Reducing Adenoviral Patient Infected Days: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reducing Adenoviral Patient Infected Days (NCT02472223), a randomized na study. The primary outcome is Percent Change From Peak Viral Load.

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel-group pilot study, listed as phase NA. The registry reports enrollment of 28 and lists Washington University School of Medicine as the sponsor. The study status is completed. The recorded start date is 2015-03-23, and primary completion is dated 2018-06-01.

Participants were assigned to one-time in-office treatment with either Betadine 5% or artificial tears. Each arm description specifies 4-5 drops, limited to 2 minutes, followed by saline lavage. The brief summary describes randomization using a masked randomization packet. Although the study is identified as triple-masked, the identities of the masked groups of people are not reported in the registry record.

The primary outcome population was not described as every enrolled participant. It was a subgroup of 16 randomized to Betadine 5% and 12 randomized to artificial tears who tested positive for adenoviral conjunctivitis by qPCR at baseline. The registry therefore distinguishes the total enrollment from the population named for the primary outcome. Further details about the eligibility criteria, the number screened, and the number excluded from this subgroup are not reported in the registry record.

The study's stated purpose was to generate data needed to design a definitive comparison of standard care with artificial tears versus Betadine 5%. That pilot purpose matters when reading the result: the record describes a small study focused on a viral-load endpoint, not a definitive assessment of every clinical outcome. The registered secondary outcome was participant-reported bothersomeness of ocular symptoms, but its results 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: Subgroup of 16 patients randomized to Betadine and 12 patients randomized to artificial tears who tested positive for adenoviral conjunctivitis by qPCR at baseline. Viral load was assessed at baseline, post treatment follow-up days at 1-2, 4-5, 7, 14 and 21.

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 Percent Change From Peak Viral Load, measured over 21 days.

The primary endpoint is titled “Percent Change From Peak Viral Load” and is reported in percent of peak viral load. The stated timeframe is 21 days. The outcome description says it was intended to compare Betadine 5% with artificial tears for change from peak viral load in adenoviral conjunctivitis. Viral load was assessed at baseline and follow-up on days 1-2, 4-5, 7, 14 and 21.

Viral load is a measure of the amount of virus detected, and repeated measurements can describe how that amount changes over follow-up. Expressing a result relative to a peak can provide a way to describe change against a reference measurement rather than reporting only a single viral-load value. This is a general explanation of the type of endpoint; the registry does not fully specify how the peak was defined, how the percentage was calculated, or how values were handled when a peak was not observed at a scheduled visit.

The record reports arm-level medians and full ranges for the primary measure. The Betadine 5% group had a median of 1.9, with a full range of 0.0 to 7.6. The artificial tears group had a median of 13.2, with a full range of 1.0 to 32.3. Because the precise coding and direction of this percentage measure are not described in detail, those numbers should be read as posted rather than translated into a claim about greater or lesser viral-load reduction.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is presented as a median with a full range for each treatment group, and the between-group analysis is identified as a Wilcoxon (Mann-Whitney) test. These summaries and the test answer related but different questions: the medians describe the center of each group's observed values, while the test evaluates evidence about the relative distributions of values in the two groups.

Why use a rank-based comparison?

In general, the Wilcoxon (Mann-Whitney) test ranks observations from both groups together and compares how those ranks are distributed across groups. It can be useful when an outcome is skewed, has outliers, or does not fit the assumptions of a standard comparison of means. The test is not simply a test of the difference between two medians in every setting. Its interpretation depends on the shape and spread of the group distributions; a shift in location is a straightforward interpretation only under additional conditions. The registry names the test but does not report diagnostic checks or further details of its implementation.

The endpoint is reported as a median and full range, rather than a mean and standard deviation. A median identifies the middle of an ordered set of observed values and is less affected by very high or low observations than a mean. A full range gives the smallest and largest observed values but does not describe how observations are distributed between those extremes. No interquartile range is reported. Because the outcome is a percentage change relative to peak viral load, details of the scale and calculation are important for interpreting the median; those details are not fully reported in the registry record.

