Rituximab in Treating Patients With Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rituximab in Treating Patients With Hodgkin's Lymphoma (NCT00003820), a na phase 2 study. The primary outcome is Progression-free Survival (PFS).

2. Clinical Question

The registry identifies rituximab as the intervention and Progression-free Survival (PFS) as the primary outcome. It also lists Overall Survival (OS) and Overall Response Rate (ORR) as secondary outcomes. The record's outcome description frames the primary measure as a count of participants meeting the PFS definition at the stated follow-up point, rather than giving an event rate or a comparative treatment effect.

The central statistical issue is therefore not a comparison of rituximab against another treatment. With a single group, the posted outcome would describe the observed experience of enrolled patients under the study's treatment approach. It cannot by itself separate treatment effects from the natural course of disease, patient selection, or other influences. The primary outcome value and estimates for the secondary outcomes are not reported in the registry record, so the clinical question cannot be answered from the posted results summarized in the record.

3. Trial Design

This was a Phase 2, completed, single-group study of rituximab for patients with lymphocyte-predominant Hodgkin's lymphoma. The registry lists enrollment of 39 and identifies Ranjana Advani as sponsor. The recorded start was 1999-01 and primary completion was 2008-08. Allocation is listed as NA and masking as NONE, consistent with the absence of a randomized, masked comparison in this record.

The intervention was rituximab 375 mg/m2 per week by intravenous infusion. The arm description specifies an initial treatment course of 4 weeks. Patients who achieved an objective response or stable disease after the initial course were permitted to continue with additional 4-week courses, with 3 additional courses starting every 6 months. This describes a treatment approach in which further treatment depended on response or stable disease after the initial course; it does not establish how many patients received additional treatment or their outcomes.

The registry notes that multiple treatment periods were added by amendment and refers to a Secondary Group. It also says this was always considered a single-arm study and there was no intent to report the initial treatment period separately as the Initial Group. The outcome description says results were reported by treatment period, but numerical period-specific results are not reported in the registry record.

Because no concurrent control group was used, the trial design supports descriptive reporting of outcomes among participants treated in the study. It does not support a randomized between-group estimate of treatment effect. Details such as the protocol's eligibility criteria, the rationale for the enrollment target, and the statistical analysis plan are not reported in the registry record. The listed enrollment is a record-level study figure, not evidence that every enrolled participant contributed data to every outcome.

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.

Cycle 1 (Initial Treatment)

Cycle 2 (Maintenance Treatment)

Cycle 3 (Maintenance Treatment)

Cycle 4 (Maintenance Treatment)

Analysis population for the primary outcome, as defined in the registry: This was a single-arm study with multiple treatment periods added by amendment (ie, Secondary Group), with results reported by treatment period. As this was always considered a single-arm study, there was no intent to report the results for the initial treatment period separately as the Initial Group vs the Secondary Group.

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: This was a single-arm study with multiple treatment periods added by amendment (ie, Secondary Group), with results reported by treatment period. As this was always considered a single-arm study, there was no intent to report the results for the initial treatment period separately as the Initial Group vs the Secondary Group.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival (PFS), measured over 5 years.

The primary endpoint is Progression-free Survival (PFS), described as the number of patients at 5 years after treatment who were alive and had no specified disease progression. Progression was defined by a 50% or greater increase from nadir in the sum of the product of the greatest lesion diameters of any previously identified abnormal node, or by the appearance of a new lesion.

This endpoint combines survival status with evidence of disease progression. In general, a progression-free outcome can capture disease worsening even when a patient remains alive, which can make it informative about the course of disease over follow-up. The registry's particular description is a count at a stated follow-up point, so interpretation depends on knowing how many patients were assessed and how missing follow-up was handled. Those details and the actual count are not reported in the registry record.

The outcome name includes survival, but the posted definition is not a reported time-to-event estimate. It specifies the number meeting the status definition at 5 years. No confidence interval, event-time analysis, or numerical PFS result is reported in the registry record. Consequently, the definition can be described, but the precision of the observed endpoint and the proportion of the study population meeting it cannot be assessed from the record.

