Safety and Tolerability of Soy Fiber: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability of Soy Fiber (NCT04499482), a non-randomized na study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events Following Each Dose of Soy.

2. Clinical Question

The study’s stated aim was to investigate dose safety and tolerability and determine the maximum tolerated dose of soy fiber delivered in foods. The registry describes the fiber as coming from whole young soy pods. The primary measure focuses on participants with adverse events, with examples including headaches, nausea, and vomiting. The record also lists fecal short-chain fatty acid effects at each of the three dose levels as secondary outcomes.

The key interpretive distinction is that this is a dose-escalation sequence, not a randomized comparison of independently assigned groups. Progression to the next dose depended on tolerating the earlier dose. That structure makes the adverse-event counts useful as a description of what was reported during the study, but it does not support treating the dose groups as exchangeable comparison arms. The record does not report a control group or a formal comparative estimate between doses.

3. Trial Design

The registry lists this as a completed study with non-randomized allocation, no masking, and a crossover model. Its phase is listed as NA. Enrollment is recorded as 8. The listed start date is 2021-10-04 and the primary completion date is 2022-04-14.

The intervention is identified as “Food.” The dose descriptions specify foods containing 10 g, 20 g, or 30 g of soy flour. Each dose was intended to be consumed every day for one week. Participants who tolerated a dose were to move to the next dose, and the descriptions for the first two dose levels explicitly state that there would be no wash-out period before escalation. The 30 g description specifies one week at that dose.

This sequence is important for interpreting the posted counts. Exposure at a later dose followed exposure at earlier doses for participants who tolerated them, so dose levels are not independent randomized groups. The registry’s own note cautions that the arms are not a like-for-like control comparison. The record does not describe a separate control condition.

The study summary identifies elderly people with obesity as the intended population and describes the aim as determining the maximum tolerated dose of a novel dietary fiber from whole young soy pods, delivered in foods. The primary outcome is the number of participants with treatment-emergent adverse events following each dose, assessed over one week at each dose. The record lists 13 outcome measures and identifies fecal short-chain fatty acids as secondary outcomes at each dose. The registry does not report a detailed protocol for how those secondary outcomes were measured or analyzed.

One subject dropped from the study at Day 3 of week one and was not included in the analysis, according to the primary outcome description. The registry does not explain the reason for withdrawal or give further detail about the analysis population.

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.

Foods Containing 10 g Soy Flour

Reasons for not completing this period:

Foods Containing 20 g Soy Flour

Foods Containing 30g Soy Flour

Analysis population for the primary outcome, as defined in the registry: One subject dropped from the study at Day 3 of week one and was not included in the analysis.

5. Baseline Characteristics

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

Population: The participant dropped from the study was excluded from the analysis. The data relates to seven participants who were tested for tolerance to the three doses of soy flour

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events Following Each Dose of Soy, measured over One week at each dose.

The primary endpoint counts participants with treatment-emergent adverse events after each soy dose. It is a count of people with an event, rather than a measure of event severity, duration, or rate per unit of exposure. The listed timeframe is one week at each dose. Examples in the outcome description include headache, nausea, and vomiting.

For a dose-escalation study, recording adverse events at each dose provides a direct descriptive account of tolerability during the planned exposure. The study description says the study physician and coordinator would review the events and determine safety. The registry does not report a formal rule defining how that review translated into a maximum tolerated dose, nor does it report a numerical threshold for stopping escalation.

In general, an event count can help identify whether any participants experienced a recorded event during a treatment period. It does not, by itself, establish that the treatment caused the event, indicate how severe an event was, or characterize risks beyond the observed study participants and exposure periods. The sequential design also matters: the dose groups are not independent randomized samples, and progression to a higher dose depended on tolerating the prior dose.

The record reports 0 participants affected by serious adverse events at each dose. For other adverse events, it reports 0 at 10 g, 1 at 20 g, and 1 at 30 g. Those counts are descriptive. The registry does not provide event-level details for the reported non-serious events in the posted safety results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the event count represent?

The primary measure is the number of participants with treatment-emergent adverse events following each dose. A participant count records whether people were affected, rather than how many separate episodes occurred. The registry labels the outcome unit as participants and gives a one-week timeframe at each dose. It does not provide a detailed operational definition of a treatment-emergent event, such as the exact timing rule used to classify an event as emerging during treatment.

In general, counting affected participants is a straightforward way to describe how many people had a recorded event during a specified observation period. It does not convey the event’s intensity, duration, or clinical importance unless those features are reported separately. The record gives examples of symptoms to be reviewed, but the posted safety results do not include a detailed account of the events reported at the higher doses.

Why does the sequence affect interpretation?

The registry describes non-randomized allocation and a crossover model. Participants who tolerated a dose were to proceed to the next dose, with no wash-out period between the 10 g and 20 g doses. This means exposure to the higher doses depended on tolerating an earlier dose. The later dose groups consequently should not be treated as independent groups assigned at random to different treatments. The registry specifically warns that the arms are not a like-for-like control comparison.

