Comparison of Corticosteroid Dosing Regimens After Endothelial Keratoplasty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Corticosteroid Dosing Regimens After Endothelial Keratoplasty (NCT01853696), a randomized phase 4 study. The primary outcome is Intraocular Pressure.

2. Clinical Question

The trial’s stated purpose was to compare the efficacy and side effects of different corticosteroid dosing regimens after endothelial keratoplasty. The posted primary outcome concerns pressure-threshold events, while immunologic graft rejection is listed as a secondary outcome. The registry record does not report a numerical result for that secondary outcome.

The primary results list 11 eyes in the loteprednol group and 27 in the prednisolone acetate group meeting the pressure criterion. These are counts, not treatment-effect estimates. The record does not provide an inferential comparison, such as a confidence interval or a p-value, for the difference between groups. The counts therefore describe the posted observations but do not, by themselves, establish the precision of a comparison or explain the extent to which the groups may differ beyond the observed data.

3. Trial Design

This was a prospective, randomized, parallel-group phase 4 trial. The registry record lists enrollment of 167 and shows group sizes of 84 for loteprednol and 83 for prednisolone acetate. The study began in 2013-03, reached primary completion in 2015-01, and is listed as completed. The sponsor was Cornea Research Foundation of America.

Participants were assigned to one of two topical corticosteroid regimens following endothelial keratoplasty. Both regimens followed a tapering schedule, beginning with 4 applications daily and progressing through less frequent dosing. Loteprednol etabonate was used as 0.5% gel, while prednisolone acetate was used as a 1% ophthalmic solution. The schedule descriptions differ slightly in their wording of the periods, but both specify 4 times daily for 2 months, 3 times daily for 1 month, twice daily for one month, and once daily for 7 months.

The design is described as single-masked. The registry record does not identify which parties were masked, so the specific masking procedure cannot be described. It also does not report details of random-sequence generation, allocation concealment, stratification, or the treatment of departures from assigned regimens. Those details should not be inferred from the randomized designation alone.

The primary outcome was the number of eyes meeting a specified intraocular-pressure criterion from 1 to 12 months after transplant. The registry also lists immunologic graft rejection as a secondary outcome. Although the record is marked completed, information about completion does not itself establish that all planned measurements were obtained or that the reported analysis included every randomized participant. Analysis-population details and numerical results for the secondary outcome are not reported in the registry record.

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

Reasons for not completing this period:

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 Intraocular Pressure, measured over from 1 to 12 months after transplant.

The primary endpoint counts eyes in which intraocular pressure reached a prespecified threshold during the period from 1 to 12 months after transplant. An eye met the endpoint if its absolute pressure equaled or exceeded 24 mm Hg, or if pressure rose by at least 10 mm Hg relative to the baseline preoperative reading. The endpoint therefore combines an absolute pressure criterion and a change-from-baseline criterion. Either condition is sufficient for an eye to be counted.

Pressure is relevant to monitoring after eye surgery, and a threshold-based endpoint can summarize whether a specified pressure event was recorded during follow-up. The two-part definition captures both an elevated absolute reading and a substantial increase relative to the individual eye’s baseline. Those two routes to meeting the endpoint are not interchangeable: one depends on the measured level, while the other depends on the change from baseline.

The reported measure is a count of eyes, rather than a continuous summary of pressure readings. It does not show the pressure values below the threshold, how often an eye crossed the threshold, how long an elevation lasted, or when within the follow-up period an event occurred. The registry record does not report those details. Nor does the count alone indicate whether the absolute-pressure criterion or the increase-from-baseline criterion was the reason an eye qualified.

Because the outcome unit is eyes, the listed group sizes should not automatically be treated as the number of eyes with complete pressure follow-up. The record does not clarify the relationship between enrolled participants and assessed eyes, or report missing pressure measurements. That context matters when interpreting counts across groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a count outcome: the number of eyes that met the registry’s intraocular-pressure definition. Counts differ from continuous outcomes, such as a group mean pressure, and from time-to-event outcomes, which record when an event occurs. Here, the record reports the number meeting the threshold during follow-up, not each eye’s pressure trajectory or time of first threshold crossing.

What can be read directly from the count?

The posted values are 11 eyes for loteprednol and 27 eyes for prednisolone acetate. These values describe the number recorded as meeting the endpoint. A count alone does not communicate the event frequency unless the relevant denominator and completeness of outcome assessment are also clear. The record lists group sizes, but does not report whether those are the denominators for the pressure endpoint or whether all eyes had evaluable follow-up.

General statistical explanation: a comparison of counts usually needs a model or test suited to the outcome and its data structure. The choice can depend on whether the count represents independent observations, whether observations have different exposure time, and whether counts are more variable than a basic model expects. Over-dispersion means that observed variability exceeds what a chosen model assumes; if ignored, uncertainty can be understated. These are general considerations, not methods reported as used in this trial.

Why is there no inferential comparison?

