Evaluation of the Advanced Hybrid Closed Loop (AHCL) System in Type 1 Adults and Pediatrics Utilizing Lyumjev®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Advanced Hybrid Closed Loop (AHCL) System in Type 1 Adults and Pediatrics Utilizing Lyumjev® (NCT05325294), a na na study. The primary outcome is Primary Safety Endpoint - Change in HbA1c.

2. Clinical Question

The study concerns use of the system and insulin together, not a randomized comparison of Lyumjev® with another insulin or of the system with another device. The registry’s stated purpose was to evaluate safety and effectiveness in adults and pediatric subjects in a home setting to support product and system labeling. That purpose describes the intended evaluation; by itself, it does not establish the direction or size of any observed result.

3. Trial Design

The registry record describes a completed, single-group study sponsored by Medtronic MiniMed, Inc. It lists 244 participants as enrolled and identifies the condition as type 1 diabetes. The study started on 2022-05-05, and the primary completion date is 2024-01-03. Its phase is recorded as NA. The brief summary describes a US study in a home setting.

The intervention is the MiniMed 780G System used with Lyumjev® insulin lispro-aabc. The arm description covers subjects aged 7-80 using the system and insulin for three months. The primary endpoint is an overall mean change in HbA1c from baseline to the end of that period. Results are reported in age groups, with separate descriptions for subjects aged 7-17 and subjects aged 18-80.

Masking is listed as none, and allocation is listed as NA. The study is not described as randomized or as having a concurrent control group. Its baseline-to-end comparison is therefore a within-group change, not an estimate of a contrast between assigned groups. Changes over the study period can be described for the participants with outcome data, but the design alone does not isolate the intervention from other possible influences on change over time.

The registry record does not report a detailed protocol, recruitment process, or justification for the enrollment target. It also does not report whether there were interim analyses. The record lists four outcome measures and eight analyses, but it does not give enough detail in the registry record to reconstruct every analysis or how the analyses were selected. The study’s single-group structure is important when interpreting its primary endpoint and when considering what causal conclusions can be drawn.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 244 subjects (120 with age 7-17 and 124 with age 18-80) enrolled at the beginning, with 23 (12 with age 7-17 and 11 with age 18-80) screen failure, 10 subjects (7 with age 7-17 and 3 with age 18-80) early withdrawn prior the study period, 211 subjects (101 with age 7-17 and 110 with age 18-80) started the study and became the Intention to Treat Population.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to Treat Population with available data. Two subjects aged 7-17 and two subject aged 18-80 did not collect A1C at the end of the study period, so 99 subjects aged 7-17 and 108 subjects aged 18-80 were analyzed at end of study period and the change from baseline to end of study period.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Intention to Treat Population

6. Primary Endpoint

The registry lists the primary outcome as Primary Safety Endpoint - Change in HbA1c, measured over 3 months.

The primary safety endpoint is the change in HbA1c from baseline to the end of the 3-month study period. HbA1c is a continuous measure reported as a percentage. The registry describes the endpoint as the overall mean change and lists standard deviation as its measure of dispersion. It also specifies an intention-to-treat population with available data, with age-specific end-of-study counts described in the record.

HbA1c is used as a measure of glycemic status over time. For a continuous endpoint, a mean change gives the average direction and magnitude of observed change among the analyzed participants. The standard deviation describes how dispersed individual values are around that mean; it is not the same as uncertainty about the mean. A confidence interval, if reported, would help convey uncertainty in the estimated mean change.

The endpoint is labelled a safety endpoint and the description says that a non-inferiority test was planned. Non-inferiority asks whether an outcome is not unacceptably worse than a specified reference according to a prespecified margin. The registry record does not report that margin or the numerical mean change, standard deviation, confidence interval, or test result. Consequently, the endpoint definition can be described, but the record does not allow the non-inferiority finding to be evaluated quantitatively.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

For a continuous outcome such as HbA1c, a change score represents the difference between a participant’s end-of-period measurement and baseline measurement. The mean change summarizes the average change among the participants included in the analysis. It is distinct from the mean value at baseline or at follow-up: a change score uses both measurements for the same participant. In this study, the registry defines the primary endpoint as the overall mean change from baseline to the end of the 3-month study period.

