this study combines four coordinated protocols sharing the same dias artificial pancreas technology conducted at the universities of padova ( italy ) and montpellier ( france ) , the university of virginia ( uva ) , and the sansum diabetes research institute , santa barbara , california . to test whether a smart phone is capable of running outpatient closed - loop control , we have configured a system comprising available components , which were linked as follows : cgm  idex  dias ( running all closed - loop computations , user interface , and communications to peripheral devices )  idex  pump . the idex is an experimental device manufactured by insulet ( bedford , ma ) , which combines a dexcom seven plus receiver and omnipod insulin pump . in addition , dias transferred data in real time to a central location allowing remote monitoring of patient state and system functions . the primary engineering end point was the percent time with all system communications working properly ; the protocol criterion for success in this early feasibility study was this time reaching > 80% of the total time of investigation . secondary end points included the estimation of the failure rates of system components , frequency analysis of lost or inaccurate cgm records , and control algorithm performance . the clinical goal was to assess patients and clinicians subjective impressions of the system , i.e. , the feasibility of its ambulatory use , including patient usability and wearability . a total of 20 adults ( age 2165 years ) with type 1 diabetes were studied ( 5 subjects at each site ) . before the tests , a pilot subject was performed in italy , france , and in the united states . all participants were experienced insulin pump users and were required to have the following : prestudy hba1c of 69% ; predefined insulin pump parameters for basal rates , carbohydrate ratios , and insulin sensitivity factors ; and proper mental status / cognition . the exclusion criteria were directed toward safety and included recent history of diabetic ketoacidosis or severe hypoglycemia , pregnancy , breastfeeding , or intention of becoming pregnant ( females ) , uncontrolled arterial hypertension , and conditions that may increase the risk of hypoglycemia or infections . in addition , the united states  based studies received food and drug administration approval ( ide # g120032 ) and the european studies received appropriate national - level certifications . all studies were registered with clinicaltrials.gov ( nct01578980 for uva / sansum , nct01447992 for padova , and nct01447979 for montpellier ) . after consent and screening , subjects were trained to use the omnipod insulin pump ( insulet ) and participated in a 3- to 7-day pump initiation if needed . two dexcom seven plus sensors ( dexcom , san diego , ca ) were inserted 2472 h before admission ; throughout the trials , the sensors were calibrated per manufacturer s instructions using commercial glucometers . a calibration was performed before dinner at 7:00 p.m. , thereby allowing for further system - required calibrations to be performed during the timeframes before dinner and before breakfast . per food and drug administration recommendation , an additional ( one - time ) calibration was entered by the study staff if there was a discrepancy in the two sensor readings of 20% or if the cgm was reading < 70 mg / dl and the hemocue value was > 85 mg / dl . participants in italy , france , and virginia stayed at hotels , and participants in california resided at a guest house  like outpatient research unit of the sansum consisting of a living room , kitchen , four bedrooms , and bathrooms . the participants in the european studies were admitted individually , one subject at a time ; uva had both single and double admissions ; at sansum , all five subjects were admitted concurrently . subjects checked in by 5:00 p.m. and met with the study team , which confirmed that the subjects had brought their insulin , pump supplies , and regular medications . the subject s pump was removed and the study pump containing the subject s insulin was started . connections were established between dias and one sensor designated as primary ( via the idex ) , the insulin pump ( via the idex ) , and the remote monitoring site . the subject was then introduced to dias operation ; the orientation took 1520 min to complete . the dias user manual ( supplementary data ) and advice from the study team were available to the subjects at all times . after this introduction , the subjects were in charge of their interactions with dias , controlling the system via its graphical user interface . the protocol continued for 42 h. during the first evening / night of study , dias was used in open - loop mode with the subject s home insulin parameters . at 7:00 a.m. on day 2 , the system was switched into closed - loop mode and remained in closed - loop control for 29 h until the subject was discharged at 12:00 p.m. on day 3 . meals were delivered to the patient s room from local restaurants or consumed at local dining facilities ( e.g. , dining out at a restaurant in padova or a hotel buffet breakfast at uva ) . the carbohydrate content of the meals was estimated by the subject and proper entry of the desired carbohydrate amount into dias was confirmed by the study physician , but there were no dietary restrictions . when the subjects were outside of their room , they were accompanied by a member of the study team and dias were remotely monitored continually . figure 1 describes the timeline of the studies in europe and in the united states . protocol design in european ( a ) and united states ( b ) investigation centers . 