This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for OTO-201 for the Treatment of Middle Ear Effusion in Pediatric Subjects Requiring Tympanostomy Tube Placement (NCT01949155), a randomized phase 3 study. The primary outcome is Percentage of Participants Who Were Treatment Failures..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01949155 |
| Phase | Phase 3 |
| Condition | Otitis Media With Effusion |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 266 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Otonomy, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Pediatric subjects with bilateral middle ear effusion who required tympanostomy tube placement. The registry identifies the primary analysis population as the Full Analysis Set, but does not report further eligibility details for that population in the results record.
Intervention
OTO-201, described as ciprofloxacin in poloxamer 407, given as a single intratympanic injection during surgery. The regimen was one injection of 6 mg into each ear.
Comparator
A sham procedure consisting of a simulated single intratympanic injection into each ear during surgery.
Primary question
What percentage of participants in each group met the registry’s cumulative treatment-failure definition through Day 15, two weeks after dosing? The definition included otorrhea determined by a blinded assessor on or after 3 days post-surgery, otic or systemic antibacterial drug use for any reason after surgery, and missed visits or loss to follow-up.
3. Trial Design
This was a prospective, randomized, double-blind, sham-controlled, multicenter phase 3 study with a parallel-group model. The registry classifies masking as triple. It records enrollment of 266 and status as completed. The study began in 2013-11, and primary completion was recorded in 2014-05.
The trial compared OTO-201 with sham during tympanostomy tube surgery in pediatric subjects with bilateral middle ear effusion. The OTO-201 description specifies a single intratympanic injection of 6 mg into each ear; the comparator involved a simulated injection into each ear. The registry identifies Otonomy, Inc. as the sponsor.
Random allocation and a sham comparator establish the intended basis for comparing the posted group results, while masking is intended to limit the influence of knowledge of assignment on study conduct or outcome assessment. The registry does not describe the allocation procedure, how the masking was maintained, which roles were masked, or the details of the multicenter organization. Those details are not reported in the registry record.
The primary endpoint was the cumulative proportion of treatment failures through Day 15, with the Full Analysis Set named as the population. The registry also lists evaluation of adverse events, otoscopic exams, audiometry and tympanometry, and microbiological response as secondary outcomes. It does not report the protocol’s sample-size justification, detailed eligibility criteria, or full statistical analysis plan.
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: Reporting group = all randomized participants (n=266). Safety analysis set = all subjects who receive study drug or sham and analyzed according to what they received. Full analysis set = all randomized subjects and analyzed according to randomized treatment regardless of the actual treatment received.
Overall Study
| Stage | OTO-201 | Sham |
|---|---|---|
| STARTED | 178 | 88 |
| COMPLETED | 176 | 88 |
| NOT COMPLETED | 2 | 0 |
Reasons for not completing this period:
| Reason | OTO-201 | Sham |
|---|---|---|
| Lost to Follow-up | 1 | 0 |
| Protocol Violation | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set
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 reporting group includes all randomized participants.
| Characteristic | Unit | OTO-201 | Sham | Total |
|---|---|---|---|---|
| Participants analysed | 178 | 88 | 266 | |
| Age, Categorical: <=18 years | Participants | 178 | 88 | 266 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 2.279 (SD 1.9010) | 2.863 (SD 2.5942) | 2.472 (SD 2.1677) |
| Sex: Female, Male: Female | Participants | 82 | 40 | 122 |
| Sex: Female, Male: Male | Participants | 96 | 48 | 144 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants Who Were Treatment Failures., measured over Day 15 - 2 weeks after dosing.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of treatment failures |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of participants classified as treatment failures by Day 15, described as two weeks after dosing. It is a cumulative endpoint: a participant was counted as a failure if any event in the registry definition occurred during the specified period. The listed events were otorrhea determined by a blinded assessor on or after 3 days post-surgery, use of otic or systemic antibacterial drugs for any reason after surgery, and missed visits or loss to follow-up.
A composite endpoint combines events into a single outcome. It can represent several ways the study defines an unfavorable course, but the combined percentage does not show which component contributed to each failure. The registry does not provide component-specific results, so the relative contribution of otorrhea, antibacterial drug use, missed visits, or loss to follow-up cannot be determined from the posted primary result.
