A Three-Arm Randomized Controlled Study Comparing Patient-Reported Outcomes in People With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion or Multiple Daily Injections.

BACKGROUND: The aim of this study was to compare patient-reported outcomes (PROs) in people with type 1 diabetes using either continuous subcutaneous insulin infusion (CSII) with two different insulin patch pumps or multiple daily injections (MDIs). MATERIALS AND METHODS: In this randomized three-arm study, people with type 1 diabetes on MDI therapy were included and used either MDI, the Accu-Chek Solo micropump system (Solo) or Omnipod for 26 weeks. From weeks 26 to 39, all participants used CSII with Solo. Patient-reported outcomes were assessed using the diabetes technology questionnaire (DTQ); in addition, HbA1c values were measured. RESULTS: Overall, 181 participants were randomized (61 MDI arm, 62 Solo arm, 58 Omnipod arm) and 142 completed the study. After 26 weeks in the study, the DTQ "change" score in the Solo group (105.9 [100.6-111.2]; baseline-adjusted mean [95% confidence interval]) was significantly higher than in the MDI group (94.8 [89.6-100.0]) (P = .001). The comparison between the Solo group (105.1 [99.1-111.1]) and the Omnipod group (108.7 [103.1-114.4]) showed no significant differences (P = .382). HbA1c increased by 0.2% ± 0.7% in the MDI group and decreased in both pump groups (Solo group -0.2% ± 0.8% and Omnipod group -0.1% ± 0.8%). Differences in HbA1c between the Solo group and the MDI group were significant (P = .009), but not between the Solo group and the Omnipod group (P = .896). CONCLUSIONS: This study showed that switching from MDI to CSII improves both psychosocial well-being and physiological outcomes. Furthermore, there were no substantial differences between the established and the recently released patch pump. Trial registration at www.clinicaltrials.gov is NCT03478969.

Diabetes management intervention studies: lessons learned from two studies.

INTRODUCTION: Several clinical studies investigated improvements of patient outcomes due to diabetes management interventions. However, chronic disease management is intricate with complex multifactorial behavior patterns. Such studies thus have to be well designed in order to allocate all observed effects to the defined intervention and to exclude effects of other confounders as well as possible. This article aims to provide challenges in interpreting diabetes management intervention studies and suggests approaches for optimizing study implementation and for avoiding pitfalls based on current experiences. MAIN BODY: Lessons from the STeP and ProValue studies demonstrated the difficulty in medical device studies that rely on behavioral changes in intervention group patients. To successfully engage patients, priority should be given to health care professionals being engaged, operational support in technical issues being available, and adherence being assessed in detail. Another difficulty is to avoid contamination of the control group with the intervention; therefore, strict allocation concealment should be maintained. However, randomization and blinding are not always possible. A limited effect size due to improvements regarding clinical endpoints in the control group is often caused by the Hawthorne effect. Improvements in the control group can also be caused with increased attention paid to the subjects. In order to reduce improvements in the control group, it is essential to identify the specific reasons and adjust study procedures accordingly. A pilot phase is indispensable for this. Another option is to include a third study arm to control for enhanced standard of care and study effects. Furthermore, retrospective data collection could be a feasible option. Adaptive study designs might reduce the necessity of a separate pilot study and combine the exploratory and confirmatory stages of an investigation in one single study. CONCLUSION: There are several aspects to consider in medical device studies when using interventions that rely on changes in behavior to achieve an effective implementation and significant study results. Improvements in the control group may reduce effect sizes and limit statistical significance; therefore, alternatives to the traditional randomized controlled trials may be considered.

Benefit of Digital Tools Used for Integrated Personalized Diabetes Management: Results From the PDM-ProValue Study Program.

