Subconjunctival Versus Direct Mitomycin C in Trabeculectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Subconjunctival Versus Direct Mitomycin C in Trabeculectomy (NCT04352660), a randomized phase 4 study. The primary outcome is Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds.

2. Clinical Question

The study asks whether the route used to apply mitomycin C is associated with different postoperative outcomes after trabeculectomy. Its primary measure concerns the proportion of participants meeting an intraocular pressure threshold: at least a 30% mean reduction from baseline and an intraocular pressure below 21 mm Hg. Participants meeting that criterion without pressure-lowering medication were designated complete successes; those meeting it while using medication were designated qualified successes. Participants who did not meet the criterion were classified as failures, with a further complete-failure category for those who also required additional glaucoma surgery.

The registry describes additional outcomes concerning bleb morphology, medications, visual acuity, surgical complications, additional surgery, and postoperative interventions. These outcomes can add context to the primary pressure-based classification, but their results are not reported in the registry record. The primary outcome category counts and between-group comparison are also not reported in the registry record. Consequently, the clinical question is clear, but the posted information does not establish how the groups compared on the intended outcome.

3. Trial Design

The registry describes a randomized, parallel-group, single-masked phase 4 trial with 100 participants and a completed status. The condition is open-angle glaucoma. One group received mitomycin C by preoperative subconjunctival injection; the other received it by intraoperative direct scleral application using impregnated cellulose sponges. The study compares application routes as part of trabeculectomy, rather than comparing mitomycin C with no antimetabolite.

The recorded study start date is 2016-05-23, and the primary completion date is 2019-04-14. The registry identifies the University of California, San Diego as sponsor. The masking entry says single, but which people involved in the trial were masked is not reported in the registry record. Details such as the method used to generate the random allocation sequence, how allocation was concealed, and whether masking was maintained are not reported in the registry record.

The primary outcome timeframe is six months. The registry says that 14 participants in the Injection group and 10 in the Sponge group were lost to follow-up at the six-month postoperative visit. It does not report the outcome denominators, the number of participants in each outcome category, or how missing visits were handled in the primary analysis. Although the safety summaries list 50 participants at risk in each group, the record does not state whether those safety populations were also the analysis populations used for the primary outcome.

Seven outcome measures are listed, including the primary measure and the secondary outcomes. The registry record lists no analyses. It does not report a statistical analysis plan, a sample-size justification for the trial, or details of interim analyses. A planning illustration based on an observed effect is not a substitute for the trial's original design justification or an analysis of the trial's results.

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

Analysis population for the primary outcome, as defined in the registry: 14 subjects in the Injection group were lost to follow up at the 6 month postoperative visit. 10 subjects from the Sponge group were lost to follow up at the 6 month postoperative visit.

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 Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds, measured over 6 months.

The primary endpoint is the number or percentage of participants meeting prespecified intraocular pressure criteria at six months after surgery. The criteria combine a relative change from baseline—at least a 30% mean reduction—with an absolute pressure threshold of less than 21 mm Hg. The endpoint separates participants who meet those criteria without pressure-lowering medication from those who meet them while using medication. It also distinguishes participants who fail to meet the criteria, including a separate complete-failure classification for those requiring additional glaucoma surgery.

This type of endpoint is used to describe whether participants reach a defined postoperative pressure target and whether that target is reached without medication. Those classifications preserve distinctions that a single undifferentiated success count would lose. They also make clear that the outcome is not simply the change in pressure: medication use and additional glaucoma surgery affect the assigned category.

The registry labels the measure as a percentage of participants, while also describing the measure in terms of participant counts. The category-specific results, the denominators used to calculate percentages, and any statistical comparison between the groups are not reported in the registry record. The record therefore supplies the endpoint definition and timeframe, but not the observed endpoint values. Without those results, the relative performance of the two application routes cannot be judged from the posted primary outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized parallel-group comparison. General: Random allocation is intended to make treatment groups comparable at the start of a trial with respect to measured and unmeasured characteristics, on average. It does not guarantee identical groups, and it does not eliminate the need to report how allocation was implemented or how outcomes were analyzed. The record identifies randomization but does not report sequence generation or allocation concealment.

What does the endpoint count?

The primary endpoint classifies participants using a combination of an intraocular pressure reduction threshold, an absolute pressure threshold, medication use, and additional glaucoma surgery. General: A binary outcome has two possible states, such as meeting or not meeting a specified criterion. This registry outcome is more detailed than a simple binary endpoint because the description distinguishes several categories. A single overall comparison would require a clearly stated rule for combining or separately analyzing those categories. The registry record does not report such an analysis, and its posted results do not give the category counts.

The outcome description uses both a percentage framing and participant-count language. General: A percentage requires a numerator—the number meeting a criterion—and a denominator—the number with outcomes included in the calculation. Clear reporting of both makes it possible to understand how missing observations affect the result. The category counts, denominators, and primary comparison are not reported in the registry record.

