A Trial Investigating the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily Plus Insulin Aspart for the Remaining Meals Versus Insulin Detemir Once or Twice Daily Plus Meal Time Insulin Aspart in Children and Adolescents With Type 1 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial Investigating the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily Plus Insulin Aspart for the Remaining Meals Versus Insulin Detemir Once or Twice Daily Plus Meal Time Insulin Aspart in Children and Adolescents With Type 1 Diabetes Mellitus (NCT01835431), a randomized phase 3 study. The primary outcome is Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, open-label, parallel-group Phase 3 trial. Participants were assigned to one of two insulin regimens: insulin degludec/insulin aspart once daily plus insulin aspart for remaining meals, or insulin detemir once or twice daily plus mealtime insulin aspart. Masking is listed as none. The record reports 362 enrolled participants and a completed trial. The recorded start date is 2013-10-17, and primary completion is listed as 2014-11-07.

The primary endpoint was change from baseline in HbA1c, expressed as a percentage, from week 0 to week 16. The posted arm summaries are means with standard deviations. The primary comparison is a mean difference between the arms. The registry describes the full analysis set as including all randomized subjects, but also states that change-from-baseline summaries at week 16 include only those with both baseline and week 16 assessments. It reports 20 withdrawals and 4 participants who completed the study without assessments. Thus, the randomized population and the population contributing to the endpoint summaries are not described as identical.

The record lists several secondary outcomes, including fasting plasma glucose, treatment-emergent adverse events, hypoglycaemic episodes, and hyperglycaemic episodes. It does not post analyses for most of those outcomes in the registry record. The trial’s detailed statistical analysis plan, allocation procedures, or any interim analyses are not reported in the registry record. The trial’s own sample-size justification is also not reported in the registry record; the planning illustrations associated with a secondary outcome are not a description of the trial’s original design assumptions.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The FAS included all randomised subjects. 20 subjects were withdrawn and only 4 subjects though completed the study did not have assesments.

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: The Full Analysis set (FAS) included all randomised subjects.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%), measured over Week 0 to week 16.

The primary endpoint is change in HbA1c from baseline at week 0 to week 16, reported in percentage points. HbA1c is a continuous measure of glycosylated haemoglobin. A change score describes how a participant’s value at follow-up differs from that participant’s baseline value; the arm mean summarizes those changes across participants with both assessments. The registry record gives mean change and standard deviation for each arm.

HbA1c is used in diabetes trials as a measure of longer-term glycaemic status. In statistical terms, it offers a continuous endpoint that can be summarized with a mean and compared between randomized groups. Such a summary captures the average change, but not the full distribution of individual changes. The standard deviation provides information about variation among participants and is distinct from the uncertainty around the arm mean or the between-arm difference.

The endpoint description specifies that the week 16 change summaries contain only participants with baseline and week 16 assessments. Consequently, the displayed mean changes describe that assessed subset, even though the full analysis set is described as including all randomized subjects. The registry record does not report further detail about how missing endpoint values were handled or how the analysis accounted for the randomized participants without both assessments.

7. Results Posted in the Registry

• IDet OD/BID: mean -0.30 versus -0.30 on control; difference 0.00 (95% CI -0.20 to 0.20), standardized effect d = 0.00; z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Fasting Plasma Glucose

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • IDet OD/BID: mean -0.10 versus -0.30 on control; difference 0.20 (95% CI -1.05 to 1.45), standardized effect d = 0.04; z-test p = 0.754.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between IDet OD/BID and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes spanning fasting plasma glucose, treatment-emergent adverse events, hypoglycaemic episodes, and hyperglycaemic episodes. These outcomes would add different perspectives to the primary HbA1c comparison: some are continuous measures, while others count events or describe whether adverse events occurred. The registry record posts an analysis for fasting plasma glucose but does not post reported analyses for the other listed secondary outcomes.

For fasting plasma glucose, the posted mean change was -0.3 mmol/L for IDegAsp OD and -0.1 mmol/L for IDet OD/BID. The estimated mean difference was 0.2 mmol/L, its interval crosses zero, and the unadjusted p-value was 0.754. This comparison does not show a clear between-arm difference in the posted analysis. It is a separate endpoint from HbA1c and should not be treated as a substitute for the primary result.

Across the wider set of outcomes, the registry record does not permit a reliable account of an overall pattern of secondary effects because analyses are not posted for most of them. The existence of an outcome in the registry is not itself evidence of a result. Nor can missing analyses be interpreted as showing no difference or no events.

