Control-IQ Observational (CLIO) Post-Approval Study
Conditions: Diabetes Mellitus, Type 1
Sponsor: Tandem Diabetes Care, Inc.

Protocol V07 Control-IQ Observational (CLIO) Study 
 
1 
 
 
 
Control-IQ Observational (CLIO) Post-Approval Study Protocol 
 
t:slim X2 insulin pump with Control-IQ technology 
Tandem Diabetes Care, Inc. 
February 17, 2022 
 
 
 
 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
2 
 
 
Protocol Identifying Number: 
CLIO Study 
Protocol Name: 
Control-IQ Observational (CLIO) US Post-Approval 
Study 
Phase 
Post-Approval 
Sponsor 
Tandem Diabetes Care, Inc. 
11075 Roselle St.  
San Diego, CA 92121 
USA 
Principal Investigator 
Jordan Pinsker, MD 
Study Device 
t:slim X2 insulin pump with Control-IQ technology 
 
This document is the confidential property of the Sponsor. No part of it may be 
transmitted, reproduced, published, or used by other persons without prior written 
permission. 
STATEMENT OF CONFIDENTIALITY 
The information contained herein is confidential information that is the sole and 
exclusive property of Tandem Diabetes Care, Inc. and may not be divulged to any 
person (except as required by law) without the prior written consent of Tandem 
Diabetes Care, Inc. No part of it may be transmitted, reproduced, published, or used by 
other persons without prior written permission. 
 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
3 
 
Table 1: Protocol Revision History 
Draft 
Number 
Amendment 
Approval Date 
Brief Description of Changes 
01 
N/A 
Initial Draft Version 
02 
April 30, 2020 
Included literature review and evaluable study 
endpoints; added severe hypoglycemia and DKA 
education to participant messaging; adjusted 
criteria for withdrawal from study; added options 
for obtaining information on inclusion/exclusion 
criteria and AEs; clarified CGM-autopopulated 
bolus analysis; and clarified definition of “CGM-
naïve” 
03 
 
Changed name to Control-IQ Observational 
(CLIO) Post-approval Study. Amended 
inclusion/exclusion criteria and enrollment targets 
to include subjects ages 6 years and older. 
04 
August 19, 2020 
In response to FDA request, adjusted enrollment 
targets for subjects ages 6-13 years old. 
05 
October 22, 2020 
Revised wording to provide clarity to the original 
intention of the target enrollment sample size for 
the study, which was to recruit a minimum of 2063 
subjects.  
06.1 
June 28, 2021 
Changed inclusion criteria to “Agree to provide 
HbA1c result, obtained within the 6-month period 
prior to enrollment”. 
 
Added to Medical History: Participants already 
recruited during the COVID emergency who did 
not have a recent HbA1c result within the past 6 
months of enrollment will not be counted toward 
overall recruitment goals, and will be analyzed 
separately. 
 
Participants will be considered screen failures if 
Control-IQ data has not been downloaded to 
t:connect 120 days after the baseline survey’s 
completion. Currently ~24% of CLIO participants 
that have completed their initial baseline 
questionnaire have not progressed to the Month 1 
Survey. To avoid prolonging the overall duration 
of the CLIO study the individuals will be 
considered screen failures if they have not 
downloaded Control-IQ data to t:connect within 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
4 
 
120 days. The period of 120 days was chosen 
because on average 98% of CLIO’s currently 
active participants initiated therapy with Control-IQ 
within that timeframe.  
 
Corrected text throughout document that 
mentioned that Medical Release Forms would be 
collected for all participants during the informed 
consent process. Medical Release Forms are only 
being collected from participants if they report 
adverse events that require additional information 
for reporting purposes. 
 
Included that participants will be contacted 
regarding reported adverse events to the Adverse 
Events section.  
 
Added that as part of the enrollment process as 
specific target subgroups are filled, we may elect 
to only enroll subjects whose subgroup 
recruitment goals have not been completed.   
 
Change PI to Dr. Jordan Pinsker 
 
07 
February 17, 2022 
Clarified throughout document which information 
would be directly entered into the EDC (i.e. 
participant survey responses) versus verified and 
entered into eCRF by trained study personnel (i.e. 
adverse event information).  
 
Additional background material added on CGM 
naïve children who started Control-IQ technology, 
with a new reference to: (10) Renard E, Tubiana-
Rufi N, Bonnemaison E, Coutant R, Della-Vale F, 
Bismuth E, et al. Outcomes of Hybrid Closed-
Loop Insulin Delivery Activated 24/7 versus 
Evening and Night in Free-living Pre-pubertal 
Children with Type 1 Diabetes. A Multicenter 
Randomized Clinical Trial. Diabetes Obes Metab. 
epub ahead of print, November 23, 2021. 
 
Removed text, “Recruitment of CGM-naïve 
children in our previous clinical trial did not 
achieve the pre-specified target of 20%”, and 
added per the recent data published in CGM 
naïve participants in (10) where 33% of 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
5 
 
participants were fully CGM naive, adjusted CGM 
naive target goals for children to represent current 
number enrolled in study (n=18). 
 
Changed 6-9 years old enrollment goal to 163, as 
recently published data of 30 children age 6-9 
shows successful use of Control-IQ technology 
(10). 
 
Clarified that all reported Adverse Events must be 
verified by trained study personnel prior to entry 
into the eCRF and that all outreach attempts to 
participants follow Tandem’s Customer Technical 
Support customer outreach procedure WIA-
000005.  
 
Removed the specific section reference within 
QS-045.   
 
Updated Appendix C to be consistent with 
Tandem’s Customer Technical Support customer 
outreach procedure WIA-000005. 
 
 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
6 
 
PRINCIPAL INVESTIGATOR SIGNATURES 
Protocol Identifying Number: 
CLIO Study 
Protocol Name: 
Control-IQ Observational (CLIO) Post-approval 
Study 
Protocol Version: 
V07 
Protocol Internal Approval Date 
February 17, 2022 
 
The Principal Investigator (undersigned) hereby declares that they have read this 
protocol and agree to its contents. 
The undersigned confirms that the trial will be conducted and documented in accordance 
with the US Federal, State and Local requirements for a post-market human clinical study, 
the protocol, and the stipulations of the clinical trial agreement. 
By written consent to this protocol, the investigators agree to the above and to fully co-
operate with all monitoring and audits in relation to this trial by allowing direct access to 
all documentation, including source data, by authorized individuals representing Tandem 
Diabetes Care, Inc., IRBs and/or by the US Federal, State and local regulatory authorities. 
Investigator Name: Jordan Pinsker, MD 
 
Investigator Signature: ________________________________________ 
 
Date (DD/MMM/YYYY): _________________________________________________ 
 
 
 
 
 
 
 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
7 
 
Terms, Acronyms, Abbreviations 
ABBREVIATION 
DEFINITION 
AP 
Artificial Pancreas 
CGM 
Continuous Glucose Monitoring 
CRF 
Case Report Form 
eCRF 
Electronic Case Report Form 
CRM 
Customer Relationship Management System 
CLC 
Closed-Loop Control 
Control-IQ System 
t:slim X2 insulin pump with Control-IQ technology 
CTS 
Customer Technical Support 
DiAs 
Diabetes Assistant 
DKA 
Diabetic Ketoacidosis 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
iCGM 
Interoperable continuous glucose monitor 
ID 
Identification 
iDCL 
International Diabetes Closed Loop 
IDE 
Investigational Device Exemption 
IOB 
Insulin-on-Board 
IQR 
Interquartile Range 
JDRF 
Juvenile Diabetes Research Foundation 
NIH 
National Institutes of Health 
PRO 
Patient Reported Outcome 
QA 
Quality Assurance 
QC 
Quality Control 
RBM 
Risk-Based Monitoring 
SAP 
Sensor-Augmented Pump 
SD 
Standard Deviation 
T1D 
Type 1 diabetes 
TDD 
Total Daily Dose 
UI 
User Interface 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
8 
 
