Treatment of Pediatric Patients That Lost Sense of Smell Due to COVID-19: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Pediatric Patients That Lost Sense of Smell Due to COVID-19 (NCT04964414), a randomized phase 1, phase 2 study. The primary outcome is Change in University of Pennsylvania Smell Identification Test (UPSIT) Score From Baseline to First Follow-up.

2. Clinical Question

3. Trial Design

The registry describes a prospective randomized controlled study of smell retraining, with or without budesonide irrigation, for pediatric and young adult patients who had lost their sense of smell following COVID-19. Its design is listed as randomized and parallel, with no masking. The trial is designated Phase 1 and Phase 2. Enrollment is recorded as 20. The listed start date is 2021-09-30, the primary completion date is 2023-01-13, and the current status is terminated. The reason for termination is not reported in the registry record.

The two groups were titled “Smell Retraining Only” and “Smell Retraining + Budesonide.” In both, participants were to practice smell retraining for 8 weeks, selecting 4 scents each week and smelling each scent close to the nose for 15 seconds once a day. The combination group was also to use a once-daily budesonide-saline irrigation, described as 0.5mg/2ml of budesonide added to saline in an irrigation bottle. The registry does not report adherence to either regimen or whether the assigned treatments were completed as planned.

The primary endpoint was change in UPSIT score from the initial consultation to the first follow-up. That follow-up was described as at 8 weeks, with an allowed range of 8 to 12 weeks. The listed secondary outcomes include changes in SNOT-22 and a loss-of-smell question score at first follow-up, and changes in UPSIT and SNOT-22 at 6 Month and 12 Month follow-up. The registry lists 9 outcome measures and 5 analyses, but does not report a full analysis plan, a participant flow, or arm-specific outcome summaries. Randomization sequence generation, allocation concealment, and the handling of deviations from assigned treatment 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.

Before assignment: One participant was placed in a treatment arm (OT + BI) different than what was randomly assigned (OT) at the initial clinic visit.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients who completed 8-12 week follow-up assessments

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 Change in University of Pennsylvania Smell Identification Test (UPSIT) Score From Baseline to First Follow-up, measured over Before and after 8-12 weeks of smell retraining.

The primary endpoint is change in University of Pennsylvania Smell Identification Test (UPSIT) score from baseline to the first follow-up. The baseline is the initial consultation appointment, and the follow-up is described as at 8 weeks, with a range of 8 to 12 weeks. The specified population for this endpoint consists of patients who completed the 8-12 week follow-up assessments.

The UPSIT is described as a smell-identification test: a 40-item scratch-and-sniff test with a four-choice multiple-choice question on each of the 10 booklet pages. The score ranges from 0 to 40. A higher score indicates better smell or outcome. The registry identifies the endpoint as a mean and names standard deviation as its dispersion measure.

As a continuous measure, change in score can represent the average movement in measured smell identification over the assessment interval. In general, measuring change from baseline can account for differences in participants’ starting scores when describing their subsequent scores. Interpretation still depends on the observed change in each group and a suitable between-group comparison. Neither the arm-level mean changes nor their standard deviations are reported in the registry record. The primary outcome is therefore described, but its magnitude, precision, and comparison between the assigned groups cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a score on a scale, summarized as a mean with standard deviation. The registered endpoint is the change in UPSIT score from baseline to first follow-up. In general, a mean describes the average value in a group, while a standard deviation describes how spread out individual values are around that average. The mean alone does not show whether participants had similar changes or widely varying changes. The registry names these summary measures but does not report the primary outcome values for either group.

What would a between-group estimate describe?

For a randomized comparison, the central quantity is the difference between the groups’ average changes, with the direction interpreted according to which group is subtracted from which. In general, this estimate describes the observed contrast in average change, rather than proving that every participant experienced that change. A confidence interval would describe the range of effect values compatible with the data and the analysis assumptions. A narrower interval indicates greater precision than a wider interval, while an interval spanning values in different directions can leave the direction of the effect uncertain. The registry record does not report a primary between-group estimate or confidence interval.

A p-value, if reported, would address how compatible the observed data are with a specified null model under the analysis assumptions. It would not give the probability that the null hypothesis is true, and it would not measure the clinical importance of a difference. Statistical significance also does not replace an effect estimate and its interval. No primary p-value or test specification is reported in the registry record, so no significance conclusion can be drawn from it.

Why does the follow-up population matter?

The primary outcome is specified for patients who completed 8-12 week follow-up assessments. In general, restricting an analysis to participants with observed follow-up scores can be problematic if the likelihood of having a score is related to assignment, baseline status, or the outcome itself. An analysis that includes everyone as randomized and a complete-case analysis can answer different questions when data are missing. The record does not report the number with observed primary outcomes, the reasons for missing data, or the analysis used to address missingness. It also does not report whether baseline and follow-up scores were analyzed as changes, with an adjusted model, or by another method beyond naming the endpoint as change in mean score.

What does randomization contribute?