1b ) were as follows : in padova and montpellier , the patient was moved to the hospital at 7:00 a.m. on day 2 of the study for initiation of closed - loop control and remained in the hospital for 10 h before returning to the hotel for the rest of the study ; in the united states studies the control algorithm was switched into  safety - only mode for the night ( 11:00 p.m. to 7:00 a.m. ) , as requested by the food and drug administration . a study physician , a nurse , and a technician were located in nearby rooms to provide assistance if needed . reference blood glucose readings were measured simultaneously by finger stick with a hemocue ( hemocue ab , ngelholm , sweden ) and a commercial glucometer beginning at 7:00 p.m. on the evening of admission and continuing every 2 h during the day . overnight , there were no scheduled finger sticks ; reference blood glucose measurements were taken only if dias or the secondary sensor alarm indicated hypoglycemia or hyperglycemia , or if the two sensors had readings diverging by > 20% . nursing staff checked dias and secondary cgm readings hourly overnight and system alarms were monitored remotely for the dias and with a baby monitor to capture alarms from the secondary cgm . any dias hypoglycemia red - light warning triggered treatment with 15 g fast - acting carbohydrate ( e.g. , juice ) , whereas hyperglycemia red - light warnings prompted checking the insulin pump for occlusion or malfunction . mmol / l ( 250 mg / dl ) was followed by a -hydroxybutyrate test ( finger stick precision xtra -ketone measurement ) ; confirmed -hydroxybutyrate level > 0.6 mmol / l was a criterion for discontinuation of the trial . any hemocue reading < 80 mg / dl was followed - up with additional finger sticks at least every 15 min and any hemocue blood glucose < 70 mg / dl was treated with fast - acting glucose . the hub of the dias system was an off - the - shelf smart phone running the android operating system . to ensure the operation of the smart phone as a medical device , its operating system was modified to disable processes not related to closed - loop control operation and to include self - checks of system integrity . the communications between dias , the idex , and the pump and the sensor were wireless , giving the patient the freedom to be fully detached from the dias controller . the system components worn by the patient included an insulet omnipod insulin pod and a dexcom seven plus sensor / transmitter . the patient additionally wore a pouch containing a communication box ( either viliv s5 tablet or galaxy nexus phone ) attached to the idex . the idex and the communication box were only needed for automated data transfer and pump control at this early feasibility stage . these devices did not have any computing or patient interaction functions and were abandoned in subsequent studies . the subject controlled dias using graphical user interface , which allowed the following : initializing the system with the average daily insulin dose , basal rate , carbohydrate ratio , and correction factor ; displaying cgm traces and insulin delivery graphs ; and real - time interaction , such as entries of sensor calibrations , meal carbohydrate content , premeal capillary glucose level , and other information the subject wished to provide ( e.g. , exercise or hypoglycemia treatment ) . two traffic - light signals presented the degree of risks for hypoglycemia or hyperglycemia as follows : green light , no risks detected ; yellow light , the system is working actively to mitigate the risks by either attenuating insulin delivery if hypoglycemia is anticipated or administering correction insulin if hyperglycemia is predicted ; and red light , which signifies that risks can not be eliminated by adjustment of insulin alone and intervention is required to either consume carbohydrate or ensure that insulin is delivered properly . dias operated in two modes , open - loop ( first 13 h of each study ) controlling the pump per each patient s preset basal / bolus delivery instructions and displaying cgm and insulin delivery information or closed - loop ( hours 1442 of each study ) running a closed - loop control algorithm . both modes of operation included fully automated transfer of data from the sensor to dias and commands from dias to the insulin pump . user input was required only before meals and whenever the system signaled imminent risk for hypoglycemia or hyperglycemia . the closed - loop control algorithm included two modules : 1 ) safety supervision responsible for prediction of hypoglycemia , attenuation , or discontinuation of insulin delivery if hypoglycemia is anticipated and warnings if hypoglycemia is imminent and can not be prevented by insulin discontinuation alone ( 19 ) and 2 ) range - correction module responsible for injecting correction boluses . the clinical use of this algorithm is described in detail in a recent publication as standard control to range ( 12 ) ; details on its engineering architecture also have been published ( 20 ) . occasional cgm data loss ( up to 20 