BACKGROUND: Integrated personalized diabetes management (iPDM) is a digitally supported therapeutic concept to improve patient-physician interaction to overcome the aspects of clinical inertia. Integrated personalized diabetes management can support decision making and improve therapeutic outcomes of suboptimally controlled persons with insulin-treated type 2 diabetes (T2D). In this paper, we report the results of an analysis of the PDM-ProValue study program on the effectiveness and perceived benefit of this approach, with a focus on how physicians used and assessed the digital tools provided for the iPDM process. MATERIALS AND METHODS: The study program included two 12-month, prospective, controlled, cluster-randomized multicenter trials. A total of 101 practices participated with 907 patients. Practices were cluster-randomized to an intervention group and a control group. Digital tools for data visualization and analysis applied were used. HCP were asked to assess the use, relevance, and usefulness of the tools. RESULTS: A clear preference was stated for the visual overview over more statistically complex analyses. A total of 83% of the participants rated a high relevance of the "daily profile," 81% of the "total profile," and 68% the "risk illustrated by traffic light symbols" for the therapy decision. The overall iPDM process was very favorably rated with respect to structuredness and potential for personalized treatment and well accepted among health care professionals (HCP). CONCLUSIONS: Embedding digital tools in a structured process (iPDM) were proved to provide a benefit for insulin-treated T2D patients and their physicians. These results offer insight for further development and improvement of the tools and add information on how to overcome clinical inertia.

Integrated personalized diabetes management improves glycemic control in patients with insulin-treated type 2 diabetes: Results of the PDM-ProValue study program.

AIMS: Globally, many patients with insulin-treated type-2 diabetes are suboptimally controlled. The PDM-ProValue study program evaluated whether integrated personalized diabetes management (iPDM) has the potential to improve clinical outcomes. METHODS: 101 practices with 907 patients participated in the 12-month, prospective, controlled, cluster-randomized study program. HbA1c levels, therapy changes, frequency of hypoglycemic episodes, patient reported outcomes, and physician satisfaction were assessed. RESULTS: iPDM led to a greater reduction in HbA1c after 12 months vs. usual care (-0.5%, p < 0.0001 vs. -0.3%, p < 0.0001), (Diff. 0.2%, p = 0.0324). Most of the HbA1c reduction occurred after 3 months and remained stable thereafter. The percentage of patients with therapy adjustments was higher in the iPDM group at all visits (p < 0.01 at week 3, month 3, month 6). Patient adherence at month 12 was higher in the iPDM group compared to baseline (Odds ratio = 2.39; p = 0.0003); also, patient treatment satisfaction (DTSQc: 12.2 vs. 10.4, δ = 1.78, p = 0.004; DTSQs: 31.0 vs. 30.0, δ = 0.924, p = 0.02), and physician satisfaction was higher in the intervention group. CONCLUSIONS: iPDM improved the use of diagnostic data leading to better glycemic control, more timely treatment adjustments (indicating reduced clinical inertia), and increased patient adherence and treatment satisfaction among patients and physicians.

Integrated Personalized Diabetes Management (PDM): Design of the ProValue Studies: Prospective, Cluster-Randomized, Controlled, Intervention Trials for Evaluation of the Effectiveness and Benefit of PDM in Patients With Insulin-Treated Type 2 Diabetes.

BACKGROUND: Collaborative use of structured self-monitoring of blood glucose (SMBG) data and data management software, utilized within a 6-step cycle enables integrated Personalized Diabetes Management (PDM). The 2 PDM-ProValue studies shall assess the effectiveness of this approach in improving patient outcomes and practice efficiencies in outpatient settings. METHODS: The PDM-ProValue studies are 12-month, prospective, cluster-randomized, multicenter, trials to determine if use of integrated PDM in daily life improves glycemic control in insulin-treated type 2 diabetes patients. Fifty-four general medical practices (GPs) and 36 diabetes-specialized practices (DSPs) across Germany will be recruited. The practices will be randomly assigned to the control groups (CNL) or the intervention groups (INT) via cluster-randomization. CNL practices will continue with their usual care; INT practices will utilize integrated PDM. The sample size is 1,014 patients (n = 540 DSP patients, n = 474 GP patients). Each study is designed to detect a between-group difference in HbA1c change of at least 0.4% at 12 months with a power of 90% and 2-sided significance level of .05. Differences in timing and degree of treatment adaptions, treatment decisions, blood glucose target ranges, hypoglycemia, self-management behaviors, quality of life, patients attitudes, clinician satisfaction, practice processes, and resource consumption will be assessed. Study endpoints will be analyzed for the modified intent-to-treat and per protocol populations. Trial results are expected to be available in late 2016. DISCUSSION: Effective and efficient strategies to optimize diabetes management are needed. These randomized studies will help determine if PDM is beneficial.

