Preliminary Proposal For Insulin Pump Standards

1. Preliminary Proposal For Insulin Pump Standards Standards to improve insulin pump use and medical outcomes These proposals are not yet final but are made available for review and editorial comment. Any suggestions you have for improvements or changes, or for additional approaches to improve diabetes care are welcomed. Any major contributions will be attributed.

2. John Walsh, PA, CDE, and Ruth Roberts, MA You (#4,6)* These Standards Are Supported By: * Any reservations you have about a particular standard will be noted

3. ReviewDefinitions • TDD – total daily dose of insulin (all basals and boluses) • Basal –background insulin pumped slowly through the day to keep BG flat • Bolus – a quick surge of insulin as • Carb boluses to cover carbs • Correction boluses to lower high readings that arise from too little basal insulin delivery or insufficient carb boluses • Bolus On Board (BOB) – the units of bolus insulin or glucose-lowering activity still working from recent boluses • Duration of Insulin Action (DIA) – time that a bolus will lower the BG. This is used to calculate BOB.

4. The Role Of Insulin Pumps Insulin pumps should • Lower A1c and eAG levels • Decrease the frequency and severity of hypoglycemia • Provide safe and reliable insulin dosing to users • Reduce complications • Improve quality of life

5. Proposal For Insulin Pump Standards These standards to improve pump use and outcomes are designed to: • Reduce inconsistencies in pump settings between pump manufacturers • Improve the accuracy and safety of carb and correction factors in use • Improve safety of DIA time increments and defaults that are in use • Consistently account for and apply BOB • Improve monitoring and identification of infusion set failure • Improve monitoring of hypoglycemia & hyperglycemia • Identify excessive use of correction boluses • Reduce blind bolusing and non-entry of glucose values into pumps

6. ReviewInconsistent Dosing From Insulin Pumps There are several significant sources for error in bolus doses from today’s insulin pumps. • Widespread use of inaccurate carb factors • Excessively large carb factor increments • Widespread use of inaccurate correction factors • Wide variations in how BOB is handled and in DIA default times between pump manufacturers • Wide variations in DIA defaults between pump manufacturers

7. Intellectual Property 1 Issue: Optimal glucose values for those who have diabetes is critical to prevention of disability and early death. Devices owned and used by those with diabetes contain unique information that can be used to improve control and reduce complication risks.

8. 1 Standard For:Intellectual Property We recommend that all existing and future patents that may contribute to improvements in glucose control be made available at a reasonable cost to any device manufacturer who wants to use them to improve glucose control.

9. Carb Factor (CarbF) Increments 2 Issue: Current carb factor increments are too large for smaller carb factor numbers. This lack of precision for carb boluses may create excess hyperglycemia or hypoglycemia for many pump users.

10. ExampleCarb Factor Increments 2 • Most pumps offer 1 gram per unit as their smallest CarbF increment. This increment becomes relatively large for CarbFs below 15 or 20 g/u. For instance, when the carb factor is reduced from 10 to 9 g/u, all subsequent carb boluses are increased by 11.1% in most pumps. • A shift in the carb factor from 1u/5g to 1u/4g causes each subsequent carb bolus to increase by 25%. • When carb boluses make up 50% of the TDD, a change in the a carb factor larger than 2.5% would be expected to create more than a 25 mg/dl shift in the glucose following each meal. • Finer CarbF increments would allow safer and more precise adjustment of subsequent carb boluses. Example: TDD = 40u, carb factor ~1u/11g, corr factor ~1u/60 mg/dl carb boluses = 20u or ~6u/meal x 6% =.36u x 60 = a 22 mg/dl change in BG

11. What Current Changes In CarbFs Do 2 Table shows how a one-step reduction in the CarbF using various CarbF increments affect the size of subsequent carb boluses. Yellow area shows impact from most pumps. Green (preferred) areas show increments that impact subsequent boluses less than 5%.

12. ExampleImpact On BG From CarbF Adjustments 2 This table shows the average additional fall in glucose that is likely after each meal of the day when a carb factor is reduced from 10 grams per unit to 9 grams per unit (for appropriate weight & TDD), and again a reduction from 5 grams per unit to 4 grams per unit. • Calculated as carb grams per day X increase in avg. carb bolus size • 3

13. 2 Standard For: Carb Factor Increments We recommend that carb factor increments be small enough that a single step adjustment in a factor causes subsequent carb boluses to change by no more than 5% from previous bolus doses for the same number of grams of carb.

