Sirolimus for Autoimmune Disease of Blood Cells: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sirolimus for Autoimmune Disease of Blood Cells (NCT00392951), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Grade 3 and 4 Toxicities of Administration of Oral Sirolimus.

2. Clinical Question

The study title and official title describe a pilot series involving patients with chronic and/or refractory autoimmune cytopenias. The listed conditions span several autoimmune disorders affecting blood cells, as well as other conditions. The registry’s brief summary gives the study rationale: autoimmune destruction of blood cells can cause illness, and the summary describes a need for treatment options. That background explains the question the study was designed to explore, but it does not establish what happened to participants during the trial.

Statistically, the primary question is about the frequency of severe toxicity in the treated group over the stated timeframe. It is not a direct test of whether sirolimus is better than another treatment, because no comparator group is recorded. The registry lists measures of disease response and biological effects as secondary outcomes, but their results are not reported in the registry record. Consequently, the clinical question and the available results must be kept distinct: the study planned to characterize toxicity and other outcomes, while the posted record supplies only limited safety counts.

3. Trial Design

NCT00392951 is recorded as a phase 1/phase 2, completed, single-group study sponsored by Children's Hospital of Philadelphia. Enrollment is listed as 30. The registry gives a start date of 2006-12 and a primary completion date of 2016-02. Sirolimus is the listed intervention, and the study arm is described as sirolimus treatment.

The design has no separate control arm. Allocation is recorded as not applicable, and masking is listed as none. These features matter for interpretation: observations in the treated group can describe what was recorded during treatment, but they cannot establish how outcomes would have differed under an alternative treatment or no treatment. Without a concurrent comparator, outcomes can also reflect participant characteristics, disease course, other care, or factors not documented in the registry.

The primary outcome is a count of participants with grade 3 or grade 4 toxicities over 6 months. Secondary outcomes include the number of participants with autoimmune disease response to oral sirolimus, trough levels produced by oral sirolimus, effects on intracellular targets, and the number of participants with a lymphoproliferation response. The registry lists five outcome measures in total, but the additional details and results for those measures are not reported in the registry record.

The record identifies a pilot series and shows a long interval between its listed start and primary completion dates. Those dates alone do not explain recruitment pace, follow-up, or changes in study conduct. Such details, along with eligibility criteria, the protocol’s analysis plan, and the rationale for the enrollment target, are not reported in the registry record. The completed status indicates the registry’s status designation; it does not by itself supply results for the primary endpoint or show that all planned analyses were reported.

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 Number of Participants With Grade 3 and 4 Toxicities of Administration of Oral Sirolimus, measured over 6 months.

The primary endpoint is the number of participants with grade 3 or grade 4 toxicities of oral sirolimus administration during 6 months. The registry’s definitions distinguish severe toxicity, including toxicity considered medically equivalent to requiring hospitalization or prolonged hospitalization, from life-threatening toxicity for which urgent intervention is indicated. The definitions are attributed to CTCAE criteria 3.0.

A participant count is a descriptive measure of how many people met the specified toxicity criteria during the stated period. It can help characterize serious safety events in the study group. By itself, a count does not describe how events were distributed over time, how long they lasted, or whether a participant had more than one event. The record’s endpoint title specifies participants, rather than total events, as the unit.

This endpoint is relevant to a treatment study because severe toxicity is an important part of the balance of outcomes being monitored. It is not a measure of autoimmune disease response or overall benefit. The registry lists disease response and other measures separately as secondary outcomes.

The primary endpoint’s timeframe and definitions are recorded, but its result is not reported in the registry record. The safety summary lists 1 participant with a serious adverse event, but the record does not identify that summary count as the reported primary-endpoint result or provide the grade-specific breakdown needed to match it to the endpoint definition. The endpoint therefore cannot be treated as fully reported from that count alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study. In this design, participants receive the listed intervention and outcomes are observed in that group; there is no separately recorded control group. As a general statistical point, a single-group design can describe outcomes in its enrolled participants, but it does not directly estimate what would have happened to comparable participants under a different treatment. Differences between observed outcomes and an assumed alternative cannot be separated from the effects of disease course, participant characteristics, or other influences without further design and analysis information.