PROTOCOL SYNOPSIS 
Protocol Number 
V07 
Protocol Title 
Control-IQ Observational (CLIO)  US Post-Approval Study 
Device 
t:slim X2 insulin pump with Control-IQ technology (Control-IQ 
System) 
Type of Protocol 
Post Approval Study 
Rational 
This post-approval study is primarily designed to collect 
safety data on this US FDA-cleared product. Several 
secondary endpoints assessing the effectiveness of this 
product in real-world use will also be collected. The t:slim X2 
insulin pump with Control-IQ technology will be used as 
intended and in accordance with FDA-approved labeling. 
Objectives 
Primary objective: To demonstrate, in a real-world setting, 
the safety of the Control-IQ System for the management of 
type 1 diabetes by assessing the rate of severe hypoglycemia 
(SH) and diabetic ketoacidosis (DKA). 
Secondary objective: To demonstrate, in a real-world 
setting, the effectiveness of the Control-IQ System for the 
management of type 1 diabetes by assessing the impact on 
patients’ glycemic outcomes and user experience in the real 
world, during the first 12 months of use. 
Primary Endpoints 
Safety Endpoints: 
1) The incidence rates of severe hypoglycemia (SH) and 
diabetic ketoacidosis (DKA), and 
2) The safety of the automatic population of CGM readings 
into the bolus calculator of the Control-IQ System 
Secondary Endpoints: 
3) To determine glycemic outcomes as a measure of efficacy 
of the Control-IQ System, and  
4) To demonstrate patient-reported satisfaction with and 
trust in the Control-IQ System, usability of the system, and 
sleep quality. 
Duration of Study 
All enrolled subjects will be monitored for outcome data for 12 
months after starting the Control-IQ System. 
Study Design 
This post-approval study is a single-arm, prospective study. It 
is designed to assess 12-month safety in a real-world setting, 
and to support the continued assessment of the Control-IQ 
System for the treatment of type 1 diabetes in the United 
States. In addition, data will be collected to assess glycemic 
outcomes and user experience. 
Study Population 
Enrollment in the study will be available to all subjects who 
start therapy with the Control-IQ System once the Institutional 
Review Board (IRB) approval is received and the subject 
meets the indications for use and the study eligibility criteria. 
As specific target subgroups are filled, we may elect to only 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
9 
 
enroll subjects whose subgroup recruitment goals have not 
been completed.  Electronic informed consent will be required 
from all subjects prior to participation in the study. 
Number of Subjects 
The study will recruit a minimum of 2,063 subjects. For the 
primary safety endpoints, the projected total recruitment 
sample size of at least 2,063 subjects (including 25% attrition) 
would provide 80% power with a 2-sided type 1 error rate of 
5%. With attrition, it is expected that 1,547 subjects will 
complete the study. Recruitment goals for study subgroups 
will include: 
• At least 385 subjects in the 6 to 13 year-old cohort, and at 
least 328 subjects in the 14 to ≤18 year-old cohort. 
Depending on the rate of recruitment in these two age 
groups, the balance of the total sample will be recruited 
from the >18 year-old subgroup.  
• Details on subgroup enrollment targets can be found on 
page 23 “Determination of Sample Size” 
 
Number and Location 
of Sites 
All data for this study will be collected remotely, with no live 
clinical visits conducted. Data will be collected electronically, 
via surveys and automated uploads of pump and CGM data, 
as well as via in- and out-bound telephone calls and SMS 
messaging. 
Inclusion/Exclusion 
Criteria 
Inclusion Criteria:  
1. Patients with self-reported type 1 diabetes who have been 
prescribed the Control-IQ system. 
2. At least 6 years of age 
3. Using Humalog or Novolog insulin 
4. For females, not pregnant or planning pregnancy in the 
next 12 months. 
5. Agreement to use the t:slim X2 with Control-IQ 
technology, and to continue use for at least 12 consecutive 
months after study enrollment.  
6. Agree to provide HbA1c result, obtained within the 6-
month period prior to enrollment. 
7. Ability to respond to alerts and alarms, and to provide 
basic diabetes self-management. 
8. Patients who reside full-time in the United States. 
9. Willingness to download the t:connect Mobile application 
to their Smartphone and keep it active throughout the 
study. Patients unable to use t:connect Mobile application 
must be willing to manually upload their insulin pump data 
to t:connect every three months and at the completion of 
the study. 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
10 
 
10. Subject has read, understood and agreed to participate in 
the study, and has electronically signed the Informed 
Consent Form (ICF). 
 
Exclusion Criteria: 
1. Self-reported type 2 diabetes 
2. < 6 years of age 
3. Use of any glucose-lowering therapy other than Humalog 
or Novolog insulin 
4. Inability to respond to alerts and alarms, or to provide 
basic diabetes self-management. 
5. Pregnancy 
6. Subjects who have not signed the ICF. 
Procedures in 
Screening/Baseline 
Period 
Study subjects will be recruited via automated electronic 
outreach from new users of the Control-IQ System. All 
customers receiving new pumps and receiving Control-IQ 
software 
updates 
will 
be 
initially 
screened 
for 
inclusion/exclusion criteria electronically via filters in the CRM 
system. Invitations to participate will be sent to all customers 
who initially qualify for the study. A positive response from a 
customer will initiate the informed consent process and 
provide a second screening and baseline survey. An 
electronic signature of consent will be obtained from 
customers who qualify after the second screening. Once 
consent is obtained, a baseline survey will collect PROs (user 
experience and adverse events) related to therapy prior to 
starting Control-IQ.  
Periodic Data 
Collection procedures 
100% of calls to Tandem Customer Technical Support will be 
screened for reportable AEs based on the definitions of SH 
and DKA included in this protocol. Outreach surveys will be 
deployed to all study participants: Monthly to collect AE 
incidence, and at 3, 6 and 12 months to collect other PROs 
(See Table 1). 
Management of 
Adverse Events 
Safety information will be collected on an ongoing basis 
throughout the study as Tandem becomes aware of device-
related AEs. These events will be recorded electronically from 
both inbound reports from customers and assessed through 
outreach to patients. The event, date of onset, severity, 
seriousness, duration and relationship to the device will be 
documented. All reported device-related AEs will be followed 
until they are adequately resolved or stabilized, until study 
completion/termination, or until number of outreach attempts 
made by clinical personnel corresponds with company’s 
Customer Technical Support policy for adverse and device 
issue event outreach, whichever comes first. Safety events 
will be summarized based on FDA codes. 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
11 
 
Statistical Analysis 
Descriptive statistics will be used to evaluate outcomes vs. a 
comparator group. The Comparator Group will be determined 
using evidence from a systematic literature review examining 
MDI, insulin pump and sensor augmented pump (SAP) use in 
patients with type 1 diabetes. Primary endpoints, the risk of 
AE (DKA, SH), represented as risk ratio per 100 patient years, 
will be compared using a single sample two-tailed exact 
binomial test (alpha=0.05) to the expected values as 
extracted in the literature review. Effect size will be defined as 
the absolute difference in risk ratios. The safety of 
automatically populating CGM readings into the bolus 
calculator will be analyzed by correlating reported AEs, 
calculator usage data and CGM readings to understand if the 
bolus calculator may have caused the AE. This analysis will 
isolate AEs where three consecutive CGM readings ≤54 
mg/dL, or ≥250 mg/dL existed within five hours after a 
correction bolus was given using an automatically populated 
CGM reading. Boluses using automatically populated CGM 
values ≥250 mg/dL will be analyzed and evaluated separately 
from boluses given for lower glucose values. 
Secondary endpoints will be calculated as means/medians as 
appropriate based on data extracted from the Tandem 
t:connect web application and patient reported outcomes. 
Sensor-glucose concentrations will be analyzed per recent 
international consensus guidelines, to include time in target 
range 70-180 mg/dL, time >180 mg/dL, time >250 mg/dL, 
time <70 mg/dL, time <54 mg/dL. 
Outcomes will be analyzed quarterly and tabulated using 
standard statistical tools such as R and Python. 
 
