An Observational Study of Bevacizumab in Combination With 5-FU-Based Chemotherapy in Chinese Participants With Metastatic Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Observational Study of Bevacizumab in Combination With 5-FU-Based Chemotherapy in Chinese Participants With Metastatic Colorectal Cancer (NCT01319877), a registered phase not stated study. The primary outcome is Percentage of Participants With Adverse Events.

2. Clinical Question

3. Trial Design

NCT01319877 is identified as an observational, multi-center study of bevacizumab plus 5-FU-based chemotherapy in Chinese participants with metastatic colorectal cancer. Its official title describes first-line and second-line treatment. The registry lists Hoffmann-La Roche as the sponsor, an enrollment of 609, a start of 2011-03, primary completion in 2015-03, and a status of COMPLETED.

The two treatment groups reflect when the combination was received: first-line or second-line. They should not be read as randomized arms or as interchangeable groups. The registry record says allocation was not stated, and the study is not a randomized comparison. Participants in the groups may therefore differ in ways that the posted data do not account for. The registry does not report an adjusted comparison that would address such differences.

The study description says data would be collected from each participant for up to 3 years. The primary adverse-event timeframe is 36 months. The record lists 16 outcome measures, including overall response, progression-free survival, one-year progression-free survival, one-year survival, and results by KRAS or chemotherapy-regimen subgroup. The listed outcomes indicate the scope of data collection; they do not by themselves establish that numerical results or analyses are reported for every outcome.

The registry lists zero analyses. This means no analyses are listed in the registry record; it does not establish what analyses may have been conducted outside the record. The protocol, analysis plan, sample-size justification, and handling of interim analyses 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: Three enrolled participants received third-line therapy and were not included in the evaluable population.

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.

Population: Safety analysis set and efficacy analysis set

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Adverse Events, measured over 36 months.

The primary outcome is the percentage of participants with adverse events over 36 months. The registry defines an adverse event as any untoward medical occurrence after administration of a pharmaceutical product, without requiring that the event be caused by the treatment. This broad definition captures events that arise during observation, including events whose relationship to treatment is uncertain.

A percentage of participants with an event is a participant-level summary: it describes how many participants experienced an event relative to the number assessed. It does not, by itself, describe how many separate events each participant had, how long events lasted, or how severe they were. Nor does an observed event establish that the medicine caused it. Attribution requires evidence beyond temporal occurrence, and the registry definition expressly does not require a causal relationship.

This endpoint is used to characterize safety experience during the stated follow-up period. The adverse-event record reports 606 participants at risk and 29 affected by serious adverse events, alongside 606 at risk and 450 affected by other adverse events. These are posted counts, not a comparison between randomized treatment groups. A percentage cannot be inferred from those counts in this explanation; the registry record’s reported endpoint is a percentage, but the primary endpoint value is not reported in the registry record. The meaning of the serious-event categories and their listed terms is discussed separately.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the study as observational and does not state how treatment allocation occurred. That design feature matters when interpreting comparisons: the treatment setting, participant characteristics, and clinical circumstances may differ between first-line and second-line treatment. The registry record does not report a randomized allocation, a direct like-for-like control group, or an adjusted analysis that accounts for potential differences. The interpretation is therefore descriptive rather than a causal estimate of treatment effect.

What does a participant percentage measure?

In general, a percentage with an event uses the number of participants affected in relation to the number assessed or at risk. It is different from an event count, because one participant can experience more than one event. The registry names the primary outcome as the percentage of participants with adverse events, and the adverse-event record supplies counts of participants affected and at risk. The primary endpoint value itself is not reported in the registry record. No percentage should be inferred from the posted counts in this explanation.

The registry’s definition is deliberately broad: an adverse event is an untoward medical occurrence after a pharmaceutical product is administered and need not have a causal relationship with treatment. This captures observed events without claiming that treatment produced them. In general, deciding whether an event is treatment-related is a separate assessment from determining whether it occurred. The registry’s broad event definition cannot on its own distinguish treatment-related events from other events.

How should uncertainty be understood?

In general, an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval describes a range of values compatible with the observed data under the statistical model and its assumptions. It does not prove that the true value lies within a particular range, and it does not correct for systematic differences between groups. No confidence interval or other uncertainty estimate for the primary endpoint is reported in the registry record.

In general, over-dispersion is relevant when outcome variability exceeds what a chosen statistical model expects. It can make standard errors too small if the model does not allow for the extra variability. The posted primary outcome is a participant-level binary measure, but no statistical model or assessment of over-dispersion is reported in the registry record. It is therefore not possible to say whether a particular model was used or whether over-dispersion was assessed.

