A Study of the Addition of Avastin (Bevacizumab) to Carboplatin and Paclitaxel Therapy in Patients With Ovarian Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Addition of Avastin (Bevacizumab) to Carboplatin and Paclitaxel Therapy in Patients With Ovarian Cancer (NCT01239732), a na phase 3 study. The primary outcome is Percentage of Participants With at Least One Adverse Event (AE).

2. Clinical Question

3. Trial Design

This was a Phase 3, open-label, non-comparative, multicenter study of bevacizumab added to carboplatin and paclitaxel as front-line treatment. The registry describes one group receiving the three-drug regimen. It lists the allocation as NA and the study model as single group; it therefore does not describe a randomized comparison or a concurrent control group. Enrollment was 1021, and the study status is completed.

The planned bevacizumab schedule was 15 mg/kg intravenously on Day 1 every 3 weeks, from Cycle 1 through Cycle 36, initially alongside chemotherapy and then as a single agent after chemotherapy ended, or until disease progression or unacceptable toxicity. Carboplatin was specified for Day 1 every 3 weeks, for a maximum of 8 cycles. Paclitaxel was scheduled on Day 1 every 3 weeks or weekly, also for a maximum of 8 cycles. The registry describes anticipated time on study drug as 108 weeks or until progression or unacceptable toxicity.

The listed start was 2010-12 and the primary completion was 2015-03. The primary endpoint observation period ran from Day 1 through 30 days after the last dose of study treatment, with data cutoff 07 December 2014, up to 4 years. The record does not report an independent control group, masking, or a comparative treatment effect. The design can describe observed safety and outcomes in participants receiving this regimen, but cannot by itself separate treatment effects from the course of disease, other care, or differences in participant characteristics.

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: This study has been completed. However, the efficacy and safety results up to the clinical database cutoff date of 07 December 2014 are provided.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population

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.

Population: Safety population: included all participants who received at least one dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With at Least One Adverse Event (AE), measured over Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years).

The primary endpoint is the percentage of participants with at least one adverse event. An adverse event was defined as any untoward medical occurrence in a participant who received study drug, without regard to whether a causal relationship to treatment was considered possible. The endpoint therefore captures events observed during treatment and follow-up, rather than only events judged to be caused by the drugs.

The registry identifies the safety population and sets the observation window from Day 1 through 30 days after the last dose, with data cutoff 07 December 2014, up to 4 years. The posted result gives 980 participants with at least one adverse event among 1021 participants in the group. A percentage result is not reported in the registry record. The safety endpoint is useful for describing how commonly any event was recorded in this treated group. Because it includes events regardless of suspected causality, it should not be interpreted as the proportion whose events were caused by the regimen. The single-group design also means the endpoint does not estimate how event frequency compares with another treatment or with no treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint count?

The primary endpoint is the proportion of participants who experienced at least one adverse event. In general, a binary endpoint assigns each participant to a category such as event or no event, even if a participant with an event experiences several different events. The endpoint description defines an adverse event broadly as any untoward medical occurrence in a participant who received study drug, without requiring a suspected causal connection. The posted result is a participant count: 980 with at least one adverse event among 1021 in the safety population. The registry record does not report the endpoint percentage or an uncertainty interval.

This distinction between a participant-level endpoint and an event-level listing matters. The primary endpoint concerns whether each participant had at least one event. A list of event terms, by contrast, describes particular types of events. A participant can contribute to multiple terms, while contributing only once to the primary endpoint count.

What does a confidence interval usually tell a reader?

In general, a confidence interval communicates uncertainty around an estimate using a specified statistical procedure. A narrow interval indicates greater precision under that procedure than a wide interval, while neither width nor location alone resolves issues such as bias, missing observations, or limited generalizability. No confidence interval for the primary endpoint is reported in the registry record, so its statistical precision cannot be described using that measure.

Why is the study structure important?

The record describes a single-group, open-label, non-comparative study. A one-group safety count can characterize what was recorded among participants receiving the combination, but it cannot estimate a difference from another treatment group. Without a concurrent comparator, observed events may reflect the medicines, the underlying conditions, other care, or factors affecting who entered and remained in the study. Open-label status means the study was not masked, as recorded. The registry does not report further details about event adjudication or other procedures that might affect event recording.

