Micronutrients to Prevent Noise-induced Hearing Loss: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Micronutrients to Prevent Noise-induced Hearing Loss (NCT00808470), a randomized phase 2 study. The primary outcome is Average Threshold Shift at 4 kHz in Both Ears.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, quadruple-masked, parallel-group trial. The recorded enrollment was 72. The registry identifies the sponsor as the University of Michigan and gives the study start as 2008-10, primary completion as 2013-12, and status as completed. The intervention and placebo arms are described as part of a University of Florida music-player study. The record does not explain the relationship between the sponsor and study site.

Participants were assigned to nutrient tablets or placebo tablets, with both arm descriptions specifying consumption for 4 days. The nutrient combination was beta-carotene, vitamins C and E, and magnesium. The study exposed participants to music and assessed temporary changes in hearing thresholds. The registry describes moderately loud music and a 4 hour music exposure. Its primary-outcome description concerns the change in the quietest decibel level participants could hear after exposure compared with baseline.

The brief summary describes 70 young adults with equal numbers of male and female participants as the intended study subjects. The recorded enrollment is 72; the record does not explain the difference between the planned description and enrollment or report the enrolled participants' sex distribution. Two subjects withdrew before music exposure. The primary-outcome population is described as all subjects who completed music exposure, but the record does not give the number analyzed for the primary outcome.

The record lists threshold shifts at individual frequencies and tinnitus among secondary outcomes. It also indicates repeated post-music measurement times for the primary endpoint. The exact randomization procedure, allocation concealment, masking details, and statistical analysis 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: All subjects that completed music exposure were analyzed; two subjects withdrew from study prior to music exposure.

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: healthy young adults that meet audiometric enrollment criteria

6. Primary Endpoint

The registry lists the primary outcome as Average Threshold Shift at 4 kHz in Both Ears, measured over 15 min, 1 hr intervals for 3 hours to measure temporary changes; additional tests at 1 day and 1 week post-exposure..

The primary endpoint was average threshold shift at 4 kHz in both ears, expressed in decibels. Hearing threshold refers to the quietest sound level a participant can hear. A threshold shift is the mean change from the pre-music baseline to a post-music measurement. The registry describes the first post-music test at 15 minutes and further tests at 1 hour intervals for 3 hours, with additional tests at 1 day and 1 week.

As a continuous measure, threshold shift retains the size and direction of changes in hearing sensitivity rather than classifying participants only as having or not having a change. A group mean can describe the average shift, while a standard deviation describes how dispersed individual measurements are around that mean. Those are general statistical interpretations of the stated outcome type; the registry record does not report the observed mean shifts or standard deviations.

The endpoint focuses on a specific frequency and captures temporary changes following music exposure. Repeated measurement can describe how the shift changes over the specified follow-up times. However, repeated observations from the same participant are related, so a statistical analysis must account for that dependence if it compares trajectories or combines time points. The registry record does not report how the repeated measurements were analyzed, nor does it provide a single treatment-effect estimate for the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean threshold shift represent?

General: A mean is an average across observations. For a continuous outcome such as hearing threshold shift in decibels, it provides a concise description of the center of the measured values. The registry specifies a mean change from baseline to post-music testing. A mean does not describe every participant's experience; individual values may vary around it. The standard deviation is a measure of that spread, not a measure of uncertainty in the mean itself.

The study specifies measurements in both ears and repeated tests after music exposure. A statistical analysis must be clear about how ear-level measurements contribute to the stated average and how multiple measurements from a participant are handled. The registry record does not report these analytic details. Because repeat observations on one person are generally correlated, treating them as independent observations can understate uncertainty. General methods for repeated data account for this within-person dependence, but the specific method used in this trial is not reported in the registry record.

Why does randomization matter?

General: Random assignment is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. This supports interpreting a between-group contrast as an estimate of the effect of assignment, subject to issues such as missing outcomes, departures from the assigned intervention, and the validity of the analysis. Randomization does not guarantee that the groups will be identical in a particular trial. The registry identifies the allocation as randomized but does not describe the sequence-generation or allocation-concealment procedures.

The parallel design means the comparison is between groups assigned to different conditions rather than a design in which each participant receives both conditions. Quadruple masking is recorded, but the registry does not specify which roles were masked or how masking was maintained. Those omissions limit assessment of how assignment and outcome measurement may have been influenced by knowledge of treatment.

What would an effect estimate and confidence interval show?

General: An effect estimate summarizes the contrast between groups on the outcome scale. For a continuous endpoint, a group difference in mean threshold shift would express the contrast in decibels. A confidence interval conveys the range of values reasonably compatible with the data and the statistical model, subject to the method's assumptions. A narrower interval indicates greater precision; a wider interval indicates greater uncertainty. A confidence interval does not show the probability that a particular fixed treatment effect is true.

