This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Malignant Pleural Effusion With ZD6474 (NCT00402896), a na phase 2 study. The primary outcome is Median Time to Pleurodesis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00402896 |
| Phase | Phase 2 |
| Condition | Lung Cancer, Pleural Effusion |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 28 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
People with lung cancer and malignant pleural effusion were the intended population. The registry record reports an enrollment of 28. For the primary outcome, it states that twenty eligible participants were analyzed; the reason the enrollment and analysis counts differ is not reported in the registry record.
Intervention
Participants received ZD6474, described as a drug given orally at 300 mg/day for 10 weeks. The study aimed to examine whether treatment affected the time until pleurodesis, operationalized as catheter removal.
Comparator
There was no separate comparator group. The design is listed as single-group, with allocation recorded as NA and masking listed as none. Consequently, the registry record does not describe a randomized or blinded comparison with another treatment or a control condition.
Primary question
The primary question was how long it took from treatment initiation and catheter insertion until catheter removal, with follow-up limited to a maximum of 10 weeks. The record describes catheter removal as a measure of improvement in pleural effusion, including the amount of fluid drained. It does not report the numerical median time, its confidence interval, or a sponsor-reported estimate of treatment effect. The study also planned to examine tumor cells, biological characteristics, fluid build-up, tumor size, blood-vessel thickness, quality of life, and shortness of breath.
3. Trial Design
This was a Phase 2, single-group study of ZD6474 in malignant pleural effusion. M.D. Anderson Cancer Center is listed as the sponsor. The registry reports an enrollment of 28, while the primary-outcome description says twenty eligible participants were analyzed. The explanation for this difference is not reported in the registry record, so the enrollment figure should not be treated as the primary-outcome analysis count.
The intervention is described as ZD6474 at 300 mg/day by mouth for 10 weeks. Allocation is listed as NA, masking as none, and the model as single-group. These design features mean that the record does not describe a concurrent comparison group or masking of participants or study personnel. The findings therefore cannot be read as a randomized between-group treatment contrast.
The primary outcome was median time to pleurodesis, in days. Its stated timeframe ran from initiation of treatment and catheter insertion up to a maximum of 10 weeks. The outcome description defines the event as catheter removal and says that a Cox model was applied to examine the effect of covariates on time to catheter removal. Numerical model estimates and the primary outcome result are not reported in the registry record.
The record says that eleven participants completed 10 weeks of treatment and that all twenty participants completed the study. These statements refer to different milestones: completion of treatment and completion of the study. The study status is terminated. A reason for termination, further details about participant disposition, and any protocol changes 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.
Before assignment: The clinical trial was terminated before reaching the target patient accrual due to ZD6474 unavailability and of the 28 enrolled but only 20 received treatment. Slow accrual was a contributing factor to early termination.
Overall Study
| Stage | ZD6474 |
|---|---|
| STARTED | 20 |
| COMPLETED | 20 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Twenty eligible participants were analyzed for the primary outcome in the trial, eleven completed 10 weeks of treatment. All twenty participants completed the 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.
| Characteristic | Unit | ZD6474 |
|---|---|---|
| Participants analysed | 20 | |
| Age, Continuous | years | 72 (46 to 80) |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 11 |
| Region of Enrollment: United States | participants | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Median Time to Pleurodesis, measured over Time from initiation of treatment and catheter insertion up to a maximum of 10 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is titled median time to pleurodesis and is measured in days. The description defines the event as catheter removal after treatment initiation and catheter insertion, with observation limited to a maximum of 10 weeks. Catheter removal was used as a practical indicator of improvement in pleural effusion, in relation to the amount of fluid drainage.
General: A time-to-event endpoint records the time until a specified event occurs. It can retain information about when events happen, rather than reducing follow-up to a simple count of participants who did or did not experience an event. The median event time is the point at which the estimated event-time distribution reaches its midpoint; a confidence interval communicates uncertainty around an estimate. The registry record identifies a 95% confidence interval as the dispersion measure, but gives no numerical median or interval limits.
The event is catheter removal, not a direct measurement of every aspect of symptoms, fluid accumulation, or tumor status. The record describes other biological and patient-reported outcomes as study aims, but those results are not reported in the registry record. Thus, the primary endpoint addresses timing of catheter removal within the specified follow-up window, rather than establishing a broader change in all dimensions of the condition.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary endpoint and its intended analysis, but does not report a numerical median time to pleurodesis or the associated 95% confidence interval. It also reports no primary-outcome analysis estimate in the listed analyses. Therefore, the posted information does not establish the observed timing of catheter removal or the precision of that timing estimate. No sponsor-reported hazard ratio is reported in the registry record.