What does a participant count represent?

The primary outcome is a count of participants with grade 3 or grade 4 toxicity during 6 months. A count answers how many participants met the specified definition, rather than how many total events occurred. This distinction matters because one participant may experience more than one event, while a participant-based endpoint counts that person according to the endpoint’s rules. The registry names participants as the unit, but the result and additional counting details are not reported in the registry record.

For a binary outcome such as whether a participant meets an event definition, the underlying information is often represented as event or no event for each participant. A group count can then describe the observed frequency. As a general statistical point, the count alone does not convey its precision; an uncertainty interval depends on the number of participants included, the observed count, and the chosen method. No interval for the primary endpoint is reported in the registry record, and no additional computation is appropriate without the relevant analysis details.

Why do event definitions matter?

The endpoint specifies grade 3 and grade 4 toxicities and gives severity descriptions attributed to CTCAE criteria 3.0. Clear definitions help determine which observations qualify for the endpoint and support consistent classification. In practice, interpretation also depends on how events were assessed, how severity was assigned, and how the timeframe was applied. Those operational details are not reported in the registry record. The separate adverse-event summary uses serious and other event categories, but the record does not establish that those categories are interchangeable with the primary endpoint’s grade-based definition.

What can the design establish?

With no comparator, the study’s outcome counts are descriptive of the recorded treatment group. A comparative treatment effect would require a contrast between groups or another clearly described comparison method. Neither is reported for this study. This does not make descriptive safety information meaningless; it does mean that the information answers a narrower question than whether outcomes differ because of treatment. General statistical interpretation should distinguish observation from causal attribution.

Masking is listed as none. Masking can, as a general matter, reduce the chance that knowledge of treatment assignment influences some assessments or reporting. The record does not describe which outcomes involved judgment, what assessment procedures were used, or whether any safeguards were applied. The absence of masking is therefore a design feature to note, not a basis for assuming a particular direction or size of bias.

How should the planning illustrations be understood?

The record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It specifies that the effect to detect is a stated fraction of the observed effect. It also distinguishes participant-per-arm calculations from event totals for time-to-event calculations. These are hypothetical planning conventions, not evidence that the actual study used a two-arm design. The registered study is single-group, and allocation is listed as not applicable. The registry does not report the study’s own sample-size justification, so the illustrations should not be mistaken for its protocol plan.

As a general statistical point, sample-size planning asks how much information a proposed design might need to detect an effect under stated assumptions. An illustration that uses an observed effect is conditional on that effect and on its assumptions. It does not establish the probability that this completed study detected a true effect, and it is not observed power. The registry record does not report a protocol-based sample-size calculation or the assumptions underlying the enrollment of 30.

What analyses are available?

The record lists no analyses. It does not report a statistical model, an inferential test, an adjusted analysis, or a confidence interval for the primary outcome. A model would specify how the outcome is summarized or compared and what assumptions support that analysis. For a single-group participant count, a descriptive presentation may be possible, but the record does not provide a reported primary result or methods that would support a more detailed inferential interpretation.

Some outcomes, such as trough levels or intracellular targets, may involve measurements rather than participant counts. The listed outcome names do not provide the observed values, timing details, or analysis methods. As a general point, continuous measurements and binary participant outcomes often require different summaries and assumptions. The registry’s absence of outcome analyses means that no such methods or results should be inferred from the outcome titles alone.

