Patent Publication Number: US-2021170104-A1

Title: Techniques and devices providing adaptivity and personalization in diabetes treatment

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of the filing date of U.S. Provisional Application Ser. No. 62/944,792, filed Dec. 6, 2019, the entire contents of which are incorporated herein by reference in their entirety. 
    
    
     BACKGROUND 
     An insulin-carbohydrate (IC) ratio, which is conversion factor of number of carbohydrates to units of insulin to be delivered, enables a user or a diabetes management device to calculate an amount of insulin to be delivered when about to eat a meal or after eating a meal. This IC ratio may be periodically tuned. However, presently, an adjustment to a user&#39;s insulin-carbohydrate (IC) ratio is a physician modification of the IC ratio after a manual review of each person&#39;s blood glucose measurement and insulin delivery histories, which may occur after as long as 3-6 months between physician visits. It would be beneficial if an artificial pancreas algorithm were operable to adjust the IC ratio on a more regular basis. 
     In addition, user&#39;s do not regularly tune their insulin-to-carbohydrate (IC) ratio, and when they do the user&#39;s often mistune the IC ratios, leading to users experiencing post prandial hyperglycemia due to under-bolusing (i.e., delivering too little insulin with a mealtime bolus dosage) or post prandial hypoglycemia due to over-bolusing (i.e., delivering too much insulin with a mealtime bolus dosage). 
     In other situations, a user&#39;s Total Daily Insulin (TDI) values may be determined by taking a simple sum of the user&#39;s insulin delivery throughout one day. This value is usually calculated by taking the sum of all insulin delivery to the user each day. However, this manner of determining TDI does not consider the quality of glucose control for the user—if the user consistently experiences hyperglycemia and underdelivers insulin, this manner of determining a quantity of TDI may continue to underestimate the TDI in which case the TDI remains low and may not accurately represent the user&#39;s true daily insulin needs. Accordingly, a new manner of determining a user&#39;s TDI that maintains the user&#39;s blood glucose measurement values within a “normal” range of approximately 70 mg/dL and 180 mg/dL. 
     It would also be helpful to provide processes, computer products, devices and techniques to assist users with the management of their diabetes treatment plan and overcome the deficiencies described above. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS. 1A and 1B  show a flow chart of an example of a process for determining an insulin-carbohydrate ratio. 
         FIG. 1C  shows a flow chart of an example of an alternate process for determining an insulin-carbohydrate ratio. 
         FIG. 2  illustrates a functional block diagram of drug delivery system suitable for implementing the example processes and techniques described herein. 
         FIG. 3  illustrates a flow chart of an example process for determining a bolus dosage that is to be administered in response to consumption of a meal. 
         FIG. 4  illustrates a flow chart of another example of a process for determining a dosage of a bolus injection for correcting a blood glucose value. 
     
    
    
     DETAILED DESCRIPTION 
     Various examples provide a method, a system, a device and a computer-readable medium for addressing issues related to updating a user&#39;s insulin to carbohydrate ratio that is used to determine meal time bolus dosages and functions for updating a user&#39;s total daily insulin that are used to update user&#39;s basal insulin doses. 
     A user&#39;s Total Daily Insulin (TDI) value is a simple sum of the user&#39;s all insulin needs throughout one day. This value is usually calculated by taking the sum of all insulin delivery to the user each day. However, this does not account for the quality of glucose control for the user—if the user consistently experiences hyperglycemia and underdelivers insulin, this TDI quantity will remain low and will not represent the user&#39;s true daily insulin needs. 
     Another example provides a process that may be used with any additional algorithms or computer applications that manage blood glucose levels and insulin therapy. Such algorithms may be referred to as an “artificial pancreas” algorithm-based system, or more generally, an artificial pancreas (AP) application, that provides automatic delivery of an insulin based on a blood glucose sensor input, such as that received from a CGM or the like. In an example, the artificial pancreas (AP) application when executed by a processor may enable a system to monitor a user&#39;s glucose values, determine an appropriate level of insulin for the user based on the monitored glucose values (e.g., blood glucose concentrations or blood glucose measurement values) and other information, such as user-provided information, such as carbohydrate intake, exercise times, meal times or the like, and take actions to maintain a user&#39;s blood glucose value within an appropriate range. The appropriate blood glucose value range may be considered a target blood glucose value of the particular user. For example, a target blood glucose value may be acceptable if it falls within the range of 80 mg/dL to 120 mg/dL, which is a range satisfying the clinical standard of care for treatment of diabetes. However, an AP application as described herein may be able to establish a target blood glucose value more precisely and may set the target blood glucose value at, for example, 110 mg/dL, or the like. As described in more detail with reference to the examples of  FIGS. 1A-4 , the AP application may utilize the monitored blood glucose values and other information to generate and send a command to a medical device including, for example, a pump, to control delivery of insulin to the user, change the amount or timing of future doses, as well as to control other functions based on the tuned IC ratio or new TDI calculation. 
     In contrast to consistently mistuning a user&#39;s insulin-carbohydrate ratio (IC), it would be more advantageous to deliver an optimal amount of insulin based on an optimal IC ratio. In some examples, the optimal IC ratio may be the ratio that is used to calculate the amount of insulin to accompanying a meal bolus that would minimize the excursions in blood glucose measurements due to the meal injection. The IC ratio is number of carbohydrates to units of insulin to be delivered. An optimal IC ratio provides the user with an exact or nearly-exact amount of insulin to compensate for the user&#39;s intake of carbohydrates. There may be a tolerance with this, for example, so that the blood glucose falls within the blood glucose level range of 70-180 mg/dL, but the intent is to provide an amount of insulin in the mealtime bolus that results in the blood glucose measurement to be at a target blood glucose level of approximately 120 mg/dL, or the like. While 70 mg/dL-120 mg/dL is an optimal range for a user&#39;s blood glucose measurement value, a normal blood glucose measurement range—where normal is a blood glucose measurement value that is considered neither hypoglycemic or hyperglycemic—may be between 70 mg/dL and 180 mg/dL. 
       FIGS. 1A and 1B  show a flowchart of a process example for determining an insulin-carbohydrate ratio. The process  100  may be implemented by programming code that is executed by a processor a d may utilize a user&#39;s glucose concentration and insulin delivery values to identify and correct IC ratios to a more optimal value. 
     For example, modification of IC ratios may be based on actual hyperglycemic or hypoglycemic blood glucose levels measured following mealtime boluses. In an example, correlation of glucose excursions to insulin-on-board (JOB) traces following mealtime boluses may be determined using the number of blood glucose measurements made before, during, and after meal times. Of course, the use of artificial pancreas algorithm enables a more accurate determination of a correlation, which results in a better estimate of JOB. 
     In a first example as shown in  FIGS. 1A and 1B , a user&#39;s post prandial glucose control quality can be assessed in terms of a % times, number of times, or amount of time, the user&#39;s measured blood glucose levels are in the hyperglycemic (&gt;180 mg/dL), hypoglycemic (&lt;70 mg/dL), and safe glycemic (70-180 mg/dL) ranges. For example, if the user experiences a high incidence of hypoglycemia (i.e., a large % times, number of times, or amount of time with a blood glucose measurement less than (&lt;) 70 mg/dL), it may indicate that the user may have over-bolused for a meal, leading to a possible recommendation for an increase in the insulin to carbohydrate ratio. Alternatively, if the user experiences a high incidence of hyperglycemia, this may indicate that the user may have under-bolused for a meal, leading to a possible recommendation for a decrease in the insulin to carbohydrate ratio. 
     In closed loop examples (such as when the artificial pancreas application is managing the user&#39;s diabetes treatment plan), if the accompanying closed loop algorithm suspends significantly following boluses, even if the user&#39;s glucose control is favorable, this may lead to a recommendation to increase the IC ratio. 
     In closed loop examples, if the accompanying closed loop algorithm delivers significant amount of insulin above basal following boluses, even if the user&#39;s glucose control is favorable, this may lead to a recommendation of decrease in IC ratios. 
     In the example equation No. 1 below, the adjustment (i.e., IC new ) can be implemented as: 
     
       
         
           
             
               
                 
                   
                     IC 
                     
                       new 
                        
                       
                           
                       
                        
                       1 
                     
                   
                   = 
                   
                     
                       
                         IC 
                         old 
                       
                        
                       
                         ( 
                         
                           1 
                           + 
                           
                             
                               ∑ 
                               
                                 i 
                                 = 
                                 1 
                               
                               N 
                             
                              
                             
                               
                                 
                                   t 
                                   hypo 
                                 
                                  
                                 