In general, secondary outcomes often play a supporting or exploratory role, particularly when many outcomes are assessed. Unadjusted results do not account for the chance of false-positive findings increasing across multiple tests. The registry record does not report a multiplicity strategy or a hierarchy for interpreting secondary outcomes. Accordingly, any individual unadjusted secondary finding would carry less weight than a prespecified primary comparison unless supported by a clear analysis plan and appropriate interpretation. The posted secondary information is best read as limited context rather than a basis for broad claims about the full range of outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Fasting Plasma Glucose
• Incidence of Treatment Emergent Adverse Events (TEAEs)
• Number of Treatment Emergent Confirmed Hypoglycaemic Episodes (Plasma Glucose (PG) Below 3.1mmol/L (56mg/dL) or Severe Hypoglycaemia)
• Number of Treatment Emergent Nocturnal Confirmed Hypoglycaemic Episodes
• Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill
• Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill With Ketosis (Blood Ketones Above 1.5 mmol/L)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it records a numerical change in HbA1c for each participant, and the posted summaries describe the mean and standard deviation in each arm. A mean is the arithmetic average of the observed changes. It gives a compact measure of the group’s central tendency, but can conceal differences in the distribution, such as whether changes were tightly clustered or varied substantially between participants. The standard deviation describes that participant-to-participant spread; it is not the same quantity as the standard error or a confidence interval.

What does a mean difference describe?

The primary comparison is the mean difference between the two arms. It places the groups’ average changes on the same scale as the endpoint. The estimate is 0.0 percentage points, with both arm means reported as -0.3 percentage points. This is a contrast of group averages, not a comparison of every individual participant, and it does not show whether particular participants improved or worsened. The direction of a difference depends on which arm is subtracted from which; the registry identifies IDet OD/BID as the comparison arm against IDegAsp OD.

What does a p-value contribute?

The posted p-value is unadjusted and equals 1.0. In general, a p-value describes how unusual data at least as discordant with a specified null hypothesis would be if that hypothesis and the analysis assumptions were true. It is not the probability that the null hypothesis is true, nor a measure of effect size, clinical importance, or certainty that the arms are equivalent. A large p-value does not prove there is no difference. It should be considered with the estimated difference, interval, endpoint definition, and analysis population.

Why does the interval matter?

A confidence interval is generally used to represent uncertainty around an estimated effect. Its width reflects both the variability in the data and the amount of information available, under the method’s assumptions. The posted interval for the primary mean difference crosses zero. That is consistent with the unadjusted p-value and indicates that the estimate does not distinguish a direction of difference at the interval’s stated level. The confidence level and full analysis method are not reported in the registry record, so the interval’s calibration cannot be fully evaluated from the record.

What does randomization add?

In general, random assignment is intended to make treatment groups comparable at the start of a trial, on average, and supports interpretation of between-arm differences as comparisons of assigned strategies. It does not guarantee identical groups on every characteristic, and it does not remove concerns about missing outcomes, adherence, measurement, or analysis choices. The registry lists randomized allocation, but does not report the sequence-generation or concealment procedures. Masking is listed as none, so participants and trial staff were not masked according to the record. The consequences of that design feature depend on the outcome and conduct of the trial and cannot be determined from the record alone.

How should the planning illustrations be read?

The registry includes planning illustrations for the secondary fasting plasma glucose comparison. They use a two-sided significance level of 0.05, equal allocation, a normal approximation, and stated fractions of the observed effect. The listed rows describe planning for 100%, 75%, and 50% of the observed effect. For the observed-effect scenario, the illustration lists 12,719 participants per arm for 80% power and 17,026 participants per arm for 90% power. For planning for 75% of the observed effect, it lists 22,610 participants per arm for 80% power and 30,269 participants per arm for 90% power. For planning for 50% of the observed effect, it lists 50,873 participants per arm for 80% power and 68,104 participants per arm for 90% power. These are hypothetical planning illustrations derived from the observed secondary-outcome effect, not observed power and not the trial’s original sample-size justification. The original justification is not reported in the registry record.

Over-dispersion is a general concern when count outcomes vary more than assumed by a simple statistical model. If variability is underestimated, uncertainty can be understated and tests can appear more decisive than warranted. The secondary outcomes include counts of hypoglycaemic and hyperglycaemic episodes, but the registry record does not provide the analyses or modeling details needed to assess whether over-dispersion was relevant or how it was handled.

11. Confidence Intervals and Precision

The primary mean difference is 0.0 percentage points, and the posted interval extends to both sides of zero. This means the point estimate alone does not convey all the uncertainty: values in either direction remain compatible with the interval. The record does not report the confidence level, so the probability coverage convention usually attached to a confidence interval cannot be stated from the registry record.

