Intrapleural Bevacizumab and Cisplatin Therapy for Malignant Pleural Effusion Caused by Non-small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intrapleural Bevacizumab and Cisplatin Therapy for Malignant Pleural Effusion Caused by Non-small Cell Lung Cancer (NCT01661790), a randomized phase 3 study. The primary outcome is Number of Participants With "Complete Response" and "Partial Response".

2. Clinical Question

The clinical question is whether adding bevacizumab to intrapleural cisplatin is associated with a different response in malignant pleural effusion. The registry describes response assessment using type-B ultrasonic tests. Complete remission required disappearance of the accumulated fluid and stability for at least four weeks. Partial remission required more than 50% of the accumulated fluid to have disappeared, improvement in symptoms, and no increase in the remaining fluid for at least four weeks. The record says the overall response rate was calculated from the sum of complete and partial responses.

Those definitions describe what the primary outcome was intended to count; they do not supply the counts needed to compare the regimens. The record does not state how many participants in either group achieved complete or partial remission, nor does it report an estimated treatment contrast or its uncertainty. Consequently, the clinical question is identifiable from the trial description, but its answer cannot be determined from the posted primary outcome information.

3. Trial Design

This was a randomized, open-label, multicenter phase III study with a parallel-group design. The registry lists an enrollment of 72 and identifies Chinese PLA General Hospital as the sponsor. The recorded status is completed. The trial start is listed as 2009-08, and primary completion as 2012-06.

The two treatment groups differed by the addition of bevacizumab to intrapleural cisplatin. The combination group received bevacizumab 300mg plus cisplatin 30mg every two weeks; the comparator group received cisplatin 30mg every two weeks. The registry does not report further administration details, such as the planned number of treatments or criteria for stopping treatment.

Random allocation is intended to support a fair comparison by reducing the influence of systematic differences in participant characteristics at assignment. It does not, by itself, establish that the groups were balanced in the enrolled trial, and the registry record does not provide baseline characteristics. Open-label means masking was absent; the record does not describe whether response assessors were masked separately from participants or treating clinicians.

The primary outcome is the number of participants with complete and partial response, assessed by type-B ultrasonic tests. Other listed outcomes include median progression-free survival, overall survival, adverse reactions, and quality of life. The registry record does not report the analysis methods for these outcomes, the timing of each secondary assessment, or the participant flow from enrollment through outcome assessment. The listed design features describe how the comparison was organized, but they do not supply the missing efficacy results.

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 Participants With "Complete Response" and "Partial Response", measured over from randomization, This treatment was given every two weeks,responses were made by biweekly.

The primary endpoint is titled as the number of participants with complete response and partial response. It is a count of participants classified by response, rather than a time-to-event measure or a continuous measurement. The registry describes type-B ultrasonic assessment and defines complete remission by disappearance of accumulated pleural fluid that remains stable for at least four weeks. Partial remission requires more than 50% of the accumulated fluid to disappear, symptoms to improve, and the remaining fluid not to increase for at least four weeks. The record states that overall response rate was calculated by adding complete and partial responses.

Response endpoints are used to summarize whether a prespecified clinical or imaging change occurred during treatment. Combining complete and partial response can capture more than complete disappearance alone, but a combined response count does not show the distribution between its component categories unless those category counts are also reported. The registry’s primary outcome description includes multiple categories and time points, and the posted information does not reduce them to one group comparison.

Most importantly, the endpoint definition is not an outcome result. The registry record does not report the numbers achieving complete response, partial response, or the combined response in either group. It also does not report a treatment effect estimate, confidence interval, or statistical test for the primary outcome. The response criteria explain how the endpoint was meant to be classified, while the efficacy comparison remains unavailable in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by identifying the outcome, the comparison, and the population to which the result applies. In this trial, the primary outcome is a participant count based on complete and partial remission, and the comparison is between the combination regimen and cisplatin alone. The registry record describes the outcome criteria but does not report a primary group comparison or analysis population. That prevents reconstruction or evaluation of an efficacy estimate.

What does a participant count represent?

For a binary response outcome, each participant is classified according to whether the specified response occurred. A group count can be interpreted alongside the number assessed in that group, while a comparative analysis can express the contrast as a difference, ratio, or another prespecified measure. Each measure answers a somewhat different question. For example, a difference describes the separation between group response proportions, whereas a ratio compares them relative to one another. These are general statistical concepts; the registry record does not identify which comparative measure was planned or report the inputs needed to calculate one.

Counts alone are not enough to assess precision. A confidence interval is a range of values compatible with the observed data under the chosen statistical model and its assumptions. A narrow interval indicates greater precision than a wide interval, though neither one proves that the model or outcome measurement is appropriate. No confidence interval for the primary response comparison is reported in the registry record.

How should randomization be understood?

Random allocation is intended to make treatment assignment independent of participant characteristics at the point of assignment. In general, this supports interpreting group differences as treatment-related, provided the study is conducted and analyzed appropriately. Randomization does not guarantee identical groups in every characteristic, especially in a finite study. Baseline summaries, participant flow, adherence, outcome availability, and the analysis population help readers assess how the randomized comparison was carried through. Those details are not reported in the registry record.

