Anti-inflammatory Therapy With Anakinra in Newly Diagnosed Type 1 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anti-inflammatory Therapy With Anakinra in Newly Diagnosed Type 1 Diabetes (NCT00645840), a na phase 1, phase 2 study. The primary outcome is Effect of Anakinra Treatment on PBMC Gene Expression for Patients.

2. Clinical Question

The study’s stated rationale was to examine whether targeting inflammatory pathways mediated by IL-1 beta would be associated with measurable changes in expression of genes described as overexpressed as a consequence of IL-1 beta effects. The summary presents preserved insulin secretory capacity as an eventual expectation, while the listed primary outcome is gene expression, not a direct demonstration of that longer-term expectation.

This distinction matters when interpreting the clinical question. The registry identifies a small exploratory study without a randomized, masked comparison. Although its outcome description refers to a control group, the record does not establish how those samples were selected or whether the groups were comparable. It therefore does not support treating the outcome as a randomized treatment contrast. The posted record also does not provide the measured gene-expression result, an effect estimate, or its uncertainty.

3. Trial Design

This was an exploratory, open-label study listed as phase 1 and phase 2. The registry classifies it as a single-group study, with allocation recorded as not applicable and masking as none. Enrollment was 15. The listed condition is type 1 diabetes mellitus, and the study title and description identify children with newly diagnosed disease as the population of interest.

All subjects were assigned to receive anakinra as a daily subcutaneous injection. The arm description states that subjects weighing >25 kg at enrollment received 100 mg daily, while those weighing <25 kg received 50 mg daily. It describes treatment as continuing for 28 d, but the treatment description is incomplete. Details beyond those stated, including a complete account of treatment exposure and adherence, are not reported in the registry record.

The registry dates the study start to 2008-03 and primary completion to 2009-09, and lists the status as completed. These dates and status describe the record; they do not establish that every planned measurement or analysis was completed. The record lists University of Texas Southwestern Medical Center as sponsor.

The primary outcome description says baseline and post-treatment expression data were available for 10 anakinra-treated patients and were compared with similarly timed samples from 10 patients in control group B. The record also says the analysis count could not be verified and that it was unclear whether 10 or 12 patients were analyzed. Because the overall study is classified as single-group and the comparator’s design is not described, this reference to control group B should not be read as evidence of a randomized control arm. The method of selecting that comparison group is not reported in the registry record.

The population account notes that three enrolled subjects were later found to have negative autoantibodies and were excluded from further analyses, and that one subject withdrew after two doses. It also says study drug was stopped for another subject after 19 days, but the description is truncated. These details make the distinction between enrolled participants, treated participants, and participants analyzed especially important.

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: We enrolled 15 subjects to receive anakinra. Of these subjects, three were later found to have negative autoantibodies and were excluded from further analyses. One subject withdrew from participation and stopped anakinra after two doses. We stopped study drug for another subject after 19 days of therapy due to an adverse event.

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 Effect of Anakinra Treatment on PBMC Gene Expression for Patients, measured over 1 month.

The primary outcome is titled as the effect of anakinra treatment on PBMC gene expression for patients. Its unit is probe sets, and the outcome is recorded as a number rather than as a single continuous summary such as a mean change. The timeframe is 1 month. The description says expression data at baseline and after treatment were available for treated patients and compared with similarly timed samples from control group B.

Gene-expression measurement is relevant to the study’s stated biological question because the summary focuses on genes described as overexpressed as a consequence of IL-1 beta effects. A comparison of expression at different time points can be used to examine whether measured expression patterns changed during the study period. The record does not identify the specific probe sets, define a single primary gene-level effect, or state how multiple probe-set measurements were combined or interpreted. Those details are not reported in the registry record.

The outcome’s designation as a count-like measure that is not reduced to one comparison means it should not be interpreted as one treatment-effect estimate without more detail. The posted record contains no verified numerical result for the primary outcome, no estimate of change, and no uncertainty interval. The biological rationale therefore does not substitute for a reported outcome result. Nor does the listed primary endpoint directly quantify insulin secretory capacity; C-peptide secretory capacity appears among the secondary outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends first on identifying the design and the outcome being analyzed. This registry classifies the study as single-group, open label, with no masking and allocation recorded as not applicable. Those classifications matter because a treatment effect is usually interpreted through a comparison: for example, change over time within participants, or a difference between treatment groups. The primary outcome description refers to both baseline and post-treatment samples and also mentions control group B. The record does not explain how the comparison was constructed or whether it was prespecified. That ambiguity prevents a confident description of the intended estimand—the precise quantity the analysis was meant to estimate.

What does the outcome represent?

The endpoint is a number of probe sets associated with PBMC gene expression, with a stated timeframe of 1 month. A count-like outcome may be analyzed differently from a continuous measure such as a mean change. Its distribution can be skewed or show greater variability than a simple model assumes. In general, over-dispersion means the observed variability exceeds the model’s expected variability; ignoring it can make uncertainty appear too small. The registry record does not report the outcome distribution, the statistical model, or whether over-dispersion was assessed. It also does not explain how individual probe sets were selected, tested, or summarized.

