Brentuximab Vedotin in Patients With Relapsed or Refractory EBV-and CD30-positive Lymphomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Brentuximab Vedotin in Patients With Relapsed or Refractory EBV-and CD30-positive Lymphomas (NCT02388490), a na phase 2 study. The primary outcome is To Evaluate the Overall Response Rate (ORR) of Brentuximab Vedotin in EBV- and CD30-positive Lymphomas.

2. Clinical Question

This design addresses response and safety in the enrolled population, rather than estimating a treatment contrast against another therapy or a control group. The registry lists an enrollment of 25. Because the record does not report the primary endpoint result, it is not possible to describe the observed response rate, the number of participants who responded, or the precision of an effect estimate from the registry information.

3. Trial Design

This was a phase II study of brentuximab vedotin in patients with relapsed or refractory EBV- and CD30-positive lymphomas. The registry describes it as open-label, non-randomized, and multicenter. Its design is listed as single-group, with allocation recorded as NA and masking as NONE. Consequently, the study did not include a randomized comparator arm in the registry record.

The registry lists enrollment of 25 and a status of COMPLETED. The recorded start date is 2016-03-25, and the primary completion date is 2019-04-02. The sponsor is Seoul National University Hospital. These registry entries describe the study's administrative and design characteristics; they do not establish that every enrolled participant contributed data to every outcome.

The intervention was brentuximab vedotin. The primary endpoint was overall response rate, with a one-year timeframe. The registry also lists secondary outcomes concerning safety, progression-free survival, duration of response, and overall survival. It records 8 outcome measures, but the endpoint-specific results and their analyses are not reported in the registry record.

With a single group, response and safety counts are descriptive observations in participants receiving the study intervention. They cannot by themselves distinguish treatment-related effects from the course of disease, other care, or other influences. The lack of randomization also means that this record does not support a direct estimate of a treatment difference versus a control. The registry record does not report a detailed protocol, enrollment rationale, or a fuller statistical analysis plan.

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: Revised tumor response criteria for lymphoma(Revised Cheson) or revised SWAT and assessed by MRI except a pregnant patient whose response evaluation can be assessed by CT scan: Complete Response (CR), Disappearance of all evidence of the disease; Partial Response (PR), Regression of measurable disease and no new lesions. The SPD of the largest 6 major nodules should decrease by ≥ 50%, and there should be no increase in the size of other nodules; Overall Response (OR) = CR + PR.

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 To Evaluate the Overall Response Rate (ORR) of Brentuximab Vedotin in EBV- and CD30-positive Lymphomas, measured over One-year.

The primary endpoint was overall response rate, or ORR, measured as a count of participants. ORR is intended to capture whether participants meet prespecified criteria for a tumor response, typically through categories such as complete or partial response. In general, response criteria make outcome assessment more structured by defining what changes in disease status qualify. In this trial, the registry specifies revised response criteria for lymphoma, or modified SWAT criteria in the case of cutaneous lymphomas.

The registry describes response assessment by MRI, with CT permitted for a pregnant participant. It identifies complete response as disappearance of all evidence of disease and begins a description of partial response as regression of measurable disease; the remaining endpoint description is not reported in the registry record. The timeframe is listed as one-year.

ORR is used in clinical studies as a direct summary of the proportion of participants meeting a response definition during the specified assessment period. A response measure can be informative about observed tumor change, but it does not by itself describe how long a response lasts, whether disease later progresses, or overall survival. The registry separately lists duration of response, progression-free survival, and overall survival as secondary outcomes. The ORR result itself is not reported in the registry record, so no observed response count or rate can be interpreted from these details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who receive the study intervention. It can summarize observed response or adverse events, provided those results and their denominators are reported. It does not provide a randomized comparison with another treatment or control group. Here, the registry identifies a single-group, non-randomized design and lists allocation as NA. Therefore, the record does not describe a treatment-effect estimate based on a between-group contrast.

What does open-label mean for interpretation?

In general, an open-label study is one in which treatment masking is not used. The registry lists masking as NONE. Knowledge of treatment assignment can matter for how outcomes are assessed or reported, especially when outcome classification involves judgment. Use of stated response criteria can support more structured assessment, but the registry record does not report whether response assessments were independently reviewed or blinded. Such procedures should not be assumed.

How should ORR be understood?

ORR is a binary outcome at the participant level: each participant is classified according to whether the response definition is met. A response rate is generally the number classified as responders relative to a defined analysis population. That denominator must be clear to interpret the result. The registry identifies the endpoint as a count of participants and gives a one-year timeframe, but does not report the observed count, rate, denominator used for analysis, or confidence interval. Accordingly, no ORR calculation can be described from the registry record.

