Safety and Efficacy of Alemtuzumab in Pediatric Intestinal Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Alemtuzumab in Pediatric Intestinal Transplantation (NCT01208337), a na phase 2 study. The primary outcome is Incidence of Post Transplant Lymphoproliferative Disorder (PTLD).

2. Clinical Question

The study is framed around both potential benefit and potential harm: alemtuzumab induction may reduce early acute cellular rejection compared with historical controls, while the endpoint description raises concern about other post-transplant complications, including PTLD. That framing is a rationale for the question, not a finding from the study. The record also lists rejection, steroid use, tacrolimus concentrations, infections, chronic rejection, and biological measures among the planned outcomes. Those aims do not substitute for a reported PTLD result or establish how the intervention compares with another treatment.

3. Trial Design

This is a Phase 2, open-label, single-group clinical trial. The registry lists allocation as NA, masking as none, and the model as single group. The intervention arm is Alemtuzumab induction: intestine transplant recipients receive alemtuzumab before transplantation. With no concurrent control arm, the design cannot provide a randomized, like-for-like comparison between treatment groups.

The registry record lists enrollment as 23. The brief summary describes an intended enrollment of 75 subjects, while the primary endpoint description refers to twenty-three pediatric intestine allograft recipients. These are different descriptions in the record: the brief summary states an intended enrollment, and the enrollment field states the recorded enrollment. The record does not explain the difference or report why enrollment was lower than the stated plan.

The study is marked completed. Its primary endpoint is PTLD incidence over a 5 Year timeframe. Other listed outcomes include biopsy-proven acute cellular rejection, steroid use, and tacrolimus concentrations at follow-up. The brief summary also describes assessments of opportunistic infections, chronic rejection, medication use, immune-cell repopulation, donor-specific alloreactivity, gene expression, and genetic variation.

The registry record does not report the detailed eligibility criteria, the follow-up completeness, the analysis population, or a statistical analysis plan. It also does not explain whether the listed biological assessments were performed for every participant. The intervention and single-group structure define what can be learned: the posted outcomes describe observations among recipients receiving induction, rather than an estimate of comparative treatment effect against a concurrent control.

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: Alemtuzumab induction at the time of transplant may reduce the rate of early acute cellular rejection compared with historical controls, but may increase rate of alternate post-transplant complications, such as Post Transplant Lymphoproliferative Disorder (PTLD).

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 Incidence of Post Transplant Lymphoproliferative Disorder (PTLD), measured over 5 Year.

The primary endpoint is the incidence of post-transplant lymphoproliferative disorder (PTLD), with a stated timeframe of 5 Year. It is a safety outcome: the registry describes evaluating PTLD occurrence among intestine allograft recipients receiving alemtuzumab with tacrolimus and steroids. The endpoint is expressed as a number of participants in the endpoint description.

Counting participants who experience an event is a way to describe how often that event is observed in a defined study population. The timeframe matters because an event count is interpretable only in relation to the period during which participants are assessed. For outcomes that can occur at different times, follow-up completeness and the handling of participants who leave observation can also affect interpretation. Those details are not reported in the registry record.

The endpoint is relevant to the safety question because the study description identifies PTLD as a potential post-transplant complication. The primary endpoint description also presents the possibility of reduced early acute cellular rejection alongside possible increases in other complications. That is the study’s rationale, not evidence that either outcome changed.

A numerical result for PTLD incidence is not reported in the registry record. The adverse-event information lists PTLD among the top serious terms at 26.1%, but that entry is not explicitly identified as the primary endpoint result. The record does not establish whether the serious-event listing uses the same definition, ascertainment period, or analysis population as the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what this record can and cannot establish. They are general explanations, not additional analyses of the trial.

What does an incidence measure?

In general, an incidence summary describes how many participants experience a defined event during a specified observation period. The event definition, the population being counted, and the observation period must align. For the primary endpoint, the record identifies PTLD, participants, and a 5 Year timeframe, but it does not report a primary-endpoint count or explain how the endpoint was adjudicated. Without those details, a reader cannot independently assess how the reported endpoint would be constructed.

Why does the single-group design matter?

In general, an uncontrolled study can describe outcomes observed among participants receiving an intervention. It cannot by itself distinguish an intervention effect from other explanations, such as underlying participant risk, transplant-related factors, or changes in care over time. A concurrent control group helps make a comparison under the same study conditions, while randomization can help balance factors that affect outcomes. This record lists a single group and no random allocation, so it does not report a randomized treatment contrast.