No primary-outcome estimate or confidence interval is reported in the registry record. The effect's direction, size, and precision therefore cannot be described. A significance test alone, even if one were reported, would not replace the estimate and its interval because it would not communicate the range of plausible effect sizes. The record also does not report the statistical model, any adjustment variables, or the treatment contrast selected for the repeated assessment times.

Why can repeated testing complicate inference?

General: Measurements taken from one participant over time are not usually independent. A person's threshold at one assessment may be related to their threshold at another. Analyses that compare groups across several times can model the pattern of change, estimate group differences at selected times, or test whether trajectories differ. These approaches answer related but distinct questions. The choice should be tied to the study objective and prespecified analysis plan.

Assessing multiple times and frequencies also creates multiplicity: the more contrasts examined, the more opportunities there are for a chance finding if each is treated as a separate test. Methods can control or describe this issue, but the appropriate approach depends on the planned questions. The registry lists multiple outcomes and assessment times, but multiplicity procedures and the prespecified hierarchy of analyses are not reported in the registry record.

What do the planning illustrations mean?

General: A sample-size planning illustration describes how many participants might be needed under specified assumptions to detect an effect at a chosen power and significance level. Such an illustration depends on assumptions about the target effect, variability, allocation, and analysis. It is not a result from the trial and does not describe the chance that this completed trial detected an effect. The registry's planning description says its illustrations are based on fractions of an observed effect and use a two-sided significance level of 0.05, equal allocation, and a normal approximation. It distinguishes participants per arm for non-time-to-event outcomes from total events for time-to-event outcomes. The record does not report the trial's own design justification or enough planning estimates to interpret a specific target sample size.

These illustrations should not be called observed power. General: Observed power calculated from an observed effect is largely a restatement of the result's statistical significance and does not resolve uncertainty about the effect. Precision is better conveyed by the effect estimate and its confidence interval. Neither is available for the primary outcome in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome was assessed at several post-exposure times, including 15 minutes, 1 hour intervals for 3 hours, 1 day, and 1 week. The record also lists secondary outcomes for threshold shifts at individual frequencies and tinnitus. It reports seven outcome measures and six analyses, but does not identify the complete set of contrasts, state which analyses were prespecified, or describe any multiplicity adjustment. When multiple outcomes, times, or contrasts are examined, the chance of at least one apparently notable result can increase. General approaches include designating a primary contrast in advance or adjusting interpretation for the family of tests. Which approach, if any, was used is not reported in the registry record.

The primary-outcome population is described as all subjects who completed music exposure. Two subjects withdrew before music exposure. The record does not state how many completed exposure, how many had outcome data at each follow-up time, or how missing post-exposure measurements were handled. It does not report imputation, sensitivity analyses, or whether participants were analyzed according to randomized assignment. These details matter because incomplete follow-up can affect both the precision and potential bias of an estimated treatment contrast.

The record does not report the statistical analysis plan, the handling of repeated measurements, or the analysis population for each secondary outcome. It also does not explain whether any outcome or analysis was added or changed after study initiation. Without those details, readers cannot assess the extent to which the reported analyses—where available—match the planned comparisons. The primary treatment comparison itself is not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events as 0 among 37 participants at risk in the nutrient group and 0 among 35 participants at risk in the placebo group. It lists other adverse events as 2 among 37 at risk in the nutrient group and 5 among 35 at risk in the placebo group. These are counts recorded for the respective groups, not estimates of a causal treatment effect.

The record does not describe the types of other adverse events, their severity, timing, or assessed relationship to the intervention. It also does not report deaths; the death entries are not populated. A blank or unspecified death entry should not be interpreted as confirmation that no deaths occurred. The record does not explain how adverse events were collected or whether all participants were followed for safety over the same period.

General: Small event counts provide limited information about uncommon harms. A count of zero serious events in a group does not establish that the risk is zero. Differences in event counts may reflect chance, differences in exposure time or reporting, or other factors, and cannot be interpreted causally without appropriate context and analysis. The registry's adverse-event figures should therefore be read as descriptive safety information rather than proof of benefit or harm.

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

The record describes a randomized comparison of a micronutrient combination with placebo in a music-exposure study. It specifies an endpoint intended to capture changes in hearing threshold after exposure and lists repeated follow-up assessments. This helps readers understand the clinical question and the measurements the study was designed to make.

