The International Diabetes Closed Loop (iDCL) Trial: Clinical Acceptance of the Artificial Pancreas - A Pilot Test of t:Slim X2 With Control-IQ Technology
Phase: NA
Conditions: Type1 Diabetes Mellitus
Sponsor: University of Virginia

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The International Diabetes Closed Loop (iDCL) trial: 
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Clinical Acceptance of the Artificial Pancreas 
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A Pilot Test of t:slim X2 with Control-IQ Technology 
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Version 1.0 
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October 16, 2017 
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Protocol Chair 
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Sue Brown, M.D., University of Virginia  
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Participating Institutions 
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University of Virginia, Charlottesville, VA 
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Coordinating Center 
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University of Virginia, Charlottesville, VA 
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TABLE OF CONTENTS 
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CHAPTER 1:  INTRODUCTION ................................................................................................. 5 
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1.1. 
Background and Rationale .................................................................................................. 5 
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1.2. 
Synopsis of Study Protocol ................................................................................................. 7 
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1.2.1. Study Objective ................................................................................................................... 7 
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1.2.2. Major Eligibility Criteria .................................................................................................... 7 
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1.2.3. Sample Size ......................................................................................................................... 7 
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1.2.4. Protocol Summary .............................................................................................................. 7 
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1.2.5. Outcomes ............................................................................................................................ 8 
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1.3. 
General Considerations ....................................................................................................... 8 
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CHAPTER 2:  VISIT 1: SUBJECT SCREENING AND ENROLLMENT ............................. 18 
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2.1. 
Study Population ............................................................................................................... 18 
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2.2. 
Eligibility and Exclusion Criteria ..................................................................................... 18 
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2.2.1. Eligibility .......................................................................................................................... 18 
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2.2.2. Exclusion .......................................................................................................................... 18 
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2.3. 
Authorization Procedures ................................................................................................. 19 
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2.4. 
Screening and Enrollment Visit Logistics ........................................................................ 19 
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2.4.1. Data Collection and Testing ............................................................................................. 19 
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CHAPTER 3:  VISIT 2: 36-48-HOUR SUPERVISED STUDY ............................................... 21 
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3.1. 
Timing ............................................................................................................................... 21 
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3.2. 
Procedures upon Arrival to the Study Site ........................................................................ 21 
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3.3. 
Study Device Initiation and Training ................................................................................ 21 
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3.4. 
Procedures during Study ................................................................................................... 22 
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3.5. 
Procedures for Monitoring ................................................................................................ 22 
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3.6 
Qualifications and Role of the Staff ................................................................................. 23 
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3.7 
Visit 3: Follow-up Visit .................................................................................................... 23 
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CHAPTER 4:  SAFETY MEASURES ........................................................................................ 24 
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4.1 
Safety Measures ................................................................................................................ 24 
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4.1.1 CGM Calibration .............................................................................................................. 24 
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4.1.2 Insulin Dosing ................................................................................................................... 24 
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4.1.3 Hypoglycemia Safety Protocol ......................................................................................... 24 
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4.1.4 Hyperglycemia Safety Protocol ........................................................................................ 24 
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4.1.5 Study Data Monitoring ..................................................................................................... 25 
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4.1.6 CGM Sensor Connection Failure ...................................................................................... 25 
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4.1.7 Control-IQ Connection Failure ......................................................................................... 25 
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4.1.8 Study System Failure ........................................................................................................ 25 
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CHAPTER 5:  ADVERSE EVENTS, DEVICE ISSUES, POTENTIAL RISKS, AND 
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STOPPING RULES ...................................................................................................................... 26 
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5.1 
Adverse Event Definition ................................................................................................. 26 
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5.2 
Recording of Adverse Events ........................................................................................... 26 
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5.3 
Reporting Serious Adverse Events or Unexpected Adverse Device Effects .................... 27 
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5.4 
Device Issues .................................................................................................................... 28 
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5.5 
Medical Monitor ............................................................................................................... 28 
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5.6 
Potential Risks and Side Effects ....................................................................................... 28 
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5.6.1 Fingerstick Risks ............................................................................................................... 28 
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5.6.2 Subcutaneous Catheter Risks (CGM) ............................................................................... 28 
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5.6.3 Risk of Hypoglycemia ...................................................................................................... 28 
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5.6.4 Risk of Hyperglycemia ..................................................................................................... 29 
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5.6.5 Risk of Device Reuse ........................................................................................................ 29 
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5.6.6 Questionnaire .................................................................................................................... 29 
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5.6.7 Other Risks ....................................................................................................................... 29 
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5.7 
Risk Assessment ............................................................................................................... 30 
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5.8 
Study Stopping Criteria .................................................................................................... 30 
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5.8.1 Criteria for Individual Subjects ......................................................................................... 30 
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5.8.2 Criteria for Suspending/Stopping Overall Study .............................................................. 30 
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CHAPTER 6:  MISCELLANEOUS CONSIDERATIONS ....................................................... 31 
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6.1 
Benefits ............................................................................................................................. 31 
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6.2 
Subject Compensation ...................................................................................................... 31 
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6.3 
Subject Withdrawal ........................................................................................................... 31 
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6.4 
Confidentiality .................................................................................................................. 31 
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CHAPTER 7:  STATISTICAL CONSIDERATIONS ............................................................... 31 
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CHAPTER 8:  DATA COLLECTION AND MONITORING.................................................. 32 
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8.1 
Case Report Forms and Device Data ................................................................................ 32 
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8.2 
Document Storage and Retention ..................................................................................... 32 
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BIBLIOGRAPHY .......................................................................................................................... 33 
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TABLE OF ACRONYMS 
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Acronym 
Abbreviation For 
AP 
Artificial Pancreas 
BG 
Blood Glucose 
BT/BTLE 
Bluetooth, Bluetooth low energy 
CRF 
Case Report Form 
CGM 
Continuous Glucose Monitoring 
CLC 
Closed-Loop Control 
CSII 
Continuous Subcutaneous Insulin Injection 
CTR 
Control-to-Range 
DiAs 
Diabetes Assistant 
DKA 
Diabetic Ketoacidosis 
EC 
European Commission 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
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 
POC 
Point-of-Care 
QA 
Quality Assurance 
QC 
Quality Control 
RBM 
Risk-Based Monitoring 
SAP 
Sensor-Augmented Pump 
SD 
Standard Deviation 
TDD 
Total Daily Dose 
UI 
User Interface 
UVA 
University of Virginia 

