Venekamp (HumaPen® Memoir™).fm
Contents
1. found to be more accurate in delivering low Figure 1 Components of the HumaPen Memoir insulin delivery system Needle parts and insulin 794 Expert Rev Med Devices 4 6 2007 screw back and with the cartridge holder aligned straightly with the pen body screw the cartridge holder onto the pen body Step 3 preparing amp priming the pen Confirm the insulin type by reading the cartridge label through the insulin viewing slot If the insulin is cloudy roll the pen between the hands gently ten times and invert it ten times until the insulin appears evenly mixed Clean the rub ber seal at the end of the cartridge with an alcohol swab To attach a needle remove the paper tab from the outer needle cap screw the outer needle cap onto the cartridge holder until completely attached and pull off the outer needle cap and set aside Turn on the pen by pressing the ON button After 3 s the display should return to READY MODE indicating time date and 0 Prime the pen before each injection to check insulin flow and remove air To prime the pen turn the dose knob to 2 U pull off the inner needle cap and discard and hold the pen with the needle tip upward and away from the face Tap the insulin cartridge holder gently with a finger to allow bubbles to collect near the top and then slowly push the dose knob Continue to hold the dose knob for another five counts after it stops moving Priming is complete when a2. 421 431 2004 4 Coutinho M Gerstein HC Wang Y Yusuf S The relationship between glucose and incident cardiovascular events a metaregression analysis of published data from 20 studies of 95 783 individuals followed for 12 4 years Diabetes Care 22 233 240 1999 Khaw K T Wareham N Bingham S Luben R Welch A Day N Association of hemoglobin A1C with cardiovascular disease and mortality in adults the ow European Prospective Investigation into Cancer in Norfolk Ann Intern Med 141 413 420 2004 6 Stratton IM Adler AI Neil HAW et al Association of glycaemia with macrovascular and microvascular complications of Type 2 diabetes UKPDS 35 prospective observational study Br Med J 321 405 412 2000 7 Cramer JA A systematic review of adherence with medications for diabetes Diabetes Care 27 1218 1224 2004 ee Demonstrates a limited rate of adherence to oral hypoglycemic agents and to insulin indicating the need for an electronic monitoring system to improve treatment adherence 9 11 13 HumaPen Memoir HumaPen Memoir The authors have no other relevant affilia review of the manuscript Saydah SH Fradkin J Cowie CC Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes JAMA 291 335 342 2004 Walker EA Molitch M Kramer MK et al Adherence to preventive medications predictors and outcomes in the Diabetes 14 Pre
3. device Compared with prestudy pens the HPM pen device received better patient ratings for ease of seeing the insulin dose used selecting the dose injecting the dose controlling blood glucose level attaching and removing the cartridge holder and convenience FIGURES 2 A amp B Patients identified HPM s memory feature functions as important including ability to confirm that an injection was taken as well as to indicate the previous insulin dose time of dosing and previ ous 16 doses FIGURE3 Less than 50 of patients did not select as one of the two most important aspects of the mem ory feature the ability to view previous dose information to make a current dose decision This value may represent an underestimation because of selection of other more general aspects listed in the questionnaire that may be interpreted as including this aspect for example the ability to view the pre vious 16 doses ability to view time of previous insulin dose and ability to view number of units of previous insulin dose Upon study completion 87 of patients reported that they high ratings from patients and healthcare providers across sev eral dimensions including ease of use Most healthcare provid ers 88 reported that the average time required to train a patient in HPM pen device use was less than 30 min and 50 reported that this training required less than 15 min 12 Future studies are necessary to further assess healthcare pro vid
4. Lenox SM Development ofan instrument to Affiliations ashi k w venekamp atriummc nl assess expectations of and preference for an Debra A Ignaut RN CDE insulin injection pen compared with the vial Clinical Research Advisor Eli Lilly and and syringe Clin Ther 26 590 597 2004 Company Diabetes Endocrine Medical 22 Clarke A Dain MP Dose accuracy of a Indianapolis IN 46285 USA reusable insulin pen using a cartridge system T l 1 317 433 3330 with an integrated plunger mechanism Expert Fas eee 5 458 Opin Drug Deliv 3 677 683 2006 ignaut_debra_a lill com 802 Expert Rev Med Devices 4 6 2007
