Beneficial Effects of Quercetin in Chronic Obstructive Pulmonary Disease (COPD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Beneficial Effects of Quercetin in Chronic Obstructive Pulmonary Disease (COPD) (NCT01708278), a randomized phase 1 study. The primary outcome is Participants Who Experienced Safety Concerns, Where Safety Concerns of Quercetin Supplementation is Indicated by Significant Change From Baseline Measures of Tests Indicated Below in Outcome Measure Description.

2. Clinical Question

This is a short-term safety question, not a test of whether quercetin improves COPD symptoms, lung function, or other clinical outcomes. The registry’s stated overall objective also includes investigating dosage, bioavailability, dose-response, and biomarkers for future research. However, the posted primary outcome is the composite indicator of safety concerns, and no analyses are posted for dose-response or clinical benefit. The central reading is therefore about the observed safety outcome over the specified timeframe, with the substantial uncertainty that comes from the small groups and brief observation period.

3. Trial Design

The registry classifies this as a Phase I, randomized, triple-masked, parallel-group study. It is marked completed, with a posted enrollment of 9. The record lists the study start as 2014-02 and primary completion as 2015-10. Those dates describe the trial record; they do not extend the primary outcome’s stated observation timeframe, which is one week in the Phase I safety study.

Six groups are listed across three cohorts. In Cohort 1, the sugar-chew group had 1 participant and the 500 mg quercetin group had 2. In Cohort 2, the sugar-chew group had 1 participant and the 1000 mg quercetin group had 2. In Cohort 3, the sugar-chew group had 1 participant and the 2000 mg quercetin group had 2. Each sugar chew contained 350 mg of vitamin C and 10 mg niacin; the quercetin chews contained those ingredients as well as the cohort-specific quercetin dose.

The parallel-group designation means participants were assigned to a group rather than all receiving each treatment in sequence, while randomization indicates that assignment was described as randomized. Triple masking is the registry’s classification; the precise parties masked and the masking procedures are not reported in the registry record. Allocation procedures, cohort progression rules, and details of how the listed dose levels were selected are also not reported in the registry record. The small group sizes mean the posted results should be read as descriptive observations within this early-stage study, not as precise comparisons between doses or against the sugar chew.

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

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Participants Who Experienced Safety Concerns, Where Safety Concerns of Quercetin Supplementation is Indicated by Significant Change From Baseline Measures of Tests Indicated Below in Outcome Measure Description, measured over One week in Phase I safety study.

The primary endpoint counts participants who experienced a defined safety concern during one week in the Phase I study. A concern was defined by a significant change from baseline in specified tests: a decline in FEV1% of predicted of more than 20%; low white blood cell count, platelet count, or hemoglobin; specified low or high sodium, potassium, or calcium values; or liver-function test values above the stated threshold. The registry describes these as criteria for identifying a participant with a safety concern.

The outcome is a composite: meeting any one of the listed criteria would count a participant as having a safety concern. A composite can bring several safety signals into one outcome, which can be useful when an early-stage study monitors multiple kinds of potential laboratory or pulmonary change. It also means the summary does not by itself show the pattern of each individual test. The registry says none of the participants had the specified outlying values, so the results are expressed as the composite rather than as individual test values.

This endpoint is used to describe short-term safety monitoring, not to measure symptom relief, disease progression, or efficacy. The registry reports zero participants with the composite outcome in every listed group. That observation applies to the defined criteria and timeframe; it does not establish that no other possible safety event occurred or that the intervention is safe in other settings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization, masking, and a parallel-group structure describe features of how a trial is organized; they do not, by themselves, determine how its results were analyzed. The registry classifies this study as randomized, triple-masked, and parallel. Random allocation can help avoid systematic differences between groups at entry, while masking can reduce the influence of expectations on care or assessment. These are general methodological roles. The record does not describe the randomization sequence, allocation concealment, which parties were masked, or whether masking was assessed.

What does the primary count represent?

The outcome is binary at the participant level: a person either meets the composite safety-concern definition or does not. The registry reports counts rather than a continuous measurement. For this endpoint, each listed group has a count of 0. The definition combines several possible triggers across pulmonary function, blood counts, metabolic measurements, and liver tests. In general, a composite outcome can provide a single summary across several events, but it can also conceal which component would have driven a positive result. In this record, no component-specific outlying values are posted because the registry says none occurred.

Counts are especially important when group sizes are very small. A count of zero is a direct description of the observed group, but it does not precisely determine the probability of an event in a wider population. Confidence intervals are one general way to communicate uncertainty around an estimate: they show a range of values compatible with the observed data under the chosen statistical method. No confidence interval is posted for the primary outcome, and the record does not give a model-based estimate of event probability. It would be inappropriate to present an invented interval or treat the zero count as proof that the true risk is zero.

Why is no two-group effect estimate available?

