Evaluation of Prednisolone in a Modified Conjunctival Allergen Challenge Model: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Prednisolone in a Modified Conjunctival Allergen Challenge Model (NCT01730872), a randomized phase 4 study. The primary outcome is Inflammation Change From Baseline to Day 6.

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase 4, randomized, parallel-group study with quadruple masking. Its official title describes a single-center, double-masked, randomized, placebo-controlled evaluation of prednisolone sodium phosphate ophthalmic solution, 1%, compared with placebo in a modified CAC model. The registry reports enrollment of 16 and a completed status. The study start is listed as 2012-11 and primary completion as 2012-12.

The active-treatment arm received Prednisolone Sodium Phosphate Ophthalmic Solution, 1%. The comparator arm received Tears Naturale II Ophthalmic Solution, 1%, described as placebo. The primary outcome summaries list 8 participants in the prednisolone group and 4 in the placebo group. The record does not explain why the posted group counts differ or how many enrolled participants contributed data to each analysis.

The primary endpoint was inflammation change from baseline to Day 6, with the assessment made 90 minutes after CAC. Ocular itching and ocular redness change from baseline to Day 6 were listed as secondary outcomes. The registry lists three outcome measures in total and two posted secondary outcomes. It does not report detailed visit procedures, the challenge protocol, allocation concealment, or the timing and process of masking beyond the labels in the trial description.

The adverse-event record also lists a Saline group, with three participants at risk. The registry does not explain that group’s role in the study, so it should not be treated as another randomized comparison arm without further information. In particular, the treatment and comparator summaries for the primary endpoint concern prednisolone and placebo, not the Saline safety group.

4. Participant Flow and Accounting

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

Overall Study

Analysis population for the primary outcome, as defined in the registry: The per-protocol (PP) population will comprise all subjects in the ITT population without protocol deviations.

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 Inflammation Change From Baseline to Day 6, measured over 90 minutes post CAC.

The primary outcome was change from baseline in ocular inflammation by Day 6. The rating was performed by a masked clinician 90 minutes after the conjunctival allergen challenge. The scale runs from 0, meaning little to no inflammation, to 4, meaning the most inflammation. It is therefore an ordered score in which lower values indicate less inflammation at a given assessment.

The registry reports this endpoint as a mean change, with standard deviation as the measure of spread. A negative change indicates a lower score relative to baseline; it does not by itself describe the final score or how participants’ scores varied over time. The posted mean changes are -1.2 in the prednisolone group and -0.19 in the placebo group. Their standard deviations are 0.78 and 0.43, respectively.

The study summary also mentions chronic allergic inflammation assessed using confocal microscopy, alongside itching and redness. However, the registry’s primary outcome description specifies a masked clinician’s 4-point inflammation rating. The detailed measurement procedures, including any relationship between the clinician rating and confocal microscopy, are not reported in the registry record. The endpoint is relevant to the challenge model because it records an inflammation measure after CAC, but interpretation depends on the measurement process and the comparison’s precision, not only on the direction of the group means.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Methods help distinguish a descriptive result from a comparison that quantifies uncertainty. The registry identifies a randomized parallel-group design with quadruple masking and reports group means and standard deviations for a continuous primary outcome. It does not report a complete statistical analysis plan or an inferential result for the primary comparison.

What does a mean change represent?

For a continuous outcome, a mean summarizes the average observed value in a group. Here, the endpoint is change from baseline in the inflammation score. A negative mean change indicates that the group’s score was lower at the measured follow-up than at baseline on average. A mean does not show whether every participant changed in the same direction, and it does not describe the full distribution of individual responses.

The reported means are -1.2 for prednisolone and -0.19 for placebo. The standard deviations are 0.78 and 0.43, respectively. Standard deviation describes how dispersed observed scores are around a group mean. It does not measure the uncertainty of the mean itself. That uncertainty depends in part on the number of observations and on the spread of the data.

Why is a between-group estimate important?

A treatment comparison is ordinarily expressed as an estimate of how outcomes differ between groups, accompanied by an uncertainty measure such as a confidence interval. A confidence interval gives a range of values compatible with the data and the statistical model; its width communicates precision. A narrow interval indicates greater precision than a wide interval. The registry record does not report a confidence interval for the primary comparison.

A p-value, when reported, addresses how compatible the data are with a specified null hypothesis under the chosen statistical model. It is not a measure of the size or clinical importance of an effect, and it does not replace an estimate with an uncertainty interval. No inferential p-value for the primary two-arm comparison is reported in the registry record. The posted record also says values are missing or not estimable for this continuous endpoint comparison.

How should the scale be understood?