5. 0 there was a 20 increased risk of cardiovascular disease 5 In addition findings from the UK Prospective Diabetes Study UKPDS suggest that any decline in HbA1c was likely to decrease the risk of microvascular complications and at HbA1c values of less than 6 0 there was no lower threshold below which further lowering did not decrease the risk of complications 6 However nonadherence to antidiabetic treat ment is common approximately one in every three patients with T2DM are not adherent to their insulin regimens 7 and according to one estimate in the USA only 37 of diabetes mel litus DM patients achieve the consensus target of HbA1c less than 7 0 8 Adherence to antidiabetes treatments including lifestyle modifications is often challenging in part because treatment may be ol Nhe a adjusting dose settings NI viewed as inconvenient and or associated with U i adverse effects e g weight gain hypoglycemia or edema 9 Forgetfulness also appears to be an aes barrier to DM treatment adher ence in many patients In a masked study of 3234 patients at high risk of developing DM the most common reason for nonadherence to treatment with the biguanide metformin or placebo reported by patients was forgetting to take doses 22 9 In this study self reported forgetting was associated with a more than five fold increased risk of nonadherence odds ratio OR 5 11 95 confidence i
6. 7 6 received complaints regarding functional ity of which 8 2 5 were related to pen device failure No pens receiving func tional complaints resulted in a serious adverse event there were no pen related hypoglycemic events and two hyper glycemic events considered possibly related to the pen device were later attrib uted to incorrect needle insertion Most patients were satisfied with the HPM pen device preferred it to their previous injection device and stated that they would use the HPM pen again or recom mend it The pen received convergently Would use recommend Appearance Mil Easy to use Easy to read numbers Digital display Easy to push the dose knob inject Can dial back easily without wasting insulin Easy to carry Easy to teach Memory feature Easy to hold Percentage 0 10 20 30 40 50 60 70 80 90 100 87 100 Size Weight Study participants jy Healthcare providers _ Other Figure 4 Top reasons selected by study patients and healthcare providers HCP for using or recommending the HumaPen Memoir pen device At study completion study patients n 290 and HCP n 16 reported whether or not they would use or recommend the HumaPen Memoir pen device and selected three reasons for using recommending it Reproduced with permission from 12 and CMRO Informa Healthcare 798 Expert Rev Med Devices 4 6 2007 HPM received high ratings for ease of use and for appear
7. FlexPen No Yes Yes 60 units 1 unit increments o OptiClik Yes No No 80 units 1 unit increments o AutoPen Yes No No 21 units 1 unit increments or No 42 units 2 unit increments Lantus OptiSet No Yes No 40 units 2 unit increments o Lantus SoloStar No Yes Yes 80 units 1 unit increments o A summary of comparative features from product manuals of insulin pen devices The table may not be inclusive of all such devices currently available in certain markets Being discontinued in 2007 tOwen Mumford device used with Sanofi Aventis insulins in some markets www future drugs com 799 Ignaut amp Venekamp Expert commentary There is a growing need for insulin therapy to optimize meta bolic control Therefore a simple and reliable way to admin ister insulin is a priority The HPM has several advantages over conventional vial and syringe and other available insulin pen injectors One key advantage of the HPM is its memory function which provides a unique tool for promoting patient adherence to insulin therapy Five year view Mechanical insulin pen injectors are at a very mature phase of evolution and can be differentiated in development only by minor improvements in what are seen as standard fea tures as well as in industrial design options Electromechan ical insulin injection pen devices while mature in their mechanical functionality may still present new opportuni ties for innovation in electr
8. SD of 9 9 2 4 versus 4 9 1 6 p lt 0 001 19 Among patients with visual and or motor disabilities use of a pen may be particularly beneficial over vial and syringe In one study involving 79 patients a higher propor tion of patients with disabilities were able to self administer insu lin independently using a pen 53 compared with vial and syringe 20 20 Using the HPM The HPM is designed for the patient to self administer 1 60 U of any Humalog or Humulin insulin from a 3 ml cartridge of 100 IU ml FIGURE 1 Doses are dialed one unit at a time and may be corrected without wasting insulin HPM also has a dose memory feature indicating the time date and doses of the 16 previously delivered insulin treatments including the prim ing doses HPM is designed for 3 years of use with replaceable cartridges After 3 years to alert the patient that a replacement pen is needed the battery symbol will flash when there are 3 weeks of battery life remaining Step 1 setting time amp date The time and date are set by pressing the ON button to put the pen in READY MODE The time setting mode is then entered by pressing and holding the ON button again for 3 s When the hour number starts flashing the dose knob is pressed and released to set the correct hour To enter another time or date mode the ON button is pressed repeatedly until that mode is flashing To save time and date settings press the ON button to return