                                   ( 
                                   N 
                                   ) 
                                 
                               
                               
                                 7 
                                  
                                 2 
                               
                             
                           
                         
                         ) 
                       
                     
                      
                     
                       ( 
                       
                         1 
                         - 
                         
                           
                             ∑ 
                             
                               i 
                               = 
                               1 
                             
                             N 
                           
                            
                           
                             
                               
                                 t 
                                 hyper 
                               
                                
                               
                                 ( 
                                 N 
                                 ) 
                               
                             
                             
                               7 
                                
                               2 
                             
                           
                         
                       
                       ) 
                     
                      
                     
                       ( 
                       
                         1 
                         + 
                         
                           
                             ∑ 
                             
                               i 
                               = 
                               1 
                             
                             N 
                           
                            
                           
                             
                               
                                 t 
                                 suspend 
                               
                                
                               
                                 ( 
                                 N 
                                 ) 
                               
                             
                             
                               7 
                                
                               2 
                             
                           
                         
                       
                       ) 
                     
                      
                     
                       ( 
                       
                         1 
                         - 
                         
                           
                             ∑ 
                             
                               i 
                               = 
                               1 
                             
                             N 
                           
                            
                           
                             
                               
                                 t 
                                 
                                   delivery 
                                    
                                   
                                       
                                   
                                    
                                   above 
                                    
                                   
                                       
                                   
                                    
                                   basal 
                                 
                               
                                
                               
                                 ( 
                                 N 
                                 ) 
                               
                             
                             
                               7 
                                
                               2 
                             
                           
                         
                       
                       ) 
                     
                   
                 
               
               
                 
                   Eq 
                   . 
                   
                       
                   
                    
                   1 
                 
               
             
           
         
       
     
     In Equation No. 1 above, N is the number of meals per day, and various t variables indicate the corresponding 6 hour post-prandial periods that meet each of the four conditions that lead to IC ratio adjustment. The denominator value 72 in each factor is a post prandial period factor and is based on 6 hours times 12 blood glucose measurements (by a continuous blood glucose monitor) per hour which equals 72. For example, a continuous blood monitor (CGM) takes a blood glucose measurement approximately every 5 minutes. The blood glucose measurement may be delivered to a processor monitoring the blood glucose of the user. The denominator value in the respective factors of equation No. 1 may be changed to more closely mirror a user&#39;s requirements or physiology. 
     In the example of  FIG. 1 , this adjustment may be conducted once per day or less frequently. In another example, the intensity of these adjustments may be modified based on the value of the blood glucose measurement values. 
     For example, a processor may execute programming code, such as an artificial pancreas application, stored in a memory accessible by the processor. The processor when executing the programming code is operable to perform various functions. For example, the various functions may include obtaining a prior insulin-carbohydrate ratio (e.g., IC old ) ( 110 ) from a memory, via an input to an input device coupled to the processor, or, via a communication from an external source, such as a cloud-based diabetes treatment plan management system or the like. For example, the prior insulin-carbohydrate ratio may be stored in a memory, such as, for example, in a settings file or the like coupled to the processor that is used by the artificial pancreas application in the calculation of dosage settings by the artificial pancreas application. 
     For a period of time (e.g., 6 hours, 12 hours or the like), different parameters related to blood glucose measurements and management of a diabetes treatment plan may be monitored by a processor. Note that the period of time may begin after the user has a meal, just before the user has a meal, after the user completes a meal, or the like. For example, the processor may receive blood glucose measurement values from a continuous glucose monitor or the like. In the example, the processor may, at  120 , monitor the received blood glucose measurement values to determine the number of received blood glucose measurement values that are below a hypoglycemic threshold value (e.g., less than 70 mg/dL). For example, the processor may, as part of the monitoring, compare each received blood glucose measurement value to a hypoglycemic threshold value and increment a hypoglycemia counter if the received blood glucose measurement value is below the hypoglycemic threshold value. 
     At  130 , the processor may determine a hypoglycemia IC correction factor based on the monitored number of blood glucose measurements below the hypoglycemic threshold. The hypoglycemia IC correction factor is represented by factor shown the first parenthetical in Eq. 1: 
     
       
         
           
             
               ( 
               
                 1 
                 + 
                 
                   
                     ∑ 
                     
                       i 
                       = 
                       1 
                     
                     N 
                   
                    
                   
                     
                       
                         t 
                         hypo 
                       
                        
                       
                         ( 
                         N 
                         ) 
                       
                     
                     
                       7 
                        
                       2 
                     
                   
                 
               
               ) 
             
             . 
           
         
       
     
     The hypoglycemia IC correction factor may be used to increase the new IC ratio if an amount of time that blood glucose measurements are below the hypoglycemic blood glucose measurement value, e.g., less than 70 mg/dL, which is a clinical threshold value for hypoglycemia. In the example, the monitored number may be converted into a time parameter. For example, the monitored number of blood glucose that are below the hypoglycemic blood glucose measurement value may be multiplied by 5 minutes, which is the amount of time between blood glucose measurements. 
     The processor, at  140 , may monitor the number of blood glucose measurement values that exceed a hyperglycemia threshold. For example, the processor may monitor the received blood glucose measurement values to determine the number of received blood glucose measurement values that exceed a hyperglycemic threshold value (e.g., greater than 180 mg/dL). For example, the processor, as part of the monitoring, may compare each received blood glucose measurement value to a hyperglycemic threshold value and increment a hyperglycemia counter if the received blood glucose measurement value is greater than the hyperglycemic threshold value. 
     The processor may determine a hyperglycemia IC correction factor based on the monitored number of blood glucose measurements that exceed a hypoglycemic threshold ( 150 ). In the example, the hyperglycemia IC correction factor is represented by the factor shown in the second parenthetical in Eq. 1: 
     
       
         
           
             
               ( 
               
                 1 
                 - 
                 
                   
                     ∑ 
                     
                       i 
                       = 
                       1 
                     
                     N 
                   
                    
                   
                     
                       
                         t 
                         hyper 
                       
                        
                       
                         ( 
                         N 
                         ) 
                       
                     
                     
                       7 
                        
                       2 
                     
                   
                 
               
               ) 
             
             . 
           
         
       
     
     The hyperglycemia IC correction factor may be used to reduce the new IC ratio if the amount of time that the blood glucose measurements are above the hyperglycemia blood glucose measurement value, e.g., greater than 180 mg/dL, which is a clinical threshold for hyperglycemia. 
     At  160 , the processor may monitor the number of times (or amount of time) the artificial pancreas application was in a suspend insulin delivery status. For example, the artificial pancreas application may determine that the delivery of insulin has exceeded their needs so a processor executing the artificial pancreas application may suspend the delivery of insulin including basal insulin doses. The artificial pancreas application may monitor the number of times or the total time that the delivery of insulin is suspended either by a user input or by a suspend delivery process determination made by the artificial pancreas application. The artificial pancreas application may be operable to determine an amount of insulin a person has in their body, referred to as insulin onboard (JOB). The IOB may be determined a number of ways and may be based on amounts of insulin delivered, a user&#39;s insulin sensitivity, duration of insulin action and the like. If the IOB is too great, the artificial pancreas application may suspend further delivery of insulin to prevent a user&#39;s blood glucose measurement values from falling outside the range of 70 mg/dL-180 mg/dL. 
     The suspend IC correction factor in the third parenthetical is based on an amount of time that the delivery of insulin was suspended so that may indicate the over-delivery of insulin and a subsequent stoppage in delivery in an attempt to compensate for the over-delivery of insulin. For example, the processor, as part of the monitoring, may receive a suspend delivery signal from a suspend delivery process of the artificial pancreas application. The processor may note a time at which the suspend delivery signal was received, and later note a time at which a resume delivery signal is received. The suspend delivery signal causes the delivery of insulin to be suspended, while the resume delivery signal cause to the delivery of insulin to be resumed. Alternatively, the delivery of insulin may be suspended for a predetermined period of time in response to the suspend delivery signal. For example, the predetermined period to time may be 30 minutes, 1 hour, 4 hours, or longer. In this alternative, the processor may keep track of the number of times N insulin delivery is suspended, for example, based on the number of times that the suspend delivery signal was initiated or received over a given period of time (e.g., 72 hours or the like). Using the predetermined period of time for suspending insulin delivery and the number of times N, an amount of time in which the delivery of insulin was suspended may be determined and may be used to determine a third factor in the IC ratio adjustment as shown in the third parenthetical of Equation No. 1 above. Pharmacokinetics (PK) and pharmacodynamics (PD) of the drug with respect to the user may be relevant to the third and fourth parenthetical factors. 
     At  170 , for example, the processor may determine a suspend IC correction factor based on the number of times in which the artificial pancreas application was in the suspend insulin delivery status. The determined value of the suspend IC correction factor in the third parenthetical may be used to increase the IC ratio so that future instances of over-delivery are reduced. In the third factor: 
     
       
         
           
             
               ( 
               
                 1 
                 + 
                 
                   
                     ∑ 
                     
                       i 
                       = 
                       1 
                     
                     N 
                   
                    
                   
                     
                       
                         t 
                         suspend 
                       
                        
                       
                         ( 
                         N 
                         ) 
                       
                     
                     
                       7 
                        
                       2 
                     
                   
                 
               
               ) 
             
             . 
           
