Bortezomib in Treating Patients With Lymphoproliferative Disorders: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bortezomib in Treating Patients With Lymphoproliferative Disorders (NCT00023764), a na phase 2 study. The primary outcome is Response Rate.

2. Clinical Question

In statistical terms, this is a question about the proportion of participants who meet the study’s response definition, rather than a comparison of response rates between treatment groups. The registry record names the endpoint “Response Rate,” gives participants as its unit, and describes estimating a response probability. It does not provide the response criteria, the number who responded, or the number included in the response analysis. Those details are not reported in the registry record.

The conditions listed are recurrent lymphomas. The study title and brief summary describe a Phase II investigation of bortezomib in low-grade lymphoproliferative disorders. The listed conditions include recurrent Grade 1, Grade 2, and Grade 3 follicular lymphoma and recurrent mantle cell lymphoma. The registry does not report response results separately by condition, so it is not possible to determine whether the endpoint was evaluated separately across these diagnoses.

The clinical question should therefore be read narrowly: what response probability was estimated in this single-group study, and how precise was that estimate? The registry describes the intended measure but leaves its numerical result unreported. It cannot support a comparative conclusion, because no control group is recorded, and it cannot establish how responses differed by diagnosis or other participant characteristics.

3. Trial Design

The registry identifies this as a Phase II study with a single-group model. Allocation is listed as NA, and masking as NONE. The record therefore describes participants receiving bortezomib without a randomized control group or masking. The enrollment is 103. Enrollment is a study-level count; it should not be assumed to be the denominator for the response endpoint, because the record does not report the response analysis population or its denominator.

The intervention is bortezomib, also called PS-341 in the official title and arm description. Participants in Arm I receive an infusion at a dose of 1.8 mg/m2 over 3-5 seconds once weekly for 4 weeks. Treatment repeats every 6 weeks if disease progression or unacceptable toxicity has not occurred. The description says that patients achieving at least a partial response lasting at least 6 months may receive retreatment. These statements describe the recorded regimen; the record does not report how many participants received each treatment cycle or retreatment.

The listed study conditions are recurrent Grade 1, Grade 2, and Grade 3 follicular lymphoma, and recurrent mantle cell lymphoma. The sponsor is the National Cancer Institute (NCI). The study start is recorded as 2001-06, primary completion as 2009-03, and status as COMPLETED.

The design is important when interpreting the primary endpoint. A response rate within a single group can describe outcomes observed among participants in that group, but it does not by itself estimate the difference between bortezomib and another treatment. Without a recorded comparator, differences in outcome cannot be attributed to treatment by comparison with a concurrent control group. The record does not report further design details such as eligibility criteria, the response assessment schedule, or the statistical analysis population; those details are not 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.

Overall Study

Reasons for not completing this period:

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 Response Rate, measured over Up to 3 years.

The primary endpoint is Response Rate, measured in participants, with a timeframe of up to 3 years. The registry description says that the response probability will be estimated and that a 95% confidence interval will be provided. In general, a response rate expresses how often a defined response occurs within the population being analyzed. The confidence interval conveys statistical uncertainty around an estimated response probability: a narrower interval indicates greater precision, while a wider interval indicates less precision.

Response is used as an endpoint because it captures whether disease measurements meet a defined criterion for improvement during the specified observation period. It is distinct from outcomes such as time until progression or overall survival. The registry record does not include the response criteria, assessment rules, or the result of the response-rate analysis. Those details are not reported in the registry record, so the endpoint cannot be reconstructed from the description alone.

The timeframe of up to 3 years identifies the period stated for the endpoint, but it does not specify how often assessments occurred, how incomplete follow-up was handled, or whether every participant was observed for the full period. Those procedures are not reported in the registry record. Nor is the number of participants included in the endpoint analysis stated.

Because the study is single-group, the endpoint is descriptive of response in the treated group rather than a direct estimate of comparative benefit. Even if a response estimate were available, its meaning would depend on the response definition, the analysis denominator, and the completeness of assessment. The registry describes the planned estimate and confidence interval but does not report either numerical result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a response probability describe?