9. dose first To see all stored doses press the dose knob repeatedly To return to READY experiencing a HumaPen Memoir MODE after End is displayed press the dose knob again Otherwise if the dose knob is not pressed the pen will return to READY MODE automatically after 15 s Care storage amp disposal The HPM pen should be kept away from dust extreme heat or cold or direct sunlight The pen and its case should also be kept away from water moisture or wet surfaces The pen should not be refrigerated The pen cap pen body and case may be cleaned with a water dampened cloth without alcohol or bleach Pen parts should not be lubricated with oil or any other lubricant Pen needles and pens which contain lithium batteries should be discarded according to local regulations Pen batteries cannot be replaced Cost effectiveness Compared with vial and syringe the use of insulin pens in general is cost effective In a longitudinal retrospective study of 1156 US adults with T2DM initiating insulin treatment with a pen device adherence increased significantly compared with vial and syringe This conclusion emerged from assessments of first the medication possession ratio MPR mean SD MPR 69 33 vs 62 28 p lt 0 01 and second pro portions of patients with MPR of 80 or above 54 6 vs 36 1 p lt 0 01 10 Compared with vial and syringe use of an insulin pen also reduced the risk of hypoglycemic eve
10. for insulin delivery systems among current insulin users and nonusers Clin Ther 26 1498 1505 2004 tions or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed Assistance in manuscript preparation was provided by Stephen W Gukin Rete Biomedical Communications Corp Ridgewood NJ USA The authors also wish to acknowledge Margaret Camp bell and Cate Jones PhD of Eli Lilly and Company for their Demonstrates that among patients with Type 1 T1 DM or T2DM including current insulin users and nonusers insulin delivering pens were preferred to vial and syringe because of greater social acceptability with pens Rubin RR Peyrot M Quality of life treatment satisfaction and treatment preference associated with use of a pen device delivering a premixed 70 30 insulin aspart suspension aspart protamine suspension soluble aspart versus alternative treatment strategies Diabetes Care 27 2495 2497 2004 Korytkowski M Bell D Jacobsen C Suwannasari RA multicenter randomized open label comparative two period crossover trial of preference efficacy and safety profiles of a prefilled disposable pen and conventional vial syringe for insulin injection in patients with Type 1 and 2 diabetes mellitus Clin Ther 25 2836 2848 2003 Graff MR McClanahan MA Ass
11. ratings of the prestudy pen device compared with the HumaPen Memoir pen device A At study completion patients n 290 rated device properties using a scale of 1 strongly disagree to 6 agree or 7 strongly agree Each bar represents the percentage of patients responding with a 6 or 7 p values were computed from the proportional odds model cumulative logits using the ordinal response scale 1 7 and hence are based on comparisons of actual scores 1 7 not the percentage of patients who agreed with the statements response of 6 or 7 B Patients rated device properties using a scale of 1 very difficult to 4 easy or 5 very easy or not applicable Each bar represents the percentage of patients rating the task as a 4 or 5 p values were computed from the proportional odds model cumulative logits based on comparisons of actual scores 1 5 and did not include responses of not applicable The p values are hence based on comparisons of actual scores 1 5 not the percentage of patients rating the task easy response of 4 or 5 For A and B p lt 0 05 indicate significant differences in scales between responses concerning prestudy pens at study baseline and the HumaPen Memoir at study completion Eligible patients had been using an insulin injection device for at least two insulin doses per day for 2 months or longer immediately before the study The mean SD duration of use of an insulin injection device at baseli
12. to the READY MODE Step 2 loading a cartridge Pull off the pen cap unscrew the cartridge holder from the pen body and insert the small end of the cartridge into the car tridge holder Use the cartridge plunger to push the injection a Other randomized open label crossover studies have demonstrated that use of an insulin pen was associated with a signifi Cap Insulin s Injection Cartridge viewing Dose screw Pen On button body knob cantly lower rate of injection pain p 0 0018 and significantly higher rates of acceptance p 0 0059 ease in setting and drawing up insulin doses p 0 0490 holder F T and preference 89 5 compared with vial and syringe among 96 initially insulin Foot Display Display symbols naive patients 17 In a recent prospective randomized open label crossover study PM indicator Dose Time Inner needle cap involving 162 patients the use of an insu ane uter needle cap lin pen was also associated with a signifi cantly reduced fear of self injection 9 5 vs 11 2 with vial and syringe p lt 0 0001 u8 Most patients 71 5 preferred the Needle Rubber eal Lilly 3 ml insulin cartridge Paper tab Battery Date mark Needle parts and insulin cartridge insulin pen Compared with an insulin vial and syringe an insulin pen was also cartridge sold separately