14. Inaccurate Carb Factors 3 Issue: A carb factor that does not match the individual using it will significantly magnify other sources of error in the calculation of carb bolus doses. Many carb factors used in insulin pumps today are poorly tuned to users.

15. Review Actual Carb Factors In Use 1 3 Avg. carb factors* for 468 consecutive Cozmo insulin pump downloads (>126,000 boluses) are shown in blue Note that they are NOT bell-shaped or physiologic People prefer “magic” numbers – 7, 10, 15, and 20 g/unit – for their carb factors * Determined directly from grams of carb divided by carb bolus units for each carb bolus 10 7 115 20 1

16. ReviewActual Carb Factors In Use 1 3 MANY magic carb factors, shown in blue, are inaccurate. A more normal or physiologic distribution is shown in green Use of magic numbers creates major, though consistent bolus errors that magnify other sources of error 10 7 115 20 1

17. 3 Standards For: Carb Factor Settings To encourage use of consistent and accurate carb factors in pumps, we request that insulin pump companies jointly determine what range of carb factor rule numbers (CarbF x TDD) provide optimal glucose results that lead to a lower eAG and less hypoglycemia for various TDD ranges and carb intakes as a percentage of calories. We request that insulin pump companies measure and publish each year the carb factors in use for 200 random downloads from pumps that use carb factors. This information is needed as an overview to guide interventions directed at reducing errors in carb factor settings. We recommend that carb factors be monitored within each pump for accuracy and effectiveness with a report available to users or clinicians.

18. ExampleCarb Factor Settings 3 To assist users in setting accurate CarbFs, insulin pumps should allow the user to compare their current CarbF against an optimal settings range of CarbF Rule Numbers. Proposed CarbF Rule Numbers for various TDDs: * Optimal ranges would be determined from research studies of best practices

19. Inaccurate Correction Factors 4 Issue: A correction factor that does not match the individual using it will significantly magnify other sources of error in the calculation of correction bolus doses. Many correction factors used in insulin pumps today are poorly tuned to users.

20. Review Actual Correction Factors In Use 1 4 Avg. correction factors in use for 452 consecutive Cozmo insulin pump downloads Like carb factors, correction factors in use are NOT bell-shaped or physiologic Users or clinicians often select “magic” numbers for their correction factors. 10 7 115 20 1

21. 4 Standards For: Correction Factor Settings To encourage use of consistent and accurate correction factors in pumps, we request that insulin pump companies jointly determine what range of correction factor rule numbers (CorrF x TDD) provide optimal glucose results that lead to a lower eAG and less hypoglycemia for various TDD ranges, and publish them for users and clinicians to use. We request that insulin pump companies voluntarily measure and publish each year the correction factors in use for 200 consecutive downloads from pumps that use correction factors. We recommend that correction factors be monitored within each pump for accuracy and effectiveness with a report available to users or clinicians.

22. ExampleCorrection Factor Settings 4 To assist users in setting accurate CorrFs, insulin pumps should allow the user to compare their current CorrF against an optimal settings range of CorrF Rule Numbers. Proposed CorrF Rule Numbers for various TDDs: * Optimal ranges would be determined from research studies of best practices

23. Basal/Carb Bolus Balance 5 Issue: Correction boluses are used to correct for deficits in insulin that arise from inadequate basal delivery or inadequate carb boluses. Because the reason for their use cannot be clearly identified as basal or bolus, they should not be included in basal/bolus balance.

24. 5 Standard For:Basal/Carb Bolus Balance We propose that basal/carb bolus balance is a more definitive term and should replace basal/bolus balance. Basal/carb bolus balance should NOT include correction bolus doses which will be listed separately to more clearly define and understand control issues.