For a binary endpoint such as whether a participant meets a response definition, the response probability is the proportion of the analysis population classified as having a response. This is a general statistical explanation. The registry names the outcome as Response Rate and says that a response probability will be estimated, but it does not state the response count, the analysis denominator, or the response criteria. No numerical response probability can therefore be recovered from the registry record.

The denominator is essential. It identifies the participants whose outcomes contribute to the estimate. Enrollment counts describe entry into a study, while the endpoint denominator is determined by the analysis rules and available outcome assessments. The registry records enrollment of 103 but does not state whether all enrolled participants were included in the response analysis. It is not appropriate to treat the enrollment count as the endpoint denominator without that information.

What does the confidence interval add?

A confidence interval is a range calculated from the observed data using a statistical procedure. As a general concept, it shows the uncertainty associated with an estimated quantity; it is not a guarantee that the true value lies in the particular reported interval. The registry’s endpoint description specifies a 95% confidence interval, but the interval itself is not reported in the registry record. Without the estimate and interval, neither the response level nor its precision can be assessed.

The method used to construct the interval is also not reported. Different methods can produce different intervals, especially when event counts are limited or the estimated probability is near the boundaries of its possible range. This is a general methodological point, not a claim about the unreported response data in this study. The record does not identify the confidence-interval procedure or describe any adjustment for design features.

Why does the single-group design matter?

A single-group analysis estimates an outcome within the group receiving the intervention. It does not directly estimate a contrast with an untreated group or another treatment. A randomized comparison can support a different type of inference because outcomes are observed under competing assigned strategies. Here, allocation is listed as NA, masking as NONE, and the model as SINGLE GROUP. The record itself notes that this is not a randomized comparison. A response probability, if reported, would therefore be an outcome description for this group, not a randomized treatment effect.

Even in a controlled study, interpretation depends on outcome definitions, follow-up, and analysis choices. In a single-group study, those considerations remain important, while the absence of a comparator also limits causal interpretation. The registry does not report a statistical plan that would address these questions beyond stating the intended response probability and confidence interval.

What can event counts tell readers?

The safety record presents counts of participants with serious adverse events and other adverse events. Counts are descriptive: they indicate how many participants in the recorded group had an event under the registry’s reporting definitions. The record lists 103 at risk for each category, with 20 affected for serious adverse events and 95 affected for other adverse events. These are not estimates of treatment differences, because the study has no recorded comparison group.

In general, event counts do not describe event severity, duration, recurrence, timing, or attribution unless those details are reported. A participant count also differs from an event count when a participant can experience multiple events. The record’s stated meaning for these outcomes is participants with an event, expressed as counts. It does not give additional detail on event-level totals or on how relatedness to treatment was assessed. Such details are not reported in the registry record.

How should planning illustrations be read?

The planning assumptions describe illustrations based on a fraction of the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe hypothetical planning calculations, not the design of this single-group trial. The record states that sample-size illustrations are not the trial’s own design and are not observed power. They should not be read as evidence that the study had a particular probability of detecting an effect.

The registry does not report the trial’s sample-size justification, an interim-analysis plan, or a statistical analysis plan. The observed effect referred to in the planning description is not numerically reported as a primary-outcome result in the registry record. Therefore, a planning illustration cannot replace the missing response estimate or establish what the study found. More generally, sample-size calculations depend on the effect, variability or event probability, design, and analysis assumptions. Those calculations answer a planning question, not the question of what outcome was observed.

