34
9.1.
Outcome Assessments..................................................................................................34
9.1.1.
Primary/Secondary Assessments ..........................................................................34
9.1.2.
Appropriateness of Assessments ..........................................................................34
9.1.2.1.
Supplemental Questions .................................................................................34
9.1.2.2.
Time-to-Train Observer Recording Sheet .......................................................34
9.1.2.3.
Demographic Form.........................................................................................35
9.1.2.4.
Interviewer Recording Sheet...........................................................................35
9.1.2.5.
Pilot Phase Interview Questions......................................................................35
9.1.2.6.
Global Preference Item...................................................................................35
9.1.2.7.
Diabetes Injection Device – Preference Questionnaire ....................................35
9.1.2.8.
Four Items from the Medication Delivery Device 
Assessment.....................................................................................................35
9.1.2.9.
Clinical Information Form..............................................................................36
9.2.
Adverse Events ............................................................................................................36
9.2.1.
Serious Adverse Events........................................................................................37
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................38
9.2.2.
Adverse Event Monitoring with a Systematic Questionnaire ................................38
9.2.3.
Complaint Handling.............................................................................................38
9.3.
Treatment of Overdose.................................................................................................38
9.4.
Safety...........................................................................................................................38


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9.4.1.
Electrocardiograms ..............................................................................................38
9.4.2.
Vital Signs ...........................................................................................................38
9.4.3.
Laboratory Tests ..................................................................................................39
9.4.4.
Safety Monitoring ................................................................................................39
9.4.4.1.
Hepatic Safety Monitoring..............................................................................39
9.5.
Pharmacokinetics .........................................................................................................39
9.6.
Pharmacodynamics ......................................................................................................39
9.7.
Pharmacogenomics or Genetics....................................................................................39
9.7.1.
Samples for Pharmacogenetic Research ...............................................................39
9.8.
Biomarkers and Other Analyses ...................................................................................39
9.9.
Health Economics or Medical Resource Utilization and Health 
Economics ...................................................................................................................39
10.
Statistical Considerations ..................................................................................................40
10.1. Sample Size Determination ..........................................................................................40
10.2. Populations for Analyses..............................................................................................40
10.3. Statistical Analyses ......................................................................................................40
10.3.1.
General Statistical Considerations ........................................................................40
10.3.2.
Treatment Group Comparability...........................................................................41
10.3.2.1.
Patient Disposition..........................................................................................41
10.3.2.2.
Patient Characteristics ....................................................................................41
10.3.2.3.
Concomitant Therapy .....................................................................................41
10.3.2.4.
Treatment Compliance....................................................................................41
10.3.3.
Statistical Analyses ..............................................................................................41
10.3.3.1.
Primary Analyses ...........................................................................................41
10.3.3.2.
Gated Secondary Analyses .............................................................................41
10.3.3.3.
Exploratory Analyses .....................................................................................42
10.3.3.3.1.
Exploratory 1.  DID-PQ Analyses of Items 1 to 8 and 
10 .............................................................................................................42
10.3.3.3.2.
Exploratory 2.  Time-to-Train Analyses....................................................42
10.3.3.3.3.
Exploratory 3.  Supplemental Question Analyses......................................42
10.3.3.3.4.
Exploratory 4.  Evaluation of the DID-PQ.................................................42
10.3.3.4.
Missing Data ..................................................................................................43
10.3.4.
Safety Analyses....................................................................................................43
10.3.5.
Pharmacokinetic/Pharmacodynamic Analyses......................................................43
10.3.6.
Evaluation of Immunogenicity .............................................................................43
10.3.7.
Other Analyses.....................................................................................................43
10.3.7.1.
Health Economics...........................................................................................43
10.3.7.2.
Subgroup Analyses.........................................................................................43


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10.3.7.3.
Pilot Phase Analyses.......................................................................................44
10.3.8.
Interim Analyses..................................................................................................44
11.
References ........................................................................................................................45
12.
Appendices .......................................................................................................................48


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List of Tables
Table
Page
Table 1.1.
Objectives/Endpoints/Statistical Analyses......................................................10
Table 2.1.
Schedule of Activities....................................................................................12
Table 4.1.
Objectives and Endpoints...............................................................................20


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List of Figures
Figure
Page
Figure 3.1.
Dulaglutide pen external view........................................................................16
Figure 3.2.
Semaglutide single-patient-use pen external view. .........................................17
Figure 5.1.
Study diagram for the patient preference study...............................................21


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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................49
Appendix 2.
Study Governance Considerations..................................................................51
Appendix 3.
Recruitment Advertisements..........................................................................55
Appendix 4.
Pilot Phase Screening Script ..........................................................................56
Appendix 5.
Pilot Phase Inclusion/Exclusion Criteria ........................................................64
Appendix 6.
Confirmation Letter/E-mail............................................................................66
Appendix 7.
Reminder Phone Call/E-mail .........................................................................67
Appendix 8.
Main Phase Screening Script..........................................................................68
Appendix 9.
Main Phase Inclusion/Exclusion Criteria........................................................71
Appendix 10.
Participant Recruitment Tracking Log ...........................................................73
Appendix 11.
Supplemental Question S1.............................................................................74
Appendix 12.
Interview and Device Training Guide ............................................................75
Appendix 13.
Time-to-Train (TTT) Observer Recording Sheet............................................88
Appendix 14.
Demographic Form........................................................................................89
Appendix 15.
Interviewer Recording Sheet..........................................................................91
Appendix 16.
Pilot Phase Interview Questions.....................................................................92
Appendix 17.
Global Preference Item ..................................................................................94
Appendix 18.
DID-PQ.........................................................................................................95
Appendix 19.
Four Items From MDDAB – Ozempic Device ...............................................96
Appendix 20.
Four Items From MDDAB – Trulicity Device................................................98
Appendix 21.
Supplemental Questions S2 and S3..............................................................100
Appendix 22.
Clinical Information Form ...........................................................................101
Appendix 23.
Protocol Amendment H9X-MC-B021(b) Summary Crossover Study 
Comparing the Dulaglutide (Trulicity) Pen and the Semaglutide 
(Ozempic) Pen.............................................................................................106


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1. Synopsis
Title of Study:  
Protocol H9X-MC-B021:  Crossover Study Comparing the Dulaglutide (Trulicity) Pen and the 
Semaglutide (Ozempic) Pen
Rationale: 
Positive perceptions of injection devices could lead to better treatment adherence, which has 
been shown to have an impact on treatment outcomes in patients with type 2 diabetes mellitus
(T2DM) (Khunti et al. 2017, 2018).  Therefore, it may be useful for clinicians to consider not 
only the efficacy, safety, and cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor 
agonists (RA) but also patient preferences of injection devices when selecting the most 
appropriate treatment for patients with T2DM.  The primary purpose of this study is to determine 
patient preferences between the injection devices used for the GLP-1 RAs dulaglutide versus 
semaglutide.  The dulaglutide single-dose pen is a single-dose autoinjector pen that does not 
require handling of the needle, which is hidden and automatically retracts after use (Eli Lilly IFU 
2017).  The semaglutide single-patient-use pen can be used more than once and does require 
handling of the needle (Novo Nordisk IFU 2017).  
This study will also evaluate the time-to-train (TTT) on using both the dulaglutide and 
semaglutide devices.  One recent study conducted in Japan found that the dulaglutide pen was 
associated with a significantly shorter mean TTT compared to the insulin degludec 
single-patient-use pen (7.4 minutes versus 19.7 minutes; p<.001) (Asakura et al. 2018).  The 
FlexTouch pen used for the insulin degludec (Asakura et al. 2018) is functionally similar to the 
one being evaluated in this study with semaglutide.  These results suggest that it is less 
burdensome for health care providers to train patients to correctly use the dulaglutide device
compared to other devices and easier for patients to learn self-injection with this device.  The 
study will examine whether differences in patient preferences and TTT follow the same pattern 
in this comparison crossover trial between the dulaglutide and semaglutide devices in a US 
sample.  
Summary of Study Design:  
Study H9X-MC-B021 is an open-label, multicenter, randomized, crossover study assessing 
patient preference (and training time) with the dulaglutide single-dose pen versus the 
semaglutide single-patient-use pen.  Study H9X-MC-B021 consists of a single study visit for 
approximately 290 self-injection naïve adults to all injectable treatment diagnosed with T2DM
and taking oral medication to treat their condition.  Self-injection naïve patients will be recruited 
from approximately 14 clinical sites in the US.  The TTT assessment will be conducted in a 
subset of 75 to 80 patients from approximately 5 of the selected US clinical sites.  All 
participants will receive training and perform mock injections on a practice pad using both 
devices.  However, the order in which the participants are exposed to the devices will be 
randomized.  Fifty percent (50%) of patients will be randomized to use the dulaglutide device 
first, while the other half will use the semaglutide device first.  Participants will be under the 


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direct supervision of a study interviewer when handling the injection devices.  Participants will 
also complete a series of questionnaires to determine their device preference.  
Prior to commencing the study, a pilot phase will be conducted with approximately 10 to 20
patients with T2DM.  The purpose of the pilot phase is to create a clear and streamlined training 
procedure for each device in order to finalize the steps of the training approach to use in the main
phase of the study.  The pilot phase data will not be included in the final sample of 
approximately 290 patients with T2DM for the analyses.  
Treatment Arms and Duration:
Patients will be randomized into 2 study arms to control for order effects based on device 
administration.  Fifty percent of patients will be randomized to use the dulaglutide device first, 
while the other half will use the semaglutide device first.  All patients will be exposed to both 
devices under investigation in this study in a 1-time interview.  
Number of Patients:
Participating patients will be randomized to ensure that there are approximately 290 completers 
for the main phase of this study.  Prior to the main phase, approximately 10 to 20 patients will be 
included in the pilot phase of this study. All patients with T2DM included in the study must be 
self-injection naïve to all injectable treatment, in efforts to minimize potential bias based on any 
previous experience.  Glucagon-like peptide-1 RAs are often the first injectable medication 
prescribed to patients with T2DM, thus the reason for targeting self-injection naïve participants.  
Statistical Analyses:  Refer to the third column below in Table 1.1.  
Table 1.1.
Objectives/Endpoints/Statistical Analyses
Objectives
Endpoints
Statistical Analyses
Primary:
Determine patient 
preference between the 2 
injection devices
The Global Preference 
Item:  “Overall, which 
device do you prefer?”
The Prescott test will be run to examine whether there 
is a statistically significant difference in preference 
between the devices, while controlling for order 
effects (significance level at p<.05).
Gated Secondary:
Compare devices with 
regard to ease of use (To 
be tested if a significant 
difference is found in the 
primary objective.)
Item 9 of the Diabetes 
Injection Device –
Preference Questionnaire 
(DID-PQ)
If the primary objective is statistically significant, 
responses to the 5-point response scale of DID-PQ 
Item 9 (ease of use) will be collapsed into 3 
categories.  The “strongly prefer” and “prefer” 
response options will be combined for each device, 
resulting in 3 categories:  prefer dulaglutide, prefer 
semaglutide, and no preference.  The Prescott test will 
be run to examine whether there is a statistically 
significant difference in preference for ease of use 
between the devices, while controlling for order 
effects (significance level at p<.05).
Exploratory 1:
Collect data to support the 
preference question in the 
primary objective
Results from the DID-
PQ Items 1 to 8 and 10
Exploratory analyses of Items 1 to 8 and 10 of the 
DID-PQ will follow the same procedures as those for 
the gated secondary objective described above. 


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Objectives
Endpoints
Statistical Analyses
Exploratory 2:
Compare time-to-train
(TTT) on the dulaglutide 
and semaglutide devices
Results from the 
Observer Recording 
Sheet
Carryover effects will be examined.  If there are no 
significant carryover effects, then TTT for both the 
first and second trainings will be used in this analysis.  
If there is a significant carryover effect, then this 
analysis will use data for whichever device is trained 
first. The average duration required to train and 
successfully inject each device will be assessed using 
the linear model appropriate for a crossover design.  
Exploratory 3:
Examine patients’ 
willingness to use each of 
the devices after being 
trained on both
Results from the 3 
Supplemental Questions
Using the data from the 3 Supplemental Questions, 
descriptive analyses will be run to examine 
willingness to use each of the devices after being 
trained on both.
Exploratory 4:
Validation of the DID-PQ 
Questionnaire validation 
analyses (i.e., known-
groups and construct 
validity)
The primary validation approach will be to examine 
known-groups validity by comparing DID-PQ 
responses of patients categorized based on the 
responses to the Global Preference Item. 
Construct validity will be assessed by comparing 
DID-PQ responses to responses on 4 items selected 
from the Medication Delivery Device Assessment 
Battery (Yu et al. 2017).  Cross-tabulation tables of 
these 4 items by response options for each of the 
DID-PQ items will be presented. 
In addition, the DID-PQ exploratory approach for 
comparing devices will be examined relative to the 
ancillary measures.


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2. Schedule of Activities
Table 2.1.
Schedule of Activities
Procedure
Pilot Phase:  Conducted at 1 US 
Location1
Approximately n ≈10 to 20
Main Phase:  Conducted at 
Approximately 14 Clinical Sites 
across US2
Approximately n ≈ 290
Screening
Study Visit
Screening
Study Visit
Conduct study screening; if eligible, schedule visit 
X
X
Main Phase:  Inclusion/Exclusion Form
X
Pilot Phase:  Inclusion/Exclusion Form
X
Completion of written informed consent 
X
X
Randomization 
X
X
Participant completes Supplemental Question S1
X
X
Participant completes training and performs mock injections with 
randomized Device 1 
X
X
If TTT, the assigned study team observer completes Observer 
Recording Sheet for Device 13
X
X
INTERVIEW BREAK 1:  Participant will be offered a restroom and 
water break
X
X
Participant completes Demographic Form 
X
X
Participant completes training and performs mock injections with 
randomized Device 2 
X
X
If TTT, the assigned study team observer completes Observer 
Recording Sheet for Device 23
X
X
Study team interviewer administers pilot phase interview questions
X
Study team interviewer completes Interviewer Recording Sheet
X
X
OPTIONAL INTERVIEW BREAK 2
X


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Procedure
Pilot Phase:  Conducted at 1 US 
Location1
Approximately n ≈10 to 20
Main Phase:  Conducted at 
Approximately 14 Clinical Sites 
across US2
Approximately n ≈ 290
Screening
Study Visit
Screening
Study Visit
Participant completes Global Preference Item
X
X
Participant completes DID-PQ
X
X
Participant completes 4 items selected from the MDDAB about each of 
the devices under investigation
X
X
Participant completes Supplemental Questions S2 and S3
X
X
Clinical site completes Clinical Information Form
X
Abbreviations:  DID-PQ = Diabetes Injection Device – Preference Questionnaire; TTT = time-to-train; MDDAB = Medication Delivery Device Assessment Battery.
1Pilot Phase:  Recruiting, screening/scheduling, and the in-person interviews will be conducted by Evidera.
2Main Phase:  Recruiting and screening/scheduling will be done by the clinical sites. The in-person interviews will be conducted by Evidera.
3TTT interviews:  All pilot phase interviews will involve the TTT assessment.  However, for the main phase, the TTT assessment will only be conducted in a subset of the main 
phase participants with approximately 75 to 80 patients across an estimated 5 clinical sites.


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3. Introduction
3.1.
Study Rationale
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are often recommended as part of 
combination therapy for type 2 diabetes mellitus (T2DM) when oral medication alone does not 
provide sufficient glycemic control (Inzucchi et al. 2012; NICE 2014).  These injectable 
treatments have been shown to be effective in lowering glycated hemoglobin A1c (HbA1c) with 
a low risk of hypoglycemia and a potential benefit of weight loss (Aroda et al. 2012; Trujillo et 
al. 2015; Htike et al. 2017).
Dulaglutide is a GLP-1 RA that was approved by the FDA and EMA in 2014 (Edwards and 
Minze 2015).  The safety and efficacy for HbA1c control were demonstrated in several clinical 
trials involving over 5000 patients (Dungan et al. 2014; Nauck et al. 2014; Umpierrez et al. 
2014; Wysham et al. 2014; Blonde et al. 2015; Giorgino et al. 2015; Dungan et al. 2016; Ludvik 
et al. 2018; Pozzilli et al. 2017; Tuttle et al. 2018).  The dulaglutide device is a single-dose 
autoinjector pen that does not require handling of the needle, which is hidden and automatically 
retracts after use (Eli Lilly IFU 2017).  The dulaglutide device is notably different from devices 
used with the other medications in this class.  In this study, the dulaglutide device will be 
compared to the semaglutide device, which is a newer weekly GLP-1 RA, administered via a 
single-patient-use pen.  The semaglutide device can be used more than once and does require 
handling of the needle (Novo Nordisk IFU 2017).  
Positive perceptions of injection devices could lead to better treatment adherence, which has 
been shown to have an impact on treatment outcomes in patients with T2DM (Khunti et al. 2017, 
2018). Therefore, it may be useful for clinicians to consider not only the efficacy, safety, and 
cardiovascular effects of GLP-1 RAs but also patient preferences of injection devices when
selecting the most appropriate treatment for patients with T2DM.  The primary purpose of this 
study is to determine patient preferences between the injection devices used for the GLP-1 RAs 
dulaglutide versus semaglutide.  This study will also evaluate the time-to-train (TTT) on using 
both the dulaglutide and semaglutide devices.  One recent study conducted in Japan found that 
the dulaglutide device was associated with a significantly shorter mean TTT than the 
single-patient use-pen used for insulin degludec (7.4 minutes versus 19.7 minutes; p<.001) 
(Asakura et al. 2018).  The FlexTouch pen used for the insulin degludec (Asakura et al. 2018) is 
functionally similar to the one being evaluated in this study with semaglutide.  These findings 
and other results suggest that it may be less burdensome for health care providers (HCPs) to train 
patients to correctly use the dulaglutide device compared to other devices and easier for patients 
to learn self-injection with this device.  The study will examine whether differences in patient 
preferences and TTT follow the same pattern in this comparison crossover trial between the 
dulaglutide and semaglutide devices in a US sample of patients with T2DM.  All patients with 
T2DM included in the study must be self-injection naïve to all injectable treatment, in efforts to 
minimize potential bias based on any previous experience.  GLP-1 RAs are often the first 
injectable medication prescribed to patients with T2DM, thus the reason for targeting 
self-injection naïve participants.  


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Please note: The protocol language will use the generic names of the medication in the 
devices (i.e., semaglutide and dulaglutide). However, to provide a naturalistic experience that 
most closely mirrors real-world treatment process, the study participants will be trained to use 
the branded injection devices that are used by patients who are actually treated with these 
medications. These pens feature the brand names (i.e., Ozempic and Trulicity) more 
prominently than the generic names. Therefore, to minimize confusion and ensure that study 
materials are clear for the respondents, the patient-completed questionnaires will use the 
brand names that are clearly presented on each pen. These names will always be presented in 
alphabetical order (i.e., Ozempic followed by Trulicity). Importantly, the use of the branded 
devices is not intended to be promotional in nature.
Appendix 1 contains the protocol abbreviations and definitions.  
3.2.
Background
Several previous studies have found that patients seem to prefer the dulaglutide single-dose pen 
over the devices used to inject other medications in the GLP-1 RA class.  For example, 2 discrete 
choice experiments (1 in the UK and the other in Japan) found that patients preferred the type of 
delivery system used for dulaglutide over the delivery system used for liraglutide 
(Gelhorn et al. 2015, 2016).  Similarly, health state utility studies conducted in the UK and Italy 
found that patients preferred the dulaglutide pen attributes over the attributes of devices used 
with comparator treatments (Matza et al. 2017a; Matza et al. 2018b).
Research on perceptions of these injection devices has also been conducted among patients who 
have personal experience with the devices.  For example, a recent naturalistic study conducted in 
over 400 patients with T2DM in the US found that the dulaglutide pen was associated with 
perceptions of greater ease-of-use and convenience than the liraglutide device (Matza et al. 
2018a).  Furthermore, the subset of 58 patients who had tried both treatments preferred the 
dulaglutide pen over the liraglutide device, as indicated across all 10 items of the Diabetes 
Injection Device – Preference Questionnaire (DID-PQ), which was designed to assess 
preferences between non-insulin injection devices.  The dulaglutide device was also preferred 
over the single-patient-use pen device (used with insulin degludec) in a recent crossover study 
conducted among self-injection naïve patients with T2DM in Japan (Asakura et al. 2018).  In 
addition, the dulaglutide pen was associated with greater ease-of-use and less time required for 
training.  The dulaglutide device was also found to be a safe and effective device for use by 
injection-naïve patients with T2DM in a 4-week Phase 3b usability trial (Matfin et al. 2015).
3.2.1. Dulaglutide Pen
The dulaglutide single-dose pen (Figure 3.1) is a single-use autoinjector designed for a 
once-weekly subcutaneous (SC) injection of dulaglutide in either a 0.75 mg or 1.5 mg dose for 
adult patients with T2DM (Eli Lilly IFU 2017).  Dulaglutide may be self-administered or 
administered by patients’ caregivers or HCPs.
The dulaglutide pen is designed to deliver a SC injection without the need for management of the 
injection site such as needle insertion into a skin fold.  The needle in the dulaglutide pen is 29


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gauge.  The dulaglutide pen is approximately 16 cm in length and is constructed of polymer 
molded components, metal springs, and the pen label.
Figure 3.1.
Dulaglutide pen external view.
The pen is prepared for use by removing the base cap (which also removes a rigid needle shield 
from the syringe), placing it at the injection site, and rotating the lock ring to unlock.  The pen is 
then used by depressing the Injection Button (green button in Figure 3.1).  This action releases a 
spring-enabled plunger rod that inserts the needle to a predetermined depth and then delivers the 
contents of the syringe into SC tissue.  The plunger rod initiates a second spring-enabled 
mechanism to automatically retract the needle after the dose is completely delivered.  The 
retracted syringe and needle is permanently contained within the structure of the pen after the 
injection cycle is complete.  The entire pen is disposed after each use.
3.2.2. Semaglutide Pen
Ozempic is a registered trademark of Novo Nordisk A/S. All other trademarks are the property of 
their respective owners.
The semaglutide single-patient-use pen (Figure 3.2) is a multi-use, disposable injection device 
designed for once-weekly SC injection of semaglutide (Novo Nordisk IFU 2017).  Adult patients 
with T2DM are prescribed semaglutide in an escalating dose regimen of 0.25 mg starting dose 
for 4 weeks, followed by 0.5 mg, and a possible dose escalation after 4 weeks to 1.0 mg. The 
0.25 mg and 0.5 mg doses are administered by 1 pen, with patients requiring 1.0 mg switching to 
the respective 1.0 mg pen device.  Semaglutide may be self-administered or administered by 
patients’ caregivers or HCPs.
The semaglutide pen is designed to deliver a SC injection in a manner similar to an insulin pen.  
The exposed needle length is variable, using NovoFine® needles ranging from 4 to 8 mm.  The 
needles used with the semaglutide pen will have a 32 gauge. 


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Figure 3.2.
Semaglutide single-patient-use pen external view.
According to the instructions for use (IFU), the semaglutide pen is prepared by attaching a new 
needle via a push-on retention mechanism, priming the pen by dialing the flow check symbol and 
depressing the dose knob, turning the dose selection knob to the appropriate dose, inserting the 
needle under the skin, and pushing the dose knob to the end of travel. The patient is then 
instructed to count to 6, remove the needle from the skin, and safely discard the used needle.
3.3.
Benefit/Risk Assessment
While there are no direct therapeutic benefits to patients participating in the study, the results 
from this study will offer valuable insights into the patient preference and TTT of different 
injection devices in the same drug class.  Injection inertia is a documented and valid concern in 
the T2DM treatment paradigm, and this study will provide a further understanding of T2DM 
patients’ preferences for injection devices themselves (Khunti et al. 2013, 2016; 
Norrbacka et al. 2018).  The risk of this study will be minimized because the mock injections 
will be performed in practice pads and participants will be under the direct supervision of a study 
interviewer when handling the injection devices.  Participants are not injecting themselves in this 
study.
3.4.
Risks and Foreseeable Adverse Events/Device Effects
The following is a list of potential risks associated with participation in this clinical study:

Accidental needlestick injury

Accidental exposure to drug product (accidental self-injection)
The following is a list of potential risks associated with the study devices:

Improper functioning and/or mechanical failure of the device or its components (for 
example, no injection, slow injection into practice pad, partial injection into practice pad, 
cracked syringes, high force to operate device, damaged needle)

Skin reaction (for example, after accidental needlestick)

Nausea, gastrointestinal event, or low blood sugar potentially associated with exposure to 
drug product
3.5.
Methods to Minimize Risks
Training on both study devices will be provided by Evidera study staff based on the approved 
IFUs (Eli Lilly IFU 2017; Novo Nordisk IFU 2017).  Training for correct sharps 
handling/disposal is part of the study training, and no cross contamination is expected due to 
each participant receiving their own device, as well as injecting drug into a practice pad instead 


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of themselves.  In order to minimize risk of accidental needle sticks, participants will not recap 
the semaglutide needle.  A sharps container will be available to permit participants to remove the 
semaglutide needle and dispose of it immediately, rather than recapping the needle for later 
disposal.  Participants will be instructed to place the outer needle cap in the sharps container 
once it is removed from the device so they do not have the temptation to recap, which was found 
to be a potential opportunity for accidental needle sticks during the pilot study.  Study staff will 
monitor the participant at all times in the room and intervene should a dangerous situation occur.  
Participants will be under direct supervision of the study interviewer when handling the devices.
If a needlestick injury occurs or if a patient is exposed to drug, medical personnel will always be 
available to address any potential medical issues or concerns.  With patients recruited from 10 of 
the 14 sites, the interviews will be conducted at the sites where there will be nurses and 
physicians on staff ready to assist if necessary.  These clinical staff members will follow 
(monitor) the patient as per clinical judgment for a potential adverse event (AE) and follow the 
appropriate device-reporting procedures.  With patients recruited from the other four sites, the 
interviews will be conducted at interview facilities where medical professionals (e.g., nurses) 
hired specifically for this study will be ready to assist if necessary in case of AEs such as 
unanticipated needlesticks or self-injection.  
It is very unlikely that a participant will receive an accidental dose of medication for several 
reasons:  
1. The participants will only handle the devices under direct supervision of a study 
interviewer after the interviewer has demonstrated how to use the device on a mock 
injection pad.
2. Patients will be told that they should not inject themselves, and these devices will only be 
used for mock injections into an injection pad.
3. If a participant appears to begin injecting themselves rather than the injection pad, the 
interviewer would immediately interrupt the process and stop the participant from 
completing this self-injection. 
4. In the unlikely circumstance that a patient does have an accidental “needle stick,” no 
medication would be injected unless the patient continues with the injection procedure.  It 
is not possible for a patient to accidentally deliver a full dose of medication without 
intending to do so because a series of steps needs to be followed to inject a medication 
dose.  These steps for dulaglutide and semaglutide are described below:
a.
Dulaglutide: The participant would need to place the device over their skin, 
unlock the device by turning a lock ring, press the injection button, and hold the 
device in place for approximately 5 – 10 seconds.  
b. Semaglutide: The participant would need to turn the dose selector to a dose, insert 
the needle into their skin, press the injection button, and wait approximately 6 
seconds.  
Even if a participant completes this highly unlikely series of events and does receive an injection 
of medication, a single dose of either drug is likely to have minimal clinical impact.  These two 
medications are GLP-1 receptor agonists, not insulin.  Therefore, the risk of hypoglycemia after 


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a single dose is low, and steady state therapeutic medication concentration is not achieved for 
approximately 25 days with dulaglutide and 4 – 5 weeks with semaglutide.  However, medical 
personnel available for the study will be aware of this risk and ready to give oral sugar 
preparations.  Medical personnel would also be informed of the potential for transient GI side 
effects of a single dose which would be easily manageable with antiemetics.  
More detailed information about the known and expected benefits and risks of dulaglutide and 
semaglutide may be found in the following:  Protocol Sections 3.3 and 3.4.