What the record does not establish is the primary effect of the micronutrients. It contains no reported primary-outcome group comparison, no estimate of the difference in mean threshold shift, and no confidence interval showing precision. The scheduled measurements alone cannot reveal whether either group had a larger shift, whether changes persisted, or how much uncertainty surrounded any contrast. A completed study status does not supply those missing results.

The stated endpoint is a temporary threshold change, not by itself a demonstration of permanent hearing loss or a long-term clinical outcome. The brief summary describes a broader hypothesis concerning acute changes induced by real-world sounds, including temporary or permanent changes, while the digital music-player experiment focuses on temporary elevations in hearing thresholds. The record does not report results that would establish an effect on permanent hearing changes.

The adverse-event counts give limited descriptive information. The registry records no serious adverse events in either group and records other adverse events in both groups, but it does not supply event details or causal assessments. These counts cannot establish that the intervention is safe or unsafe.

Accordingly, the record supports understanding the trial's design and intended measurement, but not a treatment recommendation or a conclusion that the intervention did or did not alter hearing thresholds. Interpretation of efficacy would require the primary results, the analysis method, and information about missing measurements and uncertainty. Those items are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a clear endpoint description is not the same as a reported treatment result. The record identifies a continuous hearing-threshold measure, its frequency, units, baseline comparison, and post-exposure schedule. Those details are essential for understanding the intended analysis. Without a reported between-group estimate and its uncertainty, however, the clinical question remains unanswered by the posted results.

The repeated schedule also makes the statistical question more complex than a single isolated measurement. A treatment contrast at 15 minutes may not answer the same question as a contrast at 1 day or 1 week, and a comparison of trajectories is different again. The registry does not report which contrast was primary in analysis or how repeated observations were modeled. This makes the timing and analysis plan important parts of interpreting the endpoint.

Multiplicity is another statistical consideration because the record includes multiple outcomes and assessment times. If many contrasts are tested, isolated findings can be difficult to distinguish from chance findings unless the analysis plan and interpretation account for the number of comparisons. The record does not state how this issue was handled. That absence is not evidence that the analyses were improper, but it prevents a full assessment from the registry record.

Finally, the record shows why descriptive safety counts and planning illustrations should be kept separate from efficacy evidence. Adverse-event counts do not establish causation, and sample-size illustrations based on assumptions are not observed treatment effects or observed power. For this study, the central statistical takeaway is the gap between detailed measurement plans and the absence of a reported primary comparison with an estimate of precision.

14. 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 primary limitation for interpreting this trial is that the registry record does not report the primary-outcome comparison. Without group estimates and uncertainty, the effect's direction, magnitude, and precision cannot be evaluated. The record indicates that the endpoint involved several categories or time points and was not reduced to one comparison, but it does not report the results for the individual times or explain how they were analyzed.

The analysis population is described as subjects who completed music exposure, and two subjects withdrew before exposure. The number with primary-outcome data at each later assessment is not reported. The record does not explain how missing data were handled, whether participants were analyzed as randomized, or whether sensitivity analyses were conducted. These omissions limit assessment of the robustness of any treatment comparison.

The registry reports a planned description of 70 young adults and an enrollment of 72, without explaining the difference or reporting the enrolled participants' sex distribution. The relationship between the University of Michigan sponsor and the University of Florida study description is also not explained. These details do not establish a problem with the trial, but they limit what can be reconstructed from the record.

The statistical analysis plan, randomization procedures, allocation concealment, masking details, repeated-measures methods, and multiplicity procedures are not reported in the registry record. The adverse-event section gives counts but not event types, timing, or relatedness. As a result, both efficacy and safety interpretation are limited to the descriptive information recorded, rather than a full evaluation of treatment effects and their uncertainty.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Micronutrients to Prevent Noise-induced Hearing Loss — NCT00808470.
• Registry record last updated 2017-05-19; status last verified 2017-04.
• Results first posted 2017-05-19.
• 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.

18. Record Summary

The registry describes a completed Phase 2 randomized, quadruple-masked, parallel-group study with recorded enrollment of 72. The study compared beta-carotene, vitamins C and E, and magnesium with placebo in a digital music-player experiment focused on temporary hearing-threshold changes after music exposure. Tablets were described as being taken for 4 days.

The primary endpoint was average threshold shift at 4 kHz in both ears, measured in decibels across post-exposure assessments. Two subjects withdrew before music exposure, and the primary-outcome population is described as those who completed exposure. The registry record does not report the primary treatment comparison, its uncertainty, the detailed statistical plan, or the handling of missing follow-up measurements. Serious adverse-event counts were 0 in each arm; other adverse-event counts were 2 in the nutrient arm and 5 in the placebo arm. Event details and death information are not reported in the registry record.