Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia (NCT03476330), a na phase 2 study. The primary outcome is Number of Participants With at Least 20% Reduction of Buccal Micronuclei.

2. Clinical Question

3. Trial Design

This is a Phase 2, single-group study of oral quercetin in people with Fanconi anemia. The registry lists the allocation as not applicable and masking as none. All patients in the described study arm received quercetin; the record does not describe a concurrent control arm. The study therefore does not provide a randomized, like-for-like comparison between quercetin and another treatment or no treatment.

The registry lists enrollment of 48 and a status of completed. The study start date is 2018-05-08, and the primary completion date is 2025-03-06. Completion status and dates describe the study record; they do not establish that every enrolled participant contributed an analyzable endpoint or that a result was reported.

The primary endpoint was assessed at 1 year and counted participants achieving at least 20% reduction in the average total number of buccal micronuclei. The registry states that 27 of the 48 enrolled patients had analyzable data at that time. It attributes non-analyzable data to not completing the study through 1 year, unavailable 1-year samples, or samples that could not be evaluated. The endpoint result itself is not reported in the registry record.

The registry describes the study’s rationale as investigating whether quercetin might prevent or delay squamous cell carcinoma and related complications in people with Fanconi anemia. The primary endpoint is a micronuclei measure, not a reported count of cancers prevented or delayed. Details of the protocol beyond the listed design and endpoint, including a fuller statistical plan, 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 48 patients were enrolled in the study but 27 patients had analyzable data at 1 year. Non-analyzable data includes patients who did not complete the study through 1 year, 1 year samples were not available, or 1 year samples were not evaluable.

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 Participants With at Least 20% Reduction of Buccal Micronuclei, measured over 1 year.

The primary endpoint counts participants with at least 20% reduction in the average total number of buccal micronuclei at 1 year. Buccal micronuclei are measured in samples from the inside of the mouth; the registry describes this endpoint as assessing quercetin’s efficacy in reducing them. A participant meeting the stated reduction threshold is classified as a success for this endpoint.

A binary endpoint turns each participant’s measurement into a category: met or did not meet the threshold. This can make the outcome easier to summarize as a count of participants, but it also compresses information. It does not show the size of each participant’s change beyond whether the threshold was reached. General statistical context: a threshold-based outcome can be useful when investigators want to assess the proportion of participants reaching a prespecified level of change, but its interpretation depends on the threshold and the quality and completeness of measurements.

The registry record identifies 27 patients as having analyzable data at 1 year. It does not report how many met the reduction threshold, the total number of micronuclei measured, or an estimate of uncertainty around the endpoint. It also does not report a cancer-incidence endpoint result. Thus, the posted information defines what was to be counted but does not establish the observed frequency of success or connect that frequency to a measured reduction in squamous cell carcinoma.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study with a binary primary endpoint. Each participant is classified according to whether the stated micronuclei reduction threshold was met at 1 year. A binary result can be summarized as a count of participants meeting the definition and a count not meeting it. The registry record gives neither count, so the endpoint’s observed distribution is not reported.

What does a confidence interval describe?

General statistical context: a confidence interval expresses uncertainty around an estimate, such as the frequency of participants meeting an endpoint. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. Its interpretation depends on the analysis and assumptions used. No confidence interval for the primary endpoint is reported in the registry record, so precision cannot be assessed from the posted endpoint information.

What would a hypothesis test add?

General statistical context: a hypothesis test evaluates how compatible observed data are with a specified null hypothesis under a statistical model. A p-value is not the probability that a treatment works, nor does it describe the size or clinical meaning of an effect. For this endpoint, the registry record does not report a hypothesis test, p-value, or statistical analysis. The record also does not state the inferential procedure used, so a particular test should not be assumed.

Why does the study design matter?

The study has one treatment group and no reported concurrent control group. A single-group analysis can describe outcomes among participants who received quercetin, if those outcomes are reported. It cannot provide a direct randomized comparison with an alternative. General statistical context: a control group helps account for changes that might occur over time regardless of the intervention, as well as other differences between participants or measurement occasions. Without that comparison, causal interpretation is limited.

The registry’s sample-size assumptions describe planning illustrations based on an observed effect. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These assumptions describe illustrations, not the design of this single-group study. The record does not report the trial’s own sample-size justification or establish that those illustrations were the study’s planning basis. Sample-size illustrations are planning quantities, not observed power.