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4.
Objectives and Endpoints
Table 4.1 shows the objectives and endpoints of the study.
Table 4.1.
Objectives and Endpoints
Objectives
Endpoints
Primary:
Determine patient preference between the 2 
injection devices
The Global Preference Item:  “Overall, which device do 
you prefer?”
Gated Secondary:
Compare devices with regard to ease of use (to be 
tested if a significant difference is found in the 
primary objective.)
Item 9 of the Diabetes Injection Device – Preference 
Questionnaire (DID-PQ)
Exploratory 1:
Collect data to support the preference question in 
the primary objective
Results from the DID-PQ Items 1 to 8 and 10
Exploratory 2:
Compare time-to-train on the dulaglutide and 
semaglutide devices
Results from the Observer Recording Sheet
Exploratory 3:
Examine patients’ willingness to use each of the 
devices after being trained on both
Results from the 3 Supplemental Questions
Exploratory 4:
Validation of the DID-PQ 
Questionnaire validation analyses (i.e., known-groups and 
construct validity)


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5. Study Design
5.1.
Overall Design
Study H9X-MC-B021 is an open-label, multicenter, randomized, crossover study assessing 
patient preference (and training time) for the dulaglutide pen versus the semaglutide pen (Figure 
5.1).  Approximately 290 self-injection naïve patients with T2DM and taking oral medication to 
treat their condition will be recruited from approximately 14 clinical sites in the US.  The TTT 
assessment will be conducted in a subset of 75 to 80 self-injection naïve patients from 
approximately 5 of the selected US clinical sites.  All participants will receive training and 
perform mock injections on a practice pad using both devices.  The order of device training and 
administration will be randomized.  Participants will also complete a series of questionnaires to 
determine their device preference.  All participants will attend a single in-person study visit.  
Prior to commencing the study, a pilot phase will be conducted with approximately 10 to 20 
self-injection naïve patients with T2DM.  The purpose of the pilot phase is to create a clear and 
streamlined training procedure for each device in order to finalize the steps of the training 
approach to use in the main phase of the study.  The pilot phase data will not be included in the 
final sample of approximately 290 self-injection naïve patients with T2DM for the analyses.  
Figure 5.1.
Study diagram for the patient preference study.
The devices for this study will be the commercialized injection pens containing non-modified 
commercial product with stickers on the devices indicating that the devices are intended for use 
in clinical trial.  However, no active drug will be administered as patients will not be injecting 
themselves.  Instead, patients will perform mock injections into a practice pad after being trained 
in the use of each device.  Fifty percent of patients will be randomized to use the dulaglutide 
device first, while the other half will use the semaglutide device first.  Lilly will provide all 


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injection devices that will be used in this study because commercial devices are being used 
during the interviews and mock injections.  The drug names will be visible to patients and the 
device names will not be blinded to the participants.  The devices are physically different from 
one another, thus even if the participants were blinded to the pens they could discern the name of 
each device.  More details about blinding are provided in Section 7.3.
5.2.
Number of Participants
It is expected that approximately double the estimated total sample will be screened (i.e., an 
estimated 580 participants across all clinical sites, 48 to 50 participants per site will be screened) 
to achieve 290 evaluable participants who are eligible and interested to participate in the main 
phase.  Patients will not be randomized to device training order, until they have signed consent. 
Similarly, for the preceding pilot phase, approximately 20 to 40 participants will be screened to 
reach 10 to 20 evaluable participants who are eligible and interested to participate.  
5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities (Section 2) for the last patient.
5.4.
Scientific Rationale for Study Design
The multicenter crossover study design was selected to control for order effects while allowing 
patients to directly compare 2 devices.  The order in which the participants are exposed to the
devices will be randomized.  Fifty percent of patients will be randomized to use the dulaglutide 
device first, while the other half will use the semaglutide device first.  All participants will attend 
a single in-person study visit.  Table 2.1 displays the schedule of activities for this crossover 
study.  Ethical Review Board (ERB) approval will be obtained before study implementation.  
More details about the regulatory and ethical considerations for this study, including the 
informed consent process, are provided in Appendix 2.
5.5.
Data Collection Process
An overview of the study data collection procedures is presented in this section.  Subsections are 
presented separately for the pilot and the main phase.  For the pilot phase, recruitment and data 
collection efforts will be conducted by Evidera (a business unit within Pharmaceutical Product 
Development, LLC [PPD]).  For the main phase, approximately 14 clinical sites across the US 
will be identified.  These clinical sites will recruit, confirm patient eligibility, and schedule all 
study interviews.  The interviews that do not include the TTT assessment will take place at the 
actual clinical sites.  Approximately 5 clinical sites will be selected for the subset of TTT 
interviews.  The TTT interviews will occur at interview facilities with a 1-way mirror near to the 
clinical sites selected for recruitment.  Evidera study staff will travel to all main phase interview 
locations to conduct the study interviews in-person.  
Any study interviews conducted at non-clinical facilities will require a medical professional (for 
example, nurse or paramedic) to be on site in case of AEs such as unanticipated needlesticks.  


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5.5.1. Pilot Phase:  Participant Recruitment and Screening 
Procedures
Approximately 10 to 20 participants will be recruited for the pilot phase via ERB-approved 
newspaper advertisements, internet classified advertisements, and/or other advertisements in 
social media outlets (Appendix 3).  For advertisements, study staff from Evidera will arrange 
toll-free phone numbers for interested participants to call and leave messages.  Study staff will 
also arrange a study-specific e-mail address that participants can use to respond to 
advertisements and provide their contact information via e-mail.  Study staff will regularly check 
the voicemail box and e-mail inbox to promptly respond to interested participants.  The 
voicemail box will be password protected, and only assigned study team members will have 
access to the password to obtain participants’ contact information.  For the study e-mail account, 
only the necessary study team members will be granted permission to the e-mail account by 
Evidera IT staff.
Type 2 diabetes mellitus diagnosis will be verified through proof of oral antidiabetic medication
use.  Study staff will screen potential participants who respond to the advertisement to ensure 
that they meet study inclusion criteria (Appendix 4).  In addition to the inclusion/exclusion 
criteria, several demographic questions such as age, gender, and employment status will be asked 
to monitor eligibility and sample diversity throughout the recruitment process.  If any 
inclusion/exclusion criteria cannot be confirmed via phone screening (for example, participant’s 
cognitive ability to understand the device trainings), the final eligibility determination will be 
established at the time of the interview (Appendix 5 for Inclusion/Exclusion Form will be 
completed at the beginning of the interview).  
Those participants considered eligible based on screening will be scheduled for an interview by 
study staff.  All pilot phase participants will participate in the TTT assessment.  Any identifying 
information (for example, names, addresses, telephone numbers) that is recorded on the 
screening/scheduling scripts will be kept in a limited access, locked filing cabinet.  Prior to the 
interviews, project staff will send participant’s confirmation (and directions to the interview 
location) by e-mail or mail according to participant’s preference (Appendix 6).  Reminder phone 
calls will be made to participants 1 day before the interview.  During previous studies, it has 
been found that these reminder phone calls reduce the likelihood that participants will fail to 
attend their appointment (Appendix 7).  However, it might not be possible to speak to all 
participants 1 day before the interviews (for example, no answer), if so, e-mail reminders will be 
sent (Appendix 7).  At least 1 reminder will be sent to all pilot phase participants about their 
study interview when possible from the assigned study team member. 
5.5.2. Main Phase:  Participant Recruitment and Screening 
Procedures
The Evidera clinical site database will be used to identify the appropriate US clinical sites for 
inclusion in the study.  Sites in a variety of geographical locations with diverse patient 
populations will be recruited to ensure sample diversity.  Approximately 14 sites will be targeted 
for recruitment for the total estimated sample size of 290 injection naïve patients with T2DM.


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The TTT assessment will be conducted in a subset of 75 to 80 patients from approximately 5 of 
the US clinical sites in the main phase.  Evidera will identify interview facilities in the same city 
as the selected clinical sites participating in the TTT interviews.  Study staff will determine 
facilities that are conveniently located for participants.  Facilities will provide a private interview 
room with a closed door and a 1-way mirror for the second staff member to time the training.  
The non-TTT study interviews will be conducted at the actual clinical sites the T2DM 
participants are recruited from throughout the US.
Clinical site staff will identify and verify the initial eligibility of participants through a records 
review.  A clinical site staff member will approach the potential participant in person (at the 
clinic or by phone) and briefly introduce the study using a standard screening script (Appendix 
8).  If the patient is interested, the study will be explained in full detail, and a full screening will 
be conducted to ensure eligibility (Appendix 9).  Clinical staff will schedule all study interviews 
during the specified timeframe when Evidera staff will be conducting the study interviews for 
their site.  Clinical staff will track recruitment efforts using the participant recruitment tracking 
log (Appendix 10).  Any identifying information (for example, names, addresses, telephone 
numbers) that is recorded on the screening/scheduling scripts will be kept in a limited access, 
locked filing cabinet.  
Prior to the interviews, clinical site staff will send participants confirmation (and directions to the 
interview location) by e-mail or post according to participant’s preference (Appendix 6).  
Reminder phone calls will be made to participants 1 day before the interview.  During previous 
studies, it has been found that these reminder phone calls reduce the likelihood that participants 
will fail to attend their appointment (Appendix 7).  However, it might not be possible to speak to 
all participants 1 day before the interviews (for example, no answer), if so, e-mail reminders will 
be sent (Appendix 7).  At least 1 reminder will be sent to all participants about their study 
interview when possible from the clinical sites.
5.5.3. Overview of Study Visit Procedures for the Pilot Phase
Table 2.1 provides an overview of the study schedule of activities.  During the study visit,
participants will begin with the completion of the informed consent. The order in which self-
injection naïve participants are trained on using each device will then be randomized using a 
validated software system.  More details about the randomization process are described in 
Section 7.2.  Half the participants will be randomized to be trained and perform mock injections 
on the dulaglutide device first followed by the semaglutide device and the other half of the 
participants will use the devices in the reverse order.  All participants will complete a 
Supplemental Question (Appendix 11) at the beginning of the study to determine their baseline 
willingness to use a diabetes injectable medication prior to being exposed to either the 
dulaglutide or semaglutide devices.
Trained interviewers will follow the study Interview and Device Training Guide (Appendix 12), 
in order to standardize the presentation of devices to participants and ensure that the training is 
clear and not biased in favor of either device.  For the pilot phase, the trained interviewers will 
try several training options for each device to determine the finalized steps of the training 


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approach to use in the main phase of the study.  Various approaches will include detailed 
demonstration by the interviewer, presentation of video demonstrations on tablets or laptops, 
independent reading of the IFU, and combinations of these 3 approaches.  Participants will 
perform mock injections on a practice pad after being trained in the use of each device.  
During the interview, if the participant does not complete one of the critical steps or if the steps 
are completed out of order, the Interview and Device Training Guide (Appendix 12) provides 
interviewers instructions for handling these situations.  The participant will be allowed 5 
attempts to follow the instructions and perform the mock injection(s) for each device.  If after 5 
attempts the participant is unable to successfully perform the mock injection on the practice pad 
for either device, the interviewer will instruct the participant to stop using the device and proceed 
ahead with the interview.  
The TTT assessment for each device will also be tested in the pilot phase after the near-final 
methods are determined.  The appropriate staff member will discreetly record the necessary 
training times using the TTT Observer Recording Sheet for each device (Appendix 13).  In 
between the trainings on each device, all participants will be given a restroom and water break.  
During this break, participants will also complete the Demographic Form (Appendix 14).
Once participants have attempted each device training and mock injection(s) on the practice pad, 
interviewers will complete the Interviewer Recording Sheet to document randomization order 
and if the patient was able to complete both device trainings (Appendix 15).  Pilot phase 
participants will also be administered a series of interview questions about the training 
procedures (Appendix 16).  Based on interviewer experiences and patient feedback during these 
estimated 10 to 20 pilot phase interviews, the training approach and interview procedures will be 
finalized prior to beginning the main phase with approximately 290 patients.  
After the interview questions, pilot phase participants will be given an optional second break.  
Participants will then be asked to complete questionnaires to report their preferences between the 
2 devices.  Specifically, participants will complete a Global Preference Item (Appendix 17) and 
the DID-PQ (Appendix 18).  Four items selected from the Medication Delivery Device 
Assessment Battery (MDDAB) (Matfin et al. 2015; Yu et al. 2017) will be asked of participants
about each of the devices under investigation to use in the validation of the DID-PQ (Ozempic 
device-specific questions: Appendix 19; Trulicity device-specific questions: Appendix 20).  
These additional questions will be completed in the order the participants were randomized to 
use the devices.  Participants will also complete Supplemental Questions S2 and S3 to determine 
their end of study willingness to use each of the study injection devices (Appendix 21).  
Pilot phase interview will last approximately 90 to 120 minutes including consenting and 
training in device procedures.  All pilot phase participants will be remunerated an amount 
slightly more than the main phase participants (i.e., a specified amount between $100 and $150
via Greenphire ClinCard) because they will be participating in debriefing procedures and 
possibly multiple training approaches.  The pilot phase interviews are expected to be longer than 
the main phase interviews.


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5.5.4. Overview of Study Visit Procedures for the Main Phase
Table 2.1 provides an overview of the study schedule of activities.  During the study visit, 
participants will begin with the completion of the informed consent.  The order in which 
participants are trained on using each device will then be randomized.  More details about the 
randomization process are described in Section 7.2.  Half the participants will be randomized to 
be trained and perform mock injections on the dulaglutide device first followed by the 
semaglutide device and the other half of the participants will use the devices in the reverse order.  
All participants will complete a Supplemental Question (Appendix 11) at the very beginning of 
the study to determine their baseline willingness to use a diabetes injectable medication prior to 
being exposed to either the dulaglutide or semaglutide devices.  
Trained study interviewers will follow the study Interview and Device Training Guide 
(Appendix 12) to standardize the presentation of devices to participants and ensure that the 
training is clear and not biased in favor of either device.  Based on findings from the pilot phase, 
the finalized main phase training approach will be conducted with the patients for each device
including a detailed demonstration by the interviewer.  The same standardized interview 
approach will be used for all the main phase patients.  For each device, patients will be given the 
IFU and asked to read it.  Then the interviewer will demonstrate how to use the device.  
Participants will perform mock injections on a practice pad after being trained in the use of each 
device.  Patients will have access to the IFU during the entire training and injection process.  If 
the participant does not complete one of the critical steps or if the steps are completed out of 
order, the Interview and Device Training Guide (Appendix 12) provides interviewers instructions 
for handling these situations.  The participant will be allowed 5 attempts to follow the 
instructions and perform the mock injection(s) for each device.  If after 5 attempts the participant 
is unable to successfully perform the mock injection on the practice pad for either device, the 
interviewer will instruct the participant to stop using the device and proceed ahead with the 
interview.  
For those participants selected for the TTT assessment (i.e., a subset of approximately 75 to 80 
patients across an estimated 5 clinical sites), the assessments will be done in an off-site facility to 
allow for the discreet timing of the training event (for example, 1-way mirror).  The appropriate 
staff member will discreetly record the necessary training times using the TTT Observer 
Recording Sheet for each device (Appendix 13).  In between the trainings on each device, all 
participants will complete the Demographic Form (Appendix 14).  
Once participants have attempted each device training and mock injection(s) on the practice pad, 
interviewers will complete the Interviewer Recording Sheet to document randomization order
and if the patient was able to complete both device trainings (Appendix 15).  Participants will 
then be asked to complete questionnaires to report their preferences between the 2 devices.  
Specifically, participants will complete a Global Preference Item (Appendix 17) and the DID-PQ 
(Appendix 18).  Four items selected from the MDDAB (Matfin et al. 2015; Yu et al. 2017) will 
be asked of participants about each of the devices under investigation to use in the validation of 
the DID-PQ (Ozempic device-specific questions: Appendix 19; Trulicity device-specific 
questions: Appendix 20).  These additional questions will be completed in the order the 


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participants were randomized to use the devices.  Participants will also complete Supplemental
Questions S2 and S3 to determine their end of study willingness to use each of the study 
injection devices (Appendix 21).  A Clinical Information Form (Appendix 22) will also be 
completed by the site clinical staff for each patient in the main phase.  
Main phase interview will last approximately 60 to 90 minutes including consenting and training 
in device procedures.  The maximum time for all study procedures is 90 minutes as specified in 
the consent form.  All main phase participants will be remunerated a specified amount between 
$100 and $150 (via Greenphire ClinCard) for their time and travel time to the study interview.  
5.6.
Justification for Dose
The devices used for this study will be commercialized injection pens containing non-modified 
commercial product with stickers on the devices indicating for use in clinical trial.  However, no 
active drug will be administered because patients will not be injecting themselves.  Instead, 
patients will perform mock injections into a practice pad after being trained in the use of each 
device by a study team member. Specifically, the patients will be trained on devices that contain 
the lowest dose (i.e., dulaglutide = 0.75mg; semaglutide = 0.25mg) for both treatments for safety 
concerns (for example, accidental needle stick) and because these are the typical starting and 
training doses for these 2 products in the US.  However, it is critical to acknowledge that the 
devices are very similar across all drug strengths.  Therefore, the study findings could be 
applicable to other dulaglutide and semaglutide device doses, as well as other antidiabetic drugs 
using the same devices.   


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6.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study if they meet all the following criteria at 
screening:
Participant Characteristics
[1]
are at least aged ≥18 years at the time of screening
[2]
diagnosed with type 2 diabetes
[3]
self-injection naïve to all injectable treatment (for example, diabetes 
therapies and other medical conditions)
[4]
injection naïve to performing all injectable treatment (for example, diabetes 
therapies and other medical conditions) to others
[5]
must currently receive oral treatment for their type 2 diabetes
[5a] pilot phase participants only: must be able to bring proof of their 
oral treatment prescription for type 2 diabetes to the interview (for 
example, the medication itself, the medication packaging, a prescription 
note, or a letter from their doctor).  This criterion does not apply to the 
main phase because main phase participants will have diagnoses 
confirmed by the clinical sites with awareness of the patients’ diabetes 
and treatment.
[6]
willing and able to attend an in-person interview session
[7]
able to read, speak, write, and understand the English language
[8]
able and willing to give signed informed consent prior to study entry 
[9]
able to complete the protocol requirements
6.2.
Exclusion Criteria
Participants will be excluded from study enrollment if they meet any of the following criteria at 
screening:
Medical Conditions
[1]
currently diagnosed with gestational diabetes and/or type 1 diabetes
[2]
cognitive or physical difficulties that could interfere with ability to 
understand the training, perform the injection tasks, or complete the study 
questionnaires as judged by the investigator


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Prior/Concurrent Clinical Trial Experience
[3]
are currently enrolled in any other clinical study involving an investigational 
product or any other type of medical research judged not to be scientifically 
or medically compatible with this study
[4]
have participated, within the last 30 days, in a clinical study involving an 
investigational product.  
Other Exclusions
[5]
is a health care practitioner who is trained in giving injections
[6]
for main phase participants only:  Investigator, site personnel, or 
immediate family member of investigator or site personnel.  Immediate 
family is defined as a spouse, parent, child, or sibling, whether biological or 
legally adopted
[7]
is an employee of any of the following companies:  Eli Lilly and Company, 
Novo Nordisk, Evidera, or PPD
[8]
currently pregnant
6.3.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened. 


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7. Treatments
7.1.
Treatments Administered
This study involves a comparison of marketed devices, and no treatment will be administered.
The investigator or his/her designee is responsible for the following:

Explaining the correct use of the investigational agent(s) to the patient

Verifying that instructions are followed properly

Maintaining accurate records of investigational product dispensing and collection

At the end of the study, returning all unused medication to Lilly, or its designee, 
unless the sponsor and sites have agreed all unused medication is to be destroyed 
by the site, as allowed by local law
7.1.1. Packaging and Labeling
The dulaglutide and semaglutide devices will be labeled according to applicable regulatory 
requirements. The devices used in the study shall be securely stored until returned or destroyed 
according to instructions from the sponsor. Information such as lot number, quantity, and 
disposition of device(s) used during the clinical study shall be documented.
Refer to the device labeling/instructions for use (IFU) for the following:

Instructions regarding storage and handling requirements, preparation for use, 
pre-use checks, and any precautions to be taken after use or disposal.

Summary of necessary training and experience required.

Description of procedures for use.
7.1.2. Medical Devices 
The manufactured medical devices provided for use in the study are the dulaglutide pen and the 
semaglutide pen.  
7.2.
Method of Device Assignment
For the pilot phase, assignment to device order study groups will be randomized using a 
validated software system.
For the main phase, assignment to device order study groups will be determined by a 
computer-generated random sequence using an interactive web-response system (IWRS).  The 
IWRS will be used to assign the first device to be used by the patient.  Randomization will occur 
at the study level in efforts to make sure that there are a comparable number of patients who start 
with the dulaglutide device versus the semaglutide device across the entire study population.


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7.2.1. Selection and Timing of Doses
Timing of dosing is not applicable.  The patients will be trained on devices that contain the 
lowest dose per device (i.e., dulaglutide = 0.75mg; semaglutide = 0.25mg).  
7.3.
Blinding
This is an open-label study.  All participants will be trained and perform mock injections on a 
practice pad using labeled dulaglutide and semaglutide devices with the brand names of Trulicity 
and Ozempic on the pens as displayed in Figure 3.1 and Figure 3.2, respectively.  
7.4.
Dosage Modification
Although dose modification is not an objective of this study, information on how to modify a 
dose will be provided in the training for each device as this information is typically provided by 
HCPs to patients (Appendix 12).  
7.5.
Preparation/Handling/Storage/Accountability
The investigator or his/her designee is responsible for the following:

Obtaining the correct number of devices in advance of each interview.  Staff 
performing all the trainings must have received all the necessary training for both 
devices.  

Storing the study devices in a secure and monitored area in accordance with the 
labeled storage conditions with access limited to the investigator and authorized 
study staff.

Obtaining the appropriate number of practice pads to perform all the mock 
injections and following the required instructions to dispose of all the materials 
used in the device trainings and mock injections.
7.6.
Treatment Compliance
Patient compliance with study procedures will be assessed at each visit.  Patients will be properly 
trained on how to use and perform mock injections with both the dulaglutide and semaglutide 
devices.  The patients will be allowed several attempts to follow the instructions and perform the 
mock injections.  It will be the discretion of the study interviewer to determine if the patient is
not capable of completing the study interview, including the mock injections and/or
questionnaires, and should be terminated.  More details about study discontinuation are provided 
in Section 8.
7.7.
Concomitant Therapy
All concomitant therapies that are part of routine care are allowed and can be used during the 
study so long as they are not self-injected (per the exclusion criteria).
7.8.
Treatment after the End of the Study
Not applicable.


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7.8.1. Special Treatment Considerations 
Not applicable. 


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8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Permanent Discontinuation from Study Treatment
This is a device preference study and investigational product is not being administered to any 
patients.  
8.1.2. Temporary Discontinuation from Study Treatment 
Not applicable. 
8.1.3. Discontinuation of Inadvertently Enrolled Patients
If the sponsor or investigator identifies a patient who did not meet enrollment criteria and was 
inadvertently enrolled, then the patient should be excluded from the study.
8.2.
Discontinuation from the Study
Patients will be discontinued in the following circumstances:

Enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be 
scientifically or medically compatible with this study

Participation in the study needs to be stopped for medical, safety, regulatory, 
or other reasons consistent with applicable laws, regulations, and good clinical 
practice

Investigator decision
o
The investigator decides that the patient should be discontinued from the 
study

Subject decision
o
The patient or the patient’s designee, for example, parents or legal 
guardian requests to be withdrawn from the study
Patients discontinuing from the study prematurely for any reason should complete AE and other 
safety follow-up per Section 9.2 (Adverse Events) and Section 9.4 (Safety) of this protocol.
8.3.
Lost to Follow-Up
Not applicable because this is a 1-time interview study and no additional study visits are 
required.  


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9.
Study Assessments and Procedures
Table 2.1 lists the Schedule of Activities for this crossover study for each of the study phases.  
All outcome assessments will be administered in both phases, except the pilot phase interview 
questions will only be administered during the pilot phase and the Clinical Information Form will 
only be completed by the clinical site for each patient in the main phase.  
9.1.
Outcome Assessments
9.1.1. Primary/Secondary Assessments
After participants have been trained and used both devices, they will then complete a Global 
Preference Item about which device they prefer (Appendix 17) to evaluate the primary objective.  
Specifically, participants will be asked, “Overall, which device do you prefer?”  Participants will 
also be asked to explain why they selected their response for Ozempic, Trulicity, or no 
preference.
Participants will then complete the 10-item DID-PQ to evaluate the gated secondary objective, 
which is based on Item 9 of the DID-PQ (i.e., overall ease of using the injection device).  The 
DID-PQ compares the dulaglutide and semaglutide devices head-to-head in terms of a variety of 
device characteristics (for example, ease of preparing the injection device, time it takes to 
prepare and inject each dose of medication, confidence that you are using the injection device 
correctly, and overall convenience of using the injection device) (Appendix 18).
9.1.2. Appropriateness of Assessments
9.1.2.1.
Supplemental Questions
In addition to the Global Preference Item, the DID-PQ, and the 4 items selected from the 
MDDAB for each device, Supplemental Questions will be included in the survey to elicit 
patients’ perceptions of T2DM treatment using injectable agents (Appendix 11).  The 
Supplemental Questions developed for this study are based on previous items used in the article 
by Poon et al. (2018).  The first question will be administered to participants before the device 
trainings and will determine the participants’ “willingness to use a diabetes medication that 
required an injection for each dose.”  The second and third Supplemental Questions will be 
administered to the participants after all the trainings, mock injections, and other study measures 
have been completed.  Questions S2 and S3 will ask participants specifically about their 
willingness to use the Ozempic and Trulicity devices, respectively (Appendix 21).  Responses to 
these questions will be used to determine patients’ willingness to use each of the devices after 
being trained on both.
9.1.2.2.
Time-to-Train Observer Recording Sheet
For the TTT interviews, the study staff member observing and timing behind the 1-way mirror at 
the interview facilities will record the start and end times of the key training steps for each 
device (Appendix 13).