The study is described as open-label, with no masking. In general, lack of masking can affect behavior, co-interventions, reporting, or assessment, depending on the outcome and safeguards used. The registry describes ultrasound-based response criteria, but does not say whether image assessors were masked or whether assessment was centrally reviewed. Those procedures are not reported in the registry record and should not be assumed.

What does the response definition add?

The complete and partial remission definitions give operational rules for classifying response. Complete remission requires the accumulated fluid to disappear and remain stable for at least four weeks. Partial remission requires more than 50% of the accumulated fluid to disappear, symptom improvement, and no increase in the remaining fluid for at least four weeks. Prespecified rules can make outcome classification more consistent. They do not eliminate possible differences in measurement or judgment, and the registry does not describe assessor training, reproducibility, or adjudication.

The stated overall response rate combines complete and partial response. A combined endpoint can be informative as a summary, but it can conceal differences in the mix of complete and partial responses. Separate category counts would help describe that mix. The registry’s primary outcome has several categories or time points and is not reduced to one comparison in the posted results. The category-specific counts and time-specific analysis are not reported in the registry record.

What can be inferred from the analysis information?

The registry lists six outcome measures and zero analyses. This means the entry does not contain a reported inferential analysis that can be assessed for model choice, handling of repeated assessments, or adjustment for covariates. It also does not identify a primary analysis population, such as all randomized participants or participants with an evaluable response. No missing-data method, sensitivity analysis, or treatment of participants with unevaluable assessments is reported in the registry record.

For general context, missing outcome data can compromise a comparison when the chance of missingness differs between groups or is related to outcome status. An analysis that includes only participants with observed outcomes can be biased under some patterns of missingness. A complete report would state how many outcomes were observed, how missing values were handled, and whether conclusions were checked under alternative assumptions. The registry record does not provide those details.

Multiplicity arises when several outcomes, categories, time points, or statistical comparisons are examined. Repeated testing can increase the chance of at least one apparently notable result even when no true effects exist. Prespecifying a primary comparison and describing any adjustment or hierarchy helps readers interpret a family of tests. The registry lists multiple outcomes and a primary endpoint with categories and time points, but no multiplicity strategy or statistical analysis plan is reported.

How should planning calculations be read?

General sample-size planning asks what amount of information would be needed to detect a specified effect under stated assumptions. The planning assumptions recorded for this trial describe a two-sided significance level of 0.05, equal allocation, and a normal approximation; they say the effect to detect is a stated fraction of the observed effect. For time-to-event calculations, the stated convention is a total number of events using the Schoenfeld approach; other calculations are expressed as participants per arm. These are planning assumptions, not proof that the trial used that design rationale, and the record does not report a sample-size justification or the statistical plan behind the trial.

Illustrative sample sizes based on an observed effect are conditional on that effect being a useful planning target and on the assumptions used. They are not observed power, do not establish that a result is reliable, and cannot replace the original trial analysis. The primary response results needed to evaluate the observed effect are not reported in the registry record. Over-dispersion is a general concern when observed variability exceeds what a simple model assumes; model choice should reflect the outcome and data structure. The registry does not report a model or diagnostics for the primary endpoint, so no claim about over-dispersion or its handling is possible.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes: median progression-free survival, overall survival, adverse reactions, and quality of life, in addition to the primary response endpoint. It records six outcome measures and zero analyses. The primary endpoint itself includes complete and partial response and describes assessments made over time. When multiple outcomes, categories, or time points are analyzed, a prespecified strategy is important for distinguishing a primary confirmatory comparison from additional exploratory findings. A multiplicity adjustment, testing hierarchy, or other strategy is not reported in the registry record.

The analysis population is also not described. The registry does not state whether primary response was analyzed among all randomized participants, only those assessed, or another group. Participant flow, the number with available response assessments, and reasons for missing assessments are not reported in the registry record. Without that information, readers cannot determine whether the recorded adverse-event groups correspond to the same population used for the efficacy endpoint.

No missing-data method, sensitivity analysis, or interim analysis information is reported in the registry record. These omissions do not establish that such procedures were absent from the trial; they mean they cannot be evaluated from the registry entry. Likewise, the record does not report a statistical analysis plan, sample-size justification, or how any departures from planned methods were handled. The completed trial status and the presence of outcome definitions do not resolve those reporting uncertainties.

11. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s adverse-event data list 36 participants at risk in each group for serious adverse events. Serious adverse events affecting participants are recorded as 0 in the bevacizumab-and-cisplatin group and 0 in the cisplatin group. The data also list other adverse events affecting 24 participants in the combination group and 22 in the cisplatin group, with 36 at risk in each group.

These entries are counts, not a complete safety analysis. The registry does not define the distinction between serious and other adverse events in this record, describe the specific other events, or report event severity, timing, recurrence, or attribution to treatment. It also does not report a statistical comparison or uncertainty interval for the between-group figures. The absence of listed serious adverse-event terms does not provide details beyond the recorded zero counts.