What does the p-value tell the reader?

In general, a p-value evaluates how unusual results at least as extreme as those observed would be under a statistical model that assumes no group difference. It is not the probability that the null hypothesis is true, nor does it show the probability that the result will be reproduced. The reported p = 0.02 is attached to the sponsor's Wilcoxon (Mann-Whitney) comparison. The registry does not report a confidence interval for that comparison, so the precision of the estimated difference cannot be assessed from an interval around the sponsor's estimate.

A confidence interval, in general, presents a range of effect values compatible with the data and the statistical procedure. Its width helps communicate precision, while its location helps communicate the direction and size of an effect on a defined scale. Without a reported interval, the p-value alone cannot convey the range of plausible effect sizes. The record also does not specify the effect scale sufficiently to translate the reported median difference (final values) of 90 into an intuitive change in viral load.

Why do follow-up measurements matter?

Viral load was assessed at baseline and on follow-up days 1-2, 4-5, 7, 14 and 21. Repeated measurements can help describe a changing outcome over time, but they also create analysis choices. For example, an analysis may compare a single selected follow-up value, summarize a trajectory, or use a model that accounts for repeated observations within a participant. The registry's primary outcome description names percent change from peak viral load, and the reported analysis is called a comparison of final values. The exact role of each scheduled measurement in constructing the reported statistic is not fully described in the registry record.

In general, repeated measurements from one participant are related rather than independent. A method that treats them as independent can misstate uncertainty, while a method that models their correlation can use the longitudinal structure directly. The posted method is a two-group rank-based comparison; the registry does not describe a longitudinal model, adjustment for baseline viral load, or adjustment for other variables. It is therefore not possible to infer that such adjustments were used.

Why is the analysis population important?

The primary outcome description limits the analysis to participants who tested positive for adenoviral conjunctivitis by qPCR at baseline. This restriction makes the endpoint relevant to a virologically confirmed subgroup, but it also means the result does not directly describe all enrolled participants unless all enrolled participants were in that subgroup. The registry gives the subgroup counts by assigned arm but does not report further details about missing measurements, exclusions after randomization, or the handling of participants who did not contribute a final value.

General statistical interpretation should distinguish randomization from analysis population selection. Random assignment can support a fair comparison of groups at the point of assignment, but excluding participants or requiring a post-assignment measurement can affect comparability if the analysis population is defined differently from the randomized population. The registry does not provide enough detail to assess whether that concern arose in this analysis.

What can be concluded from the reported method?

The record identifies the endpoint summaries, test, and p-value, but does not report a confidence interval, an adjusted analysis, or a detailed statistical analysis plan. The named rank-based test supports an interpretation of evidence for a group difference in the distributions of the analysed values, under its assumptions. It does not by itself identify a clinically meaningful effect or establish causation. Those judgments require a clearly defined outcome scale, an effect estimate with uncertainty, and relevant clinical context, which are not fully available in the registry record.

10. Analyses Reported by the Sponsor

The registry reports the sponsor's analysis as a Wilcoxon (Mann-Whitney) comparison, with the result described as a median difference (final values) of 90 and p = 0.02. No confidence interval is reported for that comparison. The arm-level primary-outcome summaries are medians of 1.9 for Betadine 5% and 13.2 for artificial tears, each accompanied by a full range.

The sponsor's test is the inferential result to use when describing the analysis recorded in the registry. The record does not include an independent recalculated effect estimate or confidence interval that could be compared with it. It also does not describe the calculation behind the reported median difference in enough detail to derive an equivalent comparison from the arm summaries alone. Accordingly, no separate recalculated result should be treated as a competing estimate.

