Gut Microbiome & Gastrointestinal Toxicities as Determinants of Response to Neoadjuvant Chemo for Advanced Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gut Microbiome & Gastrointestinal Toxicities as Determinants of Response to Neoadjuvant Chemo for Advanced Breast Cancer (NCT02696759), a na na study. The primary outcome is Number of Subjects Who Complete Fecal Collection.

2. Clinical Question

The broader research purpose was to investigate whether intestinal bacteria might play a role in cancer-related immune activity and how that activity could relate to response to neoadjuvant chemotherapy. That purpose provides context, but it is not itself a reported efficacy result. The primary outcome listed is a collection-completion count, not a measure of microbiome composition, immune-cell behavior, treatment response, or tumor outcome. The record does not report analyses linking collected samples or questionnaires to chemotherapy response.

Accordingly, the central question that can be evaluated from the registry entry is operational: whether participants provided at least one fecal kit. It cannot be reframed as a comparison of chemotherapy outcomes between microbiome groups, because no such comparison or analysis is reported. The early halt and incomplete analysis further limit what can be concluded about the primary question.

3. Trial Design

This registry record describes a single-group study sponsored by the University of Arkansas. The study is listed as terminated, with a recorded start of 2016-07 and primary completion of 2021-08. Enrollment is recorded as 15. The phase and allocation are listed as NA, and masking is listed as NONE. These entries do not describe a randomized or masked treatment comparison.

The listed intervention is Blood & Fecal Collection, categorized as OTHER. The arm description concerns subjects receiving neoadjuvant chemotherapy for advanced breast cancer. They would be asked to complete questionnaires, provide two blood samples, and provide 2 fecal samples while receiving standard of care neoadjuvant chemotherapy. The registry therefore describes sample collection alongside usual care, rather than assigning a chemotherapy treatment as the study intervention.

The primary outcome is the number of subjects who complete fecal collection. The outcome description defines completion as at least one fecal kit collected, and gives a timeframe of through study completion, an average of 18 months. This is a participant count, not a comparative treatment-effect measure. A single-group design can describe what was observed within the enrolled group, but without a separate comparator it cannot isolate a difference attributable to an intervention.

The record states that the study was halted prematurely and that data analysis was not complete. It reports no statistical analyses. The reason for termination, recruitment progress over time, details of how participants were approached, and whether all planned collections occurred are not reported in the registry record. The record also does not report a protocol-level statistical plan or a rationale for the enrollment target. These omissions mean the design can be described from the registered structure, but its operational history and planned inferential approach cannot be reconstructed.

The research purpose refers to possible relationships among gut microorganisms, immune activity, and response to chemotherapy. However, the listed primary outcome is collection completion. The registered design and reported outcome should therefore be distinguished from the broader biological motivation: the record does not establish that the study tested a completed statistical association between microbiome measures and cancer response.

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

Analysis population for the primary outcome, as defined in the registry: Study was halted prematurely. Data analysis not complete.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects Who Complete Fecal Collection, measured over Through study completion, an average of 18 months.

The primary endpoint is the number of subjects who complete fecal collection. Its operational definition is at least one fecal kit collected. The timeframe is through study completion, an average of 18 months. Thus the endpoint concerns whether the study obtained a fecal sample from a participant at least once; it does not require, by the stated definition, completion of every planned collection.

Collection completion is useful as an operational measure because a study that depends on biospecimens needs to know whether participants can provide the material needed for its planned investigations. In general, a feasibility-oriented count can describe the amount of participation achieved for a collection task. It is distinct from an outcome describing cancer response, immune activity, toxicity, or the composition of the gut microbiome. No such biological or clinical outcome is identified as the primary endpoint in this record.

The intervention description mentions two fecal samples, whereas the primary endpoint is defined as at least one fecal kit collected. These descriptions refer to different levels of collection: the arm description gives the requested sampling procedure, while the endpoint’s stated threshold defines what counts as completion. The registry does not explain why the endpoint uses that threshold or how partial collection was handled in analysis.