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9.1.2.3.
Demographic Form
A Demographic Form will be completed by participants in between the device trainings.  This 
form includes questions on age, sex, ethnicity, living situation, employment, education level, and 
other health conditions (Appendix 14).
9.1.2.4.
Interviewer Recording Sheet
The trained interviewer will use the Interviewer Recording Sheet to document each participant’s 
randomization order and whether or not the participant was able to complete each of the device 
trainings.  If the participant was shown the device, but did not complete the actual device 
training, the interviewer should explain what happened on this sheet (Appendix 15).  
9.1.2.5.
Pilot Phase Interview Questions
During the pilot phase, once the participants have completed both trainings and mock injections 
on the practice pad, the participants will be administered a series of interview questions about the 
training procedures (Appendix 16).  These interview questions will guide the discussion with the 
participants to determine the final training approach to use during the main phase.  
9.1.2.6.
Global Preference Item
All participants will complete the Global Preference Item after being trained and using both 
devices (Appendix 17).  Participants will be asked, “Overall, which device do you prefer?”  
Interviewers will then ask participants to explain why they selected their response for Ozempic, 
Trulicity, or no preference.  The interviewer will transcribe the participant’s response using 
quotation marks to capture the respondent’s exact words.  The Global Preference Item was 
developed specifically for use in this device preference multicenter crossover study.  To help 
participants remember the devices more accurately, colored images of the devices have been 
inserted into the questionnaire.  
9.1.2.7.
Diabetes Injection Device – Preference Questionnaire 
The Diabetes Injection Device – Preference Questionnaire (DID-PQ) was designed for the 
purpose of assessing patient preferences between 2 non-insulin injection devices (Appendix 18) 
(Matza et al. 2018a).  On the DID-PQ, each item is rated on a 5-point scale allowing patients to 
indicate whether they prefer or strongly prefer one of the devices over the other.  For each item, 
patients may also respond by selecting the “no preference” (i.e., neutral) response option, 
indicating that they have no preference between the 2 devices.  Specifically, for this study, the 
DID-PQ response options will be: Strongly Prefer Ozempic Device, Prefer Ozempic Device, 
Strongly Prefer Trulicity Device, Prefer Trulicity Device, or have No Preference.  To help 
participants remember the devices more accurately, colored images of the devices have been 
inserted into the questionnaire.  
9.1.2.8.
Four Items from the Medication Delivery Device Assessment 
The original MDDAB was adapted from insulin-specific questionnaires and has been modified 
for use in both injection-naïve and non-insulin requiring participants (Matfin et al. 2015).  Four 
items selected from the MDDAB (Matfin et al. 2015; Yu et al. 2017) will be asked of the 
participants about each of the devices under investigation in this study (Ozempic device-specific 
questions: Appendix 19; Trulicity device-specific questions: Appendix 20).  These additional 


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questions will be completed in the order the participants were randomized to use the devices.  
The first 3 questions ask participants how easy or difficult it was to: (1) learn to use the device,
(2) to follow the instructions when using the device, and (3) overall, how difficult or easy was 
the device to use?  The last question asks participants to “Please check the number that best 
indicates how willing you are to continue using the device” on a scale from 1 (“Definitely 
Unwilling”) to 5 (“Definitely Willing”).  These items will be used in the validation of the 
DID-PQ, specifically to assess construct validity of the DID-PQ by comparing responses.  
9.1.2.9.
Clinical Information Form
A Clinical Information Form will be completed by the site personnel for each participant 
completing the study visit (Appendix 22).  This form includes a question to document the 
patients’ T2DM diagnosis date, the current oral medications the patient is taking to treat their 
T2DM, and the patients’ most recent HbA1c value and date this value was measured.  
9.2.
Adverse Events
Investigators are responsible for monitoring the safety of patients who have entered this study 
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the patient.
The investigator is responsible for the appropriate medical care of patients during the study.
Investigators must document their review of each laboratory safety report.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused the patient to discontinue the investigational product before 
completing the study.  The patient should be followed until the event resolves, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  The frequency of follow-up 
evaluations of the AE is left to the discretion of the investigator.
After the informed consent form is signed, study site personnel will record via designated data 
transmission methods the occurrence and nature of each patient’s preexisting conditions, 
including clinically significant signs and symptoms of the disease under treatment in the study.  
In addition, site personnel will record any change in the condition(s) and any new conditions as 
AEs. Investigators should record their assessment of the potential relatedness of each AE to 
protocol procedure, investigational device, via designated data transmission methods.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, study device, or a study procedure, taking into account the 
disease, concomitant treatment, or pathologies.
A “reasonable possibility” means that there is a cause and effect relationship between the 
investigational product, study device and/or study procedure, and the AE.
The investigator answers yes/no when making this assessment.


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Planned surgeries and non-surgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study.
If a patient’s investigational device is discontinued as a result of an AE, study site personnel 
must report this to Lilly or its designee via designated data transmission methods, clarifying if 
possible, the circumstances leading to any dosage modifications, or discontinuations of 
treatment.  
The appropriate AE reporting procedures will be followed for each device under investigation in 
this study.  
9.2.1. Serious Adverse Events
A serious adverse event (SAE) is any AE from this study that results in one of the following 
outcomes:

Death

Initial or prolonged inpatient hospitalization

A life-threatening experience (i.e., immediate risk of dying)

Persistent or significant disability/incapacity

Congenital anomaly/birth defect

Important medical events that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the patient or may require intervention 
to prevent one of the other outcomes listed in the definition above.  Examples of 
such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug 
abuse.

When a condition related to the injection pens necessitates medical or surgical 
intervention to preclude either permanent impairment of a body function or 
permanent damage to a body structure, the serious outcome of “required 
intervention” will be assigned.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information. Patients with a serious hepatic AE should have additional data collected using the 
designated data transmission methods.
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE.  However, to fulfill regulatory requirements, any pregnancy should be 
reported following the SAE process to collect data on the outcome for both mother and fetus.


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Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued and/or completed the study (the patient disposition case report form) has been 
completed).  However, if the investigator learns of any SAE, including a death, at any time after 
a subject has been discharged from the study, and he/she considers the event reasonably possibly 
related to the study treatment or study participation, the investigator must promptly notify Lilly.
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that the 
investigator identifies as related to investigational product or procedure.  United States 21 CFR 
312.32 and European Union Clinical Trial Directive 2001/20/EC and the associated detailed 
guidances or national regulatory requirements in participating countries require the reporting of 
SUSARs. Lilly has procedures that will be followed for the identification, recording, and 
expedited reporting of SUSARs that are consistent with global regulations and the associated 
detailed guidances.
9.2.2. Adverse Event Monitoring with a Systematic Questionnaire 
Not applicable because this is a device preference study, and no active drug will be administered 
as patients will not be injecting themselves.  
9.2.3. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, to monitor quality, and to 
facilitate process and product improvements.
Patients will be instructed to contact the investigator as soon as possible if he/she has a complaint 
or problem with the investigational product or drug delivery system so that the situation can be 
assessed.
The appropriate product complaint reporting procedures will be followed for each device under 
investigation in this study.  
9.3.
Treatment of Overdose
Not applicable.
9.4.
Safety
Refer to Section 10.3.4.
9.4.1. Electrocardiograms
Not applicable. 
9.4.2. Vital Signs
Not applicable. 


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9.4.3. Laboratory Tests
Laboratory tests are not required and will not be taken for this study as this is a device preference 
study.  The protocol template language for this section is not applicable for this study.
9.4.4. Safety Monitoring 
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
9.4.4.1.
Hepatic Safety Monitoring
Not applicable.
9.5.
Pharmacokinetics
Not applicable.
9.6.
Pharmacodynamics
Not applicable.
9.7.
Pharmacogenomics or Genetics
9.7.1. Samples for Pharmacogenetic Research
Samples of whole blood and/or saliva are not required and will not be taken for this study as this 
is a device preference study.  The protocol template language for this section is not applicable for 
this study.  
9.8.
Biomarkers and Other Analyses
Samples of serum, plasma, urine, cerebral spinal fluid, whole blood RNA, whole blood for 
epigenetics, etc. are not required and will not be taken for this study as this is a device preference 
study.  The protocol template language for this section is not applicable for this study. 
9.9.
Health Economics or Medical Resource Utilization and Health 
Economics
Not applicable.


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10. Statistical Considerations
10.1. Sample Size Determination
To test the null hypothesis that patients have equal preference for either dulaglutide or 
semaglutide pen (50% of patients prefer dulaglutide pen and 50% prefer semaglutide pen), a 
sample size of 260 patients will provide 90% power against alternative hypothesis that there is a 
preference with 60% of the patients choosing the dulaglutide pen over the semaglutide pen.
Calculation is carried out using 2-sided chi-square test (normal approximation) at 0.05 level of 
significance.  Software used is Nquery + nTerim 4.0.  Assuming that approximately 10% will not 
provide any preference information by choosing the “no preference” option on the Global 
Preference Item, 290 patients will be needed to have at least 260 patients with preference 
information. The Prescott test which takes into account the order the device is used as well as 
the choice of “no preference” provides approximately 90% power against the alternative 
hypothesis of 54% choosing dulaglutide pen, 10% indicating no preference, and the remaining 
36% choosing semaglutide pen. This is based on simulation of 1000 runs and assumes that there 
is no order effect.
10.2. Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Randomized
Participants determined to be eligible and then assigned to one of 2 
device order groups (50% will be randomized to use the dulaglutide 
device first, while the other half will use the semaglutide device first).  
More details about randomization for this study are provided in 
Section 7.2.
Evaluable
Participants for whom device preference can be evaluated:
Randomized participants who are exposed to both devices (i.e., 
participant was shown both devices via demonstration, regardless of 
whether they successfully complete the training) and complete the 
Global Preference Item.
Withdrawn 
Participants who withdraw from the study before being exposed to both 
devices and completing the Global Preference item.  Details on study 
withdrawal are provided in Section 8.
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Evidera.  The statistical analyses are 
summarized by study objective and endpoint(s) in Table 1.1.  
Statistical analyses will be conducted on the evaluable patient population (i.e., patients who 
provide a response to the Global Preference Item).  


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The significance level for all statistical tests will be p<.05.  Gatekeeping strategy will be used to 
control for type 1 error for the primary and gated secondary objective. 
Any change to the statistical analysis methods described in the protocol will require an 
amendment ONLY if it changes a principal feature of the protocol.  Any other change to the 
statistical analysis methods described in the protocol, and the justification for making the change, 
will be described in the clinical study report (CSR).  A more detailed description of this 
statistical analysis will be provided in a statistical analysis plan (SAP), and additional 
exploratory analyses of the data may be conducted as deemed appropriate.
10.3.2. Treatment Group Comparability
10.3.2.1. Patient Disposition
A detailed description of patient disposition will be provided at the end of the study. 
10.3.2.2. Patient Characteristics
Descriptive statistics will summarize demographics, clinical characteristics, and patient-reported 
outcome (PRO) measures. Continuous variables will be summarized with means, standard 
deviations, ranges, and minimum and maximum values.  Categorical variables such as gender 
and race will be presented in terms of frequencies and percentages.  Demographics, clinical 
characteristics, and PRO data will be presented by assigned randomization group.  
10.3.2.3. Concomitant Therapy 
Not applicable.  
10.3.2.4. Treatment Compliance
Not applicable.  
10.3.3. Statistical Analyses
10.3.3.1. Primary Analyses
The primary analysis of this study will evaluate the results of the Global Preference Item (i.e., 
Overall, which device do you prefer?) to examine whether there is a difference in preference 
between the dulaglutide device and the semaglutide device.  The Prescott test will be run to 
determine whether there is a statistically significant difference in preference between the devices, 
while controlling for order effects.  The preference results (for example, counts, percentages and 
95% confidence interval [CI]) will also be presented.  The qualitative data capturing reasons for
the response to the Global Preference Item will also be presented.  
10.3.3.2. Gated Secondary Analyses
The gated secondary analysis of this study will be conducted if the primary objective is found 
statistically significant. The analysis will compare the dulaglutide and semaglutide devices with 
regard to ease of use.  Responses to the 5-point response scale of DID-PQ Item 9 (Overall ease 
of use) will be collapsed into 3 categories.  The “strongly prefer” and “prefer” response options 
will be combined for each device, resulting in 3 categories: prefer dulaglutide, prefer 
semaglutide, and no preference.  Then, the Prescott test will be run to examine whether there is a 


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statistically significant difference in preference between the devices, while controlling for order 
effects.  Data from global Item 9 on the DID-PQ will also be presented to illustrate the “ease of 
use” responses by device (for example, counts, percentages, and 95% CI).  
The complete scoring guide for the DID-PQ will be presented in the SAP for this study.  
10.3.3.3. Exploratory Analyses 
10.3.3.3.1. Exploratory 1.  DID-PQ Analyses of Items 1 to 8 and 10
Exploratory analyses of Items 1 to 8 and 10 of the DID-PQ will follow the same procedures as 
those for the gated secondary objective described above. 
10.3.3.3.2. Exploratory 2.  Time-to-Train Analyses 
Exploratory analysis 2 of this study will focus on the TTT for each device.  The average duration 
required to train and successfully inject each device will be assessed using the linear model 
appropriate for a crossover design. Carryover effects will be examined.  If there are no 
significant carryover effects, then TTT for both the first and second trainings will be used in this 
analysis.  If there is a significant carryover effect, then this analysis will use data for whichever 
device is trained first.  Average duration required to train and successfully inject each device will 
be reported.  
10.3.3.3.3. Exploratory 3.  Supplemental Question Analyses 
Using the data from the 3 Supplemental Questions (i.e., S1. Would you be willing to use a 
diabetes medication that required you to give yourself an injection for each dose?; S2. How 
willing would you be to use the Ozempic injection device?; and S3. How willing would you be 
to use the Trulicity injection device?), descriptive analyses will be run to examine willingness to 
use each of the devices after being trained on both.  Descriptive statistics will be reported for 
each item (i.e., frequencies, percentages).  
10.3.3.3.4. Exploratory 4.  Evaluation of the DID-PQ 
Exploratory analysis 4 will focus on psychometric evaluation of the DID-PQ.  The DID-PQ has 
been administered in 2 studies thus far: the original psychometric validation study (Matza et al. 
2017b) and the US study comparing the dulaglutide and liraglutide devices (Matza et al. 2018a).  
In both studies, the DID-PQ was administered to a relatively small subgroup of patients who had 
used more than 1 GLP-1 RA device.  Therefore, it has not previously been possible to perform 
statistical analyses examining the validity of this PRO instrument.  
Since all estimated 290 patients in this study will complete the DID-PQ, this study provides a 
unique opportunity to perform analyses evaluating the performance of this instrument.  The 
primary validation approach will be to examine known-groups validity, which is the extent to 
which scores from an instrument distinguish among groups of participants that differ in terms of 
a relevant clinical or other indicator.  By comparing DID-PQ responses of patients categorized 
based on the responses to the Global Preference Item, known-groups validity will be evaluated.  
Additional analyses will examine construct validity, which is the degree to which a measure 
performs as expected in relation to other measures.  Construct validity will be assessed by 
comparing DID-PQ responses to responses on 4 items selected from the MDDAB 


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(Matfin et al. 2015; Yu et al. 2017).  Cross-tabulation tables of these 4 items by response options 
for each of the DID-PQ items will be presented.  The 4 items assess (1) ease of learning how to 
use the device, (2) ease of following instructions when using the device, (3) overall ease-of-use, 
and (4) willingness to continue using the device.
Lastly, the DID-PQ exploratory approach for comparing devices will be examined relative to the 
ancillary measures (i.e., responses on the 4 items selected from the MDDAB for each device).  
This approach to analyzing data from the DID-PQ was developed as part of the original 
instrument development work, but it has never before been implemented and evaluated in a 
study.  Among patients indicating a preference for one device over the other, a statistical test can 
be performed to determine whether a significant preference exists. This test would assess 
whether the proportion indicating preference for one of the 2 devices differs from 0.5.  A value 
of 0.5 would indicate that there is equal preference for the 2 devices.  The frequency of 
preferences for Device 1 and Device 2 may be examined using a 2-sided binomial test for each 
item of the DID-PQ.  For each DID-PQ item, the null hypothesis would be that the probability of 
preferring one of the devices is 0.5.  If the binomial test yields a significant p-value, then the null 
hypothesis can be rejected, which would mean that significantly more respondents preferred one 
device over the other.
10.3.3.4. Missing Data
Study team members will perform a thorough review of the participants’ questionnaires prior to 
the completion of each interview to minimize missing data.  No imputations will be performed 
for missing data.  If a participant decides to withdraw from the study, data collected to the point 
of withdrawal may be used in analysis to preserve the integrity of the research project.  There 
will be no lost to follow-up data because there is no follow-up period in this study.
10.3.4. Safety Analyses
This study focuses on preference between devices, and no medication will be administered to 
study participants.  However, if a participant reports an AE related to the study, the appropriate 
reporting procedures will be followed.  See Section 9.2 for more AE details.  
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses
Not applicable as no investigational drug or treatment will be administered during this study.
10.3.6. Evaluation of Immunogenicity 
Not applicable.  
10.3.7. Other Analyses
10.3.7.1. Health Economics 
Not applicable.
10.3.7.2. Subgroup Analyses 
Not applicable.  


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10.3.7.3. Pilot Phase Analyses 
Analyses of the pilot phase data will include both descriptive statistics and a content analysis 
approach.  The purpose of the pilot phase is to ensure that the training materials and interview 
procedures are clear, comprehensible, and feasible prior to the main phase.  
Descriptive statistics (for example, mean, standard deviation, frequency) will be used to 
summarize the sample in terms of sociodemographic characteristics and on the other measures 
completed by the participants (i.e., Global Preference Item, DID-PQ, 4 items selected from the 
MDDAB for each device).  
A content analysis approach will be used to analyze the responses collected on the pilot phase
interview questions.  This content analysis applies only to the pilot phase.  Responses will be 
examined to determine answers to the following questions for each device:

Are there any ways the device training could be easier or more clear?  If yes, 
please explain. 

Would you recommend any changes to the device training procedures?  If yes, 
please explain.

How much additional guidance is appropriate and useful during the device 
training?
During the pilot phase, the principal investigator and study team will be continuously monitoring 
the interview and data as they are collected to determine if changes need to be implemented 
immediately.  If major changes are required, Evidera and Lilly will determine if the pilot phase
sample size needs to be increased.  Upon conclusion of the pilot phase, Evidera study staff will 
send to Lilly a summary document of the pilot phase, which will serve as the interim analysis.  
The pilot phase data for an estimated 10 to 20 participants will not be included in the final 
sample of approximately 290 patients with T2DM.  
10.3.8. Interim Analyses
Not applicable.


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11.
References
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GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin 
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Asakura T, Suzuki S, Aranishi T, Cai Z. Comparative usability study of the dulaglutide single-
use pen versus the insulin degludec FlexTouch® among self-injection-naïve patients with type 
2 diabetes mellitus in Japan. Curr Med Res Opin. 2018;34(6):1117-1124.
Blonde L, Jendle J, Gross J, Woo V, Jiang H, Fahrbach JL, Milicevic Z. Once-weekly 
dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, 
in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-
inferiority study. Lancet. 2015;385(9982):2057-2066.
Dungan KM, Povedano ST, Forst T, González JG, Atisso C, Sealls W, Fahrbach JL. 
Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 
2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Lancet. 
2014;384(9951):1349-1357.
Dungan KM, Weitgasser R, Perez Manghi F, et al. Pintilei E, Fahrbach JL, Jiang HH, Shell J, 
Robertson KE. A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide 
added on to glimepiride in type 2 diabetes (AWARD-8). Diabetes Obes Metab. 
2016;18(5):475-482.
Edwards KL, Minze MG. Dulaglutide: an evidence-based review of its potential in the treatment 
of type 2 diabetes. Core Evid. 2015;10:11-21.
Eli Lilly and Company. Instructions for Use: TRULICITY® (Trū-li-si-tee) (dulaglutide) 
injection, for subcutaneous use – 0.75 mg/0.5 mL Single-Dose Pen once weekly. Original: 
2014; Updated: November 16, 2017. Available at: http://pi.lilly.com/us/trulicity-lowdose-ai-
ifu.pdf.
Gelhorn HL, Bacci ED, Poon JL, Boye KS, Suzuki S, Babineaux SM. Evaluating preferences for 
profiles of glucagon-like peptide-1 receptor agonists among injection-naïve type 2 diabetes 
patients in Japan. Patient Prefer Adherence. 2016;10:1337-1348.
Gelhorn HL, Poon JL, Davies EW, Paczkowski R, Curtis SE, Boye KS. Evaluating preferences 
for profiles of GLP-1 receptor agonists among injection-naïve type 2 diabetes patients in the 
UK. Patient Prefer Adherence. 2015;9:1611-1622.
Giorgino F, Benroubi M, Sun JH, Zimmermann AG, Pechtner V. Efficacy and safety of 
once-weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin 
and glimepiride (AWARD-2). Diabetes Care. 2015;38(12):2241-2249.
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas 
A, Wender R, Matthews DR; American Diabetes Association (ADA); European Association 
for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a 
patient-centered approach: position statement of the American Diabetes Association (ADA) 
and the European Association for the Study of Diabetes (EASD). Diabetes Care. 
2012;35(6):1364-1379.


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Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Efficacy and safety of 
glucagon-like peptide-1 receptor agonists in type 2 diabetes: a systematic review and 
mixed-treatment comparison analysis. Diabetes Obes Metab. 2017;19(4):524-536.
Khunti K, Gomes MB, Pocock S, Shestakova MV, Pintat S, Fenici P, Hammar N, Medina J. 
Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: a 
systematic review. Diabetes Obes Metab. 2018;20(2):427-437.
Khunti K, Nikolajsen A, Thorsted BL, Andersen M, Davies MJ, Paul SK. Clinical inertia with 
regard to intensifying therapy in people with type 2 diabetes treated with basal insulin. 
Diabetes Obes Metab. 2016;18(4):401-409.
Khunti K, Seidu S, Kunutsor S, Davies M. Association between adherence to pharmacotherapy
and outcomes in type 2 diabetes: a meta-analysis. Diabetes Care. 2017;40(11):1588-1596.
Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies MJ. Clinical inertia in people with 
type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care. 
2013;36(11):3411-3417.
Ludvik B, Frías JP, Tinahones FJ, Wainstein J, Jiang H, Robertson KE, García-Pérez LE, 
Woodward DB, Milicevic Z. Dulaglutide as add-on therapy to SGLT2 inhibitors in patients 
with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, 
double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2018;6(5):370-381.
Matfin G, Van Brunt K, Zimmermann AG, Threlkeld R, Ignaut DA. Safe and effective use of the 
once weekly dulaglutide single-dose pen in injection-naïve patients with type 2 diabetes. J 
Diabetes Sci Technol. 2015;9(5):1071-1079.
Matza LS, Boye KS, Currie BM, Paczkowski R, Lando LF, Mody R, Jordan J. Patient 
perceptions of injection devices used with dulaglutide and liraglutide for treatment of Type 2 
diabetes. Curr Med Res Opin. 2018a;24(8):1457-1464.
Matza LS, Boye KS, Jordan J, Norrbacka K, Gentilella R, Tiebout A, Brown C, Federici MO, 
Stewart KD. Patient preferences in Italy: Health state utilities associated with attributes of 
weekly injection devices for treatment of type 2 diabetes. Patient Pref Adherence. 2018b; 
12:971-979.
Matza LS, Boye KS, Stewart KD, Davies EW, Paczkowski R. Health state utilities associated 
with attributes of weekly injection devices for treatment of type 2 diabetes. BMC Health Serv 
Res. 2017a;17(1):774.
Matza L, Stewart K, Paczkowski R, et al. Validation of a questionnaire to assess patient 
perceptions of injection devices for type 2 diabetes. ISPOR 22nd Annual International Meeting; 
Boston, MA; May 20-24, 2017b.
Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z. Efficacy and 
safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized 
controlled trial (AWARD-5). Diabetes Care. 2014;37(8):2149-2158.
[NICE] National Institute for Health and Care Excellence. Type 2 diabetes: the management of 
type 2 diabetes. NICE Clinical Guideline 87. London, UK; Issued: May 2009; Last Modified: 
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Norrbacka A, Stein D, Matza L, Jordan J, García-Pérez L, Hassan S, Boye K. Time to treatment 
intensification with GLP-1 receptor agonists for patients with type 2 diabetes in the UK: 
Medical Record Review Study. 54th Annual Meeting of the European Association for the 
Study of Diabetes (EASD); Berlin, Germany; October 1-5, 2018.
Novo Nordisk. Instructions for Use: OZEMPIC® (semaglutide) injection, for subcutaneous use –
0.5 mg/1 mg. Initial US Approval: 2017; Revised: December 2017; 13 p.
Poon JL, Boye KS, Thieu VT, Norrbacka KN, Hassan SW, Gelhorn HL. Preferences for 
attributes of medications among patients with type 2 diabetes: a cross-medication class 
comparison of injection therapies. Curr Res Diabetes Obes J. 2018;6(5):555700.
Pozzilli P, Norwood P, Jodar E, Davies MJ, Ivanyi T, Jiang H, Woodward DB, Milicevic Z. 
Placebo-controlled, randomized trial of the addition of once-weekly glucagon-like peptide-1 
receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes 
(AWARD-9). Diabetes Obes Metab. 2017;19(7):1024-1031.
Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical 
studies. Ther Adv Endocrinol Metab. 2015;6(1):19-28.
Tuttle KR, Lakshmanan MC, Rayner B, Busch RS, Zimmermann AG, Woodward DB, Botros 
FT. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe 
chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet 
Diabetes Endocrinol. 2018;6(8):605-617.
Umpierrez G, Tofe Povedano S, Perez Manghi F, Shurzinske L, Pechtner V. Efficacy and safety 
of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled 
trial (AWARD-3). Diabetes Care. 2014;37(8):2168-2176.
Wysham C, Blevins T, Arakaki R, Colon G, Garcia P, Atisso C, Kuhstoss D, Lakshmanan M. 
Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in 
type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care. 
2014;37(8):2159-2167.
Yu M, Van Brunt K, Milicevic Z, Varnado O, Boye KS. Patient-reported outcome results of 
dulaglutide added to titrated insulin glargine in patients with type 2 diabetes (AWARD-9).
Clin Ther. 2017;39:2284-2295.


