Study of Iodine-131 Anti-B1 Antibody for Patients With Non Hodgkin's Lymphoma Who Have Previously Received Rituximab: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Iodine-131 Anti-B1 Antibody for Patients With Non Hodgkin's Lymphoma Who Have Previously Received Rituximab (NCT00996593), a na phase 2 study. The primary outcome is Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator.

2. Clinical Question

3. Trial Design

This was a phase II, multicenter, open-label, single-group study of iodine-131 anti-B1 antibody for people with non-Hodgkin lymphoma previously treated with rituximab. The registry lists enrollment of 43 and the study status as completed. The recorded study start was 1998-07, and primary completion was 2001-04.

Participants received the study regimen in two phases. The dosimetric phase began with unlabeled anti-B1 antibody, followed by anti-B1 antibody labeled with 5 mCi of iodine-131. Whole-body scans were used to estimate a patient-specific iodine-131 dose for the subsequent therapeutic phase. For participants without hematologic risk factors, the described therapeutic dose aimed to deliver a whole-body dose of 75 cGy. The summary also describes dose adjustments for specified platelet counts and for obesity.

Because this was open-label and had a single group, the investigator assessed response without a concurrent control group. There was no randomized allocation. The registry record does not report a protocol-based sample-size justification or enough detail to reconstruct all eligibility and treatment procedures. The primary endpoint population was limited to participants evaluable for confirmed response, even though the defined intent-to-treat exposed population included enrolled participants who received at least one study-drug dose.

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: Participants received radioimmunotherapy of tositumomab (TST) and Iodine I 131 TST in 2 phases: Phase 1, dosimetric dose; Phase 2, therapeutic dose. After radioimmunotherapy, participants could have entered a 10-year Long-Term Follow-Up study (Study BEX104526; NCT00240591) for continued evaluation.

Dosimetric and Therapeutic Treatment

Reasons for not completing this period:

Long-Term Follow-Up

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Exposed Population: all participants who were enrolled into the study and received at least one dose of study drug. Only those participants evaluable for confirmed response were analyzed.

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 Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator, measured over Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years.

The primary endpoint was the number of participants with confirmed response as assessed by the investigator. It included complete response, clinical complete response, and partial response. Complete response required resolution of disease-related radiological abnormalities and disappearance of related signs and symptoms. Clinical complete response allowed residual foci considered to be scar tissue, provided disease-related symptoms had resolved. Partial response required at least a 50% reduction in the sum of the products of the longest perpendicular diameters of measurable lesions, with no new lesions.

Confirmation required two separate evaluations at least 4 weeks apart. Requiring confirmation makes the endpoint less dependent on a single assessment, which could be affected by measurement variability or a transient change. As a general statistical point, a response count describes how many people met the endpoint definition in the analyzed population; a response rate would also need a clearly specified denominator.

The registry record describes follow-up until death, with a timeframe of up to 80.2 months in Study BEX104507, or follow-up in a long-term follow-up study for up to 10.5 years. It does not report the confirmed-response count, the number evaluable, or a response estimate. Therefore, the endpoint definition is available, but its observed 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?

The study assigned participants to one open-label treatment group rather than comparing randomized groups. In general, a single-group study can describe outcomes observed after treatment, but it does not by itself estimate what would have happened to the same population under another treatment or under no study treatment. Differences between outcomes in this group and outcomes from another setting could reflect differences in participants, follow-up, assessment, or other factors, not only treatment.

The registry record lists allocation as not applicable and the model as single group. It does not report a statistical analysis plan that would specify adjustment for potential influences or a formal comparison with an external group. No such comparison should be inferred from the design description.

How is confirmed response defined?

The endpoint is a count of participants whose investigator-assessed response met the stated definitions and was confirmed at two separate evaluations at least 4 weeks apart. Complete response, clinical complete response, and partial response were included. For partial response, the registry specifies at least a 50% reduction in the sum of products of perpendicular lesion diameters and no new lesions. The confirmation requirement is part of the outcome definition, rather than a statistical correction applied after the response count is obtained.

As a general statistical explanation, a count and a rate answer different questions. The count is the number meeting the endpoint; a rate relates that count to a defined denominator. The denominator matters especially when some enrolled or treated participants are not evaluable. Here, the registry says only those evaluable for confirmed response were analyzed, but does not report either the count of responders or the number evaluable. A response rate and its precision therefore cannot be reconstructed from this record.

What would a confidence interval communicate?

