Safety and Efficacy Study of Besivance™ for Treatment of Congenital Nasolacrimal Duct Obstruction in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Besivance™ for Treatment of Congenital Nasolacrimal Duct Obstruction in Children (NCT01431170), a randomized phase 1 study. The primary outcome is Change in Physician-rated Scale of NLDO From Baseline to Follow-Up Visit at Week 8 or From Baseline to Time of Treatment Failure, if Earlier..

2. Clinical Question

The clinical question is whether Besivance™ ophthalmic suspension, 0.6%, can be compared with Polytrim ophthalmic solution for treatment of congenital nasolacrimal duct obstruction in children, using change in a physician-rated scale as the primary outcome. The registry record states the study hypothesis as Besivance being as safe and effective as the current standard of care. It identifies Polytrim as the comparison treatment, but does not explicitly identify it as the standard-of-care treatment.

The endpoint description includes several possible classifications of change rather than a single simple event definition. It describes treatment success, recurrence, and treatment failure, with the grade assessed in the study eye at each visit. These distinctions matter because a favorable change, return of infection after a grade of 0, and a grade that is unchanged or worse than baseline represent different clinical patterns. The registry record does not report a single comparative estimate or a statistical test answering the primary question.

3. Trial Design

The registry describes a prospective, randomized, double-blinded, parallel-group study. Its masking field specifies triple masking. The listed phase is Phase 1, and the record gives enrollment as 24. The study status is completed. The recorded start is 2011-09, and primary completion is 2014-06. Rutgers, The State University of New Jersey, is listed as the sponsor.

Participants were assigned to one of the two listed treatment groups: Besivance Treatment Group or Polytrim Treatment Group. The Besivance intervention is described as Besivance™ ophthalmic suspension, 0.6%; the Polytrim intervention is described as Polytrim ophthalmic solution. The registry does not report the allocation ratio, the randomization procedure, or details of how masking was implemented. It also does not identify which roles were masked.

A parallel-group design compares treatment groups over the same general study period, rather than switching each participant between treatments. Random assignment is intended, in general, to support a fair comparison by reducing systematic differences between groups. Masking can help limit influences on treatment delivery, outcome assessment, or reporting, depending on who is masked and how masking is maintained. Those are general design principles; the implementation details are not reported in the registry record.

The registry lists six outcome measures. Alongside the primary physician-rated scale outcome, the named secondary outcomes include recurrence count by randomization group, change in the scale after recurrence treatment, treatment failure, and medication safety outcomes. The record does not provide a participant flow, reasons for discontinuation, group-specific baseline characteristics, or an account of how many participants contributed data to each outcome. Enrollment is therefore not interchangeable with the denominators reported for the safety outcomes.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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 Physician-rated Scale of NLDO From Baseline to Follow-Up Visit at Week 8 or From Baseline to Time of Treatment Failure, if Earlier., measured over Baseline to Week 8.

The primary endpoint is described as change in the physician-rated NLDO scale from baseline to Week 8, or from baseline to the time of treatment failure if failure occurs earlier. The scale grades the study eye at each visit from 0 to +4. Grade 0 indicates no tearing and discharge; higher grades describe increasing redness, swelling, and discharge, ending with redness and swelling of the eyelid with purulent discharge at grade +4.

The endpoint description further classifies changes in relation to baseline and prior visits. Treatment success is defined as a grade of 0 or improvement by 2 or more compared with the prior visit. Recurrence is NLDO with infection returning in the study eye, indicated by a grade >0 after a grade of 0 at the prior visit. Treatment failure is a grade that is worse than or the same as the baseline visit.

A physician-rated scale can capture ordered differences in clinical findings that a simple yes-or-no outcome would not retain. It can also distinguish improvement, persistent disease, and return after an earlier grade of 0. These are general reasons for using graded outcomes. The registry does not report how the scale was validated, whether assessors were trained or calibrated, or how disagreements between assessors were handled. Although the endpoint description defines several categories and time points, the posted record does not report a single primary-outcome comparison or participant counts in each category.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute? Randomization assigns participants to treatment groups using a chance-based process. As a general statistical principle, it can reduce the risk that known or unknown participant characteristics systematically determine treatment assignment. It does not guarantee that groups will be identical, especially in a study with limited enrollment. The record identifies the study as randomized but does not report its sequence-generation method, allocation concealment, or allocation ratio.

What does masking mean? Masking is intended to reduce the influence of treatment knowledge on conduct or assessment. The registry record labels the study triple-masked. It does not specify who the masked parties were, how treatment assignment was concealed, or whether masking was assessed. Those omissions limit interpretation of how masking operated in practice. In general, masking can be particularly relevant when an outcome depends on a clinician’s rating, because awareness of treatment could influence assessment.

How should a graded endpoint be understood? The primary measure uses an ordered scale from 0 to +4. The categories rank observed NLDO findings from no tearing and discharge through findings involving redness, swelling, and increasingly specified discharge. An ordered scale carries more information than a simple binary outcome, but the distance between adjacent grades is not necessarily equal. That is a general feature of ordinal measures, not a reported finding about this particular scale. The record describes the scale and the classifications of success, recurrence, and failure, but does not report the statistical model or summary measure used to analyze it.

