A Study Evaluating Quality of Life Parameters Following Use of Emergen-C: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating Quality of Life Parameters Following Use of Emergen-C (NCT06654089), a randomized phase 4 study. The primary outcome is Adjusted Mean Change From Baseline in Multidimensional Fatigue Inventory (MFI) General Fatigue Domain Score at Week 12.

2. Clinical Question

3. Trial Design

The registry identifies NCT06654089 as a Phase 4, randomized, double-masked, parallel-group study. The condition is listed as Dietary Supplements, and HALEON is the sponsor. The registry lists an enrollment of 299 and records the study as completed. The recorded start date is 2024-10-30, and the primary completion date is 2025-02-24.

The two assigned products were Emergen-C Core Super Orange Powder and placebo. Participants were instructed to take their assigned sachet once daily, mixed in water, for up to 12 weeks. The primary endpoint was assessed at Week 12 relative to Baseline. Secondary outcomes included adjusted changes in five MFI fatigue domains at Weeks 4 and 8, as well as selected individual MFI item scores at Weeks 4, 8, and 12.

The registry describes the primary analysis population as modified Intention-To-Treat. The stated eligibility for this population required randomization, a completed Baseline visit, at least one post-Baseline MFI domain assessment, and at least one dose of allocated product. The primary result lists 146 participants in the Emergen-C arm and 147 in the placebo arm. The adverse-event results use different group counts: 147 and 150, respectively. The registry record does not explain the difference between these analysis counts.

The registry does not report the original sample-size justification, the trial’s detailed design assumptions, interim analyses, or a complete statistical analysis plan. Those details should not be inferred from the results or from the separate planning illustration.

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.

Before assignment: A total of 299 participants were enrolled and randomized into two treatment groups: 149 to the Emergen-C group and 150 to the Placebo group. A total of 146 participants from the Emergen-C group and 147 from the Placebo group completed the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The modified Intention-To-Treat (mITT) population consisted of all participants who were randomized, completed the Baseline visit, completed at least one-post Baseline MFI domain assessment, and took at least one dose of their allocated randomized product. Only those participants with data available at the specified time point were analyzed.

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 Safety population included all randomized participants who had taken at least one dose of their randomized study product. Two participants in Emergen-C group did not take any study product as the treatment package was not delivered. Therefore, there were 147 Emergen-C participants and 150 Placebo participants in the Safety population.

6. Primary Endpoint

The registry lists the primary outcome as Adjusted Mean Change From Baseline in Multidimensional Fatigue Inventory (MFI) General Fatigue Domain Score at Week 12, measured over Baseline and Week 12.

The primary endpoint was adjusted mean change from Baseline in the MFI General Fatigue Domain Score at Week 12. The Multidimensional Fatigue Inventory is described as a 20-item instrument covering general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. The general fatigue domain contains four items.

For each item, participants answered how they felt on a scale from 1, “yes, that is true,” to 5, “no, that is not true.” Positively phrased items were reverse-scored, while negatively phrased items were scored at face value. The four item scores were summed to create a general fatigue domain score ranging from 4 to 20. Lower scores indicate lower fatigue.

Change was calculated by subtracting the Baseline score from the Week 12 score. Thus, a negative change represents a lower Week 12 score than Baseline and is described in the registry as improvement in fatigue. The endpoint is useful for comparing change in a defined fatigue measure between randomized groups over the stated period. It captures this particular domain, not every aspect of fatigue or quality of life. The registry does not report a threshold for interpreting whether a change is important to participants.

7. Results Posted in the Registry

• Emergen-C Core Super Orange Powder (Test Product): mean -5.23 versus -5.48 on control; difference 0.25 (95% CI -0.55 to 1.05), standardized effect d = 0.07; z-test p = 0.542.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the reported mean difference represent?

The primary measure is continuous: it is a score on a scale, and the registry identifies the reported arm results as least-squares means with standard errors. A mean summarizes the average score change in a group. The sponsor’s adjusted mean difference compares the groups after the repeated-measures model’s adjustment. The registry does not report which covariates or other details were used for that adjustment, so those should not be inferred.

The reported adjusted mean difference is 0.25. Its sign follows the comparison of Emergen-C with placebo. The arm means are -5.23 and -5.48. Because a negative score change indicates a lower score at Week 12 than at Baseline, the direction of a change and the direction of a between-group difference need to be kept distinct. A positive difference between two negative changes does not mean that the test group had a positive change.