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CHAPTER 1:  INTRODUCTION 
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1.1. Background and Rationale 
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The Tandem X2 insulin pump with Control-IQ Technology is a third-generation closed-loop control 
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(CLC) system retaining the same control algorithm that was initially tested by UVA’s DiAs system 
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and then implemented in the inControl system. DiAs is described in 13 IDEs (see IDEs 1-12 and 14 
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in the list below) and inControl is described in IDEs G160097, G160181, G150240, G140169/S010. 
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For complete algorithmic and clinical background, we refer to these IDEs and to a number of 
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scientific publications that describe glycemic control outcomes and clinical impressions from the 
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use of these systems (see list of 25 peer-reviewed papers and scientific presentations under 
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Bibliography). Overall, this control algorithm has been implemented in two mobile platforms (DiAs 
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and inControl) and has been tested in 30 clinical trials by 450 adults and children with type 1 diabetes 
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for over 280,000 hours of use to date in the U.S. and overseas.  
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As described in the Background, this project is a result from a sequence of clinical trials that have 
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tested extensively the control system in over 280,000 hours of outpatient human use and in several 
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centers in the U.S. and overseas. The following 16 IDEs reflect this progress: 
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1. 
IDE #G110095: Feasibility study of closed loop control in type 1 diabetes using heart rate monitoring 
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as an exercise marker, approved 10/08/2011; 
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2. 
IDE #G120032: Early feasibility (pilot) study of outpatient control-to-range; 3/2/2012; 
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IDE #G120210: Early feasibility study 2 of outpatient control-to-range; 10/12/2012; 
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IDE #G130118: DiAs control-to-range nocturnal closed-loop camp study; 6/19/2013;  
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IDE #G130121: Optimizing closed-loop control of type 1 diabetes mellitus in adolescents; 6/19/2013; 
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IDE# G130142:  Closed loop control in adolescents using heart rate as exercise indicator; 7/16/13; 
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IDE #G130143: Early feasibility study of adaptive advisory/automated (AAA) control of type 1 
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diabetes; 7/19/2013; 
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IDE #G140066:  Full day and night closed-loop with DiAs platform; 5/9/14. 
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9. 
IDE #G140068: Unified Safety System (USS) Virginia Closed Loop versus sensor augmented pump 
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therapy overnight in type 1 diabetes; 5/14/2014; 
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10. IDE #G140089: Outpatient control-to-range: Safety and efficacy with day-and-night in-home use; 
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6/6/2014; 
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11. IDE #G140169: Unified Safety System (USS) Virginia Closed-Loop versus Sensor Augmented Pump 
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(SAP) therapy for hypoglycemia reduction in type 1 diabetes; 10/3/2014. 
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12. IDE #G150221: Reducing risks and improving glucose control during extended exercise in youth with 
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T1DM: The AP Ski Camp; 11/09/2015;  
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13. IDE #G150240: Project Nightlight: Efficacy and system acceptance of dinner/night vs. 24 hr closed 
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loop control; 11/12/2015; 
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14. IDE #G160047: Closed-loop in young children 5-8 years old using DiAs platform; 03/29/2016;  
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15. IDE #G160097: Clinical Acceptance of the Artificial Pancreas: the International Diabetes Closed-
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Loop (iDCL) Trial/Research Site Training Protocol; 06/03/16. 
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16. IDE#G160181: PROTOCOL 1 for “Clinical Acceptance of the Artificial Pancreas: The International 
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Diabetes Closed Loop (iDCL) Trial; 09/21/16 
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We further reference pre-submission Q170885 and our discussion with FDA on July 18, 2017 
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regarding the structure of studies intended to test inControl implemented on t:slim X2. Based on the 
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input provided by the Agency, we defined a series of three studies leading to a future pivotal trial of 
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this system. The flowchart of these studies is included in Figure 1:  
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Figure 1:  Sequence of planned studies leading to a future pivotal trial of the Tandem X2 insulin 
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pump with Control-IQ Technology. Each study will have a separate IDE submission 
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Closed-Loop Control System 
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The Closed-Loop Control System contained in t-slim X2 with Control-IQ Technology is described 
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in Master File MAF-2032/A003. Control-IQ Technology is derived from inControl previously 
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described in IDE# G160097,G160181, G150240 and G140169/S010. The CLC is an “artificial 
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pancreas” (AP) application that uses advanced closed loop control algorithms to automatically 
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manage blood glucose levels for people with Type 1 Diabetes. The system modulates insulin to keep 
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blood glucose in a targeted range. The system components include the t:slim X2 with Control-IQ 
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Technology and the Dexcom CGM G6 (Figure 2). 
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Figure 2: t:slim X2 with Control-IQ and Dexcom G6 system 
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1.2. Synopsis of Study Protocol 
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1.2.1. Study Objective 
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The objective of the study is for clinical staff to gain experience using the proposed artificial 
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pancreas system named t:slim X2 with Control-IQ Technology and assess usability in a supervised 
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setting prior to initiating home use in a Training protocol (IDE submission pending).  
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1.2.2. Major Eligibility Criteria 
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• Clinical diagnosis of type 1 diabetes, treated with insulin for at least 1 year 
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• Use of an insulin infusion pump for at least 6 months 
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• Age 18 to <75 years old 
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• Hemoglobin A1c <10.5% 
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• Currently using no insulins other than one of the following rapid-acting insulins at the time 
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of enrollment: insulin lispro (Humalog), insulin aspart (Novolog), or insulin glulisine 
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(Apidra). Willingness to switch to lispro (Humalog) or aspart (Novolog) if using glulisine 
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(Apidra). 
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• No more than one episode of diabetic ketoacidosis (DKA) or severe hypoglycemia 
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involving a seizure of loss of consciousness in the 6 months prior to enrollment 
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• Total daily insulin dose at least 10 units/day and ≤ 100 U/day 
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1.2.3. Sample Size 
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This protocol will be conducted at the University of Virginia only and may enroll up to 20 total 
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subjects with the goal that at least 4 subjects will complete the entire study. .  
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1.2.4. Protocol Summary 
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Subject participation will last approximately 36-48 hours in a supervised setting using the study 
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CGM and study pump as detailed in Figure 3 below.  
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Figure 3: Enrollment Flow Diagram 
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Visit 1: Screening / Enrollment Visit 
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Eligibility assessment and informed consent 
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HbA1c from local lab or POC device 
Visit 2: 36-48 hour Supervised Study using 
t:slim X2 with Control-IQ 
Visit 3: Study Staff Contact after 
Admission  
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Assessment within 36 hours after Visit 2 
 

