Bortezomib for Low or Intermediate-1 Myelodysplastic Syndrome (MDS) With p65 Activation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bortezomib for Low or Intermediate-1 Myelodysplastic Syndrome (MDS) With p65 Activation (NCT01891968), a na phase 2 study. The primary outcome is Overall Response (OR).

2. Clinical Question

3. Trial Design

This was a Phase II, single-group study sponsored by M.D. Anderson Cancer Center. The registry record lists an enrollment of 15 and describes bortezomib as the intervention. The study title frames the population as people with low or intermediate-1 risk MDS with p65 activation; the registry record does not provide further detail about participant selection or the assessment of p65 activation.

The intervention was bortezomib administered subcutaneously at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21 day cycle. The description calls a 21 day period a course of treatment. The registry record does not state the intended total number of courses, rules for dose modification, or what happened to treatment after response or toxicity.

Because this is a single-group study, the design can describe outcomes among participants who received the intervention, but it does not establish a randomized treatment contrast. No comparator arm is listed; allocation is NA and masking is none. Without a concurrent control group, outcome patterns cannot be separated from other influences such as the course of the condition, participant selection, or care received outside the intervention. Those influences are not quantified in the registry record.

The record lists a primary completion date of 2017-01-18 and a status of completed. It does not report the date of study start in explanatory outcome results, nor does completion status by itself establish that the primary endpoint results are available. Although an overall-response outcome is defined, no numerical response finding or analysis is 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.

Before assignment: Of the 15 participants registered, all were treated with the study medication.

Overall Study

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 Overall Response (OR), measured over 8 weeks.

The primary endpoint is overall response (OR) at 8 weeks, expressed as a count of participants. Its definition combines hematologic improvement under International Working Group (IWG) criteria with complete remission, partial remission and marrow complete remission. The endpoint therefore treats several forms of improvement or remission as response categories within one overall measure.

A binary response endpoint can be useful in a Phase II study because it asks whether participants meet a prespecified response definition within a stated assessment period. Counting participants who meet the definition can give a direct descriptive account of response in the enrolled group. The meaning of the count depends on the response criteria, assessment procedures, and the population included in the analysis.

The registry record gives the endpoint definition and timeframe, but it does not report a response count, the denominator used for an analysis, or an estimated response proportion. It also does not report uncertainty around an estimate, such as a confidence interval, or a statistical test. Therefore, the endpoint's planned meaning can be described, but the observed primary outcome cannot be interpreted from this registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary response endpoint represent?

In general, a binary endpoint assigns each participant to one of two categories for the outcome being assessed, such as meeting or not meeting a response definition. A count of participants meeting the definition can be accompanied by a proportion, provided the analysis denominator is clear. The primary endpoint in this study is described as a participant count, and its response definition combines hematologic improvement, complete remission, partial remission and marrow complete remission. The registry record does not provide the observed count or an analysis denominator, so a response proportion cannot be interpreted from it.

A composite response definition can bring related clinical categories together into a single endpoint. That may provide a concise overall measure, but it also means the combined result depends on its component criteria. A reader would ideally know how each category was assessed, whether categories could overlap, and how disagreements or missing assessments were handled. Those operational details are not reported in the registry record. The listed 8-week timeframe identifies when the primary outcome was intended to be assessed; it does not show that every enrolled participant had an assessment at that time.

What would a confidence interval add?

In general, a confidence interval communicates the uncertainty around an estimated quantity, such as a response proportion. It can show how much the estimate may vary because it is based on a finite group rather than every person in the target population. A narrower interval indicates greater precision under the assumptions of the method; a wider interval indicates less precision. The registry record does not report a response estimate or confidence interval for this endpoint, so precision cannot be evaluated from the posted outcome information.

A p-value, in general, evaluates how compatible observed data are with a specified statistical null model. Its meaning depends on the model, the hypothesis, the analysis plan and the quality of the data. A p-value alone does not measure the size or clinical importance of an effect. No primary-response p-value or inferential analysis is reported in the registry record. It would therefore be inappropriate to infer statistical significance or lack of significance.

Why does the single-group design matter?

In general, a single-group study estimates outcomes among participants who receive the intervention, rather than estimating a difference between randomized groups. The observed course of a condition, selection of participants, concurrent care and measurement practices may also influence outcomes. A concurrent control group can help distinguish treatment-group outcomes from background patterns; this study has no listed comparator. Thus, even if a response count were posted, it would not by itself be a randomized estimate of a treatment effect.