The study will be conducted and documented in accordance with the US Federal and 
Local requirements for post-market human clinical studies, the protocol, and the 
stipulations of the clinical trial agreement.  
Table 1: Timeline of Data Collection 
Procedure/Assessment 
Baseline* Monthly  Months 3 and 6 
Final 
Informed Consent 
X 
 
 
 
**Release of medical records 
 
 
 
 
Screening for eligibility 
X 
 
 
 
Report of incoming AEs 
 
X 
 
X 
Outreach for AEs 
X 
X 
 
X 
User Experience 
X 
 
X 
X 
Psychosocial Outcomes 
X 
 
X 
X 
*Includes demographics, frequency of AEs 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
12 
 
**Only requested as needed to collect additional information on reported AEs  
BACKGROUND 
Disease background 
Type 1 diabetes affects 1.25 million people in the United States. Approximately 70% of 
individuals with type 1 diabetes report poor metabolic control, and do not meet the 
American Diabetes Association’s recommended goal of hemoglobin A1c (HbA1c) level of 
7.5% for children (<18 years) and 7.0% for adults (≥18 years) (1). These findings indicate 
the need for better approaches to type 1 diabetes management. 
Recent estimates suggest that approximately 400,000 U.S. patients with type 1 diabetes 
(T1D) use insulin pumps (2). Adoption of pump therapy varies by geography and may be 
related to healthcare provider preference or patient characteristics and socioeconomic 
status. Use of insulin pumps is more common in individuals of higher socioeconomic 
status as reflected by race/ethnicity, private health insurance, family income, and 
education (3). Additionally, referrals from healthcare providers and insurance approvals 
are critical determinants for who becomes a pump user in the U.S.(4). 
The Tandem t:slim X2 insulin pump with Control-IQ Technology is a third-generation 
hybrid closed-loop system retaining the same control algorithm that was initially tested by 
UVA’s DiAs system and then implemented in the inControl system.  IDE 1-9 below are 
specific to the implementation proposed here. For complete algorithmic and clinical 
background, we refer to a number of scientific publications that describe glycemic control 
outcomes and clinical impressions from the use of the Control-IQ System (5-9). This 
extensively tested control algorithm has been embedded into the t:slim X2 insulin pump 
with Control-IQ technology, which is the device in the current study. 
The following IDEs reflect the broad scope of development and testing of the current 
Control-IQ System: 
1. IDE #G150240: Project Nightlight: Efficacy and system acceptance of 
dinner/night vs. 24 hr closed loop control; 11/12/2015. 
2. IDE #G160097: Clinical Acceptance of the Artificial Pancreas: The International 
Diabetes Closed-Loop (iDCL) Trial/Research Site Training Protocol; 06/03/16. 
3. IDE#G110095:  Clinical Acceptance of the Artificial Pancreas: The International 
Diabetes Closed-Loop (iDCL) Trial, A Pilot Test of t:slim X2 with Control-IQ 
Technology. 10/16/2017. 
4. IDE#G170267: Real-Time Monitoring and Glucose Control During Winter-Sport 
Exercise in Youth with Type 1 Diabetes: The AP Ski Camp Continued. 
12/01/2017. 
5. IDE#G180053: Protocol 3: Clinical Acceptance of the Artificial Pancreas 
(DCLP3), 6/23/2018. 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
13 
 
6. IDE#G180174: The VRIF Trial: Hypoglycemia Reduction with Automated-Insulin 
Delivery System, 10/5/2018. 
7. IDE#G180279: Safety and Efficacy of Initializing the Control-IQ Artificial 
Pancreas System Using Total Daily Insulin, 11/21/2018 
8. IDE#G180053/S008: Protocol 5: Clinical Acceptance of the Artificial Pancreas in 
Pediatrics. A Study of t:slim X2 with Control-IQ Technology (DCLP5), 12/17/2018 
9. 2018-A01152-53 
(French 
National 
Study 
ID): 
Freelife-Kid-AP 
Study: 
Assessment of the Efficacy of Closed-Loop Insulin Therapy (Artificial Pancreas) 
on the Control of Type 1 Diabetes in Prepubertal Child in Free-Life: Comparison 
Between Nocturnal and 24-Hour Use, 8/7/2018. 
 
In November 2021, Renard et al. published the results of the FreeLife Kid AP study 
(NCT03739099) in France (10). The study involved 122 children with type 1 diabetes 
ages 6-13 who were enrolled to begin Control-IQ technology use in outpatient, free-
living conditions. Participants were randomized to 24/7 use of Control-IQ technology vs. 
dinner and overnight only use for the first 18 weeks, then all participants continued 24/7 
use of Control-IQ technology for an additional 18 weeks. Phone follow up was 
performed at 48 hours, 1 week and 2 weeks after Control-IQ technology initiation, and 
scheduled in clinic visits were performed at 6, 12 and 18 weeks. During the 18-week 
extension period, clinic visits were scheduled at week 27 and at week 36 for the end of 
the study. Adverse events were solicited at all of these visits. 
Study results indicated no ketoacidosis or severe hypoglycemia for the entire study 
duration (10). Forty participants (33%) in this study were CGM naïve. Thirty were age 6-
9. Twenty-one of these CGM naïve participants were randomized to use the system all 
day for 36 weeks. The other 19 used the system with Control-IQ active at dinner and 
overnight only for the first 18 weeks, then activated it 24/7 for the next 18 weeks. Mean 
age of these CGM naive participants was 8.4 years and 50% were female. Mean time in 
range 70-180 mg/dL was 52.5% at baseline, with 5.6% time less than 70 mg/dL. Using 
Control-IQ technology 24/7, mean time in range 70-180 mg/dL increased to 67% in this 
participant group (vs. 67% for the entire study cohort), with mean time <70 mg/dL 
decreasing to 2.8% (vs 2.7% for the entire study cohort) [CGM Naïve Participant Data 
On File].  
 
General Description of Investigational Device 
The t:slim X2 insulin pump with Control-IQ technology, the hybrid closed-loop insulin 
delivery system from Tandem Diabetes Care, is intended for subcutaneous delivery of 
insulin for the management of type 1 diabetes mellitus. The system uses advanced 
closed-loop control algorithms to adjust insulin delivery to help keep blood glucose in a 
targeted range. The current Control-IQ System components include the t:slim X2 insulin 
pump with Control-IQ technology and the current generation of the Dexcom G6 CGM. 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
14 
 
Future iterations of the Control-IQ System may incorporate FDA-cleared modifications to 
the algorithm and integration with any FDA-cleared continuous glucose monitors that 
meet the iCGM criteria. Subjects in this study will be allowed to update their therapy with 
future products from Tandem Diabetes Care, Inc., and future FDA-cleared CGMs that 
meet the iCGM criteria, during the study period. 
The Control-IQ Technology uses data from the CGM and other inputs to: 
• decrease and/or suspend insulin delivery when hypoglycemia is predicted (or 
occurs);  
• increase insulin delivery when hyperglycemia is predicted (or occurs), and 
• deliver automated correction boluses when necessary to mitigate hyperglycemia  
 
The system used in this study is comprised of a CGM sensor and transmitter along with 
an insulin pump with user interface (IU) for display of system information, and a control 
algorithm. The sensor is inserted subcutaneously and transmits data every 5 minutes to 
the pump via the transmitter.   
 
Figure 1 - Tandem Pump Control-IQ System 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
15 
 
STUDY OBJECTIVES, DESIGN AND ENDPOINTS 
Study Objectives 
Primary objectives: 
1) To demonstrate, in the post-approval setting, the safety of the Control-IQ System for 
the management of type 1 diabetes by assessing the rate of severe hypoglycemia (SH) 
and diabetic ketoacidosis (DKA), 
2) To monitor the safety of the automatic population CGM readings into the bolus 
calculator of the Control-IQ System, 
Secondary objectives: 
3) To determine glycemic outcomes during real-world use of the Control-IQ System, and  
4) To demonstrate patient-reported satisfaction with the device, trust in the Control-IQ 
System, usability of the system, and sleep quality. 
Study Design 
This post-approval study is a single-arm, prospective, longitudinal study. It is designed to 
assess the 12-month safety and effectiveness of this FDA approved product in a post-
approval setting, and to support the continued assessment of the t:slim X2 insulin pump 
with Control-IQ technology for the treatment of type 1 diabetes in the US. In addition, data 
will be collected to assess the experience of patients using the Control-IQ system.  
This study will enroll a minimum of 1698 subjects over a two-year period. All enrolled 
subjects will be monitored from baseline through 12 months following the initiation of 
therapy with the Control-IQ System.  
The data collected in this study will be entered into either Qualtrics, a HIPAA compliant 
software database, or an electronic data capture system (EDC) using electronic case 
report forms (eCRFs). Subject data will include participant reported demographics, 
medical history, and baseline therapy information along with therapy data, and follow-up 
measures.  
Study Endpoints 
• Primary Safety Endpoints: Composite rate of severe hypoglycemia and diabetic 
ketoacidosis through 12 months following initiation of therapy with the Control-IQ 
System. 
• Secondary Effectiveness Endpoints  
o Glycemic outcomes (based on data from CGM sensor values): 
▪ % time in range (70-180 mg/dL) 
▪ % time <54 mg dL 
▪ % time <70 mg/dL 
▪ % time >180 mg/dL 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
16 
 
▪ %time >250 mg/dL 
o Patient-reported outcomes: 
▪ Satisfaction with device 
▪ Trust in the system 
▪ Usability of the system 
▪ Sleep quality 
 