min ) did not stop the operation of the controller ; during loss of pump communication , insulin was not delivered . in addition , dias transmitted data in real time through either 3 g ( telephone network ) or wifi to two servers ( uva and montpellier ) , which allowed team members to log - in for remote observation from their locations . the server connections were one - directional : dias transmitted data out but could not be controlled from a remote location for safety reasons . the transmitted data contained glucose traces , insulin infusion by the pump , and technical information about the functioning of the control algorithm but did not contain any subject identifiers ; the monitoring web sites were password - protected . achieving statistical significance was not an objective of this early - feasibility investigation . the data analysis corresponded to the goals of the study and included estimation of the failure rates of system components , frequency analysis of lost or inaccurate cgm records , and percent time of active system operation . post hoc analyses included t test and nonparametric comparisons of open versus closed - loop parameters of glucose control observed during the study ; however , the study was not powered for this outcome . before inclusion in the analyses , cgm data were sent through retrospective recalibration using reference blood glucose readings as discussed in a recent editorial ( 21 ) . a total of 20 adults ( age 2165 years ) with type 1 diabetes were studied ( 5 subjects at each site ) . before the tests , a pilot subject was performed in italy , france , and in the united states . all participants were experienced insulin pump users and were required to have the following : prestudy hba1c of 69% ; predefined insulin pump parameters for basal rates , carbohydrate ratios , and insulin sensitivity factors ; and proper mental status / cognition . the exclusion criteria were directed toward safety and included recent history of diabetic ketoacidosis or severe hypoglycemia , pregnancy , breastfeeding , or intention of becoming pregnant ( females ) , uncontrolled arterial hypertension , and conditions that may increase the risk of hypoglycemia or infections . all protocols were approved by the review boards of the participating institutions . in addition , the united states  based studies received food and drug administration approval ( ide # g120032 ) and the european studies received appropriate national - level certifications . all studies were registered with clinicaltrials.gov ( nct01578980 for uva / sansum , nct01447992 for padova , and nct01447979 for montpellier ) . after consent and screening , subjects were trained to use the omnipod insulin pump ( insulet ) and participated in a 3- to 7-day pump initiation if needed . two dexcom seven plus sensors ( dexcom , san diego , ca ) were inserted 2472 h before admission ; throughout the trials , the sensors were calibrated per manufacturer s instructions using commercial glucometers . a calibration was performed before dinner at 7:00 p.m. , thereby allowing for further system - required calibrations to be performed during the timeframes before dinner and before breakfast . per food and drug administration recommendation , an additional ( one - time ) calibration was entered by the study staff if there was a discrepancy in the two sensor readings of 20% or if the cgm was reading < 70 mg / dl and the hemocue value was > 85 mg / dl . participants in italy , france , and virginia stayed at hotels , and participants in california resided at a guest house  like outpatient research unit of the sansum consisting of a living room , kitchen , four bedrooms , and bathrooms . the participants in the european studies were admitted individually , one subject at a time ; uva had both single and double admissions ; at sansum , all five subjects were admitted concurrently . subjects checked in by 5:00 p.m. and met with the study team , which confirmed that the subjects had brought their insulin , pump supplies , and regular medications . the subject s pump was removed and the study pump containing the subject s insulin was started . connections were established between dias and one sensor designated as primary ( via the idex ) , the insulin pump ( via the idex ) , and the remote monitoring site . the subject was then introduced to dias operation ; the orientation took 1520 min to complete . the dias user manual ( supplementary data ) and advice from the study team were available to the subjects at all times . after this introduction , the subjects were in charge of their interactions with dias , controlling the system via its graphical user interface . the protocol continued for 42 h. during the first evening / night of study , dias was used in open - loop mode with the subject s home insulin parameters . at 7:00 a.m. on day 2 , the system was switched into closed - loop mode and remained in closed - loop control for 29 h until the subject was discharged at 12:00 p.m. on day 3 . meals were delivered to the patient s room from local restaurants or consumed at local dining facilities ( e.g. , dining out at a restaurant in padova or a hotel buffet breakfast at uva ) . the carbohydrate content of the meals was estimated by the subject and proper entry of the desired carbohydrate amount into dias was confirmed by the study physician , but there were no dietary restrictions . when the subjects were outside of their room , they were accompanied by a member of the study team and dias were remotely monitored continually . figure 1 describes the timeline of the studies in europe and in the united states . protocol design in european ( a ) and united states ( b ) investigation centers . 