These distinctions keep the statistical interpretation aligned with the record: a response-rate analysis was described, but its estimate and uncertainty are not reported; safety counts are available as descriptive information; and planning assumptions do not constitute an outcome 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("PS-341 (Bortezomib)-Relapsed Patients", "PS-341 (Bortezomib)-Refractory Patients")
n      <- c(23, 14)
events <- c(11, 6)
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  PS-341 (Bortezomib)-Relapsed Patients  23  11  47.8  26.8  69.4  29.2  67.0  29.1  67.2
ARM  PS-341 (Bortezomib)-Refractory Patients  14  6  42.9  17.7  71.1  21.4  67.4  21.3  67.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was addressed. Multiplicity arises when analyses involve multiple endpoints, subgroups, time points, or repeated opportunities to test hypotheses. In general, conducting many statistical tests without an appropriate strategy can increase the chance of finding an apparently notable result by chance. Whether that concern applies to a particular analysis depends on the planned hypotheses and reporting strategy. The record identifies Response Rate as the primary outcome but does not provide a statistical analysis plan or explain whether secondary or subgroup analyses were planned.

The record lists one outcome measure and does not report analyses. It does not describe a hierarchy of endpoints, an adjustment method, or an inferential testing strategy. Those details are not reported in the registry record. No claim about multiplicity control can therefore be made.

Missing-data procedures are also not reported. The endpoint timeframe is up to 3 years, but the registry does not say how participants without response assessments, participants who discontinue treatment, or participants with incomplete follow-up were treated in the analysis. It does not specify imputation, censoring, a missing-at-random assumption, or a sensitivity analysis. These methods should not be inferred from the endpoint description.

The analysis population is not identified in the primary outcome description. Although the registry reports enrollment of 103, it does not state the number analyzed for response or define an intention-to-treat, per-protocol, or evaluable population. The population field for the primary endpoint is blank. As a result, the relationship between enrollment and the response estimate cannot be established.

These omissions affect both reproducibility and interpretation. The response estimate depends on who was included, how incomplete observations were handled, and which analyses were designated as primary. Since these procedures and the outcome analysis are not reported in the registry record, the response result and its robustness cannot be assessed.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnea (4.9%), infection, nos (3.9%), abdominal pain (2.9%), constipation (2.9%), cardiac disorder (1.9%).

The safety record lists 103 participants at risk for serious adverse events and 20 affected, with the outcome meaning stated as participants with an event (counts). It also lists 103 at risk for other adverse events and 95 affected. These are participant counts for the bortezomib group; they should not be interpreted as event totals or as a comparison with another treatment group.

The serious adverse-event terms with reported percentages are Dyspnea, 4.9%; Infection, NOS, 3.9%; Abdominal pain, 2.9%; Constipation, 2.9%; Cardiac disorder, 1.9%; and Dehydration, 1.9%. These entries identify selected reported terms and their listed percentages. The registry record does not provide further detail on event timing, duration, recurrence, severity grades, or attribution to treatment. Those details are not reported in the registry record.

The death count is not reported in the registry record. A blank death entry should not be read as a count of zero. The serious-event counts and selected terms are descriptive safety information. With no recorded comparator, they do not establish whether event frequency was higher or lower than it would have been under another treatment or without treatment.

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

The record establishes that this was a completed Phase II, single-group study of bortezomib in patients with recurrent follicular or mantle cell lymphoma. It describes the treatment schedule and identifies response rate as the primary outcome, with a stated timeframe of up to 3 years. The endpoint description also specifies that a response probability and 95% confidence interval would be provided.

The record does not report the response count, response probability, confidence interval, or analysis denominator. It therefore does not establish the size or precision of the response outcome. The enrollment of 103 cannot fill that gap: enrollment is not necessarily the number included in the endpoint analysis, and the record does not identify the response analysis population.

The design does not include a recorded control group. This means the intended outcome is an estimate within the treated group, not a direct comparison with another treatment. A single-group response result, even if available, would not by itself show what would have happened to comparable participants under a different strategy. The registry record also does not report enough detail to assess possible influences such as response assessment rules, follow-up completeness, or analysis choices.

The safety entries describe affected participants and selected serious adverse-event terms. They do not establish a comparative safety profile, and the death count is not reported in the registry record. The presence of safety information does not compensate for the missing primary efficacy analysis.

