The primary objective of this study is to evaluate the percentage of time spent in target sensor glucose range (3.9–10.0 mmol/L (default) and 3.9–7.8 mmol/L (secondary)), comparing AID to SAPT during the RCT phase. The timing of all assessments is presented in Table 3.
Trained staff members will measure participants’ weight and height using standard procedures and calibrated instruments. Weight will be measured once to the nearest 0.1 kg, with shoes and heavy clothing removed. Height will be measured once to the nearest 0.1 cm. Height and weight will be used to calculate body mass index (BMI) which will be automatically populated by REDCap.
At the screening visit, investigative staff will collect demographic information including date of birth, gender, ethnicity, household income, and highest educational level. Participants may choose to select more than one ethnicity; however, each person will be allocated to a single ethnic group for the purposes of statistical analyses that will be prioritised in the order of Māori, Pacific, Asian and European/ Other . Total household income from all sources, before tax or anything taken out of it in the last 12 months and, the participants highest completed qualification (as well as the parent/ guardians’ if they are integral to their child’s diabetes care) will be recorded in the same manner used by the New Zealand Health Survey 2018–2019 .
HbA1c will be measured every three months throughout the RCT and continuation phases by calibrated point-of-care instruments (DCA Vantage Analyzer, Siemens Healthcare Diagnostics, Ireland), which meets acceptance criteria for HbA1c . Measurements > 130 mmol/mol (maximum reading possible) will be recorded as 130.
Individual CGM data will be pushed from the Android phone into a cloud-based server; Nightscout (this platform is better described under Data Management). CGM data will be analysed according to standardised CGM metrics for clinical care .
% CGM time 3.0–3.9 mmol/L (level 1 hypoglycemia).
% CGM time < 3.0 mmol/L (level 2 hypoglycemia).
% CGM time ≤ 2.5 mmol/L.
% CGM time 10.1–13.9 mmol/L (level 1 hyperglycemia).
% CGM time ≥ 14.0 mmol/L (level 2 hyperglycemia).
Mean sensor glucose and glucose variability (expressed primarily as a coefficient of variation and secondly as a SD).
Glycaemic outcomes differentiated as 24 h, day (0600–2159 h) and night (2200 − 0559 h).
Validated instruments will assess the self-reported impact the AID system has on participants/ their family at baseline, 24 weeks (day 168 + 7) and at 48 weeks (day 336 + 7). These instruments have been widely used in research and have demonstrated reliability and validity in our cohort completing them. Data will be collected via electronic (REDCap) questionnaires during clinical assessments and the order of administration will be standardized to increase reliability. All questionnaires are administered in English. Participant reported outcomes including fear of hypoglycaemia, eating behaviours, sleep quality, device experience and general health state will be monitored during the study and clinical teams will be alerted if participants report physical or mental problems demanding follow-up.
Hypoglycaemia Fear Survey II (HFS II)
The HFS II was developed to measure behaviours and worries related to fear of hypoglycaemia in people with T1D. It is a valid and reliable measure of fear of hypoglycaemia [33,34,35,36]. HFS II is composed of two subscales, the Behaviour (HFS-B) and Worry (HFS-W). HFS-B items describe behaviours in which people with T1D may engage to avoid hypoglycaemic episodes and/or their negative consequences (for example, maintaining higher BG levels, ensuring they are in the company of others, limiting exercise). HFS-W items describe specific concerns that people with T1D may have about their hypoglycaemic episodes (for example, being alone, episodes occurring during sleep).
Participants aged 7–17 years inclusive and their parent/ guardian will complete child and parent versions of the HFS II respectively. Participants 18 years and older will complete the adult version.
Sleep quality (Pittsburgh Sleep Quality Index; PSQI)
The PSQI is a 19-item self-report measure of subjective sleep quality and quantity in the previous month. The 19 items generate seven component scores: subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, sleep medication, and daytime dysfunction, with component scores summed to produce a global score. A global score > 5 suggests a “poor sleeper” with significant sleep complaints . The PSQI will be completed by participants 13 years inclusive and older.
Diabetes Treatment Satisfaction Questionnaire status (DTSQs)
The DTSQs is a questionnaire used to assess patients’ satisfaction with their diabetes treatment . The adult 8-item version is composed of two factors to measure treatment satisfaction and the burden from hyper/ hypoglycaemia. The DTSQs is internationally validated and officially approved by The World Health Organisation (WHO) and the International Diabetes Federation (IDF) . The 12-item DTSQs-Teen and 14-item DTSQs-Parent were developed through interviews with parents and teenagers to improve relevance, accessibility and intelligibility for teenagers .
In this study, DTSQs: Parent will be completed for participants 7–12 years inclusive. Participants 13–17 years inclusive will complete the teen version and the DTSQs: Adult will be completed by participants 18 years inclusive and older.
Health status (EuroQol 5-dimensional Questionnaire; EQ-5D)
EQ-5D is a family of three simple instruments to describe and value health. The CREATE trial will make use of two instruments; the EQ-5D-Y will be completed by subjects 8–15 years inclusive and the EQ-5D-5 L by those 16 years and older (an apt version does not exist for subjects of 7 years). Both versions comprise five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression (substituted for child friendly terms in the EQ-5D-Y). Respondents rate their health TODAY on each dimension. The EQ-5D-Y has three levels of severity (no problems, some problems and a lot of problems) and the EQ-5D-5 L five levels (no problems, slight problems, moderate problems, severe problems and extreme problems). EQ-5D is widely used and research has shown it to be valid and reliable . While the EQ-5D has not been validated in this instance to show improvement, it is still the preferred tool for including in any subsequent health economic analyses. The study has been set up to identify the burden of care in other ways, and so we are not entirely reliant on the EQ-5D for this.
