Simultaneous TransPRK and Corneal Collagen Cross-Linking: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Simultaneous TransPRK and Corneal Collagen Cross-Linking (NCT02208089), a non-randomized na study. The primary outcome is Change in LogMAR Corrected Distance Visual Acuity (CDVA).

2. Clinical Question

3. Trial Design

The registry identifies this as a prospective trial with a non-randomized allocation, no masking, and a sequential model. Enrollment is listed as 55. The trial status is completed; its recorded start was 2014-08 and its primary completion was 2016-07. The record names Bruce Allan as sponsor and lists keratoconus as the condition.

One group received simultaneous combined transPRK and CXL. The other received CXL alone, described as using the same protocol without transPRK. The registry summary frames the comparison around visual recovery after the combined procedure versus results in a similar group previously treated with CXL alone. The record does not give further details about how those groups were assembled or how long elapsed between their treatment periods.

Non-random allocation matters to interpretation. Randomization can balance measured and unmeasured characteristics on average, whereas a non-randomized comparison does not ensure this. Differences in participant characteristics, treatment selection, or timing could therefore contribute to any observed outcome contrast. The record does not report adjustments intended to address such differences.

No masking was recorded. The registry does not specify whether outcome assessors were masked, nor does it provide further detail about measurement procedures beyond the primary endpoint description. The phase is listed as NA. A sample-size justification and a detailed statistical analysis plan are not reported in the registry record. The design information describes how the groups and endpoint were framed, but it is not enough to establish that any difference in visual change was caused by the combined procedure.

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.

Before assignment: 63 eligible patients were screened; 11 declined to participate after discussing consent information; 5 patients were found to be ineligible because of insufficient residual corneal stromal depth following PRK programming, leaving 47 patients who were treated with TransPRK/CXL

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.

Population: Matched historical control cases of CXL treated using the same CXL protocol as the TransPRKCXL group prior to commencement of recruitment. These control cases were consecutive cases with 2 year follow up data, matched for age, corneal pachymetry, and corneal curvature with the TransPRK group

6. Primary Endpoint

The registry lists the primary outcome as Change in LogMAR Corrected Distance Visual Acuity (CDVA), measured over Preoperative vs 24 months.

The primary endpoint is change in spectacle-corrected distance visual acuity measured using LogMAR CDVA. The registry describes measurements in a 4m testing lane under photopic lighting conditions, comparing the preoperative measurement with the final review at 24 months. LogMAR represents visual acuity on a scale suitable for quantitative analysis; the endpoint is treated as a continuous measure, and the stated summary is a mean with standard deviation.

Change from baseline is useful because it describes how an outcome changes over the follow-up period rather than reporting only a final measurement. CDVA focuses on vision with spectacle correction, which is relevant to the stated interest in visual recovery. The record specifies the direction of change: a negative change means better vision. It also gives a clinical scale reference: 0.1 logMAR units correspond to one line on the test chart.

These definitions clarify what an estimated mean change would represent, but the registry record does not report the group means, standard deviations, or numerical change estimates. It also does not report a numerical between-group estimate or confidence interval. The endpoint description alone therefore cannot establish the size or precision of the observed visual change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The primary measure is continuous: each participant's CDVA is represented on the LogMAR scale, and the endpoint concerns change between a preoperative measurement and the 24-month review. In general, a group mean change describes the average direction and size of change across participants with measurements. It does not show whether every participant changed in the same way, nor does it describe the full distribution of individual outcomes.

The registry specifies the mean and standard deviation as the summary format. In general, the standard deviation describes how spread out individual measurements are around the mean. A small standard deviation indicates observations clustered more closely around that mean; a larger one indicates greater variation. A mean and standard deviation together are useful summaries, but they do not show the shape of the distribution or identify unusual observations.

How should the scale direction be read?

The endpoint description states that negative change means better vision. It also states that 0.1 logMAR units correspond to one line on the test chart. These details help interpret the direction and clinical scale of a change. The registry record does not report the numerical mean change, so the direction or size of the observed group changes cannot be established from the endpoint description alone.

In general, an outcome change within each group and a difference between groups answer distinct questions. Within-group change describes what happened over time among participants in that group. A between-group comparison asks whether average changes differed across the treatment groups. In a non-randomized study, even a measured contrast in average change is an association; it may reflect baseline or other group differences as well as treatment.

What would uncertainty measures add?