In general, random allocation helps make comparison groups similar on average at the outset. Without randomization, observed differences can reflect the study sequence, participant selection, prior exposure, or other factors as well as dose. A crossover design can provide within-person information when the same participants receive multiple conditions, but interpretation depends on details such as the order of treatment, wash-out, and analysis. The record describes escalation and no wash-out between the first two dose levels; it does not report a formal comparative analysis accounting for repeated observations.

How should the counts be read?

The posted results distinguish serious adverse events from other adverse events and list the number at risk and the number affected for each dose. At 10 g, 8 participants were at risk and 0 were affected in either category. At 20 g, 7 were at risk, 0 were affected by serious adverse events, and 1 was affected by another adverse event. At 30 g, 7 were at risk, 0 were affected by serious adverse events, and 1 was affected by another adverse event. Deaths are listed as 0 for all three dose levels.

In general, a denominator describes the group contributing to a particular result, but it does not resolve all questions about exposure and missing observations. The primary outcome description notes that one subject dropped out at Day 3 of week one and was not included in the analysis. The registry does not give further details on the relationship between that exclusion and the dose-specific risk sets. The figures should be reported as posted rather than reconciled through assumptions.

What can statistical uncertainty tell us?

In general, a confidence interval expresses the range of values compatible with data under a specified statistical method. For counts from a small study, uncertainty can be substantial, especially for uncommon events. The registry does not report confidence intervals or a formal statistical analysis for the primary safety outcome, and the record lists 0 analyses. Without such estimates, the event counts do not quantify the precision of a comparison between dose levels.

The record includes planning assumptions for sample-size illustrations based on the observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. These are planning illustrations, not evidence of the trial’s original design or observed power. In general, a sample-size calculation describes what a hypothetical study might require under its assumptions; it does not show that a completed study had adequate power. The registry does not report the study’s own sample-size justification or a formal statistical analysis plan.

What about over-dispersion and event models?

In general, over-dispersion occurs when count data vary more than a statistical model expects. It can affect uncertainty estimates in analyses that model event counts. This primary endpoint is defined as a count of participants with an event, and the registry does not report a model for the outcome or an over-dispersion assessment. No model-based inference should be inferred from the posted counts.

Because the outcome is binary at the participant level—affected or not affected within the stated category—the main posted information is the number affected and the number at risk. General methods for comparing proportions require assumptions about independent observations and comparable groups. The non-randomized sequential structure means those assumptions cannot simply be presumed for a dose-to-dose comparison. The record does not report an adjusted analysis or a method designed to account for repeated exposure.

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("Foods Containing 10 g Soy Flour", "Foods Containing 20 g Soy Flour", "Foods Containing 30 g Soy Flour")
n      <- c(7, 7, 7)
events <- c(0, 1, 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  Foods Containing 10 g Soy Flour  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9
ARM  Foods Containing 20 g Soy Flour  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7
ARM  Foods Containing 30 g Soy Flour  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary safety outcome and secondary fecal short-chain fatty acid outcomes at 10 g, 20 g, and 30 g. It lists 0 analyses. A multiplicity strategy—such as an order for testing outcomes or an adjustment for making multiple statistical comparisons—is not reported in the registry record. No inferential results for the secondary outcomes are included in the registry record described for this record.

The primary outcome description states that one subject dropped from the study at Day 3 of week one and was not included in the analysis. The registry does not report the reason for the dropout, whether any outcome data were available before withdrawal, or how missing measurements were handled. It also does not provide a fuller definition of the analysis population or explain how the dose-specific risk sets were determined.

In general, missing-data methods describe how analyses handle outcomes that are not observed. Different approaches can lead to different interpretations, so the method matters when some participants do not contribute complete follow-up. No imputation method, sensitivity analysis, or missing-data assumption is reported in the registry record. The listed counts should therefore be understood as the posted results, alongside the stated exclusion, rather than as evidence that missing observations had no effect.

The registry does not report a prespecified statistical analysis plan, an interim-analysis plan, or a sample-size justification. These omissions do not establish that such plans were absent; they mean their details are not reported in the registry 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 non-serious adverse event terms

The serious-adverse-event figures are zero affected participants at all three dose levels. The registry lists 8 participants at risk at 10 g and 7 at risk at both 20 g and 30 g; deaths are also listed as 0 at every dose. These are the posted counts for the one-week period at each dose.

Zero recorded serious events means that none were reported in these study results. It does not establish that the risk is zero or rule out uncommon events. The enrollment was 8, and the registry notes that one subject left at Day 3 of week one and was not included in the analysis. Details about the reason for leaving and dose-specific follow-up are not reported in the registry record.

The separate “other adverse events” figures are 0 affected at 10 g, 1 at 20 g, and 1 at 30 g. The record does not provide event-level descriptions for those counts. They should not be interpreted as showing that the same participant or the same event occurred at both later doses, since that information is not reported. Nor should the figures be compared as if participants were randomly assigned to separate dose groups: the study used sequential escalation based on tolerability.

