Control-IQ Technology in Individuals With Type 2 Diabetes (2IQ)
Phase: NA
Conditions: Type 2 Diabetes Treated With Insulin
Sponsor: Tandem Diabetes Care, Inc.

Signature Page 
Control-IQ Technology in Individuals with Type 2 Diabetes 
(2IQ) 
Protocol Identifying Number: TP-0009569 
IND/IDE Sponsor: Tandem Diabetes Care, Inc. 
Version Number: v. 3.0 
19 Oct 2021 
 
JCHR Protocol Director 
 
Name, degree 
John Lum, MS / Jaeb Center for Health Research 
Signature/Date 
 
 
Sponsor  
Tandem Diabetes Care, Inc. 
Name, degree 
Jordan Pinsker, M.D. 
Signature/Date 
 
 
Clinical Lead Investigator 
 
Name, degree 
Carol Levy, M.D. / Icahn School of Medicine at Mount Sinai 
Signature/Date 
 
 
Medical Monitor 
 
Name, degree 
Roy Beck, MD, Ph.D. / Jaeb Center for Health Research 
Signature/Date 
 
 
SIGN
SIGN
SIGN
SIGN

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2IQ PROTOCOL V3.0 
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Control-IQ Technology in Individuals with Type 2 Diabetes 
(2IQ) 
Protocol Identifying Number: TP-0009569 
IND/IDE Sponsor: Tandem Diabetes Care, Inc. 
 
 
Version Number: v3.0 
19 Oct 2021 
 

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KEY ROLES 
 
Protocol Chair/Director 
 
Name, degree 
Carol Levy, M.D. 
Institution Name 
Icahn School of Medicine at Mount Sinai 
 
JCHR Coordinating Center Director 
 
Name, degree 
John Lum, MS 
Institution Name 
Jaeb Center for Health Research 
 
Medical Monitor 
 
Name, degree 
Roy Beck, M.D., Ph.D. 
Institution Name 
Jaeb Center for Health Research 
 
Sponsor 
 
Name, degree 
Jordan Pinsker, M.D. 
Institution Name 
Tandem Diabetes Care, Inc. 
11075 Roselle Street 
San Diego, CA 92121 
 

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TABLE OF CONTENTS 
CHAPTER 1: BACKGROUND INFORMATION ............................................................................................. 15 
1.1 Disease Background .......................................................................................................................... 15 
1.2 Device Background ........................................................................................................................... 15 
1.3 Rationale ............................................................................................................................................ 16 
1.4 Potential Risks and Benefits of the Investigational Device ............................................................... 16 
1.4.1 Known Potential Risks ................................................................................................................ 16 
1.4.1.1 Potential Risks and Benefits of the CLC System ................................................................ 16 
1.4.1.2 Risk of Hypoglycemia ........................................................................................................ 16 
1.4.1.3 Risk of Hyperglycemia ....................................................................................................... 17 
1.4.1.4 Fingerstick Risks ................................................................................................................. 17 
1.4.1.5 Venipuncture Risks ............................................................................................................. 17 
1.4.1.6 Subcutaneous Catheter Risks .............................................................................................. 17 
1.4.1.7 Risk of Exercise .................................................................................................................. 17 
1.4.1.8 Risk of Device Reuse .......................................................................................................... 18 
1.4.1.9 Questionnaires and Semi-Structured Interviews ................................................................. 18 
1.4.1.10 Other Risks ........................................................................................................................ 18 
1.4.2 Known Potential Benefits ............................................................................................................ 18 
1.4.3 Risk Assessment .......................................................................................................................... 18 
1.5 General Considerations...................................................................................................................... 19 
CHAPTER 2: STUDY ENROLLMENT AND SCREENING .............................................................................. 20 
2.1 Participant Recruitment and Enrollment ........................................................................................... 20 
2.1.1 Informed Consent and Authorization Procedures ....................................................................... 20 
2.2 Participant Inclusion Criteria ............................................................................................................. 20 
2.3 Participant Exclusion Criteria ............................................................................................................ 21 
2.4 Screening Procedures ........................................................................................................................ 22 
2.4.1 Data Collection and Testing ........................................................................................................ 22 
2.5 Screen Failures .................................................................................................................................. 23 
CHAPTER 3: CGM AND PUMP RUN-IN PHASES ....................................................................................... 24 
3.1 CGM Run-in Phase Overview ........................................................................................................... 24 
3.2 Initiation of CGM .............................................................................................................................. 24 
3.2.1 CGM Training ............................................................................................................................. 24 
3.3 Blood Glucose and Blood Ketone Testing ........................................................................................ 25 
3.4 Assessment of Successful Completion of the CGM Run-in Phase ................................................... 25 
3.5 Pump Run-in Phase Overview ........................................................................................................... 26 

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3.6 Initiation of the Study Pump .............................................................................................................. 26 
3.6.1 Study Pump Training ................................................................................................................... 26 
3.6.2 Initiation of Pump by MDI Participants ...................................................................................... 27 
3.6.3 System Use Guidelines ................................................................................................................ 27 
3.7 Blood Glucose Testing ...................................................................................................................... 28 
3.8 Assessment of Successful Completion of the Pump Run-in Phase ................................................... 28 
3.9 Optimization of Insulin Therapy ....................................................................................................... 28 
CHAPTER 4: CONTROL-IQ (CLOSED-LOOP) PHASE ............................................................................... 29 
4.1 Control-IQ Phase Overview .............................................................................................................. 29 
4.1.1 Study Pump Training ................................................................................................................... 29 
4.1.2 System Use Guidelines ................................................................................................................ 29 
4.1.3 Home Use of the Study System ................................................................................................... 30 
4.1.4 Study Device Download .............................................................................................................. 31 
4.1.5 3-Day Phone Contact ................................................................................................................... 31 
4.1.6 1-Week Phone Contact ................................................................................................................ 31 
4.1.7 2-Week Visit ................................................................................................................................ 32 
4.1.8 4-Week Phone Contact ................................................................................................................ 32 
4.1.9 6-Week Visit ................................................................................................................................ 32 
4.1.10 3-Day Post-Study Call ............................................................................................................... 33 
4.1.11 Exercise Challenge Follow-Up .................................................................................................. 33 
4.2 Early Termination Visit (If Applicable) ............................................................................................ 33 
4.3 Unscheduled Visits ............................................................................................................................ 33 
CHAPTER 5: STUDY DEVICES .................................................................................................................... 34 
5.1 Description of the Investigational Device ......................................................................................... 34 
5.1.1 Insulin Pump ................................................................................................................................ 34 
5.1.2 Continuous Glucose Monitoring ................................................................................................. 34 
5.1.3 Blood Glucose Meter and Strips .................................................................................................. 34 
5.1.4 Ketone Meter ............................................................................................................................... 34 
5.1.5 Study Device Accountability Procedures .................................................................................... 34 
5.2 Safety Measures ................................................................................................................................. 34 
5.2.1 CGM Calibration ......................................................................................................................... 34 
5.2.2 Pump Failure ............................................................................................................................... 34 
5.2.3 Hypoglycemia Threshold Alarm and Safety Protocol ................................................................. 34 
5.2.4 Hyperglycemia Threshold Alarm and Safety Protocol ................................................................ 35 
5.3 Participant Access to Study Device at Study Closure ....................................................................... 35 

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CHAPTER 6: TESTING PROCEDURES AND QUESTIONNAIRES ................................................................. 36 
6.1 Laboratory Testing ............................................................................................................................ 36 
6.2 Electrocardiogram (ECG) .................................................................................................................. 36 
6.3 Questionnaires ................................................................................................................................... 36 
6.4 Semi-Structured Interviews ............................................................................................................... 37 
CHAPTER 7: UNANTICIPATED PROBLEM, ADVERSE EVENT, AND DEVICE ISSUE REPORTING ............ 38 
7.1 Unanticipated Problems ..................................................................................................................... 38 
7.2 Adverse Events .................................................................................................................................. 38 
7.2.1 Definitions ................................................................................................................................... 38 
7.2.2 Reportable Adverse Events ......................................................................................................... 40 
7.2.3 Hypoglycemic Events .................................................................................................................. 40 
7.2.4 Hyperglycemic/Ketotic Events .................................................................................................... 41 
7.2.5 Relationship of Adverse Event to Study Investigational Device ................................................. 42 
7.2.6 Severity (Intensity)  of Adverse Events ....................................................................................... 43 
7.2.7 Expectedness ............................................................................................................................... 43 
7.2.8 Coding of Adverse Events ........................................................................................................... 43 
7.2.9 Outcome of Adverse Events ........................................................................................................ 43 
7.3 Reportable Device Issues ................................................................................................................... 44 
7.4 Timing of Event Reporting ................................................................................................................ 44 
7.5 Safety Oversight ................................................................................................................................ 45 
7.6 Stopping Criteria ............................................................................................................................... 45 
7.6.1 Participant Discontinuation of Study Device .............................................................................. 45 
7.6.2 Criteria for Suspending or Stopping Overall Study ..................................................................... 46 
CHAPTER 8: MISCELLANEOUS CONSIDERATIONS ................................................................................... 47 
8.1 Drugs Used as Part of the Protocol .................................................................................................... 47 
8.2 Collection of Medical Conditions and Medications .......................................................................... 47 
8.3 Prohibited Medications, Devices, Treatments, and Procedures ......................................................... 47 
8.4 Precautionary Medications, Treatments, and Procedures .................................................................. 48 
8.5 Prophylactic Medications, Treatments, and Procedures .................................................................... 48 
8.6 Rescue Medications, Treatments, and Procedures ............................................................................ 48 
8.7 Pregnancy Reporting ......................................................................................................................... 48 
8.8 Participant Compensation .................................................................................................................. 48 
8.9 Participant Withdrawal ...................................................................................................................... 48 
8.10 Confidentiality ................................................................................................................................. 48 
CHAPTER 9: STATISTICAL CONSIDERATIONS ...................................... ERROR! BOOKMARK NOT DEFINED. 
9.1 Statistical and Analytical Plans ......................................................... Error! Bookmark not defined. 

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9.2 Statistical Hypotheses ........................................................................ Error! Bookmark not defined. 
9.3 Sample Size ....................................................................................... Error! Bookmark not defined. 
9.4 Outcome Measures ............................................................................ Error! Bookmark not defined. 
9.4.1 Primary Efficacy Endpoints ........................................................ Error! Bookmark not defined. 
9.4.2 Secondary Efficacy Endpoints .................................................... Error! Bookmark not defined. 
9.4.3 Safety Endpoints .......................................................................... Error! Bookmark not defined. 
9.5 Analysis Datasets and Sensitivity Analyses ...................................... Error! Bookmark not defined. 
9.6 Analysis of the Primary Efficacy Endpoint(s) ................................... Error! Bookmark not defined. 
9.7 Analysis of the Secondary Endpoint.................................................. Error! Bookmark not defined. 
9.8 Safety Analyses ................................................................................. Error! Bookmark not defined. 
9.9 Intervention Adherence ..................................................................... Error! Bookmark not defined. 
9.10 Protocol Adherence and Retention .................................................. Error! Bookmark not defined. 
9.11 Baseline Descriptive Statistics ......................................................... Error! Bookmark not defined. 
9.12 Device Issues ................................................................................... Error! Bookmark not defined. 
9.13 Planned Interim Analyses ................................................................ Error! Bookmark not defined. 
9.14 Sub-Group Analyses ........................................................................ Error! Bookmark not defined. 
9.15 Multiple Comparison/Multiplicity ................................................... Error! Bookmark not defined. 
9.16 Exploratory Analyses ...................................................................... Error! Bookmark not defined. 
CHAPTER 10: DATA COLLECTION AND MONITORING ............................................................................ 49 
10.1 Case Report Forms and Other Data Collection ............................................................................... 54 
10.2 Study Records Retention ................................................................................................................. 54 
10.3 Quality Assurance and Monitoring .................................................................................................. 54 
10.4 Protocol Deviations ......................................................................................................................... 55 
CHAPTER 11: ETHICS/PROTECTION OF HUMAN PARTICIPANTS ............................................................ 56 
11.1 Ethical Standard ............................................................................................................................... 56 
11.2 Institutional Review Boards ............................................................................................................ 56 
11.3 Informed Consent Process ............................................................................................................... 56 
11.3.1 Consent Procedures and Documentation ................................................................................... 56 
11.3.2 Participant and Data Confidentiality ......................................................................................... 56 
CHAPTER 12: REFERENCES ....................................................................................................................... 58 
 
 
 
 

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LIST OF ABBREVIATIONS 
ABBREVIATION 
DEFINITION 
AE 
Adverse Event 
AID 
Automated Insulin Dosing 
AUC 
(Glucose) Area under the curve  
CGM 
Continuous Glucose Monitoring 
CRF 
Case Report Form 
Control-IQ System 
t:slim X2 insulin pump with Control-IQ technology 
CSII 
Continuous Subcutaneous Insulin Infusion 
DCA2000 
Siemens/Bayer DCA 2000+ Hematology Analyzer 
DKA 
Diabetic Ketoacidosis 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture  
ECG 
Electrocardiogram 
FDA 
United States Food and Drug Administration 
HbA1c 
Hemoglobin A1c 
HCL 
Hybrid Closed-loop  
HHS 
Hyperosmolar Hyperglycemic Syndrome 
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption 
MDI 
Multiple Daily Injections of insulin 
POC 
Point-Of-Care 
QC 
Quality Control 
QoL 
Quality of Life 
SD 
Standard Deviation 
T2D 
Type 2 diabetes 
TDD 
Total Daily Dose of insulin 
TIR 
Time in range 
 

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SITE PRINCIPAL INVESTIGATOR STATEMENT OF COMPLIANCE 
Protocol Title: Control-IQ Technology in Individuals with Type 2 Diabetes (2IQ) 
Protocol Version/Date: 3.0 / 19 Oct 2021 
I have read the protocol specified above.  In my formal capacity as a Site Principal Investigator, 
my duties include ensuring the safety of the study participants enrolled under my supervision and 
providing the Jaeb Center for Health Research, which serves as the Coordinating Center for the 
protocol, with complete and timely information, as outlined in the protocol.  It is understood that 
all information pertaining to the study will be held strictly confidential and that this 
confidentiality requirement applies to all study staff at this site. 
This trial will be carried out in accordance with the principles of Good Clinical Practice (GCP) 
and as required by the following (use applicable regulations depending on study location and 
sponsor requirements; examples follow): United States (US) Code of Federal Regulations (CFR) 
applicable to clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 
312, and/or 21 CFR Part 812). 
As the Principal Investigator, I will assure that no deviation from, or changes to the protocol 
will take place without prior agreement from the sponsor and documented approval from the 
Institutional Review Board (IRB), or other approved Ethics Committee, except where necessary 
to eliminate an immediate hazard(s) to the trial participants. 
All key personnel (all individuals responsible for the design and conduct of this trial) have 
completed Human Participants Protection Training and Good Clinical Practice Training.  
Further, I agree to ensure that all staff members involved in the conduct of this study are 
informed about their obligations in meeting the above commitments. 
Investigator’s Signature __________________________________ Date: _____ / _____ / _____ 
 
dd 
mmm 
yyyy 
Investigator’s Name: ____________________________________ 
Site Name/Number: _____________________________________ 
 

