Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease (NCT00388362), a na phase 2 study. The primary outcome is Clinical Activity.

2. Clinical Question

In practical statistical terms, the study asks whether clinical activity was observed among people treated with the sirolimus-and-prednisone regimen, rather than whether the regimen performed better than a control. A single-group study can describe outcomes in the treated group, but it cannot separate treatment effects from the natural course of disease, changes in other care, or differences in who remained under observation. The trial is listed as phase II and completed. Its stated purpose was to study the effectiveness of sirolimus in combination with prednisone for chronic graft-versus-host disease. The record also lists Overall Survival as a secondary outcome, but does not report a numerical result for it.

3. Trial Design

This was a phase II, single-group trial of sirolimus and prednisone for chronic graft-versus-host disease. Stanford University is listed as the sponsor. The registry record lists enrollment as 36, allocation as NA, and masking as none. The trial began in 2005-11, had primary completion in 2010-11, and is marked completed. These features describe how the study was organized; they do not establish whether an outcome was caused by treatment.

Because the study has one treatment group, there is no concurrent control arm against which to compare clinical activity or safety. Allocation marked NA is consistent with the single-group design, not evidence of random assignment. With no masking, the registry record does not indicate blinded assessment. The record does not explain whether clinical activity was assessed by independent reviewers or whether outcome assessment used any protections against observer expectations.

The primary outcome was Clinical Activity, recorded as a participant count. The stated assessment schedule was at 3 month intervals after sirolimus initiation until 2 years after initiation. Its description says it was evaluated at 2 years after enrollment and defines activity in relation to stopping immunosuppression with resolution of reversible manifestations. It also describes a group of 23 patients who remained on study for a median of 514 days (96-814 days), with the outcome narrative referring to resolution or improvement, a median 90% reduction in prednisone dose, and no additional immunosuppressive therapy over a two-year treatment period. The record does not give the number meeting the endpoint.

The trial lists two outcome measures, including Overall Survival as a secondary outcome. The registry record does not report a statistical analysis plan, a sample-size justification, or interim-analysis details. Those omissions prevent assessment of how the planned design addressed precision, multiplicity, or monitoring. The single-group design remains the central interpretive limitation: even a clearly reported outcome proportion would describe participants in this treatment group, not a randomized treatment contrast.

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.

Enrolled

Reasons for not completing this period:

Remained on Study Median of 514 Days

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 23 patients that remained on the study for a median of 514 days (96-814 days). Numbers based on resolution/ improvement in clinical manifestations of cGVHD with a median of 90% reduction in prednisone dose and no additional immunosuppressive therapy over a two year treatment period.

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: Administration of Sirolimus and Prednisone

6. Primary Endpoint

The registry lists the primary outcome as Clinical Activity, measured over 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus.

The primary endpoint is titled Clinical Activity and is measured in participants. Its description defines the intended clinical state through discontinuation of immunosuppression together with resolution of all reversible chronic graft-versus-host disease manifestations. The record says the outcome was evaluated at 2 years after enrollment and that assessments were planned at 3 month intervals after sirolimus initiation until 2 years after initiation. The endpoint narrative also includes improvement in manifestations, a median 90% reduction in prednisone dose, and no additional immunosuppressive therapy over a two-year treatment period.

As a general statistical principle, a clinical endpoint should connect the study question to a clearly specified outcome, assessment time, and population. A participant count can be easy to interpret when both the qualifying criteria and the population assessed are explicit. Here, the record gives several pieces of endpoint context, but does not report the number of participants who met the endpoint, an outcome proportion, or an uncertainty interval. It also does not clarify how resolution and improvement were combined for the reported primary outcome, or how patients who discontinued or lacked an assessment were handled.

The endpoint is clinically oriented because it refers to manifestations and immunosuppression use, rather than a laboratory measure alone. Its usefulness for judging treatment effects is nevertheless limited without a reported result and a comparator. The endpoint description alone cannot establish how frequently the specified state occurred or whether it differed from what would have occurred under another treatment strategy.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts with the design. This trial is listed as single group, with allocation NA and masking none. General statistical principle: a randomized comparison estimates a contrast between assigned groups, while a single-group study describes outcomes within the group receiving the study regimen. Without a control group, differences from an external expectation cannot be attributed to treatment unless additional assumptions and evidence support that interpretation. The registry record does not report such a comparative analysis.

What does a participant count represent?

The primary outcome is recorded in participants, and its parameter is listed as NUMBER. In general, a count records how many people meet an outcome definition in an analysis population. A count alone does not indicate the proportion affected unless its denominator is also defined. Nor does a count explain how uncertainty was estimated. The registry record gives no numerical count of participants meeting Clinical Activity and no confidence interval for that endpoint. The narrative about the 23 patients who remained on study should not be converted into a response count or an outcome rate.

The record describes assessments at 3 month intervals after initiation through 2 years, while also saying the endpoint was evaluated at 2 years after enrollment. General principle: an endpoint assessed repeatedly can be analyzed as a sequence of status measurements, a time-to-event outcome, or a result at a designated assessment. These approaches answer different questions. The registry record does not specify which analysis was used, how multiple assessments were combined, or how a participant’s status between assessments was treated.