The phrase “not reduced to one comparison” is important: a single number does not capture all possible contrasts or probe-set results. An overall count can conceal which measurements changed, in what direction, and by how much. To interpret such an outcome, readers would ordinarily need a clear definition of what is counted, the analysis unit, and the comparison rule. Those details are not reported in the registry record, and no numerical primary result is posted.

How should an estimate and its uncertainty be read?

In general, an effect estimate describes the size and direction of a comparison, while a confidence interval expresses the range of values compatible with the data and the statistical procedure. A narrow interval indicates greater precision than a wide one, but precision does not resolve bias or design limitations. A p-value, when reported, describes how surprising the data would be under a specified null hypothesis and model; it is not the probability that a treatment works. Here, no verified effect estimate, confidence interval, or p-value for the primary outcome is reported in the registry record. There is therefore no basis for describing statistical significance or precision for that outcome.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe an illustration based on an observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. In general, a planning calculation estimates how many participants per arm would be needed under specified assumptions to detect a target effect with a chosen power. Such a calculation is not observed power, does not show that the original trial was adequately designed, and depends on the reliability of the effect estimate used. The record does not report a verified primary effect estimate, so the illustration should be treated as conditional rather than as a firm design justification.

The assumptions also describe a two-arm planning framework even though the study is classified as single-group. This mismatch is a reason to distinguish planning illustrations from the actual study design. The registry record does not report that these assumptions were used prospectively in planning the trial, nor does it report a sample-size justification or a power target for the study itself.

Why does the analysis population matter?

Statistical results can depend on who is included. Enrollment is 15, while the record describes later exclusions, a withdrawal, and a treatment stop. It also states that the number analyzed could not be verified and may have been 10 or 12. In general, an analysis based on participants with available measurements can differ from one that retains all assigned or enrolled participants. Missing observations may be related to participant characteristics, treatment exposure, or outcomes, so the handling of missing data can affect interpretation. The registry record does not report a formal missing-data method, an intention-to-treat analysis, or a per-protocol definition.

Because no analysis details or verified outcome results are posted, statistical methods can be explained only as general concepts. The record does not state which model was used, how repeated measurements were handled, whether covariates were included, how uncertainty was calculated, or whether sensitivity analyses were performed. Those omissions limit the ability to assess model assumptions, the robustness of the result, and the degree to which the reported analysis—if completed—matches the study question.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and identifies C-peptide secretory capacity as a secondary outcome. The primary outcome concerns PBMC gene expression and is expressed in probe sets. The record does not provide the detailed list of analyzed probe sets or explain how multiple measurements were handled. When many outcomes or measurements are examined, the chance of obtaining apparently notable results can increase. In general, multiplicity methods control or describe that risk, but the registry does not report a correction, testing hierarchy, or other multiplicity strategy.

The record lists zero analyses, and it does not provide a verified numerical result for the primary outcome. It also does not report analysis details for the secondary outcome. Whether analyses were planned, completed, or omitted is not reported in the registry record.

There is uncertainty about the analysis population. The record says baseline and post-treatment gene-expression data were available for 10 treated patients, but also says it could not verify whether 10 or 12 patients were analyzed. It describes three exclusions following negative autoantibody findings, one withdrawal after two doses, and a treatment stop after 19 days for another subject. The reason for the latter stop is not fully described. These events make it important to distinguish enrollment, treatment exposure, outcome availability, and analysis inclusion.

The registry does not report a missing-data method, whether incomplete observations were excluded or imputed, or whether missingness was assessed for possible bias. It also does not define an intention-to-treat or per-protocol analysis population. Those details are not reported in the registry record, so the effect of missing observations and exclusions on any analysis cannot be evaluated.

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: lymphadenopathy (8.3%).

The safety summary lists 12 subjects at risk for serious adverse events and 1 subject with a serious adverse event. It reports 0 deaths. Lymphadenopathy is listed as the leading serious-event term, at 8.3%. These figures describe the registry’s recorded safety data; they do not establish that the event was caused by anakinra or that it occurred more often than it would have without treatment.

The record separately lists 12 subjects at risk for other adverse events and 12 affected. The “other” category is distinct from the serious-adverse-event count in the registry summary. The record does not give the full list, severity, timing, duration, or clinical course of those other events in the information available for interpretation.

These counts should be read in light of the study design and analysis-population uncertainty. The study has no randomized comparison in its classification, and the safety population is not described in enough detail to reconcile it with the enrollment and outcome populations. The registry does not report a comparative safety estimate, follow-up duration for adverse events, or an attribution assessment. The figures are therefore descriptive, not evidence of a causal or comparative safety effect.

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

This record documents an exploratory study of anakinra in children with newly diagnosed type 1 diabetes, with PBMC gene expression as the primary outcome. It also records a secondary outcome of C-peptide secretory capacity. The stated biological rationale concerns IL-1 beta pathways and gene expression, while the study summary describes preserved insulin secretory capacity as an eventual expectation. These are the study’s aims and rationale, not reported proof of an outcome.

