Randomized Study of Beet Root in Locally Advanced Squamous Cell Cancer of the Head and Neck: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized Study of Beet Root in Locally Advanced Squamous Cell Cancer of the Head and Neck (NCT02058849), a randomized phase 2 study. The primary outcome is Adherence to Treatment.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-masked, parallel phase II study. Its title identifies concentrated beetroot as the intervention for participants receiving treatment for locally advanced, unresectable, previously untreated squamous cell cancer of the head and neck. The comparison is beetroot versus placebo. The record lists an enrollment of 13 and a completed status. The start is recorded as 2014-12, and primary completion as 2018-04-01.

The intervention description specifies 10 grams of concentrated organic beetroot crystals. The placebo is listed without further detail. Random allocation and double masking describe design features, but the registry does not report the randomization procedure, allocation concealment, masking procedures, or whether masking remained successful. It also does not describe the treatment schedule for the study product.

The primary outcome is adherence to treatment, defined in the endpoint description as the number completing radiotherapy and three cycles of chemotherapy with no delay, with a timeframe of up to 6 weeks. The brief summary describes the intended adherence outcome as completion of radiotherapy and three cycles of chemoradiation without dose reduction. Body composition, specifically lean body mass, and muscle strength are listed as secondary outcomes. Mucositis is part of the investigators’ rationale and appears among the conditions, but the registry record does not give a posted outcome result for mucositis in the registry record for interpretation.

The registry lists 11 outcome measures and two secondary outcomes. It reports zero analyses. The treatment-adherence counts are 4 for beetroot and 1 for placebo, but a two-arm comparison is marked as not estimable. This means the design description can be stated, while the registry record does not support a quantitative estimate of the primary comparative effect. Details of eligibility, participant flow, analysis populations, and the reasons outcome data are unavailable for comparison 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:

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 Adherence to Treatment, measured over Up to 6 weeks.

The primary endpoint is a count of participants meeting a treatment-completion criterion. The registry describes it as the number completing radiotherapy and three cycles of chemotherapy with no delay, assessed over a timeframe of up to 6 weeks. The brief study summary describes treatment adherence as completing radiotherapy and three cycles of chemoradiation without dose reduction. The wording differs, and the registry does not clarify how no delay and no dose reduction were operationalized or reconciled.

A completion count is intended to capture whether participants were able to proceed through a specified course of treatment under the study’s criterion. It is not a direct measure of tumor response, survival, symptoms, or quality of life. The investigators’ rationale connects adherence with possible preservation of muscle mass and strength and reduction of mucositis, but those proposed links should not be treated as demonstrated by this endpoint.

For a randomized comparison, counts need to be interpreted in relation to the number of participants whose outcome status was assessed in each group. The posted entries give counts of 4 for beetroot and 1 for placebo, but the registry identifies the binary two-arm comparison as not estimable. Consequently, those counts should not be treated as a complete comparative result. The record does not report a confidence interval, a test result, or sufficient explanation of the analysis denominator for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help explain why an outcome count is not, by itself, a comparative result. The study randomized participants to beetroot or placebo and specified a binary treatment-completion endpoint: each participant either met the stated criterion or did not. The registry expresses the primary outcome as a count of participants meeting that criterion. To compare groups, an analysis ordinarily needs the outcome status and relevant denominator for each group, together with a defined statistical method. The registry marks this comparison as not estimable and does not provide a comparative estimate.

What does a count show?

A count reports how many participants met a criterion. It does not alone show the proportion meeting it, because the denominator matters. If the number assessed differs from the number assigned, or if outcome data are unavailable for some participants, the interpretation can change. Here, the posted endpoint entries are 4 for beetroot and 1 for placebo, while the record does not explain the endpoint denominators or participant flow. The enrollment figure cannot substitute for group-specific analysis denominators. The adverse-event at-risk counts describe safety records and should not be assumed to be the denominators for the primary endpoint.

A comparative effect could be expressed using a difference in proportions, a ratio of proportions, or another measure suited to the outcome and analysis plan. Each requires defined data and assumptions. No such effect estimate is reported, and producing one from incomplete or ambiguous entries would go beyond the record. The registry also provides no confidence interval or primary-outcome test result. A confidence interval is a way of expressing uncertainty around an estimate; it is not merely a range of observed counts. Without a valid estimate and its analysis details, the uncertainty around a treatment contrast cannot be evaluated.

Why does a non-estimable comparison matter?

The registry’s indication that the binary comparison is not estimable is a substantive limitation. It signals that the posted information does not support the requested two-group analysis. It does not explain why: the reason is not reported in the registry record. Possibilities should not be guessed. The record does not say whether the issue arose from missing outcome data, data structure, an analysis decision, or another cause. The absence of a reported analysis is especially important because the number of analyses is listed as zero.