Why do estimates and uncertainty matter?

General: An effect estimate describes the size and direction of a group difference using a defined scale, such as a difference in proportions. A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while neither interval by itself establishes clinical importance. The registry record does not report a primary effect estimate or confidence interval. Without them, the magnitude and precision of the intended comparison cannot be evaluated from the posted results.

General: A p-value addresses how compatible the observed data are with a specified statistical model and a null hypothesis, assuming the model and analysis are appropriate. It does not measure the probability that the null hypothesis is true, nor does it describe the size of an effect. No p-value for the primary comparison is reported in the registry record. Even if one were available, it would need to be read alongside the effect estimate, its uncertainty, the endpoint definition, and the missing-data approach.

How should missing follow-up be considered?

The registry reports that 14 participants in the Injection group and 10 in the Sponge group were lost to follow-up at six months. General: When an outcome is missing, the analysis may exclude the participant, use an imputation method, or apply another stated approach. Each approach relies on assumptions. If missingness is related to outcome status or differs between groups in a way that matters to the endpoint, a complete-case comparison may not represent all randomized participants. The registry record does not report the method used, the reasons for loss, or sensitivity analyses examining alternative assumptions.

General: An intention-to-treat approach analyzes participants according to randomized assignment, regardless of the treatment actually received, and aims to preserve the comparison created by randomization. Whether that approach was used for the primary outcome is not reported in the registry record. The record also does not specify a per-protocol or other analysis population. The number at risk in the safety summaries should not be assumed to be the denominator for the primary endpoint.

Why do multiple outcomes matter?

The registry lists seven outcome measures, including the primary outcome and secondary outcomes concerning bleb morphology, medications, visual acuity, complications, additional surgery, and postoperative interventions. General: When investigators examine multiple outcomes or multiple contrasts, the chance of finding at least one apparently unusual result can increase. Statistical methods may address multiplicity, or investigators may identify a primary comparison in advance and interpret secondary findings as exploratory. The analysis plan, any multiplicity adjustment, and the handling of the primary outcome's several categories are not reported in the registry record. The record lists no analyses.

What does over-dispersion mean?

General: Over-dispersion occurs when observed variability is greater than a statistical model expects. It is especially relevant to some count outcomes, where a simple model may understate uncertainty if events vary more widely than assumed. The primary outcome is described through participant success categories, and no over-dispersion assessment or count-model analysis is reported in the registry record. The concept does not establish that over-dispersion occurred in this trial.

General: Sample-size calculations are planning tools based on assumptions about the expected effect, variability, significance level, power, and allocation. A planning illustration based on an observed effect is not the trial's original design justification and is not observed power. The registry record does not report the trial's sample-size justification. Any planning figures should be understood as conditional illustrations rather than evidence that the study had a particular probability of detecting an effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures. The primary endpoint itself has several outcome categories: complete success, qualified success, failure, and complete failure. The record does not report whether these categories were analyzed separately, combined for a particular contrast, or handled through another prespecified procedure. It also lists no analyses. The statistical plan, hierarchy of outcomes, and any adjustment for multiple comparisons are not reported in the registry record.

General: Multiplicity matters because repeated tests across outcomes or contrasts can make at least one apparently notable result more likely by chance. A prespecified primary outcome and analysis can help focus interpretation; adjustment methods can address some multiple-testing concerns. These general principles do not indicate which approach this trial used. The record does not supply the information needed to assess how multiplicity was addressed.

For missing follow-up, the registry reports losses of 14 participants in the Injection group and 10 in the Sponge group at six months. It does not report reasons for loss, outcome status for those participants, or the method used to handle missing values. Analysis populations are also not reported in the registry record. General: Missing-data assumptions matter because observed participants may not represent participants whose outcomes are unavailable. Sensitivity analyses can test how conclusions change under alternative assumptions, but whether any were performed is not reported.

These omissions limit evaluation of both robustness and reproducibility. The endpoint is defined, but the missing-data procedure, analysis population, multiplicity strategy, and statistical analysis plan are not reported in the registry record. The absence of those details does not show that no methods were used; it means their use cannot be assessed from this record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety summaries list 50 participants at risk in each group. In the Injection group, the serious adverse event count is 0, the other adverse event count is 5, and the death count is 0. In the Sponge group, the serious adverse event count is 0, the other adverse event count is 6, and the death count is 0. These figures are descriptive counts within the listed groups.

The registry record does not report the names or descriptions of the other adverse events, their severity, their timing, or whether individual participants experienced more than one event. It also does not report a statistical comparison of the safety counts. The serious adverse event terms are not reported in the registry record. The meaning of the safety follow-up period and the relationship between these safety denominators and the primary outcome analysis population are not reported either.

General: A zero count in a trial summary means that no events of that category were recorded in the stated group and reporting period; it does not establish that the underlying risk is zero. Similarly, descriptive counts alone do not establish that groups have the same safety profile. The figures should be read as the registry's reported counts, not as a complete estimate of comparative risk.