         
       
     
     The variable t suspend  (i.e., Tsuspend) stands for an amount of time that the artificial pancreas application was suspended from delivering insulin, and N may refer to the number of times the suspend delivery signal was received. 
     The processor may further monitor a number of insulin doses delivered in which the amount of insulin in the delivered dose exceeded a basal insulin dosage setting at the time the insulin dose was delivered ( 180 ). For example, a basal insulin dose may be 0.5 U/hour, while the actual delivered dosage was 1.5 U/hour. The artificial pancreas application executing on the processor may be operable to determine an over-basal IC correction factor based on the monitored number of insulin doses delivered in which the amount of insulin in the delivered dose exceeded a basal insulin dosage setting ( 185 ). In  185 , the over-basal IC factor in the fourth parenthetical is an indication of under-delivery if the algorithm is frequently delivering over the user&#39;s basal profile. If the artificial pancreas application is delivering insulin above the basal threshold, the artificial pancreas application is attempting to compensate for the user&#39;s increased glucose needs. Therefore, the IC ratio may be decreased based on the time that the automatic insulin delivery as controlled by the artificial pancreas application is delivering more insulin than the user&#39;s basal needs. 
     Upon the determination of the hypoglycemia IC correction factor, the hyperglycemia IC correction factor, the suspend IC correction factor and the over-basal IC correction factor, the artificial pancreas application executing on the processor may, at  190 , calculate a new IC ratio (i.e., IC new1 ). The new IC ratio, IC new1 , may be based on the prior IC ratio, the determined hypoglycemia IC correction factor, the determined hyperglycemia IC correction factor, the determined suspend IC correction factor, and the determined over-basal IC correction factor, as shown in Equation No. 1. 
     The artificial pancreas application may determine a new insulin dosage for the next delivery of insulin using the new IC ratio (i.e., IC new1 ). The artificial pancreas application may actuate delivery of a next insulin dose based on a calculated insulin dosage using the calculated new IC ratio ( 195 ). 
     In the forgoing examples, the respective factors included a post prandial period factor of 72. The post prandial period factor of 72 is based on 6 hours of a post prandial period. The post prandial factor may be calculated as 6 hours times 12 blood glucose measurements per hour (every 5 minutes) equals 72). The post prandial period factor may be adjusted or tuned for the proper prandial period as needed. The 6 hours may be considered a basis for delivered insulin action. Of course, a post prandial period other than 6 hours may be used. For example, 12 hours, 3 hours or the like may be used depending on the meal (e.g., breakfast may be one time period, while lunch or dinner may be a different period of time). 
     In another example, the two factors, hypoglycemia IC correction factor and the hyperglycemia IC correction factor, may be used with or without an automatic insulin delivery (AID) algorithm such as that provided by an artificial pancreas application. However, if an AID algorithm of an artificial pancreas application is being used, the suspend IC correction factor and the over-basal IC correction factor may also be used. 
     Another option for adjusting the IC ratio is also provided. In this other option, the IC ratio modification may be based on known blood glucose measurement values and insulin onboard (JOB) traces. The IOB may BE used to estimate how much insulin is in a user&#39;s body. For example, an insulin dosage recommendation may be 10 units of insulin. However, the user may have 3 units of JOB. As a result, the dosage recommendation may be reduced by simple subtraction from 10 units of insulin to 7 units of insulin (10 units of recommended dosage minus 3 units of IOB (which the body still needs to process)). 
     In another example, the user&#39;s post prandial blood glucose measurements and insulin traces can be correlated to determine if the IOB values sufficiently compensate for the resulting glucose excursions following the meals. 
     Any residual IOB that is consumed beyond the glucose excursions can be correlated with IOB values that properly compensated for meal ingestion. 
     This correlation can then be utilized to identify the correct IC ratios based on known user input values. 
     In the example, this adjustment can be implemented as shown in Equation No. 2 below: 
     
       
         
           
             
               
                 
                   
                     IC 
                     
                       new 
                        
                       
                           
                       
                        
                       2 
                     
                   
                   = 
                   
                     
                       
                         
                           ∑ 
                           
                             i 
                             = 
                             1 
                           
                           t 
                         
                          
                         
                           
                             IOB 
                             
                               post 
                                
                               
                                   
                               
                                
                               prandial 
                             
                           
                            
                           
                             ( 
                             i 
                             ) 
                           
                         
                       
                       - 
                       
                         
                           ∑ 
                           
                             i 
                             = 
                             1 
                           
                           t 
                         
                          
                         
                           
                             
                               CGM 
                                
                               
                                 ( 
                                 i 
                                 ) 
                               
                             
                             - 
                             
                               target 
                                
                               
                                 ( 
                                 i 
                                 ) 
                               
                             
                           
                           
                             CF 
                              
                             
                               ( 
                               i 
                               ) 
                             
                           
                         
                       
                     
                     
                       CHO 
                       meal 
                     
                   
                 
               
               
                 
                   Eq 
                   . 
                   
                       
                   
                    
                   No 
                   . 
                   
                       
                   
                    
                   2 
                 
               
             
           
         
       
     
     In the example of Equation No. 2, this IC estimate can be calculated for each meal that is ingested and provide an IC ratio profile that is customized to each user&#39;s meal. In the example, the numerator is a calculation of the amount of insulin that a user needs in the post prandial period (e.g., 6 hours after a meal) to compensate for the meal. The first term in the numerator, the IOB post prandial term, is the amount of insulin that a user has received during the post prandial period. While the second term, insulin delivery correction term, is an amount of insulin that would have enabled the user to meet their target blood glucose setting. The insulin delivery correction term may either be positive (meaning the user could have used more insulin) or negative (meaning the user could have used less insulin). The denominator is the amount of carbohydrates that were in a meal which is represented by the variable CHO meal . This equation (i.e., Equation No. 2) provides the IC ratio (insulin over carbohydrates) that provides the ICnew2. 
     This process may be done for each meal until there is a convergence to an optimal IC ratio. 
     A process example illustrating the implementation of the Equation No. 2 is shown in  FIG. 1C . In the example of  FIG. 1C , the artificial pancreas application executing on a processor  161  may receive, at  161 , an approximate amount of carbohydrates ingested in a meal or to be ingested in a meal ( 162 ). The artificial pancreas application may keep track or monitor the delivery of insulin over a period of time once it is determined that a meal is ingested, or to be ingested ( 163 ). For example, after users indicate a meal ingestion through the request of a meal bolus command, the process implemented by the AP application may consider a number of hours (e.g. 6 hours) as the post prandial period. The artificial pancreas application may keep track of the dosages of insulin delivered during the post prandial time period by a drug delivery device (operable to automatically deliver insulin) or based on inputs from a user regarding dosages of insulin delivered to a user. The artificial pancreas application may be operable to determine an error factor representing an amount of insulin over or under delivered during the post prandial period ( 165 ). For example, the artificial pancreas application may receive blood glucose measurements (labeled as CGM in Eq No. 2) during the post prandial period. In the determination of the error factor, the artificial pancreas application may determine a difference between a received blood glucose measurement to the target blood glucose setting for that particular iteration. The differences may be summed during the post prandial period. The summed differences may then be divided by a correction factor that accounts for the user&#39;s ability to process delivered insulin. 
     At  167 , the artificial pancreas application may be operable to determine a difference between the determined amount of insulin onboard and the error factor. This will determination provides an amount of insulin that the user was estimated to require to compensate for the ingestion of the meal. 
     The artificial pancreas application may be operable to calculate an updated insulin to carbohydrate ratio based on the determined difference and the approximate amount of carbohydrates ingested ( 168 ). The calculated updated insulin (i.e., IC new2  in Equation No. 2) may be stored by the artificial pancreas application in a memory of a mobile device. The artificial pancreas application may use the calculated updated insulin in further calculations of dosages of insulin to be delivered by a drug delivery device or by a user. 
     For example, the artificial pancreas application may be operable make a new calculation of a dosage, such as a basal dosage, a bolus dosage (for a next meal), or the like, based on the calculated updated insulin (i.e., ICnew2 in Equation No. 2). At  169 , the artificial pancreas application may be operable to modify delivery of insulin based on the updated insulin to carbohydrate ratio (i.e., IC new2 ). The modified delivery of insulin may be a newly calculated amount of insulin to be delivered in a next dosage, a time of the next dosage, or both a modification of the amount of insulin to be delivered and a time of the delivery of a next dose of insulin. 
     In another example, the accuracy of the ICnew1 or ICnew2 as determined according to the examples of  FIGS. 1A and 1B  that utilize Equation Nos. 1 and 2 may be confirmed using the following rules. For example, the new IC ratio can be compared with a correction factor (CF) that is calculated based on the user&#39;s average glucose excursions divided by the user&#39;s average insulin delivery excursions beyond the basal value. This ratio can be converted into an estimated TDI based on: 
     