What do the planning assumptions mean?

The registry-related planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are assumptions for a planning illustration, not evidence about the study’s actual design. The record does not report a sample-size justification for this observational study, and the illustration should not be read as an observed power calculation or as proof that the study had adequate power.

In general, a sample-size calculation estimates the amount of information needed to detect a specified effect under chosen assumptions. Such a calculation depends on the outcome, effect size, variability, allocation, and analysis method. Changing an assumed effect changes the planning requirement. The illustration is not a substitute for the study’s own protocol or rationale, which are not reported in the registry record. The record’s enrollment of 609 is observed enrollment information, not a sample-size justification.

For time-to-event outcomes, the planning convention in the record gives a total number of events using the Schoenfeld approach. For other outcomes, it gives participants per arm. These planning quantities are not observed results. Moreover, the study is observational and the registry does not report randomized allocation, so the equal-allocation assumption should not be mistaken for a description of actual recruitment or treatment assignment.

What can be inferred from the outcome list?

The listed secondary outcomes include response and time-to-event measures, with specified subgroup outcomes by KRAS and chemotherapy regimen. In general, response measures summarize whether a defined response criterion is met, while progression-free and overall survival outcomes concern time-to-event experience. The registry record does not report the numerical results, detailed analysis methods, subgroup definitions, censoring rules, or uncertainty estimates for those outcomes. No particular response criteria or survival-analysis procedure should be inferred from the outcome titles alone.

Likewise, the record does not report the statistical plan, model specifications, covariate adjustments, missing-data procedures, analysis populations, or interim-analysis approach. Those details are important for interpreting estimates, but their absence means that the posted record supports a limited descriptive reading rather than reconstruction of a full analysis.

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("First Line Treatment", "Second Line Treatment")
n      <- c(453, 153)
events <- c(346, 104)
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  First Line Treatment  453  346  76.4  72.2  80.2  72.3  80.1  72.3  80.1
ARM  Second Line Treatment  153  104  68.0  60.0  75.3  60.2  74.8  60.2  74.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures, including several secondary outcomes and subgroup outcomes. When many outcomes or subgroups are examined, the chance of observing an apparently notable result by chance can increase. In general, statistical plans may address this issue by defining a primary outcome, prioritizing comparisons, or applying an adjustment for multiple testing. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or numerical results for those outcomes. No conclusion about whether multiplicity was controlled can be drawn from the record.

The record lists zero analyses. This is distinct from the 16 outcome measures: an outcome list describes intended or registered measurement, while an analysis entry describes a registered analysis. The record does not give results for most listed outcomes or explain whether analyses were performed outside the registry. The analysis plan and any interim analyses are not reported in the registry record.

Missing-data information is also not reported in the registry record. The record does not state how missing observations, loss to follow-up, or incomplete outcome assessments were handled. It does not identify the analysis populations or explain whether all enrolled participants were included in each outcome analysis. Enrollment is listed as 609, whereas the adverse-event at-risk count is 606; the reason for that difference is not reported and should not be inferred.

In general, missing data can affect both the number of observations contributing to an estimate and the representativeness of those observations. If missingness is related to health status or outcome, a complete-case summary may differ from the experience of the full enrolled group. Without the missing-data rules and analysis populations, the extent or direction of any such effect cannot be assessed from this record.

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: deep vein thrombosis (0.7%), enteritis (0.3%), intestinal obstruction (0.3%), intestinal perforation (0.3%), infection (0.3%).

The adverse-event record reports 29 participants affected by serious adverse events among 606 at risk, and 450 affected by other adverse events among 606 at risk. The group is labeled First and Second Line Treatment, so the information is combined across those treatment settings rather than separated into line-specific results. The record does not report a death count.

The listed serious adverse-event terms and proportions are deep vein thrombosis, 0.7%; enteritis, 0.3%; intestinal obstruction, 0.3%; intestinal perforation, 0.3%; infection, 0.3%; and myocardial infarction, 0.3%. These are the reported top serious terms. The registry record does not state in this summary whether participants could contribute more than one term, nor does it provide further detail about event timing or duration. The term-level proportions should not be added or treated as mutually exclusive categories.

Seriousness and causality are different concepts. The registry defines an adverse event without requiring a causal relationship to treatment, and the posted serious-event terms do not by themselves establish that bevacizumab or chemotherapy caused them. The figures describe reported events in the study context; without a comparable control group, they do not estimate an excess risk relative to another treatment.