The measure is reported as a percentage, with values of 21.3% for OTO-201 and 45.5% for sham. A cumulative failure measure reflects whether a participant met the definition at any point through the stated endpoint window, rather than describing a single observation alone. The endpoint is not a direct measure of every clinical feature named among the secondary outcomes. Its interpretation depends on the precise event definition and on how missing visits and loss to follow-up are handled; in this definition, those events themselves count as treatment failure.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results report treatment-failure percentages of 21.3% for OTO-201 and 45.5% for sham through Day 15. These are descriptive group results for the Full Analysis Set named by the registry. They show that a smaller percentage of the OTO-201 group was classified as a failure under the stated composite definition than the sham group. This description does not establish the precision of the comparison or determine whether it meets a statistical criterion.
The registry record contains no posted analyses. It does not report a confidence interval, p-value, adjusted comparison, or other inferential result for this endpoint. Without such information, readers cannot assess the sampling uncertainty around the group percentages or the uncertainty around their comparison. The outcome values alone do not establish whether the observed difference is compatible with a range of underlying effects.
The group sizes listed with the primary outcome are 178 for OTO-201 and 88 for sham. The adverse-event record uses a sham group at-risk count of 87, rather than 88. The record does not explain the difference between these denominators. They should be read in the context of their respective outcome records and not treated as interchangeable.
The primary endpoint is composite and includes missed visits or loss to follow-up as failures. Consequently, the reported percentages combine clinical events with follow-up events, and the record does not show how many failures arose from each category. It also does not report how the outcome was assessed beyond specifying a blinded assessor for otorrhea, or provide participant-level outcome information.
The posted result therefore supports a narrow descriptive statement about the proportions classified as treatment failures under this definition and within this follow-up window. It does not, on its own, quantify uncertainty, explain the components of failure, or supply evidence about outcomes beyond Day 15. The sponsor’s own analysis is not available in the registry record, so there is no sponsor analysis to compare with a recalculation.
9. Statistical Methods Explained
The interpretation of a clinical-trial result depends on the outcome definition, comparison structure, analysis population, and uncertainty around the estimate. The registry describes a randomized parallel-group comparison of OTO-201 and sham, and reports the primary outcome as a cumulative percentage. The principles below are general explanations of how such results are usually read; they do not imply that any unreported analysis was performed in this trial.
What does randomization contribute?
In general, random allocation is intended to make assigned groups comparable with respect to measured and unmeasured characteristics, on average. It helps support a treatment-group comparison, but does not guarantee that every characteristic will be balanced in a particular trial. The registry identifies the allocation as randomized but does not report the sequence-generation method, concealment procedures, or balance of baseline characteristics. Those details are not reported in the registry record.
What does masking contribute?
In general, masking can reduce the possibility that expectations about assignment influence care, reporting, or outcome assessment. The registry classifies this trial as triple-masked and describes it as double-blind in the official title. It does not specify which people were masked or how masking was maintained. The endpoint definition explicitly assigns otorrhea assessment to a blinded assessor, but the record does not describe the assessment process further.
How should a percentage be read?
A group percentage describes the share of the analysis population meeting the outcome definition. It is a point estimate: a summary based on the observed participants, not a guarantee that the same value would be observed in another sample. The posted percentages are 21.3% for OTO-201 and 45.5% for sham. The registry gives the corresponding primary-outcome group sizes as 178 and 88. No confidence intervals are reported, so the uncertainty around either percentage is not quantified in the record.
A confidence interval is a statistical range used to express uncertainty about an estimated quantity under a specified method and assumptions. Its width reflects the precision of the estimate under that method. Since the registry record does not report intervals for this primary result, no interval-based assessment of precision or compatibility with other possible values can be made from the posted results.
Why does the composite definition matter?
A composite outcome classifies participants according to whether any of several specified events occurred. This can make the endpoint relevant to multiple types of failure, but it also means the overall percentage can conceal differences in the types of events. Here, the definition combines otorrhea assessed on or after 3 days post-surgery, post-surgery use of otic or systemic antibacterial drugs for any reason, and missed visits or loss to follow-up. The registry does not report the counts for these individual components. Therefore, the aggregate percentages cannot reveal which components were most frequent or whether the groups differed similarly on each component.
Composite definitions also depend on their operational rules. The specified timing and assessment conditions determine which events count. For this endpoint, missed visits and loss to follow-up are expressly included as treatment failures. This is not the same as treating an unobserved outcome as though it were known to be favorable or unfavorable through a separate imputation model. The record does not report further missing-data procedures or sensitivity analyses.
What is the role of an analysis population?
The registry names the Full Analysis Set as the primary population. An analysis population defines which participants contribute to a particular estimate. The label alone does not explain the population’s inclusion rules, how protocol deviations were handled, or whether all randomized participants were included. These details are not reported in the registry record. The number associated with an outcome can also differ from enrollment or from a safety denominator when the analysis populations or available records differ; the registry does not explain the denominator difference between the primary sham outcome and the sham adverse-event record.