Masking is recorded as none. In general, masking can reduce the influence of knowledge about treatment assignment on assessments or reporting, although its relevance varies with the endpoint and study procedures. The registry record does not describe additional safeguards for evaluating response or adverse events. Allocation is recorded as NA, consistent with the lack of a listed randomized comparison.

What can be concluded from the analysis information?

The registry record describes one primary outcome measure but reports no analyses. It does not identify a statistical model, an estimation method, an adjustment strategy, or an approach to missing outcome data. Those omissions mean the intended analysis cannot be reconstructed from the record. They do not demonstrate that no analysis was conducted elsewhere; they mean that an analysis is not reported in the registry record.

In general, over-dispersion matters when observed variability is greater than a statistical model expects. For a simple binary endpoint, the main concerns would ordinarily include the response definition, denominator, dependence among observations if present, and missing assessments. The registry record does not give evidence of over-dispersion or describe a model for which it was assessed, so it is not possible to say that it affected this study's analysis.

How should planning calculations be understood?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, significance level, allocation, and statistical method. It is not an observed study result and should not be described as observed power. The planning assumptions associated with the posted material describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. They are an illustration, not a description of this single-group trial's design. The registry record does not report the trial's own sample-size justification. The planning illustration cannot replace the missing primary outcome result or establish what the study was designed to detect.

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("Bortezomib")
n      <- c(15)
events <- c(3)
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  Bortezomib  15  3  20.0  4.3  48.1  7.0  45.2  7.3  45.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record defines one primary outcome measure: overall response at 8 weeks. It does not report whether other efficacy outcomes were assessed, whether multiple statistical hypotheses were tested, or whether any adjustment for multiple comparisons was planned. With no reported analyses, the handling of multiplicity is not reported in the registry record. It would be inappropriate to assume either that an adjustment was used or that multiplicity was not relevant.

The record also does not describe missing-data procedures. It does not state how participants without an 8-week response assessment were treated, whether assessments were repeated, or whether any imputation or sensitivity analysis was performed. The number enrolled does not reveal how many participants were included in the primary analysis. No analysis population, such as an intention-to-treat or evaluable population, is specified in the outcome information.

In general, missing outcome data can affect interpretation when the probability of being assessed is related to a participant's condition or outcome. A complete-case estimate and an estimate using a different missing-data approach can answer different questions. Without counts of assessed participants and a documented method, readers cannot determine the extent or possible direction of this concern for the response endpoint.

Interim analyses and stopping rules are also not reported in the registry record. Their absence from the record should not be interpreted as proof that no such procedures existed; it means they are not documented in the information available for this study. The record does not report a prespecified statistical analysis plan or how departures from any plan were handled.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenic fever (13.3%), congestive heart failure (6.7%), hypotension (6.7%), stroke (6.7%), transient ischemic attack (6.7%).

The safety listing gives 15 participants at risk for other adverse events, with 15 affected, and 15 at risk for serious adverse events, with 6 affected. It also records 1 death. These are participant-level figures in the registry listing; they should not be treated as counts of individual event episodes. The record does not provide a narrative about the death or establish its relationship to treatment.

The listed serious-event terms and percentages are Neutropenic Fever, 13.3%; Congestive Heart Failure, 6.7%; Hypotension, 6.7%; Stroke, 6.7%; Transient Ischemic Attack, 6.7%; and Acute Kidney Injury, 6.7%. The registry record does not give further details about timing, severity grading, duration, recurrence, or whether the events were considered related to bortezomib. Percentages in a safety listing are descriptive; they do not by themselves demonstrate causation.

The safety figures should be read alongside the small enrolled group and the single-group design, without assuming they describe risks relative to another treatment. The registry record does not report a detailed safety analysis or explain how adverse events were collected. These limitations make the figures useful as a record of reported events, but not a complete basis for comparing safety or attributing an event to the intervention.

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

The registry record establishes that a Phase II, single-group study evaluated subcutaneous bortezomib in a population described in the title as having low or intermediate-1 risk MDS with p65 activation. It gives a regimen and defines overall response at 8 weeks using hematologic improvement under IWG criteria, complete remission, partial remission and marrow complete remission. It also reports selected adverse-event figures.