How should precision be understood?

General statistical explanation: a confidence interval gives a range of values reasonably compatible with the observed data under the assumptions of the analysis. Its width reflects precision as well as the amount of information and variability. A point estimate without an interval can conceal substantial uncertainty. No confidence interval is reported for Clinical Activity in the registry record, so its precision cannot be evaluated from the posted outcome description.

A p-value, when reported, measures how compatible data are with a specified statistical model and null hypothesis; it is not the probability that a treatment works or that the null hypothesis is true. The registry record reports no analysis for the primary outcome and no p-value. The absence of a reported test does not establish that no analysis was performed outside the registry; it means the registry record does not report one.

What do the planning assumptions mean?

General explanation: sample-size planning asks how much information a future study may need to detect a chosen effect under specified assumptions. The planning description associated with this trial uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not features of the single-group trial’s observed design. The stated sample-size illustrations are not observed power and should not be read as evidence that the completed trial had a particular probability of detecting an effect. The registry record does not report the trial’s own sample-size justification. It also does not provide numerical planning estimates in the information available for this analysis.

General principle: when a planning calculation uses a previously observed effect, the result depends on that estimate and on the assumed fraction of it to be detected. If an initial estimate is imprecise, a planning exercise based on it may also be uncertain. Planning estimates do not demonstrate that the assumed effect is clinically important or that a study’s actual result is reliable.

Why does the single-group structure matter?

Without a concurrent control group, there is no between-group standard error or treatment contrast to interpret. A before-and-after change, if reported, could reflect treatment, natural variation, changing care, or assessment differences. General statistical methods can adjust for measured covariates, but adjustment cannot guarantee control of unmeasured differences. The registry record does not report an adjusted analysis, baseline outcome values, or covariate methods. No adjusted or causal effect estimate can therefore be described from this record.

The record’s listed safety counts are also descriptive. General principle: an event count is easier to interpret when the risk period, event definition, population, and handling of repeated events are clear. A count of affected participants is different from a count of event episodes. The record does not specify whether the serious-event fields count participants or episodes, or describe the risk period and event-attribution procedures. Those gaps limit interpretation beyond the posted counts and terms.

Finally, statistical significance and clinical relevance are distinct concepts. A small p-value would not establish that an effect matters to patients, while a non-significant result would not establish that there is no effect. The registry record does not report a primary-outcome effect estimate, test, or interval, so neither significance nor precision can be assessed. The most defensible reading is descriptive: the registry identifies the planned endpoint, the single-group treatment design, and selected safety counts, while leaving the primary numerical outcome and its uncertainty unreported.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures: Clinical Activity as the primary outcome and Overall Survival as a secondary outcome. It does not report a multiplicity strategy, such as whether inference was focused on one endpoint or adjusted for examining multiple outcomes. General statistical principle: testing or interpreting several outcomes can increase the chance of finding an apparently notable result by chance, depending on the testing strategy. Without a stated plan and reported analyses, the extent to which multiplicity was addressed is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The primary-outcome description refers to 23 patients who remained on the study, while enrollment is listed as 36. The record does not explain why the outcome description concerns this subset, what happened to other participants, or whether missing assessments were treated as non-response, excluded, or handled through another method. These choices can affect a participant-count endpoint, especially when continued observation may be related to health status or treatment tolerability. No conclusion about the direction or size of any such effect is justified from the available information.

The analysis population is not fully specified. The record does not say whether the primary outcome was analyzed among all enrolled participants, those who started treatment, those who completed a particular assessment, or another group. It also does not report a statistical analysis plan, interim analyses, or a rationale for the analysis population. General principle: a clear analysis population and prespecified missing-data methods help readers understand which participants contribute to an estimate and how incomplete follow-up affects it. Without those details and a numerical endpoint result, the primary finding’s robustness cannot be assessed.

11. 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: cmv resulting in death (8.6%), pulmonary (5.7%), hematological disease relapse (5.7%), recurrent viral pneumonia (5.7%), death (2.9%).

The registry record lists one Sirolimus Therapy group. It reports 35 participants at risk for serious adverse events and 14 affected. For other adverse events, it reports 35 at risk and 35 affected. These are registry counts, not comparisons with another treatment group. The record does not provide a control group, so the counts cannot establish whether event frequency was higher or lower than it would have been under another approach.

The serious adverse-event terms listed with percentages are CMV resulting in death (8.6%), Pulmonary (5.7%), Hematological Disease Relapse (5.7%), Recurrent Viral Pneumonia (5.7%), Death (2.9%), and Sirolimus associated interstitial pneumonitis (2.9%). The record does not specify the denominator or calculation method for these term percentages, whether terms can overlap, or whether they represent participants or event episodes. The term CMV resulting in death should be read as a listed event category; it does not establish that every CMV event was fatal.

General statistical principle: safety counts depend on definitions, observation time, and ascertainment. The registry record does not report detailed event definitions, severity grading, attribution to treatment, or exposure-adjusted rates. The figures therefore describe what the record lists but do not, on their own, quantify comparative risk or establish causation.

