Table 2.

Summary of included studies

Author	Device type (M or C)	Description	Sample size	Study design	Results and conclusion
Adolfsson et al34	NovoPen Echo® (Novo Nordisk A/S, Bagsvaerd, Denmark) (M)	Insulin pen designed for children. Records dose volume and hours since last injection.	Diabetes type 1 Sample size: N=358	Observational, multicenter study	Patient adherence: Fewer forgotten injections by patients/caregivers with NovoPen Echo® device (27% versus [vs] 51%, P<0.0001) compared to pre-study device. Proportion of children reporting self-injection using NovoPen Echo® was higher compared with pre-study device (71% vs 66%, P=0.006). Usability, functionality, and user/prescriber impact: Patients reported increased confidence and self-management using the NovoPen Echo® compared to the pre-study device. Conclusion: The dose-memory function of NovoPen Echo® may help reduce forgetfulness, a common form of nonadherence. Confidence and usability can be increased with this device, which could minimize double dosing and missed doses.
Andrade et al35	DMAS (The John Hopkins University, Baltimore, ML, USA) (C)	Electronic device. Records dosing times and dates that prompt patients to take antiretroviral medication.	HIV Sample size: N=58	Randomized controlled trial	Patient adherence: Patients with memory impairment who used the DMAS had significantly higher adherence rates (77%) compared to controls who did not (57%). Memory-intact patients who use the DMAS also demonstrated trends towards improved adherence (83%), compared to a control group; however, this finding was not significant. Conclusion: The DMAS significantly improved adherence for HIV patients with memory impairment but did not for memory-intact patients.
Charles et al36	Smartlnhaler (Nexus6 Ltd, Auckland, New Zealand) (C)	Metered-dose inhaler with AVRF. Emits an audible reminder at preset designated times, as well as a visual cue that shows patients whether they have taken their inhaler during a designated period.	Asthma Sample size: N=110	Randomized open-label parallel group study	Patient adherence: Median percentage of medication taken was higher in the Smartlnhaler with AVRF group compared to the control group (93% vs 74%). Absolute mean difference was 18% (P<0.001). The proportion of patients likely to take >50%, >80%, and >90% of their medication was higher in the AVRF group than the control group; 1.33 (95% CI: 1.10–1.61; P=0.003), 2.27 (95% CI: 1.56–3.3; P<0.0001), and 3.25 (95% CI: 1.74–6.1; P<0.000l), respectively. Conclusion: An AVRF can significantly improve adherence to therapy in adult asthma.
Christensen et al37	Helping hand, (Bang and Olufsen Medicom, Struer, Denmark) (HH) (C)	Tablet blister card device. AVRF to indicate when it is time to take medication. Visual feedback signal indicating the regularity of intake during the past 7 days (green for good compliance and red for poor compliance).	Hypertension Sample size: N= 1,194	Randomized controlled trial	Usability, functionality, and user/prescriber impact: The traffic light feedback system received positive feedback from 75% of patients and 78% of HCPs. 65% of patients and 70.4% of HCPs felt the device influenced the regularity of their drug intake (P<0.00l). Conclusion: The device was well-accepted by the majority of patients and HCPs in the study.
Dahlgren et al38	Easypod™ (Merck Serono International SA, Geneva, Switzerland) (M)	Auto-injector. The device digitally displays the dose pre-programmed by a physician, the dose administered, the amount remaining within the device within a dose log, and the date of the last injection and injection history in a calendar.	Patients using r-hGH. Sample size: HCPs: N=30	Open-label, uncontrolled study	Usability, functionality, and user/prescriber impact: Display of last injection date was rated as “useful” or “very useful” by 96% of patients. 96% of patients rated the audible and visual signals as “useful” or “very useful”. 69% of patients rate the dose history as “useful” or “very useful”. Conclusion: The device may facilitate patients’ adherence to the regimen of daily injections.