Use of an insulin bolus advisor facilitates earlier and more frequent changes in insulin therapy parameters in suboptimally controlled patients with diabetes treated with multiple daily insulin injection therapy: results of the ABACUS trial.

BACKGROUND: We assessed the impact of using an automated bolus advisor integrated into a blood glucose meter on the timing and frequency of adjusting insulin therapy parameter settings and whether the availability of this technology would increase blood glucose test strip utilization in diabetes patients treated with multiple daily insulin injection (MDI) therapy. SUBJECTS AND METHODS: The Automated Bolus Advisor Control and Usability Study (ABACUS) trial, a 26-week, prospective, randomized, controlled, multinational study that enrolled 218 type 1 and type 2 diabetes patients, demonstrated that use of an automated insulin bolus advisor helps improve glycemic control in suboptimally controlled, MDI-treated patients. Patient data were assessed to determine when and how often changes in insulin parameter settings occurred during the study. Patient meters were downloaded to determine blood glucose monitoring frequency. RESULTS: One hundred ninety-three patients completed the study: 93 control arm (CNL) and 100 intervention (experimental) arm (EXP). Significantly more EXP (47.5%) than CNL (30.7%) patients received one or more changes in their insulin sensitivity factor (ISF) settings during the study (P=0.0191). Changes in ISF settings occurred earlier and more frequently in EXP than CNL patients throughout the study. A similar trend was seen in changes in insulin-to-carbohydrate ratios. There were no differences in daily self-monitoring of blood glucose frequency [mean (SD)] between CNL and EXP patients: 4.7 (1.5) versus 4.6 (1.3) (P=0.4085). CONCLUSIONS: Use of an automated bolus advisor was associated with earlier, more frequent changes in key insulin parameters, which may have contributed to subsequent improvements in glycemic control but without increased glucose test strip utilization.

Use of an integrated strip-free blood glucose monitoring system increases frequency of self-monitoring and improves glycemic control: Results from the ExAct study.

AIMS: We investigated the impact of using an integrated, strip-free system compared to the use of single-strip systems on testing frequency and glycemic control in individuals with insulin-treated diabetes. METHODS: This multinational, comparative, cluster-randomized, observational study included 311 patients with type 1 and insulin-treated type 2 diabetes who were performing SMBG at suboptimal frequencies. Sites were cluster-randomized to "integrated strip-free" system (EXP group) or any "single-strip" system (CNL group). Testing frequency and HbA1c were measured at baseline, 12 weeks and 24 weeks. RESULTS: At week 24, the EXP group showed an increase in SMBG frequency from baseline of 4.17 tests/week (95% CI 2.76, 5.58) compared with an increase of 0.53 tests/week (95% CI -0.73, 1.79) among CNL patients, resulting in a between-group difference of 3.63 tests/week (p < 0.0002). Mixed-effects models for repeated measurements (MMRM) controlling for baseline frequency of testing, country and clinical site confirmed a higher SMBG testing frequency in the EXP group compared to the CNL group, with a between-group difference of 2.70 tests/week (p < 0.01). Univariate analysis showed greater HbA1c reductions in the EXP group than CNL group: -0.44% (95% CI -0.59, -0.29) vs. -0.13% (95% CI -0.27, 0.01), respectively, p < 0.0002. MMRM analyses confirmed these HbA1c reductions. A greater percentage of EXP than CNL patients achieved HbA1c reductions of ≥0.5%: 45.1% vs. 29.1%, respectively, p < 0.01. CONCLUSIONS: The use of an integrated, strip-free SMBG system improved testing adherence and was associated with improvements in glycemic control.

Use of an insulin bolus advisor improves glycemic control in multiple daily insulin injection (MDI) therapy patients with suboptimal glycemic control: first results from the ABACUS trial.