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PROTOCOL SUMMARY 
PARTICIPANT AREA 
DESCRIPTION 
Title 
Control-IQ Technology in Individuals with Type 2 Diabetes (2IQ) 
Précis 
A prospective, single-arm study of 6 weeks of home use of the Control-IQ 
automated insulin delivery system in individuals with type 2 diabetes age 
18 and older. 
Investigational Device 
t:slim X2 insulin pump with Control-IQ technology v1.5 (Control-IQ 
System) 
Objectives 
The objectives of the study are to assess safety and explore glycemic 
outcomes with use of a closed loop control (CLC) system (t:slim X2 with 
Control-IQ Technology) in adults with type 2 diabetes to provide data to 
design a subsequent larger study. 
Study Design 
After an initial run-in period to ensure that participants can successfully 
use the study CGM and study pump in open-loop mode, all participants 
will use the study system (pump and CGM) in closed-loop mode for 6 
weeks. 
Number of Sites 
~3 US clinical centers 
Key Safety Endpoints 
Key Safety Endpoints: 
• Severe Hypoglycemia 
• Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome 
• Other reportable adverse events (see section 7.2.2)  
• Unanticipated adverse device effects  
 
Other Endpoints 
Other Endpoints: 
• CGM-measured % below 54 mg/dl 
• CGM-measured % above 180 mg/dL 
• CGM-measured post-prandial glycemic peak 
• Various other CGM-measured glycemic outcomes over 24 hours, 
daytime, and nighttime, as well as CGM outcomes with respect to 
announced meals 
• Total daily insulin use, daily basal and bolus insulin, and Weight 
Primary and secondary endpoints will be analyzed in total together, as 
well as separately for Group A (prior users of basal insulin only) and 
Group B (prior users of multiple daily injections) participants. 
Population 
Inclusion Criteria 
1. 
Age ≥18 years old and residing in the US 
2. 
Clinical diagnosis, based on investigator assessment, of type 2 
diabetes for at least one year 
3. 
Using a stable insulin dose for at least 3 months, to include A) basal 
insulin only, or B) MDI, to include CSII (including use of AID 
systems other than Tandem Control-IQ) 
4. 
Total daily insulin dose ≤200 units/day 
5. 
Willing to use only aspart (novolog) or lispro (humalog) insulin with 
the study pump, with no use of concentrated insulin above U-100, 
long-acting basal insulin injections, or inhaled insulin 
6. 
For females, not currently known to be pregnant 
If female of child-bearing potential, must agree to use a form of 
contraception to prevent pregnancy while a participant in the study 
as documented in the study records. A negative serum or urine 

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PARTICIPANT AREA 
DESCRIPTION 
pregnancy test will be required for all females of child-bearing 
potential. Participants who become pregnant will be discontinued 
from the study. Also, participants who during the study develop and 
express the intention to become pregnant within the timespan of the 
study will be discontinued. 
7. 
HbA1c ≥ 7.5% and ≤ 12% at screening 
8. 
Has current glucagon product to treat severe hypoglycemia 
(injectable or nasal) at home (will provide prescription if they do not 
have one) 
9. 
Be willing to exercise for 30 minutes or more at least once per week 
during the main phase of the study 
10. Has the ability to read and understand written English. 
11. Investigator believes that the participant has the capacity such that 
they can provide informed consent and successfully and safely 
operate all study devices and is capable of adhering to the protocol 
and completing the study 
 
Exclusion Criteria 
1. 
Prior use of Tandem t:slim X2 insulin pump with Control-IQ 
technology 
2. 
Two or more episodes of severe hypoglycemia (needing assistance) 
in the past 6 months 
3. 
History of inpatient psychiatric treatment in the past 6 months 
4. 
History of drug abuse (defined as any illicit drug use) or history of 
alcohol abuse prior to screening or unwillingness to agree to abstain 
from illicit drugs throughout the study.  
5. 
History of significant heart disease, lung disease, liver disease, 
chronic kidney disease, or other systemic disease determined by 
investigator to interfere with the study, or make required exercise 
unsafe 
6. 
History of significant vision, hearing, or dexterity problems that will 
impair use of the closed loop system 
7. 
Use of glucocorticoids, beta blockers, sulfonylureas, meglitinides or 
other medications specifically listed in section 8.3 of the protocol or 
determined by investigator to interfere with the study 
8. 
Unstable dose of SGLT-2 inhibitor, GLP-1 receptor agonist, or other 
adjuvant medication specifically listed in section 8.3 of the protocol, 
or starting a new glucose lowering agent during the trial. 
9. 
Unstable dose of any medication used for weight loss, as listed in 
section 8.3 of the protocol, or starting a new medication for weight 
loss during the trial. 
10. Abnormal screening electrocardiogram consistent with increased risk 
during exercise, such as arrhythmia, ischemia, or prolonged QTc 
interval (>450 ms) 
11. History of hemodialysis  
12. History of adrenal insufficiency 
13. Uncontrolled hypo- or hyperthyroidism 
14. Significant diabetes related complications, based on investigator 
assessment 
15. Immediate family member (spouse, biological or legal guardian, 
child, sibling, parent) who is an investigative site personnel directly 
affiliated with this study or who is an employee of Tandem Diabetes 
Care, Inc. 

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PARTICIPANT AREA 
DESCRIPTION 
Sample Size 
Up to 30 individuals initiating use of the study system in closed-loop 
mode, with the goal of at least 24 completing the trial 
Treatment Groups 
All participants will use the study-assigned Control-IQ pump in closed-
loop mode. 
Participant Duration 
~8-12 weeks, depending on duration of run-in phase 
Study Duration (planned) 
~5 months from first enrollment until last participant visit 
Protocol Overview/Synopsis 
After consent is signed, eligibility will be assessed.  Eligible participants 
not currently using a Dexcom G6 CGM or using a Dexcom G6 CGM with  
<85% of possible glucose values captured during the 14 days prior to 
enrollment will initiate a CGM run-in phase of 2-4 weeks. Participants 
who skip or successfully complete the CGM run-in will be trained on use 
of the study pump in open-loop mode and will initiate a pump run-in 
phase of 2-4 weeks that will include insulin therapy adjustment to 
optimize open-loop glycemic control. 
  
Participants who successfully complete the open-loop pump run-in will be 
trained on use of the study pump in closed-loop mode and will use the 
study system (pump and CGM) in closed-loop mode for 6 weeks. 
 
Subjects will be asked to use programmed sleep activity each night and 
perform exercise challenges with exercise mode enabled at least once per 
week. 
 
Questionnaires will be given at the screening visit after consent; before 
starting closed-loop use (Control-IQ Phase); and after 6 weeks of closed-
loop use. Semi-structured interviews will be performed at the end of the 
study to better determine the experience of using the study device 
 
Study Safety Plan:  
Participants will be given a blood glucose and ketone meter to use 
throughout the study, and will be trained on their use by qualified staff. 
BGM readings will be performed in accordance with the study safety plan 
and per CGM manufacturer instructions. Ketone readings will be 
performed per the study safety plan. 
Site investigators may adjust insulin delivery profile settings as needed 
throughout the study in accordance with their clinical practice. 
 

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Figure 1: Schematic of Study Design 
Screening/Enrollment 
•
Eligibility assessment and informed consent 
•
Device download and adherence assessment for current CGM user 
CGM Placement/Training 
2-4 Week Run-In with home use of study CGM  
Tandem pump start and Open-Loop mode training 
 
Eligible to  
Skip CGM 
Run-In*? 
No 
Yes 
* Current use of Dexcom G6 CGM with at least 85% of possible readings captured during the 
  14 days prior to enrollment 
6 Weeks - End of Study 
6-Week home use of Control-IQ in Closed-Loop mode 
Phone Contact: Day 3; Weeks 1, 4 
Clinic Visit: Week 2 
2-4 Week Run-In with home use of pump in Open-Loop mode 
Run-in Review – Reassess Eligibility 
Run-in Review – Reassess Eligibility 
Control-IQ training and Closed-Loop initiation 

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Table 1: Schedule of Study Visits and Procedures 
1 Interview completed within 28 days of completion of 6-Week visit 
2 Weight only 
3 Participants will be instructed to contact study staff after each exercise challenge to review AE’s and diabetes 
management around exercise. 
 
Screen-
ing Visit 
CGM 
Run-in 
Visit (may 
be 
repeated 
after 2 
weeks) 
Pump 
Training 
Visit and 
Settings 
Optimization 
(may be 
repeated 
after 2 
weeks) 
Control-
IQ Closed-
Loop 
Training 
Visit 
Control-IQ Closed-Loop Use 
 
 
2-4 weeks 
2-4 weeks 
 
3d 
1w 
2w 
4w 
6w 
+3d 
UV 
Exercise3 
Visit (V) or Contact (C) 
V 
V 
V 
V 
C 
C 
V 
C 
V 
C 
V/
C 
C 
Informed Consent  
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history/ 
physical exam 
X 
 
 
 
 
 
 
 
 
 
 
 
Height, weight, 
blood pressure and pulse 
X 
 
 
X2 
 
 
 
 
X2 
 
 
 
HbAlc (POC or local 
lab) 
X 
 
 
 
 
 
 
 
 
 
 
 
Central Lab: C-peptide 
and Glucose; HbA1c 
X 
 
 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test (females 
of child-bearing 
potential) 
X 
 
 
X 
 
 
 
 
 
 
 
 
Questionnaires/Surveys 
X 
 
X 
X 
 
 
 
 
X 
 
 
 
Semi-structured 
interview 
 
 
 
 
 
 
 
 
X1 
 
 
 
Assessment of CGM use 
X 
X 
 
 
 
 
 
 
 
 
 
 
Study system training 
 
X 
X 
X 
 
 
 
 
 
 
X 
 
AE Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Upload device data 
from home 
 
 
 
 
X 
X 
 
X 
 
 
X 
 
Download device data 
at clinic visit 
 
X 
X 
X 
 
 
X 
 
X 
 
X 
 

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Chapter 1: Background Information 
1 
1.1 Disease Background 
2 
More than 34 million people in the United States have diabetes, with type 2 diabetes accounting 
3 
for approximately 90% to 95% of cases. In the last 20 years, the number of adults diagnosed with 
4 
diabetes has more than doubled as the American population has aged and become more overweight 
5 
or obese. Diabetes is the 7th leading cause of death in the United States (and may be 
6 
underreported). 
7 
Insulin pump use in individuals with type 2 diabetes is relatively low. However, there is an 
8 
increasing uptake of insulin pump use in this population. The benefits of insulin pump use with 
9 
Automated Insulin Dosing (AID) technology in individuals with type 2 diabetes has not been well 
10 
established in clinical trials, although long term follow-up of real-world data has shown AID use 
11 
with Control-IQ technology can show significant glycemic benefits in this population, whether 
12 
transitioning from multiple daily injections (MDI) or prior pump use. Retrospective analysis of 
13 
134 prior pump users with type 2 diabetes who purchased a new Tandem insulin pump with 
14 
Control-IQ technology showed time in range was 76% (IQR 69-82%) and time below range was 
15 
0.5% (IQR 0.2-1.0%) at 180 days out. For 173 participants transitioning from MDI, use of Control-
16 
IQ technology resulted in time of range of 74% (IQR 63-84%) and time below range 0.3% (IQR 
17 
0.1-0.6%) at 180 days of use (1). Additionally, retrospective analysis of real-world use out to one 
18 
year in 378 individuals with type 2 diabetes who software updated from Basal-IQ technology to 
19 
Control-IQ technology showed significant improvements in time in range 70-180 mg/dL (69% at 
20 
baseline, 78% at one year) (2). 
21 
 
22 
1.2 Device Background 
23 
The t:slim X2 insulin pump with Control-IQ technology is an advanced hybrid closed-loop (HCL) 
24 
system, developed and manufactured by Tandem Diabetes Care, Inc. and cleared in the U.S. by 
25 
the FDA for individuals with type 1 diabetes. Control-IQ is integrated with the Dexcom G6 
26 
continuous glucose monitor (CGM) and uses CGM values to predict glucose values 30 minutes in 
27 
the future. Based on the predicted glucose, Control-IQ modulates basal insulin delivery, and 
28 
delivers automated correction boluses to mitigate impending hyperglycemia. The current Control-
29 
IQ system is FDA approved down to age 6 years old for individuals with type 1 diabetes, and has 
30 
been found to improve time in range (70-180 mg/dL) and decrease both time <70 mg/dL and time 
31 
>180 mg/dL (3,4). There are over 150,000 users of the system since it became commercially 
32 
available in 2020.  A recent evaluation of real-world use of the system in 9,451 users age ≥6 years 
33 
with at least 12 months of system use found results comparable to those found in the randomized 
34 
trials (2).  
35 
 
36 

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37 
Figure 2. t:slim X2 with Control-IQ and Dexcom G6 system 
38 
Since the initial approval of the system, modifications have been made in the software, which is 
39 
referred to as version 1.5. These modifications include modest usability improvements and other 
40 
enhancements intended to further reduce risk. The Control-IQ 1.5 algorithm also removes the 3 
41 
units/hr basal clipping, allowing the pump to deliver programmed user profile basal rates above 3 
42 
units/hr. This has the potential to further improve outcomes in individuals with type 2 diabetes 
43 
who are often using basal rates at or above this threshold. 
44 
1.3 Rationale 
45 
The objective of this single-arm, prospective study is to assess safety and explore glycemic 
46 
outcomes associated with use of the Control-IQ system in adults with type 2 diabetes to provide 
47 
data to design a subsequent larger study.  
48 
1.4 Potential Risks and Benefits of the Investigational Device 
49 
Risks and benefits are detailed below. Loss of confidentiality is a potential risk; however, data are 
50 
handled securely to minimize this risk. Hypoglycemia and hyperglycemia and ketone formation 
51 
are always a risk in participants with type 2 diabetes and insulin treatment, and participants will 
52 
be monitored for this. 
53 
1.4.1 Known Potential Risks 
54 
1.4.1.1 Potential Risks and Benefits of the CLC System 
55 
Even though the study system has been tested prior to this study, there is still a risk that parts of 
56 
the system may not function properly. The following are possible reasons the system may deliver 
57 
too much insulin or incorrectly stop insulin delivery: 
58 
• CGM sensor reads higher or lower than the actual glucose level which increases risk for 
59 
hypoglycemia and hyperglycemia with automated insulin delivery system; 
60 
• Device malfunctions that could produce a suspension of insulin delivery or over delivery of 
61 
insulin. 
62 
1.4.1.2 Risk of Hypoglycemia 
63 
As with any person having diabetes and using insulin, there is always a risk of hypoglycemia. The 
64 
frequency of hypoglycemia should be no more and possibly less than it would be as part of daily 
65 
living. Symptoms of hypoglycemia can include sweating, jitteriness, and not feeling well. Just as 
66 
at home, there is the possibility of fainting or seizures (convulsions) and that for a few days the 
67 