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12.
Appendices


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Appendix 1.
Abbreviations and Definitions
Term
Definition
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
CI
confidence interval
Complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
Compliance
Adherence to all study-related, good clinical practice, and applicable regulatory 
requirements.
DID-PQ
Diabetes Injection Device – Preference Questionnaire
Enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the study are 
those who have been assigned to a treatment.
Enter
Patients entered into a study are those who sign the informed consent form directly or 
through their legally acceptable representatives.
ERB
ethical review board
GLP-1
Glucagon-like peptide-1
HbA1c
glycosylated hemoglobin A1c
HCP
health care provider
IFU
instructions for use 
Informed consent
A process by which a patient voluntarily confirms his or her willingness to participate 
in a particular study, after having been informed of all aspects of the study that are 
relevant to the patient’s decision to participate.  Informed consent is documented by 
means of a written, signed, and dated informed consent form.
Investigational device
The investigational devices in this study will include the 2 devices under investigation 
(i.e., Ozempic and Trulicity) that are being evaluated in this multicenter crossover 
device preference study.  


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Term
Definition
IWRS
interactive web-response system
MDDAB
Medication Delivery Device Assessment Battery
PPD
Pharmaceutical Product Development, LLC
PRO
patient-reported outcomes
RA
receptor agonist
SAE
serious adverse event
SAP
statistical analysis plan
Screen
The act of determining if an individual meets minimum requirements to become part 
of a pool of potential candidates for participation in a clinical study. 
SUSARs
suspected unexpected serious adverse reactions
TTT
time-to-train
T2DM
type 2 diabetes mellitus


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Appendix 2.
Study Governance Considerations
Appendix 2.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Appendix 2.1.1.
Informed Consent
The Evidera investigator and research staff are responsible for the following:

Ensuring that the patient understands the nature of the study, the potential risks 
and benefits of participating in the study, and that their participation is voluntary.

Ensuring that informed consent is given by each patient or legal representative.  
This includes obtaining the appropriate signatures and dates on the informed 
consent form (ICF) prior to the performance of any protocol procedures and prior 
to the administration of investigational product.

Answering any questions the patient may have throughout the study, and sharing 
in a timely manner any new information that may be relevant to the patient’s 
willingness to continue his or her participation in the study.

Ensuring that a copy of the ICF is provided to the participant or the participant’s 
legal representative and is kept on file.

Ensuring that the medical record includes a statement that written informed 
consent was obtained before the participant was enrolled in the study and the date 
when the written consent was obtained.  The authorized person obtaining the 
informed consent must also sign the ICF.
Appendix 2.1.2.
Recruitment
For the pilot phase, Evidera is responsible for the central recruitment strategy for participants.
For the main phase, the clinical sites are responsible for the central recruitment strategy for 
patients.  Individual investigators may have additional local requirements or processes.
Appendix 2.1.3.
Ethical Review
The investigator must give assurance that the ethical review board (ERB) was properly 
constituted and convened as required by International Council for Harmonisation (ICH) 
guidelines and other applicable laws and regulations.
Documentation of ERB approval of the protocol and the ICF must be provided to Eli Lilly and 
Company (Lilly) before the study may begin at the investigative site(s).  Lilly or its 
representatives must approve the ICF, including any changes made by the ERBs, before it is used 
at the investigative site(s).  All ICFs must be compliant with the ICH guideline on Good Clinical 
Practice (GCP).
The study’s ERB(s) should be provided with the following:


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
The protocol and related amendments and addenda, and updates during the 
course of the study;

ICF;

Other relevant documents (for example, curricula vitae, advertisements).
Appendix 2.1.4.
Regulatory Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethics principles derived from international ethics guidelines, 
including the Declaration of Helsinki and Council for International Organizations
of Medical Sciences International Ethical Guidelines;

Applicable ICH GCP Guidelines;

Applicable laws and regulations.
The sponsor (Lilly), Evidera investigator, and Evidera research staff are responsible for adhering 
to any regulations and/or laws pertinent to using and transferring the devices for clinical trial use.
Some of the obligations of the sponsor will be assigned to a third party.
Appendix 2.1.5.
Investigator Information
Physicians with a specialty in internal medicine, endocrinology, or primary care/family doctors
will participate as investigators in this clinical trial.
Appendix 2.1.6.
Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Appendix 2.1.7.
Final Report Signature
The sponsor’s responsible medical officer and statistician will approve the final clinical study 
report for this study, confirming that, to the best of his or her knowledge, the report accurately 
describes the conduct and results of the study.
Appendix 2.2.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Evidera will do the following:

Provide instructional material to the study sites, as appropriate;

Sponsor start-up training to instruct the investigators and study coordinators.  This 
training will give instruction on all study recruitment procedures;

Be available for consultation and stay in contact with the study site personnel by 
mail, telephone, and/or fax;


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
Train Evidera staff to deliver the standardized trainings on both devices following 
the Interview and Device Training Guide (Appendix 12);

Review and evaluate Case Report Form (CRF) data and use standard computer 
edits to detect errors in data collection;

Conduct a quality review of the database.
Data collection will be conducted according to the protocol and will progress according to the 
study procedures previously outlined in Section 5.5.
At the time of enrollment, participants will be assigned unique identification numbers.  The 
unique identifiers assigned will be used to track the participants throughout the study.  Only the 
unique participant identification and participant initials will be entered into the database and 
recorded on the participant questionnaires—not participant names.
Participants will be assured of the confidential nature of the interview.  If, at any time, 
participants become uncomfortable with a question or the process, they will be given the option 
of terminating the study interview.  All interviews will take place in a quiet and private space to 
ensure confidentiality.  Evidera study staff will review all forms for completeness prior to 
concluding the study visit.  
Only Evidera staff for the pilot phase and both Evidera and the clinical site staff for the main 
phase involved in participant recruitment and data collection, will know the identity of the 
participants.  Study staff will be instructed to maintain complete confidentiality of all collected 
data.  For both study phases, trained Evidera interviewers and research support staff will observe 
the interviews, and have access only to de-identified data on the study CRFs.  Lilly employees 
may also observe some of the study interviews.  
Extensive procedures for the careful and complete collection of data will be implemented by the 
clinical sites and Evidera.  At the completion of each interview, study staff will check every page 
of each questionnaire to ensure that no items were unintentionally skipped.  Participant 
recruitment will be monitored on a regular basis throughout the study using tracking logs.  The 
Evidera Principal Investigator and Quality Assurance Analyst will be available for consultation 
regarding study implementation, recruitment, and any other queries throughout this process.
The study may be audited by Lilly or its representatives, and/or regulatory agencies at any time.  
Investigators will be given notice before an audit occurs.
The investigator will keep records of all original source data.  If requested, the investigator will 
provide the sponsor, applicable regulatory agencies, and applicable ERBs with direct access to 
original source documents.
Appendix 2.2.1.
Data Capture System
For data collection, Evidera will use DataFax, a data management system that relies on optical 
character recognition software, for collecting study data.  The CRFs for this study will be 
formatted for the DataFax system.  DataFax improves data quality through quality control reports 
and automatic queries, while increasing speed and efficiency of data collection.  When the data is 


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received, the system identifies any problems with the data, and queries are automatically 
generated.  Evidera will implement this data entry process and prepare the data verification 
guidelines.  
For both the pilot and main phase, Evidera will be responsible for the following:

Entering and cleaning all data collection forms in DataFax;

Storing all the original patient-completed CRFs.  Retaining records for a 
minimum of 2 years on-site and an additional 5 years off-site in storage;

Managing the completed data, performing quality checks, and merging all 
participant datasets;

Following good research practice guidelines; and

Adhering to all procedures outlined in the protocol.
Evidera will maintain the originals of all patient-completed CRFs and the clinical sites will 
maintain the originals of all site-completed CRFs.  However, for the main phase, sites will 
provide Evidera scanned copies of the Inclusion/Exclusion Forms in advance of all study 
interviews to confirm patients’ eligibility.  Sites will also provide Evidera scanned copies of the 
site-completed Clinical Information Forms.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.
Appendix 2.3.
Study and Site Closure
Appendix 2.3.1.
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or Evidera, the investigator, or the ERB of 
the study site judges it necessary for medical, safety, regulatory, or other reasons consistent with 
applicable laws, regulations, and GCP.
Appendix 2.3.2.
Discontinuation of the Study
The study will be discontinued if Lilly or Evidera judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.
Appendix 2.4.
Publication Policy
The publication policy for Study H9X-MC-B021 is described in the study proposal.


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Appendix 3.
Recruitment Advertisements
RESEARCH PARTICIPANTS NEEDED
If you are currently treated for type 2 diabetes with oral medication 
and have never used self-injected medication, you may be eligible 
to participate in this study.
We are looking for people to take part in a 90–120 minute interview about 
diabetes medication.  The study does not involve treatments.  We are 
interested in your opinions.  Study visits will be held in-person in [location].
Participants will receive <$insert amount> for their time.
Please CALL Evidera at [to be inserted (free phone)] and leave a message with your name and 
telephone number or send an E-MAIL with your name and telephone number to [to be inserted].
Ref # 23274


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Appendix 4.
Pilot Phase Screening Script
Screening Script (Evidera) – Pilot Phase
My name is [XXXX], and I conduct research at Evidera, an independent healthcare research 
company.  Thank you for responding to our advertisement about the diabetes research study.
The goal of this interview study is to determine patient preferences for two type 2 diabetes 
treatment devices currently commercialized.  Your experience with type 2 diabetes can help us in 
this process.
If you qualify and choose to participate, you would be asked to attend a 90–120 minute 
individual, in-person interview with an Evidera researcher interviewer at [location].  You will 
not receive treatment with any drugs during this study. During the interview, you will be trained 
on how to use two injection devices that are currently commercialized.  You will be asked to 
perform mock injections using both devices on a pad, and then asked to complete a series of 
questionnaires related to your condition and the use of the devices.  The amount of time it takes 
for an interviewer to train you to use each device will be recorded.
The information that you provide in the interview will be kept as confidential as possible.  A 
study identification number will be assigned to the information you give and your name will be 
kept separate.
There are minimal risks to participating in the study because of being trained and performing 
mock injections on pads with devices.  For example, you could have an accidental needle stick
injury.  All interviewers have been trained on how to handle any issues that may arise from using 
the devices.  During all interviews, a medical professional (e.g., nurse or paramedic) will be on 
site in case of adverse events such as unanticipated needlesticks.  Participation is entirely 
voluntary.  You are free to withdraw from the study at any time. 
For your time and participation, you will receive <$ insert amount>, which will be given to you 
in the form of a Greenphire ClinCard that is used just like a credit card.
Would you be interested in participating?
  No - Thank him/her for his/her time and consideration.
  Yes - Continue with the script.
That’s great!  To find out if you are eligible to participate, I need to ask a few questions.  The 
information you give will be kept as confidential as possible.  You do not have to answer 
questions you do not want to, but that may disqualify you.


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ELIGIBILITY SCREENING
Note to screener:  Please complete the following inclusion/exclusion criteria table for each 
participant.  Certain inclusion/exclusion criteria may not be determined via phone screen (e.g., 
cognitive ability to understand the device trainings).  For these criteria, the final eligibility 
determination will be established at the time of the interview.
ELIGIBILITY CRITERIA
Answer
Fits criteria?
1. What is your age?  
Age:  _______ [If less than 18 years 
old, not eligible.]
Yes    No
2. Have you been diagnosed 
with type 2 diabetes?  If yes, 
in what year were you 
diagnosed?
  Yes, record diagnosis year:  _______
  No [not eligible, terminate]
Yes    No
3.  Have you been diagnosed 
with type 1 diabetes?
  Yes [not eligible, terminate]
  No 
Yes    No
4.  Are you currently pregnant?
  Yes [not eligible, terminate]
  No [continue to 5]
Yes    No
5.  Have you ever been on self-
injectable therapy (e.g., 
diabetes therapies such as 
insulin or for other medical 
conditions)?
  Yes [not eligible, terminate]
  No 
Yes    No
6.  Have you ever administered 
injectable treatment (e.g., 
diabetes therapies such as 
insulin or for other medical 
conditions) to others?
  Yes [not eligible, terminate]
  No 
Yes    No
7.  Are you a health care 
practitioner that is trained in 
giving injections?
  Yes [not eligible, terminate]
  No 
Yes    No


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ELIGIBILITY CRITERIA
Answer
Fits criteria?
8.  Do you currently receive
oral treatment for your type 2 
diabetes?
  Yes, which one(s)?: _____________
_________________________________
  No [not eligible, terminate]
Yes    No
9.  Are you able to bring proof 
of your oral treatment 
prescription for type 2 
diabetes to the interview? 
(e.g., the medication itself, 
the medication packaging, a 
prescription note, or a letter 
from your doctor).
  Yes
  No [not eligible, terminate]
Yes    No
10.  Are you willing and able to 
attend an in-person 
interview?
  Yes
  No [not eligible, terminate]
Yes    No
11.  Do you feel that you are able 
to read, speak, and 
understand English 
sufficiently to fully 
participate in an interview 
and complete questionnaires?
  Yes
  No [not eligible, terminate]
Yes    No
12.  Are you willing and able to 
provide written informed 
consent?
  Yes
  No [not eligible, terminate]
Yes    No
13.  Are you currently enrolled 
in any other clinical study 
involving an investigational 
product?
  Yes [not eligible, terminate]
No
Yes    No
14.  Have you participated, 
within the last 30 days, in a 
clinical study involving an 
investigational product?
  Yes [not eligible, terminate]
  No
Yes    No


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ELIGIBILITY CRITERIA
Answer
Fits criteria?
15.  Are you an Eli Lilly and 
Company, Novo Nordisk, 
Evidera, or PPD 
(Pharmaceutical Product 
Development) employee? 
  Yes [not eligible, terminate]
  No
Yes    No
Respondents must be able to attend interview and meet all the required criteria.  Otherwise, the 
respondent is NOT ELIGIBLE to participate.


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ELIGIBILITY RATING
Based on the eligibility responses above, the respondent is:
  Not Eligible - I’m sorry, but based on your responses I’m not able to include you in the 
study.  Thank you for your time.  [Terminate call]
  Eligible - Based on what you have told me, you are eligible to participate in the study.  
Can I ask you some additional questions?
Proceed with gathering additional demographic information from eligible & interested 
participants.
ADDITIONAL DEMOGRAPHIC 
INFORMATION
1.  What is your gender?  
  Male    Female
2a.  What is your ethnic background?  
1  Hispanic or Latino
2  Not Hispanic or Latino
3  Not applicable
2b.  What is your racial background? 
(check all that apply)
1  American Indian or Alaska Native
2  Asian
3  Black or African American
4  Native Hawaiian or Other Pacific Islander
5  White
6  Other: _________________________________
3.  What is your current employment 
status?
  Full-time work
  Part-time work
  Homemaker/housewife
  Student
  Unemployed
  Retired
  Disabled
  Other:  ______________________
4.  Where did you find out about this 
research study?
  Newspaper Ad:  ______________
  Other:  _____________________
Thank you for providing me with this information.
We are also being asked to pass on to the study sponsor any details of adverse events and product 
complaints that are mentioned during this research study. Although this is a 1-time interview 
and what you say will, of course, be treated in confidence, should you mention an adverse event 


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or product device complaint, the study team will need to report this even if it has already been 
reported by you directly to the company or the regulatory authorities. 
Are you willing to proceed with the interview?
  Yes (continue)
  No (terminate) 
Based on the answers you just gave me, you are able to participate in this study.  Are you able to 
come [insert interview location] for an in-person interview? 
  Yes (continue)
  No (terminate)


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SCHEDULING INFORMATION
Thank you for your interest in participating.  
We are trying to conduct these interviews over a period of [roughly two weeks in Month], so we 
are looking for dates that you may be available.  If one of the dates that you are available is 
selected, we will contact you soon to confirm that you are still interested and available on the 
selected date and time.  We will then send you directions to the interview location.
Schedule Interview
Participant Name
Potential Dates of 
Participation or 
Unavailability 
Finalized Date and Time of 
Study Visit
/        /
   DD / MMM / YYYY
_____:_____ AM/PM
time
Phone Numbers
Please check the box with the preferred number
  Home ________________________
  Work _______________________
  Cell ________________________
Best times to call:  
________________________________________
Information for sending a 
confirmation letter with 
directions to the interview
We need to send your interview confirmation via e-mail or 
regular mail with directions to the interview.  In addition, 
closer to the interview you will receive a reminder phone call.  
Please be aware that if you share an e-mail account with 
someone else, they may be able to read the information that we 
send.  How would you prefer to receive your interview 
information?
E-mail confirmation (Ask participant to provide e-mail 
address): 
_____________________________________________
Regular mail confirmation (Ask participant for mailing 
address to send via regular mail):
_____________________________________________
_____________________________________________
Screener Name: ___________________________________________


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Screener Signature: ___________________________________  Date: ____/______/______
              
          DD MMM  YYYY


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Appendix 5.
Pilot Phase Inclusion/Exclusion Criteria
INCLUSION/EXCLUSION CRITERIA FORM 
(EVIDERA STUDY STAFF) – PILOT PHASE
Check YES or NO for each of the following criteria: 
INCLUSION CRITERIA
YES
NO
1.
Participant is ≥18 years of age


2.
Participant has been diagnosed with type 2 diabetes


3.
Participant is self-injection naïve to all injectable treatment (e.g., diabetes therapies and other 
medical conditions) 


4.
Participant is injection naïve to performing all injectable treatment (e.g., diabetes therapies and 
other medical conditions) to others 


5.
Participant is currently receiving oral treatment for their type 2 diabetes


6.
Participant is willing and able to attend an in-person interview


7.
Participant is able to read, speak, write, and understand the English language


8.
Participant is willing and able to provide written informed consent


If ANY of the above answers are NO, the participant is NOT ELIGIBLE for participation in 
this study. Do not proceed any further with this participant. If ALL of the above items are 
YES, continue.
Please assess the exclusion criteria by checking YES or NO for each of the following criteria:
EXCLUSION CRITERIA
YES
NO
Study staff should use recruitment/screening interaction to assess these questions:
1.
Currently diagnosed with gestational diabetes and/or type 1 diabetes 


2.
Currently pregnant


3.
Cognitive or physical difficulties that could interfere with ability to understand the training, 
perform the injection tasks, or complete the study questionnaires as judged by the investigator


4.
Currently enrolled in any other clinical study involving an investigational product or any other 
type of medical research judged not to be scientifically or medically compatible with this study


5.
Has participated, within the last 30 days, in a clinical study involving an investigational product


6.
Is a health care practitioner who is trained in giving injections


7.
Is an Eli Lilly and Company, Novo Nordisk, Evidera, or PPD employee


If ANY of the above answers to the exclusion questions are YES; the participant is NOT 
ELIGIBLE for participation in this study.
CONSENT


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1. Participant has provided written consent:
Yes    No
2. Date consent obtained:
__ __/__ __ __/__ __ __ __
   DD      MMM      YYYY
INVESTIGATOR SIGNATURE
DATE
I certify that the above information is correct.
Investigator/Designee 
Signature:__________________________________________
__ __/__ __ __/__ __ __ __
   DD      MMM      YYYY


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Appendix 6.
Confirmation Letter/E-mail
PARTICIPANT CONFIRMATION LETTER/E-MAIL – PILOT & MAIN PHASE
[Date for letter]
[Participant Name and Address for letter]
Dear [Participant]:
Thank you for your interest in our research study.  We appreciate you taking the time out of your 
schedule to participate in our interview.  We have scheduled your in-person interview at <Time> 
on <Date> at <location name and address>.  We have included driving directions and [public 
transport system] directions to this facility with this [letter or e-mail].  
The purpose of this study is to better understand patients’ preferences for diabetes treatments.  
For this study, we are interviewing people with type 2 diabetes, and this study is sponsored by a 
large pharmaceutical company.  During the interview, you will be trained on how to use two 
different commercialized devices that dispense type 2 medications.  You will also be asked to 
complete a brief series of questionnaires about the devices, your diabetes condition, and your 
general health.  If you become uncomfortable with any of the interview questions, you can 
always completely terminate the interview at any time or prefer not to answer the questions that 
make you feel uncomfortable.  All information you provide will be kept confidential, you have 
the right to withdraw at any time.  Your personal information will be stored within Evidera.  This 
is not a sales promotional activity.  Aggregate study results without any of your personal 
information might be published.
The interview will last approximately [pilot phase: 1.5 to 2 hours; main phase: 1 to 1.5 hours].  
[For pilot phase only participants:  Please remember to bring proof of your type 2 diabetes oral 
medication(s) with you to the interview (e.g., the medication itself, the box the medication comes 
in, or a letter from your doctor).]  After your interview, you will be compensated a specified 
amount for your time and travel to the study interview [pilot phase: <$ insert amount>; main 
phase: <$ insert amount>].  
Upon arrival to the <location>, please <to provide instructions for checking in and proceeding to 
interview room>.  If you have any questions or concerns, please call [pilot phase: Evidera
contact person name and telephone number; main phase: Clinical site contact person name and 
telephone number].  Thank you again for your interest in this study.  We greatly appreciate your 
participation.
Sincerely, 
[pilot phase:  Evidera contact person name, title]
[main phase:  Clinical site contact person name, title]


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Appendix 7.
Reminder Phone Call/E-mail
PARTICIPANT REMINDER PHONE CALL – PILOT & MAIN PHASE
Hello [Insert Participant Greeting]
My name is [XXXX], from [pilot phase: Evidera; main phase: Clinical site name]. I am just 
calling to remind you that you are scheduled to take part in a one-on-one interview at <Time> on 
<Date> at <Location name and address>.  [For pilot phase only participants:  Please remember 
to bring proof of your type 2 diabetes oral medication(s) with you to the interview (e.g., the 
medication itself, the box the medication comes in, or a letter from your doctor).]  
Full details of the study have been previously e-mailed or sent to you by post.
Will you be able to attend?  [If no, please try and re-schedule the participant.]
PARTICIPANT REMINDER E-MAIL – PILOT AND MAIN PHASE
Dear [Insert Participant Greeting]:
You are scheduled to take part in a one-on-one interview at <Time> on <Date> at <Location 
name and address>.  The interview will last approximately [pilot phase: 1.5 to 2 hours; main 
phase: 1 to 1.5 hours].  [For pilot phase only participants:  Please remember to bring proof of 
your type 2 diabetes oral medication(s) with you to the interview (e.g., the medication itself, the 
box the medication comes in, or a letter from your doctor).]  
Please respond to this e-mail with confirmation that you are still able to attend.
Full details of the study have been previously e-mailed or sent to you by post. 
[pilot phase:  Evidera contact person name, title]
[main phase:  Clinical site contact person name, title]


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Appendix 8.
Main Phase Screening Script
Screening Script (Clinical Site) – Main Phase
The Inclusion/Exclusion Criteria Form is a separate form but there are criteria that can be 
reviewed by the clinic site prior to contacting the patient. Before you introduce the research 
study to the patient please confirm using the patient’s medical chart:
1.
Patient is ≥18 years of age
  Confirmed
2.
Patient has been diagnosed with T2DM 
  Confirmed
3.
Patient is self-injection naïve to all injectable treatment (e.g., diabetes 
therapies and other medical conditions)
  Confirmed
4.
Patient is currently receiving oral treatment for their type 2 diabetes 
  Confirmed
Once all above criteria have been confirmed, please conduct recruitment with patient according 
to the following script.  Please complete the Inclusion/Exclusion Criteria Form.
Hello, this is [name] from [clinic]. We are currently recruiting patients with type 2 diabetes to 
participate in a research study being conducted by Evidera, a health outcomes research 
organization. The goal of the interview study is to determine patient preferences for the type 2 
diabetes treatment devices currently commercialized.  
If you qualify and choose to participate, you would be asked to attend a 60-90 minute individual, 
in-person interview with an Evidera researcher at [location].  You will not receive treatment with 
any drugs during this study.  During the interview, you will be trained on how to use two 
injection devices currently commercialized.  You will be asked to perform mock injections using 
both devices on a pad, and then asked to complete a series of questionnaires related to your 
condition and the use of the devices.
[For Time-to-Train Participants:  The amount of time it takes for an interviewer to train you to 
use each device will be recorded.]  
The information that you provide in the interview will be kept as confidential as possible. A 
study identification number will be assigned to the information you give and your name will be 
kept separate.  The information you share during the interview will not be shared with your 
doctor, and will have no impact on the care that you receive or your ability to participate in 
future studies.
There are minimal risks to participating in the study because of the use of being trained and 
performing mock injections on pads with devices.  For example, you could have an accidental 
needle stick injury.  All interviewers have been trained on how to handle any issues that may 
arise from using the devices.  During all interviews, a medical professional (e.g., nurse or 
paramedic) will be on site in case of adverse events such as unanticipated needlesticks.  
Participation is entirely voluntary.  You are free to withdraw from the study at any time. 


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For your time and participation, you will receive: <$ insert amount> (via Greenphire ClinCard).
Are you interested in participating?
  No – Thank them for their time and consideration.
  Yes – Great. Now, to find out if you are eligible for this study, I need to ask a few 
questions.
Confirm any inclusion/exclusion criteria with the patient that cannot be ascertained based on the 
chart/information using the Inclusion/Exclusion Criteria Form.
If not eligible:  Thank you for your interest in the study, however you are not eligible to 
participate.
If eligible, continue.
We are also being asked to pass on to the study sponsor any details of adverse events and product 
complaints that are mentioned during this research study.  Although this is a 1-time interview 
and what you say will, of course, be treated in confidence, should you mention an adverse event 
or product device complaint the study team will need to report this even if it has already been 
reported by you directly to the company or the regulatory authorities.
Are you happy to proceed with the interview on this basis?
  Yes (continue)
  No (terminate) 
Based on the answers you just gave me, you are able to participate in this study.  Are you able to 
come [insert interview location] for an in-person interview? 
  Yes (continue)
  No (terminate)
If in-person, continue:
What is the best day and time for you to come in to complete the interview? 
[Schedule for interview]
Participant Initials:  _______
Name of Person Entering Initials:  _________________________________
Interview Date:  __________________
Time:  ___________
For all interviews, continue:
May I have your e-mail, mailing address and/or phone numbers?  We will need this information 
to contact you in the future as we arrange the scheduling of the interviews and/or to remind you 
about your interview (Please remind participant that if they share an e-mail address with 
someone, that individual may be able to read the information that we send).