The primary analysis population is described as twenty eligible participants. Eleven completed 10 weeks of treatment, while all twenty completed the study. The record does not explain why the enrollment count is 28 but the primary-outcome population is twenty, nor does it describe how participants who did not complete the treatment period contributed to the time-to-event analysis. Those gaps limit assessment of participant flow and the robustness of the endpoint analysis.
General: A median can provide a concise description of the event-time distribution, while a confidence interval indicates how much uncertainty remains around the estimate. A wide interval would indicate less precision than a narrow interval, but neither the median nor interval limits are available in the registry record. A hazard ratio, if reported, would describe the relative event rate over time under a model; it would not itself state the median time. No such estimate can be interpreted from the posted information.
The design also constrains what conclusions can be drawn. With a single group and no comparator, observed catheter-removal times would not by themselves separate an intervention-associated pattern from the natural course of the condition, other care, or participant selection. The record does not describe a randomized comparison, and masking is listed as none. These features do not negate the descriptive purpose of following time to catheter removal, but they limit causal interpretation.
The study is listed as terminated, but its reason for termination is not reported in the registry record. Termination status alone does not explain whether recruitment, follow-up, or analysis was affected. Nor does it supply the missing primary outcome result. Interpretation should therefore stay with what is explicitly recorded: the intended endpoint, the stated analysis population, treatment completion information, and the absence of numerical primary-outcome estimates.
9. Statistical Methods Explained
The registry describes a time-to-event endpoint and says a Cox model was applied to examine covariates associated with time to catheter removal. It does not report the model’s numerical estimates, covariates, or detailed analysis plan. The following explains the general statistical ideas involved, without attributing unreported choices or findings to this study.
What does a time-to-event endpoint represent?
General: A time-to-event analysis considers both whether an event occurred and the time at which it occurred. In this study, the event was catheter removal, and the stated clock began with treatment initiation and catheter insertion. Follow-up was capped at a maximum of 10 weeks. Participants who have not experienced the event by the end of observation can contribute information up to that point; this is commonly called censoring. The registry record does not describe how censoring was handled in the analysis or how many participants were censored.
The median time is a summary of the event-time distribution. It is distinct from the average time and from the proportion experiencing the event at a particular time. The record names a 95% confidence interval as the accompanying dispersion measure, but the numerical median and interval are not reported. Without those values, readers cannot assess either the observed central event time or its precision.
What does a Cox model generally estimate?
General: A Cox proportional-hazards model relates participant characteristics, or other included covariates, to the rate at which an event occurs over time. Its estimates are conditional on the variables included and on the model assumptions. The registry says that Cox model analysis was applied to examine the effect of covariates on time to catheter removal, but does not identify those covariates or report any coefficients, hazard ratios, confidence intervals, or p-values. It is therefore not possible to describe which factors were examined or what the model found.
General: The proportional-hazards assumption concerns whether the relative event rate associated with a covariate remains stable over follow-up. Assessment can matter because departures from this assumption may make a single hazard ratio a poor summary. Whether this assumption was assessed, and how it was handled, is not reported in the registry record. No diagnostic results or model-checking details are listed.
Why does the lack of a comparison group matter?
General: A single-group study can describe outcomes among participants receiving an intervention, but a change over time is not by itself a treatment effect relative to an alternative. A concurrent comparator can help account for changes that would have occurred without the intervention, subject to the design and analysis. This study is listed as single-group, with allocation NA and masking none; a concurrent control contrast is not described. The registry record therefore does not support a randomized comparative effect estimate.
General: Adjustment for covariates in a model can address measured differences represented by those variables, but it does not create randomization or automatically remove confounding. Since the covariates and model estimates are not reported, the extent and purpose of adjustment cannot be evaluated for this study.
How should precision and significance be assessed?
General: A confidence interval presents a range of values compatible with the data and the model at a stated confidence level; it is not a guarantee that the true value lies in that particular interval. A p-value, when reported, measures compatibility of data with a specified null model under its assumptions. Neither is a substitute for the effect estimate itself. The registry record identifies a 95% confidence interval for the median but supplies no limits, and it does not report a primary-outcome p-value. Statistical significance, precision, and the direction or size of the primary result cannot therefore be assessed from the posted information.