Randomization is intended to make treatment groups comparable in expectation, while masking is intended to reduce the influence of treatment knowledge on care or assessment. Neither feature supplies missing outcome data or guarantees that a particular comparison can be estimated. The record gives the broad design labels but does not report the allocation method, concealment details, masking assessment, or analysis population. Therefore, the design can be described without claiming that all protections were implemented successfully or that the posted groups remained comparable in practice.

How should precision be understood?

Precision concerns how much uncertainty surrounds an estimate. A confidence interval is commonly used to communicate that uncertainty. A narrow interval indicates greater precision than a wide interval, given the model and data; neither width nor coverage can be assessed when no interval is reported. A p-value, if reported, would address compatibility with a specified null model under assumptions, but it would not describe effect size or clinical importance by itself. Neither a p-value nor an interval for the primary comparison appears in the registry record.

For sparse binary data, general statistical practice may use methods designed for small counts rather than rely uncritically on large-sample approximations. The choice depends on the analysis objective, denominators, and planned method. This is general explanation, not a description of the trial’s analysis: its statistical method is not reported in the registry record. Over-dispersion is a concern for some count models when variability exceeds a model’s assumed level; it is not a substitute for specifying the binary outcome analysis, and the registry does not report such a model or a dispersion estimate.

What do the planning assumptions mean?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are assumptions for a planning exercise, not evidence about the trial’s actual design rationale and not observed power. Numerical planning estimates are not reported in the registry record. They should not be interpreted as the trial’s enrollment target, proof that the study was adequately powered, or a retrospective measure of whether the result was persuasive. A sample-size calculation describes a hypothetical design under assumptions; it does not repair an outcome comparison that the registry marks as not estimable.

The registry does not report a sample-size justification, interim analyses, a prespecified statistical analysis plan, handling of missing outcomes, covariate adjustment, or sensitivity analyses. These elements matter because analysis choices can affect estimates and uncertainty. Their absence from the registry record should be treated as unknown, not as evidence that no such planning occurred. The available statistical interpretation is consequently limited to describing the design, the recorded counts, and the stated non-estimability of the primary comparison.

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("Beetroot", "Placebo")
n      <- c(4, 1)
events <- c(4, 1)
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  Beetroot  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5
ARM  Placebo  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures and identifies two secondary outcomes: body composition measured as lean body mass and muscle strength. The primary endpoint is treatment adherence. When a study assesses multiple outcomes, the chance of a false-positive finding across a family of tests can increase if each is interpreted independently. A multiplicity strategy may define which outcome is primary, how secondary outcomes are ordered, or whether adjustment is used. The registry does not report a multiplicity procedure, outcome hierarchy beyond its primary and secondary labels, or a statistical analysis plan. It also reports zero analyses, so there are no posted outcome-analysis results on which to assess multiplicity handling.

Missing-data interpretation is similarly constrained. The record does not describe how many participants had outcome data, how missing outcomes were handled, or whether any participants were excluded from an analysis. It gives an enrollment of 13 but does not provide participant flow or a clear primary-outcome analysis denominator. The non-estimable status of the binary comparison does not identify the reason for non-estimability. It should not be attributed to a particular missing-data mechanism without evidence.

The analysis population is not reported in the registry record. It is unknown whether the primary analysis was intended to include all randomized participants, participants who began study product, or another defined group. In general, analysis populations influence how a randomized study is interpreted; this is a methodological point, not a claim about the approach used in this trial. No imputation method, missingness sensitivity analysis, or per-protocol definition is reported. These omissions limit reproducibility and make it difficult to connect the recorded counts to the randomized design.

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 non-serious adverse event terms

The registry records serious adverse events among 0 of 11 participants at risk in the beetroot group and 0 of 2 at risk in the placebo group. It records other adverse events among 9 of 11 and 2 of 2, respectively. Deaths are listed as 1 in the beetroot group and 0 in the placebo group. These are descriptive safety counts as recorded, not estimates of comparative risk. The registry does not provide serious-event terms, so the types of serious events cannot be described from this record.

At-risk counts differ between the groups, and the record does not explain why they differ from the enrollment figure or from the primary endpoint entries. The adverse-event entries should therefore be interpreted using their stated at-risk counts, without assuming they represent every enrolled participant or the primary endpoint population. The record also does not report timing, exposure duration, severity grading for the other events, or whether events were judged related to study product. Attribution to beetroot or placebo cannot be inferred from these counts.

Zero recorded serious adverse events in a group does not establish that serious events are impossible or that the intervention is safe. Likewise, the observed counts do not by themselves show that one group had more or fewer events on a comparable basis. Small, unequal safety groups and limited event descriptions restrict precision and comparison. The registry does not report a formal comparative safety analysis.

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

The result that can be stated directly is narrow: the registry records treatment-adherence counts of 4 for beetroot and 1 for placebo, and it marks the binary two-arm comparison as not estimable. Those entries do not provide an effect estimate, confidence interval, or test result. They therefore do not establish whether adherence differed between groups, how large any difference may have been, or how precisely a difference could be estimated.