What can planning illustrations show?

In general, sample-size calculations describe how many participants or events a hypothetical study might need under specified assumptions. The planning illustration associated with this study is explicitly based on the observed effect and assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Its target effect is stated as a fraction of the observed effect. Those assumptions do not describe the actual single-group design, and the registry record does not report that they were used to design this trial. Any such figures are planning illustrations, not observed power, proof of adequate power, or evidence that a two-arm trial was conducted. They should not be confused with enrollment, which was 1021.

What statistical plan is documented?

The registry record does not report a statistical analysis plan, the method used to calculate the primary endpoint percentage, or inferential analyses for the listed efficacy outcomes. It also does not report model specifications, adjustment variables, or a prespecified approach to uncertainty for the primary result. Without those details, it is not possible to determine from the record how analyses handled follow-up differences, repeated events, or other analytic choices. The methods that are documented support a straightforward descriptive reading of the safety counts, not reconstruction of unreported analyses.

More generally, event rates can be affected by observation time: participants followed longer have more opportunity for events to be recorded. The endpoint's observation window is specified relative to treatment, but participant-level follow-up distributions and a time-adjusted adverse-event analysis are not reported in the registry record. This limits interpretation of the counts beyond the stated population and observation period.

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("Bevacizumab + Paclitaxel + Carboplatin")
n      <- c(1021)
events <- c(999)
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  Bevacizumab + Paclitaxel + Carboplatin  1021  999  97.8  96.8  98.6  96.8  98.6  96.8  98.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including progression-free survival, response measures based on RECIST Version 1.0 and CA-125 criteria, duration of objective response, overall survival and biological progression-free interval. Listing multiple outcomes raises a general multiplicity issue: when many statistical hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of tests. The registry record does not report a multiplicity strategy, a hierarchy of endpoints, or inferential analysis results. No conclusion about adjustment or endpoint prioritization can therefore be drawn.

Missing-data methods are also not reported in the registry record. For outcomes with follow-up, missing assessments or incomplete observation can affect the number of participants contributing information and the interpretation of estimates. The registry does not state how missing outcome data, withdrawals, or incomplete follow-up were handled. It also does not report sensitivity analyses for missingness. These omissions do not establish that data were missing; they mean the handling of missing data is not described in the record.

The primary endpoint population is identified as the safety population, and the posted group has 1021 participants at risk. The registry does not report additional analysis-population definitions, such as rules for inclusion in efficacy analyses, or details about exclusions from particular outcome calculations. The safety count should accordingly be interpreted as the record's result for the stated safety population, without assuming that the same population or denominator applied to each secondary outcome.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (2.4%), neutropenia (2.1%), anaemia (1.6%), hypertension (1.6%), diarrhoea (1.3%).

The registry reports 285 participants with a serious adverse event among 1021 at risk in the bevacizumab, paclitaxel and carboplatin group. It separately lists serious-event terms and their reported percentages: febrile neutropenia, 2.4%; neutropenia, 2.1%; anaemia, 1.6%; hypertension, 1.6%; diarrhoea, 1.3%; and thrombocytopenia, 1.3%. These are term-specific entries, not a breakdown that should be added to obtain the number of participants with any serious event.

One participant may have experienced more than one serious event or more than one listed term. The percentages should therefore not be interpreted as mutually exclusive categories. The registry record does not report further details such as event-level counts for all serious-event terms, recurrent-event handling, or a comparative rate in a control group. Seriousness and causality are also distinct concepts: a serious event is not necessarily judged to have been caused by treatment. The primary adverse-event definition does not require suspected causation, and no comparative attribution can be made from this single-group result.

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

The posted results describe adverse events observed among participants receiving bevacizumab with paclitaxel and carboplatin. The primary result is 980 participants with at least one adverse event among 1021 in the safety population, and the registry reports 285 participants with a serious adverse event among 1021 at risk. The specified observation period extends from Day 1 through 30 days after the last dose, with data cutoff 07 December 2014, up to 4 years. These counts are relevant to understanding the experience recorded during the study's safety follow-up.

