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 Comparison of Two Steroid Regimens to Prevent Transplant Rejection After Corneal Transplant (DMEK) (NCT01448213), a randomized phase 2 study. The primary outcome is Number of Eyes With Immunologic Graft Rejection Episodes.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01448213 |
| Phase | Phase 2 |
| Condition | Fuchs' Dystrophy, Bullous Keratopathy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 264 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Price Vision Group |
| Results posted | Yes |
2. Clinical Question
Population
People undergoing Descemet's membrane endothelial keratoplasty (DMEK) for corneal transplant, in a study listing Fuchs' Dystrophy and Bullous Keratopathy as conditions. The registry records enrollment of 264 participants. Further eligibility criteria and details of the analysis population are not reported in the registry record.
Intervention
Treatment Regimen A used prednisolone acetate 1% in the transplant eye, starting four times a day for 3 months, then reducing to three times a day for one month, twice a day for one month, and once a day until study exit.
Comparator
Treatment Regimen B began with prednisolone acetate 1% four times a day for one month, followed by fluorometholone 0.1%. The record describes fluorometholone use four times a day for 2 months, three times a day for one month, and twice a day for one month; the remainder of the regimen description is incomplete in the registry record.
Primary question
How did the recorded number of eyes with immunologic graft rejection episodes within 1 year compare between the regimens? The registry reports 2 eyes in the fluorometholone arm and 0 in the prednisolone acetate arm, alongside a log-rank p-value of 0.17. The record does not provide an effect estimate or confidence interval.
3. Trial Design
This was a randomized, single-masked, parallel-group phase 2 study sponsored by Price Vision Group. The registry lists 264 participants and a completed study, with a start date of 2011-10 and a primary completion date of 2014-01. Those design details describe how the study was organized; they do not, on their own, establish how precise the comparison is or how broadly its result applies.
The comparison involved two corticosteroid dosing regimens after DMEK. One arm used prednisolone acetate 1% with a gradual reduction in dosing frequency. The other began with prednisolone acetate 1% and then changed to fluorometholone 0.1%. The registry's description of the fluorometholone schedule ends after the twice-a-day-for-one-month step, so the rest of that arm's schedule is not reported in the registry record. Details such as adherence assessment, permitted co-interventions, and the identity of the masked party are also not reported in the registry record.
Random allocation is intended to support a fair comparison by distributing measured and unmeasured participant characteristics without systematic assignment by investigators. Whether randomization was stratified, how the allocation sequence was generated, and how allocation was concealed are not reported in the registry record. The parallel design means participants were assigned to one regimen rather than crossing between regimens, but details of participant flow and follow-up by arm are not given in the posted information.
The registry lists Fuchs' Dystrophy and Bullous Keratopathy as conditions. It does not provide enough detail to characterize the enrolled population beyond those conditions and the DMEK context. The study's phase, masking, and allocation labels are useful descriptions, but they cannot substitute for a full protocol or a detailed account of conduct and analysis.
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
| Stage | Fluorometholone 0.1% Solution | Prednisolone Acetate 1% Solution |
|---|---|---|
| STARTED | 130 | 134 |
| COMPLETED | 113 | 112 |
| NOT COMPLETED | 17 | 22 |
Reasons for not completing this period:
| Reason | Fluorometholone 0.1% Solution | Prednisolone Acetate 1% Solution |
|---|---|---|
| Lost to Follow-up | 12 | 10 |
| Adverse Event | 4 | 10 |
| Protocol Violation | 1 | 2 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Baseline characteristics data are reported in units of "eyes" as this presentation is most relevant to the assessments presented in the Outcome Measures module.
| Characteristic | Unit | Fluorometholone 0.1% Solution | Prednisolone Acetate 1% Solution | Total |
|---|---|---|---|---|
| Participants analysed | 161 | 164 | 325 | |
| Age, Continuous | years | 69 (35 to 91) | 67 (42 to 94) | 68 (35 to 94) |
| Sex: Female, Male: Female | Participants | 107 | 105 | 212 |
| Sex: Female, Male: Male | Participants | 54 | 59 | 113 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Eyes With Immunologic Graft Rejection Episodes, measured over Within 1 year.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | eyes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of eyes with immunologic graft rejection episodes within 1 year. It is a count of affected eyes over the stated follow-up period, rather than a reported measure of symptom severity, graft function, or time to rejection. The registry gives 2 eyes for the fluorometholone arm and 0 for the prednisolone acetate arm. The arm records list 130.0 and 134.0 participants, respectively, but the posted result does not provide a confidence interval or a direct estimate of the difference between groups.
In general, graft rejection is a clinically relevant event to track after transplantation because it concerns an immune response directed against the transplanted tissue. Counting affected eyes offers a straightforward description of how many recorded events occurred during the specified period. The count alone, however, does not show when events occurred, how long participants were followed, or whether follow-up was complete for everyone. Those details matter when interpreting differences in event counts, especially if observation time varies.