SUBJECT SELECTION 
Subject Population 
Inclusion Criteria: Patients must consent to meet the following criteria in order to be 
enrolled in the study: 
1) Patients with self-reported type 1 diabetes who have been prescribed the Control-
IQ system. 
2) At least 6 years of age 
3) Using Humalog or Novolog insulin 
4) For females, not pregnant or planning pregnancy in the next 12 months. 
5) Agreement to use the t:slim X2 with Control-IQ technology, and to continue use for 
at least 12 consecutive months after study enrollment.  
6) Agree to provide HbA1c result, obtained within the 6-month period prior to 
enrollment. 
7) Ability to respond to alerts and alarms, and to provide basic diabetes self-
management. 
8) Patients who reside full-time in the United States. 
9) Willingness to download the t:connect Mobile application to their Smartphone and 
keep it active throughout the study. Patients unable to use t:connect mobile 
application must be willing to manually upload their insulin pump data to t:connect 
every three months and at the completion of the study.  
10) Subject has read, understood and agreed to participate in the study, and has 
electronically signed the Informed Consent Form (ICF). 
Exclusion Criteria: Patients with the following characteristics will not be considered 
candidates for the study:  
1) Self-reported type 2 diabetes 
2) < 6 years of age 
3) Use of any glucose-lowering therapy other than Humalog or Novolog insulin 
4) Inability to respond to alerts and alarms, or to provide basic diabetes self-
management. 
5) Pregnancy 
6) Subjects who have not signed the ICF.  

Protocol V07 Control-IQ Observational (CLIO) Study 
 
17 
 
Any discrepancy in the above criteria between data in CRM and subject’s self-reported 
criteria will be electronically alerted to study staff. Study staff will then clarify 
inclusion/exclusion criteria prior to enrolling the subject.  
Over the course of the study as specific participant recruitment subgroups are filled, we 
may enroll subjects whose subgroup goals have not been completed and elect to exclude 
otherwise applicable participants.  
 
Subject Withdrawal or Termination 
Subjects are free to withdraw from the study at any time and will be withdrawn if they 
inform Tandem that they no longer wish to participate. Data collected prior to the subject’s 
withdrawal will remain part of the study record and will be included in the analyses. All 
participants that have been successfully enrolled in the study will receive regular 
invitations to provide data. A Retention Management protocol will be initiated to attempt 
to re-engage participants that do not respond after three separate outreach attempts. 
TREATMENT OF SUBJECTS 
The t:slim X2 insulin pump with Control-IQ technology 
The Control-IQ System is a US FDA-approved device indicated for the treatment of type 
1 diabetes in people age 6 years and older. The Control-IQ System is integrated with the 
Dexcom G6 CGM and uses CGM values to adjust insulin delivery with the goal of 
improving glucose control (time in range of 70-180 mg/dL).  
Initiation of therapy with the Control-IQ System:  
• Subjects will be recruited from the population of patients initiating therapy with 
Control-IQ after it has been prescribed by a licensed healthcare professional.  
• Subjects new to the Tandem X2 insulin pump will receive a new pump with Control-
IQ technology 
o These subjects might be new to insulin pump therapy or might be switching 
from a different brand or type of insulin pump. 
• Subjects who own a t:slim X2 insulin pump will receive a remote software update 
and download the Control-IQ technology onto their existing t:slim X2 insulin pump.  
Enrollment procedure:  
The enrollment process has been detailed in the flowchart in APPENDIX A. Study 
subjects will be enrolled using customer recruitment filters and triggers from two data 
sources housed within Tandem – (a) the CRM (or the Custom Relationship Management 
Technology) and (b) the t:connect® customer portal (web secure application designed for 
Tandem users to request prescriptions for any pump-related updates and complete 
necessary trainings). Daily automatic recruitment invite contact lists, defined by study 
inclusion and exclusion criteria, will be generated for eligible Tandem users and using a 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
18 
 
secure file transfer protocol, and Qualtrics (a HIPPA compliant survey and report 
generating software) will deploy automated survey invites daily (via email or SMS text). 
The first study invite will include important information about the study eligibility criteria 
and an invitation to start the informed consent process, including a Release of Medical 
Records form and the baseline questionnaires (baseline adverse events and other PRO 
measures). Tandem users who indicate that they are not interested in participating will be 
removed from the potential recruitment list and will not receive any further communication 
about the study. The remaining users will receive reminder emails (as needed) and those 
interested will complete the IRB approved electronic consent form by providing their 
digital signature. 
Duration of therapy and follow-up: All enrolled subjects who initiate therapy with the 
Control-IQ System will be monitored from baseline through 12 months following the 
initiation of treatment. Participants will be considered screen failures if Control-IQ data 
has not been downloaded to t:connect 120 days after the baseline survey’s completion.  
MEASUREMENTS AND EVALUATIONS 
Event Schedule: The eCRFs will be completed by the investigator (or an authorized 
member of the investigator’s staff) and entered into the EDC database per the event 
schedule described below. 
Baseline Data Collection: The potential study subjects will be evaluated (initially via 
CRM filters) to ensure they are appropriate candidates for this post approval study. 
Interested subjects will be asked to sign the ICF electronically. Eligibility to enroll in the 
study will be assessed based on the inclusion/exclusion criteria and the fulfillment of 
specific target subgroup populations. The enrollment information will be entered via 
participant responses into the EDC system. In addition, demographic and relevant 
medical history will be collected at this time (see APPENDIX A for detailed steps in the 
screening and enrollment process). 
Subject Completion or Early Withdrawal: The subject completes the study one year 
after initiating therapy with Control-IQ, or when they choose to withdraw from the study, 
if earlier than 1 year.  
Data Collection:  
The data will be collected per the schedule outlined below: 
Procedure/Assessment 
Baseline* Monthly  
Months 3 and 6 
Final 
Informed Consent 
X 
 
 
 
**Release of Medical 
Records 
 
 
 
 
Screening for eligibility 
X 
 
 
 
Report of incoming AEs 
 
X 
 
X 
Outreach for AEs 
X 
X 
 
X 
User Experience 
X 
 
X 
X 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
19 
 
Psychosocial Outcomes 
X 
 
X 
X 
*Includes demographics, frequency of AEs 
**Only requested as needed to collect additional information on reported AEs  
Investigators will be provided a process for assigning a de-identified number to the subject 
and will be required to keep any study paperwork or electronic files in a secure private 
area. Electronic audits will be in place to help ensure that data entered is within 
reasonable limits.  
Informed Consent Process: All subjects must electronically sign the ICF (see 
APPENDIX B) approved by the IRB to be enrolled in the study. The subject will receive 
study team contact information (email and telephone) and be given ample opportunities 
to ask questions about the procedures, required schedule of data collection, and the 
benefits and risks of participating in the study before signing the ICF. All subjects will 
receive an electronic copy of the ICF to keep for their records. Subjects will be informed 
of any revisions to the ICF and any revisions must be electronically signed and kept in 
the subject study file. In addition, a signed Release of Medical Records form may be 
obtained if needed to collect additional information on reported Adverse Events to allow 
the investigators to obtain accurate event information when necessary. Acquisition of the 
informed consent, Release of Medical Records form (if applicable) and any revisions will 
be documented in the survey database. 
Demographics: The following demographic data will be obtained: date of birth, gender, 
race, ethnicity, educational level, socioeconomic status, residence, employment status, 
weight, height, and type of health insurance.   
Medical History: Medical history, including existing comorbidities deemed clinically 
relevant (e.g. retinopathy, nephropathy, neuropathy, history of cardiovascular events) will 
be collected at baseline. In addition, details specific to type 1 diabetes, including age at 
diagnosis, duration of disease, previous therapy, most recent HbA1c within the past 6 
months, frequency of SH and DKA, and family history will be collected from the study 
subject in the baseline questionnaire.  
Participants already recruited during the COVID emergency who did not have a recent 
HbA1c result within the past 6 months of enrollment will not be counted toward overall 
recruitment goals, and will be analyzed separately. 
Observation and Recording of Adverse Events: Subjects will be required to report 
AEs. Open-ended questions and questions specific to SH and DKA will be included in all 
subject outreach contacts. In addition, the Global Post-market Surveillance data base 
(Tandem Diabetes Care, Inc.) will be queried monthly to determine the incidence of SH 
and/or DKA reported by study subjects (see APPENDIX C for surveillance procedures). 
An AE form will be completed for every adverse event reported by a subject and verified 
by trained study personnel. Any medical management of an event and the resolution of 
the event must be recorded within the internal database utilized by Tandem’s Global Post-