The primary outcome result is not available as a verified numerical analysis in the registry record. The record gives no effect estimate, confidence interval, or p-value and states that the analysis count could not be verified. It is therefore not possible to say from the posted results whether gene expression changed, how large any change was, or how precisely it was estimated. The secondary outcome result is also not reported in the registry record.

The design does not support a straightforward causal comparison. It is classified as single-group and open label, with no masking. A control group is mentioned in the primary outcome description, but its selection and comparability are not explained, and the study is not classified as randomized. Any comparison with those samples should therefore not be interpreted as if it were a randomized treatment contrast.

Enrollment, treatment exposure, and analysis populations also differ in the record’s descriptions. The registry notes exclusions and withdrawals, and it leaves uncertainty about the number analyzed. Without a clear account of missing data and analysis inclusion, the representativeness of any analyzed sample cannot be assessed.

The serious adverse-event figures are descriptive and do not establish cause. Likewise, a sample-size planning illustration based on an observed effect would not show observed power or demonstrate that the original study was designed to detect a specified clinical effect. Overall, the record describes the study question and some design and safety details, but it does not provide a verified efficacy result or sufficient analytic detail for a precise treatment-effect conclusion.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of how a clearly stated biological rationale and an analyzable result are not the same thing. The registry describes interest in IL-1 beta pathways, PBMC gene expression, and insulin secretory capacity. Yet the primary outcome is a count-like gene-expression measure, and the record does not provide a verified numerical result or a complete description of how the measurements were analyzed. Readers must keep the research question separate from evidence that would answer it.

The record also illustrates why study design labels matter. A single-group, open-label study can describe treatment exposure and changes over time, but it does not by itself provide the protection against confounding that random allocation can offer. The outcome description’s reference to control group B adds a comparison, but without details of the group’s origin and selection, its role cannot be evaluated as a randomized comparator.

Analysis-population uncertainty is another important statistical issue. The record reports enrollment of 15 while describing exclusions, a withdrawal, a treatment stop, and uncertainty about whether 10 or 12 patients were analyzed. These distinctions affect what a result would represent. A transparent account of participant flow, outcome availability, and analysis inclusion is essential for assessing selection and missing-data concerns.

Finally, the primary endpoint is expressed in probe sets and is not reduced to one comparison. That structure raises general questions about measurement definition, multiplicity, and how results across measurements should be summarized. The registry does not report the methods used to address those questions. The record therefore underscores the value of complete outcome definitions and analysis reporting, especially in exploratory studies where multiple measurements may inform later research.

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 this specific record is the absence of a verified gene-expression result. The outcome description gives data availability and a comparator reference but not an effect estimate, uncertainty interval, or statistical test. It also says the number analyzed could not be verified. Consequently, the central outcome cannot be quantitatively interpreted.

The study is listed as single-group and open label, with no masking. Although control group B samples are mentioned, the registry does not explain how that group was assembled or whether its participants were comparable to those receiving anakinra. This leaves the comparison’s design and potential sources of bias unclear.

The participant account is incomplete. Enrollment was 15, and the record describes three exclusions, one withdrawal after two doses, and another subject whose study drug was stopped after 19 days. The description of the latter event is truncated. The analysis count is uncertain, and the record does not state how missing measurements or treatment discontinuations were handled. A complete participant-flow account and clearly defined analysis populations are not reported in the registry record.

The primary outcome is a count of probe sets, but the record does not define the counting rule, identify the analyzed probe sets, or describe the statistical model and multiplicity approach. The number of analyses is listed as zero, while the outcome description refers to comparisons. The relationship between those entries is not explained.

Safety details are also limited: the record provides summary counts and a leading serious-event term but does not report event timing, attribution, or follow-up context. Finally, the record’s sample-size assumptions describe an illustration rather than a stated trial design justification. A prospective sample-size rationale is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Anti-inflammatory Therapy With Anakinra in Newly Diagnosed Type 1 Diabetes — NCT00645840.
• Registry record last updated 2019-11-14; status last verified 2019-10.
• Results first posted 2019-11-14.
• 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

NCT00645840 is a completed, exploratory, open-label study listed as phase 1 and phase 2, sponsored by University of Texas Southwestern Medical Center. It enrolled 15 subjects with newly diagnosed type 1 diabetes for daily subcutaneous anakinra. The primary outcome concerns PBMC gene expression over 1 month; C-peptide secretory capacity is listed as a secondary outcome.

The registry classifies the design as single-group, with no masking and allocation recorded as not applicable. Its primary outcome description refers to control group B samples but does not establish a randomized comparison. The record gives no verified primary outcome estimate and is uncertain whether 10 or 12 patients were analyzed. It also describes exclusions, a withdrawal, and a treatment stop.

The safety record lists 1 serious adverse event among 12 at risk, 0 deaths, and lymphadenopathy at 8.3% as the leading serious-event term. The posted information does not establish causality or provide a comparative treatment-effect estimate.