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

The record establishes that the trial was designed to compare preoperative subconjunctival injection of mitomycin C with intraoperative direct scleral application by sponge during trabeculectomy. It also defines a six-month primary endpoint based on intraocular pressure reduction, an absolute pressure threshold, medication use, and additional glaucoma surgery. These details clarify the intended comparison and what the outcome categories mean.

The record does not report the primary outcome category counts or percentages, a group effect estimate, an uncertainty interval, or a statistical test. It therefore does not show which route had more participants in any success or failure category, nor how precise any difference might be. The registry record also does not report results for the listed secondary outcomes. No conclusion about comparative efficacy can be drawn from the endpoint definition alone.

The record reports follow-up losses at six months and descriptive safety counts, including zero serious adverse events and zero deaths in each group. Those details do not resolve the missing primary outcome results. Nor do the safety counts establish that the groups were equivalent or that no other adverse events occurred: other adverse event counts are reported, while their descriptions and comparative analysis are not.

General: A trial's design describes the question it was intended to answer; its results describe the observed data; and statistical interpretation considers both the estimates and their uncertainty, alongside limitations such as missing follow-up. Here, the design and endpoint are described, but the posted primary results are not. The distinction is important: an unavailable result is not evidence that the groups had the same outcome, and it is not evidence that one route was better. The conclusions that can be drawn are limited to the registered comparison, outcome definition, follow-up losses, and reported safety counts.

13. Why This Trial Matters Statistically

This trial poses a focused statistical question about two ways of applying mitomycin C during the same surgical procedure. Because the application route differs while the intended treatment context remains trabeculectomy, the comparison is structured around a specific procedural choice. Randomization is intended to support a fair comparison, while the parallel-group design assigns participants to one of the two routes.

The primary outcome is not simply a pressure measurement. It combines a reduction from baseline with an absolute pressure threshold and then distinguishes outcomes according to medication use and additional surgery. That structure illustrates why endpoint definitions matter: different classification rules can produce different summaries of the same clinical follow-up. Reporting the category counts and denominators would be necessary to understand how participants were distributed across those classifications.

The record also illustrates why outcome completeness and analysis methods are part of statistical interpretation. It reports losses to follow-up in both groups but does not report how missing outcomes were handled. Without the endpoint results, an effect estimate, or an uncertainty interval, the comparative result cannot be assessed. The safety counts are useful descriptive information, but they do not replace the missing primary outcome analysis.

More broadly, a registered question is not the same as a reported answer. A well-defined endpoint can support clear interpretation only when its observed results and analysis details are also available. In this record, the design and intended measures are identifiable, while the results needed to estimate the comparison are not reported in the registry record.

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 limitation for interpreting this trial from the registry record is that the primary outcome results are not reported. There are no category counts or percentages, no reported group comparison, and no effect estimate or confidence interval. The record therefore does not permit an assessment of the direction, magnitude, or precision of the primary outcome difference.

Follow-up at the primary outcome visit is incomplete: the record reports 14 participants lost in the Injection group and 10 in the Sponge group. It does not describe why participants were lost, whether their outcomes were otherwise obtained, or how missing outcomes entered the analysis. It also does not report the primary analysis population or sensitivity analyses. These gaps prevent assessment of the possible effect of missing data.

Important design and analysis details are not reported in the registry record, including which parties were masked, the randomization implementation, the original sample-size justification, the analysis plan, interim analyses, and multiplicity procedures. The record lists seven outcome measures and no analyses, but does not explain how the multiple endpoint categories or secondary outcomes were handled.

The safety information is limited to group counts. Descriptions of the other adverse events, event timing, and a comparative safety analysis are not reported. The relationship between the safety populations and the primary outcome populations is also not reported. These limitations concern the information available in the registry record; they do not establish what may have been included in other trial documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Subconjunctival Versus Direct Mitomycin C in Trabeculectomy — NCT04352660.
• Registry record last updated 2020-07-02; status last verified 2020-06.
• Results first posted 2020-07-02.
• 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 randomized, parallel-group, single-masked phase 4 trial enrolling 100 participants with open-angle glaucoma. It compares preoperative subconjunctival mitomycin C injection with intraoperative direct scleral application using impregnated cellulose sponges during trabeculectomy. The primary outcome is assessed at six months and classifies participants using intraocular pressure reduction, an absolute pressure threshold, medication use, and additional glaucoma surgery.

The record reports losses to follow-up of 14 participants in the Injection group and 10 in the Sponge group at the six-month visit. It lists 50 participants at risk in each group for the safety summaries, with zero serious adverse events and zero deaths in each group; other adverse event counts are 5 and 6, respectively. Primary outcome results, secondary outcome results, analysis methods, and handling of missing data are not reported in the registry record. The comparative outcome therefore cannot be evaluated from the posted results.