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 trial describes outcomes in the group receiving the study intervention. It does not directly estimate the difference between that intervention and a concurrent control. Random assignment in a comparative trial helps balance measured and unmeasured characteristics on average; without that structure, a favorable or unfavorable outcome in the treated group cannot be attributed solely to treatment. This registry describes no allocation, no masking, and a single-group model. It does not describe a randomized treatment comparison.

How should a count endpoint be read?

The registered primary endpoint is a participant count at 5 years, using a definition that requires patients to be alive without the specified progression criteria. A count is most informative when the record also makes clear who was eligible for assessment, who had outcome data, and how unavailable assessments were handled. If follow-up is incomplete, treating only observed cases as the denominator can differ from other reasonable approaches. The assessment denominator, missing-data method, and observed PFS count are not reported in the registry record. Therefore, no rate or uncertainty estimate can be reconstructed from the record.

In general, a confidence interval gives a range of values compatible with the observed data under a statistical model and conveys uncertainty in an estimate. Its width depends on factors such as the amount of information and the variability of the outcome. A narrow interval indicates greater precision than a wide interval, but neither establishes that the estimate is free from bias. No confidence interval for the primary endpoint is reported in the registry record. No p-value or inferential analysis is reported either; the registry lists 0 analyses.

What is the role of a significance test?

In general, a significance test evaluates how compatible data are with a specified null hypothesis under its assumptions. A p-value is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. Here, the registry does not report a randomized contrast or a p-value for PFS. The absence of a reported test should not be read as evidence for or against a treatment effect. It reflects that an inferential result is not reported in the registry record.

What do planning calculations mean?

Planning calculations are hypothetical illustrations for a future study, not observed trial outcomes and not observed power. The stated calculation assumptions are 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 fraction of the observed effect. For time-to-event outcomes, the stated planning approach expresses requirements as a total number of events using the Schoenfeld method; other outcomes are expressed as participants per arm. These assumptions do not describe the single-group design of this trial and should not be mistaken for its protocol or its analysis plan. The protocol's sample-size justification and any planned statistical methods are not reported in the registry record.

When a planning illustration uses an effect estimated from a small study, that estimate can be uncertain. In general, basing a future design on an observed effect does not guarantee the same effect will recur. The planning values are conditional on their stated assumptions, and they do not represent evidence that the present study had a particular probability of detecting an effect. No sample-size justification or prospective power calculation for this trial is reported in the registry record.

How does outcome definition affect interpretation?

The PFS definition incorporates both survival and a disease-progression criterion. It uses the sum of the product of lesion diameters relative to nadir and the appearance of a new lesion. Such definitions specify which changes count as progression and can affect the endpoint's interpretation. In general, measurement rules need consistent application, and readers benefit from knowing how assessments were scheduled, reviewed, and handled when findings were uncertain. Assessment procedures and review methods are not reported in the registry record. The endpoint definition alone does not establish how consistently it was measured.

Overall Survival and Overall Response Rate are listed as secondary outcomes, but their definitions, analysis methods, and numerical results are not reported in the registry record. A secondary outcome can address a different aspect of disease or follow-up, but conclusions depend on prespecified definitions and analysis details. The registry lists 3 outcome measures and 0 analyses; those entries do not provide the missing outcome estimates or explain how outcomes were statistically analyzed.

What can the adverse-event summaries estimate?

The safety entries report affected participants and participants at risk, alongside selected serious-event terms and percentages. These are descriptive summaries. In general, safety comparisons require attention to the groups being compared, time at risk, event definitions, and whether events are counted by participant or by occurrence. A participant count does not necessarily equal an event count when an individual may experience multiple events. The record does not report event-level detail or a causal assessment. Since there is no control group, these entries cannot identify an excess risk attributable to rituximab.

Simple recalculations from posted summary statistics, when available, would be unadjusted and would not replace a sponsor's own analysis if a discrepancy were identified. No such recalculated outcome estimates or discrepancy are reported in the registry record. Statistical interpretation should therefore remain with the registered design and the data actually reported, rather than filling missing analyses with assumptions.

