Efalizumab in Treating Patients With Graft-Versus-Host Disease of the Skin That Did Not Respond to Previous Steroids: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efalizumab in Treating Patients With Graft-Versus-Host Disease of the Skin That Did Not Respond to Previous Steroids (NCT00489216), a na na study. The primary outcome is Number of Subjects Experiencing Adverse Events.

2. Clinical Question

3. Trial Design

This was a single-group, unmasked study of efalizumab in patients with steroid-refractory graft-versus-host disease. The allocation field is listed as NA, and there was no like-for-like control group. The registry record identifies the phase as NA and reports an enrollment of 2. The sponsor was UNC Lineberger Comprehensive Cancer Center.

The study began in 2006-12, had a primary completion date of 2008-06, and is listed as terminated. The registry record does not report why the study was terminated. Its brief summary describes a study of side effects and how well efalizumab works for skin disease that did not respond to previous steroids. The official title refers to skin and liver disease.

The planned regimen was weekly subcutaneous efalizumab, with a total of 8 injections described for all patients. In the population description, one participant completed all 8 doses according to schedule. The other received 6/8 scheduled doses and was subsequently taken off study after developing transient coagulase negative staphylococcal bacteremia.

The primary objective concerned tolerability, and the primary endpoint counted participants experiencing adverse events during 120 days. Secondary outcomes were overall complete response, complete cutaneous response, and overall hepatic response. Although the registry record lists 6 outcome measures, it reports 0 analyses. No randomization, masking, comparator, or formal statistical analysis plan is reported in the registry record.

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.

Before assignment: Patients with evidence of an inflammatory, erythematous rash and skin biopsy consistent with cutaneous Graft-Versus-Host disease who had failed to improve after at least 4 weeks of methylprednisolone at 0.5mg/kg were eligible for enrollment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of the two patients, one patient completed all 8 doses of study medication according to schedule. The other patient received 6/8 scheduled efalizumab doses, but was subsequently taken off the study after developing transient coagulase negative staphylococcal bacteremia.

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: Patients with evidence of an inflammatory, erythematous rash and skin biopsy consistent with cutaneous Graft-Versus-Host disease who had failed to improve after at least 4 weeks of methylprednisolone at 0.5mg/kg were eligible for enrollment. Two patients were enrolled in the study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects Experiencing Adverse Events, measured over 120 days.

The primary endpoint is the number of participants experiencing adverse events during a timeframe of 120 days. It is a count of participants with an event, rather than a measure of how often events occurred, how long they lasted, or their severity distribution. The study description says that participants would be evaluated for drug toxicity at each visit and that toxicity would be graded using the Common Terminology Criteria for Adverse Events.

A tolerability endpoint is used to describe adverse experiences observed during treatment and follow-up. Reporting the number of participants affected gives a basic account of how many experienced an event, while toxicity grading can distinguish events by severity. Neither a count nor a grade, by itself, establishes that treatment caused an event. Attribution requires clinical assessment and an appropriate comparison, neither of which is fully described in the posted results.

The registry record reports counts for serious and other adverse events in the efalizumab group. It does not report a formal primary-endpoint analysis, a confidence interval, or participant-level detail beyond the treatment completion and bacteremia description. The endpoint therefore offers only a limited descriptive account of tolerability in this small, uncontrolled study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group study estimate?

In a single-group study, observations describe participants who received the study intervention. Without a concurrent comparator, the results cannot directly estimate how outcomes differ from those under another treatment or no study treatment. Adverse events can occur during treatment for many reasons, including the underlying condition and other care. A count observed during treatment does not, by itself, identify the cause of an event.

This is distinct from a randomized comparison, where allocation is used to create groups intended to support a treatment contrast. The registry record identifies this study as single-group, unmasked, and with allocation listed as NA. It should therefore be read as a small descriptive study rather than as a randomized treatment comparison. The absence of a comparator is not remedied by comparing the observed group with an assumed or historical rate unless such a comparison is planned and justified; no such analysis is reported in the registry record.

What does a participant count convey?

The primary endpoint is a number of participants experiencing adverse events. A participant count indicates whether people were affected, but it does not show the total number of event episodes, the duration of events, or the distribution of event severity. A person may have more than one event, and participant counts alone do not describe that pattern. The record says toxicity was to be evaluated at each visit and graded using the Common Terminology Criteria for Adverse Events, but a detailed grading distribution is not reported in the registry record.

