An Observational Study of Xeloda (Capecitabine) in Patients With Metastatic Colorectal Cancer (AXIOM): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Observational Study of Xeloda (Capecitabine) in Patients With Metastatic Colorectal Cancer (AXIOM) (NCT01697462), a registered phase not stated study. The primary outcome is Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The study also lists disease progression, progression-free survival, and hand-foot syndrome among its secondary outcomes. The registry record describes follow-up until disease progression or unacceptable toxicity in its summary, while the primary outcome timeframe is baseline through the end of study, up to 42 months. These statements describe what was to be followed; they do not establish what happened to each participant.

The clinical question is therefore primarily descriptive: what adverse events were recorded among participants receiving capecitabine in this observational cohort? It is not framed as an estimate of the treatment effect relative to another therapy, because no control group or randomized allocation is reported. Nor do the posted results establish whether capecitabine caused an event; adverse-event counts describe events observed in participants who received study drug, not necessarily events attributable to it.

3. Trial Design

The registry describes an observational, prospective study of Xeloda (capecitabine) monotherapy in people with metastatic colorectal cancer. Its stated purpose was to evaluate safety and efficacy. The study summary says participants would be followed until disease progression or unacceptable toxicity. The record reports enrollment of 258 and lists Hoffmann-La Roche as the sponsor.

The record gives a single cohort, titled mCRC Participants. It does not describe a separate control group, and allocation is not stated. As a result, there is no like-for-like treatment comparison to interpret. The study can describe events recorded in the cohort, but its design as reported does not by itself isolate an effect of treatment from other reasons events might occur. The record does not report a protocol for treatment selection or details of how clinical care was determined.

The study start is recorded as 2009-07, and primary completion as 2012-12. Its status is COMPLETED. The primary safety outcome covers baseline through the end of study, up to 42 months. The registry describes its intent-to-treat population as participants who received at least one dose of study drug and had a subsequent post-baseline assessment. It does not report the number meeting that definition separately from the cohort's listed at-risk count.

The secondary outcomes include the percentage of participants with disease progression, progression-free survival, and the number of participants with hand-foot syndrome. The registry record does not report results for these secondary outcomes. Although the record lists four outcome measures, it contains no analysis records. The sample-size illustrations associated with the posted material are planning exercises based on stated assumptions, not evidence that the observational cohort was designed as a two-arm trial.

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:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population included all participants who received at least one dose of the study drug and had a subsequent post baseline assessment.

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: Baseline population included all enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Baseline up to end of study (up to 42 months).

The primary endpoint counts participants with non-serious adverse events and participants with serious adverse events. An adverse event is defined as any untoward medical occurrence in a participant who received study drug. An event qualifies as serious when it results in a specified outcome, including death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, or congenital anomaly; the definition also includes events deemed significant for another reason.

The non-serious count is exclusive of serious events. This means the endpoint separates participants counted with non-serious events from those counted with serious events rather than including serious events in both categories. The unit is participants, so the measure is a participant count rather than a count of all event episodes. A participant could potentially experience more than one event, but the endpoint does not report an episode count.

Safety outcomes are used to describe the kinds of medical occurrences observed during treatment and follow-up. Separating serious from non-serious events distinguishes events meeting the registry's seriousness criteria from those that do not. These counts are descriptive: by themselves, they do not show whether an event was caused by capecitabine, nor do they compare the risk with that under another treatment. The outcome timeframe is baseline through the end of study, up to 42 months.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial results can be summarized in several ways, and the method needs to match the question and design. This study's primary endpoint is a binary event measure at the participant level: for each participant, the relevant classification is whether a non-serious or serious adverse event was recorded. The reported result is a count of participants in each category. It is not a count of every event episode and does not describe how often events recurred.

What does a participant count tell the reader?

A count gives the number of people meeting an outcome definition in the observed cohort. The denominator matters when interpreting how common an outcome was, and the registry lists 258 at risk for each primary safety category. The listed non-serious and serious categories are mutually exclusive by the registry definition, because non-serious adverse events are exclusive of serious adverse events. The count alone does not describe event timing, duration, severity within a category, or whether the same person experienced multiple different event terms.

A percentage expresses a count relative to a denominator. Percentages for individual serious-event terms are listed, but the registry record does not report the denominator or calculation details for those term-specific values. They should therefore be read as the percentages stated for those terms, rather than reverse-engineered into counts or used to infer a different denominator. No new count or percentage should be derived from rounded values, since rounding and denominator details can affect that calculation.

Why does the observational design matter?

In a randomized comparison, assignment to treatment and control groups is designed to support a comparison between groups. This record describes an observational study and a single cohort; it does not report random allocation or a comparator. The posted counts can describe adverse events recorded among participants who received study drug, but they cannot estimate a between-group difference. Without a comparison group, background illness, other care, and participant characteristics may also be relevant to observed events. This is a general limitation of interpreting uncontrolled observational safety data, not evidence about a particular event in this cohort.