The registry describes the endpoint in terms of eyes, while the arm records report participant counts. The relationship between eyes and participants, including whether any participant contributed more than one eye, is not reported in the registry record. The endpoint definition, event adjudication procedures, and handling of missing follow-up are likewise not reported. These omissions limit what can be inferred from the displayed counts and from the reported analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome records 2 eyes with immunologic graft rejection episodes in the fluorometholone arm and 0 in the prednisolone acetate arm, within 1 year. The registry also reports a log-rank p-value of 0.17 for the comparison. These are the available primary-outcome results; the record does not provide a confidence interval or a comparative effect estimate, so the precision and plausible range of the between-arm difference cannot be read from the posted result.
In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. A p-value of 0.17 does not by itself establish that the regimens are equivalent, that they differ, or that either regimen is preferable. Establishing similarity would require an appropriate equivalence or non-inferiority framework and a sufficiently precise estimate; such a framework is not reported in the registry record.
The group counts are sparse, with no recorded rejection eyes in one arm and 2 in the other. In general, sparse event data can make comparative estimates uncertain, and a count alone does not convey that uncertainty. The registry's log-rank result also does not show the timing of events or the follow-up pattern. A log-rank test is ordinarily interpreted in relation to event timing, but event-time summaries, censoring details, and survival estimates are not reported in the registry record.
The result should therefore be read as a limited description of the posted data, not as a definitive answer about the regimens. The p-value is the only comparative test result posted for the primary endpoint. There is no posted confidence interval, hazard ratio, or other effect estimate to show the magnitude and uncertainty of the comparison. The result does not establish whether the observed count pattern reflects a true difference or chance variation.
The registry lists intraocular pressure elevation as a secondary outcome, but a result for that outcome is not reported in the registry record. The primary result should not be extended to other outcomes, including safety or graft performance, on the basis of the rejection counts alone. Study design and endpoint details not reported in the record further limit interpretation.
9. Statistical Methods Explained
The registry reports a log-rank analysis for the primary comparison, with p = 0.17. The endpoint is described as a number of eyes with rejection episodes within 1 year, but the record does not provide the event-time data, the test statistic, or a detailed statistical analysis plan. This leaves important information about how the reported test relates to the endpoint unavailable.
What a log-rank test generally compares
In general, the log-rank test compares event-time distributions between groups. It uses information about when events occur and about participants who have not had an event by the end of their observed follow-up. Those participants contribute information up to the point when their observation ends; this is commonly called censoring. The test is often used in time-to-event analyses, where the timing of an event is part of the outcome.
A count of eyes with an event is not, by itself, a full time-to-event summary. To understand the registry's log-rank result, readers would need details about event times, follow-up, censoring, and how the unit of analysis was defined. Those details are not reported in the registry record. It is therefore not possible to reproduce the test or assess whether the assumptions and analysis choices were appropriate from the posted information alone.
How to interpret the p-value
In general, a p-value is calculated under a null hypothesis and a statistical model. It describes the compatibility of the observed data with that null model, given the assumptions used. It is not an effect size, does not quantify the probability that a result occurred by chance, and does not show whether any difference is important in practice. The posted p-value of 0.17 should be read alongside the small number of recorded rejection eyes and the absence of a confidence interval or comparative estimate.
A confidence interval would ordinarily provide a range of values compatible with the data and analysis, conveying uncertainty around an estimated effect. No confidence interval is reported for this comparison. The record also does not report a hazard ratio, a risk difference, or another effect measure. The event counts can be stated as posted, but they cannot replace an estimate of the contrast and its precision.
Why sparse counts need care
In general, when few events occur, estimates can be sensitive to individual observations and may be imprecise. A group with no recorded events does not mean its underlying event probability is zero. It means no events were recorded in that group during the observation represented by the posted data. Follow-up duration and completeness are important to this interpretation, but they are not reported in enough detail.
Over-dispersion is a general concern for count data when observed variability exceeds what a chosen count model assumes. It can affect standard errors and inference. The registry does not describe a count model for this endpoint, and a log-rank test is the method named in the posted analysis. There is no basis in the record for claiming that over-dispersion was assessed or that any particular count-model adjustment was used.
Planning estimates are not trial results
In general, sample-size calculations estimate how many participants may be needed under stated assumptions about the effect to detect, the significance level, allocation, and statistical method. Such figures are planning illustrations, not observed study outcomes and not evidence that a completed trial had a particular probability of detecting an effect. The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The actual trial's sample-size justification and design calculation are not reported in the registry record.
The record does not provide a set of recalculated comparative estimates for this count endpoint: the comparison is identified as not estimable from the posted summary statistics. Consequently, a simple unadjusted re-calculation cannot add an effect estimate or confidence interval to the reported primary result. Where a sponsor analysis is available, it should not be replaced by a reconstruction that the posted summaries cannot support.
