Evaluation of the Efficacy of Topical Ophthalmic Steroids in a Modified Conjunctival Allergen Challenge (CAC) Model: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Efficacy of Topical Ophthalmic Steroids in a Modified Conjunctival Allergen Challenge (CAC) Model (NCT01534195), a randomized phase 4 study. The primary outcome is Ocular Itching Change From Baseline to Day 11.

2. Clinical Question

3. Trial Design

The registry describes a Phase 4, randomized, double-masked, single-center, placebo-controlled adaptive clinical trial of prednisolone sodium phosphate ophthalmic solution, 1%, in subjects with allergic conjunctivitis. Its structured fields identify the allocation as randomized, the masking as quadruple, and the model as parallel. These descriptions appear together in the record; further details reconciling the masking descriptions are not reported in the registry record.

The trial compared Prednisolone Sodium Phosphate Ophthalmic Solution, 1%, with Tears Naturale II Ophthalmic Solution, 1%, listed as the placebo. The stated purpose was to evaluate the modified Conjunctival Allergen Challenge model and observe the response of challenge-produced allergic inflammation to treatment. Ocular itching and conjunctival redness were named as measures of interest.

The record lists 11 participants enrolled and a primary outcome population of participants who completed the study. The posted primary outcome has results for 4 participants in the prednisolone group and 5 in the placebo group. The study is marked completed. Its recorded start is 2012-01, and its primary completion is 2012-02.

Although the official title calls the trial adaptive, the specific adaptive features, any changes to the design, and the timing or rationale for any such changes are not reported in the registry record. Protocol details beyond the listed trial characteristics, including recruitment and visit procedures, are not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who completed the 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 Ocular Itching Change From Baseline to Day 11, measured over 5 minutes post-CAC.

The primary outcome is titled Ocular Itching Change From Baseline to Day 11. It records participant-assessed ocular itching on a 4-point scale, measured 5 minutes after the conjunctival allergen challenge. The scale is described as running from 0, no itching and best, to 4, worst itching and worst. The outcome is expressed in units on a scale, with the group summary reported as a mean and standard deviation.

Itching is a symptom directly experienced and rated by the participant. In this study, measuring it after the allergen challenge offers a way to describe the symptom response in the modified challenge model. The study description also names conjunctival redness as a measure of interest, and the record lists redness outcomes among the secondary measures.

The registry’s primary outcome population is all participants who completed the study. Its timeframe field says 5 minutes post-CAC, while the outcome title specifies change from baseline to Day 11. The relationship between the baseline assessment and the Day 11 assessment is not elaborated in the registry record. Nor does the record state the sign convention used to calculate change. The reported means therefore describe the posted changes, but the record alone does not establish how a negative value should be interpreted beyond its being a negative change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is measured in units on a scale, and the registry reports a mean and standard deviation for each group. The methods below explain what those summaries can and cannot convey in general. They do not add an analysis that is absent from the registry record.

What does a group mean describe?

A mean is a measure of the central value of a set of observations. For this outcome, the posted mean summarizes participant-assessed change in ocular itching within each treatment group. The values are -1.1 units for Prednisolone and -0.45 units for Placebo. A mean is useful for describing the group’s average recorded change, but it does not show the full pattern of participant responses. Different sets of individual responses can have the same mean.

The scale’s anchors help explain what is being rated: 0 is no itching and 4 is worst itching. The record says the outcome is change from baseline, but does not state the sign convention or give individual observations. Accordingly, the means should be presented as recorded rather than translated into an unstated direction of benefit.

What does the standard deviation describe?

A standard deviation describes how dispersed individual observations are around their group mean. The registry reports standard deviations of 0.14 for Prednisolone and 0.86 for Placebo. These figures describe variability in the recorded outcome within each group; they are not confidence limits, and they do not indicate the probability that a treatment effect is true.

Standard deviations can be difficult to assess when a group contains few observations. The posted group sizes are 4 and 5, so each summary rests on a limited set of participants. A small standard deviation in a small group does not by itself establish that the mean is precise or representative. The registry does not report confidence intervals that would directly express uncertainty around the group means or a between-group estimate.

Why is a between-group estimate important?

In a randomized comparison, the central treatment question generally concerns the difference between groups, not whether each group’s mean change is considered on its own. A between-group estimate would quantify the contrast in outcomes, and an uncertainty interval would describe the range of effect sizes compatible with the analysis. A statistical test may also be used to assess compatibility with a null hypothesis under stated assumptions. These are general statistical concepts; the registry does not report a between-group estimate, confidence interval, test statistic, or p-value for this endpoint.