The record states that values are missing or not estimable for a two-arm comparison of the binary endpoint. A comparative estimate, such as a difference in event proportions, would need to be calculated within a clearly defined pair of groups and would be highly uncertain with these sparse counts. No such estimate or inferential test is posted. The three dose cohorts are listed separately, and the registry does not provide a pooled comparison or an adjusted analysis. Thus, the reported counts support description of what was observed, but not a formal conclusion that one group has a higher or lower risk than another.

General statistical methods for sparse binary data include exact methods or models designed for small counts. Such methods can sometimes be more appropriate than large-sample approximations, which rely on data being sufficiently abundant for their assumptions to work well. This is a general point; the statistical method used by the investigators is not reported in the registry record. There are no posted analysis records for the primary outcome, and the record does not specify a statistical analysis plan, hypothesis tests, covariate adjustment, or interim analyses. No method should be attributed to the investigators without that information.

How should dose patterns be assessed?

A dose-response analysis asks whether outcomes vary systematically across dose levels. In general, that requires a prespecified approach to comparing the dose groups and enough observations to estimate the pattern with useful precision. Here, the groups have very few participants and the primary event count is zero in every group. The record posts no dose-response estimate or analysis. Comparing the raw counts across dose groups cannot establish a trend, and the result does not show that the dose levels are equivalent.

The registry’s sample-size assumptions describe planning illustrations based on an observed effect, with 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. Such calculations are general planning tools, not evidence about the trial’s actual design justification or its ability to detect an effect. The record does not report the trial’s own sample-size justification. Since a two-arm binary effect is not estimable in the posted results, no observed effect can be used to support a meaningful planning target from these data. Any sample-size illustration should be understood as a planning scenario, never as observed power or evidence that the trial could reliably rule out safety concerns.

In general, over-dispersion means that outcomes vary more than a chosen statistical model expects. It can make standard errors too small if ignored, leading to overly narrow uncertainty intervals or misleading tests. It is not a specific feature established by the posted results, and the registry does not report a model for which over-dispersion was assessed. With this binary endpoint and very sparse counts, the more immediate interpretive issue is the limited information available for estimation.

Finally, the posted outcome concerns one week and a defined collection of thresholds. A statistical method cannot extend the observation window or broaden the endpoint beyond what was recorded. The numerical results therefore describe only the specified composite during the stated timeframe. General statistical explanations help clarify the limits of such counts, but they do not substitute for analysis details that 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("Sugar Chew- Cohort 1", "Quercetin 1-Cohort 1", "Quercetin 2-Cohort 2", "Quercetin 3-Cohort 3", "Sugar Chew-Cohort 2", "Sugar Chew-Cohort 3")
n      <- c(1, 2, 2, 2, 1, 1)
events <- c(0, 0, 0, 0, 0, 0)
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  Sugar Chew- Cohort 1  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Quercetin 1-Cohort 1  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Quercetin 2-Cohort 2  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Quercetin 3-Cohort 3  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Sugar Chew-Cohort 2  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Sugar Chew-Cohort 3  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no secondary outcomes posted. It also lists 0 analyses. This means the record does not provide a family of posted outcome tests for which a multiplicity adjustment can be described. Whether the trial protocol specified additional analyses, interim looks, or correction for multiple testing is not reported in the registry record. It would be inappropriate to infer that no such plans existed solely from their absence in the posted analysis entries.

Multiplicity is a general concern when many outcomes, time points, subgroups, or comparisons are tested. The more opportunities there are to identify a result by chance, the harder it can be to interpret isolated statistical evidence without a prespecified plan. Here, the posted primary result is a descriptive composite count, and no inferential tests or p-values are reported. There is consequently no posted multiplicity-adjusted result to interpret.

Missing-data handling and analysis populations are also not reported in the registry record. The posted group counts show the numbers represented in each outcome arm, but the record does not describe whether every randomized participant was included under a particular analysis principle, whether any measurements were missing, or how missing values would have been handled. No imputation, exclusion rule, or sensitivity analysis is reported. These details matter in general because conclusions can depend on who is included and how unavailable measurements are treated. They cannot be reconstructed from the reported outcome counts alone.

The registry does not report a protocol-based statistical analysis plan, prespecified subgroup analyses, or interim monitoring procedures. Those absences should be treated as limits on what can be learned from the record, not as evidence about procedures that may or may not have been used.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event figures report 0 affected participants in each listed group. This is separate from the primary composite of safety concerns defined by specified changes from baseline. The serious adverse-event record therefore answers a different reporting question from whether a participant crossed one of the primary endpoint’s measurement thresholds.

Other adverse events were reported for 1 participant in the Cohort 1 sugar-chew group, 2 in the 500 mg quercetin group, 2 in the 1000 mg quercetin group, 1 in the 2000 mg quercetin group, 1 in the Cohort 2 sugar-chew group, and 1 in the Cohort 3 sugar-chew group. These counts describe participants affected; the registry does not provide event descriptions in the listed results or establish that the events were caused by quercetin or the sugar chew. A count of participants with an event is not necessarily a count of separate event episodes.