In general, random assignment is intended to balance measured and unmeasured baseline factors across groups on average, so that an outcome contrast can be attributed more credibly to assigned treatment than a nonrandomized contrast. That protection depends on how the sequence was generated and concealed and on how participants are analyzed after assignment. The record identifies the trial as randomized but does not describe sequence generation, concealment, stratification, or the analysis population. It lists no masking, and does not say whether outcome assessment was masked separately.

The trial is described as parallel-group, so the assigned approaches were compared as groups over the study period rather than described as a crossover. The record does not provide the statistical model, assumptions about the score distribution, covariate adjustment, or treatment of repeated outcomes. These details are not needed to define the registered endpoint, but they would help assess whether the analysis matched the design and whether uncertainty was estimated appropriately.

How should planning calculations be read?

The registry describes sample-size illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect, and that non-time-to-event illustrations are expressed as participants per arm. Such calculations are planning illustrations: they indicate what sample size would be associated with specified assumptions, not the power actually achieved by this trial. They do not explain the original enrollment decision. The trial’s sample-size justification and any prespecified target for detectable effect are not reported in the registry record. No planning result should be read as observed power.

In general, planning estimates depend on assumptions about the effect, variability, analysis, allocation, and statistical threshold. If those assumptions differ from the eventual data or analysis, a planning calculation may not describe the study’s realized precision. Here, the registry does not report the primary group means or standard deviations alongside the endpoint, so a reader cannot verify an effect-based illustration against the posted primary outcome summaries.

What is the role of dispersion?

Standard deviation is the registered dispersion measure for the mean score. In general, greater variability makes an average less precise when other features are held constant. If outcomes are more variable than a statistical model assumes, standard errors and confidence intervals may not be well calibrated. This is one reason to report the spread of observed changes and to explain the analysis model. The registry does not provide those outcome summaries or discuss distributional checks, outliers, or alternative analyses. No particular model assumption or diagnostic procedure can therefore be attributed to this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures and assessment times. The primary measure is UPSIT change to first follow-up. The secondary outcomes include SNOT-22 change and a loss-of-smell question score at first follow-up, plus UPSIT and SNOT-22 changes at 6 Month and 12 Month follow-up. The record lists 9 outcome measures and 5 analyses. It does not report a multiplicity strategy, such as a hierarchy of tests, adjustment of significance thresholds, or designation of which secondary findings would be confirmatory. When multiple outcomes or time points are tested, the chance of at least one apparently notable result can increase; in general, a prespecified strategy helps readers distinguish confirmatory from exploratory evidence. No such strategy is reported in the registry record.

The primary outcome entry is not reduced to a single comparison because it has several categories or time points. The registry does not provide arm-level primary summaries or a specified single contrast for interpretation. It also does not report whether analyses were planned for all listed outcomes or which of the listed analyses correspond to each outcome.

Missing-data handling is not reported in the registry record. The endpoint population is described as patients who completed 8-12 week follow-up assessments, but the number who completed follow-up, the number with missing scores, and reasons for missingness are not stated. The record does not describe imputation, sensitivity analyses, or a rule for including participants with incomplete outcome data.

The record does not specify whether the main analysis was based on all randomized participants, participants who received treatment, or a subset with complete data. It also does not describe a per-protocol population or deviations from assigned treatment. These omissions limit the ability to judge whether the reported analysis, if results are added elsewhere, would preserve the randomized comparison and how robust it might be to incomplete follow-up.

11. 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 registry reports safety counts for the two listed groups. For “Smell Retraining Only,” 11 participants are recorded as at risk for serious adverse events and 0 as affected; 11 are recorded as at risk for other adverse events and 0 as affected. For “Smell Retraining + Budesonide,” the corresponding at-risk counts are 9, with 0 serious adverse events and 0 other adverse events recorded. Deaths are listed as 0 in each group. The top serious-event terms list is empty.

These figures describe what is recorded in the registry’s adverse-event fields; they do not establish that every participant had complete safety follow-up. The record does not report the safety observation period, event definitions, ascertainment procedures, severity grading, or whether events were judged related to either intervention. It also does not explain whether the at-risk counts represent all participants assigned, treated, or assessed for safety. A count of 0 recorded events should therefore be read as no events entered in these fields, not as proof that no symptoms or other events occurred.

In general, safety counts are most informative when the population observed, follow-up duration, and event collection methods are clear. The registry does not provide those details, so the reported counts cannot support a detailed comparison of safety between the approaches. They also do not provide a basis for medical advice.

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

The registry record describes a randomized comparison of smell retraining alone with smell retraining plus budesonide-saline irrigation in pediatric and young adult patients with COVID-19-related loss of smell. It defines a primary outcome based on change in UPSIT score from baseline to first follow-up and lists additional outcome measures at later follow-ups. These details identify what the study set out to assess, but they do not show whether scores changed or whether changes differed between groups.

