Cornea Donor Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cornea Donor Study (NCT00006411), a non-randomized na study. The primary outcome is Graft Failure.

2. Clinical Question

The clinical question concerns donor age as a characteristic of the transplanted tissue, not the effect of assigning patients at random to two treatments. That distinction matters statistically: differences between groups may reflect donor age, other characteristics of the tissue or transplant, or differences in the recipients and their care. The registry record does not report an adjusted comparison that would help separate these explanations.

The summary also describes objectives concerning donor-recipient ABO blood type compatibility and graft failure due to rejection, and endothelial cell density as an indicator of corneal health and an alternative outcome in an optional ancillary study. These are study objectives, but the record does not provide results for them. The primary question addressed by the posted endpoint remains graft failure, defined in terms of regrafting or persistent corneal cloudiness that compromises vision.

3. Trial Design

The Cornea Donor Study is described as a prospective cohort study. Its registry design fields identify a nonrandomized allocation, a parallel model, and triple masking. The record does not identify which groups of people were masked, so the masking label cannot be interpreted more specifically. Phase is listed as NA.

The study compared corneas assigned from donor age groups <66.0 years and >= 66.0 years. These categories define the posted comparison; they are not randomized arms. As a result, the groups may differ in ways other than donor age. The record does not report details of any procedures used to address those differences or an adjusted statistical analysis.

Enrollment is listed as 1090. The study status is COMPLETED. The recorded start date is 2000-01-10 and the primary completion date is 2012-12-31. These administrative details do not establish what follow-up was achieved for each participant. The primary endpoint timeframe is listed as baseline to 10 Years of Follow Up, while the study summary describes an objective to compare graft-failure rates over a 5-year follow-up period. The registry record does not explain the relationship between those timeframes.

The intervention entry describes corneas assigned by donor age group. The primary outcome is measured at the participant level, and its definition states that only one eye per participant was included. The registry also lists endothelial cell density as a secondary outcome, but does not report its results. The record does not report a protocol, detailed eligibility criteria, recruitment procedures, or the rationale for the enrollment target. Those design details therefore cannot be used to judge how closely the recorded comparison followed a prespecified plan.

4. Participant Flow and Accounting

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

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 Graft Failure, measured over Baseline to 10 Years of Follow Up.

The primary endpoint is graft failure, measured as the number of participants with an event. The registry defines failure as a regraft or a cloudy cornea sufficiently opaque to compromise vision for a minimum of three consecutive months. It also specifies that only one eye per participant was included in the study. This endpoint therefore represents a clinically consequential problem with the graft, rather than a laboratory measurement alone.

A binary endpoint records whether each participant meets the event definition during the stated observation period. This can make the result straightforward to interpret, but it does not by itself describe when failure occurred. The listed timeframe is baseline to 10 Years of Follow Up. A time-to-event analysis could account for event timing and differing follow-up, but the registry record does not report which analysis was used.

The study summary describes a 5-year objective, while the endpoint timeframe lists 10 Years of Follow Up. The record does not explain this difference. More importantly, it does not post the number of graft failures in either donor-age group or an estimate comparing the groups. Without those results, the frequency of the endpoint and the precision of any contrast cannot be assessed from the registry entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, a clinical comparison begins by defining the outcome, the population, and the contrast of interest. In this study, the primary outcome is a binary graft-failure event, the endpoint description says one eye per participant was included, and the contrast is between donor-age groups. The registry record does not report an analysis plan, an estimated contrast, or its uncertainty. Statistical methods can explain what such quantities would mean, but cannot recover unreported results.

What does a binary outcome mean?

For a binary endpoint, each participant is classified as having or not having the defined event during the relevant observation period. The registry's event definition combines regrafting with persistent, vision-compromising corneal cloudiness. A group event proportion would describe the frequency of participants meeting that definition, while a difference or ratio between group proportions would describe a contrast. No such proportions or contrast estimates are reported in the registry record. A binary count also does not indicate when events occurred; a time-to-event method would use event timing and follow-up information if those data were available.

Why does nonrandomized allocation matter?

In general, randomization helps make comparison groups similar with respect to both measured and unmeasured prognostic characteristics, apart from chance variation. This study is labeled NON RANDOMIZED, so that protection cannot be assumed. Donor age may be associated with other tissue or donor characteristics, and recipient characteristics may differ across the groups as well. If such factors also relate to graft failure, an unadjusted group contrast could combine the association with donor age and the influence of those other factors. Adjustment can address measured factors when suitable data and a prespecified model are available, but cannot automatically remove bias from unmeasured factors. The record does not report whether adjustment was performed or which covariates were considered.

What would uncertainty measures contribute?

In general, a confidence interval expresses the range of values compatible with the observed data under the assumptions of the analysis. It conveys precision as well as direction and size of an estimated contrast. A p-value addresses compatibility with a specified null hypothesis under a statistical model; it does not measure the probability that the null hypothesis is true, nor does it by itself show whether a difference is important. Neither a confidence interval nor a p-value for graft failure is reported in the registry record. Without an estimate and uncertainty measure, the result cannot be characterized as precise, imprecise, statistically distinguishable, or compatible with equivalence.