13. 7 Caucasian 15 0 Western Asian and 0 3 African 12 www future drugs com 795 Ignaut amp Venekamp Fi Percentage agree or strongly agree 0 1o 20 30 ae 50 60 w 80 90 100 Easy to see dose 9 of insulin used A 92 Easy to select dose 96 Easy to control blood sugar 65 P lt 0 001 Easy to carry for use away from home Does not interfere with short trip plans O N Q 9 09 Easy to fit into daily life Not noticeable to others when used Reduces embarrassment when used away from home at N e QO AK On AK Convenient to use H Reduces my reluctance to take injections Helps me manage my diabetes at home Helps me manage my diabetes away from home oa Bo ajm Percentage rating easy or very easy 0 w 20 30 ao 50 60 w 80 90 we 93 97 98 Learning to use the pen Using power button to turn pen on Ability to read time and date Ability to read dose f 91 Setting time and date Attaching removing cartridge holder Holding pen while injecting 97 Injecting dose f Viewing doses in memory Understanding display messages 91 Using the user manual Using the quick guide 94 Overall ease of use goc mP aE T Prim Reproduced with permission from 12 and CMRO Informa Healthcare m E Ea BI Figure 2 Study patients
14. Device Profile dn parien ith Ty e2 diabet S 2DM su ve ithe maj or ted to HumaPen Memoir a novel insulin injecting pen with a dose memory feature Debra A Ignaut and Willem JRR Venekamp Optimizing glycemic control may help to reduce the risks of diabetes complications but it is often difficult to achieve partly owing to poor treatment adherence One barrier to adherence is forgetfulness The HumaPen Memoir pen is the only electronic reusable insulin pen with a aon i ory fea mir is enables the device to store information re regarding date ahin es of th us 16 doses of insulin in luding priming doses The pen has a digital display and a two way dial to minimize waste of insulin The digital display facilitates accurate dose selection Both patients and healthcare providers rate as important the pen s ability to confirm administered doses and times its overall ease Expert Ren M of injection ana display LEAST ed Bailes lAl 46 801 00 D gt aii aboptimal reat ent ad eren eisa ana i ts ij hieving optimal blood glucose control and is therefore an important target for disease management 1 2 Meta ana lyses suggest that increased glycemic exposure is associated with heightened cardiovascular risk 3 4 Findings from the European Prospec tive Investigation into Cancer in Norfolk EPIC Norfolk study showed that for every 1 0 rise in hemoglobin Hb Alc above 5
15. HPM a novel insulin injection system pen associated with high acceptance in DM patients HumaPen Memoir The state of science in insulin pens devices for diabetes mellitis In clinical trials patients with DM preferred pens to vial and syringe for self administering insulin Patient preferences for insu lin pens have been ascribed to ease of use lack of interference with activity as well as enhanced social acceptability convenience flexibility effectiveness and quality of life 13 14 Many patients also find pens to be more discreet and accurate less prominent sources of fear and pain and more consistent with adherence than vial and syringe Preferences for pen devices may predict the kind and nature of insulin prescribed in some countries e g The Netherlands and Germany In a randomized open label crossover trial involving 121 patients significantly higher proportions preferred an insulin pen over vial and syringe 74 vs 20 and reported the pen to be more discreet 85 vs 9 and easier to use 74 vs 21 15 In two multicenter surveys involving 1310 users of either an insulin pen or vial and syringe up to 98 of patients responded that the pen was easier to use Among a subset of pen users n 456 73 found it to be more accurate than vial and syringe and 77 associated it with easier adherence to treatment 16 insulin doses in a study of 48 subjects with absolute errors of the mean standard deviation
16. ance The most common reported disadvantages of the HPM were premature failure of the battery or electronics and the pen size However these reports were not prevalent and there were no safety concerns Alternative pens devices and how the technology fits into the field of medical devices Several reusable insulin injection devices are available TABLE 1 According to Clarke and Dain the OptiClik Sanofi Aventis facilitates cartridge changing has a clear dose display and enables large doses of insulin to be delivered with a single injection 22 For a dialed dose of 80 U the OptiClik delivered a mean dose of 79 75 0 32 U under ambient con ditions 22 The NovoPen 3 Novo Nordisk NJ USA also offers the potential advantage of a high degree of auditory confirmation of dose setting 23 In a trial involving 48 patients significantly higher proportions of patients detected an auditory confirmation of dose setting with the NovoPen 3 100 compared with the Humalog Pen 63 HumaPen Memoir HumaPen Ergo 75 or Novolin Innolet 90 The HPM is unique in being a reusable insulin pen with a dose memory feature The HPM also offers the potential advan tages of a digital display and a two way dial to minimize any waste of insulin Several prefilled disposable insulin injection devices are also available TABLE 1 Study conclusions In a clinical trial HPM pen was effective acceptable to and preferred by most p