       
         
           
             
               
                 1 
                  
                 8 
                  
                 0 
                  
                 0 
               
               TDI 
             
             = 
             
               CF 
               estimate 
             
           
         
       
       
         
           
             
               TDI 
               estimate 
             
             = 
             
               1 
                
               800 
                
               
                 CF 
                 estimate 
               
             
           
         
       
     
     This TDI can then be converted to an estimated IC from this TDI estimate based on the 800 heuristic as follows: 
     
       
         
           
             
               IC 
               estimate 
             
             = 
             
               
                 8 
                  
                 0 
                  
                 0 
               
               
                 TDI 
                 estimate 
               
             
           
         
       
     
     Based on a comparison of the new IC ratio (e.g., ICnew1 or ICnew2) to the estimated IC (i.e., IC estimate ), the artificial pancreas application may be operable to confirm that the new IC ratio was accurately calculated and are within a specified tolerance, such as a range. Based on the determination that the calculation of the new IC ratio by the artificial pancreas application is within a predetermined tolerance of the estimated IC, the artificial pancreas application may continue modification of the delivery of insulin. Conversely, if the determination that the calculation of the new IC ratio by the artificial pancreas application is not within a predetermined tolerance of the estimated IC, the artificial pancreas application may perform a further update of the IC ratio using additional blood glucose measurements received since the previous calculation of the new IC ratio, or the like. 
     It may be helpful to discuss an example of a drug delivery system that may implement the process examples of  FIGS. 1A-C  as well as the examples of  FIGS. 3 and 4 .  FIG. 2  illustrates an example of a drug delivery system  200 . 
     The drug delivery system  200  may be operable to implement an AP application that includes functionality to determine a bolus dosage, output an indication of the determined bolus dosage to actuate delivery of the bolus of insulin based on the indication of the determined bolus dosage. The drug delivery system  200  may be an automated drug delivery system that may include a medical device (pump)  202 , a sensor  204 , and a management device (PDM)  206 . The system  200 , in an example, may also include a smart accessory device  207 , which may communicate with the other components of system  200  either via a wired or wireless communication link. 
     In an example, the medical device  202  may be attached to the body of a user, such as a patient or diabetic, and may deliver any therapeutic agent, including any drug or medicine, such as insulin or the like, to a user. The medical device  202  may, for example, be a wearable device worn by the user. For example, the medical device  202  may be directly coupled to a user (e.g., directly attached to a body part and/or skin of the user via an adhesive or the like). In an example, a surface of the medical device  202  may include an adhesive to facilitate attachment to a user. 
     The medical device  202  may, for example, include a number of components to facilitate automated delivery of a drug (also referred to as a therapeutic agent) to the user. The medical device  202  may be operable to store the drug and to provide the drug to the user. The medical device  202  is often referred to as a pump, or an insulin pump, in reference to the operation of expelling a drug from the reservoir  225  for delivery to the user. While the examples refer to the reservoir  225  storing insulin, the reservoir  225  may be operable to store other drugs or therapeutic agents, such as morphine or the like, suitable for automated delivery. 
     In various examples, the medical device  202  may be an automated, wearable insulin delivery device. For example, the medical device  202  may include a reservoir  225  for storing the drug (such as insulin), a needle or cannula (not shown) for delivering the drug into the body of the user (which may be done subcutaneously, intraperitoneally, or intravenously), and a pump mechanism (mech.)  224 , or other drive mechanism, for transferring the drug from the reservoir  225 , through a needle or cannula (not shown), and into the user. The pump mechanism  224  may be fluidly coupled to reservoir  225 , and communicatively coupled to the processor  221 . The medical device  202  may also include a power source  228 , such as a battery, a piezoelectric device, or the like, for supplying electrical power to the pump mechanism  224  and/or other components (such as the processor  221 , memory  223 , and the communication device  226 ) of the medical device  202 . Although not shown, an electrical power supply for supplying electrical power may similarly be included in each of the sensor  204 , the smart accessory device  207  and the management device (PDM)  206 . 
     The blood glucose sensor  204  may be a device communicatively coupled to the processor  261  or  221  and may be operable to measure a blood glucose value at a predetermined time interval, such as every 5 minutes, or the like. The blood glucose sensor  204  may provide a number of blood glucose measurement values to the AP applications operating on the respective devices. 
     The medical device  202  may provide insulin the stored in reservoir  225  to the user based on information (e.g., blood glucose measurement values) provided by the sensor  204  and/or the management device (PDM)  206 . For example, the medical device  202  may contain analog and/or digital circuitry that may be implemented as a processor  221  (or controller) for controlling the delivery of the drug or therapeutic agent. The circuitry used to implement the processor  221  may include discrete, specialized logic and/or components, an application-specific integrated circuit, a microcontroller or processor that executes software instructions, firmware, programming instructions or programming code (enabling, for example, the artificial pancreas application (AP App)  229  as well as the process examples of  FIGS. 1 and 3 ) stored in memory  223 , or any combination thereof. For example, the processor  221  may execute a control algorithm, such as an artificial pancreas application  229 , and other programming code that may make the processor  221  operable to cause the pump to deliver doses of the drug or therapeutic agent to a user at predetermined intervals or as needed to bring blood glucose measurement values to a target blood glucose value. In an example, the AP App  229  may include programming code that is operable upon execution by the processor  221  to provide the example processes for adjusting or modifying insulin-carbohydrate ratio and total daily insulin settings as described with reference to  FIGS. 1A, 1B, 1C, 3 and 4 . The size and/or timing of the doses may be programmed, for example, into an artificial pancreas application  229  by the user or by a third party (such as a health care provider, medical device manufacturer, or the like) using a wired or wireless link, such as  220 , between the medical device  202  and a management device  206  or other device, such as a computing device at a healthcare provider facility. In an example, the pump or medical device  202  is communicatively coupled to the processor  261  of the management device via the wireless link  220  or via a wireless link, such as  291  from smart accessory device  207  or  208  from the sensor  204 . The pump mechanism  224  of the medical device may be operable to receive an actuation signal from the processor  261 , and in response to receiving the actuation signal, expel insulin from the reservoir  225  according to the set insulin bolus dosage. 
     The other devices in the system  200 , such as management device  206 , smart accessory device  207  and sensor  204 , may also be operable to perform various functions including controlling the medical device  202 . For example, the management device  206  may include a communication device  264 , a processor  261 , and a management device memory  263 . The management device memory  263  may store an instance of the AP application  269  that includes programming code, that when executed by the processor  261  provides the process examples described with reference to the examples of  FIGS. 1 and 3 . The management device memory  263  may also store programming code for providing the process examples described with reference to the examples of  FIGS. 1 and 3-7 . 
     The smart accessory device  207  may be, for example, an Apple Watch®, other wearable smart device, including eyeglasses, provided by other manufacturers, a global positioning system-enabled wearable, a wearable fitness device, smart clothing, or the like. Similar to the management device  206 , the smart accessory device  207  may also be operable to perform various functions including controlling the medical device  202 . For example, the smart accessory device  207  may include a communication device  274 , a processor  271 , and a memory  273 . The memory  273  may store an instance of the AP application  279  that includes programming code for providing the process examples described with reference to the examples of  FIGS. 1 and 3-7 . The memory  273  may also as store programming code and be operable to store data related to the AP application  279 . The sensor  204  of system  200  may be a continuous glucose monitor (CGM) as described above, that may include a processor  241 , a memory  243 , a sensing or measuring device  244 , and a communication device  246 . The memory  243  may store an instance of an AP application  249  as well as other programming code and be operable to store data related to the AP application  249 . The AP application  249  may also include programming code for providing the process examples described with reference to the examples of  FIGS. 1 and 3-7 . 