In general, a confidence interval expresses the uncertainty associated with an estimate under a specified statistical method. For a response proportion, it would help indicate how precisely the observed data locate the underlying response frequency in a population represented by the study. A confidence interval does not correct for selection, lack of a control group, or possible assessment bias. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be assessed from the recorded primary results.

What do the planning assumptions mean?

The registry describes a planning illustration based on the observed effect, not the trial's original design. It specifies a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation; the target effect is a stated fraction of the observed effect. Those are assumptions for a planning calculation, not evidence that this trial randomized participants between arms. The actual study is recorded as single-group, and the record does not report the original sample-size justification. Planning sample sizes are not observed power and do not establish what the trial could detect after the fact.

More generally, power calculations concern the chance that a planned analysis will meet a prespecified statistical criterion under assumed conditions. They depend on assumptions about the effect, variability or event frequency, significance threshold, and design. If those assumptions differ from the actual study, the planning illustration may not describe the study's operating characteristics. The registry record does not provide enough information to assess an original design calculation or an analysis plan for the primary response outcome.

How should the safety counts be read?

The registry's safety summary reports participant counts for serious adverse events and other adverse events in the study group. These are descriptive event summaries. General statistical interpretation distinguishes a count of participants with an event from an event rate over time; the record does not provide person-time or a comparative group for these figures. The listed percentages for selected serious-event terms should be read as reported, without treating them as a causal effect estimate.

Over-dispersion is a general issue for some count outcomes when variability exceeds what a simple count model assumes. It is not a reported feature or analysis issue in this registry record, and the primary endpoint is a participant count rather than a repeated-event count. The record does not identify a count model, variance adjustment, or other modeling method for the primary endpoint.

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("TST and Iodine I 131 TST")
n      <- c(34)
events <- c(26)
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  TST and Iodine I 131 TST  34  26  76.5  58.8  89.3  60.0  87.6  59.9  87.5

11. Multiplicity, Missing Data and Analysis Populations

The record lists one primary endpoint and several secondary outcomes, including adverse-event counts, infection outcomes, hematologic recovery times, and nadir values. It also reports 25 outcome measures and 11 analyses. The registry record does not report how the study handled multiplicity across outcomes or analyses, such as whether testing was hierarchical or adjusted to control the chance of false-positive findings. Without a stated approach and reported outcome estimates, the implications of testing multiple outcomes cannot be evaluated.

The primary population is described as the intent-to-treat exposed population: participants enrolled and given at least one dose of study drug. The record then specifies that only participants evaluable for confirmed response were analyzed. Thus, the endpoint analysis was not necessarily based on everyone in the defined exposed population. The number evaluable and the reasons any participants were not evaluable are not reported in the registry record.

The registry record does not report how missing response assessments were handled, whether missing outcomes were imputed, or whether sensitivity analyses were conducted. As a general statistical point, excluding participants without evaluable assessments can affect an estimate if evaluability is related to prognosis or response. The direction and size of any such effect cannot be determined without participant-level information and the missing-data methods.

There was no randomized allocation and no separate control arm, so the usual distinction between intention-to-treat and per-protocol comparisons in a randomized trial does not apply in the same way. The recorded analysis population definition should be used when interpreting the endpoint, and it should not be assumed that enrollment alone defines the response denominator.

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: hypercalcaemia (7.5%), acute myeloid leukaemia (5.0%), myelodysplastic syndrome (5.0%), malignant hepatobiliary neoplasm (2.5%), neoplasm skin (2.5%).

The safety summary lists 13 of 40 participants with serious adverse events and 37 of 40 with other adverse events for the study group. These are participant counts as recorded, not a randomized comparison. The registry record does not explain why the safety count at risk is 40 while enrollment is 43, so the difference should not be attributed to a particular reason.

The listed serious-event terms include Hypercalcaemia at 7.5%, Acute myeloid leukaemia at 5.0%, Myelodysplastic syndrome at 5.0%, Malignant hepatobiliary neoplasm at 2.5%, Neoplasm skin at 2.5%, and Non-Hodgkin's lymphoma at 2.5%. These are registry-listed percentages; the record does not give the corresponding term-specific participant counts in this summary.

The serious-event counts describe events recorded during the study, not proof that the study drug caused them. The registry separately describes a secondary outcome involving adverse events possibly or probably related to study drug and experienced by at least 5% of participants; that outcome is not interchangeable with the overall serious-event count. With no control group, the figures cannot show whether event frequency was higher or lower than it would have been under another treatment. The registry record does not report a comparative safety estimate or a causal analysis.

