Performance and patients’ satisfaction with the A7+TouchCare insulin patch pump system: A randomized controlled non-inferiority study

Coralie Amadou; Vincent Melki; Jennifer Allain; Sylvaine Clavel; Didier Gouet; Lucy Chaillous; Bogdan Catargi; Pauline Schaeplynck-Belicard; Catherine Petit; Charles Thivolet; Alfred Penfornis

doi:10.1371/journal.pone.0289684

. 2023 Aug 24;18(8):e0289684. doi: 10.1371/journal.pone.0289684

Performance and patients’ satisfaction with the A7+TouchCare insulin patch pump system: A randomized controlled non-inferiority study

Coralie Amadou ^1,^2,^*, Vincent Melki ³, Jennifer Allain ⁴, Sylvaine Clavel ⁵, Didier Gouet ⁶, Lucy Chaillous ⁷, Bogdan Catargi ⁸, Pauline Schaeplynck-Belicard ⁹, Catherine Petit ^1,², Charles Thivolet ¹⁰, Alfred Penfornis ^1,²

Editor: Aleksandra Klisic¹¹

PMCID: PMC10449223 PMID: 37616289

Abstract

Background

We assessed the performance and patient satisfaction of a new insulin patch pump, the A7+TouchCare (Medtrum), compared with the Omnipod system.

Methods

This multicenter, randomized, open-label, controlled study enrolled 100 adult patients with type 1 or type 2 diabetes mellitus (A1C ≥ 6.5% and ≤ 9.5%, i.e., 48 to 80 mmol/mol) who were assigned with the Omnipod or with the A7+TouchCare pump for 3 months. The primary study outcome was the glucose management indicator (GMI) calculated with continuous glucose monitoring (CGM).

Results

Premature withdrawals occurs respectively in 2 and 9 participants in the Omnipod and TouchCare groups. In the Per Protocol analysis, the difference in GMI between groups was 0.002% (95% confidence interval -0.251; 0.255). The non-inferiority was demonstrated since the difference between treatments did not overlap the pre-defined non-inferiority margin (0.4%). There was no significant difference in CGM parameters between groups. On average, patients in both groups were satisfied/very satisfied with the insulin pump system. Patients preferred Omnipod as an insulin management system and especially the patch delivery system but preferred the A7+TouchCare personal diabetes manager to control the system.

Conclusions

This study showed that the A7+TouchCare insulin pump was as efficient as the Omnipod pump in terms of performance and satisfaction.

Clinical trail registration

The study was registered in the ClinicalTrials.gov protocol register (NCT04223973).

Introduction

Treatment of patients with type 1 (T1D) and some type 2 (T2D) diabetes mellitus is based on insulin therapy in order to mimic the physiological pancreatic secretion according to a basal/bolus pattern obtained either by multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) with an external insulin pump. In a very large population-based study [1], the percentage of patients with T1D using insulin pump therapy increased from 1% in 1995 to 53% in 2017. There are many reasons for this rise, but the main ones are probably the effectiveness on glycemic control, safety, and the improvement of patients’ quality of life [2, 3].

However, the indications for an external pump therapy for non-pregnant adults with T1D has been summarized by the French Society for the Study of Diabetes [4] as follows 1) A1C persistently > 7.5% (58 mmol/mol) despite intensified MDI (at least 3 injections per day) 2) Recurrent severe (more than one a year) or moderate (more than four a year) hypoglycemia, 3) Marked glycemic variability, 4) Variability in insulin needs, 5) Good metabolic control under MDI, but undermining the patient’s social/professional life. For patients with T2D, the situations concerned are mostly failure of intensified MDI regimen and patients with insulin resistance or very high insulin requirements. Absolute contra-indications are infrequent and include severe psychiatric disorders, ischemic or proliferative retinopathy progressing rapidly (before laser treatment) and repeated scheduled exposition to high magnetic field.

During the current decade, there has been several innovations in the management of diabetes, including insulin pumps improvement. Pumps have become smaller, less invasive and easier to use. They now offer the possibility to be equipped with sensors and integrated algorithms allowing closed-loop insulin delivery systems (“artificial pancreas”) [5].

Conventional insulin pumps deliver insulin continuously using tubing and external catheter. These pumps have proved to be effective as intensive therapy of diabetes by improving the glycemic control and reducing hypoglycemic events [3, 6]. By comparison, patch pumps are external pumps built without tubing and do not require the installation of a catheter [7, 8]. They also deliver insulin continuously, but the insulin delivery component of the system is a consumable managed by a personal diabetes manager (PDM). The insulin delivery reservoirs adhere to the skin with an adhesive patch that lasts up to 3 days. They are changed regularly, and these devices do not require any long-term maintenance. The absence of long tubing reduces the occurrence of adverse event associated with it, like insulin delivery modified by changing position [9]. Regarding occlusion events, the alarm is more immediate in new patch pumps design due to the absence of a catheter, and therefore allow earlier occlusion detection [10, 11]. Moreover, these systems are lighter, allowing less to carry on a day-to-day basis. Wearing such devices could lead to improved compliance and patients tend to prefer this kind of models [12–14]. However, they remain a minority in the supply, especially in France where the Omnipod^® pump was until recently the only patch pump available.

The A7+TouchCare^® insulin management system (Medtrum Technologies Inc. Shanghai) is a CE marked device (Class IIB) recently available in France and other countries. This patch pump is a small device designed for continuous subcutaneous delivery of insulin, made of a durable part of the pump that functions with a specific consumable. Furthermore, the A7+TouchCare pump comes with a cloud-based data management system that can be operated from app and laptop providing real-time information.

The aim of this real-life study was to collect performance, safety, tolerability and patient’ satisfaction with the A7+TouchCare pump system in patients with T1D and T2D after 3 months of use, in comparison with Omnipod^® (Insulet Corp., Bedford, USA), a widespread used insulin patch pump system [7, 15].

Materials and methods

Study design and patients

This was a multicenter, randomized, open-label comparative study. The study was conducted between February 2020 and February 2021 in 8 hospital centers in France that recruited patients. The randomization was done in two parallel groups (1:1), with a stratified randomization by center with randomized blocks of 4. Randomization lists were produced by the CRO statistician with SAS Version 9.4. The randomization list was implemented in the Ennov Clinical eCRF.

To be enrolled in the study, patients had to fulfil the following inclusion criteria: type 1 or 2 diabetes mellitus, at least 18 years old, already using an Omnipod^® insulin patch pump and the Abbott FreeStyle Libre^® sensor version 1 (Abbott Diabetes Care, Alameda, CA), and with laboratory A1C ≥ 6.5% and ≤ 9.5% (≥ 48 mmol/mol and ≤ 80 mmol/mol). The inclusion of patients already using a pump was done to facilitate recruitment into the study. Any type of rapid insulin could be used except faster aspart insulin (in line with the device CE marking at the time of the study) which could be substituted by any other rapid insulin (60 international units (IU) max per day). After screening, patients were randomly assigned to the investigational device (A7+TouchCare) or the Omnipod system and followed for 3 months.