The clinician-rated scale ranges from 0, described as little to no inflammation, to 4, described as the most inflammation. The endpoint is reported as a mean change, treating the score numerically for the summary. General statistical practice distinguishes the recorded scale from the summary method: an average can be useful, but it does not show the number of participants at each score or whether the distribution is skewed or concentrated at a boundary. Those details are not reported in the registry record.

The assessment time is 90 minutes after CAC, while the endpoint is described as change from baseline to Day 6. Interpretation therefore depends on the recorded measurement schedule and the score definition. More detailed timing and procedures are not reported in the registry record. The record also does not describe a model accounting for repeated measurements or baseline values, so no such method should be assumed.

What can masking and randomization contribute?

Randomization is intended to make treatment groups comparable on average with respect to measured and unmeasured characteristics, while masking is intended to reduce effects of expectations on treatment delivery, assessment, or reporting. These are general design principles, not guarantees that groups are balanced in a small study. The registry identifies the study as randomized and quadruple-masked, but it does not provide the sequence-generation or concealment procedures, identify all parties covered by the masking label, or report whether masking was maintained.

The outcome description specifically says the clinician was masked. That detail is relevant because the primary endpoint involves a clinical rating. The registry does not explain how the clinician’s rating was standardized or whether duplicate ratings were obtained.

What do the planning illustrations mean?

The registry describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed with those assumptions, and the record does not report the trial’s own sample-size justification. A planning illustration estimates the participants per arm that a hypothetical study might require under specified assumptions; it is not observed power and does not add evidence to the completed trial’s results.

Observed power is not a substitute for the uncertainty interval around an estimated effect. In general, a post hoc power calculation based on an observed estimate mostly restates the information already contained in the estimate and its uncertainty. The planning illustrations should therefore be interpreted as hypothetical design calculations, not as a measure of how conclusively this study answered its question.

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("Prednisolone", "Placebo")
n   <- c(8, 4)
m   <- c(-1.2, -0.19)
sp  <- c(0.78, 0.43)
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  Prednisolone  8  -1.200  0.780  -1.852  -0.548
CARM  Placebo  4  -0.190  0.430  -0.874  0.494

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes: ocular itching change from baseline to Day 6 and ocular redness change from baseline to Day 6. It also lists three outcome measures in total. The secondary outcome results are not reported in the registry record, so they cannot be interpreted alongside the primary inflammation summaries.

When several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. Statistical methods may address this multiplicity by specifying a primary comparison, adjusting inference, or using a prespecified testing sequence. The registry record does not report a multiplicity procedure, a hierarchy for secondary outcomes, or a detailed statistical analysis plan. It is therefore not possible to determine whether any adjustment was planned or used.

The primary outcome description identifies a per-protocol population, defined as participants in the ITT population without protocol deviations. The record does not report the number in the ITT population, the number excluded from the per-protocol population, the reasons for protocol deviations, or how missing outcome values were handled. It also does not establish whether the posted primary summaries were calculated in that defined population. These details matter because exclusions and missing observations can affect which participants are represented in a result.

General methods for missing data include analyses under explicit assumptions about why values are missing, along with sensitivity analyses to assess how conclusions change under alternative assumptions. No missing-data method or sensitivity analysis is reported in the registry record. The posted sample counts for the primary outcome are n=8 for prednisolone and n=4 for placebo; the record does not account for the difference between those counts or explain the availability of outcomes for other enrolled participants.

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 reports zero serious adverse events among 8 participants at risk in the prednisolone group and zero among 5 participants at risk in the placebo group. It also lists a Saline group with 3 participants at risk and zero serious adverse events. The registry does not report serious adverse-event terms for these groups.

These are observed counts, not estimates that serious events cannot occur. A zero count in a small group does not establish the absence of risk, and the registry record does not report a statistical comparison of serious adverse events. The Saline group’s role is not reported in the registry record, so its figures should be kept separate from the prednisolone-versus-placebo comparison.

The record separately reports other, non-serious adverse events in 2 of 8 participants at risk in the prednisolone group, 1 of 5 in the placebo group, and 0 of 3 in the Saline group. Those figures are distinct from the serious-event counts. No deaths are reported in any of the listed groups. The registry does not provide event descriptions, timing, severity details, or an assessment of whether events were related to treatment. These summaries describe what was recorded, not a complete evaluation of comparative safety.

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

The posted primary outcome summaries show mean inflammation-score changes of -1.2 in the prednisolone group and -0.19 in the placebo group. Since lower values on the score indicate less inflammation, the direction of each negative mean is a decrease from baseline, and the prednisolone group’s mean change is more negative. The summaries also report standard deviations and the number of participants contributing to each group summary. They are descriptive observations from the recorded groups.