The p-value indicates statistical evidence under the sponsor's specified test, but does not give the magnitude or precision of the difference. The absence of a reported interval limits assessment of that precision. The outcome's coding and the meaning of “final values” are not fully explained in the registry record, so the reported statistic should be presented as the sponsor's analysis rather than converted into a more specific clinical interpretation.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome, “Percent Change From Peak Viral Load,” and one secondary outcome, participant-reported bothersomeness of ocular symptoms. It reports two outcome measures and one analysis. Results for the secondary outcome are not reported in the registry record. The record does not describe how many statistical comparisons were planned across the primary and secondary outcomes, follow-up times, or any additional analyses.

Multiplicity is the general statistical issue that arises when several hypotheses are tested. As the number of tests increases, the chance of observing at least one small p-value by chance can increase unless the analysis plan addresses that possibility. Methods can include defining a primary test in advance, adjusting the interpretation or threshold, or treating other analyses as exploratory. Which approach was used in this trial is not reported in the registry record. The reported p = 0.02 should therefore be read as the result of the listed comparison, without assuming that it was adjusted for other outcomes or time points.

The registry names a subgroup of baseline qPCR-positive participants as the primary outcome population, with 16 in the Betadine 5% group and 12 in the artificial tears group. It does not report the number randomized to each arm outside that subgroup, a participant flow account, or reasons why any randomized participants may not have contributed to the primary analysis. The analysis population cannot be assumed to include every randomized participant.

Missing outcome data and their handling are also not described. The record does not state whether every participant had measurements at every scheduled visit, how incomplete follow-up was handled, or whether any values were imputed. It also does not report a detailed analysis plan, the prespecification of the subgroup analysis, or interim analyses. These omissions limit assessment of whether the posted analysis reflects all randomized participants and how robust the result might be to missing data or analytic choices. They are limitations of the available registry record and do not establish that any particular problem occurred.

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.

The adverse-event figures list 16 participants at risk in the Betadine 5% group and 12 in the artificial tears group. Serious adverse events affected 0 participants in each group. Other adverse events also affected 0 participants in each group. The record lists 1 death in the Betadine 5% group and 0 in the artificial tears group.

These are counts recorded for the trial groups; they do not establish whether an event was caused by a study treatment. The registry record does not provide a cause of death or a description linking the death to treatment. It also does not list serious-event terms. The absence of reported serious or other adverse events should not be interpreted as proof that no harms occurred outside the reporting period, or as a complete comparison of safety across all possible outcomes.

Safety counts are descriptive and should be read alongside the limited size and follow-up of this pilot study. The record does not provide further information about event definitions, timing, severity beyond the serious-event classification, or attribution. Those details are not reported in the registry record, so the figures support only a narrow account of the posted event counts.

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

The posted data describe a randomized comparison of one-time Betadine 5% and artificial tears in a pilot trial. For the primary viral-load outcome, the record reports a median of 1.9 with a full range of 0.0 to 7.6 in the Betadine 5% group, and a median of 13.2 with a full range of 1.0 to 32.3 in the artificial tears group. The sponsor's Wilcoxon (Mann-Whitney) comparison is reported as a median difference (final values) of 90, with p = 0.02.

Those findings describe the analysed subgroup of participants who tested positive for adenoviral conjunctivitis by qPCR at baseline. They do not by themselves establish what happened for every enrolled participant, because the record does not clarify the primary-outcome analysis population beyond that subgroup. The endpoint's calculation and direction are also not fully described, which limits translation of the numerical summaries into a specific statement about the amount or direction of viral-load change.

A statistically significant test result does not show that an effect is large, clinically important, or certain to recur in another study. The lack of a reported confidence interval makes the precision of the sponsor's comparison difficult to assess. The observed medians and ranges also show that there was variation among participants; group summaries do not describe each person's experience.