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participant may not be as aware of symptoms of hypoglycemia. A CGM functioning poorly and 
68 
significantly over-reading glucose values could lead to inappropriate insulin delivery. 
69 
1.4.1.3 Risk of Hyperglycemia 
70 
Hyperglycemia and ketonemia could occur if insulin delivery is attenuated or suspended for an 
71 
extended period or if the pump or infusion set is not working properly. Although less common in 
72 
individuals with type 2 diabetes than in those with type 1 diabetes, DKA can still occur. Extreme 
73 
levels of hyperglycemia and dehydration can lead to hyperosmolar hyperglycemic syndrome 
74 
(HHS). A CGM functioning poorly and significantly under-reading glucose values could lead to 
75 
inappropriate suspension of insulin delivery. All subjects will be issued a glucose meter and 
76 
glucose test strips, as well as a ketone meter and ketone test strips, to use to carefully monitor for 
77 
hyperglycemia and ketones and be given instructions on how to mitigate hyperglycemia and 
78 
ketosis should it occur.  
79 
1.4.1.4 Fingerstick Risks 
80 
About 1 drop of blood will be removed by fingerstick for measuring blood glucose and sometimes 
81 
Hemoglobin A1c (HbA1c). This is a standard method used to obtain blood for routine hospital 
82 
laboratory tests. Pain is common at the time of lancing. In about 1 in 10 cases, a small amount of 
83 
bleeding under the skin will produce a bruise. A small scar may persist for several weeks. The risk 
84 
of local infection is less than 1 in 1000. This should not be a significant contributor to risks in this 
85 
study as fingersticks are part of the usual care for people with diabetes. 
86 
1.4.1.5 Venipuncture Risks 
87 
A hollow needle/plastic tube may be placed in the arm for taking blood samples. Blood draws can 
88 
cause some common reactions like pain, bruising, or redness at the sampling site. Less common 
89 
reactions include bleeding from the sampling site, formation of a small blood clot or swelling of 
90 
the vein and surrounding tissues, and fainting. 
91 
1.4.1.6 Subcutaneous Catheter Risks 
92 
Whenever the skin is broken there is the possibility of bleeding and bruising. The CGM sensor 
93 
and pump infusion sets are inserted under the skin. It is possible that any part that is inserted 
94 
under the skin may cause an infection, which could produce swelling, redness, and pain. These 
95 
occur very infrequently, but if an infection were to occur, oral and/or topical antibiotics may be 
96 
prescribed. The risk of skin problems could be greater if a sensor or infusion set is used for 
97 
longer than it is intended to be used. Therefore, participants will be carefully instructed about 
98 
proper use of these components. 
99 
On rare occasions, the CGM sensor may break and leave a small portion of the sensor probe under 
100 
the skin that may cause redness, swelling or pain at the insertion site. The participant will be 
101 
instructed to notify the site immediately if this occurs. 
102 
1.4.1.7 Risk of Exercise 
103 
Exercise may lead to injury, hypoglycemia or hyperglycemia, or significant events, such as 
104 
myocardial infarction or other significant cardiac event. Subjects will be instructed on how to 
105 
prepare for exercise by study staff, and intended use of the exercise activity feature. All subjects 
106 
will undergo a screening ECG to assure exercise can be completed safely. 
107 

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1.4.1.8 Risk of Device Reuse 
108 
All devices will be used by a single study participant only. There will be no device reuse. 
109 
1.4.1.9 Questionnaires and Semi-Structured Interviews 
110 
As part of the study, participants will complete questionnaires and participate in one-on-one semi-
111 
structured interviews which include questions about their private attitudes, feelings and behavior 
112 
related to the investigational equipment as well as managing diabetes. It is possible that some 
113 
people may find these questionnaires and interviews to be mildly upsetting. Similar questionnaires 
114 
and interviews have been used in previous research and these types of reactions have been 
115 
uncommon. 
116 
1.4.1.10 Other Risks 
117 
Some participants may develop skin irritation or allergic reactions to the adhesives used to secure 
118 
the CGM, or from tape to secure the insulin infusion sets for the continuous subcutaneous insulin 
119 
infusion. If these reactions occur, different adhesives or “under-taping” (such as with IV 3000, 
120 
Tegaderm, etc.) will be tried, sites will be rotated frequently, and a mild topical steroid cream or 
121 
other medication may be required.  
122 
Data downloaded from the CGM, pump, and the home glucose and ketone meter will be collected 
123 
for the study as measures of diabetes self-management behaviors. Downloaded data from the 
124 
participant’s personal CGM or pump (if any) will include data from prior to the date of the 
125 
screening visit. Some people may be uncomfortable with the researchers' having such detailed 
126 
information about their daily diabetes habits. 
127 
1.4.2 Known Potential Benefits 
128 
Participants may experience a significant improvement in glucose control. Hypoglycemia is the 
129 
number one fear of many individuals taking insulin and this fear often prevents optimal glycemic 
130 
control. Hyperglycemia will likely be reduced as well.  
131 
In addition, users of insulin pumps often take less insulin than users of basal/bolus injection 
132 
therapy. This may lead to weight loss, which will be tracked over the course of the study. 
133 
It is expected that this protocol will yield increased knowledge about using an automated 
134 
closed-loop to control glucose levels in people with type 2 diabetes. The individual participant 
135 
may or may not benefit from study participation. 
136 
1.4.3 Risk Assessment 
137 
It is the assessment of the investigators that this protocol is a clinical investigation involving 
138 
greater than minimal risk but that it does present the prospect of direct benefit to individual subjects 
139 
based on the following: (1) individuals with diabetes experience mild hypoglycemia and 
140 
hyperglycemia frequently as a consequence of the disease and its management, (2) the study 
141 
intervention involves periodic automated insulin dosing that may reduce the likelihood of 
142 
hypoglycemia, and periodic automated attenuation of insulin delivery that may reduce the 
143 
likelihood of hyperglycemia, (3) if any, hypo and/or hyperglycemia occur, mitigations are in place, 
144 
and have been tested in prior studies using the investigational device system in the home setting, 
145 
that limit the likelihood of excessive insulin dosing or prolonged withdrawal of insulin, and (4) 
146 

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rapid reversal of hypoglycemia and hyperglycemia can be achieved, In addition, it is the belief of 
147 
the investigators that this study also presents prospect of general benefit to others with diabetes. 
148 
1.5 General Considerations 
149 
The study is being conducted in compliance with the policies described in the study policies 
150 
document, with the ethical principles that have their origin in the Declaration of Helsinki, with the 
151 
protocol described herein, and with the standards of Good Clinical Practice (GCP). 
152 
There is no restriction on the number of participants to be enrolled by each clinical center toward 
153 
the overall recruitment goal. 
154 
In accordance with 21 CFR 812.66, the protocol is considered a significant risk device study, due 
155 
to the fact that the closed loop system is investigational in the population under study.  
156 
Therefore, an investigational device exemption (IDE) from the U.S. Food and Drug 
157 
Administration (FDA) is required to conduct the study. 
158 

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Chapter 2: Study Enrollment and Screening 
159 
2.1 Participant Recruitment and Enrollment 
160 
Enrollment will proceed with the goal of at least 30 participants initiating the main closed-loop 
161 
study phase and 24 participants completing the trial.  A maximum of 60 individuals may be 
162 
consented for screening in order to achieve this goal.  Participants who have signed consent and 
163 
started the screening process may be permitted to continue into the trial, if eligible, even if the 
164 
completion goal has been reached. 
165 
Study participants will be recruited from ~3 clinical centers in the United States.  All eligible 
166 
participants will be included without regard to gender, race, or ethnicity. Each site will be asked 
167 
to contribute ~10 participants (5 basal only / 5 MDI) toward the overall recruitment goal. 
168 
2.1.1 Informed Consent and Authorization Procedures 
169 
Potential eligibility may be assessed as part of a routine-care examination.  Before completing 
170 
any procedures or collecting any data that are not part of usual care, documented informed 
171 
consent will be obtained. 
172 
Once a potential study participant has been identified, the study protocol will be discussed with 
173 
the potential study participant by study staff.  The potential study participant will be given the 
174 
Informed Consent Form to read.  Potential study participants will be encouraged to discuss the 
175 
study with family members and their personal physicians(s) before deciding whether to 
176 
participate in the study. If the potential study participant is interested in the study, the 
177 
investigator will schedule a virtual or in-person visit to discuss study, and if the potential study 
178 
participant agrees to participate, the Informed Consent Form will be electronically signed 
179 
through the JCHR website.  A copy of the electronically signed consent form can be printed by 
180 
the participant and another copy will be printed by the site to add to the participant’s study 
181 
record. The site shall print a copy of the signed consent for the participant any time at the 
182 
participant’s request, at no cost, and without undue delay.  
183 
As part of the informed consent process, each participant will be asked to sign an authorization 
184 
for release of personal information. This will be done electronically as part of the consent 
185 
process. The investigator, or his or her designee, will review the study-specific information that 
186 
will be collected and to whom that information will be disclosed.  After speaking with the 
187 
participant, questions will be answered about the details regarding authorization. 
188 
A participant is considered enrolled when the informed consent form has been electronically 
189 
signed by both the participant and the investigator, and HIPAA authorization has been provided. 
190 
This process shall be document in the study records at each site (e.g., consent process note).  
191 
2.2 Participant Inclusion Criteria 
192 
Individuals must meet all of the following inclusion criteria in order to be eligible to participate 
193 
in the study. 
194 
1. Age ≥18 years old and residing in the US 
195 
2. Clinical diagnosis, based on investigator assessment, of type 2 diabetes for at least one 
196 
year 
197 

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3. Using a stable insulin dose for at least 3 months, to include A) basal insulin only, or B) 
198 
MDI, to include CSII (including use of AID systems other than Tandem Control-IQ) 
199 
4. Total daily insulin dose ≤200 units/day 
200 
5. Willing to use only aspart (novolog) or lispro (humalog) insulin with the study pump, 
201 
with no use of concentrated insulin above U-100, long-acting basal insulin injections, or 
202 
inhaled insulin 
203 
6. For females, not currently known to be pregnant 
204 
If female of childbearing potential, must agree to use a form of contraception to prevent 
205 
pregnancy while a participant in the study as documented in the study records. A 
206 
negative serum or urine pregnancy test will be required for all females of child-bearing 
207 
potential. Participants who become pregnant will be discontinued from the study. Also, 
208 
participants who during the study develop and express the intention to become pregnant 
209 
within the timespan of the study will be discontinued. 
210 
7. HbA1c ≥ 7.5% and ≤ 12% at screening 
211 
8. Has current glucagon product to treat severe hypoglycemia (injectable or nasal) at home 
212 
(will provide prescription if they do not have one) 
213 
9. Be willing to exercise for 30 minutes or more at least once per week during the main 
214 
phase of the study 
215 
10. Has the ability to read and understand written English 
216 
11. Investigator believes that the participant has capacity such that they can provide informed 
217 
consent and can successfully and safely operate all study devices and is capable of 
218 
adhering to the protocol and completing the study. 
219 
2.3 Participant Exclusion Criteria 
220 
Individuals meeting any of the following exclusion criteria at baseline will be excluded from 
221 
study participation. 
222 
1. Prior use of Tandem t:slim X2 insulin pump with Control-IQ technology 
223 
2. Two or more episodes of severe hypoglycemia (needing assistance) in the past 6 months 
224 
3. History of inpatient psychiatric treatment in the past 6 months 
225 
4. History of drug abuse (defined as any illicit drug use) or history of alcohol abuse prior to 
226 
screening or unwillingness to agree to abstain from illicit drugs throughout the study.  
227 
5. History of significant heart disease, lung disease, liver disease, chronic kidney disease, or 
228 
other systemic disease determined by investigator to interfere with the study, or make 
229 
required exercise unsafe 
230 
6. History of significant vision, hearing, or dexterity problems that will impair use of the 
231 
closed loop system 
232 
7. Use of glucocorticoids, beta blockers, sulfonylureas, meglitinides or other medications 
233 
specifically listed in section 8.3 of the protocol or determined by investigator to interfere 
234 
with the study 
235 
8. Unstable dose of SGLT-2 inhibitor, GLP-1 receptor agonist, or other adjuvant medication 
236 
specifically listed in section 8.3 of the protocol, or starting a new glucose lowering agent 
237 
during the trial. 
238 
9. Unstable dose of any medication used for weight loss, as listed in section 8.3 of the 
239 
protocol, or starting a new medication for weight loss during the trial. 
240 

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10. Abnormal screening electrocardiogram consistent with increased risk during exercise, 
241 
such as  arrhythmia, ischemia, or prolonged QTc interval (>450 ms) 
242 
11. History of hemodialysis  
243 
12. History of adrenal insufficiency 
244 
13. Uncontrolled hypo- or hyperthyroidism 
245 
14. Significant diabetes related complications, based on investigator assessment 
246 
15. Immediate family member (spouse, biological or legal guardian, child, sibling, parent) 
247 
who is an investigative site personnel directly affiliated with this study or who is an 
248 
employee of Tandem Diabetes Care, Inc. 
249 
2.4 Screening Procedures 
250 
After informed consent has been signed, a potential participant will be evaluated for study 
251 
eligibility through the elicitation of a medical history, performance of a physical examination by 
252 
study personnel and local laboratory testing if needed to screen for exclusionary medical 
253 
conditions. 
254 
The screening visit must be completed within 28 days of participant enrollment. 
255 
2.4.1 Data Collection and Testing 
256 
A standard physical exam (including vital signs and height and weight measurements) will be 
257 
performed by the study investigator or designee (a physician, fellow, nurse practitioner or a 
258 
physician assistant). 
259 
The following procedures will be performed/data collected/eligibility criteria checked and 
260 
documented: 
261 
• Inclusion and exclusion criteria assessed 
262 
• Demographics (date of birth, sex, race and ethnicity) 
263 
• Contact information (retained at the site and not entered into study database) 
264 
• Medical history, including existing comorbidities deemed clinically relevant (e.g. 
265 
retinopathy, nephropathy, neuropathy, history of cardiovascular events); in addition, details 
266 
specific to type 2 diabetes, including age at diagnosis, duration of disease, previous therapy, 
267 
and frequency of severe hypoglycemia will be collected 
268 
• Concomitant medications 
269 
• Physical examination to include: 
270 
 Weight, height 
271 
 Vital signs including measurement of blood pressure and pulse 
272 
• An electrocardiogram (ECG) will be administered and read locally by the investigator to 
273 
determine if the participant meets eligibility criteria with respect to the exercise component 
274 
of the study 
275 
• Fingerstick or blood draw for point-of-care or local laboratory determination of baseline 
276 
HbA1c level and any local laboratory testing required for eligibility assessment 
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• Blood draw for Central Lab determination of HbA1c and C-peptide with concurrent glucose 
278 
level 
279 
• Urine or serum pregnancy test for all women who have reached menarche and are 
280 
premenopausal and are not surgically sterile 
281 
• Barrier methods, oral contraceptives, and implantable and/or IUD-type contraceptives are 
282 
examples of methods that constitute acceptable methods of contraception for females of 
283 
child-bearing potential, and will be discussed with all such females who are not 
284 
postmenopausal or surgically sterile. 
285 
• Females are considered premenopausal per investigator discretion, typically with less 
286 
than 1 year since last menses. 
287 
• Participants will complete a set of baseline questionnaires, described in section 6.3  
288 
Screening procedures will last approximately 1-2 hours. 
289 
2.5 Screen Failures 
290 
Individuals who do not initially meet study eligibility requirements may be rescreened once at a 
291 
later date per investigator discretion. 
292 
 
293 
 
294 

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Chapter 3: CGM and Pump Run-in Phases 
295 
3.1 CGM Run-in Phase Overview 
296 
This phase must begin within 7 days of completion of the Screening visit. The purpose of this 
297 
CGM run-in phase is to 1) assess compliance with study procedures and 2) to introduce the study 
298 
CGM to study participants without current use of a Dexcom CGM. 
299 
Participants who currently use a Dexcom G6 CGM with at least 85% of possible CGM readings 
300 
captured during the 14 days prior to enrollment can skip the CGM Run-in phase. Participants who 
301 
do not currently use a Dexcom G6 CGM, or who do use that CGM but have <85% of possible 
302 
CGM readings in the 14 days prior to the time of enrollment, will be required to participate in the 
303 
CGM Run-in phase. 
304 
Participants will receive training on the study CGM as detailed below. This will be an unblinded 
305 
use of the study CGM.  
306 
3.2 Initiation of CGM 
307 
During an in-clinic visit that may coincide with the Screening visit, study CGM supplies will be 
308 
provided and the participant will be instructed to use the study CGM on a daily basis. Participants 
309 
using a personal CGM prior to the study will discontinue the personal CGM beginning in this 
310 
period. 
311 
3.2.1 CGM Training 
312 
CGM training will be provided by a qualified trainer to participants not currently using a personal 
313 
CGM identical to the study CGM as to how to use it in real-time to make management decisions 
314 
and how to review the data after an upload for retrospective review. CGM training will include: 
315 
• Instruction on how to insert the sensor and transmitter, including observation/supervision 
316 
of placement of a sensor 
317 
• Instruction on how to calibrate the CGM unit, if needed 
318 
• Guidance on accessing the CGM trace, either through a manufacturer-provided software 
319 
app or via a study-provided CGM receiver unit, or via a personal insulin pump if 
320 
participants use a pump that integrates with the study CGM 
321 
• Participants will be asked to perform fingerstick blood glucose measurements in 
322 
accordance with the labeling of the study CGM device 
323 
A copy of the study CGM user’s guide will be provided to the participant. 
324 
Participants may use available manufacturer-provided CGM software and features of the study 
325 
CGM related to mobile data access or remote monitoring, but will be instructed not to use any 
326 
third-party components for this purpose. The t:connect mobile app from Tandem Diabetes Care 
327 
will not be available for use during the trial, and will not pair to the study pump. 
328 
Upon completion of the CGM training components, study staff will document, using a checklist, 
329 
that the participant is familiar with the functions/features/tasks addressed during the training. 
330 