1b ) were as follows : in padova and montpellier , the patient was moved to the hospital at 7:00 a.m. on day 2 of the study for initiation of closed - loop control and remained in the hospital for 10 h before returning to the hotel for the rest of the study ; in the united states studies the control algorithm was switched into  safety - only mode for the night ( 11:00 p.m. to 7:00 a.m. ) , as requested by the food and drug administration . a study physician , a nurse , and a technician were located in nearby rooms to provide assistance if needed . reference blood glucose readings were measured simultaneously by finger stick with a hemocue ( hemocue ab , ngelholm , sweden ) and a commercial glucometer beginning at 7:00 p.m. on the evening of admission and continuing every 2 h during the day . overnight , there were no scheduled finger sticks ; reference blood glucose measurements were taken only if dias or the secondary sensor alarm indicated hypoglycemia or hyperglycemia , or if the two sensors had readings diverging by > 20% . nursing staff checked dias and secondary cgm readings hourly overnight and system alarms were monitored remotely for the dias and with a baby monitor to capture alarms from the secondary cgm . any dias hypoglycemia red - light warning triggered treatment with 15 g fast - acting carbohydrate ( e.g. , juice ) , whereas hyperglycemia red - light warnings prompted checking the insulin pump for occlusion or malfunction . mmol / l ( 250 mg / dl ) was followed by a -hydroxybutyrate test ( finger stick precision xtra -ketone measurement ) ; confirmed -hydroxybutyrate level > 0.6 mmol / l was a criterion for discontinuation of the trial . any hemocue reading < 80 mg / dl was followed - up with additional finger sticks at least every 15 min and any hemocue blood glucose < 70 mg / dl was treated with fast - acting glucose . the hub of the dias system was an off - the - shelf smart phone running the android operating system . to ensure the operation of the smart phone as a medical device , its operating system was modified to disable processes not related to closed - loop control operation and to include self - checks of system integrity . the communications between dias , the idex , and the pump and the sensor were wireless , giving the patient the freedom to be fully detached from the dias controller . the system components worn by the patient included an insulet omnipod insulin pod and a dexcom seven plus sensor / transmitter . the patient additionally wore a pouch containing a communication box ( either viliv s5 tablet or galaxy nexus phone ) attached to the idex . the idex and the communication box were only needed for automated data transfer and pump control at this early feasibility stage . these devices did not have any computing or patient interaction functions and were abandoned in subsequent studies . the subject controlled dias using graphical user interface , which allowed the following : initializing the system with the average daily insulin dose , basal rate , carbohydrate ratio , and correction factor ; displaying cgm traces and insulin delivery graphs ; and real - time interaction , such as entries of sensor calibrations , meal carbohydrate content , premeal capillary glucose level , and other information the subject wished to provide ( e.g. , exercise or hypoglycemia treatment ) . two traffic - light signals presented the degree of risks for hypoglycemia or hyperglycemia as follows : green light , no risks detected ; yellow light , the system is working actively to mitigate the risks by either attenuating insulin delivery if hypoglycemia is anticipated or administering correction insulin if hyperglycemia is predicted ; and red light , which signifies that risks can not be eliminated by adjustment of insulin alone and intervention is required to either consume carbohydrate or ensure that insulin is delivered properly . dias operated in two modes , open - loop ( first 13 h of each study ) controlling the pump per each patient s preset basal / bolus delivery instructions and displaying cgm and insulin delivery information or closed - loop ( hours 1442 of each study ) running a closed - loop control algorithm . both modes of operation included fully automated transfer of data from the sensor to dias and commands from dias to the insulin pump . user input was required only before meals and whenever the system signaled imminent risk for hypoglycemia or hyperglycemia . the closed - loop control algorithm included two modules : 1 ) safety supervision responsible for prediction of hypoglycemia , attenuation , or discontinuation of insulin delivery if hypoglycemia is anticipated and warnings if hypoglycemia is imminent and can not be prevented by insulin discontinuation alone ( 19 ) and 2 ) range - correction module responsible for injecting correction boluses . the clinical use of this algorithm is described in detail in a recent publication as standard control to range ( 12 ) ; details on its engineering architecture also have been published ( 20 ) . occasional