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

The registry record documents a completed phase II study with an open-label, single-group design, a defined confirmed-response endpoint, and descriptive safety information. It establishes what the investigators intended to count as a response and how confirmation was required. It also records enrollment of 43 and gives selected safety counts for the study group.

The primary outcome result itself is not reported in the registry record. In particular, the record does not state how many participants achieved confirmed response, how many were evaluable, or the estimated response rate. Without those values, the magnitude and precision of the primary finding cannot be described. The endpoint definition alone is not evidence of how many participants met it.

Even if the response result were available, the single-group design would support a descriptive account of outcomes in the treated participants, not a controlled estimate of comparative benefit. No randomized comparator was used, and allocation is recorded as not applicable. Findings cannot establish how outcomes would differ under another treatment or without the study regimen.

The safety counts similarly describe what was recorded in the study group. They do not establish causation or provide a comparison with a control group. The listed event terms and percentages should not be treated as estimates of excess risk attributable to treatment.

Therefore, the record is informative about study structure, endpoint criteria, and selected safety observations, but incomplete for judging the primary response outcome. It does not support a conclusion about treatment effectiveness or a causal safety effect. Those conclusions would require results and comparative evidence beyond the information recorded.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and endpoint results must be distinguished. The registry gives detailed criteria for confirmed response, including response categories, the lesion-measurement threshold for partial response, and the need for confirmation. Yet it does not report the observed primary response count or its denominator. A precise definition makes an endpoint interpretable, but cannot substitute for the result itself.

The record also highlights the importance of naming the analysis population. Enrollment is reported as 43, while the primary endpoint is analyzed only among participants evaluable for confirmed response. Those are not automatically the same group. Because the evaluable count and missing-assessment handling are not reported, readers cannot determine the response denominator or assess how exclusions might affect interpretation.

Design matters as much as endpoint choice. This study was open-label and single-group, without randomized allocation or a concurrent comparator. Its data can describe the study group, but do not directly answer a comparative treatment question. The safety summary has the same limitation: counts in one group do not establish a difference in risk between treatments.

Finally, the registry lists several secondary outcomes and analyses but does not report a multiplicity strategy. That gap matters when many outcomes are considered, because the interpretation of individual statistical findings depends partly on how testing was planned. Overall, the record offers useful design and measurement detail while leaving major gaps in the primary result, analysis population size, and statistical plan.

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 limitation for interpreting the primary endpoint is that the registry record does not report the confirmed-response result. It gives neither the responder count nor the number evaluable, and it does not provide a response estimate or confidence interval. Accordingly, neither the observed response frequency nor its precision can be assessed.

The study was single-group and open-label, with no randomized control group. This limits causal interpretation and prevents a direct estimate of how outcomes compare with another treatment. Investigator assessment in an open-label study may also be susceptible to assessment influences; the record does not report blinded outcome review or independent confirmation beyond the stated requirement for two evaluations.

The population definition raises an additional interpretive issue. The registry defines an intent-to-treat exposed population but analyzes only those evaluable for confirmed response. The size of the evaluable population, participant flow, reasons for unevaluable status, and missing-data procedures are not reported in the registry record. It is therefore not possible to judge whether the endpoint analysis represents all enrolled and treated participants.

The registry lists multiple secondary outcomes and analyses but does not report a multiplicity plan, the original sample-size justification, or a complete statistical analysis plan. Safety information is descriptive, and no control-group comparison or causal attribution is reported. The registry record also does not explain why the safety summary's at-risk count differs from enrollment. These omissions restrict interpretation of both efficacy and safety results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Iodine-131 Anti-B1 Antibody for Patients With Non Hodgkin's Lymphoma Who Have Previously Received Rituximab — NCT00996593.
• Registry record last updated 2016-11-23; status last verified 2016-10.
• Results first posted 2012-01-26.
• 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

NCT00996593 is a completed phase II, multicenter, open-label, single-group study of anti-B1 antibody and iodine-131 anti-B1 antibody in people with non-Hodgkin lymphoma previously treated with rituximab. Enrollment was 43. The primary endpoint was the number of participants with investigator-assessed confirmed response, requiring two evaluations at least 4 weeks apart and including complete response, clinical complete response, or partial response.

The registry record does not report the primary response count, the number evaluable, or a response estimate. Its safety summary lists 13 of 40 participants with serious adverse events and 37 of 40 with other adverse events. With no randomized comparator, the study provides no direct comparative estimate. The recorded endpoint and safety information should therefore be interpreted descriptively, with the missing primary result and analysis details kept in view.