25. ExampleBasal/Carb Bolus Balance 5 How a pump might display insulin information: TDD = 40.0 u in last 7 days: % of TDD units Basal 30% 12 u Carb boluses 50% 20 u Corr. boluses 20%(+12%) 8 u (+ 4.8 u) Basal/Carb bolus balance = 0.6 (12u/20u) or 60%. This particular imbalance would typically favor adding more of the correction bolus excess to basal delivery.

26. Duration Of Insulin Action Default Times 6 Issues: • The default DIA times in current pumps vary widely between 3 and 6 hours* • Many users shorten their default DIA to increase the size of their boluses without realizing that this introduces significant errors into bolus (and ultimately basal) doses. * DIA times that are too short hide bolus insulin activity and create insulin stacking. DIA times that are too long overestimate bolus activity.

27. 6 Standard For:Duration Of Insulin Action (DIA) Time We recommend that a panel of experts in insulin action review existing pharmacodynamic studies, consider differences between pharmacodynamics and DIA time, and provide guidance on an acceptable range of DIA times to recommend to clinicians and users to improve the accuracy of bolus calculations.

28. DIA Time Increments 7 Issue: Current DIA time increments vary from 15 minutes to 1 hour in different pumps • When a DIA time is changed in a pump, a larger time increment, such as 1 hr, can create an excessive change in subsequent estimates of BOB. • For example, when the DIA is reduced from 5 hours to 4 hours, subsequent BOB estimates are decreased, while recommendations for carb boluses would increase.

29. ReviewGlucose Infusion Rate (GIR) Studies 7 Most GIR studies suggest that pharmacodynamic action of insulin varies about 25% between individuals. For a DIA time of 5 hr, a 25% range is equivalent to 1 hr and 15 min, such as from 4 hrs and 15 min to 5hr and 30 min. A pump that has only 1 hr DIA increments would enable the user to select only one setting within a physiologic range, while a 30 min increment would allow only 2 or 3 choices that are close to a physiologic range.

30. 7 Standard For: DIA Time Increments For safety and accuracy, we recommend that DIA time increments be no greater than 15 minutes to allow more accurate estimation of residual BOB.

31. ReviewBolus On Board (BOB) 8 An accurate measurement of the glucose-lowering activity that remains from recent boluses helps: • Prevent insulin stacking • Improve bolus accuracy • Allows the current carb or insulin deficit to be determined aka: insulin on board, active insulin, unused insulin* * Introduced as Unused Insulin in 1st ed of Pumping Insulin (1989)

32. ExampleAn Accurate BOB Can Avoid Insulin Stacking 8 Bedtime BG = 173 Is there an insulin or a carb deficit? Bedtime BG = 173 mg/dl Correction Dessert Dinner 6 pm 8 pm 10 pm 12 am

33. ReviewInsulin Stacking Is Common 8 CDA1 Study Results Of 201,538 boluses, 64.8% were given within 4.5 hrs of a previous bolus An accurate DIA shows that some BOB is present for MOST boluses Note that 4.5 hours may underestimate true DIA 4.5 hrs

34. ReviewHow Current Pumps Handle BOB 8 * Except when BG is below target BG

35. ExampleBolus Recommendations Differ Significantly 8 The graphic shows how widely bolus recommendations vary from one pump to another for the same situation. Situation: BOB = 3.0 u and 30 gr. of carb will be eaten at these glucose levels Carb factor = 1u / 10 gr Corr. Factor = 1 u / 40 mg/dl over 100 Target BG = 100 TDD = ~50 u units mg/dl Omnipod bolus cannot be determined - it counts only correction bolus insulin as BOB

36. ExampleUnsafe BOB Handling 8 If a pump user gets frustrated with high BGs and they overdose to speed the drop in their BG, or they exercise longer or more intensely than they anticipated, they can acquire a significant excess in BOB. In this situation, most pumps bolus for all carb intake regardless of how much BOB is present. A subsequent bolus will deliver an excess of insulin if the glucose is not high enough to offset the excess BOB.1 This introduces a significant risk for hypoglycemia from the pump’sexcessive bolus recommendations. 1 Pumping Insulin, 1st ed, 1989, Chap 12, pgs 70-73: The Unused Insulin Rule

37. Current BOB Handling 8 Issue: Most bolus calculators in current insulin pumps assume that excess BOB does not need to be taken into account when determining the next carb bolus. Because of the way they are determined, bolus dose recommendations from most pumps can cause unexplained and unnecessary insulin stacking and hypoglycemia.