Eating behaviours (Research food diary)
All participants will be asked to complete a food diary at home using the Research Food Diary app on four non-consecutive days (three weekdays and one weekend day) over one week during the run-in period and during the last week of the RCT phase. Research Food Diary is a free app from Xyris Software (Australia) Pty Ltd available on both Android and iPhone. This app is for use by participants in research studies only. Research Food Diary enables participants to record the foods they consume by searching the food database or by scanning barcodes. Participants will be asked to share their food diary with the research team to view in Easy Diet Diary Connect and the diary will then be analysed using FoodWorks 10 Professional (Version: 10.0.4266).
Platform performance will be gauged by assessing the percentage of time using AID mode for participants in the intervention arm during the RCT phase, and all participants during the continuation phase. Any technical issues encountered/ reported, both software and hardware related will be recorded in REDCap as device deficiencies.
Human-technology interaction and online collective learning
CREATE will aim to define the collective learning of participants and HCPs using open-source technology, so an education strategy can be effectively developed for clinical translation, as open-source innovations are not accompanied by the usual commercial training manuals. Quantitative analysis as well as qualitative tools such as ongoing content analysis of online peer-to-peer learning and individual interviews of both HCPs and participants as well as a HCP focus group will be used achieve this.
A purposive sample of participants (up to 15 children and parents/ caregivers, and up to 15 adults) in the intervention arm will be invited to participate in a face-to-face interview (either at the research centre or via a video conference) to obtain user feedback within six weeks of completing the RCT phase. Participants who discontinue the study will be offered this same opportunity to participate in an interview within one month leaving the study. Participant interviews will explore usability and acceptability of the intervention.
The CREATE trial is being conducted in New Zealand and recognises Māori as the tāngata whenua (indigenous people) of Aotearoa (New Zealand). In line with the Guidelines for Researchers on Health Research involving Māori , specific interviews informed by a kaupapa Māori framework (acknowledging Māori ways of knowing and conducting research) will be held to ensure determinants of health and cultural acceptability are explored within a safe environment. The CREATE trial endeavours to recruit 10 Māori participants in total (population representation), an example that the researchers are committed to fulfilling the principles of embodied in the Treaty of Waitangi - the founding document of New Zealand . In light of these small numbers, all Māori participants will be invited to participate in such an interview whether they completed 24 weeks of AID mode during the RCT phase or continuation phase. Interviews with Māori participants will be treated as an independent data set from non-Māori.
Remote or in-person interviews will be conducted with select HCPs within four weeks of their site completing the RCT phase of the study. The selection of HCPs will be informed by the makeup and emergent findings from the HCP focus group.
Healthcare professional focus group
A remote (video link) focus group will be held for HCPs in the study using Zoom (Zoom Video Communications Inc.) The HCP focus group will occur within one month of all sites completing five participants who have experienced three months of AID mode during the RCT phase. The focus group for HCPs will converge on their experiences supporting trial participants to use the AID system and the training materials provided.
Safety/ Adverse events (AE)
In this study reportable AE’s include any untoward medical occurrence meeting criteria for an:
Adverse Device Effect (ADE): an AE related to the use of the investigational devices (that is, insulin pump infusion set, sensor, transmitter or algorithm).
Serious ADE (SADE) or Sserious AE (SAE): an AE/ADE that is fatal or, life-threatening or, causes permanent impairment to a body structure/ function or, requires hospitalisation or, demands medical/ surgical intervention to curb such serious sequalae.
AE’s that do not satisfy seriousness criteria will not be recorded (for example, inter-current illness such as a viral upper respiratory tract infection or gastro-enteritis). Furthermore, hypoglycaemia and/ or hyperglycaemia events are an expected occurrence in patients with T1D and hence are not expected to be reported as an AE. However, any glycaemic excursion consistent with severe hypoglycaemia (that is, the participant experiences altered mental consciousness and as a result is unable to assist in their care), severe hyperglycaemia (that is, blood glucose > 16.7 mmol/L, blood ketones > 1.5 mmol/L and symptomatic) or DKA (that is, blood glucose > 13.9 mmol/L, either arterial pH < 7.3 or venous pH < 7.24, bicarbonate less than < 15 mEq/L, moderate ketonuria/ ketonemia and requiring hospital treatment) is considered an untoward event and will be reported as a SAE.
Device deficiencies (DD), that is, inadequacy of a medical device with respect to its identity, quality, durability, reliability, saftey or performance (requirements of ISO 14155:2011) will be reported and assessed as to whether they possess SADE potential. A DD with SADE potential will be managed as per a SADE with expedited reporting to the Co-ordinating Investigator within one working day. Use errors will not be recorded unless they result in an ADE.
ADE, SADE, SAE and DD collection will occur unceasingly from initial product use until completion of the final study assessments. These events will be entered into REDCap in a timely manner and the following information will be captured: start/ stop date of the event, associated symptoms, seriousness, intensity, relationship to the investigational device, treatment and outcome.