What the record does not establish is the primary response result. No number of participants meeting the response definition, response estimate, confidence interval, or analysis is reported. Consequently, it is not possible to state from this record how often the endpoint occurred or how precisely it was estimated. The missing outcome information is not equivalent to a finding of no response.

The design also sets limits on causal interpretation. There is no listed control group, no masking, and no randomized comparison. In general, outcomes in a single treated group cannot show what would have happened to comparable participants under a different treatment or without the intervention. Any observed pattern could reflect more than the intervention, and the registry record does not quantify those other influences.

The safety information similarly has limits. The reported affected-participant counts and serious-event percentages are descriptive and do not by themselves show whether events were caused by bortezomib. The record does not explain the circumstances of the death, the event collection methods, or the safety analysis population.

Accordingly, the most defensible reading is that the registry record describes the trial's design, treatment schedule, intended primary outcome and selected safety entries, while leaving the primary efficacy result and several analytical details unreported. Completion status should not be mistaken for a posted result, and neither the outcome definition nor the safety listing alone answers a comparative treatment question.

14. Why This Trial Matters Statistically

This study raises statistical questions that are common in early clinical research. A Phase II, single-group design can organize the observation of an intervention and a defined outcome, but its interpretation depends heavily on transparent reporting of who was analyzed, what was observed, and how uncertain the estimate is. Here the outcome definition and assessment timeframe are stated, while the numerical response result and analysis are not reported in the registry record.

That contrast matters because a clearly specified endpoint is only one part of evidence. Readers also need the response count, denominator, assessment completeness and an estimate of precision to understand what the data show. Without those pieces, the outcome cannot be compared even descriptively with an expectation or benchmark. The record's completion status cannot fill that gap.

The single-group structure is also important statistically. Without a control group, the study does not directly estimate a difference between treatment strategies. This does not make a single-group design uninformative; it defines the kind of question it can address. But claims about comparative effects require information that this design and registry entry do not provide.

Finally, the safety entries illustrate why counts, percentages and causal conclusions must be kept distinct. Reported participant figures can identify events recorded in the study, while their interpretation depends on definitions, timing, follow-up, attribution and a comparison context. Those details are not fully. The record therefore offers a basis for discussing endpoint definition and design, while also showing why complete analysis reporting is necessary for a 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 direct limitation is that the primary overall-response result is not reported in the registry record. Although the endpoint is defined and its timeframe is stated as 8 weeks, there is no response count, denominator for an efficacy analysis, estimate of uncertainty, or inferential analysis. The reader cannot determine the observed response pattern from this entry.

The record gives an enrollment of 15 but does not report participant flow, baseline characteristics, withdrawals, or the number completing an 8-week assessment. It does not identify an analysis population or explain how missing assessments were handled. These omissions limit the assessment of whether the people enrolled and the people contributing outcome information were the same group.

The response definition combines several outcome categories, but operational details are not reported. The record does not explain assessment procedures, adjudication, or how category overlap was treated. It also does not provide detailed eligibility criteria or explain how p65 activation was established.

The single-group design, lack of masking and absence of a comparator limit causal and comparative interpretation. The registry record does not report the trial's own sample-size justification, statistical analysis plan, multiplicity procedures, interim analyses, stopping rules, or handling of protocol deviations. These items should be treated as unreported rather than inferred from the design.

Safety reporting is limited to participant-level affected figures, a death entry and selected serious-event terms with percentages. Timing, severity grading, event-level counts, attribution and detailed follow-up are not reported. The record therefore does not provide a complete account of safety outcomes or a comparative safety estimate.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bortezomib for Low or Intermediate-1 Myelodysplastic Syndrome (MDS) With p65 Activation — NCT01891968.
• Registry record last updated 2018-04-23; status last verified 2018-03.
• Results first posted 2018-04-23.
• 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

NCT01891968 is listed as a completed Phase II, single-group study sponsored by M.D. Anderson Cancer Center, with 15 participants enrolled. Its title describes bortezomib for low or intermediate-1 risk MDS with p65 activation. The regimen was subcutaneous bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21 day cycle.

The primary outcome was overall response at 8 weeks, defined to include IWG hematologic improvement, complete remission, partial remission and marrow complete remission. The registry record does not report the numerical primary response result or an analysis. Safety entries list 6 participants affected by serious adverse events among 15 at risk, 15 affected by other adverse events among 15 at risk, and 1 death. The record does not report a control-group comparison or establish event causality.