Deaths are not reported in the registry record. Zero serious adverse events in these very small groups and within this short study should not be read as proof that serious events cannot occur. Conversely, the other adverse-event counts do not by themselves establish a treatment-related harm. The figures are descriptive safety reports, interpreted in light of the limited group sizes and the one-week primary timeframe.

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

The result establishes a narrow descriptive point: the registry reports no participants with the composite safety concern during the specified one-week period, in any of the listed sugar-chew or quercetin groups. The composite was based on defined changes from baseline in pulmonary function and laboratory measures. This is what the posted primary outcome records; it is not a general guarantee about all possible safety outcomes.

The finding does not establish that quercetin is safe for all people with COPD, at other doses, or over longer periods. The groups are very small, and the timeframe is brief. Rare or delayed events may not be captured in a study of this size and duration. The record also does not provide a confidence interval or comparative estimate that would quantify uncertainty around the relative safety of the quercetin and sugar-chew groups.

Nor does the outcome establish equivalence between treatments. A lack of observed primary events in each group is not the same as evidence that their underlying risks are identical. The posted results do not support a dose ranking or show whether one dose has a different safety profile from another. The registry’s stated broader objectives include exploring bioavailability, dose-response, and biomarkers, but the posted primary result does not report analyses answering those questions.

The outcome also says nothing about whether quercetin improves COPD. The primary endpoint measures safety concerns, not clinical benefit. Other adverse events were reported in the groups, but the record does not provide event descriptions or attribute them to a particular treatment. The sensible interpretation is limited to the observed counts and definitions: no primary composite concerns were recorded, while some other adverse events were reported. Broader claims about benefit, comparative safety, or long-term effects are not established by these data.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how an early-phase safety question differs from an efficacy question. Its primary outcome is a predefined composite of threshold-based changes in pulmonary function and laboratory measures, monitored over one week. That structure makes the endpoint understandable as a safety screen, but it also determines the limits of interpretation: the result does not measure symptom improvement or disease control.

The small group sizes make the distinction between an observed count and a precise estimate especially important. Reporting zero events accurately describes the participants observed, yet it cannot establish that the underlying event probability is zero or that the groups are equivalent. Sparse data can leave wide uncertainty, and a comparative estimate may not be estimable at all. The registry explicitly does not provide a two-arm binary comparison for this endpoint.

The trial also illustrates why dose cohorts should not be treated as a dose-response result without an analysis. Three doses are listed, but there are no posted dose-response estimates, and the primary outcome is zero in each group. A visual or informal ordering of these counts would not answer whether outcomes systematically vary with dose.

Finally, the record distinguishes the composite safety outcome from adverse-event reporting. The absence of participants meeting the specified composite criteria coexists with other reported adverse events. Reading those outcomes separately prevents the safety threshold from being mistaken for a complete count of all experiences, and prevents adverse-event counts from being assumed to establish causation. These distinctions are broadly useful when interpreting small early-stage trials.

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 most important trial-specific limitation is the small number of participants in the listed groups: each group contains 1 or 2 participants. That leaves little information for estimating event frequencies or comparing doses. The zero primary outcome counts should therefore be treated as observations in these groups, not as precise evidence about a broader COPD population.

The primary outcome timeframe is one week. The registry does not report longer-term follow-up for this endpoint, so these results cannot describe later safety outcomes. The composite also covers only the specified pulmonary function and laboratory thresholds. The record says none of the listed measures reached the outlying values, but it does not provide individual measurement results or a detailed account of other possible safety outcomes.

The study has three dose cohorts, each with its own sugar-chew group. The record does not report a pooled comparison, a formal dose-response analysis, or a comparative estimate with uncertainty. The available counts therefore cannot support reliable inferences about differences among doses or between quercetin and sugar chew.

Further methodological details—including eligibility criteria, the randomization procedure, masking procedures, analysis populations, missing-data handling, and the investigators’ statistical analysis plan—are not reported in the registry record. Death counts are also not reported in the registry record. These omissions limit assessment of how the trial was conducted and how completely outcomes were captured. The absence of these details in the record should not be taken as proof that the procedures or information did not exist.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Beneficial Effects of Quercetin in Chronic Obstructive Pulmonary Disease (COPD) — NCT01708278.
• Registry record last updated 2016-12-26; status last verified 2016-10.
• Results first posted 2016-12-26.
• 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.

19. Record Summary

The registry describes a completed, randomized, triple-masked, parallel Phase I study of quercetin in people with COPD, with enrollment of 9. The record lists three quercetin doses—500 mg, 1000 mg, and 2000 mg—each in a separate cohort alongside a sugar-chew group. Both chew types contained 350 mg of vitamin C and 10 mg niacin.

The primary outcome was the number of participants meeting a composite definition of safety concern during one week. The registry reports 0 participants with the composite outcome in every listed group. Serious adverse events affected 0 participants in each group; other adverse events were reported in the listed groups. Death counts are not reported in the registry record.

No two-arm binary comparison estimate or analysis is posted. The results are descriptive and limited by very small groups and the short timeframe. They do not establish comparative safety, dose-response, or clinical benefit.