Open-Label Study of OTO-201 in Pediatric Subjects With a History of Otitis Media Requiring Tympanostomy Tubes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Study of OTO-201 in Pediatric Subjects With a History of Otitis Media Requiring Tympanostomy Tubes (NCT02600559), a na phase 3 study. The primary outcome is Number of Subjects With Post-surgical Otorrhea.

2. Clinical Question

3. Trial Design

NCT02600559 is a Phase 3, prospective, multicenter, open-label, single-group study sponsored by Otonomy, Inc. Its official title describes an 8-week study of a single administration of OTO-201 in pediatric subjects with a history of otitis media requiring tympanostomy tubes. The registry lists enrollment as 501. The listed study start is 2015-10, primary completion is 2016-07, and status is completed.

The brief summary describes treatment as 6 mg of OTO-201 to each ear for eligible subjects undergoing tube placement. It also states that the study was designed to evaluate safety and efficacy in subjects undergoing tube placement with common concurrent surgeries and any middle ear effusion status. The intervention is identified as OTO-201 (ciprofloxacin), and the arm description reads “0.1 mL OTO-201.” The record does not clarify how the dose wording and arm description relate to each other.

Open-label means masking was not used, consistent with the registry entry of NONE. The design is listed as SINGLE GROUP and allocation as NA. Thus the registry does not describe randomized assignment or a like-for-like control arm. The event counts are descriptive of the treated group; they cannot by themselves separate treatment-associated outcomes from events that might occur in the absence of treatment.

The primary outcome is the number of subjects with post-surgical otorrhea at Week 4. The stated primary analysis population is the safety analysis set, defined as all subjects who received study drug. Although the study description gives an 8-week duration, this primary endpoint is specified at Week 4. The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or a numerical primary endpoint result. Those items should not be inferred from the design label or enrollment entry.

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: There were a total of 518 subjects screened for this study. There were 17 subjects considered screen failures, with the majority (11) failing to meet inclusion/exclusion criteria. Therefore, 501 subjects were assigned for treatment in this study and are designated as "enrolled".

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set: All subjects who received study drug.

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 Number of Subjects With Post-surgical Otorrhea, measured over Week 4.

The primary endpoint counts subjects with post-surgical otorrhea at Week 4. The registry defines otorrhea as drainage from the middle ear and frames the measure as absence or presence of the event. Its unit is participants, so the endpoint is a participant count rather than a measure of the amount or duration of drainage. The listed population is the safety analysis set: all subjects who received study drug.

A binary event endpoint can summarize whether a clinically described event occurred during a specified follow-up period. It can be useful for describing the observed frequency of an event in the population under study. In general, a prespecified time point helps make clear when the event status is assessed; it does not, by itself, establish how an event was ascertained or how missing assessments were handled.

The registry record identifies the endpoint and its assessment time but does not give the number of participants with otorrhea, the number without it, or an estimated event rate. It also does not report a confidence interval or a formal analysis for this primary outcome. Consequently, the endpoint definition can be explained, but its observed result and precision cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s design and the way its outcomes are recorded determine what can be learned from the registry entries. General statistical explanations below distinguish descriptive event counts from comparative treatment-effect estimates.

What does a single-group design estimate?

A single-group study observes outcomes in participants who receive the study intervention. A count of participants with an event can describe the experience of that group over the stated observation period, provided the event and analysis population are defined. It does not include a concurrent counterfactual group: there is no randomized control group in this record against which to compare outcomes under the same study conditions.

For that reason, an event count in a single group is not, by itself, an estimate of the difference caused by treatment. Participants may experience events for many reasons, and the registry entry does not separate those possibilities. The study’s open-label status also means that masking was not used. The registry does not report additional procedures that might address assessment or reporting influences.

What does a binary participant count mean?

The primary measure is a count of subjects with post-surgical otorrhea, with the event described as present or absent at Week 4. A binary outcome places each assessed participant into an event category rather than measuring a continuous quantity such as duration or amount. A count can be easy to interpret, but its meaning depends on the population included, the event definition, the observation window, and how incomplete assessments are treated.

Here, the record identifies the safety analysis set as all subjects who received study drug. It does not provide the primary endpoint count or describe missing Week 4 assessments. As a result, the record does not allow readers to reconstruct the denominator for that endpoint, assess the extent of missingness, or estimate an event frequency. The at-risk counts in the adverse-event entry should not be substituted for a primary endpoint denominator without an explicit statement that they apply to that endpoint.

Why do uncertainty intervals matter?