cgm data loss ( up to 20 min ) did not stop the operation of the controller ; during loss of pump communication , insulin was not delivered . in addition , dias transmitted data in real time through either 3 g ( telephone network ) or wifi to two servers ( uva and montpellier ) , which allowed team members to log - in for remote observation from their locations . the server connections were one - directional : dias transmitted data out but could not be controlled from a remote location for safety reasons . the transmitted data contained glucose traces , insulin infusion by the pump , and technical information about the functioning of the control algorithm but did not contain any subject identifiers ; the monitoring web sites were password - protected . the data analysis corresponded to the goals of the study and included estimation of the failure rates of system components , frequency analysis of lost or inaccurate cgm records , and percent time of active system operation . post hoc analyses included t test and nonparametric comparisons of open versus closed - loop parameters of glucose control observed during the study ; however , the study was not powered for this outcome . before inclusion in the analyses , cgm data were sent through retrospective recalibration using reference blood glucose readings as discussed in a recent editorial ( 21 ) . the focus of this investigation was on the concept of using dias as a smart phone  based control algorithm and user interface host . we assessed dias in terms of human factors and usability , system and component performance , performance of the control algorithm , utility of remote monitoring , and clinical events . before this study , a formative evaluation of the dias user interface heuristic evaluation ( expert review ) was followed by three focus groups with type 1 diabetic patients with varying exposure to diabetes technology ( n = 13 ) . feedback was gathered on various system components addressing user interaction , system features , and capabilities . change recommendations were prioritized , and users were asked to rate the system on several criteria . users indicated the importance of maintaining all existing insulin pump and cgm device functionalities ( 22 ) . the dias graphical user interface ( supplementary data ) proved to be reliable and well - understood by the subjects . all were able to easily navigate through the graphical user interface commands on their own in both open - loop and closed - loop modes of operation , view cgm and insulin information , and administer meal or correction boluses as needed . one subject used a hotel treadmill , one subject in italy rode a bike , one subject in france walked to nearby museums , and five subjects took a shower with the pouch hanging just outside of the shower . system wearability was evaluated in relative terms , comparing dias to previous laptop - based systems . with the transition to a smart phone as a system hub and to wireless data transmission , the weight of a closed - loop control system was reduced several - fold . figure 2a presents photos of dias displaying cgm and insulin delivery traces and the entire system worn by a study subject . dias communicated wirelessly with the idex / communication box ; these devices are placed in a pouch on the patient s belt . the idex communicated wirelessly to an omnipod insulin pump and to a dexcom sensor visible as attached on the subject . the communication range of the idex with the insulin pod and dexcom sensor was 5 inches , which necessitated the use of a belt pouch . with this set - up , the subjects were able to maintain activities of daily living , a necessary first step toward routine outpatient use . a : photos of the dias smart phone displaying cgm and insulin delivery traces ( left ) and the entire system worn by a study subject ( right ) . each of the five subjects participating simultaneously in these trials is represented by an icon on the computer screen . table 1 presents metrics of the technical performance of the artificial pancreas system overall and during the open - loop and closed - loop portions of the study . two subjects described developed hyperglycemia with ketones because of pump site or pod failures in the initial open - loop portion of the study and were rescheduled . only the completed second study data for the rescheduled subjects are included in this analysis . additionally , the three pilot subjects for each country were not included in the analysis ; the data of the first two from italy and france were recently published ( 18 ) . overall , the artificial pancreas system was functional 98% of the time , which exceeded the initially set primary end point goal of 80% . performance metrics for the functioning of the artificial pancreas system used in these studies and of its primary components one element of system connectivity should be noted . in the european studies and in the first united states based studies we used a viliv s5 tablet to communicate with the idex , which was then replaced by a more reliable samsung galaxy nexus smart phone . as evident from table 1 , this replacement had a substantial effect on system reliability , reducing almost five - fold the number of unplanned system restarts because of loss of signal transmission . because the communication box was dedicated solely to data transmission , its