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1.2.5. Outcomes 
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The primary outcome is a qualitative assessment of the system’s suitability for use in an in-home 
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clinical trial based on the results of the Technology Acceptance questionnaire and feedback from 
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clinical staff. 
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Descriptive analyses for secondary safety and efficacy measures will be tabulated for each subject 
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as described in CHAPTER 7:  STATISTICAL CONSIDERATIONS. 
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1.3. General Considerations 
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The study is being conducted in compliance with the policies described in the study policies 
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document, with the ethical principles that have their origin in the Declaration of Helsinki, with the 
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protocol described herein, and with the standards of Good Clinical Practice. 
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Data will be directly collected in electronic case report forms, which will be considered the source 
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data.   
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There is no restriction on the number of subjects to be enrolled by each site towards the overall 
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recruitment goal. 
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The protocol is considered a significant risk device study, due to the fact that the closed-loop 
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system is experimental.  Therefore, an IDE from the FDA is required to conduct the study. 
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CHAPTER 2:  VISIT 1: SUBJECT SCREENING AND ENROLLMENT  
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2.1. Study Population 
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This protocol will be conducted at the University of Virginia only and may enroll up to 20 total 
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subjects with the goal that at least 4 subjects will complete the entire study. The number of 
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subjects is a convenience sample not based on statistical principles. 
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2.2. Eligibility and Exclusion Criteria 
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2.2.1. Eligibility 
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To be eligible for the study, a subject must meet the following criteria: 
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1) Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year 
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and using insulin for at least 1 year  
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2) Use of an insulin pump for at least 6 months with established parameters for basal rate(s), 
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carbohydrate ratio(s) and insulin sensitivity factor(s) for at least 3 months. 
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3) Age 18.0 to <75.0 years 
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4) Hemoglobin A1c <10.5% 
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5) For females, not currently known to be pregnant 
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If female and sexually active, must agree to use a form of contraception to prevent pregnancy 
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while a subject in the study.  A negative serum or urine pregnancy test will be required for 
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all premenopausal women who are not surgically sterile. Subjects who become pregnant will 
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be discontinued from the study. Also, subjects who during the study develop and express the 
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intention to become pregnant within the timespan of the study will be discontinued.  
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6) Willingness to suspend use of any personal CGM for the duration of the clinical trial once the 
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study CGM is in use 
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7) Investigator has confidence that the subject can successfully operate all study devices and is 
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capable of adhering to the protocol 
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8) Currently using no insulins other than one of the following rapid-acting insulins at the time 
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of enrollment: insulin lispro (Humalog), insulin aspart (Novolog), or insulin glulisine 
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(Apidra). Willingness to switch to lispro (Humalog) or aspart (Novolog) if using glulisine 
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(Apidra). 
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9) Total daily insulin dose (TDD) at least 10 U/day and ≤100 U/day 
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10) Weight at least 25 kg and not greater than 140 kg 
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2.2.2. Exclusion 
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The presence of any of the following is an exclusion for the study: 
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1) More than one episode of diabetic ketoacidosis (DKA) in the 6 months prior to enrollment 
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2) More than one episode of severe hypoglycemia involving seizure or loss of consciousness in 
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the 6 months prior to enrollment  
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3) Concurrent use of any non-insulin glucose-lowering agent (including GLP-1 agonists, 
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Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals).  
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4) Hemophilia or any other bleeding disorder 
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5) A condition, which in the opinion of the investigator or designee, would put the subject or 
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study at risk  
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6) Participation in another pharmaceutical or device trial at the time of enrollment or during the 
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study 
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7) Employed by, or having immediate family members employed by Tandem Diabetes Care, 
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Inc. or TypeZero Technologies, LLC, or having a direct supervisor at place of employment 
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who is also directly involved in conducting the clinical trial (as a study investigator, 
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coordinator, etc.); or having a first-degree relative who is directly involved in conducting the 
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clinical trial  
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2.3. Authorization Procedures 
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Written informed consent must be obtained prior to performing any study specific procedures 
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with the subject that are not part of the subject’s routine care. 
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For eligible subjects, the study will be discussed with the subject and the subject will be provided 
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with an Informed Consent Form to read and will be given the opportunity to ask questions.  If the 
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subject agrees to participate, the Informed Consent Form will be signed. A copy of the consent 
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form will be provided to the subject.  
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2.4. Screening and Enrollment Visit Logistics 
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Potential subjects will be evaluated for study eligibility through the elicitation of a medical 
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history, performance of a physical examination by study personnel and local laboratory testing if 
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needed to screen for exclusionary medical conditions.  Subject exclusion will be at the discretion 
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of the investigator based on study inclusion/exclusion criteria.    
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Subjects who do not initially meet study eligibility requirements may be rescreened once at later 
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date per investigator discretion. 
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2.4.1. Data Collection and Testing 
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A standard physical exam (including vital signs, height and weight measurements) will be 
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performed by the study investigator or designee (a physician, fellow, nurse practitioner or a 
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physician assistant).   
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The following procedures will be performed/data collected/eligibility criteria checked and 
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documented:  
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• Subject fully informed about the study and informed consent form signed according to IRB 
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requirements  
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• Inclusion and exclusion criteria assessed 
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• Demographics (date of birth, gender, race and ethnicity) 
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• Contact information 
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• Diabetic history  
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• Medical history  
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• Substance use history (drinking, smoking, and drug habits) 
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• Concomitant medications 
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• Physical examination to include: 
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o Weight, height 
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o Vital signs including measurement of temperature, blood pressure and pulse 
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• HbA1c level measured using the DCA2000 or comparable point of care device or local lab 
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(used to assess eligibility)  
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o Measurement must be made within two weeks prior to enrollment 
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o Measurement performed as part of usual clinical care prior to obtaining informed 