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

The registry record documents a completed phase II, single-group trial of sirolimus with prednisone for chronic graft-versus-host disease. It identifies Clinical Activity as the primary outcome and gives a description of how that outcome relates to immunosuppression discontinuation and resolution of reversible manifestations. It also records that 23 patients remained on the study for a median of 514 days (96-814 days), and includes a narrative about clinical improvement, prednisone reduction, and no additional immunosuppressive therapy over a two-year treatment period. These details describe the record’s outcome context, but they are not a numerical primary-outcome estimate.

The record does not report how many participants met the Clinical Activity endpoint, the proportion meeting it, or an interval expressing uncertainty. It therefore cannot establish the frequency or precision of the primary outcome from the posted information. The narrative about participants who remained on study should not be treated as a result for all enrolled participants, because the record does not explain the relationship between that group and the full enrolled population.

The design also limits what can be concluded. A single-group study has no randomized comparator, so its outcomes do not estimate a treatment difference. Any observed clinical course could reflect treatment as well as disease course, concurrent care, participant selection, or follow-up patterns. The record does not provide analyses that separate these possibilities. Overall Survival is listed as a secondary outcome, but a numerical survival result is not reported.

The safety fields provide counts and selected serious-event terms, but lack a concurrent comparison and detailed methods for defining or attributing events. These figures should not be interpreted as proof that the regimen caused the listed events or as a comparative estimate of risk. In short, the registry record describes the design, endpoint intentions, and selected safety reporting; it does not supply the numerical primary result or comparative evidence needed to quantify treatment effects.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly named endpoint is only one part of an interpretable clinical result. Clinical Activity is described in terms of clinical manifestations and immunosuppression, and the record specifies an assessment schedule. But without the number meeting the endpoint, the population analyzed, and an uncertainty estimate, readers cannot assess how often the intended outcome occurred or how precise that assessment was.

It also highlights the limits of single-group evidence. A treatment group’s clinical course can be described, but no concurrent group provides a reference for changes that might have occurred without the study regimen or under an alternative. This distinction is important when a registry narrative mentions improvement: improvement in a treated group is not itself a randomized estimate of treatment effect. Design determines which questions the data can answer.

The record also shows why enrollment and analysis populations need to be distinguished. Enrollment is listed as 36, while the primary-outcome description refers to 23 patients who remained on study. Without an explanation of that difference or a missing-data strategy, readers cannot determine how representative the described group is of the enrolled population. Transparent participant accounting is essential for judging possible selection and attrition effects.

Finally, the safety record demonstrates the need for precise event definitions and denominators. Counts, percentages, and event labels can appear informative, but their interpretation depends on who was observed, over what period, and whether repeated or overlapping events are represented. Those details are not reported in the registry record. The trial is therefore a useful example of how study design, analysis transparency, outcome reporting, and safety definitions jointly determine what readers can conclude.

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.

Several limitations are specific to the information in this registry record. The study has a single treatment group and no randomized comparator, so it cannot provide a controlled estimate of the effect of sirolimus with prednisone. Masking is listed as none, and the record does not explain how the clinical endpoint was assessed or whether outcome assessment used independent review.

The primary endpoint description contains clinically meaningful elements, but the numerical outcome is not reported. The record does not give a count meeting the endpoint, a proportion, an uncertainty interval, or a primary-outcome test. It refers to 23 patients who remained on study for a median of 514 days (96-814 days), whereas enrollment is listed as 36; it does not explain the difference, describe the outcome status of other participants, or report how missing assessments were handled.

The endpoint timing is described both as assessment at 3 month intervals through 2 years after sirolimus initiation and as evaluation at 2 years after enrollment. The registry record does not clarify how these descriptions align or how repeated assessments contributed to the endpoint. It also does not specify how resolution and improvement were combined, or how discontinuation of immunosuppression was operationalized.

For safety, the record gives at-risk and affected counts and selected serious-event terms with percentages, but does not report detailed event definitions, risk periods, attribution procedures, or the calculation basis for term percentages. Overall Survival is listed as a secondary outcome without a numerical result. The statistical analysis plan, sample-size justification, interim-analysis details, and multiplicity approach are not reported in the registry record. These omissions prevent fuller assessment of precision, analysis choices, and the robustness of the findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease — NCT00388362.
• Registry record last updated 2017-04-21; status last verified 2017-03.
• Results first posted 2017-04-21.
• 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

The registry record describes a completed phase II, single-group trial of sirolimus with prednisone for chronic graft-versus-host disease, sponsored by Stanford University. Enrollment is listed as 36; allocation is NA and masking is none. The primary outcome is Clinical Activity, with an assessment schedule described at 3 month intervals through 2 years. Overall Survival is listed as a secondary outcome.

The primary-outcome narrative refers to 23 patients who remained on study for a median of 514 days (96-814 days), and describes clinical manifestations, prednisone reduction, and no additional immunosuppressive therapy. A numerical primary-outcome result and uncertainty estimate are not reported. Safety reporting lists 14 affected among 35 at risk for serious adverse events and 35 affected among 35 at risk for other adverse events. The record does not report a comparator, a numerical survival result, or detailed analysis and missing-data methods.