ATG-GCSF in New Onset Type 1 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ATG-GCSF in New Onset Type 1 Diabetes (NCT02215200), a randomized phase 2 study. The primary outcome is Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months..

2. Clinical Question

3. Trial Design

NCT02215200 is a completed phase 2 randomized trial sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. The registry records a parallel-group, triple-masked design with three arms: ATG and placebo, ATG plus GCSF, and placebo. Its brief summary describes the study as double-blinded, while the design fields identify masking as triple. The registry record does not explain which people or roles were masked, or reconcile those descriptions.

The registry reports enrollment of 89. Its brief summary specifies a 1:1:1 allocation and says at least 28 subjects were intended for each arm. The posted endpoint results list 29 for ATG and placebo, 28 for ATG plus GCSF, and 30 for placebo. The adverse-event records use different at-risk counts, so those counts should not be treated as the endpoint analysis group sizes.

The registry records the study start as 2014-12 and primary completion as 2017-08, with status completed. The treatment window described in the brief summary is within 100 days from diagnosis. Although the arm descriptions give some administration details, parts of those descriptions are incomplete; the complete dosing and treatment procedures are not reported in the registry record.

Randomization and masking can reduce some risks of systematic differences in treatment assignment and outcome assessment. They do not, by themselves, establish that the posted arm means are causally different. That conclusion would require an appropriate between-arm analysis, along with sufficient information about analysis populations and missing data. Such an analysis is not posted in the registry record.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months., measured over -10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months.

The primary endpoint is change in the area under the stimulated C-peptide curve from baseline to 12 months. The registry describes measurements at -10, 0, 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months. It also describes the reported quantity as a C-peptide “AUC mean”: a weighted average of six timed C-peptide measurements, expressed in nmol/L. The record distinguishes this average from an area-under-the-curve quantity by describing it as the area under the curve divided by 120 minutes.

C-peptide is used as a measure of the body’s own insulin production. In this trial, the stated purpose of the endpoint was to assess whether residual beta cell function was retained or enhanced after treatment. A stimulated measurement samples C-peptide response over time following a dose, rather than relying on a single timed measurement. The posted endpoint values are 0.528 for ATG and placebo, 0.646 for ATG plus GCSF, and 0.406 for placebo, all in nmol/L, with 95% confidence intervals reported for each arm.

The endpoint’s title describes change from baseline, while the registry’s description also gives the calculation of the C-peptide AUC mean at baseline and 12 months. Further detail about how the change was calculated for analysis is not reported in the registry record. The reported endpoint should therefore be read using the registry’s label and definition, without assuming additional transformations or adjustments.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a continuous endpoint, a mean summarizes the central value of measurements in a group. In this trial, the posted primary results give an arm-specific mean for the C-peptide endpoint and a 95% confidence interval. The reported spread is represented by the interval rather than by a standard deviation or another dispersion measure. The registry record does not specify the method used to calculate these intervals.

What does a confidence interval convey?

In general, a confidence interval expresses the precision of an estimate under a statistical procedure and its assumptions. A narrower interval indicates greater precision under that procedure; a wider interval indicates more uncertainty about the estimated quantity. The interval is not a description of the range of individual participant outcomes. Nor is it the probability that the fixed, true value lies within the particular interval. The posted intervals apply to the separate arm means, not to differences between arms.

The intervals are reported as 95% confidence intervals: 0.435 to 0.627 for ATG and placebo, 0.547 to 0.75 for ATG plus GCSF, and 0.324 to 0.494 for placebo. The record does not give a standard error, a standard deviation, or a model specification alongside these intervals. Those omissions mean readers should not infer a particular calculation method from the intervals alone.

Why is an arm-to-arm estimate important?

Random assignment creates a design for comparing treatment groups, but a treatment-effect estimate still needs to be calculated and reported. For a continuous outcome, the analysis might report a difference in means or another prespecified contrast, together with uncertainty. The registry record posts no such contrast and lists zero analyses. The arm-specific means are useful descriptive results, but they do not provide the uncertainty around a comparative effect. No significance test for the treatment comparisons is reported.

The registry identifies the trial as randomized, placebo-controlled, parallel-group, and triple-masked. These design features concern how participants were assigned and how knowledge of assignment may have been restricted. The record does not report the randomization procedure, allocation concealment details, or the roles included in masking. Those details are not reported in the registry record and should not be assumed from the design labels.

What does over-dispersion mean in general?

