Anakinra to Treat Patients With Neonatal Onset Multisystem Inflammatory Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anakinra to Treat Patients With Neonatal Onset Multisystem Inflammatory Disease (NCT00069329), a na phase 1, phase 2 study. The primary outcome is Diary Symptom Sum Score (DSSS) (Fever, Rash, Joint Pain, Vomiting, and Headaches).

2. Clinical Question

3. Trial Design

This was a phase 1 and phase 2, single-group study sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The registry lists 43 enrolled participants, no allocation, and no masking. The study began in 2003-09, had a primary completion date of 2010-04, and is listed as terminated. The reason for termination is not reported in the registry record.

All enrolled patients were assigned to the NOMID treatment arm and received daily subcutaneous anakinra. The arm description says doses increased from 0.5mg/kg/day up to a maximum 10mg/kg/day, with disease remission as the stated goal. The primary measure’s population description instead says patients started at 1mg/kg, with stepwise increases of 0.5-1 mg/kg/day as frequently as every 2 weeks to achieve laboratory and organ inflammation remission. These summaries differ in their description of starting dose and dose escalation; individual dosing histories are not reported in the registry record.

The listed primary measure is a continuous mean score, with standard deviation as its dispersion measure. Its stated timeframe is baseline. The population note says the reported data are on 26 patients who completed their 3 year assessment, while the enrollment figure is 43. The registry record does not provide a participant flow account explaining the relationship between enrollment, assessment completion, and the analysis population.

This single-group design can describe participants’ symptoms and safety events during the study, but it does not offer a concurrent control group for separating treatment-related changes from other changes over time. The registry record does not report a rationale for the design, sample-size justification, or reason for the study’s terminated status.

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

Analysis population for the primary outcome, as defined in the registry: Patients started at 1mg/kg by daily subcutaneous injection. Stepwise dose increases of 0.5-1 mg/kg/day per injection were made as frequently as every 2 weeks to achieve laboratory and organ inflammation remission. Data reported is on 26 patients who completed their 3 year assessment.

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 Diary Symptom Sum Score (DSSS) (Fever, Rash, Joint Pain, Vomiting, and Headaches), measured over Baseline.

The primary measure is the Diary Symptom Sum Score (DSSS), covering fever, rash, joint pain, vomiting, and headaches. Each symptom was scored daily on a scale from 0 (no symptoms) to 4 (highest severity). The five symptom scores were summarized as a mean for a period preceding each visit, according to the outcome description.

For baseline, the score is defined as the mean over the 5-30 last days before the first dose of Kineret. For subsequent visits, the description specifies the mean over the last 30 days with data before each visit. This repeated diary approach is intended to represent symptom severity across a period, rather than relying on a single day’s report. Combining several key symptoms also gives a single summary measure of the symptom domains named in the registry description.

The listed primary timeframe is baseline. That means the stated endpoint identifies a pre-treatment symptom measure; by itself, a baseline value does not quantify change during treatment or establish a treatment effect. Although the description defines how subsequent-visit scores would be formed, a numerical follow-up result or change from baseline is not reported in the registry record. The outcome is continuous, and its listed summary is a mean with standard deviation. The registry record does not report the actual mean or standard deviation for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure summarized by a mean and standard deviation. General statistical explanation: a mean describes the average value in the analyzed group, while the standard deviation describes how dispersed individual values are around that average. The standard deviation is not the same as the uncertainty in the estimated mean. To judge uncertainty in an estimate, readers generally need an inferential quantity such as a confidence interval, together with the analysis details. The registry record does not report the primary endpoint’s mean, standard deviation, or confidence interval.

What the diary score represents

The DSSS draws on daily ratings of fever, headache, rash, joint pain, and vomiting. Each symptom is scored from 0 (no symptoms) to 4 (highest severity). The outcome description says the diary variables are evaluated as a mean over a period preceding visits. Baseline refers to the mean of the 5-30 last days before the first dose of Kineret; subsequent visit values are defined using the last 30 days with data before each visit. Averaging observations across a period can give a less day-specific summary than a single diary entry, while the resulting score still depends on the recorded symptoms and the availability of diary data.

The outcome is labeled as a sum score, while its description says each diary variable is evaluated as a mean value over a period. The record identifies five symptoms and provides the score range for each, but does not report the actual endpoint values or a detailed computational formula beyond that description. The stated primary timeframe is baseline. A baseline mean is descriptive of symptom severity before treatment; it is not an estimate of change caused by treatment.

Single-group interpretation

The study is listed as single-group, with no allocation and no masking. General statistical explanation: a single-group design can describe outcomes within participants or within the group over time, but it does not estimate a direct contrast against a concurrent control group. A change from baseline, if available, would still need cautious interpretation because time trends, measurement variation, changes in care, and other factors may also influence measurements. These are general considerations, not reported findings about this trial.