Why do time points and outcome definitions matter? The primary endpoint refers to baseline and Week 8, with measurement at the time of treatment failure if failure occurs earlier. The description also uses a prior-visit comparison to define success and recurrence. These rules make the endpoint dependent on the sequence of assessments, not just on a single final grade. In general, analysis choices for repeated or event-dependent measurements should specify how intermediate visits, early failure, and incomplete follow-up are treated. Those analysis details are not reported in the registry record.

What is a confidence interval? In general, a confidence interval expresses uncertainty around an estimated effect under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not by itself establish clinical importance, and its interpretation depends on the outcome, analysis, and assumptions. No primary-effect estimate or confidence interval is reported in the registry record, so the precision of a treatment comparison cannot be assessed.

What does a p-value convey? In general, a p-value describes how compatible the observed data are with a specified statistical model and null hypothesis. It is not the probability that a treatment is effective, nor does it measure the size or importance of an effect. A p-value is most informative alongside an effect estimate and its uncertainty. The registry record reports no primary analysis or p-value for the comparison.

What is multiplicity? When several outcomes, time points, or comparisons are examined, the chance of at least one apparently notable result can increase if all are treated as independent opportunities to test a hypothesis. Statistical approaches to multiplicity can control or describe this issue, but the appropriate approach depends on the prespecified questions and analysis plan. The registry lists six outcome measures and describes multiple categories and time points for the primary endpoint. It does not report a multiplicity strategy or analysis plan.

How should over-dispersion be understood? General explanation: over-dispersion occurs when observed variability in count data is greater than expected under a statistical model. It can make uncertainty estimates too small if an analysis assumes less variability than the data contain. The registry record includes a secondary outcome concerning recurrence counts, but does not report recurrence data or a model for analyzing counts. It is therefore not possible to say whether over-dispersion was present or relevant to the actual analysis.

What do planning calculations mean? The stated planning illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. In general, such calculations illustrate the participants per arm associated with specified assumptions. They are not observed power and do not show what the completed trial was capable of detecting unless the assumptions and analysis match the trial’s actual design. The record does not report its own sample-size justification or statistical plan.

What is not available for evaluating the analysis? The registry record does not report a primary-outcome estimate, analysis population, handling of missing data, model specification, or results for the named secondary outcomes. These details are needed to assess how the trial’s planned question was translated into an estimate and how robust that estimate might be. Their absence should not be filled by assuming a conventional method.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures, including the primary physician-rated NLDO scale and secondary measures concerning recurrence, recurrence-treatment efficacy, treatment failure, and medication safety. The primary outcome itself involves multiple classifications and time points. When several outcomes or comparisons are considered, multiplicity can affect how statistical evidence should be interpreted. In general, a prespecified hierarchy or adjustment strategy can help address this issue. The registry record does not report whether any such strategy was planned or used.

Missing data and analysis populations are also important for interpreting a randomized trial. General statistical practice distinguishes participants assigned to treatment from those with outcome data available, and specifies how missing assessments or early discontinuation are handled. The record does not report an intention-to-treat or other analysis population, the amount or pattern of missing primary-outcome data, reasons for missingness, or any method for addressing it. It also does not report participant flow by treatment group.

The primary endpoint allows assessment at Week 8 or at the time of treatment failure if earlier. The registry record does not explain how participants without an observed Week 8 assessment were handled, or how the early-failure rule was incorporated into an analysis. These are relevant details because the timing and availability of assessments can affect the interpretation of change from baseline.

No primary-outcome analyses are listed in the registry record. It therefore does not report whether analyses followed a prespecified plan, whether any sensitivity analyses were conducted, or how secondary outcomes were analyzed. The trial’s statistical plan, multiplicity approach, missing-data methods, and analysis populations are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 0 serious adverse events among 9 participants at risk in the Besivance Treatment Group and 0 among 11 at risk in the Polytrim Treatment Group. For other adverse events, it reports 0 affected among 9 at risk in the Besivance group and 0 among 11 at risk in the Polytrim group. These are the counts recorded for the stated at-risk groups.

Such counts describe what was recorded, not the full range of possible safety outcomes. A zero count does not establish that an event cannot occur or that the treatments have identical safety profiles. In general, the precision of an event-rate estimate depends on the amount of safety information and follow-up, as well as on how events were defined and collected. The registry does not report confidence intervals, adverse-event follow-up duration, or detailed ascertainment procedures.

The record does not report death counts. It also lists no serious adverse-event terms. These details should not be interpreted as evidence about unreported events beyond the posted counts. The safety figures are distinct from the primary efficacy endpoint and do not answer the question about change in physician-rated NLDO grade.

