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 Pediatric Zylet Safety and Efficacy Study (NCT00420628), a randomized phase 4 study. The primary outcome is Treatment Emergent Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00420628 |
| Phase | Phase 4 |
| Condition | Chalazion, Hordeolum |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 108 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bausch & Lomb Incorporated |
| Results posted | Yes |
2. Clinical Question
Population
Children aged 0–6 with lid inflammation associated with chalazion or hordeolum were the intended population. The study summary identifies a pediatric population, and the condition list names chalazion and hordeolum. The primary outcome is described for the safety population and the study eye; additional eligibility details are not reported in the registry record.
Intervention
The active intervention was loteprednol etabonate 0.5% with tobramycin 0.3% ophthalmic suspension, identified in the study title as Zylet. The registry record describes the study as evaluating this combination for management of lid inflammation. Details such as dosing schedule and treatment duration are not reported in the registry record.
Comparator
The comparator was vehicle. The record identifies it as a drug intervention and describes the treatment comparison as active suspension versus vehicle. Whether any additional care or restrictions applied is not reported in the registry record.
Primary question
The listed primary outcome is treatment-emergent adverse events, measured as the number of participants in the safety population at study-eye visits on day 1, day 8, and day 15. The study title and summary also describe an efficacy objective, with secondary outcomes including an investigator global assessment and ocular-sign assessments. The registry record does not provide a single primary efficacy comparison or its analyzed result.
Statistically, the record supports a description of the randomized comparison and the posted safety counts, but not a conclusion about comparative efficacy. The distinction matters: an objective stated in a study title or summary is not itself an analyzed endpoint result. The record lists five outcome measures and no analysis entries. It also indicates that the primary outcome has multiple categories or time points and was not reduced to one comparison. Thus, the posted primary-outcome label does not identify a single contrast with an accompanying estimate and uncertainty measure.
3. Trial Design
The study was randomized, quadruple masked, and used a parallel-group model. Its phase is listed as Phase 4, and its status is completed. The registry record lists enrollment as 108. It describes the study as multicenter and as comparing Zylet with vehicle for management of lid inflammation in children aged 0–6. The listed conditions are chalazion and hordeolum.
The active intervention was loteprednol etabonate 0.5% with tobramycin 0.3% ophthalmic suspension; the other arm received vehicle. A parallel design assigns participants to one of the treatment groups rather than describing a crossover between treatments. Randomization is intended to make treatment groups comparable on average, while masking is intended to limit influences of treatment knowledge on care, assessment, or reporting. The record does not describe who was included in the four masking roles, how the random sequence was generated, or how allocation was concealed.
The listed start was 2006-11 and the primary completion was 2009-01. Bausch & Lomb Incorporated is named as sponsor. These registry entries describe the trial's administrative design and timeline; they do not establish how faithfully each operational procedure was carried out. The protocol details for eligibility, intervention schedule, adherence, and follow-up beyond the stated outcome time points are not reported in the registry record.
The primary outcome is treatment-emergent adverse events, described as a participant count for the study eye in the safety population across visits on day 1, day 8, and day 15. Secondary outcomes include an investigator global assessment of the clinical condition and assessments of ocular signs in the study eye at visits 1, 2, and 3. The registry record lists five outcome measures but no analysis entries. It does not report the intended allocation ratio, sample-size justification, or a complete 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: 108 subjects were randomized to receive loteprednol/tobramycin or its vehicle in a 2:1 ratio. Subjects will receive warm compress lid treatment 2 times daily, before administration of study medication (as applicable) for the 14-day treatment duration.
Overall Study
| Stage | Loteprednol/Tobramycin | Vehicle |
|---|---|---|
| STARTED | 72 | 36 |
| COMPLETED | 63 | 32 |
| NOT COMPLETED | 9 | 4 |
Reasons for not completing this period:
| Reason | Loteprednol/Tobramycin | Vehicle |
|---|---|---|
| Withdrawn by parent or gaurdian | 5 | 2 |
| Lost to Follow-up | 3 | 2 |
| Adverse Event | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety population, Study eye
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.
| Characteristic | Unit | Loteprednol/Tobramycin | Vehicle | Total |
|---|---|---|---|---|
| Participants analysed | 72 | 36 | 108 | |
| Age, Customized: Age 0-6 years | participants | 72 | 36 | 108 |
| Sex: Female, Male: Female | Participants | 37 | 23 | 60 |
| Sex: Female, Male: Male | Participants | 35 | 13 | 48 |
| Race/Ethnicity, Customized: Asian | participants | 3 | 1 | 4 |
| Race/Ethnicity, Customized: Black or African American | participants | 10 | 7 | 17 |
| Race/Ethnicity, Customized: White | participants | 52 | 25 | 77 |
| Race/Ethnicity, Customized: Other | participants | 7 | 3 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Treatment Emergent Adverse Events, measured over day 1, day 8, day 15.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The listed primary endpoint is treatment-emergent adverse events. It is expressed as the number of participants with an event, rather than a continuous measurement such as a score or a time-to-event measure. The endpoint description places the assessment in the safety population and refers to the study eye, with the timeframe stated as day 1, day 8, and day 15. The record also describes the assessment as occurring at visits 1, 2, and 3.