In general, a confidence interval gives a range of values compatible with the data and a specified statistical procedure. It helps readers distinguish an estimate from the uncertainty around that estimate. A count alone can be difficult to interpret as evidence about the underlying event frequency, especially when the number of observations and the event count are not both reported for the relevant endpoint. No confidence interval for post-surgical otorrhea is reported in the registry record.

A confidence interval would not solve the design limitation of lacking a control group. It could describe uncertainty around a single-group event estimate, but it could not on its own establish what would have occurred under a comparator condition or identify a causal treatment effect. Statistical precision and causal interpretability are separate issues.

How should the planning illustration be read?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It describes detecting a fraction of an observed effect. Those are planning assumptions, not features of the reported single-group design. The illustration is explicitly characterized as based on the observed effect rather than the trial’s own design. Therefore, hypothetical two-arm sample-size calculations should not be read as evidence that this study enrolled randomized arms or was planned around those calculations.

In general, a sample-size calculation depends on the target effect, variability or event frequency, significance level, desired power, allocation, and statistical model. Changing the target effect changes the planning requirement. Any calculated sample size is a planning illustration under its assumptions, not a count of participants observed to benefit and not “observed power.” No numerical planning outputs or trial-specific sample-size justification are reported in the registry record.

What can adverse-event counts establish?

Adverse-event counts summarize reports within the group and categories specified in the registry. They can indicate how many participants were recorded as affected, but they do not reveal whether events were related to treatment unless attribution is reported. They also do not show event timing, duration, recurrence, or the number of events per participant unless those details are separately described. In general, comparisons of safety risks require comparable groups and clear definitions of how events were collected and classified. The record’s single-group design does not furnish a randomized safety comparison.

The registry lists no analyses. This means the record does not include a reported inferential analysis for the outcomes in the material described. It does not establish whether analyses were conducted elsewhere or whether unreported analytic procedures were used. The appropriate interpretation is limited to the design, endpoint definitions, and counts that the registry actually records.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures, including the primary post-surgical otorrhea outcome and secondary outcomes for adverse events and caregiver burden. Caregiver burden includes ear discharge control and ear-drop administration; ear discharge control appears twice in the secondary-outcome list. The record does not explain whether that repetition reflects separate measures, separate time points, or a duplicate entry. No multiple-testing strategy, endpoint hierarchy beyond the listed primary designation, or adjustment for testing several outcomes is reported in the registry record.

In general, multiplicity arises when several hypotheses or outcomes are examined. If many comparisons are tested, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for the testing structure. An adjustment or prespecified hierarchy can help control that risk, but the record does not state whether either was used. With 0 analyses listed, the registry entries do not provide inferential results for evaluating multiplicity in practice.

Missing-data methods are also not reported in the registry record. The primary analysis population is described as all subjects who received study drug, but the entry does not state how missing Week 4 outcome assessments were handled, whether participants with incomplete assessments were excluded, or whether any imputation was used. The listed adverse-event at-risk count does not answer those questions for the primary endpoint. In general, missing outcome data can affect both the number analyzed and the interpretation of an estimated event frequency. Without the number assessed for the primary outcome and the missing-data approach, that impact cannot be evaluated.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: influenza (0.2%).

The adverse-event entry for the 6 mg OTO-201 group lists 501 at risk. It records 1 participant affected by a serious adverse event, 200 affected by other adverse events, and 0 deaths. Influenza appears among the serious adverse-event terms at 0.2%. These are registry-recorded counts and a listed percentage; they should be read as descriptive entries rather than as evidence of comparative risk.

The serious-event count and the other-adverse-event count refer to different categories in the record. They should not be added together: the record does not state whether the categories overlap at the participant level, and the counts do not necessarily represent mutually exclusive groups. The number of affected participants also does not indicate how many total event episodes occurred.

In general, an adverse event is not necessarily caused by the intervention. The record does not report the event-attribution criteria, timing, duration, severity details, or the number of recurring events. Because the study is single-group and open-label, the entries do not provide a randomized comparison for assessing whether the intervention changed the occurrence of these events. The listed counts can describe what the registry recorded, but they do not establish causation or comparative safety.

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

The record establishes that a Phase 3, prospective, multicenter, open-label, single-group study of OTO-201 was completed, with enrollment listed as 501. Its stated study period was 8 weeks, and its primary endpoint was the number of subjects with post-surgical otorrhea at Week 4. It also records selected adverse-event counts. These registry entries describe the study’s design and the outcomes entered in the registry; they do not supply a numerical primary efficacy result.

