Table 2.
Primary and Secondary Hierarchical Efficacy Outcomes.*
| Outcome | Baseline | Follow-up over 13 Wk or at 13 Wk |
Adjusted Difference (95% CI)† |
P Value | ||
|---|---|---|---|---|---|---|
| Bionic Pancreas (N = 219) |
Standard Care (N = 107) |
Bionic Pancreas (N = 219) |
Standard Care (N = 107) |
|||
| Primary outcome | ||||||
| Glycated hemoglobin — % | 7.9±1.2 | 7.7±1.1 | 7.3±0.7 | 7.7±1.0 | −0.5 (−0.6 to −0.3) | <0.001 |
| Key secondary outcome | ||||||
| Median percentage of time with glucose level <54 mg/dl (IQR) — % | 0.2 (0.02 to 0.6) | 0.2 (0.0 to 0.4) | 0.3 (0.2 to 0.6) | 0.2 (0.1 to 0.6) | 0.0 (−0.1 to 0.04) | <0.001‡ |
| Other secondary hierarchical outcomes in prespecified order | ||||||
| Mean glucose level — mg/dl§ | 187±40 | 190±42 | 164±15 | 181±32 | −16 (−19 to −12) | <0.001 |
| Percentage of time with glucose level in range 70–180 mg/dl — % | 51±19 | 51±20 | 65±9 | 54±17 | 11 (9 to 13) | <0.001 |
| Percentage of time with glucose level >180 mg/dl — % | 46±20 | 47±21 | 33±9 | 44±18 | −10 (−12 to −8) | <0.001 |
| Median percentage of time with glucose level >250 mg/dl (IQR) — % | 16.0 (7.0 to 27.3) | 17.8 (6.0 to 33.5) | 8.5 (5.3 to 13.2) | 14.9 (6.3 to 25.3) | −5.0 (−6.6 to −3.6) | <0.001 |
| Glucose SD — mg/dl¶ | 67±16 | 68±18 | 60±11 | 67±16 | −7 (−8 to −5) | <0.001 |
| Median percentage of time with glucose level <70 mg/dl (IQR) — % | 1.5 (0.5 to 2.8) | 1.4 (0.4 to 2.9) | 1.8 (1.1 to 2.9) | 1.8 (0.8 to 3.1) | −0.1 (−0.3 to 0.2) | 0.51 |
| Median percentage of time with glucose level <54 mg/dl (IQR) — %∥ | 0.2 (0.02 to 0.6) | 0.2 (0.0 to 0.4) | 0.3 (0.2 to 0.6) | 0.2 (0.1 to 0.6) | 0.0 (−0.1 to 0.04) | — |
| Glucose coefficient of variation — %¶ | 36±6 | 36±6 | 36±5 | 37±5 | −0.8 (−1.6 to 0.0) | — |
Plus–minus values are means ±SD. Data on the glycated hemoglobin level at baseline were missing for one participant in the standard-care group; data on the glycated hemoglobin level at week 13 were missing for seven participants in the bionic-pancreas group and for three in the standard-care group. Follow-up continuous glucose-monitoring data were missing for one participant in the bionic-pancreas group. All the participants who had undergone randomization were included in the models. To control the type I error, a hierarchical approach was used in which hypothesis testing was performed sequentially in the order listed. When a P value of 0.05 or higher was observed, the subsequent outcomes on the list were not formally tested. All P values reflect testing for superiority, except for the P value for the key secondary outcome, which was tested for noninferiority. To convert values for glucose to millimoles per liter, multiply by 0.05551. CI denotes confidence interval, and IQR interquartile range.
The adjusted difference was computed from a mixed-effect model with adjustment for baseline value of the metric, age at randomization, and site (random effect). Differences in percentages are shown in percentage points. Missing data were handled with the use of direct-likelihood analyses. Owing to a skewed distribution, the percentages of time with the glucose level above 250 mg per deciliter (13.9 mmol per liter), below 70 mg per deciliter (3.9 mmol per liter), and below 54 mg per deciliter (3.0 mmol per liter) were transformed with the use of a rank normal transformation.
The P value for the key secondary outcome was from testing for noninferiority with a margin of 1.0 percentage point.
Shown are the means of the individual participants’ mean glucose levels.
The glucose SD and coefficient of variation values indicate within-participant variability of sensor glucose measurements.
The outcome of the percentage of time with the glucose level below 54 mg per deciliter was to be tested for superiority at this level in the hierarchical analysis. This and the subsequent analysis were not conducted since the result for the percentage of time with the glucose level below 70 mg per deciliter was not significant.