What is not documented
The statistical analysis plan, endpoint analysis population, missing-data approach, multiplicity strategy, and handling of any protocol deviations are not reported in the registry record. The record lists two analyses, but gives one primary comparative result. Without further documentation, it is not possible to determine whether the reported p-value was prespecified, whether other analyses were conducted, or how the primary result was selected and interpreted. These are limits on assessment of the analysis, not evidence that a particular method was or was not used.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Log Rank | not reported | 0.170 |
The registry posts a log-rank result for the primary comparison: p = 0.17. It also reports 2 eyes with rejection episodes in the fluorometholone arm and 0 in the prednisolone acetate arm within 1 year. Those counts and the sponsor's reported test are the available basis for describing the comparison.
The posted summary statistics do not support an additional unadjusted comparative estimate for this count endpoint. In particular, no recalculated effect estimate or confidence interval is available to place beside the log-rank result. The registry record does not provide the event times or other details needed to reconstruct the reported test. There is no numerical disagreement between a sponsor result and a recalculation to resolve; the comparison is not estimable from the posted summary statistics.
The sponsor's analysis should therefore be presented as reported, without implying that the p-value is an effect size or a measure of precision. Because the record does not include an effect estimate or confidence interval, it cannot show the size of a comparative effect or the range of values compatible with the analysis. Further analysis details and the statistical plan are not reported in the registry record.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary rejection endpoint and an intraocular pressure elevation secondary outcome. It also indicates two analyses, while the posted comparative result describes the log-rank test for the primary endpoint. Results for the secondary outcome and the details of any other analysis are not reported in the registry record.
Multiplicity arises in general when multiple outcomes, time points, or statistical tests are considered. If many comparisons are made, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. The record does not report whether the investigators prespecified a testing hierarchy, adjusted for multiple comparisons, or treated the secondary outcome as exploratory. The p-value should not be interpreted as though the multiplicity strategy were known.
The analysis population is not described in sufficient detail. The record does not state whether the primary analysis followed intention-to-treat principles, how participants were handled after discontinuation or deviations, or whether all randomized participants contributed to the outcome analysis. It lists arm counts of 130.0 and 134.0, but does not give an account of exclusions or the number with complete follow-up for the endpoint.
Missing-data procedures are also not reported in the registry record. There is no description of missing outcome assessments, loss to follow-up, censoring rules, or any imputation method. For a time-to-event test, follow-up and censoring information would be important for understanding how participants with no recorded event contributed to the analysis. The posted counts alone cannot establish whether outcome observation was complete or balanced between arms.
These omissions do not show that multiplicity, missingness, or analysis populations were handled incorrectly. They mean that readers cannot evaluate those choices from the registry information. The statistical analysis plan and a participant-flow account would be needed to clarify whether the posted test was the prespecified primary analysis and how incomplete observations were treated.
12. 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 |
|---|---|---|---|
| Fluorometholone 0.1% Solution | 0 | 130 | 0.0% |
| Prednisolone Acetate 1% Solution | 0 | 134 | 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 |
|---|---|
| Fluorometholone 0.1% Solution | 0 of 130 |
| Prednisolone Acetate 1% Solution | 13 of 134 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Fluorometholone 0.1% Solution | Prednisolone Acetate 1% Solution |
|---|---|---|---|
| Intraocular pressure control problem requiring discontinuation of study drug | Eye disorders | 0 of 130 | 13 of 134 |
The registry safety record lists 0 serious adverse events among 130 participants at risk in the fluorometholone arm and 0 among 134 participants at risk in the prednisolone acetate arm. It separately lists 0 other adverse events in the fluorometholone arm and 13 in the prednisolone acetate arm. These are the posted counts; the record does not provide event types or definitions for the other adverse events.
A zero count means that no event in the relevant category was recorded in the posted safety data. It does not establish that the underlying risk is zero. The record does not provide confidence intervals or a comparative safety estimate, and the counts alone do not show whether follow-up or event ascertainment was comparable between arms. The arm-level counts should not be interpreted as evidence of a causal difference.
Death counts are not reported in the registry record. Serious adverse events and other adverse events are distinct categories in the safety information, so the 13 other adverse events should not be described as serious events. The absence of event descriptions and reporting details limits any further assessment of safety patterns.
13. What the Result Does, and Does Not, Mean
The result establishes what the registry records for the primary endpoint: 2 eyes with immunologic graft rejection episodes in the fluorometholone arm and 0 in the prednisolone acetate arm within 1 year, with a reported log-rank p-value of 0.17. It does not provide a comparative effect estimate or confidence interval. The data as posted therefore give a limited description of observed events, rather than a precise estimate of the difference between regimens.