Those data do not by themselves answer whether the treatment groups differed with adequate statistical precision. The registry does not report a confidence interval or inferential test for the two-arm primary comparison, and it notes that values are missing or not estimable for that comparison. Without an uncertainty estimate, the degree of precision around the group contrast cannot be assessed from the record. The record also does not report baseline values, the full distribution of scores, or the detailed analysis population.

The trial was conducted using a modified CAC model. Its findings therefore concern a measured response in that challenge setting. The registry does not report details that would establish how the result relates to outcomes outside the model, or how well the enrolled participants represent a broader clinical population. The secondary itching and redness outcomes are listed, but their results are not reported in the registry record.

Accordingly, the result should not be treated as proof that prednisolone works or does not work. It also does not establish that the treatments are equivalent. A finding of equivalence or a conclusion of no effect would require an appropriate analysis and, typically, a prespecified margin or a sufficiently precise interval; these are not reported in the registry record. The available information supports a cautious description of the observed mean changes and their reported spread, while leaving the precision and broader interpretation unresolved.

14. Why This Trial Matters Statistically

This trial is statistically notable because it pairs a controlled challenge model with a clinician-rated inflammation outcome and a randomized, masked parallel-group design. The primary measure is a change score on a scale with defined anchors, making the direction of the reported means interpretable. The registry also identifies the clinician as masked, an important design feature for an outcome involving assessment.

At the same time, the primary group summaries are based on n=8 for prednisolone and n=4 for placebo. Small group counts make estimates vulnerable to imprecision and to the influence of individual observations. The reported standard deviations describe within-group spread, but without a confidence interval or inferential comparison, the uncertainty around the treatment contrast remains unclear. The registry’s note that the continuous two-arm comparison is missing or not estimable underscores the distinction between having descriptive summaries and having a reported comparative analysis.

The record also illustrates why analysis populations and outcome reporting matter. The endpoint description names a per-protocol population, but the record does not explain the actual analysis set or reconcile its definition with the posted group counts. Secondary outcomes are listed without results, and the record does not report multiplicity or missing-data procedures. These omissions limit the ability to reconstruct how the evidence was evaluated.

Finally, the planning assumptions are explicitly illustrations based on the observed effect rather than documentation of the trial’s original design rationale. Keeping hypothetical planning calculations separate from observed evidence avoids treating them as validation of the result. The statistical importance of this study is therefore as much about the limits of the reported comparison as about the direction of the descriptive changes.

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 principal limitation of interpretation is that the registry reports group means and standard deviations but no inferential estimate for the primary two-arm comparison. No confidence interval or p-value is reported, and the record states that values are missing or not estimable for the continuous endpoint comparison. The posted summaries consequently do not show how precisely the group contrast is estimated.

The primary outcome summaries have different group counts: n=8 for prednisolone and n=4 for placebo. The registry does not explain the difference, identify all participants with missing outcome values, or provide reasons for exclusions. Although the endpoint description defines a per-protocol population, the actual analysis population is not reported clearly enough to determine how it relates to the posted summaries.

The registry describes a masked clinician rating on a 4-point scale and identifies the assessment as occurring 90 minutes after CAC. It does not provide further detail on rating procedures, measurement reliability, or the relation of this primary measure to the confocal microscopy mentioned in the study summary. Baseline group summaries and individual score distributions are not reported in the registry record.

Ocular itching and ocular redness are listed as secondary outcomes, but their results are not reported in the registry record. The multiplicity strategy, missing-data methods, detailed statistical analysis plan, and trial-specific sample-size justification are also not reported. The adverse-event record includes a Saline group, but its role is not explained. Together, these gaps restrict assessment of the comparative efficacy, safety, and generalizability of the reported findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Prednisolone in a Modified Conjunctival Allergen Challenge Model — NCT01730872.
• Registry record last updated 2019-06-19; status last verified 2019-06.
• Results first posted 2019-06-19.
• 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 describes a completed Phase 4, randomized, parallel-group, quadruple-masked study of prednisolone sodium phosphate ophthalmic solution, 1%, versus Tears Naturale II ophthalmic solution, 1%, in a modified conjunctival allergen challenge model. Enrollment was 16. The study start is listed as 2012-11 and primary completion as 2012-12.

The primary outcome was change in clinician-rated ocular inflammation from baseline to Day 6, assessed 90 minutes after CAC on a 4-point scale. The posted mean changes were -1.2 (standard deviation 0.78; n=8) for prednisolone and -0.19 (standard deviation 0.43; n=4) for placebo. No inferential result for the primary comparison is reported. Ocular itching and redness were listed as secondary outcomes, but their results are not reported in the registry record.

The record reports zero serious adverse events and zero deaths in the listed groups. It does not describe the role of the Saline safety group or provide a complete account of missing data, analysis populations, multiplicity, or the statistical analysis plan.