The record says the study was halted prematurely and data analysis was not complete. It does not report how many participants met the endpoint, an estimate of the completion rate, or an uncertainty interval. Therefore, the endpoint’s definition can be explained, but its observed result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is registered? The primary outcome is a participant count: the number who complete fecal collection. The definition is at least one fecal kit collected. In general, a count endpoint records how many participants satisfy a stated condition. It differs from a continuous measurement, such as a laboratory value, and from a time-to-event endpoint, which concerns how long it takes for an event to occur. The registry identifies this outcome as a count of participants with an event. It does not report an observed count or an analysis of that count.

The endpoint definition is important because it determines what qualifies as completion. The arm description requests 2 fecal samples, while the primary outcome accepts at least one fecal kit. This means that the endpoint, as written, does not require both requested samples. The record does not describe whether the count was intended to distinguish partial from complete collection, whether kits could be unusable, or how those circumstances would be classified. Those operational details are not reported in the registry record.

What can an estimate and interval tell a reader? In general, an estimate is a numerical summary of the observed data. For a count endpoint, an analysis might also describe the share of participants meeting the definition, but no such result is reported. A confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates that the data are compatible with a broader range of values. These concepts do not supply a result when the registry reports no endpoint analysis. No estimate, interval, or inferential test for fecal collection completion is reported in the registry record.

Why does the design affect the analysis? This is a single-group study, not a randomized comparison. In general, a single-group description can characterize outcomes observed among the participants enrolled, but it does not create a concurrent control group. Without a like-for-like comparison, differences cannot be attributed to a randomized assignment within this study. The stated allocation is NA, and the record explicitly identifies that it is not a randomized comparison. The record does not report a comparative model or treatment-effect estimate.

The intervention is collection of blood and fecal samples, with questionnaires, while participants receive standard-of-care neoadjuvant chemotherapy. That makes the primary outcome a collection-process measure rather than a contrast between chemotherapy regimens. The broader interest in gut microorganisms and response to chemotherapy does not itself specify a statistical method. The registry does not report how microbiome measures would be summarized, what response measure would be analyzed, or how any association between them would be modeled.

What does incomplete analysis imply? The record states that the study was halted prematurely and data analysis was not complete. It lists zero analyses. This means no analysis result is available in the registry record to assess for the primary outcome. In general, an analysis plan specifies how outcomes will be defined and summarized, how incomplete observations will be handled, and what methods will be used to quantify uncertainty. The statistical plan, including any planned model or inferential procedure, is not reported in the registry record. It would not be appropriate to infer a method from the kind of endpoint alone.

The timing description says the outcome was to be assessed through study completion, an average of 18 months. It is not a reported follow-up result for each participant. The registry does not clarify whether all participants were followed for the same duration, how a participant who left before study completion was classified, or whether collection opportunities were scheduled at fixed intervals. Those details matter because different opportunities to provide a kit could affect the chance of meeting the endpoint. They are not reported in the registry record.

How should missing observations be considered? In general, missing data arise when a measurement or outcome is unavailable for some participants. The amount and reasons for missingness can affect interpretation, particularly if the absence of a measurement is related to the outcome or to participant circumstances. A transparent analysis usually explains which participants were included, how missing observations were handled, and whether assumptions were made. The registry does not report the number of missing fecal collections, the reasons for missingness, an imputation method, or an analysis population. It is therefore not possible to determine whether missing data affected the endpoint estimate.

What about count distributions and over-dispersion? In general, count data may vary more than a simple statistical model expects. Over-dispersion means that observed variability is greater than the model’s assumed variability; if ignored, uncertainty estimates can be misleading. This is a general consideration for count modeling, not a reported issue in this study. The registered primary outcome is a number of participants meeting a binary collection criterion, rather than a repeated count of kits per participant. The registry does not report a model for the endpoint, a dispersion assessment, or any model diagnostics. No conclusion about over-dispersion or model fit can be drawn from the record.

Was the study designed around a stated sample-size rationale? A sample-size justification generally states the target effect or precision, the assumptions used, and the intended analysis. The registry records enrollment of 15, but a sample-size justification, target power, and statistical assumptions for the trial are not reported in the registry record. A planning illustration based on an observed effect, when available, is not a report of observed power and cannot replace the trial’s own design rationale. The record does not provide a completed observed effect for this endpoint on which to base such an interpretation.