OBJECTIVE: Use of automated bolus advisors is associated with improved glycemic control in patients treated with insulin pump therapy. We conducted a study to assess the impact of using an insulin bolus advisor embedded in a blood glucose (BG) meter on glycemic control and treatment satisfaction in patients treated with multiple daily insulin injection (MDI) therapy. The study goal was to achieve >0.5% A1C reduction in most patients. RESEARCH DESIGN AND METHODS: This was a 26-week, prospective, randomized, controlled, multinational study that enrolled 218 MDI-treated patients with poorly controlled diabetes (202 with type 1 diabetes, 16 with type 2 diabetes) who were 18 years of age or older. Participants had mean baseline A1C of 8.9% (SD, 1.2 [74 mmol/mol]), mean age of 42.4 years (SD, 14.0), mean BMI of 26.5 kg/m(2) (SD, 4.2), and mean diabetes duration of 17.7 years (SD, 11.1). Control group (CNL) patients used a standard BG meter and manual bolus calculation; intervention group (EXP) patients used the Accu-Chek Aviva Expert meter with an integrated bolus advisor to calculate insulin dosages. Glucose data were downloaded and used for therapy parameter adjustments in both groups. RESULTS: A total of 193 patients (CNL, n = 93; EXP, n = 100) completed the study. Significantly more EXP than CNL patients achieved >0.5% A1C reduction (56.0% vs. 34.4%; P < 0.01). Improvement in treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire scale) was significantly greater in EXP patients (11.4 [SD, 6.0] vs. 9.0 [SD, 6.3]; P < 0.01). Percentage of BG values <50 mg/dL was <2% in both groups during the study. CONCLUSIONS: Use of an automated bolus advisor resulted in improved glycemic control and treatment satisfaction without increasing severe hypoglycemia.

Automated bolus advisor control and usability study (ABACUS): does use of an insulin bolus advisor improve glycaemic control in patients failing multiple daily insulin injection (MDI) therapy? [NCT01460446].

BACKGROUND: People with T1DM and insulin-treated T2DM often do not follow and/or adjust their insulin regimens as needed. Key contributors to treatment non-adherence are fear of hypoglycaemia, difficulty and lack of self-efficacy associated with insulin dose determination. Because manual calculation of insulin boluses is both complex and time consuming, people may rely on empirical estimates, which can result in persistent hypoglycaemia and/or hyperglycaemia. Use of automated bolus advisors (BA) has been shown to help insulin pump users to more accurately meet prandial insulin dosage requirements, improve postprandial glycaemic excursions, and achieve optimal glycaemic control with an increased time within optimal range. Use of a BA containing an early algorithm based on sliding scales for insulin dosing has also been shown to improve HbA1c levels in people treated with multiple daily insulin injections (MDI). We designed a study to determine if use of an automated BA can improve clinical and psychosocial outcomes in people treated with MDI. METHODS/DESIGN: The Automated Bolus Advisor Control and Usability Study (ABACUS) is a 6-month, prospective, randomised, multi-centre, multi-national trial to determine if automated BA use improves glycaemic control as measured by a change in HbA1c in people using MDI with elevated HbA1c levels (#62;7.5%). A total of 226 T1DM and T2DM participants will be recruited. Anticipated attrition of 20% will yield a sample size of 90 participants, which will provide #62;80% power to detect a mean difference of 0.5%, with SD of 0.9%, using a one-sided 5% t-test, with 5% significance level. Other measures of glycaemic control, self-care behaviours and psychosocial issues will also be assessed. DISCUSSION: It is critical that healthcare providers utilise available technologies that both facilitate effective glucose management and address concerns about safety and lifestyle. Automated BAs may help people using MDI to manage their diabetes more effectively and minimise the risk of long-term diabetes related complications. Findings from a recent study suggest that BA use positively addresses both safety and lifestyle concerns; however, randomised trials are needed to confirm these perceptions and determine whether bolus advisor use improves clinical outcomes. Our study is designed to make these assessments. TRIAL REGISTRATION: NCT01460446.