1. Diabetes Research in Children Network (DirecNet) Outpatient Pilot Study to Evaluate the Feasibility of Computer-Based Data Acquisition and Transmission Stuart A Weinzimer 1, Katrina Ruedy 2, Craig Kollman 2, Linda Larson 3, Jennifer Block 4, Jennifer Fisher 5, Elizabeth Doyle 1, Keisha Bird 6, and the DirecNet Study Group 1 Dept of Pediatrics, Yale University School of Medicine, New Haven, CT; 2 Jaeb Center for Health Research, Tampa, FL; 3 Dept of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IA; 4 Dept of Pediatrics, Stanford University, Stanford, CA; 5 Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, CO, 6 Nemours Children’s Clinic, Jacksonville, FL

2. Abstract Diabetes Research in Children Network (DirecNet) Outpatient Pilot Study to Evaluate the Feasibility of Computer-Based Data Acquisition and Transmission Stuart Weinzimer 1, Katrina Ruedy 2, Linda Larson 3, Jennifer Block 4, Jennifer Fisher 5, Elizabeth Doyle 1, Keisha Bird 6, and the Diabetes Research in Children Network (DirecNet) Study Group. 1 Department of Pediatrics, Yale University School of Medicine, New Haven, CT; 2 Jaeb Center for Health Research, Tampa, FL; 3 Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IA; 4 Division of Pediatric Endocrinology and Diabetes, Stanford University, Stanford, CA; 5 Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, CO; 6 Nemours Children’s Clinic, Jacksonville, FL. DirecNet is an NIH-sponsored multi-center group evaluating the effectiveness of glucose sensors in children with diabetes. Prior to performing a larger randomized trial, a 3-month pilot study was conducted to assess the feasibility of using PCs in the home for computer-based data acquisition and transmission. Fifteen subjects with T1DM (age 7.3-17.9 yrs) were given a GW2B and OneTouch Ultra® meter ("Ultra") along with a personal computer ("PC") and software for downloading glycemic data for each device. The PC was also used weekly to complete a questionnaire regarding hypoglycemia and problems with using the GW2B. Patients were able to view Ultra and GW2B data at any time on the PC. Each week data were downloaded to the study coordinating center and made available to the clinical centers on a secure website. Therapeutic changes were based on downloads, hypoglycemia questionnaires, and telephone contacts with clinical centers. Quality of life, diabetes self-management behaviors and satisfaction with GW2B use were measured periodically. Weekly GW2B use decreased significantly from a mean  SD of 3.0  1.2 at the beginning of the study to 1.4  1.1 by study end (p< 0.001). Daily Ultra use remained consistent from 6.4  1.6 at start to 6.6  3.5 at end. There was no significant difference in Ultra use between days where the GWB was and was not used. Two subjects required replacement of the hard drive for software malfunctions, and one required computer replacement for modem failure. Of the 234 data transmissions received from 15 subjects, 10 were delayed due to a severe electrical storm. This pilot study demonstrates the feasibility of home PC-based GW2B and Ultra data collection and modem- and web-based data transmission and distribution for multi-center clinical trials.

3. Background I The Diabetes Research in Children Network (DirecNet) is a multi-center group investigating the use of minimally invasive continuous glucose monitoring methods to optimize pediatric diabetes management

4. Background II Prior to conducting a large-scale outpatient trial of the GlucoWatch G2 ® Biographer (GW2B), a pilot study was conducted to determine the feasibility of a “paperless” data acquisition and reporting system using computers in the home environment for data collection and electronic data transmission

5. Objective To determine the feasibility of using home personal computers (PC) for acquisition and transmission of glucose meter and GW2B data in an outpatient trial in children and adolescents with T1DM

6. Methodology I 15 subjects were provided with: –GW2B –OneTouch ® Ultra ® blood glucose meter –Home PC (IBM-compatible, Windows XP-Pro OS) –Connection cables and software programs Subjects and families underwent a 2-hour training program on use of devices and procedures for data collection and storage and were instructed to use the GW2B at least twice weekly (at least one day and one night)

7. Methodology II Ultra meter and GW2B data were freely available for review by families to guide diabetes management Ultra meter data, GW2B downloads, and subject hypoglycemia questionnaires were uploaded to the DirecNet Coordinating Center automatically on a weekly basis by modem data transfer. These data were made available to clinical center personnel via a secure password-encoded website

8. Methodology III Therapeutic decisions based on uploaded data were made by clinical center personnel and reviewed with subjects/families during scheduled telephone contact at weeks 1, 2, 4 and 8 Non-protocol telephone contacts and problems with data collection/transmission were tracked

9. Methodology IV Data from baseline and 3-month visits, including Hemoglobin A1c measurements, psychosocial questionnaires, physical examinations, skin assessments, and GW2B/Ultra review were collected at the Clinical Centers using a tablet PC and a web- based data collection form and transmitted to the Coordinating Center via a secure password-encoded website

10. Subject Demographics Gender F / M7 / 8 Age mean ± SD (y)12 ± 3 Race / Ethnicity N White12 Hispanic or Latino1 African-American1 Other/Unknown1 Treatment modality MDI / pump7 / 8 HbA1c at study entry mean ± SD (%)7.4 ± 0.8

11. GW2B Use Declined Significantly* over Course of Study 123456789101112 Week of Study # GWB wears per week 0 1 2 3 4 5 6 7 8 9 10 * p < 0.001 Box plots denote minimum, 25th percentile, median, 75th percentile and maximum values for each week

12. Ultra Meter Use Remained Constant over Course of Study 0 5 10 15 20 123456789101112 Week of Study # Ultra use per day Box plots denote minimum, 25th percentile, median, 75th percentile and maximum values for each week

13. Frequency of SMBG use did not vary with use of GW2B* Mean # Ultra Uses per Day on the Days GWB were not Used # Average GWB Uses per Week * Each point represents one patient

14. Protocol Telephone Contact with Clinical Centers 0 1 2 1248 Week of Study Mean # calls per subject 0 10 20 # calls duration Mean duration of call per subject (min)

15. Non-Protocol Telephone Contact with Clinical Centers 0 1 2 3 4 5 123456789101112 Week of Study Mean # calls per subject 0 5 10 15 # calls duration Mean duration of call per subject (min)

16. Weekly Questionnaire Completion

17. Problems Encountered 3 subjects required replacement of hardware –error in Ultra software – hard drive replaced –incorrect initial date/time setting – hard drive replaced –modem malfunction – PC replaced Severe storms caused failure of the automatic download procedure for 10 /234 transmissions –data were successfully retrieved by dialup to home PC modems from Coordinating Center

18. Conclusions There was a significant decline in GW2B use over the course of the study It is feasible to conduct a clinical study of diabetes management using a “paper-less” data capture and reporting system using computer data collection and electronic data transmission

19. Barbara Davis Center –H. Peter Chase –Rosanna Fiallo-Scharer –Jennifer Fisher –Barbara Tallant University of Iowa –Eva Tsalikian –Michael Tansey –Linda Larson –Julie Coffey –Amy Sheehan Nemours Children’s Clinic –Tim Wysocki –Nelly Mauras –Keisha Bird –Kelly Lofton Stanford University –Bruce Buckingham –Darrell Wilson –Jennifer Block –Paula Clinton Yale University –William Tamborlane –Stuart Weinzimer –Elizabeth Doyle –Kristin Sikes –Amy Steffen Jaeb Center for Health Research –Roy Beck –Katrina Ruedy –Craig Kollman –Dongyuan Xing