A mean is a compact summary and does not show the spread of individual changes. The registry lists standard deviation as the dispersion measure. In general, standard deviation describes variability among observed values around their mean. A large or small standard deviation cannot be interpreted as uncertainty in the estimated mean without considering the amount of data and the analysis. The numerical mean change and standard deviation are not reported in the registry record, so neither the average change nor its observed spread can be assessed.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. It gives a range of values compatible with the data and method, rather than asserting that the estimate is exact. For a non-inferiority analysis, the interval is often considered in relation to a prespecified margin. The margin identifies how much worse an outcome could be while still meeting the study’s non-inferiority criterion. The registry record does not report a confidence interval or the margin for this endpoint.

A confidence interval is not a substitute for examining the design, outcome definition, or completeness of the data. Nor does a non-significant difference, by itself, establish non-inferiority. The precise interpretation depends on the prespecified margin and analysis. Since the record gives neither the margin nor numerical inferential results, the non-inferiority question cannot be independently assessed from these details.

What does the single-group design imply?

The registry identifies the study model as single-group and gives no separate comparator. The primary endpoint compares measurements over time within the study group. This can describe a before-and-after pattern among participants with recorded measurements. It cannot directly estimate a between-group treatment effect, because no control group is described. General changes over time, participant characteristics, measurement conditions, or other influences may also contribute to an observed within-group change. The design does not distinguish those influences from the effect of using the system and insulin combination.

Allocation is recorded as NA, and masking is listed as none. The record does not describe randomized allocation. It is therefore inappropriate to read the age-group reporting as evidence of randomized treatment arms: the groups are age categories, not described comparator groups. The record gives no treatment contrast between those categories as the primary question.

How should the non-inferiority language be read?

In general, a non-inferiority study evaluates whether an intervention’s outcome is not worse than a reference by more than a clinically or operationally specified margin. The analysis needs a defined reference, margin, estimate, and uncertainty measure to support that interpretation. In a single-group study, the reference and implementation of the non-inferiority test require particular care; the registry description only states that a non-inferiority test was used. It does not report the margin, reference details, or statistical model. Those elements are not reported in the registry record and should not be inferred from the endpoint label.

The registry’s sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. The record’s assumptions specify that non-time-to-event illustrations concern participants per arm. These are planning assumptions, not a description of the actual single-group study allocation. No numerical sample-size illustrations are stated in the registry record, and such illustrations are not observed power. They do not establish the trial’s original design rationale or determine whether its analysis was adequately precise.

What do the reported analysis populations tell readers?

The primary endpoint description says that the analysis used an intention-to-treat population with available data. This wording indicates that the reported change used participants for whom the relevant data were available; the record also supplies age-specific counts for end-of-study analysis. It notes missing end-of-study A1C collection for two subjects aged 7-17 and two subjects aged 18-80. It does not state why those measurements were missing, whether any values were imputed, or whether sensitivity analyses were conducted. The precise missing-data method is not reported in the registry record.

Missing outcome data can affect interpretation if participants with unobserved outcomes differ systematically from those with observed outcomes. That is a general statistical concern, not a claim about why measurements are absent in this study. Without information on reasons for missingness or methods used to address it, readers cannot determine how sensitive the mean change may be to the unavailable end measurements.

Why do multiple outcomes and analyses matter?