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

The record documents an observational study of bevacizumab combined with 5-FU-based chemotherapy in Chinese participants with metastatic colorectal cancer, with treatment given in first-line or second-line settings. It provides an adverse-event summary for the combined group and lists response, progression-free survival, survival, and subgroup outcomes. This supports a description of what the registry reports, but not a causal comparison of treatment strategies.

The adverse-event counts show that serious and other adverse events were recorded among participants at risk during the study period. Because the registry’s definition does not require a causal relationship, the counts should not be interpreted as events necessarily caused by treatment. The record does not separate results by treatment line, provide a randomized comparator, or report adjusted estimates. It therefore cannot establish whether the observed event experience was greater or smaller than it would have been under another treatment.

The secondary outcome titles do not provide results. Numerical findings for response, progression-free survival, one-year survival, and the listed subgroups are not reported in the registry record. No estimate of efficacy, difference between groups, or precision for these outcomes can be drawn from their inclusion in the outcome list.

In general, observational evidence can describe outcomes in routine or study care and can be useful for documenting experience. Its interpretation depends on how participants were selected, how treatment was assigned, what information was collected, and how confounding was addressed. Those details and the statistical analysis plan are not reported in the registry record. The posted record should therefore be read as a limited descriptive account, not as evidence that treatment does or does not work.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why study design and outcome reporting must be considered together. It concerns a defined population and treatment context, and it identifies a primary safety outcome with a 36-month timeframe. It also lists secondary outcomes that cover response, progression-free survival, survival, and biological or regimen subgroups. These features clarify the questions the study intended to examine.

At the same time, the observational design affects what comparisons can mean. First-line and second-line treatment are different clinical settings, not equivalent randomized arms. The registry does not state how treatment was allocated or report a like-for-like control comparison. A difference between treatment settings, even if reported, could reflect factors other than treatment. In this record, the listed adverse-event information is combined across the two settings, so it cannot show a line-specific pattern.

The record also illustrates the distinction between registering outcomes and reporting their results. It lists 16 outcome measures but provides zero registered analyses, and numerical results for the secondary outcomes are not reported in the registry record. Without estimates, uncertainty intervals, analysis methods, and details on missing data, readers cannot evaluate the precision or robustness of those outcomes.

Finally, event definitions matter. An adverse event is recorded after administration but need not be caused by treatment. Keeping occurrence, seriousness, and causal attribution conceptually separate prevents descriptive safety counts from being mistaken for comparative evidence. These statistical distinctions are central to interpreting clinical registries accurately.

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 does not report the protocol, detailed eligibility criteria, sample-size justification, or statistical analysis plan. It does not state how treatment allocation occurred, and the study is identified as observational rather than randomized. Consequently, the posted information does not establish comparability between first-line and second-line groups or support a causal treatment contrast.

Although 609 participants are listed as enrolled, the adverse-event summaries give 606 participants at risk. The reason for this difference is not reported in the registry record. The safety summary combines first-line and second-line treatment and does not provide separate counts for each setting. A death count is not reported.

The record lists 16 outcome measures, including several subgroup outcomes, but gives no numerical results for the listed response and survival outcomes. It also does not report confidence intervals, p-values, adjusted estimates, detailed outcome definitions beyond the adverse-event definition, or the methods used to analyze time-to-event outcomes. The record lists zero analyses.

Missing-data handling, follow-up completeness, analysis populations, multiplicity control, and interim-analysis procedures are not reported in the registry record. These omissions limit assessment of selection, precision, and the reliability of estimates. The adverse-event definition does not require causal attribution, and no comparable control group is presented. The posted safety counts therefore describe recorded events but cannot establish whether the treatment caused them or how the experience compares with another treatment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Observational Study of Bevacizumab in Combination With 5-FU-Based Chemotherapy in Chinese Participants With Metastatic Colorectal Cancer — NCT01319877.
• Registry record last updated 2016-09-07; status last verified 2016-07.
• Results first posted 2016-09-07.
• 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

NCT01319877 is a completed observational study sponsored by Hoffmann-La Roche. It enrolled 609 Chinese participants with metastatic colorectal cancer and examined bevacizumab plus 5-FU-based chemotherapy in first-line and second-line treatment settings. The registry lists a start of 2011-03 and primary completion in 2015-03, with data collected for up to 3 years.

The primary outcome is the percentage of participants with adverse events over 36 months. The combined adverse-event record reports 29 affected by serious adverse events and 450 affected by other adverse events, each among 606 at risk. The record lists 16 outcome measures and zero analyses. Numerical results for the secondary response and survival outcomes, and several key analysis details, are not reported in the registry record.