Over-dispersion is a general issue for some statistical models when observed variability is greater than the model expects. If that extra variability is ignored, uncertainty can be understated and tests can be too optimistic. This is a general statistical consideration, not a reported feature of this continuous C-peptide analysis. The registry record does not identify an over-dispersion assessment or a model for this endpoint. The concept should not be taken as evidence that over-dispersion occurred in this trial.

For a continuous outcome, the shape and spread of participant values can affect the suitability of a model and the reliability of its uncertainty estimates. The registry record does not post participant-level data, distributions, residual checks, or a description of model assumptions. It is consequently not possible to assess those features from the posted summary statistics.

How should the planning illustrations be read?

The planning illustrations are described as calculations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They consider detecting a stated fraction of the observed effect. These are planning illustrations, not results from the randomized comparison and not observed power. Their assumptions do not establish that the trial was designed around those effects. The trial’s own sample-size justification is not reported in the registry record.

More generally, a planning calculation depends on its assumed effect, variability, allocation, significance level, and target power. A calculation based on an effect observed in the same trial is illustrative and should not be presented as proof that the study had adequate power. The registry does not report the trial’s original sample-size calculation or the assumptions underlying its planned enrollment beyond the minimum arm numbers in the brief summary.

The record also does not provide details of an interim analysis, a stopping rule, covariate adjustment, or the statistical software and procedures used for the endpoint. These are not necessary to describe the posted means, but they matter when evaluating how the estimates and their uncertainty were obtained. In their absence, interpretation should remain limited to the recorded endpoint summaries rather than assuming a particular analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no posted secondary outcomes. It also lists zero analyses. Although the primary endpoint is identified, the record does not report a full statistical analysis plan or explain how any multiple comparisons among the three arms were handled. The multiplicity approach is not reported in the registry record. This matters because examining several arm-to-arm contrasts or outcomes can raise the chance of a false-positive finding if the analysis does not account for the number of comparisons.

No arm-to-arm test or contrast is posted for the primary endpoint, so there is no reported inferential result to interpret as adjusted or unadjusted for multiplicity. The arm means and confidence intervals should be treated as descriptive summaries rather than as a set of confirmed treatment comparisons. The record does not say whether any unposted analyses were conducted outside the registry.

The analysis population is not identified. The record does not say whether the endpoint summaries include all randomized participants, only participants with an available 12-month measurement, or another defined group. It does not describe missing outcome data, reasons for missingness, imputation, sensitivity analyses, or how withdrawals were handled. These details are not reported in the registry record.

Missing-data handling can affect both the estimated mean and its precision, especially when availability of measurements is related to participant outcomes or treatment assignment. In general, an analysis restricted to observed measurements and an analysis that addresses missing values can answer different questions. Without a stated analysis population and missing-data method, the posted arm summaries cannot establish how missingness influenced the results.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cd4 lymphocyte decrease or other (62.1%), all immune system disorders (51.7%), general disorders and administration (6.9%), metabolism and nutrition disorders (6.9%), gastrointestinal disorders (3.4%).

The registry’s adverse-event record gives serious-event at-risk and affected counts by arm. For ATG and placebo, it reports 29 at risk and 28 affected. For ATG plus GCSF, it reports 29 at risk and 29 affected. For placebo, it reports 31 at risk and 8 affected. The record reports zero deaths in each arm. It also lists serious-event terms with percentages, including “CD4 lymphocyte decrease or other” at 62.1% and “All immune system disorders” at 51.7%.

These are counts and categories recorded for the trial, not estimates of causal effects. The registry record does not explain the precise event definitions, the period covered by the safety reporting, or the denominator used for each listed percentage. It also does not provide comparative statistical analyses of safety between arms. The at-risk counts should not be substituted for the endpoint counts, which differ.

Serious adverse-event summaries do not capture every aspect of safety, such as severity distributions, timing, duration, or whether events were judged related to treatment. Those details are not reported in the registry record. The posted figures describe the adverse-event information recorded for the study; by themselves, they do not establish that an intervention caused or prevented an event.

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

The registry results provide descriptive information about the primary C-peptide endpoint in the three randomized arms. The reported means and confidence intervals allow readers to see the estimated endpoint values and the precision reported for each arm. The record also provides arm-specific adverse-event counts and lists serious-event categories. These are useful parts of the trial record, but they do not answer every comparative question.

Most importantly, the posted data do not include an arm-to-arm treatment-effect estimate, a confidence interval for a contrast, or a p-value. The apparent ordering of the means cannot be treated as proof of a difference caused by treatment. Nor can the arm-specific intervals alone establish whether a comparative effect is compatible with no difference. The registry record does not report a clinically meaningful threshold for this endpoint.