Can multiplicity be assessed? Multiplicity concerns the interpretation of several outcomes or statistical tests, especially when conclusions are selected from multiple analyses. One primary outcome measure is listed, but the registry reports no analyses and no statistical plan. It therefore does not establish how any multiple outcomes, exploratory measures, or subgroup comparisons would have been handled. No adjustment procedure is reported. General discussion of multiplicity cannot identify an adjustment that the record does not describe.

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("Blood & Fecal Collection")
n      <- c(10)
events <- c(10)
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  Blood & Fecal Collection  10  10  100.0  69.2  100.0  72.2  100.0  71.5  99.8

11. Multiplicity, Missing Data and Analysis Populations

One primary outcome measure is listed: the number of subjects who complete fecal collection, defined as at least one fecal kit collected. The record reports zero analyses and says the study was halted prematurely with data analysis not complete. No test results, estimates, or confidence intervals are reported. The registry does not describe a prespecified hierarchy of outcomes, a family of statistical tests, or a multiplicity adjustment. Although the listed primary outcome is identifiable, the handling of any additional or exploratory analyses is not reported in the registry record.

In general, multiplicity can arise when investigators examine several outcomes, time points, subgroups, or models. Without a statistical plan or reported analysis, it is not possible to determine how many analyses were intended or whether any adjustment was considered. The presence of a single listed primary measure does not reveal how other collected information would have been analyzed. The study description includes questionnaires, blood samples, and fecal samples, but the registry does not report an analysis plan for those data.

Missing-data handling is also not reported. The record does not state how many participants lacked a fecal collection, whether any samples were unusable, why any collection was absent, or how such participants would be treated in the endpoint analysis. It does not report an imputation method or sensitivity analysis. The primary endpoint’s threshold of at least one kit collected is clear, but the record does not explain how incomplete collection beyond that threshold would be represented.

The analysis population is not reported in the registry record. Enrollment is recorded as 15, but the record does not say how many participants were included in an analysis or whether any eligibility, follow-up, or sample-availability criteria would determine inclusion. These omissions limit assessment of both missingness and the population to which any result might apply. Because no outcome analysis is posted, the practical impact of missing data and any analysis-population decisions cannot be evaluated.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry records 15 participants at risk in the Blood & Fecal Collection group. It reports zero serious adverse events, zero other adverse events, and zero deaths. No serious adverse event terms are listed. These are the safety counts recorded for the group; the record does not provide a comparative safety analysis.

In general, a count of zero means that no events in that category were recorded in the registry data for the stated group. It does not establish that an event was impossible or that every event would necessarily have been detected and reported. Interpretation also depends on how safety information was collected, what period was covered, and which event definitions were used. Those details are not reported in the registry record.

The study has no separate control group, so the safety counts cannot be interpreted as a comparison with another group. The entries also do not establish whether events were related to sample collection, chemotherapy, or other circumstances. Attribution details and further information about safety monitoring are not reported in the registry record. The counts should therefore be read descriptively and alongside the stated study design and incomplete-analysis status.

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

The record supports a limited description of the study: it was a single-group investigation involving blood and fecal collection among people receiving neoadjuvant chemotherapy for advanced breast cancer. Enrollment is recorded as 15, and the study is listed as terminated. Its primary outcome was the number of participants with at least one fecal kit collected. The record says the study was halted prematurely and data analysis was not complete.

Those details do not provide the primary endpoint result. The number of participants who met the collection criterion is not reported in the registry record. The enrollment count cannot be substituted for that number, and no completion estimate or uncertainty interval is available. Consequently, the posted results do not establish how often participants completed fecal collection.

The research purpose discusses possible links among gut microorganisms, immune activity, and response to chemotherapy. The record does not report microbiome findings, immune measurements, treatment-response results, or statistical associations among them. The study’s motivation should not be mistaken for a finding. Nothing in the posted results demonstrates or rules out a relationship between the microbiome and treatment response.

The single-group design also does not provide a randomized control comparison. It cannot support a causal contrast between study arms. The safety counts are descriptive registry entries, not evidence from a comparative safety analysis. More generally, a result from one group would need to be interpreted in light of who participated, how measurements were obtained, and how complete the data were; several of those details are not reported in the registry record.