In general, a confidence interval gives a range of values compatible with the estimate and its statistical uncertainty under the analysis assumptions. Its width conveys precision: narrower intervals indicate greater precision, while wider intervals indicate less. A confidence interval around a mean difference would help readers assess which magnitudes of between-group difference remain compatible with the data. No numerical confidence interval for the primary outcome is reported in the registry record.

A p-value, in general, measures how unusual data at least as extreme as those observed would be under a specified null model. It does not measure the size or importance of an effect, and it does not establish that a treatment caused an outcome. The registry record does not report a primary endpoint p-value or specify the inferential test used. It is therefore not possible to characterize statistical significance for the primary comparison.

Why does allocation matter for the comparison?

Random allocation is intended to make treatment groups comparable on average, including for characteristics that may not be measured. This trial is recorded as non-randomized, so such balance is not assured. In general, differences in baseline disease features, participant selection, follow-up, or other factors can influence visual outcomes. Statistical adjustment can address measured characteristics under suitable assumptions, but it cannot guarantee removal of unmeasured confounding. The registry record does not report whether adjusted analyses were performed or what covariates they used.

The trial is also recorded as unmasked. The record does not specify whether visual-acuity assessors were masked. In general, masking can reduce the possibility that knowledge of treatment influences assessment or other aspects of study conduct. The extent to which this concern applies depends on how outcomes were measured and managed, details not reported in the registry record.

What do the planning illustrations mean?

The registry's stated sample-size assumptions describe a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The record says such illustrations report participants per arm for non-time-to-event outcomes. These are planning quantities, not observed trial results, and they are not observed power. The numerical illustration values and a trial-specific sample-size justification are not reported in the registry record.

In general, power is a design-stage probability defined for a specified effect, variability, analysis, and significance level. Calculating a sample size from an observed effect after results are available does not establish the power the completed study had in advance. Such planning calculations can show how sample requirements depend on the assumed effect, but they cannot replace an estimate and its uncertainty from the trial.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("TransPRKCXL", "CXL Only")
n   <- c(40, 47)
m   <- c(-0.13, -0.05)
sp  <- c(0.2, 0.13)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  TransPRKCXL  40  -0.130  0.200  -0.194  -0.066
CARM  CXL Only  47  -0.050  0.130  -0.088  -0.012

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes: clinically significant visual gain, clinically significant visual loss, change in Kmax, and progression rate. When several outcomes or statistical tests are examined, the chance of at least one apparently notable finding can increase. In general, a statistical analysis plan may identify a primary comparison and specify whether and how multiplicity is handled. The registry record does not report a multiplicity procedure, a hierarchy among secondary outcomes, or the number of tests intended for each outcome.

Without a stated plan, it is not possible to determine whether reported secondary findings, if available, were treated as confirmatory or exploratory, or whether any adjustment was used. Numerical results for the listed secondary outcomes are not reported in the registry record, so their estimates and uncertainty cannot be assessed.

The record does not describe missing-data methods, the amount or pattern of missing primary endpoint measurements, or how missing observations were handled. It also does not report the analysis population for the primary endpoint, such as which participants contributed to the comparison or whether all enrolled participants were included. These details affect how an estimated change should be interpreted, particularly when follow-up measurements are unavailable or when inclusion depends on post-enrollment events.

Enrollment is listed as 55, while the adverse-event record lists 47 participants at risk in each group. Those figures describe different entries in the registry and do not establish the primary endpoint sample size or explain how participants were assigned to the outcome analysis. Reasons for any difference between enrollment and participants at risk are not reported in the registry record. A complete assessment of missingness and analysis populations would require those details and the handling rules used for the visual-acuity endpoint.

12. 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 adverse-event record lists 47 participants at risk in each group. For serious adverse events, it reports 0 affected in the combined transPRK and CXL group and 0 in the CXL-only group. Deaths are reported as 0 in both groups. For other adverse events, the record reports 1 affected in the combined group and 0 in the CXL-only group.

These are event counts as recorded, not estimates of comparative safety. The registry record does not provide further detail about the single other adverse event, including its nature, timing, severity, or relationship to treatment. It also does not report the method used to collect or classify adverse events. The absence of recorded serious events in these entries does not establish that no other events occurred or that the groups had equivalent safety.

In general, adverse-event counts should be read alongside the number monitored, the follow-up period, event definitions, and completeness of reporting. The at-risk counts do not identify the sample size used for the primary visual-acuity analysis. These safety figures therefore should not be substituted for the unreported visual outcome estimates or interpreted as a causal comparison.