Protocol V07 Control-IQ Observational (CLIO) Study 
 
20 
 
market Surveillance team (CRM), as the source documentation, and on the appropriate 
eCRF using medical terminology. 
Patient-reported Outcomes: Questionnaires and surveys suitable for subjects being 
treated for type 1 diabetes (see APPENDIX D) will be electronically deployed to subjects 
at times specified in the Data Collection Timeline. 
ADVERSE EVENTS 
Adverse Event Definitions 
An adverse event (AE) is any untoward medical occurrence in a study subject, 
regardless of the relationship between the adverse event and the device under 
investigation. All AEs experienced by all subjects will be documented throughout the 
entirety of the study, as outlined below. 
In this study, the subjects will be instructed to report AEs spontaneously or in response 
to general, non-directed, or directed questions. At any time during the study, the subject 
may volunteer information that resembles an AE. Once it is determined by trained study 
personnel confirming with the subject that an AE has occurred, the investigator will obtain 
all the information required to complete the AE form. Any medical management of an 
event and the date of resolution of the event must be recorded on the appropriate eCRF 
using medical terminology. Any AE experienced by a subject will be followed until the AE 
has resolved to the clinical investigator’s satisfaction or is considered stable. If information 
about an AE (or suspected AE) is not adequately obtained via incoming calls to Customer 
Technical Support or electronic means, the study team will contact the participant, request 
medical records and/or contact the subject’s physician for more information. Trained 
study personnel will follow Tandem’s Customer Technical Support working instructions 
(WIA-000005) for customer outreach policies when confirming an adverse event for the 
study. The adverse event form will document the following: 
• AE diagnosis or definition 
• Serious/non-serious 
• Severity 
• Action taken 
• Relationship to Control-IQ System 
• Anticipated/Unanticipated 
• Date of onset 
• Date of resolution 
Additional information on specific events may be recorded in the eCRF. 
Each adverse event form that has been verified will be reviewed by the clinical investigator 
to determine the type, intensity, severity, and causality of the event, and whether 
anticipated or unanticipated, in order to verify the reporting that is required. The guidelines 
below will be followed to characterize each event. 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
21 
 
Reportable Adverse Events:  
For this protocol, a reportable adverse event includes any untoward medical occurrence 
that meets one of the following criteria, as defined below:  
1. Hypoglycemia meeting the definition of severe hypoglycemia (SH) 
2. Diabetic ketoacidosis (DKA)  
3. A serious adverse event (SAE) 
4. An adverse device effect (ADE) 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as 
adverse events unless associated with an adverse device effect (ADE). Skin reactions 
from sensor placement are only reportable if severe and/or if they required treatment. 
Severe Hypoglycemia:  
Hypoglycemia not associated with an ADE is only reportable as an adverse event when 
the assistance of another person was required in order to actively administer 
carbohydrate, glucagon, or other resuscitative actions due to altered consciousness. This 
means that the subject was impaired cognitively to the point that he/she was unable to 
treat him/herself, was unable to verbalize his/her needs, was incoherent, disoriented 
and/or combative, or experienced seizure or coma. These episodes may be associated 
with sufficient neuroglycopenia to induce seizure or coma. If glucose measurements are 
not available during such an event, neurological recovery attributable to the restoration of 
glycose to normal is considered sufficient evidence that the event was induced by a low 
glucose concentration. 
Subjects will be instructed on this specific definition of severe hypoglycemia each time 
information is requested related to this AE. 
Diabetic ketoacidosis: 
DKA is reportable as an adverse event when the subject reports the following:  
• Symptoms such as polyuria, polydipsia, nausea or vomiting, and 
• Treatment provided in a health care facility, and 
• Diagnosis of DKA made by a health care provider and self-reported by the patient. 
Subjects will be instructed on this specific definition of DKA each time information is 
requested related to this AE. 
Serious Adverse Event (SAE):  
In accordance with 21 CFR Parts 803 and 812, a SAE is defined as any untoward 
medical occurrence that:  
• Results in death, 
• Is life-threatening, 
• Requires hospitalization or prolongation of existing hospitalization,  

Protocol V07 Control-IQ Observational (CLIO) Study 
 
22 
 
• Results in persistent or significant disability/incapacity or substantial disruption of 
the ability to conduct normal life functions, 
• Is a congenital anomaly or birth defect, or  
• Is considered a significant medical event by the investigator based on medical 
judgement (e.g., may jeopardize the subject or may require medical/surgical 
intervention to prevent one of the outcomes listed above).  
Medical and scientific judgement will be exercised in deciding whether medical events 
that may not be immediately life-threatening or result in death or hospitalization, but may 
jeopardize the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above, should also be considered serious. A serious adverse event 
must be reported to the FDA as soon as possible, within a maximum of 15 calendar days. 
Unanticipated Adverse Device Effect (UADE) 
In accordance with 21 CFR Part 812, an UADE is any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, a device, if 
that effect, problem, or death was not previously identified in nature, severity, or degree 
of incidence in the risk assessment, the ICF as well as the protocol, or any other 
unanticipated serious problem associated with a device that relates to the rights, safety 
or welfare of subjects. An unanticipated device effect must be reported to the IRB within 
5 business days and to the FDA within 10 business days.  
In contrast to a UADE, an anticipated SAE is any SAE, the nature or severity of which 
has been reported in clinical trials of the Control-IQ System, or reported to Tandem 
Diabetes Care, Inc. by users of the t:slim X2 insulin pump. AEs reported during clinical 
studies of the Control-IQ system and post-market vigilance of the t:slim X2 insulin pump 
include, but are not limited to, the events shown below. The following device issues are 
anticipated and will not be reported on a Device Issue Form but will be reported as an 
Adverse Event if the criteria for AE reporting described above are met: 
• Component disconnections 
• CGM sensors lasting fewer than the number of days expected per CGM labeling  
• CGM tape adherence issues 
• Pump infusion set occlusion not leading to ketosis 
• Battery lifespan deficiency due to inadequate charging or extensive wireless 
communication  
• Intermittent device component disconnections/communication failures not leading 
to system replacement 
• Device issues clearly addressed in the user guide manual that do not require 
additional troubleshooting 
• Skin reactions from CGM sensor placement of pump infusion set placement that 
do not meet criteria for AE reporting 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
23 
 
In addition, if the device issue is listed in Tandem Procedure QS-045, FDA Medical Device 
Reporting will be anticipated and not reported on a Device Issue Form. Any other device-
related SAE will be considered an unanticipated adverse device event (UADE).  
Relationship of Adverse Event to Study Device (causality): 
The clinical investigator will assess the relationship of any adverse event to be related or 
unrelated by determining if there is a reasonable possibility that the adverse event may 
have been caused by the study device. To ensure consistency of adverse event causality 
assessments, the investigator will apply the following guidelines when determining 
whether an adverse event is related:  
YES: There is a plausible temporal relationship between the onset of the adverse event 
and the study intervention, and the adverse event cannot be readily explained by the 
subject’s clinical state, intercurrent illness or concomitant therapies; and/or the adverse 
event follows a known pattern of response to the study intervention; and/or the adverse 
event abates or resolves upon discontinuation of the study intervention.  
NO: Evidence exists that the adverse event has an etiology other than the study 
intervention (e.g., preexisting medical condition, underlying disease, intercurrent illness, 
or concomitant medication); and/or the adverse event has no plausible temporal 
relationship to study intervention. 
Adverse Device Effect (ADE):  
Any untoward medical occurrence in a study subject which the device may have caused 
or to which the device may have contributed (Note that a Device Deficiency or Issue Form 
must be completed in addition to an Adverse Event Form, if the event is determined to be 
an ADE. 
Intensity of Adverse Event: 
The intensity of an adverse event will be rated on a three-point scale: 1) mild, 2) moderate, 
or 3) severe. The term severe is a measure of intensity: thus, a severe adverse event is 
not necessarily serious. For example, itching for several days may be rated as severe, 
but may not be clinically serious. 
• Mild: Usually transient, requires no special treatment, and does not interfere with 
the subject’s daily activities. 
• Moderate: Usually causes a low level of inconvenience or concern to the subject 
and may interfere with daily activities but is usually ameliorated by simple 
therapeutic measures. 
• Severe: Interrupts a subject’s usual daily activities and generally requires systemic 
drug therapy or other treatment.  
Expedited Safety Reports:  

Protocol V07 Control-IQ Observational (CLIO) Study 
 
24 
 
As the Control-IQ System is an FDA-approved and commercially available product in the 
US, in addition to SH, DKA, SAEs and UADEs, medical device reporting requirements 
(21 CFR 803) are applicable to all AEs reported through this study. 
 