The word efficacy appears in the study purpose, and progression-related outcomes are listed. However, the registry record does not report their results. A planned or listed outcome is not itself an observed finding. The record also has no analysis records, so no model-based efficacy or safety estimate is available in the registry record.

How should uncertainty be understood?

A confidence interval, when reported, gives a range of values compatible with the data under the assumptions of the statistical method. It helps convey precision; a count alone does not show the uncertainty around an underlying event proportion. The registry record does not report confidence intervals for the primary safety counts. Consequently, the precision of the underlying event frequencies cannot be judged from the posted counts alone. In general, a narrow interval indicates more precise estimation than a wide interval, but the interval and its method must be reported to make that assessment.

Statistical tests and p-values address a specified hypothesis, usually about a contrast or model parameter. They do not establish clinical importance or causation. The record reports no analysis records and does not report p-values for the safety results. With no comparator identified, there is also no reported treatment contrast for a conventional between-group test to address. The absence of a reported p-value should not be interpreted as evidence that two treatments are equivalent.

What do the planning illustrations represent?

Sample-size calculations are prospective planning tools, not findings from the enrolled cohort. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a fraction of the observed effect. For time-to-event outcomes, the illustration is based on a total number of events, while other outcomes use participants per arm. These assumptions do not describe the reported one-cohort observational design and should not be mistaken for its original design or its observed power. The registry record does not report a sample-size justification or the trial's own statistical plan.

Over-dispersion is a general issue for count outcomes when variability exceeds what a simple model assumes; if ignored, uncertainty can be understated. It is not a reported analysis feature for this study, and the registry record does not describe a model for the primary endpoint. Likewise, adjustment for covariates, missing-data procedures, and interim analyses are not reported in the registry record. No specific method for any of these should be inferred from the outcome counts.

10. Multiplicity, Missing Data and Analysis Populations

The study lists several outcomes: the primary adverse-event endpoint and secondary outcomes for disease progression, progression-free survival, and hand-foot syndrome. When multiple outcomes are tested, the chance of at least one apparently unusual result can increase if no multiplicity strategy is used. A prespecified testing hierarchy or adjustment can address that issue, but the registry record does not report a multiplicity plan. No analysis records or secondary outcome results are reported, so the record does not show whether any formal tests were performed or adjusted.

The registry describes the intent-to-treat population as participants who received at least one dose of study drug and had a subsequent post-baseline assessment. The primary safety group lists 258 participants at risk. The registry record does not provide further detail about the analysis population, explain how the listed at-risk count relates to the stated population definition, or report the number of participants excluded for lacking a post-baseline assessment.

Missing-data handling is not reported in the registry record. It does not describe whether missing outcome assessments occurred, how follow-up ended for participants, or whether any imputation or sensitivity analysis was used. This matters because incomplete follow-up or outcome recording can affect what an observed count represents. The stated follow-up endpoint includes disease progression or unacceptable toxicity in the study summary, but the record does not give participant-level follow-up information.

The registry record also does not report an interim-analysis plan, stopping rules, or the statistical analysis plan. These omissions do not demonstrate that such plans were absent; they mean the relevant details are not reported in the registry record. The posted counts should therefore be interpreted without assuming a particular multiplicity, missing-data, or analysis procedure.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhoea (1.2%), nausea (0.8%), palmar-plantar erythrodysaesthesia syndrome (0.8%), pneumonia (0.4%), malignant neoplasm progression (0.4%).

The serious adverse-event result is 11 participants in the mCRC Participants group, with 258 listed at risk. This is a count of participants classified as having a serious adverse event, under the registry's definition. Seriousness includes specified medical consequences such as hospitalization, a life-threatening experience, persistent or significant disability or incapacity, congenital anomaly, or death, as well as events deemed significant for another reason.

The separate non-serious adverse-event result is 132 participants, also with 258 listed at risk. The registry explicitly says this category is exclusive of serious adverse events. The counts therefore refer to different seriousness categories; they are not counts of all event episodes and should not be combined to estimate a total number of events. No sum is needed to interpret the endpoint.

Listed serious-event terms include diarrhoea, nausea, palmar-plantar erythrodysaesthesia syndrome, pneumonia, malignant neoplasm progression, and cardiotoxicity, with the percentages stated in the registry record. The record does not report a death count, and it does not give denominator or ascertainment details for those term-specific percentages. The counts and terms describe reported safety observations; without a comparator, they do not quantify excess risk or establish treatment causality.

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

The results mean that the registry recorded participants in the cohort with serious and non-serious adverse events during the stated study period. The serious-event count is 11, and the non-serious-event count is 132, with 258 listed at risk in each category. The registry's definition separates serious events from non-serious events, and the outcome is expressed as participants rather than episodes. These values are useful as a descriptive record of reported safety observations.