38. 8 Standard For:BOB Handling For safe and accurate BOB measurement, we recommend that: BOB include all carb and correction boluses Residual BOB be subtracted from both carb and correction bolus recommendations delivered within the DIA* * Assumes that the DIA time chosen by the clincian or user is accurate.

39. BOB Handling 8 Exception to usual BOB handling: • When a second bolus is taken for unplanned carb intake or desert that is consumed within 60 minutes or so* of a meal bolus, BOB should not be taken into account for the second bolus because the impact of the first bolus cannot be accurately determined. • Given that, it is wise to account for BOB as soon after a meal as possible, such as within 60 to 90 minutes (adjustable), to provide early warning if the bolus given was excessive or inadequate. It is always safer, though not always more accurate, to account for and apply all BOB in subsequent boluses. * Adjustable

40. Blind Bolusing 9 Issue: Pump users often bolus for carbs without checking their glucose first. With no glucose reading, the pump does not account for BOB that may be present at the time, and the bolus is not appropriately adjusted for potentially high or low glucose levels. Blind bolusing often leads to insulin stacking.

41. 9 Standard For:Blind Bolusing We recommend that insulin pumps alert* the wearer when there is sufficient insulin stacking to introduce a significant error in a current bolus. * Adjustable for an expected mg/dl drop in glucose with visible, audio, or vibratory output.

42. ExampleInsulin Stacking or BOB Alert 9 When a carb bolus is planned without a recent BG check, but BOB is more than 1.25% of the average TDD (enough to cause about a 25 mg/dl drop in the glucose), the pump will recommend that the wearer do a BG check due to an excess in BOB. For instance, for someone with: Avg TDD 1.25%* of TDD 43 units 0.54 units This individual would be alerted whenever they give a bolus but have 0.54 u or more of BOB present. * 1.25% of TDD provides a reasonable degree of safety but may need modification

43. Inadequate Manual Entry Of BGs 10 Issue: Pump users often do not enter BG values into their pump if they must do it manually.

44. Inadequate Manual Entry Of BGs 10 Issue: In the CDA study where BG values can be entered either manually or automatically, users entered only 2.6 BG values per day manually versus 4.1 values per day for pumps that had an attached glucose meter. This means that BOB may be taken into account for 1.5 additional boluses per day when BG readings are not automatically entered.

45. 10 Standard For:Inadequate Manual Entry Of BGs Due to a significant decrease in glucose entry when BGs must be entered manually, and the benefit to control that this provides, we recommend that all pumps be enabled to have direct BG entry of BG test results from two or more meters.

46. Correction Bolus Excess 11 Issue: Hyperglycemia is more common than hypoglycemia for most people on insulin pumps. When glucose levels consistently run high, many pump users address the problem by giving frequent correction boluses rather than increasing their basal rates or carb boluses. In these cases, the correction bolus % of the TDD can become excessive, but this information is either not shown in some pumps or no alert is given regarding the excess.

47. 11 Standards For:Correction Bolus Excess We suggest that the pump wearer and clinician be alerted when the wearer uses more than 8% (adjustable) of their TDD for correction bolus doses for at least 4 days in a row (adjustable). We recommend that, once an excess in correction bolus is identified, that the user be given instruction in how to safely distribute any excess into carb boluses or basal rates.

48. Excess Hypoglycemia 12 Issue: Current insulin pumps and glucose monitors do not warn users that they are experiencing hypoglycemia that is too severe or too frequent. Although most insulin pumps contain adequate data to do so, they do not provide sufficient guidance for correcting this serious problem.

49. 12 Standard For:Excess Hypoglycemia We recommend that insulin pumps which store glucose and insulin dosing data alert users when they experience severe or excessive hypoglycemia and provide specific guidance regarding likely causes.

50. Excess Hyperglycemia 13 Issue: Current insulin pumps and glucose monitors do not warn users that they are experiencing hyperglycemia that is too severe or too frequent. Although most insulin pumps contain adequate data to do so, they do not provide sufficient guidance for correcting this serious problem.