Precision is influenced by the amount of observed information and the variability in the endpoint. The primary summaries include 173 participants in IDegAsp OD and 165 in IDet OD/BID, with standard deviations of 1.0 and 0.9, respectively. These standard deviations describe variation in individual change scores, not the uncertainty of the mean difference. The interval is the more direct posted summary of uncertainty for the contrast.

The displayed mean changes are rounded to one decimal place. Identical rounded arm means do not imply that every participant had the same change or that the underlying unrounded group means were exactly identical. The registry reports a mean difference of 0.0, while the interval and unadjusted p-value provide additional information about the comparison. The interval crossing zero means the data do not establish a difference in either direction; it does not demonstrate equivalence.

Precision must also be considered in light of the endpoint population. The record says the week 16 summaries include only participants with both baseline and follow-up assessments. It does not report the missing-data method, sensitivity analyses, or reasons for each missing assessment. Thus, the interval represents uncertainty under the analysis that produced it, but cannot address uncertainty introduced by unobserved outcomes without further information.

12. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary endpoint, change from baseline in HbA1c at week 16, and lists multiple secondary outcomes. It does not report whether the trial used a prespecified hierarchy, adjusted significance thresholds, or another method to control multiplicity. When several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. In general, adjustment or a prespecified testing sequence can help address that issue; without the analysis plan, the role intended for each secondary result is unclear.

The primary p-value is explicitly unadjusted. The registry record does not state whether that value is the sole primary test or how it fits into any broader testing strategy. The fasting plasma glucose p-value is also unadjusted. No further interpretation about multiplicity handling can be made from the registry record.

The population description needs attention. The record says the full analysis set included all randomized subjects, while also stating that the week 16 change summaries include only participants with both baseline and week 16 assessments. It reports 20 withdrawn participants and 4 who completed the study but did not have assessments. This distinction means the displayed endpoint summaries do not include every randomized participant as described by the enrollment count. The record does not explain how missing outcomes were handled, whether any values were imputed, or whether sensitivity analyses were conducted.

In general, missing outcomes can affect a comparison if the likelihood of missingness or the unobserved values differ between groups. Randomization does not by itself resolve that issue after follow-up measurements are unavailable. The registry record does not report reasons for missing assessments by arm or provide enough detail to judge whether the complete-assessment summaries are representative of all randomized participants.

The record also does not report the detailed statistical analysis plan, interim analyses, or the original sample-size justification. These are reporting gaps, not evidence that such procedures were absent. They limit assessment of prespecification, multiplicity, missing-data handling, and the relationship between the trial’s intended design and posted analyses.

13. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypoglycaemia (2.8%), fall (0.6%), diabetic ketoacidosis (0.6%), hyperglycaemia (0.6%), loss of consciousness (0.6%).

The registry reports serious adverse event figures for separate safety populations: 11 affected participants among 181 at risk in IDegAsp OD, and 7 among 179 at risk in IDet OD/BID. For other treatment-emergent adverse events, the figures are 96 among 181 and 97 among 179, respectively. These are counts of participants reported with events, not measures of the primary HbA1c endpoint. The safety denominators differ from the primary endpoint summary counts, so the two sets of figures should not be conflated.

The registry lists serious-event terms including hypoglycaemia at 2.8%, and fall, diabetic ketoacidosis, hyperglycaemia, loss of consciousness, and laryngitis each at 0.6%. Those percentages are not assigned to an arm in the listed terms, so an arm-specific interpretation is not supported. Deaths are not reported in the registry record.

These figures describe events recorded during the trial; they do not establish that a treatment caused an event. Differences in counts alone do not show whether an apparent contrast is meaningful, particularly without fuller event definitions, timing, exposure information, and statistical analyses. The registry record does not provide a comparative safety analysis sufficient to draw broader conclusions from these figures.

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

The primary result is a comparison of average HbA1c change over the specified period among participants with both baseline and week 16 assessments. Both arms have a posted mean change of -0.3 percentage points, the estimated difference is 0.0, and the unadjusted p-value is 1.0. The interval crosses zero. These observations describe the posted analysis; they do not show a detectable separation in average change in that analysis.

That finding is not the same as proof that the regimens are identical. To establish equivalence or non-inferiority, a trial generally needs a prespecified margin and an analysis designed to assess that margin. No margin or equivalence or non-inferiority analysis is reported in the registry record. Nor does a large p-value establish that no effect exists. The interval conveys uncertainty, and the registry does not state its confidence level.

The result also does not tell whether every participant experienced a similar change. Group means and standard deviations summarize distributions but cannot describe each participant’s course or the full shape of those distributions. The endpoint is limited to week 16, and should not be read as a statement about outcomes at other follow-up times.

Although the trial was randomized, the registry identifies no masking and provides limited information about allocation procedures. The endpoint summaries exclude participants without both required assessments, and the record does not explain the missing-data method or provide sensitivity analyses. These omissions constrain how confidently the complete-assessment comparison can be generalized to all randomized participants.