Because the primary endpoint result is not reported, the registry record does not show how many subjects had post-surgical otorrhea. It therefore does not support an estimate of the event frequency, an interval describing its precision, or a quantitative claim about efficacy. The listed safety counts are descriptive and do not establish that OTO-201 caused or prevented any event.

The lack of a randomized comparator is also important. An observed outcome among treated participants cannot, on its own, show what would have occurred under another treatment or without study drug. Even a precise estimate of the treated group’s event frequency would not resolve that comparative question. The record does not report an analysis that addresses it.

These limits do not make the recorded information meaningless. The registry identifies the population of interest, intervention, design, endpoint, assessment time, and selected safety counts. Those details help readers understand what was intended to be studied and what was recorded. But a purpose statement, a completed status, and an endpoint definition are not substitutes for the endpoint results and their analysis. The interpretation should remain confined to what the record documents, without extending the descriptive entries into a treatment-effect conclusion.

13. Why This Trial Matters Statistically

This study is statistically notable because its stated clinical question is paired with a single-group, open-label design. That combination determines the kind of evidence the registry can describe. The design can record outcomes among treated participants, but without a concurrent randomized comparator it cannot directly estimate a treatment-versus-control contrast. Recognizing that boundary is essential when reading event counts.

The primary endpoint is a binary participant count at a defined follow-up point: post-surgical otorrhea at Week 4. Such an endpoint is interpretable only alongside its result, the relevant analysis population, and information about missing assessments. The registry defines the measure and population but does not report the numerical outcome. That gap prevents calculation or interpretation of an observed primary endpoint frequency from this record.

The safety entries illustrate a separate statistical issue: counts can be informative as descriptions while remaining limited for causal or comparative conclusions. The record lists serious and other adverse-event counts and a serious-event term, but it does not provide a randomized comparator or event-attribution details. Readers need to distinguish the recorded occurrence of events from evidence that an intervention changed their occurrence.

Finally, the planning assumptions described for the sample-size illustration use a hypothetical two-arm framework, while the registry design is single-group. Keeping planning illustrations separate from the actual trial design prevents a sample-size calculation from being mistaken for a feature of the study or for observed evidence. Together, these points show why design, endpoint reporting, uncertainty, and causal interpretation must be considered separately.

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 central limitation for interpreting the primary outcome is that the registry defines post-surgical otorrhea at Week 4 but does not report its numerical result. The record also does not include an interval, an analysis population count specific to that endpoint, or a description of missing Week 4 assessments. Consequently, neither the observed frequency nor its precision can be evaluated from the registry record.

The single-group, open-label design has no randomized comparator listed. Any event counts describe the treated group and cannot establish what would have occurred under a different treatment or without study drug. The record does not report masking, blinded outcome assessment, or procedures that would otherwise clarify how the outcome was ascertained.

Safety reporting is limited to the listed at-risk, affected, and death counts and the serious-event term shown. Further information about event definitions, timing, duration, severity, attribution, recurrence, and overlap between categories is not reported in the registry record. The record also does not state how missing data were handled or provide a multiplicity plan for the listed outcomes.

The summary describes 6 mg to each ear, while the arm description identifies “0.1 mL OTO-201.” The registry record does not explain their relationship. It also does not report a trial-specific sample-size justification, interim analyses, or a statistical analysis plan. These omissions limit assessment of how the study was planned and how its outcomes were analyzed; they should not be filled by assumption.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open-Label Study of OTO-201 in Pediatric Subjects With a History of Otitis Media Requiring Tympanostomy Tubes — NCT02600559.
• Registry record last updated 2020-10-19; status last verified 2020-09.
• Results first posted 2020-09-22.
• 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

NCT02600559 is a completed Phase 3, prospective, multicenter, open-label, single-group study sponsored by Otonomy, Inc. It lists enrollment of 501 and concerns pediatric subjects with a history of otitis media requiring tympanostomy tubes. The study description specifies a single administration of OTO-201 and an 8-week study period.

The primary outcome is the number of subjects with post-surgical otorrhea at Week 4, defined as middle-ear drainage. The registry record does not report a numerical result for this endpoint. It lists 6 outcome measures and 0 analyses. For the 6 mg OTO-201 group, the adverse-event entry lists 1 serious adverse event, 200 affected by other adverse events, and 0 deaths; influenza is listed among serious terms at 0.2%.

The single-group design permits descriptive reporting but does not provide a randomized comparison. The primary outcome’s frequency, its precision, and a comparative treatment effect are not available from the registry record.