Pump characteristics

The A7+TouchCare pump dimensions are 56.3x33.3x13.3 mm and it is made of a durable part of the pump (the Pump Base) that functions with a specific consumable (Reservoir-Patch). The pump is strapped to the body through its adhesive base. The insulin delivery is made thanks to a 5-mm cannula in stainless steel with a 90° penetration into the dermis. The reservoir patches contain up to 200 units of rapid-acting insulin allowing delivery for up to 3 days. The pump is monitored and controlled via a wireless radiofrequency small PDM (76.2x48.4x9.4 mm) featured by its color touchscreen. The A7+TouchCare pump also offers the possibility of personalization of insulin rate and to reduce the basal rate to zero unit/hour (for pediatrics use). All patients in the A7+touchCare group received the relevant documentation and were trained by investigator for using the A7+TouchCare device, just like in real life.

Continuous glucose monitoring

All patients were equipped with the Freestyle Libre sensor, a flash continuous glucose monitoring (CGM) system. This CGM requires scanning the sensor periodically for a continuous statement of glucose level. To obtain a complete visualization of glucose level on the last three months, the sensor was replaced every 14 days and scanned by the patient at least once every 8 hours.

Clinical data collections

Clinical data were recorded by the investigators on an electronic case report form (eCRF) at Visit 1 (inclusion visit), Visit 2 (1 month) and Visit 3 (3 months). Data generated by the insulin pump systems and the CGM were recorded throughout the study and extracted from web platforms available for the study. CGM wearing rate, glucose metrics, and glycemic events were obtained automatically on the last 4 weeks at Visit 1 and Visit 2, and on the last 8 weeks at Visit 3. Time spent in range (70–180 mg/dL) (TIR), below range (< 70 mg/dL) (TBR) and above range (> 180 mg/dL) (TAR) were defined according to the recommendations from the international consensus on time in range [16].

Hypoglycemic events were defined as a glycemia under 70 mg/dL for at least 15 minutes, according to the Freestyle Libre sensor definition. Severe hypoglycemia was defined by severe cognitive impairment requiring external assistance for recovery.

Venous blood sample was taken at inclusion and at Visit 3 in order to determine the laboratory A1C.

The doses of insulin (basal and bolus) determined by the patient and injected by the pump were recorded by the medical device. These data were displayed and downloaded by the investigators using the online application provided by the manufacturer.

Study outcomes

The primary study outcome was the glucose management indicator (GMI), an estimation of the laboratory A1C based on glucose parameters collected from CGM, on the last 10 weeks [17]. Other glucose metrics calculated automatically by the CGM software and recorded by investigators were secondary study outcomes as well as A1C measured by the laboratory.

An auto-questionnaire developed for the study was filled out by the patient at each visit to determine their satisfaction when using the insulin pump device. Existing validated questionnaires did not a priori allow sufficient exploration of the differences between the two pump models. The questionnaire was composed of 16 items (one question per item, except for item 10 that included 5 questions) concerning overall satisfaction and feelings about the blood glucose control (4 items); on the start-up and placement of the system (3 items); on the daily use of the system (3 items); on the management of the system with the PDM (4 items); and on the withdrawal/replacement of the system (2 items). For each question, the satisfaction scale went from 1 (very unsatisfied) to 5 (very satisfied), except for question 7 about pain for which 5 was painful and 1 was not painful at all.

At Visit 3, patients randomized in the A7+TouchCare group were also asked to indicate their preference for the insulin management system, insulin patch and the PDM on a scale from 1 to 5 where 1 indicated the preference for the A7+TouchCare pump and 5 the preference for Omnipod pump.

Local skin tolerability at the site of the pump (irritation/itching and redness) and other adverse events related to the study devices were recorded at each visit.

Sample size

The sample size was calculated based on an average GMI level obtained using the Omnipod pump of 7.8% (62 mmol/mol) according to the scientific committee. The non-inferiority between the study insulin pump devices was defined using the commonly accepted non-inferiority margin of 0.4% in similar study related to diabetes treatments [18]. With these assumptions, a type-1 error of 2.5%, a power of 80% and a standard deviation fixed at 0.55, the calculated number of subjects necessary to demonstrate non-inferiority was 60 patients (30 patients in each group). Accounting for 20% of non-analyzable patients (e.g. due to major protocol deviations), the number of patients to be randomized was to be at least 75.

Statistical analysis

Statistical analyses were computed with SAS Version 9.4 (SAS Institute Inc., Cary, USA). Four analysis populations were defined for this study: the safety population which was composed of all patients having used the investigational device; the intent-to-treat (ITT) population composed of all included and randomized patients having used the investigational device; the modified ITT (mITT) population composed of all ITT patients excluding patients who ended the study because of the COVID-19; the per protocol (PP) population composed of all ITT patients with no major protocol deviation. Continuous and categorical variables were summarized using usual statistics. Non-inferiority analysis was made by an analysis of covariance in the PP population with the medical device as an explanatory variable and adjusted on the baseline A1C estimation. Then non-inferiority was demonstrated if the difference (LSmeans) between treatments did not overlap the non-inferiority margin (0.4%). Superiority was tested and demonstrated in the presence of a difference of 0.3% in favor of the new pump. A sensitivity analysis was performed on mITT population with imputation using the median values in case of missing data. In addition, univariate analyses were performed on age in class (according to the median value), gender, diabetes mellitus type, center, and duration of diabetes. Variables with a p-value less than 0.05 were included in the multivariate model. All other comparisons between groups were performed using Student’s t-test, a chi-squared test or a Fisher exact test.

The study was approved by an independent ethic committee and was registered in the French and European database of clinical studies (ID-RCB: 2019-A02566-51) and in the ClinicalTrials.gov protocol register under NCT04223973 (study start date: January 29, 2020; primary completion date: March 1, 2021; study completion date: June 1, 2021).

The study was performed in compliance with the General Data Protection Regulation (GDPR) and with the Data Privacy Committee CNIL MR001. The study was carried out in accordance with the Declaration of Helsinki. All patients were carefully informed about the study and gave written informed consent to participate.

Results

Patients disposition and baseline characteristics

Overall, 100 patients were included and 93 were randomized and used the allocated study device (ITT Population): 45 patients in the Omnipod group and 48 patients in the A7+TouchCare group. Among them, 78 completed the study: 43 (95.6%) in the Omnipod group and 35 (72.9%) in the A7+Touchcare group. The main reasons for premature study withdrawal were the Covid-19 context (4 patients ended the study because of the COVID-19 context and one withdrew consent), intolerance (4 patients), device dysfunction (3 patients), consent withdrawal (1 patient), or another reason (2 patients). The PP population was therefore composed of 78 patients (43 patients in the Omnipod group and 35 patients in the A7+TouchCare group). The mITT population was composed of 89 patients (45 in the Omnipod group and 44 in the A7+TouchCare group). (Fig 1)

As shown in Table 1, there was no significant or clinically relevant difference between groups in baseline characteristics including age, gender ratio, body mass index (BMI), time since diabetes diagnosis, time since the initiation of insulin pump treatment, and insulin daily doses. The last laboratory A1C value (± standard deviation, SD) was 7.8±0.8% (62 mmol/mol) in the Omnipod group and 7.8±0.7% in the A7+TouchCare group. No centre effect was found.