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consent for participation in the trial may be used 
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• Urine or serum pregnancy test for all premenopausal women who are not surgically sterile 
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Screening procedures will last approximately 1-2 hours. 
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CHAPTER 3:  VISIT 2: 36-48-HOUR SUPERVISED STUDY 
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3.1. Timing 
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Visit 2 may immediately follow Visit 1. The visit will last approximately 36-48 hours and 
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encompass two overnight periods. This visit will occur in an outpatient transitional setting such as 
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a local hotel. Below is the name and address of one possible location. This hotel is 3.3 miles from 
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the UVa Emergency Department.  
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Hyatt Place Charlottesville 
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The Shops at Stonefield 
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2100 Bond Street 
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Charlottesville, VA  22901                                      
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3.2. Procedures upon Arrival to the Study Site 
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The subjects will be assessed with vital signs. Subjects will not be allowed to initiate the study in 
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the presence of fever or other significant illness within 24-hours of admission. A fingerstick BG 
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and fingerstick ketone measurement will be performed and Glycemic Guidelines followed 
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(Appendix A-11). Female subjects of childbearing potential will perform a urine pregnancy test. 
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If positive, the subject will discontinue study participation. The subject will be asked to seek 
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confirmation of the test and the appropriate medical care. 
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3.3. Study Device Initiation and Training 
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Subjects will receive study system training by a qualified trainer. The study system includes the 
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Tandem t:slim X2 with Control-IQ technology and associated Dexcom G6 CGM. 
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Study Pump and CGM training will include: 
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• The subject will be fully instructed on the study insulin pump. A qualified staff 
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member will conduct the training and in particular discuss differences from their home 
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pump in important aspects such as calculation of insulin on board and correction 
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boluses. Additional topics not limited to but may include: infusion site initiation, 
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cartridge/priming procedures, setting up the pump, charging the pump, navigation 
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through menus, bolus procedures including stopping a bolus, etc. 
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• The study team will assist the subject in study pump infusion site initiation and will 
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start the subject on the study pump. The study pump will be programmed with the 
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subject’s usual basal rates and pump parameters. The subject’s personal pump will be 
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removed. 
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• The subject will be encouraged to review the literature provided with the pump and 
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infusion sets after the training is completed. 
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• The subject will learn how to calibrate the CGM unit during the study. 
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• The subject will learn how to access the CGM trace via the t:slim X2 with Control-IQ 
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user interface. 
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• Subjects will be asked to perform fingerstick blood glucose measurements in 
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accordance with the labeling of the study CGM device.  
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Pump training specific to the Control-IQ Technology functions will include: 
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• How to turn on and off Control-IQ technology. 
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• How to understand when Control-IQ is increasing or decreasing basal rates.  
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• How to administer a meal or correction bolus on the t:slim X2 with Control-IQ system  
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• What to do when exercising while using the system. 
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• How to enable the sleep function and set the sleep schedule. 
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• The subject will be assessed for understanding of the system interface and how to react to 
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safety/alert messages. 
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• The subject will be given a User Guide as a reference. 
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Blood glucose testing 
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• All study blood glucose meters will be QC tested with at least two different 
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concentrations of control solution if available at the start of the admission.  A tested 
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meter will not be used in a study if it does not read within the target range at each 
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concentration per manufacturer labeling.   
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• Subjects will be reminded to use the study blood glucose meter for all fingerstick BGs 
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during the study.   
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Blood ketone testing 
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• All study blood ketone meters will be QC tested with at least two different concentrations 
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of control solution if available at the start of the admission.  A tested meter will not be 
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used in a study if it does not read within the target range at each concentration per 
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manufacturer labeling  
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• Subjects will be instructed to perform blood ketone testing as described in Appendix A-
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11 or Section 4.1.4 Hyperglycemia Safety Protocol.  
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3.4. Procedures during Study 
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Study subjects will have restaurant meals and offered any snacks per their usual routine. Subjects 
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will participate in supervised exercise per their usual routine (e.g. walking 30-45 minutes). 
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Subjects will simulate an infusion site change and a sensor change during the study. 
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3.5. Procedures for Monitoring 
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Subjects will be asked to perform fingersticks prior to meals and any user-initiated correction 
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boluses. Subjects will be asked to perform a fingerstick in the event of a Control-IQ Low Alert or 
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Control-IQ High Alert. Glycemic Guidelines (Appendix A-11) will be followed during the 
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admission. 
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CGM will be recorded from the study system by the study staff at least every 2 hours during the 
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day and every 3 hours at night. 
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Bolus history will be recorded from the study system by the study staff at least every 2 hours 
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during the day and every 3 hours at night. 
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Subjects will be instructed to notify staff of any alerts/alarms received.  
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3.6 Qualifications and Role of the Staff 
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There will be at least two study staff present at all times at the study site, at least one of whom 
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will be clinical staff (e.g. nurse, physician, nurse practitioner). There will be a physician 
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available either on-site or nearby off-site at all times. Glucagon for the emergency treatment of 
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hypoglycemia will be available on-site. 
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3.7 Visit 3: Follow-up Visit 
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Subjects will be contacted by study staff within 36 hours of discharge to assess for any adverse 
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events, significant hypoglycemia or significant hyperglycemia.
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CHAPTER 4:  SAFETY MEASURES 
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4.1 Safety Measures 
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4.1.1 CGM Calibration 
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Throughout the study, subjects will be instructed to calibrate the study CGM in accordance with 
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manufacturer labelling. 
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4.1.2 Insulin Dosing 
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 When Control-IQ is turned on, subjects are expected to input carbohydrates in order to bolus for a 
425 
meal and may also administer correction boluses if desired. In case of a system crash or any 
426 
interruption of communication between t:slim X2 with Control-IQ and the CGM, the pump will 
427 
revert to open-loop basal delivery within a short period of time. The system has a Max Insulin 
428 
Alert that is triggered when the 2-hour insulin delivery has administered 50% of the Total Daily 
429 
Insulin (TDI). No further insulin will be delivered until this condition is no longer present.   
430 
 