     Instructions for determining the delivery of the drug or therapeutic agent (e.g., as a bolus dosage) to the user (e.g., the size and/or timing of any doses of the drug or therapeutic agent) may originate locally by the medical device  202  or may originate remotely and be provided to the medical device  202 . In an example of a local determination of drug or therapeutic agent delivery, programming instructions, such as an instance of the artificial pancreas application  229 , stored in the memory  223  that is coupled to the medical device  202  may be used to make determinations by the medical device  202 . In addition, the medical device  202  may be operable to communicate with the cloud-based services  211  via the communication device  226  and the communication link  288 . 
     Alternatively, the remote instructions may be provided to the medical device  202  over a wired or wireless link by the management device (PDM)  206 , which has a processor  261  that executes an instance of the artificial pancreas application  269 , or the smart accessory device  207 , which has a processor  271  that executes an instance of the artificial pancreas application  269  as well as other programming code for controlling various devices, such as the medical device  202 , smart accessory device  207  and/or sensor  204 . The medical device  202  may execute any received instructions (originating internally or from the management device  206 ) for the delivery of the drug or therapeutic agent to the user. In this way, the delivery of the drug or therapeutic agent to a user may be automated. 
     In various examples, the medical device  202  may communicate via a wireless link  220  with the management device  206 . The management device  206  may be an electronic device such as, for example, a smart phone, a tablet, a dedicated diabetes therapy management device, or the like. The management device  206  may be a wearable wireless accessory device. The wireless links  208 ,  220 ,  222 ,  291 ,  292  and  293  may be any type of wireless link provided by any known wireless standard. As an example, the wireless links  208 ,  220 ,  222 ,  291 ,  292  and  293  may enable communications between the medical device  202 , the management device  206  and sensor  204  based on, for example, Bluetooth®, Wi-Fi®, a near-field communication standard, a cellular standard, or any other wireless optical or radio-frequency protocol. 
     The sensor  204  may be a glucose sensor operable to measure blood glucose and output a blood glucose value or data that is representative of a blood glucose value. For example, the sensor  204  may be a glucose monitor or a continuous glucose monitor (CGM). The sensor  204  may include a processor  241 , a memory  243 , a sensing/measuring device  244 , and communication device  246 . The communication device  246  of sensor  204  may include one or more sensing elements, an electronic transmitter, receiver, and/or transceiver for communicating with the management device  206  over a wireless link  222  or with medical device  202  over the link  208 . The sensing/measuring device  244  may include one or more sensing elements, such as a glucose measurement, heart rate monitor, or the like. The processor  241  may include discrete, specialized logic and/or components, an application-specific integrated circuit, a microcontroller or processor that executes software instructions, firmware, programming instructions stored in memory (such as memory  243 ), or any combination thereof. For example, the memory  243  may store an instance of an AP application  249  that is executable by the processor  241 . 
     Although the sensor  204  is depicted as separate from the medical device  202 , in various examples, the sensor  204  and medical device  202  may be incorporated into the same unit. That is, in various examples, the sensor  204  may be a part of the medical device  202  and contained within the same housing of the medical device  202  (e.g., the sensor  204  may be positioned within or embedded within the medical device  202 ). Glucose monitoring data (e.g., measured blood glucose values) determined by the sensor  204  may be provided to the medical device  202 , smart accessory device  207  and/or the management device  206  and may be used to determine a bolus dosage of insulin for automated delivery of insulin by the medical device  202 . 
     The sensor  204  may also be coupled to the user by, for example, adhesive or the like and may provide information or data on one or more medical conditions and/or physical attributes of the user. The information or data provided by the sensor  204  may be used to adjust drug delivery operations of the medical device  202 . 
     In an example, the management device  206  may be a computing device operable to manage a personal diabetes treatment plan. The management device  206  may be used to program or adjust operation of the medical device  202  and/or the sensor  204 . The management device  206  may be any portable electronic, computing device including, for example, a dedicated controller, such as processor  261 , a smartphone, or a tablet. In an example, the management device (PDM)  206  may include a processor  261 , a management device management device memory  263 , and a communication device  264 . The management device  206  may contain analog and/or digital circuitry that may be implemented as a processor  261  (or controller) for executing processes to manage a user&#39;s blood glucose levels and for controlling the delivery of the drug or therapeutic agent to the user. The processor  261  may also be operable to execute programming code stored in the management device management device memory  263 . For example, the management device management device memory  263  may be operable to store an artificial pancreas application  269  that may be executed by the processor  261 . The processor  261  may when executing the artificial pancreas application  269  may be operable to perform various functions, such as those described with respect to the examples in  FIGS. 1 and 3 . The communication device  264  may be a receiver, a transmitter, or a transceiver that operates according to one or more radio-frequency protocols. For example, the communication device  264  may include a cellular transceiver and a Bluetooth transceiver that enables the management device  206  to communicate with a data network via the cellular transceiver and with the sensor  204  and the medical device  202 . The respective transceivers of communication device  264  may be operable to transmit signals containing information useable by or generated by the AP application or the like. The communication devices  226 ,  246  and  276  of respective medical device  202 , sensor  204  and smart accessory device  207  may also be operable to transmit signals containing information useable by or generated by the AP application or the like. 
     The medical device  202  may communicate with the sensor  204  over a wireless link  208  and may communicate with the management device  206  over a wireless link  220 . The sensor  204  and the management device  206  may communicate over a wireless link  222 . The smart accessory device  207 , when present, may communicate with the medical device  202 , the sensor  204  and the management device  206  over wireless links  291 ,  292  and  293 , respectively. The wireless links  208 ,  220 ,  222 ,  291 ,  292  and  293  may be any type of wireless link operating using known wireless standards or proprietary standards. As an example, the wireless links  208 ,  220 ,  222 ,  291 ,  292  and  293  may provide communication links based on Bluetooth®, Wi-Fi, a near-field communication standard, a cellular standard, or any other wireless protocol via the respective communication devices  226 ,  246  and  264 . In some examples, the medical device  202  and/or the management device  206  may include a user interface  227 ,  278  and  268 , respectively, such as a keypad, a touchscreen display, levers, buttons, a microphone, a speaker, a display, or the like, that is operable to allow a user to enter information and allow the management device to output information for presentation to the user. 
     In various examples, the drug delivery system  200  may be an insulin drug delivery system. In various examples, the medical device  202  may be the OmniPod® (Insulet Corporation, Billerica, Mass.) insulin delivery device as described in U.S. Pat. Nos. 7,303,549, 7,137,964, or U.S. Pat. No. 6,740,059, each of which is incorporated herein by reference in its entirety. 
     In various examples, the drug delivery system  200  may implement the artificial pancreas (AP) algorithm (and/or provide AP functionality) to govern or control automated delivery of insulin to a user (e.g., to maintain euglycemia—a normal level of glucose in the blood). The AP application may be implemented by the medical device  202  and/or the sensor  204 . The AP application may be used to determine the times and dosages of insulin delivery. In various examples, the AP application may determine the times and dosages for delivery based on information known about the user, such as the user&#39;s sex, age, weight, or height, and/or on information gathered about a physical attribute or condition of the user (e.g., from the sensor  204 ). For example, the AP application may determine an appropriate delivery of insulin based on glucose level monitoring of the user through the sensor  204 . The AP application may also allow the user to adjust insulin delivery. For example, the AP application may allow the user to issue (e.g., via an input) commands to the medical device  202 , such as a command to deliver an insulin bolus. In some examples, different functions of the AP application may be distributed among two or more of the management device  206 , the medical device (pump)  202  or the sensor  204 . In other examples, the different functions of the AP application may be performed by one device, such the management device  206 , the medical device (pump)  202  or the sensor  204 . In various examples, the drug delivery system  200  may operate according to or may include features or functionalities of the drug delivery systems described in U.S. patent application Ser. No. 15/359,187, filed Nov. 22, 2016, which is incorporated herein by reference in its entirety. 
