Alefacept in Subjects With Steroid-Refractory Chronic Graft-versus-Host Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Alefacept in Subjects With Steroid-Refractory Chronic Graft-versus-Host Disease (NCT01226420), a na phase 2 study. The primary outcome is Efficacy.

2. Clinical Question

The clinical question is about response after alefacept in a defined treatment context, not about whether alefacept is better than another treatment. Without a concurrent comparator, any observed response would describe outcomes among treated participants; it would not by itself establish what would have happened to similar participants without alefacept or under a different treatment. The record identifies safety of alefacept infusions as a secondary outcome and reports serious adverse-event counts. It does not report an efficacy result for the primary remission endpoint. The study enrolled 6 subjects, so any outcome estimate would also be based on a small group. The registry status is terminated, but the reason for termination is not reported in the registry record.

3. Trial Design

This is a phase II, open-label, multi-center study of alefacept in subjects with steroid-refractory chronic graft-versus-host disease. The intervention is identified as alefacept, with the arm description specifying intravenous administration. Enrollment is listed as 6, and the study status is terminated. The sponsor is Dana-Farber Cancer Institute. The record lists a start of 2010-10 and primary completion of 2012-08.

The design is single-group, with allocation recorded as not applicable and masking recorded as none. Thus, participants were not assigned within this study to alefacept and a separate control treatment, and the study was open-label. These features matter when interpreting outcomes: the design can describe observed responses and safety among treated participants, but it does not provide a randomized estimate of the difference between alefacept and a control. The record does not describe a comparator arm.

The primary outcome is titled “Efficacy” and is defined as the proportion of patients with complete or partial remission at week 12 compared with baseline, among subjects with steroid-refractory cGVHD. Its listed timeframe is 2 years. The record does not explain how that timeframe relates to the week 12 definition. The named secondary outcome concerns the safety of alefacept infusions in patients with chronic GVHD. Two outcome measures are listed, but no analysis entries are recorded.

The record does not report a reason for termination, a planned enrollment target beyond the recorded enrollment, or a statistical plan. Information about monitoring or changes to the study design is not reported in the registry record. Those omissions prevent conclusions about why enrollment ended or whether the completed study followed a particular planned analysis procedure.

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: All enrolled subjects

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 Efficacy, measured over 2 years.

The primary endpoint is a binary response measure: whether a participant had a complete or partial remission at week 12 compared with baseline. The registry defines the result as a proportion among subjects with steroid-refractory cGVHD and lists all enrolled subjects as the population. A binary endpoint reduces each participant’s assessment to whether the specified response criterion was met or not met. The registry does not provide further criteria for complete or partial remission, or details about who assessed response.

A response proportion is used to describe how often a predefined clinical state was recorded in the study population. It can be straightforward to interpret, but it does not show the degree of change within each response category, the duration of response, or how outcomes compare with an untreated or differently treated group. Those questions require additional definitions or a comparator, neither of which is described for this primary endpoint.

The outcome timeframe is listed as 2 years, whereas the endpoint description specifies assessment at week 12. The record does not reconcile these entries. No primary-endpoint response count, proportion, confidence interval, or hypothesis-test result is reported in the registry record. Consequently, the endpoint’s definition can be described, but its observed efficacy result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

General: A single-group study can describe outcomes among participants who received the intervention. For a binary endpoint such as complete or partial remission, the basic descriptive quantity is the number meeting the definition relative to the analysis population. That quantity answers how often the event was recorded in the observed group. It is not the same as a treatment effect relative to a comparator, because a treatment effect in a comparative sense requires an appropriate contrast.

In this study, the design is listed as single-group and the primary population as all enrolled subjects. The registry does not report the primary response count or its proportion, so even the descriptive primary endpoint cannot be reconstructed from the record. The safety counts are separate outcome information and should not be substituted for an efficacy result.

What does a confidence interval add?

General: A confidence interval expresses the statistical uncertainty around an estimate. For a response proportion, it reflects how much the estimate could vary because only a sample of participants was observed. A narrow interval indicates greater precision under the method’s assumptions; a wide interval indicates less precision. An interval does not correct for design limitations, measurement problems, or missing information, and it does not make a noncomparative study comparative.

No confidence interval or other uncertainty measure for the remission endpoint is reported in the registry record. With enrollment of 6, the size of the study is important context for any estimate that might be reported, but the actual response estimate and its precision cannot be inferred from enrollment alone.

How should hypothesis tests and p-values be read?

