RCT of Mushroom Based Natural Product to Enhance Immune Response to COVID-19 Vaccination: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RCT of Mushroom Based Natural Product to Enhance Immune Response to COVID-19 Vaccination (NCT04951336), a randomized na study. The primary outcome is AST Normal to Abnormal Transition.

2. Clinical Question

This question is about a laboratory-value transition during the stated 14-day timeframe. It is not a direct measure of vaccine antibody response: the listed secondary outcomes include SARS-CoV-2 Receptor Binding Domain and Spike Protein measures, while the primary endpoint is AST status. The registry record does not establish that a change in AST represents a change in vaccine response, nor does it report a clinical interpretation linking the endpoint to protection from COVID-19. The trial’s brief summary frames the study as an evaluation of a mushroom-based adjunct at the time of vaccination, but the posted primary result addresses the AST transition outcome.

3. Trial Design

The registry describes a multicenter, randomized, double-blind, placebo-controlled trial using a parallel-group model. Masking is recorded as triple. The sponsor was the University of California, San Diego. The record lists the study as completed, with phase recorded as NA. Enrollment was 90. The listed start date was 2021-06-10 and the primary completion date was 2022-01-21.

Participants were assigned to Mushrooms or Placebo. The intervention is named FoTv and classified as a dietary supplement. The arm descriptions specify 8 capsules three times a day for 4 consecutive days in each group. The placebo is described as organic brown rice. Further details about the randomization procedure, concealment, and which parties were masked are not reported in the registry record. The arm description text does not provide a complete account of missed-dose instructions, so those details cannot be characterized from the record.

The overall enrollment figure and the primary endpoint analysis groups are not the same population. For this endpoint, only participants normal at baseline were included; participants abnormal at baseline were excluded. The registry reports 50 participants in the Mushrooms endpoint group and 38 in the Placebo endpoint group. These are the group sizes associated with the endpoint result, not a replacement for the overall enrollment figure. The reasons for the difference between the endpoint groups and the full study groups are not reported in the registry record.

The primary endpoint was the percentage of baseline-normal participants whose AST values transitioned to abnormal by Day 14. Secondary outcomes listed in the registry include SARS-CoV-2 Receptor Binding Domain, SARS-CoV-2 Spike Protein, side-effect number, and side-effect severity. The record lists 8 outcome measures and 8 analyses overall, but does not give enough detail to reconstruct the full analysis plan or the role of every measure. The protocol’s sample-size justification, planned interim analyses, and detailed 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

Analysis population for the primary outcome, as defined in the registry: Number of participants who were normal at baseline. Participants who were abnormal at baseline were excluded, therefore the number of participants in this analysis is different from the total number of participants in the Mushrooms or Placebo groups described in the study arms/groups.

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 AST Normal to Abnormal Transition, measured over 14 days.

The primary endpoint measures a transition in AST status, rather than the average AST value or the number of participants with an abnormal value at a single time point. Its denominator is restricted to participants whose values were normal at baseline. The outcome is the percentage of those participants who had an abnormal value at Day 14. The stated timeframe is 14 days.

This type of transition measure can describe how often a status change occurs within a defined follow-up period. Restricting the analysis to people with normal baseline values makes the endpoint specifically about movement from normal to abnormal; people who were already abnormal cannot undergo that defined transition and were excluded. As a result, the analysis population differs from the full Mushrooms and Placebo groups, and its group sizes should be read in the context of that eligibility rule.

AST is a laboratory measure, and the posted endpoint is a classification based on normal or abnormal values. The registry record does not report the threshold used to classify values, the underlying AST measurements, or how borderline values were handled. It also does not state that this endpoint is a measure of immune response. Although the study’s broad aim involved an adjunct to COVID-19 vaccination, the primary endpoint concerns AST status. The relationship between this laboratory transition and the other listed outcomes is not reported in the registry record.

The reported percentages are 2.0% for Mushrooms and 2.6% for Placebo. The registry’s analysis compares frequencies and reports a corrected chi-squared method. No confidence interval is reported for that comparison, so the precision of the estimated contrast cannot be summarized with an interval from the posted result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a count-type outcome expressed as a percentage: participants are classified according to whether they moved from normal AST at baseline to abnormal AST at Day 14. The analysis excludes people who were abnormal at baseline. The reported endpoint group sizes are 50 for Mushrooms and 38 for Placebo. Because the denominator is selected by baseline status, the comparison does not use the full enrolled population.