The primary result is not numerically reported in the registry record. There are no group-specific mean changes, standard deviations, between-group estimate, confidence interval, or primary p-value. Without those quantities, neither the magnitude nor precision of the primary comparison can be judged. The record therefore does not establish that either approach produced a particular outcome, nor does it establish that the approaches were equivalent or different.

The record also does not report participant flow, the number with completed follow-up, adherence, missing-data handling, or the statistical analysis population. These omissions leave uncertainty about how much information contributed to the primary endpoint and how representative the observed outcomes would be if numerical results were reported. Termination status is recorded, but the reason is not; it cannot by itself explain the absence of primary numerical results or indicate the direction of findings.

The safety fields list zero serious and zero other adverse events in the groups, and zero deaths. Those entries are useful as a record of what was reported, but the safety follow-up and ascertainment details are not reported. They should not be treated as a complete characterization of all possible harms.

In general, a trial’s result is best interpreted using its effect estimate, uncertainty interval, analysis population, and handling of missing data together. Here, the registry supports a description of the comparison and outcome definitions, but not a conclusion about the comparative result. The study’s listed planning illustrations are not observed power and do not fill the gap left by missing outcome estimates.

13. Why This Trial Matters Statistically

This study raises a clear statistical comparison: whether adding budesonide-saline irrigation to smell retraining is associated with a different change in measured smell identification than smell retraining alone. Randomization and a parallel-group structure are relevant because they provide a design for comparing assigned approaches. The registered endpoint is also a defined continuous measure, with a stated follow-up window and direction in which higher UPSIT scores indicate better smell or outcome.

At the same time, the record illustrates why a defined endpoint is not the same as a reported result. Without the groups’ mean changes, variability, and between-group uncertainty, readers cannot determine the size or precision of the comparison. A clear outcome definition supports reproducibility, but interpretation requires the numerical analysis and an account of who contributed data.

The study also lists several outcomes and follow-up times. In general, examining many outcomes can make isolated findings difficult to interpret unless the analysis strategy distinguishes primary from secondary questions and addresses multiplicity. The registry identifies a primary measure and lists secondary measures, but does not report a multiplicity plan or link each listed analysis to a particular question. That makes it difficult to determine how a collection of outcome results should be weighed if they are reported elsewhere.

Finally, the endpoint population is described by follow-up completion, while participant flow and missing-data methods are not reported. For randomized studies, an account of missing outcomes and analysis populations helps readers assess whether the comparison remains informative. This trial is statistically instructive because its record contains design and measurement details but lacks the outcome and analysis information needed to evaluate the main comparison. That distinction is important in reading any clinical trial record: registration can define the question, while conclusions depend on transparent results and methods.

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.

Several limitations specific to this trial are apparent from the registry record. First, it does not report numerical results for the primary UPSIT change outcome. The absence of arm-level means, standard deviations, a between-group estimate, confidence interval, and p-value prevents assessment of effect size, direction, and precision.

Second, the primary outcome population is defined as patients who completed 8-12 week follow-up assessments, but the record does not report how many completed those assessments, how many were missing, or why data were unavailable. It also does not say whether analysis included all randomized participants or only those with observed outcomes. These omissions limit interpretation of the representativeness of the endpoint data.

Third, the status is terminated, but the reason for termination is not reported in the registry record. The record does not provide participant flow or explain whether enrollment, treatment, follow-up, and analysis concluded as planned. Enrollment is recorded as 20, but this alone does not reveal how many participants were assigned to each group or contributed to each outcome analysis.

Fourth, the registry identifies the study as randomized and unmasked but does not describe sequence generation, allocation concealment, outcome-assessor masking, adherence, or deviations from assigned interventions. It also does not report the statistical model, missing-data procedures, or a multiplicity plan for the listed outcomes and follow-up times. These details are needed to evaluate risk of bias and the reliability of any reported comparison.

Finally, adverse-event entries do not include the observation period, event definitions, or ascertainment methods. The record therefore gives limited context for interpreting the zero counts. These are limitations of the information reported in the registry, not evidence that the study necessarily had a particular methodological flaw or that a particular outcome occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment of Pediatric Patients That Lost Sense of Smell Due to COVID-19 — NCT04964414.
• Registry record last updated 2024-06-13; status last verified 2024-06.
• Results first posted 2024-02-08.
• 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 NCT04964414, a Phase 1/Phase 2 randomized, parallel-group study with no masking. It concerns pediatric and young adult patients with smell loss due to COVID-19 and compares smell retraining alone with smell retraining plus budesonide-saline irrigation. Enrollment is recorded as 20, and the status is terminated.

The primary outcome is change in UPSIT score from baseline to first follow-up, described as at 8 weeks with a range of 8 to 12 weeks. The registry lists additional SNOT-22, loss-of-smell question, and later UPSIT outcomes. Numerical results for the primary comparison, participant flow, missing-data methods, and the reason for termination are not reported in the registry record. Safety fields list no serious or other adverse events and no deaths in either group, but follow-up and ascertainment details are not reported.