In general, a confidence interval presents a range of values compatible with the data under the method used. It communicates statistical uncertainty, rather than guaranteeing that the true value lies within a particular range. For a binary endpoint, interval width depends in part on the number of participants and the observed response frequency. No interval is reported for this primary outcome, so its precision cannot be evaluated from the record.

What do the safety counts represent?

The registry reports affected-participant counts for serious adverse events and other adverse events. These are participant counts, not necessarily counts of individual event episodes. A participant may experience more than one event, and the registry counts alone do not establish the number of episodes or their causal relation to treatment. The terms and percentages listed for selected serious adverse events are registry entries; they should be read as descriptive safety information, not as comparative risk estimates. In general, a comparator group and consistent event ascertainment are important for estimating whether event frequency differs between treatment strategies.

What is a planning sample-size illustration?

In general, a sample-size calculation describes how many participants or events a study might need under stated assumptions to target a chosen statistical precision or chance of detecting an effect. Such a calculation is a planning tool, not an outcome observed in the trial. The registry's planning-illustration assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. These assumptions describe the illustration rather than the study design: the actual trial is single-group, not a two-arm randomized comparison. Any sample-size illustrations are planning quantities, not observed power. They cannot substitute for a reported primary result or justify a claim about the study's achieved power.

What is not specified about the analysis?

A statistical analysis plan would normally clarify matters such as the analysis population, endpoint handling, missing-data rules, and any planned subgroup or sensitivity analyses. The registry record lists no analyses and does not report these details. It also does not report whether the one-year response assessment was treated as a fixed visit, how assessments outside the window were handled, or how participants with missing response data were classified. These details should not be inferred from the endpoint label or the study status.

The registry lists secondary outcomes for safety, progression-free survival, duration of response, and overall survival. In general, time-to-event outcomes require a definition of the event and follow-up, and their interpretation depends on censoring and analysis methods. The record does not provide the results or analysis methods for these outcomes. The posted information therefore supports an explanation of the design and endpoint concepts, but not a reconstruction of the study's full analysis.

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("Brentuximab Vedotin")
n      <- c(25)
events <- c(12)
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  Brentuximab Vedotin  25  12  48.0  27.8  68.7  30.0  66.5  29.9  66.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary ORR endpoint and secondary outcomes concerning safety, progression-free survival, duration of response, and overall survival. When a study evaluates several outcomes, multiplicity is a general statistical consideration: examining multiple questions can affect how individual statistical findings should be interpreted. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a prespecified strategy for interpreting multiple tests. It also lists no analyses. No adjustment method or inferential plan should therefore be assumed.

Missing-data handling is not reported in the registry record. In general, missing response assessments can affect an ORR estimate because the result depends on which participants are included and how unavailable outcomes are treated. The record does not state how many participants had an assessment, whether all enrolled participants were included in the response denominator, or how missing or unevaluable responses were classified. These details are needed to assess possible bias from incomplete outcome data.

The analysis populations are not reported in the registry record. It is not specified whether the primary analysis was intended to include all enrolled participants, only participants who received treatment, or a different defined population. Nor does the record describe exclusions or protocol deviations. These omissions prevent a full assessment of the population underlying any possible endpoint estimate.

The study is marked COMPLETED, but that status does not supply missing analysis details or establish that every planned outcome was reported. The registry record does not report an interim-analysis plan, a sample-size justification, or a complete statistical analysis plan.

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: herpes zoster (12.0%), fracture (4.0%), pneumomediastinum (4.0%), anorexia (4.0%), anemia (4.0%).

The registry reports 25 participants at risk for serious adverse events and 9 participants affected. For other adverse events, it reports 25 participants at risk and 24 affected. The recorded number of deaths is 0. These are participant counts in the brentuximab vedotin group; they are not comparisons with a control group and do not by themselves show that the intervention caused an event.

The registry also lists selected serious adverse event terms with percentages: Herpes zoster, 12.0%; Fracture, 4.0%; Pneumomediastinum, 4.0%; Anorexia, 4.0%; Anemia, 4.0%; and Cytopenia, 4.0%. They are descriptive registry entries. The record does not provide enough detail to infer event timing, duration, severity grading, participant overlap across terms, or causal attribution. The percentages should not be added or treated as mutually exclusive categories.

In general, safety summaries depend on how events are defined, collected, and attributed. A single-group count can describe what was recorded among participants, but cannot show how event frequency compares with another treatment or the background rate in a similar population. The registry record does not report a comparative safety analysis.