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3.3 Blood Glucose and Blood Ketone Testing 
331 
Participants will receive supplies for blood glucose and blook ketone testing. 
332 
• Blood glucose testing 
333 
o Participants will be provided with a study blood glucose meter, test strips, and any 
334 
software/hardware needed to download meter data . 
335 
o All study blood glucose meters will be QC tested with control solution if available prior to 
336 
dispensation.  A tested meter will not be used in a study if it does not read within the target 
337 
range at each concentration per manufacturer labeling.   
338 
o Participants will be reminded to use the study blood glucose meter for all fingerstick BGs 
339 
during the study. 
340 
o Participants will be given guidelines for treatment of low or high blood glucose. 
341 
• Blood ketone testing 
342 
o Participants will be provided with a study blood glucose meter, test strips, and any 
343 
software/hardware needed to download meter data. 
344 
o All study blood ketone meters will be QC tested with control solution if available prior to 
345 
dispensation.  A tested meter will not be used in a study if it does not read within the target 
346 
range at each concentration per manufacturer labeling.   
347 
o Participants will be reminded to use the study blood ketone meters per the study 
348 
hyperglycemia safety plan 
349 
o Participants will be given guidelines for treatment of positive ketone readings. 
350 
• Participants will be required to have glucagon at home. Participants who currently do not have 
351 
one will be given a prescription for glucagon as part of standard care (either emergency kit for 
352 
injections or nasal glucagon per investigator discretion). 
353 
3.4 Assessment of Successful Completion of the CGM Run-in Phase 
354 
Enrolled participants will have a follow-up visit approximately 14 days after initiation of the run-
355 
in phase to assess progress or successful completion of the phase.  If needed, one or more interim 
356 
visits or phone contacts may occur to assist the participant with any CGM use issues. Procedures 
357 
will include downloading of the study CGM data and the following: 
358 
• Assessment of compliance with the use of CGM to obtain at least 85% of possible CGM 
359 
valued during the run-in period 
360 
• Assessment of skin reaction in areas where a CGM sensor was worn or other safety issues 
361 
associated with CGM use 
362 
• Assessment of eligibility to continue to the pump run-in phase of the study 
363 
Participants who fail to meet the minimum CGM use requirement, or who the investigator believes 
364 
may benefit from an extension of the CGM run-in period, may at the investigator’s discretion be 
365 
allowed to continue CGM run-in for a second ~2-week period. These participants will have another 
366 
follow-up visit approximately 14 days after the prior visit for a reassessment using the same 
367 
procedures as described above. 
368 

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Participants who do not meet CGM use requirements after two 2-week periods of CGM run-in or 
369 
otherwise fail to meet study eligibility requirements will be withdrawn from the study. 
370 
3.5 Pump Run-in Phase Overview 
371 
This phase must begin either on the same day as the final CGM run-in review visit (for participants 
372 
participating in CGM run-in) or within 7 days of completion of the Screening visit (for participants 
373 
skipping the CGM run-in). The purpose of the Pump Run-in phase is 1) to assess compliance with 
374 
study procedures and 2) to allow the participant to transition to the study insulin pump, learn how 
375 
to use it in open-loop mode, and learn infusion set care. 
376 
Participants will receive training on use of the study pump in open-loop mode as detailed below.  
377 
3.6 Initiation of the Study Pump 
378 
During an in-clinic visit, the study pump, associated supplies, and training will be provided to 
379 
participants and the participant will be instructed to use the pump in open-loop mode in 
380 
conjunction with the study CGM until the Pump Run-in review visit. 
381 
3.6.1 Study Pump Training 
382 
Participants will receive study pump training on use of the pump in open-loop mode by a 
383 
qualified trainer: 
384 
• Participants will be fully instructed on the study insulin pump. The trainer will discuss 
385 
differences from the participant’s personal pump, if applicable, in important aspects such 
386 
as calculation of insulin on board and correction boluses and optional additional topics 
387 
such as: infusion site initiation, cartridge/priming procedures, setting up the pump, 
388 
charging the pump, navigation through menus, bolus procedures including stopping a 
389 
bolus, etc. 
390 
• Participants will be instructed to change the study insulin pump infusion set at least once 
391 
every 3 days or per manufacturer guidelines, whichever is shorter. 
392 
• Participants using bolus insulin doses at enrollment will be trained to use the pump’s bolus 
393 
calculator. 
394 
o For subjects who may only bolus one or two meals a day, or use fixed bolus 
395 
amounts as part of their prior treatment plan, they may continue to do this in the 
396 
study, but they will be taught to enter the same number of units in the bolus 
397 
calculator (Simplified Bolus Plan). 
398 
o Additionally, it is possible during the study some subjects in the basal only group, 
399 
or using simplified boluses, may realize the need to add boluses or begin using the 
400 
bolus calculator, respectively. As such, they will be advanced in their bolus strategy 
401 
per investigator discretion.  
402 
• The study team will assist the participant in study pump infusion site initiation and will 
403 
start the participant on the study pump. The study pump will be programmed with the 
404 
participant’s usual basal rates and pump parameters, if applicable. The participant’s 
405 
personal pump, if any, will be removed. 
406 

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• The participant will be supervised with the study pump during at least one meal or snack 
407 
bolus to ensure participant understanding of the pump features. 
408 
• The participant will be encouraged to review the literature provided with the pump and 
409 
infusion sets after the training is completed. 
410 
• The participant will be trained on severe hypoglycemia emergency procedures including 
411 
removal of the study pump and administration of glucagon. 
412 
• What to do when exercising while using the system 
413 
• The participant will be assessed for understanding of the system interface and how to react 
414 
to safety/alert messages. 
415 
• To prevent insulin stacking from basal insulin that is on board, participants using basal 
416 
insulin at baseline will be instructed, and supervised by study staff, to set a temp basal rate 
417 
to 0% that will end 24 hours after last injection of long-acting insulin, at which time the 
418 
pre-programmed basal rate will be turned on. Study investigators may adjust this procedure 
419 
per their usual clinical practice, and may customize this plan based on the type of basal 
420 
insulin used (for example, insulin degludec with a longer half-life may require a basal rate 
421 
of 50% for a second day). 
422 
A copy of the study pump user’s guide will be provided to the participant. 
423 
3.6.2 Initiation of Pump by MDI Participants 
424 
For MDI participants being started on the study pump, an initial basal insulin profile will be 
425 
customized on a per-participant basis. Total daily insulin dose will be reduced by approximately 
426 
20% as a general rule, with a recommended method outlined in a separate procedures’ manual. 
427 
Further adjustments to total daily dose (TDD) and intraday basal rate profile may be made during 
428 
the Pump run-in period. 
429 
Participants will complete training on the study pump as described above, with additional 
430 
emphasis on topics relevant to new pump users, such as infusion site initiation, cartridge/priming 
431 
procedures, setting up the pump, charging the pump, navigation through menus, bolus 
432 
procedures including stopping a bolus, etc. 
433 
The study team will assist the participant in study pump infusion site initiation and will start the 
434 
participant on the study pump. The study pump will be programmed with the participant’s insulin 
435 
requirements. 
436 
3.6.3 System Use Guidelines 
437 
The participant will be instructed to use the system in open-loop mode only. 
438 
Participants will be provided with sufficient supplies to last until the subsequent visit. 
439 
Participants will be provided with contact information and will be asked to call the study 
440 
clinical staff for any health-related issues and for technical issues with the system. 
441 
Upon completion of the study pump training components, study staff will document, using a 
442 
checklist, that the participant is familiar with the functions/features/tasks addressed during the 
443 
training. 
444 

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Participants will be provided Hyperglycemia and Hypoglycemia Guidelines during closed-loop 
445 
use (section 5.2) for when their glucose levels are >300 mg/dL for more than 60 minutes or >400 
446 
mg/dL at any time or <70 mg/dL. 
447 
3.7 Blood Glucose Testing 
448 
Participants who skipped the CGM Run-in phase will receive supplies for blood glucose testing 
449 
and blood ketone testing as described above. 
450 
3.8 Assessment of Successful Completion of the Pump Run-in Phase 
451 
Participants will have a follow-up visit approximately 14 days after initiation of the Pump Run-in 
452 
phase to assess progress or successful completion of the phase.  If needed, one or more interim 
453 
visits or phone contacts may occur to assist the participant with any system use issues. Procedures 
454 
will include downloading of the study pump and CGM data and the following: 
455 
• Assessment of compliance with use of the pump, including avoidance of closed-loop mode, 
456 
timely cartridge and infusion set changes, and announcement of meal boluses throughout 
457 
the run-in period 
458 
• Review of insulin therapy settings and adjustments to pump settings (basal rates, correction 
459 
factor, insulin-to-carbohydrate ratio, etc.) or injection strategies in response to major trends 
460 
observed in the CGM data 
461 
• Assessment of eligibility to continue to the main closed-loop phase of the study 
462 
Participants who the investigator believes may benefit from an extension of the Pump Run-in 
463 
period may continue Pump Run-in for a second ~2-week period. These participants will have 
464 
another follow-up visit approximately 14 days after the prior visit for a reassessment using the 
465 
same procedures as described above. 
466 
Participants who do not meet system use compliance requirements after a second period of Pump 
467 
Run-in or otherwise fail to meet study eligibility requirements will be withdrawn from the study. 
468 
3.9 Optimization of Insulin Therapy 
469 
Data will be obtained from CGM and/or pump downloads at the CGM and pump run-in review 
470 
visit(s). Adjustments to pump settings (basal rates, correction factor, insulin-to-carbohydrate ratio, 
471 
etc.) or injection strategies will be made in response to major trends observed in the CGM data, 
472 
with flexibility for clinicians to adhere to guidelines and practices established at each individual 
473 
practice rather than a fixed set of heuristics for all clinical centers. 
474 
 
475 

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Chapter 4: Control-IQ (Closed-Loop) Phase 
476 
4.1 Control-IQ Phase Overview 
477 
Initiation of the Control-IQ study phase, involving use of the study pump in closed-loop mode for 
478 
6 weeks, will coincide with the final Pump Run-in follow-up clinic visit described above. 
479 
During the Control-IQ phase, visits and contacts will be scheduled as outlined in Table 2 below: 
480 
Table 2: Control-IQ Phase Visit and Phone Contact Schedule 
481 
Target Day/Week 
Contact Type1 
Target/Allowable Window 
(around Target Day/Week) 
3 days 
P 
± 2 days 
1 week 
P 
± 2 days 
2 weeks 
V 
± 4 days 
3 weeks 
P 
± 4 days 
6 weeks 
V 
± 4 days 
3 days post-study 
P 
± 1 days 
Post Exercise Challenge 
C 
Within 24 hours 
1 Contact Types are defined as Clinic Visit (V) or Phone call (P); Phone calls may be replaced by Videoconferences or Clinic 
482 
Visits at investigator discretion 
483 
4.1.1 Study Pump Training  
484 
Participants will receive instruction from a qualified trainer on use of the study pump in closed-loop 
485 
mode, to include the following:  
486 
• How to turn on and off Control-IQ technology 
487 
• How to understand when Control-IQ is increasing or decreasing basal rates 
488 
• How to administer a meal or correction boluses during closed-loop system use 
489 
• What to do when exercising while using the system in closed-loop mode 
490 
• How to enable the sleep function and set the sleep schedule 
491 
• The participant will be assessed for understanding of the system interface and how to react 
492 
to safety/alert messages. 
493 
Upon completion of the study pump training components, study staff will document, using a 
494 
checklist, that the participant is familiar with the functions/features/tasks addressed during the 
495 
training. 
496 
4.1.2 System Use Guidelines 
497 
The participant will be instructed to use the system in closed-loop mode except if insulin is 
498 
delivered by any means other than the study pump (e.g. injection of subcutaneous insulin via 
499 
syringe in the event of infusion site failure). If insulin is delivered by any means other than the 
500 
study pump, the participant will be instructed to turn off Control-IQ for approximately four hours. 
501 

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The participant will also be instructed to contact study staff in case of illness with an elevated 
502 
temperature >101.5 degrees Fahrenheit (38.6 degrees Celsius), other periods of significant illness, 
503 
or during periods of use of medications such as epinephrine for the emergency treatment of a 
504 
severe allergic reaction or asthma attack in addition to use of oral or injectable glucocorticoids to 
505 
determine if closed-loop use should be temporarily discontinued. 
506 
Participants will be provided with sufficient supplies to last until the subsequent visit. 
507 
Participants will be provided with contact information and will be asked to call the study 
508 
clinical staff for any health-related issues and for technical issues with the system. Participants 
509 
may use the study pump without Control-IQ activated and study CGM during periods of 
510 
component disconnections or technical difficulties. 
511 
Study staff will discuss with the participant that routine contact is required and will make 
512 
arrangements for the contacts.  If the participant cannot be reached, the participant’s other contact 
513 
methods will be utilized, including an emergency contact.  Participants who are not compliant with 
514 
the arranged contacts on two separate occasions may be discontinued at the discretion of the 
515 
investigator.  
516 
4.1.3 Home Use of the Study System 
517 
After training on closed-loop aspects of the study system has been completed, participants will 
518 
proceed with home use (meaning free-living use at school, home, etc.) of the study pump. 
519 
Participants will be asked to complete an exercise log, and use the exercise activity mode of the 
520 
study pump at least once per week for a minimum of 30 minutes of exercise.  
521 
Follow up visits will occur per the visit listing described below. If necessary, visits should be 
522 
completed out-of-window rather than missed. A visit is not considered missed until the next 
523 
visit/phone window opens.  
524 
The goal will be for all participants to complete all scheduled visits.  However, participants who 
525 
(because of unforeseen circumstances or due to changes in contact precautions that may be 
526 
needed during the evolving COVID-19 pandemic) are unable or unwilling to return for all 
527 
follow-up visits will be permitted to return for key visits only as an alternative to withdrawal 
528 
from the study.  When a participant is placed into this status, missed visits will not be recorded as 
529 
protocol deviations (since they would not be recorded as protocol deviations if the participant 
530 
was dropped from the study). 
531 
Additional office visits may occur as needed. 
532 
Study Specific Guidance for the Exercise Challenges 
533 
Study staff will review with participants that for each weekly exercise challenge, they will be 
534 
required to: 
535 
1. Have extra carbohydrate containing snacks on hand during and after exercise. 
536 
2. Consider activation of exercise activity up to 45 minutes ahead of actual exercise, to allow 
537 
for less insulin on board when starting exercise. 
538 
3. Consider reducing the last meal bolus prior to exercise as a way to reduce insulin on board 
539 
and limit hypoglycemia. 
540 