STATISTICAL CONSIDERATIONS 
Determination of Sample Size 
The approach to sample size and statistical analyses are summarized below. A detailed 
statistical analysis plan will be written and finalized prior to the first tabulation of data. In 
order to determine the incidence rates on which the power analyses were based, Tandem 
conducted a literature review (see Attachment 1 for methodology). Ranges of event rates 
reported in the literature for both severe hypo and DKA in patients with T1D are very 
broad; 0-100 events/100PY for severe hypoglycemia, and 0.4 – 26 events/100 PY for 
DKA (see Table 1, Attachment 1). Therefore, for purposes of power analyses for the 
proposed study, we used event rates from a recently published study using a large Type 
1 Diabetes Exchange cohort (Foster et al, 2019). This study used a similar design as our 
approved post-market study, the subjects represent our intended use population, and the 
event rates reported in the Foster study fall within the broader rates found in the extensive 
body of literature reviewed. 
Sample size was determined in 3 steps: 
Step 1 – Power analysis for severe hypoglycemia (SH) 
An overall incidence rate of 25.35 events per 100 patient years (PY) was used in the 
power analysis for severe hypoglycemia. We calculated that a sample size of 1,354 
individuals with T1D would provide 80% power with a type 1 error rate (two-sided) of 5% 
to detect a difference, if there is one, between the expected SH rate (25.35) and the 
proposed study sample SH event rate. 
A separate power analysis for the 14-18 age group used an overall SH incidence rate of 
19.5 events/100PY. Results indicated that a sample size of 231 individuals with 
T1D between the ages of 14-18 would provide 80% power with a type 1 error rate (two-
sided) of 5% to detect a difference, if there is one, between the expected SH rate (19.5) 
and the proposed study sample SH event rate. Of the overall sample of 1,354 subjects, 
at least 231 subjects will be 14-18 years old to provide sufficient power to detect risk of 
SH in this younger age group.  
A separate power analysis for the 6-13 year old group used a SH incidence rate of 
21.9 events/100PY, which is a weighted average of both MDI and pump users (since 
pump users were overrepresented in this age group). Results indicated that a sample 
size of 288 individuals with T1D between the ages of 6 and 13 would provide 80% power 
with a type 1 error rate (two-sided) of 5% to detect a difference, if there is one, between 
the expected SH rate (21.9) and the proposed study sample SH event rate. In addition to 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
25 
 
the overall sample, at least 288 subjects will be 6-13 years old to provide sufficient power 
to detect risk of SH in this younger age group. Step 2 – Power analysis for diabetic 
ketoacidosis (DKA) 
An overall incidence rate of 11.03 events per 100 patient years was used in the power 
analysis for DKA . We calculated that a sample size of 1,282 individuals with T1D would 
provide 80% power with a type 1 error rate (two-sided) of 5% to detect a difference, if 
there is one, between the expected DKA rate (11.03/100 PY) and the proposed study 
sample DKA event rate.  
A separate power analysis for the 14-18 age group used an overall DKA incidence rate 
of 14.2 events/100PY. Results indicated that a sample size of 328 individuals with 
T1D between the ages of 14-18 would provide 80% power with a type 1 error rate (two-
sided) of 5% to detect a difference, if there is one, between the expected DKA rate (14.2) 
and the proposed study sample DKA event rate. Of the overall sample of 1,282 subjects, 
at least 328 subjects will be 14-18 years old to provide sufficient power to detect risk 
of DKA in this younger age group.  
A separate power analysis for the 6-13 year old group used an overall DKA incidence rate 
of 13.2 events/100PY, which is a weighted average of both MDI and pump users (since 
pump users were overrepresented in this age group). Results indicated that a sample 
size of 77 individuals with T1D between the ages of 6-13 would provide 80% power with 
a type 1 error rate (two-sided) of 5% to detect a difference, if there is one, between the 
expected DKA rate (13.2/100PY) and the proposed study sample DKA event rate. In 
addition to the previously determined sample, at least 77 subjects will be 6-13 
years old to provide sufficient power to detect risk of DKA in this younger age group.  
Step 3 – Final sample size determination 
The projected total recruitment sample size of at least 2,063 subjects (including attrition) 
would provide 80% power with a 2-sided type 1 error rate of 5%. Considering the 25% 
attrition mentioned above, it is the expectation to have 1,354 subjects complete the study. 
Recruitment goals for study subgroups will include: 
• At least 385 subjects in the 6 to 13 year old cohort, and at least 328 subjects in the 
14 to ≤ 18 year old cohort. Depending on the rate of recruitment in these two age 
groups, the balance of the total sample will be recruited from the >18 year old 
subgroup. 
• Of the 6-13 year old cohort: 
o At least (n=163) will be 6-9 years old, as recently published data of 30 
children age 6-9 shows successful use of Control-IQ technology (10). 
o At least 25% (n=96) will have a baseline A1c ≥ 8.5% 
o At least 25% (n=96) will be pump naïve  
o At least 5% (n=18) will be CGM naïve. This percentage is based on clinical 
evidence of high baseline CGM use in this age group, and recently 
published data of 40 CGM naïve children who successfully used Control-IQ 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
26 
 
technology (10). With the availability of this data from these 40 participants, 
recruitment goals for the CGM naïve cohort of children in CLIO was reduced 
to 18 participants. 
 
• Of the >14 year old cohort,  
o Approximately 677 subjects each in the pump user and pump naïve 
subgroups at baseline. 
o Approximately 270 subjects that are CGM naïve (defined as not using CGM 
in the 30 days prior to enrollment). 
o Approximately 681 subjects (33% of total sample) with HbA1c ≥8.5% and 
681 subjects (33% of total sample) in the <8.5% subgroup 
Statistical Analysis 
Descriptive statistics will be used to describe outcomes vs. a comparator group. The 
Comparator Group will be determined using evidence from a systematic literature review 
examining MDI, insulin pump therapy (IPT) and sensor augmented pump (SAP) use in 
patients with type 1 diabetes. Studies published since January, 2020 will be included in 
the analysis. This will establish the baseline sample representation and outcome metrics. 
Users of automated dosing systems, including low glucose suspend, predictive low 
glucose suspend (such as Basal-IQ technology) will not be analyzed as part of the 
Comparator group. 
The publications included in the literature review have been identified to represent the 
typical population of people with type 1 diabetes, and include sample populations that 
mirror those described above in the target population for this study, including:  
• Children age 6 years old and older 
• Adolescents age 14-18 years old 
• Adults >18 years old 
• Patients with pump experience 
• Pump naïve patients 
• Patients with CGM experience 
• CGM naïve patients  
• Wide range of baseline HbA1c values 
Primary endpoints, the risk of AE (DKA, SH), represented as risk ratio per 100 patient 
years, will be compared using a single sample two-tailed exact binomial test (alpha=0.05) 
to the expected values as extracted in the literature review. Effect size will be defined as 
the absolute difference in risk ratios. 
Primary Outcome 
Incidence rate/100 patient years for both severe hypoglycemia (SH) and diabetic 
ketoacidosis (DKA). 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
27 
 
Success Criteria/Goal: Study participants will not experience a higher incidence of SH 
or DKA than incidence rates reported in the literature from analyses of similar populations. 
Overall outcomes will be compared to data below, derived from a recently published study 
using a large Type 1 Diabetes Exchange cohort (Foster et al., 2019). This study used a 
similar design as our postmarket study proposed here, the subjects represent our 
intended use population, and the event rates reported in the Foster study fall within the 
broader rates found in the extensive body of literature reviewed.  
SH Incidence Rates (all 
ages) 
SH Incidence Rates in Children 
SH Incidence Rates in 
Adults 
All ages (13-93) 
 
Ages 6-
12 
Ages 13-
17 
Ages 18-93 
All insulin 
delivery 
25/100 
PY 
All insulin 
delivery 
22/100 
PY 
20/100 
PY 
All insulin 
delivery 
30/100 
PY 
MDI 
37/100 
PY 
MDI 
28/100 
PY 
34/100 
PY 
MDI 
38/100 
PY 
IPT 
23/100 
PY 
IPT 
16/100 
PY 
13/100 
PY 
IPT 
27/100 
PY 
DKA Incidence Rates (all 
ages) 
DKA Incidence Rates in Children 
DKA Incidence Rates in 
Adults 
All ages (13-93) 
 
Ages 6-
12 
Ages 13-
17 
Ages 18-93 
All insulin 
delivery 
11/100 
PY 
All insulin 
delivery 
13/100 
PY 
14/100 
PY 
All insulin 
delivery 
9/100 
PY 
MDI 
17/100 
PY 
MDI 
22/100 
PY 
25/100 
PY 
MDI 
13/100 
PY 
IPT 
7/100 
PY 
IPT 
5/100 
PY 
9/100 PY 
IPT 
7/100 
PY 
 