General: A hypothesis test evaluates whether data are inconsistent with a stated null model under specified assumptions. A p-value describes how unusual data at least as extreme as those observed would be under that model. It is not the probability that a treatment works, nor does it measure the magnitude or clinical importance of an effect. A test result is most informative when the comparison, hypothesis, analysis population, and method are clear.

The record lists no analysis entries and does not report a p-value for the primary endpoint. It also does not describe a statistical analysis plan or identify a null hypothesis. It would therefore be inappropriate to infer a test or interpret a significance result for the remission endpoint.

What do the planning illustrations represent?

General: Sample-size planning asks how many participants may be needed to detect a prespecified effect under stated assumptions. A planning calculation is conditional on those assumptions; it is not evidence that the study had a particular probability of finding a result, and it is not an observed outcome. “Observed power” is not a substitute for reporting the estimate and its uncertainty after a study is complete.

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. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not the design used in this single-group study, and they are not the trial’s own design justification. The record does not report a sample-size justification for the actual study. Because no primary response result is reported, the observed effect needed to interpret such illustrations is also not available in the registry record.

The record notes that planning output for time-to-event outcomes is expressed as a total number of events, while other outcomes use participants per arm. That convention is relevant to interpreting a planning calculation, not to the observed enrollment of this study. A hypothetical two-arm planning exercise cannot create a comparator or supply a causal contrast for a single-group trial.

Why do outcome definitions and timepoints matter?

General: An endpoint is interpretable only when its event definition, assessment time, and analysis population are sufficiently clear. A response measured at a specified visit may differ from a response sustained over a longer period. Likewise, different rules for handling participants without an assessment can change the denominator and the resulting estimate.

Here, the primary endpoint definition specifies response at week 12 compared with baseline, while the listed timeframe is 2 years. The record does not explain whether the longer timeframe applies to follow-up, reporting, or another aspect of the endpoint. It also does not describe missing-assessment rules, response adjudication, or the handling of participants who did not complete the assessment. Those details are not reported in the registry record and should not be inferred.

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("Alefacept")
n      <- c(6)
events <- c(4)
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  Alefacept  6  4  66.7  22.3  95.7  30.0  90.3  29.0  90.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and names efficacy as the primary outcome, with safety of alefacept infusions as a secondary outcome. It records no analysis entries. The statistical analysis plan, including any prespecified handling of multiple outcomes or repeated assessments, is not reported in the registry record.

Multiplicity arises when several hypotheses or outcomes are examined: the more opportunities there are to find an apparently notable result, the more important it is to understand which analyses were planned and how results were interpreted. General statistical methods can adjust for multiple testing, but whether such adjustment is needed and how to perform it depend on the analysis plan and the questions being asked. No multiplicity adjustment is reported for this study, and none can be assumed.

The primary endpoint is defined at week 12, but its listed timeframe is 2 years. The record does not clarify whether additional assessments were included in the primary analysis. It does not report how missing response assessments were handled, whether participants who did not complete an assessment remained in the analysis population, or whether any sensitivity analyses were conducted. These items are not reported in the registry record.

The primary population is described as all enrolled subjects. Enrollment is 6, but the registry does not provide a primary-outcome denominator or response count. It is therefore not possible to determine from the record whether every enrolled participant contributed an endpoint assessment or how an incomplete assessment might affect the estimate. The record also does not describe an intention-to-treat approach or another analysis-population rule. These gaps limit reproducibility and make it impossible to assess whether the posted endpoint analysis followed a prespecified method.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: infection (otitis externa) (16.7%), febrile neutropenia (16.7%), neutropenia (16.7%).

The safety record lists an alefacept group with 6 participants at risk for serious adverse events and 2 participants affected. For other, non-serious adverse events, 6 participants are listed as at risk and 0 as affected. These are counts within a study of 6 enrolled subjects; they should be read as descriptive safety information, not as a comparison between treatments.

The listed serious adverse-event terms are infection (otitis externa), febrile neutropenia, and neutropenia, each reported at 16.7%. The registry does not give further detail about event timing, duration, severity beyond the serious classification, relatedness to alefacept, or whether an individual experienced more than one listed term. The listed percentages should not be treated as proof of causation.

The deaths field is not populated. Deaths are therefore not reported in the registry record; the empty entry should not be interpreted as confirmation that no deaths occurred. The counts are also based on a small enrolled group, so they offer limited precision and cannot characterize uncommon risks reliably. The record’s safety entries describe what was posted, without establishing a causal relationship between treatment and any event.