Danne et al39	HumaPen® Memoir™; (Eli Lilly and Company, Indianapolis, IN, USA) (M)HumaPen Luxura™ (Eli Lilly and Company) (M)	Insulin pen. Pen features a dose-memory function that records the dose, date, and time of the past 16 injections. Insulin pen. Delivers single units from 1–60 units.	Diabetes type 1 Sample size: N=257	Randomized, open-label study	Physiological outcomes: There was no significant difference in least square mean changes in HbA1c up to week 24 between HumaPen® Memoir™ and HumaPen Luxura™ (0.43% vs 0.64%, P=0.669). There were no significant differences in hypoglycemic episodes between groups (P=0.982). Conclusion: Dose-memory function was associated with neither an additional improvement in glycemic control nor with a lower rate of hypoglycemia when compared with a conventional device pen, suggesting that adherence to injections was not improved in a relevant manner by this device.
Guo et al40	NovoPen® 5 (Novo Nordisk A/S, Bagsvaerd, Denmark)	Insulin pen. Device includes a dose-memory function that records the dose and hours passed since the last injection.	Diabetes types I & II Sample size: Patients: N=278 HCPs: N= 102	Cross-over, multicenter usability study	Usability, functionality, and use/prescriber impact: 65% of patients reported feeling more confident in managing their insulin injections using the NovoPen® 5 than their pre-study device because it allowed them to review the volume (42%) and time (39%) of their last dose. 75% of HCPs reported that the NovoPen® 5 was valuable for patients who forget their injections. Conclusion: NovoPen® 5 was preferred to other devices by most patients and HCPs. The simple dose-memory function and design functions may contribute to overall preference.
	HumaPen® Memoir™ (Eli Lilly and Company) (M)	Insulin pen. Pen features a dose-memory function that records the dose, date and time of the past 16 injections.
	HumaPen Luxura™ (Eli Lilly and Company) (M) ClikSTAR® (Sanofi-Aventis, Paris, France) (M)	Insulin pen. Delivers single units from 1–60 units. Insulin pen. Delivers up to 80 units in 1 unit increments.
Ignaut and Venekamp41	HumaPen® Memoir™ (Eli Lilly and Company) (M)	Insulin pen. Pen features a dose-memory function that records the dose, date, and time of the past 16 injections.	Diabetes types I & II Sample size: N=100	Observational study	Usability, functionality, and user/prescriber impact: 81.4% of patients preferred the HumaPen® Memoir™ to their pre-study device. Patients identified the HumaPen® Memoir’s™ dose-memory functions as important, including the ability to confirm that an injection was taken, as well as indicate the previous insulin dose, time of dosing, and previous 16 doses. HCPs also reported similar findings. 54% of patients and 75% of HCPs reported that they would recommend the device to other patients because of the dose-memory function. Conclusion: Most patients rated the dose-memory feature as being amongst the top reasons for recommending the device. The ability to confirm injections was considered the most important aspect of the dose-memory feature.
Jansen et al42	Memozax® (ALK-Abelló A/S, Horsholm, Denmark) (C)	Tablet blister card device. Device stores and dispenses grass allergen tablets, reminds patients to take their medication, and keeps a record of compliance over the previous 7 days.	Rhinoconjunctivitis Sample size: N=7I	Multicenter, randomized, open-label, controlled, parallel-group trial	Usability, functionality, and user/prescriber impact: 79% of patients found the device easy to use. 46% of participants found that the compliance device made it easier or much easier to remember to take their medication. Only 32% of participants felt that the compliance feedback function made them feel motivated or highly motivated to take their tablets. Conclusion: Most patients reported that they used the device as a reminder to take their medication and found it easy to use.
Klausmann et al43	NovoPen® 5 (Novo Nordisk A/S) (M)	Insulin pen. Device includes a memory function that records the dose and hours passed since the last injection.	Diabetes types I & II Sample size: Patients: N=300 HCPs:N=150	Interview study	Usability, functionality, and user/prescriber impact: Significantly more patients rated NovoPen® 5 as their preferred pen (82%) compared with the HumaPen Luxura™ (17%) (P<0.001). The presence of a dose-memory function was cited by 56% of patients as their main reason for preferring the NovoPen® 5.
	HumaPen Luxura™ (Eli Lilly and Company) (M)	Insulin pen. Delivers single units from 1–60 units.			82% patients stated that using the NovoPen® 5 would give them more confidence in managing their insulin injections compared with the HumaPen Luxura™ (11%, P<0.001). The dose-memory function of the NovoPen® 5 was reported as the most helpful feature in this device. Patients also felt that a dose-memory function would improve the following: daily diabetes management, how often they would have to monitor their blood glucose, and keeping their blood sugar levels more stable. Conclusion: The results of this study indicate that the NovoPen® 5 insulin pen could be beneficial in everyday clinical practice.