They do not show that capecitabine caused any particular event. An adverse event is an untoward medical occurrence in a participant who received study drug; the definition does not by itself establish a causal relationship. Nor do the counts show how event occurrence compares with another treatment or with no treatment. The study is observational, and the record does not state random allocation or provide a control group.

The primary endpoint also does not reveal when an event occurred, how long it lasted, whether it recurred, or the full range of its clinical severity. The serious-event definition identifies seriousness criteria, not a complete grading scale. The term-specific percentages do not include reported denominator details in the registry record, so they should be read as listed rather than used to calculate additional results.

The study title and summary refer to safety and efficacy, and the registry lists disease progression, progression-free survival, and hand-foot syndrome as secondary outcomes. Their results are not reported in the registry record. Therefore these posted safety results do not establish an efficacy result, an overall benefit-harm balance, or a comparison with other care. The record is completed, but completion status does not fill in outcomes that are not reported.

In general, an observational cohort can contribute information about events recorded during treatment in routine or study follow-up. Interpretation remains bounded by the population, event definitions, follow-up, and analysis details that are available. Here, the registry record does not report confidence intervals, analysis methods, missing-data handling, or a comparator. The findings should consequently be treated as descriptive counts with limited information about their statistical precision and no reported comparative estimate.

13. Why This Trial Matters Statistically

This study is statistically useful as an example of how safety outcomes differ from comparative treatment effects. Its primary endpoint counts participants with adverse events, separating serious from non-serious events. That is a direct descriptive question, but it is not the same as estimating whether treatment changes risk relative to a comparator. The observational design and single cohort make that distinction central to interpretation.

The record also illustrates why endpoint definitions matter. Seriousness is determined by explicit clinical consequences and an additional significance criterion, while non-serious adverse events are exclusive of serious events. A reader needs those definitions to understand what the counts represent. The unit is participants, not event episodes, so the result answers how many participants were classified in each category rather than how many total events occurred.

Several familiar statistical details are absent from the registry record: confidence intervals, a statistical analysis plan, missing-data methods, and a multiplicity strategy. Their absence limits evaluation of precision and analytic choices. It does not prove that no analyses or procedures existed, but it does mean they cannot be assessed from the registry record. Likewise, listed secondary outcomes should not be mistaken for reported findings.

The record's planning assumptions also show why sample-size illustrations require context. The illustration describes a two-arm equal-allocation calculation, whereas the study record describes one observational cohort. Such a calculation is a planning scenario, not a characterization of the study's design, an observed power result, or evidence of a treatment comparison. Keeping design, endpoint, and analysis aligned helps prevent a descriptive safety count from being read as a causal or comparative conclusion.

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 important design limitation is that the registry record describes an observational cohort without a reported comparator or allocation method. The adverse-event counts therefore cannot be interpreted as relative risks or treatment differences. Potential differences in participant characteristics, other care, and underlying disease are not addressed by a control-group comparison in this record.

Reporting is limited for the primary outcome. The record gives participant counts and at-risk counts but no confidence intervals, event timing, episode counts, severity grades beyond the serious versus non-serious classification, or individual follow-up durations. The study summary describes follow-up until disease progression or unacceptable toxicity, while the primary timeframe extends from baseline to end of study, up to 42 months. The registry does not show how observation time varied across participants.

The record lists progression, progression-free survival, and hand-foot syndrome as secondary outcomes but does not report their results. It also does not report analysis methods, missing-data procedures, multiplicity handling, or a statistical analysis plan. Term-specific serious-event percentages are listed without denominator details, and a death count is not reported in the registry record. These gaps limit assessment of completeness and precision.

The analysis-population definition requires at least one dose and a subsequent post-baseline assessment. Although the safety results list 258 at risk, the registry record does not explain how that count relates to the population definition or describe exclusions and missing assessments. The record reports enrollment of 258, but the available information does not permit further reconstruction of analysis flow. These limitations call for a narrow descriptive reading rather than a comparative or causal interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Observational Study of Xeloda (Capecitabine) in Patients With Metastatic Colorectal Cancer (AXIOM) — NCT01697462.
• Registry record last updated 2016-01-26; status last verified 2015-11.
• Results first posted 2016-01-26.
• 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

NCT01697462 is a completed prospective observational study of capecitabine monotherapy in metastatic colorectal cancer. The registry lists Hoffmann-La Roche as sponsor, enrollment of 258, a study start of 2009-07, and primary completion of 2012-12.

The primary outcome counts participants with non-serious and serious adverse events from baseline through the end of study, up to 42 months. The posted results list 132 participants with non-serious events and 11 with serious events; 258 are listed at risk for each category. The record also lists disease progression, progression-free survival, and hand-foot syndrome as secondary outcomes, but their results are not reported in the registry record.

No comparator, random allocation, statistical analysis plan, confidence intervals, or missing-data methods are reported in the registry record. The safety findings are descriptive and do not establish treatment causality or comparative effectiveness.