The study’s stated rationale was that concentrated beetroot might support completion of cancer treatment while helping preserve fat-free mass and strength and reducing mucositis. Those statements describe the investigators’ hypothesis. The available primary outcome information does not establish that the intervention achieved these aims. Lean body mass and muscle strength are listed as secondary outcomes, but their results are not included in the registry record for interpretation. The posted safety counts likewise do not establish causal effects.

Randomization and double masking are important design features, but they do not make incomplete or non-estimable results conclusive. The record does not report enough information to determine the primary analysis population, outcome denominators, participant flow, or reason for non-estimability. Without those details, readers cannot assess whether the counts correspond to all randomized participants or to a narrower group.

This record also does not justify conclusions about other patients, cancer treatments, beetroot products, or outcomes beyond those described. The study is identified as phase II, and its enrollment is listed as 13; the record does not report a sample-size justification or a completed inferential analysis. A planning illustration, even when based on an observed effect, is not observed power and cannot replace a valid comparative result. The most defensible interpretation is that the registry documents the trial design and selected outcome counts, but leaves the primary comparative question unresolved.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a randomized design and an interpretable comparative result. Randomization and double masking describe the intended structure of the experiment. To learn from that structure, readers also need analyzable outcomes, clear denominators, and an estimate of the group contrast with its uncertainty. The registry marks the primary binary comparison as not estimable and reports zero analyses, so those elements are not available for the adherence endpoint.

The distinction matters because raw counts can appear straightforward while concealing uncertainty about who was assessed and how the endpoint was analyzed. The registry gives counts of 4 and 1 for the primary outcome, but does not explain the analysis denominators or participant flow. Without those details, the counts cannot be converted into a well-supported comparative conclusion. The separate safety at-risk counts should not be used to fill that gap.

The record also highlights the value of transparent reporting. Clear definitions of the adherence criterion, analysis populations, missing-data handling, and planned statistical methods would help readers distinguish design intentions from completed analyses. Reporting confidence intervals would communicate precision, while a transparent account of missingness would clarify what the observed data represent. These elements are not reported in the registry record.

Finally, the study’s hypothesis connects treatment adherence with body composition, strength, and mucositis, but those aims should remain distinct from demonstrated results. Listing secondary outcomes does not establish that they were analyzed or that they support the hypothesis. The statistical importance of this record is therefore less about a proven effect and more about recognizing what the posted information can and cannot answer.

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.

Several trial-specific limitations constrain interpretation. The registry’s primary endpoint description refers to completion of radiotherapy and three cycles of chemotherapy with no delay, while the brief summary describes completion without dose reduction. The record does not explain whether both conditions were required, how they were defined, or which wording governed the analysis. This ambiguity makes it harder to know exactly what the recorded counts represent.

The primary outcome entries report counts of 4 and 1, but the registry does not report their denominators or explain participant flow. Enrollment is listed as 13, while safety entries use at-risk counts of 11 and 2. The record does not reconcile these figures, and they should not be combined or treated as interchangeable. The binary comparison is explicitly marked not estimable, with no explanation of the reason.

The registry identifies the study as randomized, double-masked, parallel, and phase II, but does not describe allocation procedures, concealment, masking success, or the analysis population. It does not report a statistical analysis plan, sample-size justification, interim analyses, missing-data methods, or a primary comparative estimate with uncertainty. Although 11 outcome measures and two secondary outcomes are listed, their results are not available in the registry record used for this interpretation.

Safety reporting is also limited: serious-event terms are absent, other adverse events are not described by type, and the record does not provide event attribution or a formal safety comparison. The reported counts should remain descriptive. These limitations are specific to what the registry record reports; they do not establish that unreported procedures or analyses were never conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Randomized Study of Beet Root in Locally Advanced Squamous Cell Cancer of the Head and Neck — NCT02058849.
• Registry record last updated 2019-08-14; status last verified 2019-07.
• Results first posted 2019-08-14.
• 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, double-masked, parallel phase II study of concentrated beetroot versus placebo in participants being treated for locally advanced, unresectable, previously untreated squamous cell cancer of the head and neck. Enrollment is listed as 13. The intervention is described as 10 grams of concentrated organic beetroot crystals.

The primary outcome is treatment adherence, with a timeframe of up to 6 weeks. The posted counts are 4 for beetroot and 1 for placebo, but the binary comparison is marked not estimable. The registry lists lean body mass and muscle strength as secondary outcomes and reports zero analyses. Safety entries record serious adverse events in 0 of 11 and 0 of 2 at risk, other adverse events in 9 of 11 and 2 of 2, and deaths of 1 and 0, respectively.

The registry does not report a comparative primary estimate, confidence interval, test result, participant flow, or explanation for the non-estimable comparison. The available record supports a description of the study and its posted counts, not a conclusion about comparative efficacy or safety.