Table 1. Characteristics of study participants at baseline (ITT population).

		Omnipod N = 45	A7+Touchcare N = 48
Age (years)	Mean ± SD	50.3 ± 13.6	49.4 ± 11.7
	Min.; Max.	24; 75	22; 72
Gender	Female	29 (64.4%)	24 (50.0%)
	Male	16 (35.6%)	24 (50.0%)
BMI (kg/m ² )	Mean ± SD	25.4 ± 4.3	26.5 ± 4.1
	Min.; Max.	17.9; 37.3	17.6; 35.1
Diabetes type	Type 1	43 (95.6%)	41 (85.4%)
	Type 2	2 (4.4%)	7 (14.6%)
Time since diabetes diagnosis (yrs)	Mean ± SD	22.2 ± 11.5	22.7 ± 11.1
	Min.; Max.	3.7; 47.7	2.7; 44.0
Time since initiation of	Mean ± SD	7.1 ± 6.7	5.4 ± 4.3
insulin pump treatment (yrs)	Min.; Max.	0.1; 35.4	0.8; 19.0
Laboratory A1C (%)^*	Mean ± SD	7.8 ± 0.8	7.8 ± 0.7
	Min.; Max.	7; 9	7; 10
Basal insulin dose (IU/day)	Mean ± SD	16.1 ±5.9	18.7 ± 10.0
	Min.; Max.	6; 34	2; 43
Bolus insulin dose (IU/day)	Mean ± SD	21.5 ± 9.0	18.7 ± 10.9
	Min.; Max.	6; 41	1; 51

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Data are n (%) or means±SD; ND: not determined;

* Last laboratory A1C value of less than 1 month; No significant difference was observed between the two groups.

Primary outcome

In the PP population, the GMI after 3 months of use (Visit 3) was similar in the Omnipod group (mean ± SD: 7.4±0.8%, 57 mmol/mol) and the A7+TouchCare group (7.3±0.8%, 56 mmol/mol). As summarized in Table 2, the difference in GMI between device groups (Omnipod–A7+TouchCare) was 0.002% with a 95% CI of [-0.251; 0.255] in the PP population. The non-inferiority was demonstrated (p < 0.001) since the 95% CI of the difference did not overlap the non-inferiority margin (0.4%). This was confirmed in the mITT population. Age was the only significant covariate associated with the GMI (p = 0.0265) contrary to gender, type of diabetes, centre, and duration of diabetes (p > 0.10). Non-inferiority was also demonstrated in the PP Population in age-adjusted non-inferiority analysis. In all analyses, superiority was not demonstrated.

Table 2. Glucose management indicator (GMI): Non inferiority analysis at Visit 3 (Month 3).

	Omnipod	A7+Touchcare
Per protocol analysis	N = 43	N = 35
Estimated mean^* at Month 3	7.347 (0.085)	7.345 (0.094)
Estimated between-group difference [95%CI]	0.002 [-0.251; 0.255]
p-value for non-inferiority	<0.001
mITT analysis	N = 45	N = 44
Estimated mean^* at Month 3	7.388 (0.092)	7.287 (0.093)
Estimated between-group difference [95%CI]	0.101 [-0.158; 0.360]
P-value for non-inferiority	<0.001
Per protocol analysis adjusted for age	N = 43	N = 35
Estimated mean^* at Month 3	7.344 (0.086)	7.341 (0.095)
Estimated between-group difference [95%CI]	0.003 [-0.251; 0.257]
P-value for non-inferiority	<0.001

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* LSmeans (SEM); Difference Omnipod—A7+Touch Care; Missing values in the mITT population were replaced by the median value.

Laboratory A1C

In the mITT population, there was no relevant variation in laboratory A1C which remained stable between inclusion (mean ± SD: 7.8±0.7%, 62 mmol/mol) and Visit 3 (7.7±0.7%, 61 mmol/mol) without statistically significant difference (p = 0.565) between the two groups.

Freestyle Libre data

The mean (± SD) CGM wearing rate was not significantly different between the Omnipod group and the A7+TouchCare group at each visit: 91.3±11.4% vs. 90.0±13.6% (p = 0.625) at inclusion, 94.5±7.0% vs.91.6±11.8% (p = 0.200) at Visit 2, and 91.3±11.3% vs. 89.2±19.4% (p = 0.568) at Visit 3.

Regardless of devices, the average glucose level remained stable between inclusion (165.2±27.2 mg/dL) and Visit 3 (164.2±22.7 mg/dL) without statistically significant difference between groups (p = 0.932) (Table 3). The coefficient of variation of glucose value was 40.6% at Visit 3 similar to baseline (40.8%) without statistically significant difference between groups (p = 0.649).

Table 3. Continuous glycaemic parameters at each visit (ITTm population).

		Omnipod	A7+TouchCare	p-value
Average glucose level (mg/dL)	V1	N = 45	N = 44	0.784
	V1	164.4 ± 22.7	166.0 ± 31.4	0.784
	V2	N = 43	N = 37	0.560
	V2	163.3 ± 22.3	160.4 ± 21.9	0.560
	V3	N = 43	N = 36	0.932
	V3	164.4 ± 21.8	164.0 ± 24.0	0.932
Standard deviation of glucose values (mg/dL)	V1	N = 45	N = 44	0.970
	V1	67.2 ± 15.3	67.4 ± 16.4	0.970
	V2	N = 41	N = 36	0.912
	V2	66.1 ± 16.0	66.5 ± 15.2	0.912
	V3	N = 42	N = 35	0.895
	V3	66.6 ± 16.6	67.1 ± 14.7	0.895
Coefficient of variation (%) of glucose values	V1	N = 45	N = 44	0.564
	V1	41.3 ± 7.5	40.4 ± 7.6	0.564
	V2	N = 42	N = 35	0.546
	V2	40.7 ± 6.9	41.7 ± 7.7	0.546
	V3	N = 42	N = 35	0.649
	V3	40.2 ± 7.0	41.0 ± 8.0	0.649
Hypoglycaemic events (per week)	V1	N = 45	N = 44	0.816
	V1	5.7 ± 3.3	5.6 ± 3.4	0.816
	V2	N = 43	N = 37	0.383
	V2	5.5 ± 3.1	6.2 ± 4.1	0.383
	V3	N = 43	N = 36	0.602
	V3	5.3 ± 3.2	5.8 ± 4.1	0.602
Time below range (TBR) (%)	V1	N = 45	N = 44	0.271
	V1	7.0 ± 5.0	5.9 ± 4.2	0.271
	V2	N = 43	N = 37	0.973
	V2	7.2 ± 8.0	7.1 ± 5.5	0.973
	V3	N = 43	N = 36	0.223
	V3	5.6 ± 3.9	7.1 ± 6.4	0.223
Time in range (TIR) (%)	V1	N = 45	N = 44	0.685
	V1	56.6 ± 12.9	55.4 ± 14.7	0.685
	V2	N = 43	N = 37	0.760
	V2	58.1 ± 12.6	58.9 ± 12.1	0.760
	V3	N = 43	N = 36	0.512
	V3	58.4 ± 13.1	56.5 ± 12.3	0.512
Time above range (TAR) (%)	V1	N = 45	N = 44	0.500
	V1	36.6 ± 13.8	38.7 ± 15.8	0.500
	V2	N = 43	N = 37	0.788
	V2	34.7 ± 13.9	33.9 ± 12.4	0.788
	V3	N = 43	N = 36	0.891
	V3	36.0 ± 13.4	36.4 ± 13.4	0.891