Why do follow-up and analysis choices matter?

The outcome is listed from baseline to 10 Years of Follow Up, whereas the study summary describes an objective over a 5-year follow-up period. The record does not explain the difference or report participant-level follow-up. If participants have different observation times, a simple proportion may not represent the same underlying risk for everyone. A time-to-event analysis can use the timing of events and account for censoring, subject to assumptions about how censoring relates to risk. The record does not report whether time-to-event methods were used, how censoring was handled, or whether follow-up differed between groups.

The endpoint definition includes a duration condition for cloudiness, while regrafting is another route to meeting the definition. In general, combining event types can produce a single outcome that is easier to report, but it may obscure differences in the components. The registry record does not report the component counts, so their separate contributions cannot be examined.

How should planning calculations be interpreted?

The registry's planning assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the original study was designed using them. The record does not report numerical planning estimates or the fraction values in the registry record for this account. A sample-size illustration describes the number of participants per arm that would be needed under its assumptions; it is not observed power and does not show the probability that this completed study detected an effect. The record does not report its original sample-size justification.

General statistical modeling also requires attention to how observations are related and how outcome variability compares with model assumptions. Over-dispersion, for example, occurs when count variation exceeds what a model expects and can make standard errors too small if ignored. That concept should only be applied when the outcome and model warrant it. The primary endpoint is described as participants with an event, and the registry does not report a count model or any variance estimate. It would therefore be speculative to claim that over-dispersion occurred or that a particular modeling correction was used.

Finally, multiplicity can arise when investigators test several outcomes, subgroups, or timepoints. In general, repeated testing can increase the chance of at least one apparently unusual result, depending on the analysis strategy. The record lists a secondary outcome and multiple study objectives, but does not report a multiplicity strategy or the results of analyses. It is not possible to determine how multiplicity was handled or whether it affected interpretation.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cornea Assigned From Donor Age Group <66.0 Years", "Cornea Assigned From Donor Age Group >= 66.0 Years")
n      <- c(707, 383)
events <- c(142, 82)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cornea Assigned From Donor Age Group <66.0 Years  707  142  20.1  17.2  23.2  17.3  23.2  17.3  23.2
ARM  Cornea Assigned From Donor Age Group >= 66.0 Years  383  82  21.4  17.4  25.9  17.6  25.8  17.6  25.8

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies graft failure as the primary outcome and endothelial cell density as a secondary outcome. The study summary also describes objectives concerning ABO compatibility and graft failure due to rejection, as well as an optional ancillary study of endothelial cell density. The record does not report a multiplicity plan explaining how inferences across outcomes, analyses, or timepoints were controlled or prioritized. It also lists no analysis entries. That absence does not establish what analyses were conducted outside the registry record; it means their methods and results are not reported in the registry record.

Missing-data information is not reported in the registry record. In particular, the entry does not give the number of participants with complete primary outcome follow-up, the extent or reasons for missing outcome data, or the methods used to handle missingness. Because the endpoint timeframe extends to 10 Years of Follow Up, missing follow-up and censoring could affect interpretation. The record does not describe either.

The endpoint definition states that only one eye per participant was included, but the primary population field is blank. The record does not provide further analysis-population definitions, such as whether the primary analysis included all enrolled participants or only those with evaluable follow-up. It also does not report exclusions from analysis or deviations from an intended analysis population.

General statistical practice distinguishes missing outcomes from participants who are observed without an event; these categories should not be treated as interchangeable. The available record does not provide enough detail to determine how participants without complete follow-up were classified. As a result, the primary outcome cannot be reconstructed, and the potential influence of missingness on any group comparison cannot be assessed.

12. 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 lists serious adverse events for the two donor-age groups as 0 participants affected among 707 at risk in the <66.0 years group and 0 participants affected among 383 at risk in the >= 66.0 years group. It also lists 0 participants affected by other adverse events in each group, with the same group-specific at-risk counts. These are the posted counts; they do not supply an adverse-event definition or details of how events were collected.

Zero affected participants in the posted fields should not be expanded into a claim that no event of any kind occurred. The record does not report the event terms, duration of safety observation, completeness of ascertainment, or criteria used to classify events. It lists no serious adverse-event terms. Death counts are not reported in the registry record.

These safety entries are separate from the primary graft-failure endpoint. They do not provide the number of graft failures, nor do they resolve the nonrandomized comparison. The group-specific at-risk counts are reported as registry safety denominators and should not be assumed to describe complete primary-outcome follow-up.

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

The Cornea Donor Study addresses a clear statistical question: whether graft failure after corneal transplantation differs according to donor-age group. Its registry entry defines graft failure and describes a prospective, nonrandomized cohort comparison. That information helps readers understand what was intended to be studied and why the comparison is clinically relevant.