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4. Participants will write down the type of exercise performed, as well as the start and stop time 
541 
of each exercise session on the study logbook, as this may not correlate exactly with exercise 
542 
activity use on the pump. 
543 
5. Participants will be instructed that they may stop the exercise challenges at any point for 
544 
injury or development of new symptoms (development of chest pain/pressure, feeling unwell, 
545 
development of hypoglycemic symptoms, undue shortness of breath, signs of poor perfusion 
546 
(leg pain/claudication), or for any other reason. 
547 
6. Participants will then notify the site within 24 hours after completion of each exercise 
548 
challenge. The site staff will review for adverse events or new symptoms (See section 4.1.11) 
549 
and review guidance on the need to stop future exercise challenges if any adverse events or 
550 
new symptoms occurred per clinician judgement based on the severity of symptoms. 
551 
7. If a participant does not call within a week, study staff should perform an unscheduled 
552 
contact to remind the participant of the required follow-up and encourage completion of the 
553 
remaining exercise challenges. If a participant has to reschedule their exercise sessions, or 
554 
postpone them for any reason (for example, the gym where they walk on a treadmill is too 
555 
crowded and they did not want to enter to limit exposures due to COVID-19), they will be 
556 
allowed to do so, and this will not be considered a protocol deviation. Similarly, if future 
557 
exercise challenges are cancelled due to safety concerns, this will not be considered a 
558 
protocol deviation. 
559 
Each clinical site can customize this guidance per their established clinical practice, to include 
560 
how long to keep exercise activity active after the exercise challenge has ended. 
561 
4.1.4 Study Device Download 
562 
Participants will be instructed to download the study CGM and pump prior to each phone contact 
563 
throughout the remainder of the study. 
564 
4.1.5 3-Day Phone Contact 
565 
Study staff will perform a phone call with the participant within 3 (±2) days following initiation 
566 
of closed-loop system use. 
567 
The following will occur: 
568 
• Assessment of compliance with study device use by review of any available device data 
569 
• Assessment of adverse events, adverse device effects, and device issues 
570 
• Study staff will answer any questions related to device use and follow the procedure for 
571 
insulin pump optimization described above if necessary. 
572 
4.1.6 1-Week Phone Contact  
573 
Study staff will perform a phone call with the participant within 7 (±2) days following Initiation 
574 
of the Control-IQ study phase. 
575 
The following will occur: 
576 
• Assessment of compliance with study device use by review of any available device data 
577 
• Assessment of adverse events, adverse device effects, and device issues 
578 

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• Study staff will answer any questions related to device use and follow the procedure for 
579 
insulin pump optimization described above if necessary. 
580 
4.1.7 2-Week Visit 
581 
Participants will have a follow-up visit 14 (±4) days from the date of initiation of closed-loop 
582 
system use. 
583 
The participant will be offered review training to address any questions on the use of the study 
584 
device including meal bolus strategies and strategies related to pump use and exercise. 
585 
The following will occur: 
586 
• Assessment of compliance with study device use by review of any available device data 
587 
• Assessment of adverse events, adverse device effects, and device issues 
588 
• Study staff will answer any questions related to device use and follow the procedure for 
589 
insulin pump optimization described above if necessary. 
590 
• Download of device data (study pump, study CGM, study BG meter) as available 
591 
4.1.8 4-Week Phone Contact  
592 
Study staff will perform a phone call with the participant within 28 (±4) days from the date of 
593 
initiation of closed-loop system use. 
594 
The following will occur: 
595 
• Assessment of compliance with study device use by review of any available device data 
596 
• Assessment of adverse events, adverse device effects, and device issues 
597 
• Study staff will answer any questions related to device use and follow the procedure for 
598 
insulin pump optimization described above if necessary. 
599 
4.1.9 6-Week Visit  
600 
All participants will have a final visit within 42 (±4) days from the date of initiation of closed-loop 
601 
system use, during which the following will occur: 
602 
• Completion of questionnaires  
603 
• Collection of exercise logbook 
604 
• Weight and height measurements will be repeated 
605 
• Assessment of adverse events, adverse device effects, and device issues 
606 
• Download of device data (study pump, study CGM, study BG meter) as available 
607 
• Study staff will supervise the participant’s transition back to their prior therapy 
608 
o Study staff will re-evaluate the subject’s baseline therapy doses, noting changes in 
609 
basal rates, carbohydrate ratios, and correction factors in use at the end of the 
610 
trial. 
611 
o For those subjects using basal insulin, doses will be adjusted to best match the 
612 

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current daily insulin requirements from CSII use, typically = (total daily dose + 
613 
20%)/2, with further modification as per clinical site usual practice.  
614 
o Study staff will confirm subjects have carbohydrates on hand for their drive back 
615 
home, and instruct subjects to check their glucose levels when they arrive at 
616 
home, prior to bedtime, and at least one time overnight on the first night to 
617 
monitor for hypoglycemia, reminding subjects that insulin on board can be active 
618 
for the next few hours even after stopping their pump. 
619 
4.1.10 3-Day Post-Study Call  
620 
All participants will have a post-study phone call 3 (±1) days after the date of their 6-Week visit 
621 
and transition back to their prior insulin therapy, during which the following will occur: 
622 
• Check on transition back to usual home diabetes care 
623 
• Assessment of adverse events 
624 
4.1.11 Exercise Challenge Follow-Up  
625 
Participants will be instructed to contact study staff within 24 hours of completing each exercise 
626 
challenge, per guidance in section 4.1.3. The follow up call will review: 
627 
• The start and stop time, as well as the type of exercise performed. 
628 
• Assessment of adverse events 
629 
• Documentation of any safety concerns if future exercise challenges are cancelled. 
630 
4.2 Early Termination Visit (If Applicable) 
631 
Participants will be asked to come for an end of study visit in the event of withdrawal or early 
632 
termination. 
633 
4.3 Unscheduled Visits 
634 
Participants may have unscheduled visits during the study period if required for additional device 
635 
training or other unanticipated needs per the study investigator discretion. 
636 

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Chapter 5: Study Devices 
637 
5.1 Description of the Investigational Device 
638 
5.1.1 Insulin Pump 
639 
The study system will include the Tandem t:slim X2 insulin pump (K201214, Tandem Diabetes 
640 
Care, San Diego, CA) using firmware version 1.5. 
641 
5.1.2 Continuous Glucose Monitoring 
642 
The study CGM will include Dexcom G6 transmitter and sensors. The CGM sensor will be 
643 
replaced at least once every 10 days or as per manufacturer instructions. 
644 
5.1.3 Blood Glucose Meter and Strips 
645 
Blood glucose levels will be measured using the study-assigned blood glucose meter 
646 
(glucometer) and the CGM device will be calibrated if needed using the study glucometer and 
647 
strips in accordance with the manufacturer’s labeling. (Contour NEXT or Contour NEXT ONE, 
648 
Ascensia Diabetes Care US, Inc., 5 Wood Hollow Rd, Parsippany, NJ 07054 USA. 
649 
5.1.4 Ketone Meter 
650 
The study blood ketone meter is the Precision Xtra Blood Glucose and Ketone Monitoring 
651 
System (Abbott Diabetes Care). 
652 
Blood ketone levels will be measured when needed to evaluate prolonged hyperglycemia. The 
653 
blood glucose meter component of the Precision Xtra device will not be used. 
654 
5.1.5 Study Device Accountability Procedures 
655 
Device accountability procedures will be detailed in the site procedures manual. 
656 
5.2 Safety Measures 
657 
5.2.1 CGM Calibration 
658 
Throughout the study, participants will be instructed to calibrate the study CGM in accordance 
659 
with manufacturer labelling. 
660 
5.2.2 Pump Failure 
661 
The study insulin pump is designed to revert to open-loop delivery of preprogrammed basal 
662 
insulin levels in the event that CGM data are not available. The pump also includes various 
663 
alarms and alerts to notify the user when there is a problem with insulin delivery. 
664 
5.2.3 Hypoglycemia Threshold Alarm and Safety Protocol 
665 
When using the study device, hypoglycemia low threshold alerts will be set to no lower than 70 
666 
mg/dL, and if a participant’s CGM reading is <70 mg/dL, subjects will be instructed to treat with 
667 
~15 grams of carbohydrate and perform fingerstick testing as necessary per CGM manufacturer 
668 
instructions. 
669 

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5.2.4 Hyperglycemia Threshold Alarm and Safety Protocol 
670 
During the course of the study, participants will be permitted to change this setting, but will be 
671 
instructed to choose a value no greater than 300 mg/dL. 
672 
During the CGM run-in and open-loop pump wear period, if a participant’s CGM reading is 
673 
>300 mg/dL for over 2 hours: 
674 
• Perform a blood glucose meter check. 
675 
• For bolus insulin users, if the blood glucose is >300 mg/dL, give a correction dose of insulin 
676 
if no bolus has been given within the last hour. If blood glucose does not decrease by 50 
677 
mg/dL within 90 minutes of the correction dose, contact study staff for further instructions. 
678 
• For basal insulin users, contact study staff for further instructions. 
679 
During the time period when the closed-loop system is operational and active, if a participant’s 
680 
CGM reading is >300 mg/dL for over 1 hour or ≥400 mg/dL at any point, or the participant 
681 
experiences severe symptoms of hyperglycemia (nausea, vomiting, abdominal pain), the 
682 
participant will be instructed to take the following steps: 
683 
• Perform a blood glucose meter check. 
684 
• If the blood glucose is >300 mg/dL, check for blood ketones with the study ketone meter. 
685 
• If the ketone level is ≥ 0.6 mmol/L (or ≥ 2.5 mmol\L at any time), take correction insulin, 
686 
change insulin (pump) infusion site and contact study staff. Continue to monitor their 
687 
glucose and blood ketone levels until they return to normoglycemia and ketones are < 0.6 
688 
mmol/l. 
689 
 If ketones are <0.6 mmol/l, they will be advised to continue to monitor their glucose 
690 
until it returns to normoglycemia and to repeat the ketone measurement in 90 minutes 
691 
if necessary. 
692 
 If glucose fails to correct, or symptoms persist, contact study staff immediately for 
693 
further instructions, to include giving a correction dose by injection. 
694 
• If correction insulin is administered via insulin syringe, turn Control-IQ off for 
695 
approximately four hours and until glucose level has returned to <180 mg/dL. 
696 
• If unable to contacts study staff and the participant is vomiting, go to the Emergency 
697 
Room. 
698 
5.3 Participant Access to Study Device at Study Closure 
699 
Participants will be returned to their pre-study insulin therapy at the conclusion of the study and 
700 
must return all study-assigned materials to the clinical site.  Return of these materials must occur 
701 
within 7 weeks (49 days) of initiation of closed-loop system use.
702 

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Chapter 6: Testing Procedures and Questionnaires 
703 
6.1 Laboratory Testing 
704 
1. HbA1c: 
705 
• HbA1c level measured using the DCA2000 or comparable point of care device or local 
706 
lab at the Screening visit, if no comparable measurement is available from the 2 weeks 
707 
prior to enrollment 
708 
• HbA1c level measured at a Central Lab from blood draw performed at Screening visit 
709 
2. C-peptide/Glucose: 
710 
• C-peptide with concurrent glucose level measured at a Central Lab from blood draw 
711 
performed at Screening visit 
712 
3. Urine Pregnancy: 
713 
• Performed locally for females of child-bearing potential at Screening and at the Control-
714 
IQ phase initiation visit.  This will also be done anytime pregnancy is suspected. 
715 
Local laboratory testing will be performed if needed to screen for exclusionary medical 
716 
conditions. 
717 
6.2 Electrocardiogram (ECG) 
718 
An ECG will be administered using the clinic’s ECG machine and read locally by the 
719 
investigator at the Screening visit to determine if the participant meets eligibility criteria with 
720 
respect to the exercise component of the study. The printed ECG with the investigator’s 
721 
evaluation, signature and date must be saved in the study records (note – making a copy of the 
722 
ECG once signed preserves the integrity of the read due to the fragility of the printer paper). 
723 
6.3 Questionnaires 
724 
Questionnaires are completed by all participants at the study visits indicated in the table below. 
725 
Each questionnaire is described briefly below.  The procedures for administration are described 
726 
in the study procedures manual. 
727 
Table 3. Study Questionnaire Summary 
728 
MEASURE 
CONSTRUCT MEASURED/RELEVANT POINTS 
ADMINISTRATION 
POINTS 
Tandem Study-
Specific Baseline 
Survey 
A Tandem-specific 4-item questionnaire that captures 
information about Healthcare Provider relationships, comfort 
with new technologies for diabetes management, and comfort 
understanding written information. (3 mins) 
• Screening Visit 
Altarum Consumer 
Engagement (ACE) 
Measure – 
Commitment 
Subscale 
A 6-item questionnaire measuring commitment to everyday 
health behaviors. Predicts overall health, adherence to medical 
guidance, and success at chronic disease management. (2 mins) 
• Screening Visit 

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MEASURE 
CONSTRUCT MEASURED/RELEVANT POINTS 
ADMINISTRATION 
POINTS 
Tandem Pump 
Training Survey 
A Tandem-specific 4-item questionnaire that captures patient-
reported experience with Tandem pump training, including 
overall satisfaction and time investment. (3 mins) 
• Pump Run-In 
Initiation Visit 
• Control-IQ 
Initiation Visit 
DAWN Impact of 
Diabetes Profile 
(DIDP) 
A 7-item questionnaire providing a valid and reliable measure of 
the perceived impact of diabetes on quality of life, suitable for 
adults with Type 1 or Type 2 diabetes mellitus. (2 mins) 
• Screening Visit 
• Control-IQ 
Initiation Visit 
• 6-Week Visit 
Diabetes Impact and 
Device Satisfaction 
(DIDS) Scale 
A 12-item questionnaire focused on satisfaction related to 
insulin delivery devices (e.g., trust and ease of use) and diabetes-
related impact on daily life, such as worry around hypoglycemia 
and sleep interruptions. (3 mins) 
• Screening Visit 
• Control-IQ 
Initiation Visit 
• 6-Week Visit 
PROMIS Sleep-
Related Impairment 
Questionnaire 
An 8-item questionnaire that measures sleep disturbance and 
sleep-related impairment. (2 mins) 
• Screening Visit 
• Control-IQ 
Initiation Visit 
• 6-Week Visit 
System Usability 
Scale (SUS) 
A 10-item questionnaire that measures the overall usability of a 
system. It is a valid and reliable measure of the perceived 
usability of a system and is technology-agnostic. (2 mins) 
• Control-IQ 
Initiation Visit 
• 6-Week Visit 
 
729 
6.4 Semi-Structured Interviews 
730 
A semi-structured one-on-one interview may be completed concurrent with the 6-Week Visit or 
731 
within a 28-day period following that visit. The interview will last approximately 30 minutes and 
732 
will be conducted by Tandem staff using a script of open-ended questions to gather feedback and 
733 
reactions to the closed loop system, the clinical trial, and QoL changes. 
734 
Interview sessions may be audio- or video-taped and transcribed by a professional transcription 
735 
service. Otherwise, these recordings will not be shared for any non-study purposes. 
736 
Transcriptions will use a code for participants, such as “Participant 1”, and will not contain 
737 
names or other identifiers of participants.
738 