431 
4.1.3 Hypoglycemia Safety Protocol 
432 
All subjects will be required to set the CGM hypoglycemia threshold alarm to a value no less than 
433 
60 mg/dl. 
434 
 
435 
The t:slim X2 with Control-IQ system will issue a hypoglycemia alarm (Control-IQ Low Alert) 
436 
if the CGM is <70 mg/dL or when the system predicts BG <70 mg/dL within the next 15-30 
437 
minutes when exercise is not activated. 
438 
 
439 
If the subject receives a hypoglycemia alarm from t:slim X2 with Control-IQ, a message 
440 
appears on the UI that is accompanied by vibration followed by vibrations and/or sound if not 
441 
acknowledged by the user in 5 minutes.  This alert remains on the screen until acknowledged 
442 
by the user. The user is prompted to test blood sugar and treat with carbs.   
443 
 
444 
4.1.4 Hyperglycemia Safety Protocol 
445 
Subjects will be required to set the CGM hyperglycemia threshold alarm to a value no greater than 
446 
300 mg/dl. 
447 
 
448 
The t:slim X2 with Control-IQ system will issue a predictive hyperglycemia alarm (Control-
449 
IQ High Alert) if the system detects prolonged resistance to insulin treatment and the BG is 
450 
estimated to be above 200 mg/dL. 
451 
 
452 
If the subject receives a hyperglycemia alarm from t:slim X2 with Control-IQ, a message 
453 
appears on the UI that is accompanied by vibration followed by vibrations and/or sound if not 
454 
acknowledged by the user in 5 minutes. This alert remains on the screen until acknowledged 
455 
by the user. The user is prompted to check the site for occlusion and test blood glucose.  
456 
 
457 
If a subject’s CGM reading is ≥300 mg/dL for over 1 hour, or ≥400 mg/dL at any point, the 
458 
following steps will be taken: 
459 
• Perform a blood glucose meter check. 
460 
• If the blood glucose is >300 mg/dL, check for blood ketones with the study ketone meter. 
461 

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• If the ketone level is >0.6 mmol/L, study staff will assist subject in taking correction 
462 
insulin or changing the pump infusion set.   
463 
• If a subject administers correction insulin via insulin syringe, subjects will be instructed to 
464 
turn Control-IQ off for a few hours and can be restarted per study physician evaluation 
465 
within 4 hours. 
466 
 
467 
4.1.5 Study Data Monitoring 
468 
Study staff will download the t:slim X2 at the completion of the admission. These data will be 
469 
reviewed by the study team. The study pumps following completion of an admission will be sent 
470 
to Tandem for further analysis of pump function.  
471 
 
472 
4.1.6 CGM Sensor Connection Failure 
473 
If the CGM signal becomes unavailable for more than 20 minutes consecutively, Control-IQ or 
474 
closed loop will not operate to automatically adjust insulin. If the CGM is not connected, the 
475 
system will revert to usual function of the pump and deliver insulin with the insulin dosing 
476 
parameters programmed in the system for that individual. Resumption of Closed-Loop will resume 
477 
automatically once CGM signal is available again. 
478 
 
479 
4.1.7 Control-IQ Connection Failure 
480 
If the study system is unable to activate Control-IQ for any reason, the pump will automatically 
481 
revert to preprogrammed basal insulin delivery without any need for instruction from the user. 
482 
 
483 
4.1.8 Study System Failure 
484 
If the t:slim X2 detects a system error that does not allow the pump to operate, the Malfunction 
485 
Alarm will display and the subject will be instructed to contact Tandem Technical Support and the 
486 
study team.  
487 

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CHAPTER 5:  ADVERSE EVENTS, DEVICE ISSUES, POTENTIAL RISKS, AND 
488 
STOPPING RULES 
489 
5.1 Adverse Event Definition 
490 
A reportable adverse event for this protocol includes any untoward medical occurrence that meets 
491 
criteria for a serious adverse event or any unanticipated medical occurrence in a study subject that 
492 
is study- or device-related, including severe hypoglycemia as defined below and severe 
493 
hyperglycemia/diabetic ketoacidosis (DKA) as defined below.  Skin reactions from sensor 
494 
placement are only reportable if severe and/or required treatment. 
495 
 
496 
Hypoglycemic events are recorded as Adverse Events (severe hypoglycemic event) if the event 
497 
required assistance of another person due to altered consciousness, and required another person to 
498 
actively administer carbohydrate, glucagon, or other resuscitative actions. This means that the 
499 
subject was impaired cognitively to the point that he/she was unable to treat himself/herself, was 
500 
unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced 
501 
seizure or coma. These episodes may be associated with sufficient neuroglycopenia to induce 
502 
seizure or coma.  If plasma glucose measurements are not available during such an event, 
503 
neurological recovery attributable to the restoration of plasma glucose to normal is considered 
504 
sufficient evidence that the event was induced by a low plasma glucose concentration. 
505 
 
506 
Hyperglycemic events are recorded as Adverse Events (severe hyperglycemic event) if the event 
507 
involved DKA, as defined by the Diabetes Control and Complications Trial (DCCT) and 
508 
described below, or in the absence of DKA if evaluation or treatment was obtained at a health care 
509 
provider facility for an acute event involving hyperglycemia or ketosis.  
510 
 
511 
Hyperglycemic events are classified as DKA if the following are present:  
512 
• 
Symptoms such as polyuria, polydipsia, nausea, or vomiting;  
513 
• 
Serum ketones >1.5 mmol/L or large/moderate urine ketones;  
514 
• 
Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate <15; and 
515 
• 
Treatment provided in a health care facility    
516 
 
517 
5.2 Recording of Adverse Events 
518 
Throughout the course of the study, all efforts will be made to remain alert to possible adverse 
519 
events or untoward findings.  The first concern will be the safety of the study subject, and 
520 
appropriate medical intervention will be made. 
521 
 
522 
All reportable adverse events whether volunteered by the subject, discovered by study personnel 
523 
during questioning, or detected through physical examination, laboratory test, or other means will 
524 
be reported on an adverse event form online.  Each adverse event form is reviewed by the Medical 
525 
Monitor to verify the coding and the reporting that is required.  
526 
 
527 
The study investigator will assess the relationship of any adverse event to be related or unrelated 
528 
by determining if there is a reasonable possibility that the adverse event may have been caused by 
529 
the study intervention. 
530 
 
531 
To ensure consistency of adverse event causality assessments, investigators should apply the 
532 
following general guideline when determining whether an adverse event is related: 
533 
 
534 

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Yes 
535 
There is a plausible temporal relationship between the onset of the adverse event and the study 
536 
intervention, and the adverse event cannot be readily explained by the subject’s clinical state, 
537 
intercurrent illness, or concomitant therapies; and/or the adverse event follows a known pattern of 
538 
response to the study intervention; and/or the adverse event abates or resolves upon 
539 
discontinuation of the study intervention or dose reduction and, if applicable, reappears upon re-
540 
challenge. 
541 
 
542 
No 
543 
Evidence exists that the adverse event has an etiology other than the study intervention (e.g., 
544 
preexisting medical condition, underlying disease, intercurrent illness, or concomitant 
545 
medication); and/or the adverse event has no plausible temporal relationship to study intervention.    
546 
 
547 
The intensity of adverse events will be rated on a three-point scale: (1) mild, (2) moderate, or (3) 
548 
severe.  It is emphasized that the term severe is a measure of intensity: thus, a severe adverse event 
549 
is not necessarily serious. For example, itching for several days may be rated as severe, but may 
550 
not be clinically serious. 
551 
 