Finally, precision and completeness depend on the analysis population and the availability of outcome data. The registry does not report whether the primary analysis included all enrolled participants, how missing observations were handled, or whether follow-up differed among participants. Those details are necessary to judge how representative the observed safety counts are of the enrolled group and how much uncertainty surrounds them.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Sirolimus Treatment")
n      <- c(30)
events <- c(1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Sirolimus Treatment  30  1  3.3  0.1  17.2  0.6  16.7  0.8  16.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, including autoimmune disease response, trough levels, intracellular targets, and lymphoproliferation response. The record does not report a statistical analysis plan specifying how these outcomes were to be analyzed, which comparisons were planned, or how multiple statistical tests were to be handled. Multiplicity refers, in general, to the increased chance of at least one apparently notable result when many hypotheses are tested. The registry does not report whether any multiplicity adjustment or other strategy was planned.

No outcome analyses are listed, and results for the primary endpoint and the listed secondary outcomes are not reported in the registry record. Therefore, the available record does not support an assessment of whether an analysis was prespecified, whether analyses changed, or how secondary findings should be interpreted relative to the primary question.

The record also does not report the analysis population for the primary outcome, the number of participants with outcome data, or how missing data were handled. Missing-data methods can affect an estimate when outcomes are unavailable, particularly if the missingness relates to health status or treatment experience. That is a general statistical concern, not evidence that missing data occurred in this study. Without the relevant counts and methods, completeness and potential bias cannot be evaluated.

Enrollment is listed as 30, but that does not establish that all 30 contributed to every outcome analysis or completed the stated follow-up. The registry does not report participant flow, withdrawals, exclusions, or the handling of incomplete observation. Those elements would be needed to understand the relationship between enrollment and the population represented by each result.

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: vasculitis (3.3%).

The adverse-event summary lists 30 participants at risk, 1 participant with a serious adverse event, and 15 participants with other adverse events. Vasculitis is listed as a top serious term at 3.3%. These figures describe the safety information recorded for the sirolimus-treatment group; the record does not include a comparator group.

The serious-event count and the count for other adverse events are separate categories in the summary. The registry does not provide enough detail to determine whether participants could appear in both categories, how events were collected, or whether the event summaries cover exactly the same observation period as the primary endpoint. The serious adverse-event figure should not automatically be equated with the primary endpoint, which specifically counts participants with grade 3 or grade 4 toxicity during 6 months.

A listed event term does not by itself establish causation. The registry summary does not report an attribution assessment or provide event narratives, timing, recurrence, or outcomes. The listed 3.3% for vasculitis is quoted as recorded; it should not be treated as a comparative risk estimate. With no control group and no fuller analysis reported, the figures are descriptive and should be interpreted within the limits of the registry summary.

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

The record documents a completed single-group phase 1/phase 2 study of sirolimus with enrollment listed as 30. It identifies a primary safety outcome: the number of participants with grade 3 or grade 4 toxicities over 6 months. It also records a limited adverse-event summary, including 1 participant with a serious adverse event, 15 with other adverse events, and vasculitis as a top serious term at 3.3%.

Those details do not constitute a reported primary-endpoint result. The registry does not give the grade-specific count, a primary-outcome analysis, or an uncertainty estimate. The adverse-event summary cannot fill that gap because its event categories are not shown to match the endpoint definition. Results for autoimmune disease response and the other listed secondary outcomes are also not reported in the registry record.

The findings therefore cannot be used to estimate a comparative treatment effect. There is no control group, allocation is listed as not applicable, and masking is listed as none. Observed counts in a treated group can describe what was recorded among those participants, but they do not show what would have occurred under an alternative treatment. They also cannot establish that sirolimus caused or prevented a particular event.

The record does not report participant-level follow-up, missing-data handling, analysis populations, or the statistical plan. These gaps leave uncertainty about how complete the outcome information was and how the investigators intended to analyze it. The listed enrollment should not be assumed to equal the number analyzed for every outcome.