Finally, the primary endpoint is only one part of the trial’s outcome set. Several secondary outcomes are listed, but analyses for most are not posted in the registry record. The result therefore cannot stand in for an overall assessment of safety or all glycaemic outcomes. It supports a narrow statistical description of the posted HbA1c comparison, not medical advice or a treatment recommendation.

15. Why This Trial Matters Statistically

This trial illustrates why the estimated effect, its uncertainty, the analysis population, and the reporting record need to be considered together. The two arm means are the same at the displayed precision, and the estimated difference is 0.0. The unadjusted p-value is 1.0, but that value alone cannot establish equivalence. The interval crossing zero adds a direct account of uncertainty around the contrast, although its confidence level is not reported in the registry record.

The record also highlights an important distinction between randomization and endpoint availability. A trial can enroll and randomize participants while the endpoint summary is based on a subset with required follow-up measurements. Here, the record states that the full analysis set included all randomized subjects, but that week 16 change summaries included only those with both baseline and follow-up assessments. Evaluating how that restriction affects interpretation requires missing-data details that are not reported.

Multiplicity matters because a trial may examine several outcomes, and this registry lists a range of secondary measures. Without a reported testing hierarchy or adjustment strategy, secondary p-values should not be treated as if they were isolated confirmatory tests. The absence of posted analyses for most listed outcomes further limits any overall synthesis.

The planning illustrations also demonstrate a general statistical point: sample-size requirements depend on the effect a future study aims to detect, as well as design assumptions. The listed figures use the observed effect for a secondary endpoint and specified fractions of it. They are planning illustrations, not a measure of the power achieved in this trial and not evidence of its original design assumptions.

For clinical researchers, the central statistical lesson is to distinguish what the estimate says from what it cannot establish. The posted result gives a concise mean comparison at week 16. Its interpretation remains bounded by interval uncertainty, incomplete reporting of analysis methods, endpoint missingness, and the limited posted secondary analyses.

16. 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.

Several limitations are specific to the information reported for this trial. The primary endpoint summaries include only participants with both baseline and week 16 assessments, while the record says the full analysis set included all randomized subjects. It reports 20 withdrawals and 4 participants who completed without assessments, but does not give reasons by arm or explain the method used for missing endpoint values. The impact of those missing assessments cannot therefore be evaluated from the registry record.

The registry describes the trial as randomized and unmasked, but does not report the randomization sequence, allocation concealment, or additional details of trial conduct. The arm descriptions contain no further text. These omissions limit assessment of how assignment and follow-up were implemented, without establishing that any particular process was or was not used.

The interval confidence level and the detailed statistical analysis plan are not reported in the registry record. The record does not state whether interim analyses occurred, describe a multiplicity strategy, or provide the trial’s original sample-size justification. The secondary outcome list is broad, but analyses are posted for only a limited part of that outcome set. The absence of posted results cannot be taken to mean that no differences or events occurred.

The safety figures are descriptive counts with denominators that differ from the primary endpoint counts. The serious-event terms are listed with percentages but are not assigned to arms in the record. Deaths are not reported in the registry record. These reporting features prevent a detailed comparative safety interpretation.

The primary outcome is measured at week 16 and describes average change among assessed participants. It does not characterize longer-term outcomes, individual responses, or the full distribution of change. The record does not provide enough information to determine how these limitations may have affected the estimates.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Trial Investigating the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily Plus Insulin Aspart for the Remaining Meals Versus Insulin Detemir Once or Twice Daily Plus Meal Time Insulin Aspart in Children and Adolescents With Type 1 Diabetes Mellitus — NCT01835431.
• Registry record last updated 2019-06-11; status last verified 2019-06.
• Results first posted 2015-11-17.
• 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.

20. Record Summary

The registry record describes a completed, randomized, open-label, parallel-group Phase 3 trial of two insulin regimens for children and adolescents with type 1 diabetes. Enrollment was 362. The primary endpoint was change in HbA1c from baseline to week 16. Mean change was -0.3 percentage points in each arm, with a mean difference of 0.0 and an unadjusted p-value of 1.0; the posted interval crosses zero.

The endpoint summaries include participants with both baseline and week 16 assessments. The record reports 20 withdrawals and 4 participants who completed without assessments, but does not report the missing-data method or the interval confidence level. Several secondary outcomes are listed, though most do not have posted analyses in the registry record. The record does not report the original sample-size justification, detailed statistical analysis plan, or multiplicity approach. The primary result is therefore a narrow estimate of average HbA1c change, with important limits on interpretation from uncertainty and incomplete analysis reporting.