552 
Adverse events will be coded using the MedDRA dictionary.  
553 
 
554 
Adverse events that continue after the study subject’s discontinuation or completion of the study 
555 
will be followed until their medical outcome is determined or until no further change in the 
556 
condition is expected.   
557 
 
558 
5.3 Reporting Serious Adverse Events or Unexpected Adverse Device Effects 
559 
A serious adverse event is any untoward occurrence that: 
560 
• Results in death. 
561 
• Is life-threatening; (a non-life-threatening event which, had it been more severe, might 
562 
have become life-threatening, is not necessarily considered a serious adverse event). 
563 
• Requires inpatient hospitalization or prolongation of existing hospitalization. 
564 
• Results in persistent or significant disability/incapacity or substantial disruption of the 
565 
ability to conduct normal life functions (sight threatening). 
566 
• Is a congenital anomaly or birth defect. 
567 
• Is considered a significant medical event by the investigator based on medical judgment 
568 
(e.g., may jeopardize the subject or may require medical/surgical intervention to prevent 
569 
one of the outcomes listed above). 
570 
 
571 
An Unanticipated Adverse Device Effect is defined as any serious adverse effect on health or 
572 
safety or any life-threatening problem or death caused by, or associated with, a device, if that 
573 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence 
574 
in the investigational plan or application (including a supplementary plan or application), or any 
575 
other unanticipated serious problem associated with a device that relates to the rights, safety, or 
576 
welfare of subjects (21 CFR 812.3(s)).  
577 
 
578 

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Serious or unexpected related adverse events will be reported to the local IRB’s online adverse 
579 
event website.  
580 
 
 
581 
The principal investigator is responsible for reporting serious study-related adverse events and 
582 
abiding by any other reporting requirements specific to the local Institutional Review Board.  
583 
 
584 
5.4 Device Issues 
585 
Device malfunctions (failure of device to perform as intended) will be reported to the 
586 
manufacturer, irrespective of whether associated with an adverse event.  However, CGM sensors 
587 
lasting fewer than 10 days and tape adherence issues will not be reported unless associated with an 
588 
adverse event. Additionally, t:slim X2 with Control-IQ component disconnections will not be 
589 
reported unless associated with an adverse event. 
590 
 
591 
5.5 Medical Monitor  
592 
The Medical Monitor will be informed of all serious adverse events and any unanticipated adverse 
593 
device events that occur during the study.   
594 
 
595 
5.6 Potential Risks and Side Effects 
596 
Loss of confidentiality is a potential risk; however, data are handled to minimize this risk.  
597 
Hyperglycemia and ketone formation are always a risk in subjects with type 1 diabetes and 
598 
subjects will be closely monitored for this.  When wearing sensors and insulin infusion sets there 
599 
is always a risk of skin rashes, allergic reactions to the tape, or infections at the insertion site.  
600 
There is always a risk for a small piece of a sensor remaining under the skin or a sensor or infusion 
601 
set breaking off under the skin.  
602 
 
603 
5.6.1 Fingerstick Risks 
604 
About 1 drop of blood will be removed by fingerstick for measuring blood sugars and sometimes 
605 
HbA1c or other tests. This is a standard method used to obtain blood for routine hospital 
606 
laboratory tests.  Pain is common at the time of lancing.  In about 1 in 10 cases, a small amount of 
607 
bleeding under the skin will produce a bruise.  A small scar may persist for several weeks.  The 
608 
risk of local infection is less than 1 in 1000.  This should not be a significant contributor to risks in 
609 
this study as fingersticks are part of the usual care for people with diabetes. 
610 
 
611 
5.6.2 Subcutaneous Catheter Risks (CGM) 
612 
Subjects using the CGM will be at low risk for developing a local skin infection at the site of the 
613 
sensor needle placement.  If a catheter is left under the skin for more than 24 hours it is possible to 
614 
get an infection where it goes into the skin, with swelling, redness and pain.  There may be 
615 
bleeding where the catheter is put in and bleeding under the skin causes a bruise (1 in 10 risk).   
616 
 
617 
Study staff should verbally alert the subject that on rare occasions, the CGM may break and leave a 
618 
small portion of the sensor under the skin that may cause redness, swelling or pain at the insertion 
619 
site.  The subject should be further instructed to notify the study coordinator immediately if this 
620 
occurs. 
621 
 
622 
5.6.3 Risk of Hypoglycemia 
623 
As with any person having type 1 diabetes and using insulin, there is always a risk of having a low 
624 
blood sugar (hypoglycemia).  The frequency of hypoglycemia should be no more and possibly less 
625 
than it would be as part of daily living.  Symptoms of hypoglycemia can include sweating, 
626 

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jitteriness, and not feeling well.  Just as at home, there is the possibility of fainting or seizures 
627 
(convulsions) and that for a few days the subject may not be as aware of symptoms of 
628 
hypoglycemia.  A CGM functioning poorly and significantly over-reading glucose values could 
629 
lead to inappropriate insulin delivery.     
630 
 
631 
5.6.4 Risk of Hyperglycemia 
632 
Hyperglycemia and ketonemia could occur if insulin delivery is attenuated or suspended for an 
633 
extended period or if the pump or infusion set is not working properly.  A CGM functioning 
634 
poorly and significantly under-reading glucose values could lead to inappropriate suspension of 
635 
insulin delivery.     
636 
 
637 
5.6.5 Risk of Device Reuse 
638 
The study CGM system is intended for single use only. The sensor (the component of the system 
639 
that enters the skin) will be single use only. The transmitter and receiver may be reused during the 
640 
study after cleaning the device using a hospital-approved cleaning procedure. The transmitter is 
641 
attached to the sensor but does not enter the skin and the receiver is a hand held device. Subjects 
642 
will be informed that FDA or relevant national authorities have approved these devices for single 
643 
use and that by using them among multiple patients, bloodborne pathogens (i.e. Hepatitis B) may 
644 
be spread through the use of multiple users.  
645 
 
646 
The study insulin pump is intended for single-patient use. During the study, this device may be 
647 
reused after cleaning adhering to a hospital-approved cleaning procedure. All infusion set 
648 
equipment will be single patient use only (infusion set insertion kits, tubing, cartridges etc.)  
649 
Subjects will be informed that FDA or relevant national authorities typically approves insulin 
650 
pump devices for single use and that by using them among multiple patients, bloodborne 
651 
pathogens (i.e. Hepatitis B) may be spread through the use of multiple users. 
652 
 