17. atients over their previous insulin injec tion devices and associated with high treatment satisfaction The majority of patients stated that they would use the HPM again or recommend it to another patient Most patients rated the memory feature as being among the top reasons for recommending the HPM ease of use being the other and the ability to confirm injections taken as the most important aspect of the dose memory feature The HPM pen device also received convergently high ratings from healthcare providers across several dimensions including ease of use able 1 Comparison of insulin pens Device Reusable Prefilled Can dial forward and Maximum dose and Multiple dose backward without dose increments memory function wasting insulin HumaPen Memoir Yes No Yes 60 units tunit increments Yes 16 with date and time HumaPen Ergo Yes No Yes 60 units 1 unit increments No HumaPen Ergo ll Yes No Yes 60 units 1 unit increments No HumaPen Luxura Yes No Yes 60 units 1 unit increments o HumaPen Luxura HD Yes No Yes 30 units 0 5 unit increments No 1 30 units Humulin or No Yes Yes 60 units 1 unit increments o Humalog Pen ovoPen 3 Yes No No 70 units 1 unit increments No NovoPen 4 Yes No Yes 60 units 1 unit increments o NovoPen Junior Yes No o 35 units 0 5 unit increments No 1 35 units Novolin Innolet No Yes No 50 units 1 unit increments No ovo
18. ers perceptions of the HPM and assess the pen in more nat uralistic clinical settings in which patients may not receive thorough training Postmarketing findings The HPM received favorable feedback and no significant complaints in postmarketing findings collected in The Neth erlands The main reported advantages of the HPM pen were its ease of use appearance and dose memory function which was appreciated as a means of promoting diabetes manage ment Other reported advantages were the easy to read dis play ease of injection and screw on cartridge holder The would use the HPM pen device again or recommend it to others primarily for oe TR ease of use injection the memory fea ture ease of reading numbers the clear digital display and the ability to dial back easily without wasting insulin FIGURE 4 12 Similar results were reported by health care providers FIGURES 3 amp 4 Their ratings of HPM pens compared with prestudy devices were similar to patients ratings Compared with the most commonly used prestudy devices the HPM pen received significantly higher ratings of easy or very easy for ability to read dose 100 vs 84 and injecting dose 100 vs 90 both p lt 0 05 for comparisons of scores from 1 very difficult to 4 easy or 5 very easy These findings demonstrate that HPM pen had acceptable functionality in an outpatient setting in patients with T1DM or T2DM Of 314 pens 24
19. essment by patients with diabetes mellitus of two insulin pen delivery systems versus a vial and syringe Clin Ther 20 486 496 1998 Kadiri A Chraibi A Marouan F et al Comparison of NovoPen 3 and syringes vials in the acceptance of insulin therapy in NIDDM patients with secondary failure to oral hypoglycaemic agents Diabetes Res Clin Pract 41 15 23 1998 Stockl K Ory C Vanderplas A et al An evaluation of patient preference for an alternative insulin delivery system compared to standard vial and syringe Curr Med Res Opin 23 133 146 2007 Demonstrates that for most patients with T1DM or T2DM compared with vial and syringe an alternative insulin delivery system is preferable and associated with less psychological distress Lteif AN Schwenk WE Accuracy of pen injectors versus insulin syringes in children with Type 1 diabetes Diabetes Care 22 137 140 1999 www future drugs com 801 Ignaut amp Venekamp 20 Shelmet J Schwartz S Cappleman J et al 23 Asakura T Seino H Assessment of dose Willem JRR Venekamp MD Preference and resource utilization in elderly selection attributes with audible notification Consultant Endocrinologist Atrium Medical patients InnoLet versus vial syringe Diabetes in insulin pen devices Diabetes Tech Ther 7 Center Brunssum Kochstraat 2 6442 BE Res Clin Pract 63 27 35 2004 620 626 2005 The Netherlands 21 Szeinbach SL Barnes JH Summers KH j pe 7a s
20. lin dose Ability to view the date of previous insulin dose Ability to view the previous Percentage 0 ue 20 30 sit 50 60 fu 80 a 100 8 44 N oa 44 a oa ON wo 16 doses versus prandial treatment groups and in the simple versus complex insulin regimen groups were similar p gt 0 14 for all com parisons Functional complaints were reported by 13 3 of subjects from The Netherlands 11 5 from South Africa 10 7 from India and 2 7 from Germany Nonfunctional complaints were reported by 23 1 of subjects from South Africa 10 8 from The Netherlands 10 7 from India and 6 from Germany 12 Of 314 HPM pens 56 17 8 received complaints 24 7 6 were func tional and 33 10 5 nonfunctional Ability to view previous dose information to make current dose decision Ability to confirm injection taken Ability to use information to fill out 4 blood glucose logbook 6 Memory feature not important mee Other 2 0 k O M oa 55 63 Study participants gy Healthcare providers _ Figure 3 Most important aspects of the memory feature of HumaPen Memoir pen device selected by study patients and healthcare providers At study completion study patients n 290 and HCP n 16 selected two aspects of the memory feature thought to be most important Reproduced with permission from 12 and CMRO Informa Healthcare www future drugs com 797 Ignaut amp Venekamp
