Infliximab and Basiliximab for Treatment of Steroid Refractory Acute Graft Versus Host Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Infliximab and Basiliximab for Treatment of Steroid Refractory Acute Graft Versus Host Disease (NCT01485055), a na phase 2 study. The primary outcome is Complete Response Rate Determination.

2. Clinical Question

3. Trial Design

This was a Phase 2, single-group study sponsored by Nationwide Children's Hospital. The listed intervention combined infliximab and basiliximab. The registry describes treatment once a week for four weeks. Allocation is listed as NA, and masking as none; no randomized, masked, or concurrent control comparison is described.

The registry lists enrollment as 11, the study start as 2011-12, and primary completion as 2015-12. Its status is terminated. The stated reason for premature closure is that the sponsor could not supply the medication further. The record also says that enrollment was not sufficient for a valid statistical analysis. It does not report a separate sample-size justification, recruitment target, or explanation of how the enrollment figure was chosen.

The primary endpoint was a participant-level complete response assessment at 28 days. Its definition required complete resolution of GVHD signs and symptoms in all organs and a grade of 0 in all evaluable organs under the Modified Glucksberg scale. The registry lists one outcome measure but no analyses. The response count, response rate, and uncertainty around that result are not reported in the registry record.

A single-group design can describe what happened among participants who received the study intervention, if outcomes are reported. Without a concurrent comparator, it cannot isolate a treatment effect from other explanations for observed changes. The registry's early closure and statement about insufficient enrollment further limit what can be inferred from the response endpoint. No protocol details beyond those stated in the registry record should be assumed.

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: The study was closed prematurely as the study sponsor could not supply the medication any further. The study had not enrolled enough subjects to do a valid statistical analysis

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 Complete Response Rate Determination, measured over 28 days.

The primary endpoint was complete response at 28 days, measured as a count of participants. The definition was demanding: all signs and symptoms of GVHD had to resolve in all organs, and each evaluable organ had to have a Modified Glucksberg grade of 0. The endpoint therefore represents a participant meeting the complete-response definition, rather than a partial change in symptoms or a change in only one organ.

In general, a clearly defined binary endpoint gives each assessed participant an outcome classified as meeting or not meeting the specified criterion. The count meeting the criterion can then be interpreted in relation to the number assessed, provided both are reported and the analysis population is clear. The registry record does not report the complete-response count, the number assessed for this endpoint, or a response-rate estimate. It therefore does not establish how many participants met the definition.

A complete-response measure can be useful when the clinical question is whether the specified disease findings have resolved across the organs evaluated. Its interpretation depends on consistent assessment, the definition of evaluable organs, and how missing or unavailable assessments are handled. The record specifies the response definition and the 28-day timeframe, but does not report the assessment procedures or the handling of missing endpoint data.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either meets the complete-response definition at 28 days or does not. The definition is based on all signs and symptoms of GVHD resolving in all organs, with a Modified Glucksberg score of 0 in every evaluable organ. The registry lists the outcome unit as participants and the parameter as a count of participants. This identifies the intended form of the endpoint, but does not supply the observed count.

In general, analysis of a binary outcome begins by defining which participants belong in the analysis and how each participant's status is classified. A response proportion requires both a count meeting the criterion and a denominator of participants assessed under a stated analysis rule. The registry record does not report the response count, the number assessed, or a response proportion. It also does not identify an analysis population such as all enrolled participants or participants with an evaluable 28-day assessment. Those details are not reported in the registry record.

A confidence interval describes statistical uncertainty around an estimate. For a response proportion, its width depends on the amount of information in the observed data and on the analysis method. In general, small datasets tend to yield imprecise estimates, so a point estimate alone would not convey the full uncertainty. No response estimate or confidence interval is reported for this endpoint, and the record states that enrollment was insufficient for a valid statistical analysis. No numerical precision claim can therefore be made from the registry outcome information.

Because the study is single-group, there is no treatment-versus-control contrast to estimate. In general, a single-group result can describe the outcomes observed under the study conditions, but it does not separate treatment effects from other potential influences. A randomized comparison addresses a different question by comparing outcomes across assigned groups; that design is not described. Allocation is listed as NA, and the registry specifically identifies no like-for-like control comparison.

The record includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Such assumptions describe a planning calculation, not the design of this single-group study, and any resulting sample-size illustration would not be observed power. The observed effect used for that illustration is not reported in the registry record. No numerical planning result is reported in the registry record for this analysis, so none can be interpreted.