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

The record identifies a phase II, open-label, non-randomized, multicenter study of brentuximab vedotin in relapsed or refractory EBV- and CD30-positive lymphomas. It specifies ORR as the primary endpoint, assessed over a one-year timeframe using revised lymphoma criteria or modified SWAT criteria for cutaneous lymphomas. It also provides enrollment and selected safety information. These details explain what the study set out to assess and the broad design in which the observations were collected.

However, the primary ORR result is not reported in the registry record. No response count, rate, or confidence interval is available in the record, so it cannot establish the observed response frequency or its statistical precision. The absence of a reported result is not evidence that participants did or did not respond.

The single-group design also limits what an outcome could establish. In general, observing responses in a treated group does not isolate the effect of treatment from other influences. Without a randomized comparator, this registry record cannot support a direct estimate of how outcomes differ between brentuximab vedotin and another strategy. Similarly, the adverse-event counts describe participants in the study group, but do not demonstrate causation or comparative risk.

The record lists secondary outcomes, but does not report their results or analysis methods. Details such as missing-data handling, analysis populations, and multiplicity procedures are also not reported in the registry record. Those omissions limit assessment of the completeness and inferential basis of any outcome conclusions. The defensible reading is therefore about the study's design, stated outcome definitions, enrollment, and recorded safety counts—not a quantitative conclusion about efficacy or comparative safety.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a stated research question and a reported estimate. The registry identifies a clinically focused primary outcome, ORR, and gives a timeframe and response-assessment criteria. But without the observed response count, denominator, or uncertainty interval, the primary question cannot be answered from the registry record. A completed study status is not a substitute for an outcome estimate.

The single-group design makes the estimand especially important. A response rate in one group is a descriptive result; it is not the same as a treatment difference against a control. This distinction is central when reading phase II studies, where the study objective and design may focus on observing outcomes in a defined population rather than making a randomized comparison. The record explicitly describes a non-randomized, open-label, single-group study.

The safety information illustrates a related principle: participant counts and selected event percentages can help describe what was recorded, but they do not establish causality or comparative risk. Interpretation depends on event definitions, ascertainment, follow-up, and the underlying population. Those details are not fully reported in the registry record.

Finally, the record does not report analysis populations, missing-data rules, multiplicity methods, or a complete statistical plan. These are not merely technical extras. They determine which observations contribute to an estimate and how uncertainty across several outcomes is understood. Recognizing what is and is not documented is a key part of responsible statistical interpretation.

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 most important limitation of the registry information is that it does not report the primary ORR result. There is no reported response count, response rate, denominator, or confidence interval. Consequently, neither the observed frequency of response nor its precision can be evaluated.

The trial is single-group, open-label, and non-randomized. It therefore has no randomized control comparison in the registry record. Any observed outcomes would be descriptive of the study group and could not, on their own, establish a treatment difference or causal effect. This limitation applies to safety interpretation as well as response.

The registry lists enrollment of 25, but does not report how many participants were evaluable for the primary endpoint or included in an analysis population. Missing-data procedures, reasons for unavailable assessments, and handling of unevaluable responses are not reported in the registry record. The endpoint description is truncated after its explanation of partial response, so the complete operational criteria are not available in this record.

The record lists secondary outcomes but does not provide their results or methods. It also does not report multiplicity procedures, interim analyses, a sample-size justification, or a complete statistical analysis plan. Thus, readers cannot assess how multiple outcomes were handled or whether the planned analysis matched the reported data. The posted safety counts are useful descriptively, but the record does not provide sufficient detail to assess event timing, overlap among terms, or causal attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Brentuximab Vedotin in Patients With Relapsed or Refractory EBV-and CD30-positive Lymphomas — NCT02388490.
• Registry record last updated 2024-09-23; status last verified 2019-04.
• Results first posted 2024-09-23.
• 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 NCT02388490, a phase II, open-label, non-randomized, multicenter, single-group study of brentuximab vedotin in relapsed or refractory EBV- and CD30-positive lymphomas. It lists enrollment of 25, status COMPLETED, a start date of 2016-03-25, and a primary completion date of 2019-04-02. The sponsor is Seoul National University Hospital.

The primary endpoint was ORR over a one-year timeframe, using revised lymphoma criteria or modified SWAT criteria for cutaneous lymphomas. The primary result is not reported in the registry record. Safety entries include 9 participants with serious adverse events and 24 with other adverse events among 25 at risk in each category, with 0 deaths recorded. These counts are descriptive and do not provide a randomized comparison.

The record lists secondary outcomes and 8 outcome measures, but does not report endpoint analyses, analysis populations, missing-data handling, or a complete statistical plan.