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

The registry record establishes that a prospective, randomized, triple-masked, parallel-group study compared Besivance™ ophthalmic suspension, 0.6%, with Polytrim ophthalmic solution in children with congenital nasolacrimal duct obstruction. It describes a primary physician-rated scale outcome from baseline to Week 8, or to treatment failure if earlier, and defines success, recurrence, and failure. It also reports safety counts for each group.

What the record does not establish is the comparative primary-outcome result. No group-specific primary outcome values, effect estimate, confidence interval, or p-value are reported, and the registry lists no analyses. Without those results, it is not possible to describe whether the scale changed differently between groups, how large any difference was, or how precisely a comparative effect was estimated.

The safety figures show no reported serious or other adverse events among the participants at risk in the listed groups. They do not prove that the treatments have no risks or that their safety is equivalent. The record does not provide the detail needed to assess the precision of these counts or the completeness and duration of safety monitoring.

In general, a trial’s design can support a comparison, but the design alone is not a result. Randomization and masking address aspects of bias; they cannot replace reported outcome data, a clear analysis, or an account of missing observations. Similarly, planning calculations are illustrations under assumptions, not observed power and not evidence of efficacy.

The defensible interpretation is therefore limited: the registry describes the trial question and methods at a high level and records the stated safety counts, but does not provide the primary comparative findings. No conclusion about the size, direction, or precision of a treatment effect can be drawn from the posted primary-outcome information.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is a physician-rated scale with ordered grades and several outcome classifications. A single final score, change from baseline, treatment success, recurrence, and treatment failure represent different ways of describing the course of NLDO. Defining these clearly is essential: different definitions can yield different summaries and answer different questions. The registry provides definitions, but does not report the analysis that connects them to a group comparison.

The endpoint also refers to more than one assessment point: Week 8 or an earlier time of treatment failure, while success and recurrence use comparisons with prior visits. In general, a repeated-measure outcome requires transparent rules for how assessments over time contribute to the result. The record does not report those analysis rules or the handling of assessments that are missing or occur after treatment failure.

The design is randomized, parallel-group, and triple-masked, which identifies important elements of the intended comparison. Yet statistical interpretation depends on more than design labels. Allocation methods, masking implementation, outcome completeness, analysis population, and the prespecified statistical plan all help readers judge the risk of bias and the uncertainty of findings. Several of those details are not reported in the registry record.

The posted safety counts also illustrate why event counts need context. A zero count is a description of observed events among the stated participants at risk, not a guarantee about future risk or a demonstration of equal safety. Precision and completeness matter, and the record does not provide confidence intervals or detailed follow-up information.

Most importantly, a well-defined trial question is not the same as a reported answer. With no primary analysis or comparative estimate in the record, statistical interpretation must stop short of assessing efficacy. The gap between a clearly described endpoint and unavailable results is itself important for readers evaluating clinical trial evidence.

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 main trial-specific limitation in interpreting the registry is the absence of reported primary-outcome results. The record defines the physician-rated scale endpoint and its classifications, but does not report group-specific outcome values, a comparative estimate, uncertainty intervals, or a p-value. It also lists no analyses. Thus, the intended primary comparison cannot be evaluated from the registry record.

The endpoint description combines change from baseline, an assessment at Week 8 or earlier treatment failure, and rules based on prior visits. The record does not specify the analysis method used to handle these features, nor does it report how the ordinal grades or the success, recurrence, and failure classifications contributed to the primary analysis. No information is reported about assessor training, scale validation, or handling of rating disagreements.

The registry reports enrollment as 24, while the safety denominators are 9 in the Besivance group and 11 in the Polytrim group. The record does not explain the relationship between enrollment and these safety denominators, provide a participant-flow account, or give outcome-specific analysis populations. Reasons for any differences in available data are not reported in the registry record.

Other limitations include the absence of baseline characteristics, eligibility details, allocation procedures, masking implementation, follow-up duration for adverse events, and detailed safety-event ascertainment. The statistical plan, sample-size justification, missing-data methods, and multiplicity approach are also not reported in the registry record. These omissions limit assessment of representativeness, risk of bias, precision, and robustness. They should not be resolved by assuming methods or results that the record does not state.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Besivance™ for Treatment of Congenital Nasolacrimal Duct Obstruction in Children — NCT01431170.
• Registry record last updated 2016-07-14; status last verified 2016-03.
• Results first posted 2016-06-09.
• 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 record describes a completed Phase 1 prospective, randomized, triple-masked, parallel-group study of Besivance™ ophthalmic suspension, 0.6%, compared with Polytrim ophthalmic solution for children with congenital nasolacrimal duct obstruction. Enrollment is listed as 24. Rutgers, The State University of New Jersey, is the sponsor; the recorded start is 2011-09 and primary completion is 2014-06.

The primary outcome is change in physician-rated NLDO grade from baseline to Week 8 or earlier treatment failure. The record defines treatment success, recurrence, and treatment failure but reports no primary analysis or comparative efficacy estimate. It lists six outcome measures.

Safety counts report no serious or other adverse events among the stated at-risk participants in either treatment group. Death counts, primary-outcome results, analysis populations, missing-data methods, and the statistical plan are not reported in the registry record.