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Data are means ± SD

The mean number of hypoglycemia events per week, regardless of device, remained stable between inclusion (5.6±3.3) and Visit 3 (5.5±3.6) without difference between groups (p = 0.602, at Visit 3) (Table 3). The TBR, TIR and TAR were 6.3%, 57.5% and 36.2% at Visit 3 quite similar to values at inclusion (6.4%, 56.0%, and 37.6%, respectively). There was no statistically significant difference between device groups in hypoglycemic events, or percentage of time spent in TBR, TAR and TAR at each visit.

Insulin dose administered

As shown in Table 4, there was no statistically significant difference between groups in basal, bolus or total daily dose of insulin administered. At Visit 3, the number of bolus per day was 4.1±1.3 in the Omnipod group and 4.2±1.7 in the A7+TouchCare group (p = 0.758).

Table 4. Insulin doses administered at each visit (mITT population).

		Omnipod	A7+TouchCare	p-value
Total insulin dose (basal + bolus) (IU/day)	V1	N = 45 37.6 ± 11.8	N = 44 36.8 ± 15.0	0.788
	V2	N = 41 38.0 ± 11.5	N = 37 38.9 ± 14.1	0.757
	V3	N = 42 37.3 ± 12.6	N = 36 37.3 ± 14.9	0.984
Basal insulin dose (IU/day)	V1	N = 45 16.1 ± 5.9	N = 44 18.6 ± 9.6	0.153
	V2	N = 41 16.4 ± 5.6	N = 37 19.7 ± 9.6	0.073
	V3	N = 42 16.3 ± 5.8	N = 36 19.4 ± 9.3	0.088
Bolus insulin dose (IU/day)	V1	N = 45 21.5 ± 9.0	N = 44 18.2 ± 11.0	0.135
	V2	N = 41 21.5 ± 9.2	N = 37 19.1 ± 9.2	0.257
	V3	N = 42 21.1 ± 9.8	N = 36 17.9 ± 9.8	0.160
Number of bolus per day	V1	N = 45 4.1 ± 1.2	N = 44 3.8 ± 1.6	0.227
	V2	N = 40 4.2 ± 1.3	N = 37 4.3 ± 1.8	0.800
	V3	N = 42 4.1 ± 1.3	N = 36 4.2 ± 1.7	0.758

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Data are means±SD

Patients’ satisfaction and preference

Results of the satisfaction questionnaire at Visit 2 and Visit 3 in the mITT population are provided in Table 5. Overall, the satisfaction for the A7+TouchCare was quite similar to Omnipod. At visit 3, the mean satisfaction score was ≥ 4 (satisfied/very satisfied) for 16/19 questions in the Omnipod group and 14/19 questions in the A7+TouchCare group. On average, patients were more satisfied about pump piloting with the A7+TouchCare pump PDM (questions 11, 12, 13, & 14). This was based on PDM ease of use as understanding of the instruction displayed (questions 12 and 14) and in terms of discretion for the use of the system in public (question 13). The A7+TouchCare pump PDM was gaining better score than the Omnipod pump PDM regarding the patient satisfaction whatever the visit.

Table 5. Satisfaction questionnaire at Visit 2 and Visit 3 (mITT population).

	Visit 2		Visit 3
	Omnipod	A7+ TouchCare	Omnipod	A7+ TouchCare
1. How satisfied are you with the control of your blood sugar obtained with the pump?	N = 42	N = 35	N = 41	N = 34
	4.0 ± 0.9	4.0 ± 0.9	4.2 ± 0.7	4.0 ± 0.9
2. How would you qualify the management of your treatment with the pump?	N = 43	N = 36	N = 43	N = 36
	4.3 ± 0.7	4.0 ± 1.0	4.2 ± 0.7	3.8 ± 1.0
3. Overall, how satisfied were you with the pump?	N = 42	N = 36	N = 43	N = 36
3. Overall, how satisfied were you with the pump?	4.1 ± 0.9	3.7 ± 0.9	4.1 ± 0.7	3.5 ± 1.2
4. How would you rate your level of daily comfort after wearing the pump?	N = 43	N = 36	N = 43	N = 36
	4.2 ± 0.9	3.7 ± 1.0	3.9 ± 0.9	3.4 ± 1.1
5. Was it easy for you to insert the needle of the syringe into the reservoir of the pump?	N = 43	N = 35	N = 43	N = 36
	4.6 ± 0.7	4.3 ± 0.9	4.6 ± 0.7	3.9 ± 1.2
6. Was it easy to put down the pump you just used?	N = 43	N = 35	N = 42	N = 36
6. Was it easy to put down the pump you just used?	4.5 ± 0.7	4.2 ± 0.8	4.5 ± 0.7	4.0 ± 0.9
7. Was it painful to insert the pump needle that you just used in the past few weeks?	N = 43	N = 34	N = 43	N = 36
	2.2 ± 1.2	2.4 ± 1.4	2.6 ± 1.3	2.6 ± 1.4
8. In general, would you say giving insulin with the pump is convenient?	N = 42	N = 34	N = 42	N = 36
	4.5 ± 0.8	4.3 ± 0.9	4.5 ± 0.6	4.2 ± 0.8
9. Would you say that delivering boluses with the pump is easy?	N = 43	N = 34	N = 43	N = 36
	4.7 ± 0.5	4.4 ± 0.7	4.6 ± 0.5	4.4 ± 0.8
10a. Programming basal rates: Would you say this pump feature is easy to use?	N = 33	N = 24	N = 33	N = 25
	4.2 ± 0.7	4.1 ± 0.7	4.2 ± 0.8	4.3 ± 0.7
10b. Programming bolus: Would you say this pump feature is easy to use?	N = 32	N = 28	N = 31	N = 26
	4.5 ± 0.7	4.5 ± 0.6	4.4 ± 0.8	4.6 ± 0.6
10c. Temporary basal rate stop: Would you say this pump feature is easy to use?	N = 35	N = 25	N = 36	N = 30
	4.5 ± 0.7	4.5 ± 0.6	4.5 ± 0.7	4.4 ± 1.0
10d. Bolus calculator/bolus assistant: Would you say this pump feature is easy to use?	N = 26	N = 24	N = 28	N = 25
	4.1 ± 1.0	4.6 ± 0.6	4.2 ± 0.9	4.5 ± 0.7
10e. Insulin Active (IOB): Would you say this pump feature is easy to understand and to use?	N = 18	N = 22	N = 22	N = 25
	4.2 ± 1.1	4.3 ± 0.8	3.9 ± 1.2	4.4 ± 0.7
11. How satisfied are you overall with using the pump PDM?	N = 43	N = 35	N = 43	N = 35
	3.9 ± 0.9	4.3 ± 0.6	4.1 ± 0.8	4.1 ± 0.9
12. How do you qualify the ease of use of the pump’s PDM?	N = 43	N = 35	N = 43	N = 35
	4.1 ± 0.9	4.4 ± 0.7	4.2 ± 0.8	4.2 ± 1.0
13. How to qualify the discretion of use of the PDM of the pump?	N = 42	N = 34	N = 43	N = 36
	3.6 ± 1.2	4.3 ± 1.0	3.8 ± 1.0	4.4 ± 0.8
14. Was it easy to understand the instructions displayed on the pump PDM?	N = 43	N = 34	N = 43	N = 36
	4.3 ± 0.7	4.3 ± 0.7	4.3 ± 0.6	4.4 ± 0.8
15. Was it easy to remove the cannula from the pump?	N = 43	N = 34	N = 43	N = 36
15. Was it easy to remove the cannula from the pump?	4.6 ± 0.7	3.9 ± 1.1	4.6 ± 0.7	3.9 ± 1.2
16. How easy has it been to change the pump pods you have been wearing for the past few weeks?	N = 43	N = 34	N = 42	N = 36
	4.6 ± 0.5	4.1 ± 0.9	4.7 ± 0.5	4.0 ± 1.0