Why does the registry use a repeated-measures model?

General statistical explanation: a repeated-measures model can analyze outcome measurements collected from the same participants at more than one time. Measurements from one person are usually related rather than independent, and a model can account for that within-person structure while estimating group differences over time. The sponsor identifies its primary analysis method as Mixed Model with Repeated Measures. The registry’s primary endpoint is at Week 12, and secondary outcomes include assessments at Weeks 4 and 8. The exact model specification, covariance structure, and adjustment variables are not reported in the registry record.

General statistical explanation: adjusted estimates can differ from simple comparisons of group summaries because they are based on a model and its specified adjustments. The registry’s description of the sponsor result is an adjusted mean difference. The recalculation is explicitly unadjusted and uses posted summary statistics. It is a useful numerical cross-check, but it does not reproduce the sponsor’s model.

What is the role of the standard error and confidence interval?

The standard error describes the statistical uncertainty of an estimated mean under its analysis assumptions. It is not the spread of individual participant scores. The arm-level standard errors are 0.29 in each group. A confidence interval for the between-group estimate describes a range of values compatible with the estimate under the model and its assumptions. The sponsor reports a 95% interval from -0.56 to 1.06. Since that interval includes zero, the data do not precisely establish the sign of the group difference under this analysis.

General statistical explanation: a confidence interval is not a guarantee that the true effect lies in the particular interval, nor is it a range containing a stated proportion of individual participants. Its interpretation depends on the statistical model and the data collection process. For this result, it is most useful to consider the interval together with the estimated difference and the endpoint’s score direction.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when variability in observed data is greater than a model expects. If a model understates variability, standard errors may be too small and intervals may be too narrow. The primary endpoint is continuous, and the posted recalculation includes an approximate pooled standard deviation of 3.51. The registry does not report a separate assessment of over-dispersion, and the concept should not be treated as a finding about this trial.

How should the recalculation be understood?

The unadjusted recalculation reports a mean difference of 0.25, a 95% interval from -0.554 to 1.054, and p = 0.542. It derives a simple comparison from posted group estimates and standard errors; the pooled standard deviation is marked as approximate. This calculation does not account for the sponsor’s repeated-measures model or any model adjustments. It should therefore be read as a separate, transparent check of the posted summaries, not as a replacement for the sponsor’s analysis.

General statistical explanation: statistical significance and effect size answer different questions. A p-value summarizes compatibility with a specified null model, while the mean difference describes the estimated score contrast in the endpoint’s units. The confidence interval conveys uncertainty about that contrast. None of these quantities alone determines whether a score change is important to participants. The registry does not report a threshold for clinical importance for this endpoint.

10. Confidence Intervals and Precision

The sponsor’s adjusted estimate is 0.25, with a 95% confidence interval from -0.56 to 1.06. This interval spans zero, so it is compatible with a small difference in either direction as well as with no difference under the fitted model. Its width also signals that the estimated group contrast is not tightly pinned to a single value. The result should not be reduced to the point estimate alone.

The interval is expressed in score units, matching the endpoint. A positive difference is the Emergen-C change minus the placebo change; negative changes in either arm indicate lower fatigue scores relative to Baseline. The interval therefore describes uncertainty in the between-group contrast, not uncertainty in either arm’s change considered separately. The registry does not report a threshold that would distinguish a clinically important from an unimportant score difference.

The simple unadjusted recalculation gives a 95% interval from -0.554 to 1.054. It is close to the sponsor’s interval, but it is derived by a different method and should not be treated as the sponsor’s result. The recalculation also uses an approximate pooled standard deviation. The reported sponsor model remains the primary registry analysis.

General statistical explanation: confidence intervals reflect sampling uncertainty under the analysis assumptions, but do not account automatically for every possible source of bias, missing data, measurement limitations, or model misspecification. The registry record does not provide enough detail to assess all such issues. Thus, precision should be judged from the reported interval while keeping the analysis population and unreported model details in view.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total events: this is a continuous outcome, and the figures are participant counts per group. The illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers effects equal to 100%, 75%, and 50% of the observed effect.

In plain language, the 80% power column gives the modeled number of participants per arm for an 80% chance of detecting the stated effect under those assumptions. The 90% power column gives the corresponding modeled number per arm for a 90% chance. The rows plan for 100% of the observed effect, planning for 75% of the observed effect, and planning for 50% of the observed effect. Smaller effects need more participants to detect under the same assumptions, which is why the planning counts rise as the effect fraction becomes smaller.