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("Rituximab 375 mg/m2 Per Week")
n      <- c(39)
events <- c(18)
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  Rituximab 375 mg/m2 Per Week  39  18  46.2  30.1  62.8  31.6  61.4  31.5  61.5

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, time points, or analyses are examined. In general, the more statistical tests conducted, the greater the chance that at least one may appear notable by chance if no adjustment or testing strategy is used. The registry lists PFS as the primary outcome and OS and ORR as secondary outcomes, but a multiplicity strategy is not reported in the registry record. It is not possible to tell from the listed outcomes whether adjustments were planned, whether the outcomes had a hierarchy, or how any analyses would have been interpreted together.

Missing data matter because outcome status may be unavailable for some participants, and the handling approach can affect an estimate. The PFS definition specifies a status at 5 years, but the record does not report the number assessed at that point, the number with missing status, reasons for missingness, or an imputation or censoring approach. The registry enrollment figure does not establish the denominator for the PFS result. The endpoint result itself is not reported in the registry record, so completeness of follow-up cannot be evaluated.

Analysis populations also require definition. In general, a report should clarify which participants are included in each outcome analysis and whether inclusion follows enrollment, treatment received, or availability of outcome data. The registry notes multiple treatment periods added by amendment and describes results by treatment period, but does not report period-specific analysis populations or numerical results. It is therefore not possible to determine how participants were assigned to reported periods or how their data contributed to each outcome.

The registry's 0 listed analyses and the absence of primary and secondary numerical results leave the analysis procedures unclear. The statistical plan, interim analyses, multiplicity handling, missing-data methods, and analysis-population definitions are not reported in the registry record. None should be inferred from the phase or the outcome labels.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: relapse/progressive disease, hodgkin lymphoma (35.9%), relapse / transformation to aggressive b-cell lymphoma (23.1%), anemia (2.6%), small intestinal obstruction (2.6%), myelodysplastic syndrome (2.6%).

The safety record lists 39 participants at risk for serious adverse events and 28 affected. For other adverse events, it lists 39 at risk and 39 affected. These are counts of participants recorded as affected, not a comparison of risks between treatments. Because the study has no concurrent control group, the counts cannot show whether events occurred more often than they would have under another treatment or without treatment.

The listed serious adverse-event terms include relapse or progressive disease, Hodgkin lymphoma at 35.9%, and relapse or transformation to aggressive B-cell lymphoma at 23.1%. Anemia, small intestinal obstruction, myelodysplastic syndrome, and metastatic colon cancer are each listed at 2.6%. These percentages are presented as registry entries; they should not be added together, since the record does not establish that categories are mutually exclusive. The number of deaths is not reported in the registry record.

In general, adverse-event summaries depend on event definitions, observation time, and whether the statistic counts affected participants or separate events. The record does not provide all such detail or establish that listed events were caused by rituximab. Relapse and progression are disease outcomes as well as safety terms, so their listing does not by itself identify a treatment-related adverse effect. The safety figures are descriptive and should be read in the context of the single-group design.

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

The registry record describes a completed Phase 2 study of rituximab in patients with lymphocyte-predominant Hodgkin's lymphoma. It records enrollment of 39, a single-group design, and a primary endpoint defined as the number of patients alive without specified progression at 5 years. It also lists OS and ORR as secondary outcomes and provides adverse-event summaries.

Those details establish what the study set out to assess and how its primary endpoint was described. They do not establish the observed PFS result: that count is not reported in the registry record. Numerical results for OS and ORR are also not reported. No uncertainty estimates or inferential results are available in the registry record, so neither the magnitude nor the precision of an efficacy estimate can be assessed.

Even if a single-group outcome estimate were reported, it would describe the study participants rather than provide a randomized comparison. A comparison against a control group is needed to distinguish differences associated with treatment from other explanations, and this trial did not include a concurrent comparator. The study record therefore cannot, on its own, establish a causal treatment effect.