The death field is not reported in the registry record. The adverse-event entries should therefore be read as the posted participant counts and not as evidence about every safety outcome. They also do not answer the primary response question.

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

The registry record describes a randomized comparison of intrapleural bevacizumab plus cisplatin against intrapleural cisplatin for malignant pleural effusion in advanced non-small-cell lung cancer. It specifies how complete and partial remission were defined and records some adverse-event counts. These are useful elements for understanding the intended comparison and the scope of the posted safety information.

The record does not report the primary response counts by group, a comparative efficacy estimate, or an uncertainty interval. It therefore cannot establish whether the observed response differed between treatment groups, how large any difference was, or how precisely it was estimated. The absence of an efficacy result should not be interpreted as evidence that the regimens had the same response or that one was better.

The serious adverse-event entries show 0 participants affected in each group among 36 at risk per group, while other adverse events are recorded as affecting 24 participants in the combination group and 22 in the cisplatin group. These descriptive counts do not by themselves establish comparative safety. The event definitions and detailed event descriptions are not reported in the registry record, nor is a statistical safety analysis.

More broadly, a trial result is interpreted in light of its endpoint definition, analysis population, missing data, and uncertainty. Important details about these aspects are not reported in the registry record. Nor are the listed secondary-outcome results reported. The appropriate conclusion is therefore about the limits of the registry information: it describes the design and selected counts, but does not provide enough outcome reporting to answer the primary comparative question or characterize the full balance of benefits and harms.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines a randomized design with a primary response endpoint whose definition is described, while its primary comparative results are not reported in the registry record. That distinction matters: readers can understand the intended measurement but cannot evaluate the treatment contrast without the response counts and an analysis.

The endpoint also combines complete and partial remission into an overall response rate. Such a summary can make a response outcome easier to communicate, but the categories represent different response states. Reporting each category alongside the combined measure would help readers understand what contributes to the overall result. The registry description says the total was calculated by adding complete and partial response, but it does not report their counts.

Open-label conduct is another reason to value transparent reporting of outcome assessment. The registry says response was assessed using type-B ultrasonic tests, but does not report whether assessors were masked or whether measurements were independently reviewed. This does not show that assessment was biased; it identifies information needed to judge the possibility and handling of measurement-related bias.

Finally, the record lists multiple outcomes but no analyses. Transparent reporting of the prespecified analysis, missing-data handling, and multiplicity strategy would help distinguish confirmatory findings from other assessments. For statisticians and clinical researchers, the case illustrates that trial design information and outcome definitions are not substitutes for results, uncertainty, and analysis details. A completed status alone cannot answer the clinical question when the key endpoint comparison is absent.

14. 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 consequential limitation of the registry entry is that it does not report the primary response counts or a comparative analysis. Although it defines complete and partial remission, the record provides no group-specific efficacy results, effect estimate, confidence interval, or p-value. As a result, the primary treatment comparison cannot be interpreted statistically.

The registry does not report baseline characteristics, participant flow, the primary analysis population, or the number of participants with assessable response outcomes. It also does not report missing-data methods or sensitivity analyses. These gaps make it difficult to assess how complete the outcome data were and how the analysis related to the randomized groups.

The study is described as open-label, but assessment safeguards are not described. The registry does not say whether response assessors were masked or whether ultrasound-based classifications were reviewed independently. The response criteria are specified, but information about measurement reliability and adjudication is not reported in the registry record.

Additional limitations of the available record include the absence of reported results for the listed secondary outcomes, no reported multiplicity strategy, and no statistical analysis plan. The serious adverse-event counts are recorded as zero in each group, but details for other adverse events and the death field are not reported. These are limitations of what can be assessed from the registry record and should not be taken as proof that the trial itself did not collect or analyze the information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Intrapleural Bevacizumab and Cisplatin Therapy for Malignant Pleural Effusion Caused by Non-small Cell Lung Cancer — NCT01661790.
• Registry record last updated 2015-03-25; status last verified 2015-03.
• Results first posted 2015-03-25.
• 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.

18. Record Summary

NCT01661790 is a completed, randomized, open-label, multicenter phase III parallel-group trial sponsored by Chinese PLA General Hospital. It enrolled 72 and compared intrapleural bevacizumab 300mg plus cisplatin 30mg every two weeks with intrapleural cisplatin 30mg every two weeks. The recorded start is 2009-08, and primary completion is 2012-06.

The primary outcome concerns participants with complete and partial response, assessed by type-B ultrasonic tests. The registry defines these response categories but does not report the primary outcome counts or a comparative efficacy analysis. Serious adverse events are recorded as affecting 0 participants in each group among 36 at risk per group; other adverse events are recorded for 24 participants in the combination group and 22 in the cisplatin group.

Results for the listed secondary outcomes, the statistical analysis plan, analysis population, and missing-data handling are not reported in the registry record. The available information therefore describes the design, endpoint, and selected safety counts but does not answer the primary comparative question.