The curve should be read as a visual expression of the same planning relationship: required enrollment changes with the effect size being targeted. It is an illustration based on the observed estimate, not evidence about the original design. These figures are not observed power. The registry record does not report the trial’s original sample-size justification or original design assumptions; the planning illustration does not establish what enrollment was intended to achieve in this study.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.250; pooled standard deviation σ = 3.510.
2. n = 2 × (1.96 + 0.842)² × 3.510² / 0.250² = 3,094.5, rounded up to 3,095 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.25                      # observed difference in means
sigma <- 3.5100989304745                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(6654089)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 3,095 (80% power), 4,143 (90% power)
 75% of observed effect: n per arm = 5,502 (80% power), 7,365 (90% power)
 50% of observed effect: n per arm = 12,379 (80% power), 16,571 (90% power)
power.t.test: 3095.5 
Simulated power at n = 3,095 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The sponsor’s registry analysis uses a Mixed Model with Repeated Measures and reports an adjusted mean difference of 0.25, a 95% confidence interval from -0.56 to 1.06, and p = 0.547. This is the study’s reported primary comparison. It should be distinguished from the simple unadjusted recalculation, which gives the same point estimate of 0.25, a 95% interval from -0.554 to 1.054, and p = 0.542.

The recalculation uses posted summary statistics and an approximate pooled standard deviation; it does not reproduce the sponsor’s repeated-measures model. Similar point estimates do not remove that methodological distinction. The sponsor’s result is the relevant reported analysis, while the recalculation provides a separate unadjusted check. The registry record does not report sufficient model details to reproduce the sponsor’s adjusted analysis independently.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 33 outcome measures and 28 posted secondary outcomes. Secondary measures include adjusted changes in the MFI general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue domains at Weeks 4 and 8. Other listed measures concern selected individual MFI items at Weeks 4, 8, and 12. This range of outcomes and assessment times means that the primary endpoint is only one part of the study’s outcome set.

When many outcomes or comparisons are examined, the chance of at least one apparently unusual result can rise. General statistical explanation: multiplicity procedures can control or otherwise address this issue, but the appropriate approach depends on the prespecified analysis plan and the role of each outcome. A multiplicity adjustment is not reported in the registry record. The registry record also does not report whether the outcomes were organized into a formal testing hierarchy or how secondary findings were intended to be interpreted.

The primary population is described as modified Intention-To-Treat: participants had to be randomized, complete Baseline, provide at least one post-Baseline MFI domain assessment, and take at least one dose of assigned product. The registry further states that only participants with data available were included. The detailed handling of missing outcome data, reasons for missingness, imputation, and sensitivity analyses is not reported in the registry record. Although the sponsor used a repeated-measures model, that label alone does not establish how every missing observation was handled.

The registry record does not report interim analyses or the complete statistical analysis plan. The number of posted secondary outcomes should therefore be read as a description of the record, not as evidence about which comparisons were prespecified, adjusted, or prioritized. The primary result remains the adjusted Week 12 general fatigue comparison identified in the registry.

15. 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 adverse-event results list 147 participants at risk in the Emergen-C group and 150 in the placebo group. Serious adverse events were reported for 0 participants in each group, and deaths were 0 in each group. Other adverse events were reported for 3 participants in the Emergen-C group and 8 in the placebo group.

These are counts from the registry’s adverse-event summary. They are not the same group counts as those listed for the primary endpoint, which are 146 and 147. The registry record does not explain the difference. The serious-event counts describe what is recorded in these groups; they do not establish that no other safety outcomes occurred or provide information about event severity beyond the serious-event classification.

The record lists no top serious adverse-event terms. It does not provide, in these figures, details about the nature or timing of the other adverse events, their relationship to study product, or the methods used to collect them. These counts are descriptive and should not be used alone to make broader safety conclusions.

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

The posted primary result estimates the adjusted difference between Emergen-C and placebo in change from Baseline to Week 12 on the MFI General Fatigue Domain Score. The estimated difference is 0.25 points, with a 95% confidence interval from -0.56 to 1.06 and p = 0.547. Because the interval crosses zero, the result leaves uncertainty about the direction and size of the group contrast. The estimate does not provide precise evidence of a between-group difference under the sponsor’s analysis.