The primary endpoint description mentions historical controls when stating the study's rationale. A historical comparison is not equivalent to a concurrent randomized comparison: groups observed at different times can differ in their participants, clinical practices, outcome ascertainment, and follow-up. The record does not report a historical-control analysis, so no such comparison should be inferred.

What would a confidence interval add?

In general, a confidence interval conveys the statistical uncertainty around an estimate. A narrow interval indicates greater precision under the assumptions of the analysis, while a wide interval indicates less precision. It does not correct bias in the study design or show that a result is clinically important. No confidence interval for the primary PTLD endpoint is reported in the registry record, and no primary estimate is reported from which to assess its precision.

How should event counts be read?

Counts of participants with events are useful descriptions, but interpretation depends on who was observed, the event definition, and the duration and completeness of follow-up. A participant-level count is not necessarily the same as a count of all event episodes, because one participant may experience more than one event. The registry's adverse-event group reports affected participants, but does not provide event timing, recurrent-event details, or a fuller account of follow-up. The record also does not report whether all participants were observed for the full primary-endpoint timeframe.

For general safety reporting, serious events and other events are separate categories, and a listed event term does not necessarily show how many participants experienced that particular event unless the record gives that count. Here, PTLD appears as a top serious term at 26.1%, but the record does not explicitly connect this figure to the primary endpoint calculation. The serious-event total should therefore be kept distinct from the primary PTLD estimate.

What do planning calculations mean?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, the statistical threshold, allocation, and the statistical model. It describes a hypothetical future design rather than the strength of evidence in an already completed study. The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that the effect to detect is a specified fraction of the observed effect. These illustrations are not the trial's own design justification and do not establish observed power.

The registry does not report the trial's sample-size justification. Because this study is listed as single group, planning assumptions that specify equal allocation between two arms should not be read as a description of the actual trial design. Any planning illustration should be interpreted only in relation to the assumptions stated for that illustration, not as evidence that the trial detected or excluded a particular effect.

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("Alemtuzumab Induction")
n      <- c(23)
events <- c(6)
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  Alemtuzumab Induction  23  6  26.1  10.2  48.4  12.5  46.5  12.6  46.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes beyond the primary PTLD endpoint, including rejection, steroid use, tacrolimus concentrations, infections, chronic rejection, medication use, immune-cell measures, alloreactivity, gene expression, and genetic variation. Assessing many outcomes raises a general statistical issue: the more questions tested, the greater the chance that at least one result may appear noteworthy by chance. A prespecified hierarchy or multiplicity adjustment can help address that issue, but the registry record does not report whether either was planned or used.

No statistical analyses are listed in the record. It does not report a statistical analysis plan, inferential tests, confidence intervals, multiplicity procedures, or which outcomes were analyzed in which population. The registry entries therefore do not support conclusions about whether outcomes were selected or prioritized after data collection.

Missing-data handling is also not reported in the registry record. The record does not state how participants who missed visits, withdrew, or had incomplete follow-up were handled, nor does it report whether all enrolled participants contributed to each endpoint. This matters in general because incomplete observation can affect both the apparent event frequency and the precision of an estimate, particularly for outcomes with a specified follow-up period.

The analysis populations are not described. The enrollment field lists 23, but the registry does not specify whether the primary endpoint was analyzed in all enrolled participants, only those who received the intervention, or another defined group. It also does not explain how the primary endpoint and serious adverse-event summaries relate to one another. In the absence of these details, the reported counts should be read as registry descriptions rather than as a complete account of the planned statistical analysis.

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: ptld (26.1%).

The serious adverse-event record lists the Alemtuzumab Induction group with 23 participants at risk and 6 affected by serious adverse events. For other adverse events, it lists 23 at risk and 0 affected. These are descriptive counts from the registry record; they do not provide event timing, duration, severity grading beyond the serious classification, or participant-level clinical context.

PTLD is listed among the top serious terms at 26.1%. This term-level percentage should be distinguished from the serious-event participant count and from the primary endpoint. The record does not explicitly state that 26.1% is the primary PTLD incidence estimate, nor does it report a separate primary-endpoint count. It also does not establish whether the term-level percentage reflects participants or events, or whether its observation window matches the primary endpoint's 5 Year timeframe.

The death field is not reported in the registry record. That absence should not be interpreted as evidence that no deaths occurred. More broadly, a safety listing is a record of reported events, not by itself a comparison of safety between treatments. With no concurrent control group, these figures cannot establish whether the intervention changes event risk relative to another approach.

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

The record documents a completed, open-label, single-group study of alemtuzumab induction in intestine transplant recipients. It gives an enrollment of 23, identifies PTLD incidence over a 5 Year timeframe as the primary endpoint, and reports selected serious and other adverse-event counts. PTLD is also listed among the top serious terms at 26.1%.