21. lin lispro injection rDNA origin 100 units per mL U 100 prescribing information Eli Lilly and Company IN USA Eli Lilly and Company 2007 www humalog com Humalog Mix50 50 Pen 50 insulin lispro protamine suspension and 50 insulin lispro injection rDNA origin 100 units p r ml U 100 prescribing information Eli Lilly and Company IN USA Eli A and Company 2007 www humalog com Lantus insulin glargine rDNA injection prescribing information Sanofi Aventis NJ USA Sanofi Aventis US LLC 2006 www lantus com Novopen 3 www insulindevice com novopen OptiClik www opticlik com home do Key issues suboptimal adherence by patients e Diabetes mellitus DM is a leading cause of morbidity mortality and healthcare costs e Tight glycemic control is instrumental in reducing the risk of complications of DM but it is often difficult to achieve because of e Forgetfulness is a major contributing factor to suboptimal adherence with insulin regimens e The HumaPen Memoir HPM is an electronic reusable insulin pen device with a memory function to store the dates times and doses of up to 16 previous insulin injections including priming doses e Ina clinical study the HPM demonstrated acceptable functionality and tolerability and its memory option was highly valued e The HPM received convergently high ratings from patients as well as healthcare providers with the majority of patients
22. ne was 7 1 5 9 years range 0 25 40 0 years Most patients had been using the HumaPen Ergo Eli Lilly 63 1 or the OptiPen Pro Sanofi Aventis NJ USA series 19 2 Study patients were required to use as their prandial insulin an Eli Lilly product insulin lis pro Humalog insulin lispro low mix 25 LM25 Humalog Mix25 and or insulin lispro mix 50 LM50 Humalog Mix50 If using insulin lispro for most prandial injections patients were required to use as their basal insulin either human insulin isophane suspension NPH Humulin N or insulin glargine Lantus Sanofi Aventis 12 Methods At the first of three office visits over 6 10 weeks patients were assigned to use HPM for either their prandial or basal insulin To ensure sufficient use of the pen in the study patients using NPH were stratified in a 3 2 ratio to receive prandial or basal insulin To minimize the impact of prestudy insulin formula tion and dose patients using insulin glargine were assigned to continue insulin glargine with their prestudy insulin injec tion device and use of the HPM pen device for prandial doses Patients used the same dosing schedule and insulin doses that had been used immediately before study onset Dose adjustment was permitted as needed 12 At the first baseline prestudy pen device visit patients recorded complaints regarding HPM or the accompanying User Manual in their diaries which were reviewed by investi ga
23. nterval CI 4 30 6 07 p lt 0 0001 The use of a vial and syringe for delivering insulin has several potential disadvantages that may compromise medication adherence Many patients find the vial and syringe cumbersome and difficult to transport Oth ers experience anxiety fear and or social embarrassment or object to the training time required to master the technique of insulin delivery via vial and syringe 10 Introduced in 1987 in the USA insulin injection pen devices were developed as alternative devices to promote patient satis faction with and adherence to treatment and thus enhance glycemic control and overall treatment outcomes 11 10 1586 17434440 4 6 793 2007 Future Drugs Ltd ISSN 1743 4440 793 Ignaut amp Venekamp The HumaPen Memoir HPM Eli Lilly IN USA is an electronic reusable pen for use with prefilled cartridges with a memory feature 12 This enables the pen to store information on the previous 16 doses including the priming doses as well as the dates and times of dosing A total of 16 doses represents at least approximately 2 days of use in a patient on intensive insulin treat ment The pen device also has a digital display and two way dial to minimize any waste of insulin A potential advantage of the HPM is the ability to check previous insulin doses including their dates and times The digital display also facilitates accurate dose selec tion This article focuses on the
24. nts significantly OR 0 36 95 CI 0 25 0 53 p lt 0 05 and of hypoglycemic event OR 0 50 95 CI 0 37 0 68 p lt 0 05 Consistent with these findings mean annual healthcare costs also declined significantly from US 16 359 with vial and syringe to 14 769 with the pen p lt 0 01 10 Clinical profile results of a human study involving HPM For approval regulatory authorities do not require that manu facturers conduct clinical trials of pen devices However in a multicenter trial supported by the manufacturer of the HPM the pen device was effective well tolerated and well accepted by outpatients with DM In this 6 to 10 week open label single arm outpatient study HPM demonstrated acceptable func tionality and a favorable benefit risk profile as reported by 300 patients and 16 healthcare providers 12 Study objectives amp characteristics of patients The primary objective of the study was to determine whether HPM has acceptable functionality ability to deliver a prespeci fied dose of insulin according to patient diaries This study also assessed the pen device safety and acceptability The trial included 300 adults with a mean SD age of 51 7 14 6 years range 18 0 75 5 years who had Type 1 DM T1DM 38 or T2DM 62 for a mean SD of 13 7 9 0 years range 0 4 55 0 years Patients were recruited from 21 sites in India South Africa Germany and The Netherlands and were of vari ous racial origins 84