     As described herein, the drug delivery system  200  or any component thereof, such as the medical device may be considered to provide AP functionality or to implement an AP application. Accordingly, references to the AP application (e.g., functionality, operations, or capabilities thereof) are made for convenience and may refer to and/or include operations and/or functionalities of the drug delivery system  200  or any constituent component thereof (e.g., the medical device  202  and/or the management device  206 ). The drug delivery system  200 —for example, as an insulin delivery system implementing an AP application—may be considered to be a drug delivery system or an AP application-based delivery system that uses sensor inputs (e.g., data collected by the sensor  204 ). 
     In an example, one or more of the devices,  202 ,  204 ,  206  or  207  may be operable to communicate via a wireless communication link  288  with cloud-based services  211 . The cloud-based services  211  may utilize servers and data storage (not shown). The communication link  288  may be a cellular link, a Wi-Fi link, a Bluetooth link, or a combination thereof, that is established between the respective devices  202 ,  204 ,  206  or  207  of system  200 . The data storage provided by the cloud-based services  211  may store anonymized data, such as user weight, blood glucose measurements, age, meal carbohydrate information, or the like. In addition, the cloud-based services  211  may process the anonymized data from multiple users to provide generalized information related to the various parameters used by the AP application. For example, an age-based general target blood glucose value may be derived from the anonymized data, which may be helpful when a user first begins using a system such as  200 . The cloud-based services  211  may also provide processing services for the system  200 , such as performing the process  100  in the example of  FIG. 2  or additional processes, such as that described below with reference to  FIG. 3 . 
     In an example, the device  202  includes a communication device  264 , which as described above may be a receiver, a transmitter, or a transceiver that operates according to one or more radio-frequency protocols, such as Bluetooth, Wi-Fi, a near-field communication standard, a cellular standard, that may enable the respective device to communicate with the cloud-based services  211 . For example, outputs from the sensor  204  or the medical device (pump)  202  may be transmitted to the cloud-based services  211  for storage or processing via the transceivers of communication device  264 . Similarly, medical device  202 , management device  206  and sensor  204  may be operable to communicate with the cloud-based services  211  via the communication link  288 . 
     In an example, the respective receiver or transceiver of each respective device,  202 ,  206  or  207 , may be operable to receive signals containing respective blood glucose measurement values of the number of blood glucose measurement values that may be transmitted by the sensor  204 . The respective processor of each respective device  202 ,  206  or  207  may be operable to store each of the respective blood glucose measurement values in a respective memory, such as  223 ,  263  or  273 . The respective blood glucose measurement values may be stored as data related to the artificial pancreas algorithm, such as  229 ,  249 ,  269  or  279 . In a further example, the AP application operating on any of the management device  206 , the smart accessory device  207 , or sensor  204  may be operable to transmit, via a transceiver implemented by a respective communication device,  264 ,  274 ,  246 , a control signal for receipt by a medical device. In the example, the control signal may indicate an amount of insulin to be expelled by the medical device  202 . 
     Various operational scenarios and examples of processes performed by the system  200  are described herein. For example, the system  200  may be operable to implement the process examples of  FIG. 1A-C . In addition, the system  200  may be operable to implement a process that accounts for periodic advanced TDI adaptivity using past glucose control performance as described with reference to  FIG. 3 . 
       FIG. 3  illustrates a process example for determining periodic advanced TDI adaptivity using past glucose control performance. 
     In the example of  FIG. 3 , a user&#39;s TDI may be adapted based on glucose control performance which enables a more accurate value of the parameter to be achieved. The determination of the TDI parameter can be calculated by either taking the entire glucose control performance into account or taking individual point-wise blood glucose measurement values provided by a continuous glucose monitor (CGM). 
     The difference between daily mean glucose and the user&#39;s desired control target can be related to the user&#39;s correction factor (CF) to calculate additional insulin that the user may need throughout the day. In the example, a CGM provides performs a blood glucose measurement in approximately 5 minute intervals). In the example process of  FIG. 3 , the artificial pancreas application may calculate a point-wise excursion between the user&#39;s blood glucose measurements versus the user&#39;s target blood glucose setting. The point-wise excursion may be incorporated to generate an overall sum of additional insulin that the user may need at each cycle. 
     Prior implementations may make a total daily insulin (TDI) estimation by taking the sum of an insulin pump user&#39;s daily insulin deliveries across multiple days (i.e. one week) and taking the average of the sums as the estimate. However, TDI estimates made in the manner of prior implementations may accidently omit dosages delivered manually (i.e., manual injections) or other under or over reporting of delivery of insulin. Further, an average of past insulin deliveries indicate the dosage that the user is comfortable with, but it does not necessarily indicate that the past insulin deliveries were well matched to the user&#39;s needs. For instance, if the user&#39;s average glucose concentration was very high, e.g. above the hyperglycemic threshold of 180 mg/dL, then the average insulin delivery during this period most likely does not represent the optimal insulin delivery value needed by the user. 
     TDI may be an input into the automatic insulin delivery algorithm utilized by the artificial pancreas application. Modification of total daily insulin (TDI) may be determined based on incorporation of daily mean blood glucose measurement values. In the example of  FIG. 3 , the mean of the user&#39;s blood glucose measurements may be incorporated in addition to the user&#39;s new insulin delivery values to generate a new TDI value that more accurately reflects the user&#39;s insulin needs. For example, the process  300  may include a step of retrieving a prior TDI, the prior TDI may be the current TDI used by the artificial pancreas application to make insulin dosage calculations ( 310 ). In the example of Equation No. 3 below, the current TDI may be TDI old . 
     In the first factor, the retrieved TDI (i.e., TDI old ) may be multiplied by a first coefficient that indicates a confidence level of the TDI setting. This first factor may be a prior TDI contribution term. The artificial pancreas application may set the coefficient value to a higher value (e.g., closer to 1.0) to correspond with a higher level of confidence. For example, the consistency of the blood glucose measurement values may be used to determine coefficient values—more consistent blood glucose measurement values within a normal range may cause greater confidence while blood glucose measurement values within a normal range being less consistent may cause lower confidence. Based on the consistency of the blood glucose measurements, the artificial pancreas application may determine the value of the first confidence coefficient. To obtain the prior TDI contribution term, the retrieved total daily insulin may be multiplied by the first confidence coefficient ( 320 ). In the example of Equation No. 3, the prior TDI contribution term may be (0.8*TDI old ). The first confidence coefficient may be 0.8. Of course, the value of the first confidence may have different values, such as 0.2, 0.5, 0.6 or the like, as determined by the artificial pancreas application. 
     The process  300  may determine the average excursion of the blood glucose measurements from blood glucose target settings as represented by the second factor in the example of Equation No. 3. For example, the artificial pancreas application may obtain after a predetermined period of time, such as 12 hours, 24 hours, 48 hours, or the like, the mean of the blood glucose measurement values collected during the predetermined period of time (i.e., (G)) ( 330 ). The artificial pancreas application may further obtain the target blood glucose measurement settings for the determined period of time. Using the obtained target blood glucose measurement settings, the mean target blood glucose measurement setting (i.e., (target)) may be determined for the predetermined period of time. This may be considered be a correction factor that is determined as a point-wise excursion between the user&#39;s glucose versus the user&#39;s target, calculated during each 5 minute interval. For example, a difference between the mean of the blood glucose measurement values and the blood glucose target settings may be determined by the artificial pancreas application. The determined difference is the numerator of the second factor. The artificial pancreas application may proceed to determining the denominator of the second factor. The denominator may be a correction factor that may be determined utilizing different rules of thumb based on the type of insulin being used and a TDI setting. For example, if the user is using fast acting insulin, a value of 1800 may be divided by the retrieved total daily insulin setting (i.e., TDI old ) to calculate the correction factor value. Alternatively, if the user is using regular action insulin, a value of 1500 may be divided by the retrieved total daily insulin setting (i.e., TDI old ) to calculate the correction factor value. 
     The second factor may be a correction factor determined by dividing the difference in the numerator by the correction factor of the denominator to calculate the missing or excess insulin delivery throughout the day. The correction factor can be incorporated in the equation to generate an overall sum of additional insulin that the user may need at each cycle. A cycle being the time period that the new TDI is calculated. For example, a cycle may be 24 hours, 12 hours 8 hours or the like. 
     In one example, this adjustment can be implemented as shown in Equation No. 3 below: 
     