replacement did not affect the conceptual or the computing outcomes of the study . further , table 1 presents data on the performance of the principal system components : the cgm , dias , and the insulin pump . of particular importance for fully integrated closed - loop control is the stability of interdevice connections ( sensor  idex  smart phone  idex  insulin pump ) . table 1 presents the availability of cgm and insulin pump communications with dias during the study . although the study was not designed to test algorithm performance or to compare open - loop versus closed - loop , table 2 presents a set of glycemic control metrics and certain post hoc comparisons of open - loop versus closed - loop nights using retrospectively recalibrated cgm data ( 21 ) . the outpatient performance of the controller was similar to its inpatient performance of this same control algorithm observed in a previous study ( standard control to range , 12 ) ; thus , first indications are that a different platform ( e.g. , a smart phone ) under different outpatient conditions may achieve similar performance as a laptop - based system in the hospital . on open - loop versus closed - loop control , we observed 80 vs.72% time within target range ( p = 0.22 ) and 0.53 vs. 0.27 hypoglycemic episodes 3.9 mmol / l ( 70 mg / dl ) per 24 h ( p = 0.16 ) ; in other words , there were no significant differences between open - loop and closed - loop control overnight , which is an expected result for standard control to range ( 12 ) . performance of the control algorithm figure 2b presents a screenshot of the remote monitoring system operation during the study at sansum . each of the five subjects participating simultaneously in this study is represented by an icon on the computer screen . the icon summarizes real - time information , including patient identification number , current cgm reading and direction of change , the state of the hypoglycemia and hyperglycemia alerts , and a message informing the technician of possible risks or system malfunction . safety supervision module was active for three patients ( identification numbers 211 , 212 , and 214 ) as indicated by yellow hypoglycemia lights . each icon can be clicked during a monitoring session , which will display more detailed information for this subject , including detailed records of insulin delivery , glucose data , and the algorithm functions . throughout the study , observation of the participants was performed mainly through the remote monitoring system , which proved to be a useful tool . on six occasions during the study ( two during open - loop and four during closed - loop control ) , carbohydrate treatment was administered for blood glucose levels < 3.3 mmol / l ( 60 mg / dl ) , for a total of 0.17 events per 24 h of system operation . there were no instances of patient - initiated system shutdown , but the trials were discontinued by study staff on three occasions . the first two events occurred early , before initiation of closed - loop control , and the subjects were rescheduled for subsequent admissions , which concluded successfully . subject 1 experienced hyperglycemia of 260 mg / dl with -hydroxybutyrate level of 0.7 mmol / l 2 h after the insulin pump was initiated ( consistent with pod compared with insertion site failure ) . after the connection was reestablished with a new tablet , the insulin pod alarmed , prompting a pod change . the new pod occluded ( blood noted in pod tubing ) , resulting in -hydroxybutyrate of 1.3 mmol / l . 1 ) with the range controller switched off , delivering only basal rate ( 4.1 units in the previous 6 h ) . the subject s cgm glucose was noted to increase from 180 mg / dl to 295 mg / dl over the final 2 h , suggesting that a pod occlusion ( unconfirmed ) may have contributed to this event . these three patients were treated with subcutaneous insulin , resulting in prompt resolution of the mild ketosis . before this study , a formative evaluation of the dias user interface was conducted to evaluate the feasibility of the design for patient use . heuristic evaluation ( expert review ) was followed by three focus groups with type 1 diabetic patients with varying exposure to diabetes technology ( n = 13 ) . feedback was gathered on various system components addressing user interaction , system features , and capabilities . change recommendations were prioritized , and users were asked to rate the system on several criteria . users indicated the importance of maintaining all existing insulin pump and cgm device functionalities ( 22 ) . the dias graphical user interface ( supplementary data ) proved to be reliable and well - understood by the subjects . all were able to easily navigate through the graphical user interface commands on their own in both open - loop and closed - loop modes of operation , view cgm and insulin information , and administer meal or correction boluses as needed . one subject used a hotel treadmill , one subject in italy rode a bike , one subject in france walked to nearby museums , and five subjects took a shower with the pouch hanging just outside of the shower . system wearability was evaluated in relative terms , comparing dias to previous laptop - based systems . with the transition to a smart phone as a system hub and to wireless data transmission , figure 2a presents photos of dias displaying cgm and