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  Yes (proceed with asking for contact information)
  No (Skip to bottom of script and give participant [your site] contact information)
What is the best phone number to use? 
Patient Name: ________________________
Address: 
____________________________________
____________________________________
____________________________________
Please check the box with the preferred number
  Home ________________________
  Work _________________________
  Cell __________________________
Best times to call:  
_________________________________________________
_______________________
E-mail address: 
_________________________________________________
_______________________
Please remind participant that if they share an e-mail address 
with someone else, this other person may be able to read the 
information that we send. 
If you have any questions or if you would like to cancel/reschedule your interview, please 
contact [clinic staff name] at [clinic staff number]. Thank you very much for your time.  Have a 
nice day!
Screener Name: ___________________________________________
Screener Signature:  ___________________________________  Date: ____/______/______
  
          DD  MMM  YYYY


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Appendix 9.
Main Phase Inclusion/Exclusion Criteria
INCLUSION/EXCLUSION CRITERIA FORM (CLINICAL SITE) – MAIN PHASE
Please review the participant’s eligibility. Check YES or NO for each of the following criteria: 
INCLUSION CRITERIA
YES
NO
1.
Patient is ≥18 years of age


2.
Patient has been diagnosed with type 2 diabetes


3.
Patient is self-injection naïve to all injectable treatment (e.g., diabetes therapies and 
other medical conditions) 


4.
Patient is injection naïve to performing all injectable treatment (e.g., diabetes therapies 
and other medical conditions) to others 


5.
Patient is currently receiving oral treatment for their type 2 diabetes


These questions will need to be asked of the patient to see if he or she is eligible:


6.
Are you self-injection naïve to all injectable treatment (e.g., diabetes therapies and other 
medical conditions)?


7.
Are you injection naïve to performing all injectable treatment (e.g., diabetes therapies and 
other medical conditions) to others?


8.
Are you willing and able to attend an in-person interview?


9.
Do you feel that you are able to read, speak, write, and understand English sufficiently to 
fully participate in an interview and complete questionnaires?


10. Are you willing and able to provide written informed consent?


If ANY of the above answers are NO, the participant is NOT ELIGIBLE for participation in 
this study.  Do not proceed any further with this participant.  If ALL of the above items are 
YES, continue.
Please assess the exclusion criteria by checking YES or NO for each of the following criteria:
EXCLUSION CRITERIA
YES
NO
Clinic site should use the patient’s medical record and the recruitment/screening interaction to 
assess these questions:
1.
Currently diagnosed with gestational diabetes and/or type 1 diabetes


2.
Currently pregnant


3.
Cognitive or physical difficulties that could interfere with ability to understand the training, 
perform the injection tasks, or complete the study questionnaires as judged by the 
investigator


4.
Currently enrolled in any other clinical study involving an investigational product or any 
other type of medical research judged not to be scientifically or medically compatible with 
this study


5.
Has participated, within the last 30 days, in a clinical study involving an investigational 
product


6.
Is a health care practitioner who is trained in giving injections




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EXCLUSION CRITERIA
YES
NO
7.
Investigator, site personnel, or immediate family member of investigator or site 
personnel.  (Immediate family is defined as a spouse, parent, child, or sibling, whether 
biological or legally adopted.)


8.
Is an Eli Lilly and Company, Novo Nordisk, Evidera, or PPD employee


If ANY of the above answers to the exclusion questions are YES; the participant is NOT 
ELIGIBLE for participation in this study.
CONSENT
1. Participant has provided written consent:
Yes    No
2. Date consent obtained:
__ __/__ __ __/__ __ __ __
   DD      MMM      YYYY
INVESTIGATOR SIGNATURE
DATE
I certify that the above information is correct.
Investigator/Designee Signature:
__________________________________________
__ __/__ __ __/__ __ __ __
   DD      MMM      YYYY


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Appendix 10.
Participant Recruitment Tracking Log
Please send the Recruitment Tracking Log to Evidera every [insert day of the week] 
(Attn: XXXX at 301-654-9864 or e-mail: [insert e-mail address])
Screening 
ID
Initials
Eligible
Participant 
Age
Participant 
Gender
Participant 
ID
Interview Date and Time
(DD/MON/YYYY; time)
All Reasons Ineligible or 
Withdraw
Example
S01-001
ABC
Y 
N 
35 
F
Example
101-101
01/NOV/2018; 9:30 AM EST
Example 
S01-002 
DEF
Y 
N 
60
M
Example
101-102
01/NOV/2018; 11:30 AM 
EST
Example 
S01-003
GHI
Y 
N 
55
F
N/A
N/A
Ineligible (Inclusion #3)
Example 
S01-004
JKL
Y 
N 
17
F
N/A
N/A
Ineligible (Exclusion #1 
and 3)


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Appendix 11.
Supplemental Question S1
Supplemental Question S1
S1. Would you be willing to use a diabetes medication that required you to give yourself 
an injection for each dose?
  Not willing
  Somewhat not willing
  Neutral
  Somewhat willing
  Very willing


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Appendix 12.
Interview and Device Training Guide
Interview Guide
I. MATERIALS
1. IFU for Trulicity
2. IFU for Ozempic
3. Trulicity Injection Pen 
4. Trulicity Demonstration Pen
5. Two Ozempic Injection Pens (one for demonstration and one for participant use)
6. Sharps container (for disposal of Trulicity Devices and Ozempic Needles)
7. Injection pad
8. Alcohol wipes
9. Trash can (for pen cap)
10. Non-latex gloves
II. INTERVIEW STEPS
1. Confirm the in/ex form has been completed
2. Informed consent 
3. Complete Supplemental Question S1 
4. Randomization with IWRS system to determine which device is first
5. Explain study to the participant
6. First Device: Training and Mock Injection
7. Complete demographic form
8. Second Device: Training and Mock Injection
9. Complete Interviewer Recording Sheet
10. Complete questionnaires about device preferences and Supplemental Questions S2 and 
S3
STEP 1. CONFIRM IN/EX FORM HAS BEEN COMPLETED

Review the site-completed in/ex form for the participant to confirm eligibility.  

This form should be provided to you by the site, and it should already be completed prior 
to the interview. 
STEP 2. INFORMED CONSENT

Review the consent form with the participant and confirm comprehension.  

Provide the participant with opportunity to answer questions before signing.

Ask the participant to sign two copies of the consent form if they wish to participate.  


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
Countersign the forms and provide a copy to the participant. 
STEP 3. COMPLETE SUPPLEMENTAL QUESTION S1

Ask the participant to independently complete this question: “Please complete this 
question, and let me know when you are finished.” 
STEP 4. RANDOMIZATION WITH IWRS SYSTEM

Complete the randomization process to determine the order of device training for the 
participant. 

Record the order on the Interviewer Recording Sheet. 
STEP 5. EXPLAIN THE STUDY TO THE PARTICIPANT

“You will be trained to use two devices for injecting medication for type 2 diabetes.” 

“For each device, I will walk you through the steps for using each device and 
demonstrate the steps for you.  Then, you will use the device to administer an injection 
into an injection pad.” 

“After you have had a chance to use both devices, I will ask you to complete some 
questionnaires that ask about your preference between the devices.” 

“Do not inject medication into yourself.  You will only be injecting into the injection 
pad.”  

“Please handle the devices carefully to avoid accidently sticking yourself with the needle.  
If you appear to be handling the device incorrectly, I will try to correct you so you do not 
accidently stick yourself with the needle.” 
STEP 6. FIRST DEVICE TRAINING
Follow the Trulicity Training Guide or the Ozempic Training Guide based on the randomization 
order for the participant. 
STEP 7. DEMOGRAPHIC FORM
“Please complete this form.”
STEP 8. SECOND DEVICE TRAINING
Follow the Trulicity Training Guide or the Ozempic Training Guide based on the randomization 
order for the participant. 


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STEP 9. COMPLETE INTERVIEWER RECORDING SHEET
The interviewer completes the interviewer recording sheet to document order of device training 
and completion status. 
STEP 10. PARTICIPANT-COMPLETED QUESTIONNAIRES
Instruct the participant to complete questionnaires on device preference and supplemental 
questions S2 and S3.


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Ozempic Training Guide
A. Time to Train
The observer should complete the TTT Observer Recording Sheet.
a.
Start of the training (i.e., after reading the IFU)
b. The participant picks up the device to start the mock injection. 
c.
The participant successfully injects the medication into the injection pad and removes the 
needle/device from the pad.
d. The Ozempic pen is recapped with the pen cap (the inner needle cap and outer needle cap 
should not be placed back on the pen).
e.
The participant has completed the injection and finished asking questions.  Participants 
comments/opinions about the device after completing the injection will not be included 
unless the participant asks a question. 
B. Safety Procedures
If the participant appears to be making an error that could lead to self-harm, the trainer should 
immediately intervene and stop the injection process.
C. Introduction
Introduce the device and training steps.

“Now, you will learn to use an injection device.”

“When you feel comfortable with the procedures for using the device, you will use the 
device to perform a mock injection into the injection pad.”

“You should NOT use this device to inject yourself.  You will only be injecting 
medication into this pad.”

“This is the Ozempic device.  This device is used to administer medication once a week, 
and you would typically use it at home.” (Show the device to the participant.)  
D. Device Training
1. Open the device box and place the IFU in front of the participant.
2. Instruct the participant to “Please read the Instructions for Use and let me know when you 
are finished.  After you are done reading, I will demonstrate all of these steps for you in 
detail.  You can also refer back to this document throughout the interview as much as you 
want.”


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3. Demonstrate the injection process using the demo device. 
1. “The Ozempic device is a prefilled dial-a-dose pen.  You can select doses of 0.25 mg 
or 0.5 mg.  You will be selecting 0.25 mg for the injection today.”
2. “The needles for this device are enclosed in the package.” 
3. “Always use a new needle for each injection.”
4. Device parts
a.
“This is the pen cap.”
b. “This is the pen window.” 
c.
“This is the dose counter and dose pointer.” 
d. “This is the dose selector and the dose button.”
e.
“When you turn the dose selector, you will see the flow check symbol and the dashed 
line to guide to your dose (turn dose selector to show these symbols).  The flow check 
symbol comes right after the zero.”
f.
“The needle has an outer needle cap, inner needle cap, needle, and paper tab.”
5. Step 1: Prepare your pen with a new needle
a.
“If you were injecting, you would begin by washing your hands with soap and water. 
Since you are injecting a pad today, you do not need to wash your hands this time.”
b. “The next step is to check the name and colored label of your pen to make sure that 
it contains Ozempic.”
c.
“Then pull off the cap.”
d. “Check that the Ozempic in your pen is clear and colorless. Look through the pen 
window.  If the Ozempic is cloudy, do not use the pen.”
e.
“Take a new needle, and tear off the paper tab.”
f.
“Push the needle straight on to the pen.  Turn until it is on tight.”
g. “Pull off the outer needle cap.  You can put it in the sharps container.”


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h. “Pull off the inner needle cap, and throw it away.”
6. Step 2: Check the Ozempic flow with each new pen
a.
“Check the Ozempic flow before your first injection with each new pen.”
b. “Turn the dose selector until the dose counter shows the flow check symbol.”
c.
“Hold the pen with the needle pointing up.  Press and hold in the dose button until 
the dose counter shows 0.  The 0 must be lined up with the dose pointer.  A drop of 
Ozempic will appear at the needle tip.  The medication may spray out a bit in some 
cases, so please point the tip away from your face and away from me.”
d. “If no drop appears, repeat these flow check steps up to six more times.  Do not use 
the pen if a drop of Ozempic still does not appear.”
7. Step 3: Select your dose
a.
“Turn the dose selector until the dose counter shows your dose (0.25 mg).  If you 
select the wrong dose, you can turn the dose selector forward or backwards to the 
correct dose.” 
8. Step 4. Inject your dose
a.
“Choose your injection site.”
b. “Insert the needle into your skin [injection pad].”
c.
“Make sure you can see the dose counter.  Do not cover it with your fingers.  This 
could stop the injection.”
d. “Press and hold down the dose button until the dose counter shows 0.  The 0 must 
line up with the dose pointer.  You may then hear or feel a click.”
e.
“Keep the needle in your skin [injection pad] after the dose counter has returned to 
0 and count slowly to 6.”
f.
“If the needle is removed earlier, you may see a stream of Ozempic coming from the 
needle tip.  If this happens, the full dose will not be delivered.”
g. “Remove the needle from your skin [injection pad].”
9. Step 5. After your injection
a.
“Carefully twist the needle off of the pen.   Since we have a sharps container, 
please do not put the needle caps back on the needle to avoid needle sticks.”


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b. “Place the needle in a sharps container right away.”
c.
“Put the pen cap on your pen after each use to protect Ozempic from light.”
4. Permit the participant to ask any questions they may have about the device or IFU.

“Do you have any questions about the steps involved in the injection process?”

“Do you feel ready to administer the mock injection? Is there anything you would like to 
review before trying it?”

When the patient is ready: “I will leave the instructions for use here, and you can refer to 
them as much as you like while you go through the injection process.  Please take all the 
time you need.”
5. Participant performs mock injection into the injection pad while trainer observes and 
evaluates injection success based on the critical steps listed below.
6. The mock injection will be considered complete when the patient has successfully performed 
all critical steps listed below and recapped the pen.  
7. If the participant is struggling to remove the needle and appears to be putting themselves at 
risk of an accidental needle stick, the interviewer should volunteer to remove the needle for 
them. 

“Would you like me to remove the needle for you?”
If the interviewer removes the needle, this should be recorded on the Interviewer Recording 
Sheet. 
8. If the participant does not dispose of the needle in the sharps container independently, the 
trainer should instruct the participant on disposal using the provided sharps container.

“Please place the needle in the sharps container.”
9. Ask the participant if they have any questions, and answer them.  The training is complete 
when there are no further questions. 

“Do you have any questions?”
E. Checklist to assist interviewer in tracking critical steps


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Critical Steps
First 
attempt
Second 
attempt
Third 
attempt
Fourth 
attempt
Fifth 
attempt
1. Pull off the pen cap
□
□
□
□
□
2. Push the needle straight on to 
the pen.  Turn until it is on 
tight.
□
□
□
□
□
3. Pull off the outer needle cap 
and pull off the inner needle 
cap
□
□
□
□
□
4. Turn the dose selector until the 
dose counter shows the flow 
check symbol
□
□
□
□
□
5. Press and hold the dose button 
until the dose counter shows 0 
and a drop of Ozempic appears 
at the needle tip
□
□
□
□
□
6. If the drop does not appear on 
the first attempt, repeat flow 
check until a drop appears (up 
to 6 times).
□
□
□
□
□
7. Select your dose. Continue 
turning the dose selector until 
the dose counter shows 0.25
□
□
□
□
□
8. Insert the needle in the pad
□
□
□
□
□
9. Press and hold down the dose 
button until the dose counter 
shows 0
□
□
□
□
□
10. Slowly count to 6 
(operationally: patient pauses 
after pressing injection button). 
□
□
□
□
□
11. Remove the needle from the 
pad
□
□
□
□
□
12. Remove the needle from the 
pen (capped or uncapped)
□
□
□
□
□
F. Retraining
If the critical steps are not performed correctly on the first attempt, the participant should be 
retrained on critical steps that were missed or performed incorrectly.  The participant may have 
to repeat all or some of the injection process.  The error should be explained to the participant 
and the participant should be asked to make the correction and continue the injection process. 


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If the participant is making a mistake during the injection, you can call his or her attention to the 
mistake so that he or she can continue the injection correctly.  For example, if the participant is 
trying to do the flow check without removing the inner cap, tell him or her to remove the cap 
first. “It looks like the inner cap is still on.  Could you remove the inner cap before checking the 
flow?”


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Trulicity Training Guide
A. Time to Train
The observer should complete the TTT Observer Recording Sheet.
a.
Start of training (i.e., after reading the IFU)
b. The participant picks up the device to start the mock injection. 
c.
The participant successfully injects the medication into the injection pad and removes the 
needle/device from the pad.
d. The Trulicity pen is dropped into the sharps container.
e.
The participant has completed the injection and finished asking questions.  Participant 
comments/opinions about the device after completing the injection will not be included 
unless the participant asks a question. 
B. Safety Procedures
If the participant appears to be making an error that could lead to self-harm, the trainer should 
immediately intervene and stop the injection process.
C. Introduction
Introduce the device and training steps.

“Now, you will learn to use an injection device.”  

“When you feel comfortable with the procedures for using the device, you will use the 
device to perform a mock injection into the injection pad.” 

“You should NOT use this device to inject yourself.  You will only be injecting 
medication into this pad.”

“This is the Trulicity device.  This device is used to administer medication once a week, 
and you would typically use it at home.” (Show the device to the participant.)  
D. Device Training
1. Open the device box and place the IFU in front of the participant.
2. Instruct the participant to “Please read the Instructions for Use and let me know when you are 
finished.  After you are done reading, I will demonstrate all of these steps for you in detail.  
You can also refer back to this document throughout the interview as much as you want.”
3. Demonstrate the injection process using the demo device. 


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1. Before you get started
a.
“Check the pen label to make sure you have the right medicine and it has not 
expired.”
b. “Inspect the pen to make sure it is not damaged”
c.
“Inspect the medicine to make sure it is not cloudy or discolored, and it should not 
have particles in it.”
d. “If you were injecting yourself, you would then wash your hands.  Since you are 
injecting a pad today, you do not need to wash your hands this time.”
e.
“If you were injecting yourself, you would select an injection site.  Today, you will 
inject into this injection pad and NOT into your body.” 
2. Device parts
a.
“At the top of the device, there is a green injection button.”
b. “Beneath that is a lock ring, and an indicator which lines up with the lock and unlock 
symbols.”
c.
“Down here you can see the medicine.”
d. “At the bottom, you can see the clear base and the base cap.”
e.
“The needle is inside the device.”
3. Steps for injection
a.
Uncapping the pen. 
i)
“You would first make sure the pen is locked” 
ii) “Then pull the base cap straight off and throw it away in the trash”. 
iii) “Do not put the base cap back on – this could damage the needle.”
b. Second, place the base on the injection site and unlock the device
i)
“You would place the clear base flat and firmly against your skin (or in this case, 
the injection pad).” 
ii) “Unlock by turning the lock ring”.


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c.
Third, administer the injection
i)
“You would press and hold the green injection button.  You will hear a loud 
click.” 
ii) “When you press the button, the medication is injected.”
iii) “Continue to hold the clear base firmly against the pad until you hear a second 
click.  This happens when the needle starts retracting in about 5 – 10 seconds.  My 
demo device may be slower than the actual device you use, so listen closely for 
the click on your device.” 
iv) “Then remove the pen from your skin [injection pad].”
v) “You will know the injection is complete when the gray plunger is visible.” 
d. The final step is disposing of the pen.
i)
“Put your used pen in the sharps disposal container right away after use”.
4. Permit the participant to ask any questions they may have about the device or IFU.

“Do you have any questions about the steps involved in the injection process?”

“Do you feel ready to administer the mock injection? Is there anything you would like to 
review before trying it?”

When the patient is ready: “I will leave the instructions for use here, and you can refer to 
them as much as you like while you go through the injection process.  Please take all the 
time you need.”
5. Participant performs mock injection into the injection pad while trainer observes and 
evaluates injection success based on the critical steps listed below.
6. The mock injection will be considered complete when the patient has successfully performed 
all critical steps listed below and placed the device in the sharps container.  
7. If the participant does not dispose of the device in the sharps container independently, the 
trainer should instruct the participant on device disposal using the provided sharps container. 

“Please place the pen in the sharps container.”
8. Ask the participant if they have any questions, and answer them.  The training is complete 
when there are no further questions.

“Do you have any questions?”


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E. Checklist to assist interviewer in tracking critical steps
Critical Steps
First 
attempt
Second 
attempt
Third 
attempt
Fourth 
attempt
Fifth 
attempt
1. Take off base cap
□
□
□
□
□
2. Place on injection site
□
□
□
□
□
3. Unlock device
□
□
□
□
□
4. Press button and hold the 
device in place until the grey 
plunger is visible. The 
participant should pause. 
□
□
□
□
□
5. Remove from injection site
□
□
□
□
□
F. Retraining (if necessary)
If the critical steps are not performed correctly on the first attempt, the participant should be 
retrained on critical steps that were missed or performed incorrectly.  The participant may have 
to repeat all or some of the injection process.  The error should be explained to the participant 
and the participant should be asked to make the correction and continue the injection process. 
If the participant is making a mistake during the injection, you can call their attention to the 
mistake so that he or she can continue the injection correctly.  For example, if the participant is 
trying to press the injection button without unlocking the device, tell the participant to unlock it.  
“It looks like the device is still locked.  Can you unlock it before injecting?”


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Appendix 13.
Time-to-Train (TTT) Observer Recording 
Sheet
TTT Observer Recording Sheet
To be completed by the TTT observer:
1. Ozempic
1a. Start time of training (i.e., after reading the IFU):  0:00
1b. Start time of participant performing mock injection(s):  ______:______ 
1c. End time of successfully administered mock injection (i.e., withdrawal of needle/device from 
injection pad):  ______:______
1d. End time of mock injection procedures (Ozempic = recapping the pen): ______:______
1e. End time of training, including all procedures and questions:  ______:______
Number of interventions: _______
2. Trulicity
2a. Start time of training introduction (i.e., after reading the IFU):  0:00
2b. Start time of participant performing mock injection(s):  ______:______ 
2c. End time of successfully administered mock injection (i.e., withdrawal of needle/device from 
injection pad):  ______:______
2d. End time of mock injection procedures (Trulicity = disposing of the pen in the sharps 
container): ______:______
2e. End time of training, including all procedures and questions:  ______:______
Number of interventions: _______


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Appendix 14.
Demographic Form
Demographic Form – Participant Completed
1.  What is your age?
2.  What is your gender?
  Male   
  Female
3a.  What is your ethnic background?
  Hispanic or Latino
  Not Hispanic or Latino
  Not applicable
3b.  What is your racial background? (Please check all that apply)
  American Indian or Alaska Native
  Asian
  Black or African American
  Native Hawaiian or Other Pacific Islander
  White
  Other:  
4.  What is your marital status?
  Single
  Married
  Divorced
  Separated
  Widowed
  Other:  _____________
5.  How would you describe your employment status? (Please tick all boxes that apply)
  Full-time work
  Part-time work
  Homemaker/housewife
  Student
  Unemployed
  Stay-at-home parent
  Retired
  Disabled
  Other:  ______________________


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6. What is the highest level of education you have completed? (Please check only one)
  Elementary/primary school
  Secondary/high school
  Some college
  College degree
  Postgraduate degree
  Other:  ______________________________________
7.  Have you had any of the following health conditions? (Please tick/check all boxes that apply)
  Angina
  Arthritis
  Cancer 
  Chronic obstructive pulmonary disease/emphysema
  Heart attack or heart disease
  Hypertension 
  Stroke
  Depression
  Other mental health conditions (please specify):  ______________________
  Other health conditions (please specify): ________________________________
  None


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Appendix 15.
Interviewer Recording Sheet
Interviewer Recording Sheet
To be completed by the interviewer:
1. Device Randomized to First Training:    Ozempic Device        Trulicity Device
  Participant completed training for first device
  Participant completed training, but required interviewer’s assistance to remove the needle 
(Ozempic only)
  Participant was exposed to this device, but did not complete training.  Please explain below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
2. Device Randomized to Second Training:    Ozempic Device        Trulicity Device
  Participant completes training for second device
  Participant completed training, but required interviewer assistance to remove the needle 
(Ozempic only)
  Participant was exposed to this device but did not complete training.  Please explain below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________


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Appendix 16.
Pilot Phase Interview Questions
Pilot Phase Interview Questions
Participants Randomization Order (select one):
  1. Ozempic Device; 2. Trulicity Device
2. Trulicity Device; 1. Ozempic Device
Questions about Ozempic Device:
1.  Are there any ways the Ozempic device training could be easier or more clear?  If yes, please 
explain.
  No
  Yes, please explain:
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
2.  Would you recommend any changes to the Ozempic device training procedures?  If yes, please 
explain.
  No
  Yes, please explain:
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
3.  How much additional guidance is appropriate and useful during the Ozempic training? 
  Video  
  Interviewer uses demonstration pens to review key device steps
  Interviewer answers questions
  Other suggestions?
Please explain response:  
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________


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Questions about Trulicity Device:
1.  Are there any ways the Trulicity device training could be easier or more clear?  If yes, please 
explain. 
  No
  Yes, please explain:
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
2.  Would you recommend any changes to the Trulicity device training procedures?  If yes, please 
explain.
  No
  Yes, please explain:
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
3.  How much additional guidance is appropriate and useful during the Trulicity training? 
  Video  
  Interviewer uses demonstration pens to review key device steps
  Interviewer answers questions
  Other suggestions?
Please explain response:  
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
Thank the participant for taking part in the study.  Ask the participant to refrain from 
discussing the interview with anyone else who plans to take part in the study.


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Appendix 17.
Global Preference Item
To be completed by all participants:
1.
Overall, which device do you prefer?
  Ozempic
  Trulicity
  No Preference
To be completed by interviewer:
2. Please explain your preference indicated in Item 1 on the Global Preference Questionnaire 
(interviewer to record reasons for device preference provided by the participant, provide 
quotes with quotations marks and write neatly):
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________


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Appendix 18.
DID-PQ
Please select only one response for each item to indicate which of the two injection devices you prefer.
Ozempic Device
Trulicity Device
Strongly Prefer 
Ozempic
Device
Prefer Ozempic 
Device
No 
Preference
Prefer
Trulicity 
Device
Strongly 
Prefer Trulicity 
Device
1. Ease of preparing the 
injection device and 
medication for use





2. Ease of fitting the 
injection into your 
routine





3. Ease of bringing the 
injection device with 
you when it is 
necessary to inject 
away from home





4. Confidence that the 
injection device 
provides the correct 
dose of medication 
every time





5. Confidence that you 
are using the injection 
device correctly





6. The size of the needle





7. The time it takes to 
prepare and inject 
each dose of 
medication





8. Overall satisfaction 
with the injection 
device 





9. Overall ease of using 
the injection device





10. Overall convenience of 
using the injection 
device 







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Appendix 19.
Four Items From MDDAB – Ozempic Device
Four Items From MDDAB – Ozempic Device
Instructions:  Based on your experience with the medication delivery device used in this study, please indicate how easy or difficult 
it was to use the device. For each question, please check the number that best represents your experience with using the device.
How difficult or easy was it to do the following?
Very Difficult
Difficult
Neither 
Difficult nor 
Easy
Easy
Very Easy
1. To learn how to use the device
1
2
3
4
5
2. To follow the instructions when using the 
device
1
2
3
4
5
3. Overall, how difficult or easy was the device 
to use?
1
2
3
4
5
Instructions:  The following question asks you to think about your confidence in continuing to use the device you used in this study.  
Please think about the following question as if you were prescribed this medicine and this device would be available to you after the 
study.