The registry lists four outcome measures and eight analyses. The named secondary effectiveness outcomes concern percent of time in hypoglycemia (< 54 mg/dL) and percent of time in range (TIR 70-180 mg/dL). In general, examining multiple outcomes or analyses creates more opportunities for apparently notable findings by chance. A prespecified multiplicity approach can help clarify which results are confirmatory and how uncertainty should be interpreted across outcomes. The registry record does not report such an approach, nor does it provide numerical results for the secondary endpoints. It is therefore not possible to assess how the analyses were prioritized or adjusted.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Subjects 7-17 Years of Age", "Subjects 18-80 Years of Age")
n   <- c(99, 108)
m   <- c(-0.1, -0.4)
sp  <- c(0.7, 0.6)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Subjects 7-17 Years of Age  99  -0.100  0.700  -0.240  0.040
CARM  Subjects 18-80 Years of Age  108  -0.400  0.600  -0.514  -0.286

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary HbA1c endpoint and two secondary effectiveness endpoints: percent of time in hypoglycemia (< 54 mg/dL) and percent of time in range (TIR 70-180 mg/dL). It also reports four outcome measures and eight analyses overall. The registry entries available do not identify every outcome or analysis, or explain how the analyses relate to each other. A plan for controlling multiplicity, such as prioritizing outcomes or adjusting inference across multiple tests, is not reported in the registry record. The secondary endpoint names alone do not establish whether they were confirmatory or exploratory.

The primary endpoint population is described as intention-to-treat with available data. The record says two subjects aged 7-17 and two subjects aged 18-80 did not collect A1C at the end of the study period, and states that 99 subjects aged 7-17 and 108 subjects aged 18-80 were analyzed at end of study and for change from baseline. These details define the reported endpoint data more clearly than a general enrollment figure alone, but do not explain why the measurements were missing.

The registry record does not report the missing-data handling method, imputation, sensitivity analyses, or assumptions about outcomes for participants without end measurements. It also does not state whether missing data occurred for the secondary outcomes. These omissions limit assessment of whether the analyzed data may differ systematically from the intended population. No numerical primary or secondary estimates are reported in the registry record, so completeness and uncertainty cannot be checked against the reported outcome values.

The record does not report interim analyses or a full statistical analysis plan. Their presence or absence should not be inferred. Without the analysis plan, multiplicity procedure, and missing-data details, readers cannot reconstruct the complete inferential framework from the registry description.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events separately for subjects aged 7-17 and subjects aged 18-80. It reports zero subjects affected by serious adverse events in each group during the study period. The groups each have their own at-risk count in the record. No deaths are reported in either group.

For other adverse events, the registry reports 50 affected subjects in the 7-17 group and 47 in the 18-80 group. These are counts as recorded, not rates calculated. They do not indicate how many events occurred per affected subject, when events occurred, how severe they were, or whether they were judged related to the system or insulin. The registry entries available do not list the most frequent serious adverse-event terms, and the serious-event counts are zero in both groups.

These figures describe events recorded during the study period, not a comparison against an untreated or alternative-treatment group. A single-group design cannot establish whether the recorded events were caused by the intervention or whether their frequency differs from what would otherwise have occurred. The registry counts should therefore be read as descriptive safety reporting. They do not establish the absence of risk, particularly because the record does not provide event narratives or further detail on other adverse events.

13. What the Result Does, and Does Not, Mean

The registry record establishes that a completed, single-group study evaluated use of the MiniMed 780G System with Lyumjev® in adults and pediatric subjects with type 1 diabetes. It identifies HbA1c change over the 3-month study period as the primary endpoint and describes the planned test as non-inferiority. It also identifies secondary measures related to hypoglycemia and time in range. This information clarifies the intended research question and the main outcome domains.

The record does not report the numerical primary endpoint result, its dispersion, confidence interval, or test result. It also does not report numerical results for the named secondary outcomes. As a result, the direction and magnitude of observed changes, and the precision of those estimates, cannot be evaluated from the registry record. The non-inferiority label does not by itself show that a non-inferiority criterion was met; the margin and the relevant numerical result are not reported.

Because there is no described concurrent comparator, the baseline-to-end comparison is not a randomized estimate of an effect relative to another treatment or usual care. A within-group change can describe the observed course among participants with outcome data, but it cannot isolate why any change occurred. Findings from this design should not be recast as a controlled comparison.

The adverse-event listing reports zero serious events in each age group, along with counts for other adverse events. These figures are descriptive and do not establish causation or rule out risk. The record also gives some information about missing end-of-study A1C data, but does not report why those values were absent or how missingness was handled analytically.

