Pilot Study Using Avastin and Gleevec to Treat the Progression of Intraluminal Pulmonary Vein Stenosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study Using Avastin and Gleevec to Treat the Progression of Intraluminal Pulmonary Vein Stenosis (NCT00891527), a na phase 1, phase 2 study. The primary outcome is Number of Patients With Survival at 48 Weeks.

2. Clinical Question

The study objective was to pilot the use of targeted biologic agents for progression of multivessel intraluminal pulmonary vein stenosis in children. The treatment description does not define a single, identical regimen for every patient: imatinib was used for all, while bevacizumab use depended on the stated clinical characteristics and progression. This makes the question about the treatment approach in this study group, rather than a direct estimate of the effect of one fixed regimen against a control.

The record also names disease progression and disease stabilization at 48 weeks as secondary outcomes. Their results are not reported in the registry record. Consequently, the stated questions can be identified, but the posted information does not show how many participants met any of these outcome definitions or how precisely those outcomes were estimated.

3. Trial Design

This is a completed Phase 1 and Phase 2 study sponsored by Boston Children's Hospital. The registry records an enrollment of 50 and describes the model as single group. Allocation is listed as NA, and masking is listed as none. The study began in 2008-10 and had a primary completion date of 2015-12.

The arm is titled “Avastin and/or Gleevec.” Its description says that all patients were treated with Gleevec (imatinib mesylate), while patients without congenital heart disease and those who progressed were also treated with Avastin (bevacizumab). The wording describes treatment assignment according to patient characteristics and progression, not a randomized allocation. It also does not make clear whether the two criteria for receiving Avastin were mutually exclusive or how treatment timing was handled. Those details are not reported in the registry record.

Because there is no randomized control group, this design cannot directly separate changes associated with treatment from changes associated with disease course, patient characteristics, or other care. The treatment pathway also means that patients may not all have received the same combination. Any overall outcome count would therefore describe the study group and its treatment approach, rather than a clean comparison of one regimen with another.

The registry names one primary outcome and two secondary outcomes, each framed at 48 weeks. The primary outcome is the number of participants with survival at 48 weeks. The secondary outcomes concern progression and stabilization at 48 weeks. Enrollment is reported, but the number assessed for each outcome, the analysis population, and the handling of incomplete follow-up are not reported in the registry record. No protocol details or statistical analysis plan are described in the available 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 Number of Patients With Survival at 48 Weeks, measured over 48 weeks.

The primary endpoint is the number of participants with survival at 48 weeks. It is a count-based binary outcome: each participant's status at the stated time point is classified as survival or not, and the endpoint is expressed as a number of participants meeting the survival condition. The registry record does not give the observed count, the denominator used for the endpoint, or a definition of how survival status was established.

A fixed-time survival status can provide a direct description of the proportion or count meeting a clinically meaningful condition at a specified follow-up point. Unlike a time-to-event outcome, a single status at 48 weeks does not convey when an event occurred or how long each participant was followed before an event or censoring. This is a general distinction between endpoint types, not a claim about the analysis used in this study.

The endpoint is not, by itself, a comparison of treatment effects. In this single-group study, an observed survival count would describe outcomes among the enrolled participants under the treatment approach recorded. Without a randomized comparator, the count alone would not establish what would have happened under another treatment or without the study treatment. The registry names survival at 48 weeks as primary, but its result and inferential analysis are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study observes outcomes in participants receiving the study treatment approach. Its results can describe the observed experience of that group, provided outcome definitions and follow-up are clear. It does not create a concurrent control group by itself. Without random allocation to distinct treatments, differences in patient features, disease course, and clinical decisions may contribute to observed outcomes. This is a general limitation of interpreting single-group clinical data.

Here, the record identifies a single-group model, allocation listed as NA, and no masking. The treatment description states that all patients received imatinib and that bevacizumab was added for patients meeting the recorded criteria. Because those criteria include disease progression, treatment exposure is connected to the clinical course. The registry does not report an analysis designed to account for that relationship.

How should the primary outcome be understood?

The primary endpoint is a count of participants with survival at 48 weeks. A count is an absolute number, while a rate or proportion also requires a clearly defined denominator. The registry does not report the endpoint count or its denominator, so neither can be interpreted from the posted record. A confidence interval, when reported for an outcome estimate, describes the range of values compatible with the data and analysis under the method's assumptions. No confidence interval for this endpoint is reported.