25. onic feature sets and communica tion of data wirelessly and remotely One possible area for future innovation might be to increase the number of doses stored in memory particularly for patients using complex or intensive insulin regimens Of course the value that such innovations offers to the patient and healthcare provider comes at a cost The ability to measure improvements in health related quality of life outcomes will be critical in gaining reimbursement for innovations in electromechanical insulin injection systems Devices for alternative routes of insulin administration i e insulin inhalation devices do not currently appear to impact i the insulin pen market but may play a more prominent role in the future Information resources e American Diabetes Association www diabetes org e European Association for the Study of Diabetes www easd org International Diabetes Federation www idfiorg National Diabetes Education Initiative www ndei org National Institute of Diabetes and Digestive and Kidney Diseases www72 niddk nih gov HumaPen Memoir further information www humalog com patient humapen_memoir jsp Autopen www owenmumford com autopen html Humalog Pen insulin lispro injection USP rDNA origin 100 units per mL U 100 prescribing information Eli Lilly and Company IN USA Eli Lilly and Company 2007 www humalog com Humalog Mix75 25 Pen 75 insulin lispro protamine suspension and 25 insu
26. preferring the HPM to their previous insulin injectors and stating that they would use it again or recommend it to other patients 800 Expert Rev Med Devices 4 6 2007 Financial amp competing interests disclosure Both authors participated in the development and review of this manuscript before it was submitted Debra Ignaut RN CDE is an employee and stockholder of Eli Lilly Willem JRR Venekamp MD is a member of a European Advisory Board for Eli Lilly and serves as a speaker for Novo Nordisk All clinical trials for Eli Lilly products mentioned herein were funded by Eli Lilly and Com pany Eli Lilly and Company Battelle Science and Technology International and Nypro Inc collaborated in the development of References Papers of special note have been highlighted as e of interest ee of considerable interest 1 Goldberg RB Mellies MJ Sacks FM et al Cardiovascular events and their reduction with pravastatin in diabetic and glucose intolerant myocardial infarction survivors with average cholesterol levels subgroup analyses in the Cholesterol and Recurrent Events CARE trial Circulation 98 2513 2519 1998 2 Gerstein HC Glycosylated hemoglobin finally ready for prime time as a cardiovascular risk factor Ann Intern Med 141 475 476 2004 3 Selvin E Marinopoulos S Berkenblit G et al Meta analysis glycosylated hemoglobin and cardiovascular disease in diabetes mellitus Arch Intern Med 141
27. stream of liquid flows from the needle tip and the display is in READY MODE Step 4 setting amp injecting the insulin dose The desired dose is set by turning the dose knob If too many units are set the dial may be turned back to the desired dose without wasting insulin To inject insulin insert the needle into the injection site and then with the thumb placed directly on the dose knob slowly push the dose knob until five counts after the dose knob stops Then remove the needle from the injection site The pen should be in READY MODE If it is not an incomplete dose was administered and the number displayed on the pen is the amount that failed to be administered Dial down the dose knob to 0 and the partial dose is saved in the memory Replace the cartridge and review the instructions above to inject the remaining dose The memory feature will record the second partial dose as a separate dose Upon completing the injection replace the outer needle cap unscrew the capped needle remove it from the pen and discard Replace the pen cap The pen will turn off automatically after 30 s of inactivity Removing an insulin cartridge When an insulin cartridge is empty the needle may be removed the cartridge holder unscrewed and removed from the pen body and the empty insulin cartridge removed by tilting the cartridge holder Viewing dose memory With the pen in READY MODE press and release the dose knob to reveal the most recent