Open in a new tab

Data are means±SD

For each question, the scale went from 1 (very unsatisfied) to 5 (very satisfied), except for Question 7 about pain for which 5 was painful and 1 was not painful at all.

At Visit 3, patients randomized in the A7+TouchCare group had to indicate their preference for the insulin pump device on a scale from 1 to 5 where 1 indicated the preference for the A7+TouchCare pump and 5 the preference for Omnipod pump. The preference score was 3.2±1.4 for the insulin management system, 3.7±1.5 for the patch insulin delivery system, and 1.9±1.3 for the PDM.

Device-related adverse events

Irritation/itching were reported in 26.7% and 27.1% of patients in the Omnipod and the A7+Touch Care, respectively. Redness were reported in 24.4% and 37.5% of patients in the Omnipod and the A7+Touch Care, respectively. As shown in S1 Table, there was no statistically significant differences between device groups (p = 0.964 and p = 0.174, respectively). Other related adverse events were more frequently (p = 0.010) reported in the A7+TouchCare group (31.3%) compared with the Omnipod group (8.9%). This was mainly due to more frequent bleeding or pain at the injection site, error using the device, or connection problems in the A7+TouchCare group.

One serious adverse event related to the A7+ Touch Care pump (3 episodes of ketonemia) was reported during the study. The patient was not life-threatened and the resolution of this event was rapid and positive. However, the patient was withdrawn from the study and resumed the use of his previous pump.

Discussion

The A7+TouchCare is an insulin patch pump system recently available on the market in some European countries. The aim of the study was to determine the clinical performance and patients’ satisfaction of the A7+TouchCare compared to the Omnipod insulin patch pump, which was the only patch pump available in France to date. Here, we demonstrated similar performance to achieve glycemic control with the A7+TouchCare.

This is the first report of clinical data on this new device, through a randomized study that included middle aged adult patients (mean age: 50 years-old), mostly with T1D and a long duration of diabetes (> 20 years). Glycemic control was suboptimal at baseline (mean A1c: 7.8%, 62 mmol/mol), considering that participants were already users of an insulin pump and a flash CGM device. Moreover, it is interesting to note a mean BMI of 25.4 and 26.5 kg/m2 for Omnipod and A7+Touchcare group, respectively, despite a total daily dose of insulin limited to 60 units per day. Therefore, these baseline characteristics are representative of a real-world population [19].

The Omnipod patch pump is known to provide improved glycemic control and preference compared to MDI or conventional insulin pumps in patients with diabetes [12–14]. Although various patch pumps systems have been recently developed [15], there is a lack of head-to-head comparison between different insulin patch pump systems. Here, we demonstrated that the performance of the A7+TouchCare was non inferior compared with the Omnipod patch system, based on the GMI. Other glycemic parameters based on CGM were also not significantly different between the two insulin patch pumps, and the total dose of insulin administered including the basal and bolus infusion were comparable with both devices.

A1C is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. For this study, we made the choice of A1C evaluation obtained from sensor measurements (GMI), which is considered as a reliable estimation of the average glucose value [16, 17]. In a secondary analysis, we confirmed that there was no statistically significant difference between insulin pumps in laboratory A1C after 3 months of use. However, A1C is not informative of the percentage of time spent in hyper or hypoglycemia and does not reflect the day-to-day glucose variability. Therefore, CGM provides crucial data as the percentage of time spent in target range (70–180 mg/dL) and time spent below range (<70 mg/dL). One major goal for effective and safe glucose control is to reach a percentage of time in range of at least 70% while reducing the time below range to less than 4% [16]. In the present study, in patients with T1D or T2D, the TBR after 3 months regardless of the insulin patch pump used was 6.3±5.2%, and the TIR was 57.5±12.7%, similar to baseline values (6.4±4.6% and 56.0±13.7%, respectively). These results were closed but suboptimal compared to the recommended target values (4% and 70%, respectively) but the observation period was only 3 months. There was no statistically significant difference between groups in these metrics. The study also showed that glycemic metrics including average glucose level and variability remained stable in the A7+TouchCare group and the Omnipod group without significant difference between groups. Glycemic variability is a therapeutic challenge and a frequent issue for patients with long lasting diabetes. In addition to causing glycemic excursions or severe hypoglycemia, it places a heavy mental burden on the patient [20]. Predictive low-glucose suspend systems and hybrid closed-loop systems are the ideal solution to address this issue with a real-time adjustment of insulin infusion. These systems represent the future of insulin pump use and are already spreading with a large amount of very positive results from “real-world” data [21–24]. In this context, Medtrum has already improved its TouchCare pump by developing a next generation pump. The A8 version, also known as Nano, is designed to address most of the drawbacks reported in the present study [25].