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

This record establishes that a phase II, open-label, single-group study evaluated intravenous alefacept in subjects with steroid-refractory chronic graft-versus-host disease. It identifies remission at week 12 compared with baseline as the primary efficacy outcome and lists safety of infusions as a secondary outcome. It also records enrollment of 6 and several serious adverse-event terms. Those are useful details about the study’s design and reported outcomes.

The record does not report the primary remission count or proportion, an analysis result, or an uncertainty interval. It therefore does not show what proportion of participants met the response definition. The absence of a reported efficacy analysis is not evidence that participants did or did not respond. Similarly, the safety counts do not show that alefacept caused the reported events or establish the frequency of risks beyond this small study group.

Because there was no comparator group, even a reported response proportion would describe outcomes after treatment rather than the effect of treatment compared with an alternative. A single-group design cannot rule out other explanations for change over time. This does not negate the descriptive purpose of such a study, but it places limits on causal interpretation.

The record’s status is terminated, but it does not state why. The primary endpoint description specifies week 12 while the listed timeframe is 2 years, and that difference is not explained. These uncertainties, along with the absence of analysis details, mean the registry record supports a narrow reading: the study’s question and design are identifiable, but its efficacy result and the reason for termination are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a clinical question and the evidence needed to answer it. The primary outcome asks whether participants met a remission definition at a specified assessment. But a defined endpoint alone is not an outcome result: without a reported response count, estimate, and measure of uncertainty, readers cannot assess the observed response proportion.

Its single-group structure is also important statistically. Outcomes in treated participants can be described, but there is no concurrent control group to estimate a treatment contrast. Readers should not interpret a before-and-after response definition as a randomized comparison. The open-label design further means that the study was not masked, while the registry does not detail how response assessments were made.

Enrollment of 6 highlights the importance of precision. In small studies, each participant’s outcome can materially affect a descriptive estimate, while estimates of less common safety events are particularly limited. This is a general statistical consideration, not a conclusion about the underlying treatment risk. Confidence intervals and clear denominators would help characterize uncertainty, but primary efficacy uncertainty measures are not reported in the registry record.

Finally, the record shows why registration details need to be read together: the primary definition refers to week 12, whereas its timeframe is listed as 2 years, and no analysis entries are recorded. Those gaps do not establish a particular flaw or explain the terminated status, but they constrain what can be independently interpreted. Statistical transparency depends not only on naming an endpoint, but also on reporting the analysis, population, missing-data approach, and results.

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 main trial-specific limitation is the absence of a reported primary efficacy result. Although the registry defines remission as complete or partial response at week 12 compared with baseline, it does not report the response count, proportion, or statistical uncertainty. The record lists no analysis entries, limiting the ability to assess how the endpoint was analyzed.

The study enrolled 6 subjects and had no comparator group. Consequently, the record can describe the treatment setting and listed events but cannot provide a randomized comparison of alefacept with another approach. The small enrollment also means that any estimates from the study would be imprecise, particularly for outcomes that occur infrequently. No precision estimate is posted for the primary outcome.

The endpoint timing is not fully clear: the outcome definition specifies week 12, while the timeframe is listed as 2 years. The registry does not explain this difference. It also does not report details of remission criteria beyond complete or partial remission, assessment procedures, handling of missing assessments, or the statistical analysis plan. These aspects are not reported in the registry record.

The safety data are limited to the listed counts and terms. The record does not provide event-level timing or relatedness information, and the deaths entry is blank. The study status is terminated, but the reason for termination is not reported in the registry record. No conclusion about the cause of termination or its impact on study conduct can be drawn from the status alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Alefacept in Subjects With Steroid-Refractory Chronic Graft-versus-Host Disease — NCT01226420.
• Registry record last updated 2013-08-13; status last verified 2013-08.
• Results first posted 2013-08-13.
• 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 phase II, open-label, multi-center, single-group study of intravenous alefacept for steroid-refractory chronic graft-versus-host disease. Enrollment is listed as 6; the status is terminated. The primary endpoint is a complete or partial remission at week 12 compared with baseline, with a listed timeframe of 2 years. The record does not reconcile those timing entries.

No primary efficacy result or analysis entry is reported. Safety listings include 2 participants affected by serious adverse events among 6 at risk, with infection (otitis externa), febrile neutropenia, and neutropenia each listed at 16.7%. The reason for termination and the details of the statistical analysis are not reported in the registry record.