Accordingly, the registry information is useful for understanding the study’s design, endpoint definitions, analysis population description, and selected safety counts. It is insufficient for a quantitative judgment of the primary result or the precision of any effectiveness estimate. It does not support a conclusion about comparative benefit, and it does not provide a complete account of the analysis methods needed to assess the non-inferiority claim.

14. Why This Trial Matters Statistically

This study is statistically notable because it combines a non-inferiority question with a single-group design. Non-inferiority is usually interpreted against a defined margin and a reference. The registry record identifies a non-inferiority test for mean HbA1c change but does not report the margin or the numerical result. That gap matters: readers need the estimate and its uncertainty, as well as the criterion against which it was judged, to understand the claim.

The primary outcome is a continuous measure assessed from baseline to the end of the 3-month period. Its interpretation depends on more than the direction of the mean change. The distribution of individual changes, variability, uncertainty, and completeness of measurements all contribute to how informative the result is. The record lists standard deviation as the dispersion measure and describes missing end-of-study A1C values, but the numerical estimate and further analytic details are not reported.

The single-group model also shapes what can be learned. Baseline-to-end changes can be described, but without a separate comparator the study does not estimate a randomized contrast. This distinction is especially important when a study’s stated purpose is to support product and system labeling: the purpose does not replace a clear account of the design and the evidence needed for a particular inference.

The record’s counts for serious and other adverse events offer a descriptive safety snapshot, while the named secondary measures indicate additional effectiveness domains. Yet the absence of numerical results for the effectiveness endpoints and of a reported multiplicity approach limits the ability to assess the full pattern of evidence. The study is therefore useful as a case in how design, endpoint specification, missing data, and reporting completeness constrain statistical interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting this study from the registry record is the absence of numerical effectiveness results. The record does not report the mean HbA1c change, its standard deviation, a confidence interval, or a p-value. Although the endpoint is described as a non-inferiority test, the non-inferiority margin is not reported. Without these elements, the direction, size, precision, and inferential outcome of the primary analysis cannot be assessed.

The single-group design has no described concurrent comparator. The primary comparison is baseline with the end of the 3-month study period, so observed change cannot be separated from other influences on change over time. Age-specific reporting does not create a treatment-control comparison; the record describes age groups, not randomized arms.

The endpoint population is described as intention-to-treat with available data. The record notes missing end-of-study A1C collection for two subjects aged 7-17 and two subjects aged 18-80, and provides the analyzed end-of-study counts. It does not report the reasons for missing measurements, the method used to handle missing data, or sensitivity analyses. Those omissions constrain evaluation of potential missing-data effects.

The record names two secondary effectiveness endpoints but does not report their numerical results. It also lists four outcome measures and eight analyses without reporting a multiplicity strategy or all analysis details. The protocol, statistical analysis plan, interim-analysis information, and sample-size justification are not reported in the registry record. These limitations concern what can be evaluated from the record; they do not establish that an unreported procedure was or was not conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of the Advanced Hybrid Closed Loop (AHCL) System in Type 1 Adults and Pediatrics Utilizing Lyumjev® — NCT05325294.
• Registry record last updated 2025-01-15; status last verified 2024-12.
• Results first posted 2025-01-15.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed, single-group study sponsored by Medtronic MiniMed, Inc., evaluating the MiniMed 780G System with Lyumjev® insulin lispro-aabc in people with type 1 diabetes. It lists 244 participants enrolled, with use described for subjects aged 7-80 over three months. The study started on 2022-05-05, and the primary completion date is 2024-01-03. The brief summary describes a US home-setting study intended to evaluate safety and effectiveness in adults and pediatric subjects and support product and system labeling.

The primary endpoint is mean HbA1c change from baseline to the end of the 3-month study period, described as a non-inferiority test. The record also names secondary endpoints for time in hypoglycemia and time in range. It reports age-specific endpoint analysis counts and descriptive adverse-event counts, but numerical primary and secondary effectiveness results are not reported in the registry record. The non-inferiority margin, multiplicity approach, and detailed missing-data methods are also not reported.