What the record does not provide is equally important. It does not report primary graft-failure counts, a comparison estimate, a confidence interval, or a p-value. Therefore, the posted information cannot show whether the observed frequency was higher in one group, whether the groups appeared similar, or how precisely any difference was estimated. The study objective of determining whether rates are the same cannot be treated as a result.

Even if group outcome figures were available, a nonrandomized comparison would require careful interpretation. Differences could reflect donor age, other donor or tissue characteristics, recipient characteristics, or care. The registry record does not report adjustment methods that would allow those influences to be evaluated. A lack of a reported difference would also not, by itself, establish equivalence; that requires a suitable analysis with an appropriately precise interval and a prespecified margin, neither of which is reported.

The safety fields report zero affected participants for serious and other adverse events in both donor-age groups, while death counts are not reported. Those entries should be interpreted within the limits of the registry's reporting and do not substitute for the primary endpoint results. The additional objectives involving ABO compatibility and endothelial cell density are described, but their results are not reported in the registry record.

Accordingly, the available record supports a description of the study question, design, endpoint, and selected safety counts. It does not support a conclusion about the comparative graft-failure outcome or the strength of evidence for a donor-age association. The distinction between a study being completed and its results being reported is essential: COMPLETED status does not itself communicate an outcome.

14. Why This Trial Matters Statistically

This trial is statistically notable because it studies a donor characteristic in a prospective cohort rather than comparing randomized treatments. That design is well suited to examining an association between donor age and graft outcomes, but it does not guarantee that the age groups are otherwise comparable. Confounding is therefore central to interpretation, and readers need information about measured characteristics, adjustment, and follow-up to judge the comparison. Those analysis details are not reported in the registry record.

The endpoint also illustrates why definitions and timeframes matter. Graft failure is defined using two clinical routes to an event: regrafting or persistent cloudiness that compromises vision. The registry specifies a baseline-to-10-year timeframe, while the study summary describes a 5-year objective. Those descriptions may relate to different aspects of the study, but the record does not explain how. Clear outcome timing is necessary to understand which events count and how differing follow-up is handled.

The entry further distinguishes a study objective from an analyzable result. It states a question about whether graft-failure rates are the same across donor-age groups, yet does not report the counts or comparison estimates needed to answer it. This is a useful reminder that completion status and detailed design information do not take the place of posted outcome data.

Finally, the record describes additional objectives and an endothelial cell density outcome, but does not report those findings or a strategy for multiplicity. A complete statistical interpretation would need to know how primary and secondary questions were prioritized and how uncertainty was quantified. The record's omissions limit conclusions, but also clarify exactly what additional reporting would be needed for readers to evaluate the study's central comparison.

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.

The primary limitation of the available registry record is the absence of primary graft-failure results. Event counts by donor-age group, an effect estimate, uncertainty intervals, and a statistical test are not reported. Without them, neither the magnitude nor the direction or precision of the primary comparison can be evaluated.

The study is explicitly nonrandomized. The record does not report measured baseline characteristics, group comparability, covariate adjustment, or sensitivity analyses. Thus, potential confounding cannot be assessed from the registry entry. The record also does not explain which parties were masked despite listing triple masking.

There is a timeframe distinction between the summary's 5-year objective and the primary endpoint's baseline-to-10-year timeframe. The entry does not explain that distinction, report the achieved follow-up, or describe censoring and loss to follow-up. Missing-data methods and analysis-population definitions are also not reported. Although the endpoint description states that one eye per participant was included, the primary population field is blank.

The registry does not report the original sample-size justification, analysis plan, or methods for handling multiplicity. The listed planning assumptions describe an illustration rather than the study's own design, and numerical planning estimates are not reported in the registry record. Secondary outcome and other stated objectives are not accompanied by results. Finally, the safety fields do not give event definitions, ascertainment details, or death counts. These limitations concern what can be learned from the registry record and should not be taken as evidence that the study itself did not collect further information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cornea Donor Study — NCT00006411.
• Registry record last updated 2020-02-25; status last verified 2018-08.
• Results first posted 2020-02-25.
• 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.

19. Record Summary

The Cornea Donor Study (NCT00006411) is listed as COMPLETED and as a prospective cohort study with NON RANDOMIZED allocation, a PARALLEL model, and TRIPLE masking. Enrollment is listed as 1090. The recorded start date is 2000-01-10 and the primary completion date is 2012-12-31; phase is listed as NA.

The primary endpoint is graft failure, defined as regrafting or sufficiently persistent corneal cloudiness that compromises vision. Its timeframe is baseline to 10 Years of Follow Up, and the endpoint description states that only one eye per participant was included. The study summary describes a 5-year objective, a difference the registry record does not explain.

The registry compares donor-age groups <66.0 years and >= 66.0 years but does not report primary outcome results or an efficacy analysis. It lists endothelial cell density as a secondary outcome and describes additional study objectives, without reporting their results. Safety fields list zero affected participants for serious and other adverse events in each group; death counts are not reported.