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Chapter 7: Unanticipated Problem, Adverse Event, and Device Issue 
739 
Reporting 
740 
7.1 Unanticipated Problems 
741 
Site investigators will promptly report all unanticipated problems meeting the criteria below on 
742 
an eCRF. Sites overseen by the JCHR IRB must report Unanticipated Problems to the IRB 
743 
within seven (7) calendar days of recognition. For this protocol, an unanticipated problem is an 
744 
incident, experience, or outcome that meets all of the following criteria: 
745 
• Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures 
746 
that are described in the protocol related documents, such as the IRB-approved research 
747 
protocol and informed consent document; and (b) the characteristics of the subject 
748 
population being studied 
749 
• Related or possibly related to participation in  the research (possibly related means there 
750 
is a reasonable possibility that the incident, experience, or outcome may have been 
751 
caused by the procedures involved in the research) 
752 
• Suggests that the research places participants or others at a greater risk of harm than was 
753 
previously known or recognized (including physical, psychological, economic, or social 
754 
harm) 
755 
An example of an unanticipated problem in this study would be incidence rates of hypo- or 
756 
hyperglycemia in the study (T2D) population, related to closed-loop insulin delivery, that are 
757 
significantly higher than previously encountered when using the study system in the T1D 
758 
population. 
759 
The Coordinating Center also will report to the IRB all unanticipated problems not directly 
760 
involving a specific site such as unanticipated problems that occur study-wide or at another 
761 
participating entity such as a pharmacy or laboratory. These instances must be reported to the 
762 
JCHR IRB within seven (7) calendar days of recognition. The Director of the Human Research 
763 
Protection Program (HRPP) will report to the appropriate regulatory authorities if the IRB 
764 
determines that the event indeed meets the criteria of an Unanticipated Problem requiring 
765 
additional reporting to fulfill the reporting obligations of the HRPP. 
766 
7.2 Adverse Events 
767 
7.2.1 Definitions 
768 
Adverse Event (AE): Any untoward medical occurrence (including laboratory findings) 
769 
associated with study procedures, the use of a device, biologic, or drug in humans, including any 
770 
comparator used, whether or not the event is considered related (i.e., irrespective of the 
771 
relationship between the adverse event and the device(s) under investigation). 
772 
Serious Adverse Event (SAE): Any untoward medical occurrence that results in any of the 
773 
following outcomes: 
774 
• Death. 
775 

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• A life-threatening adverse event; (a non-life-threatening event which, had it been more 
776 
severe, might have become life-threatening, is not necessarily considered a serious adverse 
777 
event). 
778 
• Inpatient hospitalization or prolongation of existing hospitalization. 
779 
• A persistent or significant disability/incapacity or substantial disruption of the ability to 
780 
conduct normal life functions (sight threatening). 
781 
• A congenital anomaly or birth defect. 
782 
An important medical event that may not result in death, be life-threatening, or require 
783 
hospitalization may be considered serious when, based upon appropriate medical judgment, it 
784 
may jeopardize the patient or subject and may require medical and surgical intervention to 
785 
prevent one of the outcomes listed in this definition. Note: If either the Sponsor or investigator 
786 
believes that the event is serious, the event must be considered serious and evaluated by the 
787 
Sponsor for expedited reporting.  
788 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or 
789 
any life-threatening problem or death caused by, or associated with, a device, if that effect, 
790 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
791 
investigational plan or application (including a supplementary plan or application), or any other 
792 
unanticipated serious problem associated with a device that relates to the rights, safety, or 
793 
welfare of participants (21 CFR 812.3(s)). 
794 
Adverse Device Effect (ADE): An adverse event related to the use of an investigational medical 
795 
device. This definition includes adverse events resulting from insufficient or inadequate 
796 
instructions for use, deployment, implantation, installation, or operation, or any malfunction of 
797 
the investigational medical device. This definition includes any event resulting from use error or 
798 
from intentional misuse of the investigational medical device. This includes comparator if the 
799 
comparator is a medical device. (Note that an Adverse Event Form is to be completed in addition 
800 
to a Device Deficiency or Issue Form, unless excluded from reporting as defined in section 8.2). 
801 
Comparator: Medical device, therapy (e.g. active treatment, normal clinical practice), placebo or 
802 
no treatment, used in the control group in a clinical investigation. (ISO 14155:2020) 
803 
Device Complaints and Malfunctions: A device complication or complaint is something that 
804 
happens to a device or related to device performance, whereas an adverse event happens to a 
805 
participant.  A device complaint may occur independently from an AE, or along with an AE.  An 
806 
AE may occur without a device complaint or there may be an AE related to a device complaint.  
807 
A device malfunction is any failure of a device to meet its performance specifications or 
808 
otherwise perform as intended.  Performance specifications include all claims made in the 
809 
labeling for the device.  The intended performance of a device refers to the intended use for 
810 
which the device is labeled or marketed. (21 CFR 803.3).  Note: for reporting purposes, sites will 
811 
not be asked to distinguish between device complaints and malfunctions. 
812 
Use Error: User action or lack of user action while using the medical device (3.34) that leads to a 
813 
different result than that intended by the manufacturer or expected by the user. Includes the 
814 
inability of the user to complete a task. Use errors can result from a mismatch between the 
815 
characteristics of the user, user interface, task or use environment. Users might be aware or 
816 
unaware that a use error has occurred. An unexpected physiological response of the patient is not 
817 

JAEB CENTER FOR HEALTH RESEARCH 
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by itself considered a use error. A malfunction of a medical device that causes an unexpected 
818 
result is not considered a use error. (ISO 14155:2020) 
819 
 
820 
7.2.2 Reportable Adverse Events 
821 
For this protocol, a reportable adverse event includes any untoward medical occurrence that 
822 
meets one of the following criteria: 
823 
1. An SAE as defined in section 7.2.1 
824 
2. An ADE as defined in section 7.2.1, unless excluded from reporting in section 7.3 
825 
3. An AE as defined in 7.2.1 occurring in association with a study procedure 
826 
4. An AE as defined in 7.2.1 not related to a device issue which leads to temporary or 
827 
permanent discontinuation of  a study device 
828 
5. An AE as defined in 7.2.1 that affects the participant’s ability to complete any study 
829 
procedures 
830 
6. An AE as defined in 7.2.1 for which a visit is made to a hospital emergency department   
831 
7. Hypoglycemia meeting the definition of reportable hypoglycemia as defined below 
832 
8. Diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic syndrome (HHS) as defined 
833 
below; or in the absence of DKA/HHS, hyperglycemia or ketosis event meeting the criteria 
834 
defined below. 
835 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
836 
events unless associated with an Adverse Device Effect or discontinuation of the study device.  
837 
Skin reactions from sensor placement are only reportable if severe and/or required treatment. 
838 
All reportable AEs—whether volunteered by the participant, discovered by study personnel 
839 
during questioning, or detected through physical examination, laboratory test, or other means—
840 
will be reported on an AE form online.  Each AE form is reviewed by the Medical Monitor to 
841 
assess safety and to verify the coding and the reporting that is required. 
842 
7.2.3 Hypoglycemic Events 
843 
Hypoglycemia not associated with an Adverse Device Effect or discontinuation of the study 
844 
device is only reportable as an adverse event when one of the following criteria is met: 
845 
• a hypoglycemic event occurred meeting the following definition of severe hypoglycemia:  
846 
the event required assistance of another person due to altered consciousness, and required 
847 
another person to actively administer carbohydrate, glucagon, or other resuscitative 
848 
actions.  This means that the participant was impaired cognitively to the point that he/she 
849 
was unable to treat himself/herself, was unable to verbalize his/ her needs, was 
850 
incoherent, disoriented, and/or combative, or experienced seizure or loss of 
851 
consciousness.  These episodes may be associated with sufficient neuroglycopenia to 
852 
induce seizure or loss of consciousness.  If glucose measurements are not available 
853 
during such an event, neurological recovery attributable to the restoration of glucose to 
854 

JAEB CENTER FOR HEALTH RESEARCH 
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normal is considered sufficient evidence that the event was induced by a low glucose 
855 
concentration. 
856 
• evaluation or treatment was obtained at a health care provider facility for an acute event 
857 
involving hypoglycemia, or the participant contacted the site and received guidance  
858 
following the occurrence of an acute event involving hypoglycemia 
859 
When a severe hypoglycemia event occurs (as defined above), a Hypoglycemia Form should be 
860 
completed in addition to the Adverse Event Form. Severe hypoglycemia events should be 
861 
considered to be serious adverse events with respect to reporting requirements. When a severe 
862 
hypoglycemia event occurs during use of a study device, it generally will be considered to be 
863 
unrelated to the device (per section 7.2.5) if the device functioned as intended and there does not 
864 
appear to be a flaw in how the device is intended to function. 
865 
7.2.4 Hyperglycemic/Ketotic Events 
866 
Hyperglycemia not associated with an Adverse Device Effect or discontinuation of the study 
867 
device is only reportable as an adverse event when one of the following criteria is met:   
868 
• the event involved DKA, as defined by the Diabetes Control and Complications Trial 
869 
(DCCT) and described below 
870 
• the event involved hyperosmolar hyperglycemic syndrome (HHS), as defined by the 
871 
American Diabetes Association and described below 
872 
• evaluation or treatment was obtained at a health care provider facility for an acute event 
873 
involving hyperglycemia or ketosis, or the participant contacted the site and received 
874 
guidance on how to manage the hyperglycemia/ketosis 
875 
Hyperglycemic events are classified as DKA if the following are present: 
876 
• Symptoms such as polyuria, polydipsia, nausea, or vomiting; 
877 
• Serum ketones >1.5 mmol/L or large/moderate urine ketones; 
878 
• Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate (or CO2) <15; and 
879 
• Treatment provided in a health care facility 
880 
Hyperglycemic events are classified as HHS if the following are present: 
881 
• Symptoms such as polyuria, polydipsia, nausea, or vomiting; 
882 
• Plasma glucose levels are very elevated (typically > 600 mg/dL); 
883 
• Plasma effective osmolarity is >320 mOsm/L; 
884 
• Absence of significant ketones; and 
885 
• Treatment provided in a health care facility 
886 
When a hyperglycemia/ketotic event qualifies as an SAE as defined in section 7.2.1 , a 
887 
Hyperglycemia/DKA Form should be completed in addition to the Adverse Event Form. Events 
888 
meeting DKA or HHS criteria should be considered to be serious adverse events with respect to 
889 
reporting requirements. Hyperglycemia events not meeting criteria for DKA or HHS generally 
890 

JAEB CENTER FOR HEALTH RESEARCH 
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will not be considered as serious adverse events unless one of the SAE criteria in section 7.2.1 is 
891 
met. 
892 
When a hyperglycemia/DKA event occurs during use of a study device, it generally will be 
893 
considered to be unrelated to the device (per section 7.2.5) if the device functioned as intended 
894 
and there does not appear to be a flaw in how the device is intended to function. 
895 
7.2.5 Relationship of Adverse Event to Study Investigational Device 
896 
The study investigator will assess the relationship of any adverse event to be related or unrelated 
897 
by determining if there is a reasonable possibility that the adverse event may have been caused 
898 
by the study device. The Medical Monitor also will make this assessment, which may or may not 
899 
agree with that of the study investigator. Reporting requirements will be based on the Medical 
900 
Monitor’s assessment as the Sponsor’s representative. 
901 
To ensure consistency of adverse event causality assessments, investigators should apply the 
902 
following general guideline when determining whether an adverse event is related: 
903 
• Unrelated: The AE is clearly not related to a study drug/device and a likely alternative 
904 
etiology exists such as an underlying disease, environmental or toxic factors or other 
905 
therapy. 
906 
• Unlikely Related: The AE does not follow a reasonable temporal sequence during or after 
907 
use of study drug/device and a more likely alternative etiology exists such as an 
908 
underlying disease, environmental or toxic factors, or other therapy.  
909 
• Possibly Related: The AE occurred in a reasonable time during or after use of study 
910 
drug/device; but could be related to another factor such as an underlying disease, 
911 
environmental or toxic factors, or other therapy; and there is a possible, though weak, 
912 
scientific basis for establishing a causal association between the AE and the study 
913 
drug/device. 
914 
• Probably Related: The AE occurred in a reasonable time during or after use of study 
915 
drug/device; is unlikely to be related to another factor such as an underlying disease, 
916 
environmental or toxic factors, or other therapy; and there is a plausible, though not 
917 
strong, scientific basis for establishing a causal association between the AE and the study 
918 
drug/device.  
919 
• Definitely Related: The AE occurred in a reasonable time during or after use of study 
920 
drug/device; cannot be explained by another factor such as an underlying disease, 
921 
environmental or toxic factors, or therapy; and there is a strong scientific basis for 
922 
establishing a causal association between the AE and the study drug/device.  
923 
• Not Assessable: Causality of an adverse event cannot be judged because information is 
924 
insufficient or contradictory, and which cannot be supplemented or verified. 
925 
Where these relatedness categories are used, events determined to be Possibly Related, 
926 
Probably Related, or Definitely Related will be considered to meet the reasonable possibility 
927 
causality standard for relatedness and necessitate reporting as required (see 21 CFR 312.32 
928 
for more information about this standard). 
929 

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7.2.6 Severity (Intensity)  of Adverse Events 
930 
The severity  (intensity) of an adverse event will be rated on a three point scale: (1) mild, (2) 
931 
moderate, or (3) severe.  A severity assessment is a clinical determination of the intensity of an 
932 
event. Thus, a severe adverse event is not necessarily serious.  For example, itching for several 
933 
days may be rated as severe, but may not be clinically serious. 
934 
• MILD: Usually transient, requires no special treatment, and does not interfere with the 
935 
participant’s daily activities. 
936 
• MODERATE: Usually causes a low level of inconvenience, discomfort or concern to the 
937 
participant and may interfere with daily activities, but is usually ameliorated by simple 
938 
therapeutic measures and participant is able to continue in study. 
939 
• SEVERE: Interrupts a participant’s usual daily activities, causes severe discomfort, may 
940 
cause discontinuation of study device, and generally requires systemic drug therapy or other 
941 
treatment. 
942 
7.2.7 Expectedness 
943 
For a serious adverse event that is considered possibly related to study device, the Medical 
944 
Monitor will classify the event as unexpected if the nature, severity, or frequency of the event is 
945 
not consistent with the risk information previously described in the approved labelling of the 
946 
study system.  
947 
7.2.8 Coding of Adverse Events 
948 
Adverse events will be coded using the MedDRA dictionary. To facilitate coding, the site will 
949 
enter a preliminary MedDRA code which the Medical Monitor may accept or change (the 
950 
Medical Monitor’s MedDRA coding will be used for all reporting). The Medical Monitor will 
951 
review the investigator’s assessment of causality and may agree or disagree.  Both the 
952 
investigator’s and Medical Monitor’s assessments will be recorded.  The Medical Monitor will 
953 
have the final say in determining the causality as well as whether an event is classified as a 
954 
serious adverse event and/or an unanticipated adverse device effect. 
955 
7.2.9 Outcome of Adverse Events 
956 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
957 
• RECOVERED/RESOLVED – The participant recovered from the AE/SAE without sequelae.  
958 
Record the AE/SAE stop date. 
959 
• RECOVERED/RESOLVED WITH SEQUELAE – The event persisted and had stabilized 
960 
without change in the event anticipated.  Record the AE/SAE stop date. 
961 
• FATAL – A fatal outcome is defined as the SAE that resulted in death.  Only the event that 
962 
was the cause of death should be reported as fatal.  AEs/SAEs that were ongoing at the time 
963 
of death; however, were not the cause of death, will be recorded as “resolved” at the time of 
964 
death. 
965 
• NOT RECOVERED/NOT RESOLVED (ONGOING) – An ongoing AE/SAE is defined as 
966 
the event was ongoing with an undetermined outcome. 
967 