A fixed-time status differs from a time-to-event analysis. A status at one follow-up point does not retain the timing of events throughout follow-up. A time-to-event method can use event timing and account for incomplete observation under specified assumptions. The registry names a status count at 48 weeks, not a time-to-event endpoint; the statistical method for analyzing survival is not reported in the registry record.

What do the planning assumptions mean?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a description of the registered single-group design. The illustration's equal-allocation, two-arm setup does not match the recorded design. A sample-size calculation is a planning exercise: it does not establish that a study had a particular probability of detecting an effect after the results are observed. Sample sizes from such an illustration should not be described as observed power.

The record does not report the trial's own sample-size justification, a planned effect size, or a statistical analysis plan. The planning assumptions alone do not establish how the study was designed or how its outcomes were analyzed. No recalculated estimate or sponsor analysis for the primary endpoint is reported in the registry record.

Why does the treatment pathway matter statistically?

When treatment exposure depends on patient characteristics or disease progression, the groups receiving different amounts or combinations of treatment may differ in their underlying risk. A crude comparison can therefore mix treatment effects with differences in prognosis. This is a general concern known as confounding by indication. Randomization can help balance measured and unmeasured prognostic factors on average, but this study is not registered as randomized. The available record does not describe a modeling strategy to adjust for these factors.

The endpoint counts are also dependent on complete and consistent outcome ascertainment. A participant without a recorded status at the target time cannot automatically be treated as having survived, progressed, or stabilized. The registry does not state how missing outcomes were handled, how follow-up was defined, or which participants entered each outcome analysis. Those omissions limit interpretation of any counts that might otherwise be reported.

What does the safety reporting convey?

Adverse-event counts describe events recorded in the study, but they do not alone establish causation. A comparison of event rates requires comparable groups, clear follow-up, and definitions of who was at risk. In this record, the safety entries provide counts at risk and affected for serious and other adverse events, plus a death count. There is no randomized control group, and the record does not state event attribution, timing, severity criteria, or whether one participant could contribute to multiple event terms. The listed percentages for serious-event terms should not be added to create a total: the record does not say the categories are mutually exclusive.

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("Avastin and/or Gleevec")
n      <- c(48)
events <- c(42)
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  Avastin and/or Gleevec  48  42  87.5  74.8  95.3  75.3  94.1  75.2  94.1

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome, survival at 48 weeks, and two secondary outcomes, progression and stabilization at 48 weeks. It does not report results for these outcomes or an analysis plan describing how multiple outcomes were handled. When several outcomes are tested, the chance of at least one false-positive finding can increase; prespecified priorities and multiplicity adjustments are general approaches for addressing that issue. No such plan or adjustment is reported in the registry record, so no claim about multiplicity control is warranted.

Missing-data handling is not reported. The record does not state how participants without outcome information at 48 weeks were treated, whether follow-up was complete, or whether any sensitivity analyses were conducted. These details matter because an outcome count depends on knowing both the status and the relevant analysis population. The enrollment entry is not a substitute for the number assessed at each endpoint.

The analysis populations are also not described. The record does not specify whether analyses used all enrolled participants, only those who began treatment, or another defined group. It lists zero analyses, and no outcome analysis results are reported. The safety entries include 48 at risk for serious adverse events and 48 at risk for other adverse events, but these risk sets should not be assumed to be the denominators for the primary endpoint or secondary outcomes.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infection (10.4%), gastrointestinal toxicity (8.3%), bone marrow suppression (4.2%), hospitalization (4.2%), tremors (2.1%).

The registry lists 10 participants affected by serious adverse events among 48 at risk. For other adverse events, it lists 48 affected among 48 at risk. It separately lists 11 deaths. These are registry entries for the study group, not a comparison between randomized treatment arms. The record does not report when the events occurred, their relationship to treatment, or the causes and timing of the deaths.

The listed serious-event terms are Infection (10.4%), Gastrointestinal Toxicity (8.3%), Bone Marrow Suppression (4.2%), Hospitalization (4.2%), and Tremors (2.1%). These are the recorded term percentages; the record does not state whether categories overlap or provide further detail on event definitions. They should not be added together to infer a total percentage.

The death count should not be substituted for the primary survival result: the registry does not give the endpoint count or explain whether the death entry and 48-week endpoint refer to the same follow-up period or analysis population. These safety figures describe what is recorded, but do not establish that treatment caused an event or quantify comparative risk.