An important aspect of continuous insulin infusion device is to ensure that people interact properly with technology [26]. Thus, patient’s treatment satisfaction and preference are important consideration. The satisfaction questionnaire in our study showed that patients in both groups were satisfied/very satisfied with the patch delivering insulin and the PDM. Although differences between groups in each question may be not relevant, higher level of satisfaction was obtained in the A7+TouchCare group for some questions related to the use of the PDM system, such as ease of use, discretion of use, or calculator/bolus assistant usage (advanced functionalities). On the contrary, lower level of satisfaction was obtained for the ease of usage related to the insulin reservoir patch, or related to cannula including comfort on daily wear, insertion or removal. The preference questionnaire showed that patients preferred the Omnipod POD as insulin delivery device although one advantage of the A7+TouchCare is that the insulin reservoir can be replaced without having the need to replace the electronic part (located in the pump base). On the other hand, participants preferred the A7+TouchCare PDM for piloting the pump and advanced functionalities setting. However, it should be noted that all patients had been using the Omnipod pump for several months or years before the study and were thus familiar with its use. Moreover, patients in the A7+TouchCare group received only minimal training at inclusion, without any renewal of this training as it is usually done in the French daily practice by certified diabetic nurses educator from home care companies that detail and take care of patients at their home on regular basis. Finally, the Covid 19 context did not help neither as some intermediate visit (such as visit 2) where led on remote mode.

During the study period, some device errors were reported. Dysfunction reported are consistent with feedback from patients using this type of device in real life [26]: occlusion and detachment were relatively frequent in both groups but these were generally minor defects without severe consequences in terms of safety (excepted one case of ketosis leading to study withdrawal). In line with a joint statement of the European association for the study of diabetes and the American diabetes association diabetes technology working group [26], there is, for the Medtrum pump (as like other devices), a need for education and training of patients in learning how properly fixing the pump base to the reservoir-patch and identifying the best place for patch setting and skin preparation to increase adherence of patch.

Patch pumps adheres to the skin with adhesives which can induce more or less harmless skin reactions compared to conventional insulin pumps, as they require a larger adhesive area. In this study, adverse events related to the study devices were relatively frequent in both patch pump groups, but as is the case in current practice and reported by patients in real-life use [26, 27]. This included itching/irritation and redness at injection site which were specifically investigated for this study. Itching/irritation and redness were relatively frequent but without statistically significant difference between groups. No allergic reaction or infection at the administration site was reported.

One major limitation of this study is that patients were experienced in using insulin patch pump. They were equipped with an insulin pump since several years and all patients were familiar with diabetes-related technology; thus, results should be generalized with caution to other novice diabetes populations. In order to facilitate the recruitment, we decided to include all patients who already used the Omnipod pump before randomization (and thus without a change of their pump). On the other hand, patients in the A7+TouchCare group had only minimal training in using the new insulin patch pump system. This may have an impact on the study outcomes including performance, notification of malfunctions or adverse effects, satisfaction, or preference. This also draws the attention on being more specific in patients training and for the train-the-trainer programmes [26]. Obviously, it was not possible to mask the study device, and this study was designed as an open-label study. This may have an impact on the recording of adverse events, especially mild cases. Finally, although patients with T2D were included in this study, their number was too small to generalize the study results in these patients.

Conclusion

Both Omnipod and A7+TouchCare pumps showed similar performance to achieve glycemic control in patients with diabetes and the level of satisfaction was quite similar between groups. Although patients preferred the Omnipod as insulin management system and more specifically the patch delivery system (POD) of the Omnipod pump, they seem to prefer the PDM of the A7+TouchCare system for controlling and managing their pump. Overall, the A7+TouchCare may be a valuable alternative to Omnipod or other insulin patch pumps in some patients with diabetes.

Supporting information

S1 Table. Skin tolerability and adverse events between inclusion and Visit 3 (Safety population).

(DOCX)

Click here for additional data file.^{(14.4KB, docx)}

S1 Checklist. CONSORT 2010 checklist of information to include when reporting a randomised trial*.

(DOC)

Click here for additional data file.^{(217.5KB, doc)}

S1 File

(PDF)

Click here for additional data file.^{(310.7KB, pdf)}

S2 File

(PDF)

Click here for additional data file.^{(1.9MB, pdf)}

Acknowledgments

The authors would like to thank CRO Axonal-Biostatem (Castries, France) for study management, data management and statistics, and Thierry Radeau Consulting (Epinay-Sous-Senart, France) for medical writing support in accordance with Good Publication Practice (GPP3) guidelines (https://www.ismpp.org/gpp3).

Data Availability

Ethical and legal restrictions apply to the data as public data-sharing was not planned in the information letter given to and signed by participants at inclusion in the study. Data-sharing would therefore require an amendment of the information given to patients after acceptance by the ethics committee and then participants.Here is the contact access for the ethics committee that approved the study: Comité de protection des personnes VI CHU G. MONTPIED Administration centrale 58 rue Montalembert BP 69 – 63003 CLERMONT FERRAND cedex 1, FRANCE Tél: +33 4 73 75 10 73 – Fax: +33 4 73 75 10 69 mail: cpp-sudest6@chu-clermontferrand.fr

Funding Statement

Medtrum Technologies Inc. Shanghai supported this study. The funder had no role in the study design, data collection, and analysis. AP (principal investigator) takes full responsibility for the work, including the decision to submit and publish the manuscript. The findings and conclusions in this study are those of the authors and do not necessarily represent the sponsor's views.

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PLoS One. doi: 10.1371/journal.pone.0289684.r001

Decision Letter 0

Maria Elisabeth Johanna Zalm

4 Nov 2022

PONE-D-22-17489Performance and patients’satisfaction with the A7+TouchCare insulin patch pump system: a randomized controlled non-inferiority studyPLOS ONE

Dear Dr. Amadou,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Your manuscript has been assessed by two reviewers and their reports are appended below. The reviewers comment that the discussion section should comment on device disfunction and other adverse events reported for the pump. In addition, the reviewers have requested further detail and/or clarifications regarding the statistical analyses reported in this study. Furthermore, the journal's editorial team has noted that the ethics statement in this article reports that "The study was approved by an independent ethic committee" only. Please provide more details regarding the ethics committee that approved this study. Could you please revise the manuscript to carefully address the concerns raised?

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Reviewer #1: The article “Performance and patients’satisfaction with the A7+TouchCare insulin patch pump

system: a randomized controlled non-inferiority study” by Amadou and colleagues describes a clinical study with insulin pumps. The study is well-designed and results are presented in a comprehensive manner. Thank you for this nice contribution. I only have some minor comments:

General: I would recommend using the term “glucose management indicator (GMI)” instead of “estimated A1C” as this is state of the art and the methods section references the article by Bergenstal et al. that introduced the GMI

Methods: Obviously there was no inclusion criterion that describes a minimum required duration of pump use before study start. According to Table 1 the minimum duration was 0.1 years. This appears too short to be able to differentiate study outcomes from improvements in HbA1c due to change from MDI to CSII.

Results and Discussion: It seems like there is a kind of safety issue with the A7+TouchCare pumps, because 7 patients dropped out due to intolerance or device dysfunction and in general, there were more adverse events with this pump. I think this is should be paid more attention in the discussion of the article.

Author contributions: All investigators all listed as authors, but most of them did not make any further contributions to the manuscript. This is not conform with the ICMJE authorship criteria; e.g. critically revising the manuscript is another required contribution.