insulin delivery traces and the entire system worn by a study subject . dias communicated wirelessly with the idex / communication box ; these devices are placed in a pouch on the patient s belt . the idex communicated wirelessly to an omnipod insulin pump and to a dexcom sensor visible as attached on the subject . the communication range of the idex with the insulin pod and dexcom sensor was 5 inches , which necessitated the use of a belt pouch . with this set - up , the subjects were able to maintain activities of daily living , a necessary first step toward routine outpatient use . a : photos of the dias smart phone displaying cgm and insulin delivery traces ( left ) and the entire system worn by a study subject ( right ) . each of the five subjects participating simultaneously in these trials is represented by an icon on the computer screen . table 1 presents metrics of the technical performance of the artificial pancreas system overall and during the open - loop and closed - loop portions of the study . two subjects described developed hyperglycemia with ketones because of pump site or pod failures in the initial open - loop portion of the study and were rescheduled . only the completed second study data for the rescheduled subjects are included in this analysis . additionally , the three pilot subjects for each country were not included in the analysis ; the data of the first two from italy and france were recently published ( 18 ) . overall , the artificial pancreas system was functional 98% of the time , which exceeded the initially set primary end point goal of 80% . performance metrics for the functioning of the artificial pancreas system used in these studies and of its primary components one element of system connectivity should be noted . in the european studies and in the first united states based studies we used a viliv s5 tablet to communicate with the idex , which was then replaced by a more reliable samsung galaxy nexus smart phone . as evident from table 1 , this replacement had a substantial effect on system reliability , reducing almost five - fold the number of unplanned system restarts because of loss of signal transmission . because the communication box was dedicated solely to data transmission , its replacement did not affect the conceptual or the computing outcomes of the study . further , table 1 presents data on the performance of the principal system components : the cgm , dias , and the insulin pump . of particular importance for fully integrated closed - loop control is the stability of interdevice connections ( sensor  idex  smart phone  idex  insulin pump ) . table 1 presents the availability of cgm and insulin pump communications with dias during the study . although the study was not designed to test algorithm performance or to compare open - loop versus closed - loop , table 2 presents a set of glycemic control metrics and certain post hoc comparisons of open - loop versus closed - loop nights using retrospectively recalibrated cgm data ( 21 ) . the outpatient performance of the controller was similar to its inpatient performance of this same control algorithm observed in a previous study ( standard control to range , 12 ) ; thus , first indications are that a different platform ( e.g. , a smart phone ) under different outpatient conditions may achieve similar performance as a laptop - based system in the hospital . on open - loop versus closed - loop control , we observed 80 vs.72% time within target range ( p = 0.22 ) and 0.53 vs. 0.27 hypoglycemic episodes 3.9 mmol / l ( 70 mg / dl ) per 24 h ( p = 0.16 ) ; in other words , there were no significant differences between open - loop and closed - loop control overnight , which is an expected result for standard control to range ( 12 ) . figure 2b presents a screenshot of the remote monitoring system operation during the study at sansum . each of the five subjects participating simultaneously in this study is represented by an icon on the computer screen . the icon summarizes real - time information , including patient identification number , current cgm reading and direction of change , the state of the hypoglycemia and hyperglycemia alerts , and a message informing the technician of possible risks or system malfunction . safety supervision module was active for three patients ( identification numbers 211 , 212 , and 214 ) as indicated by yellow hypoglycemia lights . each icon can be clicked during a monitoring session , which will display more detailed information for this subject , including detailed records of insulin delivery , glucose data , and the algorithm functions . throughout the study , observation of the participants was performed mainly through the remote monitoring system , which proved to be a useful tool . on six occasions during the study ( two during open - loop and four during closed - loop control ) , carbohydrate treatment was administered for blood glucose levels < 3.3 mmol / l ( 60 mg / dl ) , for a total of 0.17 events per 24 h of system operation . there were no instances of patient - initiated system shutdown , but the trials were discontinued by study staff on three occasions . the first two events occurred early , before initiation of closed - loop control , and the subjects were rescheduled for subsequent admissions , which concluded successfully . subject 1 experienced hyperglycemia of 260 mg / dl with -hydroxybutyrate level of 0.7 mmol / l 2 h after the insulin pump was initiated ( consistent with pod compared with insertion site failure ) . after the connection was reestablished with a new tablet , the insulin pod alarmed , prompting a pod change . the new pod occluded ( blood noted in pod tubing ) , resulting in -hydroxybutyrate of 1.3 mmol / l . 