Those details do not amount to a complete numerical report of the primary endpoint. The registry record does not report a primary PTLD count, an uncertainty interval, or an analysis comparing PTLD incidence with another group. The serious-term percentage cannot automatically be substituted for the endpoint estimate because the record does not confirm that the definitions and observation periods match.

The single-group design also limits interpretation. Outcomes observed in a group receiving alemtuzumab induction cannot, on their own, show what would have happened to comparable recipients under another treatment. The mention of historical controls in the study rationale is not a report of a historical-control comparison. No randomized comparison or treatment-effect estimate is reported.

The record's planned outcome descriptions and biological aims indicate a broad set of research questions, but planned measurement is not a reported finding. Results for those listed outcomes are not included in the registry record. Likewise, completed status does not establish that all planned assessments were completed or that every outcome was analyzed.

The appropriate statistical reading is therefore limited and descriptive. The available information identifies the design and selected safety observations, while leaving the primary endpoint result and its precision unreported. It does not demonstrate that alemtuzumab increases or decreases PTLD, rejection, or any other outcome. No medical conclusion about treatment should be drawn from these registry entries alone.

14. Why This Trial Matters Statistically

This trial illustrates why study design and outcome reporting need to be read together. The registry identifies an important safety question—PTLD after intestine transplantation in recipients receiving alemtuzumab induction—but the primary endpoint is not accompanied by a numerical result. A clearly named endpoint does not itself provide evidence about the endpoint's frequency or uncertainty.

The study also shows the distinction between describing outcomes and estimating a treatment effect. A single-group design can record events among participants who received the intervention. Without a concurrent control group, it cannot separate the observed outcome pattern from background risks or other influences. The mention of historical controls in the rationale does not supply a comparative result.

The record's enrollment descriptions provide a further reporting consideration: the brief summary states an intended enrollment of 75, whereas the enrollment field lists 23. Reporting both figures can help readers distinguish a target from recorded enrollment, but the registry does not explain the difference. It also does not report the sample-size justification, so no design rationale can be inferred from those values.

Finally, safety summaries require careful separation of counts, event terms, and endpoint estimates. The record reports participants affected by serious events and lists PTLD as a serious term, but does not explicitly equate those entries with the primary endpoint. Keeping these measures distinct avoids overstating what a registry summary establishes and highlights the importance of complete endpoint definitions, follow-up information, and analysis reporting.

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.

Several trial-specific limitations affect interpretation. The study is open-label and single group, with no concurrent comparator. The registry record therefore does not support a randomized comparison or a causal estimate of the effect of alemtuzumab. Although the primary endpoint description mentions historical controls, no historical-control results or methods are reported.

The primary PTLD endpoint is defined by a 5 Year timeframe, but a numerical primary result is not reported in the registry record. The adverse-event listing gives PTLD as a top serious term at 26.1%, but does not explain whether that figure is calculated using the primary endpoint definition or observation period. The record does not report event timing, follow-up completeness, or how participants with incomplete observation were handled.

The brief summary states an intended enrollment of 75, while the enrollment field lists 23. The registry does not explain the difference, report the reasons for enrollment, or provide a sample-size justification. It also does not report the enrolled population's age distribution, despite the brief summary describing children and young adults and the primary endpoint description referring to pediatric recipients.

Analysis populations, statistical methods, confidence intervals, multiplicity handling, and missing-data procedures are not reported. The registry lists a range of secondary outcomes and biological aims, but does not provide results for them in the available record. Death information is also not reported in the registry record. These gaps limit both evaluation of precision and assessment of how completely the planned research questions were answered.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of Alemtuzumab in Pediatric Intestinal Transplantation — NCT01208337.
• Registry record last updated 2023-03-08; status last verified 2023-03.
• Results first posted 2016-06-20.
• 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 a completed Phase 2, open-label, single-group trial of alemtuzumab induction before intestine transplantation. It lists University of Pittsburgh as sponsor and enrollment as 23. The brief summary describes an intended enrollment of 75 and a population spanning ages 0-17 and 18-25; the record does not provide an enrolled age distribution.

The primary endpoint is PTLD incidence over a 5 Year timeframe. A numerical result for that endpoint is not reported in the registry record. The adverse-event record lists 23 participants at risk and 6 affected by serious adverse events, and 23 at risk and 0 affected by other adverse events. PTLD is among the top serious terms at 26.1%. No analyses are listed, and the record does not report a concurrent comparator, analysis population, missing-data approach, or confidence interval.