Safety outcomes are used to characterize undesirable events observed during a trial and to compare event counts between treatment groups. A participant count answers how many participants experienced an event under the endpoint's definition; it is different from a count of all event episodes, because one participant could potentially have more than one episode. The registry record does not explain whether recurrent events were counted separately, how treatment emergence was defined, how severity or relatedness was assessed, or how events spanning visits were handled.
The posted safety figures distinguish serious events from other affected participants. In the loteprednol/tobramycin group, the serious-event count is 1 among 72 at risk, while the other-event count is 0 among 72 at risk. In the vehicle group, the corresponding serious-event and other-event counts are both 0, among 36 at risk. These counts should be read as safety reporting, not as a complete estimate of efficacy. Although the study title and summary refer to efficacy, the registry record does not report an analyzed primary efficacy endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted serious adverse-event counts are 1 participant in the loteprednol/tobramycin group and 0 in the vehicle group. The listed numbers at risk are 72 and 36, respectively. For other affected participants, the posted counts are 0 in each group. The record also identifies bilateral subdural hematoma as the top serious-event term and gives 1.4%. These are descriptive safety figures; they do not, by themselves, establish whether an event was caused by treatment.
The event counts are sparse, particularly for serious events. When only a small number of events are recorded, the observed counts provide limited information about how frequently events might occur in a wider population. A zero count in a study group does not establish that the underlying risk is zero. Likewise, one recorded event in a group does not establish a treatment effect. A comparative estimate with an interval of uncertainty and a defined statistical analysis would be needed to quantify the precision of a group contrast. Such an analysis is not reported in the registry record.
The endpoint description covers day 1, day 8, and day 15, but the record does not give event counts separately for those times. It also states that the primary outcome has several categories or time points and was not reduced to one comparison. This makes it important not to treat the displayed safety counts as a complete analysis of every endpoint category or time-specific comparison. The record lists five outcome measures but does not provide analyses for them.
The study's stated aim includes both safety and efficacy, but the registry information is insufficient to assess efficacy. Secondary outcomes are named, including a global clinical assessment and ocular-sign assessments, yet their results and analysis details are not reported in the registry record. No conclusion about benefit, lack of benefit, or equivalence follows from the available safety counts.
Overall, the posted figures show one serious event in the active-treatment group and none in the vehicle group, with no other affected participants listed in either group. The interpretation should remain descriptive. The record does not report a statistical comparison, confidence interval, prespecified hypothesis test, or details needed to judge event attribution and completeness. The sparse counts warrant particular caution in any attempt to generalize beyond the participants represented in the registry results.
9. Statistical Methods Explained
The primary outcome is a binary participant-level measure: a participant either is or is not counted as having the specified event during the stated assessment period. The record gives counts for serious events and for other affected participants, along with the number at risk in each group. This format is useful for describing event occurrence, but it is not a full statistical comparison. It does not show the uncertainty around an estimated difference between groups or establish that a difference is attributable to treatment.
For binary outcomes, a common analysis compares the proportion of participants with an event in each randomized group. The registry record does not report such an analysis for the primary outcome. No risk difference, relative measure, confidence interval, or hypothesis-test result is given. The counts can therefore be read directly, but an inferential claim about a treatment contrast cannot be reconstructed from the posted outcome description alone. No recalculated comparison is reported.
A confidence interval, in general, is a range of values compatible with the data under a specified statistical model and procedure. It conveys precision as well as the direction and magnitude of an estimate. When event counts are sparse, uncertainty can be substantial, and methods that rely on large-sample approximations may perform poorly. Exact or other small-sample methods may be considered in general, but the registry record does not say which method, if any, was planned or used. No interval should be inferred from the counts alone.
Time points and outcome categories complicate interpretation. The primary endpoint description refers to day 1, day 8, and day 15, and to visits 1, 2, and 3. Repeated assessments may refer to the same participants over time, so counts at separate visits cannot automatically be treated as independent observations. An analysis would need to clarify whether the target is any event over follow-up, events at particular visits, or a change across visits. The record explicitly indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The separate visit-specific results and the analytic approach are not reported in the registry record.