In general, over-dispersion matters when observed variability is greater than a model assumes; methods that ignore it can give misleading uncertainty estimates. That issue is relevant to some outcomes, especially counts with more variability than a simple model permits. The primary endpoint in this record is a participant count for a binary response, and no dispersion estimate or model-based analysis is reported. There is no basis to claim that over-dispersion was assessed or that a particular adjustment was used.

Multiplicity concerns arise when several outcomes, time points, or comparisons are tested. In general, repeated testing can increase the chance of apparently notable findings unless the analysis plan accounts for the testing structure. The registry lists one outcome measure, with a primary timeframe of 28 days, and no analyses. It does not report a multiplicity adjustment or a statistical plan describing how multiple tests would be handled. It would be inappropriate to infer that an adjustment was either used or unnecessary beyond what the registry lists.

Missing-data rules are important because participants without a complete endpoint assessment may be handled differently under different analysis choices. In general, a complete-case analysis, a rule that treats missing outcomes as non-response, and a model-based approach answer questions under different assumptions. The registry specifies that the endpoint is assessed in evaluable organs but does not explain how unavailable organ assessments, missed visits, or other missing outcome information were treated. The number of participants with missing assessments is also not reported in the registry record.

The registry's statement that enrollment was insufficient for a valid statistical analysis takes precedence over any attempt to treat the listed endpoint as a completed efficacy analysis. No sponsor analysis, test statistic, p-value, response estimate, or interval is reported. Any calculation based on an assumed effect or an illustrative planning scenario should be distinguished from an observed study result; planning illustrations are not evidence that the trial had a particular level of power or that an outcome occurred.

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("Infliximab and Basiliximab")
n      <- c(10)
events <- c(10)
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  Infliximab and Basiliximab  10  10  100.0  69.2  100.0  72.2  100.0  71.5  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure: complete response at 28 days. It reports no analyses and does not state a statistical plan for multiplicity. In general, multiplicity becomes relevant when several outcomes, time points, or comparisons are tested, because considering many results can change how statistical evidence should be interpreted. The record does not describe additional efficacy testing, so no adjustment method can be identified. It would also be inappropriate to infer from the outcome listing alone what analyses were planned beyond the information recorded.

The endpoint definition refers to all evaluable organs, but the registry does not explain how missing organ assessments or missing 28-day status were handled. It does not report the number of missing assessments, a rule for classifying missing outcomes, or an imputation method. These omissions matter because different missing-data rules can lead to different response counts and estimates. No particular rule should be assumed.

The analysis population is not reported in the registry record. The record gives enrollment as 11 and says the study closed prematurely because the sponsor could not supply the medication further. It also says enrollment was insufficient for valid statistical analysis. The enrolled group should not automatically be treated as the endpoint analysis population: the record does not say how many participants were assessed at 28 days or how participants without an evaluable outcome were handled.

In general, a statistical analysis plan can specify the outcome analysis, populations, missing-data rules, and multiplicity approach before outcomes are examined. The registry record does not report those details. It therefore does not permit assessment of whether a prespecified analysis was followed or whether changes to an analysis plan occurred.

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

Serious events with the highest arm-level rate: alt (9.1%).

The registry reports safety counts for the Infliximab and Basiliximab group. Among 11 participants at risk for serious adverse events, one was recorded as affected. Among 11 participants at risk for other adverse events, zero were recorded as affected. The registry also lists ALT at 9.1% among the top serious terms. These are the posted counts and term; the record does not provide further event-level detail in the registry record for this analysis.

In general, an at-risk count identifies the group denominator used for the reported safety category, while the affected count describes participants recorded with an event in that category. These counts do not by themselves describe event severity beyond the registry's classification, timing, duration, or causal relationship to study treatment. The record does not provide those details, and no causal interpretation should be inferred from the counts alone.

Deaths are not reported in the registry record. That is different from a report of zero deaths: the listed value is unavailable rather than a count of none. The serious-event count and the listed term should also be kept separate from the primary complete-response endpoint, for which no result is reported.

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

The record establishes that a Phase 2, single-group study examined infliximab and basiliximab for steroid-refractory acute GVHD. It describes a planned weekly treatment schedule for four weeks and a primary complete-response assessment at 28 days. It also records enrollment of 11, premature termination because the sponsor could not supply the medication further, and the statement that enrollment was insufficient for a valid statistical analysis.

What the record does not establish is the observed complete-response rate. It provides no response count, denominator for the endpoint assessment, confidence interval, or primary endpoint analysis. Without those data, the frequency of complete response and its statistical precision cannot be described. The record consequently does not establish whether the intervention improved, worsened, or had no effect on the outcome.