28. tors at the third and final 6 10 weeks after baseline visit Complaints could also be reported by telephone to the investi gative site Complaint forms were completed and submitted for each complaint If the investigator believed that the adverse events were related to the study pen complaint forms were submitted regardless of whether the complaint was reported by the patient The study sponsor categorized each complaint as functional nonfunctional or related to the User Manual 12 796 Expert Rev Med Devices 4 6 2007 Functional complaints were defined as those interfering with the ability of the study pen to deliver a prespecified insulin dose as well as pen malfunction due to improper use Nonfunctional complaints did not concern the pen devices functionality e g aesthetic concerns Complaints were also categorized according to answers to specific questions about each complaint and free form descriptions of complaints In addition complaints were categorized based on information within the complaint forms and when applicable assessment of the pen device 12 To assess HPM pen safety patients recorded any device related hypoglycemic episodes blood glucose lt 3 5 mmol l 63 mg dl or signs symptoms of hypoglycemia hyperglycemic episodes blood glucose gt 18 mmol l 324 mg dl or other adverse events Glycemic control HbAlc and fasting plasma glucose were measured at baseline and final visit Patient satisfaction
29. vels or mean fast ing plasma glucose levels Only three treatment emergent events occurred in over 2 of patients influenza 4 7 nasopharyngitis 4 3 and headache 2 3 There were no treatment related serious adverse events and no discontinua tions due to adverse events A hypoglycemic event occurred in 106 patients 0 94 event per patient per 30 days No HPM related hypoglycemic events were reported Instances of hyperg lycemia blood glucose gt 18 mmol l potentially related to use of the HPM pen device were reported twice in one patient but were later determined to have resulted from incorrect needle insertion 12 Among 290 patients completing questionnaires 77 9 were satisfied with the HPM pen device compared with 54 2 with their prestudy device A total of 81 4 of patients preferred the HPM compared with only 18 6 preferring their prestudy person weeks The HPM pen was used to 7 administer mean SD daily doses of 24 6 12 3 U for the basal dose and 28 5 20 2 U for the prandial dose A backup insulin injection device was used in place of the HPM pen because of difficult use for 7 or more consecutive days by only 7 2 3 patients The HPM pen was replaced with another insulin injection device by 14 4 7 patients 12 Numbers of functional and nonfunctional complaints reported by patients in the basal Ability to view the number of units of previous insulin dose Ability to view the time of previous insu
30. vention Program Diabetes Care 29 1997 2002 2006 Emphasizes the importance of adherence to treatment and the key role of memory in fostering adherence Demonstrates that adherence to metformin treatment reduces the risk of developing diabetes mellitis DM The most common reported reason 15 for nonadherence was forgetting gt 20 Lee WC Balu S Cobden D Joshi AV Pashos CL Medication adherence and the associated health economic impact among patients with Type 2 diabetes mellitus converting to insulin pen therapy an analysis of third party managed care claims data Clin Ther 28 1712 1725 2006 Demonstrates that in patients with Type 2 Diabetes Mellitis T2DM switching from insulin delivery by vial and syringe to a pen improves adherence and health 16 outcomes and reduces annual costs of treatment Stewart KM Wilson MF Rider JM Insulin delivery devices J Pharm Pract 17 20 28 2004 Venekamp WJRR Kerr L Dowsett SA et al Functionality and acceptability of a new electronic insulin injection pen witha 4g memory feature Curr Med Res Opin 22 315 325 2006 Demonstrates that the HumaPen Memoir has favorable functionality higher patient and healthcare provider ratings of acceptability compared with P prestudy pens and a high rate of preference to prestudy pens largely because of the pen s dose memory function Summers KH Szeinback SL Lenox SM Preference
31. with preference for and confidence in HPM were measured using the Insulin Delivery System Evaluation questionnaire an adaptation of the previously validated Insulin Injection Preference question naire 21 Healthcare provider acceptance of the HPM pen device compared with other insulin injection devices was evaluated using a Health Care Professional Evaluation an adaptation of the patients questionnaire Results HPM was used for the basal dose by 11 3 of patients and for the prandial dose by 88 7 of whom 76 0 used it to admin ister insulin lispro 10 7 for LM25 and 2 0 for LM50 The mean SD duration of use for the HPM pen device was 8 2 1 6 weeks for a total exposure of 2446 HumaPen Memoir one pen received both complaints Of the 24 pen devices receiving functional complaints eight 2 5 were related to pen failure A further 15 4 8 pen devices received com plaints related to recoverable errors possibly cleared by manu ally resetting the pen No functional complaints resulted in a serious adverse event Of the 33 pens receiving nonfunctional complaints many were attributed to user misunderstanding of pen operation 9 33 27 3 2 9 of all 314 pens recovera ble errors 5 33 15 2 1 6 or esthetic issues 7 33 21 2 2 2 12 Insulin delivered via the HPM was well tolerated Between baseline and final visit patients maintained glycemic control with no significant changes in mean HbA1c le
Download Pdf Manuals
Related Search