The results do not establish comparative effects on symptoms, because the registered secondary outcome of participant-reported bothersomeness has no results reported in the registry record. Nor do the adverse-event counts establish a treatment-related cause for the listed death. The posted evidence is a pilot comparison intended to inform a definitive trial, not a complete assessment of efficacy or safety. No treatment recommendation follows from these registry results alone.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it links a randomized treatment comparison to a virologically defined primary analysis population. The record identifies participants who tested positive for adenoviral conjunctivitis by qPCR at baseline and reports their viral-load outcome over follow-up. That focus makes clear that the primary result is about a specific subgroup and a laboratory measure, not necessarily every person enrolled or every dimension of the condition.

The endpoint is described as percent change from peak viral load, while the sponsor's comparison is labelled a median difference (final values). Those labels raise an important interpretive issue: a statistical result is only as clear as the definition and scale of the outcome being compared. The registry provides the visit schedule and arm-level summaries, but not enough detail to reconstruct the outcome calculation or translate the reported difference into a more intuitive scale. Clear endpoint definitions are essential for readers to understand what a test result means.

The contrast between a p-value and a confidence interval is also instructive. The record gives p = 0.02 for the sponsor's test but no interval around the comparison. In general, a p-value addresses compatibility with a no-difference model, while an interval helps show the precision and range of effect estimates compatible with the data. Reporting both, with an explicit effect scale, would make the inferential result easier to interpret.

Finally, this is explicitly a pilot study intended to generate information for designing a definitive trial. Its value is not limited to whether a single test crosses a conventional threshold. The small, defined analysis population, repeated viral-load assessments, and incomplete reporting of analysis details highlight the importance of prespecified outcomes, transparent participant flow, clear handling of missing measurements, and clinically interpretable estimates in later trials.

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 details needed for a full interpretation are not reported in the registry record. The primary endpoint is named as percent change from peak viral load, but the precise definition of the peak, the calculation of the percentage, and the meaning of the reported “final values” are not explained. This makes it difficult to map the arm medians and the sponsor's reported median difference onto a single, clearly interpretable scale.

The primary analysis population is a baseline qPCR-positive subgroup of 16 participants assigned to Betadine 5% and 12 assigned to artificial tears. The registry does not report a detailed participant flow, numbers randomized by arm outside that subgroup, or reasons for any exclusions from the primary analysis. It also does not explain how missing viral-load measurements were handled, whether participants attended every scheduled visit, or whether any values were imputed.

The record reports a p-value but no confidence interval for the sponsor's comparison. It does not provide the detailed statistical analysis plan, including whether the subgroup and analysis were prespecified, how multiple outcomes or time points were handled, or whether any interim analyses occurred. Adjustment for baseline viral load or other covariates is not described. The identities of the masked groups are not reported, despite the trial being listed as triple-masked.

The secondary outcome of participant-reported bothersomeness of ocular symptoms has no results reported in the registry record. Adverse-event reporting is limited to counts; event timing, attribution, and the cause of the listed death are not described. These reporting gaps restrict interpretation but do not demonstrate that any specific design or analysis problem occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Reducing Adenoviral Patient Infected Days — NCT02472223.
• Registry record last updated 2021-01-06; status last verified 2021-01.
• Results first posted 2021-01-06.
• 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

NCT02472223, “Reducing Adenoviral Patient Infected Days,” is a completed randomized, triple-masked, parallel-group pilot study sponsored by Washington University School of Medicine. The registry lists enrollment of 28 and phase NA. Participants received one-time in-office Betadine 5% or artificial tears, followed by saline lavage.

The primary outcome was percent change from peak viral load over 21 days among baseline qPCR-positive participants: 16 assigned to Betadine 5% and 12 assigned to artificial tears. The posted arm medians were 1.9 and 13.2, respectively, with full ranges of 0.0 to 7.6 and 1.0 to 32.3. The sponsor reported a Wilcoxon (Mann-Whitney) comparison, median difference (final values) 90, p = 0.02; no confidence interval is reported.

The registered secondary outcome was participant-reported bothersomeness of ocular symptoms, with results not reported in the registry record. The record lists 0 serious adverse events in each group and 1 death in the Betadine 5% group, without a reported cause.