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Definitely 
Unwilling
Mostly 
Unwilling
Not Sure
Mostly Willing
Definitely 
Willing
1. Please check the number that best indicates 
how willing you are to continue using the 
device.
1
2
3
4
5


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Appendix 20.
Four Items From MDDAB – Trulicity Device
Four Items from MDDAB – Trulicity Device
Instructions:  Based on your experience with the medication delivery device used in this study, please indicate how easy or difficult 
it was to use the device. For each question, please check the number that best represents your experience with using the device.
How difficult or easy was it to do the following?
Very Difficult
Difficult
Neither Difficult
nor Easy
Easy
Very Easy
1. To learn how to use the device
1
2
3
4
5
2. To follow the instructions when using the 
device
1
2
3
4
5
3. Overall, how difficult or easy was the device 
to use?
1
2
3
4
5
Instructions:  The following question asks you to think about your confidence in continuing to use the device you used in this study.  
Please think about the following question as if you were prescribed this medicine and this device would be available to you after the 
study.


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Definitely 
Unwilling
Mostly 
Unwilling
Not Sure
Mostly Willing
Definitely 
Willing
1. Please check the number that best indicates 
how willing you are to continue using the 
device.
1
2
3
4
5


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Appendix 21.
Supplemental Questions S2 and S3
Supplemental Questions S2 and S3
S2. How willing would you be to use the Ozempic injection device?      
  Not willing 
  Somewhat not willing
  Neutral 
  Somewhat willing 
  Very willing
S3.  How willing would you be to use the Trulicity injection device?      
  Not willing 
  Somewhat not willing
  Neutral 
  Somewhat willing 
  Very willing


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Appendix 22.
Clinical Information Form
Clinical Information Form – Site Completed
Instructions:  Please complete the following questions for eligible patients.
1. When was the patient diagnosed with T2DM?  
If the day and month are unknown, please report the year of diagnosis, and check the box “Day and Month of T2DM diagnosis 
unknown”.
If day is unknown, please report month and year of diagnosis, and check the box “Day of T2DM diagnosis unknown”.
   
  
                              
                            D
D
      M      M      M
  Y     Y      Y      Y
Day and Month of T2DM diagnosis unknown
Day of T2DM diagnosis unknown
2. What type 2 diabetes oral medication(s) is the patient currently taking?  Please check all that apply.
Oral Class
Oral Medication Options
(select all that apply)
Estimated Start Date of 
Oral T2DM Medication
(MMM/YYYY)
Sulfonylureas
  chlorpropamide
  glibenclamide or glyburide
  glibornuride


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Oral Class
Oral Medication Options
(select all that apply)
Estimated Start Date of 
Oral T2DM Medication
(MMM/YYYY)
  gliclazide
  glimepiride
  glipizide
  gliquidone
  glisoxepide
  glyburide micronized 
  glyclopyramide
  glycyclamide or tolhexamide
  metahexamide
  tolazamide
  other
Meglitinides
  metformin
  nateglinide
  repaglinide
  other
DPP-4 Inhibitors
  alogliptin benzoate
  linagliptin
  saxagliptin
  sitagliptin
  vildagliptin                 


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Oral Class
Oral Medication Options
(select all that apply)
Estimated Start Date of 
Oral T2DM Medication
(MMM/YYYY)
  other
SGLT2 Inhibitors
  canagliflozin             
  dapagliflozin                  
  empagliflozin             
  other
Thiazolidinediones
(TZDs or Glitazones)
  pioglitazone
  rosiglitazone               
  other
Alpha-glucosidase 
inhibitors
  acarbose
  miglitol                         
  other
Combination Pills
  alogliptin benzoate/metformin 
hydrochloride
  canagliflozin/metformin 
hydrochloride
  dapagliflozin/metformin
  dapagliflozin propanediol/metformin 
hydrochloride
  empagliflozin/linagliptin                


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Oral Class
Oral Medication Options
(select all that apply)
Estimated Start Date of 
Oral T2DM Medication
(MMM/YYYY)
  glimepiride/pioglitazone
  glimepiride/rosiglitazone maleate
  metformin/empagliflozin
  metformin/glipizide
  metformin/glyburide
  metformin/linagliptin
  metformin/pioglitazone
  metformin/repaglinide
  metformin/rosiglitazone maleate
  metformin/saxagliptin
  metformin/sitagliptin
  metformin/vildagliptin
  simvastatin/sitagliptin phosphate
  other
3. Does the patient currently have any of the following comorbidities?  Please check all that apply.
  Congestive heart failure


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  Dementia 
  Chronic Pulmonary Disease
  Rheumatologic Disease
  Mild Liver Disease
  Diabetes with chronic complications
  Hemiplegia or paraplegia 
  Renal disease
  Any malignancy, including leukemia and lymphoma
  Moderate or severe liver disease
  Metastatic solid tumor
  AIDS/HIV
  None
4. Please record the patient’s most recent HbA1c value and the date this value was measured.
Date of HbA1c
measurement
HbA1c value
DD/MMM/YYYY
___%


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Appendix 23.
Protocol Amendment H9X-MC-B021(b) Summary Crossover Study 
Comparing the Dulaglutide (Trulicity) Pen and the Semaglutide (Ozempic) Pen
Overview
Protocol H9X-MC-B021(a) [Crossover Study Comparing the Dulaglutide (Trulicity) Pen and the Semaglutide (Ozempic) Pen] has 
been amended.  The new protocol is indicated by amendment (b) and will be used to conduct the study in place of any preceding 
version of the protocol.
Based on the results from pilot portion of the study, some scheduling, training, and administrative protocol elements have changed to 
reflect learnings from the pilot study.  
Changes to the protocol were made for the following reasons:

Sponsor decision to streamline study based on participant feedback
Minor editorial changes have also been made throughout the document.
The overall changes and rationale for the changes made to this protocol are described in the following table:
Amendment Summary for Protocol H9X-MC-B021 Amendment (b)
Section # and Name
Description of Change
Brief Rationale
Section 2, Synopsis Table 2.1
A break will be ‘offered’ to participants
Participants in the pilot study did not require a 
restroom or water break between device trainings. 
The break will be offered to participants, but it will 
be optional.
Section 2, Synopsis Table 2.1
Optional second interview break removed for main 
study
Participants in the pilot study did not need a break 
between device trainings and questionnaires. This 
second break will not be included in the main 
study, but participants will be permitted to take a 
break if they request it.


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Section 3.5 Methods to Minimize Risks
Guidance was added on instructing participants to
use a study-provided sharps container rather than 
attempt to recap the semaglutide needle. 
A potential for needle stick was identified in the 
pilot study, as participants may have considered
recapping the needle. 
Section 5.5.4 Overview of study visit procedures 
for the main study
Video was removed
The video was removed from the main study 
procedures based on the results of the pilot 
study. The video was not necessary in addition to 
the interviewer demonstration.
Section 5.5.4 Overview of study visit procedures 
for the main study
Optional second interview break removed for main 
study
Participants in the pilot study did not need a break 
between device trainings and questionnaires. This 
second break will not be included in the main 
study, but participants will be permitted to take a 
break if they request it.
Section 5.5.4 Overview of study visit procedures 
for the main study
IFUs are provided to participants to read, and the 
interviewer will demonstrate how to use the 
device.
The participant should have the IFU available to 
read and review during the training, so additional 
text was added to help assure clarity on this point.
Section 5.5.4 Overview of study visit procedures 
for the main study
Maximum time for all study procedures was 
added.
90 minutes, as specified in the consent form
Section 9.1.2.6 Global Preference Item
The open ended response to explain reasons for 
device preference was changed from patient 
completed to interviewer completed. 
The results of the pilot study indicate that many 
patients are not able to write a clear response to 
this question. Participants are better able to 
articulate reasons for preference when speaking 
with the interviewer. Therefore, in the main study, 
the interviewer will ask the participant for the 
reasons for their device preference and record the 
reasons for the participant using quotations marks 
to capture the respondent’s exact words.
10.2 Populations for analysis
Video removed
Based on results of the pilot study, the video will 
not be used in the main study.
Appendix 12 Interview and Device Training 
Guides
Interview guides were updated to incorporate 
revisions made during the pilot study.
The interview guides were revised during the pilot 
study to streamline language, present training 
information clearly, and address issues identified 
during the pilot study.


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Appendix 13 Time-to-Train Observer Recording 
Sheet
Training time points were revised and clarified, a 
field was added to capture the number of 
interventions.
The timing points for time to train were changed to 
capture time elapsed between start of training 
rather than time of day to increase accuracy by 
observer, time points were clarified for 
consistency, and number of interventions field was 
added based on pilot study observation that 
interviewers needed to intervene during mock 
injections.
Appendix 14 Demographic form
Subscripts removed
The subscripts are not necessary for data entry 
using the Evidera Datafax system. These 
subscripts were removed to simplify the form for 
participant completion.
Appendix 15 Interviewer Recording Sheet
Field added to capture interviewer assistance with 
Ozempic needle removal
Some participants are unable to remove the needle 
from the Ozempic device safely. In these cases, 
interviewers will offer to assist with needle 
removal to lower the risk of AEs.
Appendix 17 Global Preference Item
Item 2 changed from participant completed to 
interviewer completed.
The results of the pilot study indicate that many 
patients are not able to write a clear response to 
this question. Participants are better able to 
articulate reasons for preference when speaking 
with the interviewer. Therefore, in the main study, 
the interviewer will ask the participant for the 
reasons for their device preference and record the 
reasons for the participant using quotations marks 
to capture the respondent’s exact words.
Appendix 22 Clinical Information Form
Date reporting format changed to 
DDMMMYYYY
Change for consistency with other date reporting 
fields in the study and to remove an ambiguity in 
day and month reporting.
Appendix 22 Clinical Information Form
None added to item 3
None was added to permit a responses if a 
participant does not have any of the listed 
conditions.


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Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
The numbering system used for inclusion and exclusion criteria provides a unique number for 
each criterion and allows for efficiency in data collection.
In case an amendment to the protocol adds a criterion, that criterion will receive the next 
available number, regardless of whether it is an inclusion or exclusion criterion.
2.  Schedule of Activities
Table 2.1.
Schedule of Activities
Procedure
Pilot Phase:  Conducted 
at 1 US Location1
Approximately n ≈ 10 to 
20
Main Phase:  Conducted 
at Approximately 14
Clinical Sites across US2
Approximately n ≈ 290
Screening
Study Visit
Screening
Study Visit
INTERVIEW BREAK 1:  Participant will be given
offered a restroom and water break
X
X
OPTIONAL INTERVIEW BREAK 2
X
X
3.5.  Methods to Minimize Risks
Training on both study devices will be provided by Evidera study staff based on the approved 
IFUs (Eli Lilly IFU 2017; Novo Nordisk IFU 2017).  Training for correct sharps 
handling/disposal is part of the study training, and no cross contamination is expected due to 
each participant receiving their own device, as well as injecting drug into a practice pad instead 
of themselves.  In order to minimize risk of accidental needle sticks, participants will not recap 
the semaglutide needle.  A sharps container will be available to permit participants to remove the 
semaglutide needle and dispose of it immediately, rather than recapping the needle for later 
disposal.  Participants will be instructed to place the outer needle cap in the sharps container 
once it is removed from the device so they do not have the temptation to recap, which was found 
to be a potential opportunity for accidental needle sticks during the pilot study.  Study staff will 
monitor the participant at all times in the room and intervene should a dangerous situation occur.  
Participants will be under direct supervision of the study interviewer when handling the devices.
5.5.4.  Overview of Study Visit Procedures for the Main Phase


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Trained study interviewers will follow the study Interview and Device Training Guide 
(Appendix 12) to standardize the presentation of devices to participants and ensure that the 
training is clear and not biased in favor of either device.  Based on findings from the pilot phase, 
the finalized main phase training approach will be conducted with the patients for each device 
including a detailed demonstration by the interviewer.(for example, will include a combination 
of the following:  detailed demonstration by the interviewer, presentation of video 
demonstrations on tablets or laptops, and/or independent reading of the IFU).  The same 
standardized interview approach will be used for all of the main phase patients.  For each device, 
patients will be given the IFU and asked to read it.  Then the interviewer will demonstrate how to 
use the device.  Participants will perform mock injections on a practice pad after being trained in 
the use of each device.  Patients will have access to the IFU during the entire training and 
injection process.  If the participant does not complete one of the critical steps or if the steps are 
completed out of order, the Interview and Device Training Guide (Appendix 12) provides 
interviewers instructions for handling these situations.
5.5.4  Overview of Study Visit Procedures for the Main Phase
Once participants have attempted each device training and mock injection(s) on the practice pad, 
interviewers will complete the Interviewer Recording Sheet to document randomization order 
and if the patient was able to complete both device trainings (Appendix 15).  Next, participants 
will be offered an optional second break.  Participants will then be asked to complete 
questionnaires to report their preferences between the 2 devices.
5.5.4  Overview of Study Visit Procedures for the Main Phase
Main phase interview will last approximately 60 to 90 minutes including consenting and training 
in device procedures.  The maximum time for all study procedures is 90 minutes as specified in 
the consent form.  All main phase participants will be remunerated a specified amount between 
$100 and $150 (via Greenphire ClinCard) for their time and travel time to the study interview.
9.1.2.6.  Global Preference Item
All participants will complete the Global Preference Item after being trained and using both 
devices (Appendix 17).  Participants will be asked, “Overall, which device do you prefer?”  
Interviewers will then ask Pparticipants will also be asked to explain why they selected their 
response for Ozempic, Trulicity, or no preference.  The interviewer will transcribe the 
participant’s response using quotesation marks to capture the respondent’s exact words.  This 
item The Global Preference Item was developed specifically for use in this device preference 
multicenter crossover study.  To help participants remember the devices more accurately, colored 
images of the devices have been inserted into the questionnaire.
10.2.  Populations for Analyses
For purposes of analysis, the following populations are defined:


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Population
Description
Randomized
Participants determined to be eligible and then assigned to one of 2 device 
order groups (50% will be randomized to use the dulaglutide device first, 
while the other half will use the semaglutide device first).  More details about 
randomization for this study are provided in Section 7.2.
Evaluable
Participants for whom device preference can be evaluated: Randomized 
participants who are exposed to both devices (i.e., participant was shown both 
devices via either video or demonstration, regardless of whether they 
successfully complete the training) and complete the Global Preference Item.
Withdrawn 
Participants who withdraw from the study before being exposed to both 
devices and completing the Global Preference item.  Details on study 
withdrawal are provided in Section 8.
Appendix 12.  Interview and Device Training Guide
EVA-23274 Interview and Device Training Guide
(Will be modified based on findings from the Pilot Phase)
Updated 12Jul2018
I. NECESSARY MATERIALS
11. IFU for Trulicity
12. IFU for Ozempic
13. Trulicity Injection Pen 
14. Trulicity Demonstration Pen
15. Ozempic Injection Pen (the real Ozempic Pen will also be used for demonstrations)
16. Extra needles for Ozempic
17. Sharps container (for disposal of Trulicity Devices and Ozempic Needles)
18. Injection pad
19. Alcohol wipes
20. Trash can (for pen cap)
21. Non-latex gloves
II. INTERVIEW STEPS
11. Confirm that site has completed In/Ex form
12. Administer informed consent 
13. Complete Supplemental Question S1 
14. Randomization with IWRS system to determine which device is first
15. Explain study to the participant
16. Training and mock injection with the first device
17. Complete demographic form
18. Training and mock injection with the second device.


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19. Complete Interviewer Recording Sheet
20. Complete questionnaires about device preferences and Supplemental Questions S2 and 
S3
III. Trulicity Pen
For time-to-train participants, the observer should begin the timer when the training introduction 
is started.  The observer should also complete the TTT Observer Recording Sheet.
A. Device Training
1. Explain the overall training steps and introduce the device to the participant.
2. Open the device box and place the IFU in front of the participant.  Explain that the video 
will follow along with the instructions for use and demonstrate how the device is used.
3. Show the participant the Trulicity training video, which is based on the IFU.
4. If the participant needs additional training, demonstrate the injection process using the 
demo device.  Have the participant follow along with the steps on the IFU.
5. Permit the participant to ask any questions they may have about the device or IFU.
6. Participant performs mock injection into the injection pad while trainer observes and 
evaluates injection success based on the critical steps listed below.
7. The training will be considered complete when the patient has successfully performed all 
critical steps listed below and indicated to the trainer that they are finished (for example, by 
placing the device on the table).  For the time-to-train patients, timing will end after 
successful injection completion at the time patients indicate they are finished.
8. If the participant does not dispose of the device in the sharps container independently, the 
trainer should instruct the participant on device disposal using the provided sharps 
container.
B. Checklist of Critical Steps
Critical Steps
First 
attempt
Second 
attempt
Third 
attempt
Fourth 
attempt
Fifth 
attempt
1. Take off base cap
□
□
□
□
□
2. Place on injection site
□
□
□
□
□
3. Unlock device
□
□
□
□
□
4. Press button and hold the 
device in place until the grey 
plunger is visible.  The 
participant should pause.
□
□
□
□
□
5. Remove from injection site
□
□
□
□
□


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C. Retraining
If the first injection attempt is not successful, the participant should be retrained on the critical 
steps that they missed or performed incorrectly.  The participant will have to repeat all or some 
of the injection process.  If the participant appears to be making an error that could lead to 
self-harm or prevent successful injection (e.g., trying to inject with the cap on), the trainer should 
intervene and stop the injection process.  The error should be explained to the participant and the 
participant should be asked to restart the injection process.
IV. Ozempic Pen
For time-to-train participants, the observer should begin the timer when the training introduction 
is started.  The observer should also complete the TTT Observer Recording Sheet.
A. Device Training
1. Explain the overall training steps and introduce the device to the participant.
2. Open the device box and place the IFU in front of the participant.  Explain that the video 
will follow along with the instructions for use and demonstrate how the device is used. 
3. Show the participant the Ozempic training video, which is based on the IFU.
4. If the participant needs additional training, demonstrate the injection process using the 
demo device.  Have the participant follow along with the steps on the IFU. 
5. Permit the participant to ask any questions they may have about the device or IFU.
6. Participant performs mock injection into the injection pad while trainer observes and 
evaluates injection success based on the critical steps listed below.
7. The training will be considered complete when the patient has successfully performed all 
critical steps listed below and indicated to the trainer that they are finished (for example, by 
placing the device on the table).  For the time-to-train patients, timing will end after 
successful injection completion at the time patients indicate they are finished.
8. If the participant does not dispose of the device in the sharps container independently, the 
trainer should instruct the participant on device disposal using the provided sharps 
container.
B. Checklist of Critical Steps
Critical Steps
First 
attempt
Second 
attempt
Third 
attempt
Fourth 
attempt
Fifth 
attempt
1. Pull off the pen cap
□
□
□
□
□
2. Push the needle straight on to 
the pen.  Turn until it is on tight.  
□
□
□
□
□


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3. Pull off the outer needle cap and 
pull off the inner needle cap
□
□
□
□
□
4. Turn the dose selector until the 
dose counter shows the flow check 
symbol
□
□
□
□
□
5. Press and hold the dose button 
until the dose counter shows 0 and 
a drop of Ozempic appears at the 
needle tip
□
□
□
□
□
6. If the drop does not appear on 
the first attempt, repeat flow check 
until a drop appears (as needed).
□
□
□
□
□
7. Select your dose.  Continue 
turning the dose selector until the 
dose counter shows 0.25
□
□
□
□
□
8. Insert the needle in the pad
□
□
□
□
□
9. Press and hold down the dose 
button until the dose counter 
shows 0
□
□
□
□
□
10. Slowly count to 6 
(operationally:  patient pauses 
after pressing injection button). 
□
□
□
□
□
11. Remove the needle from the 
pad
□
□
□
□
□
12. Remove the needle (capped or 
uncapped)
□
□
□
□
□
C. Retraining
If the first injection attempt is not successful, the participant should be retrained on the critical 
steps that they missed or performed incorrectly.  The participant will have to repeat all or some 
of the injection process.  If the participant appears to be making an error that could lead to self-
harm or prevent successful injection (e.g., trying to inject with the cap on), the trainer should 
intervene and stop the injection process.  The error should be explained to the participant and the 
participant should be asked to restart the injection process.
Interview Guide
I. MATERIALS
1. IFU for Trulicity
2. IFU for Ozempic
3. Trulicity Injection Pen 


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4. Trulicity Demonstration Pen
5. Two Ozempic Injection Pens (one for demonstration and one for participant use)
6. Sharps container (for disposal of Trulicity Devices and Ozempic Needles)
7. Injection pad
8. Alcohol wipes
9. Trash can (for pen cap)
10. Non-latex gloves
II. INTERVIEW STEPS
1. Confirm the in/ex form has been completed
2. Informed consent 
3. Complete Supplemental Question S1
4. Randomization with IWRS system to determine which device is first
5. Explain study to the participant
6. First Device: Training and Mock Injection
7. Complete demographic form
8. Second Device: Training and Mock Injection
9. Complete Interviewer Recording Sheet
10. Complete questionnaires about device preferences and Supplemental Questions S2 and 
S3
STEP 1. CONFIRM IN/EX FORM HAS BEEN COMPLETED

Review the site-completed in/ex form for the participant to confirm eligibility.  

This form should be provided to you by the site, and it should already be completed prior 
to the interview. 
STEP 2. INFORMED CONSENT

Review the consent form with the participant and confirm comprehension.  

Provide the participant with opportunity to answer questions before signing.

Ask the participant to sign two copies of the consent form if they wish to participate.  

Countersign the forms and provide a copy to the participant. 
STEP 3. COMPLETE SUPPLEMENTAL QUESTION S1

Ask the participant to independently complete this question: “Please complete this 
question, and let me know when you are finished.” 


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STEP 4. RANDOMIZATION WITH IWRS SYSTEM

Complete the randomization process to determine the order of device training for the 
participant. 

Record the order on the Interviewer Recording Sheet. 
STEP 5. EXPLAIN THE STUDY TO THE PARTICIPANT

“You will be trained to use two devices for injecting medication for type 2 diabetes.” 

“For each device, I will walk you through the steps for using each device and 
demonstrate the steps for you.  Then, you will use the device to administer an injection 
into an injection pad.” 

“After you have had a chance to use both devices, I will ask you to complete some 
questionnaires that ask about your preference between the devices.” 

“Do not inject medication into yourself.  You will only be injecting into the injection 
pad.”  

“Please handle the devices carefully to avoid accidently sticking yourself with the needle.  
If you appear to be handling the device incorrectly, I will try to correct you so you do not 
accidently stick yourself with the needle.” 
STEP 6. FIRST DEVICE TRAINING
Follow the Trulicity Training Guide or the Ozempic Training Guide based on the randomization 
order for the participant. 
STEP 7. DEMOGRAPHIC FORM
“Please complete this form.”
STEP 8. SECOND DEVICE TRAINING
Follow the Trulicity Training Guide or the Ozempic Training Guide based on the randomization 
order for the participant. 
STEP 9. COMPLETE INTERVIEWER RECORDING SHEET
The interviewer completes the interviewer recording sheet to document order of device training 
and completion status. 


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STEP 10. PARTICIPANT COMPLETED-QUESTIONNAIRES
Instruct the participant to complete questionnaires on device preference and supplemental 
questions S2 and S3.
Ozempic Training Guide
A. Time to Train
The observer should complete the TTT Observer Recording Sheet.
a.
Start of training (i.e., after reading the IFU)
b. The participant picks up the device to start the mock injection. 
c.
The participant successfully injects the medication into the injection pad and removes the 
needle/device from the pad. 
d. The Ozempic pen is recapped with the pen cap (the inner needle cap and outer needle cap 
should not be placed back on the pen). 
e.
The participant has completed the injection and finished asking questions.  Participants 
comments/opinions about the device after completing the injection will not be included 
unless the participant asks a question. 
B. Safety Procedures
If the participant appears to be making an error that could lead to self-harm, the trainer should 
immediately intervene and stop the injection process.
C. Introduction
Introduce the device and training steps.

“Now, you will learn to use an injection device.”

“When you feel comfortable with the procedures for using the device, you will use the 
device to perform a mock injection into the injection pad.”

“You should NOT use this device to inject yourself.  You will only be injecting 
medication into this pad.”

“This is the Ozempic device.  This device is used to administer medication once a week, 
and you would typically use it at home.” (Show the device to the participant.)  
D. Device Training
1. Open the device box and place the IFU in front of the participant. 


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2. Instruct the participant to “Please read the Instructions for Use and let me know when you are 
finished.  After you are done reading, I will demonstrate all of these steps for you in detail.  
You can also refer back to this document throughout the interview as much as you want.”
3. Demonstrate the injection process using the demo device. 
1. “The Ozempic device is a prefilled dial-a-dose pen.  You can select doses of 0.25 mg 
or 0.5 mg.  You will be selecting 0.25 mg for the injection today.”
2. “The needles for this device are enclosed in the package.” 
3. “Always use a new needle for each injection.”
4. Device parts
a.
“This is the pen cap.”
b. “This is the pen window.” 
c.
“This is the dose counter and dose pointer.” 
d. “This is the dose selector and the dose button.”
e.
“When you turn the dose selector, you will see the flow check symbol and the dashed 
line to guide to your dose (turn dose selector to show these symbols).  The flow check 
symbol comes right after the zero.”
f.
“The needle has an outer needle cap, inner needle cap, needle, and paper tab.”
5. Step 1: Prepare your pen with a new needle
a.
“If you were injecting, you would begin by washing your hands with soap and water. 
Since you are injecting a pad today, you do not need to wash your hands this time.”
b. “The next step is to check the name and colored label of your pen to make sure that 
it contains Ozempic.”
c.
“Then pull off the cap.”
d. “Check that the Ozempic in your pen is clear and colorless. Look through the pen 
window.  If the Ozempic is cloudy, do not use the pen.”
e.
“Take a new needle, and tear off the paper tab.”


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f.
“Push the needle straight on to the pen.  Turn until it is on tight.”
g. “Pull off the outer needle cap.  You can put it in the sharps container.”
h. “Pull off the inner needle cap, and throw it away.”
6. Step 2: Check the Ozempic flow with each new pen
a.
“Check the Ozempic flow before your first injection with each new pen.”
b. “Turn the dose selector until the dose counter shows the flow check symbol.”
c.
“Hold the pen with the needle pointing up.  Press and hold in the dose button until 
the dose counter shows 0.  The 0 must be lined up with the dose pointer.  A drop of 
Ozempic will appear at the needle tip.  The medication may spray out a bit in some 
cases, so please point the tip away from your face and away from me.”
d. “If no drop appears, repeat these flow check steps up to six more times.  Do not use 
the pen if a drop of Ozempic still does not appear.”
7. Step 3: Select your dose
a.
“Turn the dose selector until the dose counter shows your dose (0.25 mg).  If you 
select the wrong dose, you can turn the dose selector forward or backwards to the 
correct dose.”
8. Step 4. Inject your dose
a.
“Choose your injection site.”
b. “Insert the needle into your skin [injection pad].”
c.
“Make sure you can see the dose counter.  Do not cover it with your fingers.  This 
could stop the injection.”
d. “Press and hold down the dose button until the dose counter shows 0.  The 0 must 
line up with the dose pointer.  You may then hear or feel a click.”
e.
“Keep the needle in your skin [injection pad] after the dose counter has returned to 
0 and count slowly to 6.”
f.
“If the needle is removed earlier, you may see a stream of Ozempic coming from the 
needle tip.  If this happens, the full dose will not be delivered.”
g. “Remove the needle from your skin [injection pad].”