The registry record identifies the primary endpoint as a count-other outcome and notes that values are missing or not estimable for a two-arm comparison. It reports no analyses for the primary outcome. Accordingly, the displayed counts do not come with a registry-reported estimate of the contrast, a p-value, or a confidence interval. There is no basis in the record for attributing a particular statistical test or model to the investigators.

General statistical explanation: an effect estimate summarizes the direction and magnitude of a comparison on a defined scale. A confidence interval adds information about uncertainty in that estimate, while a p-value addresses compatibility with a specified null hypothesis under a specified analysis. Neither statistic is a substitute for the other, and neither can be reconstructed responsibly without the necessary analysis details and data. The registry record does not report these quantities for the primary comparison.

How should the planning illustrations be understood?

Planning illustrations are based on the observed effect, use a two-sided significance level of 0.05, assume equal allocation between arms, and use a normal approximation. They consider detecting stated fractions of the observed effect. Such calculations are hypothetical planning exercises, not observed properties of the completed trial and not observed power. In general, an illustration based on a fraction of an observed effect asks what sample size might be needed to target a smaller effect under its stated assumptions. It does not show that the trial was designed around that effect, that the effect is true, or that an eventual study would achieve its planned operating characteristics.

The registry record does not report the trial’s own sample-size justification or whether the planning assumptions match the original design. A sample-size calculation based on an observed effect can be sensitive to random variation in that effect, especially when the estimate is imprecise. Therefore, it should be read as a planning aid, not evidence that the study had adequate or inadequate power for its original question.

What does the record say about other methods?

The registry gives the trial’s randomized, single-masked, parallel design, but does not report the statistical analysis plan, allocation procedure, adjustments for baseline characteristics, treatment of protocol deviations, or analysis populations. It does not report an interim-analysis plan. These omissions mean that the intended inferential approach and the choices made in any analysis cannot be evaluated from the registry record.

General statistical explanation: multiplicity can arise when investigators test several outcomes, time points, or subgroup comparisons. Conducting many tests can increase the chance of at least one apparently notable result under a null model. Methods for controlling or describing that issue depend on the planned comparisons and their hierarchy. The record lists intraocular pressure as the primary outcome and immunologic graft rejection as a secondary outcome, but does not report a multiplicity strategy.

For the primary endpoint, the posted data support a descriptive account of the event counts. They do not support a newly calculated estimate or test because the registry marks a two-arm comparison as not estimable. The sponsor’s own analysis does not take precedence in this case because no sponsor comparison is reported and the record does not indicate a discrepancy.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies intraocular pressure as the primary outcome and immunologic graft rejection as a secondary outcome. It lists two outcome measures, but does not report a multiplicity plan or describe how any inferential testing across outcomes would be handled. In general, testing several outcomes can create a multiplicity issue; the appropriate approach depends on which comparisons were planned and how they were prioritized. The record does not permit an assessment of that strategy.

The primary outcome is reported as counts, but the record does not explain the analysis population for those counts. It does not state whether analyses followed randomized assignment, included only participants or eyes with complete follow-up, or used another population definition. The relationship between the listed group sizes and the number of eyes assessed for pressure is not reported in the registry record.

Missing-data handling is also not reported. The record does not say whether pressure measurements were missing, how missing visits were treated, or whether any imputation or sensitivity analysis was used. The absence of such information should not be taken to mean there were no missing measurements.

Although the record is marked completed, that status does not establish complete outcome ascertainment or disclose how all randomized participants were handled. The numerical result for the listed secondary outcome is not reported in the registry record. These gaps limit evaluation of the completeness and robustness of the posted results.

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 5% reporting threshold.

The adverse-event summary lists zero serious adverse events and zero other adverse events for the loteprednol group, and zero serious adverse events and zero other adverse events for the prednisolone acetate group. The listed groups at risk are 84 and 83, respectively. The registry does not report death counts for either group.

These entries describe what the adverse-event fields record; they do not establish that no adverse events occurred outside the categories or reporting process represented in those fields. The registry record does not provide event definitions, collection procedures, follow-up completeness for safety, or a narrative explaining how events were classified. It also does not report an inferential comparison of safety outcomes.

Zero recorded events in a group should not be interpreted as proof that the underlying risk is zero. General statistical context: when no events are observed, uncertainty about the true event frequency can remain, and the degree of uncertainty depends on the amount and completeness of observation. The record does not provide the detail needed to quantify that uncertainty.

The serious and other adverse-event figures should therefore be read narrowly as registry-reported counts. They do not establish that the regimens have identical safety profiles, and they should not be used as a substitute for the primary endpoint analysis or the missing numerical result for graft rejection.

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

The trial addresses a clinically relevant statistical question: how two corticosteroid regimens after endothelial keratoplasty compare on a pressure-threshold outcome. Its randomized, parallel-group design is a framework for comparing assigned treatments, and the registry records the primary outcome as the number of eyes meeting the specified pressure criterion during follow-up.