Reviewer #2: Here are some comments:

Statistical methods:

“In addition, univariate analyses were performed on age in class (according to

the median value), gender, diabetes mellitus type, center, and duration of diabetes.Variables with a p-value less than 0.05 were included in the multivariate model using a stepwise strategy.” My comment here is that conclusions on these variables should be drawn from a full model i.e. a multiple model including all variables. The stepwise strategy is not needed and if any adjustment for the primary analysis is done, why not adjust for all?

Table 1. Why include statistical tests. Since this is a randomized trial this is not needed. Read about “the table 1 fallacy” and point 15 in the consort checklist http://www.consort-statement.org/checklists/view/32--consort-2010/510-baseline-data.

How was the p-value for non-inferiority calculated (table 2)? Probably through the lsmeans statement, include this in the methods.

Table S1: Please indicate which test that is used and double check the p-values, is the result for “Redness” correct?

Why is the “other adverse events” not discussed and is the conclusion “Overall, the A7+TouchCare may be a safe and valuable alternative to Omnipod..” correct?

Minor: The following sentence is repeated: “The inclusion of patients already using a pump was done to facilitate recruitment into the study. The inclusion of patients already using a pump was done to facilitate recruitment into the study.”

**********

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2023 Aug 24;18(8):e0289684. doi: 10.1371/journal.pone.0289684.r002

Author response to Decision Letter 0

28 Feb 2023

Dear Editor,

The manuscript has been revised.

You will find answers to each comment below (italics and bold).

Major and minor corrections (responding to comments) have been highlighted in yellow in the revised manuscript (“Revised Manuscript with Track Changes”). We also provide a final clean version (“'Manuscript”).

We are confident that the quality of the manuscript is now improved, and we hope our revised version will be considered suitable for publication.

“The reviewers comment that the discussion section should comment on device dysfunction and other adverse events reported for the pump. In addition, the reviewers have requested further detail and/or clarifications regarding the statistical analyses reported in this study.”

We made a detailed response for each comment.

Furthermore, the journal's editorial team has noted that the ethics statement in this article reports that "The study was approved by an independent ethic committee" only. Please provide more details regarding the ethics committee that approved this study.

The study was approved by the following French ethics committee:

CPP VI CHU G. MONTPIED – Administration centrale –

58 rue Montalembert

BP 69 – 63003 CLERMONT FERRAND cedex 1, FRANCE

Tél : +33 4 73 75 10 73 – Fax : +33 4 73 75 10 69

mail : cpp-sudest6@chu-clermontferrand.fr

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YES. The study was funded by Medtrum France (Boulogne Billancourt, France).

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Amended statement “Medtrum Technologies Inc. Shanghai supported this study. The funders had no role in study design, data collection and analysis. AP (principal investigator) takes full responsibility for the work, including the decision to submit and publish the manuscript. The findings and conclusions in this study are those of the authors and do not necessarily represent the sponsors' views”

3. Thank you for stating the following in the Competing Interests section:

I have read the journal's policy and the authors of this manuscript have the following competing interests: C.A. has received writing/consulting honoraria from Medtrum for the present study, declares congress invitations from Eli Lilly, Astrazeneca, and Sanofi; has received speaker honoraria from Diabeloop SA and Eli Lilly; has served on advisory board panels for Eli Lilly. V.M. has received congress invitations from: Novo-Nordisk, Isis, Sadir, Vitalaire, Orkyn, Medtronic, and speaker fees or consultancy for expertise from: Medtrum, ISIS, Novo-Nordis. J.A. has received congress invitations, speaker honoraria, and consultancy fees from Lilly, Sanofi and Medtronic and has served on advisory board panels for Novonordisk, Ypsomed, Medtrum and Glooko. S.C. has received no congress invitations, speaker honoraria, and consultancy fees over the last 24 months. D.G. has received congress invitations, speaker honoraria, and consultancy fees from Eli-Lilly, Novo-Nordisk, Sanofi-Diabète, Abbott, Medtronic, Astra Zeneca. L.C. declares that she has no engagement, fees or honoraria conflicting with her participation to the project. B.C. has received congress invitations, speaker honoraria, and consultancy fees from Medtronic Dexcom and Abbott. P.S.-B. has received conference invitations, honoraria and consultancies from Abbott Diabetes Care, Eli-Lilly, Novo-Nordisk, Roche Diabetes Care and Ypsomed. C.P. has received no congress invitations, speaker honoraria, and consultancy fees over the last 24 months. C.T. has received honoraria for consultancy, speaker for conferences and congress invitations, from Abbott, Janssen, Lilly, Medtronic, Roche Diabetes Care, Sanofi. A.P. has received congress invitations, speaker honoraria, and consultancy fees from Abbott, Diabeloop, Eli Lilly and Company, Insulet, Lifescan, Medtronic, Novo Nordisk, and Sanofi, and has served on advisory board panels for Abbott, Insulet, Medtrum, Novo Nordisk, and Sanofi.

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Here is the contact access for the ethics committee that approved the study:

CPP VI CHU G. MONTPIED – Administration centrale –

58 rue Montalembert

BP 69 – 63003 CLERMONT FERRAND cedex 1, FRANCE

Tél : +33 4 73 75 10 73 – Fax : +33 4 73 75 10 69

mail : cpp-sudest6@chu-clermontferrand.fr

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The ethics statement appears only in the Methods section now.

The caption for supporting information (supplemental table one) has been listed at the end of the manuscript as required.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Partly

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

3. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

Reviewer #2: No

4. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

5. Review Comments to the Author

Reviewer #1: The article “Performance and patients’ satisfaction with the A7+TouchCare insulin patch pump system: a randomized controlled non-inferiority study” by Amadou and colleagues describes a clinical study with insulin pumps. The study is well-designed and results are presented in a comprehensive manner. Thank you for this nice contribution. I only have some minor comments:

This has been corrected in the text.

We understand your concern, but the participants were randomized at baseline, so the effect of the switch from MDI to CSII is supposed to be the same in the two groups. Most patients had been using a pump for 5-7 months. The patients' motivation was to have the opportunity to test an innovative and smaller device. The aim of the study was not to demonstrate superiority of the Medtrum device but to show that the results were similar to Insulet under comparable conditions.

There are indeed more AEs and dysfunctions reported in the A7+ Touchcare group. It appeared after discussion with the centres that patients who had already been using the Omnipod pump for several months did not report all events because they were used to their occurrence. On the other hand, in the A7+ Touchcare group, patients who received minimal and rapid training did not always have a perfect mastery of the devices and probably had a more systematic notification of events. Furthermore, it should be remembered that the study was carried out in the context of the covid epidemic, with support from the health care teams that was somewhat different from a normal context, which may have increased the anxiety of the patients in the A7+ Touchcare group when events occurred.

The manuscript has been sent for review and validation to all co-investigators. The author contribution statement has now been updated.