What can be said about statistical significance?
A statistical test evaluates data relative to a specified null hypothesis and model. A p-value, when reported, is one measure related to how compatible the data are with that hypothesis under the model; it is not a measure of clinical importance or the probability that a treatment is effective. No p-value, test statistic, or inferential analysis is posted for the primary result. Statistical significance therefore cannot be assessed from the registry record.
How should planning calculations be understood?
In general, sample-size planning uses assumptions about the outcome, allocation, significance threshold, and effect to be detected. A planning illustration based on an observed effect is not the same as the trial’s original sample-size justification, and it is not observed power. The record’s planning assumptions specify a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as a stated fraction of the observed effect. The protocol’s own sample-size justification is not reported in the registry record. No planning sample-size values are included among the posted trial details, so no such values can be interpreted for this study.
Finally, unadjusted recalculation from summary values would not replace the sponsor’s analysis if the two differed. The registry record reports no analyses and no discrepancy between a sponsor result and a recalculated result. As a result, the primary interpretation should remain descriptive and limited to the posted percentages, endpoint definition, and stated population.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two secondary outcome descriptions: evaluation of adverse events, otoscopic exams, audiometry and tympanometry, and microbiological response. It does not report a multiplicity procedure for evaluating the primary and secondary outcomes, nor does it identify a hierarchy of hypotheses or an adjustment to account for multiple statistical comparisons. No analyses are posted. It is therefore not possible to determine from the record how multiplicity was handled in the trial’s statistical analysis.
The primary endpoint definition counts missed visits and loss to follow-up as treatment failures. That is a stated feature of this composite outcome, not a separately described imputation method. The registry does not report additional procedures for missing observations, sensitivity analyses, or how other missing outcome information was treated. Further details are not reported in the registry record.
The primary population is identified as the Full Analysis Set, but the registry does not give its operational definition. It does not report how participants were assigned to that population, how protocol deviations were handled, or whether the primary analysis included every randomized participant. The primary outcome lists 178 for OTO-201 and 88 for sham, while the adverse-event record lists at-risk denominators of 178 and 87, respectively. The record does not explain why the denominators differ.
These omissions limit reconstruction of the analysis and assessment of robustness. They do not establish that a particular method was or was not used outside what the registry reports; they mean that the method cannot be identified from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| OTO-201 | 0 | 178 | 0.0% |
| Sham | 0 | 87 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| OTO-201 | 75 of 178 |
| Sham | 40 of 87 |
Most frequent non-serious adverse event terms
| Event term | Organ system | OTO-201 | Sham |
|---|---|---|---|
| Pyrexia | General disorders | 25 of 178 | 11 of 87 |
| Procedural pain | Injury, poisoning and procedural complications | 13 of 178 | 11 of 87 |
| Upper respiratory tract infection | Infections and infestations | 12 of 178 | 9 of 87 |
| Teething | Gastrointestinal disorders | 13 of 178 | 5 of 87 |
| Cough | Respiratory, thoracic and mediastinal disorders | 12 of 178 | 4 of 87 |
The adverse-event record reports zero serious adverse events among 178 participants at risk in the OTO-201 group and zero among 87 participants at risk in the sham group. These are observed counts in the registry record. They should not be read as proof that serious adverse events are impossible, or that the groups have identical underlying risk. With no inferential analysis or uncertainty estimates posted, the precision of these counts cannot be assessed statistically from the record.
The safety denominators are not the same as the primary-outcome denominators: the sham adverse-event at-risk count is 87, whereas the sham primary-outcome group size is 88. The registry does not explain this difference. The record does not list serious-event terms, and deaths are not reported. The non-serious or other adverse-event counts are recorded as 75 for OTO-201 and 40 for sham, with at-risk counts of 178 and 87, respectively. These counts do not describe severity, timing, or event types in detail.
Safety counts and the primary treatment-failure outcome answer different questions. The composite primary endpoint includes several specified events and is not a serious-adverse-event measure. The registry’s safety figures should therefore be interpreted separately from the primary efficacy endpoint.
12. What the Result Does, and Does Not, Mean
The posted results describe a randomized comparison of OTO-201 and sham in pediatric subjects with bilateral middle ear effusion requiring tympanostomy tube placement. The primary endpoint is the cumulative percentage meeting a composite treatment-failure definition through Day 15. The recorded percentages are 21.3% for OTO-201 and 45.5% for sham. The registry names the Full Analysis Set as the primary population.