The posted group means should not be subtracted to create a new estimate. The record specifically notes that values are missing or not estimable for a two-arm comparison of this continuous endpoint. No recalculated comparison is available, and no sponsor analysis is posted for this endpoint. The record does not explain the reason the comparison is missing or not estimable.

What can an analysis plan establish?

A prespecified statistical plan can describe which population will be analyzed, how the outcome will be modeled, how missing observations will be handled, and whether adjustments are planned. Those choices shape the interpretation of an estimate. The registry record identifies the primary outcome population as all participants who completed the study, but a detailed statistical analysis plan is not reported in the registry record. The record also reports zero analyses, so the intended or completed inferential methods cannot be established from posted analysis results.

The official title describes the study as adaptive, but the record does not give details about adaptations, decision rules, interim analyses, or how any adaptation would affect statistical inference. Such features should not be assumed from the title alone. Their presence, timing, and analysis implications are not reported in the registry record.

How should planning illustrations be understood?

Sample-size planning illustrations based on an observed effect are not observed trial results and are not a measure of observed power. The record’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such calculations can illustrate how planning depends on assumptions, but they do not establish the trial’s original design rationale or show that the trial had a particular probability of detecting an effect.

The calculations are expressly described as planning illustrations rather than the trial’s own design. The sample-size justification, original target enrollment rationale, and any power calculation used by the investigators are not reported in the registry record. A planning result based on a small observed estimate can also be unstable because the observed effect may be imprecise. This is a general caution, not a finding about the investigators’ design.

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(4, 5)
m   <- c(-1.1, -0.45)
sp  <- c(0.14, 0.86)
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  4  -1.100  0.140  -1.323  -0.877
CARM  Placebo  5  -0.450  0.860  -1.518  0.618

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes. The primary outcome is change in ocular itching from baseline to Day 11. The secondary outcomes are conjunctival redness change from baseline to Day 11, episcleral redness change from baseline to Day 6, and ciliary redness change from baseline to Day 6. The record does not report results for these secondary outcomes in the registry record for this analysis.

When a study assesses several outcomes, repeated statistical testing can raise the chance of at least one apparently notable result arising by chance. Statistical methods can address this issue, but the appropriate approach depends on the planned outcome hierarchy and analysis strategy. The registry record does not report whether multiplicity adjustments were planned or performed, nor does it provide a detailed analysis plan. No multiplicity-adjusted findings are available in the posted analyses.

The primary outcome population is described as all participants who completed the study. The registry lists 11 enrolled participants, while the primary outcome summaries list 4 participants for Prednisolone and 5 for Placebo. A participant flow account, reasons for non-completion, and outcome availability by participant are not reported in the registry record. Missing-data mechanisms, imputation procedures, and sensitivity analyses are also not reported in the registry record.

Because the record reports zero analyses and indicates that values are missing or not estimable for the continuous two-arm comparison, it is not possible to determine how the intended analysis handled incomplete outcome data or whether the completed-participant population was the only analysis population. These omissions limit assessment of the analysis choices and the robustness of any treatment comparison.

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 posted safety figures report serious adverse events in 0 of 5 participants at risk in the Prednisolone group and 0 of 6 at risk in the Placebo group. Deaths are also reported as 0 in each group. The registry lists no serious adverse event terms among its top serious terms. These figures describe the recorded event counts and risk denominators; they are not a comparison demonstrating equivalent safety.

For other adverse events, the record reports 1 of 5 participants at risk affected in the Prednisolone group and 3 of 6 in the Placebo group. The serious-event denominators differ from the primary outcome group sizes: safety lists 5 and 6 at risk, while the primary outcome summaries list 4 and 5 participants. The registry record does not explain these differences.

Small group counts limit how much can be inferred from an absence of reported serious events. The record does not provide details about event definitions, collection methods, duration of safety follow-up, or a statistical safety comparison. These counts should be read as descriptive registry entries, not as proof that serious events could not occur or as guidance about treatment.

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

The registry record establishes that a randomized, placebo-controlled trial evaluated prednisolone in a modified conjunctival allergen challenge model for allergic conjunctivitis. Its primary outcome concerned participant-assessed ocular itching, measured 5 minutes after CAC and expressed as change from baseline to Day 11. The posted group summaries are a mean change of -1.1 units for Prednisolone and -0.45 units for Placebo, with standard deviations of 0.14 and 0.86, respectively.