653 
The study blood glucose meter and blood ketone meter are labeled for single-patient use. During 
654 
the study, only one person can use each device as there are rare risks that bloodborne pathogens 
655 
(i.e. Hepatitis B) may be spread through the use of multiple users.  
656 
 
657 
5.6.6 Questionnaire 
658 
As part of the study, subjects will complete a Technology Acceptance Questionnaire which 
659 
includes questions about their private attitudes, feelings and behavior related to t:slim X2 with 
660 
Control-IQ.  It is possible that some people may find these questionnaires to be mildly upsetting. 
661 
Similar questionnaires have been used in previous research and these types of reactions have been 
662 
uncommon. 
663 
 
664 
5.6.7 Other Risks 
665 
Some subjects may develop skin irritation or allergic reactions to the adhesives used to secure the 
666 
CGM, or to secure the insulin infusion sets for the continuous subcutaneous insulin infusion.  If 
667 
these reactions occur, different adhesives or “under-taping” (such as with IV 3000, Tegaderm, 
668 
etc.) will be tried, sites will be rotated frequently, and a mild topical steroid cream or other 
669 
medication may be required. 
670 
 
671 
Whenever the skin is broken there is the possibility of an infection.  The CGM and pump infusion 
672 
sites are inserted under the skin.  It is possible that any part that is inserted under the skin may 
673 
cause an infection.  These occur very infrequently, but, if an infection was to occur, oral and/or 
674 

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topical antibiotics can be used.  The risk of skin problems could be greater if you use a sensor for 
675 
longer than it is supposed to be used.  Therefore, subjects will be carefully instructed about proper 
676 
use of the sensor. 
677 
 
678 
Data downloaded from the CGM, pump, and the home glucose and ketone meter will be collected 
679 
for the study as measures of diabetes self-management behaviors.  Some people may be 
680 
uncomfortable with the researchers' having such detailed information about their daily diabetes 
681 
habits. 
682 
 
683 
5.7 Risk Assessment 
684 
Based on the facts that (1) adults and adolescents with diabetes experience mild hypoglycemia and 
685 
hyperglycemia frequently as a consequence of the disease and its management, (2) the study 
686 
intervention involves periodic automated insulin dosing that may increase the likelihood of 
687 
hypoglycemia, and periodic automated attenuation of insulin delivery that may increase the 
688 
likelihood of hyperglycemia, (3) mitigations are in place, and have been tested in prior studies 
689 
using similar investigational device system in the home setting, that limit the likelihood of 
690 
excessive insulin dosing or prolonged withdrawal of insulin, and (4) rapid reversal of 
691 
hypoglycemia and hyperglycemia can be achieved, it is the assessment of the investigators that 
692 
this protocol falls under DHHS 46.405 which is a minor increase over minimal risk. In addition, it 
693 
is the belief of the investigators that this study also presents prospect of direct benefit to the 
694 
subjects and general benefit to others with diabetes. 
695 
 
696 
5.8 Study Stopping Criteria 
697 
 
698 
5.8.1 Criteria for Individual Subjects 
699 
Rules for stopping the study for an individual subject are as follows: 
700 
1. System or controller malfunctions that impose on the safety of the subject, unless the 
701 
problem can be clearly identified and the system definitively repaired 
702 
2. Severe hypoglycemia or hyperglycemia/DKA (not associated with infusion set failure) as 
703 
defined in Section 5.1 
704 
3. The subject requests that the treatment be stopped 
705 
4. Subject pregnancy 
706 
 
707 
5.8.2 Criteria for Suspending/Stopping Overall Study 
708 
In case of a system malfunction resulting in a severe hypoglycemia or severe hyperglycemia event 
709 
(as defined in Section 5.1) that is thought to be device-related (either due to excess insulin 
710 
administration or suspension due to system malfunction) and occurs more than one time, the 
711 
overall study will be suspended while the problem is diagnosed.  In addition, the study could be 
712 
suspended if the manufacturer of any constituent study device requires stoppage of device use for 
713 
safety reasons (e.g. product recall). The study may resume if the underlying problem can be 
714 
corrected by a protocol or system modification that will not invalidate the results obtained prior to 
715 
suspension. 
716 
 
 
717 
As stated in section 5.5, the medical monitor will be informed of all serious adverse events and 
718 
any unanticipated adverse device events that occur during the study.  The medical monitor will 
719 
request suspension or outright stoppage of the study if deemed necessary based on the totality of 
720 
safety data available. 
721 
 
722 

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CHAPTER 6:  MISCELLANEOUS CONSIDERATIONS 
723 
 
724 
6.1 Benefits 
725 
One purpose of this research is to reduce the frequency of hypoglycemia and severe hypoglycemic 
726 
events. Hypoglycemia is the number one fear of many individuals and families with someone who 
727 
has type 1 diabetes and this fear often prevents optimal glycemic control.  
728 
 
729 
It is expected that this protocol will yield increased knowledge about using an automated closed-
730 
loop to control the glucose level.  This research is a definitive step on the path towards 
731 
development of a fully closed-loop system.  The individual subject may not benefit from study 
732 
participation. 
733 
 
734 
6.2 Subject Compensation 
735 
Subjects will be paid $150 for completing the Pilot Study.   
736 
• Visit #2 (Supervised Hotel Study):  $125 
737 
• Visit #3 (Follow-Up Visit) - $25 
738 
 
739 
6.3 Subject Withdrawal 
740 
Participation in the study is voluntary, and a subject may withdraw at any time.  For subjects who 
741 
withdraw, their data will be used up until the time of withdrawal. 
742 
 
743 
6.4 Confidentiality 
744 
For security and confidentiality purposes, subjects will be assigned an identifier that will be used 
745 
instead of their name.  De-identified data will be shared with the Jaeb Center for Health Research 
746 
in Tampa, FL.  De-identified data will also be provided to Tandem for system evaluation 
747 
purposes. 
748 

iDCL Protocol 3_PILOT Study_V1.0.docx 
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CHAPTER 7:  STATISTICAL CONSIDERATIONS 
1 
 
2 
The intent of this protocol is to introduce the t:slim X2 with Control-IQ system prior to proceeding 
3 
in a subsequent short-term home trial, which will be submitted with a separate protocol and IDE 
4 
application. The number of subjects is a convenience sample not based on statistical principles. 
5 
 