The full literature review can be found in Attachment 1 of this protocol.  
The safety of automatically populating CGM readings into the bolus calculator will be 
analyzed by correlating reported AEs, calculator usage data and CGM readings to 
understand if the bolus calculator may have caused the AE. This analysis will isolate AEs 
where three consecutive CGM readings ≤54 mg/dL, or ≥250 mg/dL existed within five 
hours of receiving a correction bolus using an automatically populated CGM reading. All 
CGM readings within 5 hours after the bolus is given will be evaluated. In addition, 
correction boluses using automatically populated CGM values ≥250 mg/dL will be 
analyzed and evaluated separately from boluses given for lower glucose values. 
Secondary endpoints will be calculated as means/medians as appropriate based on data 
extracted from the Tandem t:connect web application and patient reported outcomes. 
Sensor-glucose concentrations will be analyzed per recent international consensus 
guidelines, to include time in target range 70-180 mg/dL, time >180 mg/dL, time >250 
mg/dL, time <70 mg/dL, time <54 mg/dL. 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
28 
 
Outcomes will be analyzed quarterly and tabulated using standard statistical tools such 
as SPSS, R and Python. 
 
Data Management 
Data from the study will be collected via study databases. Data will be sent in a secured 
validated format to Tandem Diabetes Care, Inc. on an ongoing basis.  
Trained study personnel will be responsible for entering data on the adverse events, as 
specified in the protocol, applicable device issues and any unscheduled contacts with 
participants into the eCRF system and according to the eCRF instructions. All other data 
such as eligibility, medical history and other assessments will be captured directly by 
participants as part of their responses to the surveys and collected directly as part of the 
survey database. The eCRF instructions will also provide data entry instructions. Risk-
based monitoring of data will be conducted. Data entered in the eCRF will be immediately 
saved to a central database and changes tracked to provide an audit trail. When data 
have been entered, reviewed, edited and source data verification (SDV) performed as 
specified per the clinical monitoring plan, the investigator will be notified to sign the eCRF 
electronically as per the agreed upon project process, and data will be locked to prevent 
further editing. A copy of the eCRF will be archived at Tandem Diabetes Care, Inc. 
Data verification and data validation checks will be performed by Tandem Diabetes Care, 
Inc., or its designee(s), using electronic checks comprised of validated computer 
programs and manual data review. Any data discrepancies will be referred back to the 
investigator for resolution. After the database has been declared clean it will be locked, 
and editing in the database will only be allowed with the proper documentation. After 
database lock, data will be extracted for analysis.  
LEGAL/ETHICS AND ADMINISTRATIVE PROCEDURES 
Good Clinical Practice/Regulatory Compliance 
The procedures described in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study, are designed to ensure that the sponsor and investigators 
abide with FDA regulations in accordance with 21 CFR, Parts 50, 56, and 812; applicable 
state and local regulations; and the standard operating procedures (SOPs) of Tandem 
Diabetes Care, Inc., and its designee(s). 
Independent Institutional Review Boards (IRBs) will provide oversight per local 
requirements and review documents associated with the study to determine that they 
comply with all federal, state, and local laws and that the risks to subjects are minimized 
and reasonable in relation to anticipated benefits per the US Code of Federal Regulations 
(CFR), Title 21, Part 56, Section 56.111(a). 
It is the investigators’ responsibility to ensure that adequate time and appropriate 
resources are available in order to conduct the study. The investigators should also be 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
29 
 
able to estimate or demonstrate the potential for recruiting the required number of suitable 
subjects within the agreed upon recruitment period. The investigators will maintain a list 
of appropriately qualified personnel to whom the investigators have delegated significant 
study-related tasks. 
Investigator Qualification / CV 
The investigators will provide the sponsor with a current curriculum vita and any 
revisions/updates during the study, as well as those of any staff personnel with significant 
study responsibilities. 
Statement of Investigator 
The investigators are required to sign and date a Statement of Investigator form for the 
original and each subsequent amendment of the protocol, prior to enrolling any subjects 
under that protocol version.  
Financial Disclosure 
Financial disclosure statements will be completed for the investigators to disclose 
potential conflicts of interest (per 21 CFR Part 54). Financial disclosure information will 
be kept updated as necessary throughout the duration of the study.  
Investigator Training 
Investigators and their designees will be trained in the informed consent, screening and 
enrollment procedures, as well as proper documentation of all procedures. Investigators 
must provide recent certification of GCP training.  
Responsibilities 
Sponsor Responsibilities 
The sponsor of this study is Tandem Diabetes Care, Inc. of San Diego, CA, US. The 
sponsor is committed to:  
• Protecting the rights, health, safety and welfare of study subjects by the review of 
IRB approvals and verification of the subject informed consent process.  
• Verification of data in CRM, used to initially qualify customers for participation in 
the study. 
• Periodically reviewing the data to ensure that the study is being conducted in 
compliance with the protocol and the investigators’ agreement. Providing the 
investigators with access to the EDC system and study eCRFs. 
• Maintaining a system of study documentation. 
• Providing training on key elements of the protocol, including subject 
inclusion/exclusion criteria, EDC system, and all study procedures. 
• Reviewing eCRFs to ensure completeness and accuracy of study data. 
Investigators will be required to resolve discrepancies via the EDC system.  

Protocol V07 Control-IQ Observational (CLIO) Study 
 
30 
 
Responsibilities of the Principal Investigators 
The investigators will affirm by their signatures on the Investigator Agreement that they 
will fulfill their responsibilities relative to the study. The investigator responsibilities 
include:  
• Ensuring that all subjects entering the study conform to the subject inclusion 
criteria and that no exclusion criteria apply.  
• Obtaining IRB approval to conduct the study, prior to enrolling any subjects.  
• Submitting the ICF to the IRB for approval prior to initiation of the study. 
• Obtaining written informed consent from each subject prior to enrollment and 
verifying that the correct and approved IRB version is used. The electronically 
signed ICF will be maintained in the subject’s record, and a copy of the signed ICF 
will be part of each subject’s case report file retained by the investigator.  
• Accurately reporting adverse events in a timely manner by obtaining information 
from incoming calls to Customer Technical Service, by outreach via surveys, SMS 
text and phone, and by review of medical records or physician contact if necessary. 
• The investigator will review, correct as needed, and sign off on the accuracy and 
completeness of the data entered in the EDC system. Original laboratory reports, 
medical records, etc (if applicable). are to be retained by the investigator, and the 
resulting data shall be entered onto the appropriate eCRFs.  
 
Institutional approval of the protocol 
It is the responsibility of the investigator to submit this protocol, the informed consent 
form, relevant supporting information and all types of subject recruitment information to 
the IRB for review and approval prior to site initiation. A copy of the written approval of 
the protocol and ICF must be received by the sponsor prior to the recruitment of subjects.  
Prior to implementing changes in the study, the sponsor and IRB must approve any 
revised informed consent documents and amendments to the protocol with 
documentation of the approvals submitted to the sponsor. The approval document must 
clearly state the study reference, date of review, and actions taken. The investigator will 
be responsible for keeping the IRB apprised of the progress of the study, any changes to 
the protocol, deviations from the protocol, and SAEs or UADEs.  
IRB Membership Roster 
The investigator must submit a complete and current roster of the IRB to the sponsor. 
Informed Consent – Ethical Compliance 
It is the responsibility of the investigator or a trained delegate to obtain electronic informed 
consent from subjects prior to the conduct of any study procedures. All consent 
documentation must be consistent with applicable regulations and Good Clinical Practice. 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
31 
 