They do not, on their own, show how many events were caused by one or more study drugs. The primary definition includes untoward medical occurrences regardless of possible causal relationship. The single-group design offers no concurrent control rate, so it cannot quantify an excess or reduction in events relative to another treatment. It also cannot isolate the contribution of bevacizumab from the chemotherapy drugs given with it.

The record lists efficacy outcomes but does not report their results. It therefore does not support a conclusion about comparative benefit, disease control or survival. Even a result within one group would not establish what would have occurred under a different treatment without a suitable comparison and a reported analysis.

In general, a registry result is most informative when read with its population, endpoint definition, observation window, and study design. Here, those details clarify that the posted figures are descriptive safety findings in a specified treated group. The record does not report confidence intervals for the primary endpoint, the statistical analysis plan, or methods for missing data and multiplicity. These absences limit assessment of precision and analytic choices; they do not justify filling in unreported methods or outcomes.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a study's phase label and its comparison structure. Although the registry identifies it as Phase 3, it describes an open-label, non-comparative, single-group study. The design answers a descriptive question about events recorded during a treatment regimen; it does not create a randomized estimate of the regimen's effect relative to another option. Reading the design before interpreting results prevents an event count from being mistaken for a treatment difference.

The endpoint also illustrates why definitions matter. The primary measure counts participants with at least one adverse event, and its definition does not require a causal link to study drug. The number is therefore an overall safety description, not a direct count of treatment-caused harm. Serious adverse-event summaries and term-specific percentages provide additional detail but do not identify comparative risk or isolate the effect of an individual drug.

The record makes clear that safety observation continued through 30 days after the last dose, with a stated data cutoff, while the treatment plan allowed extended bevacizumab administration. In general, interpretation of event counts depends on the population observed and the time during which events could be recorded. The registry does not report time-adjusted adverse-event analyses or participant-level follow-up distributions.

Finally, the record lists several secondary outcomes but does not report their results or an analysis strategy for multiple endpoints. This makes the distinction between outcome listing and evidence especially important. The study provides a useful example of how design, endpoint definition, follow-up and reporting completeness determine what a registry result can support—and what remains unresolved.

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 central limitation for interpretation is the absence of a comparator. Because the record describes a single treatment group, the posted adverse-event counts cannot show whether event frequency was higher or lower than it would have been under another regimen. Nor can the separate contribution of bevacizumab, carboplatin or paclitaxel be isolated from these group-level results.

The primary endpoint uses a broad adverse-event definition that does not require possible causation. This makes the measure suitable for describing events in the safety population, but it limits treatment-specific attribution. The record does not report a percentage for the primary endpoint, confidence intervals, or details of event adjudication. It also does not provide event-level results for every serious-event type.

The registry lists efficacy outcomes without reporting their numerical results. The analysis plan, handling of missing data, multiplicity approach and definitions of additional analysis populations are not reported in the registry record. As a result, readers cannot assess those analytic choices or the precision of efficacy estimates from this record. The 1021 enrolled participants and the safety-population denominator should not be presumed to apply to every listed outcome.

Finally, the registry's planned treatment schedules and stated observation window describe the study framework, but the record does not provide participant-level treatment exposure or follow-up distributions. In general, differences in time under observation can affect event counts. These limitations confine interpretation to the descriptive safety findings and study details that the registry reports.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of the Addition of Avastin (Bevacizumab) to Carboplatin and Paclitaxel Therapy in Patients With Ovarian Cancer — NCT01239732.
• Registry record last updated 2016-06-10; status last verified 2016-05.
• Results first posted 2016-06-10.
• 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

NCT01239732 is a completed Phase 3, open-label, non-comparative, multicenter study of bevacizumab added to carboplatin and paclitaxel as front-line treatment for epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma. The registry lists enrollment of 1021 and a single-group design. The primary endpoint was the percentage of participants with at least one adverse event in the safety population, observed from Day 1 through 30 days after the last dose, with data cutoff 07 December 2014, up to 4 years. The posted results report 980 participants with at least one adverse event and 285 with a serious adverse event. Efficacy outcome results and a statistical analysis plan are not reported in the registry record.