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 An ongoing outcome will require follow-up by the site in order to determine the final 
968 
outcome of the AE/SAE. 
969 
 The outcome of an ongoing event at the time of death that was not the cause of death, 
970 
will be updated and recorded as “resolved” with the date of death recorded as the stop 
971 
date. 
972 
• UNKNOWN – An unknown outcome is defined as an inability to access the participant or 
973 
the participant’s records to determine the outcome (for example, a participant that was lost to 
974 
follow-up). 
975 
If any reported adverse events are ongoing when a participant completes the study (or 
976 
withdraws), adverse events classified as UADEs or related SAEs will be followed until they are 
977 
either resolved, or have no prospect of improvement or change, even after the participant has 
978 
completed all applicable study visits/contacts. For all other adverse events, data collection will 
979 
end at the time the participant completes the study. Note: participants should continue to receive 
980 
appropriate medical care for an adverse event after their participation in the study ends.  
981 
7.3 Reportable Device Issues 
982 
All UADEs and ADEs as defined in section 7.2.1 will be reported on both a device issue form 
983 
and AE form, except for skin reactions from CGM sensor placement or pump infusion set 
984 
placement that do not require pharmacologic treatment.   
985 
Device complaints and device malfunctions will be reported except in the following 
986 
circumstances. These occurrences are expected and will not be reported on a Device Issue Form 
987 
assuming criteria for a UADE or ADE have not been met: 
988 
• CGM sensor needing replacement prior to labelled maximum use duration 
989 
• Infusion set needing replacement prior to labelled maximum use duration  
990 
• CGM tape adherence issues 
991 
• Pump infusion set insertion lasting fewer days than expected per manufacturer  
992 
• Battery lifespan deficiency due to inadequate charging or extensive wireless communication 
993 
• Intermittent device component disconnections/communication failures not requiring system 
994 
replacement or workaround/resolution not specified in user guide/manual. 
995 
• Device issues clearly addressed in the user guide manual that do not require additional 
996 
troubleshooting 
997 
7.4 Timing of Event Reporting 
998 
SAEs possibly related to a study device or study participation and UADEs must be reported by 
999 
the investigator to the Coordinating Center within 24 hours of the site becoming aware of the 
1000 
event.  This can occur via phone or email, or by completion of the online serious adverse event 
1001 
form and device issue form if applicable. If the form is not initially completed, it should be 
1002 
competed as soon as possible after there is sufficient information to evaluate the event. All other 
1003 
reportable ADEs and other reportable AEs should be submitted by completion on the online form 
1004 
within 7 days of the site becoming aware of the event.  
1005 

JAEB CENTER FOR HEALTH RESEARCH 
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The Coordinating Center will notify all participating investigators of any adverse event that is 
1006 
serious, related, and unexpected. Notification will be made within 10 working days after the 
1007 
Coordinating Center becomes aware of the event. 
1008 
Each principal investigator is responsible for reporting serious study-related adverse events and 
1009 
abiding by any other reporting requirements specific to his/her Institutional Review Board or 
1010 
Ethics Committee. Where the JCHR IRB is the overseeing IRB, sites must report all serious, 
1011 
related adverse events within seven calendar days. 
1012 
Upon receipt of a qualifying event, the Sponsor will investigate the event to determine if a 
1013 
UADE is confirmed, and if indicated, report the results of the investigation to all overseeing 
1014 
IRBs, and the FDA within 10 working days of the Sponsor becoming aware of the UADE per 
1015 
21CFR 812.46(b) (2).  The Sponsor in conjunction with the Medical Monitor must determine if 
1016 
the UADE presents an unreasonable risk to participants.  If so, the Sponsor must ensure that all 
1017 
investigations, or parts of investigations presenting that risk, are terminated as soon as possible 
1018 
but no later than 5 working days after the Sponsor makes this determination and no later than 15 
1019 
working days after first receipt notice of the UADE. The investigator(s) may then be required to 
1020 
provide approval or acknowledgment of receipt of that notification, and must submit to their 
1021 
overseeing IRB as required.  
1022 
The investigators are also required to report, without unjustified delay, all device deficiencies 
1023 
that could have led to a UADE, including device deficiencies, irrespective of whether an adverse 
1024 
event occurred. 
1025 
Device malfunctions will be handled by the Sponsor or designee as described below.  In the case 
1026 
of a CGM transmitter or sensor device malfunction, information will be forwarded to Dexcom by 
1027 
the site personnel, to be handled by their complaint management system. 
1028 
7.5 Safety Oversight 
1029 
The study Medical Monitor will review all adverse events and adverse device events that are 
1030 
reported during the study.  SAEs typically will be reviewed within 24 hours of reporting.  
1031 
Other AEs typically will be reviewed on a weekly basis. Additionally, the Medical Monitor will 
1032 
review compiled safety data at periodic intervals. 
1033 
The Clinical Study Director will be informed of all cases of severe hypoglycemia and DKA 
1034 
and the Medical Monitor’s assessment of relationship to the study device; and informed of all 
1035 
reported device issues. 
1036 
7.6 Stopping Criteria 
1037 
7.6.1 Participant Discontinuation of Study Device 
1038 
In the case of an unanticipated system malfunction resulting in a severe hypoglycemia or DKA 
1039 
event (or a malfunction that could have led to severe hypoglycemia or DKA), use of closed-loop 
1040 
mode will be suspended while the problem is diagnosed. The UADE will be reported to the IRB 
1041 
and FDA. After assessment of the problem and any correction,  use of closed-loop mode will not 
1042 
be restarted until approval is received from the IRB and FDA. 
1043 
In the absence of a device malfunction, a participant will be discontinued from the study if any of 
1044 
the following occur:  
1045 

JAEB CENTER FOR HEALTH RESEARCH 
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• The investigator believes it is unsafe for the participant to continue on the intervention.  This 
1046 
could be due to the development of a new medical condition or worsening of an existing 
1047 
condition; or participant behavior contrary to the indications for use of the device that 
1048 
imposes on the participant’s safety 
1049 
• The participant requests that the treatment be stopped 
1050 
• Participant pregnancy 
1051 
• Two distinct episodes of DKA, HHS, or severe hypoglycemia as defined above, so only a 
1052 
second event of any of these types may occur prior to stopping subject participation.  
1053 
Each DKA or severe hypoglycemia event will be reviewed by the Medical Monitor with respect 
1054 
to determination of cause and whether the occurrence of the event can be attributed to use of the 
1055 
study device.  
1056 
An additional requirement for continued study participation following a single DKA or severe 
1057 
hypoglycemia event will be that (1) the site investigator believes that the event is explainable, 
1058 
unlikely to recur, and that it is safe for the participant to continue to use the system and (2) the 
1059 
Medical Monitor concurs. If the Medical Monitor determines that the occurrence of the event 
1060 
indicates that it is not safe for the participant to continue to use the study system, the participant 
1061 
will be discontinued from the study. 
1062 
Even if the study device system is discontinued, the participant will be encouraged to remain in 
1063 
the study through the final study visit. 
1064 
7.6.2 Criteria for Suspending or Stopping Overall Study 
1065 
In addition to the suspension of closed-loop mode use due to a UADE as described above, 
1066 
closed-loop system use will be suspended if there are three or more cases of severe 
1067 
hypoglycemia or three or more cases of hyperglycemia/ketotic events qualifying as SAEs across 
1068 
the entire study in participants who have initiated Control-IQ technology use. 
1069 
Study activities could be similarly suspended if the manufacturer of any constituent study device 
1070 
requires stoppage of device use for safety reasons (e.g. product recall).  The affected study 
1071 
activities may resume if the underlying problem can be corrected by a protocol or system 
1072 
modification that will not invalidate the results obtained prior to suspension. 
1073 
 
 
1074 

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Chapter 8: Miscellaneous Considerations 
1075 
8.1 Drugs Used as Part of the Protocol 
1076 
Participants will use either lispro or aspart insulin prescribed by their personal physician. 
1077 
Participants not using lispro or aspart insulin at the time of screening may not start use of the 
1078 
study device until they have one of these insulins available to them for use. 
1079 
8.2 Collection of Medical Conditions and Medications 
1080 
Pre-Existing Condition: Any medical condition that is either present at screening, a chronic 
1081 
disease, or a prior condition that could impact the participant’s health during the course of the 
1082 
study (e.g., prior myocardial infarction or stroke). 
1083 
Medical Conditions during the study: In addition to conditions meeting the reporting 
1084 
requirements for an adverse event or device issue as described above, the following medical 
1085 
conditions should also be reported: (1) new diagnosis of a chronic disease (i.e., not present at the 
1086 
time of enrollment), and (2) any medical condition that could affect the participant’s ability to 
1087 
carry out any aspect of the protocol or could affect an outcome assessment. 
1088 
Medications: All medication for the treatment of chronic pre-existing conditions, medical 
1089 
conditions (including medical conditions that do not require recording), and/or adverse events 
1090 
that the participant is currently taking at screening and during the course of the study should be 
1091 
recorded.  Nutraceuticals and preventative treatment also should be recorded.  Medications only 
1092 
taken as needed either can be recorded when prescribed or only recorded if used during the 
1093 
study.  Glucagon for treatment of severe hypoglycemia will only be recorded if used during the 
1094 
study. 
1095 
8.3 Prohibited Medications, Devices, Treatments, and Procedures 
1096 
Participants using other insulins at the time of enrollment will be asked to contact their personal 
1097 
physician to change their prescribed personal insulin to lispro or aspart for the duration of the 
1098 
trial. 
1099 
Afrezza (inhaled insulin) or concurrent use of basal insulins will not be permitted during device 
1100 
use in the trial. Additional medications to treat glycemia (such as SGL-2 inhibitors or GLP-1 
1101 
receptor agonists), commonly used by individuals with type 2 diabetes concurrently with insulin 
1102 
use, will be allowed if the participant is on a stable dose of such medication for the last 3 months. 
1103 
Sulfonylurea use and meglitinide use will not be allowed during the trial. 
1104 
No new additional glucose lowering medications may be added during the trial. 
1105 
Medications used for weight loss will be allowed if the participant is on a stable dose of such 
1106 
medication for the last 3 months. No new medications for weight loss may be added during the 
1107 
trial. 
1108 
Additional medications may be excluded per judgement of the investigator. 
1109 
The investigational study devices (study insulin pump, study CGM system) must be removed 
1110 
before Magnetic Resonance Imaging (MRI), Computed Tomography (CT) or diathermy treatment. 
1111 
Participants may continue in the trial after temporarily discontinuing use if requiring one of the 
1112 
treatments above. 
1113 

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8.4 Precautionary Medications, Treatments, and Procedures 
1114 
Not applicable. 
1115 
8.5 Prophylactic Medications, Treatments, and Procedures 
1116 
Not applicable. 
1117 
8.6 Rescue Medications, Treatments, and Procedures 
1118 
All participants will be required to have a commercially available glucagon (or glucagon analog) 
1119 
preparation for treatment as needed of severe hypoglycemia. 
1120 
8.7 Pregnancy Reporting 
1121 
If pregnancy occurs, the participant will be discontinued from the study.  The occurrence of 
1122 
pregnancy will be reported to the Coordinating Center within seven days and to the JCHR IRB as 
1123 
an Unanticipated Problem within seven calendar days.  
1124 
8.8 Participant Compensation 
1125 
Participant compensation will be specified in the informed consent form. 
1126 
8.9 Participant Withdrawal 
1127 
Participation in the study is voluntary, and a participant may withdraw at any time.  For 
1128 
participants who withdraw, their data will be used up until the time of withdrawal. 
1129 
8.10 Confidentiality 
1130 
For security and confidentiality purposes, participants will be assigned an identifier that will be 
1131 
used instead of their name.  Protected health information gathered for this study will be shared 
1132 
with the coordinating center, the Jaeb Center for Health Research in Tampa, FL.  De-identified 
1133 
participant information may also be provided to research sites involved in the study.
1134 

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Chapter 9: Statistical Considerations 
1135 
9.1 Statistical and Analytical Plans 
1136 
The approach to sample size and statistical analyses are summarized below.   
1137 
9.2 Statistical Hypotheses 
1138 
The primary outcomes for this study are CGM-measured percentage below 54 mg/dl and CGM-
1139 
measured percent above 180 mg/dl over a 6-week period. The intervention will be considered 
1140 
effective if the 6-week follow-up % above 180 mg/dl value is superior and % below 54 mg/dl 
1141 
value is non-inferior to the corresponding baseline values using a statistical significance of 
1142 
α=0.05 and the analysis specified below in Section 6 (i.e., p < 0.05). 
1143 
The null/alternative hypotheses are: 
1144 
 
1145 
Percentage below 54 mg/dl: 
1146 
a. Null Hypothesis: The difference in mean CGM-measured % below 54 mg/dl between the 
1147 
6 weeks follow-up and baseline is greater than or equal to +1% (non-inferiority). 
1148 
b. Alternative Hypothesis: The difference in mean CGM-measured % below 54 mg/dl 
1149 
between the 6 weeks follow-up and baseline is less than +1%. 
1150 
 
1151 
Percentage above 180 mg/dl: 
1152 
a. Null Hypothesis: There is no difference in mean CGM-measured % above 180 mg/dL 
1153 
between the 6 weeks of follow-up and baseline (superiority).  
1154 
b. Alternative Hypothesis: The mean CGM-measured % above 180 mg/dL is different at 
1155 
baseline than the mean over 6 weeks of follow-up. 
1156 
 
1157 
9.3 Sample Size 
1158 
The planned cohort of N=30 participants with the goal of at least N=24 completing the study is a 
1159 
convenience sample not based on statistical principles. 
1160 
9.4 Outcome Measures 
1161 
9.4.1 Primary Efficacy Endpoints 
1162 
• CGM-measured percentage below 54 mg/dl 
1163 
• CGM measured percentage above 180 mg/dl 
1164 
9.4.2 Secondary Efficacy Endpoints 
1165 
• CGM-measured metrics: 
1166 
➢ Percentage in range 70-180 mg/dL 
1167 
➢ Percentage < 70 mg/dL 
1168 
➢ Percentage > 250 mg/dL 
1169 
➢ Percentage in tight glycemic range 70-140 mg/dL 
1170 
➢ Mean glucose 
1171 

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1172 
➢ Up to 4hr post-prandial glycemic metrics: 
1173 
▪ Peak  
1174 
▪ Area Under the Curve (AUC) 
1175 
 
1176 
• Insulin metrics 
1177 
➢ Total daily insulin use 
1178 
➢ Total basal insulin 
1179 
➢ Total bolus insulin 
1180 
• Weight 
1181 
• Questionnaires  
1182 
➢ Tandem Study-Specific Baseline Survey  
1183 
➢ Altarum Consumer Engagement Measure 
1184 
➢ Tandem Pump Training Survey 
1185 
➢ DAWN Impact of Diabetes Profile 
1186 
➢ Diabetes Impact and Device Satisfaction Scale 
1187 
➢ PROMIS Sleep-Related Impairment Questionnaire 
1188 
➢ System Usability Scale 
1189 
 
1190 
Calculation of CGM metrics 
1191 
• Baseline values will be taken from the last 7 days of the run-in, or for participants who 
1192 
can skip the run-in baseline values will be taken from their personal CGM during the 7 
1193 
days prior to initiating CLC. At least 24hr of data during this baseline period are required 
1194 
for the glycemic metrics to be calculated. 
1195 
• Follow-up values will be calculated using CGM data from the 6-week period of CLC use. 
1196 
These will be limited to participants who have at least 168 hours of CGM data available 
1197 
during the 6-week CLC use period. 
1198 
• Exploratory analyses will include all CGM data between the initiation of Open-Loop use 
1199 
and the start of CLC will be used. At least 24hr of data during this period are required for 
1200 
the glycemic metrics to be calculated. 
1201 
• Separate values for each CGM metric (except for post-prandial peak and 4-hour AUC) 
1202 
will be calculated for: 
1203 
➢ Overall: 24 hours of the day 
1204 
➢ Daytime: CGM readings from 6:00 am – 11:59 pm 
1205 
➢ Nighttime: CGM readings from midnight – 5:59 am 
1206 
➢ During logged exercise challenges 
1207 
9.4.3 Safety Endpoints 
1208 
• Severe hypoglycemia (needing assistance) 
1209 
• DKA 
1210 
• Hyperosmolar Hyperglycemic Syndrome 
1211 
• Serious Adverse Events 
1212 
• Unanticipated adverse device effects  
1213 
 