Both arm-level adjusted mean changes are negative: -5.23 for Emergen-C and -5.48 for placebo. Under the registry’s scoring description, a negative change indicates a lower score at Week 12 than at Baseline. These within-group changes do not answer the comparative question on their own. The primary inference concerns whether the groups differed, and the reported adjusted comparison is the relevant estimate for that question.

The endpoint is a specific fatigue domain with a defined score range. It is not a complete measure of quality of life, and the registry does not report a threshold for judging clinical importance. A statistical estimate in score units cannot by itself establish how participants experienced the change or whether it matters to them.

The result is limited to the registered analysis population, endpoint, and follow-up period. The registry record does not report full details of the model adjustments, missing-data handling, multiplicity procedures, or original sample-size justification. Those omissions limit how fully the analysis can be independently assessed. The outcome counts and estimates describe the posted study results; they do not establish effects on outcomes that were not measured or reported.

17. Why This Trial Matters Statistically

This trial illustrates why a clinical result needs to be read through its endpoint definition and its comparison. The MFI General Fatigue Domain Score has an explicit range and direction: lower scores indicate lower fatigue, and negative change indicates a decrease from Baseline. Without that scoring context, the sign of the arm estimates and the positive between-group estimate could be misread.

It also illustrates the difference between change within each group and the contrast between randomized groups. The arm-level changes are both negative, while the primary question concerns the difference between those changes. The adjusted estimate and its confidence interval are more informative for that comparison than either group’s change considered alone.

A further statistical point is the distinction between a sponsor-reported adjusted repeated-measures analysis and a simple unadjusted recalculation. The recalculation can serve as a transparent check based on posted summaries, but it cannot reproduce the sponsor’s model. Reporting both types of estimates requires clear labeling so readers do not treat them as identical analyses.

Finally, the record includes multiple fatigue outcomes and assessment times, while the primary result is one designated endpoint. The status of multiplicity adjustment and several analysis details is not reported in the registry record. Recognizing those unknowns helps keep the interpretation aligned with what the result can support: a specific estimated score contrast, with uncertainty, rather than a broad conclusion about all quality-of-life outcomes.

18. 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 registry record gives limited detail about the statistical model beyond identifying a Mixed Model with Repeated Measures and reporting an adjusted mean difference. The adjustment variables, model specification, and covariance structure are not reported in the registry record. The sponsor’s analysis therefore cannot be fully reconstructed from the information recorded.

The primary analysis population is modified Intention-To-Treat rather than all randomized participants as described by the stated criteria. The endpoint population counts are 146 and 147, while the adverse-event population counts are 147 and 150. The reasons for these differing counts are not reported in the registry record. Detailed missing-data methods and sensitivity analyses are also not reported in the registry record.

The registry lists 33 outcome measures and 28 posted secondary outcomes, but does not report a multiplicity adjustment or a formal hierarchy for interpreting the secondary comparisons. This limits interpretation across the broader outcome set. The registry record also does not report the original sample-size justification or the assumptions used in the trial’s own design.

The primary endpoint is one fatigue domain, assessed at Week 12. The record does not report a threshold for clinical importance, so the score difference cannot be classified from the registry information as meaningful or not meaningful to participants. The adverse-event summary provides counts but not the event details needed to characterize the reported other adverse events. These limitations concern what can be established from the registry record and should not be filled by assumptions.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study Evaluating Quality of Life Parameters Following Use of Emergen-C — NCT06654089.
• Registry record last updated 2026-04-07; status last verified 2026-03.
• Results first posted 2026-03-10.
• 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.

22. Record Summary

NCT06654089 is a completed Phase 4, randomized, double-masked, parallel-group study sponsored by HALEON. It compared Emergen-C Core Super Orange Powder with placebo, taken once daily for up to 12 weeks. The registry lists enrollment of 299 and records a start date of 2024-10-30 and primary completion date of 2025-02-24.

The primary endpoint was adjusted change from Baseline to Week 12 in MFI General Fatigue Domain Score. The sponsor reported an adjusted mean difference of 0.25, with a 95% confidence interval from -0.56 to 1.06 and p = 0.547. A separate unadjusted recalculation gives a similar point estimate but is not the sponsor’s repeated-measures analysis. The registry does not report several details needed to assess the full analysis plan, including the original sample-size justification, multiplicity approach, and detailed missing-data methods.