1 ) with the range controller switched off , delivering only basal rate ( 4.1 units in the previous 6 h ) . the subject s cgm glucose was noted to increase from 180 mg / dl to 295 mg / dl over the final 2 h , suggesting that a pod occlusion ( unconfirmed ) may have contributed to this event . these three patients were treated with subcutaneous insulin , resulting in prompt resolution of the mild ketosis . technology advancements in the past year made possible the development of dias , wearable ambulatory artificial pancreas platforms using an off - the - shelf smart phone as a computational hub . besides more user - friendly touch - screen interface and wireless connectivity , one easily quantifiable result of the transition from a laptop - based to a phone - based closed - loop control is a significant reduction in the system weight , which brings the system one important step closer to ambulatory use . ultimately , this would lead to  closing the loop  with a portable minimally invasive system suitable for home use . industry is currently transitioning cgms and pumps to include wireless connectivity ; thus , dias is only the first of many portable devices that will be capable of wireless data exchange and fully integrated closed - loop control . at the time of this outpatient trial , the dexcom seven plus and the omnipod insulet pump had short - range wireless capability to communicate with an idex research platform . also , for the idex to establish wireless communication with dias , an intermediary tablet ( or a cell phone ) needed to be connected to the idex . hence , there was short - range wireless communication from the patient ( wearing a pod and sensor / transmitter ) to a pouch containing the idex and tablet ( or cell phone ) , and long - range wireless communication between the pouch and the dias artificial pancreas platform . these intermediate devices are now being phased out ; communication boxes are no longer necessary . such a technology improvement was anticipated in our study ; thus , we focused on the smart phone computing and user - interface capabilities of the dias , assuming that this would be the device that is here to stay . special emphasis should be placed on the fact that the subjects were operating the system by themselves most of the time . to the best of our knowledge , this is the first trial in which the subjects were responsible for the oversight of their closed - loop systems , a step that is critical for outpatient deployment of closed - loop control . based on this feedback , we conclude that the form factor of dias as an artificial pancreas platform is appropriate for outpatient use . however , before long - term efficacy studies comparing outpatient artificial pancreas with sensor - augmented pump therapy can proceed , system wearability during daily living and the reliability of device communications must be ensured . testing of the system at four different sites in three countries and in a variety of hotel and restaurant settings using one , two , or five systems concurrently provided an opportunity to challenge dias with multiple scenarios that are likely to be encountered in nonhospital and , ultimately , home settings . in general , the technical performance of the dias system with overall operational time of 98% exceeded the set goal of 80% . in retrospect , this goal may have been conservative , but before this study it was generally unclear whether a smart phone can run closed - loop control , and there was no experience to guide the choice of this goal . the principal system components  sensor , dias , and insulin pump  were reasonably reliable , with 0.03 , 0.09 , and 0.12 malfunction events necessitating device replacement per 24 h , respectively . occasional cgm data points were lost ( 8.1% ) , but this did not result in skipping control cycles or discontinuation of the study ; by design , control to range would function during transient absence of cgm data because the controller intervenes only if risks for hypoglycemia or hyperglycemia are detected ( 20 ) . finally , we must emphasize the utility of remote monitoring , which was available on site and at remote locations ( i.e. , studies in europe or in california were observed from virginia and vice versa in real time ) . this was a critical aspect for patient safety that allowed close supervision so that intervention could occur quickly if needed . our system allowed monitoring concurrently multiple patients , a feature that was tested at sansum with five patients simultaneously . this feature alone will allow acceleration of the number of subjects who could be studied at the same time , reducing staffing costs and making artificial pancreas research more efficient . in summary , a wearable inexpensive closed - loop control platform ( dias ) combined with real - time remote monitoring , this system opens the possibility for large pivotal trials that will establish the artificial pancreas as a viable mainstream treatment strategy in type 1 diabetes .