In general, an incomplete study record can still describe what was intended and the status of reporting, but it cannot replace a completed outcome analysis. Here, the most defensible reading is that the record documents a collection-focused study that ended before its analysis was complete. It does not supply enough outcome information to quantify collection completion or answer the broader biological question. Any stronger claim would go beyond the results reported in the registry.

14. Why This Trial Matters Statistically

This study is statistically notable because its broad research motivation and its registered primary outcome address different questions. The motivation concerns gut microorganisms, immune activity, and response to neoadjuvant chemotherapy. The primary endpoint, by contrast, is a count of participants who completed fecal collection, defined as having at least one kit collected. Keeping feasibility or collection outcomes distinct from biological and clinical outcomes is essential for interpreting what a study actually measures.

The record also illustrates the importance of reporting outcome results, not only outcome definitions. A clearly defined endpoint can make the intended measurement understandable, but without the observed count and an analysis, readers cannot estimate how often the task was completed or how precise that estimate would be. The registry states that analysis was incomplete after the study was halted prematurely, and it reports no analyses. That information places a firm boundary on interpretation.

Design is equally important. The single-group structure, allocation listed as NA, and absence of a comparator mean that the study is not a randomized treatment comparison. The sample-collection activity may be studied as a process, but the record cannot support a comparative estimate of treatment response. This distinction helps prevent the scientific rationale from being read as evidence of a causal effect.

Finally, the registry’s safety counts show how descriptive numbers should be handled when context is limited. Zero recorded events is a specific entry, but it is not a comparative safety conclusion and does not answer questions about detection or attribution. Together, the incomplete endpoint analysis, absence of a comparator, and unreported analysis details make this record a useful example of why statistical interpretation depends on both design and reporting, not on the research question alone.

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 main limitation is that the record states the study was halted prematurely and data analysis was not complete. No primary outcome count is reported, despite the endpoint being defined as fecal collection completion. Enrollment of 15 does not reveal how many participants provided at least one kit. Without an observed endpoint result, there is no estimate or uncertainty measure to interpret.

The design is single-group and has no randomized comparator. This limits the questions that can be answered using the registered structure: it cannot provide a like-for-like comparison of treatment groups. The intervention is sample collection while participants receive standard-of-care neoadjuvant chemotherapy, not a randomized assignment to a chemotherapy approach. The record does not report an analysis of microbiome measures, immune activity, or treatment response.

Important operational details are not reported in the registry record, including the reason for termination, the number of participants who attempted or completed each collection, whether any samples were unusable, and the reasons for any missing collections. The record does not explain how the requested 2 fecal samples relate to the endpoint threshold of at least one kit in the analysis. It also does not report participant characteristics, collection schedules, or whether follow-up duration varied.

The statistical plan, sample-size justification, handling of missing data, analysis population, model choice, and multiplicity approach are not reported in the registry record. The absence of these details prevents assessment of whether any planned analyses were suitable or how robust they would have been. Safety results are also limited to descriptive counts, without reported information about attribution or ascertainment. These limitations reflect gaps in the registry record; they do not establish what may or may not exist outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gut Microbiome & Gastrointestinal Toxicities as Determinants of Response to Neoadjuvant Chemo for Advanced Breast Cancer — NCT02696759.
• Registry record last updated 2022-03-16; status last verified 2022-01.
• Results first posted 2021-09-24.
• 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

NCT02696759 is a University of Arkansas study titled Gut Microbiome & Gastrointestinal Toxicities as Determinants of Response to Neoadjuvant Chemo for Advanced Breast Cancer. The registry lists the study as terminated, with a start of 2016-07, primary completion of 2021-08, and enrollment of 15. It is described as a single-group study with allocation listed as NA and masking listed as NONE.

The listed intervention is Blood & Fecal Collection. Participants receiving standard-of-care neoadjuvant chemotherapy were asked to complete questionnaires and provide two blood samples and 2 fecal samples. The primary outcome was the number of subjects completing fecal collection, defined as at least one fecal kit collected, through study completion, an average of 18 months.

The registry says the study was halted prematurely and data analysis was not complete. It reports zero analyses and does not report the primary outcome count. Safety entries record 15 at risk, zero serious adverse events, zero other adverse events, and zero deaths. The broader biological question is not answered by the posted results.