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

The registry record describes a pilot study of targeted biologic treatment in children with multivessel intraluminal pulmonary vein stenosis. It records imatinib for all patients and additional bevacizumab for patients meeting the stated criteria. It also identifies survival at 48 weeks as the primary outcome and progression and stabilization at 48 weeks as secondary outcomes. These registry entries define the study question and the treatment approach; they do not provide the outcome results.

The primary survival count is not reported in the registry record. Neither are the results for progression or stabilization. Without those results, there is no estimate to judge for size or precision, and no basis in the posted record for saying whether outcomes were more or less frequent than expected. The record also does not provide a control group against which to compare the treatment approach.

Even if outcome counts were available, a single-group observation would describe the study participants and would not by itself show what would have happened under an alternative treatment. The conditional use of bevacizumab further means that treatment exposure is linked to recorded patient characteristics and progression. A causal interpretation would require appropriate design or analysis details, which are not reported in the registry record.

The safety entries provide counts and selected serious-event terms, but do not establish treatment causation. The listed deaths are not a substitute for the missing primary endpoint result. Thus, the posted information is useful for understanding the registered design, endpoints, and selected safety reporting, but it is insufficient to assess the magnitude, precision, or comparative meaning of clinical outcomes.

14. Why This Trial Matters Statistically

This study illustrates why a registered endpoint and a reported endpoint result are not the same thing. The record names survival at 48 weeks as the primary outcome, but does not report the count, denominator, or uncertainty around that outcome. Without those pieces, readers cannot evaluate the observed survival status or its precision.

It also highlights the distinction between a treatment description and a treatment comparison. Although the intervention names imatinib and bevacizumab, the record describes a single group in which bevacizumab was used according to patient characteristics and progression. That design can document treatment experience, but it does not provide a randomized contrast that isolates the effect of a specific regimen.

The planning assumptions offer another statistical lesson. An illustration based on equal allocation between two arms is not equivalent to the recorded single-group design. Planning calculations depend on assumptions about design and effect; they are not evidence of observed power and cannot replace reported outcome estimates.

Finally, safety counts need context: at-risk populations, follow-up, event definitions, and attribution all shape interpretation. The registry provides some counts and term percentages, but not the details needed for comparative or causal safety claims. Together, these features show why complete outcome reporting and alignment between design, analysis, and interpretation matter in clinical research.

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 registry record gives limited detail about eligibility, treatment timing, and the clinical criteria used to add bevacizumab. Its description says patients without congenital heart disease and those who progressed also received bevacizumab, but it does not clarify how those criteria were applied or whether they overlapped. This limits understanding of treatment exposure and patient pathways.

The primary and secondary outcomes are named at 48 weeks, but their results, denominators, definitions, and analysis populations are not reported. The record also does not describe loss to follow-up, missing-data methods, or how outcome status was established. These omissions prevent assessment of outcome completeness and precision.

The nonrandomized, single-group design has no like-for-like control comparison. Since bevacizumab use was conditional, an unadjusted contrast by exposure would be vulnerable to differences in prognosis. The registry lists zero analyses and does not report an adjusted approach, so no such correction can be assumed.

Safety reporting is also limited: the record does not describe event timing, attribution, definitions, or whether serious-event categories overlap. The death count is not tied in the record to the primary endpoint's analysis population or timeframe. The protocol, statistical analysis plan, sample-size justification, interim analyses, and missing-data procedures are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study Using Avastin and Gleevec to Treat the Progression of Intraluminal Pulmonary Vein Stenosis — NCT00891527.
• Registry record last updated 2019-06-19; status last verified 2019-06.
• Results first posted 2017-05-31.
• 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

NCT00891527 is a completed Phase 1 and Phase 2, single-group study sponsored by Boston Children's Hospital. It records enrollment of 50, no masking, and allocation listed as NA. The study began in 2008-10 and its primary completion date is 2015-12.

The study objective was to examine targeted biologic agents for progression of multivessel intraluminal pulmonary vein stenosis in children. The treatment description states that all patients received imatinib, with bevacizumab also given to patients meeting the stated criteria. Survival at 48 weeks is the primary outcome; progression and stabilization at 48 weeks are secondary outcomes.

The record does not report results for these outcomes or analyses. It lists serious and other adverse-event counts, selected serious-event terms, and deaths, but does not provide the contextual details needed for causal or comparative interpretation.