General statistical context: power is a design property tied to assumptions about an effect, variability, sample size, and analysis. It is not a measure of whether an observed result is true. Calculating power after observing results does not resolve uncertainty in the estimate. The registry record does not report the inputs or a trial-specific power calculation, so no such calculation can be attributed to the study.

How should missing endpoint data be considered?

The record identifies 48 enrolled patients and 27 with analyzable data at 1 year. It says that non-analyzable data include patients who did not complete follow-up through 1 year, unavailable samples, or samples that were not evaluable. These are distinct reasons for missing endpoint measurements. The record does not report how many fell into each category, whether missingness was related to participant characteristics or outcomes, or how missing data were handled in an analysis.

General statistical context: an analysis restricted to participants with observed measurements can be biased if the likelihood of having an evaluable measurement is related to the outcome. Different approaches to missing data rely on different assumptions; those assumptions should be stated and assessed. Because the registry does not describe an analysis population beyond the analyzable count or a missing-data method, the impact of missing endpoint data cannot be quantified.

The registry lists one outcome measure and no analyses. Consequently, the posted record does not provide a statistical estimate that can be checked for model choice, adjustment, or uncertainty. Details of any prespecified statistical analysis plan, including handling of the binary endpoint and any interim analyses, are not reported in the registry record.

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("Quercetin")
n      <- c(27)
events <- c(13)
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  Quercetin  27  13  48.1  28.7  68.1  30.7  66.0  30.6  66.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analyses. It does not report a set of additional efficacy endpoints or statistical tests, nor does it describe an adjustment for multiple comparisons. Whether multiplicity was addressed in the study’s protocol or analysis plan is not reported in the registry record. Without a reported analysis plan and results, it is not possible to assess how multiple outcomes or repeated testing might affect interpretation.

For the primary endpoint, 48 patients were enrolled and 27 had analyzable data at 1 year. The record identifies three reasons for non-analyzable data: not completing the study through 1 year, a 1-year sample not being available, or a sample not being evaluable. The number of participants in each category is not reported in the registry record. Nor does the record state whether any missing measurements were imputed, excluded under a stated rule, or handled in another way.

General statistical context: missing outcomes can affect both the size and the precision of an estimate. If the participants with observed measurements differ in relevant ways from those without them, a complete-case summary may not represent all enrolled participants. The direction and size of any such effect cannot be known without further information and assumptions.

The registry does not describe an intention-to-treat analysis population, a per-protocol population, or another prespecified analysis set. The analyzable count identifies the number with endpoint data, but does not alone establish which participants were included in any inferential analysis. As no primary endpoint result or analysis is reported, neither multiplicity handling nor the consequences of missing data can be evaluated from the posted record.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: other: crohn's disease flare (2.1%), lung infection (2.1%), urinary tract infection (2.1%), upper respiratory infection (2.1%), pneumonthorax (2.1%).

The serious adverse event figures for the quercetin group list 47 participants at risk and 3 affected. The registry also lists 10 participants affected by other, non-serious adverse events and 0 deaths. These are safety summaries, separate from the primary micronuclei endpoint. The record does not provide a comparator group, so these counts do not support a comparative estimate of safety.

The serious adverse event terms listed include Crohn's disease flare, lung infection, urinary tract infection, upper respiratory infection, pneumonthorax, and respiratory distress. Each is reported as 2.1%. Crohn's disease flare is listed twice. The registry does not clarify whether the term list represents unique participants, event counts, or overlapping categories; a participant may contribute to more than one event category in safety reporting. The listed percentages should therefore be read as the registry’s term-level figures, not added together or treated as a rate for all serious events.

General statistical context: adverse event counts depend on the definitions, observation period, and reporting procedures used. The registry record does not provide enough detail to determine event duration, severity grades, relatedness to quercetin, or whether events led to treatment changes. The listed figures describe reported safety events in this group; they do not establish that quercetin caused them or that an event would not have occurred without treatment.

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

The registry record establishes that the study assessed oral quercetin in a single group of people with Fanconi anemia and defined a primary endpoint based on buccal micronuclei reduction at 1 year. It reports enrollment of 48 and analyzable endpoint data for 27. It does not report the number meeting the endpoint, an estimate of effect, or an uncertainty interval. Therefore, the posted information does not show the observed frequency of participants achieving the stated reduction.

The study’s stated scientific rationale was to investigate whether quercetin could prevent or delay squamous cell carcinoma and associated complications. The listed primary endpoint measures micronuclei reduction, not cancer incidence or time to cancer. The record does not report results for prevention or delay of squamous cell carcinoma, nor does it report a comparison with an untreated or alternative-treatment group. A cancer-prevention conclusion cannot be drawn from the endpoint definition or the completed study status.