Counts and percentages are especially unstable in very small groups. Each observed participant has a large influence on the apparent proportion. A percentage calculated from a small denominator can look precise because it is written with a decimal place, while still representing very limited information about what might occur in other patients. A confidence interval, when reported, expresses uncertainty around an estimate under specified statistical assumptions; it does not remove the underlying limitations of sparse data. No confidence interval is reported for the adverse-event figures.

Why does follow-up and exposure matter?

Interpreting safety counts also requires knowing how long participants were observed and how much treatment they received. The primary endpoint has a timeframe of 120 days, and the regimen description specifies a total of 8 injections. The population description reports different treatment exposure: one participant completed the planned doses, while the other received 6/8 before being taken off study after bacteremia. Differences in exposure can affect how much opportunity there was to observe events. The record does not provide participant-level follow-up times or event timing, so event rates per unit of follow-up cannot be assessed.

For the same reason, an event count should not be interpreted as a rate unless the relevant person-time and method of calculation are available. The registry record reports neither an event-rate analysis nor a time-to-event analysis. The listed deaths count is also not accompanied by cause or timing, so it cannot be placed in a detailed event sequence.

How should missing analyses be understood?

The registry record lists secondary response outcomes but reports 0 analyses. This means the posted record does not provide statistical results for those listed outcomes. It does not establish whether outcomes were never collected, whether analyses were conducted but not entered, or whether there was another reason they are absent. Those explanations are not reported in the registry record.

Likewise, the record does not report a formal statistical analysis plan, a sample-size justification, interim analyses, or a method for handling missing outcome data. These details matter because an analysis plan specifies how endpoints, incomplete observations, and multiple outcomes are handled. In their absence, no unreported procedure should be assumed. The sample-size planning assumptions listed for two-arm illustrations do not describe this single-group trial's design and cannot be treated as its planned analysis.

General statistical interpretation distinguishes a descriptive observation from an estimate intended to generalize. The adverse-event counts are descriptive observations from this group. Without a comparison, sufficient follow-up detail, and reported uncertainty analysis, they do not provide a precise general estimate or a causal effect. Their value is in documenting what the registry record reports, while keeping the uncertainty and missing information explicit.

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("Efalizumab")
n      <- c(2)
events <- c(2)
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  Efalizumab  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record names three secondary response outcomes: overall complete response, complete cutaneous response, and overall hepatic response. It lists 6 outcome measures but reports 0 analyses. No results, estimates, or statistical tests for those response outcomes are reported in the registry record. Their absence should not be taken to mean that no responses occurred; the posted record does not provide analyses that would establish that.

Multiplicity arises when several outcomes or statistical tests are considered. In general, examining multiple outcomes can increase the chance of finding an apparently notable result by chance, so an analysis plan may specify which outcomes are primary and how secondary analyses will be interpreted. The registry record does not report a multiplicity adjustment or a plan for interpreting the listed secondary outcomes. Since no analyses are posted, there are no reported response tests to evaluate or adjust.

Missing-data handling and analysis populations are also not described in sufficient detail. The record reports the treatment exposure of each participant in the population description, but does not report a formal analysis population, rules for incomplete observations, or whether any endpoint data were missing. It is therefore not possible to determine how incomplete follow-up or outcomes were handled in an analysis.

These omissions limit reproducibility and interpretation. They do not establish that a particular method was or was not used outside the registry record. The reason the study was terminated, the rationale for enrollment, and any interim statistical review are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: transient coagulase negative staphylococcal bacteremia (50.0%).

The efalizumab group lists 1 participant with a serious adverse event and 1 participant with another adverse event. The listed serious term is transient coagulase negative staphylococcal bacteremia, reported as 50.0%. The population description connects this bacteremia with the participant who received 6/8 scheduled doses and was subsequently taken off study. The other participant completed all 8 doses according to schedule.

The record also lists 1 death. It does not report the cause or timing of the death, or its relationship to treatment. It is not possible to determine from the registry record whether the death and the bacteremia describe the same participant or a linked clinical sequence. The serious-event count and death count should therefore be read as separate reported figures, without assuming a relationship.

These are counts from a group of 2, not a controlled comparison or a reliable estimate of event frequency in a broader population. The percentage is descriptive and does not establish causation. The record does not provide event onset dates, detailed severity grades, or an attribution assessment.