       
         
           
             
               
                 
                   
                     TDI 
                     
                       new 
                        
                       
                           
                       
                        
                       3 
                     
                   
                   = 
                   
                     
                       
                         0 
                         . 
                         8 
                       
                        
                       
                         TDI 
                         old 
                       
                     
                     + 
                     
                       8 
                        
                       
                         
                           
                             G 
                             _ 
                           
                           - 
                           
                             target 
                             _ 
                           
                         
                         
                           1 
                            
                           8 
                            
                           0 
                            
                           
                             0 
                             / 
                             
                               TDI 
                               old 
                             
                           
                         
                       
                     
                     + 
                     
                       
                         0 
                         . 
                         2 
                       
                        
                       
                         
                           ∑ 
                           
                             t 
                             = 
                             1 
                           
                           
                             2 
                              
                             8 
                              
                             8 
                           
                         
                          
                         
                           I 
                            
                           
                             ( 
                             t 
                             ) 
                           
                         
                       
                     
                   
                 
               
               
                 
                   Eq 
                   . 
                   
                       
                   
                    
                   No 
                   . 
                   
                       
                   
                    
                   3 
                 
               
             
           
         
       
     
     where ( G ) may be the mean of the blood glucose measurement values collected during the predetermined period of time,  target  may be the mean of the blood glucose measurement target values during the predetermined period of time and I(t) is the insulin delivered at time t. 
     In the second factor of equation No. 3 example, the coefficient of 8 represents 24 hours divided by different segments of 3 hours each, given the assumption that it will take a number of hours approximately equal to the duration of insulin action (DIA) for a user to reduce the mean blood glucose measurement to the target blood glucose setting. The correction factor (for example, 1800/TDI old ) in the denominator of the second factor incorporates the 1800 rule instead of utilizing the user&#39;s correction factor (CF) to reduce vulnerability to human error. Of course, other rules, such as the 1500 rule, may be used. 
     The third term may be a delivered TDI term that is determined using data collected by the artificial pancreas application at  340 . Since the artificial pancreas application controls how much insulin is delivered, the artificial pancreas application may store the amount of insulin delivered with each dose in a memory coupled to the processor executing the artificial pancreas application. For example, the artificial pancreas application may deliver insulin is a number of small doses over a period of time. In the example of Equation No. 3, the summation of the delivered insulin is over 288 doses of insulin. In this example, the insulin may be delivered every 5 minutes or 12 time an hour. Over a period of 24 hours, the artificial pancreas application send instructions for the delivery of 288 doses of insulin. In addition, this sum of delivered insulin may be multiplied by a second confidence factor that is the difference between 1.0 and the first confidence factor. In the example of Equation No. 3, the first confidence factor to 0.8, so the difference between 1.0 and 0.8 is 0.2. 
     At  350 , a new TDI setting (i.e., TDI new3 ) may be determined by summing the prior TDI contribution term, the correction factor term and the delivered insulin term. Based on the new TDI setting, the artificial pancreas application may modify a next delivery of insulin ( 360 ). For example, a new insulin dosage may be determined, and the delivery of insulin may be actuated by the artificial pancreas application. 
     Of course, different numbers used in Equation No. 3 may be parameterized. For example, the first and second confidence factors may be parameterized so that some of the changes to the user&#39;s blood glucose measurements may occur more quickly. For example, the first confidence factor may be set to 0.5 in which case the second confidence factor may also be 0.5. In addition, the coefficient 8 in the second factor may be based on the duration of insulin action (DIA). If the user&#39;s DIA is 6 hours instead of the 3 hours in the example of Equation No. 3, then the coefficient may be 4 (i.e., 24 hours/6=4). 
     In another example, the adjustment to TDI may be segmented to avoid adjusting the TDI if the mean glucose blood glucose measurement is close to the target and to reduce vulnerability to noise, as shown in Equation No. 4 shown below: 
     
       
         
           
             
               
                 TDI 
                 
                   new 
                    
                   
                       
                   
                    
                   4 
                 
               
               = 
               
                 
                   
                     0 
                     . 
                     8 
                   
                    
                   
                     TDI 
                     old 
                   
                 
                 + 
                 
                   8 
                    
                   
                     I 
                     e 
                   
                 
                 + 
                 
                   
                     0 
                     . 
                     2 
                   
                    
                   
                     
                       ∑ 
                       
                         t 
                         = 
                         1 
                       
                       
                         2 
                          
                         8 
                          
                         8 
                       
                     
                      
                     
                       I 
                        
                       
                         ( 
                         t 
                         ) 
                       
                     
                   
                 
               
             
             ; 
           
         
       
       
         
           
             
               I 
               e 
             
             = 
             
               { 
               
                 
                   
                     
                       
                         abs 
                          
                         
                           ( 
                           
                             
                               G 
                               _ 
                             
                             - 
                             
                               target 
                               _ 
                             
                           
                           ) 
                         
                       
                       &gt; 
                       40 
                     
                   
                   
                     
                       
                         
                           G 
                           _ 
                         
                         - 
                         
                           target 
                           _ 
                         
                       
                       
                         1 
                          
                         8 
                          
                         0 
                          
                         
                           0 
                           / 
                           
                             TDI 
                             old 
                           
                         
                       
                     
                   
                 
                 
                   
                     
                       
                         abs 
                          
                         
                           ( 
                           
                             
                               G 
                               _ 
                             
                             - 
                             
                               target 
                               _ 
                             
                           
                           ) 
                         
                       
                       ≤ 
                       40 
                     
                   
                   
                     0 
                   
                 
               
             
           
         
       
     
     In the example of Equation No. 4, the threshold of 40 (mg/dL) that is compared to the excursion of the blood glucose measurements from the target blood glucose measurement setting is selected based on the correction factor. The correction factor may be close to 40 for a typical user, the basis for the selection of 40 is that at times the excursions in blood glucose measurements may be due to noise or other extraneous inputs and the threshold 40 represents a reciprocal of the correction factor and is approximately equivalent to one unit of insulin. This is intended to avoid over compensating for excursions in the blood glucose measurements. 
     In another example, the TDI modification that produces TDI new4  may be based on a point-by-point residual insulin needs after an IOB is determined. 
     For example, point-by-point excursions of the user&#39;s blood glucose measurements versus the user&#39;s blood glucose measurement target setting may be related to the user&#39;s correction factor to enable the artificial pancreas application to adjust the user&#39;s TDI dynamically. 
     In another example, the modification of TDI based on point-by-point residual insulin needs after an insulin onboard (IOB) is provided may be determined as shown in the example of equation no. 5 and  FIG. 4 . This may be a periodic adjustment or modification of TDI. 
     In an example shown in Equation No. 5, this adjustment can be implemented as: 
     
       
         
           
             
               
                 
                   
                     TDI 
                     
                       new 
                        
                       
                           
                       
                        
                       5 
                     
                   
                   = 
                   
                     
                       
                         0 
                         . 
                         8 
                       
                        
                       
                         TDI 
                         old 
                       
                     
                     + 
                     
                       
                         0 
                         . 
                         2 
                       
                        
                       
                         
                           ∑ 
                           
                             t 
                             = 
                             1 
                           
                           
                             2 
                              
                             8 
                              
                             8 
                           
                         
                          
                         
                           I 
                            
                           
                             ( 
                             t 
                             ) 
                           
                         
                       
                     
                     + 
                     
                       
                         
                           
                             
                               G 
                                
                               
                                 ( 
                                 t 
                                 ) 
                               
                             
                             - 
                             
                               target 
                               ( 
                               t 
                               ) 
                             
                           
                           
                             1 
                              
                             8 
                              
                             
                               00 
                               / 
                               TDI 
                             
                           
                         
                         - 
                         
                           IOB 
                            
                           
                             ( 
                             t 
                             ) 
                           
                         
                       
                       36 
                     
                   
                 
               
               
                 
                   Eq 
                   . 
                   
                       
                   
                    
                   No 
                   . 
                   