The registry record does not report an analysis method for estimating change, the handling of repeated observations, covariate adjustment, or a statistical model. It also does not report inferential results for the primary outcome. Any such method or result should not be inferred from the endpoint’s measurement description alone.

Precision and over-dispersion

General statistical explanation: a confidence interval communicates uncertainty around an estimated quantity, conditional on the analysis method and its assumptions. Wider intervals indicate less precision, while narrower intervals indicate greater precision. No confidence interval for the primary DSSS result is reported in the registry record, so the precision of a treatment-effect estimate cannot be assessed.

General statistical explanation: over-dispersion arises when observed variability is greater than a statistical model expects. It can make standard errors too small if a model assumes less variability than the data contain. The primary outcome is described as a continuous measure with a standard deviation; the registry record does not report whether over-dispersion was assessed or whether any model requiring that assessment was used. No conclusion about over-dispersion can be drawn from the available outcome description.

Sample-size illustrations

The planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It uses a fraction of the observed effect as the effect to detect. General statistical explanation: such a calculation asks how many participants per arm would be needed under specified assumptions to detect a hypothetical effect with a chosen power. It is a planning exercise, not observed power and not evidence that the original study had that design.

The actual study is single-group, rather than a two-arm equal-allocation comparison. The registry record does not report the study’s sample-size justification, and no numerical planning estimate or observed effect is reported in the registry information. Thus, the planning assumptions should not be read as the study’s protocol or as a reconstruction of its actual design. If an illustration uses a fraction of an observed effect, that effect and the related participant counts remain planning inputs, not observed outcomes or proof that the study was adequately powered.

The record lists no analyses. Statistical methods for handling missing diary entries, calculating endpoint summaries across participants, estimating treatment effects, or assessing precision are not reported in the registry record. Without these details and numerical results, statistical interpretation must stay with the design and endpoint definitions rather than an unreported estimate.

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("NOMID")
n   <- c(26)
m   <- c(0.75741904)
sp  <- c(0.08370955)
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  NOMID  26  0.757  0.084  0.724  0.791

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 21 outcome measures and no analyses. The primary DSSS is one listed outcome, but the record does not describe how outcomes were prioritized for statistical testing, whether there was a prespecified testing hierarchy, or whether any adjustment was made for multiple comparisons. A multiplicity strategy is not reported in the registry record.

General statistical explanation: when many outcomes or hypotheses are examined, the chance of obtaining an apparently noteworthy result by chance can increase. Prespecifying a primary outcome and defining how other outcomes will be interpreted can help readers understand the role of each result. The registry identifies a primary endpoint, but does not report the full analysis plan or the statistical handling of the other outcome measures.

Missing-data methods are also not reported in the registry record. The endpoint description refers to diary data over defined periods, including the last 30 days with data before later visits, but it does not explain how missing diary entries, incomplete visit windows, or participants without later measurements were handled. The record does not state whether any imputation, complete-case analysis, or other approach was used.

The enrollment figure is 43, while the primary outcome population description refers to data on 26 patients who completed their 3 year assessment. A full analysis-population definition, participant disposition, and reasons for non-completion are not reported in the registry record. These omissions limit assessment of selection into the reported endpoint population and of how missing observations could affect its interpretation. No claim about the direction or magnitude of any missing-data bias can be made from the information recorded.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: headache (11.6%), lung infection (4.7%), hospital admission for cardiac catheterization (2.3%), uveitis (2.3%), diarrhea (2.3%).

The safety record lists 43 participants at risk for serious adverse events, with 18 affected. It also lists 43 participants at risk for other adverse events, with 43 affected. These are registry counts of participants affected, not estimates of a treatment effect against a control group. The record lists no deaths value; the death count is not reported in the registry record.

The serious-event terms with the largest listed percentages are headache (11.6%), lung infection (4.7%), hospital admission for cardiac catheterization (2.3%), uveitis (2.3%), diarrhea (2.3%), and gastritis (2.3%). The percentages are reproduced as stated in the record; event-level timing, duration, severity beyond the serious classification, and attribution to treatment are not reported in the registry record. The listing should not be interpreted as establishing that anakinra caused any particular event.

General statistical explanation: adverse-event counts describe what was recorded in the study population during the relevant reporting period. In a single-group study, those counts do not provide a direct comparison of event frequency with an untreated or alternative-treatment group. The record does not provide a basis for estimating comparative safety or assigning causality.

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

The registry record establishes that a single-group phase 1 and phase 2 study of anakinra in NOMID enrolled 43 participants. It identifies a symptom diary measure covering fever, rash, joint pain, vomiting, and headaches, and defines how baseline and later visit scores were intended to be summarized. The record also reports safety counts and selected serious-event terms.