1214 

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9.5 Analysis Datasets and Sensitivity Analyses 
1215 
This is not a randomized trial so intent-to-treat does not apply. The primary analysis will be 
1216 
limited to participants with at least 168 hours of CGM data during the 6-week CLC use period. 
1217 
 
1218 
A per-protocol analysis will be limited to participants who used the CLC for at least 80% of the 
1219 
time during the 6-week period. If fewer than 10% of the study participants would be excluded 
1220 
based on this criterion, then the per-protocol analysis will not be performed. 
1221 
 
1222 
Safety analyses will include all participants. 
1223 
9.6 Analysis of the Primary Efficacy Endpoint(s) 
1224 
Summary statistics appropriate to the distribution (e.g., mean and standard deviation, or median 
1225 
and quartiles) will be for each of the primary efficacy endpoints (CGM-measured percentage 
1226 
below 54 mg/dl and percentage above 180 mg/dl) at baseline, during CLC use, and for the 
1227 
change values. Scatterplots and boxplots will be constructed to show the distribution of values at 
1228 
baseline and during CLC use. 
1229 
 
1230 
A pre- and post-CLC comparison will be performed using a paired t-test for each metric. If the 
1231 
paired differences (i.e., change values) do not follow an approximate normal distribution, then a 
1232 
non-parametric comparison based on ranks will be performed. 
1233 
 
1234 
9.7 Analysis of the Secondary Endpoint 
1235 
Analysis of secondary endpoints will parallel the analysis described above for the primary 
1236 
endpoints over 24 hours, daytime, and nighttime. For the post-prandial CGM metrics (4 hour 
1237 
peak and AUC) and during exercise challenges, there will be no corresponding pre-study 
1238 
baseline. Descriptive analyses of these metrics will be limited to values during CLC use. 
1239 
9.8 Safety Analyses 
1240 
All participants will be included in the safety analyses. All adverse events will be tabulated with 
1241 
separate lists for events that occur before, during OL, and during CLC use. 
1242 
 
1243 
Additionally, the number of events and the event rate per 100 person-years during CLC use will 
1244 
be calculated for each of the safety outcomes listed above: 
1245 
• Severe hypoglycemia (needing assistance) 
1246 
• DKA 
1247 
• Hyperosmolar Hyperglycemic Syndrome 
1248 
• All Serious Adverse Events 
1249 
• Unanticipated adverse device effects  
1250 
 
1251 

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9.9 Intervention Adherence 
1252 
Descriptive summary statistics will be given for the percentage of time that the CLC is in active 
1253 
mode and the amount of CGM use over the 6-week period. A scatterplot of these two 
1254 
percentages will be constructed. Boxplots will be given for each of these percentages for each of 
1255 
the 6 weeks of follow-up. Descriptive statistics will be given for the percentage of time spent in 
1256 
each of the CLC operational modes.  
1257 
9.10 Protocol Adherence and Retention 
1258 
The following measures of adherence will be tabulated during the 6-week follow-up period: 
1259 
• Number of protocol and procedural deviations  
1260 
• Flow chart accounting for all enrolled participants up to the end of study 
1261 
• Flow chart of all enrolled participants at all scheduled visits and phone contacts post 
1262 
treatment initiation 
1263 
• Number of and reasons for unscheduled visits and phone calls 
1264 
• Number of participants who stopped OL or CLC use and reasons 
1265 
 
1266 
9.11 Baseline Descriptive Statistics 
1267 
Baseline demographic and clinical characteristics of the cohort of all enrolled participants will be 
1268 
summarized in a table using summary statistics appropriate to the distribution of each variable. 
1269 
Descriptive statistics will be displayed for the following: 
1270 
• Age 
1271 
• Sex 
1272 
• Race/Ethnicity 
1273 
• Diabetes duration 
1274 
• Insulin method before enrollment (basal only or multiple daily injections) 
1275 
• CGM use before enrollment 
1276 
• HbA1c 
1277 
• BMI 
1278 
• Participant-reported number of SH and DKA 12 months prior to the start of the study 
1279 
• Baseline CGM metrics including: 
1280 
• % time < 54 mg/dl 
1281 
• % time > 180 mg/dl 
1282 
• % in range 70-180 mg/dl 
1283 
• mean glucose 
1284 
• % time < 70 mg/dl 
1285 
 
1286 
9.12 Device Issues 
1287 
The following tabulations and analyses will be performed to assess device issues: 
1288 
• Device malfunctions requiring study team contact and other reported device issues 
1289 

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• Rate of different failure events and alarms per 24 hours recorded by the Control-IQ system – 
1290 
overall and by study week 
1291 
9.13 Planned Interim Analyses 
1292 
No formal interim efficacy analyses are planned. 
1293 
9.14 Sub-Group Analyses 
1294 
In exploratory analyses, the primary outcomes (percent <54 mg/dl and percent >180 mg/dl) will 
1295 
be compared in baseline subgroups. A least squares regression will be fit with the dependent 
1296 
variable being the paired difference (value during CLC use minus value at baseline) and the 
1297 
subgroup factor as an independent variable. 
1298 
Interpretation of subgroup analyses will be viewed with caution, particularly in the absence of an 
1299 
overall significant difference. Subgroups will be analyzed according to the following baseline 
1300 
factors: 
1301 
• Gender 
1302 
• Race/Ethnicity (if sufficient numbers in more than one category) 
1303 
• Insulin 
1304 
➢ Basal only (Group A) 
1305 
➢ Multiple daily injections (Group B) 
1306 
9.15 Multiple Comparison/Multiplicity 
1307 
There will be no formal correction for multiple comparisons in this pilot study. 
1308 
9.16 Exploratory Analyses 
1309 
The primary analysis described above in Section 9.6 will be repeated with the CGM-measured 
1310 
percentage below 54 mg/dl and percentage above 180 mg/dl during follow-up limited to times 
1311 
when the CLC was in active mode. 
1312 
Weekly boxplots for selected glycemic and insulin metrics will be generated. 
1313 
In addition to the baseline and 6 weeks CLC use period, the glycemic and insulin analyses will 
1314 
be extended to include the 2-4 weeks of OL use. Only descriptive summary statistics and plots 
1315 
will be generated for these new analyses. 
1316 

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Chapter 10: Data Collection and Monitoring 
1317 
10.1 Case Report Forms and Other Data Collection 
1318 
The main study data are collected on electronic case report forms (CRFs). When data are directly 
1319 
collected in electronic case report forms, this will be considered the source data. For any data 
1320 
points for which the eCRF is not considered source (e.g. lab results that are transcribed from a 
1321 
printed report into the eCRF), the original source documentation must be maintained in the 
1322 
participant’s study chart or medical record. This source must be readily verifiable against the 
1323 
values entered into eCRF. Even where all study data are directly entered into the eCRFs at office 
1324 
visits, evidence of interaction with a live subject must be recorded (e.g., office note, visit record, 
1325 
etc.)    
1326 
Electronic device data files are obtained from the study software and individual hardware 
1327 
components.  These electronic device files are considered the primary source documentation. 
1328 
10.2 Study Records Retention 
1329 
Each participating site will maintain appropriate medical and research records for this trial, in 
1330 
compliance with ICH E6 and regulatory and institutional requirements for the protection of 
1331 
confidentiality of participants. 
1332 
Study documents should be retained for a minimum of 2 years after the last approval of a 
1333 
marketing application in an ICH region and until there are no pending or contemplated marketing 
1334 
applications in an ICH region or until at least 2 years have elapsed since the formal 
1335 
discontinuation of clinical development of the investigational product.  These documents should 
1336 
be retained for a longer period, however, if required by local regulations.  No records will be 
1337 
destroyed without the written consent of the sponsor, if applicable.  It is the responsibility of the 
1338 
sponsor to inform the investigator when these documents no longer need to be retained. 
1339 
10.3 Quality Assurance and Monitoring 
1340 
Designated personnel from the Coordinating Center will be responsible for maintaining quality 
1341 
assurance (QA) and quality control (QC) systems to ensure that the clinical portion of the trial is 
1342 
conducted and data are generated, documented and reported in compliance with the protocol, 
1343 
Good Clinical Practice (GCP) and the applicable regulatory requirements, as well as to ensure 
1344 
that the rights and wellbeing of trial participants are protected and that the reported trial data are 
1345 
accurate, complete, and verifiable.  Adverse events will be prioritized for monitoring. 
1346 
A risk-based monitoring (RBM) plan will be developed and revised as needed during the course 
1347 
of the study, consistent with the FDA “Guidance for Industry Oversight of Clinical 
1348 
Investigations — A Risk-Based Approach to Monitoring” (August 2013).  Study conduct and 
1349 
monitoring will conform with 21 Code of Federal Regulations (CFR) 812. This plan describes in 
1350 
detail who will conduct the monitoring, at what frequency monitoring will be done, at what level 
1351 
of detail monitoring will be performed, and the distribution of monitoring reports. 
1352 
The data of most importance for monitoring at the site are participant eligibility and adverse 
1353 
events.  Therefore, the RBM plan will focus on these areas.  As much as possible, remote 
1354 
monitoring will be performed in real-time with on-site monitoring performed to evaluate the 
1355 
verity and completeness of the key site data.  Elements of the RBM may include: 
1356 

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• Qualification assessment, training, and certification for sites and site personnel 
1357 
• Oversight of Institutional Review Board (IRB) coverage and informed consent procedures 
1358 
• Central (remote) data monitoring: validation of data entry, data edits/audit trail, protocol 
1359 
review of entered data and edits, statistical monitoring, study closeout 
1360 
• On-site monitoring (site visits): source data verification, site visit report 
1361 
• Agent/Device accountability 
1362 
• Communications with site staff 
1363 
• Patient retention and visit completion 
1364 
• Quality control reports 
1365 
• Management of noncompliance 
1366 
• Documenting monitoring activities 
1367 
• Adverse event reporting and monitoring 
1368 
Coordinating Center representatives or their designees may visit the study facilities at any time in 
1369 
order to maintain current and personal knowledge of the study through review of the records, 
1370 
comparison with source documents, observation and discussion of the conduct and progress of 
1371 
the study. The investigational site will provide direct access to all trial related sites, source 
1372 
data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and 
1373 
inspection by local and regulatory authorities. 
1374 
10.4 Protocol Deviations 
1375 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or procedure 
1376 
requirements.  The noncompliance may be either on the part of the participant, the investigator, 
1377 
or the study site staff.  A significant (or major) deviation is any deviation that departs from the 
1378 
established materials in such a way that it poses an increase in the risk to subjects, adversely 
1379 
affects the welfare, rights, or safety of the research subjects, or negatively influences the 
1380 
scientific study integrity. As a result of a significant deviation, a corrective and preventive action 
1381 
plan shall be developed by the site and implemented promptly. 
1382 
The site PI/study staff is responsible for knowing and adhering to their IRB requirements.  
1383 
Further details about the handling of protocol deviations will be included in the monitoring plan. 
1384 

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Chapter 11: Ethics/Protection of Human Participants 
1385 
11.1 Ethical Standard 
1386 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
1387 
the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 
1388 
21 CFR Part 56, and/or the ICH E6. 
1389 
11.2 Institutional Review Boards 
1390 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
1391 
be submitted to the IRB for review and approval.  Approval of both the protocol and the consent 
1392 
form must be obtained before any participant is enrolled.  Any amendment to the protocol will 
1393 
require review and approval by the IRB before the changes are implemented to the study.  All 
1394 
changes to the consent form will be IRB approved; a determination will be made regarding 
1395 
whether previously consented participants need to be re-consented. 
1396 
11.3 Informed Consent Process 
1397 
11.3.1 Consent Procedures and Documentation 
1398 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
1399 
the study and continues throughout the individual’s study participation.  Extensive discussion of 
1400 
risks and possible benefits of participation will be provided to the participants and their families.  
1401 
Consent forms will be IRB-approved and the participant will be asked to read and review the 
1402 
document.  The investigator will explain the research study to the participant and answer any 
1403 
questions that may arise.  All participants will receive a verbal explanation in terms suited to 
1404 
their comprehension of the purposes, procedures, and potential risks of the study and of their 
1405 
rights as research participants.  Participants will have the opportunity to carefully review the 
1406 
written consent form and ask questions prior to signing. 
1407 
The participants should have the opportunity to discuss the study with their surrogates or think 
1408 
about it prior to agreeing to participate.  The participant will sign the informed consent document 
1409 
prior to any procedures being done specifically for the study.  The participants may withdraw 
1410 
consent at any time throughout the course of the trial.  A copy of the informed consent document 
1411 
will be given to the participants for their records.  The rights and welfare of the participants will 
1412 
be protected by emphasizing to them that the quality of their medical care will not be adversely 
1413 
affected if they decline to participate in this study. 
1414 
11.3.2 Participant and Data Confidentiality 
1415 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, 
1416 
and the sponsor(s) and their agents.  This confidentiality is extended to cover testing of 
1417 
biological samples and genetic tests in addition to the clinical information relating to 
1418 
participants.  Therefore, the study protocol, documentation, data, and all other information 
1419 
generated will be held in strict confidence.  No information concerning the study or the data will 
1420 
be released to any unauthorized third party without prior written approval of the sponsor. 
1421 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB, 
1422 
regulatory agencies or  company supplying study product may inspect all documents and records 
1423 

JAEB CENTER FOR HEALTH RESEARCH 
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required to be maintained by the investigator, including but not limited to, medical records 
1424 
(office, clinic, or hospital) and pharmacy records for the participants in this study.  The clinical 
1425 
study site will permit access to such records. 
1426 
The study participant’s contact information will be securely stored at each clinical site for 
1427 
internal use during the study.  At the end of the study, all records will continue to be kept in a 
1428 
secure location for as long a period as dictated by the reviewing IRB, institutional policies, or 
1429 
sponsor requirements. 
1430 
Study participant research data, which is for purposes of statistical analysis and scientific 
1431 
reporting, will be transmitted to and stored at the Jaeb Center for Health Research (JCHR).  This 
1432 
will not include the participant’s contact or identifying information, unless otherwise specified in 
1433 
the informed consent form.  Rather, individual participants and their research data will be 
1434 
identified by a unique study identification number.  The study data entry and study management 
1435 
systems used by clinical sites and by JCHR research staff will be secured and password 
1436 
protected.  At the end of the study, all study databases will be archived at the JCHR. 
1437 

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Chapter 12: References 
1438 
1. Morberg JN, Singh H, McElwee-Malloy M, Habif S, Constantin A. Real-World 
1439 
Evaluation of Glycemic Outcomes by Prior Therapy for People with Type 1 and Type 2 
1440 
Diabetes Onboarding to Control-IQ Technology. Diabetes. 2021; 70(Supplement 1):710-
1441 
P. 
1442 
2. Breton MD, Kovatchev BP. One Year Real-World Use of the Control-IQ Advanced 
1443 
Hybrid Closed-Loop Technology. Diabetes Technol Ther. 2021; 
1444 
3. Brown SA, Kovatchev BP, Raghinaru D, Lum JW et al. Six-month randomized, 
1445 
multicenter trial of closed-loop control in type 1 diabetes. N Engl J Med. 2019; 
1446 
381(18):1707-1717.  
1447 
4. Breton MD, Kanapka LG, Beck RW, Ekhlaspour L et al. A randomized trial of closed-
1448 
loop control in children with type 1 diabetes. N Engl J Med. 2020; 383(9):836-845.  
1449 
 
1450