What does the chi-squared method do?

In general, a chi-squared test assesses whether categorical outcome frequencies differ across groups under a null hypothesis of no association between group and outcome. The registry labels the method “Chi-squared, Corrected” and the reported parameter “ratio of frequencies.” It does not identify the specific correction or give the complete frequency table. Without those details, the analysis cannot be independently reproduced from the posted result alone.

The reported analysis gives a ratio-of-frequencies value of 0.04 and p = 1.000. The p-value is a measure of compatibility between the observed data and the test’s null model, conditional on the model and method. It is not a measure of the probability that the intervention has no effect, and it does not establish equivalence. The ratio is an estimate on the scale named by the registry; it should not be reinterpreted as a risk ratio, percentage-point difference, or other measure unless the precise definition is available. The record does not supply a confidence interval for the estimate.

Why does the endpoint denominator matter?

A transition outcome requires an eligible starting state. Here, only participants with normal baseline AST values are counted in the primary analysis, while baseline-abnormal participants are excluded. The resulting endpoint group sizes are 50 and 38. This selection defines the question being answered, but it also means these results describe a subset rather than the entire enrolled group. The registry does not report why the groups differ in size or provide a participant-flow account that would explain all exclusions and missing observations.

In general, sparse categorical outcomes can produce imprecise estimates, and some large-sample approximations may be less dependable when event counts are small. That is a general methodological issue, not a finding that a particular assumption was violated in this trial. The underlying event counts and the exact correction are not reported in the registry record, so it is not possible to assess those details from this result alone.

How should a confidence interval be understood?

In general, a confidence interval describes uncertainty around an estimate under a specified statistical procedure. It gives a range of values compatible with the observed data and method, rather than a guarantee that the true value lies within that particular interval. No confidence interval is reported for the primary comparison. Therefore, the p-value and point estimate are not accompanied by an interval that communicates the estimated precision of the ratio of frequencies.

What can planning calculations tell readers?

General sample-size planning calculations depend on assumptions about the significance level, allocation, statistical approximation, and effect size to detect. The planning description associated with this analysis uses a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence about the trial’s original design rationale. They do not constitute observed power, and they should not be read as the actual number of participants needed or as a justification for the enrollment. The protocol’s sample-size justification is not reported in the registry record.

The registry record does not report an interim-analysis plan, the handling of multiple comparisons, the definition of the AST normal range, or a full statistical analysis plan. The secondary outcome list includes SARS-CoV-2 Receptor Binding Domain, SARS-CoV-2 Spike Protein, side-effect number, and side-effect severity. The record lists 8 outcome measures and 8 analyses, but those totals do not explain which analyses were primary, secondary, or exploratory, or whether any adjustment for multiplicity was planned. These details are important when interpreting a collection of analyses, because separate tests can create multiple opportunities for chance findings.

Finally, a reported test is only one component of interpretation. The endpoint definition, analysis population, estimate, uncertainty, and prespecified role of the outcome all matter. For this result, the endpoint and exclusion of baseline-abnormal participants are stated, as are the method, estimate, and p-value. The confidence interval, complete outcome frequencies, test correction details, and several analysis-plan details are not reported in the registry record.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a corrected chi-squared analysis of the frequency outcome. The listed estimate is a ratio of frequencies of 0.04, with p = 1.000. The registry does not report a confidence interval for this estimate. The endpoint percentages are 2.0% for Mushrooms and 2.6% for Placebo, among the groups of 50 and 38 participants who were normal at baseline.

No recalculated comparison is reported for this count-type endpoint: the available analysis information is not sufficient to estimate a two-arm recalculation. Consequently, there is no independent unadjusted recalculated estimate to set beside the sponsor’s reported result. The sponsor’s value should therefore be presented as the reported analysis, without implying that an independent calculation confirms or contradicts it.