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

The record documents a terminated, single-group study of efalizumab in patients with steroid-refractory graft-versus-host disease. It reports an enrollment of 2, treatment exposure for both participants, and counts of serious and other adverse events. One participant completed all 8 scheduled doses; the other received 6/8 and was taken off study after transient coagulase negative staphylococcal bacteremia. These details describe the experience recorded for the study participants.

They do not establish that efalizumab caused the bacteremia, the other adverse event, or the reported death. The registry record does not report the death's cause, timing, or relationship to treatment. With no comparator, it is not possible to distinguish treatment-related effects from events due to the disease, other care, or other causes using this study alone.

The record also does not establish whether efalizumab improved graft-versus-host disease. Although response outcomes are listed, no analyses are reported for them. No inferential estimates or confidence intervals are reported for the safety figures, and the very small enrollment means the observed counts give limited information about how often events might occur elsewhere.

Accordingly, the findings are best understood as a record of limited exposure and reported events, not as proof of benefit, proof of harm, or a precise estimate of risk. The trial cannot provide a treatment comparison, and its termination should not be assigned a reason that the registry record does not give.

14. Why This Trial Matters Statistically

Statistically, this study illustrates how much the design and amount of data constrain what can be concluded. A single-group study can record events and treatment experience, but it cannot estimate a treatment contrast against a concurrent control. That distinction matters even when an event occurs during treatment: timing alone does not establish causation.

The enrollment of 2 makes the results especially sensitive to each individual observation. The reported serious adverse event and the different treatment exposure of the participants are important descriptive details, but they cannot support a precise estimate of event frequency. A percentage can be reported for the group while still carrying substantial uncertainty about outcomes beyond it.

The study also distinguishes planned outcomes from analyzed outcomes. Response measures are listed, yet the registry record reports 0 analyses. This gap prevents readers from assessing response estimates or their uncertainty. It underscores why complete reporting of endpoint results and analysis methods is important, particularly when a study is small and uncontrolled.

Finally, the record shows why event counts need context. Follow-up timeframe, dose exposure, event timing, severity, and attribution all help readers interpret safety observations. Some treatment exposure information is reported, but several other details are not. Clear recognition of those limits allows the posted results to be read as a narrow descriptive record rather than as stronger evidence than the design can support.

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 major limitation is the very small enrollment: the registry record reports 2 participants. The design is single-group and unmasked, with no comparator. As a result, the study cannot estimate a difference in safety or response between efalizumab and another treatment, and observed events cannot be attributed to treatment based on this design alone.

Exposure was not identical: one participant completed all 8 scheduled doses, and the other received 6/8 before being taken off study after bacteremia. The record does not provide event timing, detailed follow-up by participant, or person-time, making it difficult to relate safety observations to duration of exposure. It also does not report the cause, timing, or treatment relationship of the listed death.

The study is listed as terminated, but the reason is not reported in the registry record. The registry record also does not report a sample-size justification, formal statistical analysis plan, missing-data procedures, analysis populations, interim analyses, or confidence intervals. Although secondary response outcomes are listed, no analyses are reported for them. The stated phase is NA, and the record's brief summary and official title differ in whether they emphasize skin disease alone or skin and liver disease.

Together, these limitations mean that the posted results are descriptive and incomplete for assessing either response or the broader frequency of adverse events. They do not support causal conclusions or a precise general estimate.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efalizumab in Treating Patients With Graft-Versus-Host Disease of the Skin That Did Not Respond to Previous Steroids — NCT00489216.
• Registry record last updated 2017-05-23; status last verified 2017-04.
• Results first posted 2017-04-06.
• 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

This terminated study evaluated weekly subcutaneous efalizumab in a single group of patients with steroid-refractory graft-versus-host disease. The primary objective was general tolerability, with the primary endpoint defined as the number of participants experiencing adverse events during 120 days. The planned regimen was a total of 8 injections.

The registry record reports an enrollment of 2. One participant completed all 8 doses; the other received 6/8 and was taken off study after transient coagulase negative staphylococcal bacteremia. The adverse-event listing reports 1 serious event, 1 other event, and 1 death. The cause and treatment relationship of the death are not reported in the registry record.

Three secondary response outcomes are listed, but the record reports 0 analyses. With no comparator and very limited enrollment, the posted findings are descriptive and do not establish treatment effects.