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

The record documents a small, non-randomized dose-escalation study in elderly people with obesity, with soy flour foods given daily for one week at each planned dose. The posted primary safety results record no serious adverse events and no deaths at any dose. They also record no other adverse events at 10 g and one affected participant at each of 20 g and 30 g.

These results describe what was recorded during the study; they do not establish that soy flour caused or prevented an event. The study did not use randomized, independent dose groups, and participants who tolerated one dose were to proceed to the next. Prior exposure and the selection of participants who advanced complicate direct comparisons across the dose levels. The registry itself cautions against treating the arms as a like-for-like control comparison.

The event counts also do not give a complete picture of severity, duration, recurrence, or clinical interpretation. The registry’s primary outcome description says the physician and coordinator would review events and determine safety, but the posted figures do not include their event-level judgments. The numerical results alone do not establish a maximum tolerated dose; the registry does not report a formal decision rule or a specific maximum tolerated dose in the registry record for this record.

In general, a small study with short observation periods can describe events observed during those periods but has limited ability to characterize uncommon or delayed outcomes. The findings do not establish safety for populations beyond the elderly people with obesity described in the summary, or for exposure longer than the specified one-week periods. The registry record does not report a formal statistical comparison, confidence intervals, or analyses of the secondary fecal short-chain fatty acid outcomes. The results are best read as a descriptive account of recorded adverse events within this particular dose-escalation study.

14. Why This Trial Matters Statistically

This study illustrates why a clear distinction between dose escalation and randomized comparison matters. The same participants could progress through increasing doses if they tolerated earlier exposure, and there was no wash-out period between the first two dose levels. The resulting groups are not like-for-like control groups, as the registry itself notes. A simple contrast between their event counts would not isolate the effect of dose.

It also shows the limits of interpreting zero-event findings. The registry reports no serious adverse events and no deaths, but the study’s enrollment was 8 and the observation period was one week at each dose. In general, a lack of recorded events in a small, short study does not by itself establish that an event is impossible or that its frequency is precisely known. The record does not provide uncertainty estimates for the safety counts.

The stated primary outcome—participants with treatment-emergent adverse events—is a direct descriptive measure, but it does not answer every safety question. Event type, severity, duration, and the investigator’s assessment would add context; the posted safety figures do not report those details for the non-serious events. The one subject excluded after leaving at Day 3 of week one also makes the analysis-population description relevant to interpretation.

Finally, the record lists multiple outcomes but no statistical analyses. That makes it especially important not to infer a planned hypothesis test or a definitive comparative conclusion from the counts. The study is statistically informative as an example of how small dose-escalation records can describe observed tolerability while leaving uncertainty about comparative effects, missing observations, and generalizability.

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 principal limitation is the non-randomized sequential design. Participants who tolerated a dose were to receive the next dose, so exposure to later doses depended on earlier tolerability. The dose levels are not independent randomized groups, and the registry cautions that they are not a like-for-like control comparison. The record does not report a separate control condition or a formal analysis accounting for repeated exposure.

Exposure was described as one week at each dose, with no wash-out period between the first two doses. Without a wash-out, effects from an earlier dose could carry into a later period; whether that occurred is not reported in the registry record. The record also does not provide a detailed account of actual adherence or exposure for each participant.

The enrollment was 8, and one subject left at Day 3 of week one and was excluded from the analysis. The reason for withdrawal, the extent of any data collected before leaving, and the handling of missing data are not reported. Although risk sets are listed for each dose, the record does not explain their relationship to the withdrawal in further detail.

The posted safety results do not give event-level descriptions for the other adverse events recorded at 20 g and 30 g. The record does not report their severity, duration, timing within the dose period, or whether events recurred. It also does not report confidence intervals, inferential analyses, a statistical analysis plan, a multiplicity strategy, or the study’s sample-size justification. These limitations restrict interpretation to the descriptive results recorded for this study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Tolerability of Soy Fiber — NCT04499482.
• Registry record last updated 2023-05-18; status last verified 2023-05.
• Results first posted 2023-05-18.
• 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 describes a completed, non-randomized crossover dose-escalation study of soy flour foods in elderly people with obesity. The listed enrollment is 8. Participants were intended to consume foods containing 10 g, 20 g, and 30 g of soy flour every day for one week at each dose, progressing when the previous dose was tolerated.

The primary outcome was the number of participants with treatment-emergent adverse events following each dose. The posted results report no serious adverse events or deaths at any dose, and other adverse events affecting 0 participants at 10 g, 1 at 20 g, and 1 at 30 g. One subject dropped from the study at Day 3 of week one and was not included in the analysis.

The record lists fecal short-chain fatty acid outcomes at each dose as secondary outcomes. It lists 13 outcome measures and 0 analyses. The non-randomized sequence and the limited information about event details, missing data, and statistical methods mean the safety counts are descriptive rather than a randomized comparison between doses.