Masking and randomization are features of design, not substitutes for an analysis plan. Randomization can support a fair comparison when assignment and follow-up are implemented as intended, while masking can reduce some assessment and reporting influences. The registry record labels the study randomized and quadruple masked, but the sequence-generation method, allocation concealment, details of masking, and assessment of masking are not reported. These omissions limit evaluation of how the design was put into practice.
The record lists five outcome measures and no analysis entries. It does not report a prespecified primary comparison, model specification, covariate adjustment, handling of repeated measurements, or statistical test. It also does not report interim analyses or a multiplicity procedure. Multiplicity is a general concern when several outcomes, time points, or comparisons are examined: the chance of at least one apparently unusual result can increase as the number of statistical tests grows. Whether or how that concern was addressed in this trial is not reported in the registry record.
Sample-size planning is distinct from analysis of observed results. A planning illustration based on an observed effect is not the trial's original design justification and is not observed power. In general, a sample-size calculation depends on the effect to detect, the assumed variability or event frequency, the significance level, allocation, and desired power. The registry record states that its planning illustration uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, with effects expressed as fractions of the observed effect. It does not report the trial's own sample-size justification or establish that those illustration assumptions were used to design the study.
For this binary endpoint, over-dispersion is not the central issue in the way it can be for count outcomes with variance greater than a simple model expects. More generally, over-dispersion means that observed variability exceeds a model's assumed variability; ignoring it can make standard errors too small and intervals too narrow. The registry record does not report an over-dispersion assessment or a model that would require one. No model-based result is available to evaluate.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists five outcome measures, including the primary safety outcome, an investigator global assessment, and ocular-sign assessments across visits. It does not provide a multiplicity adjustment or describe how the primary and secondary outcomes were prioritized in statistical testing. When many outcomes or time points are examined, general statistical practice recognizes that isolated findings can arise by chance more often than in a single planned test. The record does not report whether this concern was addressed.
Missing-data handling is not reported in the registry record. The information does not describe withdrawals, incomplete visits, exclusions from analyses, imputation, or sensitivity analyses. Without those details, it is not possible to assess whether all randomized participants contributed to each outcome or whether missing assessments could have affected the observed counts.
The primary endpoint refers to the safety population and study eye. The record does not define that population in detail or explain how it differs from the randomized population. It also does not report an intention-to-treat analysis, a per-protocol analysis, or the rules for inclusion in any analysis population. The counts at risk are listed by group, but the registry record does not explain how those denominators were determined or whether they changed over time.
The record lists no analysis entries and does not specify a statistical analysis plan, interim analyses, or methods for handling repeated measurements. These omissions mean the posted counts can be described, but the analysis choices and the potential effects of missingness and multiple comparisons cannot be evaluated 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 |
|---|---|---|---|
| Loteprednol/Tobramycin | 1 | 72 | 1.4% |
| Vehicle | 0 | 36 | 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 |
|---|---|
| Loteprednol/Tobramycin | 0 of 72 |
| Vehicle | 0 of 36 |
Most frequent serious adverse event terms
| Event term | Organ system | Loteprednol/Tobramycin | Vehicle |
|---|---|---|---|
| bilateral subdural hematoma | Vascular disorders | 1 of 72 | 0 of 36 |
Serious events with the highest arm-level rate: bilateral subdural hematoma (1.4%).
For serious adverse events, the posted count is 1 participant among 72 at risk in the loteprednol/tobramycin group and 0 among 36 at risk in the vehicle group. For other affected participants, the count is 0 in both groups, with 72 and 36 at risk, respectively. The serious-event term listed is bilateral subdural hematoma, with 1.4% reported.
These figures describe what the registry record lists, not the cause of an event. The record does not report whether the serious event was judged related to treatment, its timing, its outcome, or the criteria used to classify seriousness. The listed term should therefore not be interpreted as proof that the intervention caused the event. Nor does a zero count establish that an event cannot occur.
The record does not provide a statistical comparison or an uncertainty interval for the serious-event counts. With sparse counts, a difference in observed counts can be unstable and may not precisely characterize the underlying event rates. The figures are safety observations in the recorded study population, not a definitive estimate of comparative risk.
12. What the Result Does, and Does Not, Mean
The posted results support a narrow descriptive statement: the registry lists one serious adverse event among participants at risk in the loteprednol/tobramycin group and none in the vehicle group, with no other affected participants listed in either group. Bilateral subdural hematoma is the serious-event term reported, accompanied by 1.4%. These registry entries characterize the safety reporting in the registry; they do not determine whether treatment caused the event or quantify the precision of a group difference.