The posted counts are 11 eyes in the loteprednol group and 27 in the prednisolone acetate group. They describe the recorded observations, but the registry does not provide a comparative estimate or uncertainty interval. The count outcome is not accompanied by a reported denominator for complete pressure assessment, and the analysis population and missing-data handling are not reported. Thus, the counts alone cannot establish how precise a comparison would be or how robust it is to incomplete follow-up or other analytic choices.

The record does not establish that one regimen is superior, that the regimens are equivalent, or that either regimen does or does not affect pressure outcomes. Those conclusions would require a suitable comparative analysis and adequate information about outcome assessment. A failure to report a statistical comparison is not evidence that the groups are the same.

Likewise, the adverse-event fields report zero serious and zero other adverse events in both groups, but do not provide the definitions or safety ascertainment details needed for a broad conclusion about safety. The registry lists immunologic graft rejection as a secondary outcome, yet its numerical result is not reported in the registry record.

The appropriate reading is therefore limited and descriptive: the record documents trial design, treatment schedules, and primary event counts, while leaving important components of comparative inference unavailable. The posted results can inform what was recorded, but they do not provide a complete estimate of the treatment contrast or its precision.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its primary endpoint is a threshold-based count rather than a continuous pressure summary or a time-to-event measure. That distinction shapes what the result can communicate. The count identifies how many eyes met either of two criteria, but does not show the pressure values, timing, duration, or route by which each eye met the endpoint.

The endpoint also combines an absolute threshold with a relative change from baseline. This can capture more than one kind of pressure event, but the reported total does not separate the two criteria. A reader therefore cannot tell from the count whether the recorded events were driven mainly by high absolute readings, increases over baseline, or both.

The record illustrates why randomization and an inferential result are separate parts of trial interpretation. Random assignment is part of the design, but a comparative conclusion also depends on how outcomes were analyzed, how complete follow-up was, and how uncertainty was quantified. The registry does not report an estimable two-arm comparison for this count endpoint, nor the analysis population or missing-data approach.

The presence of a completed trial record and posted event counts may look informative, but completeness of the record’s status does not supply missing statistical details. Likewise, a planning illustration based on the observed effect cannot be treated as evidence of observed power or as a reconstruction of the original sample-size plan. The distinction between descriptive evidence, inferential evidence, and planning calculations is central to reading these results carefully.

These features make the record useful for understanding what was measured and how the treatment groups were organized, while also showing the limits of interpreting counts without a reported comparative analysis.

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 the primary result is that the registry does not report an estimable two-arm analysis of the count outcome. The listed values are raw counts, without a comparative estimate, confidence interval, or p-value. The record also does not explain the statistical method intended for this endpoint.

The endpoint is defined per eye, while the record lists group sizes without explaining whether those group sizes are the denominators for the eye-level outcome. It does not report how many eyes had complete pressure follow-up, whether any participant contributed more than one eye, or how such data would have been handled. These details matter for understanding the observational unit and the precision of a group comparison.

Follow-up completeness and missing-data methods are not reported. The record does not state how pressure measurements were collected across the 1-to-12-month timeframe, whether every scheduled assessment was available, or how missing measurements were treated. It also does not report the analysis populations or provide a numerical result for the secondary graft-rejection outcome.

Although the trial is described as randomized and single-masked, the registry does not identify the masked party or give details of sequence generation, allocation concealment, or protocol deviations. The statistical analysis plan, any interim analyses, and multiplicity methods are not reported. The record also does not provide enough detail about adverse-event definitions or ascertainment to support broad conclusions from the zero counts.

These limitations are limitations of what can be interpreted from the registry record; they do not establish that the trial itself lacked procedures or analyses that were not reported there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparison of Corticosteroid Dosing Regimens After Endothelial Keratoplasty — NCT01853696.
• Registry record last updated 2015-05-15; status last verified 2015-04.
• Results first posted 2015-04-30.
• 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

NCT01853696 is a completed, prospective, randomized, single-masked, parallel-group phase 4 trial sponsored by Cornea Research Foundation of America. It compared topical loteprednol etabonate 0.5% gel with prednisolone acetate 1% ophthalmic solution after endothelial keratoplasty. The registry lists enrollment of 167 and group sizes of 84 for loteprednol and 83 for prednisolone acetate.

The primary outcome counted eyes meeting an intraocular-pressure threshold from 1 to 12 months after transplant: an absolute pressure of at least 24 mm Hg or a relative increase of at least 10 mm Hg over the baseline preoperative reading. The posted counts are 11 and 27 eyes, respectively. A two-arm statistical comparison is not reported as estimable, and the registry does not report an analysis population or missing-data methods.

Immunologic graft rejection is listed as a secondary outcome, but its numerical result is not reported in the registry record. The adverse-event summary lists zero serious and zero other adverse events in both groups; death counts are not reported.