In general, a p-value does not establish that treatments are equivalent when it does not indicate a statistically notable difference under a particular testing convention. Equivalence requires a defined margin and an analysis designed to assess whether effects fall within that margin. Such a margin and an equivalence or non-inferiority analysis are not reported in the registry record. Nor does the result prove that one regimen is better: the event counts are sparse, and the record does not quantify uncertainty around their comparison.
The result also does not show the timing of rejection episodes, the duration of observation for each participant, or the completeness of follow-up. Those details affect interpretation of a time-to-event analysis. The description of the endpoint is in eyes, whereas arm sizes are recorded in participants; the way eyes and participants correspond in the analysis is not reported. The primary result cannot be extended to intraocular pressure elevation or other outcomes, because a result for the listed secondary outcome is not reported in the registry record.
More broadly, these data do not establish the regimens' effects in populations or settings beyond the enrolled study population. Eligibility criteria, outcome adjudication, analysis population, and details of masking are not available in the registry information. The record supports a factual account of the observed counts and the reported test, but a full assessment requires additional methods and follow-up information.
14. Why This Trial Matters Statistically
This study raises a useful statistical question about how to analyze uncommon events in a randomized comparison. The posted primary outcome has 2 recorded rejection eyes in one arm and 0 in the other. With sparse counts, a simple description of event totals can be informative, but it gives little information about uncertainty or timing. A comparative test and an effect estimate answer different questions, and readers benefit when both the method and the estimate are fully reported.
The registry names a log-rank test, a method generally associated with time-to-event comparisons, while describing the endpoint as the number of eyes with rejection episodes within 1 year. This makes clear why endpoint and analysis descriptions need to align transparently. Event dates, follow-up, censoring, and the unit of analysis would help readers understand the role of event timing and reproduce the analysis. Those details are not reported in the registry record.
The comparison also illustrates why a p-value alone cannot establish equivalence. The posted result does not give an effect estimate or confidence interval, and the registry does not report a non-inferiority or equivalence framework. Without an estimate and its precision, a reader cannot distinguish a genuinely small difference from an uncertain result based on few events.
Finally, registry reporting is most useful when it connects the planned analysis, participant flow, endpoint definitions, and results. Here, the available information identifies the design, regimens, endpoint, event counts, and reported test, while leaving several analysis details unresolved. Recognizing both the useful information and the gaps is central to responsible interpretation of clinical trial statistics.
15. 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.
Several limitations specific to this record restrict interpretation. The primary endpoint is expressed as a number of eyes, but the arm sizes are expressed as participants. The registry does not state whether any participant contributed more than one eye or how the analysis accounted for the relationship between eyes and participants. The endpoint definition also does not describe how rejection episodes were confirmed or adjudicated.
The reported log-rank test cannot be independently assessed from the posted summaries. Event times, censoring, follow-up distributions, survival estimates, and the test statistic are not reported in the registry record. Although the outcome is described as a count within 1 year, the timing information that would generally underpin a log-rank analysis is unavailable. No effect estimate or confidence interval is posted, and the count-based comparison is not estimable from the available summary statistics.
The description of the fluorometholone regimen is incomplete: it stops after the twice-a-day-for-one-month step. The continuation of that regimen is not reported in the registry record. The record also does not identify who was masked, describe the allocation procedure, or give detailed eligibility criteria. These omissions prevent a complete account of the treatment contrast and study conduct.
Participant flow, missing outcome data, analysis-population definitions, and adherence information are not reported. The registry lists intraocular pressure elevation as a secondary outcome but does not post its result. It does not provide event descriptions for the other adverse events or death counts. These gaps limit assessment of follow-up, outcome completeness, secondary findings, and safety patterns.
Finally, the statistical analysis plan and sample-size justification for the trial are not reported in the registry record. The stated planning assumptions are not a substitute for the study's own design justification. The posted information is sufficient to describe the reported primary counts and p-value, but not to resolve these methodological questions.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Comparison of Two Steroid Regimens to Prevent Transplant Rejection After Corneal Transplant (DMEK) — NCT01448213.
- Registry record last updated 2014-09-03; status last verified 2014-08.
- Results first posted 2014-08-25.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
NCT01448213 is a completed randomized, single-masked, parallel-group phase 2 study sponsored by Price Vision Group. It enrolled 264 participants and compared prednisolone acetate 1% with a regimen that began with prednisolone acetate and then used fluorometholone 0.1% after DMEK.
The primary endpoint was the number of eyes with immunologic graft rejection episodes within 1 year. The registry records 2 eyes in the fluorometholone arm and 0 in the prednisolone acetate arm, with a reported log-rank p-value of 0.17. It provides no effect estimate or confidence interval. Intraocular pressure elevation is listed as a secondary outcome, but its result is not reported in the registry record. Analysis details, missing-data handling, and the full fluorometholone schedule are also not reported.