The record does not report a statistical test, comparative effect estimate, or confidence interval for these safety figures. It also does not provide the primary efficacy analysis. Therefore, these data cannot establish that the active intervention improved the condition, failed to improve it, or was equivalent to vehicle. The study objective included efficacy, and several clinical and ocular-sign outcomes are named, but their results are not reported in the registry record.
A zero event count in one group is not evidence that the true event risk is zero. A single event in another group is not, by itself, evidence of a treatment-related increase. Interpretation depends on the endpoint definitions, completeness of follow-up, event review, and statistical analysis. Those details are not reported in the registry record.
The randomized, quadruple-masked, parallel design is relevant context for understanding the intended comparison. However, the registry description alone does not show how randomization, masking, outcome assessment, and follow-up were implemented. Nor does it provide enough information to assess missing data, multiplicity, or the prespecified analysis plan. The appropriate conclusion is consequently limited to the listed counts and design features, without a causal or efficacy claim.
13. Why This Trial Matters Statistically
This trial is statistically notable because its registry record pairs a randomized, quadruple-masked design with a sparse primary safety outcome. Such a design can be useful for comparing groups, but the value of randomization is realized through clear outcome definitions, complete follow-up, and an analysis suited to the endpoint. The record identifies a participant-count outcome and the assessment period, yet does not report an inferential comparison or a detailed analysis plan.
The contrast between an outcome label and an outcome analysis is important. The title and summary describe safety and efficacy, while the listed primary outcome is treatment-emergent adverse events. Secondary outcomes include a global assessment and ocular signs, but their analyzed results are not reported. A registry record that names outcomes without reporting estimates or analysis methods cannot answer the efficacy question on its own.
The record also illustrates why sparse safety counts need careful interpretation. A single serious event and zero in the comparator group make the observed counts easy to state, but not sufficient to establish a stable comparative risk. Uncertainty, event attribution, follow-up completeness, and the endpoint's handling across visits all matter. The registry record does not report enough detail to resolve those questions.
Finally, planning illustrations should be kept separate from trial design and observed evidence. General calculations based on observed effects cannot replace a documented original sample-size justification or serve as observed power. The record states that the planning assumptions are illustrative and does not report the trial's own justification. This distinction helps prevent planning quantities from being mistaken for evidence about treatment effects.
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 does not report a primary efficacy result, despite describing efficacy as a study objective. It names secondary clinical and ocular-sign outcomes but provides no analyzed results for them. The primary outcome itself is described across several categories or time points and was not reduced to one comparison, so a single effect estimate cannot be read from the record.
Important analysis details are absent. The record lists no analysis entries and does not report a statistical analysis plan, hypothesis tests, confidence intervals, adjustment for multiple comparisons, handling of repeated visits, or interim analyses. Sample-size justification for the trial is also not reported. These gaps prevent assessment of whether the analysis matched a prespecified plan or how precise any intended treatment comparison would be.
The safety information is limited to participant counts and the listed serious-event term. Event definitions, relatedness, severity grading, timing, outcomes, and methods of collection or review are not reported. Missing-data procedures, withdrawals, and details of the safety analysis population are also not reported in the registry record. Although the record lists numbers at risk, it does not explain how they were determined or whether denominators varied over follow-up.
Finally, design labels do not document implementation. Randomization and quadruple masking are recorded, but the sequence-generation method, allocation concealment, masking roles, adherence, and protocol deviations are not described. The study is identified as multicenter and as enrolling children aged 0–6, but further site and eligibility details are not reported. These limitations constrain both statistical interpretation and generalization from the posted record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pediatric Zylet Safety and Efficacy Study — NCT00420628.
- Registry record last updated 2011-10-07; status last verified 2011-09.
- Results first posted 2010-09-22.
- 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.
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18. Record Summary
NCT00420628 is a completed Phase 4, randomized, quadruple-masked, parallel study comparing loteprednol etabonate 0.5% with tobramycin 0.3% ophthalmic suspension against vehicle. The record describes a multicenter study in children aged 0–6 with chalazion or hordeolum and lists enrollment as 108. Bausch & Lomb Incorporated is named as sponsor.
The primary outcome is treatment-emergent adverse events in the safety population, assessed for the study eye on day 1, day 8, and day 15. The registry lists one serious event in the active-treatment group and none in the vehicle group; other affected-participant counts are zero in both groups. Bilateral subdural hematoma is listed as the top serious-event term at 1.4%.
The record names five outcome measures but no analysis entries. It does not report a primary efficacy result, statistical comparison, confidence interval, missing-data method, or the trial's sample-size justification. The available information supports descriptive reporting of the listed design and safety counts, not a conclusion about efficacy or event causation.