Reviewer #2: Here are some comments:

Statistical methods:

“In addition, univariate analyses were performed on age in class (according to

the median value), gender, diabetes mellitus type, center, and duration of diabetes. Variables with a p-value less than 0.05 were included in the multivariate model using a stepwise strategy.” My comment here is that conclusions on these variables should be drawn from a full model i.e. a multiple model including all variables. The stepwise strategy is not needed and if any adjustment for the primary analysis is done, why not adjust for all?

Indeed, only one variable was significant at the 5% level, so we removed the stepwise strategy in the article since it was considered but not used.

You are right, the p-values should not be displayed in table 1. We removed it from the table.

How was the p-value for non-inferiority calculated (table 2)? Probably through the lsmeans statement, include this in the methods.

We have added this precision in the text.

Table S1: Please indicate which test that is used and double check the p-values, is the result for “Redness” correct?

Thank you for your attention. The value for redness was wrong (but still not significant) and has been modified.

Why is the “other adverse events” not discussed and is the conclusion “Overall, the A7+TouchCare may be a safe and valuable alternative to Omnipod..” correct?

Only the main adverse events usually described in the use of pumps and sensors were retained, the other AEs being minor. In addition, it should be noted that there is a potential bias because the patients in the Omnipod pump group had all been using the system for several months prior to inclusion and were therefore already sufficiently tolerant. This had the consequence of reducing or even not reporting tolerance problems that patients in this group are used to. We agree to change the conclusion sentence to “Overall, the A7+TouchCare may be a valuable alternative to Omnipod or other insulin patch pumps in some patients with diabetes.”

This has now been corrected in the text.

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Reviewer #1: No

Reviewer #2: No

Attachment

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PLoS One. doi: 10.1371/journal.pone.0289684.r003

Decision Letter 1

Aleksandra Klisic

16 Jun 2023

PONE-D-22-17489R1Performance and patients’satisfaction with the A7+TouchCare insulin patch pump system: a randomized controlled non-inferiority studyPLOS ONE

Dear Dr. Amadou,

Please submit your revised manuscript by Jul 31 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

6. Review Comments to the Author

Reviewer #2: (No Response)

Reviewer #3: PONE-D-22-17489R1

This is an interesting and well written study, as we lack RCTs regarding the achievements of insulin patch pumps. The current report adresses both performance and satisfaction with a new insulin patch pump in an appopriate, randomized design.

My main concern is that the abstract does not mention about the flow chart and premature study withdrawals, which were more frequent in the Touchcare group, leading to a desequilibrium between the two groups in the per protocol analysis.

Regarding satisfaction, the sentence on page 12 about the preference score is unclear, as the insulin management system, opposed to the patch insulin delivery system and the PDM, have not been clearly defined in the Materials section.

Minor comment: in the Method section, please state whether the fast insulin analog URLI was allowed or not.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

**********

PLoS One. 2023 Aug 24;18(8):e0289684. doi: 10.1371/journal.pone.0289684.r004

Author response to Decision Letter 1

6 Jul 2023

Dear Editor,

The manuscript has been revised.

You will find answers to each comment below (italics and bold).

We are confident that the quality of the manuscript is now improved, and we hope our revised version will be considered suitable for publication.

The original comments of reviewers are written in blue and our response in black just below.

� We have modified the abstract and added the number of premature withdrawals in each group.

� We agree that the sentence is not clear. The insulin management system designs the patch insulin delivery system and the PDM as a whole. We propose to modify the sentence by writing: “The preference score was 3.7±1.5 for the patch insulin delivery system, 1.9±1.3 for the PDM and 3.2±1.4 for the insulin management system (designing the patch insulin delivery and PDM as a whole).

Minor comment: in the Method section, please state whether the fast insulin analog URLI was allowed or not.

� The fast insulin analog URLI was not allowed in this study as it was not available in France at the moment of the study protocol development.

Dr Coralie Amadou, for all authors.

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file.^{(21KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0289684.r005

Decision Letter 2

Aleksandra Klisic

25 Jul 2023

Performance and patients’satisfaction with the A7+TouchCare insulin patch pump system: a randomized controlled non-inferiority study

PONE-D-22-17489R2

Dear Dr. Amadou,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Aleksandra Klisic

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Author,

The manuscript PONE-D-22-17489R2

"Performance and patients’ satisfaction with the A7+TouchCare insulin patch pump system: a randomized controlled non-inferiority study" by Dr Coralie Amadou is accepted for publication in PLOS ONE.

Sincerely,

Aleksandra Klisic

PLoS One. doi: 10.1371/journal.pone.0289684.r006

Acceptance letter

Aleksandra Klisic

14 Aug 2023

PONE-D-22-17489R2

Performance and patients’satisfaction with the A7+TouchCare insulin patch pump system: a randomized controlled non-inferiority study

Dear Dr. Amadou:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Aleksandra Klisic

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Table. Skin tolerability and adverse events between inclusion and Visit 3 (Safety population).

(DOCX)

Click here for additional data file.^{(14.4KB, docx)}

S1 Checklist. CONSORT 2010 checklist of information to include when reporting a randomised trial*.

(DOC)

Click here for additional data file.^{(217.5KB, doc)}

S1 File

(PDF)

Click here for additional data file.^{(310.7KB, pdf)}

S2 File

(PDF)

Click here for additional data file.^{(1.9MB, pdf)}

Attachment

Submitted filename: Response to editor and reviewers.docx

Click here for additional data file.^{(32KB, docx)}

Attachment

Submitted filename: Response to Reviewers.docx

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Data Availability Statement

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PERMALINK

Performance and patients’ satisfaction with the A7+TouchCare insulin patch pump system: A randomized controlled non-inferiority study

Coralie Amadou

Vincent Melki

Jennifer Allain

Sylvaine Clavel

Didier Gouet

Lucy Chaillous

Bogdan Catargi

Pauline Schaeplynck-Belicard

Catherine Petit

Charles Thivolet

Alfred Penfornis

Roles

Abstract

Background

Methods

Results

Conclusions

Clinical trail registration

Introduction

Materials and methods

Study design and patients

Pump characteristics

Continuous glucose monitoring

Clinical data collections

Study outcomes

Sample size

Statistical analysis

Results

Patients disposition and baseline characteristics

Fig 1. Flow chart.

Table 1. Characteristics of study participants at baseline (ITT population).

Primary outcome

Table 2. Glucose management indicator (GMI): Non inferiority analysis at Visit 3 (Month 3).

Laboratory A1C

Freestyle Libre data

Table 3. Continuous glycaemic parameters at each visit (ITTm population).

Insulin dose administered

Table 4. Insulin doses administered at each visit (mITT population).

Patients’ satisfaction and preference

Table 5. Satisfaction questionnaire at Visit 2 and Visit 3 (mITT population).

Device-related adverse events

Discussion

Conclusion

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Decision Letter 0

Maria Elisabeth Johanna Zalm

Roles

Author response to Decision Letter 0

Decision Letter 1

Aleksandra Klisic

Roles

Author response to Decision Letter 1

Decision Letter 2

Aleksandra Klisic

Roles

Acceptance letter

Aleksandra Klisic

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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