In short, the registry provides study-design information and limited descriptive safety counts, but not enough outcome reporting to draw a statistical conclusion about the primary toxicity endpoint or disease response. The distinction is important: an endpoint can be specified without its result being reported, and a rationale for studying a treatment is not evidence of an observed treatment effect.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between a defined endpoint and a reported result. The registry clearly identifies a six-month count of participants with grade 3 or grade 4 toxicities as the primary outcome and gives severity definitions. Yet the primary endpoint’s result and analysis are not reported in the registry record. Readers therefore have a precise description of what was intended to be measured, but not the reported value needed to characterize that outcome.

The single-group design also illustrates why the question answered by a study depends on its structure. A treatment group can be described, and events observed in that group can be summarized. Without a comparator, however, the study does not produce a direct estimate of a difference between treatments. This distinction is central when interpreting adverse-event counts: a number can be useful as a description without serving as evidence of comparative safety or causation.

The record also separates the primary toxicity outcome from secondary measures of disease response and biological effects. Listing multiple outcomes signals a broad set of questions, but outcome names alone do not show what was observed or how evidence across those questions was evaluated. With no analyses listed, the statistical treatment of the different outcomes cannot be assessed.

Finally, the planning illustrations are described as hypothetical calculations using assumptions that differ from the registered single-group design. This is a useful reminder that sample-size planning figures are conditional on their assumptions and are not observed study outcomes or proof of statistical power. The record does not report the trial’s own sample-size justification.

Together, these features make careful separation of design, endpoint definition, safety summaries, and outcome analysis essential. The available record supports a limited descriptive account, while leaving important questions about primary results, precision, and completeness unanswered.

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 principal limitation for interpretation is that the primary outcome result is not reported in the registry record. Although the endpoint definition and 6-month timeframe are stated, no grade-specific participant count, estimate, or statistical analysis is given. The listed serious adverse-event count cannot be assumed to be the primary endpoint because the registry does not establish that the definitions and observation periods align.

The single-group design has no recorded comparator. It can describe outcomes among participants receiving sirolimus, but it cannot directly distinguish treatment effects from other explanations. The registry also lists masking as none. How outcome assessment was conducted and whether assessment procedures could have been influenced by treatment knowledge are not reported in the registry record.

Additional information needed to interpret the study is unavailable in the registry record, including eligibility criteria, dosing and treatment schedule, participant flow, follow-up completeness, outcome-specific analysis populations, and handling of missing observations. Enrollment is listed as 30, but the number contributing to each outcome is not reported. The protocol-based sample-size rationale and statistical analysis plan are also not reported.

The adverse-event summary is limited to participant counts and a listed serious term. Event timing, duration, recurrence, severity details beyond the summary classification, and attribution are not reported. The registry does not clarify how the safety summary relates to the primary grade 3/4 endpoint. Results for the listed secondary outcomes are not reported either.

These limitations do not show that particular analyses or procedures were absent from the study; they describe what the registry record does not report. They restrict what can be concluded from the posted information and make it inappropriate to infer comparative efficacy or safety from the available counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sirolimus for Autoimmune Disease of Blood Cells — NCT00392951.
• Registry record last updated 2019-11-19; status last verified 2019-11.
• Results first posted 2017-12-06.
• 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

NCT00392951 is a completed phase 1/phase 2, single-group study of sirolimus for patients with chronic and/or refractory autoimmune cytopenias. Enrollment is listed as 30, and the sponsor is Children's Hospital of Philadelphia. The record lists no masking and no comparator group.

The primary outcome is the number of participants with grade 3 or grade 4 toxicities during 6 months. The registry defines those toxicity grades but does not report the primary endpoint result or an outcome analysis. The adverse-event summary lists 1 participant with a serious adverse event, 15 with other adverse events, and vasculitis at 3.3% as a top serious term.

Several secondary outcomes are listed, but their results are not reported in the registry record. The record also does not report the statistical plan, analysis populations, or missing-data methods. The posted information supports only a limited descriptive interpretation and does not provide a controlled estimate of treatment effect.