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

The registry record defines a prospective, non-randomized comparison of simultaneous transPRK and CXL with CXL alone. It specifies a visual-acuity endpoint based on mean change from the preoperative measurement to 24 months, including how to read the direction of change. Those details establish the question and the intended interpretation of the measurement.

The record does not include numerical results for the primary endpoint. It therefore does not show the size of the mean change in either group, the difference between groups, or the precision of any estimate. Nor does it report numerical results for the listed secondary outcomes. The record can be used to understand what investigators aimed to evaluate, but it cannot support a conclusion about the magnitude or direction of the comparative visual outcome.

Even with outcome estimates, this design would not make a treatment effect certain. Because participants were not randomly allocated, differences between groups could contribute to a difference in outcomes. In general, adjustment for measured characteristics may help with some imbalances, but it cannot rule out unmeasured confounding. The record does not report details of any adjusted analysis.

The safety entries report no serious adverse events or deaths in either group among the participants listed at risk, and one other adverse event in the combined group versus none in the CXL-only group. These counts are limited by the event details and collection methods not reported in the registry record. They do not establish that the treatments are equally safe or that one caused a particular event.

The most defensible reading is therefore bounded: the record describes a clinical comparison, a defined visual endpoint, and limited adverse-event counts, but it does not report the numerical efficacy results needed to judge the observed visual changes. The absence of reported estimates is not evidence that the groups had no difference.

14. Why This Trial Matters Statistically

This trial raises a useful design question: whether visual recovery differs when transPRK and CXL are performed simultaneously rather than using CXL alone. The primary endpoint is framed as change in corrected distance visual acuity over a defined follow-up period. Specifying the scale direction and its relation to a test-chart line helps make a future estimate interpretable rather than leaving readers with an unexplained numerical score.

Statistically, the comparison illustrates why design and outcome reporting must be considered together. A mean change can summarize a continuous endpoint, but readers also need information about variation, uncertainty, and the actual between-group estimate. The registry record does not report those primary outcome values. Consequently, the clinical question is identifiable while the numerical answer is not.

The non-randomized allocation also makes confounding an important consideration. A difference in observed visual change would not, by itself, show that treatment caused the difference. Group comparability, analysis choices, missing follow-up, and measurement procedures would all inform how strongly the data support a causal interpretation. Several of these details are not reported in the registry record.

The record's planning assumptions also point to a general distinction between design planning and study findings. Sample-size illustrations based on an observed effect are not observed power and do not replace a pretrial justification or the completed study's outcome estimates. Clear reporting of the numerical endpoint results and analysis methods would be necessary to evaluate precision and compare the observed findings with the stated clinical question.

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 most consequential limitation for interpreting the registry record is that it does not report numerical results for the primary endpoint. Without group-level changes, a between-group estimate, or a measure of uncertainty, the magnitude and precision of the visual outcome comparison cannot be evaluated. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The comparison is non-randomized, and the groups are not established as like-for-like controls. The registry does not report baseline characteristics or methods used to address group differences. Consequently, even if an outcome contrast were available, its interpretation would depend on potential confounding and the adequacy of any adjustment.

The record does not report the primary endpoint analysis population, missing-data handling, or the number of participants contributing visual-acuity measurements at follow-up. Although enrollment is listed as 55, the adverse-event entries list 47 participants at risk in each group; the record does not explain how these figures relate to the primary outcome population. The reason for any difference cannot be inferred from these entries.

Other information needed for a fuller assessment is not reported in the registry record, including a trial-specific sample-size justification, a detailed statistical plan, multiplicity handling, and whether outcome assessors were masked. The adverse-event record provides limited counts without further event descriptions or collection details. These gaps constrain interpretation of both outcome reporting and safety reporting; they should not be filled by assumptions about the protocol or conduct.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Simultaneous TransPRK and Corneal Collagen Cross-Linking — NCT02208089.
• Registry record last updated 2019-02-08; status last verified 2018-09.
• Results first posted 2019-02-08.
• 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 registry record describes a completed prospective, non-randomized, unmasked trial with a sequential model and enrollment of 55. It compares simultaneous transPRK and CXL with CXL alone for progressive early-stage keratoconus. The primary endpoint is mean change in LogMAR CDVA from preoperative measurement to 24 months; negative change represents better vision.

The record does not report numerical primary or secondary outcome results, confidence intervals, or primary endpoint analysis details. It lists 47 participants at risk in each group for adverse-event reporting, with 0 serious adverse events and 0 deaths in both groups, and 1 other adverse event in the combined group versus 0 in the CXL-only group. These counts do not provide the missing visual-acuity comparison or establish a causal treatment effect.