Even if a response result were available, the design would limit causal interpretation. In general, a single-group study has no concurrent comparator to help separate outcomes associated with the intervention from other explanations. The registry lists allocation as NA and masking as none. It is therefore not a randomized, masked comparison, and it does not provide a like-for-like control group.

The safety data show one participant with a serious adverse event among 11 at risk and zero participants with other adverse events among 11 at risk. ALT is listed at 9.1% among the top serious terms. These counts do not establish a causal relationship, and deaths are not reported in the registry record. They also cannot substitute for the absent primary endpoint analysis.

The appropriate reading is narrow: the record documents a study that ended early for a stated medication-supply reason, with enrollment that the sponsor considered insufficient for valid statistical analysis. The design and endpoint are described, but the primary response result is not. No treatment conclusion, comparative claim, or estimate of response probability can be drawn from the information reported.

14. Why This Trial Matters Statistically

This study matters statistically because its record illustrates the difference between defining an endpoint and reporting an analyzable result. The primary outcome is described in detail: complete resolution of GVHD signs and symptoms in all organs, with a grade of 0 in every evaluable organ, assessed at 28 days. Yet the registry provides no response count or rate and states that the study did not enroll enough subjects for a valid statistical analysis. A precise endpoint definition cannot replace the outcome data needed to estimate its frequency.

The early termination is also central to interpretation. The registry attributes closure to the sponsor's inability to supply the medication further. This is a documented operational reason, while the record separately states that enrollment was inadequate for valid statistical analysis. The result is a study record with a stated clinical question but no reported efficacy analysis. The missing estimate should not be interpreted as a response of zero or as evidence of no effect.

The single-group design highlights another statistical distinction: describing outcomes in a treated group is not the same as estimating a comparative treatment effect. In general, a concurrent comparator can help contextualize outcomes, whereas a single-group study cannot make that direct contrast. Here, no concurrent comparator is listed, and the response result itself is not reported.

The safety counts are also a reminder to distinguish what is recorded from what is not. Serious and other adverse-event counts are listed, while deaths are not reported. Neither the safety counts nor the listed serious term resolve the missing primary outcome information. Keeping these types of evidence separate helps prevent an incomplete record from being read as a complete efficacy or safety assessment.

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 is that the registry reports no valid statistical analysis of the primary endpoint. It states that the study had not enrolled enough subjects for such an analysis, and it does not provide a complete-response count, response rate, confidence interval, or test result. The endpoint definition is available, but its observed result is not reported.

The study closed prematurely because the sponsor could not supply the medication further. The record does not report further detail about the interruption, its timing, or its effect on individual treatment or assessment. It also does not report a recruitment target or a sample-size justification. No assumptions about the intended enrollment or statistical power should be made.

There was no concurrent control comparison: the design is single-group, allocation is listed as NA, and masking as none. This limits comparative interpretation even if an outcome estimate were available. In this record, the missing response result prevents description of the endpoint itself as well as any comparison.

Additional limitations concern outcome handling. The registry does not report the analysis population, the number assessed for the 28-day endpoint, how missing assessments were handled, or whether participants with incomplete organ evaluations were included. It does not report a detailed statistical plan, multiplicity approach, or analysis method. These omissions prevent evaluation of the intended analysis procedures.

The safety information is limited to the listed participant counts, the ALT term, and the at-risk counts. Deaths are not reported in the registry record, and further event details are not included in the registry record for this analysis. No causal relationship between the intervention and the reported events can be established from these counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Infliximab and Basiliximab for Treatment of Steroid Refractory Acute Graft Versus Host Disease — NCT01485055.
• Registry record last updated 2019-04-05; status last verified 2019-04.
• Results first posted 2019-04-05.
• 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

The registry record describes NCT01485055, a Phase 2, single-group study of infliximab and basiliximab for steroid-refractory acute GVHD. The intervention was planned once a week for four weeks. The primary endpoint was complete response at 28 days, defined by resolution of all GVHD signs and symptoms in all organs and a grade of 0 in each evaluable organ.

Enrollment was 11. The record lists the study as terminated and says it closed prematurely because the sponsor could not supply the medication further. It also states that enrollment was insufficient for a valid statistical analysis. No primary response count, estimate, or analysis is reported.

Safety counts include one participant with a serious adverse event among 11 at risk and zero with other adverse events among 11 at risk. ALT is listed at 9.1% among the top serious terms. Deaths are not reported in the registry record.