The record includes a planning-illustration assumption describing two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. It explicitly characterizes this as a planning illustration rather than the trial’s own design. Because the trial is single-group, those two-arm assumptions should not be mistaken for its actual allocation or analysis. A planning calculation is also not observed power and cannot replace reported outcome estimates.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure, the median time to pleurodesis, and describes several additional study aims, including biological measures, fluid build-up, tumor size, quality of life, and shortness of breath. It does not report a multiplicity strategy, such as a hierarchy of outcomes or an adjustment for testing multiple hypotheses. Whether any such strategy was specified in the protocol is not reported in the registry record.
The numerical primary-outcome result is not reported, and the listed analyses count is zero. The record does not give a missing-data plan, describe censoring decisions, or state how incomplete outcome information was handled. It also does not explain why the enrolled population of 28 differs from the twenty eligible participants analyzed for the primary outcome. The reason is not reported in the registry record; no assumptions about excluded participants or missing observations can be made from these counts alone.
For analysis populations, the record states that twenty eligible participants were analyzed for the primary outcome and that all twenty completed the study. It separately states that eleven completed 10 weeks of treatment. It does not define an intention-to-treat population, describe exclusions, or say whether all eligible participants were included in every analysis. Interim analyses and their timing are not reported in the registry record. These omissions make it difficult to assess the relationship between the planned study, participant follow-up, and the analysis actually performed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| ZD6474 | 12 | 20 | 60.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ZD6474 | 20 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | ZD6474 |
|---|---|---|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 3 of 20 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 3 of 20 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 3 of 20 |
| Atrial Fibrillation | Cardiac disorders | 2 of 20 |
| R. Pneumothorax | Infections and infestations | 2 of 20 |
| Hyponatremia | Metabolism and nutrition disorders | 2 of 20 |
| CNS Ischemia | Nervous system disorders | 1 of 20 |
| Creatinine | Renal and urinary disorders | 1 of 20 |
| Diarrhea | Gastrointestinal disorders | 1 of 20 |
| Pain | General disorders | 1 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ZD6474 |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 12 of 20 |
| Fatigue | General disorders | 7 of 20 |
| Weight loss | General disorders | 5 of 20 |
| Prolonged QTc | Cardiac disorders | 5 of 20 |
| Hypomagnesemia | Blood and lymphatic system disorders | 5 of 20 |
| Erythema multiforme | Skin and subcutaneous tissue disorders | 4 of 20 |
| Rash/desquamation | Skin and subcutaneous tissue disorders | 4 of 20 |
| Hypokalemia | Blood and lymphatic system disorders | 4 of 20 |
| Nausea | Gastrointestinal disorders | 3 of 20 |
| Cardiac arrhythmia | Cardiac disorders | 3 of 20 |
Serious events with the highest arm-level rate: hypoxia (15.0%), dyspnea (15.0%), pneumonia (15.0%), atrial fibrillation (10.0%), r. pneumothorax (10.0%).
The adverse-event record lists 20 participants at risk for other adverse events and 20 affected. For serious adverse events, it lists 20 at risk and 12 affected. The listed serious-event terms and percentages are Hypoxia, 15.0%; Dyspnea, 15.0%; Pneumonia, 15.0%; Atrial Fibrillation, 10.0%; R. Pneumothorax, 10.0%; and Hyponatremia, 10.0%. The registry record does not report deaths.
General: An at-risk count is the recorded group size used for the safety summary, while an affected count describes participants recorded as having an event in that category. Listed event terms may not represent mutually exclusive groups of participants: one person can experience more than one event type. The registry record does not specify the denominator or calculation basis for each term percentage, so those percentages should be read as reported rather than converted into participant counts.
These figures describe safety reporting for the ZD6474 group; they do not provide a comparison with an untreated or alternative-treatment group. They also do not establish whether an event was caused by the study drug. The listed terms are safety observations, and the registry record does not provide further detail about event timing, severity grading, or attribution.
12. What the Result Does, and Does Not, Mean
The record describes a study designed to examine time from treatment initiation and catheter insertion to catheter removal in people with malignant pleural effusion. It identifies the primary endpoint as median time to pleurodesis and names a 95% confidence interval as the dispersion measure. However, the numerical median and interval are not reported in the registry record. No numerical primary-outcome effect, precision estimate, or p-value can be interpreted from the posted results.
The record does establish some features of the study: it was Phase 2, single-group, unmasked, and terminated; the intervention was ZD6474 at 300 mg/day orally for 10 weeks. Twenty eligible participants were analyzed for the primary outcome, eleven completed 10 weeks of treatment, and all twenty completed the study. These details describe the study’s conduct as recorded, but they do not reveal the outcome distribution.