The absence of a recalculation is not evidence that the sponsor’s result is correct or incorrect. Reproducing a comparison would require adequate underlying counts and a clearly defined effect measure. The registry gives the method label and result but does not provide the full frequency table, confidence interval, or details of the correction. The discrepancy flag is false, but that does not supply the missing information needed to reconstruct the result. The sponsor’s reported p-value should also not be interpreted as proof of no difference or of equivalence.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists SARS-CoV-2 Receptor Binding Domain, SARS-CoV-2 Spike Protein, side-effect number, and side-effect severity as secondary outcomes. It also records 8 outcome measures and 8 analyses. These registry entries indicate that the study included multiple outcomes or analyses, but the registry record does not describe how they were prioritized or whether a multiplicity adjustment was planned. The primary result’s p = 1.000 can be reported as the result of its named test; the record does not establish how it should be interpreted relative to all other analyses.

In general, testing multiple outcomes can increase the chance that at least one result appears notable by chance if each is considered separately. Methods such as adjusted significance thresholds or hierarchical testing can address that issue, but the choice depends on the prespecified analysis plan. No such plan is reported in the registry record, so it is not possible to say whether multiplicity was controlled, or how the primary and secondary outcomes were ordered for interpretation. Results for the secondary outcomes are not included in the registry record for this analysis, so their estimates and uncertainty cannot be assessed.

The analysis population is partly described: the primary endpoint includes participants whose AST values were normal at baseline and excludes those who were abnormal. The endpoint group sizes are 50 and 38. The registry says these numbers differ from the total participants in the study arms, but does not provide a full account of eligibility, follow-up, or reasons for any missing endpoint data. Missing-data methods, imputation, and sensitivity analyses are not reported in the registry record.

The record also does not specify whether the analysis followed an intention-to-treat, per-protocol, or other population definition. The baseline-normal restriction is clear, but it does not by itself identify how participants with unavailable Day 14 results were handled. Details about protocol deviations, adherence, and the handling of incomplete measurements are not reported in the registry record. These uncertainties matter because outcome availability and analysis-population choices can affect a group comparison.

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: er visit (0.0%), hospitalization (0.0%), urgent care visit (0.0%).

The serious adverse event figures are reported separately from the primary AST endpoint. The registry lists zero serious adverse events among 52 participants at risk in the Mushrooms safety group and zero among 38 participants at risk in the Placebo safety group. Deaths are also recorded as zero in both groups. The listed serious-event terms—ER visit, hospitalization, and Urgent Care Visit—each have a reported value of 0.0%.

These figures describe what was recorded in the registry for the stated safety groups. They do not mean that no adverse events of any kind occurred. The record separately reports other, non-serious adverse events affecting 8 participants in the Mushrooms group and 4 in the Placebo group. The serious-event counts and the counts of other adverse events address different categories and should not be combined or treated as interchangeable.

In general, observing zero serious events in a study does not establish that the underlying risk is zero; the information is limited by the number of participants observed and the period and methods of follow-up. The registry record does not give further details about event ascertainment, severity grading beyond the serious/non-serious distinction, or follow-up completeness. These figures are therefore a description of reported safety events, not a definitive estimate of risk.

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

The primary result describes AST transitions over 14 days among participants whose AST values were normal at baseline. The reported percentages were 2.0% for Mushrooms and 2.6% for Placebo. The corrected chi-squared analysis reported a ratio of frequencies of 0.04 and p = 1.000. These are the posted results for this endpoint and analysis population.

The result does not answer whether FoTv changes vaccine-induced immune response. Although the trial’s broad purpose concerned use of the mushroom product as an adjunct to COVID-19 vaccination, the primary outcome recorded is a laboratory status transition for AST. The receptor-binding-domain and spike-protein measures are listed as secondary outcomes, but their results are not included in the registry record for this analysis. The AST finding should not be substituted for those outcomes.

The reported p-value does not show that the groups are identical, and it does not establish equivalence. A confidence interval is not reported, which limits assessment of the precision of the comparison. The group percentages are descriptive results for the baseline-normal subset; they should not be treated as results for every participant enrolled. The registry record does not report the full outcome counts, the AST classification threshold, or detailed handling of missing Day 14 measurements.