These summaries do not establish a statistically significant difference between groups. The registry reports no inferential analysis for the primary outcome, and states that values are missing or not estimable for a two-arm comparison. There is no posted confidence interval or p-value for a treatment contrast. The record also does not state the sign convention for change, so the negative values should not be assigned a direction of clinical effect solely on their signs.

The outcome is a participant-rated symptom on a 4-point scale, with 0 defined as no itching and 4 as worst itching. The record does not provide a threshold for a clinically important change, the distribution of individual responses, or details that would connect a mean change to a meaningful experience for participants. Such interpretation therefore cannot be established from the posted summaries alone.

The result is also bounded by the small reported outcome group sizes, the absence of a participant disposition account, and missing details about analysis methods and missing-data handling. The study’s official title calls it adaptive, but the specific adaptation procedures are not described. Neither the trial design label nor the descriptive means fill these gaps.

Overall, the posted data describe outcome summaries from this trial; they do not support a definitive inferential conclusion about the between-group effect. They should not be treated as medical advice or as evidence applicable beyond the trial population and setting without further evidence.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between reporting group summaries and reporting a comparative treatment effect. A randomized design creates the framework for comparing groups, but interpretation of the primary question depends on an estimate of the between-group contrast and information about its uncertainty. The registry reports means and standard deviations for each group but does not report that comparative analysis.

The outcome is a participant-rated scale measure, and its interpretation depends on both the scale anchors and the definition of change. The record specifies the anchors and assessment timing, but does not give a sign convention for the change score. That makes transparent outcome definitions important: a numerical change is easier to interpret when the direction and calculation are stated explicitly.

The record also highlights the importance of distinguishing enrolled participants, participants at risk for safety outcomes, and participants included in efficacy summaries. It lists 11 enrolled participants, safety denominators of 5 and 6, and primary outcome group sizes of 4 and 5. Without a participant flow account, readers cannot determine how these populations relate or why their counts differ.

Finally, a trial described as adaptive needs enough design and analysis detail for readers to understand how its adaptations were governed and incorporated into inference. The registry’s title uses that description, but the record does not report the specific adaptive procedures. More complete reporting of the analysis plan, participant disposition, and comparative estimates would help readers distinguish design intent from the results actually available.

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 posted primary outcome information is limited to group-level means, standard deviations, and group sizes. The record does not report a between-group estimate, confidence interval, test statistic, or p-value, and it explicitly notes that values are missing or not estimable for the continuous two-arm comparison. The reason for that missing or non-estimable comparison is not reported in the registry record.

The outcome summaries list 4 participants for Prednisolone and 5 for Placebo, while enrollment is listed as 11. The primary outcome population is described as all participants who completed the study, but the number who completed, participant disposition, and reasons for missing outcome data are not reported in the registry record. The safety denominators are 5 and 6, with no explanation of how they relate to the outcome populations.

The record names the endpoint’s scale anchors and assessment timing but does not state the sign convention for change or explain the baseline assessment procedure. It does not report individual observations, a clinically important change threshold, or a detailed statistical analysis plan. Missing-data methods, sensitivity analyses, and multiplicity procedures are also not reported in the registry record.

The official title describes an adaptive trial, but the registry does not describe adaptation rules, interim analyses, or their statistical handling. The record identifies the study as single center, but does not provide further details to assess the implications of that setting. These reporting gaps limit interpretation of the descriptive findings and prevent assessment of the robustness of a comparative conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of the Efficacy of Topical Ophthalmic Steroids in a Modified Conjunctival Allergen Challenge (CAC) Model — NCT01534195.
• Registry record last updated 2019-03-26; status last verified 2012-07.
• Results first posted 2019-01-15.
• 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 Phase 4 randomized, double-masked, placebo-controlled parallel-group trial of Prednisolone Sodium Phosphate Ophthalmic Solution, 1%, versus Tears Naturale II Ophthalmic Solution, 1%, in allergic conjunctivitis. It lists 11 participants enrolled and identifies the primary outcome as change in participant-assessed ocular itching from baseline to Day 11, assessed 5 minutes after CAC on a 4-point scale.

The posted primary outcome summaries are -1.1 units with standard deviation 0.14 and 4 participants for Prednisolone, and -0.45 units with standard deviation 0.86 and 5 participants for Placebo. No inferential analysis is reported, and the registry notes that values are missing or not estimable for the continuous two-arm comparison. The record also lists three secondary outcomes and descriptive safety counts, but does not report detailed analysis methods, participant disposition, or missing-data procedures.