The endpoint is tied to stimulated C-peptide measurements and is described as change from baseline to 12 months. It does not, on its own, establish a broader clinical outcome or describe how each participant’s disease course changed. The record does not report the endpoint analysis population, missing-data methods, or baseline values by arm, limiting assessment of how the endpoint summaries were constructed and how representative they are.

Similarly, the safety counts describe events recorded in the trial, but the registry does not provide enough detail to assess event timing, attribution, or comparative risk statistically. Zero deaths are recorded in each arm, but that observation should not be extended to a conclusion about safety beyond the trial data and reporting available in the registry.

Overall, the posted results support a careful description of arm-specific endpoint estimates and recorded safety events. They do not establish whether ATG alone or ATG with GCSF differs from placebo on the primary endpoint, and they do not establish clinical benefit or harm. Comparative conclusions require analyses and reporting that are not present in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between reporting group summaries and reporting a randomized comparison. The registry describes a randomized, parallel-group, placebo-controlled study and posts an endpoint mean with a confidence interval for each arm. Those summaries show what was recorded by group, but the randomized design’s comparative question is not resolved without an estimate of the treatment contrast and its uncertainty.

The endpoint also illustrates why the definition of a continuous outcome matters. The registry specifies stimulated C-peptide measurements at multiple time points and describes a weighted average in nmol/L, while the primary endpoint title refers to change from baseline to 12 months. Clear reporting of the analyzed quantity and its calculation is important for interpreting results and comparing them with other analyses. The record gives the measurement schedule and general definition, but does not report further detail on the analysis calculation.

The trial’s arm-specific confidence intervals provide a way to assess precision of the means, but they are not a replacement for confidence intervals around treatment differences. This distinction is central to clinical trial interpretation: a treatment question is comparative, while an arm mean is a group description. The absence of posted analyses, population definitions, and missing-data methods further limits what can be inferred.

The adverse-event record adds a separate statistical consideration. Safety counts are descriptive and depend on clear event definitions, denominators, follow-up, and attribution. Some of that context is not reported in the registry record, so the counts should not be read as comparative causal estimates. Together, these features make the record a useful case for separating observed summaries, inferential evidence, and uncertainty about analysis methods.

14. 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 the efficacy results is that the registry posts arm-specific means and confidence intervals but no treatment contrast or analysis. It lists zero analyses, so there is no reported statistical test with which to evaluate the randomized comparison. The reported confidence intervals apply to individual arm means, not to differences between arms.

The endpoint description identifies a change from baseline to 12 months and gives the C-peptide measurement schedule and AUC mean definition. The registry does not give further detail about the change calculation or the statistical model. It also does not report baseline endpoint values by arm, the analysis population, missing-data handling, or sensitivity analyses. These omissions limit assessment of how the endpoint estimates were produced and how robust they are.

Although the design fields state triple masking, the brief summary describes a double-blinded trial. The record does not explain this discrepancy or identify which study roles were masked. Some treatment descriptions are incomplete, limiting what can be said about the full intervention procedures based on this record.

For safety, the registry gives at-risk and affected counts, death counts, and selected serious-event terms. It does not report event definitions, the period covered, the denominator for each listed percentage, attribution to treatment, or comparative statistical analyses. The safety figures therefore cannot be used to establish comparative causal effects.

The registry record does not report a sample-size justification, an interim analysis plan, or a complete statistical analysis plan. These missing details should not be filled in by inference from the trial’s phase, enrollment, or posted summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: ATG-GCSF in New Onset Type 1 Diabetes — NCT02215200.
• Registry record last updated 2020-03-02; status last verified 2020-02.
• Results first posted 2020-03-02.
• 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.

18. Record Summary

NCT02215200 is a completed, randomized, parallel-group, placebo-controlled phase 2 trial of ATG, ATG plus GCSF, and placebo in new-onset type 1 diabetes. The sponsor is the National Institute of Diabetes and Digestive and Kidney Diseases. The registry records enrollment of 89, a start date of 2014-12, and primary completion in 2017-08.

The primary endpoint is change in the stimulated C-peptide AUC mean from baseline to 12 months. The posted arm means are 0.528 nmol/L for ATG and placebo, 0.646 nmol/L for ATG plus GCSF, and 0.406 nmol/L for placebo, each with a 95% confidence interval. The registry posts no analyses or secondary outcomes. It also records serious adverse-event counts and zero deaths in each arm.

The results are descriptive arm summaries. A comparative treatment-effect estimate, analysis population, missing-data method, and full statistical analysis plan are not reported in the registry record.