6 
We will observe, record, and tabulate any t:slim X2 with Control-IQ errors that would inform us 
7 
whether system fixes would be needed prior to its deployment in the home trial.  We will tabulate 
8 
technical performance metrics including: 
9 
• % time in closed-loop and any other relevant operational modes 
10 
• % time CGM data available to the controller 
11 
• Rate of relevant failure events and alarms per 24 hours 
12 
 
13 
In addition, descriptive glycemic analyses for secondary efficacy measures will be tabulated for 
14 
each subject based on CGM data, including: 
15 
• mean glucose  
16 
• percentage of readings in the target range of 70-180 and 70-140 mg/dl  
17 
• glucose variability measured with the standard deviation and coefficient of variation  
18 
• percentage of readings <70, 60, and 54 mg/dl 
19 
• nadir  
20 
• AUC glucose <70, 60, and 54 mg/dl  
21 
• low blood glucose index 
22 
• percentage of readings >180, 250, and 300 mg/dl  
23 
• AUC glucose >180 mg/dl  
24 
• high blood glucose index  
25 
 
26 
The technical performance, errors, and glycemic analyses will be split by time of the day: daytime 
27 
vs. nighttime 
28 
 
29 
 
 
30 

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Page 32 
 
 
CHAPTER 8:  DATA COLLECTION AND MONITORING 
31 
 
32 
8.1 Case Report Forms and Device Data 
33 
The main study data are collected through a combination of electronic case report forms (CRFs) 
34 
and electronic device data files obtained from the study software and individual hardware 
35 
components.  These electronic device files and electronic CRFs are considered the primary source 
36 
documentation. 
37 
 
38 
8.2 Document Storage and Retention 
39 
• The Investigator will retain all records and documents pertaining to this study. They will 
40 
be available for inspection by the appropriate regulatory agencies. In addition, the 
41 
Investigator will retain the source documents from which the information entered on the 
42 
CRFs was derived. These records are to be retained in a secure storage facility maintained 
43 
by the investigational center until 3 years (or longer/shorter if local laws require) after 
44 
approval of the above-listed study devices or termination of the study, whichever is longer. 
45 
The investigator should take measures to prevent accidental or early destruction of the 
46 
clinical study related materials.  
47 
 
48 
 
49 
 
 
50 

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BIBLIOGRAPHY 
51 
 
52 
(1) Kovatchev, B.P., Breton, M.D., Keith-Hynes, P.T., Patek, S.D. The Diabetes Assistant (DiAs) – 
53 
Unified platform for monitoring and control of blood glucose levels in diabetic patients; 
54 
PCT/US12/43910, 2012. 
55 
(2) Keith-Hynes, P., Guerlain, S., Mize, L.B., Hughes-Karvetski, C., Khan, M., McElwee-Malloy, M. & 
56 
Kovatchev, B.P. DiAs user interface: A patient-centric interface for mobile artificial pancreas systems. 
57 
J Diabetes Sci Technol, 7, 1416–1426 (2013). PMID: 24351168 
58 
(3) Place, J., Robert, A., Ben Brahim, N., Keith-Hynes, P., Farret, A., Pelletier, M.J., Buckingham, B., 
59 
Breton, M., Kovatchev, B.P. & Renard, E. DiAs web monitoring: A real-time remote monitoring 
60 
system designed for artificial pancreas outpatient trials. J Diabetes Sci Technol, 7, 1427–1435. (2013). 
61 
PMID: 24351169 
62 
(4) Keith-Hynes, P., Mize, B., Robert, A., Place, J. The Diabetes Assistant: A smartphone-based system 
63 
for real-time control of blood glucose. Electronics 2014, 3, 609-623; doi:10.3390/electronics3040609 
64 
(5) Kovatchev, B.P., Renard, E., Cobelli, C., Zisser, H., Keith-Hynes, P., Anderson, S.M. Brown, S.A. 
65 
Chernavvsky, D.R., Breton, M.D., Farret, A., Pelletier, M.J., Place, J., Bruttomesso, D., Del Favero, S., 
66 
Visentin, R., Filippi, A., Scotton, R., Avogaro, A. & Doyle III, F.J. Feasibility of outpatient fully 
67 
integrated closed-loop control: First studies of wearable artificial pancreas. Diabetes Care, 36, 1851-
68 
1858 doi: 10.2337/dc12-1965 (2013). PMID: 23801798, PMCID: PMC3687268 
69 
(6) Kovatchev, B.P., Renard, E., Cobelli, C., Zisser, H., Keith-Hynes, P., Anderson, S.M., Brown, S.A., 
70 
Chernavvsky, D.R., Breton, M.D., Mize, L.B., Farret, A., Place, J., Bruttomesso, D., Del Favero, S., 
71 
Boscari, F., Galasso, S., Avogaro, A., Magni, L., Di Palma, F., Toffanin, C., Messori, M., Dassay, E., 
72 
Doyle, F. III. Safety of outpatient closed-loop control: First randomized crossover trials of a wearable 
73 
artificial pancreas. Diabetes Care, 37, 1789-1796 doi: 10.2337/dc13-2076 (2014). PMID: 24929429, 
74 
PMCID: PMC4067397 
75 
(7) DeSalvo, D., Keith-Hynes, P., Peyser, T., Place, J., Caswell, K., Wilson, D., Harris, B., Clinton, P., 
76 
Kovatchev, B.P., Buckingham, B.A. Remote glucose monitoring in camp setting reduces the risk of 
77 
prolonged nocturnal hypoglycemia. Diabetes Technol Ther, 16, 1-7 doi:10.1089/dia.2013.0139 (2013). 
78 
PMID: 24168317 
79 
(8) Ly, T.T., Breton, M.D., Keith-Hynes, P., De Salvo, D., Clinton, P., Benassi, K., Mize, L.B., 
80 
Chernavvsky, D.R., Place, J., Wilson, D.M., Kovatchev, B.P., Buckingham, B.A. Overnight glucose 
81 
control with an automated, unified safety system in children and adolescents with type 1 diabetes at 
82 
diabetes camp. Diabetes Care, 37, doi: 10.2337/dc14-0147 (2014). PMID: 24879841, PMCID: 
83 
PMC4179507 
84 
(9) Kropff, J., Del Favero, S., Place, J., Toffanin, C., Visentin, R., Monaro, M., Messori, M., Di Palma, F., 
85 
Lanzola, G., Farret, A., Boscari, F., Galasso, S., Magni, P., Avogaro, A., Keith-Hynes, P., Kovatchev, 
86 
B.P., Bruttomesso, D., Cobelli, C.,  DeVries, J.H., Renard, E., Magni, L., for the AP@home 
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