Accordingly, the registry supports conclusions about the study’s recorded design, intended endpoint, regimen, and selected safety reporting. It does not support a conclusion about the numerical response outcome, its precision, or a comparative treatment effect. This is a limitation of what is reported in the registry record, not a claim that an unreported analysis had a particular result.

14. Why This Trial Matters Statistically

This trial illustrates why design and reporting must be read together. A response rate is an interpretable descriptive measure only when the response definition, analysis population, count of responses, and denominator are clear. The registry describes a response-probability estimate and a 95% confidence interval, but does not report the numerical estimate or the information needed to reconstruct it. Statistical interpretation must stop short of conclusions that require those results.

The study’s single-group structure is equally important. It can describe outcomes among participants who received bortezomib, but it does not create a randomized contrast with another treatment. Naming a response endpoint does not make it comparative. This distinction is central when readers move from an observed outcome to a claim about what caused it.

The record also demonstrates that enrollment, endpoint analysis, and safety summaries answer different questions. Enrollment describes study participation; the endpoint analysis requires its own denominator and handling rules; safety counts describe participants with reported events. The record reports enrollment and selected safety counts but does not state the response analysis population or missing-data procedures.

Finally, planning calculations should not be mistaken for observed evidence. The stated planning assumptions refer to hypothetical two-arm illustrations and explicitly distinguish those calculations from the trial’s own design and observed power. This distinction prevents a planning scenario from being treated as a finding.

For biostatisticians and clinical researchers, the record is a useful example of the limits imposed by incomplete outcome reporting. A precise question and planned interval are not substitutes for the estimate, uncertainty, analysis denominator, and methods needed to evaluate the result. Transparent reporting of those elements is essential for readers to assess both statistical precision and the scope of inference.

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 primary limitation for interpretation is that the registry describes the response endpoint without reporting its result. The response count, response probability, confidence interval, and analysis denominator are not reported in the registry record. Consequently, the principal study question cannot be answered from the posted record.

The primary endpoint description does not specify the response criteria or assessment procedures. It gives a timeframe of up to 3 years but does not report assessment timing, follow-up completeness, or how observations outside the stated timeframe were handled. These details are not reported in the registry record. Without them, readers cannot determine how response was operationalized or how consistently outcomes were assessed.

The analysis population and treatment of missing outcomes are also not specified. Enrollment is 103, but the registry does not state how many participants contributed to the response estimate or whether participants with incomplete assessments were included. The primary population field is blank. No missing-data strategy or sensitivity analysis is reported.

The single-group model, allocation listed as NA, and masking listed as NONE limit the types of comparisons supported by the design. There is no recorded randomized control group for estimating a between-group treatment contrast. The registry also does not report a statistical analysis plan, sample-size justification, or interim-analysis plan.

Safety information is limited to participant counts and selected serious adverse-event terms and percentages. The record does not report the death count, event timing, duration, severity grades, attribution, or further event-level detail. These omissions do not show that such analyses were absent from the conduct of the study; they mean that they are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bortezomib in Treating Patients With Lymphoproliferative Disorders — NCT00023764.
• Registry record last updated 2015-12-08; status last verified 2012-12.
• Results first posted 2014-04-01.
• 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 completed Phase II, single-group study of bortezomib in recurrent Grade 1, Grade 2, and Grade 3 follicular lymphoma and recurrent mantle cell lymphoma. Enrollment is 103. The study start is recorded as 2001-06 and primary completion as 2009-03. The sponsor is the National Cancer Institute (NCI).

The intervention is an infusion of bortezomib under the schedule described in the arm record. The primary endpoint is Response Rate, with a timeframe of up to 3 years; the description specifies estimating a response probability and providing a 95% confidence interval. The response result and its analysis details are not reported in the registry record.

The registry records serious adverse events affecting 20 participants among 103 at risk and other adverse events affecting 95 participants among 103 at risk. Selected serious-event terms and percentages are listed. The record does not report the death count. Since the study is single-group, its recorded safety information is descriptive rather than comparative.