These figures do not by themselves establish the precision or statistical significance of the comparison. The registry record reports no confidence interval, p-value, or posted analysis for the primary endpoint. It also does not provide component-specific failure results, so the overall percentages cannot show how much each listed event contributed.
The findings are tied to the study’s setting and endpoint: an intra-operative injection into each ear, with sham injection as comparator, and follow-up through Day 15. The registry does not report longer-term primary results. The listed secondary outcomes include adverse events, otoscopic exams, audiometry and tympanometry, and microbiological response, but results for those outcomes are not detailed in the registry record for this analysis.
The result should not be treated as a complete account of all benefits or harms, or as a prediction for every patient or setting. The record does not supply enough information to judge the effects of participant characteristics, the individual components of the composite, or outcomes beyond the stated time frame. It also does not provide the analysis plan needed to evaluate the full inferential framework.
In statistical terms, the percentages are observed summaries, not a complete uncertainty assessment. They document how the registry classified the groups under its stated endpoint definition. Any broader interpretation would require information not reported in the registry record, including inferential results, detailed analysis methods, and additional outcome reporting.
13. Why This Trial Matters Statistically
This trial illustrates why a clinical result must be read together with its design and endpoint definition. The randomized, sham-controlled parallel-group structure frames the comparison, while the primary endpoint combines several events into one cumulative treatment-failure measure. The posted percentages are interpretable only in relation to that specific definition and its Day 15 time frame.
It also shows how endpoint composition affects meaning. Otorrhea, post-surgery antibacterial drug use, missed visits, and loss to follow-up all count as failure under the registry definition. An overall percentage can be useful as a summary, but without results for its components it cannot explain what drove the outcome. This distinction matters when interpreting composite endpoints generally.
The registry record also demonstrates the difference between a point estimate and an inferential result. Group percentages and denominators describe the recorded data, while confidence intervals and statistical tests would address uncertainty under specified methods. Those inferential analyses are not posted for this endpoint. The absence of such results limits assessment of precision and statistical evidence; it does not change the descriptive values themselves.
Finally, the discrepancy between the listed primary sham group size and the sham safety denominator underscores that outcome records may use different available populations or denominators, though this registry does not explain the reason. Clear reporting of analysis populations, missing-data methods, endpoint components, and statistical procedures is important for readers seeking to reproduce or critically evaluate a trial’s findings.
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 registry record gives limited detail about the statistical methods. It reports no analyses for the trial and no confidence interval, p-value, or adjusted comparison for the primary endpoint. The protocol’s statistical analysis plan, sample-size justification, and any interim-analysis procedures are not reported in the registry record.
The Full Analysis Set is named, but its membership and operational rules are not described. The registry does not explain how the primary endpoint’s sham denominator of 88 relates to the adverse-event at-risk count of 87. It also does not provide component-level counts for the composite treatment-failure definition, or additional missing-data methods and sensitivity analyses.
The outcome window is limited to Day 15 for the primary endpoint. The registry entries do not include longer-term primary results. They also do not provide detailed results for the listed secondary outcomes, serious-event terms, or deaths. The record reports non-serious or other adverse-event counts, but does not give event types, timing, or severity detail for those counts.
Further design details are also absent, including the randomization procedure, concealment methods, which roles were masked, and detailed eligibility criteria. The registry identifies the study as multicenter and triple-masked, but does not elaborate on those features. These limitations restrict interpretation of the posted summaries and prevent a fuller reconstruction of the conduct and analysis from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: OTO-201 for the Treatment of Middle Ear Effusion in Pediatric Subjects Requiring Tympanostomy Tube Placement — NCT01949155.
- Registry record last updated 2016-11-11; status last verified 2016-09.
- Results first posted 2016-11-11.
- 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.
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18. Record Summary
NCT01949155 is a completed randomized, sham-controlled phase 3 parallel-group study of OTO-201 during tympanostomy tube placement in pediatric subjects with bilateral middle ear effusion. The registry records enrollment of 266, a start in 2013-11, and primary completion in 2014-05. OTO-201 was described as a single intratympanic injection of 6 mg into each ear; the sham group received simulated injections.
The primary endpoint was cumulative treatment failure through Day 15, defined to include specified otorrhea, antibacterial drug use, missed visits, or loss to follow-up. Reported percentages were 21.3% for OTO-201 and 45.5% for sham, with the Full Analysis Set identified as the analysis population. No analyses are posted in the registry record. Safety data report zero serious adverse events in each group, with different sham denominators between the primary and safety records. The registry lists adverse-event assessment and microbiological response among the secondary outcomes.