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9. Step 5. After your injection
a.
“Carefully twist the needle off of the pen.   Since we have a sharps container, 
please do not put the needle caps back on the needle to avoid needle sticks.”
b. “Place the needle in a sharps container right away.”
c.
“Put the pen cap on your pen after each use to protect Ozempic from light.”
4. Permit the participant to ask any questions they may have about the device or IFU.

“Do you have any questions about the steps involved in the injection process?”

“Do you feel ready to administer the mock injection? Is there anything you would like to 
review before trying it?”

When the patient is ready: “I will leave the instructions for use here, and you can refer to 
them as much as you like while you go through the injection process.  Please take all the 
time you need.”
5. Participant performs mock injection into the injection pad while trainer observes and 
evaluates injection success based on the critical steps listed below.
6. The mock injection will be considered complete when the patient has successfully performed 
all critical steps listed below and recapped the pen.  
7. If the participant is struggling to remove the needle and appears to be putting themselves at 
risk of an accidental needle stick, the interviewer should volunteer to remove the needle for 
them. 

“Would you like me to remove the needle for you?”
If the interviewer removes the needle, this should be recorded on the Interviewer Recording 
Sheet. 
8. If the participant does not dispose of the needle in the sharps container independently, the 
trainer should instruct the participant on disposal using the provided sharps container.

“Please place the needle in the sharps container.”
9. Ask the participant if they have any questions, and answer them.  The training is complete 
when there are no further questions. 

“Do you have any questions?”


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E. Checklist to assist interviewer in tracking critical steps
Critical Steps
First 
attempt
Second 
attempt
Third 
attempt
Fourth 
attempt
Fifth 
attempt
1. Pull off the pen cap
□
□
□
□
□
2. Push the needle straight on to 
the pen.  Turn until it is on 
tight.  
□
□
□
□
□
3. Pull off the outer needle cap 
and pull off the inner needle 
cap
□
□
□
□
□
4. Turn the dose selector until the 
dose counter shows the flow 
check symbol
□
□
□
□
□
5.
Press and hold the dose button 
until the dose counter shows 0 
and a drop of Ozempic appears 
at the needle tip
□
□
□
□
□
6. 6. If the drop does not appear 
on the first attempt, repeat flow 
check until a drop appears (up 
to 6 times).
□
□
□
□
□
7. Select your dose. Continue 
turning the dose selector until 
the dose counter shows 0.25
□
□
□
□
□
8. Insert the needle in the pad
□
□
□
□
□
9. Press and hold down the dose 
button until the dose counter 
shows 0
□
□
□
□
□
10. Slowly count to 6 
(operationally: patient pauses 
after pressing injection button). 
□
□
□
□
□
11. 11. Remove the needle from the 
pad
□
□
□
□
□
12. Remove the needle from the 
pen (capped or uncapped)
□
□
□
□
□


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F. Retraining
If the critical steps are not performed correctly on the first attempt, the participant should be 
retrained on critical steps that were missed or performed incorrectly.  The participant may have 
to repeat all or some of the injection process.  The error should be explained to the participant 
and the participant should be asked to make the correction and continue the injection process. 
If the participant is making a mistake during the injection, you can call his or her attention to the 
mistake so that he or she can continue the injection correctly.  For example, if the participant is 
trying to do the flow check without removing the inner cap, tell him or her to remove the cap 
first. “It looks like the inner cap is still on.  Could you remove the inner cap before checking the 
flow?”


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Trulicity Training Guide
A. Time to Train
The observer should complete the TTT Observer Recording Sheet.
a. Start of training (i.e., after reading the IFU)
b. The participant picks up the device to start the mock injection. 
c. The participant successfully injects the medication into the injection pad and removes the 
needle/device from the pad. 
d. The Trulicity pen is dropped into the sharps container.
e. The participant has completed the injection and finished asking questions.  Participants 
comments/opinions about the device after completing the injection will not be included unless 
the participant asks a question. 
B. Safety Procedures
If the participant appears to be making an error that could lead to self-harm, the trainer should 
immediately intervene and stop the injection process.
C. Introduction
Introduce the device and training steps.

“Now, you will learn to use an injection device.”  

“When you feel comfortable with the procedures for using the device, you will use the 
device to perform a mock injection into the injection pad.” 

“You should NOT use this device to inject yourself.  You will only be injecting 
medication into this pad.”

“This is the Trulicity device.  This device is used to administer medication once a week, 
and you would typically use it at home.” (Show the device to the participant.)  
D. Device Training
1. Open the device box and place the IFU in front of the participant.
2. Instruct the participant to “Please read the Instructions for Use and let me know when you are 
finished.  After you are done reading, I will demonstrate all of these steps for you in detail.  
You can also refer back to this document throughout the interview as much as you want.”
3. Demonstrate the injection process using the demo device. 
1. Before you get started
a.
“Check the pen label to make sure you have the right medicine and it has not 
expired.”


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b. “Inspect the pen to make sure it is not damaged”
c.
“Inspect the medicine to make sure it is not cloudy or discolored, and it should not 
have particles in it.”
d. “If you were injecting yourself, you would then wash your hands.  Since you are 
injecting a pad today, you do not need to wash your hands this time.”
e.
“If you were injecting yourself, you would select an injection site.  Today, you will 
inject into this injection pad and NOT into your body.” 
2. Device parts
a.
“At the top of the device, there is a green injection button.”
b. “Beneath that is a lock ring, and an indicator which lines up with the lock and unlock 
symbols.”
c.
“Down here you can see the medicine.”
d. “At the bottom, you can see the clear base and the base cap.”
e.
“The needle is inside the device.”
3. Steps for injection
a.
Uncapping the pen. 
i)
“You would first make sure the pen is locked” 
ii) “Then pull the base cap straight off and throw it away in the trash”. 
iii) “Do not put the base cap back on – this could damage the needle.”
b. Second, place the base on the injection site and unlock the device
i)
“You would place the clear base flat and firmly against your skin (or in this case, 
the injection pad).” 
ii) “Unlock by turning the lock ring”.
c.
Third, administer the injection


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i)
“You would press and hold the green injection button.  You will hear a loud 
click.” 
ii) “When you press the button, the medication is injected.”
iii) “Continue to hold the clear base firmly against the pad until you hear a second 
click.  This happens when the needle starts retracting in about 5 – 10 seconds.  My 
demo device may be slower than the actual device you use, so listen closely for 
the click on your device.” 
iv) “Then remove the pen from your skin [injection pad].”
v) “You will know the injection is complete when the gray plunger is visible.” 
d. The final step is disposing of the pen. 
i)
“Put your used pen in the sharps disposal container right away after use”.
4. Permit the participant to ask any questions they may have about the device or IFU.

“Do you have any questions about the steps involved in the injection process?”

“Do you feel ready to administer the mock injection? Is there anything you would like to 
review before trying it?”

When the patient is ready: “I will leave the instructions for use here, and you can refer to 
them as much as you like while you go through the injection process.  Please take all the 
time you need.”
5. Participant performs mock injection into the injection pad while trainer observes and 
evaluates injection success based on the critical steps listed below.
6. The mock injection will be considered complete when the patient has successfully performed 
all critical steps listed below and placed the device in the sharps container.  
7. If the participant does not dispose of the device in the sharps container independently, the 
trainer should instruct the participant on device disposal using the provided sharps container. 

“Please place the pen in the sharps container.”
8. Ask the participant if they have any questions, and answer them.  The training is complete 
when there are no further questions.

“Do you have any questions?”


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E. Checklist to assist interviewer in tracking critical steps
Critical Steps
First 
attempt
Second 
attempt
Third 
attempt
Fourth 
attempt
Fifth 
attempt
1. Take off base cap
□
□
□
□
□
2. Place on injection site
□
□
□
□
□
3. Unlock device
□
□
□
□
□
4. Press button and hold the 
device in place until the grey 
plunger is visible. The 
participant should pause. 
□
□
□
□
□
5. Remove from injection site
□
□
□
□
□
F. Retraining (if necessary)
If the critical steps are not performed correctly on the first attempt, the participant should be 
retrained on critical steps that were missed or performed incorrectly.  The participant may have 
to repeat all or some of the injection process.  The error should be explained to the participant 
and the participant should be asked to make the correction and continue the injection process. 
If the participant is making a mistake during the injection, you can call their attention to the 
mistake so that he or she can continue the injection correctly.  For example, if the participant is 
trying to press the injection button without unlocking the device, tell the participant to unlock it.  
“It looks like the device is still locked.  Can you unlock it before injecting?”
Appendix 13.  Time-to-Train (TTT) Observer Recording Sheet
TTT Observer Recording Sheet
(Will be modified based on findings from the Pilot Phase)
To be completed by the TTT observer:
1. Ozempic    Ozempic Device        Trulicity Device
1a. Start time of training introduction (i.e., after reading the IFU): 0:00
1b. Start time of participant performing mock injection(s):  ______:______ 
1c. End time of successfully administered mock injection (i.e., withdrawal of needle/device from 
injection pad):  ______:______
1d. End time of mock injection procedures (Ozempic = recapping the pen): ______:______


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1e. End time of training, including all procedures and questions:  ______:______
Number of interventions: _______
Key Steps of Training For Device Used First
Check If 
Not 
Applicable
1a. Start time of training introduction:  ______:______:______ am/pm
1b. Finished time of training introduction:  ______:______:______ am/pm

1c. Start time of training video:  ______:______:______ am/pm
1d. Finished time of training video:  ______:______:______ am/pm

1e. Start time of training and questions after video:  ______:______:______ am/pm
1f. End time of training and questions after training:  ______:______:______ am/pm

1g. Start time of participant performing mock injection(s):  ______:______:______ 
am/pm
1h. End time of participant performing mock injection(s):  ______:______:______ 
am/pm

1i. Start time of answering remaining questions: ______:______:______ am/pm
1j. End time of answering remaining questions: ______:______:______ am/pm

2. Trulicity    Ozempic Device        Trulicity Device
2a. Start time of training introduction (i.e., after reading the IFU): 0:00
2b. Start time of participant performing mock injection(s):  ______:______ 
2c. End time of successfully administered mock injection (i.e., withdrawal of needle/device from 
injection pad):  ______:______
2d. End time of mock injection procedures (Trulicity = disposing of the pen in the sharps 
container): ______:______
2e. End time of training, including all procedures and questions:  ______:______
Number of interventions: _______
Key Steps of Training For Device Used Second
Check If 
Not 
Applicable


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2a. Start time of training introduction:  ______:______:______ am/pm
2b. Finished time of training introduction:  ______:______:______ am/pm

2c. Start time of training video:  ______:______:______ am/pm
2d. Finished time of training video:  ______:______:______ am/pm

2e. Start time of training and questions after video:  ______:______:______ am/pm
2f. End time of training and questions after training:  ______:______:______ am/pm

2g. Start time of participant performing mock injection(s):  ______:______:______ 
am/pm
2h. End time of participant performing mock injection(s):  ______:______:______ 
am/pm

2i. Start time of answering remaining questions: ______:______:______ am/pm
2j. End time of answering remaining questions: ______:______:______ am/pm

Appendix 14.  Demographic Form
Demographic Form – Participant Completed
1.  What is your age?
2.  What is your gender?
1  Male   
2  Female
3a.  What is your ethnic background?
1  Hispanic or Latino
2  Not Hispanic or Latino
3  Not applicable
3b.  What is your racial background? (Please check all that apply)
1  American Indian or Alaska Native
2  Asian
3  Black or African American
4  Native Hawaiian or Other Pacific Islander
5  White
6  Other:  
4.  What is your marital status?
1  Single
2  Married
3  Divorced
4  Separated


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5  Widowed
6  Other:  _____________
5.  How would you describe your employment status? (Please tick all boxes that apply)
  Full-time work
  Part-time work
  Homemaker/housewife
  Student
  Unemployed
  Stay-at-home parent
  Retired
  Disabled
  Other:  ______________________
7. What is the highest level of education you have completed? (Please check only one)
1  Elementary/primary school
2  Secondary/high school
3  Some college
4  College degree
5  Postgraduate degree
6  Other:  ______________________________________
7.  Have you had any of the following health conditions? (Please tick/check all boxes that apply)
  Angina
  Arthritis
  Cancer 
  Chronic obstructive pulmonary disease/emphysema
  Heart attack or heart disease
  Hypertension 
  Stroke
  Depression
  Other mental health conditions (please specify):  ______________________
  Other health conditions (please specify):  ________________________________
  None
Appendix 15.  Interviewer Recording Sheet
Interviewer Recording Sheet
(May be modified based on findings from the Pilot Phase)


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To be completed by the interviewer:
1. Device Randomized to First Training:    Ozempic Device        Trulicity Device
  Participant completed training for first device
  Participant completed training, but required interviewer assistance to remove the needle 
(Ozempic only)
  Participant was exposed to this device but did not complete training.  Please explain below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
2. Device Randomized to Second Training:    Ozempic Device        Trulicity Device
  Participant completes training for second device
  Participant completed training, but required interviewer assistance to remove the needle 
(Ozempic only)
Appendix 17.  Global Preference Item
To be completed by all participants:
3.
Overall, which device do you prefer?
  Ozempic
  Trulicity
  No Preference
4.
Please explain your preference indicated above in Item 1.
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________


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To be completed by interviewer:
5. Please explain your preference indicated in Item 1 on the Global Preference Questionnaire 
(interviewer to record reasons for device preference provided by the participant, provide 
quotes with quotations marks and write neatly):
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
Appendix 22.  Clinical Information Form
Clinical Information Form – Site Completed
Instructions:  Please complete the following questions for eligible patients.
5. When was the patient diagnosed with T2DM?  
If the day and month are unknown, please report the year of diagnosis, and check the box “Day 
and Month of T2DM diagnosis unknown”.
If day is unknown, please report month and year of diagnosis, and check the box “Day of T2DM 
diagnosis unknown”.
   
  
                              
                           MD MD
    DM    DM   M
    Y     Y       Y      Y
Day and Month of T2DM diagnosis unknown
Day of T2DM diagnosis unknown


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6. What type 2 diabetes oral medication(s) is the patient currently taking?  Please check 
all that apply.
Oral Class
Oral Medication Options
(select all that apply)
Estimated Start Date of 
Oral T2DM Medication
(MMM/YYYY)
Sulfonylureas
  chlorpropamide
  glibenclamide or glyburide
  glibornuride
  gliclazide
  glimepiride
  glipizide
  gliquidone
  glisoxepide
  glyburide micronized 
  glyclopyramide
  glycyclamide or tolhexamide
  metahexamide
  tolazamide
  other
Meglitinides
  metformin
  nateglinide
  repaglinide
  other
DPP-4 Inhibitors
  alogliptin benzoate
  linagliptin
  saxagliptin
  sitagliptin
  vildagliptin                 
  other
SGLT2 Inhibitors
  canagliflozin             
  dapagliflozin                  


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Oral Class
Oral Medication Options
(select all that apply)
Estimated Start Date of 
Oral T2DM Medication
(MMM/YYYY)
  empagliflozin             
  other
Thiazolidinediones
(TZDs or Glitazones)
  pioglitazone
  rosiglitazone               
  other
Alpha-glucosidase 
inhibitors
  acarbose
  miglitol                         
  other
Combination Pills
  alogliptin benzoate/metformin 
hydrochloride
  canagliflozin/metformin 
hydrochloride
  dapagliflozin/metformin
  dapagliflozin propanediol/metformin 
hydrochloride
  empagliflozin/linagliptin                
  glimepiride/pioglitazone
  glimepiride/rosiglitazone maleate
  metformin/empagliflozin
  metformin/glipizide
  metformin/glyburide
  metformin/linagliptin
  metformin/pioglitazone
  metformin/repaglinide
  metformin/rosiglitazone maleate
  metformin/saxagliptin


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Oral Class
Oral Medication Options
(select all that apply)
Estimated Start Date of 
Oral T2DM Medication
(MMM/YYYY)
  metformin/sitagliptin
  metformin/vildagliptin
  simvastatin/sitagliptin phosphate
  other
7. Does the patient currently have any of the following comorbidities?  Please check all 
that apply.
  Congestive heart failure
  Dementia 
  Chronic Pulmonary Disease
  Rheumatologic Disease
  Mild Liver Disease
  Diabetes with chronic complications
  Hemiplegia or paraplegia 
  Renal disease
  Any malignancy, including leukemia and lymphoma
  Moderate or severe liver disease
  Metastatic solid tumor
  AIDS/HIV
  None
8. Please record the patient’s most recent HbA1c value and the date this value was 
measured.
Date of HbA1c
measurement
HbA1c value
MMDD/DDMMM/YYYY
___%

SAP_001.pdf: 
Statistical Analysis Plan H9X-MC-B021 
 
Crossover Study Comparing Dulaglutide (Trulicity) Pen and the Semaglutide (Ozempic) Pen 
 
NCT03724981 
 
Approval Date: 09-Oct-2018 


H9X-MC-B021 Statistical Analysis Plan Version 1
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LY2189265
1.
Statistical Analysis Plan:
H9X-MC-B021:  Crossover Study Comparing the Dulaglutide 
(Trulicity) Pen and the Semaglutide (Ozempic) Pen
Confidential Information
The information contained in this document is confidential and the information contained 
within it may not be reproduced or otherwise disseminated without the approval of Eli Lilly 
and Company or its subsidiaries.  
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
dulaglutide (LY2189265) T2DM
Study H9X-MC-B021 is an open-label, multicenter, randomized, crossover study assessing 
patient preference (and training time) for the dulaglutide pen versus the semaglutide pen 
among a sample of self-injection naïve patients with type 2 diabetes mellitus who are taking 
oral medication.  
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol H9X-MC-B021
Statistical Analysis Plan electronically signed and approved by Lilly on date provided 
below.
Approval Date: 09-Oct-2018 GMT


H9X-MC-B021 Statistical Analysis Plan Version 1
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LY2189265
2.
Table of Contents
Section
Page
1.
Statistical Analysis Plan: H9X-MC-B021:  Crossover Study 
Comparing the Dulaglutide (Trulicity) Pen and the Semaglutide 
(Ozempic) Pen ....................................................................................................................1
2.
Table of Contents................................................................................................................2
3.
Revision History .................................................................................................................4
4.
Study Objectives.................................................................................................................5
4.1.
Primary Objective ..........................................................................................................5
4.2.
Secondary Objectives.....................................................................................................5
4.3.
Exploratory Objectives...................................................................................................5
5.
Study Population and Determination of Sample Size...........................................................6
5.1.
Selection of Study Population.........................................................................................6
5.1.1.
Inclusion Criteria ...................................................................................................6
5.1.2.
Exclusion Criteria ..................................................................................................6
5.2.
Sample Size Determination ............................................................................................7
5.3.
Populations for Analyses................................................................................................7
6.
A Priori Statistical Methods ................................................................................................9
6.1.
General Statistical Considerations ..................................................................................9
6.2.
Adjustments for Covariates ............................................................................................9
6.3.
Handling of Dropouts or Missing Data...........................................................................9
6.4.
Multicenter Studies ........................................................................................................9
6.5.
Multiple Comparisons/Multiplicity.................................................................................9
6.6.
Use of “Efficacy Subset” of Patients ..............................................................................9
6.7.
Active-Control Studies Intended to Show Equivalence.................................................10
6.8.
Patient Disposition .......................................................................................................10
6.9.
Patient Characteristics and Patient-Reported Outcome Data .........................................10
6.9.1.
Patient Characteristics..........................................................................................10
6.9.2.
Patient-Reported Outcomes..................................................................................10
6.9.2.1.
Global Preference Item...................................................................................11
6.9.2.2.
Diabetes Injection Device – Preference Questionnaire ....................................11
6.9.2.3.
Four Items from the Medication Delivery Device 
Assessment (MDDAB)...................................................................................11
6.10. Treatment Compliance .................................................................................................12
6.11. Concomitant Therapy...................................................................................................12
6.12. Efficacy Analyses ........................................................................................................12
6.12.1.
Primary Analysis..................................................................................................12


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LY2189265
6.12.2.
Gated Secondary Analysis....................................................................................13
6.12.3.
Exploratory Analyses...........................................................................................13
6.12.3.1.
Exploratory 1.  DID-PQ Analyses of Items 1-8 and 10....................................13
6.12.3.2.
Exploratory 2.  Time-to-Train Analyses (TTT)...............................................13
6.12.3.3.
Exploratory 3.  Supplemental Question Analyses............................................14
6.12.3.4.
Exploratory 4.  Evaluation of the DID-PQ ......................................................14
A.  Construct Validity of the Categorical Approach to Analyzing 
the DID-PQ ..............................................................................................15
B.  Statistical Significance of Differences in Preference for Each 
Item of the DID-PQ ..................................................................................16
C.  Aggregate Scoring of the Seven Device Characteristics Items 
of the DID-PQ ..........................................................................................17
6.12.4.
Additional Exploratory Analyses..........................................................................18
6.12.5.
Other Analyses.....................................................................................................18
6.12.5.1.
Pilot Phase Analyses.......................................................................................18
6.13. Health Outcomes/Quality-of-Life Analyses..................................................................18
6.14. Bioanalytical and Pharmacokinetic/Pharmacodynamic Methods...................................19
6.15. Pharmacogenomic Methods .........................................................................................19
6.16. Safety Analyses............................................................................................................19
6.17. Subgroup Analyses.......................................................................................................19
6.18. Interim Analyses and Data Monitoring.........................................................................19
6.19. Study Unblinding Plan .................................................................................................19
7.
References ........................................................................................................................20


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3.
Revision History
Statistical Analysis Plan (SAP) Version 1 was approved prior to the first visit when a subject 
receives study drug or any other protocol intervention. 


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4.
Study Objectives
4.1.
Primary Objective
The primary objective is to determine patient preference between the dulaglutide and 
semaglutide injection devices.
4.2.
Secondary Objectives
A gated secondary objective of this study is to compare the two injection devices with regard to 
ease of use.  This objective will be tested if a significant difference is found in the primary 
objective.
4.3.
Exploratory Objectives 
This study has four exploratory objectives:  (1) to collect data to support the preference question 
in the primary objective; (2) to compare time to train on the dulaglutide and semaglutide devices; 
(3) to examine patients’ willingness to use each of the devices after being trained on both, and; 
(4) to validate the Diabetes Injection Device Preference Questionnaire (DID-PQ).


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5.
Study Population and Determination of Sample Size
5.1.
Selection of Study Population 
5.1.1. Inclusion Criteria
Patients are eligible to be included in the study if they meet all the following criteria at 
screening:
Participant Characteristics
[1]
Are at least aged ≥18 years at the time of screening
[2]
Diagnosed with type 2 diabetes
[3]
Self-injection naïve to all injectable treatment (for example, diabetes 
therapies and other medical conditions)
[4]
Injection naïve to performing all injectable treatment (for example, diabetes 
therapies and other medical conditions) to others
[5]
Must currently receive oral treatment for their type 2 diabetes
[5a]  Pilot phase participants only:  must be able to bring proof of their 
oral treatment prescription for type 2 diabetes to the interview 
(e.g., the medication itself, the medication packaging, a prescription 
note, or a letter from their doctor).  This criterion does not apply to the 
main phase because main phase participants will have diagnoses 
confirmed by the clinical sites with awareness of the patients’ diabetes 
and treatment. 
[6]
Willing and able to attend an in-person interview session
[7]
Able to read, speak, write, and understand the English language
[8]
Able and willing to give signed informed consent prior to study entry 
[9]
Able to complete the protocol requirements
5.1.2. Exclusion Criteria
Participants will be excluded from study enrollment if they meet any of the following criteria at 
screening:
Medical Conditions
[1]
Currently diagnosed with gestational diabetes and/or type 1 diabetes
[2]
Cognitive or physical difficulties that could interfere with ability to 
understand the training, perform the injection tasks, or complete the study 
questionnaires as judged by the investigator


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Prior/Concurrent Clinical Trial Experience
[3]
Are currently enrolled in any other clinical study involving an 
investigational product or any other type of medical research judged not to 
be scientifically or medically compatible with this study 
[4]
Have participated, within the last 30 days, in a clinical study involving an 
investigational product.  
Other Exclusions
[5]
Is a health care practitioner who is trained in giving injections
[6]
For Main Phase participants only: Investigator, site personnel or 
immediate family member of investigator or site personnel.  Immediate 
family is defined as a spouse, parent, child, or sibling, whether biological or 
legally adopted
[7]
Is an employee of any of the following companies:  Eli Lilly and Company, 
Novo Nordisk, Evidera or PPD
[8]
Currently pregnant
5.2.
Sample Size Determination
To test the null hypothesis that patients have equal preference for either dulaglutide or 
semaglutide pen (50% of patients prefer dulaglutide pen and 50% prefer semaglutide pen), a 
sample size of 260 patients will provide 90% power against alternative hypothesis that there is a 
preference with 60% of the patients choosing the dulaglutide pen over the semaglutide pen. 
Calculation is carried out using 2-sided chi-square test (normal approximation) at 0.05 level of 
significance.  Software used is Nquery + nTerim 4.0.  Assuming that approximately 10% will not 
provide any preference information by choosing the “no preference” option on the Global 
Preference Item, 290 patients will be needed to have at least 260 patients with preference 
information.  The Prescott test which takes into account the order the device is used as well as 
the choice of “no preference” provides approximately 90% power against the alternative 
hypothesis of 54% choosing dulaglutide pen, 10% indicating no preference, and the remaining 
36% choosing semaglutide pen.  This is based on simulation of 1000 runs and assumes that there 
is no order effect.
5.3.
Populations for Analyses
For purposes of analysis, the following populations are defined:


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Population
Description
Randomized
Participants determined to be eligible and then assigned to one of 2 
device order groups (50% will be randomized to use the dulaglutide 
device first, while the other half will use the semaglutide device first).  
More details about randomization for this study are provided in 
Section 7.2 of the protocol.
Evaluable
Participants for whom device preference can be evaluated: Randomized 
participants who are exposed to both devices (i.e., participant was shown 
both devices via either video or demonstration, regardless of whether 
they successfully complete the training) and complete the Global 
Preference Item.
Withdrawn 
Participants who withdraw from the study before being exposed to both 
devices and completing the Global Preference item.  Details on study 
withdrawal are provided in Section 8 of the protocol.