General statistical context: a surrogate or marker outcome can be informative about a biological process, but a change in that measure does not automatically establish a change in a clinical outcome. Whether a marker predicts a clinical benefit requires evidence beyond the marker’s definition. The registry record does not report such evidence for this study.

The safety record lists serious and other adverse event counts in the quercetin group, including 0 deaths. These figures describe events recorded for the group and do not establish causation or comparative risk. A single-group design cannot distinguish the observed safety experience from what might have occurred in a comparable group not receiving quercetin.

In short, the record documents the intended question, treatment, endpoint, enrollment, analyzable population, and safety counts. It does not report enough outcome or analysis information to estimate efficacy, assess precision, or determine whether the hypothesized cancer-related effects occurred. The missing result should not be replaced by an inference from the trial’s rationale or status.

14. Why This Trial Matters Statistically

This trial raises a statistical distinction between a study’s clinical motivation and the outcome it actually measures. The registry describes a concern about squamous cell carcinoma in people with Fanconi anemia, while the primary endpoint is the number of participants with at least 20% reduction in buccal micronuclei at 1 year. Keeping those outcomes distinct prevents a marker-based result from being mistaken for a direct cancer outcome.

The single-group design also defines what the study can estimate. If reported, the endpoint count could describe the experience of participants receiving quercetin who had evaluable samples. It would not provide a randomized comparison with people who did not receive quercetin. General statistical context: estimates from treatment-only cohorts can be useful descriptively, but a causal claim requires careful consideration of what comparison is available and what alternative explanations remain.

The difference between enrollment and analyzable endpoint population is another important feature. The record reports 48 enrolled and 27 with analyzable data at 1 year. That gap makes the handling and reasons for missing data relevant to interpretation. The registry identifies broad reasons, but does not report their counts or the analysis method. Without those details and the endpoint result, the effect of incomplete outcome data cannot be assessed.

Finally, the registry offers planning assumptions for sample-size illustrations that use a two-arm framework, while the trial itself is listed as single-group. Recognizing that distinction prevents planning illustrations from being mistaken for the trial’s actual design or evidence of observed power. Together, these features show why clear reporting of the endpoint result, analysis population, missing-data approach, and statistical plan matters when evaluating what a clinical study can establish.

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 primary limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. It defines success as at least 20% reduction in average total buccal micronuclei at 1 year, but does not state how many participants met that criterion. No estimate, uncertainty interval, or inferential test is reported.

The study is single-group, with all patients treated with oral quercetin and no reported concurrent comparator. This prevents a direct within-trial comparison with an untreated group or another intervention. The registry does not report randomization or masking; masking is listed as none. These design features limit the conclusions that could be drawn even if the endpoint count were available.

Endpoint availability is incomplete relative to enrollment: 48 patients were enrolled and 27 had analyzable data at 1 year. The record gives several reasons for non-analyzable data but does not report how many participants were affected by each reason, whether missingness was associated with outcomes, or how missing data were handled. The resulting risk of selection or attrition bias cannot be assessed.

The primary endpoint is a buccal micronuclei measure, whereas the stated rationale concerns squamous cell carcinoma and related complications. The registry does not report a cancer outcome or establish how the marker relates to cancer outcomes in this study. Details of the statistical analysis plan, including the intended analysis population, handling of the endpoint, multiplicity, interim analyses, and trial-specific sample-size justification, are not reported in the registry record.

The safety summaries also lack a concurrent comparator and do not report event relatedness, severity grading, or the observation details needed for fuller comparison. These limitations mean that the posted record is insufficient to estimate the intervention’s effect on the primary endpoint or to attribute safety events to quercetin.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia — NCT03476330.
• Registry record last updated 2026-04-20; status last verified 2026-04.
• Results first posted 2026-04-20.
• 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

The registry record identifies NCT03476330 as a Phase 2 study titled “Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia.” It lists a single-group, unmasked design, with all patients receiving oral quercetin. Enrollment was 48, and the study status is completed. The recorded start date is 2018-05-08, and the primary completion date is 2025-03-06.

The primary endpoint was the number of participants with at least 20% reduction in average total buccal micronuclei at 1 year. The registry says 27 patients had analyzable data at that time. It does not report the endpoint result or a statistical analysis. Safety figures list 47 at risk, 3 affected by serious adverse events, 10 affected by other adverse events, and 0 deaths. The record does not include a concurrent comparator.