The safety entries indicate that adverse events were recorded among participants, including serious-event terms associated with disease progression and other conditions. These counts and listed percentages do not establish that rituximab caused the events, and they cannot quantify comparative safety without a control group and fuller information about follow-up and event ascertainment. The count of deaths is not reported in the registry record.

In short, the record is useful for identifying the intervention, design, outcome definitions, and some safety reporting. It does not furnish the numerical primary or secondary outcome results needed to judge efficacy, nor the comparison or detail needed to make causal or comparative safety conclusions. Missing results should remain unresolved rather than being interpreted as evidence of either benefit or lack of benefit.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary endpoint is recognizable as a progression-free survival measure, yet the registry describes it as a participant count at a specific follow-up point. That distinction matters. A count at 5 years is not interchangeable with a time-to-event estimate that uses information across follow-up. Readers need to know the assessment denominator, follow-up completeness, and analysis method to interpret a fixed-time count; those details and the numerical result are not reported in the registry record.

The single-group design is another central statistical feature. It can describe outcomes observed in people receiving the study intervention, but it cannot supply the randomized contrast that would help estimate how outcomes differ under an alternative. This is a design limitation rather than a problem solved by a more elaborate calculation. Even a precise estimate in the treated group would not, by itself, establish a causal effect.

The amendment and treatment-period description also shows why analysis populations and reporting structure matter. The registry says multiple periods were added and refers to reporting by treatment period, while stating that the study remained single-arm and that the initial period was not intended to be reported separately. Without period-specific counts and methods, readers cannot evaluate how those periods contribute to outcome interpretation.

Finally, registry completeness shapes what can be learned. The record identifies primary and secondary outcomes but does not report their numerical results or analyses. This is a reminder that an endpoint name and definition are not a substitute for outcome estimates, uncertainty, and a clear account of who was analyzed. The trial's design and registry entries can be described, while its efficacy findings remain unassessable from the record.

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 limitations are specific to the information recorded for this trial. First, it is a single-group study with no allocation and no masking. There is no concurrent control arm, so the design does not support a randomized comparison or a direct estimate of relative effect. Outcomes observed in participants cannot be attributed solely to the intervention on the basis of this design.

Second, the primary PFS endpoint is defined as a count at 5 years, but the count and its assessment denominator are not reported in the registry record. The record does not report follow-up completeness, missing outcome status, or how patients without an assessment were handled. These omissions prevent assessment of the endpoint's numerical result and precision.

Third, OS and ORR are listed as secondary outcomes, but their numerical findings and analysis details are not reported in the registry record. The record lists 0 analyses. The statistical analysis plan, multiplicity approach, and any interim analyses are not reported in the registry record, so they cannot be inferred.

Fourth, the registry describes treatment periods added by amendment and says results were reported by treatment period, but it does not give period-specific results or analysis populations. It also says the initial treatment period was not intended to be reported separately. This limits interpretation of how the treatment-period structure relates to the outcomes.

Finally, the serious and other adverse-event entries are descriptive and lack a control-group context. The registry does not report a causal assessment or the count of deaths. These limits apply to interpretation of the record; they should not be converted into assumptions about unreported outcomes or study procedures.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rituximab in Treating Patients With Hodgkin's Lymphoma — NCT00003820.
• Registry record last updated 2017-04-20; status last verified 2017-03.
• Results first posted 2017-04-20.
• 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 identifies NCT00003820 as a completed Phase 2, single-group study of rituximab for lymphocyte-predominant Hodgkin's lymphoma. Enrollment was 39; the recorded start was 1999-01 and primary completion was 2008-08. The intervention was rituximab 375 mg/m2 weekly, with an initial 4-week course and additional treatment permitted for patients with an objective response or stable disease.

The primary outcome was PFS, defined as the number alive without specified progression at 5 years. OS and ORR were listed as secondary outcomes. Numerical results for these outcomes, analysis details, and the statistical plan are not reported in the registry record. Safety entries list 28 affected among 39 at risk for serious adverse events and 39 affected among 39 at risk for other adverse events. The record has no concurrent comparator, so outcome and safety summaries are descriptive rather than randomized comparisons.