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6.
A Priori Statistical Methods
6.1.
General Statistical Considerations 
Statistical analysis of this study will be the responsibility of Evidera.  The primary analyses will 
be conducted on the evaluable patient population (i.e., patients who provide a response to the 
Global Preference Item).  No imputation will be performed for missing data, and the analysis 
will be performed on observed cases.  
The significance level for all statistical tests will be p <0.05.  A serial gatekeeping strategy will 
be used to control for type 1 error for the primary and gated secondary objectives.  The gated 
secondary hypothesis will be tested only if the primary null hypothesis (i.e., that there is no 
difference in the preference for dulaglutide and semaglutide devices) is rejected.
Any change to the statistical analysis methods described in the SAP will require an amendment 
ONLY if it changes a principal feature of the SAP.  Any other change or addition to the 
statistical analysis methods described in the SAP, and the justification for making the change, 
will be described in the clinical study report (CSR).  
6.2.
Adjustments for Covariates
There are no planned adjustments for covariates for the primary or secondary analyses. For 
exploratory analyses involving Time-To-Train (TTT) as a continuous dependent variable, 
covariates such as age and gender will be used.  
6.3.
Handling of Dropouts or Missing Data
Study team members will perform a thorough review of the participants’ questionnaires prior to 
the completion of each interview to minimize missing data.  No imputations will be performed 
for missing data, and the analysis will be performed on observed cases.  If a participant decides 
to withdraw from the study, data collected to the point of withdrawal may be used in analysis to 
preserve the integrity of the research project.  There will be no lost to follow-up data because 
there is no follow up period in this study.
6.4.
Multicenter Studies
Approximately 14 clinical sites will recruit patients for this study.  Descriptive statistics (e.g., 
frequencies, percentages) for patient demographics will be presented by clinical site as described 
in Section 6.9.
6.5.
Multiple Comparisons/Multiplicity
Gatekeeping strategy will be used to control for type 1 error for the primary and gated secondary 
objective. There are no other plans to adjust for multiplicity. 
6.6.
Use of “Efficacy Subset” of Patients
Not applicable.


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6.7.
Active-Control Studies Intended to Show Equivalence
Not applicable.
6.8.
Patient Disposition
A detailed description of the patient disposition will be displayed in a figure.  The figure will 
present information including but not limited to:  1) number of eligible patients; 2) number of 
enrolled patients; 3) number of patients in final analysis sample; 4) number of patients 
randomized to dulaglutide as the first device in the administration sequence (also referred to as 
the “dula-sema” group); and, 5) number of patients randomized to semaglutide as the first device
in the administration sequence (also referred to as the “sema-dula” group).
6.9.
Patient Characteristics and Patient-Reported Outcome Data
6.9.1. Patient Characteristics
The frequency of patients assigned to each device sequence will be presented by clinical site.  
Descriptive statistics will be used to summarize the demographic and clinical characteristics of 
the total analysis sample as well as by the assigned device sequence group (i.e., sema-dula and 
dula-sema).  Descriptive statistics will also be presented by TTT assignment group (i.e., assigned 
to TTT vs. not assigned to TTT), and by individual clinical sites to ensure there are no systematic 
differences between the TTT and non-TTT groups.  Continuous variables (e.g., age) will be 
summarized with means, standard deviations, ranges, and minimum and maximum values, while 
categorical variables (e.g., gender, race) will be presented in terms of frequencies and 
percentages.  Patient-reported characteristics for the device sequence and TTT assignment 
groups will be compared (i.e., t-tests for continuous variables and chi-square tests for categorical 
variables) to determine if there are significant group differences.
Site-reported clinical characteristics will be presented descriptively; these statistics will be 
presented by the total analysis sample as well as by the assigned device sequence group, by TTT 
assignment group, and by individual clinical sites.  Site-reported characteristics for the device 
sequence and TTT assignment groups will be compared (i.e., t-tests for continuous variables and 
chi-square tests for categorical variables) to determine if there are significant group differences.
To understand the geographic representation of the sample (total sample and by randomization 
group), counts and percentages of patients recruited from each US geographic region (i.e., 
Northeast, Midwest, South, West) will be presented. 
6.9.2. Patient-Reported Outcomes
Distributional characteristics (frequencies and percentages of responses) for all patient-reported 
outcome (PRO) data, including data from the Global Preference Item, DID-PQ, MDDAB-
semaglutide, and the MDDAB-dulaglutide will be presented by total sample and by assigned 
device sequence group. Descriptions of these PRO measures are below. 


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6.9.2.1.
Global Preference Item
All participants will complete the Global Preference Item after being trained and using both 
devices.  Participants will be asked, “Overall, which device do you prefer?”  Participants will 
also be asked to explain why they selected their response for Ozempic, Trulicity, or no 
preference.  This item was developed specifically for use in this device preference multicenter 
crossover study.  To help participants remember the devices more accurately, colored images of 
the devices have been inserted into the questionnaire.  
6.9.2.2.
Diabetes Injection Device – Preference Questionnaire 
The DID-PQ was designed for the purpose of assessing patient preferences between two non-
insulin injection devices (Matza et al. 2018a; Matza et al. 2018b).  The DID-PQ is completed 
only by patients who have used devices for at least two injectable medications.  In the current 
study, patients will be using two devices to inject an injection pad, but will not be injecting 
themselves.  
The DID-PQ has 10 items developed based on qualitative research with patients and validated in 
a psychometric study (Matza et al. 2018a; Matza et al. 2018b).  Items 1 to 7 focus on specific 
characteristics of injection delivery systems, and these seven items comprise the Device 
Characteristics subscale.  Items 8 to 10 are three global items assessing preference based on 
overall satisfaction, ease of use, and convenience of the injection devices.  
On the DID-PQ, each item is rated on a 5-point scale allowing patients to indicate whether they 
prefer or strongly prefer one of the devices over the other.  For each item, patients may also 
respond by selecting the “no preference” (i.e., neutral) response option, indicating that they have 
no preference between the two devices.  Importantly, the response options of the DID-PQ are not 
on an ordinal scale assessing a single dimension.  These five response options of the DID-PQ 
comprise a non-linear scale for which mean scores are not calculated.  
Specifically, for this study, the DID-PQ response options will be:  Strongly Prefer Ozempic 
Device, Prefer Ozempic Device, Strongly Prefer Trulicity Device, Prefer Trulicity Device, or 
have No Preference.  To help participants remember the devices more accurately, colored images 
of the devices have been inserted into the questionnaire.  
For individual items of the DID-PQ, data will not be imputed.  If a response to one of these items 
is missing, then it is not possible to derive a score for that item. 
6.9.2.3.
Four Items from the Medication Delivery Device Assessment (MDDAB)
The original MDDAB was adapted from insulin-specific questionnaires and has been modified 
for use in both injection-naïve and non-insulin requiring participants (Matfin et al. 2015).  Four 
items selected from the MDDAB (Matfin et al. 2015; Yu et al. 2017) will be asked of the 
participants about each of the two devices under investigation in this study (Ozempic and 
Trulicity).  These additional questions will be completed in the order the participants were 
randomized to use the devices.  The first 3 questions ask participants how easy or difficult it was 
to:  (1) learn to use the device, (2) to follow the instructions when using the device, and (3)
overall, how difficult or easy was the device to use?  The last question asks participants to 


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“Please check the number that best indicates how willing you are to continue using the device” 
on a scale from 1 (“Definitely Unwilling”) to 5 (“Definitely Willing”).  
6.10. Treatment Compliance
Not applicable.
6.11. Concomitant Therapy
Not applicable.
6.12. Efficacy Analyses 
This study focuses on preference between devices. No investigational drug or treatment will be 
administered during this study.  Therefore, no efficacy analyses will be conducted.  The primary, 
secondary, and exploratory analyses are detailed below.
6.12.1. Primary Analysis
The primary analysis will examine whether there is a difference in preference between the 
semaglutide device and dulaglutide device as indicated by responses to the Global Preference 
Item (i.e., Overall, which device do you prefer?).  The Prescott test will be run to determine 
whether there is a statistically significant difference in preference between the devices, while 
controlling for order effects and taking into account the neutral responses.  This test is based on a 
comparison of the difference between the number of patients who prefer the first device and the 
number of patients who prefer the second device in each crossover group (Prescott 1981; Pictor 
2003).
For this analysis, the data are conceptualized as a 2x3 contingency table with rows consisting of 
the two crossover groups and columns indicating preference for the first device used, no 
preference, or preference for second device used.  
Crossover Group
Prefers First 
Device
No Preference
Prefers Second 
Device
Total
Dulaglutide-
Semaglutide
a
b
c
Row 1
Semaglutide-
Dulaglutide
d
e
f
Row 2
Total
Column 1
Column 2
Column 3
Total study N
The test considers the difference in counts of the first and third columns in each group computed 
as first device minus second device (a - c and d - f).  These represent the difference between 
patients preferring the first device and patients preferring the second device within each 
crossover group.  The difference between differences in numbers of patients (∆= [a - c] – [d - f]) 
represents the preference for one device over the other.  A mathematically equivalent way to 
present this analysis is as ∆ = [a + f] – [d + c].  In this equation, the term “a + f” represents all 


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patients preferring the dulaglutide device, and the term “d + c” is the sum of all patients 
preferring the semaglutide device across the two crossover groups.  A positive ∆would indicate 
more frequent preference for dulaglutide, while a negative ∆would indicate more frequent 
preference for semaglutide.
The p-value of the test is based on calculating the probability of finding a ∆by chance alone that 
is equal to or more extreme than (i.e., greater than a positive ∆ or less than a negative ∆) the ∆ 
that is observed (when row and column totals are held constant).  The device preference results 
(e.g., counts, percentages) will be presented by total sample and by assigned randomization 
group using the contingency structure above.  
For patients who express a preference on the Global Preference Item, the self-reported reason for 
this preference will be presented in a separate table.  These qualitative data (i.e., open-ended 
patient responses on the Global Preference Item CRF) will be summarized and collapsed into 
categories of reasons (e.g., needle size, injection frequency), and the frequencies and percentages 
of patients reporting each category will be presented by device. 
6.12.2. Gated Secondary Analysis
The secondary analysis will compare the dulaglutide and semaglutide devices with regard to ease 
of use.  Responses to the five-point response scale of the DID-PQ global item 9 (Overall ease of 
use) will be collapsed into three categories with the “strongly prefer” and “prefer” options being 
combined for each device.  The resulting three categories will include:  prefer dulaglutide, no 
preference, and prefer semaglutide.  The Prescott test will then be run to examine if a statistically 
significant difference in preference between the devices exists, while controlling for order 
effects.  
6.12.3. Exploratory Analyses 
6.12.3.1. Exploratory 1.  DID-PQ Analyses of Items 1-8 and 10
Exploratory analyses of items 1–8 and 10 of the DID-PQ will follow the same procedures as 
those for the gated secondary objective described above.  The responses for each item will be 
collapsed to create three categories (prefer dulaglutide, no preference, and prefer semaglutide) 
and the Prescott test will be run to examine whether there is a statistically significant difference 
in preference between the devices, while controlling for order effects.
6.12.3.2. Exploratory 2.  Time-to-Train Analyses (TTT)
Time-To-Train with each device will be measured in a subset of patients.  Of the approximately 
14 sites expected to recruit patients for the study, four sites will be selected to participate in the 
TTT assessment.  The TTT assessment will require interview facilities with interview rooms 
allowing for observation from behind a one-way mirror.  Therefore, the TTT sites will be 
selected based on proximity to suitable facilities, while taking into account geographic diversity 
and the split between general practice and endocrinology sites.  
Time-To-Train will be reported for the total time spent for each device, including the time for the 
video component as well as the time after subtracting the video component.  Average duration


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required to train each device will be reported and presented for each device (e.g., dulaglutide and 
semaglutide) and by administration sequence (i.e., dula-sema and sema-dula).  
A linear mixed modeling framework accounting for the crossover design with the appropriate 
terms for device (either dulaglutide device or semaglutide device), sequence (either dula-sema or 
sema-dula), and period (either trained first or trained second) will be used to compare TTT 
between the devices The model will include device, sequence, and period as fixed effects and 
patient as a random effect.  Least square means, 95% confidence interval, and p-values will be 
calculated from this model.  If a carryover (sequence) effect is found to be significant, an 
analysis based on data from the first period only will also be carried out.  
The balance in baseline characteristics of patients randomized to the TTT sequence groups will 
be assessed and appropriate analysis conducted to explain the results.
Linear model assumptions, such as normality and common variance, will be assessed by 
examining the residuals.  Linear models tend to be robust to violations of these assumptions, but 
if there are any substantial violations of the assumptions, then alternative approaches such as 
non-parametric methods may be utilized.  
6.12.3.3. Exploratory 3.  Supplemental Question Analyses 
Supplemental Questions are included in the survey to examine willingness to use each of the 
devices after being trained on both.  The Supplemental Questions developed for this study are 
based on previous items used in a study by Poon et al. (2018).  The first question will be 
administered to participants before the device trainings and will determine the participants’ 
“willingness to use a diabetes medication that required an injection for each dose.”  The second 
and third Supplemental Questions will be administered to the participants after all the trainings, 
mock injections, and other study measures have been completed.  Questions S2 and S3 will ask 
participants specifically about their willingness to use the Ozempic and Trulicity devices, 
respectively.  Descriptive statistics will be reported for each item (i.e., frequencies, percentages). 
6.12.3.4. Exploratory 4.  Evaluation of the DID-PQ 
A psychometric evaluation of the DID-PQ and assessment of various scoring approaches 
proposed in the DID scoring guide will be performed.  The DID-PQ has been administered in 
two studies thus far:  the original psychometric validation study (Matza et al. 2018b) and the US 
study comparing the dulaglutide and liraglutide devices (Matza et al. 2018c).  In both studies, the 
DID-PQ was administered to a relatively small subgroup of patients who had used more than one 
GLP-1 receptor agonist device.  Therefore, it has not previously been possible to perform 
psychometric analyses examining the validity of this PRO instrument nor the proposed scoring 
approaches.  Since it is anticipated that the entire sample in this study will complete the DID-PQ, 
this study provides a unique opportunity to perform analyses evaluating the performance of this 
instrument.  
Three approaches to analyzing the DID-PQ will be examined, as described in sections A, B, and 
C below: 
A. Categorical descriptive analyses


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B. Testing for significant differences between devices on individual items of the DID-PQ
C. Aggregate scoring for the seven device characteristics items of the DID-PQ
A. Construct Validity of the Categorical Approach to Analyzing the DID-PQ 
In publications thus far, DID-PQ data has been presented descriptively and categorically without 
additional quantitative analysis.  Results have been presented as descriptive statistics for each
individual item (i.e., frequency and percent of patients selecting each response).  This descriptive 
approach to analyzing DID-PQ data will first be examined by comparing DID-PQ responses to 
responses on the global preference item.  These analyses are examining the instrument’s 
construct validity, which is the extent to which an instrument performs as expected relative to an 
ancillary measure.  
First, patients’ responses to each of the 10 items of the DID-PQ will be collapsed from five 
levels to three levels, by combining the “prefer” and “strongly prefer” response options for 
dulaglutide and semaglutide.  These collapsed three-level DID-PQ responses will be compared to 
responses on the Global Preference Item in a frequency table so that agreement between the two 
instruments can be assessed.  Each item on the DID-PQ will be assessed for concordance as 
indicated by percent agreement, Gwet’s AC1 statistic (Gwet 2014), and the prevalence-adjusted, 
bias-adjusted kappa (PABAK) statistic (Byrt et al. 1993).  
The AC1 is an agreement statistic that is similar to kappa, but uses a different definition of 
chance agreement.  The AC1 is designed to be less affected by high prevalence or marginal 
imbalance compared to kappa.  This approach yields a slightly conservative estimate of 
agreement, because it assumes the scale is nominal and any disagreement is an equal amount of 
disagreement.  The PABAK statistic takes a slightly different approach to dealing with either 
high prevalence or bias in marginal distributions.  The PABAK calculates its estimate of chance 
agreement using different assumptions regarding high prevalence or bias in marginal 
distributions than the plain kappa.
After these 3x3 tables, a series of 5x3 tables (one for each DID-PQ item) will be presented to 
compare the un-collapsed 5-level categorical responses of the DID-PQ to the Global Preference 
Item.  Because of the unequal number of response options in this comparison, the summary 
statistics will not be run.  Instead, results will provide a general picture of whether all five levels 
of the DID-PQ are performing as expected.  For example, it is expected that patients who choose 
either prefer dulaglutide or strongly prefer dulaglutide on the DID-PQ would also tend to report a 
preference for dulaglutide on the global preference item.
Construct validity will further be assessed by comparing DID-PQ responses to responses on four
items selected from the MDDAB (Matfin et al. 2015; Yu et al. 2017).  The four items of the 
MDDAB assess (1) ease of learning how to use the device, (2) ease of following instructions 
when using the device, (3) overall ease-of-use, and (4) willingness to continue using the device.  
These analyses will be run with selected DID-PQ items hypothesized to be related to these four 
constructs assessed by the MDDAB.


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B. Statistical Significance of Differences in Preference for Each Item of the DID-
PQ
After reporting DID-PQ findings descriptively, it may also be useful to determine whether 
significantly more respondents preferred one device over the other with regard to specific items 
of the DID-PQ.  The current crossover study will be the first sample with a large enough sample 
size to perform and evaluate the usefulness of this approach to significance testing.  
These comparisons will be performed according to the following steps:
1.  Determine whether a statistical test is needed for any individual item: 

If preference for one of the devices on an item is unanimous, the pattern of results 
is clearly interpretable, and a statistical comparison between devices should not be 
performed for that item.  

If ≥50% of the sample provided a neutral response for an item, a statistical
comparison between devices should not be performed for that item.  If <50% of 
the sample provided a neutral response for an item, proceed with steps 2 to 4
below.  
2.  Respondents who provide a neutral response for each item should be dropped from 
analysis of that item.  
3.  For each item, patients’ responses should be grouped into two categories:  (1) preference 
for Device 1 and (2) preference for Device 2 (in the current study, these devices are the 
semaglutide injection device and the dulaglutide injection device).  These two categories 
of responses can be used to calculate the proportion who prefer each device.  These two 
proportions are dependent, as they always add to 1. 
4.  Among patients indicating a preference for one device over the other, a statistical test 
can be performed to determine whether a significant preference exists:  

This test would assess whether the proportion indicating preference for one of the 
two devices differs from 0.5.  A value of 0.5 would indicate that there is equal 
preference for the two devices.  

The frequency of preferences for Device 1 and Device 2 will be examined using a 
two-sided binomial test for each item of the DID-PQ.  

For each DID-PQ item, the null hypothesis is that the probability of preferring one 
of the devices is 0.5.  If the binomial test yields a significant p-value, then the null 
hypothesis can be rejected, which would mean that significantly more respondents 
preferred one device over the other.
These results will be presented in a series of three tables.  The first will present results for the 
total sample.  Then, the same significance testing will be performed within two subsets of 
patients:  those who preferred semaglutide on the Global Preference Item and those who 
preferred dulaglutide on the Global Preference Item.  It is expected that within each of these two 
preference subgroups, results of binomial tests will favor the preferred device.  For example, 
patients who express a preference for dulaglutide on the Global Preference Item are expected to 


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be more likely to have statistically significant preferences for the dulaglutide device on items of 
the DID-PQ.
C. Aggregate Scoring of the Seven Device Characteristics Items of the DID-PQ
For the Device Characteristics items of the DID-PQ (i.e., items 1-7), another possible analysis 
approach is to perform a statistical test to assess whether one of the devices tended to be 
preferred more frequently than the other across the seven items.  
This comparison will be performed according to the following steps:
1.  For each individual respondent, compute three sums: 

The number of items on which the respondent preferred Device 1 

The number of items on which the respondent preferred Device 2 

The number of items to which the respondent provided a neutral response (i.e., no 
preference between Device 1 and Device 2) 
If all items were answered, the sum of these three values will equal 7.
2.  Items receiving a neutral response (i.e., no preference between Device 1 and Device 2) 
should be excluded from the analysis.  
3.  For each respondent, compute a proportion of the frequency of items on which Device 1 
was preferred divided by the total number of items on which a preference was indicated 
for either device.  For example, if a respondent preferred Device 1 on four items and 
Device 2 on two items, with no preference for one item, then the proportion would be 
0.67 (i.e., four preferences for Device 1 divided by 6 items on which either device was 
preferred).  Patients who have all neutral responses will not be included in this analysis.
4.  A mean of this proportion may be calculated for a patient sample.  Then, a single sample 
t-test may be performed to assess whether this mean is significantly different from 0.5.  
5.  The null hypothesis would be that the mean proportion is 0.5.  If the t-test yields a 
significant p-value, then the null hypothesis can be rejected, which would mean that 
significantly more respondents preferred one device across the Device Characteristics
items.
These results will be presented in a series of three tables.  The first will present results for the 
total sample.  Then, the same significance testing will be performed within two subsets of 
patients:  those who preferred semaglutide on the Global Preference Item and those who 
preferred dulaglutide on the Global Preference Item.  It is expected that within each of these two 
preference subgroups, results of this aggregate scoring approach will favor the preferred device.  
For example, patients who express a preference for dulaglutide on the Global Preference Item 
should be more likely to have statistically significant difference favoring the dulaglutide device 
with this aggregate scoring approach for the DID-PQ.
The aggregate analysis described above can be conducted if <50% (i.e., three or fewer items) of 
the seven Device Characteristics items are missing.  In this case, items that are not answered 


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would be excluded from calculation of the proportion.  If >50% of the items are missing for any 
respondent, this respondent’s data should not be used in the aggregate scoring approach.
6.12.4. Additional Exploratory Analyses
Additional exploratory analyses may be performed to further evaluate the individual factors 
associated with device preference. Logistic regressions with device preference as the dependent 
variable (i.e., sema vs. dula; or this could be dula vs. other response including preference for 
sema and no preference, depending on N in each preference group) may be performed to 
evaluate the impact of each DID-PQ item on device preference. If performed, model fit will be 
evaluated by receiver operating characteristic (ROC) curves as well as the Hosmer-Lemeshow 
goodness of fit test. 
6.12.5. Other Analyses
6.12.5.1. Pilot Phase Analyses 
Analyses of the pilot phase data will include both descriptive statistics and a content analysis 
approach.  The purpose of the pilot phase is to ensure the training materials and interview 
procedures are clear, comprehensible, and feasible prior to the main phase.  
Descriptive statistics (e.g., mean, standard deviation, frequency) will be used to summarize the 
sample in terms of sociodemographic characteristics and on the other measures completed by the 
participants (i.e., Global Preference Item, DID-PQ, four items selected from the MDDAB for 
each device).  
A content analysis approach will be used to analyze the responses collected on the pilot phase 
interview questions. This content analysis applies only to the pilot phase. Responses will be 
examined to determine answers to the following questions for each device:

Are there any ways the device training could be easier or more clear?  If yes, please 
explain. 

Would you recommend any changes to the device training procedures?  If yes, please 
explain.

How much additional guidance is appropriate and useful during the device training?
During the pilot phase, the PI and study team will be continuously monitoring the interview and
data as they are collected to determine if changes need to be implemented immediately.  If major 
changes are required, Evidera and Lilly will determine if the pilot phase sample size needs to be 
increased.  Upon conclusion of the pilot phase, Evidera study staff will send to Lilly a summary 
document of the pilot phase, which will serve as the interim analysis.  
The pilot phase data for an estimated 10–20 participants will not be included in the final sample 
of approximately 290 patients with Type 2 Diabetes Mellitus.  
6.13. Health Outcomes/Quality-of-Life Analyses
Not applicable.


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6.14. Bioanalytical and Pharmacokinetic/Pharmacodynamic Methods
Not applicable.
6.15. Pharmacogenomic Methods
Not applicable. 
6.16. Safety Analyses
This study focuses on preference between devices, and no medication will be administered to 
study participants.  However, if a participant reports an adverse event (AE) related to the study, 
the appropriate reporting procedures will be followed.  See Section 9.2 of the protocol for more 
AE details.  
6.17. Subgroup Analyses
Not applicable.
6.18. Interim Analyses and Data Monitoring
No interim analyses will be reported but an interim dataset will be provided to the Evidera 
programming staff prior to data lock to allow programming work to begin before end of study.
6.19. Study Unblinding Plan
Not applicable.


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7.
References
Byrt T, Bishop J, Carlin JB. Bias, prevalence and kappa. J Clin Epidemiol. 1993;46(5):423-429.
Gwet KL. Handbook of inter-rater reliability: The definitive guide to measuring the extent of 
agreement among raters. Fourth ed. Gaithersburg, MD: Advanced Analytics, LLC; 2014.
Matfin G, Van Brunt K, Zimmermann AG, Threlkeld R, Ignaut DA. Safe and effective use of the 
once weekly dulaglutide single-dose pen in injection-naïve patients with type 2 diabetes. J 
Diabetes Sci Technol. 2015;9(5):1071-1079.
Matza LS, Boye KS, Stewart KD, Paczkowski R, Jordan J, Murray L. Patient perceptions of non-
insulin injection devices: Qualitative research to support development of the Diabetes Injection 
Device Experience Questionnaire (DID-EQ) and Diabetes Injection Device Preference 
Questionnaire (DID-PQ). J Patient-Rep Outcomes. In press; 2018a.
Matza LS, Stewart KD, Paczkowski R, Coyne KS, Currie B, Boye KS. Psychometric evaluation 
of the Diabetes Injection Device Experience Questionnaire (DID-EQ) and Diabetes Injection 
Device Preference Questionnaire (DID-PQ). J Patient-Rep Outcomes. In press; 2018b.
Matza LS, Boye KS, Currie BM, et al. Patient perceptions of injection devices used with 
dulaglutide and liraglutide for treatment of type 2 diabetes. Curr Med Res Opin. 
2018;34(8):1457-1464.
Pictor A. Analysing Binary Outcome Data from a Crossover Design Study using the SAS® 
System. SAS VIEWS 2003; 8 pgs. Available at: 
https://www.lexjansen.com/views/2003/statpharm/st02.pdf. 
Poon JL, Boye KS, Thieu VT, Norrbacka KN, Hassan SW, Gelhorn HL. Preferences for 
attributes of medications among patients with type 2 diabetes: a cross-medication class 
comparison of injection therapies. Curr Res Diabetes Obes J. 2018;6(5):555700.
Prescott RJ. The comparison of success rates in cross-over trial sin the presence of an order 
effect. Appl Statist. 1981 Jan;30(1):9-15. 
Yu M, Van Brunt K, Milicevic Z, Varnado O, Boye KS. Patient-reported outcome results of 
dulaglutide added to titrated insulin glargine in patients with type 2 diabetes (AWARD-9). 
Clin Ther. 2017;39:2284-2295.


Leo Document ID = 6ca3362a-f941-4920-886e-b8a3d5715ed3
Approver: 
Approval Date & Time: 09-Oct-2018 02:03:49 GMT
Signature meaning: Approved
PPD