                       
                   
                    
                   5 
                 
               
             
           
         
       
     
     In the process  400  of  FIG. 4 , the artificial pancreas application executed by the processor may, at  410 , obtain a current TDI setting (e.g., TDI old ) either from a memory or user input. At  420 , the artificial pancreas application may determine a first factor in a new TDI function of Equation No. 5 using the current TDI setting by multiplying the current TDI by a first coefficient, where the first coefficient indicates a confidence level of the TDI setting. This first factor may be a prior TDI contribution term. The artificial pancreas application may set the coefficient value a higher to correspond with a higher level of confidence. At  430 , the artificial pancreas application may determine a second factor in the new TDI function (Equation No. 5) by retrieving amounts of insulin delivered over a period of time, such as every 5 minutes over 24 hours or 288 delivered doses, summing the amounts of insulin delivered, and multiplying the sum by a second confidence factor. Note similar to the earlier examples the first and second confidence factors in this example when added together equal 1.0 (e.g., 0.8+0.2=1.0). In other examples, the first and second confidence values may equal a value different from 1.0. 
     In process  400 , a third factor may be determined, at  440 , that accounts for the excursions of IOB that occur in 3 hour increments and since there are 12 blood glucose measurements received every hour (e.g., 3 time 12 equals 36). The third factor accounts for the deviation of blood glucose measurements from target blood glucose measurement settings (e.g., G(t))−target (t)) which is converted to an amount of insulin by dividing that difference using the 1800 rule (which may be a 1500 rule or the like depending upon the type of insulin being used (e.g., fast acting versus regular acting). 
     Upon the determination of the third factor, the artificial pancreas application may sum the first factor, the second factor and the third factor to arrive at a new TDI (i.e., TDI new5 ) at  450 . The new TDI (i.e., TDI new2 ) may be used by the artificial pancreas application in the calculation of a new dosage of insulin to be provided by a drug delivery device to the user. Upon calculating the new dosage of insulin, the artificial pancreas application may generate control commands that are sent to the drug delivery device instructing the drug delivery device to deliver a dose of insulin according the control command ( 460 ). The dose of insulin may be delivered by the drug delivery device according to the control command. 
     The foregoing process may also be implemented using other equations, such as equation nos. 6 and 7 below, related to the determination of TDI based on the insulin onboard. 
     In another example, this adjustment can be conducted in real time, as: 
     
       
         
           
             
               
                 
                   
                     TDI 
                      
                     
                       ( 
                       
                         t 
                         + 
                         1 
                       
                       ) 
                     
                   
                   = 
                   
                     
                       
                         287 
                         · 
                         
                           TDI 
                            
                           
                             ( 
                             t 
                             ) 
                           
                         
                       
                       
                         2 
                          
                         8 
                          
                         8 
                       
                     
                     + 
                     
                       I 
                        
                       
                         ( 
                         t 
                         ) 
                       
                     
                     + 
                     
                       
                         
                           
                             
                               G 
                                
                               
                                 ( 
                                 t 
                                 ) 
                               
                             
                             - 
                             
                               target 
                               ( 
                               t 
                               ) 
                             
                           
                           
                             1 
                              
                             8 
                              
                             
                               00 
                               / 
                               TDI 
                             
                           
                         
                         - 
                         
                           IOB 
                            
                           
                             ( 
                             t 
                             ) 
                           
                         
                       
                       36 
                     
                   
                 
               
               
                 
                   Eq 
                   . 
                   
                       
                   
                    
                   No 
                   . 
                   
                       
                   
                    
                   6 
                 
               
             
           
         
       
     
     where the factors 287/288 represent the number of five-minute control cycles in one day minus 1 and the number of five-minute control cycles in one day, respectively. Calculation of TDI in this manner allows a revised “moving average” of the TDI that is recalculated at every 5 minute cycle. 
     In other examples, the periodicity of TDI adjustments for either option does not need to be either real-time or daily—the factors of 0.8 and 0.2 can be made variable depending on the duration of available data, as: 
     
       
         
           
             
               
                 
                   
                     TDI 
                     
                       new 
                        
                       
                           
                       
                        
                       7 
                     
                   
                   = 
                   
                     
                       
                         ( 
                         
                           1 
                           - 
                           
                             0.2 
                             · 
                             
                               T 
                               new 
                             
                           
                         
                         ) 
                       
                        
                       
                         TDI 
                         old 
                       
                     
                     + 
                     
                       8 
                        
                       
                         
                           T 
                           new 
                         
                         
                           2 
                            
                           8 
                            
                           8 
                         
                       
                     
                     + 
                     
                       
                         
                           G 
                           _ 
                         
                         - 
                         
                           target 
                           _ 
                         
                       
                       
                         1 
                          
                         8 
                          
                         
                           00 
                           / 
                           
                             TDI 
                             old 
                           
                         
                       
                     
                     + 
                     
                       
                         0.2 
                         · 
                         
                           T 
                           new 
                         
                       
                        
                       
                         
                           ∑ 
                           
                             t 
                             = 
                             1 
                           
                           
                             T 
                             new 
                           
                         
                          
                         
                           I 
                            
                           
                             ( 
                             t 
                             ) 
                           
                         
                       
                     
                   
                 
               
               
                 
                   Eq 
                   . 
                   
                       
                   
                    
                   No 
                   . 
                   
                       
                   
                    
                   7 
                 
               
             
           
         
       
     
     where T new  is a number of new 5 minute segments of data available at time of TDI adjustment. 
     In the example of Eq. 7, the factor 8 represents the maximum duration of insulin action, to apply a conservative estimate of TDI modification assuming that an increase in glucose can be covered by 8 hours of insulin delivery. This value can be adjusted as a tuning parameter to different values, such as 2, 3, 4, 5, 6, 7, or 8. Thus, the first term represents the duration of time of new data available (“weighing of the previous TDI estimate”), the second term represents adjustment of the current TDI estimate based on deviation in average glucose during this new data versus the target, modified by duration in insulin action, and the third term represents the actual insulin delivery that occurred during this period of new data. 
     The techniques described herein for providing a determination of a new insulin-to-carbohydrate ratio and a new total daily insulin factor for a drug delivery system (e.g., the system  200  or any component thereof) may be implemented in hardware, software, or any combination thereof. For example, the system  200  or any component thereof may be implemented in hardware, software, or any combination thereof. Software related implementations of the techniques described herein may include, but are not limited to, firmware, application specific software, or any other type of computer readable instructions that may be executed by one or more processors. Hardware related implementations of the techniques described herein may include, but are not limited to, integrated circuits (ICs), application specific ICs (ASICs), field programmable arrays (FPGAs), and/or programmable logic devices (PLDs). In some embodiments, the techniques described herein, and/or any system or constituent component described herein may be implemented with a processor executing computer readable instructions stored on one or more memory components. 
     Some embodiments of the disclosed device may be implemented, for example, using a storage medium, a computer-readable medium, or an article of manufacture which may store an instruction or a set of instructions that, if executed by a machine (i.e., processor or microcontroller), may cause the machine to perform a method and/or operation in accordance with embodiments of the disclosure. Such a machine may include, for example, any suitable processing platform, computing platform, computing device, processing device, computing system, processing system, computer, processor, or the like, and may be implemented using any suitable combination of hardware and/or software. The computer-readable medium or article may include, for example, any suitable type of memory unit, memory, memory article, memory medium, storage device, storage article, storage medium and/or storage unit, for example, memory (including non-transitory memory), removable or non-removable media, erasable or non-erasable media, writeable or re-writeable media, digital or analog media, hard disk, floppy disk, Compact Disk Read Only Memory (CD-ROM), Compact Disk Recordable (CD-R), Compact Disk Rewriteable (CD-RW), optical disk, magnetic media, magneto-optical media, removable memory cards or disks, various types of Digital Versatile Disk (DVD), a tape, a cassette, or the like. The instructions may include any suitable type of code, such as source code, compiled code, interpreted code, executable code, static code, dynamic code, encrypted code, programming code, and the like, implemented using any suitable high-level, low-level, object-oriented, visual, compiled and/or interpreted programming language. The non-transitory computer readable medium embodied programming code may cause a processor when executing the programming code to perform functions, such as those described herein. 
     Certain examples of the present disclosure were described above. It is, however, expressly noted that the present disclosure is not limited to those examples, but rather the intention is that additions and modifications to what was expressly described herein are also included within the scope of the disclosed examples. Moreover, it is to be understood that the features of the various examples described herein were not mutually exclusive and may exist in various combinations and permutations, even if such combinations or permutations were not made express herein, without departing from the spirit and scope of the disclosed examples. In fact, variations, modifications, and other implementations of what was described herein will occur to those of ordinary skill in the art without departing from the spirit and the scope of the disclosed examples. As such, the disclosed examples are not to be defined only by the preceding illustrative description. 
     Program aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of executable code and/or associated data that is carried on or embodied in a type of machine readable medium. Storage type media include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non-transitory storage at any time for the software programming. It is emphasized that the Abstract of the Disclosure is provided to allow a reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, various features are grouped together in a single example for streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed examples require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed example. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate example. In the appended claims, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein,” respectively. Moreover, the terms “first,” “second,” “third,” and so forth, are used merely as labels and are not intended to impose numerical requirements on their objects. 
     The foregoing description of example embodiments has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the present disclosure to the precise forms disclosed. Many modifications and variations are possible in light of this disclosure. It is intended that the scope of the present disclosure be limited not by this detailed description, but rather by the claims appended hereto. Future filed applications claiming priority to this application may claim the disclosed subject matter in a different manner and may generally include any set of one or more limitations as variously disclosed or otherwise demonstrated herein.