These data also do not by themselves establish the cause of an observed transition or its clinical importance. The record does not report how an AST category change relates to symptoms, vaccine response, or a longer-term outcome. No medical conclusion follows from the posted primary comparison alone. The most bounded interpretation is that the registry reports low percentages in both analyzed groups and a p-value of 1.000 from the named test, without a confidence interval or enough detail to independently reconstruct the comparison.

14. Why This Trial Matters Statistically

This trial illustrates why defining the analysis population is central to interpreting a clinical result. Enrollment was 90, but the primary AST analysis excluded participants who were abnormal at baseline. The endpoint group sizes were 50 for Mushrooms and 38 for Placebo. Thus the primary comparison concerns people eligible to experience the specified normal-to-abnormal transition, not the whole enrolled population. Reading the endpoint without its eligibility rule could give a misleading impression of whom the percentages describe.

It also shows why an outcome should be distinguished from the study’s broader rationale. The trial was framed as evaluating a mushroom-based adjunct to vaccination, while its primary posted endpoint is AST transition. Separate secondary measures concern SARS-CoV-2 receptor-binding domain and spike protein. Different outcomes answer different questions, and a finding on a laboratory status transition cannot stand in for an immune-response outcome.

Finally, the record illustrates the value of reporting uncertainty and analysis details alongside a test result. A point estimate and p-value are available, but no confidence interval is reported, and the complete frequency table and correction details are not reported. The result cannot be independently reconstructed from those details alone. The absence of a confidence interval limits how precisely readers can judge the estimate, while the absent analysis-plan information makes it difficult to assess how the primary result fits among the listed outcomes. These are important distinctions in statistical interpretation even when the reported result itself is straightforward to quote.

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 of interpretation follow from the registry record. The primary endpoint population was restricted to participants with normal AST values at baseline, excluding those who were abnormal. The analysis groups therefore differ from the full study groups, and the record does not provide a complete participant-flow account explaining the endpoint group sizes of 50 and 38.

The posted comparison lacks a confidence interval and the complete frequency table. Although the method is described as corrected chi-squared and the estimate as a ratio of frequencies, the specific correction and the underlying counts are not reported. This prevents independent reconstruction of the comparison and limits assessment of its precision. The AST normal-range threshold and handling of borderline values are also not reported.

Missing-data handling and the exact analysis population beyond the baseline-normal restriction are not reported. The record does not specify how unavailable Day 14 values, protocol deviations, or incomplete follow-up were addressed. It also does not report whether analyses were intention-to-treat, per-protocol, or defined by another approach. Such information would help clarify the interpretation of the observed percentages.

The registry lists secondary immune-related and side-effect outcomes, but their results are not included in the registry record for this analysis. The plan for multiplicity, any interim analyses, and the detailed statistical analysis plan are not reported in the registry record. The sample-size justification is also not reported, so the enrollment figure cannot be treated as evidence that the study was designed for a particular precision or power. These limitations constrain what can be concluded from the primary posted result, without changing the figures that the registry reports.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: RCT of Mushroom Based Natural Product to Enhance Immune Response to COVID-19 Vaccination — NCT04951336.
• Registry record last updated 2025-08-17; status last verified 2025-08.
• Results first posted 2025-08-17.
• 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

NCT04951336 is a completed, randomized, parallel-group, triple-masked, placebo-controlled trial sponsored by the University of California, San Diego. The registry lists enrollment of 90 and a study period beginning 2021-06-10, with primary completion on 2022-01-21. The study evaluated FoTv as an adjunct to COVID-19 vaccination, with organic brown rice placebo.

The primary outcome was the percentage of participants with normal baseline AST who transitioned to abnormal by Day 14. The reported endpoint groups were 50 for Mushrooms and 38 for Placebo; the percentages were 2.0% and 2.6%. The corrected chi-squared comparison reported a ratio of frequencies of 0.04 and p = 1.000, with no confidence interval. The record lists secondary outcomes involving receptor-binding domain, spike protein, side-effect number, and side-effect severity. Details on multiplicity, missing-data handling, the complete analysis plan, and the sample-size justification are not reported in the registry record.