General: A treatment effect is most directly interpreted through a contrast between outcomes under different treatment conditions. In a single-group study, an observed time to catheter removal can be described for participants in that group, but it cannot alone show what would have happened under another treatment or without the intervention. The registry record does not describe a comparator group or randomized allocation.
The listed safety figures document recorded adverse events, including serious events, in the ZD6474 group. They should not be read as a comparative safety estimate or as proof that the intervention caused the events. Likewise, the study’s stated aims concerning tumor characteristics, fluid accumulation, quality of life, and shortness of breath are not numerical findings. The reason for termination and the explanation for the difference between enrollment and the primary analysis population are not reported in the registry record.
Accordingly, the posted information supports a description of the endpoint, intervention, design, participant counts, and recorded safety summaries. It does not support a conclusion about the size, direction, or precision of the primary outcome, nor a causal comparison with another treatment.
13. Why This Trial Matters Statistically
This study illustrates why a clearly defined endpoint and a reported estimate are both necessary for statistical interpretation. The endpoint is described in operational terms: time to catheter removal, used as a measure related to pleural-effusion improvement, within a maximum follow-up of 10 weeks. The record also identifies a median and 95% confidence interval as the intended summary. Without the actual estimate and interval, readers cannot determine the observed timing or its uncertainty.
The design makes the distinction between description and comparison especially important. A single-group study can characterize the experience of participants who received ZD6474, but it does not provide a concurrent control contrast. The registry record lists allocation as NA and masking as none. A model that adjusts for covariates does not, by itself, create a randomized comparison; moreover, the covariates and model estimates are not reported.
Participant accounting is another statistical concern. The registry reports enrollment of 28, twenty eligible participants analyzed for the primary outcome, eleven completing 10 weeks of treatment, and all twenty completing the study. Those counts refer to different study milestones, and the record does not explain the differences. Clear reporting of analysis populations and follow-up is needed to understand which participants contribute to an endpoint estimate and how incomplete observation is treated.
Finally, the study status is terminated, while the reason is not reported. That status does not itself explain the study’s results or establish why the record lacks numerical outcome estimates. Together, the missing effect estimate, uncertainty interval, participant-flow explanation, and model details limit reproducibility and interpretation. These are statistical reporting issues, distinct from the clinical importance of the research question.
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 direct limitation for interpreting the primary outcome is that the registry record does not report a numerical median time to pleurodesis or its 95% confidence interval. Although the record states that a Cox model was applied to examine covariates, it provides no numerical model results, covariate list, or diagnostic information. The direction, magnitude, and precision of any association therefore cannot be assessed.
The single-group design has no concurrent comparator, and masking is listed as none. Any observed event-time pattern would be descriptive of this group rather than a randomized comparison. The record also does not explain the difference between enrollment of 28 and the twenty eligible participants analyzed for the primary outcome. It reports that eleven completed 10 weeks of treatment and all twenty completed the study, but gives no further participant-flow details or missing-data procedures.
The study is listed as terminated, but the reason and its consequences for enrollment, follow-up, or analysis are not reported in the registry record. The record does not report interim analyses, multiplicity handling, protocol deviations, or the criteria used for catheter removal beyond the endpoint description. These details should not be inferred from the study’s status or its stated aims.
The safety record includes affected counts and listed serious-event terms, but does not provide additional information about event timing, attribution, or the calculation basis for the listed percentages. These limitations concern the amount and detail of information in the registry record; they do not establish that unreported analyses or procedures did or did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Malignant Pleural Effusion With ZD6474 — NCT00402896.
- Registry record last updated 2016-03-09; status last verified 2016-02.
- Results first posted 2016-03-09.
- 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.
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18. Record Summary
The registry record describes NCT00402896, a Phase 2, single-group study of ZD6474 for malignant pleural effusion. The intervention was 300 mg/day orally for 10 weeks. Allocation is listed as NA, masking as none, and the study status as terminated.
The primary outcome was median time to pleurodesis, measured in days, defined by time to catheter removal from treatment initiation and catheter insertion up to a maximum of 10 weeks. Twenty eligible participants were analyzed for this outcome; eleven completed 10 weeks of treatment, and all twenty completed the study. The enrollment count was 28.
The numerical primary-outcome result, confidence-interval limits, and Cox model estimates are not reported in the registry record. Safety summaries list 12 affected among 20 at risk for serious adverse events and 20 affected among 20 at risk for other adverse events. The reason for termination and the explanation for the enrollment and analysis-count difference are not reported.