Olsen et al44	NovoPen Echo® (Novo Nordisk A/S) (M) NovoPen® Junior (Novo Nordisk A/S) (M) HumaPen Luxura™ (Eli Lilly and Company) (M)	Insulin pen designed for children. Records dose volume and hours since last injection. Insulin pen for children and adolescents. Delivers half unit dosing from 1–35 units. Insulin pen. Delivers single units from 1–60 units.	Diabetes type 1 Sample size: Pediatric subjects: N=79 Parents: N=78 HCPs: N=48	Design: Observational study	Usability, functionality and user/prescriber impact: 89% of pediatric subjects and 94% of parents rated the user-friendliness of the dose-memory function as “very easy/easy” to use. 87% of pediatric subjects and 81% of parents successfully activated the dose-memory function and read the amount and time of the last dose. Most pediatric subjects, parents, and HCPs considered the dose-memory function of the device as completely meeting their needs. Conclusion: The simple dose-memory function of the NovoPen Echo may contribute to the success of this pen in the pediatric setting.
Santschi et al45	IDAS II (Bang and Olufsen Medicom) (C)	Tablet blister card device. Records the date and hour the drug was removed from the packet.	Hypertension Sample size: N=25	Randomized controlled trial, crossover study	Patient adherence: Median adherence was 99.2% and did not differ between patients using the IDAS II and MEMS devices. Regularity of drug intake timing, however, was significantly higher with the IDAS II compared with the MEMS (P<0.00l). Usability, functionality, and user/prescriber impact: Most of the patients characterized the display information of the IDAS II (88%) and the MEMS devices (84%) as “easy to understand”.
		The device has a visual reminder that indicates the time elapsed since the last dose and an audible sound that is triggered at a preset time for 1 minute or until the patient opens the device.			The MEMS LCD showed information indicating the number of doses taken and hours elapsed since the last dose, which was considered useful by 64% and 28% of patients, respectively. The IDAS digital display indicating time elapsed since last dose and visual and audio reminder were considered to be useful by 46%, 38%, and 42%, respectively.
	MEMS 6 SmartCap (Aardex Ltd., Zug, Switzerland) (C)	Device which records date and hour of each bottle opening. The cap also has a LCD display indicating the number of daily openings and the number of hours lapsed since the last opening.			Drug intake: 56% of patients with the MEMS and 50% with the IDAS II reported that the device helped them maintain more regular drug dose intake. The majority of patients considered both devices to be a reliable reminder (84% MEMS; 75% IDAS II); however, more patients preferred the IDAS II as a supporting device over the MEMS. Nine patients did, however, suggest that neither device was helpful as they already had a strong daily routine for drug intake. Conclusion: IDAS II appears to be a well-accepted device. Use and acceptability of both devices were similar but IDAS II could be a useful tool for the management of long-term therapies.
Venekamp et al46	HumaPen® Memoir™ (Eli Lilly and Company) (M)	Insulin pen. Pen features a dose-memory function that records the dose, date, and time of the past 16 injections.	Diabetes types I & II Sample size: N=300	Multinational, multicenter, open-label, single-arm study	Usability, functionality, and user/prescriber impact: 81.4% of patients preferred the HumaPen® Memoir™ to their pre-study pen. The most important aspects of the dose-memory feature of the HumaPen® Memoir™ according to patients and HCPs were: the ability to view the number of previous insulin doses, ability to view the time of a previous dose, and confirm that an injection had been taken. 15% of patients, however, stated that the dose-memory feature was not important at all. 54% participants and 75% HCPs stated the dose-memory feature as a reason for recommending the device. Conclusion: The HumaPen® Memoir™ pen with dose-memory feature offers potential advantages over some currently available pens.

Abbreviations: AVRF, audiovisual reminder function; C, combined dose-memory and dose-reminder function device; CI, confidence interval; DMAS, Disease Management Assistance System; HbA_1c, glycated hemoglobin; HCP, health care professional; IDAS II, Intelligent Drug Administration System; LCD, liquid-crystal display; M, dose-memory function device; MEMS, medication event monitoring system; r-hGH, recombinant human growth hormone.