Each subject or the subject’s legally authorized representative is required to sign the ICF 
after the subject has received and read the information and received an explanation of 
the study, including but not limited to: a description of the study, expected duration, 
statement of the subject’s right to decline to participate or to withdraw from the study at 
any time and for any reason without fear of retribution, potential risks and benefits, limits 
of confidentiality, and contact information of the research personnel. A copy of the 
informed consent documentation must be provided to the subject or the subject’s legally 
authorized representative. 
Acquisition of the informed consent will be documented in the subject record, and the ICF 
must be electronically signed and dated by the subject. Signed consent forms must 
remain in each subject’s study file and must be available for verification by study monitors 
at any time.  
Subject Privacy and Confidentiality 
The sponsor and investigators affirm and uphold the principle of the subject’s right to 
protection against invasion of privacy. Throughout this study, all data collected and 
analyzed by the sponsor or designee will be treated confidentially and identified by an 
identification number.  
To verify compliance with the protocol, the sponsor will periodically audit the subject’s de-
identified study record (including but not limited to laboratory results and medical records, 
if applicable). 
Data collected during this study may be used to support the development, approval or 
marketing of Tandem products. Collected data may be reviewed by the sponsor and/or 
its representatives, independent auditors who validate the data on behalf of the sponsor, 
third parties with whom the sponsor may collaborate, national or local regulatory 
authorities, and the IRB which granted approval for the study to proceed.  
Study Monitoring 
Monitoring of the study will be detailed in the study clinical monitoring plan and will be 
performed by qualified personnel from the sponsor or sponsor designee. At the monitoring 
visits, the progress of the study will be discussed with the investigators or designees. The 
ICFs will be reviewed for signatures and the eCRFs checked for completeness and 
accuracy. Subject source data must be available for review. The investigator and staff are 
expected to cooperate with the study monitor and be available during at least a portion of 
the monitoring visit to review the eCRFs and any queries/resolutions, answer questions, 
and provide any missing information.  
Modification of the Protocol 
All amendments to the protocol must be documented in writing, reviewed and approved 
by the investigators and sponsor, and submitted to the IRB for approval prior to initiation. 
If the protocol amendment substantially alters the study design or potential risk to the 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
32 
 
subject, new written informed consent must be obtained from each subject for continued 
participation in the study.  
Suspension or Termination of the Study 
If conditions arise requiring further clarification before the decision can be reached to 
proceed with or terminate the study, the study will be suspended until the situation has 
been resolved.  
The sponsor has the right to terminate this study at any time.  
Departure from Protocol 
No deviation may be made from the protocol except to protect the health and welfare of 
a study subject. Further, changes to the study protocol will be implemented only after an 
amendment has been agreed to in writing by the sponsor, and the protocol amendment 
is approved by the IRB.  
Protocol deviations will be tracked according to the following categories:  
• Major protocol deviations 
• Minor protocol deviations 
Major protocol deviations are defined as:  
• Enrollment eligibility criteria deviations 
• Informed consent process not followed 
All other protocol deviations will be classified as minor protocol deviations.  
Potential Risks to Subjects 
There are limited risks to subjects as a result of having their data collected for this study. 
The study procedures and data being collected are part of routine subject follow-up or 
standard of care.  
Potential Benefits to Subjects and Society 
In the future, subjects may benefit from results that lead to a better understanding of the 
safety and effectiveness of the t:slim X2 insulin pump with Control-IQ technology in the 
broader context of other options for the treatment of type 1 diabetes. The healthcare 
system may benefit from a better overall understanding of effectiveness and costs of this 
system. The study may also help define new standards of care for the treatment of type 
1 diabetes.  
Financial Considerations 
Subject Compensation 
Each study subject will potentially receive $110 for completing the study. Participants who 
complete all assessments (including monthly AEs) will receive a bonus of $40 (a total of 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
33 
 
$150 for completing the study. Compensation will be weighted toward the end of the study 
to incentivize completion. 
Recording, Access to and Retention of Source Data 
Investigators are required to prepare and maintain adequate source documentation which 
includes records covering subject participation in the study including basic identification 
information, and medical records obtained during the study. In most cases, information is 
documented directly per survey responses into the study database, which act as source 
documentation.  
The monitor (auditors, IRB or regulatory inspectors) may check the eCRF entries against 
the source documents. The consent form will include a statement by which the subjects 
allow access to source data that substantiate information recorded in the eCRF. In 
addition, the Release of Medical Records form will allow for the review of medical records 
and contact with the subject’s physician when necessary. Study personnel, bound by 
professional ethics, will not disclose any personal information or personal health 
information.  
As described in the US FDA regulation 21 CFR 812.140, investigator records, including 
eCRFs, source documents, consent forms, laboratory test results (if applicable), and 
device records, should be retained by the investigator until at least two years after the 
date on which the investigation is terminated or completed, or the date that the records 
are no longer required.  
Electronic Case Report Forms 
The investigator is responsible for maintaining adequate and accurate source documents 
from which accurate information will be transcribed into eCRFs that have been designed 
to capture all observations and other data pertinent to the clinical investigation. eCRFs 
should be completed by the investigator or delegate as states on the Delegation of 
Authority Log. Overwriting of information or use of correcting fluid or tape is not allowed 
in source documentation.  
Once the study monitor has verified the contents of the completed eCRFs against the 
source data, queries may be raised if the data are unclear or contradictory. The eCRFs 
must be reviewed and electronically signed and dated by the investigator as required by 
the clinical monitoring plan, once all data has been entered and all queries resolved.  
Audits/Inspections 
To ensure compliance with relevant regulations, data generated by this study must be 
available for inspection upon request by representatives of the FDA, the sponsor and its 
representatives, and the IRB.  
 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
34 
 
BIBLIOGRAPHY 
1. 
Miller KM, Foster NC, Beck RW, Bergenstal RM, DuBose SN, DiMeglio LA, et al. 
Current State of Type 1 Diabetes Treatment in the U.S.: Updated Data From the 
T1D Exchange Clinic Registry. 2015;38(6):971-8. 
2. 
Umpierrez GE, Klonoff DC. Diabetes Technology Update: Use of Insulin Pumps and 
Continuous Glucose Monitoring in the Hospital. 2018;41(8):1579-89. 
3. 
7. Diabetes Technology: <em>Standards of Medical Care in Diabetes—2019</em>. 
2019;42(Supplement 1):S71-S80. 
4. 
Grunberger G, Abelseth J, Bailey T, Bode B, Handelsman Y, Hellman R, et al. 
Consensus 
Statement 
by 
the 
American 
Association 
of 
Clinical 
Endocrinologists/American College of Endocrinology Insulin Pump Management 
Task Force. 2014;20(5):463-89. 
5. 
Brown S, Raghinaru D, Emory E, Kovatchev B. First Look at Control-IQ: A New-
Generation Automated Insulin Delivery System. Diabetes Care. 2018;41(12):2634-
6. 
6. 
Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, et al. 
Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 
Diabetes. New England Journal of Medicine. 2019;381(18):1707-17. 
7. 
Ekhlaspour L, Forlenza GP, Chernavvsky D, Maahs DM, Wadwa RP, Deboer MD, 
et al. Closed loop control in adolescents and children during winter sports: Use of 
the Tandem Control-IQ AP system. Pediatric Diabetes. 2019;20(6):759-68. 
8. 
GP F, L E, MD B, DM M, RP W, MD D, et al. Successful At-Home Use of the Tandem 
Control-IQ Artificial Pancreas System in Young Children During a Randomized 
Controlled Trial. Diabetes Technology & Therapeutics. 2019;21(4):159-69. 
9. 
Kovatchev BP, Kollar L, Anderson SM, Barnett C, Breton MD, Carr K, et al. Evening 
and overnight closed-loop control versus 24/7 continuous closed-loop control for 
type 1 diabetes: a randomised crossover trial. The Lancet Digital Health. epub ahead 
of print, January 3, 2020. 
10.  Renard E, Tubiana-Rufi N, Bonnemaison E, Coutant R, Della-Vale F, Bismuth E, et 
al. Outcomes of Hybrid Closed-Loop Insulin Delivery Activated 24/7 versus Evening 
and Night in Free-living Pre-pubertal Children with Type 1 Diabetes. A Multicenter 
Randomized Clinical Trial. Diabetes Obes Metab. 2022;24(3): 511-521. 
doi:10.1111/dom.14605 
 
 
 
List of Appendices: 
 
APPENDIX A: Flow chart of recruitment, enrollment and retention procedures 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
35 
 
APPENDIX B: Informed Consent Form  
 
APPENDIX C: Tandem procedure: Adverse Event Management in Control-IQ Post-
market Study 
 
APPENDIX D: Questionnaires and surveys to collect patient reported outcomes (PROs) 
 
 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
36 
 
 
 
 
 
 
 
 
 
 
APPENDIX A: Flow Chart of Recruitment, Enrollment and 
Retention Procedures 
 
 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
37 
 
 
 
 
 
 
 
 
 
 
APPENDIX B: Informed Consent Form 
 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
38 
 
 
 
 
 
 
 
 
 
APPENDIX C: Tandem Procedure—Adverse Event 
Management in Control-IQ Post-market Study 
 
 

Protocol V07 Control-IQ Observational (CLIO) Study 
 
39 
 
 
 
 
 
 
 
 
APPENDIX D: Questionnaires and surveys to collect 
patient reported outcomes (PROs)