Those details do not establish the amount of symptom change during treatment. The stated primary timeframe is baseline, and a numerical primary endpoint result, change estimate, confidence interval, or statistical test is not reported in the registry record. The treatment goal described in the arm summary is not evidence that the goal was reached. The registry record does not report the proportion of participants achieving remission or a numerical assessment of effectiveness.

The safety counts show that serious adverse events were recorded among 18 of 43 participants at risk and other adverse events among 43 of 43 participants at risk. They do not show whether the events were caused by treatment, nor do they permit comparison with a group not receiving anakinra. The registry lists several serious-event terms but does not provide the event-level information needed to interpret their timing or attribution.

General statistical explanation: a treatment-effect conclusion ordinarily depends on a clearly defined contrast, an estimate, and information about its uncertainty, interpreted in light of the study design. Here, there is no concurrent comparator, and the primary numerical effect and its uncertainty are not reported in the registry record. The study description can therefore inform readers about what was planned and recorded, but it cannot support a quantitative conclusion about treatment effect from the information available.

14. Why This Trial Matters Statistically

This study is statistically informative because its design and endpoint definition make clear what questions the registry can and cannot answer. The record describes a single-group investigation in a disease population, a daily symptom diary, and a summary measure combining five key symptoms. These details help readers understand how symptom severity was intended to be represented and what the safety counts refer to.

The measure’s baseline timeframe is an important distinction. A carefully defined baseline endpoint can characterize symptoms before treatment, but it is not itself a treatment-effect estimate. Without numerical follow-up results or a reported change from baseline, the symptom scale’s definition cannot substitute for outcome evidence. This distinction is central when interpreting registries, where an endpoint description may appear alongside a study objective without the numerical analysis needed to answer that objective.

The single-group design also matters. It means the record does not furnish a randomized, concurrent contrast against another treatment or a control condition. General statistical explanation: comparative designs can help distinguish intervention-associated patterns from background changes; a single-group record has fewer grounds for that separation. This limitation applies regardless of whether outcomes are measured repeatedly.

Finally, the gap between 43 enrolled participants and the primary measure’s reference to 26 patients completing their 3 year assessment highlights the importance of transparent participant flow and analysis populations. The registry does not report a full account of completion, missing data, or outcome analyses. Together, these features show why endpoint definitions, denominators, analysis methods, and uncertainty estimates are necessary for a complete statistical interpretation. The record provides useful design and measurement information, while leaving the primary treatment-effect question quantitatively unresolved.

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 registry’s single-group design is a central limitation for causal interpretation. There is no concurrent control group, no allocation, and no masking. The record therefore does not provide a like-for-like randomized comparison that could estimate how outcomes differed under an alternative condition.

The primary endpoint information is also incomplete for evaluating effectiveness. The DSSS is defined, and its stated timeframe is baseline, but the numerical primary result and any follow-up change are not reported in the registry record. The record does not provide a confidence interval or statistical test for the primary endpoint. It also does not report the analysis method used to summarize repeated diary measurements.

Enrollment was 43, while the primary outcome population description refers to 26 patients who completed their 3 year assessment. The registry record does not provide participant flow, reasons for non-completion, a complete analysis-population definition, or methods for handling missing diary data. This limits assessment of how the analyzed participants relate to all enrolled participants.

Safety information includes affected-participant counts and selected serious-event terms, but death count, event-level details, and treatment attribution are not reported in the registry record. Consequently, these reports cannot establish comparative safety or causality. The record’s terminated status is stated, but the reason is not reported in the registry record.

The registry also does not report sample-size justification, a statistical analysis plan, multiplicity handling, or numerical treatment-effect results. Its dose descriptions differ regarding the starting dose and escalation; individual dosing histories are not reported. These limitations constrain interpretation without establishing that any particular result was favorable, unfavorable, or biased.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Anakinra to Treat Patients With Neonatal Onset Multisystem Inflammatory Disease — NCT00069329.
• Registry record last updated 2016-12-01; status last verified 2016-10.
• Results first posted 2016-12-01.
• 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

NCT00069329 is a phase 1 and phase 2 single-group study of daily subcutaneous anakinra in patients with NOMID/CINCA syndrome. The record lists 43 enrolled participants, no allocation, and no masking. The study began in 2003-09, had a primary completion date of 2010-04, and is listed as terminated.

The primary measure is the DSSS, a mean diary score for fever, rash, joint pain, vomiting, and headaches. Its stated timeframe is baseline; the record does not report a numerical primary treatment-effect result. The outcome population note refers to 26 patients who completed their 3 year assessment. Safety reporting lists serious adverse events among 18 of 43 participants at risk and other adverse events among 43 of 43 at risk. The reason for termination, analysis methods, and missing-data methods are not reported in the registry record.